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OBJECTIVES:

Given earlier effects found in randomized clinical trials of the Nurse-Family Partnership, we examined whether this program would improve 18-year-old first-born youths' cognition, academic achievement, and behavior and whether effects on cognitive-related outcomes would be greater for youth born to mothers with limited psychological resources (LPR) and on arrests and convictions among females.

METHODS:

We enrolled 742 pregnant, low-income women with no previous live births and randomly assigned them to receive either free transportation for prenatal care plus child development screening and referral (control; n = 514) or prenatal and infant home nurse visit (NV) plus transportation and screening (n = 228). Assessments were completed on 629 18-year-old first-born offspring to evaluate these primary outcomes: (1) cognitive-related abilities (nonverbal intelligence, receptive language, and math achievement) and (2) behavioral health (internalizing behavioral problems, substance use and abuse, sexually transmitted infections, HIV risk, arrests, convictions, and gang membership).

RESULTS:

Compared with control-group counterparts, NV youth born to mothers with LPR had better receptive language (effect size = 0.24; 95% confidence interval [CI]: 0.00 to 0.47; P = .05), math achievement (effect size = 0.38; 95% CI: 0.14 to 0.61; P = .002), and a number of secondary cognitive-related outcomes. NV females, as a trend, had fewer convictions (incidence ratio = 0.47; 95% CI: 0.20 to 1.11; P = .08). There were no intervention effects on other behaviors.

CONCLUSIONS:

The program improved the cognitive-related skills of 18-year-olds born to mothers with LPR and, as a trend, reduced female convictions but produced no other effects on youth behavioral health.

What’s Known on This Subject:

Two randomized trials of prenatal and infant home visit by nurses found effects on children’s behavioral problems, early adolescent substance use, and among children born to mothers with limited psychological resources, cognitive outcomes. One trial found fewer convictions among females.

What This Study Adds:

This trial extends earlier estimates of intervention impact: compared with control-group counterparts, nurse-visited 18-year-olds born to mothers with limited psychological resources exhibited better cognitive functioning; females, as a trend, had fewer convictions. There were no significant effects on behavioral health.

The potential of early intervention to improve the lives of children born into disadvantaged families has gained considerable attention.1,2  Pregnancy and the early years of life are opportune times to intervene because of significant neuroendocrine changes in mothers, developing fetuses, and young children.3,4  Prenatal and early childhood exposures to toxicants, maltreatment, and stress are thought to amplify one another over time, contributing to compromised life-course development and making this an opportune time to intervene to improve vulnerable children’s development.5  Our team has been conducting a series of pragmatic randomized clinical trials (RCTs) of a program of prenatal, infant, and toddler home visiting by nurses for low-income mothers and their children known as the Nurse-Family Partnership (NFP).620  The current study assesses 629 primarily African American first-born 18-year-old youth whose mothers participated in the second RCT of NFP in Memphis, Tennessee.1117 

Findings from the current trial1116  and NFP trials conducted earlier in Elmira, New York,610  and later in Denver, Colorado,1820  led us to hypothesize that NFP would improve 18-year-old youth language, cognition, and math achievement and that effects in this broad domain would be most pronounced for youth born to mothers with limited psychological resources (LPR) to cope with adversity: in the lower half of the distribution on an index composed of maternal intellectual functioning,21  mental health,22  and sense of mastery23  plus self-efficacy (mothers’ beliefs about the importance of and her confidence in accomplishing key NFP behavioral objectives)24  measured at baseline.11 

Given NFP effects on substance use and antisocial behavior through age 15 among youth born to disadvantaged mothers in the Elmira trial9  and substance-use and internalizing disorders in the current trial at age 12,15  we hypothesized that the program would reduce 18-year-olds’ internalizing disorders, substance use, and abuse disorders. In light of intervention effects on the number of lifetime sex partners through age 15 among youth born to disadvantaged mothers in Elmira9  and anticipated effects on substance abuse disorders in the current trial, we hypothesized that nurse visited (NV) 18-year-olds would have fewer pregnancies and births and a lower risk for HIV. Given NFP effects on arrests, convictions, and violations of probation among 15-year-olds born to disadvantaged mothers in the Elmira trial9  and substance use at age 12 in the current trial,15  we hypothesized that the program would reduce rates of gang membership, arrests, and convictions among 18-year-olds.

