High-risk neighbourhoods and behaviour outcomes in children born extremely preterm.

AIM: Study the association between neighbourhood risk and behaviour in extreme preterm (EPT) children. We hypothesised that EPT children living in high-risk neighbourhoods have increased risk of clinical range behaviour problems at age 30-36 months. METHODS: Retrospective analyses of Child Behavior Checklist (CBCL)scores for 739 EPTs born 2005-2016. Addresses were geocoded to identify census block groups and create high versus low-risk groups. Regression analyses assessed the impact of neighbourhood risk on behaviour. RESULTS: Children from high-risk (N = 272, 39%) and low-risk (N = 417, 61%) neighbourhoods were compared. In adjusted analyses, odds of clinical range scores remained greater in high-risk neighbourhoods for Emotionally Reactive (OR: 4.32, CI: 1.13, 16.51), Somatic Complaints (2.30, CI 1.11,4.79), Withdrawn (OR: 2.56, CI: 1.21, 5,42), Aggressive Behaviour (OR: 4.12, CI: 1.45, 11.68), Internalising (OR: 1.96, CI: 1.17, 3.28), and Total score (OR: 1.86, OR: CI: 1.13, 3.07). Cognitive delay was higher in high-risk neighbourhoods and a risk factor for Attention Problems (2.10,1.08, 4.09). Breast milk was protective for Emotionally Reactive (OR: 0.22, CI: 0.06, 0.85) and Sleep Problems (OR: 0.47, CI:0.24, 0.94). CONCLUSION: Neighbourhood risk provided an independent contribution to preterm adverse behaviour outcomes with cognitive delay an additional independent risk factor. Breast milk at discharge was protective.

Social Determinants of Health and Redirection of Care for Infants Born Extremely Preterm.

Importance: Redirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding. Objective: To examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm. Design, Setting, and Participants: This is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks' gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic). Main Outcomes and Measures: The primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks' gestation, death and neurodevelopmental impairment at 22 to 26 months' corrected age. Results: Of the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type. Conclusions and Relevance: For infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Association of maternal pre-pregnancy or first trimester body mass index with neurodevelopmental impairment or death in extremely low gestational age neonates.

OBJECTIVE: To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first-trimester maternal body mass index (BMI). METHODS: This retrospective cohort study included extremely preterm infants (gestational age 220/7-266/7 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. The primary outcome was death or sNDI at 2 years. RESULTS: Data on the primary outcome were available for 1208 children. Death or sNDI was not different among the three groups: 54.9% in normal, 56.1% in overweight, and 53.4% in obese group (p = 0.39). There was no significant difference in mortality, sNDI, moderate/severe cerebral palsy, Bayley Scales of Infant Development (BSID)-III cognitive composite score <70, BSID-III language composite score <70 in adjusted models. CONCLUSION: Neurodevelopmental outcome was not significantly associated with maternal pre-pregnancy BMI among extreme preterm infants.

Increasing Prevalence of Cerebral Palsy Among Two-Year-Old Children Born at <27 Weeks of Gestation: A Cohort Study.

OBJECTIVE: To evaluate changes in prevalence and severity of cerebral palsy (CP) among surviving children born at <27 weeks of gestation over time and to determine associations between CP and other developmental domains, functional impairment, medical morbidities, and resource use among 2-year-old children who were born extremely preterm. STUDY DESIGN: Retrospective cohort study using prospective registry data, conducted at 25 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Participants were children born at <27 weeks of gestation and followed at 18 through 26 months of corrected age from 2008 through 2019. Outcomes of interest were changes in prevalence of any CP and severity of CP over time and associations between CP and other neurodevelopmental outcomes, functional impairment, and medical comorbidities. Adjusted logistic, linear, multinomial logistic, and robust Poisson regression evaluated the relationships between child characteristics, CP severity, and outcomes. RESULTS: Among 6927 surviving children with complete follow-up data, 3717 (53.7%) had normal neurologic examinations, 1303 (18.8%) had CP, and the remainder had abnormal neurologic examinations not classified as CP. Adjusted rates of any CP increased each year of the study period (aOR 1.11 per year, 95% CI 1.08-1.14). Cognitive development was significantly associated with severity of CP. Children with CP were more likely to have multiple medical comorbidities, neurosensory problems, and poor growth at follow-up. CONCLUSIONS: The rate of CP among surviving children who were born extremely preterm increased from 2008 through 2019. At 18 to 26 months of corrected age, neurodevelopmental and medical comorbidities are strongly associated with all severity levels of CP.

A Randomized Controlled Trial of a Neonatal Intensive Care Unit Language Intervention for Parents of Preterm Infants and 2-Year Language Outcomes.

