Fernández Ibieta M, Ramos Amador J T, Bellón Cano J M, González-Tomé M I, Guillén Martín S, Navarro Gómez M, de José M I, Beceiro J, Iglesias E, Prieto L, Santos M J, Martínez Guardia N, Roa M A, Regidor J
Servicio de Pediatría, Hospital Universitario de Getafe, Madrid, España.
An Pediatr (Barc). 2009 Mar;70(3):253-64. doi: 10.1016/j.anpedi.2008.10.021. Epub 2009 Feb 25.
Mother-to-Child HIV transmission is now just 1% in western countries, due to prevention measures. Antiretroviral Treatment (ART) drugs do have adverse effects, anaemia and myelosupression caused by cidovudina being the most commonly observed effects. In the present study, we have analysed the proportion and characteristics of congenital malformations (CM) or birth defects (BD) in a cohort of uninfected children born to HIV-infected women.
A total of 623 uninfected children belonging to the FIPSE cohort were followed up according to standardised protocols. This cohort includes 8 public hospitals from Madrid and follows up HIV-infected pregnant women and their children. Children were classified according to prematurity, ethnic origin, birth weight, withdrawal syndrome, in-utero treatment. Birth defects were described and defined according to the EUROCAT, the European registry for BD. Mild errors of morphogenesis were excluded from the analysis. Categorical variables were compared with the X(2) or the Fisher test.
A total of 78% (486) of the mothers were of Caucasian origin; 18.8% (117) used some illicit drug (heroine, cocaine or methadone) during gestation; 51 mothers (8.1%) received no ART, 10 (1.6%) received monotherapy and 469 (75.3%) received HAART. BD were seen in 52 children, with the most frequent being genitourinary and cardiological. Anaemia in the first trimester was an associated risk for BD (17.9% vs. 8.1%, P = 0,04). Similarly, mothers who used any illicit drug (plus methadone), had a slightly higher risk for BD in their offspring (13.8% vs. 7.6%, P = 0,04) There was no increased risk for BD significantly associated with any of the in-utero used antiretrovirals, although Nevirapine use in-utero showed a protective effect. Children born to mothers who received ART in the first trimester had the same rate of BD (7.4%) as those whose mothers started ART in the second trimester (8.8%), P = 0,67.
The proportion of BD that we have observed seems higher than those shown in other European teratogenicity studies and also higher than those shown in cohorts with HIV and antiretroviral exposed infants. This may be due to the fact that our series show the results of an active surveillance system (that includes ultrasound), where BD classically appear in a higher proportion. Immunovirological characteristics of the mother did not influence the proportion of BD, but anaemia in the fist trimester and the use of illicit drugs (or methadone) did. No specific antiretroviral drug was associated with an increase in BD, although Nevirapine showed a possible protective effect in the statistical analysis. Mothers who started antiretrovirals in the first trimester do not have more BD in their offspring than mothers who started on antiretrovirals later on.
由于预防措施，西方国家母婴传播艾滋病病毒的比例目前仅为1%。抗逆转录病毒治疗（ART）药物确实有不良反应，齐多夫定引起的贫血和骨髓抑制是最常见的不良反应。在本研究中，我们分析了一组感染艾滋病病毒的妇女所生未感染儿童的先天性畸形（CM）或出生缺陷（BD）的比例及特征。
根据标准化方案对属于FIPSE队列的623名未感染儿童进行随访。该队列包括来自马德里的8家公立医院，对感染艾滋病病毒的孕妇及其子女进行随访。儿童根据早产、种族、出生体重、戒断综合征、宫内治疗情况进行分类。出生缺陷根据欧洲出生缺陷登记处EUROCAT进行描述和定义。分析中排除了轻度形态发生错误。分类变量采用X(2)检验或Fisher检验进行比较。
共有78%（486名）母亲为白种人；18.8%（117名）母亲在孕期使用过某些非法药物（海洛因、可卡因或美沙酮）；51名母亲（8.1%）未接受抗逆转录病毒治疗，10名（1.6%）接受单药治疗，469名（75.3%）接受高效抗逆转录病毒治疗。52名儿童出现出生缺陷，最常见的是泌尿生殖系统和心血管系统缺陷。孕早期贫血是出生缺陷的相关危险因素（17.9%对8.1%，P = 0.04）。同样，使用任何非法药物（加美沙酮）的母亲，其后代出现出生缺陷的风险略高（13.8%对7.6%，P = 0.04）。虽然宫内使用奈韦拉平显示出保护作用，但没有任何一种宫内使用的抗逆转录病毒药物与出生缺陷风险显著增加相关。孕早期接受抗逆转录病毒治疗的母亲所生儿童的出生缺陷发生率（7.4%）与孕中期开始接受抗逆转录病毒治疗的母亲所生儿童（8.8%）相同，P = 0.67。
我们观察到的出生缺陷比例似乎高于其他欧洲致畸性研究中的比例，也高于艾滋病病毒和抗逆转录病毒药物暴露婴儿队列中的比例。这可能是因为我们的系列研究显示了一个主动监测系统（包括超声检查）的结果，在该系统中出生缺陷通常以更高的比例出现。母亲的免疫病毒学特征不影响出生缺陷的比例，但孕早期贫血和非法药物（或美沙酮）的使用会影响。没有特定的抗逆转录病毒药物与出生缺陷增加相关，尽管在统计分析中奈韦拉平显示出可能的保护作用。孕早期开始使用抗逆转录病毒药物的母亲，其后代的出生缺陷并不比后期开始使用抗逆转录病毒药物的母亲更多。
