Standardized Prone Positioning Compared to Usual Positioning of Very Low Birth Weight Infants Receiving Respiratory Support and the Effect on Bronchopulmonary Dysplasia
Phase: NA
Conditions: Prone Positioning, Bronchopulmonary Dysplasia
Sponsor: Montefiore Medical Center

Title:   Pr o ne Vers us S u pi ne P ositi o ni n g a n d t he I m p act o n 
Br o nc h o p ul m o n ar y D ys pl asi a i n Ver y L o w Birt h Wei g ht I nf a nts
N C T 0 4 8 9 0 1 5 8
I R B A p pr o ve d:  2 7- O C T- 2 0 2 1

Title: Sta n dar dize d pr o ne p ositi o ni n g c o m pare d t o us ual p ositi o ni n g of ver y l o w birt h wei g ht 
i nfa nts recei vi n g res pirat or y s u p p ort a n d t he effect o n br o nc h o p ul m o nar y d ys plasia ( b p d).
H y p ot hesis: Sta n dar dize d  pr o ne p ositi o ni n g i n ve ntilate d, ver y l o w birt h 
wei g ht, preter m i nfa nts will lea d t o a re d ucti o n i n m o derate ( Gra de 2) t o se vere ( Gra de 
3) B P D as assesse d at 3 6 wee ks p ost c o nce pti o nal a ge ( P C A).
B ac k gr o u n d : Br o nc h o p ul m o nar y D ys plasia ( B P D) occ urs m ost ofte n i n t h ose i nfa nts b or n less 
t ha n 3 2 wee ks gestati o n a n d i n t h ose wei g hi n g less t ha n 1 5 0 0 gra ms at birt h. W hile its defi niti o n 
is s o me w hat varia ble, t he dia g n osis us uall y rests o n t he d urati o n of nee d f or o x y ge n a n d use of 
p ositi ve press ure ve ntilati o n. T hat is, o x y ge n use f or > 2 8 da ys, bef ore 3 6 wee ks P C A or 
disc har ge, w hic he ver is earlier, c o u ple d wit h use of p ositi ve press ure ve ntilati o n 
i ncl u di n g i n vasi ve ( via e n d otrac heal t u be or trac he ost o m y t u be) as well as n o n-i n vasi ve 
m o dalities s uc h as nasal c o nti n u o us p ositi ve air wa y press ure ( N C P A P), n o n-i n vasi ve p ositi ve 
press ure ve ntilati o n ( NI P P V), nasal ca n n ula ( N C)  or hi g h fl o w nasal ca n n ula ( H F N C).( 1)  Wit h 
t hree cli nical classificati o ns of se verit y, mil d, m o derate a n d se vere, we fi n d t hat 1 6 % of 
i nfa nts i n lar ge c o h ort st u dies wit h a wei g ht less t ha n 1 0 0 0 gra ms at birt h will ha ve se vere 
B P D.( 2)  H o we ver de pe n di n g o n t he defi niti o n of â € œse vere B P Dâ € � use d, it c o ul d e nc o m pass 
u p t o o ne t hir d of all pre mat ure i nfa nts( 1). F or 2 0 1 9, T he C hil dre nâ € ™s H os pital at M o ntefi ore-
Weiler Di visi o n Ne o natal I nte nsi ve Care U nit ha d 3 4 of 1 0 7 ( 3 1. 7 %) ver y l o w birt h wei g ht 
i nfa nts ( V L B W), i.e t h ose b or n less t ha n 1 5 0 0 gra ms, w h o were dia g n ose d wit h m o derate t o 
se vere B P D. B P D was defi ne d as utilizati o n of a ve ntilat or or c o nti n u o us p ositi ve air wa y 
press ure ( C P A P), use of H F N C or re g ular fl o w N C > 2 L at 3 6 wee ks P C A. Of t he 1 0 7 V L B W 
i nfa nts i de ntifie d, 9 die d. 
T here is c o nsi dera ble practice variati o n i n t he res pirat or y ma na ge me nt of B P D patie nts. 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

Si g nifica nt practiti o ner a n d i nstit uti o nal variati o n e xists i n t he â € œ preferre dâ € � m o de of 
ve ntilati o n f or t hese patie nts.  V ol u me a n d press ure tar gete d ve ntilati o n, or t he h y bri d press ure 
re g ulate d v ol u me li mite d strate g y, as well as ne urall y a dj uste d ve ntilat or y assist 
( N A V A) ve ntilati o n are o pti o ns f or ve ntilat or ma na ge me nt t hat ma y be utilize d i n t he care of 
B P D pate nts.  A d diti o nall y, s u p p orti ve t hera pies s uc h as gastr oes o p ha geal 
refl u x ( G E R) pre ve nti o n a n d/ or treat me nt, use of ot her res pirat or y me dicati o ns ( br o nc h o dilat ors, 
i n hale d ster oi ds a n d caffei ne) a n d r o uti ne use of se dati ves are a m o n g ot her strate gies t hat s o me 
ha ve e m pl o ye d. Ot her ma na ge me nt o pti o ns ma y i ncl u de prefere ntial pr o ne p ositi o ni n g of t he 
i nfa nt t o facilitate gas e xc ha n ge. 
