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OBJECTIVE: To examine resource and service use after discharge among infants born extraordinarily preterm in California who attended high-risk infant follow-up (HRIF) clinic by 12 months corrected age. STUDY DESIGN: We included infants born 2010-2017 between 22 + 0/7 and 25 + 6/7 weeks' gestational age in the California Perinatal Quality Care Collaborative and California Perinatal Quality Care Collaborative-California Children's Services HRIF databases. We evaluated rates of hospitalization, surgeries, medications, equipment, medical service and special service use, and referrals. We examined factors associated with receiving ≥ 2 medical services, and ≥ 1 special service. RESULTS: A total of 3941 of 5284 infants received a HRIF visit by 12 months corrected age. Infants born at earlier gestational ages used more medications, equipment, medical services, and special services and had higher rates of referral to medical and special services at the first HRIF visit. Infants with major morbidity, surgery, caregiver concerns, and mothers with more years of education had higher odds of receiving ≥ 2 medical services. Infants with Black maternal race, younger maternal age, female sex, and discharge from lower level neonatal intensive care units (NICUs) had lower odds of receiving ≥ 2 medical services. Infants with more educated mothers, multiple gestation, major morbidity, surgery, caregiver concerns, and discharge from lower level NICUs had increased odds of receiving a special service. CONCLUSIONS: Infants born extraordinarily preterm have substantial resource use after discharge. High resource utilization was associated with maternal/sociodemographic factors and expected clinical factors. Early functional and service use information is valuable to parents and underscores the need for NICU providers to appropriately prepare and refer families.

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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.

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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.

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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.

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OBJECTIVE: To determine the rate and trend of active treatment in a population-based cohort of infants born at 22-25 weeks of gestation and to examine factors associated with active treatment. STUDY DESIGN: This observational study evaluated 8247 infants born at 22-25 weeks of gestation at hospitals in the California Perinatal Quality Care Collaborative between 2011 and 2018. Multivariable logistic regression was used to relate maternal demographic and prenatal factors, fetal characteristics, and hospital level of care to the primary outcome of active treatment. RESULTS: Active treatment was provided to 6657 infants. The rate at 22 weeks was 19.4% and increased with each advancing week, and was significantly higher for infants born between days 4 and 6 at 22 or 23 weeks of gestation compared with those born between days 0 and 3 (26.2% and 78.3%, respectively, vs 14.1% and 65.9%, respectively; P < .001). The rate of active treatment at 23 weeks increased from 2011 to 2018 (from 64.9% to 83.4%; P < .0001) but did not change significantly at 22 weeks. Factors associated with increased odds of active treatment included maternal Hispanic ethnicity and Black race, preterm premature rupture of membranes, obstetrical bleeding, antenatal steroids, and cesarean delivery. Factors associated with decreased odds included lower gestational age and small for gestational age birth weight. CONCLUSIONS: In California, active treatment rates at 23 weeks of gestation increased between 2011 and 2018, but rates at 22 weeks did not. At 22 and 23 weeks, rates increased during the latter part of the week. Several maternal and infant factors were associated with the likelihood of active treatment.

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OBJECTIVE: To determine follow-up rates for the high-risk infant follow-up (HRIF) visit at 18-36 months among infants with very low birthweights and identify factors associated with completion. STUDY DESIGN: We completed a retrospective cohort study using linked California Perinatal Quality of Care Collaborative neonatal intensive care unit, California Perinatal Quality of Care Collaborative California Children's Services HRIF, and Vital Statistics Birth Cohort databases. We identified maternal, sociodemographic, neonatal, clinical, and HRIF program level factors associated with the 18- to 36-month follow-up using multivariable Poisson regression. RESULTS: From 2010 to 2015, among 19 284 infants with very low birthweight expected to attend at least 1 visit at 18-36 months, 10 249 (53%) attended. On multivariable analysis, factors independently associated with attendance at an 18- to 36-month visit included estimated gestational age (relative risk [RR], 1.21; 95% CI, 1.15-1.26; <26 weeks vs ≥31 weeks), maternal education (RR, 1.09; 95% CI, 1.06-1.12; college degree or more vs high school), distance from clinic (RR, 0.92; 95% CI, 0.89-0.97; fourth quartile vs first quartile), and Black non-Hispanic race vs White race (RR, 0.88; 95% CI, 0.84-0.92). However, completion of an initial HRIF visit within the first 12 months was the factor most strongly associated with completion of an 18- to 36-month visit (RR, 6.47; 95% CI, 5.91-7.08). CONCLUSIONS: In a California very low birthweight cohort, maternal education, race, and distance from the clinic were associated with sustained HRIF participation, but attendance at a visit by 12 months was the most significantly associated factor. These findings highlight the importance of early engagement with all families to ensure equitable follow-through for children born preterm.

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OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. STUDY DESIGN: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. RESULTS: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. CONCLUSIONS: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00614744.

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OBJECTIVE: To determine if preterm infants with surgical necrotizing enterocolitis (sNEC) or spontaneous intestinal perforation (SIP) with short bowel syndrome (SBS) have worse neurodevelopmental and growth outcomes than those with sNEC/SIP without SBS, and those with no necrotizing enterocolitis, SIP, or SBS. STUDY DESIGN: We undertook a retrospective analysis of prospectively collected data from infants born between 22 and 26 weeks of gestation in the National Institute of Child Health and Human Development Neonatal Research Network centers from January 1, 2008, to December 31, 2016. Survivors were assessed at 18-26 months corrected age by standardized neurologic examination and Bayley Scales of Infant and Toddler Development, Third Edition. The primary outcome was moderate-severe neurodevelopmental impairment. Growth was assessed using World Health Organization z-score standards. Adjusted relative risks were estimated using modified Poisson regression models. RESULTS: Mortality was 32%, 45%, and 21% in the 3 groups, respectively. Eighty-nine percent of survivors were seen at 18-26 months corrected age. Moderate-severe neurodevelopmental impairment was present in 77% of children with SBS compared with 62% with sNEC/SIP without SBS (adjusted relative risk, 1.22; 95% CI, 1.02-1.45; P = .03) and 44% with no necrotizing enterocolitis, SIP, or SBS (adjusted relative risk, 1.60; 95% CI, 1.37-1.88; P < .001). Children with SBS had lowcognitive, language, and motor scores than children with sNEC/SIP without SBS. At follow-up, length and head circumference z-scores remained more than 1 SD below the mean for children with SBS. CONCLUSIONS: Preterm infants with sNEC/SIP and SBS had increased risk of adverse neurodevelopmental outcomes at 18-26 months corrected age and impaired growth compared with peers with sNEC/SIP without SBS or without any of these conditions.

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OBJECTIVE: To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation. STUDY DESIGN: Observational study of infants born April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley Scales of Infant and Toddler Development, 3rd edition, cognitive or motor score <70, blindness, or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education, and parenchymal hemorrhage. RESULTS: Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119 of 815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation, and normal head ultrasound, respectively; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs no intervention (80% vs 65%; aOR 2.2 [1.38-3.8]). Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex, and surgery for retinopathy; odds decreased with each additional gestational week. CONCLUSIONS: PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.

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