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Impact of Maternal-Fetal Environment on Mortality in Children With Single Ventricle Heart Disease.

ABSTRACT: BACKGROUND Children with single ventricle heart disease have significant morbidity and mortality. The maternal-fetal environment (MFE) may adversely impact outcomes after neonatal cardiac surgery. We hypothesized that impaired MFE would be associated with an increased risk of death after stage 1 Norwood reconstruction. METHODS AND RESULTS We performed a retrospective cohort study of children with hypoplastic left heart syndrome (and anatomic variants) who underwent stage 1 Norwood reconstruction between 2008 and 2018. Impaired MFE was defined as maternal gestational hypertension, preeclampsia, gestational diabetes, and/or smoking during pregnancy. Cox proportional hazards regression models were used to investigate the association between impaired MFE and death while adjusting for confounders. Hospital length of stay was assessed with the competing risk of in-hospital death. In 273 children, the median age at stage 1 Norwood reconstruction was 4 days (interquartile range [IQR], 3-6 days). A total of 72 children (26%) were exposed to an impaired MFE; they had more preterm births (18% versus 7%) and a greater percentage with low birth weights <2.5 kg (18% versus 4%) than those without impaired MFE. Impaired MFE was associated with a higher risk of death (hazard ratio [HR], 6.05; 95% CI, 3.59-10.21; P<0.001) after adjusting for age at surgery, Hispanic ethnicity, genetic syndrome, cardiac diagnosis, surgeon, and birth era. Children with impaired MFE had almost double the risk of prolonged hospital stay (HR, 1.95; 95% CI, 1.41-2.70; P<0.001). CONCLUSIONS Children exposed to an impaired MFE had a higher risk of death following stage 1 Norwood reconstruction. Prenatal exposures are potentially modifiable factors that can be targeted to improve outcomes after pediatric cardiac surgery.

SUBMITTER: Savla JJ

PROVIDER: S-EPMC9238520 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is conducted within the first few weeks of birth, the second between 4 to 6 months, and the third and final surgery within the first 4 years. At the conclusion of the third surgery, systemic perfusion is provided by the right ventricle (RV), and deoxygenated blood flows passively to the pulmonary vasculature. Despite these palliative interventions, the RV, which is ill suited to provide long-term systemic perfusion, is prone to eventual failure. In the absence of satisfying curative treatments, stem cell therapy may represent one innovative approach to the management of RV dysfunction in HLHS patients. Several stem cell populations from different tissues (cardiac and non-cardiac), different age groups (adult- vs. neonate-derived), and different donors (autologous vs. allogeneic), are under active investigation. Preclinical trials in small and large animal models have elucidated several mechanisms by which these stem cells affect the injured myocardium, and are driving the shift from a paradigm based upon cellular engraftment and differentiation to one based primarily on paracrine effects. Recent studies have comprehensively evaluated the individual components of the stem cells' secretomes, shedding new light on the intracellular and extracellular pathways at the center of their therapeutic effects. This research has laid the groundwork for clinical application, and there are now several trials of stem cell therapies in pediatric populations that will provide important insights into the value of this therapeutic strategy in the management of HLHS and other forms of CHD. This article reviews the many stem cell types applied to CHD, their preclinical investigation and the mechanisms by which they might affect RV dysfunction in HLHS patients, and finally, the completed and ongoing clinical trials of stem cell therapy in patients with CHD.

Project description:Background The impact of neighborhood socioeconomic status (SES) on outcomes following first-stage palliation of single ventricle heart disease remains incompletely characterized. Methods and Results This was a single-center, retrospective review of consecutive patients who underwent the Norwood procedure from January 1, 1997 to November 11, 2017. Outcomes of interest included in-hospital (early) mortality or transplant, postoperative hospital length-of-stay, inpatient cost, and postdischarge (late) mortality or transplant. The primary exposure was neighborhood SES, assessed using a composite score derived from 6 US census-block group measures related to wealth, income, education, and occupation. Associations between SES and outcomes were assessed using logistic regression, generalized linear, or Cox proportional hazards models, adjusting for baseline patient-related risk factors. Of 478 patients, there were 62 (13.0%) early deaths or transplants. Among 416 transplant-free survivors at hospital discharge, median postoperative hospital length-of-stay and cost were 24 (interquartile range, 15-43) days and $295 000 (interquartile range, $193 000-$563 000), respectively. There were 97 (23.3%) late deaths or transplants. On multivariable analysis, patients in the lowest SES tertile had greater risk of early mortality or transplant (odds ratio [OR], 4.3 [95% CI, 2.0-9.4; P<0.001]), had longer hospitalizations (coefficient 0.4 [95% CI, 0.2-0.5; P<0.001]), incurred higher costs (coefficient 0.5 [95% CI, 0.3-0.7; P<0.001]), and had greater risk of late mortality or transplant (hazard ratio, 2.2 [95% CI, 1.3-3.7; P=0.004]), compared with those in the highest tertile. The risk of late mortality was partially attenuated with successful completion of home monitoring programs. Conclusions Lower neighborhood SES is associated with worse transplant-free survival following the Norwood operation. This risk persists throughout the first decade of life and may be mitigated with successful completion of interstage surveillance programs.

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Impact of Maternal-Fetal Environment on Mortality in Children With Single Ventricle Heart Disease.

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