T here is e vi de nce i n a d ults t hat pr o ne p ositi o ni n g ma y a u g me nt o x y ge nati o n d uri n g treat me nt of 
ac ute res pirat or y distress s y n dr o me ( A R D S).( 3) A s yste matic re vie w s h o we d t hat it ma y c o nfer a 
decrease d ris k of deat h as well i n a d ults wit h se vere A R D S.( 4) Pr o ne p ositi o ni n g of i nfa nts a n d 
c hil dre n has bee n s u g geste d t o als o res ult i n i m pr o ve me nt i n arterial o x y ge n c o nte nt w he n 
c o m pare d t o s u pi ne p ositi o n f or res pirat or y distress.( 5)  I n a C oc hra ne re vie w b y Gillies a n d 
c ollea g ues, pr o ne p ositi o ni n g was s u peri or t o s u pi ne p ositi o ni n g wit h s mall b ut si g nifica nt 
i ncreases i n Pa O 2 a n d Sa O 2. Decrease d e pis o des of h y p o xia a n d decrease d res pirat or y rates 
were o bser ve d. T he be nefit see me d t o be pre d o mi na ntl y i n preter m ve ntilate d 
ne o nates.( 5) C oc hra ne s yste matic re vie ws d o ne i n 2 0 1 6 b y Ri vas- Fer na n dez a n d 
c ollea g ues; Bala g uer a n d c ollea g ues i n 2 0 1 3 n ote d si milar res ults.( 6, 7)
 I n m ost NI C Us, p ositi o ni n g of a n i nfa nt is n ot sta n dar dize d; he nce a mec ha nicall y ve ntilate d 
i nfa nt ma y rest i n lateral, s u pi ne or pr o ne p ositi o n at a n y gi ve n ti me a n d alter nate d per 
t he i n di vi d ual n ursi n g r o uti ne or perce pti o n of patie nt prefere nce.  T here is a s pecific a nat o mical 
distri b uti o n of airfl o w s uc h t hat i n s p o nta ne o usl y breat hi n g pre mat ure i nfa ntsâ € ™ p osteri or 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

p orti o ns of t he l u n g fill first. A d diti o nall y, it was n ote d t hat t he ri g ht l u n g fills first i n t his sa me 
patie nt p o p ulati o n, li kel y d ue t o its m ore vertical a nat o mic p ositi o n.( 8) Gra vit y ha d little effect 
o n re gi o nal ve ntilati o n distri b uti o n. I n 2 0 1 5 Ve n dett u oli a n d c ollea g ues e val uate d p ositi o nal 
effects o n l u n g mec ha nics i n preter m i nfa nts wit h ac ute as well as c hr o nic l u n g disease. Ei g htee n 
i nfa nts were assesse d, 9 i n b ot h t he ac ute a n d c hr o nic l u n g disease gr o u ps res pecti vel y. 
T here was n o statistical i m pr o ve me nts n ote d f or ac ute res pirat or y distress, h o we ver a decrease i n 
res pirat or y s yste m resista nce was n ote d f or i nfa nts wit h B P D d uri n g pr o ne p ositi o ni n g.( 9)  I n 
2 0 1 8 Z h o n g a n d c ollea g ues ra n d o mize d 7 9 preter m mec ha nicall y ve ntilate d i nfa nts t o s u pi ne vs 
pr o ne p ositi o ni n g.  Fracti o n of i ns pire d o x y ge n ( Fi O 2), pea k i ns pirat or y press ure, mea n 
i ns pirat or y press ure, a n d d urati o n of ve ntilati o n were si g nifica ntl y l o wer i n t he pr o ne gr o u p t ha n 
i n t he s u pi ne gr o u p ( P < 0. 0 5).( 1 0)
T here were n o re p orts of a d verse e ve nts i n pe diatric patie nts i n t he 
af ore me nti o ne d st u dies. H o we ver i n a d ult patie nts a d verse effects s uc h as press ure s ores a n d 
trac heal o bstr ucti o n were re p orte d. 
W hile t he pri or st u dies ha ve s h o w n te m p oral be nefit f or preter m, ve ntilate d i nfa nts w h o u n der g o 
pr o ne p ositi o ni n g, ma n y are s h ort ter m st u dies a n d n o ne ha ve assesse d its i m pact o n se verit y of 
B P D.  
O bjecti ve: We ai m t o e val uate i n t his pil ot st u d y w het her sta n dar dize d pr o ne p ositi o ni n g 
c o m pare d t o us ual p ositi o ni n g i m pr o ves m o derate t o se vere B P D rates as assesse d at 3 6 
wee ks p ost c o nce pti o nal a ge i n V L B W preter m i nfa nts wit h B P D. 
