Maternal and infant microbiome and birth anthropometry.

Preterm birth is the leading cause of neonatal mortality and morbidity. Microbiome dysbiosis in the mother and infant may contribute to their adverse outcomes. 16S rRNA amplicon sequencing was performed on all samples. Phyloseq, microbiomeSeq, and NetCoMi were utilized for bioinformatics analysis. Statistical tests included the Wilcoxon test, ANOVA, permutational multivariate analysis of variance (PERMANOVA), and linear regression. Statistical significance was set at p value <0.05. The establishment of an infant's microbiome most likely begins in utero and is influenced by the maternal microbiome. Infants' samples were enriched with Salmonella. There is a complex interplay among the microbial taxa noticeable at birth, exhibiting variability in interaction within the same host and across different hosts. Both maternal and infant microbiomes influence the anthropometric measures determined at birth, and a sex-based difference in correlation exists. This study highlights the potential role of maternal and infant microbiomes in improving pregnancy and neonatal outcomes.

Effectiveness and Safety of Dexmedetomidine in Neonates With Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia.

OBJECTIVE: The objective of this study was to evaluate and compare the effectiveness and safety of dexmedetomidine as monotherapy between neonates with mild hypoxic ischemic encephalopathy (HIE) and moderate to severe HIE treated with therapeutic hypothermia (TH). METHODS: This retrospective study included neonates of gestational age ≥36 weeks with a diagnosis of HIE and undergoing TH between January 2014 and December 2021. Patients were included if they received at least 6 hours of continuous sedation with dexmedetomidine. Baseline characteristics, dose and duration of medication, adverse events, liver and kidney function tests, and hospital course were reviewed. RESULTS: Of the 97 neonates included, 46 had mild, 42 had moderate, and 9 had severe HIE. Dexmedetomidine was initiated at a median 5 hours of life, and the median infusion duration was 77 (46-87) hours. Fifty-two (53.6%) required at least 1 breakthrough opioid or sedative during the first 24 hours of dexmedetomidine infusion. Overall, 40 patients (41.2%) had at least 1 bradycardia episode with heart rate <80 beats/min and 14 patients (14.4%) had heart rate <70 beats/min. Hypotension was experienced by 7 patients (7.2%). Fifty-two patients (53.6%) were intubated in the delivery room and 33/52 (63.5%) were extubated on day of life 1 during dexmedetomidine infusion. CONCLUSIONS: Dexmedetomidine as monotherapy was effective and safe sedation for infants with HIE undergoing hypothermia. The most common side effect of dexmedetomidine was bradycardia. -Dexmedetomidine may be considered as first and single agent for neonates with HIE undergoing TH.

Glucose instability and outcomes of neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia.

BACKGROUND: To investigate the prevalence and associated outcomes of glucose abnormalities in infants with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS: Glucose values were reviewed in all HIE infants. Pearson's correlation was used to assess the association of hypo- and hyperglycemic episodes with neonatal brain MRI and neurodevelopmental outcomes (NDO) at 12 & 24 months. RESULTS: Of 153 infants included, 31, 56 and 43 had episodes of hypo-, hyperglycemia and combined, respectively. Hyperglycemia and combined hypo/hyper had higher mortality (p = 0.035), seizures (p = 0.009), and longer hospitalization (p = 0.023). Hypo- and hyperglycemia were associated with parenchymal hemorrhages (p = 0.028 & p = 0.027, respectively). Hypoglycemia was associated with restricted diffusion (p = 0.014), while hyperglycemia was associated with cortical injuries (p = 0.045). Each hour of hyper- or hypoglycemia was associated with 5.2-5.8 times unfavorable outcomes (p < 0.001). CONCLUSION: Blood glucose aberrations were detrimental in HIE infants treated with TH. Optimizing glucose management is crucial in this setting.

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.

Trends in Procedures in the Neonatal Intensive Care Unit.

