Meeraus, W; (2015) Adverse paediatric outcomes of antibiotic treatment in pregnancy. Doctoral thesis , UCL (University College London).

Abstract

Although most antibiotics are considered safe, evidence from a mega-trial suggests that antibiotic use during pregnancy may increase the risk of adverse paediatric neurological outcomes. Understanding the results and potential implications of this mega-trial is important. However, evidence which could corroborate or refute the mega-trial is unlikely to be obtained from new trials. I considered two potential explanations for the unanticipated results of the mega-trial. First, I conducted a systematic review and meta-analysis to determine whether antibiotic treatment in pregnancy could prolong survival of neurologically damaged fetuses. I hypothesised that prolonged fetal survival in the mega-trial could have resulted in a spurious association between prenatal antibiotic treatment and adverse neurological outcome in surviving children. I found no evidence to support or contradict this explanation. Second, I conducted a cohort study using primary-care data to understand whether antibiotic treatment may have had a direct adverse effect on fetuses in the mega-trial. Whilst I found no evidence to suggest that prenatal antibiotic prescribing in general was associated with an adverse childhood outcome of cerebral palsy and/or epilepsy (adjusted hazard ratio [HR] 1.04; 95% confidence interval [CI] 0.9-1.19), I found that macrolide versus penicillin prescribing in pregnancy was associated with an increased risk of cerebral palsy and/or epilepsy. This risk remained after controlling for potential confounders including maternal infection (adj.HR 1.78; 95% CI 1.18-2.69). Of the two hypotheses I considered, the former is unlikely to account for the unanticipated findings of the mega-trial, while the latter is both unsupported (in general) and supported (for specific antibiotics). Regardless, the finding of harm associated with macrolide prescribing in pregnancy cannot be ignored, particularly given the growing body of evidence of harm with macrolide antibiotics in pregnant and non-pregnant populations. Further research on the effect of macrolide antibiotics on the fetus is warranted.

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