Isolated fetal neural tube defects associate with increased risk of placental pathology: evidence from the Collaborative Perinatal Project

Objective To compare placental pathology and fetal growth in pregnancies with an isolated fetal neural tube defect (NTD; cases) to those without congenital anomalies (controls). We hypothesised that cases would be at an increased risk of placental pathology and poorer anthropometric outcomes at birth compared to controls Methods We performed a matched case-cohort study using data from the Collaborative Perinatal Project. Cases (n=74) and controls (n=148) were matched (1:2 ratio) for maternal pre-pregnancy BMI, maternal race, infant sex, gestational age at birth and study site. Primary outcomes were placental characteristics (weight and size measurements, pathology). Secondary outcomes were infant birth outcomes. Subgroup analysis was done by type of NTD (spina bifida, anencephaly or encephalocele), infant sex, and preterm/term delivery. Data were analysed using adjusted generalized linear and nominal logistic regression models. Results are presented as adjusted β or adjusted odds ratio (aOR; 95% confidence interval). Results Cases had lower placental weight (β=-22.2 g [-37.8 – −6.6]), surface area (β=-9.6 cm 2 [-18.3 – −1.0]) and birth length z-scores (β=-0.4 [-0.7 – −0.001]) compared to controls. Cases were more likely to have a single umbilical artery (vs. two; 6 [8.1%] vs. 1 [0.7%]; aOR=301 [52.6 – 1726]), overall placental hypermaturity (9 [12.2%] vs. 5 [3.4%]; aOR=6.8 [3.1 – 14.7]), and many (vs. few) Hofbauer cells (9 [12.2%] vs. 7 [4.7%]; aOR=3.02 [1.2 – 7.3]), stromal fibrosis (9 [12.2%] vs. 10 [6.8%]; aOR=3.0 [1.4 – 6.3]) and pathological edema (11 [14.9%] vs. 12 [8.1%]; aOR=3.04 [1.4 – 6.7]) in placental terminal villi compared to controls. Placental pathology varied across NTD subtypes, infant sex, and preterms vs. term pregnancies. Conclusions Fetuses with isolated NTDs may be at increased risk of placental pathology, which could be contributing to poor fetal growth in these pregnancies and subsequent postnatal morbidities.