OBJECTIVE: To test whether a neonatal intensive care unit-based language curriculum for families with preterm infants enhances the language environment and postdischarge Bayley Scales of Infant and Toddler Development (BSID)-III language and cognitive scores. METHODS: A randomized controlled trial was conducted with infants born at ≤32 weeks assigned to a parent-driven language intervention or health-safety lessons (controls). Recordings of adult word counts (AWC), conversational turns, and child vocalizations were captured at 32, 34, and 36 weeks. Primary outcomes included 2-year BSID-III language and cognitive scores. RESULTS: We randomized 95 infants; 45 of the 48 intervention patients (94%) and 43 of the 47 controls (91%) with ≥2 recordings were analyzed. The intervention group had higher AWCs (rate ratio, 1.52; 95% CI, 1.05-2.19; P = .03) at 36 weeks, increased their AWCs between all recordings, and had lower rates of 2-year receptive language scores <7 (10% vs 38%; P < .02). The intervention was associated with 80% decreased odds of a language composite score of <85 (aOR, 0.20; 95% CI, 0.05-0.78; P = .02), and 90% decreased odds of a receptive score of <7 (0.10; 95% CI, 0.02-0.46; P = .003); there was no association found with cognitive scores. Increases in AWC and conversational turns between 32 and 36 weeks were independently associated with improved 2-year BSID-III language scores for both study groups. CONCLUSIONS: Short-term parent-driven language enrichment in the neonatal intensive care unit contributes to increased AWCs at 36 weeks and improved 2-year language scores. In adjusted analyses, increases in conversational turns and AWCs at 36 weeks were independently associated with improved language scores. This low-cost, easily implemented intervention can potentially help to mitigate speech delays among preterm infants. TRIAL REGISTRATION: Registered with www. CLINICALTRIALS: gov, NCT02528227.

Do Bayley-III Composite Scores at 18-22 Months Corrected Age Predict Full-Scale IQ at 6-7 Years in Children Born Extremely Preterm?

OBJECTIVE: To determine the ability of the Bayley-III cognitive and language composite scores at 18-22 months corrected age to predict WISC-IV Full Scale IQ (FSIQ) at 6-7 years in infants born extremely preterm. STUDY DESIGN: Children in this study were part of the Neuroimaging and Neurodevelopmental Outcome cohort, a secondary study to the SUPPORT trial and born 240/7-276/7 weeks gestational age. Bayley-III cognitive and language scores and WISC-IV FSIQ were compared with pairwise Pearson correlation coefficients and adjusted for medical and socioeconomic variables using linear mixed effect regression models. RESULTS: Bayley-III cognitive (r = 0.33) and language scores (r = 0.44) were mildly correlated with WISC-IV FSIQ score. Of the children with Bayley-III cognitive scores of <70, 67% also had FSIQ of <70. There was less consistency for children with Bayley-III scores in the 85-100 range; 43% had an FSIQ of <85 and 10% an FSIQ of <70. Among those with Bayley-III language scores >100, approximately 1 in 5 had an FSIQ of <85. A cut point of 92 for the cognitive composite score resulted in sensitivity (0.60), specificity (0.64). A cut point of 88 for the language composite score produced sensitivity (0.61), specificity (0.70). CONCLUSIONS: Findings indicate the Bayley-III cognitive and language scores correlate with later IQ, but may fail to predict delay or misclassify children who are not delayed at school age. The Bayley-III can be a useful tool to help identify children born extremely preterm who have below average cognitive scores and may be at the greatest risk for ongoing cognitive difficulties. TRIAL REGISTRATION: Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.

Use of term reference infants in assessing the developmental outcome of extremely preterm infants: lessons learned in a multicenter study.

OBJECTIVE: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital. STUDY DESIGN: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age. RESULTS: We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting TR patients at 2 years extended the study by 14 months and affected their demographics. CONCLUSION: Impairment rates among EP infants appear to be substantially underestimated from Bayley III norms. These rates may be best assessed by comparison with healthy term infants followed with minimal attrition from birth in the same centers. GOV ID: Term Reference (under the Generic Database Study): NCT00063063.

Early-Life Outcomes in Relation to Social Determinants of Health for Children Born Extremely Preterm.

