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Medicaid supports 41% of all births in the US and nearly 347,580 admissions to neonatal intensive care units in 2022. Medicaid reimbursement is critical to child health inclusive of departments of Pediatrics and children's hospitals. Low Medicaid reimbursement is one of the causes for low pediatric subspecialist salaries and has led to workforce challenges. The National Academies of Science, Engineering, and Medicine (NASEM) recently suggested increased Medicaid reimbursement as a strategy to sustain pediatric subspecialist workforce. This review article briefly outlines the importance of Medicaid reimbursement to Neonatal-Perinatal Medicine and its role in providing coverage for preterm births. We also highlight the recommendations of NASEM pertaining to reimbursement that are relevant to neonatal care and its impact on providers, patients, and families. It is imperative that neonatologists join the rest of pediatric subspecialists in lending their support to demonstrate unity in ensuring success in the implementation of the NASEM recommendations.

BackgroundHypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal azithromycin administration in near-term lambs following global ischemic injury to support earlier treatment approaches.MethodsEwes and their lambs of both sexes (n=34, 141-143 days) were randomly assigned to receive azithromycin or placebo before delivery as well as postnatally. Lambs were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Outcomes were assessed over a 6-day period.ResultsWhile maternal azithromycin exhibited relatively low placental transfer, azithromycin-treated lambs recovered spontaneous circulation faster following the initiation of cardiopulmonary resuscitation and were extubated sooner. Additionally, peri- and postnatal azithromycin administration was well tolerated, demonstrating a 77-hour plasma elimination half-life, as well as significant accumulation in the brain and other tissues. Azithromycin administration resulted in a systemic immunomodulatory effect, demonstrated by reductions in proinflammatory IL-6 (interleukin-6) levels. Treated lambs exhibited a trend toward improved neurodevelopmental outcomes while histological analysis revealed that azithromycin supported white matter preservation and attenuated inflammation in the cingulate and parasagittal cortex.ConclusionsPerinatal azithromycin administration enhances neonatal resuscitation, attenuates neuroinflammation, and supports limited improvement of select histological outcomes in an ovine model of hypoxic-ischemic brain injury/encephalopathy.

ObjectiveTo obtain preliminary validity data for a hypoxemic respiratory failure/pulmonary hypertension (HRF/PH) score for classifying persistent pulmonary hypertension of the newborn (PPHN).Study designRetrospective chart review of 100 consecutive neonates admitted to a Children's hospital from 2016-2021 with PPHN, gestational age ≥34 weeks, and echocardiograms in the first week. We assessed the correlation between HRF/PH score and short-term outcomes using linear and logistic regressions.ResultsHRF/PH scores ranged 2-12 (mean 8.5), and were classified mild (0-5), moderate (6-10), and severe (11-15), with 6%, 77% and 17% infants in respective categories. HRF/PH score category correlated with invasive ventilation, nitric oxide, high frequency ventilation, vasoactive infusions, extracorporeal life support and death. HRF/PH score category did not correlate with duration of support or length of stay.ConclusionThe HRF/PH score offers a promising representation of disease severity for PPHN. The tool requires further validation in prospective studies and evaluation for long-term outcomes.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has impacted all patient populations including pregnant mothers. There is an incomplete understanding of SARS-CoV-2 pathogenesis and transmission potential at this time and the resultant anxiety has led to variable breastfeeding recommendations for suspected or confirmed mothers with novel coronavirus disease 2019 (COVID-19). Due to the potential concern for transmission of infection from maternal respiratory secretions to the newborn, temporary separation of the maternal-baby dyad, allowing for expressed breast milk to be fed to the infant, was initially recommended but later revised to include breastfeeding by the American Academy of Pediatrics in contrast to international societies, which recommend direct breastfeeding. This separation can have negative health and emotional implications for both mother and baby. Only two publications have reported SARS-CoV-2 in human breast milk but the role of breast milk as a vehicle of transmission of COVID-19 to the newborns still remains unclear and may indeed be providing protective antibodies against SARS-CoV-2 infection even in infected neonates. Other modes of transmission of infection to neonates from infected mothers or any care providers cannot be overemphasized. Symptomatic mothers on hydroxychloroquine can safely breastfeed and no adverse effects were reported in a baby treated with remdesivir in another drug trial. The excretion of sarilumab in human breast milk is unknown at this time. Hence, given the overall safety of breast milk and both short-term and long-term nutritional, immunological, and developmental advantages of breast milk to newborn, breast milk should not be withheld from baby. The setting of maternal care, severity of maternal infection and availability of resources can impact the decision of breastfeeding, the role of shared decision making on breastfeeding between mother and physician needs to be emphasized. We strongly recommend direct breastfeeding with appropriate hygiene precautions unless the maternal or neonatal health condition warrants separation of this dyad. KEY POINTS: · Breastmilk does not appear to play a significant role in transmission of SARS-CoV-2.. · Mother-baby separation has negative health and emotional consequences.. · Mothers with suspected or confirmed COVID-19 can directly breastfeed with appropriate precautions..

Pregnancy-related acute respiratory distress syndrome (ARDS) is fast becoming a growing and clinically relevant subgroup of ARDS amidst global outbreaks of various viral respiratory pathogens that include H1N1-influenza, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and the most recent COVID-19 pandemic. Pregnancy is a risk factor for severe viral-induced ARDS and commonly associated with poor maternal and fetal outcomes including fetal growth-restriction, preterm birth, and spontaneous abortion. Physiologic changes of pregnancy further compounded by mechanical and immunologic alterations are theorized to impact the development of ARDS from viral pneumonia. The COVID-19 sub-phenotype of ARDS share overlapping molecular features of maternal pathogenicity of pregnancy with respect to immune-dysregulation and endothelial/microvascular injury (i.e., preeclampsia) that may in part explain a trend toward poor maternal and fetal outcomes seen with severe COVID-19 maternal infections. To date, current ARDS diagnostic criteria and treatment management fail to include and consider physiologic adaptations that are unique to maternal physiology of pregnancy and consideration of maternal-fetal interactions. Treatment focused on lung-protective ventilation strategies have been shown to improve clinical outcomes in adults with ARDS but may have adverse maternal-fetal interactions when applied in pregnancy-related ARDS. No specific pharmacotherapy has been identified to improve outcomes in pregnancy with ARDS. Adjunctive therapies aimed at immune-modulation and anti-viral treatment with COVID-19 infection during pregnancy have been reported but data in regard to its efficacy and safety is currently lacking.

