A Randomized Controlled Trial to Improve Mother-Infant Synchrony Among Women With Childhood Adversity
Phase: NA
Conditions: Parent-Child Relations, Maternal Behavior, Infant Behavior
Sponsor: University of Arizona

 
 
A R a n d o miz e d C o ntr oll e d Tri al t o I m pr ov e M ot h er -I nf a nt Sy nc hr o ny A m o n g W o m e n w it h 
C hil d h o o d A d v ersity  
 
N C T 0 4 8 1 8 1 1 2  
 
Pr ot oc ol & St a tis tic al A n al ysis Pl a n Versi o n  1. 6  0 1 /3 1 /2 0 2 4  
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1  
Pr ot oc ol  f or 
 
“A R a n d o miz e d C o ntr oll e d Tri al t o I m pr o v e 
M ot h er -I nf a nt S y nc hr o n y a m o n g W o m e n wit h 
C hil d h o o d A d v ersit y ” 
 
Pr ot oc ol N u m b er 2 0 0 9 0 5 0 7 5 6  
N ati o n al Cli nic al Tri al ( N C T) I d e ntifi e d N u m b er:  N C T 0 4 8 1 8 1 1 2  
Pri nci p al I n v esti g at or : Al e ec a F. B ell , P h D R N C N M  
 
 
 
 
 
 
 
 
 
 
 
 
F u n d e d b y : N ati o n al I nstit ut e of N ursi n g R es e arc h 
 
V ersi o n N u m b er:  1 .6  
 
3 1 J a n u ar y 2 0 2 4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
2  
 
T A BL E O F C O N T E N T S  
 
 
 
S ecti o n  
 P a g e N u m b er  
St at e m e nt of C o m pli a nc e  
2  
PI A p pr ov al  
3 -4  
1. 0  S u m m ar y  D oc u m e nt s 
5 -8  
2. 0  I ntr o d ucti o n 
9 -1 2  
3. 0 O bj ectiv es & E n d p o ints  
1 3 -1 6  
4. 0 St u dy D esi g n   
1 6 -2 3  
5. 0 Q u alit y M a n a g e m e nt   
2 4  
6. 0  D at a, S af ety, & M o nit ori n g Pl a n   
2 4 -2 9  
7. 0 Pr oj ect M a n a g e m e nt  
2 9 -3 1  
R ef er e nc es  
R e m ov e d   
 
 
S T AT E M E N T OF C O M PLI A N C E  
 
T h is tri al will b e c arri e d o ut i n acc or d a nc e wit h I nt er n ati o n al C o nf er e nc e o n H ar m o ni sati o n  G o o d Cli nic al Pr actic e (I C H 
G C P) a n d t h e f oll o wi n g:  
 
•  
U nit e d St at es ( U S) C o d e of F e d er al R e g ul ati o ns ( C F R) a p plic a bl e t o cli nic al st u di es ( 4 5 C F R P art 4 6, 2 1 C F R P art 
5 0, 2 1 C F R P art 5 6 ) will b e f oll o w e d.  
 
•  
N ati o n al I nstit ut es of H e alt h ( NI H) -f u n d e d i nv esti g at ors a n d cli nic al tri al sit e st aff w h o ar e r es p o nsi bl e f or t h e 
c o n d uct, m a n a g e m e nt, or o v ersi g ht of NI H -f u n d e d cli nic al tri als will  c o m pl et e H u m a n S u bj ects Pr ot ecti o n a n d 
I C H G C P Tr ai ni n g. 
 
•  
All a p plic a bl e p olici es a n d g ui d eli n es fr o m U ni v ersit y of Ariz o n a ’s R es e arc h, Disc ov ery,  a n d I n n ov ati o n  pr o gr a ms  
( HI P A A Priv acy Pr o gr a m, R es e arc h L a b or at or y & S af ety S ervic es, a n d H u m a n S u bj ects  Pr ot ecti o n Pr o gr a m ) will 
b e f oll o w e d.  
 
I n s u m m ar y, t h e pr ot oc ol, i nf or m e d c o ns e nt f or m(s), r ecr uit m e nt m at eri als, a n d all p artici p a nt m at eri als h av e b e e n  
s u b mitt e d t o sit e r es e arc h c o m mitt e es a n d t o t h e U niv ersity of Ariz o n a’s I nstit uti o n al R evi e w B o ar d (I R B) f or r e vi e w a n d 
a p pr o v al.  A p pr o v al of pr ot oc ol el e m e nts  a n d t h e c o ns e nt f or m s w er e o bt ai n e d  pri or  t o p artici p a nt e nr oll m e nt. 
A d diti o n ally, a ny a m e n d m e nts t o t his  pr ot oc ol will b e r e vi e w e d a n d a p pr o v e d b y t h e  U ni v ersity of Ariz o n a’s  I R B pri or t o 
i m pl e m e nt ati o n.  F urt h er m or e, all c h a n g es t o t h e c o ns e nt f or m will b e I R B-a p pr ov e d a n d a d et er mi n ati o n will b e m a d e 
r e g ar di n g w h et h er a n e w c o ns e nt n e e ds t o b e o bt ai n e d fr o m p artici p a nts w h o pr o vi d e d c o ns e nt usi n g a pr evi o usly 
a p pr o v e d c o ns e n t f or m. 
 
 
 
 
 
 
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
4  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. 0  S U M M A R Y  D O C U M E N T S  
1. 1  A bstr act  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
5  
 
Titl e: A r a n d o miz e d c o ntr oll e d tri al t o i m pr o v e m ot h er-i nf a nt s y nc hr o ny a m o n g w o m e n wit h c hil d h o o d a d v ersit y 
 
B ac k gr o u n d:  T his  4 -y e ar, si n gl e -sit e, r a n d o miz e d, att e nti o n-c o ntr oll e d cli nic al tri al s e eks t o e v al u at e t h e effic ac y  of a n 
i nf a nt-m ass a g e i nt erv e nti o n  ( A T V V) t o i m pr o v e r eci pr oc al c o m m u nic ati o n p att er ns b et w e e n m ot h er a n d i nf a nt  c all e d 
m ot h er -inf a nt sy nc hr o ny . I d e all y, as a m ot h er r ec o g niz es a n d is s e nsiti v e t o h er i nf a nt’s c u es, s h e a d a pts h er n urt uri n g 
b e h a vi or t o m axi miz e t h e i nf a nt’s a bilit y t o r es p o n d wit h cl e ar er c u es a n d gr e at er s elf -r e g ul ati o n. T h e q u alit y of m ot h er -
i nf a nt ( M-I) s y nc hr o ny pr e dicts h e alt hy i nf a nt att ac h m e nt a n d l o n g-t er m p hysic al, c o g nitiv e, a n d e m oti o n al d e v el o p m e nt 
of t h e c hil d. ( 7, 1 3, 1 8, 1 9) A d diti o n ally,  t h e n e ur o p e pti d e o x yt oci n ( O X T)  is critic al i n pr o m oti n g M-I sy nc hr o ny. ( 7-1 1) 
H o w ev er,  c hil d h o o d a d v ersit y is c o m m o n  (1 -4) a n d c a us es p ot e nt l o n g-t er m d a m p e ni n g of t h e O X T syst e m, p ot e nti ally 
pl aci n g M -I s y nc hr o ny a n d f ut ur e d ev el o p m e nt of t h e c hil d at ris k.  
 
H y p ot h esis:  W e p osit  t h at t h os e m ot h ers wit h c hil d h o o d a dv ersit y will h av e m or e diffic ult y wit h m ot h er -i nf a nt 
s y nc hr o ny a n d will b e n efit fr o m i nt erv e nti o ns s uc h as i nf a nt ma ss a g e A T V V , w hic h i m pr ov e n urt uri n g e n g a g e m e nt  
t hr o u g h a u dit ory, t actil e, vis u al, a n d v esti b ul ar ( A T V V) c o m m u nic ati o n p att er ns w hic h  i nfl u e nc e e pi g e n etic r e g ul ati o n of 
t h e ox yt oci n ( O X T) syst e m. O ur o bj ecti v es ar e  t h e f oll o wi n g- 
•  
Ai m 1 - E v al u at e t h e effic ac y of d ail y A T V V o v er 3 p ost n at al m o nt hs a m o n g m ot h ers wit h c hil d h o o d a d v ersit y. 
C o m p ar e d t o t h e Att e nti o n C o ntr ol gr o u p ( n = 1 2 5), m ot h er -i nf a nt d y a ds i n t h e A T V V gr o u p (n = 1 2 5) will 
e x hi bit:   
o  H 1:  Hi g h er ox yt oci n f u ncti o n at 1, 2, a n d 3 p ost n at al m o nt hs as c o m p ar e d t o pr e n at al b as eli n e a n d   
o  H 2:  M or e m ot h er -i nf a nt ( M-I) sy nc hr o ny at 3 p ost n at al m o nt hs.  
•  
Ai m 2 - I d e ntif y m ol ec ul ar m ec h a nis ms i n t h e O X T s yst e m u n d erl yi n g M-I s y nc hr o n y (N = 2 5 0).  
o   H 1:  L o w er M-I sy nc hr o ny will b e ass oci at e d wit h d a m p e ni n g of t h e O X T s yst e m i n m at er n al p eri p h er al 
bl o o d a n d d ecr e as e d O X T i n i nf a nt s aliv a at 3 -p ost n at al m o nt hs.  
 
M et h o ds: T h e i nf a nt-m ass a g e i nt erv e nti o n, A T V V ( A u dit or y, T actil e, Vis u al, V esti b ul ar) , c o nsists of i nf a nt-dir ect e d 
s p e ec h, m o d er at e t o uc h m ass a g e, ey e t o ey e g az e, a n d h oriz o nt al r ocki n g. T h e pri m ar y o utc o m e,  M -I s y nc hr o ny, is 
c oll ect e d 3 m o nt hs p ost birt h  i n 2 5 0 first-ti m e m ot h ers ( a n d t h eir f ull-t er m i nf a nts) r a n d o miz e d t o a p ply A T V V d aily fr o m 
birt h t o 3 m o nt hs ( n = 1 2 5) or r ec eiv e i nf a nt c ar e e d uc ati o n i n a n Att e nti o n C o ntr ol gr o u p ( n = 1 2 5).  M -I sy nc hr o ny is 
m e as ur e d usi n g 3 -mi n ut es of vi d e o -r ec or d e d i nt er acti o n t o micr o-c o d e s h ar e d g az e (pri m ary o utc o m e ), aff ect (pri m ar y 
o utc o m e ), s p eec h, a n d t o uc h. O X T l e v el  is a k n o w n bi o m ar k er of s y nc hr o ny . S ec o n d ar y o utc o m es i ncl u d e a 
c o m pr e h e nsiv e a n alysis of t h e O X T syst e m i ncl u di n g  i d e ntific ati o n of a p ot e nti al e pi g e n etic r ol e of t h e oxyt oci n r ec e pt or 
g e n e ( O X T R). W e a n alyz e m at er n al bl o o d i n pr e g n a nc y a n d at 1, 2, a n d 3 m o nt hs p ost birt h ( a n d i nf a nt s aliv ar y O X T).   
W e ai m t o i d e ntif y m ol ec ul ar m ec h a nis ms i n t h e O X T s yst e m u n d erl yi n g M -I s y nc hr o ny i n m at er n al bl o o d a n d disc ov er 
m ol ec ul ar pr ofil es. R e gr essi o n b as e d m et h o ds ass ess A T V V eff ects o n a n d r el ati o ns a m o n g M -I s y nc hr o ny a n d O X T 
m e as ur es .   
 
I m p act: T his st u dy will a dv a nc e u n d erst a n di n g of A T V V’s effic acy t o i m pr o v e M -I s y nc hr o ny a n d t h e u n d erl yi n g 
e pi g e n etic m ec h a nis ms t o pr o m ot e sy nc hr o ny i n a n u n d erst u di e d p o p ul ati o n. B ec a us e t his e arl y lif e a n d h o m e -b as e d 
i nt er v e nti o n is e asy t o t e ac h a n d p erf or m, it h as hi g h tr a nsl ati o n al  p ot e nti al f or pr actic e. F urt h er m or e, t his  st u dy d esi g n 
s er v es as a m o d el f or t esti n g i n ot h er at-ris k gr o u ps. T h e s oci al a n d ec o n o mic c ost s a vi n gs ass oci at e d wit h r e d uci n g t h e 
p ot e nt i m p act of a dv ers e ev e nts o n m at er n al a n d i nf a nt o utc o m es c a n n ot b e u n d er esti m at e d. ( 2, 5, 1 4 1-1 4 2)  
 
 
 
 
 
1. 2  S y n o psis  
Titl e: A ra n d o miz e d co ntr oll e d tri al t o im pr o v e m ot h er -inf a nt sy nc hr o ny a m o n g w o m e n wit h chil d h o o d a dv ersit y  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
6  
St u d y D esi g n : A 4 -y e ar si n gl e -sit e, r a n d o miz e d, t w o-gr o u p, att e nti o n -c o ntr oll e d cli nic al tri al   
H y p ot h esis:  M ot h ers wit h c hil d h o o d a dv ersity will h av e m or e diffic ult y wit h m ot h er -i nf a nt s y nc hr o ny, d u e i n p art t o a 
d a m p e n e d oxyt oci n syst e m, a n d  will b e n efit fr o m  t h e i nf a nt-m ass a g e i nt erv e nti o n a p pl yi n g  n urt uri n g e n g a g e m e nt 
t hr o u g h a u dit ory, t actil e, vis u al, a n d v esti b ul ar ( A T V V) c o m m u nic ati o n p att er ns w hic h will  i nfl u e nc e e pi g e n etic 
r e g ul ati o n of t h e ox yt oci n ( O X T) s yst e m. 
I nt er v e nti o n: A  m ultis e ns or y  i nf a nt-m ass a g e c o nsisti n g of a u dit or y, t actil e, vis u al, a n d v esti b ul ar ( A T V V) sti m uli 
a d mi nist er e d b y t h e m ot h er t o t h e i nf a nt o n e ti m e e ac h d a y f or 3 m o nt hs.  
C o m p aris o n: A tt e nti o n-co ntr ol  m ot h ers  r ec ei vi n g s a m e a m o u nt of t e m p or al att e nti o n as r ec eiv e d by t h e i nt er v e nti o n 
gr o u p . 
O bj ecti v es  a n d  W or ki n g H y p ot h es es :  Ai m 1 - E v al u at e t h e effic acy of d ail y A T V V ov er 3 p ost n at al m o nt hs a m o n g 
m ot h ers wit h c hil d h o o d a dv ersity. C o m p ar e d t o t h e Att e nti o n C o ntr ol gr o u p ( n = 1 2 5), m ot h er -i nf a nt dy a ds i n t h e A T V V 
gr o u p ( n = 1 2 5) will ex hi bit : H 1  - Hi g h er ox yt oci n f u ncti o n at 1, 2, a n d 3 p ost n at al m o nt hs  as c o m p ar e d t o pr e n at al 
b as eli n e a n d  H 2  - M or e m ot h er -i nf a nt ( M-I) s y nc hr o ny as m e as ur e d by r eci pr oc al g az e, aff ect, s p e ec h, a n d t o uc h at 3 
p ost n at al m o nt hs .  Ai m 2 - I d e ntif y m ol ec ul ar m ec h a nis ms i n t h e O X T s yst e m u n d erl yi n g M -I s y nc hr o ny (N = 2 5 0).  H 1 - 
Lo w er M -I sy nc hr o ny will b e ass oci at e d wit h d a m p e ni n g of t h e O X T syst e m i n m at er n al p eri p h er al bl o o d a n d d ecr e as e d 
O X T i n i nf a nt s ali v a at 3 -p ost n at al m o nt hs.  
Pri m ar y  O utc o m e : M ot h er -inf a nt S y nc hr o ny  as m e as ur e d by  ti m e s p e nt e n g a gi n g i n s y nc hr o n o us e y e-t o-e y e g az e a n d 
p ositi v e aff ect . 
S ec o n d ar y O utc o m e s: M ot h er -I nf a nt S y nc hr o ny as m e as ur e d b y ti m e s p e nt e n g a gi n g i n s y nc hr o n o us p ositiv e s p e ec h 
a n d aff ecti o n at e t o uc h. F u ncti o ni n g of m at er n al O X T s yst e m as m e as ur e d b y e pi g e n etic m ar ks i n  t h e O X T r ec e pt or 
( O X T R) g e n e, ex pr essi o n of t h e O X T R  g e n e , q u a ntity of O X T R pr ot ei n  pr o d uc e d , a n d q u a ntit y of O X T p e pti d e  i n m at er n al 
p eri p h er al bl o o d a n d  O X T p e pti d e i n  i nf a nt s aliv a. 
I ncl usi o n Crit eri a: Pr e g n a nt w o m e n ar e eli gi bl e if t h ey ar e   
•  
h e alt h y ( g est ati o n al di a b et es is acc e pt a bl e) , 
•  
gr e at er t h a n or e q u al t o 1 8 y e ars ol d,   
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ex p ecti n g t h eir first c hil d  ( pr e vi o us misc arri a g e(s) a n d a b orti o n(s) acc e pt a bl e),  
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s p e a k a n d r e a d E n glis h or S p a nis h,  
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sc or e gr e at er t h a n or e q u al t o 2 o n t h e A dv ers e C hil d h o o d Ex p eri e nc e ( A C E) s urv ey,  
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ex p ect t o d eliv er a h e alt hy i nf a nt , 
•  
ex p ect t o d eliv er a f ull -t er m i nf a nt ( gr e at er t h a n or e q u al t o 3 7 w e e ks a n d 0/ 7 d a ys), a n d  
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ex p ect t o d eliv er a si n gl et o n i nf a nt .  
E xcl usi o n Crit eri a:   Pr e g n a nt w o m e n ar e i n eli gi bl e if t h e y  
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h a v e giv e n birt h t o >  1 c hil d  
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h a v e n o acc ess t o a c ell p h o n e d uri n g t h e first 3 p ost n at al m o nt hs , 
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c arr yi n g m ulti pl e f et us es,  
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t a ki n g illicit dr u gs, 
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e v er di a g n os e d wit h bi p ol ar,  
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e v er di a g n os e d wit h a utis m , 
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e v er di a g n os e d wit h psyc h osis , 
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i nf a nt di a g n os e d as s m all f or g est ati o n al a g e ( S G A) d efi n e d b y b o dy m ass, h e a d circ u mf er e nc e, a n d b o dy l e n gt h 
l ess t h a n t h e 1 0t h p erc e ntil e f or t h e g est ati o n al a g e at birt h , 
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i nf a nt di a g n os e d wit h a c hr o m os o m al a n o m aly,  
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i nf a nt di a g n os e d wit h a c o n g e nit al a n o m al y,  
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i nf a nt h as a s eri o us ill n ess w hic h w o ul d i nt erf er e wit h m ot h er -i nf a nt i nt er acti o n  
L e n gt h of Ti m e R e q uir e d f or P artici p ati o n i n St u d y: 6  - 9  m o nt hs  
I niti ati o n D at e: 2 3  J u n e 2 0 2 1 
 
I niti al E nr oll m e nt D at e:  1 2  J ul y 2 0 2 1 
 
 
Fi n al D at a C oll ecti o n D at e:  pr oj ect e d 3 1  M arc h  2 0 2 4  
Pr oj ect C o m pl eti o n D at e:  pr oj ect e d 3 1 J a n u ary 2 0 2 5  
 
1. 3  Fl o w Di a gr a m  
E nr oll m e nt  
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A n al y s e d  ( n =)  
 E x cl u d e d fr o m a n al y si s ( gi v e r e a s o n s) ( n =  )  
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n = )  
Wit h dr a w n ( gi v e r e a s o n s) ( n = )  
 
   
  
  
  
 
 
  
  
  
 
 
All o c at e d t o i nt er v e nti o n ( n = )  
 R e c ei v e d i nt er v e nti o n ( n =  )  
 Di d n ot r e c ei v e i nt er v e nti o n ( gi v e r e a s o n s) ( n =  ) 
 
   
  
 
 
 
 
  
   
 
  
  
 
  
  
  
   
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n = )  
Wit h dr a w n ( gi v e r e a s o n s) ( n =)  
 
   
  
  
  
 
 
  
  
 
 
All o c at e d t o e d u c ati o n c o ntr ol ( n =)  
 R e c ei v e d e d u c ati o n ( n =  )  
 Di d n ot r e c ei v e e d u c ati o n ( gi v e r e a s o n s) ( n =  ) 
 
    
  
 
 
 
  
  
   
 
  
  
  
  
  
  
   
A n al y s e d  ( n =)  
 E x cl u d e d fr o m a n al y si s ( gi v e r e a s o n s) ( n =  ) 
 
 
  
 
 
  
  
  
  
  
   
 
A n al ysis  
E x cl u d e d  ( n =   )  
   N ot m e eti n g i n cl u si o n crit eri a ( n =  )  
   D e cli n e d t o p arti ci p at e ( n =  )  
   Ot h er r e a s o n s ( n =  )  
 
   
    
   
  
  
  
  
   
   
    
  
   
   
 
  
   
F oll o w -U p T 2  
 
 
 
A s s e s s e d f or eli gi bilit y ( n = ) 
 
  
 
 
 
F oll o w -U p T 4  
 
 
 
F oll o w -U p T 3  
 
 
 
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n = )  
Wit h dr a w n ( gi v e r e a s o n s) ( n =  )  
 
   
 
  
 
  
  
  
  
