3児の親さん薬剤師のブログ

とある薬剤師です。感染症治療を考える素材をちょこっと提供。noteもあります https://note.com/twin1980

Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study

BMJに報告された、英国における妊娠中のマクロライド系抗生物質処方と小児の有害転帰との関連について。とても貴重な報告です。

 

Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study | The BMJ

 

 感想

 

マクロライドと新生児といえば、BMJから2014年に報告された乳児肥厚性幽門狭窄症があります(BMJ 2014;348:g1908.)。

妊娠中とマクロライド使用については、Plos oneからてんかんなどとの関連性の報告があります( PLoS ONE 10(3): e0122034)。

また、流産リスクの可能性もあると報告されてます()。

 

今回の報告は、

妊娠中のマクロライド系抗菌薬服用は、胎児奇形のリスク上昇と相関する。ということ
かなり影響がありそうな研究結果です。

 

日本でも同じなのかどうかは追加検証が必要ですが、

性器クラミジア感染症の場合はマクロライド系抗菌薬を用いていますが、やはり重要なのは妊娠前に性感染を予防することでしょう。

 

 

 

Abstract


Objective

To assess the association between macrolide antibiotics prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder in children.

 

Design

Population based cohort study.

 

Setting

The UK Clinical Practice Research Datalink.

 

Participants

The study cohort included 104 605 children born from 1990 to 2016 whose mothers were prescribed one macrolide monotherapy (erythromycin, clarithromycin, or azithromycin) or one penicillin monotherapy from the fourth gestational week to delivery. Two negative control cohorts consisted of 82 314 children whose mothers were prescribed macrolides or penicillins before conception, and 53 735 children who were siblings of the children in the study cohort.

 

Main outcome measures

Risks of any major malformations and system specific major malformations (nervous, cardiovascular, gastrointestinal, genital, and urinary) after macrolide or penicillin prescribing during the first trimester (four to 13 gestational weeks), second to third trimester (14 gestational weeks to birth), or any trimester of pregnancy. Additionally, risks of cerebral palsy, epilepsy, attention deficit hyperactivity disorder, and autism spectrum disorder.

 

Results

Major malformations were recorded in 186 of 8632 children (21.55 per 1000) whose mothers were prescribed macrolides and 1666 of 95 973 children (17.36 per 1000) whose mothers were prescribed penicillins during pregnancy. Macrolide prescribing during the first trimester was associated with an increased risk of any major malformation compared with penicillin (27.65 v 17.65 per 1000, adjusted risk ratio 1.55, 95% confidence interval 1.19 to 2.03) and specifically cardiovascular malformations (10.60 v 6.61 per 1000, 1.62, 1.05 to 2.51). Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (4.75 v 3.07 per 1000, 1.58, 1.14 to 2.19, mainly hypospadias). Erythromycin in the first trimester was associated with an increased risk of any major malformation (27.39 v 17.65 per 1000, 1.50, 1.13 to 1.99). No statistically significant associations were found for other system specific malformations or for neurodevelopmental disorders. Findings were robust to sensitivity analyses.

 

Conclusions

Prescribing macrolide antibiotics during the first trimester of pregnancy was associated with an increased risk of any major malformation and specifically cardiovascular malformations compared with penicillin antibiotics. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations. These findings show that macrolides should be used with caution during pregnancy and if feasible alternative antibiotics should be prescribed until further research is available.

 

Trial registration ClinicalTrials.gov NCT03948620