Placental and Fetal In Utero Growth Among Fetuses With Congenital Heart Disease

Abstract

Importance: At birth, neonates with congenital heart disease (CHD) have smaller placentas, lower birth weight, and smaller head circumferences compared with healthy neonates. The onset of feto-placental growth disturbances, however, is not well known.

Objective: To compare fetal body volumes, assess differences in the fetal to placental volume ratios (placental growth relative to the fetus), and investigate the association between in utero fetal body and total brain volume in fetuses with and without CHD.

Design, setting, and participants: This case-control study enrolled pregnant women with a fetal diagnosis of CHD and those with healthy pregnancies at Children's National Hospital in Washington, DC, from April 2018 to July 2023. Fetal magnetic resonance imaging was obtained up to 2 time points during pregnancy. The fetal to placental ratio was calculated using 3-dimensional magnetic resonance image fetal body volumes and placental volumes.

Exposure: In utero environment CHD.

Main outcomes and measures: The main outcomes were the trajectories of body, brain, and placental volumetric growth in fetuses with CHD and in control fetuses. Generalized linear regression and mixed-effects models were applied to identify associations for fetal body volume and fetal to placental volume ratios between CHD and control groups adjusting for fetal sex and gestational age at the time of the magnetic resonance imaging scan.

Results: The study included 108 fetuses (59 male [54.6%]), of which 55 were in the healthy control group (with 55 scans), and 53 had CHD (with 77 scans). Fetal body volumes in fetuses with CHD were smaller compared with control fetuses (β = -193.60 [SE, 44.42]; P < .001) with larger fetal to placental volume ratios (β = 0.23 [SE, 0.10]; P = .02). The total brain volume was smaller in fetuses with CHD compared with control fetuses (β = -10.87 [SE, 5.09]; P = .04).

Conclusions and relevance: In this case-control study of fetuses with and without CHD, those with CHD demonstrated impaired fetal body growth with higher fetal to placental volume ratios and smaller total brain volume, suggesting that placental failure was associated with growth disturbances in CHD, as demonstrated by the large fetal to placental volume ratios. Additional studies should assess the onset and progression of placental dysfunction and how the timing of placental failure may contribute to neurodevelopmental disability in survivors of CHD.

Figure.. Scatterplots of the Association of Unadjusted (Raw) Placental Volumes, Fetal Body Volumes, Total Brain Volumes, and Fetal Body to Placental Volume Ratios With Congenital Heart Disease (CHD) vs Control Groups Across Gestational Age

Solid curves indicate placental volumes, fetal body volumes, total brain volumes, and fetal body to placental volume ratios across gestation for the control group (blue) and the CHD group (orange).