Hypoglycemia in neonates is associated with long-term neurodevelopmental effects. Hyperinsulinemic hypoglycemia (HH) is the most common cause of persistent hypoglycemia in neonatal intensive care units. Diazoxide is the only medication that is currently recommended for treatment of HH in neonates. However, the use of diazoxide in neonates is associated with pulmonary hypertension as an adverse effect. In this article, we review the literature on the mechanism of action and adverse effects with the use of diazoxide in neonatal hyperinsulinism. We then present a case series of neonates treated with diazoxide in our neonatal intensive care unit over a 5-year period. Among 23 neonates who received diazoxide, 4 developed pulmonary hypertension and 1 died. All infants who developed pulmonary hypertension were born preterm at less than 36 weeks gestation and had pre-existing risk factors for pulmonary hypertension. HH in preterm neonates, with pre-existing pulmonary hypertension or with risk factors for pulmonary hypertension requires thoughtful management.

BackgroundNeonatal Resuscitation Program does not recommend placental transfusion in depressed preterm neonates.MethodsOur objectives were to study the effect of delayed cord clamping (DCC) with ventilation for 5 min (DCCV, n-5), umbilical cord milking (UCM) without ventilation (n-6), UCM with ventilation (UCMV, n-6), early cord clamping followed by ventilation (ECCV, n-6) on red cell volume (RCV), and hemodynamic changes in asphyxiated preterm lambs. Twenty-three preterm lambs at 127-128 days gestation were randomized to DCCV, UCM, UCMV, and ECCV. We defined asphyxia as heart rate

Volume expanders are indicated in the delivery room when an asphyxiated neonate is not responding to the steps of neonatal resuscitation and has signs of shock or a history of acute blood loss. Fetal blood loss (e.g., feto-maternal hemorrhage) may contribute to perinatal asphyxia. Cord compression or a tight nuchal cord can selectively occlude a thin-walled umbilical vein, resulting in feto-placental transfusion and neonatal hypovolemia. For severe bradycardia or cardiac arrest secondary to fetal blood loss, Neonatal Resuscitation Program (NRP) recommends intravenous volume expanders (crystalloids such as normal saline or packed red blood cells) infused over 5 to 10 min. Failure to recognize hypovolemia and subsequent delay in volume replacement may result in unsuccessful resuscitation due to lack of adequate cardiac preload. However, excess volume load in the presence of myocardial dysfunction from hypoxic-ischemic injury may precipitate pulmonary edema and intraventricular hemorrhage (especially in preterm infants). Emergent circumstances and ethical concerns preclude the performance of prospective clinical studies evaluating volume replacement during neonatal resuscitation. Translational studies, observational data from registries and clinical trials are needed to investigate and understand the role of volume replacement in the delivery room in term and preterm neonates. This article is a narrative review of the causes and consequences of acute fetal blood loss and available evidence on volume replacement during neonatal resuscitation of asphyxiated neonates.

ObjectiveTo evaluate the short-term outcomes of non-vigorous infants born through meconium-stained amniotic fluid (MSAF) before and after implementation of no-tracheal suctioning guidelines.Study designSingle-center retrospective study of ≥36-week gestation neonates with MSAF.ResultsDuring routine-suction era (9/2013-12/2014), 280/2306 neonates (12%) were born through MSAF and 39 (14%) were non-vigorous. Thirty (77%) of non-vigorous infants underwent tracheal suctioning. In the no-suction era (1/2017-12/2018), 282/2918 neonates (9.7%) were born through MSAF and 30 (10.6%) were non-vigorous and one needed intubation. Admissions for meconium aspiration syndrome (15% vs 53%) and respiratory distress (18% vs 57%) were significantly higher among non-vigorous infants in the no-suction era.ConclusionsIn this single-center study, non-vigorous infants born through MSAF without routine-tracheal suctioning had a higher incidence of NICU admission for MAS and respiratory distress compared to the routine-suction era. Multicenter randomized trials evaluating tracheal suction in non-vigorous infants with MSAF are warranted.

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near-term lambs (n = 27) were resuscitated after the induction of 5 min of asystole. Following recovery, lambs were assessed to define neurodevelopmental outcomes. At the end of this period, lambs were euthanized, and brains were harvested for histological analysis. Compared with prior models that typically follow lambs for 3 days, the observation of neurobehavioral outcomes for 6 days enabled identification of animals that recover significant neurological function. Approximately 35% of lambs exhibited severe motor deficits throughout the entirety of the 6-day course and, in the most severely affected lambs, developed spastic diparesis similar to that observed in infants who survive severe neonatal HIE (severe, UCOs). Importantly, and similar to outcomes in human neonates, while initially developing significant acidosis and encephalopathy, the remainder of the lambs in this model recovered normal motor activity and exhibited normal neurodevelopmental outcomes by 6 days of life (improved, UCOi). The UCOs group exhibited gliosis and inflammation in both white and gray matters, oligodendrocyte loss, neuronal loss, and cellular death in the hippocampus and cingulate cortex. While the UCOi group exhibited more cellular death and gliosis in the parasagittal cortex, they demonstrated more preserved white matter markers, along with reduced markers of inflammation and lower cellular death and neuronal loss in Ca3 of the hippocampus compared with UCOs lambs. Our large animal model of moderate HIE with prolonged follow-up will help further define pathophysiologic drivers of brain injury while enabling identification of predictive biomarkers that correlate with disease outcomes and ultimately help support development of therapeutic approaches to this challenging clinical scenario.

There are potential benefits and risks to the infant with higher and lower oxygen saturation (SpO2) targets, and the ideal range for infants with pulmonary hypertension (PH) remains unknown. Targeting high SpO2 can promote pulmonary vasodilation but cause oxygen toxicity. Targeting lower SpO2 may increase pulmonary vascular resistance, especially in the presence of acidosis and hypothermia. We will conduct a randomized pilot trial to compare two ranges of target preductal SpO2 in late-preterm and term infants with hypoxic respiratory failure (HRF) and acute pulmonary hypertension (aPH) of the newborn. We will assess the reliability of a newly created HRF/PH score that could be used in larger trials. We will assess trial feasibility and obtain preliminary estimates of outcomes. Our primary hypothesis is that in neonates with PH and HRF, targeting preductal SpO2 of 95-99% (intervention) will result in lower pulmonary vascular resistance and pulmonary arterial pressures, and lower the need for pulmonary vasodilators (inhaled nitric oxide-iNO, milrinone and sildenafil) compared to targeting SpO2 at 91-95% (standard). We also speculate that a higher SpO2 target can potentially induce oxidative stress and decrease response to iNO (oxygenation and pulmonary vasodilation) for those patients that still require iNO in this range. We present considerations in planning this trial as well as some of the details of the protocol design (Clinicaltrials.gov (NCT04938167)).