   
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n =) 
Wit h dr a w n ( gi v e r e a s o n s) ( n =  )  
 
   
  
  
 
 
  
  
  
   
L o st t o f oll o w-u p ( gi v e r e a s o n s) ( n =)  
Wit h dr a w n ( gi v e r e a s o n s) ( n =  )  
 
   
  
  
 
 
  
  
  
   
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n =)  
Wit h dr a w n ( gi v e r e a s o n s) ( n =  )  
 
   
  
  
 
 
  
  
  
   
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n =)  
Wit h dr a w n ( gi v e r e a s o n s) ( n =  )  
 
   
  
  
 
 
  
  
  
   
L o st t o f oll o w -u p ( gi v e r e a s o n s) ( n =)  
Wit h dr a w n ( gi v e r e a s o n s) ( n =  )  
 
   
  
  
 
 
  
  
  
   
F oll o w -U p T1  
 
  
E x cl u d e d ( n =   )  
   C o n s e nt e d b ut n o b a s eli n e d at a  
   N ot m e eti n g i n cl u si o n crit eri a at birt h ( n =  )  
   L o s s t o f oll o w u p ( n =   )  
   D e cli n e d t o p arti ci p at e ( n =  )  
   Ot h er r e a s o n s ( n =  )  
 
  
    
   
  
  
 
 
 
   
  
  
  
    
  
   
   
    
  
  
    
   
    
  
   
   
  
  
   

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
8  
1. 4  Sc h e d ul e of E v e nts f or “ Ra n d o miz e d C o ntr oll e d T ri al t o Im pr o v e M ot h er -Inf a nt S y nc hr o n y a m o n g W o m e n wit h C hil d h o o d A d v ersit y ” 
 
E v e nt / Ti m e p oi nt & L oc ati o n  
I nstr u m e nts / O utc o m e M e as ur es  
R ecr uit m e nt (l ast 
tri m est er) 
B as eli n e ( 3 3 w ks +  2 w ks g a)  Birt h ( pri or t o disc h ar g e)  
Birt h ( aft er 
disc h ar g e)  
T 1 ( 2 8 d a ys - 
7 d a ys / + 1 4 d a ys ) 
T 2 ( 5 6 d a ys -7 
d a ys / + 1 4 d a ys ) 
T 3 ( 8 4 d a ys -7 
d a ys / + 1 4 d a ys ) 
T 4 ( 6 m os +  4 w ks)  
R E D C a p  / C oll e g e of N ursi n g ( C o N) r o o m 4 1 8 C 
Cli nics  
C oll e g e o f N ursi n g  
T M C , B U M C  or Z o o m  
P h o n e /t ext 
C oll e g e o f N ursi n g  
C oll e g e o f N ursi n g  
C oll e g e o f N ursi n g  
p h o n e  
R ecr uit m e nt/ Scr e e ni n g  
 
x  
 
 
 
 
 
 
 
I nf or m e d C o ns e nt 
 
 
x  
 
 
 
 
 
 
R a n d o miz ati o n  
 
 
 
x  
 
 
 
 
 
A T V V/ Att n C o ntr ol Tr ai ni n g  
 
 
 
x  
x  
x  
x  
x  
 
T ext R es p o ns es ( d ail y)  
 
 
 
 
x  
x  
x  
x  
 
T ext R e mi n d er ( m o nt hl y)  
 
 
 
 
x  
x  
x  
x  
 
P h o n e C all ( w e e kly)  
 
 
 
 
x  
x  
x  
x  
 
I nt erv e nti o n Fi d elit y Vi d e os 
 
 
 
 
 
x  
x  
x  
 
R E D C a p Q u esti o n n air es  
Scr e e ni n g Q u esti o n n air e ( p h o n e)  
x  
 
 
 
 
 
 
 
a dv ers e c hil d h o o d ex p eri e nc es a m b * A C E ( p h o n e)  
x  
 
 
 
 
 
 
 
D e m o gr a p hics Q u esti o n n air e  
 
x  
 
 
 
 
 
 
m at er n al att ac h m e nt a m b M A A S  
 
x  
 
 
 
 
 
 
r esili e nc e a m b B R C S 
 
x  
 
 
 
x  
 
 
e m oti o n al s u p p ort a m b P R O MI S -ES  
 
x  
 
 
 
x  
 
x  
st ess mi n ds et a m b S M M  
 
x  
 
 
 
x  
 
 
p erc ei v e d str ess a m b P S S -1 0  
 
x  
 
 
x  
x  
x  
x  
d e pr essi v e sy m pt o ms a m b P H Q -8  
 
x  
 
 
x  
x  
x  
x  
a nxi et y a m b G A D -7  
 
x  
 
 
x  
x  
x  
x  
P T S D a m b D S M -5 ( P CL -5)  
 
x  
 
 
 
 
 
 
a ut o n o mic r e acti vit y a m b B P Q -A N S  
 
x  
 
 
 
 
x  
x  
p ar e nti n g r ec ei v e d a m b P BI -M  
 
x  
 
 
 
 
 
 
p ar e nti n g r ec ei v e d a m b P BI -P  
 
x  
 
 
 
 
 
 
hist ory of a dv ersit y a m b A T ES  
 
x  
 
 
 
 
 
 
C hil d birt h & I nf a nt S urv e y  
 
 
x  
 
 
 
 
 
F oll o w Q u esti o n n air e  
 
 
 
 
x  
x  
x  
 
birt h ex p eri e nc e a m b C E Q  
 
 
 
 
x  
 
 
 
birt h ex p eri e nc e a m b P T S D -c hil d birt h 
 
 
 
 
x  
 
 
 
p ar e nti n g a m b P SI -S F  
 
 
 
 
x  
x  
x  
x  
F oll o w u p Q u esti o n n air e at T 4  
 
 
 
 
 
 
 
x  
R es e arc h P artici p a nt P erc e pti o n S urv e y  
 
 
 
 
 
 
 
x  
P eri p h er al b l o o d dr a w 
e pi g e n etic m arks a m b % D N A m et hyl ati o n at C p G sit es 
( n = 6) 
 
x  
 
 
x  
x  
x  
 
O X T R ex pr essi o n a m b q R T -P C R of m R N A  
 
x  
 
 
x  
x  
x  
 
O X T R t ot al pr ot ei n a m b W est er n Bl ot  
 
x  
 
 
x  
x  
x  
 
O X T p e pti d e a m b ELI S A ass a y  
 
x  
 
 
x  
x  
x  
 
I nf a nt S ali v a 
O X T p e pti d e a m b ELI S A ass a y  
 
 
 
 
x  
x  
x  
 
M ot h er -I nf a nt S y nc hr o ny 
Vi d e os  
Aff ect S y nc hr o ny  
 
 
 
 
 
 
x  
 
G az e S y nc hr o ny  
 
 
 
 
 
 
x  
 
V oc al S y nc hr o ny  
 
 
 
 
 
 
x  
 
T o uc h S y nc hr o ny  
 
 
 
 
 
 
x  
 
* a m b = as m e as ur e d by  
 
 
 
 
 
 
 
 
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
9  
2. 0  I N T R O D U C TI O N 
2. 1  B ac k gr o u n d/ Sci e ntific R ati o n al  
2. 1. 1  C hil d h o o d A d v ersit y  
C hil d h o o d a d v ersity ( d efi n e d as a b us e, n e gl ect, or h o us e h ol d d ysf u ncti o n ex p eri e nc e d u p t o a g e 1 8) ex erts  p ot e nt 
m e nt al a n d p hysic al b ur d e ns o n i n di vi d u als by alt eri n g n er v o us, e n d ocri n e, a n d i m m u n e syst e ms w ell i nt o a d ult h o o d, 
a n d acts as a d os e -r es p o ns e ris k f act or f or t h e l e a di n g c a us es of dis e as e. ( 2, 5) C hil d h o o d a dv ersit y is c o m m o nly 
ex p eri e nc e d, u n d er -r e p ort e d, a n d ex erts a n ec o n o mic t oll.( 5 3, 1 4 1-1 4 2) T h e ori gi n al A dv ers e C hil d h o o d Ex p eri e nc es ( A C E) 
st u dy of > 9, 0 0 0 U S a d ults d e m o nstr at e d > 5 0 % of a d ults ex p eri e nc e d at l e ast 1 A C E.( 2) T h e l ar g est m ost div ers e A C E 
st u dy t o d at e (n = 2 4 9, 9 3 4) acr oss 2 3 st at es r ev e al e d 6 2 % of r es p o n d e nts h a d at l e ast 1 A C E, 2 5 % h a d at l e ast 3 A C Es, a n d 
si g nific a ntl y hi g h er A C Es r e p ort e d by mi n oriti es a n d t h os e wit h l o w i nc o m e. ( 3) N arr o wi n g t h e pr ev al e nc e of A C E t y p es t o 
w o m e n acr oss 3 p o p ul ati o n st u di es r ev e al t h at 2 7 -3 4 % r e p ort e d e m oti o n al a b us e, 1 5 -2 0 % r e p ort e d p hysic al a b us e, a n d 
1 6 -3 2 % r e p ort e d s ex u al a b us e. ( 1, 3, 4) A d diti o n ally, a ni m al m o d el s of e arl y-lif e a dv ersit y (i. e., p o or m at er n al c ar e), fr a m e d 
wit hi n t h e D ev el o p m e nt al Ori gi ns of H e alt h a n d Dis e as e p ar a di g m ( D O H a D), ( 5 4) d e m o nstr at e t h at  offs pri n g w h o w er e 
ex p os e d t o e arly lif e a dv ersit y gr o w u p t o ex hi bit p o or m at er n al c ar e t o w ar ds t h eir offs pri n g. ( 5 5) ) W o m e n wit h c hil d h o o d 
a dv ersity m a y b e at hi g h er ris k f or p o or M -I sy nc hr o ny. ( 7-1 1) 
 
2. 1. 2  C hil d h o o d A d v ersit y a n d t h e O x yt oci n S yst e m  
Fr a m e d wit hi n t h e D e v el o p m e nt al Ori gi ns of H e alt h Dis e as e ( D O H a D) p ar a di g m, offs pri n g ex p os e d t o e arly lif e a d v ersit y 
(i. e., p o or m at er n al c ar e) gr o w u p t o ex hi bit p o or m at er n al c ar e t o w ar ds t h eir offs pri n g.( 5 4)  R at p u ps r ec ei vi n g p o or 
m at er n al c ar e (l o w licki n g a n d gr o o mi n g) ex hi bit e d e pi g e n etic m o dific ati o ns i n t h e str ess r es p o ns e s yst e m t h at p ersist e d 
i nt o a d ult h o o d.(r ef 5 5) Si mil arly, r at p u ps r ec ei vi n g l o w m at er n al lic ki n g a n d gr o o mi n g ex hi bit e d O X T r ec e pt or g e n e ( O X T R ) 
m o dific ati o n, l o w er O X T R ex pr essi o n, a n d l o w er O X T l e v els t h at p ersist e d i nt o a d ult h o o d r es ulti n g i n i ncr e as e d a nxi ety 
a n d str ess; ( 4 5, 5 1) h o w e v er, a n i nt er v e nti o n t o i m pr ov e t h e q u alit y of m at er n al c ar e t h e n r es ult e d i n i m pr ov e d O X T 
f u ncti o n.( 5 6) I n n e w b or n v ol es a o n e-w e ek i nt erv e nti o n mi mic ki n g p o or m at er n al c ar e, v ers us us u al m at er n al c ar e, 
r es ult e d i n d e n ov o  hi g h er O X T R  m et h yl ati o n (i n bl o o d) c orr el ati n g wit h l o w er O X T R g e n e ex pr essi o n a n d f e w er O X T R 
bi n di n g sit es (i n t h e br ai n), s h o wi n g t h at n ot o nl y c a n O X T R  m et h yl ati o n r es p o n d q uic kl y t o m at er n al c ar e b ut t h at 
p eri p h er ally m e as ur e d m et hyl ati o n r efl ects br ai n f u ncti o n. ( 1 4 3) I n t h es e D O H a D a ni m al m o d els, e pi g e n etic m o dific ati o n 
of syst e ms t h at r e g ul at e a s e ns e of s af et y v ers us f e ar, s uc h as t h e O X T syst e m, ar e t h e u n d erlyi n g m ec h a nis ms r e g ul ati n g 
m at er n al b e h a vi or.  Si mil arly, h u m a n st u di es als o s h o w a li n k b et w e e n t h e q u alit y of e arly p ar e nti n g a n d O X T l e v els of 
t h e c hil d w ell i nt o a d ult h o o d.( 6, 3 4, 5 7-5 9, 1 5 1) T h e r el ati o ns hi p b et w e e n O X T l ev el a n d o bs erv e d m at er n al n urt uri n g b e h avi or 
m a y b e diff er e nt i n m ot h ers wit h, v ers us wit h o ut, a hist ory of c hil d h o o d a d v ersity.
( 6 0) W hil e e pi g e n etic ef f ects fr o m 
c hil d h o o d a dv ersity ar e f o u n d i n g e n o m e -wi d e a n d c a n di d at e g e n e st u di es o n str ess h or m o n es, ( 6 1) e vi d e nc e of O X T R  
e pi g e n etic eff ects is li mit e d t o 3 st u di es s h o wi n g i ncr e as e d O X T R  D N A m et hyl ati o n (i. e., d a m p e ni n g) aft er p o or m at er n al 
c ar e i n e arly lif e, ( 5 0) i n a d ol esc e nt a nxi o us n ess,( 6 2) a n d i n a d ult ps yc h osis ( 4 9) aft er c hil d h o o d a d v ersity .  
 
2. 1. 3  M ot h er -I nf a nt S y nc hr o n y 
M ot h er -I nf a nt (M -I) sy nc hr o ny, o ur pri m ar y o utc o m e, is a c o or di n at e d a n d fl ui d pr oc ess i n v ol vi n g aff ecti o n at e 
“ m ot h er es e” s p e ec h, t o uc h, g az e, a n d aff ect. ( 1 2-1 4) W h e n a m ot h er is s e nsiti v e, r es p o nsi v e, a n d a d a ptiv e t o h er i nf a nt’s 
c u es t hr o u g h n urt uri n g b e h avi or, t h e i nf a nt r es p o n ds wit h gr e at er s elf -r e g ul ati o n a n d al ert n ess, a n d vic e v ers a. B ot h 
m ot h er a n d i nf a nt ex p eri e nc e t h e p hysic al b e n efits of s ec ur e att ac h m e nt: l ess str ess r e activit y a n d a c al m er a ut o n o mic 
n er v o us s yst e m. ( 7 3-7 5) M -I sy nc hr o ny is m ut u all y r e w ar di n g t o m ot h ers a n d i nf a nts e m oti o n ally, b e h avi or ally, a n d 
p hysi ol o gic all y. ( 1 9) C o nstr ucts t h at d escri b e h e alt hy M -I i nt er acti o n (s uc h as M-I s y nc hr o ny a n d r es p o nsiv e c ar e givi n g) 
h a v e b e e n w ell -r es e arc h e d f or d ec a d es as ess e nti al pr er e q uisit es f or s h a pi n g t h e e arl y arc hit ect ur e of h e alt hy br ai n 
circ uits t h at e n h a nc e m or e c o m pl ex br ai n  d e v el o p m e nt .( 1 7) R es p o nsiv e c ar e givi n g is a pr ot ectiv e f act or t h at l ess e ns t h e 
eff ects of c u m ul ati v e a dv ersit y o n h e alt h a n d s af e g u ar ds a g ai nst lif e -l o n g s oci o ec o n o mic h e alt h dis p ariti es.( 1 5, 1 6)  P o or 
m ot h er -i nf a nt ( M-I) s y nc hr o ny ex erts a str o n g eff ect o n i m p airi n g t h e s oci al, e m oti o n al, c o g nitiv e, a n d p hysi ol o gic 
d e v el o p m e nt of c hil dr e n. ( 7, 1 3, 1 8, 1 9) I m p air m e nts i ncl u d e b e h a vi or pr o bl e ms, l o w e m p at h y, att ac h m e nt i ns ec urit y, p o or 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1 0  
s oci al a d a pt ati o n i n p e er gr o u ps, c o g niti v e d eficits, psyc h o p at h ol o gi es, a n d p o or a ut o n o mic r e g ul ati o n  a n d str ess 
r e activit y, i n b ot h l o w- a n d hi g h - ris k c o h orts.( 7, 1 3, 1 8, 1 9)  
 
2. 1. 4  M ot h er -I nf a nt S y nc hr o n y a n d t h e O x yt oci n S yst e m 
A hi g h f u ncti o ni n g O X T syst e m m ay b e i m p ort a nt f or m ot h ers b ec a us e t h e m ost li k el y bi ol o gic c orr el at e of M-I 
s y nc hr o ny is t h e n e ur o p e pti d e O X T, k n o w n f or its k e y r ol e i n pr o m oti n g  n urt uri n g m at er n al b e h a vi or, att ac h m e nt, s oci al 
affili ati o n, e m p at h y, str ess r e d ucti o n, a n d p ositiv e m o o d. ( 7-1 1, 6 3, 6 4) O X T a p p e ars t o i nfl u e nc e b e h avi or by acti n g o n t h e 
n er v o us s yst e m as a m et a p h or f or ps yc h ol o gic al s af et y. ( 6 5) M at er n al O X T acts p eri p h er ally s u p p orti n g birt h a n d l act ati o n, 
a n d i n m ulti pl e  s p eci es acts c e ntr ally i n t h e r e g ul ati o n of M-I att ac h m e nt.( 9, 6 6) F el d m a n a n d ot h ers r e p ort M -I 
att ac h m e nt a n d s y nc hr o ny ar e ass oci at e d wit h i ncr e as e d p eri p h er al O X T l e v els, O X T R  si n gl e-n ucl e oti d e p oly m or p his ms, 
i ncr e as e d br ai n acti v ati o n i n O X T r e gi o ns, a n d a d mi nistr ati o n of ex o g e n o us O X T.( 3 3, 3 6, 6 4, 6 7) F el d m a n als o f o u n d a 
si g nific a nt c orr el ati o n of 0. 3 0 b et w e e n l o w er pl as m a O X T a n d l o w er p ar e nt al b o n di n g t h at b ot h m ot h ers a n d f at h ers 
ex p eri e nc e d as c hil dr e n. ( 3 4) H o w ev er , n o i n v esti g ati o n h as ext e n d e d t h es e O X T s yst e m fi n di n gs t o O X T R e pi g e n etic 
m ec h a nis ms. E vi d e nc e t o s u p p ort a r ol e f or O X T R  e pi g e n etic r e g ul ati o n i n M -I s y nc hr o ny s h o ws a n ass oci ati o n b et w e e n 
i ncr e as e d O X T R  D N A m et h yl ati o n a n d ps yc h os oci al b e h a vi ors: d e pr essi o n, a nxi ety a b o ut att ac h m e nt, s oci al p h o bi a, 
c all o us-e m oti o n al tr aits, a utis m s p ectr u m dis or d er, a n or exi a -n er v os a, sl o w er pr oc essi n g of f aci al e m oti o n, a n d l o w er 
br ai n acti v ati o n i n ar e as of s oci al c o g ni ti o n.( 3 8-4 4, 4 6 -4 8, 5 2, 6 8, 6 9) T h e oxyt oci n syst e m is hi g hl y pl astic i n e arly lif e ( 7 0, 7 1) w h e n  
t h e O X T R  c a n b e e pi g e n etic ally pr o gr a m m e d f or v ul n er a bilit y t o psyc h o p at h ol o gi es gr o u n d e d i n d ef e ns e, f e ar a n d 
a nxi et y. ( 6 2) T h e q u alit y of e arly p ar e nti n g t h at  a n i nf a nt r ec ei v es c a n aff ect t h eir O X T l e v els w ell i nt o a d ult h o o d. ( 6, 3 4, 5 7-5 9, 
7 2) W hil e o ur pr o p os al is n ot a tr a ns g e n er ati o n al st u dy d esi g n a n d will n ot c oll ect bl o o d t o m e as ur e e pi g e n etic o utc o m es 
i n t h e i nf a nt, e vi d e nc e s u g g ests t h at e arly lif e ex p eri e nc es b ec o m e e m b e d d e d i nt o t h e c hil d’s g e n o m e;( 6 1, 7 1) t h us, o ur 
fi n di n gs o n i nf a nt O X T l ev els fr o m t h e pr o p os e d st u dy m a y w arr a nt f oll o w-u p t o d et er mi n e o ur b e h avi or al i nt er v e nti o n’s 
eff ect o n e pi g e n etic m o dific ati o n of t h e c hil d’s l o n g -t er m O X T s yst e m. 
 
