ArticleDrug safety2015
P-Glycoprotein-Mediated Drug Interactions in Pregnancy and Changes in the Risk of Congenital Anomalies: A Case-Reference Study.
Article in Drug safety, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- A systematic review of pregnancy-related clinical intervention of drug regimens due to pharmacokinetic reasons.Frontiers in medicine · 2023Pooled it
- Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review.Pediatrics · 2017Pooled it
- Placental transfer of third-generation antiepileptic drugs: in vivo lacosamide case study and in vitro investigation of transporter inhibition by lacosamide and perampanel.Journal of pharmaceutical health care and sciences · 2026Article
- Alterations in P-glycoprotein Expression in the Placenta of Obese Rats and Humans.International journal of molecular sciences · 2025Article
- Changed expression of placental transporters and disrupted epigenetic patterns in a rat model of schizophrenia.Frontiers in pharmacology · 2025Article
- Changes in Expression and Function of Placental and Intestinal P-gp and BCRP Transporters during Pregnancy.International journal of molecular sciences · 2023Review
- ABCB1 expression is increased in human first trimester placenta from pregnant women classified as overweight or obese.Scientific reports · 2023Article
- Inflammatory factor tumor necrosis factor-α (TNF-α) activates P-glycoprotein (P-gp) by phosphorylating c-Jun and thus promotes transportation in placental cells.Translational pediatrics · 2022Article
- ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection.Cellular and molecular life sciences : CMLS · 2022Review
- Functional role and regulation of permeability-glycoprotein (P-gp) in the fetal membrane during drug transportation.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Article
- Pregnancy and perinatal pharmacology: A paradigm shift is needed.Acta obstetricia et gynecologica Scandinavica · 2022Article
- Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes.Frontiers in pharmacology · 2022Article
- Using Pharmacogenetics of Direct Oral Anticoagulants to Predict Changes in Their Pharmacokinetics and the Risk of Adverse Drug Reactions.Biomedicines · 2021Review
- Chiral Transplacental Pharmacokinetics of Fexofenadine: Impact of P-Glycoprotein Inhibitor Fluoxetine Using the Human Placental Perfusion Model.Pharmaceutical research · 2021Article
- Placental transporter-mediated drug interactions and offspring congenital anomalies.British journal of clinical pharmacology · 2020Article
- Article
- Disease-Associated Changes in Drug Transporters May Impact the Pharmacokinetics and/or Toxicity of Drugs: A White Paper From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2018Article
- Discontinuation and dose adjustment of metoprolol after metoprolol-paroxetine/fluoxetine co-prescription in Dutch elderly.Pharmacoepidemiology and drug safety · 2018Article
- Placental control of drug delivery.Advanced drug delivery reviews · 2017Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDrug use in pregnancy is very common but may cause harm to the fetus. The teratogenic effect of a drug is partly dependent on the drug level in the fetal circulation, which is associated with the transport across the placenta. Many drugs are substrates of P-glycoprotein (P-gp), an efflux transporter that acts as a protective barrier for the fetus. We aim to identify whether drug interactions associated with P-gp promote any changes in fetal drug exposure, as measured by the risk of having children with congenital anomalies.
methodsIn this study, cases (N = 4634) were mothers of children with congenital anomalies registered in the EUROCAT Northern Netherlands registry, and the reference population were mothers of children (N = 25,126) from a drug prescription database (IADB.nl).
resultsDrugs that are associated with P-gp transport were commonly used in pregnancy in cases (10 %) and population (12 %). Several drug classes, which are substrates for P-gp, were shown to have a higher user rate in mothers of cases with specific anomalies. The use of this subset of drugs in combination with other P-gp substrates increased the risk for specific anomalies (odds ratio [OR] 4.17, 95 % CI 1.75-9.91), and the addition of inhibitors further increased the risk (OR 13.03, 95 % CI 3.37-50.42). The same pattern of risk increment was observed when the drugs were analyzed separately according to substrate specificity.
conclusionsThe use of drugs associated with P-gp transport was common during pregnancy. For several drug classes associated with specific anomalies, P-gp-mediated drug interactions are associated with an increased risk for those specific anomalies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.