Obesity and gestational diabetes independently and collectively induce specific effects on placental structure, inflammation and endocrine function in a cohort of South African women.

Maternal obesity and gestational diabetes mellitus (GDM) are associated with insulin resistance and health risks for mother and offspring. Obesity is also characterized by low-grade inflammation, which in turn, impacts insulin sensitivity. The placenta secretes inflammatory cytokines and hormones that influence maternal glucose and insulin handling. However, little is known about the effect of maternal obesity, GDM and their interaction, on placental morphology, hormones and inflammatory cytokines. In a South African cohort of non-obese and obese pregnant women with and without GDM, this study examined placental morphology using stereology, placental hormone and cytokine expression using real-time PCR, western blotting and immunohistochemistry, and circulating TNFα and IL-6 concentrations using ELISA. Placental expression of endocrine and growth factor genes was not altered by obesity or GDM. However, LEPTIN gene expression was diminished, syncytiotrophoblast TNFα immunostaining elevated and stromal and fetal vessel IL-6 staining reduced in the placenta of obese women in a manner that was partly influenced by GDM status. Placental TNFα protein abundance and maternal circulating TNFα concentrations were reduced in GDM. Both maternal obesity and, to a lesser extent, GDM were accompanied by specific changes in placental morphometry. Maternal blood pressure and weight gain and infant ponderal index were also modified by obesity and/or GDM. Thus, obesity and GDM have specific impacts on placental morphology and endocrine and inflammatory states that may relate to pregnancy outcomes. These findings may contribute to developing placenta-targeted treatments that improve mother and offspring outcomes, which is particularly relevant given increasing rates of obesity and GDM worldwide. KEY POINTS: Rates of maternal obesity and gestational diabetes (GDM) are increasing worldwide, including in low-middle income countries (LMIC). Despite this, much of the work in the field is conducted in higher-income countries. In a well-characterised cohort of South African women, this study shows that obesity and GDM have specific impacts on placental structure, hormone production and inflammatory profile. Moreover, such placental changes were associated with pregnancy and neonatal outcomes in women who were obese and/or with GDM. The identification of specific changes in the placenta may help in the design of diagnostic and therapeutic approaches to improve pregnancy and neonatal outcomes with particular significant benefit in LMICs.

Pharmacokinetics and placental transfer of dolutegravir in pregnancy.

Dolutegravir is currently recommended by the WHO as the preferred first-line treatment for all people with HIV, including pregnant women. Estimates indicate that, by 2024, nearly 22 million adults in low- and middle-income countries will have transitioned to dolutegravir-based ART. It is therefore critical that there is a clear appreciation and understanding of the risks that may be associated with in utero exposure to dolutegravir. In this review we consolidate data from studies on dolutegravir and the placenta. The studies have largely focused on the pharmacokinetics and placental transfer of dolutegravir in pregnancy. These include studies on transplacental transfer of dolutegravir, ex vivo placenta perfusion models, physiologically based pharmacokinetic (PBPK) models and animal studies. The data available clearly demonstrate that placental transfer of dolutegravir occurs in moderate to high concentrations. Intracellular placental dolutegravir has been demonstrated in the placental villous tissue. There are limited data suggesting that pregnancy is associated with decreased maternal dolutegravir levels. In addition, PBPK models have great potential in predicting the passage of drugs through the placenta and further contributing towards the elucidation of fetal exposure. The animal studies available demonstrate that in utero dolutegravir exposure can be associated with neural tube defects. Taking into consideration that antiretroviral exposure may be associated with poor placental development or function and increased risk of adverse effects to the fetus, it is crucially important that these risks are evaluated, especially with the rapid scale up of dolutegravir-based ART into national treatment programmes.

Pregnancy outcomes in women living with HIV and HIV-negative women in South Africa: Cohort analysis based on bias-corrected gestational age.

