Resource and Service Use after Discharge Among Infants 22-25 Weeks Estimated Gestational Age at the First High-Risk Infant Follow-Up Visit in California.

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.

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.

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.

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.

Active Treatment of Infants Born at 22-25 Weeks of Gestation in California, 2011-2018.

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.

Disparities and Early Engagement Associated with the 18- to 36-Month High-Risk Infant Follow-Up Visit among Very Low Birthweight Infants in California.

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.

Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy in the Late Hypothermia Trial.

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.

Neurodevelopmental and Growth Outcomes of Extremely Preterm Infants with Short Bowel Syndrome.

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.

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Infants of Extremely Low Gestational Age.

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.

Hand Function at 18-22 Months Is Associated with School-Age Manual Dexterity and Motor Performance in Children Born Extremely Preterm.

OBJECTIVES: To determine associations between hand function at age 18-22 months (early) and scores on the Movement Assessment Battery for Children, 2nd edition (MABC) at 6-7 years of age (school age) in extremely preterm children. STUDY DESIGN: Prospective multicenter cohort of 313 extremely preterm children with early hand function assessment and school-age MABC testing. Early hand function was compared with "definite deficits" (MABC <5th percentile) and MABC standard scores. Early hand function was categorized as "no deficit" vs "any deficit." Mixed-effects regression models were used to evaluate the association of early hand function with MABC deficits, controlling for multiple demographic, neonatal, and childhood factors. RESULTS: Children with early hand function deficits were more likely to have definite school-age deficits in all MABC subtests (Manual Dexterity, Aiming and Catching, and Balance) and to have received physical or occupational therapy (45% vs 26%; P < .001). Children with early hand function deficits had lower Manual Dexterity (P = .006), Balance (P = .035), and Total Test (P = .039) scores. Controlling for confounders, children with early hand function deficits had higher odds of definite school-age deficits in Manual Dexterity (aOR, 2.78; 95% CI, 1.36-5.68; P = .005) and lower Manual Dexterity (P = .031) and Balance (P = .027) scores. When excluding children with cerebral palsy and those with an IQ <70, hand function deficits remained significantly associated with manual dexterity. CONCLUSION: Hand function deficits at age 18-22 months are associated with manual dexterity deficits and motor difficulties at school age, independent of perinatal-neonatal factors and the use of occupational or physical therapy. This has significant implications for school success, intervention, and rehabilitative therapy development.

Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia.

OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD). STUDY DESIGN: We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior. RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P < .001) and pervasive developmental problems (P < .001) increased with worsening BPD grade. Sleep problems (P = .008) and aggressive behavior (P = .023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values < .05). CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

Improved Referral of Very Low Birthweight Infants to High-Risk Infant Follow-Up in California.

OBJECTIVE: To examine changes in referral rates of very low birthweight (birthweight <1500 g) infants to high-risk infant follow-up in California and identify factors associated with referral before and after implementation of a statewide initiative in 2013 to address disparities in referral. STUDY DESIGN: We included very low birthweight infants born 2010-2016 in the population-based California Perinatal Quality Care Collaborative who survived to discharge home. We used multivariable logistic regression to examine factors associated with referral and derive risk-adjusted referral rates by neonatal intensive care unit (NICU) and region. RESULTS: Referral rate improved from 83.0% (preinitiative period) to 94.9% (postinitiative period); yielding an OR of 1.48 (95% CI, 1.26-1.72) for referral in the postinitiative period after adjustment for year. Referral rates improved the most (≥15%) for infants born at ≥33 weeks of gestation, with a birthweight of 1251-1500 g, and born in intermediate and lower volume NICUs. After the initiative, Hispanic ethnicity, small for gestational age status, congenital anomalies, and major morbidities were no longer associated with a decreased odds of referral. Lower birthweight, outborn status, and higher NICU volume were no longer associated with increased odds of referral. African American race was associated with lower odds of referral, and higher NICU level with a higher odds of referral during both time periods. Referral improved in many previously poor-performing NICUs and regions. CONCLUSIONS: High-risk infant follow-up referral of very low birthweight infants improved substantially across all sociodemographic, perinatal, and clinical variables after the statewide initiative, although disparities remain. Our results demonstrate the benefit of a targeted initiative in California, which may be applicable to other quality collaboratives.

Cranial Ultrasound and Minor Motor Abnormalities at 2 Years in Extremely Low Gestational Age Infants.