OBJECTIVE: To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. STUDY DESIGN: This is a cohort study of infants born at 22-26 weeks of gestation in National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2017) who survived to discharge. Infants were classified by 3 maternal SDOH: education, insurance, and race. Outcomes included postmenstrual age (PMA) at discharge, readmission, neurodevelopmental impairment (NDI), and death postdischarge. Regression analyses adjusted for center, perinatal characteristics, neonatal morbidity, ethnicity, and 2 SDOH (eg, group comparisons by education adjusted for insurance and race). RESULTS: Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37 weeks, 95% CL 0.06, 0.68) and readmission more likely (aOR 1.27, 95% CL 1.12, 1.43) for infants whose mothers had public/no insurance vs private. Neither PMA at discharge nor readmission varied by education or race. NDI was twice as likely (aOR 2.36, 95% CL 1.86, 3.00) and death 5 times as likely (aOR 5.22, 95% CL 2.54, 10.73) for infants with 3 risk-associated SDOH compared with those with none. CONCLUSIONS: Children born to mothers with public/no insurance were older at discharge and more likely to be readmitted than those born to privately insured mothers. NDI and death postdischarge were more common among children exposed to multiple risk-associated SDOH at birth compared with those not exposed. Addressing disparities due to maternal education, insurance coverage, and systemic racism are potential intervention targets to improve outcomes for children born preterm.

Outcomes of Preterm Infants: Shifting Focus, Extending the View.

Advances in perinatal care have led to remarkable long-term survival for infants who are born preterm. This article reviews the broader context of follow-up care, highlighting the need to reenvision some areas, such as improving parental support by embedding parental involvement in the neonatal intensive care unit, incorporating parental perspectives about outcomes into follow-up care models and research, supporting their mental health, addressing social determinants of health and disparities, and advocating for change. Multicenter quality improvement networks allow identification and implementation of best practices for follow-up care.

Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years.

BACKGROUND: Severe retinopathy of prematurity (ROP) is associated with adverse outcomes. Relationships between milder ROP and outcomes have not been defined. We hypothesized that children with ROP stage ≤3 who did not receive ophthalmologic intervention would have worse motor, cognitive, and language skills and more vision abnormalities than children without ROP. METHODS: This was a secondary analysis of a randomized trial evaluating the effects of myo-inositol on ROP in the NICHD Neonatal Research Network. Primary outcomes were Bayley Scales of Infant Development composite scores; secondary outcomes included behavioral difficulties and ophthalmologic measures. Outcomes were compared using adjusted linear or modified Poisson models. RESULTS: Of 506 children, 173 (34%) had no ROP, 262 (52%) had ROP stage ≤3 without intervention, and 71 (14%) had ROP with intervention. There was no difference in motor, cognitive, or language scores between children with ROP stage ≤3 without intervention and children without ROP. Children with ROP stage ≤3 without intervention had a higher rate of strabismus compared to children without ROP (p = 0.040). CONCLUSION: Children with ROP stage ≤3 without intervention did not have adverse neurodevelopmental outcomes at 2 years' corrected age compared to children without ROP but did have an increased incidence of strabismus. IMPACT: This study addresses a gap in the literature regarding the relationship between milder forms of retinopathy of prematurity (ROP) that regress without intervention and neurodevelopment and vision outcomes. Children with a history of ROP stage ≤3 without intervention have similar neurodevelopmental outcomes at 2 years' corrected age as children born extremely preterm without a history of ROP and better outcomes than children with a history of ROP with ophthalmologic intervention. Counseling about likely neurodevelopment and vision outcomes for children born extremely preterm with a history of ROP may be tailored based on the severity of ROP. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: Inositol to Reduce Retinopathy of Prematurity Trial: NCT01954082.

Cortisol awakening response and developmental outcomes at 6-7 years in children born extremely preterm.

BACKGROUND: Extremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children. METHODS: This secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed. RESULTS: Cortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p < 0.05) only. CONCLUSIONS: Among children born EPT, we identified an association of blunted cortisol awakening response with memory and inattention problems. This may have implications related to stress reactivity and its relationship to learning problems in children born EPT. GOV ID: Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324. IMPACT: In children born EPT, stress reactivity may have a relationship to learning problems. Cortisol awakening response should be a component for follow-up in EPT born children. Components of executive function, such as memory and attention, are related to stress reactivity.

Early neurodevelopmental follow-up in the NICHD neonatal research network: Advancing neonatal care and outcomes, opportunities for the future.

At the inception of the Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network (NRN), provision of care for extremely preterm (EPT) infants was considered experimental. The NRN Follow-up Study Group, initiated in 1993, developed infrastructure with certification processes and standards, allowing the NRN to assess 2-year outcomes for EPT and to provide important metrics for randomized clinical trials. This chapter will review the NRN Follow-up Study Group's contributions to understanding factors related to improved neurodevelopmental, behavioral, and social-emotional outcomes of EPT infants. We will also discuss follow up challenges, including reassessing which outcomes are most meaningful for parents and investigators. Finally, we will explore how outcome studies have informed clinical decisions and ethical considerations, given limitations of prediction of complex later childhood outcomes from early neurodevelopmental findings.

The critical importance of follow-up to school age: Contributions of the NICHD Neonatal Research Network.