BACKGROUND: Antiretroviral therapy (ART) use during pregnancy may be associated with adverse outcomes, but findings have been inconsistent, at least in part due to unreliably estimated gestational age. OBJECTIVE: To quantify the association between HIV status, ART initiation timing and adverse birth outcomes, with reliably assessed gestational age at booking, in a public sector primary care facility in Cape Town, South Africa. METHODS: Pregnant women, HIV-negative or living with HIV (WLHIV), were enrolled at first antenatal care visit and followed through delivery. Ultrasound-assessed gestational age was deemed the gold standard. Based on quantitative bias analysis for outcome misclassification, gestational age by non-ultrasound assessment was corrected using multiple overimputation, which deals with missing data and measurement error simultaneously. Using bias-corrected gestational age, birth outcomes were compared between WLHIV and HIV-negative women, and among WLHIV who initiated ART before versus during pregnancy, further divided into trimesters. RESULTS: Of 3952 women enrolled, 37% were WLHIV (mostly using tenofovir + emtricitabine + efavirenz). Last menstrual period (LMP)-based gestational age was identified to be biased, and LMP measures were thus corrected using multiple overimputation. Comparing WLHIV and HIV-negative women, adjusted risk ratio (aRR) of overall pregnancy loss was 1.26 (95% confidence interval [CI] 0.98, 1.61); aRR of preterm delivery was 1.02 (95% CI 0.88, 1.20); aRR of small for gestational age infants was 1.43 (95% CI 1.14, 1.80). Among WLHIV, outcomes were similar by ART initiation timing. CONCLUSIONS: In this routine care cohort, risk of SGA, and possibly of pregnancy loss, was increased in WLHIV compared with HIV-negative women, with no evidence of increased risk of preterm delivery. Further research is needed to improve mechanistic understanding of the contribution of ART to adverse birth outcomes to optimize treatment for pregnant WLHIV and ensure optimal maternal and infant outcomes.

HIV, Placental Lesions, and Adverse Perinatal Outcomes.

Africa has the highest number of pregnant women with human immunodeficiency virus (HIV). In some studies, HIV has been associated with adverse perinatal outcomes. However, the pathophysiological mechanism leading to adverse fetal outcomes is not known. Maternal vascular malformation, chorioamnionitis, and decreased placental weight have been described as placental features associated with HIV in some studies. The use of antiretroviral therapy has reduced perinatal transmission of HIV and adverse fetal outcomes. However, placental mechanisms associated with HIV and the fetal immune response to maternal HIV infection are poorly understood. Additional research is required to understand whether altered maternal immunity in women living with HIV can trigger fetal responses leading to stillbirth or preterm birth.

The effect of COVID-19 on maternal newborn and child health (MNCH) services in Bangladesh, Nigeria and South Africa: call for a contextualised pandemic response in LMICs.

Global response to COVID-19 pandemic has inadvertently undermined the achievement of existing public health priorities and laregely overlooked local context. Recent evidence suggests that this will cause additional maternal and childhood mortality and morbidity especially in low- and middle-income countries (LMICs). Here we have explored the contextual factors influencing maternal, neonatal and children health (MNCH) care in Bangladesh, Nigeria and South Africa amidst the pandemic. Our findings suggest that between March and May 2020, there was a reduction in utilisation of basic essential MNCH services such as antenatal care, family planning and immunization due to: a) the implementation of lockdown which triggered fear of contracting the COVID-19 and deterred people from accessing basic MNCH care, and b) a shift of focus towards pandemic, causing the detriment to other health services, and c) resource constraints. Taken together these issues have resulted in compromised provision of basic general healthcare. Given the likelihood of recurrent waves of the pandemic globally, COVID-19 mitigation plans therefore should be integrated with standard care provision to enhance system resilience to cope with all health needs. This commentary suggests a four-point contextualised mitigation plan to safeguard MNCH care during the pandemic using the observed countries as exemplars for LMIC health system adaptations to maintain the trajectory of progress regarding sustainable development goals (SDGs).

Blood pressure trajectories during pregnancy and associations with adverse birth outcomes among HIV-infected and HIV-uninfected women in South Africa: a group-based trajectory modelling approach.

