Gestational Age, Birth Weight, and Outcomes Six Years After the Norwood Procedure

Abstract

Background: Preterm delivery and low birth weight (LBW) are generally associated with worse outcomes in hypoplastic left heart syndrome (HLHS), but an individual preterm or small neonate may do well. We sought to explore the interactions between gestational age, birth weight, and birth weight for gestational age with intermediate outcomes in HLHS.

Methods: We analyzed survival, growth, neurodevelopment, length of stay, and complications to age 6 years in subjects with HLHS from the Single Ventricle Reconstruction trial. Univariate and multivariable survival and regression analyses examined the effects and interactions of LBW (<2500 g), weight for gestational age, and gestational age category.

Results: Early-term delivery (n = 234) was more common than term (n = 219) delivery. Small for gestational age (SGA) was present in 41% of subjects, but only 14% had LBW. Preterm, compared with term, delivery was associated with an increased risk of death or transplant at age 6 years (all: hazard ratio = 2.58, confidence interval = 1.43-4.67; Norwood survivors: hazard ratio = 1.96, confidence interval = 1.10-3.49) independent of LBW and weight for gestational age. Preterm delivery, early-term delivery, LBW, and SGA were each associated with lower weight at 6 years. Neurodevelopmental outcomes were worst in the LBW cohort.

Conclusions: Preterm delivery in HLHS was associated with worse survival, even beyond Norwood hospitalization. LBW, SGA, and early-term delivery were associated with worse growth but not survival. LBW was associated with worse neurodevelopment, despite similar length of stay and complications. These data suggest that preterm birth and LBW (although often concomitant) are not equivalent, impacting clinical outcomes through mechanisms independent of perioperative course complexity.

Trial registration: ClinicalTrials.gov NCT00115934.

Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Copyright © 2019 by the American Academy of Pediatrics.

Figures

FIGURE 1

Cohort distribution. Number of subjects (n = 537) in each gestational age and birth weight category are shown according to sex (A). aLate-term delivery and LGA infants were excluded from analyses because of the small numbers. Intersection of gestational age category with LBW and SGA, in the cohort excluding LGA and late-term infants (n = 509), demonstrated all individuals who were categorized as LBW were also SGA, but not all SGA were LBW. There were LBW and SGA individuals distributed across all gestational age categories (B).

FIGURE 2

Transplant-free survival. Freedom from transplant or death is shown from enrollment to 6 years for the entire cohort (A) and from Norwood discharge to 6 years for those who survived to Norwood discharge (B).

FIGURE 3

Growth. Weight- and length-for-age z scores at age 6 years are plotted by gestational age and birth weight (mean ± SD). * P ≤ .05, compared with reference group for male and female combined.

FIGURE 4

Neurodevelopmental outcomes. Vineland-II subdomain scores (mean ± SD) are shown for each gestational age and birth weight category (A). From the many significant subdomain interactions in Table 2, 1 example of a significant interaction in the BASC Adaptive Skills composite score (mean ± SD) between birth weight and sex is shown (B). * P ≤ .05, compared with reference group.

FIGURE 5

LOS and complications. LOS distribution for those that survived to hospital discharge after the Norwood (blue), stage II (red), and Fontan (green) surgeries (A). Outliers with hospital stay >130 days were not included in the graph. The mean (yellow diamond), median (bar), and distribution for the number of complications for survivors up to Norwood discharge (blue) and from Norwood discharge to 6 years (red) are shown (B). * P ≤ .05, compared with reference group, with Cox competing risk for the LOS and Wilcoxon rank test for complications.