Fetal Major Cardiac Defects and Placental Dysfunction at 11-13 Weeks' Gestation

Major congenital heart defects (CHDs) are those that require invasive interventions within the first year following birth and are often associated with fetal growth restriction (FGR). A recent study on isolated major CHDs found evidence of impaired placental angiogenesis in the absence of impaired placental perfusion and function in pregnancies with fetal CHD. This prospective screening study aimed to investigate the relationship between major fetal CHDs and markers of placental perfusion and function in singleton pregnancies at 11 to 13 weeks' gestation. Data were obtained from screening for adverse prenatal outcomes during routine pregnancy care visits between March 2006 and October 2015 at King's College Hospital and Medway Maritime Hospital, United Kingdom. Measurements recorded during these visits included uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein A (PAPP-A), and placental growth factor (PlGF), whichwere used to calculate multiples of the normal median (MoM). MedianMoMvalues of biomarkerswere then compared between outcome groups. All cases with major fetal CHDs diagnosed by cardiologists in the neonatal period or those diagnosed prenatally that resulted in termination of pregnancy and miscarriage at less than 24 weeks or stillbirth at more than 24 weeks were included. Major CHDs were subdivided into 3 categories: conotruncal cardiac defects, left ventricular outflow tract defects, and valvular defects. The total study cohort included 50,094 pregnancies of which 196 (0.4%) had major congenital cardiac defects. Of the 196 pregnancies with major CHDs, 73 (37.2%) had conotruncal defects, 63 (32.1%) had left ventricular outflow tract defects, and 60 (30.6%) had valvular abnormalities. Compared with the control group, the cardiac defect group was found to have lower median PAPP-A MoM (0.81 vs 1.00, P < 0.0001) and PlGF MoM (0.78 vs 1.00, P < 0.0001) but no significant difference in UtA-PI MoM(1.01 vs 1.00, P = 0.162). A significant association was found in the cardiac defect group between PIGF MoM and delta fetal nuchal translucency (NT); this difference was not present in the control group. Compared with the control group, the cardiac defect group had increased fetal NT and in those with high NT, serum PlGF was lower than in those with normal NT. This study found that in pregnancies with major fetal CHDs, serum PAPP-A, and PlGF are significantly lower compared with pregnancies with normal fetal cardiac anatomy. The results also show no significant difference in UtA-PI between the 2 groups. These findings are in accord with previously published literature and suggest that in the presence of major fetal CHDs, there is evidence of placental dysfunction without impairment of placental perfusion.