An Interdisciplinary Consensus Approach to Pulmonary Hypertension in Developmental Lung Disorders.

It is increasingly recognised that diverse genetic respiratory disorders present as severe pulmonary hypertension (PH) in the neonate and young infant, but many controversies and uncertainties persist regarding optimal strategies for diagnosis and management to maximize long-term outcomes. To better define the nature of PH in the setting of developmental lung disorders (DEVLD), in addition to the common diagnoses of bronchopulmonary dysplasia and congenital diaphragmatic hernia, we established a multidisciplinary group of expert clinicians from stakeholder paediatric specialties to highlight current challenges and recommendations for clinical approaches, as well as counselling and support of families. In this review, we characterise clinical features of infants with DEVLD/DEVLD-PH and identify decision-making challenges including genetic evaluations, the role of lung biopsies, the use of imaging modalities, and treatment approaches. The importance of working with team members from multiple disciplines, enhancing communication and providing sufficient counselling services for families is emphasized to create an interdisciplinary consensus.

Pulmonary hypertension in the intensive care unit after pediatric allogeneic hematopoietic stem cell transplant: incidence, risk factors, and outcomes.

Objective: To determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT). Methods: This was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed. Results: Among 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74-3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%). Conclusions: PH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.

Defining the Typical Course of Persistent Pulmonary Hypertension of the Newborn: When to Think Beyond Reversible Causes.

OBJECTIVES: To describe the typical clinical course of reversible persistent pulmonary hypertension of the newborn (PPHN) from perinatal etiologies and compare that with the clinical course of PPHN due to underlying fetal developmental etiologies. STUDY DESIGN: This was a single-center, retrospective cohort study of liveborn newborns either born or transferred to our facility for higher level of care between 2015 and 2020 with gestational age ≥35 weeks and a clinical diagnosis of PPHN in the electronic health record. Newborns with complex congenital heart disease and congenital diaphragmatic hernia were excluded. Using all data available at time of collection, newborns were stratified into 2 groups by PPHN etiology - perinatal and fetal developmental causes. Primary outcomes were age at initiation, discontinuation, and total duration of extracorporeal life support, mechanical ventilation, supplemental oxygen, inhaled nitric oxide, inotropic support, and prostaglandin E1. Our secondary outcome was age at echocardiographic resolution of pulmonary hypertension. Groups were compared by t-test. Time-to-event Kaplan Meier curves described and compared (log-rank test) discontinuation of each therapy. RESULTS: Sixty-four (72%) newborns had perinatal etiologies whereas 24 (28%) had fetal developmental etiologies. The resolution of perinatal PPHN was more rapid compared with fetal developmental PPHN. By 10 days of age, more neonates were off inotropes (98% vs 29%, P < .01), decannulated from extracorporeal life support (100% vs 0%, P < .01), extubated (75% vs 37%, P < .01), and had echocardiographic resolution of PH (35% vs 7%, P = .02). CONCLUSIONS: An atypical PPHN course, characterized by persistent targeted therapies in the second week of life, warrants further work-up for fetal developmental causes.

Management of pulmonary vascular disease associated with congenital left-to-right shunts: A single-center experience.

OBJECTIVE: The study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First). METHODS: We performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m2) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed. RESULTS: Of 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m2). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77). CONCLUSIONS: In children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension-targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients.

A single institution anesthetic experience with catheterization of pediatric pulmonary hypertension patients.

