Human Development Neonatal Research Network 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.

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

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

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula

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

Survival Rate and Short-term Outcomes of Extremely Preterm Infants: A Tertiary Care Center Experience from the Private Sector

Background: Premature birth is one of the leading causes of death in the world. The global incidence of prematurity ranges from 5% to 11% of all births. The aim of this study was to assess the outcome of extremely preterm infants born below 29 weeks in our institution, with regard to survival and major short-term outcomes, and compare our results with national and international centers. This study is the first to be conducted in a private tertiary care hospital in Saudi Arabia. Materials and Methods: This was a retrospective descriptive cohort study that reviewed the medical records of preterm infants admitted to the neonatal intensive care unit at the International Medical Center, Jeddah, Kingdom of Saudi Arabia, between January 2014 and January 2020. We compared our results to the national data from King Faisal Specialist Hospital and Research Center-Riyadh, King Abdulaziz Medical City (KAMC)-Jeddah and KAMC Riyadh, King Abdulaziz Medical City-Alhasa, the National Institute of Child Health and Human Development Neonatal Research Network, and the Canadian Neonatal Network. Results: A total of 92 preterm infants were included: 3, 8, 17, 17, 29, and 18 infants with a gestational age of 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, and 28 weeks, respectively. The mean gestational age was 25 weeks and 5 days. Fifty-four infants (58.7%) survived to hospital discharge. In terms of short-term outcomes, 13% had bronchopulmonary dysplasia, hemodynamically significant ductus arteriosus was present in 27%, and retinopathy of prematurity was found in 13%, necrotizing enterocolitis was diagnosed in 5.4%, while late-onset sepsis was reported in 23.9% of infants. Conclusion: Our study represents outcomes of Extremely Preterm Infants in a single Private tertiary Care Center from Saudi Arabia with a comparison to national and international data. Though it cannot be generalized our data can be used as an add-value cohort toward establishing countrywide neonatal network to better plan regional resource allocation and utilization and facilitate ongoing audit, benchmarking, and overall quality improvement initiatives.

Secular Trends in Patent Ductus Arteriosus Management in Infants Born Preterm in the National Institute of Child Health and Human Development Neonatal Research Network

We evaluated changes in patent ductus arteriosus (PDA) diagnosis and treatment from 2012 through 2021 in a network of US academic hospitals. PDA treatment decreased among infants born at 26-28weeks but not among infants born at 22-25weeks. Rates of indomethacin use and PDA ligation decreased while acetaminophen use and transcatheter PDA closure increased.

Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants

Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes. To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age. This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022. Near-infrared spectroscopy monitoring of Csat and Msat. Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment. A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03). In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia. ClinicalTrials.gov Identifier: NCT01702805.

Heterogeneity of Treatment Effects of Hydrocortisone by Risk of Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants in the National Institute of Child Health and Human Development Neonatal Research Network Trial

Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death. To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death. This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023. Infants were randomized to 10 days of hydrocortisone or placebo treatment. Infants' baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up. Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4. In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death. ClinicalTrials.gov Identifier: NCT01353313.

Generalizability of the Necrotizing Enterocolitis Surgery Trial to the Target Population of Eligible Infants

The objective of this study was to evaluate whether infants randomized in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Necrotizing Enterocolitis Surgery Trial differed from eligible infants and whether differences affected the generalizability of trial results. Secondary analysis of infants enrolled in Necrotizing Enterocolitis Surgery Trial (born 2010-2017, with follow-up through 2019) at 20 US academic medical centers and an observational data set of eligible infants through 2013. Infants born ≤1000g and diagnosed with necrotizing enterocolitis or spontaneous intestinal perforation requiring surgical intervention at ≤8weeks were eligible. The target population included trial-eligible infants (randomized and nonrandomized) born during the first half of the study with available detailed preoperative data. Using model-based weighting methods, we estimated the effect of initial laparotomy vs peritoneal drain had the target population been randomized. The trial included 308 randomized infants. The target population included 382 (156 randomized and 226 eligible, non-randomized) infants. Compared with the target population, fewer randomized infants had necrotizing enterocolitis (31% vs 47%) or died before discharge (27% vs 41%). However, incidence of the primary composite outcome, death or neurodevelopmental impairment, was similar (69% vs 72%). Effect estimates for initial laparotomy vs drain weighted to the target population were largely unchanged from the original trial after accounting for preoperative diagnosis of necrotizing enterocolitis (adjusted relative risk [95% CI]: 0.85 [0.71-1.03] in target population vs 0.81 [0.64-1.04] in trial) or spontaneous intestinal perforation (1.02 [0.79-1.30] vs 1.11 [0.95-1.31]). Despite differences between randomized and eligible infants, estimated treatment effects in the trial and target population were similar, supporting the generalizability of trial results. ClinicalTrials.gov ID: NCT01029353.

