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Objective The objective of our study was to examine factors associated with distance to care for first surgical repair among infants with myelomeningocele in California. Study Design A total of 677 eligible cases with complete geocoded data were identified for birth years 2006 to 2012 using data from the California Perinatal Quality Care Collaborative linked to hospital and vital records. The median distance from home to birth hospital among eligible infants was 9 miles, and from birth hospital to repair hospital was 15 miles. We limited our analysis to infants who lived close to the birth hospital, creating two study groups to examine transfer distance patterns: “lived close and had a short transfer” (i.e., lived Results We found that low birth weight (aRR = 1.44; 95% CI = 1.04, 1.99) and preterm birth (aRR = 1.41; 95% CI = 1.01, 1.97) were positively associated, whereas initiating prenatal care early in the first trimester was inversely associated (aRR = 0.64; 95% CI = 0.46, 0.89) with transferring a longer distance (≥15 miles) from birth hospital to repair hospital. No significant associations were noted by maternal race-ethnicity, socioeconomic indicators, or the level of hospital care at the birth hospital. Conclusion Our study identified selected infant factors associated with the distance to access surgical care for infants with myelomeningocele who had to transfer from birth hospital to repair hospital. Distance-based barriers to care should be identified and optimized when planning deliveries of at-risk infants in other populations. Key Points

ImportanceLate-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm.ObjectiveTo report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months’ corrected age.Design, Setting, and ParticipantsThis cohort study is a secondary analysis of a multicenter prospective cohort of children born at 22 to 26 weeks’ gestation between 2003 and 2017 with follow-up from 2004 to 2021. The study was conducted at 25 Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers.ExposuresCulture-confirmed LOM.Main Outcomes and MeasuresIncidence and microbiology of LOM (2003-2017); lumbar puncture (LP) performance in late-onset sepsis (LOS) evaluations (2011-2017); composite outcome of death or neurodevelopmental impairment (NDI; 2004-2021).ResultsAmong 13 372 infants (median [IQR] gestational age, 25.4 [24.4-26.1] weeks; 6864 [51%] boys), LOM was diagnosed in 167 (1%); LOS without LOM in 4564 (34%); and neither LOS nor LOM in 8641 (65%). The observed incidence of LOM decreased from 2% (95% CI, 1%-3%) in 2003 to 0.4% (95% CI, 0.7%-1.0%) in 2017 (P P P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P P Staphylococcus (98 [59%]), Candida albicans (38 [23%]), and Escherichia coli (27 [16%]). Death or NDI occurred in 22 of 46 children (48%) with LOM due to coagulase-negative Staphylococcus, 43 of 67 (64%) due to all other bacterial pathogens, and 26 of 33 (79%) due to fungal pathogens. The adjusted relative risk of death or NDI was increased among children with LOM (aOR, 1.53; 95% CI, 1.04-2.25) and among those with LOS without LOM (aOR, 1.41; 95% CI, 1.29-1.54) compared with children with neither infection.Conclusions and RelevanceIn this cohort study, LP was performed with decreasing frequency, and the observed incidence of LOM also decreased. Both LOM and LOS were associated with increased risk of death or NDI; risk varied by LOM pathogen. The full association of LOM with outcomes of children born extremely preterm may be underestimated by current diagnostic practices.

Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases.Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements.Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns - one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

OBJECTIVE: This study evaluates the 24 month follow up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial. STUDY DESIGN: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score

To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly. We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit. Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p = 0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p = 0.02) were significantly higher among women with a positive PPD screen. In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

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.

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.