Cardiac catheterization remains the gold standard for the diagnosis and management of pediatric pulmonary hypertension (PH). There is lack of consensus regarding optimal anesthetic and airway regimen. This retrospective study describes the anesthetic/airway experience of our single center cohort of pediatric PH patients undergoing catheterization, in which obtaining hemodynamic data during spontaneous breathing is preferential. A total of 448 catheterizations were performed in 232 patients. Of the 379 cases that began with a natural airway, 274 (72%) completed the procedure without an invasive airway, 90 (24%) received a planned invasive airway, and 15 (4%) required an unplanned invasive airway. Median age was 3.4 years (interquartile range [IQR] 0.7-9.7); the majority were either Nice Classification Group 1 (48%) or Group 3 (42%). Vasoactive medications and cardiopulmonary resuscitation were required in 14 (3.7%) and eight (2.1%) cases, respectively; there was one death. Characteristics associated with use of an invasive airway included age <1 year, Group 3, congenital heart disease, trisomy 21, prematurity, bronchopulmonary dysplasia, WHO functional class III/IV, no PH therapy at time of case, preoperative respiratory support, and having had an intervention (p < 0.05). A composite predictor of age <1 year, Group 3, prematurity, and any preoperative respiratory support was significantly associated with unplanned airway escalation (26.7% vs. 6.9%, odds ratio: 4.9, confidence interval: 1.4-17.0). This approach appears safe, with serious adverse event rates similar to previous reports despite the predominant use of natural airways. However, research is needed to further investigate the optimal anesthetic regimen and respiratory support for pediatric PH patients undergoing cardiac catheterization.

Congenital Diaphragmatic Hernia: Pulmonary Hypertension and Pulmonary Vascular Disease.

This review provides a comprehensive summary of the current understanding of pulmonary hypertension (PH) in congenital diaphragmatic hernia, outlining the underlying pathophysiologic mechanisms, methods for assessing PH severity, optimal management strategies, and prognostic implications.

The effect of fertility treatment and socioeconomic status on neonatal and post-neonatal mortality in the United States.

OBJECTIVE: To determine the association between fertility treatment, socioeconomic status (SES), and neonatal and post-neonatal mortality. STUDY DESIGN: Retrospective cohort study of all births (19,350,344) and infant deaths from 2014-2018 in the United States. The exposure was mode of conception-spontaneous vs fertility treatment. The outcome was neonatal (<28d), and post-neonatal (28d-1y) mortality. Multivariable logistic models were stratified by SES. RESULT: The fertility treatment group had statistically significantly higher odds of neonatal mortality (high SES OR 1.59; CI [1.5, 1.68], low SES OR 2.11; CI [1.79, 2.48]) and lower odds of post-neonatal mortality (high SES OR 0.87, CI [0.76, 0.996], low SES OR 0.6, CI [0.38, 0.95]). SES significantly modified the effect of ART/NIFT on neonatal and post-neonatal mortality. CONCLUSIONS: Fertility treatment is associated with higher neonatal and lower post-neonatal mortality and SES modifies this effect. Socioeconomic policies and support for vulnerable families may help reduce rates of infant mortality.

Prostaglandin-E1 infusion in persistent pulmonary hypertension of the newborn.

BACKGROUND: Neonates with persistent pulmonary hypertension of the newborn (PPHN) can present with hypoxia and right ventricular dysfunction with resultant inadequate oxygen delivery and end-organ damage. This study describes the use of prostaglandin-E1 (PGE) for ductal patency to preserve right ventricular systolic function and limit afterload in newborns with PPHN. METHODS: This is a retrospective cohort study that follows the hemodynamics, markers of end-organ perfusion, length of therapeutics, and echocardiographic variables of 57 newborns who used prostglandin-E1 in the setting of PPHN. RESULTS: Tachycardia, lactic acidosis, and supplemental oxygen use improved following PGE initiation. Fractional area change (FAC), to assess right ventricular systolic function, and pulmonary arterial acceleration time indexed to right ventricular ejection time (PAAT/RVET), to assess right ventricular afterload, also improved over three time points relative to PGE use (before, during, and after). CONCLUSIONS: Overall, we described the safety and utility of PGE in newborns with severe PPHN for stabilization while allowing natural disease progression.

Fertility treatment increases the risk of preterm birth independent of multiple gestations.