Assessment of Corticosteroid Therapy and Death or Disability According to Pretreatment Risk of Death or Bronchopulmonary Dysplasia in Extremely Preterm Infants

Meta-analyses suggest that corticosteroids may be associated with increased survival without cerebral palsy in infants at high risk of bronchopulmonary dysplasia (BPD) but are associated with adverse neurologic outcomes in low-risk infants. Whether this association exists in contemporary practice is uncertain because most randomized clinical trials administered corticosteroids earlier and at higher doses than currently recommended. To evaluate whether the pretreatment risk of death or grade 2 or 3 BPD at 36 weeks' postmenstrual age modified the association between postnatal corticosteroid therapy and death or disability at 2 years' corrected age in extremely preterm infants. This cohort study analyzed data on 482 matched pairs of infants from 45 participating US hospitals in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database (GDB). Infants were included in the cohort if they were born at less than 27 weeks' gestation between April 1, 2011, and March 31, 2017; survived the first 7 postnatal days; and had 2-year death or developmental follow-up data collected between January 2013 and December 2019. Corticosteroid-treated infants were propensity score matched with untreated controls. Data were analyzed from September 1, 2019, to November 30, 2022. Systemic corticosteroid therapy to prevent BPD that was initiated between day 8 and day 42 after birth. The primary outcome was death or moderate to severe neurodevelopmental impairment at 2 years' corrected age. The secondary outcome was death or moderate to severe cerebral palsy at 2 years' corrected age. A total of 482 matched pairs of infants (mean [SD] gestational age, 24.1 [1.1] weeks]; 270 males [56.0%]) were included from 656 corticosteroid-treated infants and 2796 potential controls. Most treated infants (363 [75.3%]) received dexamethasone. The risk of death or disability associated with corticosteroid therapy was inversely associated with the estimated pretreatment probability of death or grade 2 or 3 BPD. The risk difference for death or neurodevelopmental impairment associated with corticosteroids decreased by 2.7% (95% CI, 1.9%-3.5%) for each 10% increase in the pretreatment risk of death or grade 2 or 3 BPD. This risk transitioned from estimated net harm to benefit when the pretreatment risk of death or grade 2 or 3 BPD exceeded 53% (95% CI, 44%-61%). For death or cerebral palsy, the risk difference decreased by 3.6% (95% CI, 2.9%-4.4%) for each 10% increase in the risk of death or grade 2 or 3 BPD and transitioned from estimated net harm to benefit at a pretreatment risk of 40% (95% CI, 33%-46%). Results of this study suggested that corticosteroids were associated with a reduced risk of death or disability in infants at moderate to high pretreatment risk of death or grade 2 or 3 BPD but with possible harm in infants at lower risk.

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 &lt; 0.001); 23 weeks: aRR, 3.24; 95% CI, 2.44–4.29; P &lt; 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 &lt; 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 &lt; 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.

Antiseizure medication at discharge in infants with hypoxic-ischaemic encephalopathy: an observational study

ObjectivesTo assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic...

Incidence of and Neurodevelopmental Outcomes After Late-Onset Meningitis Among Children Born Extremely Preterm

Late-onset meningitis (LOM) has been associated with adverse neurodevelopmental outcomes in children born extremely preterm. To report the incidence of LOM during birth hospitalization and neurodevelopmental outcomes at 18 to 26 months' corrected age. This 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. Culture-confirmed LOM. Incidence 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). Among 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 < .001). LP performance in LOS evaluations decreased from 36% (95% CI, 33%-40%) in 2011 to 24% (95% CI, 21%-27%) in 2017 (P < .001). Among infants with culture-confirmed LOS, LP performance decreased from 58% (95% CI, 51%-65%) to 45% (95% CI, 38%-51%; P = .008). LP performance varied by center among all LOS evaluations (10%-59%, P < .001) and among those with culture-confirmed LOS (23%-79%, P < .001). LOM occurred in the absence of concurrent LOS in 27 of 167 cases (16%). The most common LOM isolates were coagulase-negative 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. In 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.

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the United States, 2013-2018

(JAMA. 2022;327:248–263. doi: 10.1001/jama.2021.2358) While mortality rates of preterm infants have decreased over time, differences in age assessment, assessment instruments, and other factors have made determining neurodevelopmental outcomes difficult. This study used data collected from preterm infants born before the gestational age of 29 weeks between January 1, 2013 and December 31, 2018 from 19 network centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.