The diagnosis of congenital diaphragmatic hernia (CDH) is associated with significant morbidity and mortality. Survival of neonates with CDH has improved recently, although the clinical course is complicated by sequelae of hypoplastic pulmonary parenchyma and vasculature, pulmonary hypertension, ventilation/perfusion (V/Q) mismatch, reduced pulmonary function and poor somatic growth. In this case report, we describe an infant with an antenatal diagnosis of CDH with a poor prognosis who underwent initial surgery followed by a tracheostomy but had a worsening clinical course due to a large area of ventilated but poorly perfused lung based on a V/Q nuclear scintigraphy scan. The emphysematous left lung was causing mediastinal shift and compression of the right lung, further compromising gas exchange. The infant had clinical improvement following bronchial blockade of the under-perfused left lung. This paved the way for further management with resection of the under-perfused lung lobe and continued clinical improvement. We present the novel use of selective bronchial blockade in a challenging case of CDH to determine if surgical lung resection may benefit the infant. We also review the physiology of gas exchange during the use of a bronchial occluder and the relevant literature.

BackgroundThe Neonatal Resuscitation Program (NRP) recommends using 100% O2 during chest compressions and adjusting FiO2 based on SpO2 after return of spontaneous circulation (ROSC). The optimal strategy for adjusting FiO2 is not known.MethodsTwenty-five near-term lambs asphyxiated by umbilical cord occlusion to cardiac arrest were resuscitated per NRP. Following ROSC, lambs were randomized to gradual decrease versus abrupt wean to 21% O2 followed by FiO2 titration to achieve NRP SpO2 targets. Carotid blood flow and blood gases were monitored.ResultsThree minutes after ROSC, PaO2 was 229 ± 32 mmHg in gradual wean group compared to 57 ± 13 following abrupt wean to 21% O2 (p

In persistent pulmonary hypertension of the newborn (PPHN), the ratio of pulmonary vascular resistance to systemic vascular resistance is increased. Extrapulmonary shunts (patent ductus arteriosus and patent foramen value) allow for right-to-left shunting and hypoxaemia. Systemic hypotension can occur in newborns with PPHN due to variety of reasons, such as enhanced peripheral vasodilation, impaired left ventricular function and decreased preload. Systemic hypotension can lead to end organ injury from poor perfusion and hypoxaemia in the newborn with PPHN. Thus, it must be managed swiftly. However, not all newborns with PPHN and systemic hypotension can be managed the same way. Individualised approach based on physiology and echocardiographic findings are necessary to improve perfusion to essential organs. Here we present a review of the physiology and mechanisms of systemic hypotension in PPHN, which can then guide treatment.

ObjectiveTo compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants

The coronavirus disease 2019 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept across the world like an indiscriminating wildfire. Pregnant women and neonates are particularly vulnerable to this infection compared with older children and healthy young adults, with unique challenges in their management. Unfamiliarity with the consequences of this novel virus and lack of high-quality data led to considerable heterogeneity in obstetrical and neonatal management early in the pandemic. The aim of the this review is to summarize the impact of SARS-CoV-2 infection on pregnancy and childbirth and to examine care and possible outcomes for neonates with Covid-19-positive mothers. A brief review of vaccines currently approved by the United States Food and Drug Administration for emergency use and their potential effects on pregnant and lactating women in included.

Pulse oximetry oxygen saturation (SpO 2 )-based critical congenital heart disease (CCHD) screening is effective in detection of cyanotic heart lesions. We report a full-term male infant with normal perfusion who had passed the CCHD screening at approximately 24 hours after birth with preductal SpO 2 of 99% and postductal SpO 2 of 97%. Detection of a loud systolic cardiac murmur before discharge led to the diagnosis of pulmonary atresia (PA) with ventricular septal defect (PA-VSD) by echocardiogram. The infant was transferred to a tertiary care center after initiation of prostaglandin E1 (PGE1) therapy. Throughout the initial course, he was breathing comfortably without respiratory distress or desaturations on pulse oximetry. We believe that this is the first documented report of PA missed by CCHD screening. Thorough and serial clinical examinations of the newborn infant proved vital in the timely diagnosis of this critical disease. We review the hemodynamics and the recent literature evaluating utility of CCHD screening in the diagnosis of PA-VSD. Pulse oximetry-based CCHD screening should be considered a tool to enhance CCHD detection with an emphasis on detailed serial physical examinations in newborn infants.

ObjectiveTo determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia.MethodsWe compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT.ResultsAmong 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively.ConclusionsPPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.

The development of the control of breathing begins in utero and continues postnatally. Fetal breathing movements are needed for establishing connectivity between the lungs and central mechanisms controlling breathing. Maturation of the control of breathing, including the increase of hypoxia chemosensitivity, continues postnatally. Insufficient oxygenation, or hypoxia, is a major stressor that can manifest for different reasons in the fetus and neonate. Though the fetus and neonate have different hypoxia sensing mechanisms and respond differently to acute hypoxia, both responses prevent deviations to respiratory and other developmental processes. Intermittent and chronic hypoxia pose much greater threats to the normal developmental respiratory processes. Gestational intermittent hypoxia, due to maternal sleep-disordered breathing and sleep apnea, increases eupneic breathing and decreases the hypoxic ventilatory response associated with impaired gasping and autoresuscitation postnatally. Chronic fetal hypoxia, due to biologic or environmental (i.e. high-altitude) factors, is implicated in fetal growth restriction and preterm birth causing a decrease in the postnatal hypoxic ventilatory responses with increases in irregular eupneic breathing. Mechanisms driving these changes include delayed chemoreceptor development, catecholaminergic activity, abnormal myelination, increased astrocyte proliferation in the dorsal respiratory group, among others. Long-term high-altitude residents demonstrate favorable adaptations to chronic hypoxia as do their offspring. Neonatal intermittent hypoxia is common among preterm infants due to immature respiratory systems and thus, display a reduced drive to breathe and apneas due to insufficient hypoxic sensitivity. However, ongoing intermittent hypoxia can enhance hypoxic sensitivity causing ventilatory overshoots followed by apnea; the number of apneas is positively correlated with degree of hypoxic sensitivity in preterm infants. Chronic neonatal hypoxia may arise from fetal complications like maternal smoking or from postnatal cardiovascular problems, causing blunting of the hypoxic ventilatory responses throughout at least adolescence due to attenuation of carotid body fibers responses to hypoxia with potential roles of brainstem serotonin, microglia, and inflammation, though these effects depend on the age in which chronic hypoxia initiates. Fetal and neonatal intermittent and chronic hypoxia are implicated in preterm birth and complicate the respiratory system through their direct effects on hypoxia sensing mechanisms and interruptions to the normal developmental processes. Thus, precise regulation of oxygen homeostasis is crucial for normal development of the respiratory control network. © 2021 American Physiological Society. Compr Physiol 11:1653-1677, 2021.