Objective: To investigate the complex interplay between fertility treatment, multiple gestations, and prematurity. Design: Retrospective cohort study linking the national Center for Disease Control and Prevention infant birth and death data from 2014 to 2018. Setting: National database from Center of Disease Control and Prevention. Patients: In total, 19,454,155 live-born infants with gestational ages 22-44 weeks, 114,645 infants born using non IVF fertility treatment (NIFT), and 179,960 via assisted reproductive technology (ART). Intervention: Noninvasive fertility treatment or ART vs. spontaneously conceived pregnancies. Main Outcome Measures: The main outcome assessed was prematurity. Formal mediation analysis was conducted to calculate the percentage mediated by multiple gestations. Results: Newborns born using NIFT or ART compared with those with no fertility treatment had a higher incidence of multiple gestation (no fertility treatment = 3.0%; NIFT = 24.7%; ART = 32.7%; P<.001) and prematurity (no fertility treatment = 11.2%; NIFT = 23.4%; ART = 28.4%; P<.001). Mediation analysis demonstrates that 76.8% (95% confidence interval [CI], 75.2%-78.1%) of the effect of NIFT on prematurity was mediated through multiple gestations. Similarly, 71.2% (95% CI, 70.8%-72.7%) of the effect of ART on prematurity is mediated through multiple gestation. However, the direct effect of NIFT on prematurity is 20.4% (95% CI, 19.0%-22.0%). The direct effect of ART was 24.7% (95% CI, 23.7%-25.6%). Conclusion: A significant proportion of prematurity associated with fertility treatment is mediated by the treatment itself, independent of multiple gestations.

Safety and tolerability of continuous inhaled iloprost in critically ill pediatric pulmonary hypertension patients: A retrospective case series.

Inhaled iloprost (iILO) has shown efficacy in treating patients with hypoxic lung disease and pulmonary hypertension, inducing selective pulmonary vasodilation and improvement in oxygenation. However, its short elimination half-life of 20-30 min necessitates frequent intermittent dosing (6-9 times per day). Thus, the administration of iILO via continuous nebulization represents an appealing method of drug delivery in the hospital setting. The objectives are: (1) describe our continuous iILO delivery methodology and safety profile in mechanically ventilated pediatric pulmonary hypertension patients; and (2) characterize the initial response of iILO in these pediatric patients currently receiving iNO. Continuous iILO was delivered and well tolerated (median 6 days; range 1-94) via tracheostomy or endotracheal tube using the Aerogen® mesh nebulizer system coupled with a Medfusion® 400 syringe pump. No adverse events or delivery malfunctions were reported. Initiation of iILO resulted in an increase in oxygen saturation from 81.4 ± 8.6 to 90.8 ± 4.1%, p < 0.05. Interestingly, prior iNO therapy for >1 day resulted in a higher response rate to iILO (as defined as a ≥ 4% increase in saturations) compared to those receiving iNO <1 day (85% vs. 50%, p = 0.06). When the use of iILO is considered, continuous delivery represents a safe, less laborious alternative and concurrent treatment with iNO should not be considered a contraindication. However, given the retrospective design and small sample size, this study does not allow the evaluation of the efficacy of continuous iILO on outcomes beyond the initial response. Thus, a prospective study designed to evaluate the efficacy of continuous iILO is necessary.

Sociodemographic factors associated with tracheostomy and mortality in bronchopulmonary dysplasia.

OBJECTIVES: We sought to investigate how race, ethnicity, and socioeconomic status relate to tracheostomy insertion and post-tracheostomy mortality among infants with bronchopulmonary dysplasia (BPD). METHODS: The Vizient Clinical Database/Resource Manager was queried to identify infants born ≤32 weeks with BPD admitted to US hospitals from January 2012 to December 2020. Markers of socioeconomic status were linked to patient records from the Agency for Healthcare Research and Quality's Social Determinants of Health Database. Regression models were used to assess trends in annual tracheostomy insertion rate and odds of tracheostomy insertion and post-tracheostomy mortality, adjusting for sociodemographic and clinical factors. RESULTS: There were 40,021 ex-premature infants included in the study, 1614 (4.0%) of whom received a tracheostomy. Tracheostomy insertion increased from 2012 to 2017 (3.1%-4.1%), but decreased from 2018 to 2020 (3.3%-1.6%). Non-Hispanic Black infants demonstrated a 25% higher odds (aOR 1.25, 1.09-1.43) and Hispanic infants demonstrated a 20% lower odds (aOR 0.80, 0.65-0.96) of tracheostomy insertion compared with non-Hispanic White infants. Patients receiving public insurance had increased odds of tracheostomy insertion (aOR 1.15, 1.03-1.30), but there was no relation between other metrics of socioeconomic status and tracheostomy insertion within our cohort. In-hospital mortality among the tracheostomy-dependent was 14.1% and was not associated with sociodemographic factors. CONCLUSIONS: Disparities in tracheostomy insertion are not accounted for by differences in socioeconomic status or the presence of additional neonatal morbidities. Post-tracheostomy mortality does not demonstrate the same relationships. Further investigation is needed to explore the source and potential mitigators of the identified disparities.