Follow-up studies are essential for understanding outcomes and informing the care of infants with high risk for medical and developmental consequences because of extreme prematurity or perinatal illness. Studies that extend to school age often identify sequelae that go unrecognized in neonatal or short-term follow-up studies. Many critical neurocognitive, behavioral, functional, and health outcomes are best assessed beginning at school age. The Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network (NRN) has performed comprehensive school age evaluations of several key trial cohorts. This manuscript summarizes the important contributions of school age follow-up studies in the NRN, both historically and in ongoing research. We describe in detail the clinical questions that have been answered by the completed studies and new questions about the outcomes of high-risk infants that must be addressed by ongoing and future studies.

Randomised controlled trial of maternal infant-directed reading among hospitalised preterm infants.

AIM: A randomised trial to study the impact of a maternal-driven, infant-directed reading intervention on preterm infant language compared with matched controls. METHODS: Infants born at 22-32 weeks in Women & Infants Neonatal Intensive Care were gestationally stratified to a reading intervention (n = 33) or standard care (n = 34). At 32-, 34- and 36-weeks postmenstrual age, 16-h language recordings were obtained in the hospital. Bivariate group comparisons and regressions adjusting for gestational age and multiples were run to predict word counts and conversational turns. Longitudinal analyses were conducted by negative binomial models containing intervention, randomised gestation group, recording number (1-3), an intervention × recording number interaction term and multiple birth adjustment by generalised estimating equations. RESULTS: In adjusted analyses, by 36-weeks postmenstrual age, infants in the reading group had twice the number of conversational turns as infants receiving standard care (Rate ratio 1.98, 95% CI 1.33-2.93, p < 0.05). In longitudinal analyses, only infants in the reading group had a significant increase in the conversational turns between 32- and 36-weeks postmenstrual age (Rate ratio 2.45, 95% CI 1.45-4.14, p < 0.05). CONCLUSIONS: A maternal infant-directed reading curriculum in the hospital demonstrated a positive impact on interactive conversations by 36-weeks postmenstrual age.

Neurodevelopmental outcomes of premature infants with intraventricular hemorrhage across a lifespan.

Neurodevelopmental impairment rates remain high among extremely preterm and very low birth weight infants. This review describes the rates of brain injury and neuro-developmental impairment at 2,3 years, early school age, adolescence, and young adulthood for survivors with intraventricular hemorrhage (IVH). Former preterm infants with a history of high-grade IVH are at the greatest risk of adverse neurodevelopmental outcomes. There is variability, however, in definitions of brain injury, methods for assessing brain injury, and definitions of adverse outcomes among multicenter networks. Despite differences in methods described in publications, perinatal grade III-IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus, and white matter injury are consistently associated with increased rates of adverse motor and cognitive outcomes in the first 2,3 years of life, at early school age, in adolescence and early adulthood. Effects of socioeconomic status on outcomes, however, increase with the increasing age of the child. In summary, although preterm survivors of IVH are at an increased risk of adverse outcomes across a lifetime, there is evidence that social and environmental factors contribute to recovery over time.

High-Risk Neighborhoods and Neurodevelopmental Outcomes in Infants Born Preterm.

OBJECTIVE: To study the association between neighborhood risk and moderate to severe neurodevelopmental impairment (NDI) at 22-26 months corrected age in children born at <34 weeks of gestation. We hypothesized that infants born preterm living in high-risk neighborhoods would have a greater risk of NDI and cognitive, motor, and language delays. STUDY DESIGN: We studied a retrospective cohort of 1291 infants born preterm between 2005 and 2016, excluding infants with congenital anomalies. NDI was defined as any one of the following: a Bayley Scales of Infant and Toddler Development-III Cognitive or Motor composite score <85, bilateral blindness, bilateral hearing impairment, or moderate-severe cerebral palsy. Maternal addresses were geocoded to identify census block groups and create high-risk versus low-risk neighborhood groups. Bivariate and regression analyses were run to assess the impact of neighborhood risk on outcomes. RESULTS: Infants from high-risk (n = 538; 42%) and low-risk (n = 753; 58%) neighborhoods were compared. In bivariate analyses, the risk of NDI and cognitive, motor, and language delays was greater in high-risk neighborhoods. In adjusted regression models, the risks of NDI (OR, 1.43; 95% CI, 1.04-1.98), cognitive delay (OR, 1.62; 95% CI, 1.15-2.28), and language delay (OR, 1.58; 95% CI, 1.15-2.16) were greater in high-risk neighborhoods. Breast milk at discharge was more common in low-risk neighborhoods and was protective of NDI in regression analysis. CONCLUSIONS: High neighborhood risk provides an independent contribution to preterm adverse NDI, cognitive, and language outcomes. In addition, breast milk at discharge was protective. Knowledge of neighborhood risk may inform the targeted implementation of programs for socially disadvantaged infants.