Systematic review with meta-analysis: the risks of proton pump inhibitors during pregnancy.
Abnormalities, Drug-Induced
/ epidemiology
Case-Control Studies
Cohort Studies
Congenital Abnormalities
/ epidemiology
Female
Heartburn
/ drug therapy
Histamine H2 Antagonists
/ adverse effects
Humans
Infant, Low Birth Weight
Infant, Newborn
Infant, Small for Gestational Age
Male
Pregnancy
Pregnancy Complications
/ drug therapy
Pregnancy Outcome
/ epidemiology
Premature Birth
/ epidemiology
Proton Pump Inhibitors
/ adverse effects
Risk Factors
Stillbirth
/ epidemiology
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
18
09
2019
revised:
14
10
2019
accepted:
23
11
2019
pubmed:
8
1
2020
medline:
29
8
2020
entrez:
8
1
2020
Statut:
ppublish
Résumé
There have been safety concerns considering long-term proton pump inhibitor (PPI) use, also during pregnancy. To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta-analysis. The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting ≥1 adverse pregnancy outcome comparing PPI users to non-users. Histamine-2 receptor antagonists (H2RA) were also compared to both non-users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random-effects modelling. PROSPERO study-protocol: CRD42018103320. In total, 26 observational studies (20 cohort, 6 case-control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR 1.28, 95% CI 1.09-1.52), especially in case-control studies (OR 2.04, 1.46-2.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low-birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02-1.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies. This meta-analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.
Sections du résumé
BACKGROUND
There have been safety concerns considering long-term proton pump inhibitor (PPI) use, also during pregnancy.
AIMS
To assess the risk of adverse neonatal outcomes associated with maternal intake of PPIs by means of systematic review and meta-analysis.
METHODS
The systematic search included PubMed, Web of Science, Cochrane Database and Embase (inception until June 2019). All studies reporting ≥1 adverse pregnancy outcome comparing PPI users to non-users. Histamine-2 receptor antagonists (H2RA) were also compared to both non-users and PPI users. Outcomes included congenital malformations, abortion, stillbirth, neonatal death, preterm birth, small for gestational age and low birth weight. Pooled odds ratios (OR) and 95% confidence intervals (CI) were obtained by random-effects modelling. PROSPERO study-protocol: CRD42018103320.
RESULTS
In total, 26 observational studies (20 cohort, 6 case-control studies) were identified, of which 19 assessed PPIs and 12 H2RA. PPI use was associated with an increased risk of congenital malformations (OR 1.28, 95% CI 1.09-1.52), especially in case-control studies (OR 2.04, 1.46-2.86). No associations were found between H2RA and congenital malformations. No significant associations were found between PPI use and abortions, stillbirth, neonatal death, preterm birth and low-birth weight, although H2RA use may be associated with an increased risk of preterm birth (OR 1.25, 95% CI 1.02-1.56). Although statistical heterogeneity and the risk of bias were overall low, clinical heterogeneity, information and selection bias may be present in the individual studies.
CONCLUSIONS
This meta-analysis suggests an association between maternal PPI use and congenital malformations in humans, yet power was insufficient to assess specific malformations and drugs.
Substances chimiques
Histamine H2 Antagonists
0
Proton Pump Inhibitors
0
Types de publication
Journal Article
Meta-Analysis
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
410-420Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 John Wiley & Sons Ltd.
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