Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life ( <.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.

There may be long-term adverse health effects of in-utero antiretroviral therapy exposure. Data on children reported through national HIV surveillance were linked to routinely collected cancer and death data: a process known as "flagging". Ninety-five per cent (2612) of reported children born in 2001-2004 in England or Wales who were uninfected or of indeterminate infection status were flagged. By the end of 2005, no cancers and 14 deaths (three uninfected and 11 indeterminate) had been notified.

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Against a background of increasing numbers of uninfected children born to HIV-infected women in Europe, we describe the social environment and occurrence of infectious disease in 1,667 infants enrolled in the European Collaborative Study (ECS) and followed prospectively. In the ECS, the proportion of children born to black women from Sub-Saharan Africa who acquired their HIV infection heterosexually has increased since the mid-1980s, while the proportion of those born to white women with a history of illicit drug use has decreased, in both northern and southern Europe. The percentage of children who had been in alternative (non-parental) care decreased from 17% (82/469) in 1985-1989 to 5% (23/436) in 1999-2002. A total of 135 infants (with 1,475 child-years of follow-up) experienced at least one moderate/severe infective or febrile episode requiring medical attention in the first year of life; there was little correlation with recorded sociodemographic and child characteristics. The rate of hospitalization remained relatively stable over the study period at between 243-299 admissions per 1,000 child-years. Description of disease burden and social circumstances of uninfected children is needed, not only because of their increasing numbers but also because they are often used as controls in studies addressing vertically-acquired HIV infection.

Most uninfected children born to diagnosed HIV-infected women in the United Kingdom (UK) are exposed to antiretroviral therapy (ART) in utero and neonatally, and concerns exist about potential adverse effects of such exposure. We explored the feasibility of using national clinic-based follow-up to investigate the association between ART exposure and adverse health events occurring after the neonatal period. (33.5%) were enrolled in CHART; parents of 4.8% (100/2104) declined, 2.8% (59/2104) had gone abroad, 21.6% (455/2104) were not contactable, and the remaining 37.3% (786/2104) were not enrolled mainly because of lack of clinic resources or unwillingness of health professionals to approach the families.Demographic characteristics and type of ART exposure for enrolled and non-enrolled children were similar. Latest information on enrolled children was available at a median age of 24 months. Minor childhood ailments were reported in the majority of children, febrile seizures in 1.6% (11/704), and major health problems in 3.8% (27/704). It was 3 reassuring that prevalence of these outcomes was within UK norms, but numbers were small and duration of follow-up was limited.The difficulties encountered in enrolling and retaining children in this study indicate that comprehensive clinic-based follow-up of ART-exposed uninfected children is not practical. Alternative approaches are required; a robust, secure data linkage protocol would provide a more feasible and sustainable system for long term monitoring of in utero ART exposure.4