Maternal race/ethnicity is associated with mortality in neonates with hypoplastic left heart syndrome (HLHS). We investigated whether maternal race/ethnicity and other sociodemographic factors affect timing of transfer after birth and whether timing of transfer impacts mortality in infants with HLHS. We linked two statewide databases, the California Perinatal Quality Care Collaborative and records from the Office of Statewide Health Planning and Development, to identify cases of HLHS born between 1/1/06 and 12/31/11. Cases were divided into three groups: birth at destination hospital, transfer on day of life 0–1 (“early transfer”), or transfer on day of life ≥ 2 (“late transfer”). We used log-binomial regression models to estimate relative risks (RR) for timing of transfer and Cox proportional hazard models to estimate hazard ratios (HR) for mortality. We excluded infants who died within 60 days of life without intervention from the main analyses of timing of transfer, since intervention may not have been planned in these infants. Of 556 cases, 107 died without intervention (19%) and another 52 (9%) died within 28 days. Of the 449 included in analyses of timing of transfer, 28% were born at the destination hospital, 49% were transferred early, and 23% were transferred late. Late transfer was more likely for infants of low birthweight (RR 1.74) and infants born to US-born Hispanic (RR 1.69) and black (RR 2.45) mothers. Low birthweight (HR 1.50), low 5-min Apgar score (HR 4.69), and the presence of other major congenital anomalies (HR 3.41), but not timing of transfer, predicted neonatal mortality. Late transfer was more likely in neonates born to US-born Hispanic and black mothers but was not associated with higher mortality. Supplementary Information The online version of this article (10.1007/s00246-021-02561-w) contains supplementary material, which is available to authorized users.

Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

Objective To determine the rates of high-risk infant follow-up (HRIF) attendance and the characteristics associated with follow-up among infants with hypoxic-ischemic encephalopathy (HIE) in California. Study design Using population-based datasets, 1314 infants with HIE born in 2010-2016 were evaluated. The characteristics associated with follow-up were identified through multivariable logistic regression. Results 73.9% of infants attended HRIF by age 1. Follow-up rates increased and variation in follow-up by clinic decreased over time. Female infants; those born to African-American, single, less than college-educated, or publicly insured caregivers; and those referred to high-volume or regional programs had lower follow-up rates. In multivariable analysis, Asian and Pacific Islander race/ethnicity had lower odds of follow-up; infants with college- or graduate school-educated caregivers or referred to mid-volume HRIF programs had greater odds. Conclusion Sociodemographic and program-level characteristics were associated with lack of follow-up among HIE infants. Understanding these characteristics may improve the post-discharge care of HIE infants.

Objective To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone. Methods This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics. Results Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups. Conclusion In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone. Clinical trial registration ClinicalTrials.gov, NCT00063063.

Objective The aim of this study is to examine factors associated with early neonatal (death within first 7 days of birth) and infant (death during the first year of life) mortality among infants born with myelomeningocele. Study design We examined linked data from the California Perinatal Quality Care Collaborative, vital records, and hospital discharge records for infants born with myelomeningocele from 2006 to 2011. Survival probability was calculated using Kaplan-Meier Product Limit method and 95% confidence intervals (CI) using Greenwood's method; Cox proportional hazard models were used to estimate unadjusted and adjusted hazard ratios (HR) and 95% CI. Results Early neonatal and first-year survival probabilities among infants born with myelomeningocele were 96.0% (95% CI: 94.1-97.3%) and 94.5% (95% CI: 92.4-96.1%), respectively. Low birthweight and having multiple co-occurring birth defects were associated with increased HRs ranging between 5 and 20, while having congenital hydrocephalus and receiving hospital transfer from the birth hospital to another hospital for myelomeningocele surgery were associated with HRs indicating a protective association with early neonatal and infant mortality. Conclusion Maternal race/ethnicity and social disadvantage did not predict early neonatal and infant mortality among infants with myelomeningocele; presence of congenital hydrocephalus and the role of hospital transfer for myelomeningocele repair should be further examined. Key points · Mortality in myelomeningocele is a concern. · Social disadvantage was not associated with death. · Hospital-based factors should be further examined.

