Influence of Prenatal and Early Childhood Home-Visiting by Nurses on Development of Chronic Disease: 29-year Follow-Up of a Randomized Clinical Trial
Phase: NA
Conditions: Chronic Disease
Sponsor: University of Colorado, Denver

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Title: Influence of Prenatal and Early Childhood Home Visiting by Nurses on Development of Chronic 
Disease: 29-Year Follow-Up of a Randomized Clinical Trial 
ClinicalTrials.gov Identifier: NCT06160037 
 
Date: June 5, 2024 

Protocol # 20-0794 
Version Date: 
06/05/2024 
 
PI: David L. Olds, PhD 
PI: Susan W. Groth, PhD, RN 
COMIRB #:20-0794 
New Mothers Study - COMIRB # 20-0794 
 
Influence of Prenatal and Early Childhood Home-Visiting by Nurses on Development of 
Chronic Disease: 29-year Follow-Up of a Randomized Clinical Trial 
 
I. PURPOSE OF THE STUDY AND BACKGROUND 
 
 
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Purpose of the study. This study consists of a 29-year follow-up of participants (N=742) in a randomized 
clinical trial of the Nurse-Family Partnership (NFP), a program of prenatal and infant/toddler home-visiting by 
nurses for low-income women with no previous live births, focusing on emergent chronic disease in mothers 
and first-born offspring. Previous assessments were conducted at registration, at the 36th week of gestation, 
and at the child’s 6th month and years 1, 2, 4.5, 6, 9, 12, and 18. NFP nurses are charged with improving: 1) 
pregnancy outcomes; 2) children’s health and development; and 3) women’s health and economic self-
sufficiency. They do this by promoting women’s health behaviors, care of their child, planning subsequent 
pregnancies, completing their educations and finding work. Nurses explicitly promote women’s self-
efficacy/mastery in managing challenges, foster informal social support (including involving fathers), and link 
families with health and human services. The goal is to continue surveillance of health outcomes among 
mothers and firstborn offspring enrolled in this second NFP trial, which focused on very low-income, primarily 
African American (89%) women and their offspring. Eighty five percent of the randomized mothers and 
offspring were assessed at the most recent 18-year follow-up. NFP effects have been found on a range of 
maternal outcomes through child age 18, including Pregnancy-Induced Hypertension (PIH), closely spaced 
subsequent pregnancies, marriage, sense of mastery, use of government benefits; and among mothers of 
females, reduced BP and self-reported kidney and heart problems. Nurse-visited offspring, through age 18, 
had lower rates of preventable mortality; among those born to mothers with limited coping capacity, lower rates 
of low birthweight and compromised cognitive functioning, receipt of Social Security Disability; and, among 
females, lower rates of obesity. 
At the 29-year follow-up, we expect to complete assessments on approximately 80% of those randomized. 
Findings from earlier follow-ups have led to our general hypothesis that, over the life-course, the 
intervention will lead to reductions in the emergence of cardiovascular disease (CVD), chronic kidney 
disease (CKD), type 2 diabetes (T2D), and premature mortality among both mothers and their first-born 
offspring. We will a) conduct anthropometric assessments; b) draw blood to measure cardio-metabolic and 
immune-inflammatory factors; c) collect random urines to measure the microalbumin/creatinine ratio; d) 
evaluate arterial stiffness using SphygmoCor Xcel and a standard BP instrument; and e) classify timing and 
causes of death from National Death Index (NDI) records. To help with interpretation, we will conduct 
interviews to assess history of diagnoses, medications, menopause, hospitalizations, disability, sedentary and 
physical activity, sleep, diet, substance use, depression, anxiety, mastery, duration and quality of partnered 
relationships, education, work, and incarceration; and review hospitalization records, and state records of 
government-benefits use. We will estimate Nurse-Visited (NV) - Control (C) differences in these outcome 
domains for both mothers and first-born offspring. Given that previous follow-ups of the Memphis sample for 
determinations of maternal and offspring mortality have involved all four of the original treatment conditions in 
this study, we will assess maternal and offspring mortality in all four of those treatment conditions for this 
phase of follow-up. Moreover, given that maternal mortality due to natural causes will increase as the mothers 
age, we plan to follow this sample through 2026. The rates of mortality among offspring also will increase over 
this age-range, so we will assess offspring mortality over the same years. Earlier phases of this study (protocol 
04-0518—now closed) examined neighborhood adversity for treatment groups 1 and 3, which involved sending 
participants’ baseline addresses in these groups at the time of registration in this trial to Geolytics, a firm we 
used to calculate neighborhood adversity scores. Registration in this trial took place in 1989 and 1990. We now 
wish to include measures of neighborhood adversity in this study four all four treatment groups. Neighborhood 
adversity can be treated as a baseline factor that may either moderate treatment effects on mortality or 
account for variance in our estimates of mortality by treatment condition. We now realize the value in obtaining 

Protocol # 20-0794 
Version Date: 
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approval to gather data on neighborhood adversity for allreatment groups through Geolytics. 

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Our specific aims are: 
Aim 1: Estimate NV-C differences in markers of chronic disease and mortality. The NV group is hypothesized 
to have: H1: lower measures of obesity; H2: lower risks for macrovascular disease reflected in measures of 
functional arterial stiffness; H3: fewer markers of chronic kidney disease (CKD); H4: better metabolic 
outcomes; H5: lower levels of immune/inflammatory markers; and H6: lower mortality rates. 
Aim 2: 
Examine modifiers of the intervention on outcomes in H1-5. H7: Given results through age 18, NV 
effects on H1-5 outcomes will be greater for mothers of females and female offspring. 
Aim 3: Explore mediators of NV on selected outcomes: H8: NV effects on maternal outcomes will be mediated, 
in part, by earlier NV beneficial effects on prenatal health behaviors, PIH, preterm delivery in first and 
subsequent births, closely spaced subsequent pregnancies, maternal sense of mastery, stable family structure, 
family economic resources, and hypertension at 12 and 18 years postpartum. H9: NV effects on offspring 
outcomes will be mediated, in part, by NV beneficial effects on prenatal health behaviors, PIH, preterm 
delivery, breastfeeding, qualities of parental care, lower screen-time, stable family structure, family economic 
resources, and obesity at ages 12 and 18. 
Background 
Significance 
Addressing the extraordinarily high rates of chronic disease and premature mortality among low-income 
African Americans, in spite of recent reductions in white-black disparities, is a public health imperative.1,2 In the 
US, non-Hispanic (NH) blacks, compared to NH whites, have higher rates of CVD mortality;3 T2D;4 and kidney 
failure.5 These differences emerge in the context of large racial disparities in socioeconomic position (SEP)6 
and modifiable individual risks indexed by diet, physical activity, smoking, BMI, blood pressure, blood glucose, 
and total cholesterol.6-11 Disparities begin with compromised health and development during pregnancy and 
early childhood.12-15 Women’s first pregnancies and births set in motion significant changes in their immune,16 
endocrine,17,18 cardiovascular,19 and neurologic systems,20 including the development of maternal protective 
behaviors designed to promote offspring survival.21-24 Under conditions of concentrated adversity, these 
changes create risks for subsequent maternal health,24 including maternal risk for gestational hypertension,25 
and future CVD risk.26-30 Note that there is a relationship between LBW and the development of subsequent 
hypertension, a relationship most pronounced among black women.31 Important early influences on children’s 
risk for chronic disease include exposures to prenatal tobacco, 32 nutritional factors,33 hypertensive disorders of 
pregnancy,34,35 low birthweight,36 socioeconomic adversities,37-39 and “toxic” stress, including child abuse and 
neglect. 40,41 
The NH black-white difference in individual risks is most pronounced among black females. 8 And SEP 
adversities and child maltreatment increase the risk for CVD most among females,8,40,41 a finding replicated in 
an animal model.42 but not consistent across epidemiologic studies.12 Sex-based differences in response to 
stress begin in pregnancy,43,44 with female newborns expressing heighten androgen activity in response to 
uncontrollable significant stressors.44 Pregnant women bearing female fetuses have heightened risk for PIH 
and pre-eclampsia.45-47 PIH is a unique risk for CVD over the life-course for mothers,48 and for offspring.49 
These early exposures appear to have both direct effects on maternal and offspring biologic development, and 
indirect effects mediated by changes in subsequent behavior and context, amplifying effects of early 
exposures. 
Epidemiologic studies provide clues for the development of preventive interventions, but lack the 
scientific rigor needed to guide policy and practice more definitively. That rigor will come from long-term follow-
ups of RCT’s. Starting risk-reduction early in life has considerable promise, 50,51 but trials conducted to date 
have not yet revealed the potential of early interventions to alter adult risks for chronic disease. Some RCT’s 
have tested the effects of diet and physical-activity interventions among children and youth, but most are 
challenged with small samples and attrition bias, and have not yet followed participants into adulthood.52-54 Two 
trials of childhood interventions have followed participants into adulthood, but they also have been challenged 
with either small samples and/or attrition bias. 55,56 To our knowledge, there are no adult follow-ups of RCT’s of 
prenatal and infant/toddler interventions designed to reduce adversities that compromise cardio-metabolic 
functioning. 

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One of the difficulties with such trials is that improving at-risk individuals’ behavior is challenging.11 The 
Nurse-Family Partnership–NFP, a program of prenatal and infant/toddler home-visiting by nurses for low-
income mothers bearing first children, explicitly leverages new mothers’ and fathers’ developing motivations to 
protect their offspring.20-24 Nurses guide mothers and other caregivers to improve pregnancy outcomes, early 
child health and development, maternal health and economic self-sufficiency.57 Replicated effects found in a 
series of RCT’s have been found in these outcome domains across separate NFP trials with different 
populations.57-75 One of these trials with 89% AA families in Memphis, TN (N=742), serves as the foundation 
for the current proposal; it has found program effects on a range of maternal and offspring outcomes of clear 
public health importance,63-72 including hypertension among mothers of females and obesity in female offspring 
at child-ages 12 and 18.72 
The proposed follow-up builds upon trials of other interventions and expands the list of outcomes to 
include state-of-the-art measures of obesity and fat distribution, arterial stiffness, CKD, metabolic outcomes, 
immune/inflammatory markers, and mortality–for both mothers and their firstborn offspring. By examining the 
impact of a comprehensive program of prenatal and infant/toddler home-visiting by nurses on maternal and 
offspring adult chronic-disease risk in an RCT, the current study holds considerable promise for addressing this 
critical public health challenge. 
Sampling Design of Original Clinical Trial 
Original Sample Characteristics. We invited 1,290 women from the obstetrical clinic of the Regional 
Medical Center in Memphis to participate (Table 1). We recruited women <29 weeks pregnant if they had no 
previous live births, no specific chronic illnesses thought to contribute to fetal growth retardation or preterm 
delivery, and at least 2 sociodemographic risks (unmarried, <12 years of education, unemployed). Eighty-eight 
percent (1138/1289) completed informed consent and were randomized to 1 of 4 treatment conditions.63 
Treatment Conditions 
Table 1 summarizes services provided and numbers of participating families randomized into each of 4 
treatment conditions in this trial. The study was designed to follow 742 families in 2 treatment conditions after 
delivery (Treatments 2 and 4). Details of the allocation procedures are found in our original publication.63 
 
Table 1. Services provided in each treatment condition 
Services 
Treatment 1 
N=166 
Treatment 2 
N=514 
Treatment 3 
N=230 
Treatment 4 
N=228 
Transportation for prenatal care 
X 
X 
X 
X 
Screening and referral for children 
 
X 
 
X 
Prenatal/postpartum home visiting 
 
 
X 
X 
Infant and toddler home visiting 
 
 
 
X 
 
Treatment 1 - Transportation during Pregnancy. The 166 families in this treatment condition 
received free round-trip taxicab transportation for scheduled prenatal care appointments. This group did not 
receive any postpartum services or assessments (with the exception of maternal death records described 
below). 
Treatment 2 - Transportation during Pregnancy and Screening during Infancy. The 514 families in 
this condition received: 1) free transportation for scheduled prenatal care; and 2) developmental screening and 
referral services for the child at the 6th, 12th, and 24th months of the child's life. 
Treatment 3 - Transportation and Nurse-Visitation during Pregnancy Only. The 230 families in this 
condition received: 1) free transportation for scheduled prenatal care; and 2) intensive nurse home-visitation 
services during pregnancy and one postpartum visit in the hospital before discharge and one postpartum visit 
in the home. This group did not receive any other postpartum services or assessments (except death records). 
Treatment 4 - Transportation and Nurse-Visitation during Pregnancy and Infancy. The 228 
families in this condition received: 1) free transportation for scheduled prenatal care; 2) intensive nurse home-
visitation services during pregnancy and through the child's second birthday; and 3) developmental screening 
and referral services for the child at the 6th, 12th, and 24th months of the child's life. 
Note that the trial was structured to follow Treatments 2 and 4 after delivery to minimize study costs, 
and these two groups have been followed through offspring age 18. In planning the current follow-up, we 
conducted pilot work and found that our success in tracing T1 and T3 participants would be significantly less 