Inhaled nitric oxide is approved by FDA for the management of hypoxemic respiratory failure in term and near-term infants. However, approximately a third of patients treated with inhaled nitric oxide fail to have a sustained improvement in oxygenation. Recruitment of the lung with surfactant enables optimal delivery of nitric oxide to the alveolar space leading to effective pulmonary vasodilation.

Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147-150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.

During transition at birth with ventilation of the lungs, pulmonary vascular resistance (PVR) decreases from high fetal values, leading to an 8 to 10-fold increase in pulmonary blood flow (Qp). In some infants, this transition does not occur, resulting in pulmonary hypertension (PH). In infants, PH can present as: (a) primary PH in term neonates (idiopathic), (b) PH secondary to lung disease or hypoplasia in term infants, (c) acute PH in preterm infants with respiratory distress syndrome (RDS), (d) chronic PH with bronchopulmonary dysplasia (BPD) in preterm infants and (e) post-neonatal PH. A hemodynamically significant patent ductus arteriosus (PDA) can exacerbate PH in preterm infants due to increased Qp. Pulmonary vein stenosis (PVS) can complicate BPD with PH. Diagnosis of PH is based on clinical features, echocardiography and, in some intractable cases, cardiac catheterization. Therapy of PH includes oxygen, invasive or non-invasive ventilation, correction of acidosis, surfactant and selective and non-selective pulmonary vasodilators such as inhaled nitric oxide and sildenafil, respectively. Early closure of a hemodynamically significant PDA has the potential to limit pulmonary vascular remodeling associated with BPD and PH. The role of thiamine in pathogenesis of PH is also discussed with the recent increase in thiamine-responsive acute pulmonary hypertension in early infancy. Recognition and prompt therapy of PH can prevent right ventricular dysfunction, uncoupling and failure.

IntroductionAccess to patient medical data is critical to building a real-time data analytic pipeline for improving care providers' ability to detect, diagnose, and prognosticate diseases. Critical congenital heart disease (CCHD) is a common group of neonatal life-threatening defects that must be promptly diagnosed to minimize morbidity and mortality. CCHD can be diagnosed both prenatally and postnatally. However, despite current screening practices involving oxygen saturation analysis, timely diagnosis is missed in approximately 900 infants with CCHD annually in the USA and can benefit from increased data processing capabilities. Adding non-invasive perfusion measurements to oxygen saturation data can improve the timeliness and fidelity of CCHD diagnostics. However, real-time monitoring and interpretation of non-invasive perfusion data are currently limited.MethodsTo address this challenge, we created a hardware and software architecture utilizing a Pi-top™ for collecting, visualizing, and storing dual oxygen saturation, perfusion indices, and photoplethysmography data. Data aggregation in our system is automated and all data files are coded with unique study identifiers to facilitate research purposes.ResultsUsing this system, we have collected data from 190 neonates, 130 presumably without and 60 with congenital heart disease, in total comprising 1665 min of information. From these data, we are able to extract non-invasive perfusion features such as perfusion index, radiofemoral delay, and slope of systolic rise or diastolic fall.ConclusionThis data collection and waveform analysis is relatively inexpensive and can be used to enhance future CCHD screening algorithms.

Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious immune-mediated condition, seen 3-5 weeks after COVID-19. Maternal SARS-CoV-2 may potentially cause a similar hyperinflammatory syndrome in neonates due to transplacental transfer of antibodies. We reviewed the perinatal history, clinical features, and outcomes of 20 neonates with features consistent with MIS-C related to maternal SARS-CoV-2 in Kolhapur, India, from 1 September 2020 to 30 April 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Fifteen singletons and five twins born to eighteen mothers with a history of COVID-19 disease or exposure during pregnancy presented with features consistent with MIS-C during the first 5 days after birth. Nineteen were positive for anti-SARS-CoV-2 IgG and all were negative for IgM antibodies. All mothers were asymptomatic and therefore not tested by RTPCR-SARS-CoV-2 at delivery. Eighteen neonates (90%) had cardiac involvement with prolonged QTc, 2:1 AV block, cardiogenic shock, or coronary dilatation. Other findings included respiratory failure (40%), fever (10%), feeding intolerance (30%), melena (10%), and renal failure (5%). All infants had elevated inflammatory biomarkers and received steroids and IVIG. Two infants died. We speculate that maternal SARS-CoV-2 and transplacental antibodies cause multisystem inflammatory syndrome in neonates (MIS-N). Immunomodulation may be beneficial in some cases, but further studies are needed.

The initial colonization of the neonatal intestinal tract is influenced by delivery mode, feeding, the maternal microbiota, and a host of environmental factors. After birth, the composition of the infant's microbiota undergoes a series of significant changes particularly in the first weeks and months of life ultimately developing into a more stable and diverse adult-like population in childhood. Intestinal dysbiosis is an alteration in the intestinal microbiota associated with disease and appears to be common in neonates. The consequences of intestinal dysbiosis are uncertain, but strong circumstantial evidence and limited confirmations of causality suggest that dysbiosis early in life can influence the health of the infant acutely, as well as contribute to disease susceptibility later in life.