BACKGROUND: High blood pressure (BP) late in pregnancy is associated with preterm delivery (PTD); BP has also been associated with HIV and antiretroviral therapy (ART), but whether the relationship between BP assessed longitudinally over pregnancy and PTD and low birthweight (LBW) is modified by HIV/ART is unclear. We hypothesise the presence of distinctive BP trajectories and their association with adverse birth outcomes may be mediated by HIV/ART status. METHODS: We recruited pregnant women at a large primary care facility in Cape Town. BP was measured throughout pregnancy using automated monitors. Group-based trajectory modelling in women with ≥3 BP measurements identified distinct joint systolic and diastolic BP trajectory groups. Multinomial regression assessed BP trajectory group associations with HIV/ART status, and Poisson regression with robust error variance was used to assess risk of PTD and LBW. RESULTS: Of the 1583 women in this analysis, 37% were HIV-infected. Seven joint trajectory group combinations were identified, which were categorised as normal (50%), low normal (25%), high normal (20%), and abnormal (5%). A higher proportion of women in the low normal group were HIV-infected than HIV-uninfected (28% vs. 23%), however differences were not statistically significant (RR 1.27, 95% CI 0.98-1.63, reference category: normal). In multivariable analyses, low normal trajectory (aRR0.59, 0.41-0.85) was associated with decreased risk of PTD, while high normal (aRR1.48, 1.12-1.95) and abnormal trajectories (aRR3.18, 2.32-4.37) were associated with increased risk of PTD, and abnormal with increased risk of LBW (RR2.81, 1.90-4.15). CONCLUSIONS: While HIV/ART did not appear to mediate the BP trajectories and adverse birth outcomes association, they did provide more detailed insights into the relationship between BP, PTD and LBW for HIV-infected and uninfected women.

Effects of individual drug and combination antiretroviral therapy on trophoblast proliferation.

BACKGROUND: Combination antiretroviral therapy (cART) has been reported to reduce perinatal transmission of human immunodeficiency virus (HIV) and improve maternal survival outcomes. Recent studies have associated in-utero exposure to cART drugs with adverse outcomes such as pre-eclampsia, preterm delivery, low birth weight and small-for-gestational-age births. However, the exact molecular mechanisms underlying cART-induced adverse pregnancy outcomes remain poorly defined. OBJECTIVES: To investigate the effects of cART drugs on trophoblast proliferation in the HTR-8/SVneo cell line. STUDY DESIGN: HTR-8/SVneo cells were exposed to tenofovir (0.983-9.83 µM), emtricitabine (0.809-8.09 µM) and efavirenz (0.19-1.09 µM), the individual drugs of the first-line single tablet cART regimen termed 'Atripla', and zidovudine (1.12-1.12 µM), lamivudine (0.65-6.5 µM), lopinavir (0.32-3.2 µM) and ritonavir (0.69-6.9 µM), the individual drugs of the second-line single tablet cART regimen termed 'Aluvia'. The cells were treated for 24, 48, 72 and 96 h, and trophoblast proliferation was assessed using a colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltretrazolium bromide assay. RESULTS: Two-way analysis of variance showed a significant dose-dependent decrease (p < 0.05) in trophoblast proliferation in response to individual and combined drug components of first- and second-line antiretroviral therapy. CONCLUSIONS: First- and second-line cART drugs inhibit trophoblast proliferation, and may contribute to placenta-mediated adverse pregnancy outcomes in patients with HIV.

Kisspeptin signalling and its correlation with placental ultrastructure and clinical outcomes in pregnant South African women with obesity and gestational diabetes.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a major pregnancy metabolic disorder and is strongly linked with obesity. Kisspeptin is a hormone that increases several thousand-fold in the maternal circulation during human pregnancy, with placenta as its main source. Studies have suggested that kisspeptin regulates trophoblast invasion and promotes pancreatic insulin secretion and peripheral insulin sensitivity. METHODS: In a well-characterized cohort of pregnant South African women and molecular and histological techniques, this study explored the impact and interaction of maternal obesity and GDM on kisspeptin (KISS1) signalling in relation to placental morphology and maternal and neonatal parameters. RESULTS: We found that GDM had no effect on placental KISS1 and KISS1R (KISS1 receptor) mRNA and/or protein expression. However, obesity reduced placental KISS1R mRNA expression even though overall KISS1 protein abundance or localization was not different from the non-obese group. Maternal and cord circulating KISS1 concentrations did not vary with obesity or GDM, but maternal circulating KISS1 was positively correlated with placenta weight in non-GDM obese women, and negatively correlated with placental intervillous space volume in non-GDM non-obese women. Cord serum KISS1 was positively correlated with infant weight in GDM obese women, but negatively correlated with maternal BMI in the non-obese GDM group. Placental syncytiotrophoblast extracellular vesicles exhibited detectable KISS1 and its abundance was ∼50 % lower in those from obese GDM compared to non-GDM women. DISCUSSION: This study shows maternal obesity and GDM can modulate placental kisspeptin signalling and placental morphological development with potential pathophysiological implications for clinically-relevant pregnancy and perinatal outcomes.

