Association between hypertensive disorders and fetal growth restriction in twin compared with singleton gestations

Hypertensive disorders of pregnancy (including preeclampsia or gestational hypertension) are associated with fetal growth restriction in singleton pregnancies, an association that may be attributed to abnormal placentation as the shared etiology between these conditions. Given that the pathogenesis of these conditions in twin pregnancies may involve mechanisms other than abnormal placentation, it is unclear whether a similar association between hypertensive disorders of pregnancy and fetal growth restriction is present in twins. Data on the relationship between hypertensive disorders of pregnancy and fetal growth restriction in twins are limited and conflicting. This controversy may be attributed to limitations of existing studies including the use of a singleton-based birthweight reference to define fetal growth restriction in twins and the lack of a positive control group of singleton gestations.

The objective of the study was to determine the association between hypertensive disorders of pregnancy and fetal growth restriction in dichorionic twin gestations, using both a singleton- and a twin-based birthweight reference, and to compare this association with that observed in singleton gestations.

We performed a retrospective cohort study of all women with dichorionic twin or singleton gestations giving birth in a single tertiary center during 2003-2015. Fetal growth restriction was defined in separate analyses as birthweight <10th percentile for gestational age using either a singleton- or a twin-based birthweight reference. The association between hypertensive disorders of pregnancy and fetal growth restriction was determined separately for twin and singleton gestations and was expressed as adjusted relative risk with 95% confidence interval.

A total of 1520 twin and 48,943 singleton gestations were included. In singleton gestations, hypertensive disorders of pregnancy were associated with an increased risk of fetal growth restriction (16.6% vs 7.4%, adjusted relative risk, 2.07, 95% confidence interval, 1.87-2.30). In twins, there was no association between hypertensive disorders of pregnancy and fetal growth restriction when a singleton-based reference was used to define fetal growth restriction. However, when using a twin-based reference to define fetal growth restriction, hypertensive disorders of pregnancy in twin gestations were associated with a similar increase in the risk of fetal growth restriction to that seen in singletons (11.8% vs 4.7%, adjusted relative risk, 2.37, 95% confidence interval, 1.69-3.34). Findings were similar with regard to the reverse association between fetal growth restriction and hypertensive disorders of pregnancy: in women with twin gestations, the increase in the risk of hypertensive disorders of pregnancy in pregnancies complicated by fetal growth restriction of 1 twin was similar to that observed in singletons only when a twin-based reference was used to define fetal growth restriction (twins: 21.3% vs 9.8%, adjusted relative risk, 2.15, 95% confidence interval, 1.63-3.06; singletons: 8.8% vs 3.7%, adjusted relative risk, 2.19, 95% confidence interval, 1.95-2.44).

The association between hypertensive disorders of pregnancy and fetal growth restriction in dichorionic twins is similar in magnitude to that observed in singletons so long as appropriate birthweight references are applied. Therefore, women with a twin gestation complicated by one of these conditions should be closely monitored for the other. Our findings suggest that the use of a twin-based reference to diagnose fetal growth restriction in twin gestations may be more informative and clinically relevant than using a singleton-based reference.