Growth in Congenital Heart Disease: Outcome or Predictor?

A ccording to the Greek historian Plutarch, small, deformed, or ill-appearing newborns, deemed by the elders to be unfit for development into strong Spartan warriors, were abandoned in Apothetae. Although we would like to think that our current evaluation of a neonate’s fate is not only more humane, but also more nuanced than the methods of the Gerousia of Sparta, the current approach of assessing comorbid risk for infants undergoing congenital heart disease (CHD) surgery remains blunt. Specifically, the risk classification of children with CHD based solely on their birth weight or gestational age ignores the heterogeneity in the pathophysiological characteristics of the in utero environment, early development, and subsequent outcomes within these populations. In the era of personalized medicine, premature and small neonates should not be considered a homogeneous high-risk category. Although prematurity (<37 weeks’ gestation) and low birth weight (<2.5 kg) increase risk on a population basis, the individual preterm or small infant may actually do well. Extrapolating risk from the outcomes of a diverse cohort to an individual is unreliable and potentially misleading, whether it be for counseling a family or discovering novel interventions to improve outcomes. Better understanding the pathophysiological characteristics underlying earlier birth and lower birth weights in CHD will drive more precise risk assessment for counseling, and will expand our knowledge surrounding the impact of early life events and environment on disease and disease progression. At the crux of our current knowledge gap is whether somatic growth in CHD is the manifestation of a more complicated course and, therefore, should be considered an outcome, or is a reflection of intrinsic genetic, cardiovascular, and placental factors and should, therefore, be considered a predictor of risk. Considering first birth anthropometry, it is important to recognize that low birth weight, small for gestational age (SGA), and intrauterine growth restriction are distinct entities. Low birth weight refers to a cut point based solely on weight, irrespective of whether that weight is appropriate for gestational age or growth potential. Although SGA takes into account gestational age and sex, it is based on a distribution of a normative population with a distinct cut point at the 10th percentile, and does not account for an individual’s or population’s growth potential. Intrauterine growth restriction is conceptually straightforward but difficult to delineate clinically because it refers to an in utero environment that leads to a fetus failing to meet its growth potential; the complexity is in assessing “potential.” Defining intrauterine growth restriction is even more perplexing in the population with CHD because growth potential may be debated, given the well-described lesion-specific differences in birth weight. Steurer and colleagues, in this issue of the Journal of the American Heart Association (JAHA), provide further evidence that CHD lesions are associated with lower birth weight for gestational age. In their cohort of almost 7000 infants with critical CHD in the state of California, >16% were SGA. Which of those individuals were growth restricted, however, is unknown. Their cohort included multiple Risk Adjustment for Congenital Heart Surgery categories, and it is possible that if they filtered for higher-risk lesions, the SGA percentage would be even greater. In a single institution cohort limited to infants requiring surgery before 60 days of age, the rate of SGA was 23% and was associated with an increased risk of 30-day postoperative mortality. Further narrowing down a cohort to single-ventricle heart disease, a 41% incidence of SGAwas reported for patients enrolled in the Pediatric Heart Network SVR (Single Ventricle Reconstruction) Trial. In the California cohort, being born SGA was associated with a higher incidence of oligohydramnios, preeclampsia, and an underweight maternal body mass index, suggesting SGA birth may be the result of a more complex fetal course and, therefore, should be considered an outcome. But if a large percentage of SGA neonates had no maternal comorbidity, it is possible many attained an appropriate, albeit lower, growth potential, thereby making birth anthropometry simply a marker of risk; this possibility is supported by the known The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the Department of Pediatrics, University of Utah, Salt Lake City, UT. Correspondence to: Thomas A. Miller, DO, University of Utah, 81 N Mario Capecchi Dr, Salt Lake City, UT 84113. E-mail: thomas.a.miller@hsc.utah.edu J Am Heart Assoc. 2018;7:e010262. DOI: 10.1161/JAHA.118.010262. a 2018 The Author. Published on behalf of the American Heart Association, Inc., by Wiley. 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