Human cord plasma proteomic analysis reveals sexually dimorphic proteins associated with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is associated with increased risk of cardiometabolic disease later in life and has been shown to affect female and male offspring differently, but the mechanisms remain unclear. The purpose of this study was to identify proteomic differences and metabolic risk markers in IUGR male and female neonates when compared to appropriate for gestational age (AGA) babies that will provide a better understanding of IUGR pathogenesis and its associated risks. Our results revealed alterations in IUGR cord plasma proteomes with most of the differentially abundant proteins implicated in peroxisome pathways. This effect was evident in females but not in males. Furthermore, we observed that catalase activity, a peroxisomal enzyme, was significantly increased in females (p < 0.05) but unchanged in males. Finally, we identified risk proteins associated with obesity, type-2 diabetes, and glucose intolerance such as EGF containing fibulin extracellular matrix protein 1 (EFEMP1), proprotein convertase subtilisin/kexin type 9 (PCSK9) and transforming growth factor beta receptor 3 (TGFBR3) proteins unique to females while coagulation factor IX (C9) and retinol binding protein 4 (RBP4) are unique in males. In conclusion, IUGR may display sexual dimorphism which may be associated with differences in lifelong risk for cardiometabolic disease between males and females.

Caffeine and kidney function at two years in former extremely low gestational age neonates.

BACKGROUND: Extremely low gestational age neonates (ELGANs) are at risk for chronic kidney disease. The long-term kidney effects of neonatal caffeine are unknown. We hypothesize that prolonged caffeine exposure will improve kidney function at 22-26 months. METHODS: Secondary analysis of the Preterm Erythropoietin Neuroprotection Trial of neonates <28 weeks' gestation. Participants included if any kidney outcomes were collected at 22-26 months corrected age. Exposure was post-menstrual age of caffeine discontinuation. PRIMARY OUTCOMES: 'reduced eGFR' <90 ml/min/1.73 m2, 'albuminuria' (>30 mg albumin/g creatinine), or 'elevated blood pressure' (BP) >95th %tile. A general estimating equation logistic regression model stratified by bronchopulmonary dysplasia (BPD) status was used. RESULTS: 598 participants had at least one kidney metric at follow up. Within the whole cohort, postmenstrual age of caffeine discontinuation was not associated with any abnormal measures of kidney function at 2 years. In the stratified analysis, for each additional week of caffeine, the no BPD group had a 21% decreased adjusted odds of eGFR <90 ml/min/1.73m2 (aOR 0.78; CI 0.62-0.99) and the BPD group had a 15% increased adjusted odds of elevated BP (aOR 1.15; CI: 1.05-1.25). CONCLUSIONS: Longer caffeine exposure during the neonatal period is associated with differential kidney outcomes at 22-26 months dependent on BPD status. IMPACT: In participants born <28 weeks' gestation, discontinuation of caffeine at a later post menstrual age was not associated with abnormal kidney outcomes at 22-26 months corrected age. When assessed at 2 years of age, later discontinuation of caffeine in children born <28 weeks' gestation was associated with a greater risk of reduced eGFR in those without a history of BPD and an increased odds of hypertension in those with a history of BPD. More work is necessary to understand the long-term impact of caffeine on the developing kidney.

The effect of cesarean delivery on the neonatal gut microbiome in an under-resourced population in the Bronx, NY, USA.

BACKGROUND: Neonatal and early-life gut microbiome changes are associated with altered cardiometabolic and immune development. In this study, we explored Cesarean delivery effects on the gut microbiome in our high-risk, under-resourced Bronx, NY population. RESULTS: Fecal samples from the Bronx MomBa Health Study (Bronx MomBa Health Study) were categorized by delivery mode (vaginal/Cesarean) and analyzed via 16 S rRNA gene sequencing at four timepoints over the first two years of life. Bacteroidota organisms, which have been linked to decreased risk for obesity and type 2 diabetes, were relatively reduced by Cesarean delivery, while Firmicutes organisms were increased. Organisms belonging to the Enterococcus genus, which have been tied to aberrant immune cell development, were relatively increased in the Cesarean delivery microbiomes. CONCLUSION: Due to their far-reaching impact on cardiometabolic and immune functions, Cesarean deliveries in high-risk patient populations should be carefully considered.

Building Relationships: Advanced Practice Providers and Fellows in Neonatal-Perinatal Medicine.