Objective Pulmonary hypertension (PH) has been described in the neonatal omphalocele population. This study was aimed to describe cardiac function and PH severity using echocardiography in newborns with giant omphalocele (GO) and with non-GO and determine if right ventricular (RV) dysfunction is associated with mortality. Study Design Retrospective, single-center analysis of first echocardiography among neonatal omphalocele patients born between 2004 and 2017 was conducted. Multivariate logistic and univariate Cox's regression was constructed to measure hazard ratio (HR) for death outcome. Results There were 32 newborns, of whom 18 were GO and 7 died. GO had increased systolic pulmonary arterial to systolic systemic blood pressure ratio (97% [isosystemic] vs. 73% [three-fourths systemic] p = 0.03). RV performance parameters (tricuspid annular plane excursion, HR = 0.40; fractional area change, HR = 0.90; and RV peak global longitudinal strain, HR = 1.39) were associated with mortality. These RV performance parameters remained associated in a multiple logistic regression accounting for gestational age and GO status. The overall population had abnormal eccentricity index and pulmonary artery acceleration time to RV ejection time ratio, two markers of PH. Conclusion Patients with omphalocele have increased pulmonary pressure, with GO being worse than non-GO. RV dysfunction at initial echocardiography was significantly associated with mortality.

Prior studies report a lower risk of mortality among neonates with hypoplastic left heart syndrome (HLHS) who are born at a cardiac surgical center, but many neonates with HLHS are born elsewhere and transferred for repair. We investigated the associations between the distance from maternal home to birth hospital, the need for transfer after birth, sociodemographic factors, and mortality in infants with HLHS in California from 2006 to 2011.We used linked data from two statewide databases to identify neonates for this study. Three groups were included in the analysis: "lived close/not transferred," "lived close/transferred," and "lived far/not transferred." We defined "lived close" versus "lived far" as 11 miles, the median distance from maternal residence to birth hospital. Log-binomial regression models were used to identify the association between sociodemographic variables, distance to birth hospital and transfer. Cox proportional hazards models were used to identify the association between mortality and distance to birth hospital and transfer. Models were adjusted for sociodemographic variables.Infants in the lived close/not transferred and the lived close/transferred groups (vs. the lived far/not transferred group) were more likely to live in census tracts above the 75th percentile for poverty with relative risks 1.94 (95% confidence interval [CI] 1.41-2.68) and 1.21 (95% CI 1.05-1.40), respectively. Neonatal mortality was higher among the lived close/not transferred group compared with the lived far/not transferred group (hazard ratio 1.77, 95% CI 1.17-2.67).Infants born to mothers experiencing poverty were more likely to be born close to home. Infants with HLHS who were born close to home and not transferred to a cardiac center had a higher risk of neonatal mortality than infants who were delivered far from home and not transferred. Future studies should identify the barriers to delivery at a cardiac center for mothers experiencing poverty.

Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown.We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age.We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups.In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

OBJECTIVE To test the hypothesis that an Apgar score at 10 minutes is independently predictive for death or moderate or severe disability. METHODS A secondary analysis of the Optimizing Cooling Trial (NCT01192776) including 347 infants with ≥36 weeks’ gestational age at birth and hypoxic-ischemic encephalopathy and 18- to 22-month outcomes from 18 US centers in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome was the composite of death or moderate/severe disability at 18 to 22 months of age. Generalized estimating equation models were used to examine the relationship between Apgar scores and outcomes, controlling for center, hypothermia treatment, and severity of hypoxic-ischemic encephalopathy (HIE). Classification and regression tree analyses were conducted to identify combinations of variables available during resuscitation that were most predictive for the composite outcome and death. RESULTS The study revealed that 50% (13 of 26) of infants with a 10-minute Apgar score of 0 survived; 46% (6 of 13) had no disability, 16% (2 of 13) had mild disability, and 38% (5 of 13) had moderate or severe disability. The 10-minute Apgar score of 0 was independently associated with death or moderate or severe disability (adjusted relative risk = 1.72, 95% confidence interval 1.11–2.68, P value = .016), but the area under the curve analysis (AUC) was low (AUC = 0.56). The predictive accuracy improved when the 10-minute Apgar score was combined with other risk variables available during resuscitation by using a classification and regression tree analysis (AUC = 0.66). CONCLUSIONS A 10-minute Apgar score of 0 alone does not predict the risk of death or moderate or severe disability well. The current study provides evidence in support of the 2020 American Heart Association/International Liaison Committee on Resuscitation recommendation for continuing resuscitative efforts for infants who need cardiopulmonary resuscitation at 10 minutes after birth.