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than those in T2 and T4, so we chose not to attempt to follow them. 
Program Plan and Implementation 
NFP nurses in T4 had three goals: 1) to improve the outcomes of pregnancy by helping women 
improve their prenatal health; 2) to improve children’s subsequent health and development by helping mothers 
and other caregivers provide competent care of the child; and 3) to improve women’s health and economic 
self-sufficiency by helping them develop self-care practices, plan subsequent pregnancies, complete their 
educations, and find work. Nurses systematically involved fathers and other supportive family 
members/friends and linked families with needed health and human services. They promoted women’s 
protection of their personal health, providing guidance on topics such as diet, exercise, hygiene, use of 
substances, advocating for themselves with providers of office-based care, and risky behavior and social 
relationships.57 Nurses supported mothers’ and other caregivers’ efforts to care well for their children, 
including promoting breast feeding, healthy diets, “back to sleep,” safe bedding, regular sleep times, reducing 
hazards in the home, and supporting regulated and responsive care of the child.57 The program is structured, 
but nurses adapted it to the needs and of individual families, helping mothers accomplish program goals that 
aligned with their aspirations. Nurses completed a mean of 7 visits during pregnancy and 26 between birth and 
child age 2.63 
Sample Retained at Most Recent Phase of Follow-Up 
Table 2 shows elements of the CONSORT diagram for participants in the trial through the first-born 
offspring’s 18th birthday and those available for the 29-year follow-up. Recall that for the postnatal phase of the 
trial, we followed families assigned to treatments 2 (n=514) and 4 (n=228) for primary assessments. We 
reviewed medical records on participants for the prenatal phase of the trial, and well-child, emergency-
department, and hospital records through child age two. We interviewed participants and conducted tests at 
intake, 36 weeks of gestation, and child age 6 months, and 1, 2, 4.5, 6, 9,12 and 18 years of the first-born 
child’s life. At the 18-year follow-up, we completed assessments on 618 mothers and 629 youth, for 
completion rates of 83% of the mothers and 85% of the children originally randomized, and 86% of the mothers 
and 90% of the children who had not died prior to the 18-year assessment. Obtaining high rates of sample 
retention is crucial for ensuring accurate estimates of intervention effect. We will conduct maternal 
assessments on all cases where the mother had not miscarried, the child had not died in the first two years of 
life, and the mother had not died or refused by age 18. In the current phase, we will conduct assessments on 
first-born offspring, irrespective of their mothers’ refusal or mortality status. 657 mothers and 687 offspring are 
available for the year-29 follow-up. Note that we completed an update of participants’ current addresses in the 
spring of 2018. They are displayed at the bottom of Table 2. Among mothers, 84% of those available and 
found for the 29-year follow-up live in the Memphis metropolitan area, and an additional 3% live within a 3-hour 
drive of Memphis. Among the 687 offspring available and found, 81% live in the Memphis metropolitan area, 
and an additional 3% live within a 3-hour drive. It is important to note that all participants in this study received 
services beyond “usual care.” Our experience with mothers and children enrolled in this trial has been that 
they experience participating in this study as helpful to them, given that health conditions identified in the 
course of conducting assessments are referred for further evaluation and treatment. We will follow this same 
procedure in the 29-year follow-up. 
Table 2. Sample Recruitment, randomization, attrition, and completed assessments at 18 Years and sample 
availability for 29-year follow-up 
Eligible Subjects Invited to Participate 
1289 
 
Number Refused 
151 
 
Number Randomized 
1138 
 
Treatment Group Assignment 
1a 
2 
3a 
4 
Total 
(TX 2 & 4) 
Number Allocated to Each Treatment 
166 
514 
230 
228 
742 
Not Available for 29-year follow-up 
 
 
 
 
 
Miscarriages (first born) not followed 
6 
19 
6 
8 
27 
Stillbirths (first born) not followed 
0 
5 
3 
2 
7 
Offspring deaths before age two (not followed) 
 
7 
 
1 
8 
Maternal deaths through 18 years postpartum 
 
15 
 
3 
18 
Post-randomization maternal refusals/drops 
 
14 
 
11 
25 

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Offspring Deaths (after age 2) 
 
9 
 
2 
11 
Post-randomization offspring refusals/drops 
 
1 
 
1 
2 
Mothers Available for 29 year follow up 
 
454 
 
203 
657 
Current mother address in Memphis metro area 
 
380 
 
163 
543 
Current mother address < 3 hrs. drive Memphis 
 
13 
 
8 
21 
Current mother address > 3 hrs. drive Memphis 
 
50 
 
29 
79 
First-Born Offspring Available for 29 year follow FU 
 
473 
 
214 
687 
Current study child address in Memphis metro area 
 
378 
 
178 
556 
Current study child address < 3 hrs. drive Memphis 
 
16 
 
6 
22 
Current study child address > 3 hrs. drive Memphis 
 
79 
 
30 
109 
a Sample not followed after birth by design 
 
Summary of NFP Effects from Pregnancy through Child Age 18 on Maternal Outcomes in Memphis 
Trial 
Table 3 summarizes key Control-NV effects found for mothers over the 18-year period following registration in 
the program during pregnancy. We summarize offspring effects below. 
Prenatal/Newborn Health. Nurse-visited women (T3+T4) had fewer first pregnancies compromised by 
Pregnancy-Induced-Hypertension (PIH) than did women in the control group (T1+T2).63 While this difference 
was only statistically significant when T3 and T4 were contrasted with T1 + T2, the pattern held for the two 
groups followed after delivery, T2 and T4. Nurse-visited women overall had lower rates of preterm birth, and 
those with low psychological resources (LPR) measured at registration had fewer low birth weight newborns 
than did their control-group counterparts.72 This reduction was significant when the contrast was limited to the 
two groups followed after delivery (T2 vs T4). Note also differences in self-reported prenatal health behaviors 
at 36 weeks of gestation for mothers of females. 
Short Inter-Pregnancy Intervals. Nurse-visited women (T4) had greater intervals between their first and 
second births,63-65 and had fewer closely spaced subsequent births over the 12-year period following birth of 
the first child,68 an important contributor to maternal health.76 

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Table 3. Program effects on selected maternal outcomes through age 18 
Outcome and Age of Assessment 
Sample 
Comparison 
Nurse 
Comp vs. Nurse 
Prenatal/Newborn Health 
 
Mean/Rate 
Mean/Rat 
p- 
Effect size* 
Pregnancy-Induced Hypertension, %1 
Whole-T1+2 vs T3+4 
20.0 
13.0 
.009 
OR=0.65 
Preterm delivery1 
Whole 
13.3 
7.3 
.020 
OR=0.51 
Low birthweight, %1 
LPR8 
19.8 
9.5 
.010 
OR=0.42 
High birthweight - % 
Mothers of F’s 
5.3 
0.0 
.005 
Not est 
Health behavior index, % – 36 wks.2 
Mothers of F’s 
67.8 
80.2 
.038 
OR=1.18 
Inter-Pregnancy Intervals 
Time to first subsequent birth (0-72 mo.) 3 
Whole 
30.23 
34.38 
.01 
ES=0.26 
Count of closely spaced subsequent births–age 0-
124 
Whole 
0.51 
0.34 
.019 
IR=0.67 
Maternal Economic & Behavioral Resources 
Count of Substances Used – child age 9 
Whole 
0.17 
0.10 
.075 
IR=0.62 
Role Impairment due to Substance Use–ages 9 & 
12 
Whole 
0.25 
0.00 
.04 
Not est. 
Sense of mastery – 36 wks preg to 18 yrs5 
Whole 
99.62 
100.95 
.009 
ES=0.13 
% live with partner – across time6 
Whole 
32.8 
36.8 
.09 
OR=1.20 
% married – across time6 
Whole 
10.7 
14.9 
.03 
OR=1.37 
Public Benefits costs (summed-birth-age 18 yrs)7 
Whole 
$192,836 
$175,525 
.03 
ES=-0.13 
Maternal Death over 21-year Period after Birth 
 
 
 
 
 
All-cause mortality, % 
Whole-T1+T2vs T3+4 
3.7 
1.3 
.008 
Not Est. 
External-cause mortality, % 
Whole-T1+T2vs T3+4 
1.7 
0.2 
.02 
Not Est. 
Measured Maternal Obesity & Hypertension, and Self-Reported Health Problems – through Child Age 18 
Systolic BP – age 18 
Mothers of F’s 
128.85 
123.50 
.024 
ES=0.30 
Diastolic BP – age 18 
Mothers of F’s 
90.03 
87.02 
.044 
ES=0.34 
Systolic BP – age 12 
Mothers of F’s 
118.40 
112.11 
.010 
ES=0.31 
Diastolic BP – age 12 
Mothers of F’s 
82.51 
77.73 
.010 
ES=0.33 
Stage 1 Hyperten (Sys>120 or Dias >80) % – age 
18 
Mothers of F’s 
84.1 
66.3 
.002 
OR=0.79 
Stage 1 Hyperten (Sys >120 or Dias >80) % – age 
12 
Mothers of F’s 
63.5 
45.8 
.025 
OR=0.72 
Thyroid Problems (self-report), %- age 18 
Whole 
6.6 
2.6 
.030 
OR=0.38 
Kidney Problems (self-report), % - age 18 
Whole 
2.5 
0.5 
.037 
OR=0.18 
Memory problems (self-report) % - age 18 
Mothers of F’s 
2.1 
0.0 
.038 
Not Est. 
High Cholesterol (self-report), % - age 18 
Whole 
8.3 
14.4 
.023 
OR= 1.87 
1 Derived from labor, delivery, and newborn medical record; 2derived from interview, responded “yes definitely” to all questions: 1) “I 
picture myself feeding the baby”, 2) “I do things to try to stay healthy that I would not do if I were not pregnant”, 3) “I eat meat and 
vegetables to be sure my baby gets a good diet”, and 4) “I give up certain things to help the baby”; 32-, 4.5-, and 6-year postpartum 
interviews;4derived from 2-, 4.5--, 6-, 9-, and 12-year postpartum interviews; 536 wks. pregnancy, 6-, 24-, 54 mo. postpartum, plus 6-
,9-12-, and 18-years after birth; 6 2,4.5,6,9,12, and 18 year interviews;7sum of annual estimates following birth of first child; 8LPR – 
sample defined by mothers being in lower half of distribution for psychological resources (intellectual functioning, mental health 
mastery/self-efficacy).61 
 
Maternal Economic and Behavioral Resources. By child age 9, nurse visited (T4) women reported, 
as a trend, using fewer substances,66 and at age 12, fewer behavioral impairments due to substance use than 
control-group women (T2).68 Over the 18-year period following birth of the first child, nurse-visited (T4) women 
reported a greater sense of mastery than did women assigned to the control group (T2).71 By child age 18, 
nurse-visited (T4) women reported higher rates of marriage, cohabitation, and received fewer public benefits 
(discounted) for Supplemental Food and Nutrition, Medicaid, and cash assistance welfare than did those 
assigned to the control group (T2), an effect mediated by their having fewer closely spaced subsequent 
births.71 
Maternal Death over 21-year Period Following Birth of First Child. Nurse-visited women assigned 
to receive visitation during pregnancy alone (T3) or to receive NFP visits during pregnancy through child age 2 
(T4), were less likely to have died from all causes than were women in the control group (T1+T2), an effect 
particularly pronounced for death due to external causes (drug overdose, suicide, injury, and homicide). 69 
These effects were in the same direction for women visited during pregnancy and through child age 2 (T4), but 
not statistically significant. 

