Neonatal Research Network Centers Research Articles

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

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

Potential Missed Opportunities for Antenatal Corticosteroid Exposure and Outcomes Among Periviable Births: Observational Cohort Study

ABSTRACT Antenatal corticosteroid (ANCS) exposure reduces preterm infant death and morbidities, such as intracranial hemorrhage. Although observational studies suggest periviable infants may benefit from this treatment, many eligible women do not receive ANCSs due to unclear policies, lack of opportunity, or inconsistent care. Professional societies and the Eunice Kennedy Shriver National Institute of Child Health and Human Development recommend administering ANCSs at 24 weeks' gestation for all at-risk pregnancies and as early as 22 weeks with planned postnatal treatment. The aim of this study was to assess whether potential missed opportunities for ANCSs increase as gestational age decreases and are associated with higher rates of hospital mortality or severe brain injury. This was an observational cohort study of infants born at 24 National Institute of Child Health and Human Development Neonatal Research Network centers from 2006 to 2018. Included were infants at 220/7 to 256/7 weeks of gestation, without major birth defects, and a birth weight of 401 to 1000 g. Data were collected prospectively from birth to discharge, transfer, death, or 120 days. Antenatal corticosteroid exposure was defined as infants who received partial, complete, or repeat courses of the treatment. Potential missed opportunities for exposure were defined as infants who received no ANCSs, despite potentially having sufficient time to receive prenatal antibiotics, were administered magnesium sulfate, or experience prolonged rupture of membranes. Severe brain injury was defined as intracranial hemorrhage or periventricular leukomalacia on cranial imaging. The primary outcome was the rate of ANCS exposure and potential missed opportunities at each gestational age. Secondary outcomes included death and severe brain injury. A total of 7957 infants who were actively treated postnatally were included in the primary analysis. Of these, 87.6% had ANCS exposure, 5.7% had no exposure but potential missed opportunities for exposure, and 6.7% had no exposure and no potential missed opportunities. Potential missed opportunities for exposure were more common in infants born at 22 and 23 weeks versus 25 weeks (22 weeks: adjusted risk ratio [aRR], 11.06; 95% confidence interval [CI], 7.52–16.27; P < 0.001); 23 weeks: aRR, 3.24; 95% CI, 2.44–4.29; P < 0.001). No difference was observed between 24 and 25 weeks (24 weeks: aRR, 1.08; 95% CI, 0.82–1.42). From 2006 to 2018, infants at 22 weeks saw the largest increase in exposure to ANCSs (12.5%–87.2%) and a decrease in the rate of potential missed opportunities (68.8%–2.6%). Overall, the rate of mortality was 23% lower among infants in the exposure group than for those in the missed opportunities group (31% vs 54.8%; aRR, 0.77; 95% CI, 0.70–0.84; P < 0.001). Infants in the exposure group had lower risk of severe brain injury than those in the missed opportunities group (25% vs 44.5%; aRR, 0.64; 95% CI, 0.55–0.73; P < 0.001), with no significant variation by gestational age. In conclusion, the potential for missed opportunities for ANCS exposure was more common among periviable infants at 22 and 23 weeks compared with those at 25 weeks of gestation. Moreover, exposure to ANCSs was associated with lower rates of mortality and severe brain injury.

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

To characterize the relationships between social determinants of health (SDOH) and outcomes for children born extremely preterm. This is a cohort study of infants born at 22-26weeks 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). Of 7438 children, 5442 (73%) had at least 1 risk-associated SDOH. PMA at discharge was older (adjusted mean difference 0.37weeks, 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. 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.

Noninvasive Ventilation and Exogenous Surfactant in Times of Ever Decreasing Gestational Age: How Do We Make the Most of These Tools?

Noninvasive Ventilation and Exogenous Surfactant in Times of Ever Decreasing Gestational Age: How Do We Make the Most of These Tools?

Antimicrobial Susceptibility Profiles Among Neonatal Early-onset Sepsis Pathogens.