Cardiometabolic Health in Pregnancy and Postpartum: Findings From a Prospective Cohort Study in South Africa.

Background: The cardiometabolic impact of HIV infection and treatment with antiretroviral therapy (ART) in pregnancy and the postpartum period remains unclear. Methods: We enrolled pregnant persons with (PHIV) and without HIV in Cape Town, South Africa, who were ≥18 years old at 24-28 weeks' gestation and followed them up to 32 months postpartum. We estimated associations between HIV status and cardiometabolic risk including body mass index (BMI), obesity (BMI ≥30 kg/m2), blood pressure (BP; elevated systolic BP ≥130 and/or diastolic ≥85 mmHg), lipid levels, and metabolic syndrome according to the Joint Interim Statement criteria using multivariable log binomial or linear regression models. Subgroup analyses compared PHIV on efavirenz (EFV)- vs dolutegravir (DTG)-based ART. Results: Among 400 participants (n = 200 without HIV, n = 200 PHIV), 52% had prepregnancy obesity and 9% had elevated BP. Postpartum, 57% were classified with obesity, 31% had elevated BP, and 29% had metabolic syndrome. In multivariable analyses, HIV was associated with a lower BMI prepregnancy but not postpartum; however, mean indices were in the obese range regardless of HIV status. Neither BMI nor obesity prepregnancy or postpartum differed by ART regimen. Among PHIV, participants on DTG had higher levels of elevated BP in pregnancy and postpartum, compared with PHIV on EFV. Conclusions: We observed high levels of obesity, elevated BP, and metabolic syndrome in the perinatal period but few differences by HIV status. Participants on DTG may be more likely to have elevated BP in pregnancy and postpartum. Monitoring of cardiometabolic health for pregnant persons on DTG is warranted.

Integrated health system intervention aimed at reducing type 2 diabetes risk in women after gestational diabetes in South Africa (IINDIAGO): a randomised controlled trial protocol.

INTRODUCTION: South Africa has a high prevalence of gestational diabetes mellitus (GDM; 15%) and many of these women (48%) progress to type 2 diabetes mellitus (T2DM) within 5 years post partum. A significant proportion (47%) of the women are not aware of their diabetes status after the index pregnancy, which may be in part to low postnatal diabetes screening rates. Therefore, we aim to evaluate a intervention that reduces the subsequent risk of developing T2DM among women with recent GDM. Our objectives are fourfold: (1) compare the completion of the nationally recommended 6-week postpartum oral glucose tolerance test (OGTT) between intervention and control groups; (2) compare the diabetes risk reduction between control and intervention groups at 12 months' post partum; (3) assess the process of implementation; and (4) assess the cost-effectiveness of the proposed intervention package. METHODS AND ANALYSES: Convergent parallel mixed-methods study with the main component being a pragmatic, 2-arm individually randomised controlled trial, which will be carried out at five major referral centres and up to 26 well-baby clinics in the Western Cape and Gauteng provinces of South Africa. Participants (n=370) with GDM (with no prior history of either type 1 or type 2 diabetes) will be recruited into the study at 24-36 weeks' gestational age, at which stage first data collection will take place. Subsequent data collection will take place at 6-8 weeks after delivery and again at 12 months. The primary outcome for the trial is twofold: first, the completion of the recommended 2-hour OGTT at the well-baby clinics 6-8 weeks post partum, and second, a composite diabetes risk reduction indicator at 12 months. Process evaluation will assess fidelity, acceptability, and dose of the intervention. ETHICS AND DISSEMINATION: Ethics approval has been granted from University of Cape Town (829/2016), University of the Witwatersrand, Johannesburg (M170228), University of Stellenbosch (N17/04/032) and the University of Montreal (2019-794). The results of the trial will be disseminated through publication in peer-reviewed journals and presentations to key South African Government stakeholders and health service providers. PROTOCOL VERSION: 1 December 2022 (version #2). Any protocol amendments will be communicated to investigators, Human Ethics Research Committees, trial participants, and trial registries. TRIAL REGISTRATION NUMBER: PAN African Clinical Trials Registry (https://pactr.samrc.ac.za) on 11 June 2018 (identifier PACTR201805003336174).

