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    • Clomiphene Citrate Medication for Infertility and Risk of Stillbirth or Neonatal Death: a Population-Based Cohort Study

    Vivienne Moore,Alice Rumbold,Renae Fernandez,Heather McElroy,Lynette Moore,Lynne Giles,Luke Grzeskowiak,Elizabeth Roughead,Michael Stark,Darryl Russell,Michael Davies

    JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM（2024）

    Univ Adelaide | South Australian Hlth & Med Res Inst | Univ South Australia

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    Abstract
    CONTEXT:Women achieving pregnancy with infertility treatment may be at increased risk of stillbirth and neonatal death. OBJECTIVE:To assess associations between clomiphene citrate (CC) use and perinatal death. DESIGN:Whole of population data linkage cohort. SETTING:South Australia. PARTICIPANTS:All women giving birth between July 2003 and December 2015 (n=242,077). METHODS:All births of at least 20 weeks were linked to government records of dispensed medications. A pregnancy was considered exposed to CC if a prescription was dispensed from 90 days before through to the end of a conception window. Descriptive statistics for stillbirths and neonatal deaths were stratified by multiplicity. For singletons, multivariable logistic regression models were used to examine the association of CC exposure with the combined outcome of perinatal death. MAIN OUTCOME MEASURES:Stillbirths and neonatal deaths (with 28 days of birth) combined as perinatal deaths. RESULTS:Among singletons, the prevalence of stillbirth was 6.6 per 1,000 births, with neonatal deaths of 2.1 per 1,000 live births. Among singletons conceived with CC, stillbirth and neonatal death had prevalence of 10.2 and 3.1 per 1,000, respectively. For the combined outcome of perinatal death, the odds ratio was 1.54 (95% confidence interval 1.15, 2.07), stable upon adjustment for factors conveying biological (e.g. obesity, pre-gestational diabetes) and social (e.g. disadvantage) risks for perinatal death. CONCLUSION:Risk of perinatal death may be increased in pregnancies that follow use of CC. While established confounding factors related to infertility were taken into account, there may be some residual contribution of underlying infertility.
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    polycystic ovary syndrome,clomiphene citrate,stillbirth,neonatal death,perinatal death
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    【要点】：该研究通过人群队列分析发现，使用氯米芬 citrate（CC）的孕妇相比未使用者，其围产期死亡（包括死产和新生儿死亡）的风险增加。
    

    【方法】：研究采用南澳大利亚全人口数据链路队列，将至少20周的所有出生记录与政府药物分发记录相链接，使用描述性统计和多元逻辑回归模型分析CC使用与围产期死亡之间的关联。
    

    【实验】：研究收集了2003年7月至2015年12月间所有分娩妇女的数据（n=242,077），通过政府记录的药物分发数据确定CC暴露情况，分析得出使用CC的 singleton 孕妇围产期死亡的发生率及调整后的风险比值。
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