Disparity in neonatal abstinence syndrome by race/ethnicity, socioeconomic status, and geography, in neonates ≥ 35 weeks gestational age.

Neonatal abstinence syndrome (NAS) is associated with a range of adverse health outcomes, exorbitant health care costs, and race/ethnicity disparity. We examined key sociodemographic factors that may influence the national race/ethnicity disparity in the prevalence of NAS among Whites, Blacks and Hispanics. 2016 and 2019 cycles of cross-sectional data from HCUP-KID national all-payer pediatric inpatient-care database were used to estimate NAS prevalence (ICD-10CM code P96.1) in newborns ≥ 35 weeks gestational-age, excluding iatrogenic-cases (ICD-10CM code P96.2). Multivariable generalized-linear-models with predictive-margins were used to produce race/ethnicity-specific stratified-estimates for select sociodemographic factors, reported as risk-differences (RD) with 95% confidence-intervals (CI). Final models were adjusted for sex, payer-type, ecologic income-level, and hospital size, type, and region. The overall survey weighted-sample prevalence of NAS was 0.98% (i.e., 6282/638100) and did not differ over cycles. Blacks and Hispanics were significantly more likely than Whites to be in the lowest ecologic income quartile and on Medicaid. In fully-specified models, NAS prevalence among Whites was 1.45% (95% CI: 1.33, 1.57) higher than Blacks and 1.52% (95% CI: 1.39, 1.64) higher than Hispanics; and NAS among Blacks was 0.14% higher than Hispanics (95% CI: 0.03, 0.24). NAS prevalence was highest among Whites on Medicaid (RD: 3.79%; 95% CI: 3.55, 4.03) compared to Whites on private-insurance (RD: 0.33%; 95% CI: 0.27, 0.38), and Blacks (RD: 0.73%; 95% CI: 0.63, 0.83; RD: 0.15%; 95% CI: 0.08, 0.21), or Hispanics, with either payer-type (RD: 0.59%; 95% CI: 0.5, 0.67; RD: 0.09%; 95% CI: 0.03, 0.15) respectively. NAS prevalence was higher among Whites in the lowest income-quartile (RD: 2.22%; 95% CI: 1.99, 2.44) compared with Blacks (RD: 0.51%; 95% CI: 0.41, 0.61) and Hispanics (RD: 0.44%; 95% CI: 0.33, 0.54) in the same quartile, and all subgroups in other quartiles. NAS prevalence was higher among Whites in the Northeast (RD: 2.19%; 95% CI: 1.89, 2.5) compared to Blacks (RD: 0.54%; 95% CI: 0.33, 0.74) and Hispanics (RD: 0.31%; 95% CI: 0.17, 0.45). Although Blacks and Hispanics were more likely to be in the lowest income quartile and have Medicaid insurance, Whites on Medicaid, in the lowest income quartile, and in the Northeast, were found to have the highest NAS prevalence.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

BACKGROUND AND OBJECTIVES: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study. Kidney function, urine albumin, and BP were measured at 2-year (24±2 months) corrected gestational age. We compared outcomes across gestational age categories and evaluated associations between kidney-related outcomes and neonatal and maternal characteristics. The primary outcome was eGFR <90 ml/min per 1.73 m2 (CKD); secondary outcomes were spot urine albumin-creatinine ratio ≥30 mg/g (albuminuria) and either systolic BP or diastolic BP >90th percentile for height, age, and sex. RESULTS: A total of 832 survived to 2 years, and 565 (68%) had at least one outcome measured. Overall, 297 (53%) had one abnormal kidney outcome; 61 (18%) had an eGFR <90 ml/min per 1.73 m2, 155 (36%) had albuminuria, 65 (22%) had elevated systolic BP, and 128 (44%) had elevated diastolic BP. Gestational age (odds ratio, 0.94; 95% confidence interval, 0.89 to 0.99), birth weight z-score (odds ratio, 0.92; 95% confidence interval, 0.85 to 0.98), and prenatal steroids (odds ratio, 1.23; 95% confidence interval, 1.08 to 1.39) were associated with an eGFR <90 ml/min per 1.73 m2. An elevated systolic BP was associated with indomethacin use (odds ratio, 1.18; 95% confidence interval, 1.04 to 1.33) and Black race (odds ratio, 1.19; 95% confidence interval, 1.01 to 1.39); elevated diastolic BP was associated with male sex (odds ratio, 1.29; 95% confidence interval, 1.12 to 1.49), severe AKI (odds ratio, 1.24; 95% confidence interval, 1.04 to 1.48), and indomethacin use (odds ratio, 1.16; 95% confidence interval, 1.01 to 1.33). CONCLUSIONS: Approximately 18% of extremely low gestational age neonates have CKD, 36% have albuminuria, 22% have an elevated systolic BP, and 44% have an elevated diastolic BP at 2 years of age. Gestational age, birthweight z-score, and prenatal steroids were associated with CKD. Male sex, Black race, indomethacin use, and severe AKI were associated with elevated BP. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_19_CJN15011121.mp3.