Gestational weight gain and adverse birth outcomes in South African women with HIV on antiretroviral therapy and without HIV: a prospective cohort study.

INTRODUCTION: Outside of pregnancy, evidence shows that persons with HIV initiating or switching to dolutegravir (DTG)-based antiretroviral therapy (ART) experience greater weight gain compared to those on other ART classes. However, there are few data on the impact of DTG-based ART on gestational weight gain (GWG) in sub-Saharan Africa where HIV is most common. According to the National Academy of Medicine (NAM), GWG below and above NAM guidelines is associated with adverse birth outcomes. Therefore, the objective of this study was to describe GWG by HIV status and ART regimen, and examine the associations with adverse birth outcomes. METHODS: We enrolled pregnant women with HIV (WHIV) and without HIV (≥18 years) in a peri-urban primary healthcare facility in Cape Town, South Africa between 2019 and 2022. GWG was study-measured at 24-28 (baseline) and 33-38 weeks gestation and converted to GWG rate (kg/week) in accordance with NAM guidelines. GWG z-scores were generated using the INTEGROWTH-21 and US standards to account for differing lengths of gestation. Birth outcome data were obtained from medical records. Associations of GWG z-score with adverse birth outcomes were assessed using multivariable linear or log-binomial regression. RESULTS: Among 292 participants (48% WHIV), median age was 29 years (IQR, 25-33), median pre-pregnancy body mass index (BMI) was 31 kg/m2 (IQR, 26-36) and 20% were primiparous at baseline. The median weekly rate of GWG was 0.30 kg/week (IQR, 0.12-0.50), 35% had GWG below NAM standards (59% WHIV) and 48% had GWG above NAM standards (36% WHIV). WHIV gained weight more slowly (0.25 vs. 0.37 kg/week, p<0.01) than women without HIV. Weekly rate of GWG did not differ by ART regimen (DTG-based ART 0.25 vs. efavirenz-based ART 0.27 kg/week, p = 0.80). In multivariable analyses, GWG z-score was positively associated with continuous birth weight (mean difference = 68.53 95% CI 8.96, 128.10) and categorical high birth weight of >4000 g (RR = 2.18 95% CI 1.18, 4.01). CONCLUSIONS: Despite slower GWG among WHIV, nearly half of all women gained weight faster than recommended by the NAM. GWG was positively associated with infant birth weight. Interventions to support healthy GWG in sub-Saharan Africa are urgently needed.

Polycystic ovary syndrome and recurrent pregnancy loss, a review of literature.

Objective: PCOS is a syndrome of ovarian dysfunction associated with recurrent pregnancy loss. Several correlating factors have been investigated that influence the risk of pregnancy loss in PCOS. However, uncertainty remains about their contribution to pregnancy loss and prognosis. This review of literature aims to identify what is known and what requires further investigation on the relationship between PCOS and recurrent pregnancy loss, to guide future research and optimize medical guidance throughout pregnancy. Study design: a review of literature was performed on several search engines using the following terms; polycystic ovarian syndrome, PCOS, recurrent pregnancy loss, recurrent miscarriage, RPL, aborted fetus, abortus provocatus, miscarriage and habitual abortion. Results: 37 articles were included; 3 systematic reviews, 1 meta-analysis, 2 randomized controlled trials, 6 prospective cohort studies, 22 case-control studies and 3 case series. The main objectives investigated by studies were pregnancy complications, pregnancy loss and live birth in the PCOS population. Conclusion: Studies that investigated the relationship between PCOS and recurrent pregnancy loss are few and inconsistent and warrant further research. Factors apt for further investigation include the extent to which PCOS phenotypes, BMI, obesity, insulin resistance, hyperandrogenemia, SHBG, hs-CRP, CTRP6, adiponectin, plasma leptin, homocysteine, AMH and thrombophilia contribute to further risk of miscarriage. Other factors requiring further exploration in relation to risk for miscarriage in PCOS patient with RPL include sOB-R, PAI-Fx and the Factor-V-Leiden mutations.