Empiric administration of ampicillin and gentamicin is recommended for newborns at risk of early-onset sepsis (EOS). There are limited data on antimicrobial susceptibility of all EOS pathogens. Retrospective review of antimicrobial susceptibility data from a prospective EOS surveillance study of infants born ≥22 weeks' gestation and cared for in Neonatal Research Network centers April 2015-March 2017. Nonsusceptible was defined as intermediate or resistant on final result. We identified 239 pathogens (235 bacteria, 4 fungi) in 235 EOS cases among 217,480 live-born infants. Antimicrobial susceptibility data were available for 189/239 (79.1%) isolates. Among 81 Gram-positive isolates with ampicillin and gentamicin susceptibility data, all were susceptible in vitro to either ampicillin or gentamicin. Among Gram-negative isolates with ampicillin and gentamicin susceptibility data, 72/94 (76.6%) isolates were nonsusceptible to ampicillin, 8/94 (8.5%) were nonsusceptible to gentamicin, and 7/96 (7.3%) isolates were nonsusceptible to both. Five percent or less of tested Gram-negative isolates were nonsusceptible to each of third or fourth generation cephalosporins, piperacillin-tazobactam, and carbapenems. Overall, we estimated that 8% of EOS cases were caused by isolates nonsusceptible to both ampicillin and gentamicin; these were most likely to occur among preterm, very-low birth weight infants. The vast majority of contemporary EOS pathogens are susceptible to the combination of ampicillin and gentamicin. Clinicians may consider the addition of broader-spectrum therapy among newborns at highest risk of EOS, but we caution that neither the substitution nor the addition of 1 single antimicrobial agent is likely to provide adequate empiric therapy in all cases.

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

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. We undertook a retrospective analysis of prospectively collected data from infants born between 22 and 26weeks 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 18-26months 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. Mortality was 32%, 45%, and 21% in the 3 groups, respectively. Eighty-nine percent of survivors were seen at 18-26months 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. Preterm infants with sNEC/SIP and SBS had increased risk of adverse neurodevelopmental outcomes at 18-26months corrected age and impaired growth compared with peers with sNEC/SIP without SBS or without any of these conditions.

Impact of Early-Onset Sepsis and Antibiotic Use on Death or Survival with Neurodevelopmental Impairment at 2 Years of Age among Extremely Preterm Infants

To evaluate the hypothesis that early-onset sepsis increases risk of death or neurodevelopmental impairment (NDI) among preterm infants; and that among infants without early-onset sepsis, prolonged early antibiotics alters risk of death/NDI. Retrospective cohort study of infants born at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers (2006-2014) at 22-26weeks of gestation andbirth weight 401-1000g. Early-onset sepsis defined as growth of a pathogen from blood or cerebrospinal fluidculture ≤72hours after birth. Prolonged early antibiotics was defined as antibiotics initiated ≤72hours and continued ≥5days without culture-confirmed infection, necrotizing enterocolitis, or spontaneous perforation. Primary outcome was death before follow-up or NDI assessed at 18-26months corrected age. Poisson regression was used to estimate adjusted relative risk (aRR) and CI for early-onset sepsis outcomes. A propensity score for receiving prolonged antibiotics was derived from early clinical factors and used to match infants (1:1) with and without prolonged antibiotic exposure. Log binomial models were used to estimate aRR for outcomes in matched infants. Among 6565 infants, those with early-onset sepsis had higher aRR (95% CI) for death/NDI compared with infants managed with prolonged antibiotics (1.18 [1.06-1.32]) and to infants without prolonged antibiotics (1.23 [1.10-1.37]). Propensity score matching was achieved for 4362 infants. No significant difference in death/NDI (1.04 [0.98-1.11]) was observed with or without prolonged antibiotics among the matched cohort. Early-onset sepsis was associated with increased risk of death/NDI among extremely preterm infants. Among matched infants without culture-confirmed infection, prolonged early antibiotic administration was not associated with death/NDI.

Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.

Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.

Are Neurodevelopmental Outcomes of Infants Born Extremely Preterm Improving Over Time?

* Abbreviations: Bayley-III — : Bayley Scales of Infant and Toddler Development, Third Edition NDI — : neurodevelopmental impairment NRN — : Neonatal Research Network Accurate data on rates of mortality and of neurodevelopmental impairment (NDI) in survivors are critical in decision-making for infants born at 22 to 24 weeks’ gestation, the borderline of viability. Despite many studies reporting on mortality and NDI rates, it is concerning that health care professionals continue to overestimate rates of mortality and NDI of infants at the borderline of viability.1 Because survival rates may have plateaued in recent years,2 there is an increasing emphasis on their rates of NDI. In the current issue of Pediatrics , Adams-Chapman et al3 from the Neonatal Research Network (NRN) hypothesized that NDI in children born at <27 completed weeks’ gestation would decrease over a 3.75-year period beginning in 2011. The authors reported on neurodevelopmental outcomes at 18 to 26 months’ corrected age for 2113 children who had been born and cared for in an NRN center and who were involved in the NRN’s follow-up study. NDI comprised any of the following: gross motor impairment as defined by using a Gross Motor Function Classification System4 of level 2 or more; a Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III)5 cognitive or motor score <70; bilateral blindness; or hearing impairment. The rate of NDI did … Address correspondence to Lex W. Doyle, MD, MSc, FRACP, Research Precinct, Level 7, The Royal Women’s Hospital, 20 Flemington Rd, Parkville, VIC 3052, Australia. E-mail: lwd{at}unimelb.edu.au

Neurodevelopmental Impairment Among Extremely Preterm Infants in the Neonatal Research Network.

