Infant Outcomes After Maternal Antiretroviral Exposure in Resource-Limited Settings

Nielsen‐Saines, Karin; Komarow, Lauren; Cu‐Uvin, Susan; Jourdain, Gonzague; Klingman, Karin L.; Shapiro, David E.; Mofenson, Lynne; Moran, Laura; Campbell, Thomas; Hitti, Jane; Fiscus, Susan A.; Currier, Judith S.

doi:10.1542/peds.2011-2340

Cited by 14 publications

(14 citation statements)

References 19 publications

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“…(31, 32, 35-37) (38-42) Existing research on HIV-exposed infants has suggested that HIV exposure alone may be a risk factor for other infections, particularly in infants born to women with advanced HIV infection, due to genital colonization of pathogens, subclinical chorioamnionitis, and lower protective antibody titers resulting in decreased transfer of passive immunity across the placenta. (43) However, while our infant cohort appeared to be at risk for adverse outcomes from HIV-exposure at baseline, we still found that infants born to CT and/or NG-infected mothers were more likely to have an adverse outcome, irrespective of infant HIV-infection.…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Adachi

Klausner

et al. 2016

Pediatric Infectious Disease Journal

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BACKGROUND Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. METHODOLOGY Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. RESULTS Of 1373 maternal urines, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG, and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery, death) were noted in infants of women with CT and NG (23/35, 65.7%) compared to NG (16/28, 57.1%), CT (84/214, 39.3%), and no STI (405/1096, 37%, p=0.001). Death (11.4% vs. 3%, p=0.02), low birth weight (42.9% vs. 16.9%, p=0.001), and preterm delivery (28.6% vs. 10.2%, p=0.008) were higher among infants of CT and NG co-infected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV-infected after controlling for maternal syphilis (OR 3.5, 95% CI 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (OR 1.35, 95% CI 1.03-1.76). CONCLUSION STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.

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Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Adachi

Klausner

et al. 2016

Pediatric Infectious Disease Journal

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“…What dictates “substantial” is debatable, but many consider outcomes involving birth weight [66–75], congenital defects [76–81], early neurodevelopment [82–84] and growth [70,75,85–87] as significant, and none of these have demonstrated a clear association with in utero HIV/ARV exposure (Table 3). Even pre-term birth, which has been shown in several studies to be associated with ART [74,89–92,95] is still an early infant outcome and would occur and be managed well before adolescence, the time of disclosure.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to antenatal AZT has not been found to be associated with SGA in the United States [66] or LBW in Europe [67]. In addition, studies in the United States [72,74] and another multi-country study [75] have reported no associations between antenatal ART and LBW/SGA. A large study in Latin America also did not find risks for LBW when comparing classes of ARVs [73].…”

Section: Discussionmentioning

confidence: 99%

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Jao

Hazra

Mellins

et al. 2016

Journal of the International AIDS Society

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IntroductionThe tremendous success of antiretroviral therapy has resulted in a diminishing population of perinatally HIV-infected children on the one hand and a mounting number of HIV-exposed uninfected (HEU) children on the other. As the oldest of these HEU children are reaching adolescence, questions have emerged surrounding the implications of HEU status disclosure to these adolescents. This article outlines the arguments for and against disclosure of a child's HEU status.DiscussionDisclosure of a child's HEU status, by definition, requires disclosure of maternal HIV status. It is necessary to weigh the benefits and harms which could occur with disclosure in each of the following domains: psychosocial impact, long-term physical health of the HEU individual and the public health impact. Does disclosure improve or worsen the psychological health of the HEU individual and extended family unit? Do present data on the long-term safety of in utero HIV/ARV exposure reveal potential health risks which merit disclosure to the HEU adolescent? What research and public health programmes or systems need to be in place to afford monitoring of HEU individuals and which, if any, of these require disclosure?ConclusionsAt present, it is not clear that there is sufficient evidence on whether long-term adverse effects are associated with in utero HIV/ARV exposures, making it difficult to mandate universal disclosure. However, as more countries adopt electronic medical record systems, the HEU status of an individual should be an important piece of the health record which follows the infant not only through childhood and adolescence but also adulthood. Clinicians and researchers should continue to approach the dialogue around mother–child disclosure with sensitivity and a cogent consideration of the evolving risks and benefits as new information becomes available while also working to maintain documentation of an individual's perinatal HIV/ARV exposures as a vital part of his/her medical records. As more long-term adult safety data on in utero HIV/ARV exposures become available these decisions may become clearer, but at this time, they remain complex and multi-faceted.

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“…The study did not report multivariate analyses adjusting for these or other factors such as maternal regimen or immunosuppression. (33)…”

Section: Intrauterine Growthmentioning

confidence: 99%

“…AZT. (33) Lastly, a secondary analysis of two RCTs in Botswana reported no differences in WAZ or WLZ by 6 months of age in infants exposed to in utero cART vs. AZT prophylaxis. (41)…”

Section: Postnatal Growthmentioning

confidence: 99%

Metabolic Complications of in utero Maternal HIV and Antiretroviral Exposure in HIV-exposed Infants

Jao

Abrams

2014

Pediatric Infectious Disease Journal

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Background Despite a wide body of literature supporting the use of antenatal antiretrovirals (ARV) for the prevention of mother to child transmission, there remains a need for continued monitoring as the intrauterine interval is a critical period during which fetal programming influences the future health and development of the child. Methods We conducted a systematic review of the current literature addressing potential metabolic complications of in utero HIV and ARV exposure. We describe studies evaluating metabolic outcomes such as intrauterine and early postnatal growth, bone health, and mitochondrial toxicity. Results Overall, infants exposed to HIV/ARV do not appear to exhibit vastly compromised intrauterine or early postnatal growth. However, some studies on the effect of combination antiretroviral therapy (cART) on small for gestational age (SGA) and low birth weight (LBW) outcomes in low-middle income countries show a risk for SGA/LBW while those in the U.S. do not. Postnatal growth to 1 year does not appear to be affected by intrauterine tenofovir exposure in African studies, but a U.S. study found statistically significant differences in length for age z scores (LAZ) at 1 year. Little data exists on long term bone health. Mitochondrial toxicity including abnormal mitochondrial morphology and DNA content, as well as neurologic deficits and death have been demonstrated in HIV/ARV–exposed infants. Conclusion Though gross measures of metabolic well-being appear to be reassuring, careful vigilance of even small risks for potential serious adverse effects to infants exposed to intrauterine HIV/ARVs is warranted as intrauterine fetal metabolic programming may substantially impact the future health of the child.

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Infant Outcomes After Maternal Antiretroviral Exposure in Resource-Limited Settings

Cited by 14 publications

References 19 publications

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

Metabolic Complications of in utero Maternal HIV and Antiretroviral Exposure in HIV-exposed Infants

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