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.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.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).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.

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.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.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).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.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.ClinicalTrials.gov ID: Inositol to Reduce Retinopathy of Prematurity Trial: NCT01954082.

Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined.A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables.In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p 0.001).Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population.Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

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.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.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.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.Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.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.

Objective: To explore the relationship between neonatal oxygen saturation and BP at age 6-7 years in a cohort of infants born extremely preterm. Study Design: Infants

Objective. To understand factors associated with care and survival among babies with congenital diaphragmatic hernia (CDH). Study design. We used data on California births (2006–2011) to examine birth hospital level of care, hospital transfer before repair, and survival. Result. Among 577 infants, 25% were born at lower-level hospitals, 62% were transferred, and 31% died during infancy. Late or no prenatal care had the strongest association with birth at lower-level hospitals (adjusted Relative Risk (ARR)=1.9, 95% confidence interval (CI)=1.0–3.6). Birth at lower-level hospitals was associated with transfer (ARR=1.2, CI=1.1–1.4), and transferred infants tended to be less clinically complex. Infants with low birthweight, other birth defects, low Apgar scores, and late or no prenatal care had 2–4-fold higher risk of mortality than their comparison groups. Conclusions. These data support the importance of prenatal care and delivery planning into higher-level hospitals for optimal care and outcomes for newborns with CDH.

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

INTRODUCTION The clinical importance of mass effect from congenital lung masses on the fetal heart is unknown. We aimed to report cardiac measurements in fetuses with congenital lung masses and to correlate lung mass severity/size with cardiac dimensions and clinical outcomes. METHODS Cases were identified from our institutional database between 2009 and 2016. We recorded atrioventricular valve (AVVz) annulus dimensions and ventricular widths (VWz) converted into z scores, ratio of aortic to total cardiac output (AoCO), lesion side, and congenital pulmonary airway malformation volume ratio (CVR). Respiratory intervention (RI) was defined as intubation, extracorporeal membrane oxygenation (ECMO), or use of surgical intervention prior to discharge. RESULTS Fifty-two fetuses comprised the study cohort. Mean AVVz and VWz were below expected for gestational age. CVR correlated with ipsilateral AVVz (RS = -.59, P < .001) and ipsilateral VWz (-0.59, P < .001). Lower AVVz and AoCO and higher CVR were associated with RI. No patient had significant structural heart disease identified postnatally. CONCLUSION In fetuses with left-sided lung masses, ipsilateral cardiac structures tend to be smaller, but in our cohort, there were no patients with structural heart disease. However, smaller left-sided structures may contribute to the need for RI that affects a portion of these fetuses.

Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology.A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher's exact test was used for categorical variables and the Kruskal-Wallis test was used for continuous variables. The level of significance wasOf 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.

To investigate the effect of preterm gestational age (GA) on neonatal outcomes of gastroschisis and to compare the neonatal outcomes after spontaneous labor versus iatrogenic delivery both in the preterm and early term gestational periods.A retrospective study of prenatally diagnosed gastroschisis cases born at Loma Linda University Medical Center and Lucile Packard Children's Hospital (Loma Linda, CA) between January 2009 and October 2016. A total of 194 prenatally diagnosed gastroschisis cases were identified and included in the analysis. We compared infants delivered37 0/7 to those ≥37 0/7 weeks' gestation. Adverse neonatal outcome was defined as any of: sepsis, short bowel syndrome, prolonged ventilation, or death. Prolonged length of stay (LOS) was defined as ≥75th percentile value. Outcomes following spontaneous versus iatrogenic delivery were compared. Analyses were performed using chi-squared test or Fisher's exact test for categorical variables, and Student'sOne hundred and six neonates were born37 weeks and 88 at ≥37 weeks. Adverse outcome was statistically similar among those born37 weeks compared to ≥37 weeks (48 versus 34%,Neonates with gastroschisis delivered37 weeks had prolonged LOS whereas the rate of adverse neonatal outcomes was similar between those delivered preterm versus term. Neonates born after spontaneous preterm labor had a higher rate of bowel atresia compared to those born after planned iatrogenic preterm delivery.

