Anders Husby, Kim D Jakobsen, Jan Wohlfahrt, Mads Melbye
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Using long-term follow-up of a nationwide sibling cohort in Denmark with information on maternal antimicrobial prescriptions in community pharmacies and in-patient hospitalizations for infection, we aimed to estimate the effect of maternal infections during pregnancy on offspring school grades and intelligence test results in adolescence.</p><p><strong>Methods and findings: </strong>From population-based national registries we defined a cohort of all full-siblings, born from January 1, 1996 to December 31, 2,003 in Denmark, and linked them to maternal filled prescription for antimicrobial pharmaceuticals and maternal hospitalizations for infection during pregnancy. Standardized examination grades in language and mathematics at the final year of compulsory schooling, in addition to intelligence test scores (calculated as IQ) for a nested sub-cohort of full brothers, were used as outcomes. Among 274,166 children in the full-sibling cohort, 80,817 (29.5%) had a mother who during her pregnancy filled a prescription for a systemic antimicrobial, while 5,628 (2.1%) had a mother who during her pregnancy was hospitalized due to an infection. We found no consistent difference in school grades in language (z-score difference, 0.0, 95% confidence interval [CI] [-0.0,0.0]; p = 0.920) and mathematics (z-score difference, -0.0, 95% CI [-0.0,-0.0]; p = 0.042), and in IQ (IQ-difference, 0.3, 95% CI [-0.2,0.7]; p = 0.217), in children whose mother filled one antimicrobial prescription compared with children whose mother did not fill any, when taking shared family factors into account, while many associations were consistently significant when not taking shared family factors into account. Furthermore, we found no indication of an impact of maternal in-patient hospitalizations for infections during pregnancy on school grades (z-score difference for language, -0.0, 95% CI [-0.1,0.0]; p = 0.103; z-score difference for mathematics, 0.0, 95% CI [-0.0,0.0]; p = 0.809) or IQ (IQ-difference, 0.4, 95% CI [-0.8,1.6]; p = 0.545), when also taking shared family factors into account. Similar findings were found when considering infections in bi-weekly exposure periods during gestation. 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Using long-term follow-up of a nationwide sibling cohort in Denmark with information on maternal antimicrobial prescriptions in community pharmacies and in-patient hospitalizations for infection, we aimed to estimate the effect of maternal infections during pregnancy on offspring school grades and intelligence test results in adolescence.</p><p><strong>Methods and findings: </strong>From population-based national registries we defined a cohort of all full-siblings, born from January 1, 1996 to December 31, 2,003 in Denmark, and linked them to maternal filled prescription for antimicrobial pharmaceuticals and maternal hospitalizations for infection during pregnancy. Standardized examination grades in language and mathematics at the final year of compulsory schooling, in addition to intelligence test scores (calculated as IQ) for a nested sub-cohort of full brothers, were used as outcomes. 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引用次数: 0
摘要
