Background: The placenta and heart develop concurrently and share developmental pathways, but the association between placental abnormalities and congenital heart disease (CHD) is not clear. This study seeks to understand the prevalence of placental abnormalities in mothers of fetuses with critical CHD and associated in utero ultrasound abnormalities.

Methods: Pregnant mothers of fetuses with critical CHD were prospectively enrolled to evaluate placental function by ultrasound and pathology. Maternal subjects underwent ultrasound evaluation of maternal uterine artery and fetal extracardiac Dopplers of the umbilical artery, umbilical vein, ductus venosus and middle cerebral artery, with calculations of pulsatility index (PI) Z-scores for gestation age (GA) as markers for vessel resistance. Placentas were analyzed by pathology postnatally. Fetal vascular malperfusion (FVM) was diagnosed in the presence of any of the following: intramural fibrin deposition, stem vessel obliteration, recent or remote thrombus formation, avascular villi, villous-stromal-vascular karyorrhexis; this was graded as low vs high per Amsterdam criteria. Maternal vascular malperfusion (MVM) was diagnosed by the presence of accelerated villous maturation, villous infarction, infarction hematoma, or decidual arteriopathy/vasculopathy. 

Results: Seventeen mothers and infants had complete data. Mean maternal age was 31 years. Seven (41%) had maternal conditions including two pre-gestational diabetes, four gestational diabetes, and one depression. Mean GA at ultrasound was 34 5/7 weeks (range 27 weeks to 38 5/7 weeks). Mean GA at birth was 39 weeks (range 37 weeks to 41 1/7 weeks) and mean birthweight was 3309 (± 476) grams. Cardiac diagnoses, placental pathology, and fetal ultrasound measures are categorized in the table.  All patients but one had placental perfusion defects, either MVM (82%), FVM (41%) or both. There was evidence of hypervascularity (chorangiosis, delayed villous maturation) in 11 (61%) and chronic inflammation in 4 (23%). Placental weight was small for GA in 6 (35%) and large for GA in 2 (12%). Maternal uterine PI Z-score was >2 (abnormal) in 2 mothers, umbilical artery PI Z-score was >2 in 7 (41%), and umbilical vein mean velocity Z-score was >2 in 5 (29%). Only 3 patients had abnormal ductus venosus absence/reversed diastolic flow and only 2 patients had abnormal middle cerebral artery Doppler PI Z-score.

Conclusions: Placental defects, including both maternal and fetal vascular malperfusion, are common in fetal CHD. While this cohort is limited by small sample size, it is notable that while abnormal maternal and fetal extracardiac Dopplers were observed, they do not match the degree of placental abnormalities seen in this cohort.  Further investigation in a larger cohort and more refined imaging modalities are needed to better assess placental function in this high-risk CHD population.