Before analysis of intervention-control differences, we found that program effects on arrests and convictions in Elmira were limited to females through age 19,10  leading us to hypothesize the presence of corresponding female effects in Memphis. Also, given the presence of little meaningful variation in neighborhood disadvantage (2.4 SDs above the national mean25 ), we eliminated, before analysis of intervention effects, a hypothesis that program effects would be greater among youth whose mothers lived in the most distressed neighborhoods at registration.

The basic features of this study have been reported earlier.11  We conducted this RCT in a public system of obstetric and pediatric care in Memphis, Tennessee, with registration of the original sample completed between June 1990 and August 1991. Given that program effects were more pronounced for mothers and children from more disadvantaged families in the preceding trial,610  we focused sampling in Memphis on those with overlapping sociodemographic risks. We enrolled women <29 weeks’ gestation with no previous live births and at least 2 sociodemographic risks (unmarried, <12 years of education, or unemployed). Ninety-two percent of the women were African American, and at enrollment, 98% were unmarried, 64% were <18 years of age, and 85% were from households with incomes below the federal poverty guidelines. For the current follow-up, participating mothers, other caregivers, and youth completed informed consent procedures approved by the University of Rochester Institutional Review Board.

Table 1 summarizes the Consolidated Standards of Reporting Trials information. Eighty-eight percent (n = 1138) of 1289 eligible pregnant women who were offered participation completed informed consent and were randomly assigned to 1 of 4 treatment conditions following a procedure that concealed assignment from individuals involved in gathering participant data.11  We assigned 742 participants to 2 treatment conditions created to estimate program effects on postnatal outcomes: 514 to Treatment 2 (control) and 228 to Treatment 4 (NV), both described below. Sample size and assignment ratios were derived from statistical power calculations in the original phase of the trial.11 Table 1 shows those lost to follow-up because of miscarriage or child death, maternal or child refusal to participate at earlier phases, and the number evaluated with youth assessments and maternal and/or other-custodian interviews at youth age 18.

Interviews for this follow-up were conducted between October 2008 and September 2014, and reviews of school records were conducted by December 2015 by staff masked to treatment assignment. Most assessments were conducted after youth 18th birthdays (mean age 18.67 years; SD = 0.95; range: 17.5–23.9). Repeated measures of some outcomes over time increased the numbers and are noted by “all” under the column "Child Age ge at Assessment” in Tables 3 and 4.

Interviews were completed with 629 of the 669 available youth. Interviews were conducted with mothers and other caregivers to augment youth report of arrest outcomes (n = 621) and externalizing and total behavior problems (n = 615) and to determine Supplemental Social Security Income (SSI) for disability (n = 619). High school graduation records were collected for 619 youth, and urine was collected for 606 youth.

Women in the control group (n = 514) were provided with free transportation for scheduled prenatal care plus developmental screening and referral for children at 6, 12, and 24 months of age. Women in the NV condition (n = 228) were provided with the same services as the control group plus prenatal and infancy home visitation through age 2.

NFP was designed to (1) improve pregnancy outcomes by promoting women’s prenatal health behaviors, (2) improve children’s health and development by promoting parents’ care of their children, and (3) enhance parents’ health and life course by encouraging women to plan the timing of subsequent pregnancies, complete their educations, and find work. Nurses linked families with needed services and, when possible, involved other family members (especially children’s fathers and grandmothers).5  Program protocols were grounded in developmental epidemiology and theories of human attachment, human ecology, and self-efficacy and adjusted to families’ individual needs.5 

The program was implemented by the Memphis and Shelby County Health Department during a nursing shortage, leading to nurse turnover for 37% of the families.11  Nurses carried a maximum caseload of 25 families each and relied on detailed visit-by-visit guidelines structured around 62 home visits. It is impossible for nurses to complete 62 visits for all families, and most families do not need this level of service. Nurses used their clinical judgment to adjust dosage and visit content, as well as telephone communications when in-person visits were not possible, to address individual needs revealed in the conduct of visits.

