PDF(Pubmed)
Abstract：
BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy.
METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model.
RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy.
CONCLUSIONS: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.
METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model.
RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy.
CONCLUSIONS: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.
摘要：
背景：口服类维生素A用于治疗各种皮肤病，在育龄妇女中，它们的使用正在增加。然而,目前对妊娠期类维生素A暴露后不良结局的发生率了解有限.我们的目的是评估妊娠期间与口服类维生素A相关的不良结局的风险。
方法：我们使用韩国NHIS母婴关联医疗数据库进行了一项回顾性队列研究。我们包括2009年4月1日至2020年12月31日期间活产的所有妇女及其子女。暴露定义为异维甲酸处方≥1，阿利维甲酸,从怀孕前一个月到分娩。感兴趣的结果是不良的儿童结果，包括主要的先天性畸形，低出生体重,和神经发育障碍（自闭症谱系障碍和智力障碍），和不良妊娠结局，包括妊娠期糖尿病，先兆子痫,产后出血。使用基于倾向得分的匹配权重来控制各种潜在的混杂因素。对于先天性畸形，低出生体重,和不良的妊娠结局，我们使用广义线性模型和神经发育障碍以95%置信区间(CI)计算相对危险度(RR),我们使用Cox比例风险模型以95%CI估计风险比(HR).
结果：在3,894,184次怀孕中，我们确定720例妊娠(0.02%)为口服类维生素A暴露组.口腔类维生素A暴露组的主要先天性畸形发生率为400.6/10,000，未暴露组的357.9/10,000，加权RR为1.10（95％CI，0.65-1.85）与未暴露组相比。神经发育障碍显示出潜在的风险增加，自闭症谱系障碍的加权HR为1.63（95％CI，0.60-4.41），智力障碍的加权HR为1.71（95％CI，0.60-4.93），虽然没有达到统计学意义。对于低出生体重和不良妊娠结局，未观察到与孕期口服类维生素A相关.
结论：这项研究发现先天性畸形的风险没有明显增加，自闭症谱系障碍，与怀孕期间口服类维生素A接触相关的智力残疾；然而，考虑到限制，如只包括活产和增加点估计，不能完全排除潜在风险。
方法：我们使用韩国NHIS母婴关联医疗数据库进行了一项回顾性队列研究。我们包括2009年4月1日至2020年12月31日期间活产的所有妇女及其子女。暴露定义为异维甲酸处方≥1，阿利维甲酸,从怀孕前一个月到分娩。感兴趣的结果是不良的儿童结果，包括主要的先天性畸形，低出生体重,和神经发育障碍（自闭症谱系障碍和智力障碍），和不良妊娠结局，包括妊娠期糖尿病，先兆子痫,产后出血。使用基于倾向得分的匹配权重来控制各种潜在的混杂因素。对于先天性畸形，低出生体重,和不良的妊娠结局，我们使用广义线性模型和神经发育障碍以95%置信区间(CI)计算相对危险度(RR),我们使用Cox比例风险模型以95%CI估计风险比(HR).
结果：在3,894,184次怀孕中，我们确定720例妊娠(0.02%)为口服类维生素A暴露组.口腔类维生素A暴露组的主要先天性畸形发生率为400.6/10,000，未暴露组的357.9/10,000，加权RR为1.10（95％CI，0.65-1.85）与未暴露组相比。神经发育障碍显示出潜在的风险增加，自闭症谱系障碍的加权HR为1.63（95％CI，0.60-4.41），智力障碍的加权HR为1.71（95％CI，0.60-4.93），虽然没有达到统计学意义。对于低出生体重和不良妊娠结局，未观察到与孕期口服类维生素A相关.
结论：这项研究发现先天性畸形的风险没有明显增加，自闭症谱系障碍，与怀孕期间口服类维生素A接触相关的智力残疾；然而，考虑到限制，如只包括活产和增加点估计，不能完全排除潜在风险。