Associations of HIV and antiretroviral therapy with gestational diabetes in South Africa.

OBJECTIVE: To estimate associations of HIV status and antiretroviral (ART) regimen with gestational diabetes (GDM) and postpartum glucose metabolism. DESIGN: Prospective cohort study. METHODS: We enrolled pregnant persons with HIV (PWH) and without HIV in Cape Town, South Africa who were at least 18 years of age at 24-28 weeks' gestation and followed up to 26 months postpartum. Participants were tested for GDM in pregnancy and for diabetes postpartum using a 75 g 2 h oral glucose tolerance test (OGTT) and diagnosed via WHO criteria. We estimated associations of HIV status and ART regime [efavirenz (EFV) versus dolutegravir (DTG)] with GDM and postpartum impaired glucose metabolism using multivariable log binomial or linear regression models. RESULTS: Among 397 participants [median age 30 (interquartile range (IQR) 25-34; n  = 198 without HIV, n  = 199 PWH], the prevalence of GDM was 6% (9 PWH versus 3% without HIV). In multivariable analyses, PWH were at higher risk of GDM [risk ratio (RR) 3.9, 95% confidence interval (CI) 1.4-10.7] after adjustment for prepregnancy BMI and other confounders. GDM risk did not differ by ART regimen (unadjusted prevalence 8.1% DTG versus 5.6% EFV, adjusted RR 1.1, 95% CI 0.2-6.6). Few participants had diabetes, impaired glucose tolerance (IGT), or impaired fasting glucose postpartum ( n  = 13, 6%) with no differences by HIV or ART status. CONCLUSION: In a setting of universal GDM testing, PWH had an increased risk of impaired glucose metabolism during pregnancy but not postpartum. Among PWH, GDM risk was similar regardless of EFV or DTG use. Given concerns about DTG and weight gain, diabetes risk should continue to be monitored.

Preterm Birth in Women With HIV: The Role of the Placenta.

Maternal HIV infection is associated with an increased risk of preterm birth (PTB). However, the mechanisms underlying this increased risk in women with HIV remain poorly understood. In this regard, it is well-established that labor is an inflammatory process and premature activation of the pro-inflammatory signals (associated with labor) can result in preterm labor which can subsequently lead to PTB. HIV infection is known to cause severe immune dysregulation within its host characterized by altered immune profiles, chronic inflammation and eventually, the progressive failure of the immune system. The human placenta comprises different immune cell subsets, some of which play an important role during pregnancy including participating in the inflammatory processes that accompany labor. It is therefore plausible that HIV/antiretroviral therapy (ART)-associated immune dysregulation within the placental microenvironment may underlie the increased risk of PTB reported in women with HIV. Here, we review evidence from studies that point toward the placental origin of spontaneous PTB and discuss possible ways maternal HIV infection and/or ART could increase this risk. We focus on key cellular players in the maternal decidua including natural killer cells, CD4+ T cells including CD4+ regulatory T cells, CD8+ T cells as well as macrophages.

Kisspeptins and Glucose Homeostasis in Pregnancy: Implications for Gestational Diabetes Mellitus-a Review Article.

