In women with chronic hypertension, does fetal growth restriction increase progression to maternal preeclampsia?

Objectives

Among women with chronic hypertension, it is unclear whether uteroplacental dysfunction should be classified as indicating superimposed preeclampsia, or be considered direct complications of chronic hypertension.

Study design

We undertook a secondary analysis of a prospectively-evaluated cohort of women with chronic hypertension and singleton pregnancies, who underwent routine fetal ultrasound at 35+0-36+6 weeks’ gestation. We compared the incidence of preeclampsia and other adverse pregnancy outcomes, between cases and propensity score-matched (PSM) controls; cases had estimated fetal weight (EFW) <10th percentile, with and without fetal growth restriction (FGR), defined as abnormal fetal Dopplers (uterine artery pulsatility index [PI] >95th centile, umbilical artery PI >95th centile, or middle cerebral artery PI <5th centile), and controls had EFW ≥10th percentile. Superimposed preeclampsia was defined by maternal criteria, either traditionally by development of new-onset proteinuria at ≥20 weeks’, or by additional maternal criteria, by 2019 American College of Obstetricians and Gynecologists or 2021 International Society for the Study of Hypertension in Pregnancy guidance. Covariates included in PSM were: maternal race/ethnicity, mode of conception, smoking status, systemic lupus erythematosus, parity, history of preeclampsia, history of a baby with birthweight <10th centile, maternal age, body mass index, and gestational weight gain (kg). Matching was conducted using: a nearest-neighbor algorithm without replacement, a ratio of one case to two controls, and a caliper width of 0.2 SD of the logit of the propensity score. Balance between groups after matching was assessed using standardised mean differences, with values <0.1 considered indicative of adequate balance.

Results

Of 1258 included pregnancies with chronic hypertension, there were 167 (13.3%) cases (64, 38.3% designated as FGR cases with abnormal fetal Dopplers), and 1091 (86.7%) controls. 234/1258 (18.6%) women went on to develop preeclampsia. After PSM analysis, there were no differences between the 167 cases and 334 PSM controls in baseline maternal or 35-36 weeks’ characteristics. Cases with FGR (vs. PSM controls) more often: developed preeclampsia (regardless of definition), underwent labour induction, had Caesarean birth, and had a shorter ultrasound-to-birth interval by 1.8 weeks; they also delivered 1.7 weeks earlier, and more often had babies with birthweight <10th percentile for gestational age, or those admitted to the neonatal unit. There was no difference between groups in the composite neonatal outcome. Cases without FGR (vs. PSM controls) did not differ with regards to development of preeclampsia, but they did have a shorter ultrasound-to-birth interval (by 0.8 weeks), delivered 0.7 weeks earlier, and more often had babies with birthweight <10th percentile.

Conclusions

Our findings suggest that women with chronic hypertension who have evidence of FGR at 35-36 weeks’ gestation (but not those with only EFW <10th percentile) more frequently develop maternal manifestations of superimposed preeclampsia, and should be considered for enhanced maternal and fetal surveillance. These findings should be replicated at earlier gestational ages.