Low soluble Fms-like tyrosine kinase (sFlt-1) has been reported in women with suspected or confirmed preeclampsia (PE) coincidentally using proton pump inhibitors (PPIs), suggesting a role for these agents as potential treatment for PE. Here, we examined whether administration of omeprazole to women with PE could acutely reduce their circulating levels of sFlt-1 or enhance their placental growth factor (PlGF) concentrations. We performed a randomized controlled trial in which women (≥ 18 years) with confirmed preeclampsia and a gestational age between 20
+0
and 34
+6
weeks were allocated to receive 40mg omeprazole once daily or no omeprazole. Blood was collected at baseline and days 1,2,4,8 followed by twice-weekly until delivery. Primary outcome was specified as the difference in sFlt-1 or PlGF 4 days after omeprazole initiation compared to the non-omeprazole group. Secondary outcomes were defined as between-group differences in longitudinal course of sFlt-1 and PlGF and pregnancy outcomes. Between Dec 2018 and June 2021, 50 women with PE were randomized, of which 40 women remained pregnant after 4 days. Mean maternal age was 30 years, and median gestational age was 31 weeks. Baseline sFlt-1 levels did not differ between non-omeprazole (n=20) and omeprazole group (n=20) (10743 vs. 7110pg/mL, p=0.11), neither did the levels of PlGF (p=0.14). After 4 days, sFlt-1 levels remained similar in women receiving omeprazole compared to women not receiving omeprazole (8364 vs. 13017pg/mL, p=0.14), and the same was true for PlGF (90 vs. 55pg/mL, p=0.14). Using linear mixed models, no difference in longitudinal course of sFlt-1 or PlGF could be attributed to the treatment group, when adjusted for baseline values and GA at enrollment (p=0.47). Women receiving omeprazole had a similar length of pregnancy compared with those not receiving this drug (median 15 vs. 14 days, p=0.70). Except for a higher neonatal intubation rate in the non-omeprazole group (31% vs 4%, p=0.02) there were no differences in maternal/perinatal complications between the two groups. Our findings suggest that daily administration of 40mg in women with PE do not alter their circulating levels of sFlt-1 and PlGF, arguing against a role for this drug as a potential treatment for this syndrome.
Prediction of small-for-gestational-age neonates: screening by placental growth factor and soluble fms-like tyrosine kinase-1 at 35-37 weeks