Expected small left heart size in the presence of congenital diaphragmatic hernia: Fetal values and Z-scores for infants confirmed to have no heart disease postnatally.

Objectives: In fetuses with left-sided congenital diaphragmatic hernia (CDH), left heart structures may appear small, but usually normalize after birth in the absence of structural cardiac anomalies. To decrease the possibility of an erroneous diagnosis of structural heart disease, we identify normal values for left heart structures in the presence of left CDH and secondarily investigate the relationship of left heart size and survival to neonatal hospital discharge. Methods: Left heart structures [mitral valve (MV) and aortic valve (AoV) annulus diameter, left ventricle (LV) length and width] were measured by fetal echocardiogram in fetuses with left CDH and no congenital heart disease. We generated linear regression models to establish the relationship of gestational age for each left heart structure using data from fetuses who survived after birth. We calculated z-scores (normalized to gestational age), and assessed the relationship of survival to the size of each structure. Results: One hundred forty-two fetuses underwent fetal echocardiogram (median 25 weeks' gestation, IQR 23, 27 weeks). Left heart structures were deemed small when using published normative data from unaffected fetuses (z-scores: MV -1.09 ± 1.35, AoV -2.12 ± 1.16, LV length -1.36 ± 1.24, LV width -4.79 ± 0.79). CDH-specific models derived from log-transformed values yielded left-shifted distributions, reflecting the small structures (mean z-score lower by: MV 0.99 ± 0.30, AoV 2.04 ± 0.38, LV length 1.30 ± 0.36, and LV width 4.69 ± 0.28; p < 0.0001 for all comparisons). Non-survivors had worse z-scores than survivors for all measurements, but this did not reach statistical significance. Conclusions: Log-transformed linear models generated new normative data for fetal left heart structures in left CDH, which may be used to allay antenatal concerns regarding structural left heart anomalies. There were no significant differences in z-scores between survivors and non-survivors, suggesting that in the absence of true structural disease, cardiac evaluation is not predictive in isolation and that causes of mortality are likely multifactorial in this population.

Persistence of persistent pulmonary hypertension of the newborn: A case of de novo TBX4 variant.

We present a case of a late preterm infant placed on extracorporeal life support in the first day of life for persistent pulmonary hypertension of the newborn. Developmental arrest, pulmonary vascular hypertensive changes, and pulmonary interstitial glycogenosis were present on lung biopsy at 7 weeks of age. Pulmonary hypertension has persisted through childhood. Genetic testing at 8 years identified a novel mutation in TBX4.

Pulmonary artery acceleration time in young children is determined by heart rate and transpulmonary gradient but not by pulmonary blood flow: A simultaneous echocardiography-cardiac catheterization study.

