Effect of Maternal Use of Antiretroviral Agents on Serum Insulin Levels of the Newborn Infant

Abstract

OBJECTIVE -The aim of this study was to investigate the effect of antiretroviral drugs on neonatal serum insulin levels. RESEARCH DESIGN AND METHODS-A prospective study was conducted on 57 pregnant women divided into three groups: the zidovudine (ZDV) group, HIV-infected women taking ZDV (n ϭ 20); the triple treatment group, HIV-infected women taking triple antiretroviral agents ZDV ϩ lamivudine ϩ nelfinavir (n ϭ 25); and the control group, pregnant women considered normal from a clinical and laboratory standpoint (n ϭ 12). Blood was collected from the umbilical cord of newborn infants upon delivery for measurement of insulin level. The insulin measurements were performed in duplicate by radioimmunoassay.RESULTS -Demographic and anthropometric data were homogeneous, and pregnant women with a personal and family history of diabetes were excluded. There was no difference between groups regarding glycemia in the newborn. Median newborn insulin doses were 2.9, 4.8, and 6.5 U/ml for the triple treatment, ZDV, and control groups, respectively (P Ͻ 0.05).CONCLUSIONS -Use of triple therapy during pregnancy induced a significant decrease in serum levels of neonatal insulin compared with the control group. Active surveillance of shortand long-term adverse events is imperative to issue a definitive statement regarding the impact that use of protease inhibitors during pregnancy will have on infant metabolism. Diabetes Care 28:856 -859, 2005T he objective reduction of vertical transmission of HIV type 1 (HIV-1) with the use of antiretroviral drugs represents one of the most notable advances in the fight against the infection because it permits a reduction of Ͼ70% of this form of transmission. However, some adverse effects are associated with the use of these medications. Among these possible adverse effects are changes in glucose metabolism, especially with the use of protease inhibitors (1,2).Despite the association between the use of protease inhibitors and adverse glycemic metabolic effects, little evidence is available regarding unequivocal proof of the safety on uninfected infants born to HIV-infected mothers taking antiretroviral drugs (3). In the present series, we evaluated the effect of antiretroviral drugs during gestation on the glucose and insulin levels from the newborn infant. RESEARCH DESIGN AND METHODS-A prospective cohort study was conducted from September 2001 to March 2003 on 57 women aged 16 -43 years with singleton gestations.A total of 45 of these women were infected with HIV-1; the remaining 12 women were normal in both clinical and laboratory terms and were selected at the time they started prenatal care. The present study was approved by the research ethics committee of the institution, and written informed consent to participate was obtained from each subject.Women were considered infected with HIV-1 when two different serum samples were found to be positive for HIV-1 antibodies by enzyme-linked immunoassay and confirmed by Western blot. Only HIV-infected patients who had not been treated previously...

Effects of antiretroviral agents during pregnancy on liver enzymes and amylase in HIV-exposed, uninfected newborn infants

“…It has been suggested that limited transfer of protease inhibitors may result from their high degree of plasma protein binding and their backwards transport through P-glycoprotein, largely expressed in the placenta [7]. Although there have been few studies analyzing adverse metabolic and biochemical effect of maternal ARV drugs on infant health [8], there have been no reports of the hepatic parameters of newborn infants during the immediate postnatal period [3].…”

“…While our data are reassuring, we emphasize the need for careful monitoring for hepatotoxicity after initiation of antiretroviral therapy. Follow-up is still limited and needs to be continued into adulthood before it can be concluded that there is no potential toxicity of maternal ARV treatment [8,19].…”

Estratégias que reduzem a transmissão vertical do vírus da imunodeficiência humana tipo 1

“…Dos efeitos fetais indesejáveis referentes ao uso dos inibidores da protease, os mais relatados são a prematuridade e a restrição de crescimento intra-útero 21,22 , mas existem discordâncias 23 . Recentemente, foi relatada também a ocorrência de insulinopenia neonatal em crianças nascidas de mães que utilizaram estes fármacos durante a gravidez 24 .…”

Managing Mother-to-Child Transmission of HIV Infection in Developed-Country Settings

“…• Glucose intolerance and gestational diabetes risk may be increased among women on highly active antiretroviral therapy (HAART), particularly in those receiving protease inhibitors, and reduced serum insulin levels have been reported in HAART-exposed newborns [104][105][106][107] Lactic acidosis…”