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Symptoms of gastroesophageal reflux disease (GERD) occur in 40-85% of pregnancies. Due to its negative impact on quality of life, adequate treatment is indicated. However, medications to treat GERD have not been tested rigorously in pregnant women. This project aims to increase knowledge on benefits, particularly prevention of gestational hypertension and preeclampsia, and risks of calcium-based antacids during pregnancy. The results may lead to more evidence-based decisions on the treatment of GERD in pregnancy.



Low-dose calcium-supplementation seems to be effective in preventing hypertensive disorders of pregnancy; calcium-based antacids may exert similar effects. As prenatal use of acid-suppressive medication was recently suggested to increase the risk of asthma and allergy in offspring, however, potential risks should also be determined.



Prospective cohort study with already collected data.



More than 12,000 Dutch pregnant women enrolled in the PRIDE Study and pREGnant in 2011-2018, who completed Web-based questionnaires at multiple time points during and after pregnancy, providing detailed data on exposures, outcomes, and potential confounders.



Calcium-based antacids, based on unsupervised clustering using the k-means method to model exposure status, corresponding to the real-world situation.



Primary: diagnosis of gestational hypertension and preeclampsia.

Secondary: preterm birth, low birth weight, small and large-for gestational age, Ponderal index, and infant respiratory conditions and reflux.



Based on Directed Acyclic Graphs the most appropriate methods for confounding control will be applied. Modified Poisson models and multivariable log-binomial regression analyses will be used to estimate adjusted relative risks. With outcome prevalences >3.0%, we will have sufficient power to answer our research questions, even for the smallest exposure cluster.

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