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抗肿瘤坏死因子 α 抗体在炎症性肠病孕妇中的应用对暴露儿童长期结局的影响。

Impact of anti-tumor necrosis factor alpha antibodies administered to pregnant women with inflammatory bowel disease on long-term outcome of exposed children.

机构信息

*IBD Clinical and Research Centre, ISCARE, Charles University, Prague, Czech Republic; †Department of Internal Medicine, Military Hospital, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; ‡Department of Internal Medicine, University Hospital Plzen, Plzen, Czech Republic; §Department of Internal Medicine, Thomayer University Hospital, Prague, Czech Republic; ‖Department of Paediatrics, 2nd Faculty of Medicine, University Hospital Motol, Charles University, Prague, Czech Republic; ¶Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic; and **General University Hospital in Prague, Prague, Czech Republic.

出版信息

Inflamm Bowel Dis. 2014 Mar;20(3):495-501. doi: 10.1097/01.MIB.0000440984.86659.4f.

DOI:10.1097/01.MIB.0000440984.86659.4f
PMID:24407486
Abstract

BACKGROUND

Prenatal exposure to anti-tumor necrosis factor α (TNF-α) antibodies seems to be safe for fetal development. Data on long-term outcome of exposed children are missing. Our aim was to assess long-term postnatal development of children exposed to anti-TNF-α during pregnancy.

METHODS

Consecutive children aged ≥ 12 months exposed to anti-TNFs prenatally for maternal inflammatory bowel disease in 3 centers in the Czech Republic were enrolled. Data on psychomotor development, infections, antibiotics, vaccination, and allergy were retrospectively obtained from mothers, treating pediatricians, and children's vaccination cards. Furthermore, standardized laboratory tests on humoral and cellular immunity were performed.

RESULTS

Twenty-five children exposed to biologicals were included (median age, 34 mo; range, 14-70 mo). All children had normal growth, and all but 1 had normal psychomotor development. Majority (80%) experienced at least 1 infection (mainly respiratory), and 60% of infants received antibiotics, 32% of those within the first year of life. Vaccination was undertaken according to vaccination protocol to 23 infants (92%). Fifteen children also had tuberculosis vaccination without serious complication. Immunological investigation was performed with 17 children (68%). Cellular immunity was normal in all infants, and 7 children had mild decrease in IgA and/or IgG immunoglobulins without clinical significance. All children had a detectable serologic response to vaccination.

CONCLUSIONS

Exposure to anti-TNF-α antibodies seems to be safe for growth and psychomotor development of children, although clinical significance of relatively high frequency of infections and antibiotic use among infants remains questionable because of the lack of a control group. Continuous follow-up of exposed children is absolutely warranted.

摘要

背景

产前接触抗肿瘤坏死因子α(TNF-α)抗体似乎对胎儿发育安全。关于暴露儿童的长期结局的数据尚缺乏。我们的目的是评估在捷克共和国 3 个中心暴露于抗 TNF-α的孕妇所生儿童的长期出生后发育情况。

方法

连续纳入在 3 个中心因母亲炎症性肠病而在孕期接受抗 TNF 治疗的≥12 月龄的连续暴露于抗 TNF 药物的儿童。从母亲、治疗儿科医生和儿童疫苗接种卡中回顾性获得关于精神运动发育、感染、抗生素、疫苗接种和过敏的数据。此外,还进行了体液和细胞免疫的标准化实验室检测。

结果

共纳入 25 名接受生物制剂治疗的儿童(中位年龄 34 月龄;范围 14-70 月龄)。所有儿童均生长正常,除 1 名外所有儿童均精神运动发育正常。大多数(80%)经历了至少 1 次感染(主要为呼吸道感染),60%的婴儿接受了抗生素治疗,其中 32%在 1 岁以内接受了治疗。23 名婴儿(92%)按照疫苗接种方案进行了疫苗接种。15 名儿童还进行了结核菌素疫苗接种,无严重并发症。17 名儿童(68%)进行了免疫研究。所有婴儿的细胞免疫均正常,7 名儿童的 IgA 和/或 IgG 免疫球蛋白轻度下降,但无临床意义。所有儿童对疫苗接种均有可检测的血清学反应。

结论

暴露于抗 TNF-α抗体似乎对儿童的生长和精神运动发育是安全的,尽管由于缺乏对照组,婴儿感染和抗生素使用的相对较高频率的临床意义仍存在疑问。绝对需要对暴露儿童进行持续随访。

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