2. 1. 5   A T V V I nt er v e nti o n  
A T V V ( A u dit ory, T actil e, Vis u al, V esti b ul ar sti m ul ati o n) is a 1 5 mi n ut e m ultis e ns ory b e h avi or al i nt erv e nti o n c o nsisti n g of 
i nf a nt-dir ect e d aff ecti o n at e “ m ot h er es e” s p e ec h, m o d er at e t o uc h m ass a g e, e y e t o e y e g az e, a n d h oriz o nt al r ocki n g. ( 2 4, 
7 6, 7 7)  I d e all y, A T V V s h o ul d b e a d mi nist er e d by m ot h ers s o o n aft er birt h; ( 2 9, 3 0, 7 8) w h e n ex p eri e nc e -d e p e n d e nt n e ur al 
pl asticit y is hi g h i n m at er n al a n d i nf a nt br ai ns. ( 2 2, 2 3) T h es e e arl y f ac e -t o-f ac e i nt er acti o ns pr ovi d e critic al sti m uli f or 
m at ur ati o n of t h e "s oci al br ai n".
( 7) M et a -a n al ys es r e p ort t h at t h e m ost pr o misi n g i nt er v e nti o ns ar e t h e o n es t h at h el p 
m ot h ers e n g a g e wit h t h eir i nf a nt, a n d pr ovi d e o p p ort u niti es f or pr actici n g pl ay a n d r es p o nsiv e t al k.
( 1 6, 2 0, 2 1) I n 
a d mi nist eri n g A T V V, m ot h ers l e ar n t o b e c o mf ort a bl e r ec o g nizi n g a n d a d a pti n g t h eir b e h a vi or w h e n t h e i nf a nt is 
si g n ali n g c u es t o e n g a g e or dis e n g a g e. A T V V is a n e nj oy a bl e d ail y o p p ort u nit y f or m ot h ers t o pr actic e m o d eli n g M -I 
s y nc hr o ny b y usi n g e y e t o e y e g az e, aff ecti o n at e “ m ot h er es e” s p e ec h a n d s o ot hi n g t o uc h.( 7 8) M at er n al n urt uri n g a n d 
att ac h m e nt b e h a vi or i m pr o v e d i n t w o R C Ts wit h A T V V a n d K a n g ar o o C ar e ( w h er e pr e -t er m i nf a nts ar e h el d s ki n-t o-
s ki n); ( 2 8, 7 9) h o w ev er, A T V V h as a d d e d v al u e b e y o n d t h e t o uc h el e m e nt d u e t o t h e e n g a g e d r es p o nsi v e c ar e givi n g 
el e m e nt n ot f o u n d i n K a n g ar o o C ar e. A T V V i m pr ov es m at er n al s e nsiti vity t o pr et er m i nf a nt c u es a n d r es p o nsi v e n ess 
d uri n g pl ay, ( 2 9, 3 0) gr e at er m at er n al c o nfi d e nc e, ( 8 0) l o w er m at er n al distr ess,( 2 8) a n d e n h a nc e pr et er m i nf a nt b e h a vi or al 
d e v el o p m e nt, ( 2 5-2 7) t h us s u p p orti n g a n e e d t o ext e n d t h es e fi n di n gs t o f ull-t er m i nf a nts. 
 
2. 1. 6   Will A T V V b e Ass oci at e d wit h I m pr o v e d  O X T f u ncti o n ?  
T h e A T V V i nt er v e nti o n is lik el y t o i m pr ov e O X T f u ncti o n i n m ot h ers a n d i nf a nts. O X T w ill li k el y i ncr e as e b y t h e s o ot hi n g 
eff ect of A T V V, as s h o w n by n u m er o us st u di es o n t o uc h a n d O X T. ( 8 1, 8 2) N urt uri n g s oci al t o uc h sti m ul at es t h e r e w ar d 
r es p o ns e a n d i ncr e as es O X T l ev els.( 8 1) S p ecific ally, pl e as a nt affili ativ e t o uc h activ at es C -t actil e aff er e nt n erv e fi b ers t h at 
m e di at e t h e r el e as e of O X T.
( 8 1) I n t hr e e s e p ar at e R C Ts wit h f ull-t er m i nf a nts ( < 4 8 h o urs ol d) o ur t e a m s h o w e d t h at wit h 
j ust o n e a d mi nistr ati o n of A T V V (c o m p ar e d t o c o ntr ols) m ot h ers ex p eri e nc e d i ncr e as es i n m at er n al O X T, w hil e i nf a nts 
h a d l o w er v al u es of c ortis ol a n d d e m o nstr at e d a ut o n o mic st a bilit y, w hic h O X T h el ps t o r e g ul at e. A d diti o n ally, i nf a nts 
m o difi e d t h eir b e h a vi or fr o m sl e e p t o al ert n ess - t h e o pti m al st at e f or f acilit ati n g M-I s y nc hr o ny.( 8 3-8 5 )  
 

 
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2. 1. 7   Will A T V V b e Ass oci at e d wit h I m pr o v e d  M ot h er -I nf a nt S y nc hr o n y ? 
Dr. F el d m a n h as d ev el o p e d a m et h o d ol o gy  of  micr o -c o di n g m at er n al a n d i nf a nt  b e h a vi ors t o m e as ur e M -I sy nc hr o ny, 
a n d h as d e m o nstr at e d  a cl e ar li n k wit h p eri p h er al O X T l ev els .( 7, 1 2, 1 9, 3 1, 3 2) Usi n g vi d e o r ec or di n gs  of m ot h er -i nf a nt dy a ds 
i nt er acti n g, b e h avi or al i nt er acti o ns ar e micr o -c o d ed a n d  q u a ntif i e d s ec o n d-by -s ec o n d t o c h ar act eriz e t h e s y nc hr o ny of 
m ot h er a n d i nf a nt s p e ec h, t o uc h, g az e, a n d aff ect . Usi n g t h es e micr o -c o d e d M-I b e h a vi ors, w e ar e a bl e t o o bj ecti v el y 
m e as ur e p att er ns of d y n a mic M -I c o m m u nic ati o n, c o nv e yi n g m at er n al aff ecti o n a n d s e nsiti vit y t o c u es, as w ell as i nf a nt 
r es p o nsiv e n ess a n d r e a di n ess t o i nt er act.( 3 1) Ass ess m e nt of t h es e b e h avi ors i n o nl y a 3 -mi n ut e wi n d o w yi el ds ric h d et ail 
of sy nc hr o ny. Ov er t h e first p ost n at al m o nt hs,  m or e c o or di n at e d e pis o d es of s y nc hr o ny t a k e o n a l ar g er pr o p orti o n of 
t h e p ar e nt-i nf a nt i nt er acti o n, a n d b y 3-m o nt hs of a g e f ull -t er m i nf a nts c a n e n g a g e i n a cl e ar, m e as ur a bl e, t e m p or al 
str uct ur e of M-I sy nc hr o ny.( 1 8, 3 1, 3 2, 7 4, 1 0 2, 1 0 4) St u di es b y F el d m a n d e m o nstr at e t h at p ar e nts wit h hi g h er pl as m a a n d 
s aliv ar y O X T l ev els dis pl a y m or e sy nc hr o ny wit h t h eir i nf a nts, ( 3 4) as w ell as m or e  c o or di n at e d n e ur al circ uits f or e m p at hy 
a n d s oci al c o g niti o n. ( 8 6, 8 7)  Hi g h er l e v els of micr o -c o d e d M-I s y nc hr o ny ar e ass oci at e d wit h hi g h er O X T l e v els i n b ot h t h e 
p ar e nt a n d t h e i nf a nt, a n d  wit h hi g h er c orr el ati o ns b et w e e n p ar e nt a n d i nf a nt O X T l ev els. ( 3 3) Si mil arly, a d mi nistr ati o n of 
i ntr a-n as al O X T t o t h e p ar e nt r es ults i n hi g h er p ar e nt O X T l e v els i n t h e c o nt ext of hi g h er s y nc hr o ny; a n d i m p ort a ntly 
r es ults i n hi g h er i nf a nt O X T l e v els, a n d m or e c orr el at e d l e v els b et w e e n t h e p ar e nt a n d t h e i nf a nt i n m or e sync hr o n o us 
i nt er acti o ns.( 6 7) Wit h t his s oli d f o u n d ati o n of r es e arc h l i nki n g O X T p e pti d e l e v els wit h micr o-c o d e d M-I s y nc hr o ny, t h e 
n ext critic al st e p is t o f urt h er i d e ntify m ol ec ul ar m ec h a nis ms of sy nc hr o ny b y li n ki n g M -I s y nc hr o ny t o O X T R  e pi g e n etic 
m ar ks a n d g e n e ex pr essi o n . 
   
W e p osit t h at m ot h ers wit h c hil d h o o d a dv ersit y will h a v e m or e diffic ult y wit h M -I s y nc hr o ny, d u e i n p art t o a d a m p e n e d 
O X T syst e m, a n d will b e n efit fr o m i nt er v e nti o ns t h at i m pr ov e n urt uri n g e n g a g e m e nt b y e pi g e n etic r e g ul ati o n of t h e O X T 
s yst e m. M ost i nt er v e nti o ns ar e c ostly, c o m pl ex, ti m e-c o ns u mi n g, ( 2 0, 2 1) a n d miss a n i m p ort a nt o p p ort u nity of i nt er v e ni n g 
d uri n g  e arl y M -I ex p eri e nc e-d e p e n d e nt n e ur al br ai n pl asticit y. ( 2 2, 2 3) W e ai m t o fill t his g a p b y t esti n g t h e effic ac y of a n 
e as y t o l e ar n, e arl y b e h avi or al i nt er v e nti o n t o i m pr ov e O X T s yst e m f u ncti o n a n d M -I s y nc hr o ny. 
 
2. 2  S af et y C o nsi d er ati o ns  
T his st u dy will r ecr uit pr e g n a nt w o m e n, a  v ul n er a bl e p o p ul ati o n ( 4 5 C F R 4 6. 2 0 4) . W hil e pr e g n a nt w o m e n, m ot h ers a n d  
t h eir h e alt hy f ull-t er m i nf a nts ar e v ul n er a bl e p o p ul ati o ns, t h e i nf a nt m ass a g e i nt er v e nti o n i ncl u d es b e h avi ors t h at 
m ot h er s t y pic ally us e w h e n i nt er acti n g wit h t h eir i nf a nts a n d is l o w ris k.  All pr ot oc ol el e m e nts  h a v e b e e n  s u b mitt e d t o 
t h e U ni v ersity of Ariz o n a I nstit uti o n al R evi e w B o ar d w hic h h as d et er mi n e d t h at t h er e is n o m or e  t h a n mi ni m al risk 
ass oci at e d wit h p artici p ati n g i n t his st u dy  f or pr e g n a nt w o m e n , t h eir f et us es, or  t h eir i nf a nts ( 4 5 C F R § 4 6. 4 0 4/ 2 1 C F R 
§ 5 0. 5 1). (S e e I R B a p pr o v al l ett er d at e d S e pt e m b er 2 8, 2 0 2 0  i n A p p e n dix A.) 
 
2. 2. 1  E x p ect e d Ris ks  
P hysic al ris ks ass oci at e d wit h t h e m at er n al bl o o d dr a w m a y i ncl u d e disc o mf ort (c o m m o n risk), bl e e di n g or br uisi n g 
( occ asi o n al risk), f ai nti n g (r ar e ris k), a n d i nf ecti o n (r ar e ris k). T h er e is a bi o h az ar d ris k t o st aff i n h a n dli n g bl o o d a n d 
s aliv a s p eci m e ns. T h er e is a ris k of C O VI D 1 9 i nf ecti o n tr a ns mitt e d fr o m as y m pt o m atic i n di vi d u als. T h e ris ks ass oci at e d 
wit h  gi vi n g bl o o d a n d s aliv a s a m pl es ar e  v er y l o w, es p eci all y i n a st u dy t h at is n ot c o n d ucti n g g e n o m e -wi d e ass oci ati o n 
a n al ys es  a n d is n ot a bl e t o i d e ntif y m e dic al pr o bl e ms or dis e as es . H o w ev er, w e ar e n ot a bl e t o k n o w all  t h e ris ks fr o m 
t a ki n g p art i n g e n etic r es e arc h st u di es. A d diti o n ally, s o m e  w o m e n m a y b e u nc o mf ort a bl e or a nxi o us w h e n c o m pl eti n g 
q u esti o n n air es a b o ut m o o d, a dv ersit y,  or h e alt h. F urt h er m or e , t h er e is p ot e nti al ris k ass oci at e d wit h l oss of priv acy or 
c o nfi d e nti ality. 
 
2. 2. 2  A m eli or ati o n of Ris ks  
2. 2. 2. 1  A m eli or ati o n of  P h ysic al R is ks 
T o mi ni miz e disc o mf ort a n d ris ks ass oci at e d wit h t h e m at er n al bl o o d dr a w, w e  e m pl oy ex p eri e nc e d p hl e b ot o mist s 

 
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tr ai n e d i n c o n d ucti n g v e ni p u nct ur e. T o mi ni miz e ris k fr o m h a n dli n g bl o o d a n d s aliv a s p eci m e ns, all r es e arc h t e a m 
m e m b ers ar e r e q uir e d b y O S H A t o h a v e a n n u al tr ai ni n g i n Bl o o d b or n e P at h o g e ns a n d L a b or at or y S af ety at t h e 
U ni v ersity of Ariz o n a . P hysic al ris ks t o t h e i nf a nt p artici p a nts ar e mi ni m al. Ty pic ally, m ot h ers d escri b e t h e m ass a g e as a n 
e nj o y a bl e ex p eri e nc e f or t h e m a n d t h eir i nf a nt. F or o v er 3 5 y e ars, t h e A T V V i nt er v e nti o n h as b e e n a d mi nist er e d s af el y 
t o m or e t h a n  8 0 0 i nf a nts, i ncl u di n g pr e m at ur e i nf a n ts wit h s e v er e br ai n i nj ury. It is d oc u m e nt e d i n t h e lit er at ur e t h at 
A T V V h as a p ositiv e eff ect o n t h e pr e m at ur e i nf a nt.     
 
2. 2. 2. 2  A m eli or ati o n  C O VI D -1 9 Ris ks  
All r es e arc h p ers o n n el ar e  tr ai n e d i n s af et y m e as ur es s p ecific t o C O VI D 1 9.  St a n d ar d o p er ati n g pr oc e d ur es d escri bi n g 
s af et y m e as ur es t a k e n b y a n d o n t h e b e h alf of p ers o n n el a n d r es e arc h p artici p a nts w er e s u b mitt e d t o R es e arc h, 
I n n o v ati o n, a n d I m p act i niti all y f or pr ot oc ol-d ev el o p m e nt activiti es w hic h w as  a p pr o v e d o n  F e br u ar y 1 7 , 2 0 21 , a n d t h e n 
f or r es e arc h activiti es w hic h w as  a p pr o v e d o n  A pril 6, 2 0 2 1. ( S e e S o P C o n d ucti n g a Cli nic al R es e arc h Pr oj ect d uri n g a 
P a n d e mic .) 
 
2. 2. 2. 3  A m eli or ati o n of E m oti o n al Disc o mf ort  or Distr ess  
S elf -r e p ort q u esti o n n air es i ncl u d e m e as ur e m e nt of s y m pt o ms of d e pr essi o n, g e n er al a nxi et y, a n d a d v ers e ex p eri e nc es  
w hic h m ay c a us e s o m e  w o m e n t o b ec o m e u nc o mf ort a bl e or a nxi o us w h e n c o m pl eti n g t h es e q u esti o n n air es w hic h 
e nc o ur a g e s elf -r efl ecti o n r e g ar di n g m o o d, a dv ersit y, or h e alt h.  P artici p a nts ar e e nc o ur a g e d t o i nf or m t h e r es e arc h t e a m 
m e m b er if t h ey f e el u nc o mf ort a bl e c o m pl eti n g a n y q u esti o n n air e or q u esti o n . If c o nti n ui n g t o c o m pl et e t h e 
q u esti o n n air es c a us es disc o mf ort, t h ey m a y c h o os e t o s ki p c ert ai n q u esti o ns, c o m pl et e t h e s ur v e y at h o m e, c o m pl et e it 
l at er, or wit h dr a w fr o m t h e st u dy  wit h o ut c o ns e q u e nc e.  
 
A d diti o n ally, o ur t e a m h as ext e nsiv e ex p eri e nc e wit h d e v el o pi n g i nt ervi e w g ui d es o n s e nsitiv e t o pics a n d h as d esi g n e d 
t h e c o nt e nt a n d or d eri n g of q u esti o ns t o mi ni miz e distr ess. H o w e v er, w e h av e cr e at e d a n  e m er g e ncy pr oc ess  w hic h  will 
b e p ut i nt o acti o n i n t h e u nli k el y circ u mst a nc e t h at distr ess c o nti n u es or esc al at es d uri n g t h e i nt ervi e ws. T h e s p ecific 
e m er g e nc y pl a n t h at will b e i m pl e m e nt e d will b e b as e d o n t h e pr es e nc e or a bs e nc e of s uici d e risk.  ( S e e S o P A dv ers e 
E v e nts ). 
   
2. 2. 2. 4  A m eli or ati o n of Pri v ac y Ris k  
El ectr o nic d at a will b e st or e d o n t w o s ec ur e syst e ms t h at us e e ncr y pti o n - R es e arc h El ectr o nic D at a C a pt ur e ( R E D C a p) 
a n d U niv ersity of Ariz o n a B ox H e alt h ( U A B ox H e alt h). All st u dy l a pt o ps a n d t a bl ets will us e p ass w or d e ncr y pti o n f or 
acc ess t o t h e l a pt o p or t a bl et.  All d at a o utsi d e of t h es e s yst e ms will h a v e u ni q u e a n o ny m o us c o d es  or i n t h e c as e of 
p a p er d at a, b e s ec ur e d i n a l oc k e d fil e c a bi n et i n a l oc k e d r o o m. L a b or at or y s p eci m e ns (l a b el e d wit h u ni q u e a n o ny m o us 
c o d es) will b e pr oc ess e d a n d st or e d i n fr e ez er syst e ms wit hi n l oc k e d k eyc ar d acc ess r o o ms at t h e U A C oll e g e of N ursi n g, 
Bi ol o gic al C or e L a b or at ory.  
 
2. 2. 2. 5  C o m p e ns ati o n f or R es e arc h -R el at e d I nj ur y  
P artici p ati o n i n t his r es e arc h st u dy p oss ess es n o m or e t h a n mi ni m al  ris k f or i nj ur y or a dv ers e eff ects. T h er ef or e , n o 
c o m p e ns ati o n f u n ds i n t h e e v e nt of r es e arc h r el at e d i nj ur y h a v e b e e n s et asi d e . I n t h e p ast 3 5 y e ars of NI H-f u n d e d 
r es e arc h wit h t h e A T V V, t h er e h as n ot b e e n a n a dv ers e ev e nt dir ectly r el at e d t o t h e A T V V i nt er v e nti o n, e v e n w h e n 
i nf a nts wit h br ai n i nj ury w er e e nr oll e d. T his st u dy will e nr oll l o w-risk h e alt hy m ot h ers a n d i nf a nts. I nf ants ar e excl u d e d 
fr o m t h e st u dy if b or n wit h a si g nific a nt c o n g e nit al a n o m al y or m e dic al c o n diti o n w hic h i n hi bits m ot h er -i nf a nt b o n di n g.  
 
2. 3  
Et hic al C o nsi d er ati o ns  
2. 3. 1  O bs er v ati o n of A b us e or N e gl ect  
R es e arc h ers a n d pr of essi o n als w h o w or k wit h f a mili es wit h c hil dr e n u n d er t h e a g e of 1 8 ar e r es p o nsi bl e f or t h e w elf ar e 
of c hil dr e n. If t h e r es e arc h t e a m s us p ects a n i nf a nt h as b e e n p hysic ally or e m oti o n ally a b us e d or n e gl ect e d, f oll o wi n g 
t h e g ui d eli n es s et by t h e Ariz o n a D e p art m e nt of C hil d S af et y ( D C S), it is o ur m a n d at ory r es p o nsi bilit y t o r e p ort it t o t h e 
Ariz o n a D C S. M ot h ers will b e i nf or m e d i n writi n g vi a t h e c o ns e nt f or m of o ur r es p o nsi bilit y t o r e p ort s us p ect e d c hil d 
n e gl ect or a b us e.  (S e e S o P ) 
 

 
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2. 3. 2  P artici p ati o n of C hil dr e n i n R es e arc h  
T h e U ni v ersity of Ariz o n a r e q uir es t h at t h e ass e nt f or m , si g n e d by t h e m ot h er of t h e i nf a nt fr o m w h o m t h e s aliv a is 
o bt ai n e d,  a n d a g gr e g at e d at a b e r et ai n e d u ntil t h e c hil d r e ac h es 2 4 y e ars of a g e ( 6 y e ars aft er t h e c hil d r e ac h es 1 8 y e ars  
of a g e i n t h e st at e of Ariz o n a ). Pl e as e s e e dis p ositi o n of d at a i n s ecti o n 7. 2 6.  
3. 0  O BJ E C TI V E S A N D E N D P OI N T S  
3. 1   St u d y O v er vi e w  
W e  will t est t h e A T V V, a m ultis e ns ory b e h avi or al i nt erv e nti o n,  w h er e m ot h ers l e ar n t o e n g a g e wit h t h eir i nf a nt w hil e 
a d mi nist eri n g A u dit or y (i nf a nt dir ect e d s p e ec h), T actil e ( m ass a g e), V is u al ( e y e t o e y e g az e), a n d V esti b ul ar (r oc ki n g) 
sti m ul ati o n. ( 2 4) W e b uil d o n A T V V’s s ucc ess wit h pr et er m i nf a nts a n d t h eir m ot h ers ( e. g., i m pr ov e d m at er n al s e nsiti vit y, 
l o w er m at er n al distr ess, a n d e n h a nc e d i nf a nt b e h avi or a n d d e v el o p m e nt) t o d et er mi n e b e n efits f or f ull-t er m M-I 
dy a ds. ( 2 5-3 0) W e will t ar g et first -ti m e m ot h ers wit h c hil d h o o d a dv ersity. M ot h ers r a n d o miz e d t o A T V V will a d mi nist er it 
o nc e d aily f or t h e first 3 p ost n at al m o nt hs. At 3 m o nt hs, w h e n f ull -t er m i nf a nts r eli a bl y ex hi bit cl e ar c u es an d m ai nt ai n 
al ert n ess, w e will a p pl y a ri g or o us b e h a vi or al m e as ur e of M -I sy nc hr o ny d ev el o p e d b y a m e m b er of o ur t e a m usi n g 
fr a m e-by -fr a m e vi d e o of micr o-c o d e d M-I b e h avi or q u a ntif yi n g r eci pr oc al s p e ec h, t o uc h, g az e, a n d aff ect. ( 3 1, 3 2, 7 3) Micr o -
c o d e d b e h avi or yi el ds ric h d et ail of i nt er acti o n p att er ns k n o w n t o i nfl u e nc e l o n g -t er m d ev el o p m e nt al o utc o m es.( 7, 1 8, 1 9) 
O ur f e asi bility pil ot s h o w e d si g nific a nt a n d str o n g c orr el ati o ns b et w e e n A T V V fr e q u e nc y a n d i m pr ov e d M -I sy nc hr o ny 
o v er o n e m o nt h.  
 
