Adverse birth outcomes and their clinical phenotypes in an urban Zambian cohort

Price, Joan T.; Vwalika, Bellington; Rittenhouse, Katelyn J.; Mwape, Humphrey; Winston, Jennifer; Freeman, Bethany L.; Sindano, Ntazana; Stringer, Elizabeth M.; Kasaro, Margaret P.; Benjamin, H.; Stringer, Jeffrey S. A.

doi:10.12688/gatesopenres.13046.2

Cited by 15 publications

(18 citation statements)

References 59 publications

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“…The low overall risk of preterm birth and stillbirth in our trial might also be partly attributed to differences in HIV disease severity, immune sup pression, or ART use com pared with earlier reports. However, two contemporaneous cohorts drawn from the same patient population in Lusaka reported substantially higher rates of this composite outcome, 25,26 a finding that persisted even after applying the IPOP trial's inclusion and exclusion criteria (data not shown). One important way that the IPOP trial differs from these studies is in its weekly visit schedule.…”

Section: Discussionmentioning

confidence: 97%

Weekly 17 alpha-hydroxyprogesterone caproate to prevent preterm birth among women living with HIV: a randomised, double-blind, placebo-controlled trial

et al. 2021

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Background Women with HIV face an increased risk of preterm birth. 17 alpha-hydroxyprogesterone caproate (17P) has been shown in some trials to reduce early delivery among women with a history of spontaneous preterm birth. We investigated whether 17P would reduce this risk among women with HIV. MethodsWe did a randomised, double-blind, placebo-controlled trial in pregnant women with HIV at the University Teaching Hospital and Kamwala District Health Centre in Lusaka, Zambia. Eligible patients were women aged 18 years or older with confirmed HIV-1 infection, viable intrauterine singleton pregnancy at less than 24 weeks of gestation, and were receiving or intending to commence antiretroviral therapy during pregnancy. Exclusion criteria were major uterine or fetal anomaly; planned or in situ cervical cerclage; evidence of threatened miscarriage, preterm labour, or ruptured membranes at screening; medical contraindication to 17P; previous participation in the trial; or history of spontaneous preterm birth. Eligible participants provided written informed consent and were randomly assigned (1:1) to receive 250 mg intramuscular 17P or placebo once per week, starting between 16 and 24 weeks of gestation until delivery, stillbirth, or reaching term (37 weeks). Participants and study staff were masked to assignment, except for pharmacy staff who did random assignment and prepared injections but did not interact with participants. The primary outcome was a composite of delivery before 37 weeks or stillbirth at any gestational age. Patients attended weekly visits for study drug injections and antenatal care. We estimated the absolute and relative difference in risk of the primary outcome and safety events between treatment groups by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03297216, and is complete.Findings Between Feb 7, 2018 and Jan 13, 2020, we assessed 1042 women for inclusion into the study. 242 women were excluded after additional assessments, and 800 eligible patients were enrolled and randomly assigned to receive intramuscular 17P (n=399) or placebo (n=401). Baseline characteristics were similar between groups. Adherence to study drug injections was 98% in both groups, no patients were lost to follow-up, and the final post-partum visit was on Aug 6, 2020. 36 (9%) of 399 participants assigned to 17P had preterm birth or stillbirth, compared with 36 (9%) of 401 patients assigned to placebo (risk difference 0•1, 95% CI -3•9 to 4•0; relative risk 1•0, 95% CI 0•6 to 1•6; p=0•98). Intervention-related adverse events were reported by 140 (18%) of 800 participants and occurred in similar proportions in both randomisation groups. No serious adverse events were reported.Interpretation Although 17P seems to be safe and acceptable to participants, available data do not support the use of the drug to prevent preterm birth among women whose risk derives solely from HIV infection. The low risk of preterm birth in both randomisation groups warrants further investigation.Funding US National Institutes ...

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Section: Discussionmentioning

confidence: 97%

Weekly 17 alpha-hydroxyprogesterone caproate to prevent preterm birth among women living with HIV: a randomised, double-blind, placebo-controlled trial

et al. 2021

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“…ZAPPS is an ongoing observational antenatal cohort established at the Women and Newborn Hospital of the University Teaching Hospital in Lusaka to characterize factors associated with adverse birth outcomes. The data and specimens used in the current analysis are all derived from participants in the first phase of ZAPPS, which completed enrollment in September 2017 and follow-up in June 2018 [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…Participants who enroll in ZAPPS are provided routine antenatal care at enrollment and monthly thereafter in line with Zambian guidelines. At delivery, research nurses collect details regarding each participant’s labor and delivery course, as well as maternal and neonatal outcomes by either direct observation/record review at the time of delivery, or at first contact with the participant postpartum [ 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study

