Fetal growth and parental cardiovascular risk: preterm birth matters.

Abstract

It is now well established, but poorly understood, that preterm birth marks an excess cardiovascular risk among mothers. The study by Morken et al. (BJOG 2018;336–41) provides new and important insights into these links by integrating preterm birth and fetal growth abnormalities as metrics of long-term parental cardiovascular disease (CVD) mortality risk. They report that both small and large infants delivered preterm are linked to excess maternal CVD risk, but these features are only weakly associated with paternal CVD. In contrast, growth-restricted (but not macrosomic) births delivered at term are associated with higher maternal CVD risk. Surprisingly, overgrowth among term births in this Norwegian cohort of more than 700 000 mothers and fathers followed for up to 42 years was unrelated to parental cardiovascular risk. There are several important observations that this study contributes. First, infant birthweight confers ten times higher CVD risk in mothers relative to fathers. This evidence makes a compelling case that the maternal associations are biological whereas the paternal associations may quantify the proportion of risk that is due to shared lifestyle features. Second, the authors empirically confirm two critical inflections in the risk trajectory relating infant characteristics to parental long-term health. Maternal CVD risk increased monotonically as birthweight decreased, but only up to 3500 g, the average birthweight for a healthy term infant. In addition, although small infant birthweight was related to excess maternal risk regardless of gestational age, overgrowth was related to maternal risk only among women delivering preterm. The authors note that the magnitude of risk associated with overgrowth of preterm infants is surprising. Indeed, studies that have focused exclusively on absolute birthweight distort these associations by not considering the concomitant contribution of preterm birth. It is worth noting that an earlier paper from this group reported more than a decade ago that there was excess overgrowth among preterm infants (Morken et al. Am J Obstet Gynecol 2006;195:154–61). Now, these data are extended to report that this unexpected fetal overgrowth pattern (z-score > 2.5) among preterm infants is related to a three-fold excess risk of maternal cardiovascular mortality. The authors note that these patterns can help to identify groups of women at delivery who may be predisposed to a high-risk trajectory leading to early CVD death. The potential impact of their findings is actually larger. Preterm birth is known to be a heterogeneous condition, with multiple pathways converging to a final, common endpoint of early delivery. Adjoining gestational age at delivery with fetal growth abnormalities may help to disentangle subtypes that mark distinct CVD trajectories. Could the preterm births with growth restriction be related to endothelial dysfunction and vascular abnormalities, whereas the preterm births with overgrowth be more strongly related to metabolic abnormalities and inflammation? These possibilities warrant further exploration as we seek to understanding the intractable public health crisis of prematurity, as well as the long-term sequelae for mothers and their children. In addition, this evidence may help interrupt the intergenerational contribution to prematurity and fetal growth abnormalities, and thus have important public health consequences. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.