OBJECTIVE: Advanced practice providers (APPs) are a critical component of health care teams, especially in the neonatal intensive care unit. At times, APPs and neonatal-perinatal medicine (NPM) fellows may experience tension in their professional relationship. They may perceive the other's performance and abilities differently. We hypothesized that satisfaction with the APP-NPM fellow interprofessional relationship would be associated with higher perception of APP competence by NPM fellows. STUDY DESIGN: We surveyed 274 medical providers: NPM fellows (24.8%), NPM program directors (24.5%), and APPs (50.7%). APPs were defined as neonatal nurse practitioners, pediatric nurse practitioners, physician assistants, or neonatal hospitalists. We obtained demographic data, information about sources of conflict in the APP-NPM fellow relationship, level of satisfaction with the relationship, and targeted interventions for improvement. NPM fellow perception of APP competence as well as APP self-assessed competence were elicited. Statistical analyses were performed with chi-square tests and Fisher's exact tests. RESULTS: Overall, APPs and NPM fellows were generally satisfied with their relationship. All groups reported APP competence as equivalent to a third-year NPM fellow. NPM fellow perception of APP competence increased with year of fellow training. Higher perceived APP competence by NPM fellows correlated with higher relationship satisfaction scores. Difficulties with teamwork, communication and respect were associated with lower satisfaction within the APP-NPM fellow relationship. CONCLUSION: The professional working dynamic between these two groups is viewed positively by all. Satisfaction with the APP-NPM fellow relationship correlated with higher perception of APP competence by NPM fellows. Targeted interventions that increase NPM fellow perception of APP competence and ameliorate the difficulties encountered in the APP-NPM fellow relationship may improve this interprofessional relationship. KEY POINTS: · Advanced practice providers and NPM fellows may have similar responsibilities leading to challenges.. · NPM fellows with higher perceived competence of APPs had higher satisfaction with their relationship.. · Training APPs to teach, creating interprofessional education, and routine debrief sessions may help..

Late onset neonatal acute kidney injury: results from the AWAKEN Study.

BACKGROUND: Most studies of neonatal acute kidney injury (AKI) have focused on the first week following birth. Here, we determined the outcomes and risk factors for late AKI (>7d). METHODS: The international AWAKEN study examined AKI in neonates admitted to an intensive care unit. Late AKI was defined as occurring >7 days after birth according to the KDIGO criteria. Models were constructed to assess the association between late AKI and death or length of stay. Unadjusted and adjusted odds for late AKI were calculated for each perinatal factor. RESULTS: Late AKI occurred in 202/2152 (9%) of enrolled neonates. After adjustment, infants with late AKI had higher odds of death (aOR:2.1, p = 0.02) and longer length of stay (parameter estimate: 21.9, p < 0.001). Risk factors included intubation, oligo- and polyhydramnios, mild-moderate renal anomalies, admission diagnoses of congenital heart disease, necrotizing enterocolitis, surgical need, exposure to diuretics, vasopressors, and NSAIDs, discharge diagnoses of patent ductus arteriosus, necrotizing enterocolitis, sepsis, and urinary tract infection. CONCLUSIONS: Late AKI is common, independently associated with poor short-term outcomes and associated with unique risk factors. These should guide the development of protocols to screen for AKI and research to improve prevention strategies to mitigate the consequences of late AKI.

Effect of Vitamin D Supplementation on Recurrent Wheezing in Black Infants Who Were Born Preterm: The D-Wheeze Randomized Clinical Trial.

Importance: Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. Objective: To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing. Design, Setting, and Participants: A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks' gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. Interventions: Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. Main Outcomes and Measures: Recurrent wheezing by 12 months' adjusted age was the primary outcome. Results: Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, -10.7% [95% CI, -27.4% to -2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, -1.6% [95% CI, -17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, -3.6% [95% CI, -16.4% to 4.4%]). Conclusions and Relevance: Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months' adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of vitamin D supplementation on wheezing in children born preterm. Trial Registration: ClinicalTrials.gov Identifier: NCT01601847.

DNA hypermethylation of CD3(+) T cells from cord blood of infants exposed to intrauterine growth restriction.

