Objectives

To examine the risks of neonatal and infant mortality in relation to infertility treatment and to quantify the extent to which preterm delivery mediates this relationship.

Design

Cross-sectional study.

Setting

United States, 2015–2018.

Patient(s)

A total of 14,961,207 pregnancies resulting in a singleton live birth.

Intervention(s)

Any infertility treatment, including assisted reproductive technology and fertility-enhancing drugs.

Main Outcome Measure(s)

Neonatal (<28 days) mortality. The effect measure, risk ratio (RR), and 95% confidence interval (CI) were derived from log-linear Poisson models. A causal mediation analysis of the relationship between infertility treatment and mortality associated with preterm delivery (<37 weeks) was performed. The effects of exposure misclassification and unmeasured confounding biases were assessed.

Result(s)

Any infertility treatment was documented in 1.3% (n = 198,986) of pregnancies. Infertility treatment was associated with a 51% increased risk of neonatal mortality (RR 1.51, 95% CI 1.39–1.64), with a slightly higher risk for early neonatal mortality (RR 1.57, 95% CI 1.43–1.73) than late neonatal mortality (RR 1.33, 95% CI 1.11–1.58). These risks were similar for pregnancies conceived through assisted reproductive technology and fertility-enhancing drugs. The mediation analysis showed that 72% (95% CI 59–85) of the total effect of infertility treatment on neonatal mortality was mediated through preterm delivery. In a sensitivity analysis, following corrections for exposure misclassification and unmeasured confounding biases, these risks were higher for early, but not for late, neonatal mortality.

Conclusion(s)

Pregnancies conceived with infertility treatment are associated with increased neonatal mortality, and this association is largely mediated through preterm delivery. However, given the substantial underreporting of infertility treatment, these associations must be cautiously interpreted.

中文翻译：

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接受不孕症治疗的单胎妊娠以及新生儿和婴儿死亡的风险

目标

研究与不孕症治疗相关的新生儿和婴儿死亡风险，并量化早产在多大程度上调节这种关系。

设计

横断面研究。

环境

美国，2015-2018 年。

耐心）

共有 14,961,207 次怀孕导致单胎活产。

干预措施

任何不孕症治疗，包括辅助生殖技术和生育增强药物。

主要观察指标）

新生儿（<28 天）死亡率。效应量度、风险比 (RR) 和 95% 置信区间 (CI) 来自对数线性泊松模型。对不孕症治疗与早产（<37 周）相关死亡率之间的关系进行了因果中介分析。评估了暴露错误分类和未测量的混杂偏差的影响。

结果）

在 1.3% (n = 198,986) 的怀孕中记录了任何不孕症治疗。不孕症治疗与新生儿死亡风险增加 51% 相关（RR 1.51，95% CI 1.39–1.64），早期新生儿死亡风险（RR 1.57，95% CI 1.43–1.73）比晚期新生儿死亡率略高（ RR 1.33，95% CI 1.11–1.58）。这些风险与通过辅助生殖技术和生育增强药物怀孕的风险相似。中介分析显示，不孕症治疗对新生儿死亡率的总影响的 72% (95% CI 59–85) 是通过早产介导的。在敏感性分析中，在对暴露错误分类和未测量的混杂偏倚进行校正后，早期新生儿死亡率的风险较高，但晚期新生儿死亡率并非如此。

结论

接受不孕症治疗的妊娠与新生儿死亡率增加有关，而这种关联主要是通过早产来介导的。然而，鉴于不孕症治疗的大量漏报，必须谨慎解释这些关联。