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Measured Maternal Obesity, Hypertension, and Self-Reported Health Problems. By the first 
offspring’s 18th birthday, nurse-visited (T4) women were less likely to have stage-1 hypertension (at the year 12 
and 18 assessments) than women in the control group (T2), effects limited to mothers of females.72 In addition, 
nurse-visited (T4) women reported fewer thyroid problems, kidney problems, and among mothers of females, 
fewer memory problems.72 The presence of hypothyroidism among women with chronic kidney disease 
increases the risk for serious heart disease. 77 The one exception to this pattern is that nurse-visited women 
reported more problems with high cholesterol, an effect essentially limited to those who gave birth to males 
(not shown). 72 
Hypothesized Pathways of Program Effects on Maternal Chronic Disease 
Figure 1 summarizes how the effects reported in Table 3 are thought to reduce risks for the development of 
CVD, CKD, and T2D, in mothers. The bold lines show those effects that are established; the lighter lines 
represent hypothesized relationships; and the dotted lines represent hypothesized relationships between 
earlier effects and outcomes to be measured in the 29-year follow-up. Program effects on aspects of prenatal 
health (reductions in PIH, PTD, and LBW) are thought to play a role in reducing maternal hypertension and 
reported thyroid problems, which in turn will contribute to reductions in measured risks for CVD, T2D, CKD, 
and mortality in this 29-year follow-up. Note for example that in the control group (T1+T2), 30% of the women 
who died during the first two decades following birth of the first child had PIH; the corresponding rate among 
those who died in the T3 nurse-visited condition was 25%, and 14% in the T4 condition. This suggests that 
part of the reduction in maternal mortality may be explained by or at least correlated with the improvement in 
conditions for prenatal health that led to PIH in the control group. Moreover, the reduction in short inter-
pregnancy intervals is expected to help explain the treatment effect on risks for maternal morbidity and 
mortality. The reduction in short inter-pregnancy intervals was a major contributor to the reduction in mothers’ 
reliance on public benefits. Intervention effects on economic and social/behavioral resources have implications 
for the development of chronic disease among 
mothers, as well as their offspring, especially 
girls, given that economic adversity is 
particularly predictive of risks for CVD among 
females.12 Note also that the reduction in 
behavioral dysregulation on the part of nurse-
visited children shown in Table 4 below is also 
likely to play a role in reducing maternal 
stress, which contributes to inflammation and 
risk for chronic-disease. We have not 
attempted full-blown mediation analyses of the 
inter-relationships among the outcome 
domains in Figure 1, as the model is complex, 
with different domains of maternal functioning 
likely to play a role in both mediating the effect of 
the program over time and moderating adverse 
influences on the development of chronic 
disease. 
Figure 1. Model of NFP Program Effects on Maternal 
Risks for Chronic Disease in Memphis Trial 
 
Summary of NFP Effects on Offspring Outcomes in Memphis Trial 
Table 4 summarizes key Control-NV effects found for first-born offspring through age 18. 
Maternal Caregiving Dysfunction/Investment. Nurse-visited women (T4), especially those with LPR 
measured at registration, exhibited significantly better care of their children than did their control-group 
counterparts (T2). 63,65 These effects included fewer beliefs about infants and caregiving predictive of child 
abuse, home environments that were more conducive to children’s emotional and cognitive development, 63,65 
and among girls, higher rates of breastfeeding in the first two years of life.72 

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Offspring Injuries/Ingestions in Medical Record. Nurse-visited (T4) children born to mothers with LPR were 

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less likely to have healthcare encounters of all types for injuries/ ingestions in the first 2 years of life than 
children in the control group (T2).63 Moreover, they had far fewer days of hospitalization for injuries/ingestions 
during that time;63 all fractures and head trauma, markers for maltreatment, were in the control group.63 
Offspring Language, Achievement and Cognition. Nurse-visited (T4) children born to mothers with LPR 
had better language development and math achievement over the first 18 years of life than their control-group 
counterparts (T2).63,65-67,70 At age 18, they also scored better on a test of working-memory.70 Nurse-visited 
mothers/caregivers reported that T4 offspring were receiving SSI disability income less frequently than did 
those in the control group (T2), an effect concentrated among those born to LPR mothers.70 
 
Table 4. Program effects on selected caregiving and child outcomes through age 18 
Outcome and Age of Assessment 
Sample 
Comparison 
Nurse 
Comp vs. Nurse 
Maternal Caregiving Dysfunction/Investment 
Beliefs predictive of child abuse, 6 & 24 mo. 
Whole 
LPR1 
100.5 
102.5 
98.7 
100.2 
.003 
.01 
ES=-0.23 
ES=-0.29 
Emotional/cognitive stimulation (Home total score) 12 & 24 
mo. 
Whole 
LPR1 
30.9 
30.3 
32.3 
31.5 
.003 
.05 
ES=0.24 
ES=0.21 
Ever Breast Fed, % - 24 mo. 
Mothers of F’s 
12.3 
24.3 
.0086 
OR=2.28 
Child Injuries/Ingestions in Medical Record 
Incidence of encounters (all types) 0-24 mo. 
LPR1 
0.67 
0.41 
.01 
IR=0.61 
Incidence of days hospitalized—0-24 mo. 
LPR1 
0.26 
0.02 
.01 
IR=0.08 
Child Language, Achievement, & Cognition 
Receptive Language (PPVT) – ages 6 & 18y 
LPR1 
79.91 
82.79 
.03 
ES=0.21 
Math Achievement (PIAT), ages 6, 12 & 18 y 
LPR1 
82.89 
86.70 
.001 
ES=0.31 
Working Memory – age 18y 
LPR1 
7.90 
8.51 
.045 
ES=0.23 
% SSI Disability – 18y 
LPR1 
11.3 
4.0 
.011 
OR=0.33 
Child Emotional/Behavioral Regulation, Mental Health, Substance Use 
Dysregulated Aggression- MSSB - age 6 
LPR1 
101.10 
98.58 
.04 
ES=-0.25 
Incoherent Stories- MSSB - age 6 
LPR1 
29.84 
20.90 
.006 
ES=-0.34 
Total Behavior Problems - Borderline/Clinical, CBCL, % 6y 
Whole 
5.4 
1.8 
.04 
OR=0.32 
Count of Failed Conduct Grades–males (grades 1-6)y 
Whole 
0.10 
0.06 
.044 
IR=0.56 
Used alcohol, cigarettes, or cannabis, % - age 12 
Whole 
5.2 
1.6 
.024 
OR=0.29 
No. days used substances-last 30 days - age 12y 
Whole 
0.18 
0.03 
<.001 
IR=0.17 
Ever Sent to Juvenile Detention, % - age 12y 
Whole 
9.4 
7.2 
.080 
OR=0.52 
Internalizing Disorders Borderline/Clinical, %– age 12y 
Whole 
31 
22 
.044 
OR=0.63 
No. hrs./day screen time video/computer–age 12y 
Females 
0.49 
0.28 
.028 
ES=0.21 
Count of convictions - age 18y 
Females 
.22 
.09 
.0504 
IR=0.42 
Child Death over 21-year Period after Birth 
All-cause mortality rate, % 
Whole 
2.7 
0.9 
.11 
Not est 
Preventable-cause mortality rate, % 
Whole 
1.6 
0.0 
.04 
Not est 
Child Obesity 
Obese, % (CDC standard – 18 y) 
Females 
30.2 
21.2 
.035 
OR=0.70 
Obese,% (CDC standard – 12 y) 
Females 
31.8 
15.9 
.003 
OR=0.50 
 
1LPR – Sample defined by Mothers being in lower half of distribution for Psychological Resources 
 
Offspring Emotional/Behavioral Regulation, Mental Health, Substance Use. Nurse-visited (T4) children 
born to LPR mothers exhibited less dysregulated aggression and incoherent stories in response to examiners’ 
story stems at age 6 than did their counterparts in the control group (T2). 65 Overall, nurse-visited (T4) children 
were identified as having fewer behavioral problems in the borderline/clinical range on the Achenbach child 
behavioral checklist at age 6 than did children assigned to the control group (T2). 65 By age 12, nurse-visited 
(T4) children were less likely to be using substances, to have been sent to juvenile detention, and to have 
internalizing disorders in the borderline/clinical range.67 By age 18, nurse-visited (T4) females reported fewer 
convictions than did their control-group (T2) counterparts,70 a sex-moderated effect replicated in a prior trial of 
the NFP.62 
Offspring Death over 21-year Period after Birth. Over the 21-year period following their birth, nurse-visited 
(T4) offspring were less likely to have died for preventable causes than those in the control group (T2).69 

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Hypothesized Pathways of Program Effects on Offspring Chronic Disease 
Figure 2 summarizes how the Nurse-
Control differences in caregiving 
reported in Table 4 over the 18-year 
period following birth of the first child are 
hypothesized to reduce risks for the 
development of CVD, CKD, and T2D in 
first-born offspring. In this figure, the bold 
lines show those effects that are 
established; the lighter lines represent 
hypothesized relationships; and the 
dotted lines represent hypothesized 
relationships between earlier effects and 
outcomes to be measured at 29 years. 
The findings in Table 4, in general, 
suggest that the long-term effects of the 
program on offspring health are likely 
due to improvements in offspring 
neurobiological functioning and reductions in 
over-nutrition set in motion during gestation 
78,79 that are amplified over time by improved 
Figure 2. Model of NFP Program Effects on Offspring Risks 
for Chronic Disease in Memphis Trial. 
maternal caregiving, increased inter-pregnancy intervals, improved family economic resources, improvements 
in offspring development and behavior, and reductions in obesity, all of which will reduce stress and 
inflammation, that iteratively contribute to reductions in offspring developing risks for chronic disease. 
We are particularly interested in understanding the interplay of contextual and behavioral factors that 
contribute to sex differences in risks for emerging chronic disease over the course of development, including 
sex differences in offspring reactivity to various forms of stress40-44 and increased parental caregiving 
investments in female offspring under conditions of adversity and the absence of fathers in households.80-83 
We have not yet attempted full-blown mediation analyses of the interrelationships among the outcome domains 
in Figure 2, as the model is complex, with different domains of maternal and child functioning likely to play a 
role in both mediating the effect of the program and moderating adverse influences on the development of 
chronic disease. 
 
I. 
CHARACTERISTICS OF THE RESEARCH SAMPLE 
1. Number of subjects. Recruit approximately 1344 people who participated in the New Mothers Study. 
 
2. Gender of Subjects. Recruited participants will be approximately 75% female and 25% male. 
3. Age of Subjects. We will recruit men and women who are > 18 years of age. 
 
4. Racial and Ethnic Origin. We anticipate that the racial and ethnic distribution of the study subjects will 
be approximately 89% African American and 11% Caucasian. 
5. Inclusion Criteria. Participated in the New Mothers Study as mothers or their firstborn offspring 
 
6. Exclusion Criteria. Not a participant in the New Mothers Study 
 
7. Vulnerable Subjects. This study focuses on participants from the New Mothers Study and there is a 
possibility the potential participants could be incarcerated, pregnant, lack capacity to consent, or disabled. 
 
II. SUBJECT IDENTIFICATION, RECRUITMENT, AND CONSENT 

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The recruitment and assessment plans are adjusted to ensure the safety of participants and data-
gathering staff in light of the COVID-19 pandemic. We will inform study participants at the stage of 
recruitment that the assessment will take place in two parts – a telephone interview (Part One) and a 
second, face-to-face assessment, to be conducted at a later time (Part Two). For in-office interviews 
and health assessments, to assess subject COVID status and insure appropriate steps are taken to 
minimize subject and staff risk: a phone pre-screen will be administered prior to the visit; an in-person 
screen will be administered at the start of the visit; and necessary sanitization procedures will be 
followed.We will conduct the Part Two interview by phone or by HIPPA-compliant Zoom with a limited 
number of subjects who are unable or unwilling to travel to the Memphis office to complete the face-to 
face Part Two interview. For this limited number of Part Two interviews that will be virtual, no in-office 
health assessment will take place. For participants who are currently incarcerated, a prisoner interview 
will include portions of the Part 1 and the Part 2 interview, will last approximately one hour, will take 
place in a private room at the prison either via secure video conferencing, or by phone, or in person, 
and will be administered only after staff obtains verbal consent from the prisoner at the start of the 
interview session. 
Information regarding research safety during the COVID-19 pandemic: 
To ensure appropriate safety precautions when conducting in-person study procedures, the process 
for conducting in-person visits outlined in the University of Rochester Guidance for Human Subject 
Research will be followed. The study team will continue to monitor the guidance provided by UR/URMC 
for updates and revisions to ensure all study activities are conducted according to current safety 
guidelines. Since guidance will change over time, appropriate changes to COVID risk assessment and 
office sanitization tasks will be implemented as needed. 
 
1. Method of Subject Identification and Recruitment. Over the past 28 years, we have continuously traced 
the sample between assessment phases (through regular birthday and holiday cards and use of internet), 
and have built in intrinsic incentives to optimize participation. These incentives include having the same 
primary local study leader (the wife of a local minister) develop trust within the community and be 
responsible for engaging the sample; referring participants for further evaluation and treatment when health 
problems are identified; and remunerating participants adequately for their travel and time. We will employ 
the same procedures for this next phase of follow-up. To reconnect with study participants, several 
methods for re-contact will be used. Letters will be sent announcing this new phase of the study. Phone 
calls using contact information provided by subjects at the previous phase of the study will be used, along 
with emails provided to us in the previous study phase. Study participants will be traced as needed through 
telephone directories and the internet. In addition, we will use social media, e.g. Facebook. Study 
participants either will call the study office to indicate their desire to participate in the follow-up or the 
interviewing staff will call the study participants to determine their interest in continued participation. To 
facilitate confidentiality, all use of social media for reconnecting with study participants will be administered 
and maintained by study staff, and individuals who are not study staff will not be able to post information on 
such study-related social media platforms. When social media platforms are used, we will not collect 
information from participants, including health information or information that might be used to identify 
them. The e-mail address associated with any social media used for recruitment will be: 
NewMothersStudy@urmc.rochester.edu or Evelyn_Collins@urmc.rochester.edu . Language in the study’s 
chosen social media will be as follows: “The Memphis New Mothers Study would like to contact you 
because we have a new opportunity for you to participate. Please contact us today at: (901) 452-6180.” 
 