W e will als o ass ess A T V V’s eff ect o n m at er n al a n d i nf a nt p eri p h er al O X T l e v els, ( 7, 1 9) a k n o w n bi o m ar k er of M -I s y nc hr o ny. 
W e, a n d ot h ers, h av e s h o w n t h at d a m p e ni n g  i n t h e O X T syst e m (i. e., a b n or m ally l o w O X T bl o o d a n d s aliv a l ev els) is 
e vi d e nt i n p o or M -I s y nc hr o ny a n d m at er n al b e h avi or,( 3 3-3 7) y et littl e is k n o w n a b o ut O X T’s e pi g e n etic r e g ul ati o n of 
s y nc hr o ny or m at er n al b e h a vi or i n h u m a ns. T h us, w e will t ar g et r e gi o ns of t h e O X T r ec e pt or g e n e ( O X T R)  w h er e D N A 
m et hyl ati o n is li n k e d t o m at er n al b e h avi or i n r o d e nts, ps yc h os oci al b e h avi ors i n h u m a ns, a n d i n o ur pil ot st u dy t o M -I 
s y nc hr o ny. ( 3 8-5 2) W e will ex a mi n e w h et h er o ur O X T m e as ur es e m er g e e arl y t o pr e dict effic ac y of A T V V a n d q u alit y of M -I 
s y nc hr o ny at 3 m o nt hs.  W e a n al yz e m at er n al bl o o d i n pr e g n a nc y a n d at 1, 2, a n d 3 m o nt hs p ost birt h ( a n d i nf a nt 
s aliv ar y O X T).  W e ai m t o i d e ntif y m ol ec ul ar m ec h a nis ms i n t h e O X T s yst e m u n d erl yi n g M -I sy nc hr o ny i n m at er n al bl o o d 
a n d disc o v er m ol ec ul ar pr ofil es. R e gr essi o n b as e d  m et h o ds ass ess A T V V eff ects o n a n d r el ati o n s a m o n g M-I s y nc hr o ny 
a n d O X T m e as ur es.   
 
3. 2  Ai ms  
T o m e et t h es e o bj ectiv es, w e h av e d esi g n e d a 4 -y e ar, si n gl e -sit e, r a n d o miz e d, att e nti o n-c o ntr oll e d cli nic al tri al wit h t h e 
f oll o wi n g ai ms: 
Ai m 1: Ev al u at e t h e effic acy of d ail y A T V V o v er 3 p ost n at al m o nt hs a m o n g m ot h ers wit h c hil d h o o d a d v ersity.  
W e h y p ot h esiz e t h at c o m p ar e d t o t h e Att e nti o n C o ntr ol gr o u p ( n = 1 2 5), m ot h er -i nf a nt dy a ds i n t h e A T V V gr o u p ( n = 1 2 5) 
will ex hi bit:  
 
•  
H 1: Hi g h er oxyt oci n ( O X T) f u ncti o n (i. e., d ecr e as e d oxyt oci n r ec e pt or ( O X T R) g e n e m et h yl ati o n at c a n di d at e 
sit es, a n d i ncr e as e d O X T R m R N A, O X T R pr ot ei n, a n d O X T i n m at er n al pl as m a, a n d i ncr e as e d O X T i n i nf a nt s aliv a) 
at 1, 2, a n d 3 p ost n at al m o nt hs.  
 
•  
H 2: M or e sy nc hr o n o us e y e -t o-ey e g az e [ pri m ary], p ositi v e aff ect [ pri m ary], s p e ec h, a n d t o uc h at 3 p ost n at al 
m o nt hs.  
 
Ai m 2: I d e ntify m ol ec ul ar m ec h a nis ms i n t h e O X T s yst e m u n d erl yi n g m ot h er -i nf a nt s y nc hr o ny ( N = 2 5 0). 
 
•  
H 1: W e hy p ot h esiz e t h at l o w er m ot h er -i nf a nt s y nc hr o ny will b e ass oci at e d wit h d a m p e ni n g of t h e O X T syst e m, 
e vi d e nc e d b y i ncr e as e d O X T R m et hyl ati o n at c a n di d at e sit es, a n d d ecr e as e d O X T R m R N A, O X T R pr ot ei n, a n d 
O X T i n m at er n al pl as m a, a n d d ecr e as e d O X T i n i nf a nt s ali v a at 3 -p ost n at al m o nt hs.  
  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1 5  
extr e miti es (t o uc h of i nf a nt's h a n ds or f e et oft e n wit h a n ot h er o bj ect); f u ncti o n al t o uc h (t o uc h t h at h as a f u ncti o n al g o al 
s uc h as wi pi n g t h e i nf a nt's m o ut h); pr o pri oc e ptiv e t o uc h (i ncl u d es t o uc h t h at c h a n g es t h e i nf a nt's p ositi o n i n s p ac e ( e. g., 
p ulli n g t h e i nf a nt t o a sitti n g p ositi o n); sti m ul at ory t o uc h (i n dic ati n g t o uc h t h at i nt e n ds t o sti m ul at e a n d i ncr e as e 
ar o us al); a n d n o t o uc h.   
 
 
 
3. 3. 1. 3  Micr o -c o di n g I nf a nt B e h a vi ors    
I nf a nt G az e is c o d e d si mil ar t o p ar e nt's g az e al o n g t h e f oll o wi n g c o d es: g az e t o p ar e nt, g az e t o o bj ect or e n vir o n m e nt, 
a n d g az e a v ersi o n. I nf a nt Aff ect is c o d e d as hi g h p ositiv e (l a u g h, gi g gl e, s mil e), p ositi v e (s mil e, bri g ht f ac e), n e g ati v e (s a d 
f ac e, occ asi o n al w hi m p er), hi g h n e g ati v e (cr y, str o n g w hi ni n g), or n e utr al ( n o n e of t h e a b ov e).  I nf a nt v oc aliz ati o ns 
i ncl u d e p ositiv e (s uc h as p ositi v e b a b bli n g, c o oi n g, or gi g gl es) a n d n e g ativ e (s uc h as f ussi n g a n d cr yi n g). I nf a nt T o uc h 
i ncl u d es i nt e nti o n al, acci d e nt al, a nd n o t o uc h.   
 
3. 3. 1. 4  C at e g ori es of S y nc hr o n y   
T w o v ari a bl es ar e cr e at e d as m e as ur es of s y nc hr o ny vi a c o n diti o n al pr o b a biliti es ( p ar e nt i n b e h avi or X w hil e i nf a nt i n 
b e h a vi or Y). Aff ect S y nc hr o ny : e pis o d es i n w hic h p ar e nt a n d i nf a nt si m ult a n e o usly ex pr ess p ositiv e aff ect. G az e 
S y nc hr o ny:  e pis o d es i n w hic h m ot h er a n d c hil d b ot h l o ok at e ac h ot h er’s f ac e. V oc al Sy nc hr o ny : m ot h er ex pr ess es 
" m ot h er es e" v oc aliz ati o n w hil e i nf a nt e mits p ositi v e v oc aliz ati o ns. T o uc h S y nc hr o ny : m ot h er t o uc h es i nf a nt 
aff ecti o n at ely w h e n m ot h er a n d i nf a nt s h ar e s oci al g az e.  
 
3. 3. 1. 5  C o di n g  Pr oc e d ur es  
At t h e st u dy s essi o n, o nc e t h e i nf a nt is i n a n al ert st at e, m ot h ers ar e i nstr uct e d t o fr e el y i nt er act wit h t h eir i nf a nt d uri n g 
4 mi n ut es of vi d e o r ec or di n g. W h e n c o di n g, t h e first mi n ut e is i g n or e d a n d c o di n g occ urs o n t h e fi n al 3 -mi n ut es. 
I nt er acti o ns ar e micr o -c o d e d fr a m e by fr a m e o n a c o m p ut eriz e d s yst e m ( N ol d us, W a g g e ni g e n, T h e N et h erl a n ds), 
c o nsist e nt wit h pr evi o us r es e arc h o n p ar e nt -i nf a nt s y nc hr o ny.( 3 1, 1 0 2-1 0 3)  C o d ers of t h e vi d e os ar e bli n d e d t o gr o u p 
c o n diti o n. T h e y will pr e p ar e t h e vi d e os f or c o di n g, c o d e t h e d at a, a n d tr a nsf er d at a i nt o a f or m r e a dy f or a n al ysis. 
C o d ers ar e tr ai n e d t o 9 0 % i nt er -r at er r eli a bility, a n d 2 0 % of vi d e os will b e d o u bl e c o d e d f or i nt er-r at er r eli a bilit y. C o di n g 
of m ot h er -i nf a nt sy nc hr o ny h as b e e n v ali d at e d i n m ulti pl e st u di es a n d m e as ur es of sy nc hr o ny h a v e s h o w n t o c orr el at e 
wit h m at er n al a n d i nf a nt ris k c o n diti o ns, ox yt oci n a n d c ortis ol l e v els, m at er n al br ai n r es p o ns e t o i nf a nt c u es, a n d t o 
pr e dict b ett er s oci al a dj ust m e nt, c o g niti v e f u ncti o ns, a n d a ut o n o mic r e g ul ati o n i n r es e arc h s p a n ni n g birt h t o 
a d ol esc e nc e. ( 7, 1 9, 6 3) 
 
3. 3. 2  O x yt oci n S yst e m  
T o u n d erst a n d t h e bi ol o gy u n d erl yi n g M -I sy nc hr o ny, a n d t h e effic ac y of A T V V, w e ar e c o m pr e h e nsi v e i n a n al yzi n g t h e 
O X T p at h w a y:  e pi g e n etic r e g ul ati o n a n d ex pr essi o n of t h e r ec e pt or g e n e, ex pr essi o n of t h e r ec e pt or pr ot ei n, a n d 
p e pti d e l ev el fr o m m at er n al bl o o d, a n d p e pti d e l e v el fr o m i nf a nt s aliv a . O ur a p pr o ac h ex p a n ds u p o n m ost sy nc hr o ny 
st u di es li mit e d t o o nly O X T p e pti d e l ev el. S a m pl es will b e i niti all y pr oc ess e d at t h e C oll e g e of N ursi n g ( C O N) Bi ol o gic al 
C or e L a b or at ory  wit hi n 2 h o urs of c oll ecti o n. S a m pl e I D, c oll ecti o n ti m e,  v ol u m e, ti m e r ec ei v e d, a n d d at e of 
extr acti o n  will b e r ec or d e d a n d  e nt er e d i nt o d at a st or a g e s oft w ar e f or s p eci m e n tr ac ki n g.  Pr oc ess e d s a m pl es will b e 
l a b el e d a n d st or e d at -8 0 C i n t h e l a b’s fr e ez er b a nk u ntil n e e d e d f or t h e pr oj ect’s a n al ys es. Fr e ez ers ar e i n a s ec ur e  k ey 
c ar d acc ess r o o m a n d ar e c o nti n u o usly m o nit or e d wit h a m alf u ncti o n al ar m s yst e m.    
 
3. 3. 2. 1  O X T R D N A m et h yl ati o n fr o m m at er n al pl as m a   
M et hyl ati o n will b e m e as ur e d at t h e U niv ersity of Ariz o n a’s G e n etic C or e usi n g bis ulfit e c o nv ersi o n, f oll o w e d b y hi g h -
t hr o u g h p ut n ext-g e n er ati o n s e q u e nci n g of P C R a m plic o ns. Bri efly, bis ulfit e c o nv ersi o n will b e p erf or m e d usi n g t h e E Z 
D N A Li g ht ni n g Kit ( Z y m o R es e arc h, Irvi n e, C A; D 5 0 3 1). Aft er c o nv ersi o n, D N A will b e P C R a m plifi e d usi n g pr evi o usly 
p u blis h e d pri m ers T SL 1 0 1 F ( 5’ -T T G A G T T T T G G A T T T A G A T A A T T A A G G A T T -3’) a n d T SL 1 0 1 R ( 5’ -bi oti n -
A A T A A A A T A C C T C C C A C T C C T T A T T C C T A A -3’). ( 3 9) T h es e pri m ers a m plify a r e gi o n b et w e e n -1 0 0 1 a n d -8 5 6 (r el ati v e t o t h e 
tr a nsl ati o n st art sit e) all o wi n g us t o m e as ur e m et hyl ati o n l ev els of C p G sit es at -1 0 0 1, -9 5 9, -9 3 4, -9 2 4, -9 0 1, a n d -8 6 0. ( 3 8-

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1 6  
4 4) Pri m ers will b e m o difi e d wit h 5’ li n k er s e q u e nc es, as pr e vi o usl y d escri b e d, ( 1 0 5) a n d a t w o -st a g e P C R pr oc ess will b e 
us e d t o i nc or p or at e s a m pl e -s p ecific b arc o d es a n d Ill u mi n a s e q u e nci n g a d a pt ers i nt o e ac h a m plic o n. ( 1 0 6) D e e p 
s e q u e nci n g ( > 1 0 0 0 s e q u e nc es/ a m plic o n/ s a m pl e) of a m plic o ns will b e p erf or m e d usi n g a n d Ill u mi n a Mi S e q (Ill u m n a, 
I nc., S a n Di e g o, C A) i nstr u m e nt, a n d p erc e nt m et hyl at e d cyt osi n e at e ac h p ositi o n al o n g t h e O X T R a m plic o n will b e 
e v al u at e d b y a n alysis of  s e q u e nc e d at a, all o wi n g f or hi g h r es ol uti o n a n alysis of p erc e nt m et hyl ati o n. Effic acy of bis ulfit e 
c o nv ersi o n a n d s e q u e nci n g err or r at es will b e ev al u at e d usi n g c yt osi n e p ositi o ns t h at ar e n ot p art of C p G sit es, a n d 
t hr o u g h m et hyl at e d a n d u n m et hyl at e d st a n d ar ds. R a w r e a ds will b e m a p p e d t o ex p ect e d a m plic o n s e q u e nc es i n a 
bis ulfit e c o nv ersi o n -a w ar e m a n n er. ( 1 0 7) M et hyl ati o n will b e q u a ntifi e d at e ac h C p G b as e d o n t h e distri b uti o n of 
m et hyl at e d a n d u n m et h yl at e d b as es ali g n e d t o t h at p ositi o n.  A d diti o n al ex pl or at or y C p G sit es h av e b e e n s el ect e d  b as e d 
o n t h eir i m plic ati o n i n pr e vi o us st u di es ( 4 6-5 0, 6 9) a n d c ost -eff ecti v e n ess i n c o -t ar g eti n g a d diti o n al r e gi o ns usi n g t h e 
s el ect e d ass ay. 
 
3. 3. 2. 2  O X T R m R N A e x pr essi o n fr o m m at er n al pl as m a   
T ot al O X T R  R N A will b e m e as ur e d at t h e C O N Bi ol o gic al C or e L a b or at ory  a n d extr act e d fr o m w h ol e bl o o d usi n g t h e 
si m pl y R N A Bl o o d Kit, i ncl u di n g a D N As e tr e at m e nt st e p. R N A will b e r ev ers e tr a nscri b e d usi n g a Hi g h-C a p acit y c D N A 
R e v ers e Tr a nscri pti o n kit ( T h er m o Fis h er Sci e ntific). T ar g et g e n e ex pr essi o n ( i. e., O X T R; Hs 0 1 0 4 1 2 1 3 _ m 1) will b e 
n or m aliz e d t o t h e g e o m etric m e a n of Gl yc er al d e hy d e 3 -p h os p h at e d e h y dr o g e n as e ( G A P D H; Hs 9 9 9 9 9 9 0 5 _ m 1), B et a -2 
micr o gl o b uli n ( B 2 M; Hs 0 0 1 8 7 8 4 2 _ m 1) a n d h y p ox a nt hi n e p h os p h ori b os yltr a nsf er as e 1 ( H P R T 1; Hs 0 2 8 0 0 6 9 5 _ m 1). All 
ass a ys wi ll b e T a q m a n  g e n e ex pr essi o n ass ays, sy nt h esiz e d b y Lif e T ec h n ol o gi es, a n d will i ncl u d e ex o n -ex o n j u ncti o ns, t o 
r e d uc e b ac k gr o u n d g e n o mic D N A a m plific ati o n. Q u a ntit ati v e P C R will b e c o n d uct e d o n a n A BI Vii A 7 r e al-ti m e P C R 
i nstr u m e nt, e m pl oyi n g T a q M a n ® F ast A dv a nc e d M ast er Mix (Lif e T ec h n ol o gi es). All ass a ys will b e p erf or m e d i n t ec h nic al 
tri plic at es, an d f ol d c h a n g es i n g e n e ex pr essi o n will b e ass ess e d usi n g t h e c o m p ar ati v e C T m et h o d.  
 
3. 3. 2. 3  O X T R pr ot ei n e x pr essi o n fr o m m at er n al pl as m a    
O X T R pr ot ei n will b e m e as ur e d at t h e C O N Bi ol o gic al C or e L a b or at ory  a n d is ol at e d usi n g N E -P E R ™ N ucl e ar a n d 
C yt o pl as mic Extr acti o n R e a g e nts ( T h er m o Fis h er, 7 8 8 3 3). Pr ot ei n will b e s e p ar at e d o n a N u P A G E ™ 4 -1 2 % Bi s -Tri s 
pr ot ei n g el s  ( T h er m o Fis h er, N P 0 3 4 2 B O X) wit h c o nst a nt v olt a g e 1 3 0 V f or 0. 5 h o urs a n d tr a nsf err e d f or 2 hrs o nt o P V D F 
m e m br a n es. M e m br a n e will t h e n b e i nc u b at e d o n e h o ur i n 5 % bl ocki n g s ol uti o n, t h e n ov er ni g ht wit h r a b bit a nti -O X T R 
a nti b o dy ( A bc a m, a b 1 8 1 0 7 7) at a 1: 2 0 0 d il uti o n i n T B S T. A nti-r a b bit s ec o n d ar y a nti b o dy ( C ell Si g n ali n g; 7 0 7 6 S) will t h e n 
b e us e d at a 1: 2 0, 0 0 0 dil uti o n i n T B S T. β -acti n will b e d et ect e d usi n g m o us e a nti -β -acti n a nti b o dy ( Si g m a -Al dric h; A 5 3 1 6) 
at a 1: 2 0 0 0 dil uti o n i n 1 % bl oc ki n g s ol uti o n ov er ni g ht at 4 oC f oll o w e d by a nti -m o us e s ec o n d ar y a nti b o dy ( C ell Si g n ali n g; 
7 0 7 6 S) at a 1: 5 0 0 0 dil uti o n i n 1 % bl oc ki n g s ol uti o n f or 2 hrs. W est er n bl ots will b e d e v el o p e d usi n g S u p er Si g n al ™ 
W e st Pi c o P L U S C h e mil u mi n e s c e nt S u b str at e  ( T h er m o Fis h er; 3 4 5 8 0), d et ect e d usi n g a Bi o R a d C h e mi D oc™ M P 
S yst e m a n d q u a ntifi e d usi n g Q u a ntit y O n e s oft w ar e. St a n d ar d c ur v e f or O X T R pr ot ei n will b e c o nstr uct e d b y  m a ki n g 
st a n d ar d s ol uti o n wit h diff er e nt c o nc e ntr ati o ns. 
 
3. 3. 2. 4  O X T p e pti d e fr o m m at er n al pl as m a    
O X T p e pti d e will b e m e as ur e d at t h e L a b or at ory f or t h e E v ol uti o n ar y E n d ocri n ol o gy of Pri m at es (L E E P). Bl o o d s a m pl es 
will b e dr a w n i nt o pr e -c hill e d E D T A ( 1 m g/ mL bl o o d) t u b es a n d pl ac e d o n ic e. T u b es ar e c e ntrif u g e d at 1 6 0 0 x g f or 1 5 
mi n ut es at 4° C. Pl as m a will b e tr a nsf err e d t o a pr e -c hill e d 1. 5 ml e p p e n d orf pl astic t u b e a n d st or e d first at -2 0° C f or at 
l e ast 2 4 h o urs, t h e n at -7 0° C f or l o n g t er m st or a g e.  S a m pl es ar e s e nt t o L E E P t o b e a n al yz e d i n d u plic at e by e nzy m e 
i m m u n o ass ay ( EI A) usi n g t h e Oxyt oci n ELI S A kit ( E nz o; A DI-9 0 1 -1 5 3 A -0 0 0 1).  
 