M ateri al a n d met h o ds
St u d y pl a n : 
We ai m t o e nr oll a n d ra n d o mize i nfa nts b or n at less t ha n 1 5 0 0 gra ms at birt h, w h o re mai n 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

o n p ositi ve press ure s u p p ort f or at least 7 da ys after birt h A N D/ O R o n a n y ot her res pirat or y 
de vice s uc h as nasal ca n n ula wit h fl o w rates greater t ha n 2 L P M recei vi n g s u p ple me ntal o x y ge n 
of greater t ha n 2 1 % f or at least 7 da ys after birt h. P ositi ve press ure f or t he p ur p oses of t his 
st u d y is defi ne d a  nasal ca n n ula deli veri n g a fl o w of 2 L P M or hi g her, c o nti n u o us p ositi ve 
air wa y press ure ( C P A P), n o n-i n vasi ve p ositi ve press ure ve ntilati o n or n o n-i n vasi ve mec ha nical 
ve ntilati o n ( NI P P V/ NI M V), as well i nfa nts w h o are i nt u bate d or ha ve a trac he ost o m y f or 
o x y ge nati o n a n d ve ntilati o n relate d t o t heir l u n g disease, irres pecti ve of t he m o de of ve ntilati o n.  
We will e xcl u de i nfa nts w h o were pre vi o usl y o n r o o m air wit h o ut a res pirat or y de vice w h o were 
i nt u bate d f or t he p ur p oses of s ur ger y a n d were n ot recei vi n g res pirat or y s u p p ort as defi ne d a b o ve 
pri or, t h ose i nt u bate d f or ot her air wa y iss ues s uc h as trac heal ste n osis, br o nc he o- or 
trac he o malacia, etc a n d n ot f or t he ma na ge me nt of B P D. A d diti o nal patie nts t o be e xcl u de d 
i ncl u de t h ose wit h s us pecte d or pr o ve n ge netic or ot her maj or c o n ge nital a n o malies t hat ma y 
i m pact car diac a n d l u n g f u ncti o n i ncl u di n g car diac a n d l u n g a n o malies, as well as t h ose at t he 
ti me of e nr oll me nt w h o re q uire s ur geries t hat will i m pact t heir a bilit y t o be place d i n pr o ne 
p ositi o ni n g (e g gastr osc hisis, o m p hal ocele, etc). 
Patie nts meeti n g t he af ore me nti o ne d criteria will be assi g ne d t o 1. us ual care i n w hic h 
p ositi o ni n g a n d d urati o n i n eac h p ositi o n is ra n d o m per us ual n ursi n g r o uti ne O R 2. 
Recei ve sta n dar dize d sc he d ule d dail y pr o ne p ositi o ni n g starti n g o n da y of life 7. 
As part of n or mal de vel o p me ntal care, m ost i nfa nts are e val uate d a n d ha ve care re n dere d (t o uc h-
ti me), if sta ble, a n d re p ositi o ne d at set t hree- h o ur i nter vals t o per mit u ni nterr u pte d slee p 
a n d/ or rest. T he ha n ds- off i nter val will be mai ntai ne d t hr o u g h o ut t he st u d y 
i nter val. I nfa nts ra n d o mize d t o t he sta n dar dize d sc he d ule d dail y pr o ne p ositi o ni n g will be place d 
i n pr o ne b o d y p ositi o n f or a t otal of 6 h o urs dail y, t hat is pr o ne p ositi o n f or 3 h o urs, f oll o we d 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

b y s u pi ne p ositi o ni n g f or 3 hrs, t he n place d i n pr o ne p ositi o n f or a n ot her 3- h o ur 
i nter val. Sta n dar dize d dail y p ositi o ni n g will occ ur f or ra n d o mize d patie nts u ntil 3 6 wee ks or 
disc har ge w hic he ver is first.  If nee de d, p ositi o n ai ds, w hic h are part of t he n or mal care r o uti ne i n 
o ur I C U, ma y be use d t o facilitate mai nte na nce of pr o ne or s u pi ne p ositi o ni n g. 
I de ntific ati o n: Eac h da y, NI C U a d missi o ns will be re vie we d via t he electr o nic me dical 
rec or d a n d i nfa nts w h o are b or n wit h a birt h wei g ht of less t ha n 1 5 0 0 gra ms will be i de ntifie d. O n 
da y of life ( D O L) 5- 7, of t h ose i nfa nts i de ntifie d, t h ose pare nts of i nfa nts w h o are still 
mai ntai ne d o n p ositi ve press ure ve ntilati o n a n d or > 2 1 % Fi O 2, will be a p pr oac he d a n d c o nse nte d 
f or i ncl usi o n i n t he st u d y.  
C o nse nt: Fa milies will be a p pr oac he d i n pers o n i n t he Ne o natal I nte nsi ve Care U nit or P ost-
Part u m U nit bet wee n D O L 5- 7 a n d c o nse nt o btai ne d f or partici pati o n i n t he st u d y b y Dr. 
T h o m ps o n- Bra nc h or Dr. Ha vra ne k. O ne pare ntal si g nat ure will be re q uire d.  Writte n st u d y 
material a n d c o pies of c o nse nt f or ms will be pr o vi de d f or fa milies t o kee p. T here will be n o c ost 
t o t he patie nt a n d n o re m u nerati o n offere d. Fa milies ma y wit h dra w c o nse nt at a n y p oi nt of t he 
st u d y. See se parate c o nse nt f or m, a p pe n di x 1. 
