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Abstract：
OBJECTIVE: The aetiology of gastroschisis is considered multifactorial. We conducted a systematic review and meta-analysis to assess whether the use of medications during pregnancy, is associated with the risk of gastroschisis in offspring.
METHODS: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I2 statistic for heterogeneity and publication bias was calculated.
RESULTS: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%).
CONCLUSIONS: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
METHODS: PubMed, EMBASE, and Scopus were searched from 1st January 1990 to 31st December 2020 to identify observational studies examining the association between medication use during pregnancy and the risk of gastroschisis. The Newcastle-Ottawa Scale was used for the quality assessment of the individual studies. We pooled adjusted measures using a random-effect model to estimate relative risk [RR] and the 95% confidence interval [CI]. I2 statistic for heterogeneity and publication bias was calculated.
RESULTS: Eighteen studies providing data on 751,954 pregnancies were included in the meta-analysis. Pooled RRs showed significant associations between aspirin (RR 1.66, 95% CI 1.16-2.38; I2 = 58.3%), oral contraceptives (RR 1.52, 95% CI 1.21-1.92; I2 = 22.0%), pseudoephedrine and phenylpropanolamine (RR 1.51, 95% CI 1.16-1.97; I2 = 33.2%), ibuprofen (RR 1.42, 95% CI 1.26-1.60; I2 = 0.0%), and gastroschisis. No association was observed between paracetamol and gastroschisis (RR 1.16, 95% CI 0.96-1.41; I2 = 39.4%).
CONCLUSIONS: These results suggest that the exposure in the first trimester of pregnancy to over the counter medications (OTC) such as aspirin, ibuprofen, pseudoephedrine and phenylpropanolamine as well as to oral contraceptives, was associated with an increased risk of gastroschisis. However, these associations are significant only in particular subgroups defined by geographic location, adjustment variables and type of control. Therefore, further research is needed to investigate them as potential risk factors for gastroschisis, to assess their safety in pregnancy and to develop treatment strategies to reduce the risk of gastroschisis in offspring. PROSPERO registration number: CRD42021287529.
摘要：
目的：胃裂的病因被认为是多因素的。我们进行了系统评价和荟萃分析，以评估是否在怀孕期间使用药物，与后代腹裂的风险有关。
方法：PubMed，EMBASE,我们从1990年1月1日至2020年12月31日对Scopus进行了检索,以确定观察性研究,这些研究检查了妊娠期药物使用与腹裂风险之间的关系.Newcastle-Ottawa量表用于个体研究的质量评估。我们使用随机效应模型汇总调整后的测量值，以估计相对风险[RR]和95%置信区间[CI]。计算异质性和发表偏倚的I2统计量。
结果：提供751,954例妊娠数据的18项研究纳入荟萃分析。汇总的RR显示阿司匹林之间存在显着关联（RR1.66，95％CI1.16-2.38；I2=58.3％），口服避孕药（RR1.52，95%CI1.21-1.92；I2=22.0%），伪麻黄碱和苯丙醇胺（RR1.51，95%CI1.16-1.97；I2=33.2%），布洛芬（RR1.42，95%CI1.26-1.60；I2=0.0%），和胃裂。在扑热息痛和腹裂之间未观察到相关性（RR1.16，95％CI0.96-1.41；I2=39.4％）。
结论：这些结果表明，在怀孕的头三个月暴露于非处方药（OTC），如阿司匹林，布洛芬,伪麻黄碱和苯丙醇胺以及口服避孕药，与腹裂的风险增加有关。然而,这些关联仅在由地理位置定义的特定子组中才是重要的，调整变量和控制类型。因此,需要进一步的研究来调查它们是胃裂的潜在危险因素，评估其在怀孕期间的安全性，并制定治疗策略以降低后代腹裂的风险。PROSPERO注册号：CRD42021287529。
方法：PubMed，EMBASE,我们从1990年1月1日至2020年12月31日对Scopus进行了检索,以确定观察性研究,这些研究检查了妊娠期药物使用与腹裂风险之间的关系.Newcastle-Ottawa量表用于个体研究的质量评估。我们使用随机效应模型汇总调整后的测量值，以估计相对风险[RR]和95%置信区间[CI]。计算异质性和发表偏倚的I2统计量。
结果：提供751,954例妊娠数据的18项研究纳入荟萃分析。汇总的RR显示阿司匹林之间存在显着关联（RR1.66，95％CI1.16-2.38；I2=58.3％），口服避孕药（RR1.52，95%CI1.21-1.92；I2=22.0%），伪麻黄碱和苯丙醇胺（RR1.51，95%CI1.16-1.97；I2=33.2%），布洛芬（RR1.42，95%CI1.26-1.60；I2=0.0%），和胃裂。在扑热息痛和腹裂之间未观察到相关性（RR1.16，95％CI0.96-1.41；I2=39.4％）。
结论：这些结果表明，在怀孕的头三个月暴露于非处方药（OTC），如阿司匹林，布洛芬,伪麻黄碱和苯丙醇胺以及口服避孕药，与腹裂的风险增加有关。然而,这些关联仅在由地理位置定义的特定子组中才是重要的，调整变量和控制类型。因此,需要进一步的研究来调查它们是胃裂的潜在危险因素，评估其在怀孕期间的安全性，并制定治疗策略以降低后代腹裂的风险。PROSPERO注册号：CRD42021287529。