One hundred years after the 1918 influenza pandemic, we now face another pandemic with the severe acute respiratory syndrome-novel coronavirus-2 (SARS-CoV-2). There is considerable variability in the incidence of infection and severe disease following exposure to SARS-CoV-2. Data from China and the United States suggest a low prevalence of neonates, infants, and children, with those affected not suffering from severe disease. In this article, we speculate different theories why this novel agent is sparing neonates, infants, and young children. The low severity of SARS-CoV-2 infection in this population is associated with a high incidence of asymptomatic or mildly symptomatic infection making them efficient carriers. KEY POINTS: · There is a low prevalence of novel coronavirus disease in neonates, infants, and children.. · The fetal hemoglobin may play a protective role against coronavirus in neonates.. · Immature angiotensin converting enzyme (ACE2) interferes with coronavirus entry into the cells..

BackgroundLittle is known about the perinatal aspects of COVID-19.ObjectiveTo summarize available evidence and provide perinatologists/neonatologists with tools for managing their patients.MethodsAnalysis of available literature on COVID-19 using Medline and Google scholar.ResultsFrom scant data: vertical transmission from maternal infection during the third trimester probably does not occur or likely it occurs very rarely. Consequences of COVID-19 infection among women during early pregnancy remain unknown. We cannot conclude if pregnancy is a risk factor for more severe disease in women with COVID-19. Little is known about disease severity in neonates, and from very few samples, the presence of SARS-CoV-2 has not been documented in human milk. Links to websites of organizations with updated COVID-19 information are provided. Infographics summarize an approach to the pregnant woman or neonate with suspected or confirmed COVID-19.ConclusionsAs the pandemic continues, more data will be available that could lead to changes in current knowledge and recommendations.

Premature neonates 30-55 mm Hg promotes pulmonary vasodilation. Targeting saturations of 80-85% by 5 min, 85-95% by 10 min during resuscitation and 90-95% during the postnatal course are appropriate targets for routine management of preterm infants. Among preterm infants with PHT, avoiding hypoxia/hyperoxia by titrating supplemental oxygen to maintain saturations in low to mid 90s with alarm limits at 90 and 97% seems to be a reasonable approach pending further studies. Further high-quality evidence generated from randomized trials is required to guide oxygen therapy in preterm PHT.

BackgroundNitric oxide (NO) plays an important role in normal postnatal transition. Our aims were to determine whether adding inhaled NO (iNO) decreases supplemental oxygen exposure in preterm infants requiring positive pressure ventilation (PPV) during resuscitation and to study iNO effects on heart rate (HR), oxygen saturation (SpO2), and need for intubation during the first 20 min of life.MethodsThis was a pilot, double-blind, randomized, placebo-controlled trial. Infants 25 0/7-31 6/7 weeks' gestational age requiring PPV with supplemental oxygen during resuscitation were enrolled. PPV was initiated with either oxygen (FiO2-0.30) + iNO at 20 ppm (iNO group) or oxygen (FiO2-0.30) + nitrogen (placebo group). Oxygen was titrated targeting defined SpO2 per current guidelines. After 10 min, iNO/nitrogen was weaned stepwise per protocol and terminated at 17 min.ResultsTwenty-eight infants were studied (14 per group). The mean gestational age in both groups was similar. Cumulative FiO2 and rate of exposure to high FiO2 (>0.60) were significantly lower in the iNO group. There were no differences in HR, SpO2, and need for intubation.ConclusionsAdministration of iNO as an adjunct during neonatal resuscitation is feasible without side effects. It diminishes exposure to high levels of supplemental oxygen.

BackgroundPostnatal growth restriction (PNGR) in premature infants increases risk of pulmonary hypertension (PH). In a rodent model, PNGR causes PH, while combining PNGR and hyperoxia increases PH severity. We hypothesized that PNGR causes intestinal dysbiosis and that treatment with a probiotic attenuates PNGR-associated PH.MethodPups were randomized at birth to room air or 75% oxygen (hyperoxia), to normal milk intake (10 pups/dam) or PNGR (17 pups/dam), and to probiotic Lactobacillus reuteri DSM 17938 or phosphate-buffered saline. After 14 days, PH was assessed by echocardiography and right ventricular hypertrophy (RVH) was assessed by Fulton's index (right ventricular weight/left ventricle + septal weight). The small bowel and cecum were analyzed by high-throughput 16S ribosomal RNA gene sequencing.ResultsPNGR with or without hyperoxia (but not hyperoxia alone) altered the microbiota of the distal small bowel and cecum. Treatment with DSM 17938 attenuated PH and RVH in pups with PNGR, but not hyperoxia alone. DSM 17938 treatment decreased α-diversity. The intestinal microbiota differed based on oxygen exposure, litter size, and probiotic treatment.ConclusionPNGR causes intestinal dysbiosis and PH. Treatment with DSM 17938 prevents PNGR-associated RVH and PH. Changes in the developing intestine and intestinal microbiota impact the developing lung vasculature and RV.

BackgroundIn extremely premature infants, postnatal growth restriction (PNGR) is common and increases the risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Mechanisms by which poor nutrition impacts lung development are unknown, but alterations in the gut microbiota appear to play a role. In a rodent model, PNGR plus hyperoxia causes BPD and PH and increases intestinal Enterobacteriaceae, Gram-negative organisms that stimulate Toll-like receptor 4 (TLR4). We hypothesized that intestinal dysbiosis activates intestinal TLR4 triggering systemic inflammation which impacts lung development.MethodsRat pups were assigned to litters of 17 (PNGR) or 10 (normal growth) at birth and exposed to room air or 75% oxygen for 14 days. Half of the pups were treated with the TLR4 inhibitor TAK-242 from birth or beginning at day 3. After 14 days, pulmonary arterial pressure was evaluated by echocardiography and hearts were examined for right ventricular hypertrophy (RVH). Lungs and serum samples were analyzed by western blotting and immunohistochemistry.ResultsPostnatal growth restriction + hyperoxia increased pulmonary arterial pressure and RVH with trends toward increased plasma IL1β and decreased IκBα, the inhibitor of NFκB, in lung tissue. Treatment with the TLR4 inhibitor attenuated PH and inflammation.ConclusionPostnatal growth restriction induces an increase in intestinal Enterobacteriaceae leading to PH. Activation of the TLR4 pathway is a promising mechanism by which intestinal dysbiosis impacts the developing lung.