Pr oce d ures:  C o nse nt will be o btai ne d bet wee n D O L 5- 7. S u bjects will u n der g o bl oc k 
ra n d o mizati o n. O nce ra n d o mize d, t h ose patie nts w h o are assi g ne d 
t o sta n dar dize d, sc he d ule d pr o ne p ositi o ni n g, will be place d i n pr o ne p ositi o n, wit h t he hea d 
t ur ne d eit her ri g ht or left per n ursi n g or patie nt desire, f or a t otal of 6 h o urs dail y, d uri n g da yti me 
h o urs, if cli nicall y sta ble.  T he y will be place d i n pr o ne p ositi o n f or 3 h o urs, f oll o we d b y s u pi ne 
p ositi o ni n g f or 3 h o urs, t he n place d i n pr o ne p ositi o n f or a n ot her 3- h o ur i nter val. If nee de d, 
p ositi o n ai ds, w hic h are part of t he n or mal care r o uti ne i n o ur I C U ma y be use d t o facilitate 
mai nte na nce of pr o ne or s u pi ne p ositi o ni n g. If a n i nfa nt is felt t o be t o o u nsta ble, or si g nifica ntl y 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

i nt olera nt of pr o ne p ositi o ni n g, t he y ma y be p ositi o ne d per n ursi n g or patie nt c o mf ort.  If i nfa nt 
was alrea d y i n t he pr o ne p ositi o n per n ursi n g r o uti ne pri or t o t he start of pr o ne p ositi o ni n g per 
st u d y pr ot oc ol, we will a wait c ha n ge t o a differe nt p ositi o n bef ore i nitiati n g st u d y pr ot oc ol f or 
i nfa nts assi g ne d t o sc he d ule d pr o ne p ositi o ni n g. T his is t o a v oi d i nfa nts bei n g place d i n pr o ne 
p ositi o n f or > 3 c o nsec uti ve h o urs at a ti me). Alter nati n g bet wee n s u pi ne a n d p ositi o n all o ws us 
t o detect a n y s h ort ter m i m me diate c ha n ges i n o x y ge nati o n a n d vital si g ns attri b uta ble t o a 
c ha n ge i n p ositi o ni n g bet wee n pr o ne a n d s u pi ne.t he t w o p ositi o ns. 
B ot h i nfa nts ra n d o mize d t o sta n dar dize d pr o ne p ositi o ni n g a n d us ual p ositi o ni n g will ha ve a 
be dsi de car d car d i de ntif yi n g t hat t he i nfa nt is a st u d y partici pa nt a n d will ser ve as a wa y t o 
d oc u me nt t he n u m ber of ti mes a n y i nfa nt e nr olle d i n t he st u d y is place d i n pr o ne p ositi o ni n g 
e ve n if n ot ra n d o mize d t o sta n dar dize d pr o ne p ositi o ni n g. T he be dsi de car d als o 
facilitates t he i nfa ntâ € ™s n urse bei n g a ware of t he ti me of da y f or pr o ne i nt o s u pi ne p ositi o n 
c ha n ge f or t h ose w h o are ra n d o mize d t o pr o ne p ositi o ni n g.  O n t he wee kl y a n ni versar y of t he 
i nfa ntâ € ™s first place me nt i n pr o ne p ositi o n f or t he st u d y, p h ysi ol o gic a n d cli nical data will be 
retrie ve d.  
Ris k/ Be nefit: a ntici pate d me dical, s ocial, ps yc h ol o gical, a n d/ or le gal ris ks are 
mi ni mal; h o we ver u nc o m m o n ris ks t o be bei n g place d pr o ne ma y i ncl u de m o ve me nt or 
disl o d ge me nt of a breat hi n g t u be or of a n i ntra ve n o us (I V) cat heter. T hese u nc o m m o n ris ks will 
be mi ni mize d b y staff pa yi n g strict atte nti o n t o t he p ositi o ns of t hese de vices d uri n g m o ve me nt 
fr o m pr o ne t o s u pi ne p ositi o n a n d vice versa. A d diti o nall y, d oc u me ntati o n of t he p ositi o ns of 
t hese de vices is r o uti ne a n d will per mit trac ki n g of c ha n ge i n p ositi o n of t he de vices. P ote ntial 
be nefits i ncl u de a decrease i n t he se verit y a n d occ urre nce of m o derate t o se vere B P D, a c o m m o n 
c o n diti o n of t he l u n g relate d t o pre mat ure birt h.
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

D at a st or a ge a n d m ai nte n a nce of c o nfi de nti alit y: Data will be re vie we d a n d retrie ve d fr o m 
t he electr o nic me dical rec or d i nt o a c o m p uterize d st u d y data f or m ke pt o n a pass w or d pr otecte d 
c o m p uter i n a l oc ke d office. O nl y t he 2 st u d y pers o n nel, Dr. T h o m ps o n- Bra nc h a n d 
Dr. Ha vra ne k will access st u d y files t o c hec k or e dit data. C o nse nt f or ms will als o be ke pt i n a 
l oc ke d office. T he st u d y data base will be per ma ne ntl y delete d a n d pa per data c ollecti o n t o ols 
will be s hre d de d. S u bjects will n ot be vi de o or a u di ota pe d d uri n g t his st u d y. 