AIMS/HYPOTHESIS: Intrauterine growth restriction (IUGR) is associated with increased susceptibility to obesity, metabolic syndrome and type 2 diabetes. Although the mechanisms underlying the developmental origins of metabolic disease are poorly understood, evidence suggests that epigenomic alterations play a critical role. We sought to identify changes in DNA methylation patterns that are associated with IUGR in CD3(+) T cells purified from umbilical cord blood obtained from male newborns who were appropriate for gestational age (AGA) or who had been exposed to IUGR. METHODS: CD3(+) T cells were isolated from cord blood obtained from IUGR and AGA infants. The genome-wide methylation profile in eight AGA and seven IUGR samples was determined using the HELP tagging assay. Validation analysis using targeted bisulfite sequencing and bisulfite massARRAY was performed on the original cohort as well as biological replicates consisting of two AGA and four IUGR infants. The Segway algorithm was used to identify methylation changes within regulatory regions of the genome. RESULTS: A global shift towards hypermethylation in IUGR was seen compared with AGA (89.8% of 4,425 differentially methylated loci), targeted to regulatory regions of the genome, specifically promoters and enhancers. Pathway analysis identified dysregulation of pathways involved in metabolic disease (type 2 diabetes mellitus, insulin signalling, mitogen-activated protein kinase signalling) and T cell development, regulation and activation (T cell receptor signalling), as well as transcription factors (TCF3, LEF1 and NFATC) that regulate T cells. Furthermore, bump-hunting analysis revealed differentially methylated regions in PRDM16 and HLA-DPB1, genes important for adipose tissue differentiation, stem cell maintenance and function and T cell activation. CONCLUSIONS/INTERPRETATION: Our findings suggest that the alterations in methylation patterns observed in IUGR CD3(+) T cells may have functional consequences in targeted genes, regulatory regions and transcription factors. These may serve as biomarkers to identify those at 'high risk' for diminished attainment of full health potential who can benefit from early interventions. ACCESS TO RESEARCH MATERIALS: HELP tagging data: Gene Expression Omnibus database (GSE77268), scheduled to be released on 25 January 2019.

CRIB scores as a tool for assessing risk for the development of pulmonary hypertension in extremely preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) increases the risk for developing pulmonary hypertension (PH). However, the risk factors associated with BPD-associated PH remain unclear. Our primary aim was to determine perinatal risk factors associated with the development of PH in infants with BPD. STUDY DESIGN: We retrospectively reviewed medical records of 303 infants born at ≤ 28 weeks' gestation. Infants were categorized as having no, mild, moderate, or severe BPD. PH was diagnosed by echocardiogram. Data were analyzed using Fisher exact test, two-sample t-test, and multivariable logistic regression. RESULTS: The incidence of PH in our cohort was 12%. Infants with PH had lower birth weights and gestational ages (p < 0.001). After controlling for confounding variables, severe BPD (p < 0.001), and higher Clinical Risk Index for Babies (CRIB) scores (p = 0.04) were associated with the development of PH. CONCLUSION: Severe BPD increases the risk for developing PH. Higher CRIB scores correlate with PH development in infants with BPD. We speculate that CRIB scores may allow for early categorization of preterm infants with a higher likelihood of developing PH.

Critical periods of increased fetal vulnerability to a maternal high fat diet.

BACKGROUND: Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression. METHODS: Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, 9.5% fat) for 2 wk before mating until e9.5 of pregnancy (periconception-midpregnancy). At e9.5 dams were switched to the opposite diet (C-HF or HF-C). RESULTS: Exposure to HF diet throughout pregnancy reduced maternal weight gain compared to C diet (p < 0.02 HF vs. C). HF-C dams had significantly decreased adiponectin levels and litter size when compared to C-HF (p < 0.02 HF-C vs C-HF). Independent of the timing of exposure to HF, fetal weight and length were significantly decreased when compared to C diet (HF, C-HF and HF-C vs. C p < 0.02). HF diet during the second half of pregnancy increased expression of genes in the fetal liver associated with fetal growth (C-HF vs C p < 0.001), glucose production (C-HF vs C p < 0.04), oxidative stress and inflammation (C-HF vs C p < 0.01) compared to C diet. CONCLUSIONS: This model defines that there are critical periods during gestation in which the fetus is actively shaped by the environment. Early exposure to a HF diet determines litter size while exposure to HF during the second half of pregnancy leads to dysregulation of expression of key genes responsible for fetal growth, hepatic glucose production and oxidative stress. These findings underscore the importance of future studies designed to clarify how these critical periods may influence future risk of developing MetS later in life.

Research Ethics in Pregnancy: The Maternal-Fetal Dyad.