If we learn that a study participant (either mother or firstborn child) is in prison, either from newspaper 
listings or through their personal contacts, the project coordinator will be responsible for both recruitment 
and consent procedures. We will follow the procedures approved by IRB and used successfully in the 18 
year follow-up. The project coordinator will write to the prison’s warden to explain the nature of the current 
study, outline the study participant’s previous involvement in this research, and ask for the warden’s email 
permission to request one interview with the study participant. If the warden gives his/her approval, he/she 
will be provided with a list of names of subject prisoners, and will be asked to give the recruitment letter 

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and a copy of the verbal consent document to the study participant for his/her review. If the study 
participant prisoner indicates that he/she wants to participate, he/she will be instructed by the warden to let 
the warden know of their decision, and the warden will contact the New Mothers Study project coordinator 
and make arrangements for the scheduling and setup of the interview. There will be no physical 
assessment with any prisoner participants. 
 
 
2. Process of Consent. Trained staff will administer all consenting procedures. Initial consent for Part 1 will 
be obtained over the phone prior to the interview. If the participant verbally agrees to participate, and the 
study team member assesses that the participant demonstrates comprehension of the information, the 
study staff member will proceed with collection of interview data. If the study team member concludes that 
the participant is unable to give verbal informed consent, the Part 1 interview will not go forward and plans 
will be made to bring the individual to the study site for both Part 1 and 2 consent and data collection - with 
the participant accompanied by a Legally Authorized Representative (LAR). For Part 2, consent will be 
obtained in a private office where, prior to data collection, participants will be informed of the nature of 
voluntary participation, time commitment, possible risks, and remuneration. Occasionally, particularly if they 
are physically disabled, subjects may be given an option for study staff to visit their homes to complete the 
visit activities; in these cases, consent will be obtained in a private space in the home. The study staff 
member will review the informed consents, including review of the interview and physical assessments with 
the study participant. In all instances, if the study participant agrees to participate in the Part 2 assessment 
and is deemed competent to provide consent, study staff will proceed with the interview and other data 
gathering procedures. If, during the Part 2 physical health assessment, the study nurse determines that 
any of the physical measures cannot be completed during that office visit, study subjects will have the 
opportunity to return to the office for a brief follow-up visit to complete those physical measures. That brief 
follow-up visit will take about 30 minutes and subjects will receive a small honorarium for their time. First-
born study children will now be adults (~30 years of age) and will have had experience with prior 
interviews/assessments that are similar. Interviewers trained in the consenting/assenting process will 
assess subjects’ comprehension of the information provided. Note that we will enroll some decisionally-
challenged participants if their LAR agrees that participation aligns with the participant’s values and with 
the understanding that the procedure will be terminated or certain sections skipped if the participant 
experiences discomfort. 
For a small subset of participants with whom the Part Two interview will be completed by phone or by 
HIPPA-compliant Zoom, a newly created Part Two written consent form will be mailed to these subjects 
along with written release forms for administrative records. A stamped, return-addressed envelope will be 
sent along with the forms to facilitate mailing for subjects. No virtual Part Two data collection will take place 
with these subjects until signed forms have been returned by US mail to the Memphis New Mothers Study 
office. 
 
For prisoner participants, verbal consent will be administered. All questions will be answered to the 
participant’s satisfaction prior to study staff asking for their decision about whether or not he/she chooses 
to participate. The interview will not take place without study staff obtaining verbal consent. All prisoner 
subjects will be informed that participation in this study will not have any effect on any court decisions, 
parole, or probation. 
 
3. Subject Capacity/Representative Comprehension. In order to ensure adequate knowledge and 
comprehension on the part of potential study subjects, each potential subject will be asked to describe 
his/her understanding of the purpose of the study and what his/her participation will include following a 
subset of COMIRB-recommended questions to determine capacity for consent. All questions will be 
answered to the potential subject's or LAR's satisfaction before informed consent is obtained. Adequacy is 
required to continue with the consenting process. Those individuals found to be decisionally-challenged will 
be guided through the interview portions of the assessment, with the LAR serving as an interpreter. The 
study staff member will work with the LAR to ensure that the participant is comfortable and capable of 

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answering questions about particular topics. In the case of decisionally-challenged participants,, the 
participant’s LAR is designated in order of preference as one of the following: 
 
a. 
The person identified above is: 
• 
An adult 
• 
Who has exhibited special care and concern for the patient 
• 
Who is familiar with the patient’s personal values AND 
• 
Who is reasonably available to serve as a surrogate 
b. The person can make health care decisions for the patient in accordance with the patient’s 
individual healthcare instructions, if any, and other wishes, if known to the health care decision 
maker. If the patient has not given individual healthcare instructions, and the patient’s specific 
wishes are not known, the health care decision maker can make a determination of the patient’s 
desires or best interests in light of the patient’s personal values and beliefs to the extent they are 
known. 
c. This person may include, in order of descending preference, the patient’s spouse, the patient’s 
adult child, the patient’s parent, the patient’s adult sibling, any other adult relative of the patient or 
another adult who satisfies the requirements listed above. 
 
4. Prisoner status. If a study participant is in prison, the study staff will not be scheduled to administer verbal 
consent and conduct the interview until the warden relates the study participant’s express agreement to the 
New Mothers Study project coordinator. Before the interview, the study staff will review the verbal informed 
consent with the study participant specifically approved for use with incarcerated subjects. The study staff 
will remind the participant that participation will not affect consideration for probation or parole in any way, 
that she or he is under no obligation to participate in the study, and that she or he has the right to refuse to 
answer questions or to terminate the interview at any time. If the participant agrees to participate in the 
study, the study staff will proceed with the consenting process.Release forms will not be used. 
x 
Care will be taken in enrolling prisoners as those incarcerated are a vulnerable population. The 
recruitment and consent procedures we have outlined earlier are designed to protect all incarcerated 
subjects in our study from being coerced to participate in any way. If a study participant is incarcerated 
in a prison outside the Memphis area, the same process will take place for them as for the prisoners in 
the Memphis area. Prior to the start of an interview, those participants will be asked if they have any 
questions regarding the interview, and will provide verbal consent. Additionally, a private room for 
conducting the interview will be made available at the prison. 
 
5. Consent Forms. See consent form. 
6. Documentation of Consent. Informed consent will be obtained by research study personnel. For Part 1 
consent will be obtained verbally and for Part 2 it will be obtained and documented on Research Subjects 
Review Board-approved consent forms. Consent for Part Two virtual (phone or HIPPA-compliant Zoom) 
interviews will be obtained and documented on Research Subjects Review Board-approved consent forms. 
For the Part 2 additional brief office visit opportunity, consent will be obtained verbally. Consent forms will 
be kept in locked office files (originals will be sent to Colorado study office and copies maintained at the 
Memphis site). All prisoner participants will be consented using a verbal consent form. 
7. Costs to the Subject. There are no costs to the subject. Any procedures that are for study purposes will 
be billed to the grant. 
 
8. Payment for Participation. Participants will be remunerated with $50 at the completion of Part 1 data 
gathering process. They will receive $200 if they complete the Part 2 interview and assessments. In 
addition, they will receive a possible $25 incentive if they complete the Part 2 interview on the first 
scheduled appointment. Further, if it is determined by a study nurse that a study subject needs to return for 

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an additional brief visit to the study office to obtain a measure of PWV (pulse wave velocity), body 
composition, or to obtain their blood or urine sample, the participant will be compensated with an additional 
$30. For subjects who are uncomfortable or unwilling to provide a blood and/or urine sample (or if we are 
unable to obtain) for various reasons during their office visit, we will ask those subjects to provide lab 
results from within their past year’s medical records. Such results may include the following: Urine – 
Markers of Chronic Kidney Disease (CKD) including Glomerular Filtration Rate (eGFR) and the 
microalbumin/creatinine ratio. Blood – Metabolic Outcomes including Glycosylated Hemoglobin (HbA1C), 
dyslipidemia (TC, LDL, HDL, TG), and the AST/ALT ratio). Cab or public transportation to the study office 
also will be covered on an as needed basis. Round trip mileage for those who drive themselves will be 
reimbursed at the current IRS mileage reimbursement rate if the round trip is over 50 miles. Travel from 
locations that are not a reasonable distance from the office will be covered by study funds as well as 
overnight hotel stays if warranted, determined on a case by case basis. For incarcerated participants, 
payment of $150 will be given to them unless receiving payment is in violation of penal institution policy. If 
receipt of payment is in violation of penal institution policy, incarcerated participants may elect to have their 
payment given to a family member or other designee. 
The Part Two virtual interviews may be administered in two parts, which could take up to 1.5 hours in total 
if completed during one data collection meeting by phone or HIPPA-compliant Zoom. Subjects who 
complete this interview in one session will be paid $125 plus an additional $25 for keeping their first 
appointment. Subjects who require two separate sessions to complete the interview will be paid $50 for the 
first session plus an additional $25 for keeping their first appointment, and then another $75 for completing 
the second interview session, 
 
 
III. METHODS AND PROCEDURES 
Data Collection. Tables 5 and 6 summarize the measures to be gathered in this 29-year follow-up. All data 
will be gathered by staff masked to original treatment assignment. 
Part 1: Overview: once verbal consent is obtained the participant will be interviewed by the study staff member 
using interview 1. In addition, contact information will be obtained that can be used to contact them for the Part 
2 interview/assessment. All interview data will be entered into Redcap. On occasion we may email a link to the 
redcap questionnaire to the study participant directly for them to complete. Once the interview is completed the 
participant will be paid $50 for their participation and will be reminded that we will be in contact with them for 
the part 2 interview. 
Table 5. Part 1 Telephone or Computer Interview Content (RedCap) 
 
Alterations due to COVID-19 
Experience 
Health 
Employment 
Childcare 
Access to food and services 
Comfort with office visit 
Household Composition 
Name of residents 
Age 
Relationship 
Housing type 
Number of rooms 
Mortgage and rent payment 
Education and Training 
High school 
Training 
Licensure 
College 
Graduate school 
Armed Services 
Residence History 
State location 
Receipt of benefits 
Employment History 
Job Type 
Earnings 
Elder care/Handicapped children 
Tobacco Use 
Cigarettes, Cigars, Pipe, Hookah, 
Smokless Tobacco Products and 
Vaping 
Healthcare Providers 
Medications, Insurance, self-
report height and weight 
Hospital Admissions – self-
report 
Births and Children 
Since last data collection point 
Birth outcomes 
Social Security Benefits 
 

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The interview includes all the areas listed in table 5. 
Part 2 
Overview: Once we are able to see people face-to-face safely study staff will contact participants to schedule 
an appointment for the Part 2 assessments. Following informed consent the Part 2 assessments will 
commence collecting the data indicated in table 6. These assessments consist of completion of several 
questionnaires (interview 2) and physical assessments. These include weight, height, bioelectrical impedance 
analysis (BIA), waist and hip circumference, blood draws, urine sample, BP, augmentation index (AI), pulse 
wave velocity (PWV) and the questionnaires included in the part 2 interview. The questionnaires will be 
administered in a private space and entered into Redcap. 
Rarely, subjects will be given an option for study staff to visit their homes to complete the visit activities, 
particularly if they are physically disabled. Study activities completed at home will remain the same as the in-
person visit, with an exception of BIA, PWV and AI. 
 
Anthropometric assessments: We will conduct anthropometric assessments to measure obesity and fat 
distribution, given that they are well established risks for CVD, CKD, and T2D. To assess obesity, fat, and fat 
distribution, we will measure, in centimeters, height in bare feet (including sitting height) using a stationary 
stadiometer with headpiece; waist (after exhaling, just above iliac crest); and hip circumference (at point of 
greatest protrusion of gluteal muscles). Waist and hip circumference will be measured with a flexible ribbon of 
non-stretchable cloth. The Tanita-780U Multifrequency Segmental Body Composition Analyzer will be used in 
the study office to derive an estimate of segmental fat mass in arms, trunk, legs, and total body. Prior to BIA, 
the Tanita Questionnaire will be administered to assess factors which may impact the BIA measurement. 
For assessments conducted outside of our offices, we will use the Omron hand-held body fat analyzer. 
 
