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.