OBJECTIVES: The objectives of this study are to determine whether abnormalities on neonatal cranial ultrasound (CUS) are associated with minor motor abnormalities at 2 years' corrected age (CA) and to assess functional outcomes and resource utilization among children with minor motor abnormalities. METHODS: Infants born at <27 weeks in the National Institute of Child Health and Human Development Neonatal Research Network between January 1, 2010, and December 31, 2014, who underwent neuroimaging with CUS at both <28 days and ≥28 days and were evaluated at 18 to 26 months' CA, were included. Follow-up included Bayley-3, neuromotor examination, Gross Motor Function Classification System (GMFCS) level, and parent questionnaires about special services and resource needs. Children were classified by the most severe motor abnormality at 18 to 26 months' CA as follows: none, minor, or major motor function abnormality. Minor motor abnormalities were defined as any of the following: (1) Bayley-3 motor composite, fine motor score, or gross motor score 1 to 2 SDs below the test normative means; (2) mild abnormalities of axial or extremity motor skills on standardized neuromotor examination; or (3) GMFCS level 1. RESULTS: A total of 809 (35%) of 2306 children had minor motor function abnormalities alone. This did not increase substantially with CUS findings (no intraventricular hemorrhage [IVH]: 37%, grade I IVH: 32%, grade II IVH: 38%, grade III/IV IVH: 30%, isolated ventriculomegaly: 33%, and cystic periventricular leukomalacia: 24%). The adjusted odds of minor axial and upper extremity function abnormalities and GMFCS level 1 were significantly higher in children with more severe CUS findings. Children with minor motor abnormalities had increased resource utilization and evidence of functional impairment compared with those without motor function abnormalities. CONCLUSION: Minor motor abnormalities at 2 years' CA are common and cannot be predicted by neonatal CUS abnormalities alone. Minor motor abnormalities are associated with higher resource utilization and evidence of functional impairment. These findings have important implications for early counseling and follow-up planning for extremely preterm infants.

Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision.

OBJECTIVE: To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision. STUDY DESIGN: For infants born at <27 weeks of gestation between 2006 and 2013, prospectively collected maternal and neonatal characteristics and 18- to 26-month corrected age follow-up data were analyzed. Bayley-III cognitive and language scores of infants with discharge CPS supervision were compared with infants without CPS supervision using regression analysis while adjusting for potentially confounding variables, including entering CPS after discharge from the hospital. RESULTS: Of the 4517 preterm infants discharged between 2006 and 2013, 255 (5.6%) were discharged with a need for CPS supervision. Mothers of infants with CPS supervision were significantly more likely to be younger, single, and gravida ≥3; to have less than a high school education; and to have a singleton pregnancy and less likely to have received prenatal care or antenatal steroids. Despite similar birth weight and medical morbidities, the CPS group had longer hospital stays compared with the non-CPS group. In adjusted analysis, cognitive scores were points lower (B = -1.94; 95% CI, -3.88 to -0.08; P = .04) in the CPS at discharge group compared with the non-CPS group. In children who entered CPS supervision after hospital discharge (an additional 106 infants), cognitive scores were 4 points lower (ß = -4.76; 95% CI, -7.47 to -2.05; P < .001) and language scores were 5 points lower (ß = -4.93; 95% CI, -8.00 to -1.86; P = .002). CONCLUSION: Extremely preterm infants discharged from the hospital with CPS supervision or entering CPS postdischarge are at increased risk for cognitive delay at 2 years of age. Opportunities exist to intervene and potentially improve outcomes in this vulnerable group of children.

Factors Associated with Successful First High-Risk Infant Clinic Visit for Very Low Birth Weight Infants in California.