Pregnant persons and their physicians often make decisions for health care without clinical evidence to guide their choices. Years of exclusionary practices in research, dominated by fears of fetal harm, have resulted in limited evidence on therapies for pregnancy-specific conditions. It has also eroded pregnant persons' rights as autonomous individuals capable of weighing risks and benefits to make choices for themselves and their infants based on sound evidence. A paradigm shift from "routine exclusion" to "fair inclusion" of pregnant persons in clinical trials is needed to ensure that ethical principles are upheld when undertaking research in this population. This article will provide a brief review of the historical aspects of clinical research ethics for pregnant persons, focus on some key concepts within the context of the maternal-fetal dyad, and include a recent example from the coronavirus disease 2019 (COVID-19) pandemic to understand how society has interpreted tensions among the ethical principles of justice, beneficence, nonmaleficence, and autonomy. Note: This review uses the term "pregnant person(s)" to include women and people who are pregnant and do not identify themselves as women.

Corrigendum: Association of parent-child interactions with parental psychological distress and resilience during the COVID-19 pandemic.

[This corrects the article DOI: 10.3389/fped.2023.1150216.].

Association of parent-child interactions with parental psychological distress and resilience during the COVID-19 pandemic.

Introduction: The effects of psychological distress/resilience on parent-child engagement (e.g., family dinners, reading) during the COVID-19 pandemic have not been well studied. Among very young children from underrepresented backgrounds enrolled in the ongoing longitudinal Bronx Mother Baby Health Study of healthy term infants, we (1) examined associations between exposures to COVID-19-related events, demographic factors and parental psychological distress and resilience; and (2) correlated these factors with parent-child engagement activities. Methods: Between June 2020-August 2021, parents of 105 Bronx Mother Baby Health Study participants aged birth-25 months completed questionnaires related to exposures to COVID-19-related events, frequency of positive parent-child engagement activities, food and housing insecurity, and parental psychological distress and resilience. Families were also asked open ended questions about the pandemic's impact. Results: 29.8% and 47.6% of parents reported food and housing insecurity, respectively. Greater exposures to COVID-19-related events were associated with increased parental psychological distress. Positive parent-child interactions were associated with demographic factors and higher levels of maternal education, but not with exposures to COVID-19-related events. Discussion: This study adds to a growing body of literature on the negative impacts of COVID-19 exposures and psychosocial stressors on families during the pandemic, supporting the need for enhanced mental health resources and social supports for families.

Ethical Considerations in Neonatal Research.

Children are considered a vulnerable population and have traditionally been excluded from research studies. This exclusion of children in general, and neonates in particular, from clinical research hampers the development of safe and effective therapies in this population. However, research involving children (including infants) is essential to guide therapy and optimize care. Neonatal research is complex, time intensive, difficult and expensive to conduct, and raises some unique ethical considerations. The complexity of research in this population is highlighted by the fear of causing harm to fragile sick infants which has led to the creation of special regulations on the degree of risk exposure permissible in research involving infants. This is further compounded by the inability of infants to provide informed consent or assent and the reliance on obtaining surrogate consent from parents who may themselves be vulnerable and overwhelmed by their infant's illness and the amount of information provided to them. In this review, we discuss the evolution of ethical regulations related to research, the justification for research in infants, and some of the ethical nuances of research in this population.

Fetal Growth and Intrauterine Epigenetic Programming of Obesity and Cardiometabolic Disease.

Epidemiologic studies have shown an association between an adverse intrauterine environment (eg, exposure to malnutrition) and an increased risk of developing cardiometabolic disease in adulthood. These studies laid the foundation for the developmental origins of health and disease hypothesis, which states that limited nutrient supply to the fetus results in physiologic and metabolic adaptations that favor survival but result in unfavorable consequences in the offspring if there is excess nutrition after birth. This discrepancy in the pre- and postnatal milieus, perceived as stress by the offspring, may confer an increased risk of developing cardiometabolic disease later in life. Thus, early life exposures result in programming or changes in cellular memory that have effects on health throughout the life course. One of the mechanisms by which programming occurs is via epigenetic modifications of genes, processes that result in functionally relevant changes in genes (ie, gene expression) without an alteration in the genotype. In this review, we will describe how fetal exposures, including under- and overnutrition, affect neonatal and childhood growth and the future risk for cardiometabolic disease.

Association of early dysnatremia with mortality in the neonatal intensive care unit: results from the AWAKEN study.