Smithmyer

Mabula-Bwalya²,

Mwape³

et al. 2021

BMC Pregnancy Childbirth

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Background Maternal HIV increases the risk of adverse birth outcomes including preterm birth, fetal growth restriction, and stillbirth, but the biological mechanism(s) underlying this increased risk are not well understood. We hypothesized that maternal HIV may lead to adverse birth outcomes through an imbalance in angiogenic factors involved in the vascular endothelial growth factor (VEGF) signaling pathway. Methods In a case–control study nested within an ongoing cohort in Zambia, our primary outcomes were serum concentrations of VEGF-A, soluble endoglin (sEng), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFLT-1). These were measured in 57 women with HIV (cases) and 57 women without HIV (controls) before 16 gestational weeks. We used the Wilcoxon rank-sum and linear regression controlling for maternal body mass index (BMI) and parity to assess the difference in biomarker concentrations between cases and controls. We also used logistic regression to test for associations between biomarker concentration and adverse pregnancy outcomes (preeclampsia, preterm birth, small for gestational age, stillbirth, and a composite of preterm birth or stillbirth). Results Compared to controls, women with HIV had significantly lower median concentrations of PlGF (7.6 vs 10.2 pg/mL, p = 0.02) and sFLT-1 (1647.9 vs 2055.6 pg/mL, p = 0.04), but these findings were not confirmed in adjusted analysis. PlGF concentration was lower among women who delivered preterm compared to those who delivered at term (6.7 vs 9.6 pg/mL, p = 0.03) and among those who experienced the composite adverse birth outcome (6.2 vs 9.8 pg/mL, p = 0.02). Median sFLT-1 concentration was lower among participants with the composite outcome (1621.0 vs 1945.9 pg/mL, p = 0.04), but the association was not significant in adjusted analysis. sEng was not associated with either adverse birth outcomes or HIV. VEGF-A was undetectable by Luminex in all specimens. Conclusions We present preliminary findings that HIV is associated with a shift in the VEGF signaling pathway in early pregnancy, although adjusted analyses were inconclusive. We confirm an association between angiogenic biomarkers and adverse birth outcomes in our population. Larger studies are needed to further elucidate the role of HIV on placental angiogenesis and adverse birth outcomes.

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“…Enrollment occurs over eight district clinics with delivery in the Lusaka University Hospital, creating a population representative sample for peri-urban Zambian women. This site has an estimated preterm birth rate of 15% by ultrasound 11 . The goal sample size for this site is estimated to be 600 cord and heel samples, all paired with ultrasound.…”

Section: Methodsmentioning

confidence: 99%

Metabolic gestational age assessment in low resource settings: a validation protocol

Bota¹,

Ward

Hawken³

et al. 2020

Gates Open Res

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Preterm birth is the leading global cause of neonatal morbidity and mortality. Reliable gestational age estimates are useful for quantifying population burdens of preterm birth and informing allocation of resources to address the problem. However, evaluating gestational age in low-resource settings can be challenging, particularly in places where access to ultrasound is limited. Our group has developed an algorithm using newborn screening analyte values derived from dried blood spots from newborns born in Ontario, Canada for estimating gestational age within one to two weeks. The primary objective of this study is to validate a program that derives gestational age estimates from dried blood spot samples (heel-prick or cord blood) collected from health and demographic surveillance sites and population representative health facilities in low-resource settings in Zambia, Kenya, Bangladesh and Zimbabwe. We will also pilot the use of an algorithm to identify birth percentiles based on gestational age estimates and weight to identify small for gestational age infants. Once collected from local sites, samples will be tested by the Newborn Screening Ontario laboratory at the Children’s Hospital of Eastern Ontario (CHEO) in Ottawa, Canada. Analyte values will be obtained through laboratory analysis for estimation of gestational age as well as screening for other diseases routinely conducted at Ontario’s newborn screening program. For select conditions, abnormal screening results will be reported back to the sites in real time to facilitate counseling and future clinical management. We will determine the accuracy of our existing algorithm for estimation of gestational age in these newborn samples. Results from this research hold the potential to create a feasible method to assess gestational age at birth in low- and middle-income countries where reliable estimation may be otherwise unavailable.

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Adverse birth outcomes and their clinical phenotypes in an urban Zambian cohort

Cited by 15 publications

References 59 publications

Weekly 17 alpha-hydroxyprogesterone caproate to prevent preterm birth among women living with HIV: a randomised, double-blind, placebo-controlled trial

Weekly 17 alpha-hydroxyprogesterone caproate to prevent preterm birth among women living with HIV: a randomised, double-blind, placebo-controlled trial

Circulating angiogenic factors and HIV among pregnant women in Zambia: a nested case–control study

Metabolic gestational age assessment in low resource settings: a validation protocol

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