LAUSR

We read with interest the paper by Änghagen et al. [1] describing the evolution of echocardiographic parameters during the first 3 months in neonates with intrauterine growth restriction (IUGR). IUGR was associated with a blunted increase in left ventricular longitudinal strain (LVLS) during the first months of extrauterine life compared to healthy controls. The authors should be commended for undertaking this longitudinal study, which contributes to our understanding of the mechanisms by which prenatal risk factors might alter postnatal cardiac development. Ever since the formulation of the Barker hypothesis, the intrauterine environment has been considered an important determinant of overall health later in life [2]. More recently, it has become clear that factors affecting the duration or nature of intrauterine life can affect cardiac structure and function from birth to adulthood [3–6]. These factors, including small for gestational age (SGA), IUGR, preeclampsia, and gestational diabetes, are often collectively referred to as “impaired maternal–fetal environment (MFE).” In the congenital heart disease (CHD) community, impaired MFE has received increasing attention as it has been associated with worse postoperative survival in neonates with critical CHD in a number of studies [7–9]. The large hazard ratios identified in these studies—ranging from 1.5 to 8—suggest that these factors may lead to considerable net reclassification benefit when incorporated into contemporary risk stratification systems. The above risk factors often coincide in a single individual, as illustrated by the lower mean gestational age and birth weight in the IUGR group in the article by Änghagen et al. [1]. The authors acknowledge the difficulties of separating the effects of IUGR from those of other prenatal factors, especially because mediation could not be excluded in their analyses. However, some recent publications have demonstrated that sophisticated statistical models based on inverse probability weighting [10] or mediation analysis [9] may provide a more definitive answer. These studies have estimated that only part of the relationship between prenatal factors and mortality is mediated by gestational age. The study by Änghagen et al. [1] has provided incremental evidence that IUGR is a prenatal risk factor worthwhile of further investigation. It also underscores the unmet need for more longitudinal data to establish long-term effects of IUGR on cardiac phenotype and outcomes later in life. As we will gain more insight into the role of prenatal factors in cardiovascular disease progression, targeted screening and prevention strategies incorporating prenatal information should eventually find their way into clinical practice.