Macrolide in Pregnancy and Adverse Child Outcomes
Macrolide in Pregnancy and Adverse Child Outcomes
Over the last 20 years, concerns have been raised about rare but serious adverse outcomes
 associated with macrolide use during pregnancy. The strongest evidence comes from a large
 randomised controlled trial (RCT, ORACLE Child Study II) of women with spontaneous preterm
 labour (SPL), which reported an increased risk of cerebral palsy in children whose mothers
 received erythromycin compared with no erythromycin. A recent systematic review on macrolides
 prescription during pregnancy showed consistent associations with miscarriage, and less
 consistent associations with adverse child outcomes such as congenital malformations,
 cerebral palsy and epilepsy. In this study, the investigators will evaluate associations
 between macrolide antibiotics prescription during pregnancy and a range of adverse child
 outcomes.

 The investigators compare children whose mothers were prescribed an only monotherapy of
 macrolides or penicillins during pregnancy (from 5 gestational week (GW) to delivery and by
 trimesters). The investigators estimate the risk ratios of major malformation (overall and
 five system-specific) and hazard ratios of four neurodevelopmental disorders (cerebral palsy,
 epilepsy, attention-deficit/hyperactivity disorder, and autism spectrum disorder) with
 control for potential confounders. The associations will also be examined by subtype of
 macrolides and treatment duration.

 Mother-child pairs will be analysed in a cohort selected from the UK Clinical Practice
 Research Database (CPRD) between 1990 and 2016.
Inclusion Criteria:

 -  Children whose mother was prescribed an only monotherapy of macrolides or penicillins
 during pregnancy (between 5 GW and delivery).

 -  Children born from Jan 1st 1990 to June 30th 2016 in the CPRD Mother Baby Link.

 -  Children who registered with the GP within 6 months of birth

 -  Children whose mother was aged 14 to 50 years and had been registered with GP at least
 50 weeks before estimated conception date until after delivery

 Exclusion Criteria:

 -  Children with known chromosomal abnormalities and pregnancies with exposure to known
 teratogenic medications (warfarin, angiotensin-converting enzyme (ACE) inhibitors,
 antineoplastic agents, isotretinoin, misoprostol, and thalidomide)