Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Olof Palmes Allé 43-45, 8200, Aarhus N, Denmark.
Centre for Pharmacoepidemiology, Karolinska Institutet, Karolinska University Hospital, 171 76, Stockholm, Sweden.
Drug Saf. 2023 Jul;46(7):661-675. doi: 10.1007/s40264-023-01307-2. Epub 2023 Apr 26.
Pregabalin is an antiepileptic drug frequently prescribed to pregnant women. Risks of adverse birth and postnatal neurodevelopmental outcomes following prenatal exposure to pregabalin are uncertain.
To investigate the association between prenatal exposure to pregabalin and the risks of adverse birth and postnatal neurodevelopmental outcomes.
This study was conducted using population-based registries in Denmark, Finland, Norway, and Sweden (2005-2016). We compared pregabalin exposure against no exposure to antiepileptics and against active comparators lamotrigine and duloxetine. We obtained pooled propensity score-adjusted estimates of association using fixed-effect and Mantel-Haenszel (MH) meta-analyses.
The total number of pregabalin-exposed births was 325/666,139 (0.05%) in Denmark, 965/643,088 (0.15%) in Finland, 307/657,451 (0.05%) in Norway, and 1275/1,152,002 (0.11%) in Sweden. The adjusted prevalence ratios (aPRs) with 95% confidence interval (CI) following pregabalin exposure versus no exposure were 1.14 (0.98-1.34) for major congenital malformations and 1.72 (1.02-2.91) for stillbirth, which attenuated to 1.25 (0.74-2.11) in MH meta-analysis. For the remaining birth outcomes, the aPRs were close to or attenuated toward unity in analyses using active comparators. Adjusted hazard ratios (95% CI) contrasting prenatal pregabalin exposure versus no exposure were 1.29 (1.03-1.63) for ADHD and attenuated when using active comparators, 0.98 (0.67-1.42) for autism spectrum disorders, and 1.00 (0.78-1.29) for intellectual disability.
Prenatal exposure to pregabalin was not associated with low birth weight, preterm birth, small for gestational age, low Apgar score, microcephaly, autism spectrum disorders, or intellectual disability. On the basis of the upper value of the 95% confidence interval, increased risks greater than 1.8 were unlikely for any major congenital malformation and ADHD. For stillbirth and most groups of specific major congenital malformations, the estimates attenuated in MH meta-analysis.
普瑞巴林是一种常用于孕妇的抗癫痫药物。产前暴露于普瑞巴林与不良出生和产后神经发育结局风险之间的关系尚不确定。
调查产前暴露于普瑞巴林与不良出生和产后神经发育结局风险之间的关系。
本研究使用丹麦、芬兰、挪威和瑞典的基于人群的登记处（2005-2016 年）进行。我们将普瑞巴林暴露与无抗癫痫药物暴露和活性对照药物拉莫三嗪和度洛西汀进行了比较。我们使用固定效应和 Mantel-Haenszel（MH）荟萃分析获得了经倾向评分调整的关联的汇总估计值。
在丹麦，普瑞巴林暴露的出生总数为 325/666,139（0.05%），芬兰为 965/643,088（0.15%），挪威为 307/657,451（0.05%），瑞典为 1275/1,152,002（0.11%）。与无暴露相比，普瑞巴林暴露后的调整后比值比（aPR）及其 95%置信区间（CI）为 1.14（0.98-1.34），主要先天性畸形，1.72（1.02-2.91）为死产，MH 荟萃分析中减弱为 1.25（0.74-2.11）。对于其余的出生结局，使用活性对照药物时，aPR 接近或减弱至 1。与无暴露相比，产前普瑞巴林暴露的调整后的危险比（95%CI）为 ADHD 为 1.29（1.03-1.63），使用活性对照药物时减弱，自闭症谱系障碍为 0.98（0.67-1.42），智力残疾为 1.00（0.78-1.29）。
产前暴露于普瑞巴林与低出生体重、早产、小于胎龄、低 Apgar 评分、小头畸形、自闭症谱系障碍或智力残疾无关。基于 95%置信区间的上限，任何主要先天性畸形和 ADHD 的风险增加超过 1.8 的可能性不大。对于死产和大多数特定主要先天性畸形组，MH 荟萃分析中的估计值减弱。