INTRODUCTION: Pulmonary artery acceleration time (PAAT) is considered useful for the non-invasive evaluation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). PAAT is dependent on PAP, PVR, pulmonary artery compliance, stroke volume, and heart rate. Its relative dependency on these determinants may differ between young and older children, raising uncertainty regarding its utility in young children. We aim to identify the primary determinants of the PAAT in children less than 36 months undergoing cardiac catheterization and its utility for the diagnosis of elevated PVR. METHODS: We prospectively studied 42 children undergoing cardiac catheterization and simultaneous echocardiography. We determined the correlations of PAAT to the above-mentioned determinants and evaluated receiver operator characteristic (ROC) curves for diagnosis of PVR indexed to body surface area (PVRi) ≥3 Wu*m2 . RESULTS: Median age was 11.5 (IQR 5.2, 21.2) months. Moderate correlations were found between PAAT and mean PAP (R = -.66, p < .001), PVRi (R = -.54, p = .004), pulmonary artery compliance (R = .65, p < .001), transpulmonary gradient (R = -.67, p < .001), stroke volume (R = .61, p = .002), and heart rate (R = -.63, p < .001). In multivariate regression modeling, only transpulmonary gradient and heart rate were independent determinants of PAAT. PAAT ≤77 msec had acceptable utility for diagnosing PVRi ≥ 3 Wu*m2 (AUC .8 [.64, .95], n = 36), low sensitivity (59%), and excellent specificity (94%). CONCLUSION: Transpulmonary gradient and heart rate, but not pulmonary blood flow, are important determinants of PAAT in children <36 months undergoing cardiac catheterization. PAAT has low sensitivity for diagnosing elevated PVRi, therefore, should not be solely relied upon in screening for elevated PVRi in young children.

Doppler Echocardiographic Features of Pulmonary Vein Stenosis in Ex-Preterm Children.

BACKGROUND: Echocardiography is used to screen for the presence of pulmonary vein stenosis (PVS) in ex-preterm infants and children. However, there are no standard accepted criteria for screening or diagnosis of PVS by echocardiography. The aim of this study was to identify Doppler waveform features and Doppler systolic and diastolic velocity cutoff values associated with a diagnosis of PVS by cardiac catheterization. METHODS: In this retrospective observational study, the echocardiograms of ex-preterm children <3 years old who underwent cardiac catheterization at a single institution were reviewed. PVS on cardiac catheterization was defined by a mean pressure gradient of >3 mm Hg in the pulmonary vein, with angiographic evidence of stenosis. Pulmonary vein Doppler waveforms, from echocardiograms obtained before catheterization, in children with and without PVS were compared. Nonstenosed veins in patients with PVS were excluded. The systolic and diastolic velocities of blood flow, phasic flow, and return of the Doppler waveform to baseline were analyzed. RESULTS: Forty-seven children were analyzed in the study, 18 children with 25 stenosed pulmonary veins and 29 children with 78 nonstenosed pulmonary veins. Stenosed pulmonary veins had higher peak systolic and diastolic velocities and higher peak and mean pressure gradients as measured by spectral Doppler. Peak systolic and diastolic velocities had areas under the receiver operating characteristic curve of 0.89 (95% CI, 0.79-0.99) and 0.93 (95% CI, 0.85-0.99) for PVS, respectively, and a threshold velocity of 0.7 m/sec had sensitivity of 80% and 84% and specificity of 94%. There was no correlation between Doppler-derived pulmonary vein mean gradient and measured pulmonary vein mean gradient during cardiac catheterization in stenosed pulmonary veins. Presence of phasic flow in the pulmonary vein and return of the Doppler waveform to baseline were associated with a nonstenosed pulmonary vein (sensitivity of 94% and 60% and specificity of 52% and 60%, respectively). CONCLUSIONS: Systolic and diastolic Doppler velocities and features of the waveform can discriminate stenosed pulmonary veins confirmed by cardiac catheterization in ex-preterm children. These results suggest the use of lower systolic and diastolic Doppler velocity cutoff values than currently published to screen for PVS in ex-preterm children. These cutoff values require validation in prospective studies.

Oral Feeding in Infants After Congenital Diaphragmatic Hernia Repair While on Non-invasive Positive Pressure Ventilation: The Impact of a Dysphagia Provider-Led Protocol.