Pers o n nel: Ne o nat ol o gists Dr. Alecia T h o m ps o n- Bra nc h a n d Dr. T o mas Ha vra ne k will be 
res p o nsi ble f or c o nse nti n g fa milies a n d deter mi ni n g ra n d o mizati o n assi g n me nt. Be dsi de n urses 
al o n g wit h res pirat or y t hera pists will be res p o nsi ble f or p ositi o n c ha n ges a n d d oc u me ntati o n of 
p h ysi ol o gic metrics a n d vital si g ns as part of t he n or mal I C U care practice. Dr. T h o m ps o n-
Bra nc h will c ollect st u d y data f or a nal ysis. N urse practiti o ner Nefertiti Ca n o, R N, B S N, D N P, 
will be res p o nsi ble f or assi g ni n g t he pri mar y o utc o me of m o derate or se vere B P D, at or after 3 6 
wee ks p ost c o nce pti o nal a ge. S he will be pr o vi de d a list of st u d y partici pa nts i de ntifie d o nl y 
st u d y n u m ber at 3 6 wee ks p ost c o nce pti o nal a ge, t heir res pirat or y s u p p ort para meters a n d 
will assi g n t he pri mar y o utc o me of m o derate ( Gra de 2) or se vere ( Gra de 3) B P D. 
R a n d o miz ati o n:  Bl oc k ra n d o mizati o n wit h varia ble bl oc k sizes will be perf or me d i n or der t o 
e ns ure e q ual sa m ple sizes o ver ti me.  T he treat me nt (sta n dar dize d pr o ne p ositi o ni n g) rati o t o 
c o ntr ol ( us ual p ositi o ni n g) rati o will be 1: 1. T he ra n d o mizati o n list will be ge nerate d b y t he 
st u d y statisticia n a n d will be mai ntai ne d u n der l oc ke d c o n diti o ns. Bli n di n g of staff is i n here ntl y 
n ot feasi ble as sc he d ule d pr o ne p ositi o n c ha n ges are o b vi o us t o careta kers.  
E v al u ati o ns a n d me as ures : I nci de nce a n d se verit y of B P D will be assesse d at 3 6 wee ks p ost 
c o nce pti o nal a ge.  As part of us ual NI C U care, i nfa nts, es peciall y t h ose o n res pirat or y s u p p ort 
ha ve vital si g ns a n d ot her p h ysi ol o gic para meters rec or de d r o uti nel y e ver y 3 h o urs, 
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I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

b ut t his ma y occ ur as fre q ue ntl y as e ver y h o ur i n t he sic kest i nfa nts. E nr olle d i nfa nts will ha ve 
p h ysi ol o gic data a n d vital si g ns e val uate d a n d rec or de d at start of ha n ds- o n ti me, at t he 1 h o ur 
mar k after sc he d ule d p ositi o n c ha n ge t o pr o ne, at t he ti me of s witc h t o s u pi ne, 1 h o ur after 
2 n d s witc h t o pr o ne p ositi o n, a n d at t he ti me of c o ncl usi o n of st u d y p ositi o nal c ha n ges.  F or 
i nfa nts ra n d o mize d t o us ual care, we will rec or d si milar data fr o m a peri o d of 3 ha n ds- o n 
i nter vals (t otal of 9 h o urs).  
We ai m t o rec or d a n d c ollect t he f oll o wi n g data o nce wee kl y o n t he wee kl y a n ni versar y of t he 
i nfa ntâ € ™s first st u d y pr o ne p ositi o ni n g a n d t he date of ra n d o mizati o n o nt o t he st u d y f or t h ose 
st u d y partici pa nts w h o were ra n d o mize d t o us ual care: tra nsc uta ne o us C O 2 ( T C O 2) if a vaila ble 
or P C O 2 fr o m a n y bl o o d gas, Sa O 2 fr o m car di o p ul m o nar y m o nit ors, Pa O 2 fr o m arterial bl o o d 
gases wit hi n 1 h o ur of p ositi o nal c ha n ge (if a vaila ble), ve ntilat or or ot her res pirat or y s u p p ort 
m o dalit y setti n gs a n d directi o n of c ha n ges  wit hi n 1 h o ur of p ositi o nal 
c ha n ge.  S pecificall y, perce nt c ha n ge i n i ns pire d o x y ge n, c ha n ge i n ve ntilat or rate ( breat hs per 
mi n ute), ti dal v ol u me ( milliliters), pea k i ns pirat or y press ure (c m H 2 O), p ositi ve e n d e x pirat or y 
press ure (c m H 2 O) a n d t he n u m ber of e pis o des of o x y ge n desat urati o ns will be 
c ollecte d.  C urre nt c o m or bi dities, m ost rece nt c hest x-ra y fi n di n gs wit hi n a 7 da y i nter val will 
als o be d oc u me nte d o nce wee kl y. 