All families were scheduled to receive 4 weekly visits at the beginning of the program to facilitate nurses’ and mothers’ getting to know one another as early in the pregnancy as possible and to develop a trusting relationship founded on nurses’ understanding of mothers’ aspirations and concerns about their prenatal health, the developing fetus, birth, and the challenges of caring for a newborn. Newborn health and mother’s adjustment to caregiving were critical factors in nurses’ decisions about visit dose and content. Nurses recorded features of program implementation on every attempted and completed visit.5,26,27 

Overall, nurses completed a mean of 7 home visits during pregnancy and 26 visits during the first 2 years postpartum.11,27  Mothers in the lowest quartile of psychological resources (PR) at baseline received the highest number of home visits (mean = 37.67; SE = 2.38), those in the middle 2 quartiles had the fewest (mean = 32.02; SE = 1.68), and those in the highest quartile of PR received an intermediate number of visits (mean = 34.26; SE = 2.38).

Table 2 shows that outcomes were divided into 2 broad categories: (1) cognitive-related outcomes (nonverbal intelligence, language, math achievement, sustained attention, working memory, emotion recognition, risky decision-making, SSI for disability, high school graduation, and graduation with honors) and (2) behavioral health (mental health [internalizing, externalizing, and total behavioral problems], substance use and abuse, sexually transmitted infections [STIs], HIV risk, arrests and convictions, and gang membership). Within these broad categories, we separated primary from secondary outcomes. Table 2 shows the specific measures used and bases for hypotheses. Primary outcomes were predicted from previous intervention effects on the same measures or constructs in earlier phases of the current trial or other NFP trials and, for some outcomes, from effects found at earlier phases. Secondary outcomes were selected on the basis of their epidemiological and theoretical associations with earlier effects in the Elmira, Memphis, or Denver trials.59,1116,1820  We included 2 exploratory outcomes: high school graduation with honors and mother and/or caregiver report of youth receipt of SSI for disability.

Data analyses are reported on all cases randomized insofar as outcome data were available. The analysis adhered to a statistical analysis plan established before examination of data from the intervention group.

The primary statistical model for cognitive-related outcomes consisted of a 2-level treatment factor (control versus NV) and a 2-level factor reflecting mothers’ PR (above versus below the sample median), focusing on treatment differences for the LPR group, in models that included 3 covariates (household poverty index, maternal attitudes predictive of child abuse [CAA],43  and youth sex). The first 2 covariates, consistent predictors of a range of outcomes, adjusted for treatment nonequivalence at registration; the third was added because of its strong relationship with some outcomes. The household poverty index incorporates 3 variables: discretionary household income, housing density, and head-of-household employment. For emotion-recognition analyses, we added age-18 nonverbal intelligence to the model to reduce the likelihood that intervention effects would simply reflect differences in intelligence.

For arrest and conviction outcomes, we examined NV-control differences in a model that included sex as a classification factor, examining treatment differences separately for females and males, in models that included 3 covariates: maternal PR, household poverty, and CAA.43 

Given that rates of pregnancies, births, and STI outcomes were operationalized differently for males and females, we examined NV-control differences separately for males and females and included 3 covariates: maternal PR, household poverty, and CAA.43 

For analysis of HIV risk, we examined NV-control differences in a model that included covariates for maternal PR, youth sex, youth age at assessment, household poverty, and CAA.43 

For all remaining behavioral health outcomes, we examined NV-control differences in models that included covariates for maternal PR, youth sex, household poverty, and CAA.43 

For continuous and dichotomous outcomes on which we had repeated assessments for each child over time, we analyzed outcomes using generalized mixed models that included, in addition to variables from the primary model, children as levels of a random factor, a fixed repeated-measures classification factor for time of assessment, and all interactions of time with the other fixed classification factors.

