Acute Maternal Infection and Risk of Pre-Eclampsia: A Population-Based Case-Control Study

BackgroundInfection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia.Methods and FindingsWe used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n = 1533) were individually matched with up to ten controls (n = 14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14–1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03–1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72–1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings.ConclusionsWomen who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia.研究背景 妊娠期间的感染可能与先兆子痫（pre-eclampsia）的病因学相关。然而，目前尚未明确母体急性感染与先兆子痫之间的确切关联。本研究旨在评估妊娠期间的急性尿路感染（acute urinary tract infection）、呼吸道感染（respiratory tract infection）以及抗生素处方（可作为母体感染的潜在替代指标）是否与先兆子痫风险升高存在关联。 研究方法与结果 本研究采用匹配巢式病例对照设计，使用英国全科医学研究数据库（UK General Practice Research Database）的数据，探究母体感染与先兆子痫之间的关联。1987年1月至2007年10月期间在参与研究的全科诊所注册、年龄≥13岁的初产妇符合纳入标准。本研究纳入所有先兆子痫病例，并随机抽取未发生先兆子痫的初产妇作为对照。按照就诊诊所与分娩年份进行个体匹配，每例病例（共1533例）最多匹配10例对照（共14236例）。本研究采用多变量条件logistic回归，对比暴露于感染与未暴露于感染的女性，计算先兆子痫的比值比（odds ratio）与95%置信区间（confidence interval）。在校正母体年龄、妊娠前高血压、糖尿病、肾脏疾病以及多胎妊娠等混杂因素后，服用抗生素药物的女性（校正后比值比：1.28；95%置信区间：1.14~1.44）以及罹患尿路感染的女性（校正后比值比：1.22；95%置信区间：1.03~1.45）的先兆子痫发病风险均有所升高。本研究未发现母体呼吸道感染与先兆子痫存在关联（校正后比值比：0.91；95%置信区间：0.72~1.16）。进一步校正母体吸烟情况与妊娠前体重指数后，研究结果未发生显著改变。 研究结论 妊娠期间罹患尿路感染的女性先兆子痫发病风险升高，而罹患呼吸道感染的女性则无此风险升高情况。母体使用抗生素处方也与先兆子痫风险升高存在关联。未来仍需开展进一步研究，以阐明该关联的潜在机制，并明确对于妊娠期间发生感染的女性，及时的感染治疗或预防措施是否能够降低其先兆子痫的发病风险。