PDF(Pubmed)
Abstract：
UNASSIGNED: The short- and long-term consequences of restricted fetal growth cause considerable concern, and how prenatal exposure to different antiseizure medications (ASMs) affects fetal growth remains uncertain.
UNASSIGNED: This was a population-based cohort study of liveborn singleton children born in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2017. Prenatal exposure was defined as maternal filling of prescriptions for ASM during pregnancy registered in national prescription registries and primary outcomes were adjusted odds ratios (aORs) of microcephaly or being born small for gestational age.
UNASSIGNED: We identified 4,494,918 children (males: 51.3%, 2,306,991/4,494,918), including 38,714 (0.9%) children of mothers with epilepsy. In the overall population, prenatal monotherapy exposure with carbamazepine (aOR: 1.25 (95% CI: 1.12-1.40)), pregabalin (aOR: 1.16 (95% CI: 1.02-1.31)), oxcarbazepine (aOR: 1.48 (95% CI: 1.28-1.71)), clonazepam (aOR: 1.27 (95% CI: 1.10-1.48)), and topiramate (aOR: 1.48 (95% CI: 1.18-1.85)) was associated with risk of being born small for gestational age, and carbamazepine was associated with microcephaly (aOR: 1.43 (95% CI: 1.17-1.75)). In children of mothers with epilepsy, prenatal exposure to carbamazepine (aOR: 1.27 (95% CI: 1.11-1.47)), oxcarbazepine (aOR: 1.42 (95% CI: 1.18-1.70)), clonazepam (aOR: 1.40 (95% CI: 1.03-1.89)), and topiramate (aOR: 1.86 (95% CI: 1.36-2.54)) was associated with being born small for gestational age; carbamazepine, with microcephaly (aOR: 1.51 (95% CI: 1.17-1.95)). No associations with small for gestational age and microcephaly were identified after prenatal exposure to lamotrigine, valproate, gabapentin, levetiracetam, phenobarbital, acetazolamide, phenytoin, clobazam, primidone, zonisamide, vigabatrin, ethosuximide and lacosamide, but except for lamotrigine, valproate, gabapentin, and levetiracetam, numbers of exposed children were small.
UNASSIGNED: Prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate was associated with increased risk of being born small for gestational age in both the overall population and in children of women with epilepsy suggesting that prenatal exposure to these drugs is associated with fetal growth restriction.
UNASSIGNED: The NordForsk Nordic Program on Health and Welfare (83539), the Independent Research Fund Denmark (1133-00026B), the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and the Lundbeck Foundation (R400-2022-1205).
UNASSIGNED: This was a population-based cohort study of liveborn singleton children born in Denmark, Finland, Iceland, Norway, and Sweden from 1996 to 2017. Prenatal exposure was defined as maternal filling of prescriptions for ASM during pregnancy registered in national prescription registries and primary outcomes were adjusted odds ratios (aORs) of microcephaly or being born small for gestational age.
UNASSIGNED: We identified 4,494,918 children (males: 51.3%, 2,306,991/4,494,918), including 38,714 (0.9%) children of mothers with epilepsy. In the overall population, prenatal monotherapy exposure with carbamazepine (aOR: 1.25 (95% CI: 1.12-1.40)), pregabalin (aOR: 1.16 (95% CI: 1.02-1.31)), oxcarbazepine (aOR: 1.48 (95% CI: 1.28-1.71)), clonazepam (aOR: 1.27 (95% CI: 1.10-1.48)), and topiramate (aOR: 1.48 (95% CI: 1.18-1.85)) was associated with risk of being born small for gestational age, and carbamazepine was associated with microcephaly (aOR: 1.43 (95% CI: 1.17-1.75)). In children of mothers with epilepsy, prenatal exposure to carbamazepine (aOR: 1.27 (95% CI: 1.11-1.47)), oxcarbazepine (aOR: 1.42 (95% CI: 1.18-1.70)), clonazepam (aOR: 1.40 (95% CI: 1.03-1.89)), and topiramate (aOR: 1.86 (95% CI: 1.36-2.54)) was associated with being born small for gestational age; carbamazepine, with microcephaly (aOR: 1.51 (95% CI: 1.17-1.95)). No associations with small for gestational age and microcephaly were identified after prenatal exposure to lamotrigine, valproate, gabapentin, levetiracetam, phenobarbital, acetazolamide, phenytoin, clobazam, primidone, zonisamide, vigabatrin, ethosuximide and lacosamide, but except for lamotrigine, valproate, gabapentin, and levetiracetam, numbers of exposed children were small.
UNASSIGNED: Prenatal exposure to carbamazepine, oxcarbazepine, clonazepam, and topiramate was associated with increased risk of being born small for gestational age in both the overall population and in children of women with epilepsy suggesting that prenatal exposure to these drugs is associated with fetal growth restriction.
UNASSIGNED: The NordForsk Nordic Program on Health and Welfare (83539), the Independent Research Fund Denmark (1133-00026B), the Danish Epilepsy Association, the Central Denmark Region, the Novo Nordisk Foundation (NNF16OC0019126 and NNF22OC0075033), and the Lundbeck Foundation (R400-2022-1205).
