Trends of neonatal hypoxic-ischemic encephalopathy prevalence and associated risk factors in the United States, 2010 to 2018.

BACKGROUND: Despite recent advances in perinatal care, neonatal hypoxic-ischemic encephalopathy remains one of the most common causes of neonatal morbidity and mortality. The trends for prevalence and mortality of neonatal hypoxic-ischemic encephalopathy have not been examined in the era of therapeutic hypothermia in the United States. OBJECTIVE: This study aimed to determine (1) the overall and gestational age-specific (35-36, ≥37, and >42 weeks) trends of hypoxic-ischemic encephalopathy prevalence and use of therapeutic hypothermia, (2) the trends of mortality in association with hypoxic-ischemic encephalopathy, (3) the confounding variables associated with hypoxic-ischemic encephalopathy, and (4) the clinical outcomes of neonates with hypoxic-ischemic encephalopathy. STUDY DESIGN: This study used National Inpatient Sample datasets from 2010 to 2018. Moreover, the study included infants with a gestational age of ≥35 weeks with a documented hypoxic-ischemic encephalopathy diagnosis (mild, moderate, severe, or unspecified). We calculated trends in hypoxic-ischemic encephalopathy prevalence and the use of therapeutic hypothermia using chi-squared testing. Furthermore, this study used logistic regression models to control for confounders. RESULTS: A total of 32,180,617 infants were included, of which 31,249,100 were term (gestational age of ≥37 weeks) and 931,517 were late preterm (gestational age of 35-36 weeks). Hypoxic-ischemic encephalopathy prevalence slightly increased from 0.093% in 2010-2012 to 0.097% in 2016-2018 (P=.01) in term infants and did not significantly change in late preterm infants (P=.20). There were 6235 term infants (20.8%) and 449 late preterm infants (21.1%) with hypoxic-ischemic encephalopathy who were managed with therapeutic hypothermia. The use of therapeutic hypothermia in both term and late preterm infants has increased over the years (P<.01). The mortality rate with hypoxic-ischemic encephalopathy decreased over time from 11.5% to 12.3% between 2010 to 2012, and from 8.3% to 10.6% betweenn 2016 to 2018 (P<.01). The factors with the strongest association with hypoxic-ischemic encephalopathy were placental infarction or insufficiency (odds ratio, 144; 95% confidence interval, 134-157), placental abruption (odds ratio, 101; 95% confidence interval, 91-112), cord prolapse (odds ratio, 74; 95% confidence interval, 65-84), and maternal anemia (odds ratio, 26; 95% confidence interval, 20-37). CONCLUSION: Hypoxic-ischemic encephalopathy prevalence in neonates essentially remained the same at 1 per 1000 live births. The use of therapeutic hypothermia increased, and the mortality rate decreased in infants with hypoxic-ischemic encephalopathy. The identification of hypoxic-ischemic encephalopathy-associated factors should promote increased vigilance to optimize newborn outcomes.

Trends and racial disparities for acute kidney injury in premature infants: the US national database.

BACKGROUND: To assess prevalence and outcomes of acute kidney injury (AKI) in very-low-birth-weight infants. METHODS: This cross-sectional study utilized the National Inpatient Sample (NIS) dataset for years 2000-2017. All premature infants with birth weight (BW) <1500g and/or gestational age (GA) ≤32 weeks were included. Analyses were conducted for overall population and two BW categories: <1000g and 1000-1499g. Adjusted odds ratios were calculated after controlling for confounding variables in logistic regression analysis. Cochrane-Armitage test was used to assess for statistically significant trends in AKI frequency over the years. RESULTS: In total, 1,311,681 hospitalized premature infants were included; 19,603 (1.5%) were diagnosed with AKI. The majority (74.3%) were BW <1000g and 63.9% ≤28 weeks gestation. Prevalence of AKI differed by ethnicity; White had significantly less AKI than Black (OR=0.79, p<0.001) and Hispanic (OR=0.83, p<0.001). AKI was significantly associated with higher mortality compared to controls (35.1 vs. 3.0%, p<0.001). AKI was associated with comorbidities such as necrotizing enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular hemorrhage, and septicemia. In a regression model, AKI was associated with higher mortality after controlling confounding factors (aOR=7.79, p<0.001). AKI was associated with significant increase in length of stay (p<0.001) and cost of hospitalization in survivors (p<0.001). There is a significant trend for increased AKI frequency over the years (Z score=4.33, p<0.001). CONCLUSION: AKI is associated with increased mortality and comorbidities in preterm infants, especially in infants with BW <1000g. Further studies are needed to understand precipitating factors and assess preventative measures for this serious complication.