Persistent pulmonary hypertension of the newborn (PPHN) is a syndrome of high pulmonary vascular resistance (PVR) commonly seen all over the world in the immediate newborn period. Several case reports from India have recently described severe pulmonary hypertension among infants in the postneonatal period. These cases typically present with respiratory distress in 1-6-month-old infants, breastfed by mothers on a polished rice-based diet. Predisposing factors include respiratory tract infection such as acute laryngotracheobronchitis with change in voice, leading to pulmonary hypertension, right atrial and ventricular dilation, pulmonary edema and hepatomegaly. Mortality is high without specific therapy. Respiratory support, pulmonary vasodilator therapy, inotropes, diuretics and thiamine infusion have improved the outcome of these infants. This review outlines four typical patients with thiamine-responsive acute pulmonary hypertension of early infancy (TRAPHEI) due to thiamine deficiency and discusses pathophysiology, clinical features, diagnostic criteria and therapeutic options.

ObjectiveTo identify current maternal and infant predictors of infant mortality, including maternal sociodemographic and economic status, maternal perinatal smoking and obesity, mode of delivery, and infant birthweight and gestational age.MethodsThis retrospective study analyzed data from the linked birth and infant death files (birth cohort) and live births from the Birth Statistical Master files (BSMF) in California compiled by the California Department of Public Health for 2007-2015. The birth cohort study comprised 4,503,197 singleton births including 19,301 infant deaths during the nine-year study period. A subpopulation to study fetal growth consisted of 4,448,300 birth cohort records including 13,891 infant deaths.ResultsThe infant mortality rate (IMR) for singleton births decreased linearly (p

Effective ventilation of the lungs is essential in mediating pulmonary vasodilation at birth to allow effective gas exchange and an increase in systemic oxygenation. Unsuccessful transition prevents the increase in pulmonary blood flow after birth resulting in hypoxemia and persistent pulmonary hypertension of the newborn (PPHN). Management of neonates with PPHN includes ventilation of the lungs with supplemental oxygen to correct hypoxemia. Optimal oxygenation should meet oxygen demand to the tissues and avoid hypoxic pulmonary vasoconstriction (HPV) while preventing oxidative stress. The optimal target for oxygenation in PPHN is not known. Animal models have demonstrated that PaO2

ObjectiveTo determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm.Study designThis was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP.ResultsThere were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups.ConclusionsChanging SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.

ObjectiveTo evaluate variations in practice for the management of neonates born to mothers with clinical chorioamnionitis.MethodsThis was a prospective cross-sectional survey consisting of 10 multiple choice questionnaires distributed to 2,900 members of the Perinatal Section of American Academy of Pediatrics. Variations in responses were assessed and compared between the various groups.ResultsA total of 682 members (23.5%) completed the survey; 169 (24.8%) indicated that they use the neonatal early-onset sepsis (EOS) risk calculator for the management of neonates born to mothers with clinical chorioamnionitis. More respondents from the western region of United States and level III units are using the EOS risk calculator compared with the south and level II units. Approximately 44% of the respondents indicated that they will not stop antibiotics at 48 to 72 hours in asymptomatic neonates born to mothers with chorioamnionitis with negative blood culture if the complete blood count (CBC) and C-reactive protein (CRP) are abnormal.ConclusionA large number of practitioners are using the neonatal EOS risk calculator for neonates born to mothers with chorioamnionitis. Despite a clear guideline from the Committee on Fetus and Newborn, almost 44% will treat healthy-appearing neonates born to mothers with chorioamnionitis with a prolonged course of antibiotics solely for abnormal CBC or CRP.

The optimal oxygenation target needed to prevent the extremes of hypoxia and oxygen toxicity in premature and sick newborns has been the subject of much research and debate. The advent of the pulse oximeter has allowed the continuous monitoring of oxyhemoglobin saturation and the delivery of oxygen with greater precision. Well-run, large clinical trials to determine the safest oxygen concentration have led to several revisions in guidelines for neonatal care. However, monitoring of oxyhemoglobin saturation has its limitations and does not provide a comprehensive assessment of tissue oxygenation. To identify optimal oxygen therapy, various other factors (partial pressure of arterial carbon dioxide, hemoglobin concentration, blood pH, and tissue metabolic demand) that influence perfusion and tissue oxygenation need to be considered.

BackgroundDistressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts.Methods15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured.ResultsPeak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ± 135.5 ng/ml vs 553.54 ± 215 ng/ml, p  0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group.ConclusionsIn the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted.

ObjectivesTherapeutic hypothermia is standard of care in management of moderate/severe hypoxic-ischemic encephalopathy. Persistent pulmonary hypertension of the newborn is associated with hypoxic-ischemic encephalopathy and is exacerbated by hypoxemia and hypercarbia. Gas exchange is assessed by arterial blood gas analysis (with/without correction for body temperature), pulse oximetry, and end-tidal CO2.DesignA retrospective chart review.SettingsRegional perinatal center in Western New York.PatientsFifty-eight ventilated neonates with indwelling arterial catheter on therapeutic hypothermia.InterventionNone.Measurement and main resultsWe compared pulse oximetry, PaO2, end-tidal CO2, and PaCO2 during hypothermia and normothermia in neonates with hypoxic-ischemic encephalopathy using 1,240 arterial blood gases with simultaneously documented pulse oximetry. During hypothermia, pulse oximetry 92-98% was associated with significantly lower temperature-corrected PaO2 (51 mmHg; interquartile range, 43-51) compared with normothermia (71 mmHg; interquartile range, 61-85). Throughout the range of pulse oximetry values, geometric mean PaO2 was about 23% (95% CI, 19-27%) lower during hypothermia compared with normothermia. In contrast, end-tidal CO2 accurately assessed temperature-corrected PaCO2 during normothermia and hypothermia.ConclusionsHypothermia shifts oxygen-hemoglobin dissociation curve to the left resulting in lower PaO2 for pulse oximetry. Monitoring oxygenation with arterial blood gas uncorrected for body temperature and pulse oximetry may underestimate hypoxemia in hypoxic-ischemic encephalopathy infants during whole-body hypothermia, while end-tidal CO2 reliably correlates with temperature-corrected PaCO2.