3. 3. 2. 5  O X T p e pti d e fr o m i nf a nt s ali v a    
O X T p e pti d e will b e m e as ur e d at L E E P. S ali v a s a m pl es will b e c oll ect e d usi n g S ali m etric’s s w a b m et h o d f or i nf a nts ( us e d 
i n o ur pil ot). A 9 0 m m x 6. 5 m m p oly m er s w a b ( a bl e t o wit hst a n d c h e wi n g) is h el d fir ml y i n t h e i nf a nt’s m o ut h f or 9 0 
s ec o n ds. T u b es ar e ce ntrif u g e d at 5 0 0 -1 0 0 0 r p m f or 5 mi n ut es at 4° C.  T h e s u p er n at a nt is ali q u ot e d i nt o 1. 5 mL t u b es 
a n d fr oz e n at -8 0. S a m pl es ar e s e nt t o L E E P t o b e a n alyz e d i n d u plic at e b y e nzy m e i m m u n o ass a y ( EI A) usi n g t h e Oxyt oci n 
ELI S A kit ( E nz o; A DI -9 0 1 -1 5 3 A -0 0 0 1).  
 
4. 0  S T U D Y D E SI G N  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1 7  
T h e si n gl e -sit e st u dy d esi g n is a 4-y e ar, r a n d o miz e d, t w o -gr o u p, att e nti o n -c o ntr oll e d cli nic al tri al. W o m e n ( N = 2 5 0) will 
b e scr e e n e d  f or c hil d h o o d a dv ersity, e nr oll e d i n pr e g n a nc y t o o bt ai n b as eli n e O X T d at a. S o o n  
aft er birt h ( pr e -h os pit al disc h ar g e), M -I dy a ds w h o c o nti n u e t o b e eli gi bl e ar e r a n d o miz e d i nt o t h e i nt er v e nti o n 
gr o u p ( n = 1 2 5) a n d t a u g ht t o a d mi nist er t h e A T V V i nt er v e nti o n d ail y f or 3 m o nt hs or r a n d o miz e d i nt o t h e  
att e nti o n c o ntr ol gr o u p ( n = 1 2 5) a n d t a u g ht s af e i nf a nt c ar e. T h er e ar e a t ot al of 5 st u dy visits ( 3r d tri m est er,  
s o o n aft er birt h, 1st p ost n at al m o nt h, 2 n d p ost n at al m o nt h, 3r d p ost n at al m o nt h), pl us a f oll o w -u p p h o n e c all at 6  
p ost n at al m o nt hs t o ass ess q u alit y of p ar e nti n g usi n g a s elf -r e p ort q u esti o n n air e.  
 
T his is a r a n d o miz e d c o ntr oll e d tri al ( R C T) c o m p ari n g d at a b et w e e n t h e A T V V a n d Att e nti o n C o ntr ol gr o u ps.  R a n d o m 
assi g n m e nt is c e ntr ally c o ntr oll e d by o ur st atistici a n usi n g a c o m p ut er -g e n er at e d list of r a n d o m  n u m b ers  
( 0 =i nt er v e nti o n a n d 1 =c o ntr ol), b al a nc e d s o t h at h alf t h e M-I dy a ds ar e i n t h e A T V V gr o u p. M ot h ers  will b e as k e d t o n ot 
discl os e t h eir gr o u p assi g n m e nt t o m ot h ers i n t h e p ost n at al u nit . 
 
4. 1  St u d y P o p ul ati o n  
T h e st u dy p o p ul ati o n s a m pl e a n d s etti n g is p eri n at al w o m e n givi n g birt h at eit h er T ucs o n M e dic al C e nt er ( T M C) , B a n n er  
U ni v ersity M e dic al C e nt er ( B U M C) , or a n alt er n ati v e sit e. As t h e r e gi o n’s l ar g est birt hi n g f acilit y, T M C h a d 5 5 8 2 liv e 
birt hs i n 2 0 1 9.  
Of t h e birt hs at T M C, 8 9 % w er e f ull -t er m ( > 3 7 0/ 7 w e e ks), 9 9 % w er e > 1 8 y e ars, 3 9 % w er e first-ti m e m ot h ers, 
5 9 % w er e L ati n a W hit e, 1 0 % w er e n o n -L ati n a W hit e, 8 % w er e A m eric a n I n di a n, 4 % w er e Bl ack, a n d m a ny  
liv e d i n zi p c o d es wit h i nc o m e b el o w t h e p ov ert y l e v el. T h e B U M C (l oc at e d a dj ac e nt t o t h e C oll e g e of N ursi n g) 
h a d 1 7 3 3 liv e birt hs i n 2 0 1 9. Of t h e birt hs at B U M C, 9 0 % w er e f ull -t er m ( > 3 7 0/ 7 w e e ks), 9 0 % w er e > 1 8 y e ars 
a n d 3 1 % w er e first -ti m e m ot h ers. A d diti o n ally, 7 9 % of birt hi n g w o m e n at B U M C s elf-i d e ntifi e d as W hit e, 7 % as 
Bl ac k, a n d 4 % as L ati n a. B ot h T M C a n d B U M C ar e wit hi n Pi m a C o u nt y, w h er e i n 2 0 1 8 L ati n a w o m e n  
r e pr es e nt e d 4 8 % of birt hs a n d n o n-L ati n a W hit e w o m e n r e pr es e nt e d 3 9 % of t h e birt hs, t h us w e ex p ect a b o ut  
h alf of o ur s a m pl e will b e L ati n a.  
 
4. 1. 1  I ncl usi o n Crit eri a 
Pr e g n a nt w o m e n ar e eli gi bl e if t h ey ar e a d ults > 1 8 y e ars ol d, givi n g birt h t o t h eir first c hil d ( will b e pri mi p ar o us),  
s p e a k a n d r e a d E n glis h or S p a nis h, sc or e > 2 o n t h e A dv ers e C hil d h o o d Ex p eri e nc es ( A C E) q u esti o n n air e,  h av e acc ess t o a 
c ell p h o n e d uri n g t h e first t hr e e m o nt hs aft er d eliv ery, a n d ex p ect t o d eliv er a h e alt hy f ull -t er m, si n gl et o n i nf a nt ( > 
3 7 0/ 7 w e eks) wit h o ut s eri o us c o n diti o ns t h at w o ul d  i m p act n or m al d ev el o p m e nt ( e. g. i ntr a-ut eri n e gr o wt h r et ar d ati o n, 
c hr o m os o m al or c o n g e nit al a n o m ali es, or  s eri o us ill n ess). Aft er givi n g birt h, M-I dy a ds c a n r e m ai n i n t h e st u dy if t h e 
i nf a nt is f ull-t er m wit h o ut s eri o us c o n diti o ns t h at w o ul d i m p act n or m al  d ev el o p m e nt ( e. g. i ntr a -ut eri n e gr o wt h 
r et ar d ati o n, c hr o m os o m al or c o n g e nit al a n o m ali es, s m all f or g est ati o n al a g e ( S G A)  or M -I i nt er acti o n.  
 
4. 1. 2  E xcl usi o n Crit eri a  
Pr e g n a nt w o m e n ar e excl u d e d if t h ey ar e y o u n g er t h a n 1 8 y e ars ol d, ar e givi n g birt h t o t h eir s ec o n d c hil d  ( pri mi p ar o us) 
or hi g h er ( m ulti p ar o us), ar e u n a bl e t o s p e a k or r e a d E n glis h, sc or e l ess t h a n 2 o n t h e A dv ers e C hil d h o o d Ex p eri e nc e 
( A C E) s urv e y, d o n ot h a v e acc ess t o a c ell p h o n e d uri n g t h e first 3 p ost n at al m o nt hs, ar e c arr yi n g m ulti pl e f et us es ( e. g., 
t wi ns), t a k e illicit dr u gs, h av e e v er b e e n  di a g n os e d wit h bi p ol ar, a utis m, or sc hiz o p hr e ni a,  d eli v ers a pr et er m i nf a nt 
(l ess t h a n 3 7 0/ 7 w e e ks), or d eliv ers a n i nf a nt wit h a s eri o us c o n diti o n t h at w o ul d i m p act n or m al d ev el o p m e nt ( e. g.  
c hr o m os o m al or c o n g e nit al a n o m ali es,  S m all f or G est ati o n al A g e  ( S G A) d efi n e d b y b o dy m ass, h e a d circ u mf er e nc e, a n d 
b o dy l e n gt h l ess t h at t h e 1 0 t h p erc e ntil e f or t h e g est ati o n al a g e at birt h , or s eri o us ill n ess).   
 
4. 1. 3  Lif est yl e C o nsi d er ati o ns 
T h e p artici p a nts ar e fr e e t o e n g a g e i n acti viti es as us u al w hil e p artici p ati n g i n t his cli nic al tri al. H o w e v er, w e r e q u est t h at 
t h e y n ot  s h ar e h o w t o c o n d uct t h e i nf a nt m ass a g e.   
 
4. 1. 4  Str at e gi es f or R ecr uit m e nt  
4. 1. 4. 1  W ai v er of A ut h oriz ati o n a n d L ett er  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1 8  
Usi n g a W aiv er of A ut h oriz ati o n  a n d sit e p er missi o n  t o i d e ntify p ot e nti ally eli gi bl e w o m e n t hr o u g h t h e El ectr o nic H e alt h 
R ec or ds s yst e ms of t h e r ecr uit m e nt sit es ( T M C a n d B U M C),  p ot e nti al p artici p a nts  ar e a p pr o ac h e d by cli nic st aff d uri n g 
t h eir pr e n at al visits at t h e r ecr uit m e nt sit es. If a gr e e a bl e, th e R ecr uit er  i ntr o d uc es t h e st u dy. W h e n  a n eli gi bl e w o m a n is 
i nt er est e d, t h e R ecr uit er i nvit es h er t o c o m pl et e a 1 0 -it e m A C E s urv ey t o ass ess l ev el of c hil d h o o d a dv ersit y. D uri n g a  
p a n d e mic, m a ny pr e g n a nt w o m e n r ec eiv e  c ar e t hr o u g h t el e h e alt h visits r at h er t h a n  i n-p ers o n visits. T h e r es e arc h t e a m 
m e m b er pr e -scr e e ns us i n g a n eli gi bilit y c h ec klist a n d t h e n m ail s p ot e nti all y eli gi bl e  pr e g n a nt w o m e n a l ett er i ntr o d uci n g 
t h e st u dy. T h e c o nt e nt of t h e l ett er is dict at e d b y t h e sit es.   
 
4. 1. 4. 2  R ecr uit m e nt M at eri als  i n Pr e n at al Cli nics 
Aft er h a vi n g o bt ai n e d  a p pr o pri at e a p pr ov als, r ecr uit m e nt m at eri als ar e  pl ac e d i n t h os e cli nics pr o vi di n g f ac e -t o-f ac e 
visits . S e e A p p e n dix B f or ex a m pl es of t h e R ecr uit m e nt M at eri als. F or pr o vi d ers or t h eir d el e g at es  as ki n g p ati e nts if t h e y 
w o ul d b e willi n g t o disc uss t h e st u dy wit h o ur  r es e arc h t e a m, w e o bt ai n t h e c o nt act i nf or m ati o n, pr escr e e n, a n d c all t h e 
i nt er est e d p ot e nti al p artici p a nts.  A t el e p h o n e scri pt is f oll o w e d by r es e arc h p ers o n n el t o d escri b e t h e st u dy a n d c o nfir m 
eli gi bilit y  i ncl u di n g c o m pl eti n g t h e 1 0-it e m A C E s urv e y. If t h e w o m a n sc or es >  2 o n t h e A C E  a n d m e ets t h e ot h er 
i ncl usi o n/ excl usi o n crit eri a i ncl u di n g ex pr essi n g i nt er est i n r evi e wi n g t h e c o ns e nt f or m, w e will m ail or e m ail (t h eir 
c h oic e) a n i nf or m e d c o ns e nt t o r evi e w. T h e c o ns e nt f or m i n dic at es t h at w e will us e t h e r es ults of t h e A C E i nstr u m e nt i n 
t h e st u dy. W e c all a g ai n t o a ns w er a ny st u dy q u esti o ns a n d as k if t h ey ar e i nt er est e d i n p artici p ati n g. If t h e y ar e 
a gr e e a bl e, w e c o ns e nt i n R E D C a p. W o m e n ar e  sc h e d ul e d f or a b as eli n e d at a c oll ecti o n st u dy visit i n pr e g n a nc y w h er e 
t h e y c o nti n u e t h e c o ns e nt pr oc ess t o e ns ur e t h ey h av e u n d erst o o d t h e r e q uir e m e nts of p artici p ati o n.   
 
4. 1. 4. 3  R ef err als, Pr e n at al Cl ass es, a n d C o m m u nit y Or g a niz ati o ns  
W e n et w or k wit h ot h er r es e arc h st u di es r ecr uiti n g fr o m O B/ G Y N w hic h  r ef er p ati e nts w h o h av e giv e n p er missi o n t o b e 
c o nt act e d b y ot h er r es e arc h st u di es.  A d diti o n ally, w e r ecr uit vi a c o m m u nity or g a niz ati o ns s uc h t h os e off eri n g pr e n at al 
cl ass es. W e pr es e nt a o n e -mi n ut e d escri pti o n of t h e st u dy a n d pr ovi d e  o ur st u dy c o nt act i nf or m ati o n o n a p o w er p oi nt 
sli d e. S e e A p p e n dix B f or R ecr uit m e nt M at eri als.  
 
4. 1. 5   Scr e e n F ail ur es  
If a m ot h er sc or es l ess t h a n 2 o n t h e A C E, w e will r e m ov e all 1 3 el e m e nts of i d e ntific ati o n a n d r et ai n o nl y t h e A C E sc or e 
wit h o ut t h e c orr es p o n di n g a ns w ers t o t h e 1 0 q u esti o ns . W e w o ul d li k e t o d et er mi n e if t h e i ncl usi o n/ excl usi o n crit eri a 
s uc h as t h e r e q uir e m e nt t o h a v e acc ess t o a c ell p h o n e, scr e e ns o ut a ny p orti o n of t h e  p o p ul ati o n wit h hi g h A C E sc or es.  
A d diti o n ally, t his  st u dy h as a s ec o n d l ev el of scr e e ni n g w hic h occ urs at t h e birt h of t h e b a by.  If a p artici p a nt d eli v ers a 
b a by n ot m e eti n g t h e i ncl usi o n crit eri a s uc h as f ull t er m ( 3 7 w e e ks 0/ 7 d a ys) a n d h e alt h y, t h e y ar e wit h dr a w n fr o m t h e 
st u dy a n d ar e n ot r a n d o miz e d. A mi ni m al s et of scr e e n f ail ur e i nf or m ati o n is r e q uir e d t o e ns ur e tr a ns p ar e nt r e p orti n g of 
scr e e n f ail ur e p artici p a nts, t o m e et t h e C o ns oli d at e d St a n d ar ds of R e p orti n g Tri als ( C O N S O R T) p u blis hi n g r e q uir e m e nts 
a n d t o r es p o n d t o q u eri es fr o m r e g ul at or y a ut h oriti es. Mi ni m al i nf or m ati o n i ncl u d es d e m o gr a p hy, scr e e n f ail ur e d et ails, 
eli gi bilit y crit eri a, a n d a ny s eri o us a dv ers e ev e nt ( S A E)  w hic h ar e r et ai n e d wit h st u dy r ec or ds. B ec a us e t h er e ar e n o 
m o difi a bl e f act ors ass oci at e d wit h scr e e n f ail ur e, w e d o n ot r escr e e n p artici p a nts.  
 
4. 1. 6  Str at e gi es f or R et e nti o n  
W e ex p ect a n 8 0 % r et e nti o n r at e. 
 pr e vi o us R 0 1 st u di es d e m o nstr ate d  8 5 % r et e nti o n wit h w o m e n 
a d mi nist eri n g A T V V t o t h eir n e w b or n  pr et er m i nf a nt aft er h os pit al disc h ar g e f or 2 -m o nt hs  a n d  d e m o nstr at e d  7 2 % 
r et e nti o n f or 2-3  m o nt hs i n a n ot h er st u dy. I n t his pr o p os al, c o nsi d eri n g 2 0 % attriti o n a n d  c oll ecti n g d at a t hr o u g h 3 -
p ost n at al m o nt hs, w e ex p ect t o ac q uir e c o m pl et e d at a i n 2 4 m o nt hs; t h us, w e r e q uir e  e nr olli n g 3 -4 w o m e n p er w e e k 
a n d r et ai ni n g  2 -3 w o m e n p er w e e k.  
 
4. 1. 6. 1  Tr ac k E nr oll m e nt a n d R et e nti o n R at es  
As p art of o ur q u alit y c o ntr ol pr oc ess, w e m o nit or wit h m o nt hly exc el gr a p hs o ur t ar g et e d v ers us act u al  e nr oll m e nt a n d 
r et e nti o n r at es. W e m e et e ac h w e e k t o r evi e w t h es e t w o gr a p hs a n d t h e n disc uss w h et h er w e s h o ul d c o nti n u e f or w ar d 
wit h t h e pl a n , disc uss h o w t o t w e ak t h e c urr e nt c o urs e, or  s et a n e w c o urs e of acti o n.   
 
4. 1. 6. 2  Est a blis h R el ati o ns hi ps  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
1 9  
T o m ai nt ai n a c ult ur ally s e nsiti v e r es e arc h t e a m i n t his  st u dy, w e hir e d  L ati nx ( bili n g u al E n glis h a n d S p a nis h) t e a m 
m e m b ers.  A d diti o n ally, o ur ov er all a p pr o ac h t o e n h a nc e r et e nti o n is t o fr e q u e ntly r e ac h o ut t o m ot h ers t o d e v el o p a 
str o n g tr usti n g r el ati o ns hi p t h at r ei nf orc es h o w v al u a bl e t h eir ti m e is a n d h o w m uc h w e a p pr eci at e t h eir p artici p ati o n.  
W e will s e n d  h oli d a y a n d birt h d a y c ar ds, a n d i n a d diti o n t o t h e a ut o m atic, d ail y, p us h -o ut t exts w e will s e n d p ers o n al 
t exts. W e’ v e l e ar n e d t h at m ot h ers pr ef er p h o n e or t ext c o m m u nic ati o n v ers us e m ail or m ail.  
 
4. 1. 6. 3 P artici p a nt G ui d a nc e M at eri als  
W e c o m bi n e w h at w e l e ar n e d b et w e e n o ur f e asi bilit y pil ot a n d t h e R C T st u di es t h at C o -I Dr. W hit e -Tr a ut h as c o n d uct e d 
wit h pr et er m i nf a nts.   W e pr o vi d e  m ot h ers wit h l ar g e c ol orf ul m a g n ets w hic h m a p o ut t h e st u dy visits a n d ex p ect ati o ns 
ass oci at e d wit h p artici p ati n g i n t h e st u dy. S e e A p p e n dix A.  A d diti o n ally, w e h av e a p p oi nt m e nt c ar ds t o pr ovi d e t o t h e 
m ot h ers w h e n w e visit t h e m i n t h e h os pit al aft er birt h of t h eir b a by. T h es e a p p oi nt m e nts c ar ds ar e us e d f or all 3 p ost -
n at al visits.   
 
4. 1. 6. 4 R e mi n d er C alls, M ulti pl e C o nt act N u m b ers, a n d Fl e xi bl e Sc h e d uli n g  
St aff s e n d a t ext m ess a g e a n d/ or c all o n e w e e k b ef or e, t w o d ays b ef or e, a n d t h e d a y of a sc h e d ul e d st u dy  visit f or 
c o nfir m ati o n. W h e n a p artici p a nt c a n n ot b e r e ac h e d f or o n e w e ek at t h e l ast k n o w n p h o n e n u m b er,  pr e vi o usl y pr ovi d e d  
c o nt acts ar e  as k e d f or assist a nc e i n l oc ati n g h er. Fl exi bl e sc h e d uli n g of a p p oi nt m e nts a n d r esc h e d uli n g  if n ec ess ar y,  will 
acc o m m o d at e m ot h ers’ sc h e d ul es. At e ac h m o nt hly st u dy visit, w e will pr ovi d e  p ositiv e u plifti n g f e e d b ac k t o m ot h ers i n 
b ot h gr o u ps o n t h eir ex p eri e nc e wit h ei t h er A T V V a n d/ or m at er n al c ar e givi n g i n g e n er al. 
 
4. 1. 6. 5 C o m p e ns ati o n  
M ot h ers will b e pr ovi d e d  c o m p e ns ati o n f or t h eir ti m e t ot ali n g $ 3 0 0: $ 5 0 at e nr oll m e nt, $ 5 0 at birt h, $ 5 0 at T 1, $ 5 0 at 
T 2, a n d $ 1 0 0 at T 3.  T h er e is n o c o m p e ns ati o n f or t h e p h o n e c all at 6 m o nt hs.  A d diti o n ally, tr a ns p ort ati o n f e es ar e 
c o m p e ns at e d at $ 4 p er visit or if t h e p artici p a nt is tr av eli n g vi a t h eir o w n v e hicl e, t h e C oll e g e of N ursi n g m ai nt ai ns a 
r es erv e d p ar ki n g  s p ot f or r es e arc h p artici p a nts. 
 