Objective This study aimed to examine factors associated with timely (0–2 days after birth) myelomeningocele surgical repair. Study Design We examined 2006 to 2011 births from the California Perinatal Quality Care Collaborative, linking to hospital discharge and vital records. Selected maternal, infant, and delivery hospital characteristics were evaluated to understand disparities in timely repair. Poisson regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). Results Overall, 399 of the 450 (89%) infants had a timely repair and approximately 80% of them were delivered in level III/IV hospitals. Infants with hydrocephalus were significantly less likely to have a delayed myelomeningocele repair compared with those without (aRR = 0.22; 95% CI = 0.13, 0.39); infants whose medical care was paid by Medi-Cal or other nonprivate insurance were 2.2 times more likely to have a delayed repair compared with those covered by a private insurance (aRR = 2.23; 95% CI = 1.17, 4.27). Low birth weight was a significant predictor for delayed repair (aRR = 2.06; 95% CI = 1.10, 3.83). Conclusion There was a significant disparity in myelomenigocele repair based on medical care payer. Families and hospitals should work together for timely repair in hospitals having specialized multidisciplinary teams. Findings from the study can be used to follow best clinical practices for myelomeningocele repair.

To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases. Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed. Out of 63 fetal cases, 33 were live-born, > 50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach to omphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3–422), p = 0.006). Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

The Induced Hypothermia (IH) and Optimizing Cooling (OC) trials for hypoxic–ischemic encephalopathy (HIE) had similar inclusion criteria. The rate of death/moderate–severe disability differed for the subgroups treated with therapeutic hypothermia (TH) at 33.5 °C for 72 h (44% vs. 29%, unadjusted p = 0.03). We aimed to evaluate differences in patient characteristics and care practices between the trials. We compared pre/post-randomization characteristics and care practices between IH and OC. There were 208 patients in the IH trial, 102 cooled, and 364 in the OC trial, 95 cooled to 33.5 °C for 72 h. In OC, neonates were less ill, fewer had severe HIE, and the majority were cooled prior to randomization. Differences between IH and OC were observed in the adjusted difference in the lowest PCO2 (+3.08 mmHg, p = 0.005) and highest PO2 (−82.7 mmHg, p

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.

OBJECTIVE: To determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18–22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage (adjusted relative risk [aRR] = 1.0; 95% confidence interval [CI]: 0.87–1.14). A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (p = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR=0.81; 95% CI: 0.64 to 1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference

Importance Both preterm birth and increased screen time are known to be associated with an increase in risk of developmental and behavioral sequelae. The association between high screen time or a television or computer in the bedroom in early school age and adverse cognitive, executive function, language, and behavior outcomes of extremely preterm children (EPT) is not well understood. Objective To assess the association of high screen time with cognition, language, executive function, and behavior of EPT children aged 6 to 7 years; a second objective was to examine the association between high screen time and rates of structured physical activity and weight. Design, setting, and participants This cohort study was a secondary analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial Neuroimaging and Neurodevelopmental Outcomes school-aged cohort and includes 414 EPT children born between February 1, 2005, and February 28, 2009, and evaluated in between 2012 and 2016 at ages 6 years 4 months to 7 years 2 months. The study was conducted from July 7, 2012, and August 15, 2016, and data were analyzed between December 10, 2018, and April 1, 2021. Exposures Cohorts included children exposed to low (≤2 hours per day) vs high (>2 hours per day) amounts of screen time and by the presence (no vs yes) of a television/computer in the bedroom. Main outcomes and measures In addition to growth parameters, assessments included the Wechsler Intelligence Scale for Children-IV, the Behavior Rating Inventory of Executive Function, the Developmental Neuropsychological Assessment, the Conners 3rd Edition-Parent Short-Form, and the Social Communication Questionnaire. Results Of the 414 children included in the analysis, 227 (55%) were boys; mean (SD) birth weight was 870.6 (191) g. A total of 238 children (57%) had high screen time and 266 (64%) had a television/computer in their bedroom. In multivariable linear regressions adjusted for center, male sex, gestational age, and social determinants of health, high screen time was independently associated with the following mean (SE) test score changes: lower full-scale IQ (-3.92 [1.64]; P = .02); an increase in association with deficits in executive functions, including metacognition (8.18 [3.01]; P = .007), global executive function (7.49 [2.99]; P = .01), inhibition (-0.79 [0.38]; P = .03), and Conners 3rd Edition-Parent Short-Form inattention (3.32 [1.67]; P = .047). A television/computer in the bedroom was associated with an increase in inhibition (-0.80 [0.39]; P = .04) and hyperactivity/impulsivity (3.50 [1.75]; P = .046) problems. Conclusions and relevance The findings of this study suggest that high screen time contributes to adverse cognitive, executive function, and behavior outcomes at ages 6 to 7 years in children born at less than 28 weeks. These findings support the need for clinicians to have heightened awareness of the risks for EPT children and discuss both the benefits and risks of screen time with families.