Can Functional Polymorphisms in VEGF and MMP Predict Intraventricular Hemorrhage in Extremely Preterm Newborns?

BACKGROUND: The pathophysiology of intraventricular hemorrhage (IVH) is multifactorial. This study attempts to identify genetic and clinical factors contributing to IVH in newborns with a focus on those born ≤28 weeks of gestation. METHODS: This was a prospective study of 382 consecutive newborns admitted to the neonatal intensive care unit. DNA purification was conducted using standard methods. TaqMan SNP assays were conducted for functional polymorphisms in VEGF (RS699947, RS2010963, RS3025039, and RS1570360) and MMP2 (RS243685 and RS2285053) genes. An RFLP assay was done for a polymorphism in MMP9 (RS3918242). RESULTS: The GG genotype in VEGF RS1570360 (p = 0.013) and the CC genotype in VEGF RS699947 (p = 0.036) were associated with a lower incidence of IVH amongst newborns ≤28 weeks of gestation. Chorioamnionitis, Caucasian race, and patent ductus arteriosus were associated with a higher incidence of IVH. A binary logistic regression analysis of clinical and SNP data that was significant from bivariate analysis demonstrated that VEGF RS1570360 was significantly associated with IVH (p = 0.017). CONCLUSION: This study demonstrated that the GA/AA genotype in VEGF RS1570360 and the AA/AC genotype in VEGF RS699947 were associated with higher incidence rates of IVH in newborns ≤28 weeks of gestation. A future study is warranted to comprehensively examine VEGF polymorphisms in association with IVH.

Placental abruption and risk for intraventricular hemorrhage in very low birth weight infants: the United States national inpatient database.

OBJECTIVE: To examine the association of placental abruption with intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. METHODS: We examined the National Inpatient Sample (NIS) datasets. Preterm infants <1500 g birth weight (BW) were included. The odds ratios (OR) of developing IVH and severe IVH in association with placental abruption were calculated. Adjusted OR (aOR) were calculated using logistic regression models. RESULTS: The study included 113,445 VLBW infants. IVH occurred in 18.7% in the infants who were born to mothers with history of placental abruption versus 14.7% in infants without placental abruption, aOR 1.25 (95%CI: 1.13-1.38), p < 0.001. Severe IVH occurred in 6.4% in infants born to mothers with history of placental abruption versus 4.0% in those without placental abruption, aOR 1.53 (95%CI: 1.30-1.78), p < 0.001. CONCLUSION: Placental abruption is associated with increased prevalence of IVH and severe IVH in VLBW infants.

Neonatal outcomes of preterm infants with in-utero exposure to drugs of substance use: US national data.

BACKGROUND: Infants exposed prenatally to drugs of substance use are at increased risk for seizures, strabismus, feeding difficulty, and neurodevelopmental delays. Exposed preterm infants may have additional morbidities related to prematurity. There is limited literature on national outcomes of preterm infants exposed to drugs of substance use. We aimed to evaluate the trends and neonatal outcomes of preterm infants born in the USA who were exposed in-utero to drugs of substance use. METHODS: Retrospective cohort study of preterm live born (<37 weeks gestation) exposed in-utero to opioids, hallucinogens, or cocaine in the Healthcare Cost and Utilization Project database from 2002 to 2017. Neonatal outcomes were identified using international classification of diseases 9&10 codes. RESULTS: Of the 54,469,720 live-born infants, 7.7% (4,194,816) were preterm, and 58 679 (1.4%) were exposed in-utero to maternal opioids/hallucinogens (n = 39,335) or cocaine (n = 19,344). There was a trend for increased exposure to opioids/hallucinogens (Z score = 76.14, p < 0.001) during the study period. Exposed preterm infants had significantly more neurological anomalies, intra-ventricular hemorrhage and periventricular leukomalacia (p < 0.001). CONCLUSIONS: There was a trend for increased in-utero exposure to opioids and hallucinogens in the preterm infants in the USA. Exposed preterm infants had more neurological morbidities.

Neonatal stroke: Clinical characteristics and neurodevelopmental outcomes.