Continuous dependent variables were analyzed in the general linear model, and dichotomous outcomes were analyzed in the logistic linear model. For low-frequency count outcomes, we analyzed data in generalized linear models with negative binomial error assumptions. We examined low-frequency outcomes with rerandomization tests to determine model fit44  and truncated 1 outlier for the count-of-convictions outcome. Substance-use disorders and timing to first pregnancy and birth were analyzed over time by using Cox proportional-hazards models. We present survival rates at age 18 along with hazard ratios.

Supplemental Tables 6 and 7 show estimates of NV-control differences without covariate adjustments.

The NV and control groups were similar on background characteristics for participants for whom 18-year follow-up assessments were conducted (Table 3), with these exceptions: at intake, NV women, compared with controls, lived in households with less discretionary income, higher person-per-room density, higher scores on a household poverty index, and higher scores on CAA.43 

Table 4 summarizes estimates of youth functioning in the cognitive, language, achievement, and executive functioning domains for the sample as a whole and for youth born to mothers with LPR. With the exception of NV youth having higher rates of graduation with honors (adjusted odds ratio [aOR] = 2.12; 95% confidence interval [CI]: 1.09 to 4.13; P = .028) and trends (P < .10) of NV youth having higher math scores and better emotion recognition, there were no intervention-control differences for the sample as a whole. NV children born to mothers with LPR, on the other hand, had better receptive language (effect size [ES] = 0.24; 95% CI: 0.00 to 0.47; P = .048) and math achievement (ES = 0.38; 95% CI = 0.14 to 0.61; P = .002) at age 18. For both of these outcomes, there were longitudinal effects over time. There were no intervention-control differences in nonverbal intelligence.

NV children born to mothers with LPR also had better working memories (ES = 0.23; 95% CI = 0.01 to 0.46; P = .045) and emotion-recognition abilities (ES = 0.22; 95% CI: 0.01 to 0.44; P = .040), lower SSI for disability (aOR = 0.33; 95% CI: 0.13 to 0.84; P = .011), and higher rates of high school graduation with honors (aOR = 3.34; 95% CI: 1.19 to 9.34; P = .022) than their control-group counterparts.

There were no intervention-control differences in children’s sustained attention, risky decision-making, or high school graduation.

Table 5 shows that NV females, as a trend, had fewer criminal convictions than control females (incidence ratio [IR] = 0.47; 95% CI 0.20 to 1.11; P = .080). There were no intervention-control differences in internalizing, externalizing, or total behavioral problems or in substance use or substance use disorders. There was a marginally significant difference for NV males, compared with control males, to report more convictions for interpersonal violence (IR = 2.15; 95% CI 0.90 to 5.27; P = .082; data not shown). There were no overall NV-control differences in STIs, timing to first pregnancy, timing to first live birth, HIV risk, gang participation, counts of arrests, convictions, and arrests or convictions for interpersonal violence.

There were no overall intervention-control differences for any of the behavioral health outcomes, but the program improved the receptive language and math achievement of 18-year-olds born to mothers with LPR and, as a trend, reduced convictions among females. In addition, NV youth graduated with honors more frequently, and those born to mothers with LPR, compared with control-group counterparts, had better working memories and emotion-recognition skills and fewer disabilities leading to receipt of SSI. High rates of sample retention increase the validity of these findings.

The program effect on cognitive-related outcomes was, with the exception of graduation with honors, limited to youth born to mothers with LPR, conditional effects consistent with earlier phases of this trial,1115  and a subsequent trial.1820  Most of these effects, except for the twofold increase in graduation with honors overall and threefold reduction in SSI for disability in the LPR group, are small by conventional standards45  but important because they reflect different aspects of cognition, disability, and academic success relevant to adult functioning. Moreover, most of these outcomes are based on directly measured abilities.

