Statin use in pregnancy and risk of congenital malformations: a Norwegian nationwide study.

Therefore, this study aimed to examine the associations between statin and LMA exposure in pregnancy and congenital malformations in offspring, while updating a 2022 meta-analysiswith the results from the present study.

因此，本研究旨在检查孕期接触他汀类药物和LMAs与后代先天性畸形之间的关联，同时用本研究的结果更新了2022年的荟萃分析。

Methods

National registry data were linked for all pregnant women in Norway in 2005-18.

挪威2005-2018年间所有孕妇的国家登记数据已进行关联。

Associations between first-trimester statin prescription fills and congenital malformations were estimated with mixed-effects logistic regression, adjusting for age, parity, pre-pregnancy folate use, smoking in early pregnancy, comorbidity, and co-medication.

使用混合效应逻辑回归估计了第一孕期他汀类药物处方填充与先天性畸形之间的关联，同时对年龄、产次、孕前叶酸使用、早孕期吸烟、共病和合并用药进行了调整。

Meta-analyses were performed with the generic inverse-variance method and random-effects model.

使用通用逆方差方法和随机效应模型进行了荟萃分析。

Results

Congenital malformations occurred among 34 755 out of 803 830 (4.3%) statin non-exposed pregnancies, 74 out of 1255 (5.9%) statin-discontinuer pregnancies, and 19 out of 283 (6.7%) statin-exposed pregnancies.

在803,830例未暴露于他汀类药物的妊娠中，有34,755例（4.3%）发生了先天性畸形；在1,255例停用他汀类药物的妊娠中，有74例（5.9%）发生了先天性畸形；在283例暴露于他汀类药物的妊娠中，有19例（6.7%）发生了先天性畸形。

Adjusted odds ratios (ORs) for exposed vs non-exposed pregnancies were 1.30 [95% confidence interval(CI) .81-2.09] for any, 1.15 (.61-2.19) for major, and 1.47 (.75-2.89) for minor malformations.

暴露与未暴露妊娠的调整后优势比(ORs)分别为：任何畸形1.30（95%置信区间(CI) .81-2.09），主要畸形1.15（.61-2.19），次要畸形1.47（.75-2.89）。

In analyses of exposed vs discontinuer pregnancies, there were no associations between statin exposure and any (adjusted OR 1.01, 95% CI .59-1.72), major (1.08, .52-2.25), or minor malformations (.94, .44-2.00).

在暴露与停止妊娠的分析中，他汀类药物暴露与任何（调整后OR 1.01，95% CI .59-1.72）、主要（1.08，.52-2.25）或次要畸形（.94，.44-2.00）之间没有关联。

Results were similar across sensitivity analyses.

在敏感性分析中，结果相似。

There was also no association between any LMA exposure and heart malformations (adjusted OR 1.22, 95% CI .50-3.01).

也没有发现任何局部麻醉药暴露与心脏畸形之间存在关联（调整后的OR为1.22，95%置信区间为0.50-3.01）。

The updated meta-analysissuggested no increased risk of major (adjusted OR 1.06, 95% CI .86-1.31) or heart malformations (1.24, 95% CI .94-1.64).

这项最新的荟萃分析表明，主要畸形（调整后OR 1.06，95% 置信区间 .86-1.31）或心脏畸形（1.24，95% 置信区间 .94-1.64）的风险并没有增加。

Conclusions

In this large, nationwide study and updated meta-analysis, no significant association was observed between first-trimester exposure to statins or other LMAs and congenital malformations.

在这项大规模的全国性研究和最新的荟萃分析中，未观察到孕期前三个月暴露于他汀类药物或其他脂质调节剂与先天性畸形之间存在显著关联。

Although limited power may have prevented detection of weak but clinically relevant associations, the findings do not support a strong or independent association between statin exposure in pregnancy and congenital malformations.

尽管有限的样本量可能阻止了对弱但具有临床相关性的关联的检测，但研究结果并不支持孕期他汀类药物暴露与先天性畸形之间存在强烈或独立的关联。