OBJECTIVE: The aim of the study is to identify the rates and trends of various procedures performed on newborns. STUDY DESIGN: The Healthcare Cost and Utilization Project (HCUP) database for the years 2002 to 2015 was queried for the number of livebirths, and various procedures using International Classification of Diseases, Ninth Revision (ICD-9) codes. These were adjusted to the rate of livebirths in each particular year. A hypothetical high-volume hospital based on data from the last 5 years was used to estimate the frequency of each procedure. RESULTS: Over the study period, there was a decline in the rates of exchange transfusions and placement of arterial catheters. There was an increase in the rates of thoracentesis, abdominal paracentesis, placement of umbilical venous catheter (UVC) lines, and central lines with ultrasound or fluoroscopic guidance. No change was observed in the rates of unguided central lines, pericardiocentesis, bladder aspiration, intubations, and LP. Intubations were the most performed procedures. Placement of UVC, central venous lines (including PICCs), arterial catheters, and LP were relatively common, whereas others were rare such as pericardiocentesis and paracentesis. CONCLUSION: Some potentially lifesaving procedures are extremely rare or decreasing in incidence. There has also been an increase in utilization of fluoroscopic/ultrasound guidance for the placement of central venous catheters. KEY POINTS: · Advances in neonatal care have impacted the number of procedures performed in the NICU.. · It is unclear whether invasive procedures occur at rates sufficient for adequate training and maintenance of skills.. · Understanding the NICU procedural trends is important in designing simulation and competency-based medical education programs..

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.

Changing Course of an Umbilical Cord Mass - Chasing the Diagnosis of Angiomyxoma.

Angiomyxoma of the umbilical cord is a rare benign vascular malformation with potential for fetal morbidity and mortality. Gross and histologic features of this lesion are identical to those described as "hemangioma," however "angiomyxoma" is a preferable term as current practice restricts the term "hemangioma" to infantile capillary proliferations that express glucose transporter 1. Here we describe the case of an umbilical cord angiomyxoma with associated pseudocysts diagnosed after delivery at 33 weeks. It presented as a heterogeneous-appearing mass near the fetal cord insertion and mimicked serious fetal anomalies throughout gestation. We found fetal MRI helpful for monitoring this lesion, narrowing the differential, and informing management. Proximity to the fetal end of the cord and uncertainty about diagnosis also required surgical resection of the mass after delivery with umbilicoplasty.

Epidemiologic evaluation of inhaled nitric oxide use among neonates with gestational age less than 35 weeks.

BACKGROUND AND OBJECTIVES: The use of inhaled nitric oxide (iNO) in +late preterm and term infants with pulmonary hypertension is Food and Drug Administration (FDA) approved and has improved outcomes and survival. iNO use is not FDA approved for preterm infants and previous studies show no mortality benefit. The objectives were 1) to determine the usage of iNO among preterm neonates <35 weeks before and after the 2010 National Institutes of Health consensus statement and 2) to evaluate characteristics and outcomes among preterm neonates who received iNO. METHODS: This is a population-based cross-sectional study. Billing and procedure codes were used to determine iNO usage. Data were queried from the National Inpatient Sample from 2004 to 2016. Neonates were included if gestational age was <35 weeks. The epochs were spilt into 2004-2010 (Epoch 1) and 2011-2016 (Epoch 2). Prevalence of iNO use, mortality, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage, length of stay, mechanical ventilation, and cost of hospitalization. RESULTS: There were 4865 preterm neonates <35 weeks who received iNO. There was a significant increase in iNO use during Epoch 2 (p < 0.001). There was significantly higher use in Epoch 2 among neonates small for gestational age (SGA) 2.3% versus 7.2%, congenital heart disease (CHD) 11.1% versus 18.6%, and BPD 35.2% versus 46.8%. Mortality was significantly lower in Epoch 2 19.8% versus 22.7%. CONCLUSION: Usage of iNO was higher after the release of the consensus statement. The increased use of iNO among preterm neonates may be targeted at specific high-risk populations such as SGA and CHD neonates. There was lower mortality in Epoch 2; however, the cost was doubled.

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.

Platelet Transfusion and Outcomes of Preterm Infants: A Cross-Sectional Study.