4. 2  A T V V I nt er v e nti o n 
4. 2. 1  D escri pti o n of  A T V V  I nt er v e nti o n 
T h e  A T V V ( A u dit ory, T actil e, Vis u al, V esti b ul ar sti m ul ati o n) is a 1 5 mi n ut e m ultis e ns or y b e h a vi or al i nt er v e nti o n 
c o nsisti n g of i nf a nt-dir ect e d aff ecti o n at e “ m ot h er es e” s p e ec h, m o d er at e t o uc h m ass a g e, ey e t o ey e g az e, a n d h oriz o nt al 
r oc ki n g.( 2 4, 7 6, 7 7) T h e A T V V i nt er v e nti o n pr ovi d es cli nici a ns a l o w -c ost, e asily acc essi bl e i nt erv e nti o n f or m ot h ers t o 
i m pl e m e nt t h at h as b e e n w ell r es e arc h e d b y o ur t e a m wit h pr et er m i nf a nts.( 2 5-3 0) T h e P at h w ays F o u n d ati o n, w h os e 
e d uc ati o n al m at eri als ar e a p pr o v e d by t h e A m eri c a n Ac a d e my of P e di atrics, i ncl u d es A T V V i n t h eir e d uc ati o n f or p ar e nts 
wit h pr et er m i nf a nts ( htt ps:// p at h w ays. or g/ gr o wt h -d e v el o p m e nt/ m ass a g e -3 0 -1 0 -5/). A T V V is a n e nj o y a bl e d ail y 
o p p ort u nity f or m ot h ers t o pr actic e m o d eli n g M -I sy nc hr o ny by usi n g ey e t o ey e g az e, aff ecti o n at e s p e ec h a n d s o ot hi n g 
t o uc h.  
  
D uri n g t h e 1 5 -mi n ut es i n w hic h A T V V is a d mi nist er e d, m ultis e ns ory sti m uli ar e pr es e nt e d i n gr a d u al pr o gr essi o n:
( 2 4, 7 6, 7 7) 
" m ot h er es e" s p e ec h w hic h is i nf a nt-dir ect e d s p e ec h ty pic all y hi g h -pitc h e d wit h a si n g -s o n g r h yt h m f or 3 0 s ec o n ds, 
f oll o w e d by m ass a g e f or 1 0 mi n ut es, wit h ey e t o e y e g az e a d d e d as t h e i nf a nt b ec o m es al ert (i d e all y at t h e b e gi n ni n g of 
t h e i nt erv e nti o n), a nd e n di n g wit h r oc ki n g f or t h e r e m ai ni n g 5 mi n ut es. I m p ort a ntl y, “ m ot h er es e” is m ai nt ai n e d 
t hr o u g h o ut t h e e ntir e 1 5-mi n ut e i nt er v e nti o n as l o n g as dis e n g a g e m e nt c u es ar e n ot ex hi bit e d. M -I e n g a g e m e nt is 
att e m pt e d t hr o u g h o ut t h e i nt er v e nti o n; t h us, m ot h ers l e ar n t o i d e ntif y, i nt er pr et a n d a d a pt t o t h eir i nf a nt’s 
d e v el o p m e nt ally a p pr o pri at e c u es. T h e A T V V is a p plic a bl e t hr o u g h o ut t h e st u dy p eri o d b ec a us e it c a n b e giv e n ev e n if 
t h e i nf a nt is t o o y o u n g f or e y e t o ey e g az e. R e g ar dl ess of w h et h er t h e i nf a nt is 1, 6, or 1 2 w e eks ol d, A T V V is al w a ys 
off er e d c o nti n g e nt o n i nf a nt c u es t o pr o m ot e s elf -r e g ul ati o n a n d is wit h dr a w n if t h e i nf a nt ex hi bits p ersist e nt 
dis e n g a g e m e nt c u es. ( 2 4, 7 6)    
 
4. 2. 2  A d mi nistr ati o n of I nt er v e nti o n  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
2 0  
A T V V is a d mi nist er e d b y m ot h ers s o o n aft er birt h; ( 2 9, 3 0, 7 8) t h us, filli n g a g a p f or si m pl e i nt er v e nti o ns t o pr o m ot e 
e n g a g e m e nt b et w e e n m ot h er a n d i nf a nt i n e arly i nf a nc y w h e n ex p eri e nc e -d e p e n d e nt n e ur al pl asticit y is hi g h i n 
m at er n al a n d i nf a nt br ai ns.
( 2 2, 2 3) I n a d mi nist eri n g A T V V, m ot h ers l e ar n t o b e c o mf ort a bl e r ec o g nizi n g a n d a d a pti n g t h eir 
b e h a vi or w h e n t h e i nf a nt is si g n ali n g c u es t o e n g a g e or dis e n g a g e. A T V V is a n e nj o y a bl e d ail y o p p ort u nit y f or m ot h ers t o 
pr actic e m o d eli n g M -I s y nc hr o ny b y usi n g ey e t o e y e g az e, aff ecti o n at e “ m o t h er es e” s p e ec h a n d s o ot hi n g t o uc h.( 7 8)   
M ot h ers will b e i nstr uct e d t o a d mi nist er A T V V f or 3 m o nt hs, o nc e d ail y at a ny ti m e of t h eir c h o osi n g, as l o n g as it is i n -
b et w e e n f e e di n gs w h e n t h e i nf a nt is r e a d y t o i nt er act b ut n ot t o o h u n gr y (r es ulti n g i n f ussi n ess) a n d n ot t o o f ull 
(r es ulti n g i n sl e e pi n ess). D aily us e all o ws f or A T V V t o fr e q u e ntl y r ei nf orc e p ositiv e M-I i nt er acti o n. W hil e t wic e v ers us 
o nc e d aily (i n c o m p aris o n t o c o ntr ols) yi el ds m or e si g nific a nt i m pr ov e m e nts i n bi ol o gic ally at -ris k pr et er m i nf a nts,( 2 3, 2 7, 2 9, 
3 0) o ur pil ot s h o w e d t h at o nc e v ers us t wic e d aily is m or e acc e pt a bl e f or m ot h ers of h e alt hy f ull -t er m i nf a nts. A r es e arc h 
t e a m m e m b er will t e ac h t h e i nt erv e nti o n wit h t h e assist a nc e of t h e A T V V I nt erv e nti o n M a n u al f or P ar e nts, a n d t h e 
o nli n e A T V V t e ac hi n g vi d e o t ar g eti n g n e w b or ns. T h e A T V V is e asily l e ar n e d wit hi n o n e h o ur a n d s h o w n t o b e hi g hl y 
acc e pt a bl e b y m ot h ers i n t h e lit er at ur e a n d i n o ur pil ot ( > 9 0 % a gr e e m e nt wit h t h e A T V V R eli a bilit y C h ec klist. ( 9 7) I n 
a d diti o n t o t aki n g h o m e  t h e A T V V m a n u al, m ot h ers c a n acc ess o ur o nli n e t e ac hi n g vi d e os wit h i nf a nts at t hr e e diff er e nt 
a g es ( n e wl y b or n, 6 w e eks, a n d 3 m o nt hs ol d).  
 
4. 2. 3  C o nc o mit a nt Acti viti es  
 W e will n ot m e nti o n t h e us e of oils or ot h er m ass a g e t ec h ni q u es  d uri n g i nstr ucti o n. If w e ar e as k e d a b o ut t h eir us e 
d uri n g t h e w e e kl y p h o n e c alls, w e will disc o ur a g e t h eir us e.  A d diti o n ally, a  br e astf e e di n g g ui d e is i ncl u d e d i n t h e h os pit al 
m at eri als, b ut q u esti o ns r e g ar di n g br e astf e e di n g ar e r ef err e d t o t h eir pri m ary c ar e pr ovi d er or ot h er r es o urc es.  
 
4. 3  I nt er v e nti o n C o m pli a nc e 
T o m o nit or m ot h ers’ fi d elity a n d d os a g e of A T V V o nc e d ail y, w e will us e t ext m ess a gi n g t hr o u g h T wili o, a n el ectr o nic 
c o m m u nic ati o ns pl atf or m wit hi n R E D C a p. T o h av e acc ess t o a p h o n e c a p a bl e of t ext m ess a gi n g  is a n i ncl usi o n crit eri o n 
t o p artici p at e i n t h e st u dy. P artici p a nts m a y tir e of r es p o n di n g t o d aily t exts, b ut o ur d ail y t ext is extr e m el y bri ef 
r e q uiri n g o nl y a k eystr o k e t o r es p o n d. If a p h o n e b ec o m es l ost, w e will pr ovi d e a t e m p or ary o n e.  E ac h ev e ni n g, T wili o  
will t ext t h e f oll o wi n g - 
•  
Pl e as e t ell us h o w m a ny mi n ut es y o u g av e y o ur b a by t h e M ass a g e Pl us t o d a y. C h o os e b et w e e n 0 -1 5 mi n ut es.  
•  
Pl e as e t ell us t h e l ev el of str ess y o u m ay h a v e ex p eri e nc e d t o d a y o n a sc al e of 0 -1 0.  
T h e q u esti o n o n str ess is i ncl u d e d b ec a us e t h e att e nti o n -c o ntr ol m ot h ers als o r ec ei v e t h e i d e ntic al t ext m ess a g e a n d 
str ess is a c ov ari at e. S e e s ecti o n 4. 5.  W e will m o nit or R E D C a p d aily, a n d c all m ot h ers if w e i d e ntify n o nc o m pli a nc e t w o 
d a ys i n a r o w. S ec o n d, w e will as k  d uri n g t h e w e e kly p h o n e c alls  if a n y o n e els e b esi d es t h e m ot h er g av e t h e m ass a g e.  At 
e ac h w e e kly p h o n e c all a n d m o nt hly st u dy visit, w e will r e vi e w h o w oft e n m ot h ers us e t h e i nt erv e nti o n (s elf -r e p ort vs 
R E D C a p d at a) a n d disc uss s ol uti o ns t o b arri ers of fi d elit y ( e. g. l ac k of ti m e, f ussy or sl e e py i nf a nt). W e will als o disc uss 
w h o els e m ay b e givi n g t h e m ass a g e t o t h eir b a by.  
  
4. 4   Att e nti o n -C o ntr ol C o m p aris o n  
4. 4. 1    D escri pti o n of Att e nti o n -C o ntr ol Gr o u p.  
T h e Att e nti o n C o ntr ol gr o u p  is d esi g n e d t o pr o vi d e a si mil ar a m o u nt of r es e arc h st aff att e nti o n w hil e  i n t h e h os pit al 
aft er birt h, d uri n g w e ekl y p h o n e c alls , a n d at 3 p ost n at al st u dy visits b ut wit h t h e f oc us o n di d actic e d uc ati o n (c o nt e nt 
disti nctl y diff er e nt fr o m t h e i nt erv e nti o n). T h e Att e nti o n C o ntr ol e d uc ati o n pr ot oc ol h as b e e n us e d f or ov er 1 5 y e ars i n 
t hr e e of o ur pr evi o us R C Ts, d e m o nstr ati n g acc e pt a bility t o m ot h ers, e asy i m pl e m e nt ati o n, a n d ri g or i n is ol ati n g t h e 
i m p act of A T V V.( 2 8-3 0, 7 8) I n o ur Att e nti o n C o ntr ol, m ot h ers w ill r ec ei v e e d uc ati o n o n s af e i nf a nt c ar e i ncl u di n g c o nt e nt o n 
di a p ers, i nf a nt cl ot hi n g, bl a n k ets, b at hi n g, sl e e p p ositi o ns, sl e e p h a bits, h ol di n g t h e b a by, s af ety of i nf a nt e q ui p m e nt, 
br e astf e e di n g, f or m ul a, a n d a g e -a p pr o pri at e t o ys. T h e r es e arc h m e m b er w ill us e a pr e p ar e d scri pt a n d r ec or d in t h e 
Att e nti o n C o ntr ol R ec or d t h e i nf or m ati o n disc uss e d . Si nc e t h e A T V V i nt er v e nti o n m ot h ers will b e c o nt act e d by a w e ekl y 
p h o n e c all, t h e r es e arc h m e m b er will als o c o nt act t h e Att e nti o n C o ntr ol m ot h ers b y w e e kly c all s t o r ei nf orc e e d uc ati o n. 
F or b ot h gr o u ps, w e e kly c alls will i ncl u d e st a n d ar d mil est o n es i n i nf a nt d e v el o p m e nt.   
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
2 2  
* B as eli n e ( B), I n -h os pit al (I), a n d p ost n at al m o nt hs T 1, T 2, T 3; * * A v ail a bl e i n S p a nis h  
 
4. 6  Mi ni miz ati o n of Bi as  
4. 6. 1  R a n d o miz ati o n  a n d Bli n di n g  
T his is a n R C T c o m p ari n g d at a b et w e e n t h e A T V V a n d Att e nti o n C o ntr ol gr o u ps. R a n d o m assi g n m e nt is c e ntr all y 
c o ntr oll e d b y o ur st atistici a n usi n g a c o m p ut er -g e n er at e d list of r a n d o m n u m b ers ( 0 =i nt er v e nti o n a n d 1 =c o ntr ol), 
b al a nc e d s o t h at h alf t h e m ot h er -i nfa nt ( M -I) d y a ds ar e i n t h e A T V V gr o u p.  Bl oc k r a n d o miz ati o n is us e d t o r a n d o miz e 
p artici p a nts i nt o t w o gr o u ps of 1 2 5. T h e al g orit h m will c o nsi d er bl ocks of siz e 2, 4, 6 a n d 8 a n d c o nstr ai n t h e n u m b er of 
bl oc ks of e ac h siz e s o t h at t h e t ot al n u m b er of p artici p a nts is 2 5 0. T h e bl ock l a b els will b e s h uffl e d a n d assi g n m e nts t o 
t h e c o ntr ol a n d i nt erv e nti o n gr o u ps will b e ev e nly s plit at r a n d o m wit hi n bl oc ks. A d diti o n ally, t o r e d uc e all oc ati o n bi as 
w e will us e s e al e d all oc ati o n a n d a n a u dit tr ail. T h e d at a b as e m a n a g er will cr e at e a n d r et ai n a p df v ersi o n wit h ti m e a n d 
d at e “s e al” f or t h e all oc ati o n s e q u e nc e. T h e d at a b as e m a n a g er will als o e ncr y pt/ hi d e t h e c o nt e nts of t h e c ells c o nt ai ni n g 
t h e all oc ati o n. All oc ati o n will b e m a d e by t e m p or al s e q u e nc e of 1) d at e a n d ti m e of n otific ati o n, t h e n 2) d at e a n d ti m e 
of birt h. A s p ecifi e d m e m b er of t h e r es e arc h t e a m will i n p ut t h e d at e a n d ti m e of birt h of t h e i nf a nt t o “ u ns e al”/r e v e al 
t h e all oc ati o n. T h e d at e a n d ti m e of u ns e ali n g pr ovi d es a n a u dit tr ail.  T h e r es e arc h t e a m a n d PI ar e bli n d e d t o t h e 
all oc ati o n s e q u e nc e. T h e e d uc at or of t h e A T V V I nt erv e nti o n gr o u p a n d t h e e d uc at or of t h e Att e nti o n C o ntr ol gr o u p will 
n ot h av e acc ess t o t h e r a n d o miz ati o n fil es a n d will b e n otifi e d of all oc ati o n at t h e ti m e of i niti ati o n of sc h e d ulin g t h e 
h os pit al visit.  
 
4. 6. 2  Di visi o n of R es p o nsi biliti es  
T h e Att e nti o n C o ntr ol E d uc at or  (
) t e ac hes  i nf a nt c ar e t o t h e Att e nti o n C o ntr ol w o m e n b ef or e h os pit al 
disc h ar g e.  Si mil arly, t h e A T V V I nt er v e nti o n E d uc at or  (
 te ac h es  A T V V t o t h e A T T V w o m e n b ef or e h os pit al 
disc h ar g e.  I nstr ucti o n f or b ot h gr o u p c o n diti o ns t a k e a p pr oxi m at ely 3 0 mi n ut es . T o pr e v e nt bi as, o nl y Att e nti o n C o ntr ol 
E d uc at ors will w ork wit h t h e Att e nti o n C o ntr ol gr o u p, a n d o nl y 
 will w or k wit h t h e A T V V gr o u p. T h e 
Pr o gr a m C o or di n at or assists wit h b as eli n e  d at a c oll ecti o ns  as n e e d e d t o m ai nt ai n t his divisi o n of r es p o nsi bi lit y. 
H o w ev er, p ers o n n el m a n a g e m e nt a n d p artici p a nt -l a n g u a g e n e e ds n ec essit at e  s o m e fl exi bility.   
 
4. 7  P o w er A n al ysis  
O ur fi n al s a m pl e siz e at t h e 3 -m o nt h e n d p oi nt is esti m at e d t o b e at l e ast 1 0 0 p er tr e at m e nt ar m, aft er a  pr oj ect e d 2 0 % 
attriti o n fr o m e nr oll m e nt of 2 5 0 w o m e n. T his s a m pl e siz e will ac hi e v e 8 0 % p o w er t o d et ect as  si g nific a nt a 0. 4 4 st a n d ar d 
d e vi ati o n diff er e nc e i n pri m ar y o utc o m es ( M -I sy nc hr o ny g az e a n d aff ect) b et w e e n tr e at m e nt ar ms ass u mi n g α = 0. 0 2 5 
a n d a 2 -si d e d t est. Si mil ar i nt er v e nti o ns o n a r el at e d o utc o m e ( m at er n al s e nsitivit y), a n d pr eli mi n ary d at a fr o m 
m e m b ers of o ur t e a m ( o n O X T l e v el), s h o w e d b et w e e n gr o u p eff ect  siz es r a n gi n g fr o m 0. 2 8 t o 0. 6 2. I n a d diti o n, t h e 
st a n d ar diz e d diff er e nc es i n M-I sy nc hr o ny r a n g e d b et w e e n 0. 1 2 a n d 0. 7 c o m p ari n g at -ris k (i. e., pr e m at ur e i nf a nts, 
m at er n al d e pr essi o n) a n d n or m al c o m p aris o n gr o u ps at  3 a n d 9 m o nt hs, s u p p orti n g o ur c h oic e of 0. 4 as a f e asi bl e a n d 
cli nic all y m e a ni n gf ul eff ect siz e. F or ai m 2 w e  h av e 8 0 % p o w er t o d et ect m o d est c orr el ati o ns of 0. 2 2 a n d l ar g er ass u mi n g 
a c o ns er v ati v e α = 0. 0 1.  
 
4. 8  St atistic al A n al ysis Pl a n  
O ur pri m ary st atistic al a p pr o ac h is r e gr essi o n b as e d, usi n g a g e n er al li n e ar m o d el t o c o n d uct biv ari at e c orr el ati o ns, 
m ulti pl e li n e ar r e gr essi o n, a n al ysis of v ari a nc e or c ov ari a nc e, as w ell as t ests of m e di ati o n a n d/ or m o d er ati o n a n d a 
mix e d -eff ect m o d el f or r e p e at e d m e as ur es ( M M R M) r ec o m m e n d e d f or pri m ary a n al ysis of cli nic al tri als wit h c o nti n u o us 
e n d p oi nts. ( 1 3 6) W e will scr e e n m e as ur es f or vi ol ati o ns of ass u m pti o ns a n d us e r o b ust st a n d ar d err ors or p o w er 
tr a nsf or m ati o ns if ass u m pti o ns ar e n ot m et. All r egr essi o n -b as e d a n alys es will b e p erf or m e d usi n g eit h er S A S s oft w ar e, 
v ersi o n 9. 4 ( S A S I nstit ut e I nc., C ar y, N C), or St at a, v ersi o n 1 5. 1 ( 1 3 7) W e will als o a d o pt a disc ov ery -b as e d a n alysis of 
p ati e nt s u b -gr o u pi n gs. T his a n alysis will b e b as e d o n a n u ns u p er vis e d cl ust eri n g of all p ati e nts acr oss all m ol ec ul ar 
m e as ur e m e nts, wit h t w o pri m ar y o utc o m es. W e will i d e ntif y ( 1) p att er ns of m ol ec ul ar ex pr essi o n li n ki n g diff er e nt 
P ar e nti n g 
Str ess * *  
P ar e nti n g Str ess I n d e x ( P SI -S F) : 3 6-it e ms( 1 2 3, 1 2 4) 3 d o m ai ns: p ar e nt al distr ess, p ar e nt -c hil d dysf u ncti o n al 
i nt er acti o n, & diffic ult c hil d. A p pr o pri at e fr o m 0 - 3 y e ars. Ass oci at e d wit h m at er n al i ntr usiv e n ess & 
s e nsitivity ( el e m e nts of s y nc hr o n y). ( 1 2 5) T est -r et est = 0. 8 5, α= 0. 9 1. ( 1 2 3) 
 
 
 
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
2 3  
m et hyl ati o n pr ofil es t o g e n e a n d pr ot ei n ex pr essi o n t o e v al u at e t h e ty p es of m ol ec ul ar si g n at ur es t h at discri mi n at e 
s a m pl e gr o u pi n gs, a n d ( 2) s ets of cli nic al c ov ari at es t h at ar e ass oci at e d wit h s a m pl e s u b -gr o u ps t o d et er mi n e t h e cli nic al 
a n d p h e n ot y pic f a ct ors t h at d escri b e a n d diff er e nti at e s a m pl e cl ust ers. T h es e a n al ys es will b e p erf or m e d usi n g R 
s oft w ar e.  
 
