Martina A. Steurer

Neurodevelopmental impairments are common in congenital heart disease (CHD) and fetal brain volume is an important predictor of outcomes. Social determinants of health (SDOH) and environmental factors influence brain growth in other populations and likely play a neurodevelopmental role in CHD. This study evaluated the influence of SDOH and environmental factors on fetal and neonatal brain volume, growth, and risk of brain injury in CHD. This prospective single-center longitudinal cohort study enrolled fetuses with severe CHD to undergo third-trimester fetal and preoperative brain MRIs. Controls underwent third-trimester brain MRIs. Participants completed SDOH and environmental exposure surveys. Fetal and neonatal brain volumes, brain growth, and presence of white matter injury (WMI) were assessed. 57 CHD patients and 24 controls were enrolled, resulting in 33 fetal and 44 neonatal MRIs in the CHD group and 21 fetal control MRIs. Several SDOH and environmental factors, including maternal smoking, were associated with smaller brain volume and slower brain growth in CHD but not in controls. With CHD, repeated-measures analysis showed smaller fetal brain volume (coeff: − 13.3, 95% CI − 25.5, − 1.1, p = 0.03) and slower growth (coeff: − 2.5, 95% CI − 5.0, − 0.07, p = 0.04) with exposure to any risk factor. Patients with moderate to severe WMI had significantly lower mean COI scores compared to those with no or minimal WMI (58.28 vs. 37.28, p = 0.04), but lost significance when adjusted for GA. SDOH and environmental exposures influence fetal brain growth and preoperative brain injury risk in CHD. These results highlight additive environmental prenatal risks which may be amenable to early intervention.

Introduction: Emerging evidence suggests that an impaired foetal environment—defined as maternal factors such as hypertensive disorders and diabetes—might contribute to outcomes in neonates with CHD. With this multicentre study, we prospectively collected data regarding impaired foetal environment to assess the impact on mortality in two ventricle and single ventricle neonates with CHD. Materials and methods: A module of prospectively collected maternal-foetal environment data was linked to established Pediatric Cardiac Critical Care Consortium data from June 2019 to July 2020. All neonates undergoing cardiothoracic surgery were included in this study. The outcome was in-hospital mortality. The primary predictor was the degree of impaired foetal environment defined as none, mild, or significant based on the presence of maternal hypertensive and glucose homeostasis disorders. Results: There were a total of 1913 neonates included in this study from 26 different centres. 218 patients had at least 1 missing impaired foetal environment data field (11.8%). Impaired foetal environment was not associated with increased mortality; however, there was a strong trend in the preterm single ventricular population. Discussion: While the overall cohort did not demonstrate a statistically significant relationship between impaired foetal environment and mortality, a notable trend emerged among preterm infants with single-ventricle physiology, suggesting increased mortality associated with more severe impaired foetal environment. The absence of statistical significance in this subgroup is likely attributable to the limited sample size and the substantial proportion of missing data highlighting the challenges of the mother-baby dyad in data collections.

Objective The aim of this quality improvement project was to increase preoperative enteral feeding and breastfeeding rates in term neonates with congenital heart disease (CHD). Methods A multidisciplinary team developed and implemented a preoperative feeding protocol for neonates with congenital heart disease. The primary outcome was the presence of preoperative enteral feeding by May 2025. Secondary outcomes included breastfeeding rates and time to first feed. The process measure was the rate of reference to the feeding protocol in provider notes. Our balancing measure was a rule out or diagnosis of necrotizing enterocolitis requiring medical or surgical treatment in the preoperative period. Infants were identified using the Pediatric Cardiac Critical Care Collaborative (PC4). Data was collected from chart review and analyzed with statistical process control charts. The pre-implementation period was from June 2022 to June 2023, the implementation period was from July 2023 to June 2024, and the sustainment period was from July 2024 through May 2025. Results The number of neonates that met the inclusion criteria was 121. The rate of overall enteral feeding increased significantly from 72% in the pre-implementation phase (June 2022-June 2023) to 93% in the sustainment phase (July 2024–May 2025) (p = 0.026). Additionally, we found an improvement in our secondary outcomes and no change to the balancing measures. Conclusion This quality improvement initiative, which centered on creating and implementing a clear, standardized, evidence-based feeding protocol while utilizing interdisciplinary collaboration, led to an increase in overall rates of preoperative enteral feeding for newborns with CHD in a level IV intensive care nursery.