Evaluate the spectrum of neurodevelopmental outcome in a contemporary cohort of extremely preterm infants. We hypothesize that the rate of severe neurodevelopmental impairment (NDI) decreases over time. Retrospective analysis of neurodevelopmental outcome of preterm infants ≤27 weeks' gestational age (GA) from a Neonatal Research Network center that completed neurodevelopmental follow-up assessments between April 1, 2011, and January 1, 2015. The Bayley Scales of Infant Development-III (BSID III) and a standardized neurosensory examination were performed between 18 and 26 months' adjusted age. Outcome measures were neurologic examination diagnoses, BSID III cognitive and motor scores, sensory impairment, and the composite outcome of NDI, based on the BSID III cognitive score (analyzed by using a cutoff of <85 or <70), BSID III motor score of <70, moderate or severe cerebral palsy (CP), bilateral blindness, and hearing impairment. Two thousand one hundred and thirteen infants with a mean GA of 25.0 ± 1.0 weeks and mean birth weight of 760 ± 154 g were evaluated. The 11% lost to follow-up were less likely to have private insurance, late-onset sepsis, or severe intraventricular hemorrhage. Neurologic examination results were normal in 59%, suspect abnormal in 19%, and definitely abnormal in 22%. Severe CP decreased 43% whereas mild CP increased 13% during the study. The rate of moderate to severe NDI decreased from 21% to 16% when using the BSID III cognitive cutoff of <70 (P = .07) or from 34% to 31% when using the BSID III cognitive cutoff of <85 (P = .67). Extremely preterm children are at risk for NDI. Over time, the rate of moderate to severe NDI did not differ, but the rates of severe CP decreased, and mild CP increased.

Identification of Extremely Premature Infants at Low Risk for Early-Onset Sepsis.

Premature infants are at high risk of early-onset sepsis (EOS) relative to term infants, and most are administered empirical antibiotics after birth. We aimed to determine if factors evident at birth could be used to identify premature infants at lower risk of EOS. Study infants were born at 22 to 28 weeks' gestation in Neonatal Research Network centers from 2006 to 2014. EOS was defined by isolation of pathogenic species from blood or cerebrospinal fluid culture at ≤72 hours age. Infants were hypothesized as "low risk" for EOS when delivered via cesarean delivery, with membrane rupture at delivery, and absence of clinical chorioamnionitis. Frequency of prolonged antibiotics (≥5 days) was compared between low-risk infants and all others. Risks of mortality, EOS, and other morbidities were assessed by using regression models adjusted for center, race, antenatal steroid use, multiple birth, sex, gestation, and birth weight. Of 15 433 infants, 5759 (37%) met low-risk criteria. EOS incidence among infants surviving >12 hours was 29 out of 5640 (0.5%) in the low-risk group versus 209 out of 8422 (2.5%) in the comparison group (adjusted relative risk = 0.24 [95% confidence interval, 0.16-0.36]). Low-risk infants also had significantly lower combined risk of EOS or death ≤12 hours. Prolonged antibiotics were administered to 34% of low-risk infants versus 47% of comparison infants without EOS. Delivery characteristics of extremely preterm infants can be used to identify those with significantly lower incidence of EOS. Recognition of differential risk may help guide decisions to limit early antibiotic use among approximately one-third of these infants.

Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy

Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0°C (acceptable range, 36.5°C-37.3°C). The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively. Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness. clinicaltrials.gov Identifier: NCT00614744.

Late-onset Sepsis in Extremely Premature Infants: 2000-2011.