4. 8. 1  E v al u at e Effic ac y of A T V V  
Ai m 1:  E v al u at e t h e effic ac y of d ail y A T V V a m o n g m ot h ers wit h c hil d h o o d a d v ersit y o n b e h a vi or al a n d p h ysic al 
m e as ur es of M -I s y nc hr o n y i n a r a n d o miz e d st u d y wit h a n Att e nti o n C o ntr ol gr o u p. T h e g o al of o ur a n alysis is t o 
d et er mi n e tr e at m e nt ar m diff er e nc es at t h e st u dy e n d p oi nt ( 3 p ost n at al m o nt hs), usi n g a 2. 5 % t y p e I err or r at e a n d t w o -
si d e d t est f or o ur pri m ary o utc o m es. W e will us e 5 % ty p e I err or r at e a n d B e nj a mi ni H oc h b er g c orr ecti o n a m o n g r el at e d 
gr o u ps of s ec o n d ar y o utc o m es. ( 1 4 7) W e will esti m at e tr e at m e nt  eff ects wit h a n d wit h o ut k ey c ov ari at es k n o w n t o b e 
ass oci at e d wit h M -I s y nc hr o ny ( e. g., m e nt al h e alt h, a dv ersity, i nf a nt f e e di n g m et h o d, i nf a nt h e alt h st at us, a n d 1-m o nt h 
P ar e nti n g Str ess I n d ex) w hic h will i ncr e as e t h e p o w er of t h e t est. F or i nf a nt o utc o m es, w e will i ncl u d e s ex as a c o v ari at e 
a n d t est f or tr e at m e nt eff ect diff er e nc es by s ex usi n g a n i nt er acti o n t er m.  O ur st atistic al m et h o d f or t h e p hysic al 
m e as ur es, m e as ur e d at b as eli n e (l at e pr e g n a ncy) a n d m o nt hly i nt er v als ( 1 -, 2-, a n d 3- p ost n at al m o nt hs), will b e M M R M 
r e gr essi n g t h e o utc o m e o n i n dic at ors f or tr e at m e nt, ti m e, a n d t h eir i nt er acti o n. F or t h e p hysic al m e as ur es t h e g o al is t o 
d et er mi n e tr e at m e nt ar m diff er e nc es i n c h a n g e fr o m b as eli n e t o t h e st u dy e n d p oi nt. I n c o ntr ast, o ur m et h o d f or t h e 
b e h a vi or al o utc o m es, m e as ur e d o nc e at t h e st u dy e n d p oi nt, will b e a g e n er al li n e ar m o d el r e gr essi n g t h e o utc o m e o n a n 
i n dic at or f or tr e at m e nt ar m.  W e will c o n d uct i nt e nti o n t o tr e at (I T T) a n d p er pr ot oc ol a n alys es ( d efi n e d as c o m pl eti n g 
8 0 % or m or e of d ail y A T V V s essi o ns) a n d c o m p ar e o ur fi n di n gs. W hil e missi n g d at a will b e mi ni miz e d t hr o u g h c ar ef ul 
pr oc e d ur es, s o m e missi n g d at a ar e i n e vit a bl e wit h l o n git u di n al st u di es. I n or d er t o r et ai n all r a n d o miz e d p artici p a nts f or 
I T T, w e will us e m ulti pl e i m p ut ati o n t o pr e dict missi n g o utc o m es wit h all a v ail a bl e m e as ur es, a n d m o d el a g gr e g at e d 
r es ults acr oss i m p ut ati o n d at as ets.( 1 3 8) F or p hysic al m e as ur es w h er e w e h av e r e p e at e d m e as ur e m e nts, w e will c o m p ar e 
m ulti pl e i m p ut ati o n r es ults t o t h e f ull i nf or m ati o n m axi m u m li k eli h o o d a p pr o ac h a v ail a bl e t hr o u g h M M R M. W e will us e 
i ncl usi v e m o d els wit h a uxili ar y v ari a bl es r el at e d t o missi n g n ess, a m o n g c ov ari at es c oll ect e d at b as eli n e, if n e e d e d t o 
s u p p ort t h e missi n g at r a n d o m ass u m pti o n. ( 1 3 8, 1 3 9) S e nsiti vity a n alys es will ass ess t h e r o b ust n ess of o ur fi n di n gs if w e 
fi n d i m b al a nc e d b as eli n e c h ar act eristics i n s pit e of r a n d o miz ati o n, c h ar act eristics ass oci at e d wit h attriti o n, or n o n-
i g n or a bl e missi n g d at a. W e will c o n d uct fi d elit y a n d d os e r es p o ns e a n alys es i n a d diti o n t o o ur m ai n  eff ects m o d els. D os e 
(fr e q u e nc y of A T V V s essi o ns) will b e c oll ect e d d aily f or t hr e e m o nt hs fr o m t h e tr e at m e nt ar m p artici p a nts a n d c a n b e 
us e d t o ex pl or e t h e p att er ns of a d h er e nc e ov er ti m e as w ell as o pti m al d os e ass oci at e d wit h O X T syst e m c h a n g es by 
m o n t h. 
 
4. 8. 2  I d e ntif y O X T-S yst e m M ec h a nis ms Ass oci at e d wit h M -I S y nc hr o n y 
Ai m 2: I d e ntif y m ol ec ul ar m ec h a nis ms i n t h e O X T s yst e m u n d erl yi n g M -I s y nc hr o n y. W e will ex a mi n e t h e ti m e c h a n g e 
p att er n of O X T el e m e nts t o u n d erst a n d t h e f or m of t h eir tr aj ect or y ( e. g., asc e n di n g or d esc e n di n g, li n e ar, q u a dr atic) 
usi n g l oc ally w ei g ht e d r e gr essi o n (l o w ess) gr a p hs, str atifi e d b y tr e at m e nt ar m. W e will als o ass ess t h e f or m of 
hy p ot h esiz e d r el ati o ns hi ps b et w e e n el e m e nts (i. e., O X T R  m et hyl ati o n n e g ativ ely r el at e d t o O X T R  m R N A, O X T R pr ot ei n, 
a n d O X T p e pti d e - w hic h ar e p ositi v ely r el at e d t o e ac h ot h er) str atifi e d by tr e at m e nt gr o u p a n d ti m e. W e will m o d el 
t h es e ti m e c h a n g e p att er ns wit h M M R M a n d us e i nt er acti o ns of ti m e, i nt er v e nti o n, a n d t h e O X T el e m e nt t o esta blis h if 
as p ects of t h e O X T s yst e m a n d/ or t h eir i nt err el ati o ns hi ps c h a n g e ov er ti m e a n d if t h at c h a n g e is i nfl u e nc e d by t h e A T V V 
i nt er v e nti o n. Ulti m at ely, w e will ass ess if t h e b e h avi or al m e as ur e of M-I sy nc hr o ny is ass oci at e d wit h t h e O X T s yst e m 
a n d its c o m p o n e nts, i ncl u di n g m et hyl ati o n at b as e p airs a n d ti m e tr e n ds acr oss r e p e at e d m e as ur e m e nts. W e will 
ex a mi n e c o v ari at es s uc h as c hil d h o o d a dv ersit y a n d c u m ul ativ e str ess f or t h eir s u bst a nti v e c o ntri b uti o n t o 
u n d erst a n di n g t h e r el ati o ns hi p b et w e e n M -I s y nchr o ny a n d O X T f u ncti o ni n g, i ncl u di n g eff ect m o dific ati o n wit h 
i nt er acti o n t er ms. W hil e w e will t est f or h et er o g e n eity i n r a n d o m c o effici e nts t hr o u g h M M R M, w e will f urt h er ex pl or e 
p o p ul ati o n h et er o g e n eit y usi n g bi oi nf or m atics m et h o ds, d escri b e d b el o w, w hic h  will pr ovi d e a c o m pl e m e nt ar y, p ers o n -
c e nt er e d a p pr o ac h t o u n d erst a n di n g h o w s u b gr o u ps i nf err e d fr o m t h e O X T i n dic at ors ar e r el at e d t o p ers o n al 
c h ar act eristics, d os e, a n d o utc o m es. 
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
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M ol ec ul ar Pr ofil es:  T o a d dr ess h et er o g e n eity i n m ol ec ul ar pr ofil es w e will p erf or m a cl ust eri n g a n alysis t o i d e ntif y 
p ot e nti al s u b gr o u ps wit h diff eri n g p att er ns of ass oci ati o ns wit hi n t h e O X T s yst e m. W e will us e k -m e a ns cl ust eri n g, d oi n g 
a s e arc h f or t h e o pti m al n u m b er of cl ust ers k by r e p e ati n g cl ust eri n g s e v er al ti m es f or e ac h k ov er a wi d e r a n g e a n d 
usi n g c o ns e ns us cl ust eri n g st atistics t o d et er mi n e t h e v al u es of k t h at yi el d hi g hl y r e pr o d uci bl e cl ust eri n g r es ults. T his 
will yi el d s a m pl e s u b -gr o u ps t h at f ait hf ully c a pt ur e t h e h et er o g e n eit y i n t h e d at a s et wit h o ut ov er-fitti n g cl ust ers t o 
n ois e. W e c a n t h e n pr ofil e t h e s u b gr o u ps usi n g t h e k ey c o v ari at es, tr e at m e nt ar m, a n d MI sy nc hr o ny usi n g d escri pti v e 
a n d bi v ari at e i nf er e nti al st atistics. I n a d diti o n, w e  c a n ex a mi n e t h e diff er e nt m ol ec ul ar pr ofil es t h at discri mi n at e 
diff er e nt s u b -p o p ul ati o ns t o d et er mi n e p ut ativ e m ol ec ul ar m ec h a nis ms li n k e d t o diff er e nt o utc o m es o bs er v e d i n t h e 
c o v ari at e a n alysis. W e will e v al u at e s uc h diff er e nc es b ot h q u alit ativ ely, usi n g h e at m a p vis u aliz ati o ns, a n d q u a ntit ati v el y, 
b as e d o n diff er e nc es b et w e e n cl ust er c e ntr oi ds. T his will all o w us t o g e n er at e hy p ot h es es a b o ut bi o m ark ers t h at mi g ht 
disti n g uis h i n di vi d u als m ost li k ely t o b e n efit fr o m t h e i nt er v e nti o n. T h es e c o m bi n e d m et h o ds  will i nf or m us a b o ut t h e 
effic ac y of t h e A T V V i nt er v e nti o n, i ncr e as e o ur u n d erst a n di n g of t h e O X T syst e m ass oci at e d wit h M -I sy nc hr o ny, a n d 
s u p p ort o ur f ut ur e r es e arc h t o e n h a nc e t ar g et e d or t ail or e d i nt er v e nti o n eff orts.  
 
 
 
 
5. 0  Q u alit y M a n a g e m e nt  
5. 1  Pri m ar y O utc o m e : M ot h er-I nf a nt S y nc hr o n y 
All M -I dy a ds will b e vi d e o r ec or d e d fr e el y i nt er acti n g wit h e ac h ot h er f or 4 mi n ut es (c o di n g occ urs o n t h e l ast 3 
mi n ut es). Vi d e o r ec or di n g occ urs w h e n t h e i nf a nt is al ert  a n d r e a dy t o i nt er act, > 3 0 mi n ut es aft er t h e e n d of a 
br e astf e e di n g or f or m ul a f e e di n g, a n d d at a c oll ecti o n or d er  m ay b e a dj ust e d if t h e b a by is sl e e py or f ussy. As p er 
F el d m a n’s st a n d ar diz e d pr oc e d ur e, w e will us e t w o  c a m er as o n tri p o ds t o z o o m i n o n t h e m ot h er’s a n d i nf a nt’s f ac es 
s e p ar at ely; d uri n g c o di n g t h e s oft w ar e sy nc hr o niz es t h e t w o r ec or di n gs. T o a v oi d distr acti n g t h e M-I dy a d, r es e arc h 
m e m b ers ar e o utsi d e of t h e dy a d’s  r o o m a n d a bl e t o vi e w r e m ot ely o n a l a pt o p t h e r e al-ti m e r ec or di n gs. L at er, vi d e os 
will b e c o d e d f or M -I sy nc hr o ny by t e a m m e m b ers bli n d e d t o gr o u p assi g n m e nt.  C o d ers ar e tr ai n e d t o 9 0 % i nt er -r at er 
r eli a bilit y, a n d 2 0 % of vi d e os will b e d o u bl e c o d e d f or i nt er-r at er r eli a bility. 
 
5. 1. 1  D o u bl e C o di n g M ot h er -I nf a nt S y nc hr o n y Vi d e os 
T h e PI will tr ai n ( bli n d e d t o gr o u p assi g n m e nt) r es e arc h p ers o n n el c o di n g vi d e o -r ec or di n gs f or m ot h er-i nf a nt s y nc hr o ny 
t o > 9 0 % i nt er-r at er r eli a bilit y b y t h e e n d of t h eir tr ai ni n g p eri o d.  A d diti o n ally , a c oll a b or at or’s l a b or at or y 
 
will pr ovi d e a s ervic e of c o di n g 1 0 0 % of t h e 
st u dy’s vi d e o r ec or di n gs f or r eli a bilit y of t h e m ot h er-i nf a nt s y nc hr o ny m e as ur e. C oll a b or at ors will f oll o w t h e U A I R B 
a p pr o v e d  pr ot oc ol f or s af e a n d s ec ur e h a n dli n g of s p eci m e ns a n d vi d e o r ec or di n gs l a b el e d wit h u ni q u e a n o ny m o us  
c o d es. C oll a b or at ors will n ot h av e acc ess t o p artici p a nt i d e ntifi ers. D at a will b e s h ar e d usi n g t h e U A B ox  
H e alt h cl o u d -b as e d s ec ur e s yst e m. 
 
 
 T h e U niv ersit y of Ariz o n a will c o d e 2 0 % of t h e vi d e os f or r eli a bility. 
 
5. 1. 2  C o ns ult ati o n M e eti n gs  
 
 
   
 
5. 2  R eli a bilit y of A T V V  I nstr ucti o n 
T h e PI is f ully tr ai n e d t o crit eri o n ( > 9 0 % a gr e e m e nt wit h t h e A T V V  R eli a bility C h ec klist) o n t h e i nt erv e nti o n. 
 
 will tr ai n 
 t o crit eri o n est a blis hi n g > 9 0 % r eli a bilit y.  
  
 will t e ac h t h e A T V V t o 

 
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m ot h ers b ef or e t h e y ar e  disc h ar g e d fr o m t h e  h os pit al  aft er birt h. I nt er -r at er r eli a bilit y will b e p eri o dic all y m e as ur e d b y 
 f or 2 0 % of vi d e or ec or d e d s essi o ns a n d m ai nt ai n e d a b o v e 9 0 %.  
 
5. 3  Fi d elit y of A T V V M et h o d o l o g y 
At e ac h  st u dy visit ( 1, 2, a n d 3 m o nt hs), w e will r et est p ar e nt al r eli a bility ( A T V V R eli a bilit y C h ec klist) a n d i nstr uct 
m ot h ers h o w t o a d a pt t h e A T V V wit h t h eir m at uri n g i nf a nt.  
 
6. 0  D at a, S af et y, & M o nit ori n g Pl a n  
T his r a n d o miz e d c o ntr oll e d tri al h as  I nstit uti o n al R evi e w B o ar d (I R B) a p pr ov al fr o m t h e U ni v ersity of Ariz o n a ( U A). T h e 
ris ks ass oci at e d wit h t his st u dy ar e mi ni m al a n d t h e p ot e nti al f or a d v ers e e v e nts ar e l o w. T h e pr o p os e d st u dy m e ets t h e 
NI H crit eri a f or a p h as e II cli nic al tri al. T h e A T V V m ultis e ns ory m ass a g e  i nt erv e nti o n will occ ur i n 1 2 5 m ot h er-i nf a nt 
dy a ds t o pri m aril y d et er mi n e its effic acy  at i m pr o vi n g m ot h er -i nf a nt i nt er acti o n, c o m p ar e d t o a n att e nti o n c o ntr ol gr o u p 
of 1 2 5 w o m e n. W hil e pr e g n a nt w o m e n, m ot h ers a n d  t h eir h e alt hy f ull-t er m i nf a nts ar e v ul n er a bl e p o p ul ati o ns, t h e 
i nf a nt m ass a g e i nt er v e nti o n i ncl u d es b e h a vi ors t h at m ot h er t y pic ally us e w h e n i nt er acti n g wit h t h eir i nf a nts a n d is l o w 
ris k. F or ov er 3 0 y e ars, w e h a v e a p pli e d t h e A T V V i nt er v e nti o n t o o v er 8 0 0 i nf a nts ( w h o w er e pri m arily v ul n er a bl e 
pr et er m i nf a nts) a n d h a v e n e v er h a d  t o t er mi n at e t h e A T V V i nt erv e nti o n b ec a us e of p hysi ol o gic i nst a bilit y. D at a 
c oll ecti o n m et h o ds ar e als o l o w -ris k, i nv ol vi n g q u esti o n n air es, m at er n al v e ni p u nct ur e, b ucc al s w a b f or i nf a nt s aliv a, a n d 
a vi d e o r ec or di n g of  m ot h er -i nf a nt i nt er acti o n. A d diti o n ally, o ur o nly c o nt act wit h pr e g n a nt w o m e n is f or e nr oll m e nt, 
a n d o n e st u dy  visit w h e n t h e y will c o m pl et e q u esti o n n air es a n d all o w c oll ecti o n of o n e  m at er n al bl o o d s a m pl e. Gi v e n 
t h e l o w risk of t his st u dy, o ur D S M pl a n will us e a S af et y M o nit ori n g C o m mitt e e (S M C) t o all o w f or a n i n d e p e n d e nt 
c o m mitt e e t o r e vi e w d at a. Acc or di n g t o t h e P olicy of t h e N ati o n al I nstit ut e of N ursi n g R es e arc h ( NI N R) f or D at a  a n d 
S af et y M o nit ori n g of Extr a m ur al Cli nic al Tri als, a n S M C is “ a gr o u p of t w o or m or e ex p erts, w h o ar e  i n d e p e n d e nt of t h e 
pr ot oc ol, w hic h r e vi e ws d at a fr o m a p artic ul ar st u dy.” G e n er ally, o n e of t h es e ex p erts is a  bi ost atistici a n.  
 
6. 1  M o nit ori n g E ntit y  
T h e Pri nci p al I nv esti g at or ( PI) h ol d s pri m ary r es p o nsi bilit y f or d at a s af ety a n d m o nit ori n g. T h e pl a n i ncl u d es  a S M C wit h 
t w o c o m mitt e e m e m b ers, o utsi d e of t h e U niv ersit y of Ariz o n a, w h o ar e i n d e p e n d e nt fr o m t h e st u dy pr ot oc ol, h av e 
ex p eri e nc e i n cli nic al tri als, a n d d o n ot h a v e c o nflicti n g i nt er ests. 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
6. 2  Pr oc e d ur es f or M o nit ori n g S t u d y S af et y a n d t o M i ni miz e R is k 
T o pr o m ot e st u dy s af et y, t h er e ar e w e e kly r es e arc h t e a m m e eti n gs f or t h e i niti al 6 -m o nt hs, a n d bi -w e e kl y t e a m  
m e eti n gs aft er t h e i niti al 6 -m o nt hs. T e a m m e eti n gs ( wit h t h e PI, pr o gr a m c o or di n at or, r es e arc h assist a nts, a n d  s el ect c o 
i nv esti g at ors) i ncl u d es m o nit ori n g of t h e f oll o wi n g  it e ms- 
•  
r ecr uit m e nt,  
•  
r et e nti o n,  
•  
attriti o n,  

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
2 6  
•  
p erf or m a nc e of t h e st u dy sit e,   
•  
r eli a bilit y a n d fi d elit y of t h e i nt erv e nti o n,  
•  
c o nfi d e nti al d at a c oll ecti o n a n d d at a m a n a g e m e nt,  
•  
q u alit y a n d i nt e grity  of d at a, a n d   
•  
p artici p a nt s af et y.  
T h e r es e arc h t e a m m e m b ers i d e ntif y p ot e nti al s af ety iss u es a n d s ol uti o ns.   
 
T h e S M C m e ets s e mi a n n u ally t o r evi e w d at a s af et y a n d m o nit ori n g. T h e S M C will c o nv e n e m or e oft e n if n ec ess ar y. T h e 
S M C r evi e ws  m at eri als pr ovi d e d t o t h e m b y t h e PI o n t h e f oll o wi n g –  
•  
st u dy pr o gr ess,  
•  
st u dy pr oc e d ur es a n d pr ot oc ol,  
•  
p erf or m a nc e of t h e st u dy sit e,   
•  
c o nfi d e nti al d at a c oll ecti o n a n d d at a m a n a g e m e nt,  
•  
q u alit y a n d  i nt e grity of d at a, a n d  
•  
p artici p a nt s af et y.  
 
T h e S M C  c o n d ucts a n a u dit of t h e f oll o wi n g –  
•  
r a n d o mly s el ect e d 2 5 % of p artici p a nt c o ns e nt/ p ar e nt al p er missi o n f or ms t o ass ur e c o m pli a nc e wit h I R B 
r e q uir e m e nts; 
•  
r a n d o mly s el ect e d 2 5 % of p artici p a nt d at a r ec or ds t o ass ur e r eli a bility of d at a e ntr y i ncl u di n g ass essi n g all  
v ari a bl es t h at ar e missi n g, i nv ali d or i nc o nsist e nt ; 
•  
m o nt hly q u ality  ass ur a nc e r e p orts ; a n d  
•  
u n a ntici p at e d pr o bl e ms a n d a d v ers e ev e nts ( s e e 6. 4 ). 
 