Ot her data:  d urati o n of ti me o n a n y res pirat or y s u p p ort ( da ys), d urati o n of use of e n d otrac heal 
t u be, n o n-i n vasi ve p ositi ve press ure ve ntilati o n ( NI P P V) a n d c o nti n u o us p ositi ve air wa y 
press ure ( C P A P), ti me t o Fi O 2 of 2 1 % (irres pecti ve of t y pe of res pirat or y i nterface), t y pe of 
me dicati o ns t o treat B P D ( use of oral, i n hale d or i ntra ve n o us p ost natal ster oi ds f or miti gati o n of 
B P D, caffei ne, di uretics dail y or i nter mitte nt), prese nce of p ul m o nar y h y perte nsi o n as 
d oc u me nte d b y ec h ocar di o gra m, use of se dati ves a n d a nal gesics, p har mac ol o gic treat me nt of 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

G E R D,  use of i n hale d nitric o xi de o n D O L 7 or later.  A d diti o nall y, t he m o de of ve ntilati o n at 7 
da ys after birt h, D O L w he n ma xi mal fee ds ac hie ve d (t otal fl ui ds of 1 6 0 milliliters per kil o gra m 
per da y), D O L at w hic h fee di n g b y m o ut h was i nitiate d a n d D O L at w hic h fee ds were 
a d mi nistere d b y m o ut h o nl y, dia g n osis of pla gi oce p hal y, a n d t he d urati o n of NI C U sta y. 
De m o gra p hic data of i nterest i ncl u de gestati o nal a ge at birt h ( wee ks), mater nal c o m or bi dities, 
i nfa nt c o m or bi dities, gr o wt h stat us (s mall, a p pr o priate or lar ge f or gestati o nal a ge), wei g ht at 
birt h ( kil o gra ms) a n d use of a nte natal ster oi ds. 
Wee kl y p h ysi ol o gic a n d ve ntilat or y data will be c ollecte d u ntil t he i nfa nt 
reac hes 3 6 wee ks p ostc o nce pti o nal a ge or disc har ge fr o m t he NI C U, or is o n 
2 1 % Fi O 2, i.e â € œr o o m air,â € � wit h o ut a n y res pirat or y i nterface, w hic he ver is earlier. F or t he 
p ur p oses of o ur st u d y, t he pri mar y o utc o me of m o derate ( Gra de 2)  t o se vere ( Gra de 3) B P D will 
be cli nicall y defi ne d a n d assi g ne d at 3 6 wee ks P C A base d o n t he 2 0 1 9 st u d y b y t he E u nice 
Ke n ne d y S hri ver Nati o nal I nstit ute of C hil d Healt h a n d H u ma n De vel o p me nt Ne o natal Researc h 
Net w or k  w hic h assesse d t he defi niti o n of B P D t hat best pre dicte d earl y c hil d h o o d 
m or bi dit y.( 1 1) T he defi niti o ns are as f oll o ws:
Se vere ( Gr a de 3) B P D :  If a n i nfa nt re q uires i n vasi ve p ositi ve press ure ve ntilati o n via a n 
e n d otrac heal or trac he ost o m y irres pecti ve of t he a m o u nt of Fi O 2.
M o der ate ( Gr a de 2) B P D : If a n i nfa nt re q uires n C P A P, NI P P V, H F N C, or N C > 2 liters per 
mi n ute fl o w a n d recei vi n g > 2 1 % Fi O 2. 
I nfa nts recei vi n g N C 2 liters per mi n ute or l o wer fl o w rates, irres pecti ve of t he Fi O 2 recei ve d, 
will be c o nsi dere d as ha vi n g mil d ( Gra de 1) B P D a n d will n ot be assi g ne d t he pri mar y o utc o me. 
St atistic al C o nsi der ati o ns : De m o gra p hic a n d cli nical varia bles assesse d at baseli ne 
will i nitiall y be s u m marize d b y i nter ve nti o n ar m usi n g sta n dar d descri pti ve statistics t o c o nfir m 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

t hat patie nt c haracteristics are distri b ute d si milarl y acr oss gr o u ps.  T he differe nce bet wee n t he 
i nter ve nti o n a n d c o ntr ol ar ms i n t he rate of B P D at 3 6 wee ks p ost-c o nce pti o nal a ge a n d ot her 
o utc o mes will be esti mate d, al o n g wit h c orres p o n di n g 9 5 % c o nfi de nce i nter vals. I n e x pl orat or y 
a nal yses, t he c hi-s q uare test will als o be a p plie d t o assess w het her t he rates of B P D a n d ot her 
bi nar y o utc o mes are si g nifica ntl y differe nt bet wee n gr o u ps, a n d t he t w o-sa m ple t-test will be 
use d c o m pare t he mea n val ues of c o nti n u o us varia bles meas ure d at a s pecific visit.  L o gistic a n d 
li near re gressi o n m o dels will als o be fit t o t he data t o a dj ust f or a n y baseli ne c haracteristics t hat 
are n ot bala nce d acr oss gr o u ps des pite ra n d o mizati o n.  Wee kl y p h ysi ol o gic, ve ntilat or a n d ot her 
cli nical data will be o btai ne d a n d a nal yze d usi n g ge neralize d li near mi xe d m o dels, wit h t he l o git 
li n k f or bi nar y o utc o mes a n d t he i de ntit y li n k f or c o nti n u o us o utc o mes, t o acc o u nt f or t he 
c orrelati o n i n re peate d meas ures fr o m t he sa me i nfa nt.  Missi n g data will be ha n dle d b y 
a nal yzi n g t he a vaila ble data as well as b y m ulti ple i m p utati o n usi n g c hai ne d e q uati o ns. All 
a nal yses will be base d o n t he i nte nt-t o-treat a p pr oac h, a n d res ults will be vie we d as e x pl orat or y 
a n d h y p ot hesis ge nerati n g. 
