Association Between Antibiotic Prescribing in Pregnancy and Cerebral Palsy or Epilepsy in Children Born at Term: a Cohort Study Using the Health Improvement Network

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Mar 26

PMID 25807115

Citations 26

Authors

Wilhelmine Hadler Meeraus

Irene Petersen

Ruth Gilbert

Affiliations

Soon will be listed here.

Abstract

Background: Between 19%-44% pregnant women are prescribed antibiotics during pregnancy. A single, large randomised-controlled-trial (ORACLE Childhood Study II) found an increased risk of childhood cerebral palsy and possibly epilepsy following prophylactic antibiotic use in pregnant women with spontaneous preterm labour. We ascertained whether this outcome could be reproduced across the population of babies delivered at term and prospectively followed in primary-care using data from The Health Improvement Network.

Methods: We determined the risk of cerebral palsy or epilepsy in children whose mothers were prescribed antibiotics during pregnancy using a cohort of 195,909 women linked to their live, term-born, singleton children. We compared the effect of antibiotic class, number of courses and timing of prescribing in pregnancy. Analyses were adjusted for maternal risk factors (e.g. recorded infection, age, chronic conditions, social deprivation, smoking status). Children were followed until age seven years or cessation of registration with the primary-care practitioner.

Results: In total, 64,623 (33.0%) women were prescribed antibiotics in pregnancy and 1,170 (0.60%) children had records indicating cerebral palsy or epilepsy. Adjusted analyses showed no association between prescribing of any antibiotic and cerebral palsy or epilepsy (adj.HR 1.04, 95%CI 0.91-1.19). However, compared with penicillins, macrolides were associated with an increased risk of cerebral palsy or epilepsy (adj.HR 1.78, 95%CI 1.18-2.69; number needed to harm 153, 95%CI 71-671).

Conclusions: We found no overall association between antibiotic prescribing in pregnancy and cerebral palsy and/or epilepsy in childhood. However, our finding of an increased risk of cerebral palsy or epilepsy associated with macrolide prescribing in pregnancy adds to evidence that macrolide use is associated with serious harm.

Citing Articles

Prevalence of systemic antibacterial use during pregnancy worldwide: A systematic review.

Guimaraes F, Dal-Pizzol T, Silveira M, Bertoldi A PLoS One. 2024; 19(9):e0309710.

PMID: 39240933 PMC: 11379220. DOI: 10.1371/journal.pone.0309710.

Association between exposure to antibiotics during pregnancy or early infancy and risk of autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children: population based cohort study.

Choi A, Lee H, Jeong H, Lee S, Kwon J, Han J BMJ. 2024; 385:e076885.

PMID: 38777351 PMC: 11109903. DOI: 10.1136/bmj-2023-076885.

Frontiers in the Etiology and Treatment of Preterm Premature Rupture of Membrane: From Molecular Mechanisms to Innovative Therapeutic Strategies.

Xu L, Yang T, Wen M, Wen D, Jin C, An M Reprod Sci. 2023; 31(4):917-931.

PMID: 37989803 DOI: 10.1007/s43032-023-01411-9.

Duration of Neonatal Antibiotic Exposure in Preterm Infants in Association with Health and Developmental Outcomes in Early Childhood.

Deianova N, de Boer N, Aoulad Ahajan H, Verbeek C, Aarnoudse-Moens C, Leemhuis A Antibiotics (Basel). 2023; 12(6).

PMID: 37370287 PMC: 10295560. DOI: 10.3390/antibiotics12060967.

Women's experiences of over-the-counter and prescription medication during pregnancy in the UK: findings from survey free-text responses and narrative interviews.

Sanders J, Blaylock R, Dean C, Petersen I, Trickey H, Murphy C BMJ Open. 2023; 13(3):e067987.

PMID: 36858469 PMC: 9990671. DOI: 10.1136/bmjopen-2022-067987.

