INTRODUCTION
Preeclampsia is a common pregnancy complication, affecting approximately 4.6% of pregnancies worldwide, with a wide variation across different regions.1 It is characterized by the new onset of hypertension and proteinuria after gestational week 20 and is one of the leading causes of maternal and perinatal morbidity and mortality.2-5 The only curative treatment is delivery, which emphasizes the need for preventive measures. A promising intervention seems to be calcium supplementation: in a meta-analysis, the risk of preeclampsia was decreased by more than 50% after both low-dose calcium supplementation (<1 g/day, risk ratio [RR] 0.38, 95% confidence interval [CI] 0.28-0.52; 9 trials) and high-dose calcium supplementation (≥1 g/day, RR 0.45, 95% CI 0.31-0.65; 13 trials) compared to placebo.6 In addition to calcium supplements, multivitamin-multimineral supplements, and nutritional intake, many over-the-counter antacids represent a substantial source of calcium with up to 680 mg of calcium carbonate per tablet. Antacids are used to treat symptoms of gastroesophageal reflux and are among the most commonly used medications during pregnancy, with prevalence estimates up to 37%.7,8 Whether using calcium-based antacids during pregnancy is associated with a decreased risk of preeclampsia, however, has not been studied yet.
If symptoms of gastroesophageal reflux persist, second-line treatment options include histamine-2 receptor antagonists (H2RA) and proton pump inhibitors (PPI). The latter are also hypothesized to have the potential for preventing preeclampsia by reducing the secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) from primary placental cells, placental tissue, and primary endothelial cells.9,10 The few epidemiologic studies on the association between PPIs and preeclampsia generally showed no decreased risks,11-13 with the exception of PPI use recorded after gestational week 28 in a study using data from the Swedish Pregnancy Register.11
Potential beneficial effects of gastroesophageal reflux medication during pregnancy on the risk of preeclampsia may influence the choice of treatment. However, the current level of knowledge is insufficient to make a fair benefit-risk assessment. Therefore, we aimed to determine the potential beneficial side effects of using calcium-based antacids and PPIs during pregnancy in the prevention of late-onset preeclampsia, taking dosage and timing of use into account.