Background Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. Methods Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. Discussion The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity. Trial registration ClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019.
The evidence that perioperative antibiotics for caesarean delivery are effective in reducing infective morbidity is unequivocal. In developing countries, especially those with high HIV-prevalence, clinicians have increasingly become anxious about the efficacy of perioperative antibiotics, hence the adoption of treatment regimens, as described in this study. We set out to investigate if these fears have a basis by conducting a randomised clinical trial. The setting was two tertiary units in a developing country with a significant HIV-prevalence. The outcome measures assessed were: pyrexia, wound infection, admission with puerperal sepsis, laparotomy for pelvic abscess and duration of hospital stay. There was no statistically significant difference between the two arms of the study with regard to the above outcomes. Our conclusion is that the two antibiotic regimens are equivalent in preventing infection, therefore there is no justification for subjecting patients to week-long antibiotics and the unnecessary increase in nurse workload.
Pregnant women with severe mitral stenosis tend to experience clinical decompensation with approximately 50% mortality and they may experience adverse effects of the medication they are taking, notably congenital malformations from warfarin exposure. Corrective heart surgery may increase the risk of pregnancy loss. We present 2 cases of RHD in pregnancy. The first case was a 27-year-old patient in her first pregnancy with severe mitral stenosis. Caesarean section was done for foetal distress and she delivered a small for gestational age baby. She was closely monitored postpartum and was stable on discharge. She presented with supraventricular tachycardia and died in the coronary care unit 4 weeks postpartum. The second case was a 28-year-old who was on warfarin for a mechanical mitral valve. A foetal anomaly scan done at 20 weeks showed severe congenital malformations which were not compatible with extra-uterine life. The pregnancy was terminated and she recovered well. The first case illustrates the significant mortality risk with uncorrected severe rheumatic heart disease. The second case highlights the risks of warfarin on the foetus and the need to avoid mechanical heart valves if possible in young women. RHD patients require preconception counselling so they can make informed reproductive choices.
Introduction Despite being a leading infectious cause of childhood disability globally, testing for cytomegalovirus (CMV) infections in pregnancy is generally not done in Sub-Sahara Africa (SSA), where breastfeeding practice is almost universal. Whilst CMV and human immunodeficiency virus (HIV) are both endemic in SSA, the relationship between antenatal plasma CMV-DNA, HIV-1-RNA levels and HIV-1-mother to child transmission (MTCT) including pregnancy outcomes remains poorly described. Methods Pregnant women at least 20 weeks’ gestational age at enrolment were recruited from relatively poor high-density suburbs in Harare, Zimbabwe. Mother-infant dyads were followed up until 6 months postpartum. In a case–control study design, we tested antenatal plasma CMV-DNA levels in all 11 HIV-1 transmitting mothers, as well as randomly selected HIV-infected but non-transmitting mothers and HIV-uninfected controls. CMV-DNA was detected and quantified using polymerase chain reaction (PCR) technique. Antenatal plasma HIV-1-RNA load was quantified by reverse transcriptase PCR. Infants’ HIV-1 infection was detected using qualitative proviral DNA-PCR. Predictive value of antenatal plasma CMV-DNAemia (CMV-DNA of > 50 copies/mL) for HIV-1-MTCT was analyzed in univariate and multivariate regression analyses. Associations of CMV-DNAemia with HIV-1-RNA levels and pregnancy outcomes were also explored. Results CMV-DNAemia data were available for 11 HIV-1 transmitting mothers, 120 HIV-infected but non-transmitting controls and 46 HIV-uninfected mothers. In a multivariate logistic regression model, we found a significant association between CMV-DNAemia of > 50 copies/mL and HIV-1 vertical transmission (p = 0.035). There was no difference in frequencies of detectable CMV-DNAemia between HIV-infected and -uninfected pregnant women (p = 0.841). However, CMV-DNA levels were higher in immunosuppressed HIV-infected pregnant women, CD4 < 200 cells/µL (p = 0.018). Non-significant associations of more preterm births (< 37 weeks, p = 0.063), and generally lower birth weights (< 2500 g, p = 0.450) were observed in infants born of HIV-infected mothers with CMV-DNAemia. Furthermore, in a multivariate analysis of HIV-infected but non-transmitting mothers, CMV-DNAemia of > 50 copies/mL correlated significantly with antenatal plasma HIV-1-RNA load (p = 0.002). Conclusion Antenatal plasma CMV-DNA of > 50 copies/mL may be an independent risk factor for HIV-1-MTCT and higher plasma HIV-1-RNA load, raising the possibility that controlling antenatal CMV-DNAemia might improve infant health outcomes. Further studies with larger sample sizes are warranted to confirm our findings.
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