Long-term impact of giving antibiotics before skin incision versus after cord clamping on children born by caesarean section: protocol for a longitudinal study based on UK electronic health records

BMJ Open. 2019 Sep 26;9(9):e033013. doi: 10.1136/bmjopen-2019-033013.

Abstract

Introduction: In the UK, about a quarter of women give birth by caesarean section (CS) and are offered prophylactic broad-spectrum antibiotics to reduce the risk of maternal postpartum infection. In 2011, national guidance was changed from recommending antibiotics after the umbilical cord was cut to giving antibiotics prior to skin incision based on evidence that earlier administration reduces maternal infectious morbidity. Although antibiotics cross the placenta, there are no known short-term harms to the baby. This study aims to address the research gap on longer term impact of these antibiotics on child health.

Methods and analysis: A controlled interrupted time series study will use anonymised mother-baby linked routine electronic health records for children born during 2006-2018 recorded in UK primary care (The Health Improvement Network, THIN and Clinical Practice Research Datalink, CPRD) and secondary care (Hospital Episode Statistics, HES) databases. The primary outcomes of interest are asthma and eczema, two common allergy-related diseases in childhood. In-utero exposure to antibiotics immediately prior to CS will be compared with no exposure when given after cord clamping. The risk of outcomes in children delivered by CS will also be compared with a control cohort delivered vaginally to account for time effects. We will use all available data from THIN, CPRD and HES with estimated power of 80% and 90% to detect relative increase in risk of asthma of 16% and 18%, respectively at the 5% significance level.

Ethics and dissemination: Ethical approval has been obtained from the University of Birmingham Ethical Review Committee with scientific approvals obtained from the independent scientific advisory committees from the Medicines and Healthcare products Regulatory Agency for CPRD and the data provider, IQVIA for THIN. The results will be published in peer-reviewed journals, presented at national and international conferences and disseminated to stakeholders.

Keywords: antibiotic prophylaxis; asthma; caesarean section; child; eczema; immune system diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis / adverse effects
  • Antibiotic Prophylaxis / methods*
  • Asthma / etiology
  • Asthma / prevention & control
  • Cesarean Section / adverse effects*
  • Child
  • Child Health*
  • Constriction
  • Databases, Factual
  • Eczema / etiology
  • Eczema / prevention & control
  • Electronic Health Records
  • Female
  • Humans
  • Infant, Newborn
  • Interrupted Time Series Analysis
  • Maternal Health
  • Parturition
  • Placenta
  • Pregnancy
  • Pregnancy Complications, Infectious / prevention & control*
  • Research Design
  • Surgical Wound Infection / etiology
  • Surgical Wound Infection / prevention & control*
  • Umbilical Cord*
  • United Kingdom

Substances

  • Anti-Bacterial Agents