OBJECTIVES: To determine rates of at least 1 high-risk infant follow-up (HRIF) visit by 12 months corrected age, and factors associated with successful first visit among very low birth weight (VLBW) infants in a statewide population-based setting. STUDY DESIGN: We used the linked California Perinatal Quality of Care Collaborative and California Perinatal Quality of Care Collaborative-California Children's Services HRIF databases. Multivariable logistic regression examined independent associations of maternal, sociodemographic, neonatal clinical, and HRIF program factors with a successful first HRIF visit among VLBW infants born in 2010-2011. RESULTS: Among 6512 VLBW children referred to HRIF, 4938 (76%) attended a first visit. Higher odds for first HRIF visit attendance was associated with older maternal age (OR, 1.48; 95% CI, 1.27-1.72; 30-39 vs 20-29 years), lower birth weight (OR, 2.11; 95% CI, 1.69-2.65; ≤750 g vs 1251-1499 g), private insurance (OR, 1.65; 95% CI, 1.19-2.31), a history of severe intracranial hemorrhage (OR, 1.61; 95% CI, 1.12-2.30), 2 parents as primary caregivers (OR, 1.18, 95% CI 1.03-1.36), and higher HRIF program volume (OR, 2.62; 95% CI, 1.88-3.66; second vs lowest quartile); and lower odds with maternal race African American or black (OR, 0.65; 95% CI, 0.54-0.78), and greater distance to HRIF program (OR, 0.69; 95% CI, 0.57-0.83). Rates varied substantially across HRIF programs, which remained after risk adjustment. CONCLUSIONS: In a population-based California VLBW cohort, maternal, sociodemographic, and home- and program-level disparities were associated with HRIF non-attendance. These findings underscore the need to identify challenges in access and resource risk factors during hospitalization in the neonatal intensive care unit, provide enhanced education about the benefits of HRIF, and create comprehensive neonatal intensive care unit-to-home transition approaches.

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth.

OBJECTIVE: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. STUDY DESIGN: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. RESULTS: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. CONCLUSIONS: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. TRIAL REGISTRATION: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).

Extreme Preterm Infant Rates of Overweight and Obesity at School Age in the SUPPORT Neuroimaging and Neurodevelopmental Outcomes Cohort.

OBJECTIVE: To identify rates of overweight (body mass index [BMI] ≥85th percentile) and obesity (BMI ≥95th percentile) at 6-7 years of age and associated risk factors among extremely preterm infants born at <28 weeks of gestation. STUDY DESIGN: Anthropometrics, blood pressure, and active and sedentary activity levels were prospectively assessed. Three groups were compared, those with a BMI ≥85th percentile (overweight or obese for age, height, and sex) and ≥95th percentile (obese) vs <85th percentile. Multiple regression analyses estimated the relative risks of BMI ≥85th percentile and ≥95th percentile associated with perinatal and early childhood factors. RESULTS: Of 388 children, 22% had a BMI of ≥85th percentile and 10% were obese. Children with obesity and overweight compared with normal weight children had higher body fat (subscapular skinfold and triceps skinfold >85th percentile), central fat (waist circumference >90th percentile), spent more time in sedentary activity (20.5 vs 18.2 vs 16.7 hours/week), and had either systolic and/or diastolic hypertension (24% vs 26% vs 14%), respectively. Postdischarge weight gain velocities from 36 weeks postmenstrual age to 18 months, and 18 months to 6-7 years were independently associated with a BMI of ≥85th percentile, whereas weight gain velocity from 18 months to 6-7 years was associated with obesity. CONCLUSIONS: One in 5 former extremely preterm infants is overweight or obese and has central obesity at early school age. Postdischarge weight gain velocities were associated with overweight and obesity. These findings suggest the obesity epidemic is spreading to the most extremely preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063 and NCT0000.

Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age.

OBJECTIVE: To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies. STUDY DESIGN: Infants ≤26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression. RESULTS: Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomalacia. Among the 433 infants with cystic periventricular leukomalacia, cystic periventricular leukomalacia disappeared in 76 (18%), persisted in 87 (20%), and 270 (62%) had late cystic periventricular leukomalacia. Loss to follow-up ranged between 3% and 13%. Death or NDI was more common in infants with disappeared cystic periventricular leukomalacia compared with those with no cystic periventricular leukomalacia (38 of 72 [53%] vs 1776 of 6376 [28%]; OR [95% CI] 2.8 [1.8-4.6]). Disappeared, persistent, and late cystic periventricular leukomalacia were all also independently associated with NDI (OR 1.17, 1.21, and 1.16, respectively). CONCLUSIONS: Infants with "disappeared" cystic periventricular leukomalacia are at increased risk of adverse outcome similar to infants with persistent or late cystic periventricular leukomalacia.

Acute Perinatal Sentinel Events, Neonatal Brain Injury Pattern, and Outcome of Infants Undergoing a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy.

Infants with perinatal sentinel events in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Hypothermia for Encephalopathy Trial had more basal ganglia and thalamus lesions on brain magnetic resonance imaging but similar neurodevelopmental outcomes at 18 months of age than infants without perinatal sentinel events. Outcomes correlated with the neonatal magnetic resonance imaging findings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00005772.