We pla n t o ra n d o mize a t otal of 6 0 patie nts 1: 1 t o i nter ve nti o n a n d c o ntr ol ( N = 3 0 per 
ar m).  Si nce t his is a pil ot trial, t he g oal is t o o btai n preli mi nar y data o n effect sizes.  T heref ore, 
f or mal p o wer calc ulati o ns were n ot perf or me d. Wit h 3 0 patie nts per ar m, t he precisi o n, as 
meas ure d b y t he wi dt h of t he 9 5 % CI, wit h w hic h t he tr ue i nter ve nti o n effect (i.e., differe nce 
bet wee n gr o u ps) ca n be esti mate d is +/- 2 5 % or better. F or e xa m ple, t o ga u ge t he ma g nit u de of 
t he pri mar y o utc o me of B P D i nci de nce a n d t he p ote ntial be nefit of sta n dar dize d pr o ne 
p ositi o ni n g, we e val uate d 2 0 1 9 B P D rates i n o ur NI C U. T here were 1 0 7 patie nts descri be d as 
V L B W at birt h. Of t h ose, 3 4 i nfa nts de vel o pe d m o derate t o se vere B P D, a rate of 3 1 %. If t he 
o bser ve d B P D rate is re d uce d t o 2 1 % i n t he i nter ve nti o n ar m f or a bet wee n gr o u p differe nce of 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

1 0 %, t he n t he c orres p o n di n g wi dt h of t he 9 5 % CI f or t he tr ue differe nce will be +/- 2 2 %.   We 
a ntici pate perf or mi n g t his pil ot st u d y o ver 2- 3 years t o acc o u nt f or yearl y variati o ns i n t he 
a d missi o n of V L B W patie nts.   
D at a S afet y M o nit ori n g : W hile n o maj or safet y e ve nts were re p orte d i n t he st u dies i n t he 
pe diatric p o p ulati o n, t he safet y of o ur ne o nates a n d i nfa nts are of ut m ost c o ncer n. Safet y 
c o ncer ns will be m o nit ore d real ti me b y be dsi de n urses a n d res pirat or y t hera pists a n d a d dresse d 
b y t he atte n di n gs a n d me dical pers o n nel o n cli nical ser vice i n de brief sessi o ns as is c ust o mar y, 
s h o ul d a n e ve nt occ ur. D uri n g t he dail y NI C U m or ni n g h u d dle, st u d y patie nts will s pecificall y be 
disc usse d t o ascertai n if a n y safet y e ve nts occ urre d i n t he pri or t we nt y-f o ur h o urs. T his data will 
be d oc u me nte d i n t he st u d y data c ollecti o n f or m. S pecific atte nti o n will be pai d t o i n d welli n g 
de vices s uc h as ce ntral ve n o us cat heters, c ut d o w n ve n o us cat heters, perc uta ne o usl y i nserte d 
ce ntral cat heters, i nci de ntal e xt u bati o n, s ki n i nte grit y, a n d nee d f or se dati o n a b o ve a n d be y o n d 
t he n or m f or t he i n di vi d ual patie nt. 
“ Bac k t o slee p” messa gi n g pr o m oti n g re d ucti o n of s u d de n I nfa nt Deat h S y n dr o me ( SI D S) b y 
placi n g i nfa nts, w h o are cl ose t o disc har ge h o me, o n t heir bac ks t o slee p, will be rei nf orce d wit h 
fa milies a n d staff per o ur us ual u nit i nitiati ve. A be dsi de pr oce d ure d oc u me nt will be pr o vi de d t o 
sta n dar dize t he tec h ni q ue f or alteri n g bet wee n pr o ne a n d s u pi ne p ositi o ns. We will esta blis h a 
data safet y m o nit ori n g b oar d c o m prise d of a se parate gr o u p of t w o u ni n v ol ve d ne o nat ol o gists 
a n d a n u ni n v ol ve d statisticia n t o re vie w t he safet y data after e ver y 1 5t h patie nt e nr olle d i n t he 
st u d y. T he statisticia n will be res p o nsi ble f or e val uati n g if t here is a statisticall y si g nifica nt 
i ncrease i n safet y e ve nts; t he ne o nat ol o gists will assess t he se verit y a n d cli nical i m pact of t he 
safet y e ve nts. S h o ul d t he data safet y m o nit ori n g b oar d i n dicate a c o ncer n of i ncrease d safet y 
e ve nts i n t he pr o ne p ositi o n gr o u p c o m pare d t o t he us ual p ositi o ni n g gr o u p, at t heir discreti o n 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1

t he y ma y ma ke s u g gesti o ns f or disc o nti n ui n g t he st u d y or s u g gest m o dificati o ns t o t he c urre nt 
pr ot oc ol t o per mit c o nti n uati o n of t he st u d y. 