背景:母体感染在怀孕期间很常见,但目前尚不清楚它们如何影响后代的认知结果,许多研究表明有不良影响。我们对丹麦全国范围内的兄弟姐妹队列进行了长期随访,了解了社区药房的母亲抗微生物药物处方和因感染而住院的信息,目的是估计怀孕期间母亲感染对子女学业成绩和青春期智力测试结果的影响。方法和研究结果:从以人口为基础的国家登记中,我们定义了一个由1996年1月1日至2003年12月31日在丹麦出生的所有全兄妹组成的队列,并将他们与母亲在怀孕期间服用抗菌药物的处方和母亲因感染住院的情况联系起来。在义务教育的最后一年,语言和数学的标准化考试成绩,以及一个嵌套的全兄弟子队列的智力测试分数(以智商计算)被用作结果。在全同胞队列的274,166名儿童中,80,817名(29.5%)的母亲在怀孕期间服用了全身性抗菌药物,而5,628名(2.1%)的母亲在怀孕期间因感染住院。我们发现学校成绩在语言方面没有一致的差异(z-score difference, 0.0, 95%置信区间[CI] [-0.0,0.0];p = 0.920)和数学(z-score difference, -0.0, 95% CI [-0.0,-0.0];p = 0.042),在智商(IQ-difference, 0.3, 95%可信区间(-0.2,0.7);P = 0.217),当考虑到共同的家庭因素时,母亲服用一种抗菌药物处方的儿童与母亲不服用任何一种抗菌药物处方的儿童相比,而当不考虑共同的家庭因素时,许多关联始终显著。此外,我们没有发现任何迹象表明孕妇在怀孕期间因感染住院治疗对学校成绩有影响(语言z-score差异,-0.0,95% CI [-0.1,0.0];p = 0.103;数学z-score差异,0.0,95% CI [-0.0,0.0];p = 0.809)或智商(IQ-difference, 0.4, 95%可信区间(-0.8,1.6);P = 0.545),同时考虑到共同的家庭因素。在考虑妊娠期间每两周接触一次的感染时,也发现了类似的结果。该研究的主要局限性是缺乏关于医院内部药物处方和潜在致病微生物的信息。结论:我们的研究不支持妊娠期常见的母体感染对后代认知结果的主要影响,并支持妊娠期常用的抗微生物药物对后代长期认知结果的安全性。
Maternal infections during pregnancy and offspring cognitive outcome: A nationwide full-sibling cohort study.
Background: Maternal infections are common during pregnancy, but it is unclear how they impact the cognitive outcome of the offspring, with many studies suggesting adverse effects. Using long-term follow-up of a nationwide sibling cohort in Denmark with information on maternal antimicrobial prescriptions in community pharmacies and in-patient hospitalizations for infection, we aimed to estimate the effect of maternal infections during pregnancy on offspring school grades and intelligence test results in adolescence.
Methods and findings: From population-based national registries we defined a cohort of all full-siblings, born from January 1, 1996 to December 31, 2,003 in Denmark, and linked them to maternal filled prescription for antimicrobial pharmaceuticals and maternal hospitalizations for infection during pregnancy. Standardized examination grades in language and mathematics at the final year of compulsory schooling, in addition to intelligence test scores (calculated as IQ) for a nested sub-cohort of full brothers, were used as outcomes. Among 274,166 children in the full-sibling cohort, 80,817 (29.5%) had a mother who during her pregnancy filled a prescription for a systemic antimicrobial, while 5,628 (2.1%) had a mother who during her pregnancy was hospitalized due to an infection. We found no consistent difference in school grades in language (z-score difference, 0.0, 95% confidence interval [CI] [-0.0,0.0]; p = 0.920) and mathematics (z-score difference, -0.0, 95% CI [-0.0,-0.0]; p = 0.042), and in IQ (IQ-difference, 0.3, 95% CI [-0.2,0.7]; p = 0.217), in children whose mother filled one antimicrobial prescription compared with children whose mother did not fill any, when taking shared family factors into account, while many associations were consistently significant when not taking shared family factors into account. Furthermore, we found no indication of an impact of maternal in-patient hospitalizations for infections during pregnancy on school grades (z-score difference for language, -0.0, 95% CI [-0.1,0.0]; p = 0.103; z-score difference for mathematics, 0.0, 95% CI [-0.0,0.0]; p = 0.809) or IQ (IQ-difference, 0.4, 95% CI [-0.8,1.6]; p = 0.545), when also taking shared family factors into account. Similar findings were found when considering infections in bi-weekly exposure periods during gestation. The main limitations of the study were lacking information on within hospital pharmaceutical prescriptions and the underlying pathogenic microorganisms.
Conclusions: Our study does not support major effects of common maternal infections during pregnancy on offspring cognitive outcomes, and support the safety of commonly prescribed antimicrobials during pregnancy with respect to the long-term cognitive outcomes of the offspring.
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