OBJECTIVE This study was aimed to determine factors associated with attendance at the second high-risk infant follow-up (HRIF) visit (V2) by 20 months of corrected age after a successful first visit (V1), and the impact of rural residence on attendance rates in a statewide population of very low birth weight (VLBW

Continuous quality improvement (CQI) has become a vital component of newborn medicine. Applying core principles - robust measurement, repeated small tests of change, collaborative learning through data sharing - have led to improvements in care quality, safety, and outcomes in the Neonatal Intensive Care Unit (NICU). High-risk infant follow-up programs (HRIF) have historically aided such quality improvement efforts by providing outcomes data about NICU interventions. Though as a discipline, HRIF has not universally embraced CQI for its own practice. In this review, we summarize the history of CQI in neonatology and applications of improvement science in healthcare and describe examples of CQI in HRIF. We identify the need for consensus on what defines 'high-risk' and constitutes meaningful outcomes. Last, we outline four areas for future investment: establishing evidence-based care delivery systems, standardizing outcomes and their measures, embracing a family-centered approach prioritizing parent goals, and developing professional standards of care for HRIF.

Background There is increased risk of cardiovascular, metabolic, and hypertensive disorders in later life in the preterm population. We studied school-age children who had been born extremely premature who had undergone endocrine, cardiovascular, and anthropometric evaluations. Methods School age measurements of salivary cortisol, adrenal androgens, blood pressure, and anthropometric markers were correlated with DNA methylation of 11-betahydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element. Results We observed a modest correlation between log AUC for salivary cortisol and methylation of leptin in preterm infants and a negative correlation between methylation of region 1 of the glucocorticoid receptor (GR in term-born infants. There was an association between LINE1 methylation and cortisol response to awakening and a negative correlation between LINE1 and systolic blood pressure at 6-7 years. Methylation of the GR promoter region showed a positive association with systolic blood pressure at 6-7 years of age. Conclusions These results show that extremely preterm birth, followed by complex patterns of endocrine, cardiovascular, and metabolic exposures during early postnatal life, is associated with lasting changes in DNA methylation patterns in genes involved in hypothalamic pituitary adrenal axis function, adrenal hormonal regulation, and cardiometabolic risk. Impact Preterm infants have significant environmental and physiological exposures during early life that may have lasting impact on later function. Alterations in hypothalamic pituitary adrenal axis (HPA) function have been associated with these exposures. We examined the associated changes in DNA methylation of important genes involved in HPA function, metabolism, and global DNA methylation. The changes we saw in DNA methylation may help to explain associated cardiovascular, metabolic, and growth disturbance in these children in later life.