6. 2. 1  PI R es p o nsi biliti es  
T h e PI is r es p o nsi bl e f or c o or di n ati n g S M C activiti es a n d i ncl u d es t h e sc h e d uli n g of m e eti n gs a n d pr ovi di n g  a p pr o pri at e 
m at eri als t o b e pr es e nt e d t o t h e S M C. Pri or t o t h e first m e eti n g, t h e PI d oc u m e nts t h at m e m b ers d o n ot h a v e c o nflicts 
of i nt er est. All disc ussi o ns a n d r ec o m m e n d ati o ns ar e s u m m ariz e d a n d distri b ut e d vi a  m e eti n g mi n ut es. T h e PI d ev el o ps 
t h e S M C m e eti n g a g e n d a, s u p pli es t h e S M C m e m b ers wit h d at a t h e y r e q uir e, a n d v erifi es r e p orts a n d r ec o m m e n d ati o ns 
of t h e S M C.  
 
6. 2. 2  S M C R es p o nsi biliti es  
T h e S M C a d vis es t h e PI o n a ny i d e ntifi e d  iss u es a n d m a y dict at e m o dific ati o n of st u dy pr oc e d ur es if t h er e ar e c o nc er ns 
wit h a d h er e nc e t o r ecr uit m e nt  pr ot oc ol, q u ality a n d i nt e grit y of d at a c oll ecti o n a n d d at a m a n a g e m e nt, a n d p artici p a nt 
s af et y.  
 
6. 2. 3  R e p orts  
Wit hi n 1 0 d a ys of  e ac h S M C m e eti n g, a r e p ort will b e pr e p ar e d by t h e PI, c o nfir m e d b y m e m b ers of t h e S M C, a n d  
s u b mitt e d t o t h e i nstit uti o n’s I R B a n d t h e f u n di n g a g e nc y ( NI N R) as r e q uir e d by r e p orti n g m ec h a nis ms. R e p orti n g als o 
i ncl u d es a n a n n u al r e p ort t o I R B, r e g ul at or y a n d s p o ns ori n g a g e nci es as r e q u est e d, a n d a p pr o pri at e r e p orts i n t h e ev e nt 
of a n a dv ers e ev e nt(s). T h e S M C is t h e e ntity r es p o nsi bl e f or s u b mitti n g n ec ess ary r e p orts t o NI N R. 
   
6. 3  D escri pti o n of D at a M a n a g e m e nt  
6. 3. 1  D at a I nt e grit y Pr oc e d ur es  
T h e i nt e grity of t h e i nt erv e nti o n a n d q u alit y of t h e d at a will b e m o nit or e d pri m aril y by t h e PI, Al e ec a B ell,  P h D, R N, C N M, 
w h o is a n ex p ert i n t h e s af e cli nic al c ar e of p eri n at al w o m e n. 
 
 
 
R a n d o m assi g n m e nt is c e ntr ally  c o ntr oll e d b y o ur st atistici a n 
as d escri b e d i n 4. 6. 1. T h e R ecr uit er will o bt ai n i nf or m e d c o ns e nt i n pr e g n a nc y.  Dr. B ell will tr ai n all  r es e arc h t e a m 

 
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m e m b ers wit h att e nti o n t o e d uc ati n g m e m b ers o n p artici p a nts’ a ut o n o my, h o w t o av oi d  a p pl yi n g u n d u e pr ess ur e f or 
e nr oll m e nt, a n d p artici p a nts’ ri g ht t o wit h dr a w at a ny ti m e. All pr oc e d ur es ar e  writt e n, a n d t e a m m e m b ers will b e 
r e q uir e d t o r evi e w writt e n p olici es. 
  
6. 3. 2  S ec urit y M e as ur es  
 D at a will b e s ec ur el y st or e d o n t w o s ec ur e el ectr o nic s yst e ms t h at us e e ncr y pti o n: R es e arc h El ectr o nic  D at a C a pt ur e  
( R E D C a p) a n d U niv ersity of Ariz o n a B ox H e alt h ( U A B ox H e alt h). R E D C a p will b e pri m aril y  us e d t o st or e i nf or m e d c o ns e nt  
a n d p ar e nt al p er missi o n P D Fs, d e m o gr a p hics, h e alt h d at a extr act e d fr o m  m e dic al r ec or ds, a n d c o m pl et e d  
q u esti o n n air es. Wit hi n R E D C a p w e us e T wili o f or d ail y t ext m ess a gi n g  wit h p artici p a nts. U A B o x H e alt h will b e us e d t o 
st or e vi d e o-r ec or di n gs, b e h a vi or al c o di n g of t h e c o nt e nt wit hi n vi d e o r ec or di n gs, a n d r es ults of l a b or at ory a n al ys es. All 
el ectr o nic d at a o utsi d e of t h es e syst e ms will h av e u ni q u e a n o ny m o us c o d es.  
 
All st u dy l a pt o ps a n d t a bl ets will us e p ass w or d e ncr y pti o n. A s ec o n d  p ass w or d will b e r e q uir e d t o o p e n st u dy d at a b as es. 
T h e C oll e g e of N ursi n g ( C O N) n et w or k is l oc at e d  b e hi n d a c a m p us a d mi nist er e d fir e w all. T h e C O N s yst e ms ar e o n a 
“ pri v at e I P” n et a n d acc ess fr o m o utsi d e is ti g htl y c o ntr oll e d at t h e Fir e w all. Tr affic fr o m O utsi d e t o I nsi d e n et w ork is 
bl oc k e d a n d o nly p orts  r e q uir e d f or n or m al o p er ati o ns a n d s p eci al p ur p os e p orts f or a p plic ati o ns/s ervic es ar e all o w e d 
f or o utsi d e acc ess. T h er e is als o a n I ntr usi o n D et ecti o n S yst e m, a n d it is r e g ul arl y m o nit or e d f or s ec urit y br e ac h es.  
Wir el ess n et w ork tr affic is is ol at e d fr o m Wir e d n et w ork tr affic.   
 
I n a d diti o n t o el ectr o nic d at a, h ar d c o py d at a, s uc h as i nf or m e d c o ns e nts a n d p ar e nt al p er missi o ns, will b e l oc k e d i n a 
c a bi n et wit hi n t h e PI’s l ock e d offic e wit hi n t h e C O N. S e p ar at e fr o m i d e ntifi a bl e d at a, is a n ot h er  l oc k e d c a bi n et wit hi n a 
l oc k e d C O N offic e f or d at a wit h u ni q u e a n o ny m o us c o d es. O nl y t h e PI a n d pr o gr a m c o or di n at or will h av e acc ess t o t h es e 
l oc k e d fil e syst e ms. L a b or at or y s p eci m e ns (l a b el e d wit h u ni q u e a n o ny m o us c o d es) will b e pr oc ess e d a n d st or e d i n 
fr e ez er syst e ms wit hi n l ock e d k eyc ar d acc ess r o o ms at t h e U A C oll e g e of N ursi n g, Bi ol o gic al C or e L a b or at ory.  Fr e ez ers 
ar e c o nti n u o usly m o nit or e d wit h a m alf u ncti o n al ar m s yst e m. T h e Bi ol o gic al C or e L a b or at or y will  als o c o n d uct t h e 
a n al ys es of oxyt oci n r ec e pt or g e n e ex pr essi o n a n d ox yt oci n r ec e pt or pr ot ei n. S a m pl es will  b e tr a ns p ort e d o n dr y ic e t o 
t h e U A G e n etic C or e f or a n al ysis of ox yt oci n r ec e pt or g e n e m et hyl ati o n.  S a m pl es will b e tr a ns p ort e d o n dr y ic e t o t h e U A 
L a b or at ory f or t h e Ev ol uti o n ar y E n d ocri n ol o gy of Pri m at es  (L E E P) f or a n al ysis of ox yt oci n p e pti d e. 
  
6. 3. 3  D at a H a n dli n g Pr actic es  
M e dic al r ec or d d at a fr o m r ecr uit m e nt sit es ( B a n n er U ni v ersity M e dic al C e nt er a n d T ucs o n M e dic al C e nt er)  will b e 
vi e w e d i n t h e el ectr o nic syst e ms a n d e nt er e d dir ectly i nt o R E D C a p / B ox-H e alt h  usi n g p ass w or d e ncr y pt e d  l a pt o ps or 
t a bl ets. Pr e-scr e e ni n g pr oc e d ur es ( as d escri b e d i n t h e s ecti o n b el o w o n d at a c o nfi d e nti alit y) will  n ot us e p a p er b ut will 
b e e nt er e d i n a p ass w or d pr ot ect e d E X C EL fil e st or e d o n t h e e ncry pt e d U A B ox  H e alt h. P HI c oll ect e d o n p a p er ( e. g., 
i nf or m e d c o ns e nts a n d p ar e nt al p er missi o ns) will be k e pt i n a l oc k e d  c a bi n et i n a l oc k e d offic e at t h e C oll e g e of N ursi n g ; 
P D Fs ar e cr e at e d a n d u pl o a d e d i nt o R E D C a p.  T h e sc a n n er i n t h e C oll e g e of N ursi n g s uit e is e ncr y pt e d. D at a fr o m 
q u esti o n n air es a n d i nf or m ati o n fr o m m ot h ers c oll ect e d at st u dy s essi o ns will als o b e e nt er e d  dir ectl y i nt o R E D C a p. 
Bl o o d a n d s ali v a s p eci m e ns ar e l a b el e d wit h u ni q u e c o d es  wit h o ut i d e ntifi a bl e  i nf or m ati o n a n d h a n d d eli v er e d o n ic e by 
a r es e arc h t e a m m e m b er fr o m t h e d at a c oll ecti o n r o o m  ( 2 n d fl o or of t h e C oll e g e of N ursi n g) t o t h e Bi ol o gic al C or e 
L a b or at ory ( 4t h fl o or of t h e C oll e g e of N ursi n g) f or  pr oc essi n g a n d s ec ur e st or a g e. El ectr o nic vi d e o r ec or di n gs of m ot h er -
i nf a nt i nt er acti o n at t h e fi n al d at a c oll ecti o n s essi o n will b e l a b el e d wit h u ni q u e c o d es wit h o ut i d e ntifi a bl e i nf or m ati o n 
a n d st or e d o n t h e e ncr y pt e d U A B ox H e alt h f or c o di n g of  d at a. C o m plyi n g wit h f e d er al g ui d eli n es, r a w d at a (i ncl u di n g 
vi d e o  r ec or di n gs a n d bi ol o gic al s p eci m e ns) will b e d estr o y e d t hr e e y e ars aft er s u b missi o n of o ur fi n al NI H r e p ort.    
 
6. 3. 4  Q u alit y Ass ur a nc e M e as ur es  
T o e ns ur e q u ality of d at a a n d c o m pli a nc e wit h I R B r e q uir e m e nts, t h e f oll o wi n g pr oc ur es will b e f oll o w e d:  
 
• T h e PI will a u dit t h e i nf or m e d c o ns e nts/ p ar e nt al p er missi o ns i n e ac h of t h e first 2 0 e nr oll e d p artici p a nts  a n d t h e n 2 0 % 
of e nr oll e d p artici p a nts t hr o u g h o ut t h e st u dy p eri o d.  
 

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
2 8  
• T h e PI a n d 
 will tr ai n t o crit eri o n t h e A T V V t o r es e arc h p ers o n n el (
 
) a n d c h ec k i nt er-r at er r eli a bilit y i n t h e first 1 0 e nr oll e d p artici p a nts a n d 2 0 % of all s essi o ns t hr o u g h o ut t h e 
st u dy p eri o d. 
 
• T h e PI will a u dit t h e first 1 0 s e q u e nti al d at a c oll ecti o n visits a n d t h e n 2 0 % of all s essi o ns t hr o u g h o ut t h e  st u dy p eri o d. 
 
• T h e PI will tr ai n ( bli n d e d t o gr o u p assi g n m e nt) r es e arc h p ers o n n el c o di n g vi d e o -r ec or di n gs f or m ot h er-i nf a nt 
s y nc hr o ny t o > 9 0 % i nt er-r at er r eli a bilit y by t h e e n d of t h eir tr ai ni n g p eri o d. 
 
 will 
a u dit 2 0 % of all vi d e o -r ec or di n gs a n d r ec o d e t h e m t o m ai nt ai n r eli a bilit y. 
 
6. 3. 5  D at a C o nfi d e nti alit y  
T o mi ni miz e ris k r el at e d t o l oss of c o nfi d e nti ality, t h e PIs a n d ot h er a ut h oriz e d st u dy p ers o n n el will h av e  I R B r e q uir e d 
tr ai ni n g i n r ecr uit m e nt, i nf or m e d c o ns e nt pr oc e d ur es, h u m a n s u bj ects R es e arc h, HI P A A, a n d  d at a m a n a g e m e nt usi n g  
t h e i nstit uti o n’s tr ai ni n g m o d ul es a n d c ertific ati o ns. N o i nf or m ati o n a b o ut p artici p a nts d uri n g t h e r es e arc h will b e  
discl os e d t o ot h ers wit h o ut a p artici p a nt’s writt e n p er missi o n, exc e pt  if n ec ess ary t o pr ot ect t h eir ri g hts or w elf ar e or if 
r e q uir e d b y l a w. O nl y a g gr e g at e d at a will b e p u blis h e d or  disc uss e d i n c o nf er e nc es, a n d n o i n di vi d u al i nf or m ati o n will b e 
i ncl u d e d t h at w o ul d r ev e al a p artici p a nt’s i d e ntit y. S ec ur e el ectr o nic s yst e ms ( R E D C a p a n d U A B ox H e alt h) ar e d escri b e d 
a b o v e i n t h e s ecti o n o n  d at a s ec urity.  
 
 
 
 
 
 
6. 4  Id e ntif yi n g, R e vi e wi n g, a n d R e p orti n g A d v ers e E v e nts a n d  U n a ntici p at e d P r o bl e ms 
6. 4. 1   D efi niti o ns  
 
6. 4. 1. 1  A d v ers e E v e nts  
A dv ers e ev e nt m e a ns a ny u nt o w ar d m e dic al occ urr e nc e ass oci at e d wit h t h e us e of a n i nt erv e nti o n i n h u m a ns, w h et h er  
c o nsi d er e d i nt erv e nti o n r el at e d or n ot. Acc or di n g  t o t h e U A I R B, a n a d v ers e e v e nt  ( A E) is f urt h er ex pl ai n e d as a n 
u nt o w ar d p hysic al or psyc h ol o gic al occ urr e nc e i n a h u m a n  s u bj ect p artici p ati n g i n r es e arc h w hic h occ urs d uri n g t h e 
st u dy h a vi n g b e e n a bs e nt at b as eli n e or, if pr es e nt at b as eli n e, a p p e ars t o w ors e n. T h e ev e nt m ay b e a n y u nf a v or a bl e 
o utc o m e, i ncl u di n g a b n or m al l a b or at or y  r es ult, s y m pt o m, dis e as e,  or i nj ury.  
 
6. 4. 1. 2 S eri o us A d v ers e E v e nts  
A dv ers e ev e nts cl assifi e d as s eri o us i ncl u d e t h os e r es ulti n g i n d e at h, lif e -t hr e at e ni n g i nj ur y, h os pit aliz ati o n,  or 
pr ol o n g ati o n of h os pit aliz ati o n, p ersist e nt or si g nific a nt dis a bilit y, or a c o n g e nit al a n o m al y or  birt h d ef ect. Ev e nts n ot 
m e eti n g t h e a b ov e crit eri a b ut r e q uiri n g i nt er v e nti o n t o pr ev e nt o n e of t h es e o utc o m es  ar e als o c o nsi d er e d s eri o us 
a dv ers e ev e nts.   
 
6. 4. 1. 3 U n a ntici p at e d Pr o bl e ms  
Acc or di n g t o t h e U A I R B, u n a ntici p at e d pr o bl e ms i nv ol vi n g risks t o s u bj ects or ot h ers r ef ers t o a pr o bl e m, ev e nt or 
i nf or m ati o n it e m t h at is u n ex p ect e d, giv e n t h e n at ur e of t h e r es e arc h pr oc e d ur es a n d t h e s u bj ect p o p ul ati o n b ei n g 
st u di e d. P ot e nti al ris ks ass oci at e d wit h p artici p ati n g i n t his st u dy h a v e b e e n d eli n e at e d i n s ecti o n 2. 2. 
 
6. 4. 2  Pr oc e d ur e t o Cl assif y a n A d v ers e E v e nt  
A Es ar e cl assifi e d i nt o t h e f oll o wi n g t hr e e c at e g ori es - 
•  
Mil d –  E v e nts r e q uir e mi ni m al or n o tr e at m e nt a n d d o n ot i nt erf er e wit h t h e p artici p a nt’s d aily activiti es. 
B ec a us e t his st u dy h as b e e n cl assifi e d b y t h e I R B as r es e arc h i nv olvi n g n o m or e t h a n mi ni m al ris k ( A p p e n dix A –  
A p pr o v al D oc u m e nts), w e will n ot d oc u m e nt mil d a d v ers e e v e nts.   

 
NI H, 7 R 0 1 N R 0 1 8 8 2 8  M ot h ers & B a bi es Pr ot oc ol, V 1 .6 , 2 0 24 .0 1 .3 1  
 
 
 
3 2  
 
 
 
7. 3 S etti n gs, F aciliti es, a n d E q ui p m e nt  
 
7. 3. 1 U ni v ersit y of Ariz o n a: C oll e g e of N ursi n g ( C O N):  
T h e PI ( Dr. B ell) h as a priv at e l oc k e d f ac ulty offic e l oc at e d i n t h e Divisi o n of Bi o b e h a vi or al H e alt h Sci e nc es. T h e pr oj ect’s  
r es e arc h t e a m will occ u py l oc k e d offic es a dj ac e nt t o t h e C O N B e h a vi or al C or e L a b or at or y (s e e d escri pti o n b el o w). 
R es e arc h st aff offic es all o w f or c o nfi d e nti al r es e arc h acti viti es. T h e r es e arc h t e a m will h a v e s h ar e d acc ess t o all f aciliti e s 
i n t h e B e h avi or al C or e L a b or at or y. D at a c oll ecti o n will occ ur i n t h e C O N B e h avi or al C or e L a b or at or y. A w aiti n g ar e a f or 
st u dy p artici p a nts is av ail a bl e u p o n e nt eri n g t h e l a b or at ory. W e will utiliz e a c o nf er e nc e r o o m d e dic at e d t o c o m pl eti n g 
i nf or m e d c o ns e nt a n d s elf-r e p ort s urv e ys, t e ac hi n g w o m e n eit h er t h e i nt erv e nti o n or att e nti o n c o ntr ol e d uc ati o n, 
c h ec ki n g i nt erv e nti o n fi d elit y, a n d vi d e o r ec or di n g m ot h er -i nf a nt i nt er acti o n. W e will utiliz e t h e cli nic al m e as ur e m e nt 
r o o m t o c oll ect i nf a nt s aliv a a n d f or v e ni p u nct ur e t o coll ect m at er n al bl o o d. I n t h e C O N Bi ol o gic al C or e L a b or at ory, 
l a b or at or y p ers o n n el will pr e p ar e all st u dy s a m pl es f or st or a g e. L a b or at ory p ers o n n el will als o c o n d uct oxyt oci n r ec e pt or 
( O X T R) pr ot ei n a n d O X T R g e n e ex pr essi o n a n alys es. 
 
7. 3. 2 U ni v ersit y of Ariz o n a: G e n etics C or e:  
 T h e U niv ersity of Ariz o n a G e n etics C or e ( U A G C) will c o n d uct t h e pr oj ect’s O X T R g e n e D N A m et hyl ati o n a n alysis usi n g 
Ill u mi n a Mi S e q f or d e e p s e q u e nci n g. T h e U A G C off ers acc ess t o st at e-of -t h e-art r es o urc es a n d s er vic es t o h el p 
i nv esti g at ors, e d uc at ors, st u de nts a n d t h e bi ot ec h c o m m u nit y c o n d uct a n d pr o m ot e r es e arc h i n t h e fi el ds of g e n etic a n d 
g e n o mics.  
 
7. 3. 3 U ni v ersit y of Ariz o n a: L a b or at or y f or t h e E v ol uti o n ar y E n d ocri n ol o g y of Pri m at es (L E E P):  
T h e L a b or at or y f or t h e E v ol uti o n ar y E n d ocri n ol o gy of Pri m at es (L E E P) is a n e n d ocri n ol o gy l a b wit h e nzy m e -i m m u n o ass ay 
c a p a biliti es i n t h e E mil W. H a ur y A nt hr o p ol o gy b uil di n g. L E E P h o us es all e q ui p m e nt r e q uir e d t o p erf or m t h e pr oj ect’s 
pl as m a a n d s aliv a oxyt oci n ass a ys l e d b y 
 
 
 
7. 3. 4 U ni v ersit y of Ariz o n a: St atistics L a b or at or y F aciliti es:  
T h e St atistics C o ns ulti n g L a b or at or y ( St at L a b), i ncl u d es C o -I 
 
 St at L a b p ers o n n el w or k cl os el y wit h t h e U niv ersit y of Ariz o n a G e n etics C or e t o e ns ur e 
a n effici e nt, s ec ur e, a n d r eli a bl e i nfr astr uct ur e f or d at a m a n a g e m e nt a n d a n alysis of g e n etic d at a. T his c o or di n a t e d 
a p pr o ac h str e a mli n es t h e i nt e gr ati o n of hi g h -di m e nsi o n al s e q u e nci n g d at a.  
 
R E F E R E N C E S