An assessment of prevalence and expenditure associated with discharge brain MRI in preterm infants.

To assess national expenditure associated with preterm-infant brain MRI and potential impact of reduction per Choosing Wisely campaign 2015 recommendation to "avoid routine screening term-equivalent or discharge brain MRIs in preterm-infants". Cross-sectional U.S. trend data from the Agency for Healthcare Research and Quality (AHRQ), Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) database (2006, 2009, 2012, 2016) was used to estimate overall national expenditure associated with brain MRI among infants with gestational age (GA) ≤36 weeks, and also when classified as 'not indicated' (NI-MRI) i.e., equivalent to routine use without clinical indications and regarded as low-value service (LVS). Associated cost was determined by querying CMS-database for physician-fee-schedules to find the highest global procedure-cost per cycle, then adjusting for inflation. Sensitivity-analyses were conducted to account for additional clinical charges associated with NI-MRI. 3,768 (0.26%) of 1,472,236 preterm-infants had brain MRI across all cycles (inflation-adjusted total $3,690,088). Overall proportion of brain MRIs increased across 2006-2012 from 0.25%-0.33% but decreased in 2016 to 0.16% (P<0.001). Inflation-adjusted overall expenditure by cycle was: 2006, $1,299,130 (95% CI: $987,505, $1,610,755); 2009, $1,194,208 (95% CI: $873,487, $1,516,154); 2012, $931,836 (95% CI: $666,114, $1,197,156); and 2016, $264,648 (95% CI: $172,061, $357,280). Prevalence for NI-MRI in 2006, 2009, 2012 and 2016 was 86% (n = 809), 88% (n = 940), 89% (n = 1028) and 50% (n = 299), respectively; and 70% were in infants 35-36 weeks GA. NI-MRI prevalence was not different over time by payer-type (Medicaid, private), sex or race/ethnicity (white, black, Hispanic); larger hospital size was significantly associated across 2006-2012 but this declined for all sizes in 2016, with most decline in larger hospitals (P for interaction <0.05). NI-MRI expenditure sensitivity-analysis with addition of cycle median total-admission-charge to inflation-adjusted CMS-fee was $1,190,919/$518,343, for 2012/2016 cycles respectively. National MRI prevalence in preterm infants (both overall and LVS) and associated expenditure decreased substantially post recommendation; however, annual savings are modest and unlikely to be >$1.2 million.

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.

BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established. METHODS: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition. RESULTS: A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events. CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).

Evaluation of Introduction of a Delayed Cord Clamping Protocol for Premature Neonates in a High-Volume Maternity Center.