To investigate factors associated with positive postpartum depression (PPD) screen in pregnancies complicated by fetal congenital cardiac anomaly.We reviewed all records of pregnancies complicated by fetal congenital cardiac anomaly receiving prenatal, intrapartum and postpartum care at our single center, October 2016-October 2019. Maternal, obstetric, and neonatal data were compared between women with and without a positive PPD screen at the 6-week postpartum visit.Out of 415 women referred for fetal congenital cardiac anomaly, 86 women had complete inclusion criteria. Twenty-four women (28%) had a positive PPD screen. The frequencies of planned future infant surgery (73.9 vs. 26.2%, p = 0.01) and neonatal death prior to postpartum visit (12.5 vs. 0%, p = 0.02) were significantly higher among women with a positive PPD screen.In pregnancies complicated by fetal congenital cardiac anomaly, mothers of infants with planned future surgery or neonatal death are at significant risk for postpartum depression.

The novel coronavirus disease 2019 (COVID-19) pandemic is affecting care for high-risk newborns in ways that will likely be sustained beyond the initial pandemic response. These novel challenges present an urgent imperative to understand how COVID-19 impacts parent, family, and infant outcomes. We highlight three areas that warrant targeted attention: (1) inpatient care: visitation policies, developmental care, and communication practices; (2) outpatient care: high-risk infant follow-up and early intervention programs; and (3) parent psychosocial distress: mental health, social support, and financial toxicity. Changes to care delivery in these areas provide an opportunity to identify and implement novel strategies to provide family-centered care during COVID-19 and beyond. KEY POINTS: · The COVID-19 pandemic is influencing care delivery for high-risk newborns and their families.. · Rapid changes to care delivery are likely to be sustained beyond the initial pandemic response.. · We have an urgent imperative to understand how COVID-19 impacts infant, parent, and family outcomes..

To determine the rates of high-risk infant follow-up (HRIF) attendance and the characteristics associated with follow-up among infants with hypoxic-ischemic encephalopathy (HIE) in California.Using population-based datasets, 1314 infants with HIE born in 2010-2016 were evaluated. The characteristics associated with follow-up were identified through multivariable logistic regression.73.9% of infants attended HRIF by age 1. Follow-up rates increased and variation in follow-up by clinic decreased over time. Female infants; those born to African-American, single, less than college-educated, or publicly insured caregivers; and those referred to high-volume or regional programs had lower follow-up rates. In multivariable analysis, Asian and Pacific Islander race/ethnicity had lower odds of follow-up; infants with college- or graduate school-educated caregivers or referred to mid-volume HRIF programs had greater odds.Sociodemographic and program-level characteristics were associated with lack of follow-up among HIE infants. Understanding these characteristics may improve the post-discharge care of HIE infants.

OBJECTIVES: To examine trends in survival without major morbidity and its individual components among very low birth weight infants across California and assess remaining gaps that may be opportune targets for improvement efforts. METHODS: The study population included infants born between 2008 and 2017 with birth weights of 401 to 1500 g or a gestational age of 22 to 29 weeks. Risk-adjusted trends of survival without major morbidity and its individual components were analyzed. Survival without major morbidity was defined as the absence of death during birth hospitalization, chronic lung disease, severe peri-intraventricular hemorrhage, nosocomial infection, necrotizing enterocolitis, severe retinopathy of prematurity or related surgery, and cystic periventricular leukomalacia. Variations in adjusted rates and/or interquartile ranges were examined. To assess opportunities for additional improvement, all hospitals were reassigned to perform as if in the top quartile, and recalculation of predicted numbers were used to estimate potential benefit. RESULTS: In this cohort of 49 333 infants across 142 hospitals, survival without major morbidity consistently increased from 62.2% to 66.9% from 2008 to 2017. Network variation decreased, with interquartile ranges decreasing from 21.1% to 19.2%. The largest improvements were seen for necrotizing enterocolitis and nosocomial infection. Bronchopulmonary dysplasia rates did not change significantly. Over the final 3 years, if all hospitals performed as well as the top quartile, an additional 621 infants per year would have survived without major morbidity, accounting for an additional 6.6% annual improvement. CONCLUSIONS: Although trends are promising, bronchopulmonary dysplasia remains a common and persistent major morbidity, remaining a target for continued quality-improvement efforts.