Late-onset sepsis (LOS) is an important cause of death and neurodevelopmental impairment in premature infants. The purpose of this study was to assess overall incidence of LOS, distribution of LOS-causative organisms and center variation in incidence of LOS for extremely premature infants over time. In a retrospective analysis of infants 401-1000 g birth weight and 22-28 6/7 weeks of gestational age born at 12 National Institute of Child Health and Human Development Neonatal Research Network centers in the years 2000-2005 (era 1) or 2006-2011 (era 2) who survived >72 hours, we compared the incidence of LOS and pathogen distribution in the 2 eras using the χ test. We also examined the effect of birth year on the incidence of LOS using multivariable regression to adjust for nonmodifiable risk factors and for center. To assess whether the incidence of LOS was different among centers in era 2, we used a multivariable regression model to adjust for nonmodifiable risk factors. Ten-thousand one-hundred thirty-one infants were studied. LOS occurred in 2083 of 5031 (41%) infants in era 1 and 1728 of 5100 (34%) infants in era 2 (P < 0.001). Birth year was a significant predictor of LOS on adjusted analysis, with birth years 2000-2009 having a significantly higher odds of LOS than the reference year 2011. Pathogens did not differ, with the exception of decreased fungal infection (P < 0.001). In era 2, 9 centers had significantly higher odds of LOS compared with the center with the lowest incidence. The incidence of LOS decreased over time. Further investigation is warranted to determine which interventions have the greatest impact on infection rates.

Efficacy of pharmacologic closure of patent ductus arteriosus in small-for-gestational-age extremely preterm infants

BackgroundOptimal management of the patent ductus arteriosus (PDA) in preterm infants remains controversial. Therefore, studies identifying infants who are most likely to benefit from PDA treatment are needed. AimWe sought to examine if significant intrauterine growth restriction, defined by birth weight z-score, reduces the efficacy of PDA closure with indomethacin or ibuprofen and thereby increases the need for surgical closure of PDA after pharmacologic treatment. Study design, subjects, and outcome measuresWe studied infants 23–28weeks' gestation born 2006–2013 at NICHD Neonatal Research Network centers. We examined the responses to PDA treatment with indomethacin and/or ibuprofen and whether the PDA was subsequently closed surgically. Logistic regression generated adjusted odds ratios (ORs) for the associations between the z-score groups (<−2, −2 to −0.5, and >−0.5) and PDA surgery following pharmacologic treatment. Results5606 infants were diagnosed with PDA; 3587 (64.0%) received indomethacin or ibuprofen or both, and 909 (25.3%) underwent PDA surgery. Mothers of infants with PDA non-closure were less likely to have hypertension (19% vs. 28%). Infants with non-closure were more likely to be female (53% vs. 49%), have lower gestational age and birth weight and to develop sepsis (42% vs. 31%). Compared to infants with z-score>−0.5, PDA surgery was increased among infants with z-score −2 to −0.5 (OR=1.23; 95% CI 1.02–1.47) but not among infants with z-score<−2. ConclusionInfants with birth weight z-score −2 to −0.5 are more likely than normally grown infants to require PDA surgery following pharmacologic treatment.

Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993 to 2012

(JAMA. 2015;314(10):1039–1051) Extremely preterm infants contribute disproportionately to the burden of neonatal morbidity, mortality, and long-term neurodevelopmental disability. This study of extremely preterm infants born at Human Development Neonatal Research Network (NRN) centers is the first comprehensive review to evaluate how care practices, major morbidities, and mortality have evolved over a 20-year period.

Outcomes of Extremely Preterm Infants Born to Insulin-Dependent Diabetic Mothers.

Little is known about in-hospital morbidities and neurodevelopmental outcomes among extremely preterm infants born to women with insulin-dependent diabetes mellitus (IDDM). We examined risks of mortality, in-hospital morbidities, and neurodevelopmental outcomes at 18 to 22 months' corrected age between extremely preterm infants of women with insulin use before pregnancy (IBP), with insulin use started during pregnancy (IDP), and without IDDM. Infants 22 to 28 weeks' gestation born or cared for at a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network center (2006-2011) were studied. Regression models compared the association between maternal IDDM and timing of insulin use and the outcomes of the 3 groups. Of 10 781 infants, 536 (5%) were born to women with IDDM; 58% had IBP, and 36% had IDP. Infants of mothers with IBP had higher risks of necrotizing enterocolitis (adjusted relative risk [RR] = 1.55 [95% confidence interval (CI) 1.17-2.05]) and late-onset sepsis (adjusted RR = 1.26 [95% CI 1.07-1.48]) than infants of mothers without IDDM. There was some indication of higher in-hospital mortality risk among infants of mothers with IBP compared with those with IDP (adjusted RR = 1.33 [95% CI 1.00-1.79]). Among survivors evaluated at 18 to 22 months' corrected age, average head circumference z score was lower for infants of mothers with IBP compared with those without IDDM, but there were no differences in risk of neurodevelopmental impairment. In this cohort of extremely preterm infants, infants of mothers with IBP had higher risks of necrotizing enterocolitis, sepsis, and small head circumference.