Macrovascular disease assessments: We will measure risks for macrovascular disease using a 
sphygmomanometer, SphygmoCor Xcel. We will obtain 3 independent brachial-cuff BP measurements, 
standardized for the instrument, size of cuff to arm circumference, cuff placement, prior resting time (at least 30 
minutes into the session and after 5 minutes of rest), and then one minute apart, after which the system will 
average the successfully completed assessments to provide a brachial BP, body position, and Phase I and IV 
sounds.84  The SphygmoCor Xcel device will be used to estimate carotid femoral Pulse Wave Velocity 
(cfPWV) and the Augmentation Index (AI). These measures of arterial stiffness are proximal risks for the 
diseases addressed in this study. 
In addition we will use sphygmomanometer, SphygmoCor Xcel. We will obtain 3 independent brachial-cuff BP 
measurements, standardized for the instrument, size of cuff to arm circumference, cuff placement, prior resting 
time (at least 30 minutes into the session, and then one minute apart, discarding the first and taking the 
average of the second and third readings), body position, and Phase I and IV sounds.84  The SphygmoCor 
Xcel device will be used to estimate carotid femoral Pulse Wave Velocity (cfPWV) and the Augmentation Index 
(AI). These measures of arterial stiffness are proximal risks for the diseases addressed in this study. 
 
Table 6. Part 2 Face-to-Face Assessment 
Physical Measurements 
Interview measures 
 
 
Obesity, Fat and Fat Distribution 
Illness History & System Review 
Height (standing & sitting), weight, waist & hip 
circumference 
Diagnoses, signs & symptoms, chronic conditions, 
hospital encounters 
Body Composition (segmented & % body fat, visceral 
fat, muscle mass) (Tanita-780 Multifrequency) 
Current Medications 
 
Disability–Injury/physical/mental Illness 
Cardio-Metabolic Risks – Blood 
Eating 
TC, HDL, (calculated) LDL 
Diet (% energy scale; eating at America’s table); 
3-factor eating questionnaire 
Reason for benefits 

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Triglycerides 
Substance Use 
Glycosylated hemoglobin 
TAPS; rehabilitation for substance use 
GF-1; FSH 
 
 
Physical Activities & Sleep 
Kidney Function–Blood/Urine 
Physical activity: IPAQ, Sedentary activity, 
U. Albumin; creatinine 
SF-20 Physical functioning, role functioning, health 
perceptions, pain 
eGFR 
Sleep: (PSQI) 
Immune-Inflam. Markers - Blood 
Arrests and Incarceration 
hs-CRP, IL-6, ICF-1 
Raising children (Bavolek) 
Fibrinogen 
Adverse childhood experiences 
TNF-alpha receptor 2 
Depression, Anxiety, Mastery 
Risks for Macrovascular Disease - Arterial Measures 
Depression (PROMIS) 
Pulse wave velocity; Augmentation Index 
(SphygmoCorXCEL) 
Anxiety (PROMIS) 
Resting BP 
Mastery (Pearlin) 
Mortality – NDI: Cause, date 
Marriage & Partnered Relationships 
 
Duration, Support, Cohabitation, Commitment, 
Satisfaction, Partner hostility and warmth 
 
Births, pregnancies, and outcomes, partner involvement 
 
Subjects will be asked to give biospecimens: We will draw blood to measure cardio-metabolic factors (see 
table). We will collect urine samples from all subjects to measure the microalbumin/creatinine ratio. Subjects 
will undergo a blood draw of approximately 50 ml of blood (up to 50 ml are permitted according to established 
IRB guidelines), which will be collected by a trained phlebotomist/nurse and processed using standard 
methods provided by the Medpace Reference Laboratories. Aliquots will be frozen at -80ºC for future analysis 
of immune, endocrine, and metabolic markers. The study staff will measure the specific gravity (dilution) and 
temperature of the sample using a handheld refractometer and record the time of collection. Blood and urine 
samples will be aliquotted and stored at -80ºC using protocols provided by the Medpace Reference 
Laboratories. Samples will be shipped on a weekly/bi-weekly basis on dry ice to the Medpace Reference 
Laboratories for analysis and storage for future use. 
 
Administrative data: We will review National Death Index (NDI) records to obtain dates and causes of death. 
We will send identifying information for all mothers enrolled and children born alive to NDI; this includes 
maternal and child names, social security numbers, dates of birth, and gender. NDI is the “gold standard” for 
ascertainment of mortality and cause of death in the US. Estimates of NV-C differences in all of these 
outcome domains will be interpreted in light of data derived from participant interviews conducted at this phase 
of follow-up, assessments conducted at earlier phases, and medical/hospitalization records. Other 
administrative data that will be obtained include medical records, Medicaid, TANF, SNAP and birth certificates. 
Neighborhood Adversity Data: We would like to include measures of neighborhood adversity in this study. 
Neighborhood adversity can be treated as a baseline factor that may either moderate treatment effects on 
morality or account as a baseline factor that may either moderate treatment effects on mortality or account for 
variance in our estimates of mortality by treatment condition. We plan to include data on maternal and offspring 
neighborhood adversity for study participants in treatment groups 1 and 3. A previous study, protocol #04-
0518, which is now closed, examined neighborhood adversity for participants in all three original trials. We will 
send participants’ baseline addresses in these groups at the time of registration in this trial to Geolytics, the 
firm we used to calculate neighborhood adversity at earlier phases of this study (the 04-0518 study 
mentioned). There was approval to evaluate neighborhood adversity scores in T2 and T4 in that protocol, but 
not T1 and T3. We would like to examine neighborhood adversity scores for all four treatment groups in this 
phase of the study. 
 
Interviews: The majority of subjects will be interviewed in person for Part Two; a small number of Part Two 
interviews will be conducted virtually. Subjects who complete virtual interviews for Part 2 will not be in the 
Memphis office and therefore will not be participating in the physical assessment. Registered nurses (RN) will 
interview participants directly on the components that are health related (systematic health histories, including 

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signs, symptoms, health care provider diagnoses of chronic diseases, history, medications, surgeries, 
hospitalizations). Other components of the interview may be conducted by other trained study staff. Some of 
the measures consist of repeated measures of outcomes examined in earlier phases of the trial. Others, 
focusing on key behaviors for this phase of follow-up are new measures appropriate to the life stages of the 
participants and the outcomes being examined. These include measuring physical activity and sedentary 
activity levels which influence disease risk, dietary assessments, and the PSQI for measurement of sleep. The 
study staff will also collect information on use of substances, depression, anxiety, sense of mastery, duration 
and quality of partnered relationships, education, work, and incarceration. We will assess the availability and 
source of medical care. This information will be used to make judgements about referrals (addressed below) in 
light of abnormal physical assessments and lab results. 
 
Sharing results of clinically relevant laboratory results and physical assessments with participants. We will 
share results of key physical health measurements at the time of assessment in the study office. Serious 
conditions reflective of imminent risk will be referred for emergency care (e.g. elevated BP). We will send the 
results of the clinically relevant urine and blood assays to subjects once results are analyzed, and encourage 
them to seek care if values exceed clinical cut-offs. If participants have no providers, we will refer them to their 
State Health Insurance program for help in gaining access to care. 
All biological analyses will be done in the Medpace Reference Laboratories. Overview: The following will be 
analyzed: Lipid Profile (TC, HDL, LDLc, TG), Chemistry Panel (AST, ALT, Serum Albumin and Serum 
Creatinine), eGFR (calculation), ALT/AST ratio (calculation), HbA1c, Urine Albumin/Creatinine, FSH, hsCRP, 
Fibrinogen, IL-6, TNF-alpha receptor 2 and IGF-1 (total). 
 
Data Processing. Blood and urine samples will be processed for storage on site in Memphis, stored at -80 
Celsius, and shipped weekly/bi-weekly to the Medpace Reference Laboratories, where the MedPace team will 
conduct standard assessments for the clinically relevant analytes as they are received. MedPace will only have 
unique codes which are not the same as study IDs and they will not have access to individual identifiers. They 
will send results to the University of Rochester as they are analyzed through Box; the UR team will be 
responsible for creating a work file for analysis and one of the RNs on the Rochester team will notify 
participants of the results of their clinically relevant blood and urine assays (e.g. lipid panel, HbA1c). 
Specimens for less commonly assayed analytes (those used for research purposes only - IL-6, TNF-alpha 
receptor 2, IGF-1) will be stored and assayed in batches. 
 
All interview data will be entered into REDCap by study staff and/or study participants. Physical assessment 
data will be entered into REDCap by the Memphis study staff, These data will be accessed by UR data 
management staff for the construction of data files. Signed consents to review medical and/or hospitalization 
records will be sent to the UR data processing team where they will process requests for records. Upon receipt 
of medical records, the UR team will code lengths of stay and I-CD 10 diagnoses. Biomarker and assessment 
results will be interpreted in light of self-reported diagnoses, medications, and medical/hospitalization records. 
Original singed consents and releases will be forwarded to and stored in Denver. 
Analysis 
Approach to Addressing Specific Aim One 
For Hypotheses 1-5, we will examine NV-C adjusted mean differences in the individual measures 
specified in each of the primary outcome domains, (as well as values that exceed clinical thresholds) 
employing statistical models described below in the Statistical Models and Methods section. For Hypothesis 6, 
we will employ survival analysis to examine differences. 
H1: Measures of Obesity, Fat, and Fat Distribution. We will compare NV and C participants on 
standard measures of BMI, waist and hip circumference, as well as segmental fat mass in arms, trunk, legs, 
and total body. Note that for assessments conducted outside of the Memphis office, we will resort to % total 
body fat. 
H2: Risks for Macrovascular Disease. We will compare NV and C participants on measures of 
arterial stiffness: peripheral systolic and diastolic BP (averaged over the two assessments), cfPWV, and AI. 

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H3: Markers of Chronic Kidney Disease (CKD). We will compare NV and C participants on the 
estimated Glomerular Filtration Rate (eGFR) and the microalbumin/creatinine ratio. 
H4: Metabolic Outcomes: We will compare NV and C participants on measures of Glycosylated 
Hemoglobin (HbA1C), dyslipidemia (TC, LDL, HDL, TG), and the AST/ALT ratio. 
H5: Immune/Inflammatory Markers: We will compare NV and C participants on immune/ 
inflammatory markers [hsCRP, fibrinogen, interleukin 6 (IL-6), tumor necrosis factor alpha-receptor 2 (TNF-2), 
and insulin-like growth factor-1 (IGF-1 – free and total]. 
H6: Mortality. We will compare NV and C participants on rates, ages, and causes of death. 
The interpretation of outcomes specified in H1-6 will take into consideration the presence of existing 
disease and disabilities, based upon interviews, records of medication, diagnoses, and hospitalization records. 
Approach to Specific Aim Two (Examine Moderators of Intervention Effects) 
As elaborated below, we will examine all outcomes in this study in statistical models that employ sex of 
offspring as a classification factor and maternal psychological resources cross-classified with Treatment 
condition (NV-C). We have hypothesized (H7) that intervention effects (H1-5) will be more pronounced among 
females and mothers who gave birth to females, so analyses of NV-C differences will focus on these groups. 
We have elaborated methods to address this aim under the statistical methods and models below. 
 
Approach to Specific Aim Three (Explore Mediators of NV Effects) 
We have hypothesized (H8) that NV effects on maternal primary outcomes will be mediated by 
earlier NV effects on the index of prenatal health behaviors, pregnancy outcomes (PIH in first births, preterm 
delivery), closely spaced subsequent pregnancies, sense of mastery, stable family structure following offspring 
birth, government benefit payments to the family, and hypertension at 12 and 18 years postpartum. We also 
have hypothesized (H9) that NV effects on offspring outcomes (H1-6) will be mediated, in part, by NV effects 
on the index of prenatal health behaviors, PIH, preterm delivery, breast feeding, maternal caregiving 
dysfunction (an index composed of maternal beliefs associated with child maltreatment and observed qualities 
of the home environment in the first 2 years of life), screen time at age 12, duration and quality of relationships, 
government benefit payments to the family, and obesity and prehypertension at ages 12 and 18. 
Data from current participant interviews on sedentary and physical activity, sleep, diet, use of 
substances (especially cigarette smoking), depression, anxiety, sense of mastery, chronic pain, 
stable/supportive partnered relationships, educational achievement, paid employment, health insurance, and 
incarceration will be used as sources of data to explore other potential mediators of NV effects. Among 
offspring, we will gather reports of pregnancies and births since last interview dates. These sources of data 
will be explored as possible additional mediators on NV effects. 
Statistical Models and Methods of Analysis 
The primary analyses will make use of general linear model methods and their extensions.89-94 The focus 
will be on (1) full model specification to account for all sources of variation, and full examination of interactions 
among model factors, including examination of homogeneity of regressions to understand interactions between 
classification effects and covariates; (2) generalized models to analyze dichotomous outcomes with binomial 
error distributions and count data assumed to have negative binomial distributions; (3) generalized linear mixed 
models (including repeated measures and growth-curve models) to account for correlated data and to examine 
differences in change over time; (4) semiparametric methods to model relations between variables without 
requiring a specific functional form;95 (5) survival analyses including Kaplan-Meier, competing risks and Cox 
hazard models; 96-99 (6) mediation analyses using structural equation models to examine causal processes, 
including the direct and indirect effects of treatment on outcomes. 100,101 
The primary classification factors for examination in our models, as determined by our hypotheses and 
earlier work, include treatments (Control vs. Nurse Visited - T), maternal psychological resources (low versus 
high based on a median split – P), sex of offspring (S), and follow-up time (A) for outcomes assessed at 
multiple time points (e.g. obesity) – T|P|S and T|P|S|A. Covariates will be selected using a post-double-
selection lasso (least absolute shrinkage and selection operator) procedure.102-104 This procedure will select 
covariates that are most related to intervention status (i.e. differences at randomization) or related to the 
dependent variable. Candidate covariates will include an index of household poverty, obesity, and maternal 

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pre-pregnancy BMI. 
 