OBJECTIVE: To evaluate adherence to a delayed cord clamping protocol for preterm births in the first 2 years after its introduction, perform a quality improvement assessment, and determine neonatal outcomes associated with protocol implementation and adherence. METHODS: This is a retrospective cohort study of women delivering singleton neonates at 23-32 weeks of gestation in the 2 years before (preprotocol) and 2 years after (postprotocol) introduction of a 30-second delayed cord clamping protocol at a large-volume academic center. This policy was communicated to obstetric and pediatric health care providers and nurses and reinforced with intermittent educational reviews. Barriers to receiving delayed cord clamping were assessed using χ tests and multivariable logistic regression. Neonatal outcomes then were compared between all neonates in the preprotocol period and all neonates in the postprotocol period and between all neonates in the preprotocol period and neonates receiving delayed cord clamping in the postprotocol period using multivariable linear and logistic regression analyses. RESULTS: Of the 427 eligible neonates, 187 were born postprotocol. Of these, 53.5% (n=100) neonates received delayed cord clamping according to the protocol. The rate of delayed cord clamping preprotocol was 0%. Protocol uptake and frequency of delayed cord clamping increased over the 2 years after its introduction. In the postprotocol period, cesarean delivery was the only factor independently associated with failing to receive delayed cord clamping (adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.25-0.96). In comparison with the preprotocol period, those who received delayed cord clamping in the postprotocol period had significantly higher birth hematocrit (ß=2.46, P=.007) and fewer blood transfusions in the first week of life (adjusted OR 0.49, 95% CI 0.25-0.96). CONCLUSION: After introduction of an institutional delayed cord clamping protocol followed by continued health care provider education and quality feedback, the frequency of delayed cord clamping progressively increased. Compared with historical controls, performing delayed cord clamping in eligible preterm neonates was associated with improved neonatal hematologic indices, demonstrating the effectiveness of delayed cord clamping in a large-volume maternity unit.

Growth and Development in Extremely Low Birth Weight Infants After the Introduction of Exclusive Human Milk Feedings.

Objective To estimate associations of exclusive human milk (EHM) feedings with growth and neurodevelopment through 18 months corrected age (CA) in extremely low birth weight (ELBW) infants. Study Design ELBW infants admitted from July 2011 to June 2013 who survived were reviewed. Infants managed from July 2011 to June 2012 were fed with bovine milk-based fortifiers and formula (BOV). Beginning in July 2012, initial feedings used a human milk-based fortifier to provide EHM feedings. Infants were grouped on the basis of feeding regimen. Primary outcomes were the Bayley-III cognitive scores at 6, 12, and 18 months and growth. Results Infants (n = 85; 46% received EHM) were born at 26 ± 1.9 weeks (p = 0.92 between groups) weighing 776 ± 139 g (p = 0.67 between groups). Cognitive domain scores were similar at 6 months (BOV: 96 ± 7; EHM: 95 ± 14; p = 0.70), 12 months (BOV: 97 ± 10; EHM: 98 ± 9; p = 0.86), and 18 months (BOV: 97 ± 16; EHM: 98 ± 14; p = 0.71) CA. Growth velocity prior to discharge (BOV: 12.1 ± 5.2 g/kg/day; EHM: 13.1 ± 4.0 g/kg/day; p = 0.33) and subsequent growth was similar between groups. Conclusion EHM feedings appear to support similar growth and neurodevelopment in ELBW infants as compared with feedings containing primarily bovine milk-based products.

Clinical Outcomes Associated with a Failed Infant Car Seat Challenge.

OBJECTIVE: To assess comorbid conditions and clinical outcomes among late preterm and low birth weight term infants (<2.5 kg) who failed the Infant Car Seat Challenge (ICSC) on the Mother-Baby Unit. STUDY DESIGN: This was a retrospective chart review of consecutive infants who failed ICSC on the Mother-Baby Unit and were subsequently admitted to the neonatal intensive care unit at Prentice Women's Hospital between January 1, 2009, and December 31, 2015. Regression models were used to estimate risk differences (RDs) with 95% CIs for factors related to length of stay. RESULTS: A total of 148 infants were studied (43% male; 37% delivered via cesarean). ICSC failure in the Mother-Baby Unit was due to desaturation, bradycardia, and tachypnea in 59%, 37%, and 4% of infants, respectively. During monitoring on the neonatal intensive care unit, 39% of infants experienced apnea (48% in preterm vs 17% in term infants) in the supine position, 19% received phototherapy, and 2% and 6.8% received nasogastric and thermoregulatory support, respectively. Univariate predictors of increased duration of stay (days) were younger gestational age, apnea, nasogastric support, intravenous fluids, and antibiotics (all P < .05). In multivariable analysis adjusted for gestational age and discharge weight, only apnea (RD, 4.87; 95% CI, 2.99-6.74; P < .001), administration of antibiotics (RD, 3.25; 95% CI, 0.29-6.21; P < .032), and intravenous fluid support (RD, 4.87; 95% CI, 0.076-9.66; P < .047) remained independent predictors of a longer duration of stay. CONCLUSION: Infants who failed ICSC were at risk for comorbid conditions that prolonged hospital stay beyond the neonatal intensive care unit observation period. Almost one-half of late preterm infants who failed ICSC had apnea events in the supine position.

