Defining early vs late fetal growth restriction by placental pathology

Although early and late fetal growth restriction have been suggested to be distinct entities, the optimal gestational age cut-off that differentiates the two conditions is currently unclear and has been arbitrarily set in previous studies between 32 and 37 weeks. We aimed to use placental pathology findings to determine that optimal gestational age cut-off between early and late fetal growth restriction.

A retrospective cohort study of all women with singleton gestation who gave birth to a neonate diagnosed as small-for-gestational age (small-for-gestational age, defined as birthweight <10th percentile for gestational age) at a tertiary referral center between January 2001 and December 2015, and for whom placental pathology was available. Placental abnormalities were classified into lesions associated with maternal vascular malperfusion (MVM), fetal vascular malperfusion, placental hemorrhage and chronic villitis. Placental findings were analyzed as a function of gestational age at birth. The analysis was repeated in the subgroups of women without hypertensive complications of pregnancy (to reflect changes associated with isolated small-for-gestational age) and of neonates with severe small-for-gestational age (defined as birthweight <5th percentile), which are more likely to represent true fetal growth restriction.

A total of 895 women met the inclusion criteria. The only histological finding that changed with gestational age was MVM pathology, which decreased in frequency with increasing gestational age. We identified a considerable drop in the rate of MVM lesions at 33 weeks of gestation. The rate of MVM pathology in placentas of infants born before 33^0/7  weeks was significantly higher than that observed in placentas of infants born at 33^0/7  weeks or longer: 71.6% vs 27.4%, P < 0.001 for ≥2 MVM lesions, and 35.5% vs 3.5%, P < 0.001 for ≥3 MVM lesions. These findings persisted in the subgroups of women without hypertensive complications of pregnancy (n = 662) and of neonates with severe small-for-gestational age (n = 464).

Using placental pathology as a direct measure of the mechanisms underlying fetal growth restriction, the optimal gestational age at birth cut-off which differentiates early from late fetal growth restriction appears to be 33^0/7  weeks.