ObjectiveWe studied decision making regarding inhaled nitric oxide (iNO) in preterm infants with Pulmonary Hypertension (PH).Study designWe asked members of the AAP-Society of Neonatal-Perinatal Medicine and Division-Chiefs to select from three management options- initiate iNO, engage parents in shared decision making or not consider iNO in an extremely preterm with PH followed by rating of factors influencing their decision.ResultsThree hundred and four respondents (9%) completed the survey; 36.5% chose to initiate iNO, 42% to engage parents, and 21.5% did not consider iNO. Provider's prior experience, safety, and patient-centered care were rated higher by those who initiated or offered iNO; lack of effectiveness and cost considerations by participants who did not chose iNO.ConclusionsMost neonatologists offer or initiate iNO therapy based on their individual experience. The minority who chose not to consider iNO placed higher value on lack of effectiveness and cost. These results demonstrate a tension between evidence and pathophysiology-based-therapy/personal experience.

The current recommendation for umbilical cord management of non-vigorous infants (limp, pale, and not breathing) who need resuscitation at birth is to immediately clamp the umbilical cord. This recommendation is due in part to insufficient evidence for delayed cord clamping (DCC) or umbilical cord milking (UCM). These methods may provide a neuroprotective mechanism that also facilitates cardiovascular transition for non-vigorous infants at birth.

ObjectiveTo determine recent trends in maternal prepregnancy body mass index (BMI) and to quantify its association with birth and maternal outcomes.MethodsA population-based retrospective cohort study included resident women with singleton births in the California Birth Statistical Master Files (BSMF) database from 2007 to 2016. There were 4,621,082 women included out of 5,054,968 women registered in the database. 433,886 (8.6%) women were excluded due to invalid or missing information for BMI. Exposures were underweight (BMI < 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥ 30 kg/m2) at the onset of pregnancy. Obesity was subcategorized into class I (30.0-34.9 kg/m2), class II (35.0-39.9 kg/m2), and class III (≥ 40 kg/m2), while adverse outcomes examined were low birth weight (LBW), very low birth weight (VLBW), macrosomic births, preterm birth (PTB), very preterm birth (VPTB), small-for-gestational-age birth (SGA), large-for-gestational-age birth (LGA), and cesarean delivery (CD). Descriptive analysis, simple linear regression, and multivariate logistic regression were performed, and adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations were estimated.ResultsOver the ten-year study period, the prevalence of underweight and normal weight women at time of birth declined by 10.6% and 9.7%, respectively, while the prevalence of overweight and obese increased by 4.3% and 22.9%, respectively. VLBW increased significantly with increasing BMI, by 24% in overweight women and by 76% in women with class III obesity from 2007 to 2016. Women with class III obesity also had a significant increase in macrosomic birth (170%) and were more likely to deliver PTB (33%), VPTB (66%), LGA (231%), and CD (208%) than women with a normal BMI. However, obese women were less likely to have SGA infants; underweight women were 51% more likely to have SGA infants than women with a normal BMI.ConclusionsIn California from 2007 to 2016, there was a declining trend in women with prepregnancy normal weight, and a rising trend in overweight and obese women, particularly obesity class III. Both extremes of prepregnancy BMI were associated with an increased incidence of adverse neonatal outcomes; however, the worse outcomes were prominent in those women classified as obese.

The Textbook of Neonatal Resuscitation, seventh edition, does not suggest routine endotracheal suctioning for non-vigorous infants born through meconium-stained amniotic fluid. We compared 301,150 infants at ≥35 weeks' gestational age inborn at 311 Vermont Oxford Network member centers in the United States (U.S.) and admitted to neonatal intensive care units (NICU) who were born before (2013 to 2015) and after (2017) the guideline change. Logistic regression models adjusting for clustering of infants within centers were used to calculate risk ratios. NICU admissions for infants with a diagnosis of meconium aspiration syndrome (MAS) decreased from 1.8% to 1.5% (risk ratio: 0.82; 95% confidence interval: 0.68, 0.97) and delivery room endotracheal suctioning in this group decreased from 57.0% to 28.9% (0.51; 0.41, 0.62). Treatment with conventional or high frequency ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation remained unchanged 42.3% vs. 40.3% (0.95; 0.80, 1.13) among infants with MAS and 9.1% vs. 8.2% (0.91; 0.87, 0.95) among infants without MAS. The use of surfactant among infants with MAS increased from 24.6% to 30% (1.22; 1.02, 1.48). Mortality (2.6 to 2.9%, 1.12; 0.74, 1.69) and moderate/severe hypoxic-ischemic encephalopathy (5.4 to 6.8%, 1.24; 0.91, 1.69) increased slightly in 2017. Subgroup analyses of infants with 1 min Apgar scores of ≤3 found similar results. While NICU admissions for MAS and tracheal suctioning decreased after the introduction of the new guideline with no subsequent increase in severe respiratory distress among infants with and without a MAS diagnosis, limitations in our study preclude inferring that the new guideline is safe or effective.

The International Liaison Committee on Resuscitation (ILCOR) recommends the initiation of chest compressions (CC) during neonatal resuscitation after 30 s of effective ventilation if the infant remains bradycardic (defined as a heart rate less than 60 bpm). The CC are performed during bradycardia to optimize organ perfusion, especially to the heart and brain. Among adults and children undergoing cardiopulmonary resuscitation (CPR), CC is indicated only for pulselessness or poor perfusion. Neonates have a healthy heart that attempts to preserve coronary and cerebral perfusion during bradycardia secondary to asphyxia. Ventilation of the lungs is the key step during neonatal resuscitation, improving gas exchange and enhancing cerebral and cardiac blood flow by changes in intrathoracic pressure. Compressing the chest 90 times per minute without synchrony with innate cardiac activity during neonatal bradycardia is not based on evidence and could potentially be harmful. Although there are no studies evaluating outcomes in neonates, a recent pediatric study in a hospital setting showed that when CC were initiated during pulseless bradycardia, a third of the patients went into complete arrest, with poor survival at discharge. Ventilation-only protocols such as helping babies breathe are effective in reducing mortality and stillbirths in low-resource settings. In a situation of complete cardiac arrest, CC reinitiates pulmonary flow and supports gas exchange. However, the benefit/harm of performing asynchronous CC during bradycardia as part of neonatal resuscitation remains unknown.

Epinephrine is the only medication recommended by the International Liaison Committee on Resuscitation for use in newborn resuscitation. Strong evidence from large clinical trials is lacking owing to the infrequent use of epinephrine during neonatal resuscitation. Current recommendations are weak as they are extrapolated from animal models or pediatric and adult studies that do not adequately depict the transitioning circulation and fluid-filled lungs of the newborn in the delivery room. Many gaps in knowledge including the optimal dosing, best route and timing of epinephrine administration warrant further studies. Experiments on a well-established ovine model of perinatal asphyxial cardiac arrest closely mimicking the newborn infant provide important information that can guide future clinical trials.