Beyond Necrotizing Enterocolitis Prevention: Improving Outcomes with an Exclusive Human Milk-Based Diet.

OBJECTIVE: The aim of this study was to compare outcomes of infants pre and post initiation of a feeding protocol providing an exclusive human milk-based diet (HUM). MATERIALS AND METHODS: In a multicenter retrospective cohort study, infants with a birth weight <1,250 g who received a bovine-based diet (BOV) of mother's own milk fortified with bovine fortifier and/or preterm formula were compared to infants who received a newly introduced HUM feeding protocol. Infants were excluded if they had major congenital anomalies or died in the first 12 hours of life. Data were collected 2-3 years prior to and after introduction of an exclusive HUM diet. Primary outcomes were necrotizing enterocolitis (NEC) and mortality. Secondary outcomes included late-onset sepsis, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD). RESULTS: A total of 1,587 infants were included from four centers in Texas, Illinois, Florida, and California. There were no differences in baseline demographics or growth of infants. The HUM group had significantly lower incidence of proven NEC (16.7% versus 6.9%, p < 0.00001), mortality (17.2% versus 13.6%, p = 0.04), late-onset sepsis (30.3% versus 19.0%, p < 0.00001), ROP (9% versus 5.2%, p = 0.003), and BPD (56.3% versus 47.7%, p = 0.0015) compared with the BOV group. CONCLUSIONS: Extremely premature infants who received an exclusive HUM diet had a significantly lower incidence of NEC and mortality. The HUM group also had a reduction in late-onset sepsis, BPD, and ROP. This multicenter study further emphasizes the many benefits of an exclusive HUM diet, and demonstrates multiple improved outcomes after implementation of such a feeding protocol.

Developmental changes in murine brain antioxidant enzymes.

Reactive oxygen species produced in cells during normal aerobic metabolism have the ability to induce lipid peroxidation and protein oxidation; therefore, their detoxification and elimination are necessary for physiologic cellular activity and survival. The changes in neuronal antioxidant enzymes from fetal life to adulthood have not been fully described. We investigated protein expression, using Western blot analysis, and enzymatic activity of the antioxidant system-copper-zinc superoxide dismutase (SOD), manganese SOD, catalase, and glutathione peroxidase, as well as reduced glutathione level as an indicator of the nonenzymatic system-in CD1 murine brain at embryonic d 18 (E18), and postnatal d 1 (P1), d 4, d 7, d 14, and d 21. Copper-zinc SOD and glutathione peroxidase protein levels were low, whereas manganese SOD and catalase protein levels were high at E18 and P1. Total SOD activity was high at E18 and P1 and paralleled elevated manganese SOD activity; however, copper-zinc SOD activity was relatively unchanged throughout development. Catalase activity doubled and glutathione peroxidase activity tripled between E18 and P1. Reduced glutathione increased between E18 and P1. Except for catalase and manganese SOD, peak protein levels do not occur until later developmental ages. We suggest that as the fetus moves from an in utero hypoxic to a relatively hyperoxic environment with an approximate 4-fold elevation in oxygen concentration, these developmental changes in antioxidant enzymes are compensatory mechanisms aimed at protecting the newborn from oxidative stress. These data will be important in our future understanding of the mechanisms by which hypoxia mediates injury in the immature and the mature brain.