Program effects on emotion-recognition abilities and working memory, although not examined in other NFP trials, are consistent with a reduction in child maltreatment46,47  and earlier program effects on maltreatment-related outcomes.11,13,17  By age 2, for example, control children, compared with those visited by nurses, were hospitalized for fewer days for injuries and ingestions11 ; all admissions for fractures and/or head trauma occurred in control infants born to mothers with LPR.5,11  Control children born to mothers with LPR were less communicative and responsive to their mothers than those visited by nurses through 24 months11 ; and through age 18, they exhibited more compromised development and achievement.13,15  All preventable child mortality through age 20 occurred in the control group.17 

The improvements in cognitive outcomes and reductions in disability in the LPR group at age 18 suggest that the intervention may lead to additional functional and societal savings for this group, including possible reductions in Alzheimer disease and related disorders, given their relationship with adolescent cognitive functioning.48,49 

In interpreting the more pronounced program effect on the cognitive-related outcomes of children born to mothers with LPR, it is important to note that nurses visited the most vulnerable mothers more frequently, a consistent feature of NFP program design beginning with the Elmira trial.26  Moreover, children born to mothers with LPR had greater room for improvement.

Note that families were not randomly assigned to different visitation schedules, so discerning the role of visit patterns on outcomes is challenging. In exploratory latent class analyses of home visits in the current trial, 3 patterns were uncovered: low attendance (33% of those visited), high attendance (48%), and increasing attendance (18%). Those in the low-visit group had the highest educations at baseline; those in the increasing group had low education, the lowest number of prenatal visits, and high rates of preterm delivery; and those in the high-visit group also had low education at baseline. These findings highlight the role that mothers, in addition to nurses, play in shaping visit attendance patterns and the methodologic challenges involved in estimating intervention effects for those with different visitation patterns.27 

In using the visit patterns found here to guide community replication,5  it is important to emphasize that the dosage metric that the NFP is designed to achieve is the one actually delivered in the original RCTs and that nurses adjusted visit frequency and content in an effort to ensure that they address specific risks and guide responsive caregiving in the most vulnerable subgroups.

The program effect on convictions among females, although a trend, is consistent with a corresponding finding in the Elmira trial,10  reduced physical aggression among females at age 2 in the current trial,50  and intervention effects on trajectories of externalizing problems in the subsequent Denver trial among females, but not males, at ages 2, 4, 6, and 9.51  These female-limited beneficial effects may be connected to females’ particular susceptibility to the effects of prenatal stress on androgen activity during gestation52  and hormone-dependent endpoints, including conduct disorder.53  Moreover, females, compared with males, are particularly susceptible to the effects of harsh parenting on health,54,55  including the development of aggression.56 

There were no beneficial intervention effects in the current trial on 18-year-olds’ substance-use disorders, substance use, or internalizing disorders despite significant intervention effects in these domains at age 12 in the current trial15  and on substance use, arrests, and convictions through age 15 in the Elmira trial.9  The trend for NV males to report higher rates of conviction for interpersonal violence was not predicted. The absence of overall beneficial intervention effects on antisocial behavior at the end of adolescence, especially among males, is consistent with age-19 findings in the Elmira trial.10  There are at least 2 possible explanations for this pattern of results.

The first is that NFP’s promotion of sensitive, responsive care and avoidance of harsh treatment may have decreased parents’ attention to setting effective limits, especially among noncompliant males.56  The increase in NV males’ self-reported convictions for interpersonal violence found here, although not hypothesized, suggests that greater attention may be needed to address effective limit setting in NFP and to link this program to effective toddler and preschool parenting interventions.5760 

Second, the nearly normative rise in male adolescent–limited antisocial behavior not linked to maltreatment or early adversity61  may mask intervention effects on life-course–persistent antisocial behavior linked to early maltreatment that may become evident once adolescents assume adult roles. Note, however, that adolescents who become ensnared in substance abuse and criminal activity are at risk for long-term criminal involvement.6163 

The current report has limitations. The first is that nearly all of the behavioral health findings were based on self-report, and some evidence suggests that NV women become more accurate reporters of socially undesirable behavior, such as smoking.6  Although a case might also be made that NV youth were more attentive listeners and reporters (given program effects on verbal working memory), measurement of STIs and use of substances included urine assays, so this form of treatment-related report bias does not account for the absence of an intervention effect for these outcomes.

Second, we included 2 exploratory outcomes (high school graduation with honors and SSI for disability) that were not part of the original measurement design, so these findings need to be treated with caution.