Association of Antenatal Corticosteroids With Mortality, Morbidity, and Neurodevelopmental Outcomes in Extremely Preterm Multiple Gestation Infants.

Little is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples. To examine if use of ANS is associated with improvement in major outcomes in extremely preterm multiples. Infants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables. Antenatal corticosteroids. In-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment. A total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01). Compared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.

Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012.

Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality. To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers. Prospective registry of 34,636 infants, 22 to 28 weeks' gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012. Extremely preterm birth. Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex. Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants]; P < .001), as did cesarean delivery (44% [625 of 1431 births] to 64% [1227 of 1921]; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27% {85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks' gestation (26 weeks, 50% [130 of 258] to 55% [164 of 297]; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks' gestation (27% [41 of 152] to 33% [50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63% [156 of 248] to 65% [174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks' gestation, and no change for infants at 22, 26, and 28 weeks' gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks' gestation, with no change for infants at 22 to 24 weeks' gestation. Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks' gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions. clinicaltrials.gov Identifier: NCT00063063.

Developmental outcomes of extremely preterm infants born to adolescent mothers.

Extremely preterm infants and infants born to adolescent mothers are at risk for adverse developmental. The objectives were to evaluate development and behavior outcomes of extremely low birth weight (ELBW) infants born to adolescent mothers <20 compared with adult mothers ≥20 years and to identify socioeconomic risk factors that affect outcomes. Retrospective cohort analysis of 211 infants >27 weeks of adolescent mothers and 1723 infants of adult mothers at Neonatal Research Network centers from 2008 to 2011. Groups were compared and regression models were run to predict 18- to 22-month adverse outcomes. Primary outcomes were Bayley-III scores, neurodevelopmental impairment, and Brief Infant Toddler Social Emotional Assessment problem scores (BITSEA/P) ≥75th percentile. Adolescent mothers were more often single, Hispanic, less educated, and had public insurance. By 18 to 22 months, their children had significantly increased rates of having lived ≥3 places (21% vs 9%), state supervision (7% vs 3%), rehospitalization (56% vs 46%), and BITSEA/P ≥75th percentile (50% vs 32%) and nonsignificant Bayley-III language scores <85 (56% vs 49%, P = .07). In regression analysis, children of adolescent mothers were more likely to have BITSEA/P ≥75th percentile (relative risk 1.50, 95% confidence interval 1.08-2.07). Living ≥3 places and nonwhite race were predictors of adverse behavior. State supervision was an independent predictor of each Bayley-III composite <70 and neurodevelopmental impairment. ELBW infants of adolescent mothers experience high social and environmental risks that are associated with adverse behavior outcomes. These findings inform the need for comprehensive follow-up, coordinated care services, and behavior interventions for ELBW infants of adolescent mothers.

Death or survival with major morbidity in VLBW infants born at Brazilian neonatal research network centers

Objective: To analyze unfavorable outcomes at hospital discharge of preterm infants born at Brazilian public university centers.Methods: Prospective cohort of 2646 inborn infants with gestational age 23–33 weeks and birth weight 400–1499 g, without malformations, born at 20 centers in 2012–2013. Unfavorable outcome was defined as in-hospital death or survival at hospital discharge with ≥1 major morbidities: bronchopulmonary dysplasia (BPD) at 36 corrected weeks, intraventricular hemorrhage (IVH) grades 3–4, periventricular leukomalacia (PVL) or surgically treated retinopathy of prematurity (ROP).Results: Among 2646 infants, 1390 (53%) either died or survived with major morbidities: 793 (30%) died; 497 (19%) had BPD; 358 (13%) had IVH 3–4 or PVL; and 84 (3%) had ROP. Logistic regression adjusted by center showed association of unfavorable outcome with: antenatal steroids (OR 0.70; 95%CI 0.55–0.88), C-section (0.72; 0.58–0.90), gestational age <30 (4.00; 3.16–5.07), being male (1.44; 1.19–1.75), small for gestational age (2.19; 1.72–2.78), 5th-min Apgar <7 (3.89; 2.88–5.26), temperature at NICU admission <36.0 °C (1.42; 1.15–1.76), respiratory distress syndrome (3.87; 2.99–5.01), proven late sepsis (1.33; 1.05–1.69), necrotizing enterocolitis (3.10; 2.09–4.60) and patent ductus arteriosus (1.69; 1.37–2.09).Conclusions: More than half of the VLBW infants born at public university level 3 Brazilian hospitals either die or survive with major morbidities.