摘要：
■胎儿生长受限的短期和长期后果引起相当大的关注，产前暴露于不同的抗癫痫药物（ASM）如何影响胎儿生长仍不确定。
这是一项基于人口的队列研究，研究对象是在丹麦出生的单胎活体婴儿，芬兰,冰岛,挪威,瑞典从1996年到2017年。产前暴露被定义为在国家处方登记处登记的妊娠期间母体填写ASM处方，主要结局是小头畸形或小于胎龄出生的调整比值比（aOR）。
■我们确定了4,494,918名儿童（男性：51.3%，2,306,991/4,494,918)，包括38,714名（0.9％）癫痫母亲的孩子。在总人口中,产前单药治疗卡马西平（AOR：1.25（95％CI：1.12-1.40）），普瑞巴林（AOR：1.16（95%CI：1.02-1.31）），奥卡西平（AOR：1.48（95%CI：1.28-1.71）），氯硝西泮（AOR：1.27（95%CI：1.10-1.48）），和托吡酯（aOR：1.48（95％CI：1.18-1.85））与出生小于胎龄的风险相关，卡马西平与小头畸形相关(aOR:1.43(95%CI:1.17-1.75))。在患有癫痫的母亲的孩子中，产前卡马西平暴露(aOR：1.27(95%CI：1.11-1.47))，奥卡西平（AOR：1.42（95%CI：1.18-1.70）），氯硝西泮（AOR：1.40（95%CI：1.03-1.89）），和托吡酯(aOR:1.86(95%CI:1.36-2.54))与小于胎龄出生有关；卡马西平，小头畸形（aOR：1.51（95％CI：1.17-1.95））。产前暴露于拉莫三嗪后，未发现与胎龄小和小头畸形的关联，丙戊酸盐,加巴喷丁,左乙拉西坦,苯巴比妥,乙酰唑胺,苯妥英,Clobazam,普米酮,唑尼沙胺，vigabatrin,乙苏肟和拉科沙胺，但除了拉莫三嗪,丙戊酸盐,加巴喷丁,和左乙拉西坦,暴露儿童的数量很少。
■产前接触卡马西平，奥卡西平,氯硝西泮,在总体人群和癫痫女性儿童中,托吡酯与出生小于胎龄的风险增加相关,提示产前接触这些药物与胎儿生长受限相关.
■NordForsk北欧卫生与福利计划（83539），丹麦独立研究基金（1133-00026B），丹麦癫痫协会,丹麦中部地区,诺和诺德基金会（NNF16OC0019126和NNF22OC0075033），和伦德贝克基金会（R400-2022-1205）。
这是一项基于人口的队列研究，研究对象是在丹麦出生的单胎活体婴儿，芬兰,冰岛,挪威,瑞典从1996年到2017年。产前暴露被定义为在国家处方登记处登记的妊娠期间母体填写ASM处方，主要结局是小头畸形或小于胎龄出生的调整比值比（aOR）。
■我们确定了4,494,918名儿童（男性：51.3%，2,306,991/4,494,918)，包括38,714名（0.9％）癫痫母亲的孩子。在总人口中,产前单药治疗卡马西平（AOR：1.25（95％CI：1.12-1.40）），普瑞巴林（AOR：1.16（95%CI：1.02-1.31）），奥卡西平（AOR：1.48（95%CI：1.28-1.71）），氯硝西泮（AOR：1.27（95%CI：1.10-1.48）），和托吡酯（aOR：1.48（95％CI：1.18-1.85））与出生小于胎龄的风险相关，卡马西平与小头畸形相关(aOR:1.43(95%CI:1.17-1.75))。在患有癫痫的母亲的孩子中，产前卡马西平暴露(aOR：1.27(95%CI：1.11-1.47))，奥卡西平（AOR：1.42（95%CI：1.18-1.70）），氯硝西泮（AOR：1.40（95%CI：1.03-1.89）），和托吡酯(aOR:1.86(95%CI:1.36-2.54))与小于胎龄出生有关；卡马西平，小头畸形（aOR：1.51（95％CI：1.17-1.95））。产前暴露于拉莫三嗪后，未发现与胎龄小和小头畸形的关联，丙戊酸盐,加巴喷丁,左乙拉西坦,苯巴比妥,乙酰唑胺,苯妥英,Clobazam,普米酮,唑尼沙胺，vigabatrin,乙苏肟和拉科沙胺，但除了拉莫三嗪,丙戊酸盐,加巴喷丁,和左乙拉西坦,暴露儿童的数量很少。
■产前接触卡马西平，奥卡西平,氯硝西泮,在总体人群和癫痫女性儿童中,托吡酯与出生小于胎龄的风险增加相关,提示产前接触这些药物与胎儿生长受限相关.
■NordForsk北欧卫生与福利计划（83539），丹麦独立研究基金（1133-00026B），丹麦癫痫协会,丹麦中部地区,诺和诺德基金会（NNF16OC0019126和NNF22OC0075033），和伦德贝克基金会（R400-2022-1205）。