Third, the age range for completing 18-year assessments was larger than anticipated but not different by treatment. Adjusting for youth age at assessment does not alter the findings (data not shown).

The fourth limitation is that the number of outcomes analyzed raises challenges with multiple comparisons. We have not adjusted for multiple comparisons in NFP trials.6467  We have focused instead on determining if findings replicate with different populations living in different contexts in separate trials. The long-term program effect on cognitive-related outcomes through the end of adolescence has not yet been tested in other trials, so particular caution is warranted in interpreting these outcomes.

This study found enduring program effects on the cognitive functioning of youth born to the mothers least capable of coping with the adversities that come with living in poverty and a trend for reduced convictions among females but no effects on other adolescent health behavior.

The current phase of this research was supported by the National Institute on Drug Abuse (1R01DA021624). Mr Knudtson had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the analysis. We thank Evelyn Collins for tracing and engaging the study participants and managing the Memphis study office since 1991, Benjamin Jutson (University of Colorado Anschutz Medical Campus) for helping prepare this article, and Wendy Gehring (University of Colorado Anschutz Medical Campus) for her help with data management. Evelyn Collins, Benjamin Jutson, and Wendy Gehring received compensation from research grants for their work.

Deidentified individual participant data (including data dictionaries) will be made available in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available on publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Please contact Michael Knudtson, the study biostatistician, at michael.knudtson@cuanschutz.edu or 303-724-3199 for additional details.

Dr Olds conceptualized and designed the study, drafted the manuscript, and supervised the study; Dr Kitzman conceptualized and designed the study, obtained funding, and supervised the study; Dr Cole conceptualized and designed the study and obtained funding; Mr Knudtson acquired data and performed statistical analysis on the data; Dr Smith and Ms Anson acquired data; Drs Fishbein, DiClemente, Wingood, Caliendo, Hopfer, and Miller conceptualized and designed the study; and all authors analyzed and interpreted data, critically revised the manuscript for important intellectual content, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

This trial has been registered at www.clinicaltrials.gov (identifier NCT00708695).

FUNDING: Supported by the National Institutes of Health (research grant R01DA021624). Funded by the National Institutes of Health (NIH).

COMPANION PAPER: Companions to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2019-2606 and www.pediatrics.org/cgi/doi/10.1542/peds.2019-3889.

     
  • aOR

    adjusted odds ratio

  •  
  • CAA

    maternal attitudes predictive of child abuse

  •  
  • CI

    confidence interval

  •  
  • ES

    effect size

  •  
  • IR

    incidence ratio

  •  
  • LPR

    limited psychological resources

  •  
  • NFP

    Nurse-Family Partnership

  •  
  • NV

    nurse visit

  •  
  • PR

    psychological resources

  •  
  • RCT

    randomized clinical trial

  •  
  • SSI

    Supplemental Social Security Income

  •  
  • STI

    sexually transmitted infection

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Competing Interests

POTENTIAL CONFLICT OF INTEREST: The Prevention Research Center for Family and Child Health, directed by Dr Olds at the University of Colorado School of Medicine, has a contract with the Nurse-Family Partnership (NFP) to conduct research to improve the NFP program and its implementation; this contract covers part of Dr Olds’s salary and part of Mr Knudtson’s salary. Dr Olds and Mr Knudtson were employed by this center at the time the study was conducted. Dr Olds is the founder of NFP and, with the University of Colorado, owns the NFP intellectual property. The University of Colorado receives royalties from governments and organizations outside of the United States that implement NFP and has contracts with those entities to guide the implementation of NFP with quality, but none of the royalties or fees go to Dr Olds personally; they are used to support the Prevention Research Center for Family and Child Health research and implementation guidance. Dr Miller performs economic analyses under contract for the nonprofit Nurse-Family Partnership National Service Office; the other authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: Dr Olds receives personal honoraria and travel expenses from philanthropies and organizations for speaking about the Nurse-Family Partnership and early intervention; the other authors have indicated they have no financial relationships relevant to this article to disclose, beyond those already listed in the Potential Conflict of Interest.

Supplementary data