Refere nces
1.  
P oi n de xter B, Fe n g R, Sc h mi dt B, Asc h ner J L, Ballar d R A, Ha m vas A, et al. C o m paris o ns a n d 
li mitati o ns of c urre nt defi niti o ns of br o nc h o p ul m o nar y d ys plasia f or t he pre mat urit y a n d res pirat or y 
o utc o mes pr o gra m. A n n A m T h orac S oc. 2 0 1 5; 1 2: 1 8 2 2- 3 0.
2.  
E hre n kra nz R, Wals h M, V o hr B, J o be A H, Wri g ht L L, Fa nar off A A, et al. Nati o nal I nstit utes of 
C hil d Healt h a n d H u ma n De vel o p me nt Ne o natal Researc h Net w or k. Vali dati o n of t he Nati o nal I nstit utes 
of Healt h C o nse ns us defi niti o n of br o nc h o p ul m o nar y d ys plasia. Pe diatr. 2 0 0 5; 1 1 6( 6): 1 3 5 3- 6 0.
3.  
Pel osi P, Tacc o ne P C P, Brazzi L. Pat h o p h ysi ol o g y of pr o ne p ositi o ni n g i n t he healt h y l u n g a n d i n 
A LI/ A R D S. Mi ner va A nestesi ol. 2 0 0 1; 6 7( 4): 2 3 8- 4 7.
4.  
Bl o o mfiel d R, N o ble D, S u dl o w A. Pr o ne p ositi o n f or ac ute res pirat or y fail ure i n a d ults. 
C oc hra ne Data base S yst Re v. . 2 0 1 5; 1 3( 1 1): C D 0 0 8 0 9 5.
5.   
Gillies D, Wells D, B ha n dari A. P ositi o ni n g f or ac ute res pirat or y distress i n h os pitalize d i nfa nts 
a n d c hil dre n. C oc hra ne Data bases of S yste matic Re vie ws 2 0 1 2( 7).
6.  
Ri vas- Fer na n dez M, M M Ri F, Diez-Iz q uier d o A, Escri ba n o J, Bala g uer A. I nfa nt p ositi o n i n 
ne o nates recei vi n g mec ha nical ve ntilati o n. C oc hra ne Data base of S yste matic Re vie ws. 2 0 1 6( 1 1).
7.  
Bala g uer A, Escri ba n o J, Fi g uls M Ri, Ri vas- Fer na n dez M. I nfa nt p ositi o n i n ne o nates recei vi n g 
mec ha nical ve ntilati o n. C oc hra ne Data base of S yste matic Re vie ws. 2 0 1 3( 3).
8.   
H o u g h J, J o h nst o n L, Bra uer S, W o o d gate P, Sc hi bler A. Effect of b o d y p ositi o n a n d ve ntilati o n 
distri b uti o n i n ve ntilate d preter ms. Pe d Crit Care Me d. 2 0 1 3; 1 4( 2): 1 7 1- 7 7.
9.   
Ve n dett u oli V, Ver o ni C, Za n ni n E, Merca da nte D, Ma ntassa P, Pe d otti A, et al. P ositi o nal 
Effects o n L u n g Mec ha nics of Ve ntilate d Preter m I nfa nts wit h Ac ute a n d C hr o nic L u n g Disease. Pe diatr 
P ul m o n ol. 2 0 1 5; 5 0: 7 9 8- 8 0 4.
1 0.  
Z h o n g Q, Jia n g D, Z ha n g C, Fe n g Y, Qi Z, He X, Lia n g, K. Effect of pr o ne p ositi o ni n g o n 
res pirat or y f u ncti o n i n ver y preter m i nfa nts u n der g oi n g mec ha nical ve ntilati o n. C hi nese J o ur nal 
C o nte m p orar y Pe diatrics. 2 0 1 8; 2 0( 8): 6 0 8- 1 2.
1 1. 
Je nse n E A, D ysart K, Ga ntz M G, Mc D o nal d S, Ba mat N A, Keszler M, Kir pala ni H, La u g h o n 
M M, P oi n de xter B B, D u nca n A F, Y o der B A, Eic he n wal d E C, De Ma ur o S B. T he Dia g n osis of 
Br o nc h o p ul m o nar y D ys plasia i n Ver y Preter m I nfa nts. A n E vi de nce- base d A p pr oac h. A m J Res pir Crit 
Care Me d. 2 0 1 9 Se p 1 5; 2 0 0( 6): 7 5 1- 5 9. 
1
 
I R B N U M B E R: 2 0 2 1- 1 3 0 5 9
I R B A P P R O V A L D A T E: 1 0/ 2 7/ 2 0 2 1