近日，美国贝斯以色列女执事医疗中心教授Rebecca Zash及其课题组探讨了博茨瓦纳神经管缺陷新生儿和抗逆转录病毒治疗（ART）方案的关系。相关论文2019年8月29日发表在《新英格兰医学杂志》上。

研究人员在博茨瓦纳各地的医院开展了分娩结果监测，从2018年的8个点扩大到18个点。训练有素的助产士对所有活产和死产婴儿进行表面检查。研究助理在获得母亲同意后拍摄异常情况。2014年8月至2019年3月，研究组共监测了119477例分娩，其中119033例（99.6%）进行了可评估的婴儿表面检查，共发现98例神经管缺陷（0.08%）。

1683例怀孕时服用dolutegravir的母亲娩出5例神经管缺陷儿（占分娩的0.30%），包括两例脊髓脊膜膨出，一例无脑畸形，一例脑膨出和一例枕骨裂脑露畸形。相比之下，14792例怀孕时接受非dolutegravir ART的母亲娩出15例（0.10%）神经管缺陷儿，7959例怀孕时服用依法韦仑的母亲娩出3例（0.04%）神经管缺陷儿，3840例妊娠期才开始服用dolutegravir的母亲娩出1例神经管缺陷儿（0.03%），而在89372例未感染艾滋病的母亲中，共娩出70例神经管缺陷儿（0.08%）。

神经管缺陷的发生率与怀孕时使用dolutegravir治疗的相关性高于怀孕时进行非dolutegravir ART（差值为0.2个百分点）或其他类型的ART。怀孕时接触dolutegravir的母亲娩出的婴儿发生重大外部结构缺陷的风险为0.95%，而怀孕时接触非dolutegravir的母亲娩出的婴儿风险为0.68%，差异为0.27个百分点。

据悉，神经管缺陷的初步安全信号与受孕时dolutegravir暴露有关，这影响了对HIV感染的育龄妇女进行ART的选择。

附：英文原文

Title: Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana

Author: Rebecca Zash, M.D., Lewis Holmes, M.D., Modiegi Diseko, et al

Issue&Volume: Vol 381 No 9, 29 August 2019

Abstract: 

BACKGROUND
A preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)–infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies.

METHODS
We conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals.

RESULTS
From August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, −0.13 to 0.87).

CONCLUSIONS
The prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.)

DOI: 10.1056/NEJMoa1905230

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905230