Historically, pre-eclampsia was defined as proteinuric gestational hypertension or that superimposed on chronic hypertension. The 2021 International Society for the Study of Hypertension in Pregnancy (ISSHP) guidelines updated the broad definition of pre-eclampsia 1. One controversy has been whether women with chronic hypertension whose pregnancies are complicated by fetal growth restriction (FGR) fulfil a clinically relevant definition of pre-eclampsia or whether FGR is solely a complication of chronic hypertension, based on the shared pathophysiology of placental dysfunction. Therefore, we examined Control of Hypertension in Pregnancy Study (CHIPS) trial data 2 to determine whether or not including pregnant women living with chronic hypertension whose pregnancies are complicated by small-for-gestational age (SGA) infants is at increased risk of adverse perinatal and, in particular, maternal events, compared with women with chronic hypertension who give birth to babies with birthweights at or above the 10th percentile for gestational age. This was a secondary analysis limited to those women with chronic hypertension who participated in the international CHIPS trial in which randomisation was stratified by type of hypertension 2. Women were included if they had non-severe, non-proteinuric pre-existing/chronic hypertension; a diastolic blood pressure (dBP) of 90–105 mmHg if they were not receiving antihypertensive therapy, or 85–105 mmHg if they were receiving such treatment; and a live singleton fetus at 14+0 weeks to 33+6 weeks of gestation (determined in most cases by early pregnancy ultrasound examination). Chronic hypertension was defined as dBP ≥ 90 mmHg before pregnancy or at < 20+0 weeks' gestation. Women were randomised to ‘tight’ (target dBP = 85 mmHg) versus ‘less tight’ (target dBP = 100 mmHg) control. To be conservative, infants who were SGA, defined as birthweight < 10th percentile for sex and gestational age 3, were selected as a surrogate for FGR, recognising that ≈50% of SGA infants are growth-restricted due to placental dysfunction 4. We compared the rates of the CHIPS trial outcomes between women who gave birth to infants who were SGA, compared with those with birthweights ≥ 10th percentile, using logistic regression, with adjustment for maternal age, parity, group allocation in CHIPS and CHIPS adjustment factors (see Table footnote). A p < 0.05 was considered statistical significance (SAS 9.4, SAS Institute Inc., Cary, NC). No adjustment was made for multiple comparisons. 987 women participated in the CHIPS trial, of whom 727 women had chronic hypertension and known birthweights and gestational age at birth; 122/727 (16.8%) gave birth to SGA infants (Table 1). Recruited women were generally in their 30s, parous and recruited during the second trimester. About two-thirds were on antihypertensive at randomisation, with 15% having had prior severe hypertension in the index pregnancy. 5%–6% had gestational diabetes. Women who gave birth to SGA infants were slightly older, less frequently overweight or obese and more frequently randomised to ‘tight’ control (Table 1). Women with chronic hypertension complicated by SGA (vs those without SGA) experienced significantly more often: episodes of severe hypertension; maternal manifestations of pre-eclampsia, including new proteinuria (with all definitions provided in the Table footnotes); and preterm birth (< 34+0 or < 37+0 weeks), receipt of high-level neonatal care ≥ 48 h, or pregnancy loss or receipt of high-level neonatal care ≥ 48 h. (N = 112 liveborns) 63/112 (50.8) (N = 600 liveborns) 134/600 (22.3) That adverse perinatal events were more common among women with chronic hypertension who gave birth to SGA infants was unsurprising, but these women were also more likely to develop maternal manifestations of pre-eclampsia, including severe maternal hypertension, a surrogate for stroke risk 5. Data from this secondary analysis of the CHIPS trial support inclusion of FGR as a diagnostic criterion for pre-eclampsia in women whose pregnancies are complicated by chronic hypertension to highlight the need for maternal surveillance 1. P.v.D. and L.A.M. developed the question. T.L., with supervision by J.S., undertook the analyses. All authors contributed to writing the manuscript. This work was supported by Canadian Institutes of Health Research (grant number: MCT 87522). The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Dadelszen et al. (Wed,) studied this question.