Statistical Power/Smallest Detectable Differences for Proposed Follow-Up 
Given that sample size is fixed, we show below calculations of the smallest detectable treatment-control 
differences for the 29-year follow-up. Calculations for representative outcomes were carried out with the following 
assumptions: a Type I error of .05, Type II error of .20 (power of .80), 2-tailed tests, 10 percent of the variance 
accounted for by other terms in the model for normally distributed variables and N=600. Disproportionate sample 
sizes in Control and Nurse-Visited groups are taken into account. 
Smallest Detectable Program Effects. Table 6 displays the smallest detectable treatment differences. 
The study has sufficient power to detect small to moderate effect sizes for normally distributed variables for tests 
of treatment main effects (.24 SD) and moderate effect sizes (.33 SD) for tests conditioned by a single factor that 
is evenly distributed between two levels (e.g., offspring sex). For outcomes that are dichotomous, our calculations 
of smallest detectable treatment differences are calculated in the binomial logistic-linear model and shown for a 
range of base rates likely to be found in our outcomes. It is important to note that we have detected program 
effects of this magnitude in earlier phases of the trial and that we have seen that some intervention effects are 
larger as the mothers and offspring age. We will not make adjustments for multiple comparisons of the primary 
outcomes (Hypotheses 1-5), but will interpret findings with a critical eye concerning chance effects. 
Table 7. Smallest detectable treatment effects for treatment main effects and for subgroups defined by sex 
Base Rate for OR 
Smallest Detectable Treatment Contrasts for ORs 
Smallest Detectable Treatment Contrasts for ORs 
 
Whole Sample 
N=600 
One Half of Sample (e.g., Mothers of Females) 
N=300 
10% 
.33 
.14 
20% 
.49 
.33 
30% 
.55 
.42 
40% 
.59 
.46 
 
Smallest Detectable Treatment Contrasts for ESs 
Smallest Detectable Treatment Contrasts for ESs 
 
.24 
.33 
Note OR = T4 odds/T2 odds; ES = (T4 mean minus T2 mean)/pooled standard deviation 
 
Tests of Hypotheses 
Hypotheses 1-6 (primary): The NV group is hypothesized to have: H1: lower measures of obesity, 
(BMI, waist to hip ratios, segmental and % body fat, visceral fat); H2: lower risks for macrovascular 
disease, reflected in measures of functional arterial stiffness (peripheral BP, cfPWV, AI); H3: fewer 
markers of CKD - higher eGFR and lower microalbumin/creatinine ratios; H4: better metabolic outcomes 
(lower levels of HbA1C, TC, HDL, LDLc, TG, AST/ALT ratio); H5: lower levels of immune/inflammatory 
markers (hsCRP, fibrinogen, IL-6, TNF-alpha receptor 2, IGF-1); and H6: lower mortality rates. We will 
test Hypotheses 1-5 by examining each of the primary outcomes listed above as dependent variables in our 
primary T|P|S model, plus covariates from the post-double-selection lasso results. Outcomes also measured at 
earlier time points will include an additional classification factor for first-born offspring age at assessment (A). 
We will examine treatment–control difference summing across levels of maternal psychological resources and 
sex. In addition, we will examine planned contrasts for males and females, and mothers of males and females. 
Outcomes for hypotheses 1-5 are normally distributed and will be examined in the general linear model or mixed 
linear model for repeated measure outcomes. Secondary analyses will examine some outcomes in their 
dichotomous form for those values that cross clinical thresholds (e.g., obesity), which will be analyzed in the 
logistic model or generalized linear mixed model for repeated measure outcomes. 90 Hypothesis 6, related to 
mortality 6, will be examined in survival analysis by treatment condition without additional classification factors 
consistent with our earlier report on mortality.99,69 
Hypotheses 7: NV effects on H1-5 outcomes will be greater for female offspring and mothers who 
gave birth to females. Planned contrasts in the above aforementioned models for all primary outcomes, with 
the exception of mortality (given low base rates), will focus on female offspring and mothers of females. 
Hypothesis 8: NV effects on maternal outcomes (H1-6) will be mediated, in part, by NV effects on 
prenatal health behaviors, preterm delivery in first and subsequent births, and PIH in first births; closely 
spaced subsequent pregnancies, maternal sense of mastery, stable/supportive partnered 

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relationships, family economic resources, and hypertension at 12 and 18 years postpartum. H9: NV 
effects on offspring outcomes (H1-6) will be mediated, in part, by NV effects on prenatal health behaviors, 
preterm delivery, PIH, breast feeding, screen time at age 12, improved partner relationships, family 
economic resources through age 18, and obesity and prehypertension at ages 12 and 18. Tests of 
mediation will follow the empirical and theoretical model shown in Figures 1 and 2. We will employ mediation 
analyses using structural equation models to examine causal processes, including the direct and indirect effects 
of treatment on outcomes.100,101 To illustrate, we have hypothesized that NV will have an indirect effect on 
maternal arterial stiffness through its effect on PIH, preterm delivery, and the count of short inter-pregnancy 
intervals. To test one aspect of this hypothesis, we will regress maternal arterial stiffness on the count of closely 
spaced subsequent children (child density) within the control group; we also will regress child density on the 
treatment contrast. If the paths from the control sample to child density and from density to arterial stiffness are 
both significant, we will have met the joint significance test criterion. We will next calculate the indirect effect, 
based on these same two path coefficients, and compare the resultant z’ to Mackinnon’s table of critical values. 
If the z’ is equal to or higher than the appropriate critical value, we will conclude that density of subsequent 
children mediates the effect of nurse visitation on maternal arterial stiffness. We will use this approach for each 
hypothesized mediator separately and jointly to develop a map of mediation. 
Challenges in the Conduct of This Work 
Missing Data. Missing data in this trial have been remarkably low. We are sensitive to the potential 
pitfalls of analyzing only cases with complete data.105 We have complete data on all relevant background 
characteristics, which we will examine to address potential attrition bias. We also will compare our analyses to 
the same analyses employing inverse proportional weighting. We will perform sensitivity analyses to ensure that 
results are similar under various assumptions. We will determine whether imputation is valid and has sufficient 
added value with our data to justify the complexity involved in reporting these analyses. 
Increased Difficulty in Tracing and Engaging Participants. The most significant challenge to this work 
is attrition bias. While this problem is minimized for the mortality outcome, it is a challenge for those that depend 
on direct assessments. The best solution is to invest sufficient resources into locating and engaging participants. 
Note that this study: 1) employs the same local study leader (the wife of a local minister) who will continue to 
engage the sample; 2) refers participants for further evaluation and treatment for health problems; and 3) 
remunerates participants adequately for travel and time. These factors reduce participant attrition. 
Conducting Assessments among those Outside of the Memphis Region. We have chosen 
measures that, for the most part, can be assessed in both home and office, except for body fat and arterial 
stiffness, which creates possible cross-context challenges with validity and reliability, which we will examine as 
part of this study. 
Multiple Comparisons. If we were to make Bonferroni-like adjustments to our statistical tests in this 
study, the cost of conducting such studies with adequate power would be prohibitive, given the large number of 
outcomes examined over time. Our approach has been to make specific hypotheses for primary outcomes, look 
for coherence across outcomes, and to emphasize the importance of replication.106 This is a sensible strategy 
that in the long-run minimizes costs and accelerates scientific discovery. 
 
 
IV. RISK/BENEFIT ASSESSMENT 
 
1. Risk Category. Minimal risk. 
 
Potential Risk. Risk to participants for this study are expected to be minimal; these minimal risks will 
be minimized by using appropriate space and equipment, attending to all protocols/procedures, and 
providing adequate personnel selection, training, and supervision. The collection of questionnaire data 
has inherent risk to confidentiality, however prior to and during study implementation study personnel 
will be trained to follow protocols to minimize that risk. All study personnel will follow HIPAA regulations 
and be trained and certified in Human Subjects Protections by the relevant university or institution. We 
expect that most study activities will pose little discomfort or risk to subjects. If needed, this study will be 
able to refer to local support services. A blood draw is planned. In no instance will we collect more than 

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the allowable volume of blood (50 ml), based on consideration of body weight. Risks from blood draws 
are minimal and may include fainting, dizziness, ill feeling, and bruising during and/or after the blood 
draw and there is a low risk of infection. To minimize the risk trained nurses/phlebotomists will perform 
blood draws while participants are sitting or lying down. Collection of urine samples is done as a part of 
the standard of care and is not likely to cause distress. Measurement of weight and blood pressure is 
done as part of the standard of care and is not likely to cause distress. Bioelectrical impedance analysis 
is similar to standing on a scale and not likely to elicit additional distress beyond what weight 
measurement might. SphygmoCor EXCEL is not likely to elicit additional distress as it is a painless 
procedure. Anthropometric measurements of obese individuals may cause mild distress. To minimize 
this distress, the proposed assessments will be detailed during the consent process and confidentiality 
will be assured. Information will be provided to participants regarding the handling and the identification 
process involved with the data. Information that identifies subjects and subject number will be kept in 
the secure servers. Only study staff who have contact with participants will have access to this 
information. Note that the safety of the Tanita Body-Composition analyzer has not been established for 
pregnant women, so women who are pregnant or may be pregnant will not have this procedure 
conducted. 
 
The potential risks to the participants involve the breach of confidentiality. To the extent that the data 
gathered are divulged to those who are not involved in the data gathering and processing, the subjects 
are at risk for a breach of their confidentiality. The potential for this problem is reduced by the use of 
identification codes rather than names on the data collection forms, keeping the data and consent 
forms in locked file cabinets, and instituting procedures whereby breach of confidentiality by the data 
gathering and clerical staff is grounds for immediate termination. Individuals with access to the research 
data are the study staff located at the Memphis site, data management staff based in Rochester, NY, 
and the Colorado and Rochester-based programming and analysis staff, along with study PIs. All 
computers will be password protected. Data files will be encrypted during transfer between 
organizations (e.g. Rochester and Colorado) and stored on servers only accessible to those mentioned 
above and who have undergone Human Subjects Training. Note that the Tanita body-composition 
analysis will not be conducted with pregnant women or women who may be pregnant. 
 
Respondent Boredom/Fatigue. The time for data- collection may seem long to some participants. 
Based on our experience at the 18 year follow-up, total expected time required for the assessment is 
approximately 2.5 hours which will be acceptable to participants given that prior follow-up assessments 
have been of comparable length. Nevertheless, some participants may experience boredom or fatigue. 
 
Abnormal BP measurements may indicate a serious health problem. 
Protection against Risks. Risks to the participants will be fully explained during the informed consent 
process and repeated as needed during data collection activities. All study personnel will undergo 
extensive, standardized training and certification with ongoing quality control monitoring. We will 
adhere to strict data storage and confidentiality procedures to ensure the privacy and confidentiality of 
the participants. Only trained phlebotomists/nurses will collect blood samples and only trained study 
team members will have contact with the subjects. To address concerns about psychological issues 
(including anxiety and depression), all individuals will be informed about mental health services that are 
available and will be encouraged to discuss concerns that they may have with their mental health with 
their clinicians. Wherever possible, the study will make use of existing resources. 
Interviewers/researchers will be familiar with clinic resources and will be trained in the administration of 
the questionnaire measures. If patients are highly distressed or show signs of serious depression or 
psychiatric illness during the study, they will be referred for help through their local county mental health 
services. Disclosure of child abuse or neglect revealed during the study or observed by study staff will 
be referred to Child Protective Services in the county in which the child (or parent) lives. Reporting of 
child abuse or neglect may have psychological and legal ramifications for the family; we will manage 
any potential disclosures in cooperation with local child welfare services. If an individual reports being 

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a victim of domestic violence, they will be referred to domestic violence services in the county in which 
they live. If study staff is concerned about any information shared by a prisoner participant regarding 
the possibility of self-harm or harm to others, study staff will inform the prison warden or his/her 
designee via telephone call and will document this call. 
 