BackgroundPreterm birth (PTB) is associated with increased infant mortality, and neurodevelopmental abnormalities among survivors. The aim of this study is to investigate temporal trends, patterns, and predictors of PTB in California from 2007 to 2016, based on the obstetric estimate of gestational age (OA).MethodsA retrospective cohort study evaluated 435,280 PTBs from the 5,137,376 resident live births (8.5%) documented in the California Birth Statistical Master Files (BSMF) from 2007 to 2016. The outcome variable was PTB; the explanatory variables were birth year, maternal characteristics and health behaviors. Descriptive statistics and logistic regression analysis were used to identify subgroups with significant risk factors associated with PTB. Small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) infants were identified employing gestational age based on obstetric estimates and further classified by term and preterm births, resulting in six categories of intrauterine growth.ResultsThe prevalence of PTB in California decreased from 9.0% in 2007 to 8.2% in 2014, but increased during the last 2 years, 8.4% in 2015 and 8.5% in 2016. Maternal age, education level, race and ethnicity, smoking during pregnancy, and parity were significant risk factors associated with PTB. The adjusted odds ratio (AOR) showed that women in the oldest age group (40-54 years) were almost twice as likely to experience PTB as women in the 20- to 24-year reference age group. The prevalence of PTB was 64% higher in African American women than in Caucasian women. Hispanic women showed less disparity in the prevalence of PTB based on education and socioeconomic level. The analysis of interactions between maternal characteristics and perinatal health behaviors showed that Asian women have the highest prevalence of PTB in the youngest age group (

BackgroundThe Neonatal Resuscitation Program recommends initial resuscitation of preterm infants with low oxygen (O2) followed by titration to target preductal saturations (SpO2). We studied the effect of resuscitation with titrated O2 on gas exchange, pulmonary, and systemic hemodynamics.MethodologyTwenty-nine preterm lambs (127 d gestation) were randomized to resuscitation with 21% O2 (n = 7), 100% O2 (n = 6), or initiation at 21% and titrated to target SpO2 (n = 16). Seven healthy term control lambs were ventilated with 21% O2.ResultsPreductal SpO2 achieved by titrating O2 was within the desired range similar to term lambs in 21% O2. Resuscitation of preterm lambs with 21% and 100% O2 resulted in SpO2 below and above the target, respectively. Ventilation of preterm lambs with 100% O2 and term lambs with 21% O2 effectively decreased pulmonary vascular resistance (PVR). In contrast, preterm lambs with 21% O2 and titrated O2 demonstrated significantly higher PVR than term lambs on 21% O2.Conclusion(s)Initial resuscitation with 21% O2 followed by titration of O2 led to suboptimal pulmonary vascular transition at birth in preterm lambs. Ventilation with 100% O2 in preterm lambs caused hyperoxia but reduced PVR similar to term lambs on 21% O2. Studies evaluating the initiation of resuscitation at a higher O2 concentration followed by titration based on SpO2 in preterm neonates are needed.

Necrotizing enterocolitis (NEC) is a devastating morbidity usually seen in preterm infants, with extremely preterm neonates (EPT ≤28 weeks) considered at highest risk. Moderately preterm infants (MPT 28-34 weeks) constitute a large percentage of NICU admissions. In our retrospective data analysis of NEC in a single regional perinatal center, NEC was observed in 10% of extremely EPT and 7% of MPT, but only 0.7% of late-preterm/term admissions. There was an inverse relationship between postnatal age at onset of NEC and gestational age at birth. Among MPT infants with NEC, maternal hypertensive disorders (29%) and small for gestational age (SGA-15%) were more common than in EPT infants (11.6 and 4.6%, resp.). Congenital gastrointestinal anomalies were common among late preterm/term infants with NEC. SGA MPT infants born to mothers with hypertensive disorders are particularly at risk and should be closely monitored for signs of NEC. Identifying risk factors specific to each gestational age may help clinicians to tailor interventions to prevent NEC.

Birth asphyxia accounts for nearly one million deaths worldwide each year, and is one of the primary causes of early neonatal morbidity and mortality. Many aspects of the current neonatal resuscitation guidelines remain controversial given the difficulties in conducting randomized clinical trials owing to the infrequent and often unpredictable need for extensive resuscitation. Most studies on neonatal resuscitation stem from manikin models that fail to truly reflect physiologic changes or piglet models that have cleared their lung fluid and that have completed the transition from fetal to neonatal circulation. The present protocol provides a detailed step-by-step description on how to create a perinatal asphyxiated fetal lamb model. The proposed model has a transitioning circulation and fluid-filled lungs, which mimics human newborns following delivery, and is, therefore, an excellent animal model to study newborn physiology. An important limitation to lamb experiments is the higher associated cost.

OBJECTIVE:To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE). METHODS:We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial. RESULTS:Among 303 infants with HIE from these 2 studies, 67 (22%) had PPHN and 236 (78%) did not. We compared infants with PPHN with those without PPHN. The proportion of patients treated with therapeutic hypothermia was similar in PPHN and no-PPHN groups (66% vs 65%). Medication use during resuscitation (58% vs 44%), acidosis after birth (pH: 7.0 ± 0.2 vs 7.1 ± 0.2), severe HIE (43% vs 28%), meconium aspiration syndrome (39% vs 7%), pulmonary hemorrhage (12% vs 3%), culture-positive sepsis (12% vs 3%), systemic hypotension (65% vs 28%), inhaled nitric oxide therapy (64% vs 3%), and extracorporeal membrane oxygenation (12% vs 0%) were more common in the PPHN group. Length of stay (26 ± 21 vs 16 ± 14 days) and mortality (27% vs 16%) were higher in the PPHN group. CONCLUSIONS:PPHN is common among infants with moderate/severe HIE and is associated with severe encephalopathy, lung disease, sepsis, systemic hypotension, and increased mortality. The prevalence of PPHN was not different between those infants receiving therapeutic hypothermia at 33.5°C in these 2 trials (44/197 = 22%) compared with infants receiving normothermia in the induced hypothermia trial (23/106 = 22%).