BACKGROUND: Prophylactic platelet transfusion has been adopted as a ubiquitous practice in management of thrombocytopenia in preterm infants to reduce the risk of bleeding. OBJECTIVES: The objectives of this study were to report the prevalence of platelet transfusion among preterm infants with thrombocytopenia and to assess the association of platelet transfusion with mortality and morbidity in this population. METHODS: A cross-sectional study that utilized National Inpatient Sample for the years 2000-2017 was conducted. All preterm infants delivered nationally with birth weight (BW) <1,500 g or gestational age <32 weeks were included. Analyses were repeated after stratifying the population into 2 BW subcategories <1,000 g and 1,000-1,499 g. Logistic regression analysis was performed to adjust for confounding variables. RESULTS: The study included 1,780,299 infants; of them, 22,609 (1.27%) were diagnosed with thrombocytopenia and 5,134 (22.7%) received platelet transfusion. Platelet transfusion was associated with significant increase in mortality (24.8 vs. 13.8%), retinopathy of prematurity (22.3 vs. 19.2%), severe intraventricular hemorrhage (18.3 vs. 10.1%), median length of hospital stays (51 vs. 47 days), and cost of hospitalization (USD 298,204 vs. USD 219,760). Increased mortality was noted in <1,000-g infants (aOR = 1.96, CI: 1.76-2.18, p < 0.001) and 1,000-1,499-g infants (aOR = 2.02, CI: 1.62-2.53, p < 0.001). Platelet transfusion increased over the years in infants with BW <1,000 g (p = 0.001) and in infants with BW 1,000-1,499 g (p < 0.001). CONCLUSIONS: Platelet transfusion is associated with increased mortality and comorbidities in premature infants. There is a trend for increased utilization of platelet transfusions over the study period.

Late preterm infants - Changing trends and continuing challenges.

Late preterm infants, defined as newborns born between 340/7-366/7 weeks of gestational age, constitute a unique group among all premature neonates. Often overlooked because of their size when compared to very premature infants, this population is still vulnerable because of physiological and structural immaturity. Comprising nearly 75% of babies born less than 37 weeks of gestation, late preterm infants are at increased risk for morbidities involving nearly every organ system as well as higher risk of mortality when compared to term neonates. Neurodevelopmental impairment has especially been a concern for these infants. Due to various reasons, the rate of late preterm births continue to rise worldwide. Caring for this high risk population contributes a significant financial burden to health systems. This article reviews recent trends in regarding rate of late preterm births, common morbidities and long term outcomes with special attention to neurodevelopmental outcomes.

Non-invasive Respiratory Support of the Premature Neonate: From Physics to Bench to Practice.

Premature births continue to rise globally with a corresponding increase in various morbidities among this population. Rates of respiratory distress syndrome and the consequent development of Bronchopulmonary Dysplasia (BPD) are highest among the extremely preterm infants. The majority of extremely low birth weight premature neonates need some form of respiratory support during their early days of life. Invasive modes of respiratory assistance have been popular amongst care providers for many years. However, the practice of prolonged invasive mechanical ventilation is associated with an increased likelihood of developing BPD along with other comorbidities. Due to the improved understanding of the pathophysiology of BPD, and technological advances, non-invasive respiratory support is gaining popularity; whether as an initial mode of support, or for post-extubation of extremely preterm infants with respiratory insufficiency. Due to availability of a wide range of modalities, wide variations in practice exist among care providers. This review article aims to address the physical and biological basis for providing non-invasive respiratory support, the current clinical evidence, and the most recent developments in this field of Neonatology.

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.

Variability in Apgar Score Assignment among Clinicians: Role of a Simple Clarification.

Objective We aimed to evaluate variability in Apgar score (AS) assignment among health care providers (HCPs) and to evaluate whether a simple clarification improves accuracy and consistency of AS assignment. Study Design An electronic questionnaire survey was provided to pediatric residents, nurse practitioners, neonatal fellows, and faculty in level III neonatal intensive care unit and major academic centers in the United State to assign AS for three clinical scenarios. Next, we provided a simple clarification on various components of AS. After review of clarification, responders were asked to provide AS for the same scenarios. We also sought the opinion of responders on the subjectivity of five components of AS. Results A total of 107 responses were collected. Correct assignment before and after clarification improved significantly: heart rate (78 vs. 90%, p = 0.02), reflex (63 vs.75%, p = 0.06), and breathing (82 vs. 96%, p = 0.003). Correct scoring for color and tone were 86 and 67%, respectively. Interobserver agreement improved significantly after clarification. Conclusion There was variability among HCPs for AS assignment, with improvement in correct response as well as consistency after a simple clarification. Availability of this clarification, along with the AS table in delivery room, will improve the correct assignment and consistency of AS for high-risk infants.