Boredom/fatigue risk. This risk will be reduced by: 1) respecting participants’ time and contribution; 2) 
creating a comfortable, welcoming environment; 3) providing a clear explanation of procedures and 
length of time required during the recruitment, scheduling, and consenting processes; 4) providing 
transportation and remuneration to participants to reduce associated stress; 5) varying the activities 
within the assessment; 6) providing a break/refreshment time in the middle of the session; and 7) 
offering the opportunity for additional breaks or terminating the assessment. 
 
If the blood pressure readings are abnormally high, defined as average systolic BP (SBP) readings 
greater than or equal to 180 mmHg and/or an average diastolic (DBP) readings greater than or equal to 
110 mmHg), participants will have their blood pressure re-checked and assessed by a RN. Participants 
will be provided with a handout indicating their blood pressure measurements and advised to follow up 
with their primary care provider or the emergency department as soon as possible. If the subject does 
not have a primary care provider a referral will be provided. 
 
2. Potential Benefits to the Subjects. The participants themselves will receive no direct benefit from this 
study, although those with potential health problems identified during the course of the assessment will 
be encouraged to seek further evaluation and treatment through existing health and human services in 
their community. 
 
Confidentiality of Data and Computer Records for all Coordinating Sites. It is important to note that 
this study will be conducted in collaboration with the University of Rochester (FWA00009386), and the 
Medpace Reference Laboratories; and, directly obtained participant data will be collected under the 
oversight of University of Rochester investigators in a Project controlled office in Memphis, Tennessee. The 
Medpace Reference Laboratories will not have access to individual identifiers. In all sites, staff given 
access to the data will have all human subjects training up to date and have read and agreed to everything 
in the confidentiality agreement. A log will be kept of any staff granted access to the data. We will take the 
following steps to protect the confidentiality of our data and computer records: 
x 
All study staff will receive extensive training in maintaining participant confidentiality.
x 
Identification codes rather than names will be used on all data collection forms and data transfers.
x 
The handling of data generally will be limited to the numerical values and statistical summaries.
x 
The identifiers linking identification codes with individual names are only available to the Memphis staff, 
Rochester staff and PI and co-PIs. They will be kept in a secure database on an encrypted server.
< 
 PHI is stored in File Maker Pro 18 which is maintained by the University of Rochester 
School of Nursing. This same software has been used to store participants PHI for past 
phases of the Memphis New Mothers Study. FileMaker Pro: University of Rochester, 
School of Nursing runs a FileMaker Pro (FMP) 18 server that is used for protecting 
Protected Health Information (PHI) (including name, phone number, email address, home 
address, and Social Security Number (SSN)). This database will hold the link between 
participant ID and actual identity and is designed to ensure that authorized users have 
minimal data access as possible in their roles. 
x 
Only those who need to assess PHI information will have access granted by their login 
name privilege set. Usernames and passwords are managed by Rochester study office and 
a list of usernames and allowable PHI access will be obtained on a log in Rochester study 
office.
x 
The FileMaker server is housed in the UR Medical Center's internal network, which is 
protected from the public Internet by firewalls, along with the UR Medical Center's electronic

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health record and other restricted assets. The server runs Cylance anti-virus and is backed 
up nightly with 30 days' retention with replication to a off-site facility. 
x 
Consents and any data collection forms that are in paper format will be stored in a locked file drawer, in 
a room that is locked when it is unoccupied.
x 
 Data collection forms will be shredded when they are no longer relevant (e.g., after entered into 
REDCap).
x 
To ensure that data are not co-mingled with data from other projects, data will be stored in its own 
subdirectory with access only granted to individuals approved to work on this project.
x 
The data received will not be used for purposes other than what is described in this application, or 
consented to for future research by study participants.
o Personal computers will be logged off at the end of each work day to prevent inadvertent access 
to the network and to data stored on the computer hard drive. 
o A screensaver password will be engaged during the day to prevent people from accessing data 
while individuals are out of the office. 
o An access control list through arrangements with network administrators will be used to limit the 
number of people who have permission to access the network subdirectory where sensitive data 
are stored. 
o Consideration may be given to storing sensitive data only on the secure network when it is 
being analyzed. More permanent storage would then be on an encrypted drive on a server at 
the University of Rochester. . 
o Sending sensitive data via email will be minimized. 
o Email within the University of Rochester and University of Colorado is automatically 
encrypted 
o All data transfers will be done via Box (from Memphis to UR; from UR to Colorado; from 
Medpace to UR). See flow chart at end of document. 
 
x 
Confidentiality of Data and Computer Records Specific to Denver
< 
Physical Control. Paper associated with study PHI will be stored in a locked cabinet in our 
locked file room which is accessible to a very limited number of people who must use their ID 
badge to electronically unlock the door. During non-work hours the building itself is locked and 
an ID badge is required for admittance. All output that is identifiable will be recycled using a 
protocol for sensitive data (i.e. put in a locked trash container in a secure room and ultimately 
shredded by a company that deals with sensitive data). 
< 
Technical Control. Data will be stored on the University of Colorado network on a drive called 
"Sensitive" which has very limited access (i.e. one statistician and the data coordinator). 
Programs and output will be on the same "Sensitive" shared drive. No identifiable data will be 
stored outside of this Sensitive drive. 
< 
Administrative control. As part of the university network the Office of Information Technology 
provides an enterprise level backup service for backup of data. Data on the server are backed 
up the night the file is first created; As the file is modified, each revision of that file is also 
backed up and is kept for 30 days; At day 31, the earliest revision is removed from the backup 
environment; The last copy of the file is kept (assuming no additional modifications) until it is 
deleted from the server; Secondary of backup data is retained off-site for disaster recovery 
purposes. 
x 
Confidentiality of Data Specific to University of Rochester, the Memphis Study Office, and the Medpace 
Reference Laboratories. The use of the following modalities ensures secure transfer of data between 
Memphis where the data are gathered and University of Rochester where the data are processed and 
stored and the finished file sent to University of Colorado.
< 
University of Rochester School of Nursing’s Windows File Server – This is the site where 
information private to Memphis/SON will be stored. Connection to it from a non-direct site 
requires use of the University of Rochester Medical Center (URMC) VPN (Cisco AnyConnect, 
which requires Duo multi-factor authentication). This server is in the University of Rochester’s 

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Primary Data Center, which provides adequate physical security controls to meet its Electronic 
Medical Record requirements. 
< 
Memphis Computers — All of the desktop and laptop PCs will be secured to meet URMC 
standards: managed full disk encryption (Microsoft BitLocker) plus anti-virus (Cylance). 
< 
Memphis Network — We have a permanent VPN in place between the Memphis network and 
the URMC network to protect data in motion. 
x 
REDCap — The University of Rochester manages a REDCap database instance. Access to the site 
requires HTTPS / TLS transport security. This service is also hosted in the University of Rochester’s 
Primary Data Center.
x 
Box — University of Rochester has a HIPAA BAA with Box for storage of data and sharing with 
collaborating institutions / researchers. This is the University of Rochester’s preferred method of 
transporting data electronically. BOX is the primary place where information is to be shared, 
between Memphis (Rochester employees), University of Rochester, MedPace, and University of 
Colorado. Box protects the data during transmission by HTTPS / TLS security. Strict, streamlined 
procedures will be followed regarding data transmission and its confirmation.
o Memphis staff will upload data into Box at the end of each data collection day and send 
confirmation to Rochester staff on identification codes uploaded. Rochester staff will be 
responsible for confirming receipt of data by identification codes and the transfer of data from 
BOX to the University of Rochester file server. All files will be removed from BOX once files 
transfer is complete. A similar process was in place at the 18 year follow up between the 
Memphis office and the University of Rochester. 
o Memphis staff will ship blood and urine samples to the Medpace Reference Laboratories 
labeled by an identification number that is different from the main study identification number 
used in data collection. MedPace staff will transfer blood and urine results to the University of 
Rochester in Box. Rochester staff will be responsible for confirming receipt of data by 
identification codes and the transfer of data from BOX to the University of Rochester file server. 
All files will be removed from BOX once file transfers are complete. 
o University of Rochester will upload the final analysis file via BOX to the University of Colorado 
using the same process. 
o University of Rochester Box will have separate shares with the Memphis office, Medpace 
Reference Laboratories, and University of Colorado with separate permissions. 
 
Data and Safety Monitoring Plan 
Monitoring: We have created an independent Data Safety Monitoring Board (DSMB) consisting of 
Allison Kempe, M.D., Professor of Pediatrics at the University of Colorado, Zhaoxing Pan, 
biostatistician from The Children’s Hospital Research Institute in Denver, and Sara Brewer. MPA, 
instructor, Department of Family Medicine, and chair of the DSMB. This group will meet as needed (and 
at least yearly) to review any reports of untoward events and to monitor their resolution. At the stage of 
analysis and interpretation of data from the next phase of follow-up, this group will meet with the 
principal investigators and members of our biostatistical team to review the findings to determine 
whether there are any negative side effects. Minutes will be kept of the meeting and following DSMB 
meetings, the results of the meeting concerning possible negative side effects will be documented by 
Ms. Brewer and sent to the PIs and appropriate NIH staff, or other appropriate institutions depending 
upon the nature of risk identified. 
 
Management of Untoward Events 
How an “Untoward Effect” May Be Discovered: 
x 
Data analysis uncovers treatment effects with higher rates of adverse events or outcomes in the 
nurse-visited groups compared to the control groups. While statistically significant differences 
may not pose a problem for individuals, the possibility of adverse program effects needs to be 
considered carefully. 
x 
Staff member discovers that participant personal health information has been revealed to 
individual or group who does not have permission for this information. 

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x 
Participant verbalizes or displays high level anxiety or fear to the interviewer or other staff 
member regarding research procedures. 
How an Untoward Effect Will Be Reported: 
x 
At the stage of data analysis, data analysts and investigators will keep a log of any test of 
treatment contrasts that produce statistically significant effects in the unexpected direction, or a 
pattern of trends in the unexpected direction. The Data Safety Monitoring Board group will meet 
with the principal investigators and members of our biostatistical team to review the findings to 
determine whether there are any negative side effects. Following the DSMB meeting, the results 
of the meeting concerning possible negative side effects will be documented by Ms. Sara 
Brewer (a member of our Data-Safety Monitoring Board) and sent to the PIs, the IRB, and 
appropriate NIH staff. 
x 
Any breach of confidentiality is cause for termination. Breaches of confidentiality will be 
identified and reported to the DSMB and IRB by the PI whenever they occur. The DSMB will 
report these infractions to the IRB and NIH. 
x 
Instances of extreme anxiety or fear will be noted in a confidential log and reported to the PI, 
who in turn will report this information to the DSMB. A record of these problems will be 
submitted to the IRB. Referral of Cases for Further Evaluation and Treatment: Should an 
Untoward Event occur, the data gathering staff in Memphis will discuss the untoward event with 
their supervisor, who will make an appropriate referral for further evaluation and treatment within 
the health and human service delivery system in Memphis. The Memphis leadership staff 
members have been with the study for nearly 15 years and are well-positioned to evaluate and 
make appropriate community referrals, given the types of untoward effects that may occur in 
this study. 
Follow-up and Referral: The PI will be informed of all reported adverse outcomes, including who is 
referred for further evaluation and treatment and the outcomes. 
Confidentiality: The PI will maintain information on monitoring untoward events, but will do so without 
specific patient identifiers. 
 
Implementation of Monitoring Recommendations: The monitoring board will review cases and make 
written recommendations to the PI and investigative team regarding safety procedures and the 
procedures employed in the study to ensure participant safety. These recommendations will be 
reviewed at special meetings of investigators and research team members to institute any changes in 
procedures that would improve participant safety and that would ensure that they receive appropriate 
treatment and follow-up in a timely way. 

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Version Date: 
06/05/2024 
 
 
 
 
 
 
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1. Carnethon MR, Pu J, Howard G, et al. Cardiovascular health in African Americans: A scientific statement 
from the American Heart Association. Circulation. 2017;136(21):e393-423. 
 
2. Cunningham TJ, Croft JB, Liu Y, Lu H, Eke PI, Giles WH. Vital signs: Racial disparities in age-specific 
mortality among blacks of African Americans – United States 1999-2015. MMWR Morb Mortal Wkly Rep. 
2017;66(17):444-56. 
 
3.  Mozaffarian D, Benjamin EJ, Go AS, et al. Heart Disease and Stroke Statistics-2016 Update: A report 
from the American Heart Association. Circulation. 2016;133(4):e38-e360. 
4.  Menke A, Casagrande S, Geiss L, Cowie CC. Prevalence of and trends in Diabetes among adults in the 
United States, 1988-2012. JAMA. 2015;314(10):1021–1029. 
 
5. United States Renal Data System. 2014 USRDS annual data report: Epidemiology of kidney disease in 
the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney 
Diseases: Bethesda, MD, 2014. 
6.  Havranek, EP, Mujahid, MS, Barr, DA, et al. Social determinants of risk and outcomes for cardiovascular 
disease: A scientific statement from the American Heart Association. Circulation. 2015;132(9):873-898. 
 