References

Bakker M, Jentink J, Vroom F, van den Berg P, de Walle H, de Jong-van den Berg L . Drug prescription patterns before, during and after pregnancy for chronic, occasional and pregnancy-related drugs in the Netherlands. BJOG. 2006; 113(5):559-68. DOI: 10.1111/j.1471-0528.2006.00927.x. View

Norgaard M, Ehrenstein V, Nielsen R, Bakketeig L, Sorensen H . Maternal use of antibiotics, hospitalisation for infection during pregnancy, and risk of childhood epilepsy: a population-based cohort study. PLoS One. 2012; 7(1):e30850. PMC: 3266299. DOI: 10.1371/journal.pone.0030850. View

Koren G, Bologa M, Long D, Feldman Y, Shear N . Perception of teratogenic risk by pregnant women exposed to drugs and chemicals during the first trimester. Am J Obstet Gynecol. 1989; 160(5 Pt 1):1190-4. DOI: 10.1016/0002-9378(89)90186-5. View

Stokholm J, Schjorring S, Pedersen L, Bischoff A, Folsgaard N, Carson C . Prevalence and predictors of antibiotic administration during pregnancy and birth. PLoS One. 2013; 8(12):e82932. PMC: 3858309. DOI: 10.1371/journal.pone.0082932. View

Charlton R, Neville A, Jordan S, Pierini A, Damase-Michel C, Klungsoyr K . Healthcare databases in Europe for studying medicine use and safety during pregnancy. Pharmacoepidemiol Drug Saf. 2014; 23(6):586-94. DOI: 10.1002/pds.3613. View

Traerup Andersen J, Petersen M, Jimenez-Solem E, Broedbaek K, Andersen N, Torp-Pedersen C . Clarithromycin in early pregnancy and the risk of miscarriage and malformation: a register based nationwide cohort study. PLoS One. 2013; 8(1):e53327. PMC: 3534696. DOI: 10.1371/journal.pone.0053327. View

Webster W, Abela D . The effect of hypoxia in development. Birth Defects Res C Embryo Today. 2007; 81(3):215-28. DOI: 10.1002/bdrc.20102. View

Matsui D . Adherence with drug therapy in pregnancy. Obstet Gynecol Int. 2012; 2012:796590. PMC: 3253470. DOI: 10.1155/2012/796590. View

Schembri S, Williamson P, Short P, Singanayagam A, Akram A, Taylor J . Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies. BMJ. 2013; 346:f1235. DOI: 10.1136/bmj.f1235. View

10.

Kenyon S, Pike K, Jones D, Brocklehurst P, Marlow N, Salt A . Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial. Lancet. 2008; 372(9646):1319-27. DOI: 10.1016/S0140-6736(08)61203-9. View

11.

Bril F, Gonzalez C, Di Girolamo G . Antimicrobial agents-associated with QT interval prolongation. Curr Drug Saf. 2010; 5(1):85-92. DOI: 10.2174/157488610789869184. View

12.

Danielsson B, Danielsson C, Nilsson M . Embryonic cardiac arrhythmia and generation of reactive oxygen species: common teratogenic mechanism for IKr blocking drugs. Reprod Toxicol. 2007; 24(1):42-56. DOI: 10.1016/j.reprotox.2007.04.005. View

13.

Ray W, Murray K, Hall K, Arbogast P, Stein C . Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012; 366(20):1881-90. PMC: 3374857. DOI: 10.1056/NEJMoa1003833. View

14.

Sun Y, Vestergaard M, Christensen J, Nahmias A, Olsen J . Prenatal exposure to maternal infections and epilepsy in childhood: a population-based cohort study. Pediatrics. 2008; 121(5):e1100-7. DOI: 10.1542/peds.2007-2316. View

15.

Kallen B, Olausson P, Danielsson B . Is erythromycin therapy teratogenic in humans?. Reprod Toxicol. 2005; 20(2):209-14. DOI: 10.1016/j.reprotox.2005.01.010. View

16.

Lewis J, Schinnar R, Bilker W, Wang X, Strom B . Validation studies of the health improvement network (THIN) database for pharmacoepidemiology research. Pharmacoepidemiol Drug Saf. 2006; 16(4):393-401. DOI: 10.1002/pds.1335. View

17.

Devasia R, Jones T, Collier B, Schaffner W . Compliance with azithromycin versus erythromycin in the setting of a pertussis outbreak. Am J Med Sci. 2009; 337(3):176-8. DOI: 10.1097/maj.0b013e318184e72f. View

18.

Blak B, Thompson M, Dattani H, Bourke A . Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates. Inform Prim Care. 2012; 19(4):251-5. DOI: 10.14236/jhi.v19i4.820. View

19.

Crider K, Cleves M, Reefhuis J, Berry R, Hobbs C, Hu D . Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study. Arch Pediatr Adolesc Med. 2009; 163(11):978-85. DOI: 10.1001/archpediatrics.2009.188. View

20.

Altman D, Andersen P . Calculating the number needed to treat for trials where the outcome is time to an event. BMJ. 1999; 319(7223):1492-5. PMC: 1117211. DOI: 10.1136/bmj.319.7223.1492. View