Contemporary United States (US) data on the survival of preterm infants with congenital heart disease (CHD) are unavailable despite the over-representation of CHD and improving surgical outcomes in the preterm population. The aim of this study is to use population-based data to compare 1-year survival and early mortality (< 3 days) by gestational age (GA) between preterm infants with and without cyanotic CHD (CCHD) in the US. This national retrospective cohort included all liveborn, preterm infants between 21 and 36 weeks GA with a birth certificate indicating the presence or absence of CCHD (n = 2,654,253) born between 2014 and 2019 in the US. Data were provided by the US Center for Disease Control database linking birth and death certificates. Of liveborn preterm infants, 0.13% (n = 3619) had CCHD. 1-year survival was significantly lower in infants 23–36 weeks with CCHD compared to those without. The greatest survival gap occurred between 28 and 31 weeks (28 weeks adjusted risk difference 37.5%; 95% CI 28.4, 46.5; 31 weeks 37.9%; 30.5, 45.3). Early mortality accounted for more than half of deaths among infants 23–31 weeks with CCHD (23 weeks-68%, CI 46.7, 83.7; 31 weeks-63.9%, 52.9, 73.6). Survival trends demonstrated worsened 1-year survival in infants 35–36 weeks with CCHD over the study period. The pattern of mortality for preterm infants with CCHD is distinct from those without. The significant survival gap in the very preterm population and notably high rate of early death in the infants with CCHD calls for renewed attention to early neonatal intensive care for this dually affected population.

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.

Objective: Infants of mothers with adult congenital heart disease (ACHD) are at increased risk for adverse pregnancy and neonatal outcomes. We aim to identify mediators in the relationship between ACHD and pregnancy and infant outcomes. Study design: Case-control study using linked maternal and infant hospital records. Structural equation modeling was performed to assess for potential mediators of pregnancy and infant outcomes. Result: We showed an increased risk of multiple adverse infant and pregnancy outcomes among infants born to mothers with ACHD. Maternal placental syndrome and congestive heart failure were mediators of prematurity. Prematurity and critical congenital heart disease in the infant were mediators of infant outcomes. However, the direct effect of ACHD on outcomes beyond that explained by these mediators remained significant. Conclusion: While significant mediators of infant and pregnancy outcomes were identified, there was a large direct effect of maternal ACHD. Further studies should aim to identify more factors that explain these infants’ vulnerability.

Objective: To describe changes over time in resuscitation, survival, and morbidity of extremely preterm infants in California. Study design: This population-based, retrospective cohort study includes infants born ≤28 weeks. Linked birth certificates and hospital discharge records were used to evaluate active resuscitation, survival, and morbidity across two epochs (2011–2014, 2015–2019). Results: Of liveborn infants, 0.6% were born ≤28 weeks. Active resuscitation increased from 16.9% of 22-week infants to 98.1% of 25-week infants and increased over time in 22-, 23-, and 25-week infants (p-value ≤ 0.01). Among resuscitated infants, survival to discharge increased from 33.2% at 22 weeks to 96.1% at 28 weeks. Survival without major morbidity improved over time for 28-week infants (p-value < 0.01). Conclusion: Among infants ≤28 weeks, resuscitation and survival increased with gestational age and morbidity decreased. Over time, active resuscitation of periviable infants and morbidity-free survival of 28-week infants increased. These trends may inform counseling around extremely preterm birth.

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential for sustaining premature infants until they transition to enteral feeds, but there is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23–30 days of life from 314 infants born p < 0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants in a longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with the initiation of enteral feeds. These infants had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting the nutritional benefit of an enteral feeding regimen.

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential in sustaining premature infants until they transition to enteral feeds. There is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23-30 days of life from 314 infants born <29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN as compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status. Among 913 metabolites that passed quality control filters, 609 varied in abundance between infants on TPN vs enteral feeds at p<0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants with longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with initiation of enteral feeds. Infants on enteral feeds had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting a nutritional benefit of an enteral feeding regimen.