7.  Pool LR, Ning H, Lloyd-Jones DM, Allen NB. Trends in racial/ethnic disparities in cardiovascular health 
among US adults from 1999-2012. J Am Heart Assoc. 2017;6(9):e006027. 
 
8. Bancks MP, Kershaw K, Carson AP, Gordon-Larsen P, Schreiner PJ, Carnethon MR. Association of 
modifiable risk factors in young adulthood with racial disparity in incident Type 2 Diabetes during middle 
adulthood. JAMA. 2017;318(24):2457–2465. 
 
9. Signorello LB, Schlundt DG, Cohen SS, et al. Comparing diabetes prevalence between African Americans 
and Whites of similar socioeconomic status. Am J Public Health. 2007;97(12):2260–2267. 
10. Norton JM, Moxey-Mims MM, Eggers PW, et al. Social determinants of racial disparities in CKD. J Am Soc 
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11. Stuart-Shor EM, Berra KA, Kamau MW, Kumanyika SK. Behavioral strategies for cardiovascular risk 
reduction in diverse and underserved racial/ethnic groups. Circulation. 2012;125(1):171–184. 
 
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outcomes: A scientific statement from the American Heart Association. Circulation. 2018;137(5):e15-28. 
13. Slopen N, Loucks EB, Appleton AA, et al. Early origins of inflammation: An examination of prenatal and 
childhood social adversity in a prospective cohort study. Psychoneuroendocrinology. 2015;51:403-13. 
 
14. Loria AS, Ho DH, Pollack JS. A mechanistic look at the effects of adversity early in life on cardiovascular 
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15. Alexander BT, Dasinger JH, Intapad S. Fetal programming and cardiovascular pathology. Compr Physiol. 
2015;5(2):997-1025. 

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16. Mor G, Cardenas I. The Immune System in Pregnancy: a unique complexity. Am J Reprod Immunol. 
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17. Brunton PJ, Russell JA. Endocrine induced changes in brain function during pregnancy. Brain Res. 
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18. Fisher C, MacLean M, Morecroft I, et al. Is the pregnancy hormone relaxin also a vasodilator peptide 
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19. Sanghavi M, Rutherford JD. Cardiovascular physiology of pregnancy. Circulation. 2014;130(12):1003-8. 
 
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21.  JE, Kim P, Spicer J, et al. Approaching the biology of human parental attachment: brain imaging, oxytocin 
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22.  Faraji J, Karimi M, Soltanpour N, et al. Intergenerational sex-specific transmission of maternal social 
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23.  Wan L, Tu T, Zhang QL, Jiang J, Yan XX. Pregnancy promotes maternal hippocampal neurogenesis in 
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period: links to maternal caregiving and mental health. Arch Womens Ment Health. 2019;22(2):289–299. 
25. Zhang S, Ding Z, Chen Z, et al. Association between mental stress and gestational 
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26. Ying W, Catov JM, Ouyang P. Hypertensive disorders of pregnancy and future maternal cardiovascular 
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27. Bergen NE, Schalekamp-Timmermans S, Roos-Hesselink J, Roeters van Lennep JE, Jaddoe VVW, 
Steegers EAP. Hypertensive disorders of pregnancy and subsequent maternal cardiovascular health. Eur 
J Epidemiol. 2018;33(8):763-771. 
 
28. Grandi SM, Filion KB, Yoon S, et al. Cardiovascular disease-related morbidity and mortality in women with 
a history of pregnancy complications. Circulation. 2019;139(8):1069–79. 
 
29. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and 
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31. Xu J, Barinas-Mitchell E, Kuller LH, Youk AO, Catov JM. Maternal hypertension after a low-birth-weight 
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33. Gaillard R. Maternal obesity during pregnancy and cardiovascular development and disease in the 
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34. Mamum AA Kinarvala MK, O’Callaghan M, Williams G, Jajman J, Callaway L. Does hypertensive disorder 
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35. Kajantie E, Erikson JG, Osmond C, Thornburg K, and Barker DJ. Pre-eclampsia is associated with 
increased risk of stroke in the adult offspring: The Helsinki birth cohort study. Stroke. 2009;40(4):1176-
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36. Smith CJ, Ryckman KK, Barnabei VM, et al. The impact of birthweight on cardiovascular disease risk in 
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37. Doom JR, Mason SM, Suglia SF, Clark CJ. Pathways between childhood/adolescent adversity, 
adolescent socioeconomic status, and long-term cardiovascular disease risk in young adulthood. Soc Sci 
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38. Gebreab SY, Rouox AV, Brenner AB, et al. The impact of lifecourse socioeconomic position on 
cardiovascular disease events in African Americans: the Jackson Heart Study. J Am Heart Assoc. 
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39. Danese A, Moffitt TE, Harrington HL, et al. Adverse childhood experiences and adult risk factors for age-
related disease: Depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolsec 
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40. Suglia SF, Clark CJ, Boynton-Jarrett R, Kressin NR, Koenen KC. Child maltreatment and hypertension in 
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41. Garad Y, Maximova K, MacKinnon, McGrath JJ, Kozyrskyj, Colman I. Sex-specific differences in the 
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42. Murphy MO, Herald JB, Leachman J, Tezanos AV, Cohn DM, Loria AS. A model of neglect during 
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43. Wainstock T, Shoham-Vardi I, Glasser S, Eyal Anteby E, Lerner-Geva L. Fetal sex modifies effects of 
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44. Barrett ES, Swan SH. Stress and androgen activity during fetal development. Endocrinology. 
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45. Shiozaki A, Matsuda Y, Satoh S, Saito S. Impact of fetal sex in pregnancy-induced hypertension and 
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46. Taylor BD, Ness RB, Klebanoff MA, Tang G, et al. The impact of female fetal sex on preeclampsia and the 
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47. Jaskolka D, Retnakaran R, Zinman B, Kramer CK. Fetal sex and maternal risk of pre-
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48. Valdiviezo C, Garovic, VD, Ouyang, P. Preeclampsia and hypertensive disease in pregnancy: Their 
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49. Davis EF, Lazdam M, Lewandowski AJ, et al. Cardiovascular risk factors in children and young adults 
born to preeclamptic pregnancies: A systematic review. Pediatrics. 2012;129(6):e1552-e1561. 
 
50. Daniels SR, Pratt CA, Hayman LL. Reduction of risk for cardiovascular disease in children and 
adolescents. Circulation. 2011;124(15):1673-86. 
51.  Daniels SR, Pratt C, Holister EB, et al. Promoting cardiovascular health in early childhood and transitions 
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52.  Van Buren DJ, Tibbs T. LIfestyle interventions to reduce diabetes and cardiovascular disease risk among 
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53.  Sung-Chan P, Sung YW, Zhao X, and Brownson RC Family-based models for childhood-obesity 
intervention: a systematic review of randomized controlled trials. Obesity Reviews. 2013;14:265-278. 
 
54.  Loveman E, Al-Khudairy L, Robertson W, et al. Parent-only interventions for childhood overweight or 
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55. Campbell F, Conti G, Heckman JJ, et al. Early childhood investments substantially boost adult health. 
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56. Brody, GH, Yu, T, Miller, GE, Ehrlich, KB, Chen, E. Preventive parenting intervention during childhood and 
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57. Olds DL. Prenatal and infancy home visiting by nurses: From randomized trials to community replication. 
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59.  Olds D, Henderson CR Jr, Tatelbaum R, Chamberlin R. Preventing child abuse and neglect: A 
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61.  Olds D, Henderson CR Jr, Cole R, et al. Long-term effects of nurse home visitation on children’s criminal 
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62.  Eckenrode J, Campa M, Luckey DW, et al. Long-term effects of prenatal and infancy home visitation on 
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63.  Kitzman H, Olds DL, Henderson CR Jr, et al. Effect of prenatal and infancy home visitation by nurses on 
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64.  Kitzman H, Olds DL, Sidora K, et al. Enduring effects of nurse home visitation on maternal life course: A 
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65.  Olds DL, Kitzman H, Cole R, et al. Effects of nurse home visiting on maternal life-course and child 
development: Age-six follow-up of a randomized trial. Pediatrics. 2004;114(6):1550-1559. 
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67.  Kitzman H, Olds DL, Cole RE, et al. Enduring effects of prenatal and infancy home visiting by nurses on 
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68.  Olds DL, Kitzman H, Cole R, et al. Enduring effects of prenatal and infancy home visiting by nurses on 
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70. Kitzman H, Olds DL, Knudtson MD, et al. Enduring effects of prenatal and infancy home visiting by nurses 
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72. Conti G, Kitzman H, Smith JA, Olds DL. Effects of prenatal/Infancy home visiting on maternal and 
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98. Gray RJ. A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat. 
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among high-dimensional controls. Rev Econ Stud. 2014;81(2):608-650. 
 
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problems. IMA J Numerical Analysis. 2000;20:389–404. 
 
105. Little RJA, Rubin DB. Statistical analysis with missing data, 2nd ed. New York, NY:John Wiley and 
Sons;2002. 
106. Olds DL, Kitzman K, Anson E, et al. Prenatal and infancy nurse home visit effects on mothers: 18-
year follow-up of a randomized trial. In Reply Pediatrics. 2019. 
 
107. Cheng, S. The accumulation of (dis)advantage: The intersection of gender and race in the long-
term wage effect of marriage. Am Sociol Rev. 2016;81(1):29–56. 
108. Waite, LJ. Does marriage matter? Demography. 1995;32:483–508. 
 
109. Ludwig, V., Brüderl, J. Is there a male marital wage premium? New evidence from the United 
States. Am Sociol Rev. 2018;83(4):744–770. 
110. Barr, AB, Culatta, E, & Simons, RL. Romantic relationships and health among African American young 
adults: Linking patterns of relationship quality over time to changes in physical and mental health. J 
Health Soc Behav. 2013;54(3):369–385. 

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Page 35 of 37
Protocol # 20-079
Version Date:
06/05/2024
SymphCor-BP 
ID#
4
Memphis Data 
Collection & 
Processing
Memphis 
uploads file 
daily to UR 
BOX ID#
Data to 
analysis file 
ID#
UR retrieves data from UR 
BOX daily and downloads to 
UR server, deletes data from 
UR BOX
Redcap
Part 1 Interview-ID#
Part 2 Interview-ID#
Redcap
Data saves to UR
server at 
completion of 
interview
Data to 
analysis file 
ID#
Biospecimens 
Unique Code-
MedPAce assigns 
to tubes for 
Blood/Urine
Memphis RN 
enters Unique 
code in FMP 
Ships to MedPace
MedPace 
uploads 
results to UR 
BOX by 
Unique code
UR RN retrieves 
data from UR 
BOX and 
downloads to UR 
server, deletes 
data from UR 
BOX
UR RN links 
Unique
code to 
Study PHI
to send out 
results letter
UR RN
replaces 
Unique code 
with ID#, for 
Blood/Urine 
results dataset
Data to 
analysis 
file
ID#
Tanita-Body Fat 
ID#
Memphis 
uploads file 
daily to UR 
BOX ID#
UR retrieves data from UR 
BOX daily and downloads to 
UR server, deletes data from 
UR BOX
Data to 
analysis file 
ID#

Page 36 of 37
Versio
e:
06/05/2024
Protocol # 20-0794
Clerk enters 
updated PHI and 
SSN’s into FMP
n Dat
Memphis Data PHI
Evelyn 
Collins/Recruiter 
obtains PHI from 
FMP to contact 
participant via 
phone, email
Evelyn Collins/Recruiter 
prints out PHI on letters 
and envelopes from FMP 
to mail participants 
recruitment letter
Evelyn 
Collins/Recruiter 
schedules Part 1
Interview
Evelyn 
Collins/Recruiter 
obtain PHI from 
FMP to send 
reminder for Part 1
Interview
Add 
payment 
process 
Part 1
Interview
PHI and SSN exported and 
password protected file 
transferred to Denver Study 
Office via BOX for purpose of 
obtaining administrative data
Clerk shreds 
CONTACT 
FORM.
Documents entry 
and destruction 
in FMP
Part 2 Interview
Interviewer obtains updated
PHI (addresses, phone 
numbers) on CONTACT 
FORM, and SSN’s for 
participant’s biological children
Evelyn Collins/Recruiter 
obtains PHI from FMP to 
contact participant to 
schedule Part 2 Interview
Evelyn 
Collins/Recruiter 
obtain PHI from FMP 
to send reminder for 
Part 2 Interview
Add payment 
process Part 2
Interview
Part 2 Interview
Evelyn Collins reviews
consent and release forms 
with participant, obtains 
signature
Clerk provides copy of consent 
and release forms to 
participant, documents in FMP
Clerk mails original signed consent 
and release forms to Denver Study 
Office where stored in locked file 
cabinet, documents in FMP