OBJECTIVE: To determine the association of dysnatremia in the first postnatal week and risk of acute kidney injury (AKI) and mortality. STUDY DESIGN: A secondary analysis of 1979 neonates in the AWAKEN cohort evaluated the association of dysnatremia with (1) AKI in the first postnatal week and (2) mortality, utilizing time-varying Cox proportional hazard models. RESULT: Dysnatremia developed in 50.2% of the cohort and was not associated with AKI. Mortality was associated with hyponatremia (HR 2.15, 95% CI 1.07-4.31), hypernatremia (HR 4.23, 95% CI 2.07-8.65), and combined hypo/hypernatremia (HR 6.39, 95% CI 2.01-14.01). In stratified models by AKI-status, hypernatremia and hypo/hypernatremia increased risk of mortality in neonates without AKI. CONCLUSION: Dysnatremia within the first postnatal week was associated with increased risk of mortality. Hypernatremia and combined hypo/hypernatremia remained significantly associated with mortality in neonates without AKI. This may reflect fluid strategies kidney injury independent of creatinine and urine-output defined AKI, and/or systemic inflammation.

Burden of prematurity-associated recurrent wheezing: caregiver missed work in the D-Wheeze trial.

OBJECTIVE: This study describes the burden of prematurity-associated wheezing in black infants with respect to caregiver missed work. STUDY DESIGN: We analyzed data from the D-Wheeze trial (ClinicalTrials.gov identifier NCT01601847). Black infants between 28-0/7 to 36-6/7 weeks' gestational age at birth receiving <28 days of supplemental oxygen were enrolled. The primary outcome was missed work to care for the infant in the first year. RESULTS: 147/277 (53.1%) infants had caregivers who reported time off. In an adjusted model, vitamin D supplementation (OR 0.52 [95% CI 0.30-0.89]; P = 0.018), recurrent wheeze (OR 2.26 [95% CI, 1.15-4.44]; P = 0.018), and other children in the household <5 years old (OR 0.45 [95% CI 0.26-0.78]; P = 0.004) were significantly associated with caregiver missed work. CONCLUSIONS: Black premature infants had a significant burden of caregiver missed work, emphasizing the impact of prematurity-associated wheezing.

Antenatal betamethasone alters vascular reactivity in adult female ovine cerebral arteries.

Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta-exposed and control sheep, whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there seemed to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep.

Incidence and Risk Factors of Early Onset Neonatal AKI.

BACKGROUND AND OBJECTIVES: Neonatal AKI is associated with poor short- and long-term outcomes. The objective of this study was to describe the risk factors and outcomes of neonatal AKI in the first postnatal week. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The international retrospective observational cohort study, Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN), included neonates admitted to a neonatal intensive care unit who received at least 48 hours of intravenous fluids. Early AKI was defined by an increase in serum creatinine >0.3 mg/dl or urine output <1 ml/kg per hour on postnatal days 2-7, the neonatal modification of Kidney Disease: Improving Global Outcomes criteria. We assessed risk factors for AKI and associations of AKI with death and duration of hospitalization. RESULTS: Twenty-one percent (449 of 2110) experienced early AKI. Early AKI was associated with higher risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.7 to 4.7) and longer duration of hospitalization (parameter estimate: 7.3 days 95% confidence interval, 4.7 to 10.0), adjusting for neonatal and maternal factors along with medication exposures. Factors associated with a higher risk of AKI included: outborn delivery; resuscitation with epinephrine; admission diagnosis of hyperbilirubinemia, inborn errors of metabolism, or surgical need; frequent kidney function surveillance; and admission to a children's hospital. Those factors that were associated with a lower risk included multiple gestations, cesarean section, and exposures to antimicrobials, methylxanthines, diuretics, and vasopressors. Risk factors varied by gestational age strata. CONCLUSIONS: AKI in the first postnatal week is common and associated with death and longer duration of hospitalization. The AWAKEN study demonstrates a number of specific risk factors that should serve as "red flags" for clinicians at the initiation of the neonatal intensive care unit course.

Persistent pulmonary hypertension of the newborn.

Failure of the normal circulatory adaptation to extrauterine life results in persistent pulmonary hypertension of the newborn (PPHN). Although this condition is most often secondary to parenchymal lung disease or lung hypoplasia, it may also be idiopathic. PPHN is characterized by elevated pulmonary vascular resistance with resultant right-to-left shunting of blood and hypoxemia. Although the preliminary diagnosis of PPHN is often based on differential cyanosis and labile hypoxemia, the diagnosis is confirmed by echocardiography. Management strategies include optimal lung recruitment and use of surfactant in patients with parenchymal lung disease, maintaining optimal oxygenation and stable blood pressures, avoidance of respiratory and metabolic acidosis and alkalosis, and pulmonary vasodilator therapy. Extracorporeal membrane oxygenation is considered when medical management fails. Although mortality associated with PPHN has decreased significantly with improvements in medical care, there remains the potential risk for neurodevelopmental disability which warrants close follow-up of affected infants after discharge.