Exposure to umbilical cord management approaches and death or neurodevelopmental impairment at 22–26 months’ corrected age after extremely preterm birth

ObjectiveTo compare death or severe neurodevelopmental impairment (NDI) at 22–26 months’ corrected age (CA) among extremely preterm infants following exposure to different forms of umbilical cord management.DesignRetrospective study.SettingEunice Kennedy Shriver...

Association of Antenatal Steroid Exposure at 21 to 22 Weeks of Gestation With Neonatal Survival and Survival Without Morbidities

The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials. To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids. This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network. Infants who did not receive intensive care and infants with antenatal steroid exposure after GA 22 6/7 weeks were excluded. Infants were classified as having no, partial, or complete exposure to antenatal steroids. The primary outcome was survival to discharge. The main secondary outcome was survival without major neonatal morbidity. The associations of differential exposures to antenatal steroids with outcomes were evaluated using logistic regression, adjusting for GA, sex, race, maternal education, small for GA status, mode of delivery, multiple birth, prolonged rupture of membranes, year of birth, and Neonatal Research Network center. A total of 431 infants (mean [SD] GA, 22.6 [0.5] weeks; 232 [53.8%] boys) were included, with 110 infants (25.5%) receiving no antenatal steroids, 80 infants (18.6%) receiving partial antenatal steroids, and 241 infants (55.9%) receiving complete antenatal steroids. Seventeen infants were exposed to antenatal steroids at GA 21 weeks. Among infants exposed to complete antenatal steroids, 130 (53.9%) survived to discharge, compared with 30 infants (37.5%) with partial antenatal steroid exposure and 239 infants (35.5%) with no antenatal steroids. Infants born after complete antenatal steroid exposure, compared with those without antenatal steroid exposure, were more likely to survive to discharge (adjusted odds ratio [aOR], 1.95 [95% CI, 1.07-3.56]) and to survive without major morbidity (aOR, 2.74 [95% CI, 1.19-6.30]). In this retrospective cohort study, among infants born between GA 22 0/7 and 23 6/7 weeks who received intensive care, exposure to a complete course of antenatal steroids at GA 22 6/7 weeks or less was independently associated with greater odds of survival and survival without major morbidity. These data suggest that the use of antenatal steroids in patients at GA 22 6/7 weeks or less could be beneficial when active treatment is considered.

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013–2018

(Abstracted from JAMA 2022;327:248–263) Although mortality and short-term morbidities have declined in extremely preterm infants, there is still a need for the ongoing review of longer-term health and neurodevelopmental outcomes. Since 1991, the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network tracks such outcomes in infants born &lt;29 weeks' gestation.

Outcome prediction in newborn infants: Past, present, and future

The perinatal and neonatal periods are the periods of considerable organ development and maturation. Perinatal and neonatal illnesses can result in mortality and morbidities that burden families and the healthcare system. Outcome prediction is essential for informing perinatal and intensive care management, prognosis, and post-discharge interventions. The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) research databases include hospital and neurodevelopment follow-up outcomes of infants with various underlying diseases and conditions receiving intensive care, providing a unique opportunity to assess outcome risk prediction. The NRN has developed outcome risk prediction tools for use in infants with various diseases and conditions that allow data-driven, transparent discussions to inform family-focused communications and clinical management. This review presents the published neonatal outcome risk prediction research from the NRN, their present clinical utility, and possible future directions for advanced individualized risk prediction.

Contributions of the NICHD neonatal research network's generic database to documenting and advancing the outcomes of extremely preterm infants

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.

Contributions of the NICHD neonatal research network to the diagnosis, prevention, and treatment of bronchopulmonary dysplasia

Despite improvements in the care and outcomes of infants born extremely preterm, bronchopulmonary dysplasia (BPD) remains a common and frustrating complication of prematurity. This review summarizes the BPD-focused research conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN). To improve disease classification and outcome prediction, the NRN developed new data-driven diagnostic criteria for BPD and web-based tools that allow clinicians and investigators to reliably estimate BPD risk in preterm infants. Randomized trials of intramuscular vitamin A and prophylactic nasal continuous positive airway pressure conducted by the NRN have contributed to our current use of these therapies as evidence-based approaches to reduce BPD risk. A recent large, randomized trial of hydrocortisone administered beginning between the 2nd and 4th postnatal weeks provided strong evidence that this therapy promotes successful extubation but does not lower BPD rates. Ongoing studies within the NRN will address important, unanswered questions on the risks and benefits of intratracheal surfactant/corticosteroid combinations and treatment versus expectant management of the patent ductus arteriosus to prevent BPD.