Infants with congenital diaphragmatic hernia (CDH) who require non-invasive positive pressure ventilation or high flow nasal cannula are at risk for aspiration and delayed initiation of oral feeding. We developed a dysphagia provider-led protocol that involved early consultation with an occupational therapist or speech/language pathologist and modified barium swallow study (MBSS) to assess for readiness for oral feeding initiation/advancement on non-invasive positive pressure ventilation. The objective of this study was to retrospectively compare this intervention cohort to a historical control cohort to evaluate the protocol's impact on the time to initiate oral feeding. We describe the development and implementation of the protocol, the MBSS findings of the intervention cohort, and compared the control (n = 64) and intervention (n = 37) cohorts using Fischer's exact test and Mann-Whitney test. We found that both cohorts had similar prenatal and neonatal characteristics including age at extubation. Significantly more infants in the intervention cohort were on non-invasive positive pressure ventilation or high flow nasal cannula at the time of oral feeding initiation (84% vs. 28%, p < 0.0001). None of the control cohort infants underwent MBSS while on respiratory support. Of the intervention cohort, 15 infants underwent a MBSS while on non-invasive positive pressure ventilation; 6 had no evidence of laryngeal penetration and/or aspiration during swallowing. Infants in the control cohort initiated oral feeds significantly sooner after extubation (6 versus 11 days, p = 0.001) and attained full oral feeds earlier (20 days versus 28 days, p = 0.02) than the intervention group. There was no difference in the rate of gastrostomy tube placement (38%). Appropriate monitoring by a dysphagia provider and evaluation with clinical and radiological means are crucial to determine the safety of initiating oral feeding in term infants with CDH. Continued surveillance is needed to determine the long-term impact on oral feeding progression in this population.

Hemodynamic optimization for neonates with neonatal encephalopathy caused by a hypoxic ischemic event: Physiological and therapeutic considerations.

Neonatal encephalopathy due to a hypoxic-ischemic event is commonly associated with cardiac dysfunction and acute pulmonary hypertension; both therapeutic hypothermia and rewarming modify loading conditions and blood flow. The pathophysiological contributors to disease are complex with a high degree of clinical overlap and traditional bedside measures used to assess circulatory adequacy have multiple confounders. Comprehensive, quantitative echocardiography may be used to delineate the relative contribution of lung parenchymal, pulmonary vascular, and cardiac disease to hypotension and/or hypoxemic respiratory failure. In this review, we provide a detailed overview of the contributors to hemodynamic instability following perinatal hypoxic-ischemic injury. Our proposed approach to therapy focuses on physiopathological considerations with interventions individualized to this potentially complex condition and considers the pharmacological idiosyncrasies, which may occur among neonates with NE presenting with multiorgan dysfunction while undergoing therapeutic hypothermia.

Outcomes of Very Preterm Infants Conceived with Assisted Reproductive Technologies.

OBJECTIVE: To compare mortality and early respiratory outcomes of very preterm infants conceived via assisted reproductive technology (ART) vs spontaneously. STUDY DESIGN: We identified inborn infants (July 2014-July 2019) with gestational age <32 weeks (n = 439); 54 cases were ART conceived. Spontaneously conceived controls (n = 103) were matched by multiple gestation status and gestational age. Primary outcome was 1-year mortality. Secondary outcomes were receipt of respiratory support and supplemental oxygen at 7 and 28 days and 36 weeks of postmenstrual age. We evaluated the association between conception method and outcomes by logistic regression, with adjustment for sociodemographic status. RESULTS: Women who conceived via ART had increased rates of prepregnancy and gestational diabetes, and no differences in rates of hypertensive disorders. Infant 1-year mortality was not different by mode of conception (ART 11.8% vs spontaneous 7.1%, P = .49). Infants conceived by ART were less likely to receive respiratory support or supplemental oxygen at all time points, but this relationship only reached significance for receipt of oxygen at 28 days (ART 20.8% vs spontaneous 39.0%, P = .03); this remained true after adjustment for race/ethnicity and socioeconomic index. CONCLUSIONS: When controlling for gestational age and multiple gestation status, very preterm infants conceived following ART had similar outcomes as those conceived spontaneously.