BACKGROUND: Neonatal stroke can potentially result in significant neurological sequelae in affected infants. Studies on neurodevelopmental outcomes and the need for rehabilitation therapies in the first two years are limited. We aimed to describe the clinical characteristics, diagnostic evaluation, and neurodevelopmental outcomes of a cohort of infants with neonatal stroke. METHODS: A retrospective cohort study of infants with neonatal stroke, from 2011 to 2020. Maternal and infant characteristics were described. Placental pathology, echocardiogram results, and prothrombotic evaluations were reported. The neurodevelopmental outcomes using Bayley scale of infant development (BSID III), rates of epilepsy and cerebral palsy, and the need for rehabilitation therapies at two years were described. RESULTS: During the study period, 55 infants had neonatal stroke. Majority (93%) were term or late preterm infants. Maternal chorioamnionitis and perinatal HIE were diagnosed in about a third of the infants. Most (66%) of the infants presented with seizures. On brain MRI, the lesions were unilateral in 76% and arterial in origin in 86% of the infants. Meconium exposure (42%), intrauterine inflammation/infection (37%) and fetal vascular malperfusion (16%) were seen on placental histopathology. At two-year BSID III assessment, median (min, max) composite cognitive, language, and motor scores were 100 (55-145), 97 (47-124), and 100 (46-141), respectively. Among this cohort, epilepsy (27%), cerebral palsy (16%) and the need for rehabilitation therapies (physical -24%, occupational -18%, speech -21%) were reported at two years. CONCLUSION: Neonatal stroke presented commonly in term or late preterm infants with seizures. It was unilateral and arterial in origin in most infants. Maternal chorioamnionitis and perinatal HIE were the most commonly associated conditions at birth. About one-fifth of the infants had mild or severe developmental delays at two years. Epilepsy, cerebral palsy, and need for rehabilitation therapies were noted in a significant proportion of infants at two years.

Vitamin D deficiency and respiratory morbidity among African American very low birth weight infants.

BACKGROUND: Very low birth weight infants (VLBWI) have unexplained variation in respiratory morbidity, including respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD). We examined a potential association to serum 25-hydroxyvitamin D (s-25OHD) on day one. STUDY DESIGN: Prospective, observational study on 89 VLBWI (≤1250 g). S-25OHD (day one and 21) and respiratory severity score (RSS) (day one) were examined. Other respiratory morbidities including BPD were compared between infants with s-25OHD ≤ 10 ng/ml (deficient) versus >10 ng/ml (adequate). RESULTS: Eighty one neonates (91%) were African Americans. The mean (SD) birthweight was 868 (229) g, gestational age 27 (2) weeks. On day one, mean (SD) s-25OHD was 15.48 (8.31) ng/ml, with 32 (37%) being vitamin D deficient. The deficiency and adequate VLBWI groups had similar birthweight; 860 (262) vs 873 (210) g, and gestational age; 27 (2) vs 27 (2) weeks. In 78 survivors, s-25OHD rose from 15.48 (8.31) ng/ml day one to 52.36 (22.49) ng/ml day 21 after supplementation, p < 0.001. On day one, increasing RSS was inversely related to s-25OHD, trend p = 0.054. Compared to the adequate group, the deficiency group had higher RSS (5.0 ±â€¯2.7 vs 3.6 ±â€¯1.9), required surfactant therapy more frequently (91% vs 72%), and needed home oxygen therapy more often (48% vs 26%), p ≤ 0.05 for all. Among infants with BPD, the severity of disease was inversely related to s-25OHD, trend p < 0.09. CONCLUSION: Lower levels of s-25OHD were associated with increased severity of RDS and BPD among a cohort of mostly African American VLBWI.

Does vitamin D deficiency affect placental inflammation or infections among very low birth weight infants?

OBJECTIVE: Examine the association between placental inflammation and neonatal infections, and 25OH vitamin D (25OH D) levels at birth among very low birth weight infants (VLBWI). STUDY DESIGN: Serum 25OH D levels were measured in 89 VLBWI (≤1250 g) and 47 mothers on day one, and in 78 infants on day 21. Placentas were examined for maternal and fetal inflammation. Infants were divided into deficient (≤10 ng/ml) and adequate (>10 ng/ml) groups based on 25OH D levels on day 1. RESULTS: Mean ± SD maternal levels of 25OH D (21 ± 9 ng/ml) correlated with infants' levels (15 ± 8 ng/ml), (p < .001). 25OH D levels were lower in deficient (32/89) than in adequate group (8 ± 2 versus 20 ± 7 ng/ml, p = .011). Infants' 25OH D levels rose significantly by day 21 (p < .001). Univariate analyses showed no differences between infant groups in maternal or fetal inflammation, or neonatal infections (p > .05). Logistic regression analyses revealed no association between deficient 25OH D levels and the odds of maternal or fetal inflammation or other infections. Levels of 25OH D did not correlate with severity of placental inflammation. CONCLUSIONS: Deficient levels of 25OH D at birth are not associated with the occurrence of placental inflammation or neonatal infections among VLBWI.