Gestational diabetes mellitus (GDM) is becoming an increasingly common complication of pregnancy with the global rise of obesity. The precise pathophysiological mechanisms underpinning GDM are yet to be fully elucidated. Kisspeptin, a peptide encoded by the KISS1 gene, is mainly expressed by placental syncytiotrophoblasts during pregnancy. It is an essential ligand for kisspeptin 1 receptor (KISS1R), which is expressed by both the villous and invasive extravillous cytotrophoblast cells. Circulatory kisspeptins rise dramatically in the second and third trimester of pregnancy coinciding with the period of peak insulin resistance. Kisspeptins stimulate glucose-dependent insulin secretion and decreased plasma levels inversely correlate with markers of insulin resistance. Additionally, kisspeptins play a critical role in the regulation of appetite, energy utilisation and glucose homeostasis. GDM pregnancies have been associated with low circulatory kisspeptins, despite higher placental kisspeptin and KISS1R expression. This review evaluates the role of kisspeptin in insulin secretion, resistance and regulation of appetite as well as its implications in GDM.

Placental pathology in women with HIV.

Recognizing the importance of placental features and their unique functions can provide insight into maternal health, the uterine environment during the course of pregnancy, birth outcomes and neonatal health. In the context of HIV and antiretroviral therapy (ART), there have been great strides in the prevention of mother to child transmission of HIV. However, there is still paucity of data on the impact of HIV/ART exposure on placental pathology and studies available only examine specific patterns of placental injury, further justifying the need for a more defined and comprehensive approach to the differential diagnoses of HIV/ART-exposed placentae. The purpose of this review is to consolidate findings from individual studies that have been reported on patterns of placental injury in the context of HIV/ART exposure. In both the pre- and post-ART eras HIV and/or ART has been associated with placental injury including maternal vascular malperfusion as well as acute and chronic inflammation. These patterns of injury are further associated with adverse birth outcomes including preterm birth and current evidence suggests an association between poor placental function and compromised fetal development. With the ever increasing number of pregnant women with HIV on ART, there is a compelling need for full incorporation of placental diagnoses into obstetric disease classification. It is also important to take into account key elements of maternal clinical history. Lastly, there is a need to standardize the reporting of placental pathology in order to glean additional insight into the elucidation of HIV/ART associated placental injury.

Outcomes of hyperglycaemia in pregnancy in Africa: systematic review study protocol.

INTRODUCTION: The prevalence of diabetes mellitus globally has increased considerably over the past decades with a resultant increase in the incidence of diabetes-complicated pregnancies. Hyperglycaemia in pregnancy is the most common metabolic complication encountered during pregnancy and is associated with adverse maternal and fetal outcomes. This systematic review aims to examine maternal, fetal, neonatal, childhood and long-term maternal outcomes of hyperglycaemia in pregnancy in Africa. METHODS AND ANALYSIS: A systematic review of all studies that investigated hyperglycaemia in pregnancy outcomes, carried out in Africa from 1998 to 2019. A comprehensive search of all published articles indexed in PubMed-MEDLINE, Cochrane Library, Scopus, CINAHL (EBSCOhost), Embase and Web of Science databases will be performed. Studies will be screened for eligibility by title, abstract and full text in duplicate by two independent reviewers. For data where meta-analysis is not possible, narrative analysis will be carried out using themes from data. For data where meta-analysis is possible, random effects meta-analysis will be conducted. This systematic review will be reported according to the Meta-analyses of Observational Studies in Epidemiology. ETHICS AND DISSEMINATION: Ethical approval is not required for this study considering this is a systematic review protocol that uses only published data. The findings of this study will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020184573.

Differential impact of antiretroviral therapy initiated before or during pregnancy on placenta pathology in HIV-positive women.

OBJECTIVE: To examine the association between timing of antiretroviral treatment (ART) initiation in HIV-infected women and placental histopathology. DESIGN: A nested substudy in a larger cohort of HIV-infected women which examined the association between ART status and birth outcomes. METHODS: Placentas (n = 130) were examined for histopathology from two ART groups: stable (n = 53), who initiated ART before conception and initiating (n = 77), who started ART during pregnancy [median (interquartile range) 15 weeks gestation (11-18)]. Using binomial regression we quantified associations between ART initiation timing with placental histopathology and pregnancy outcomes. RESULTS: One-third of all placentas were less than 10th percentile weight-for-gestation and there was no significant difference between ART groups. Placental diameter, thickness, cord insertion position and foetal-placental weight ratio were also similar by group. However, placentas from the stable group showed increased maternal vascular malperfusion (MVM) (39.6 vs. 19.4%), and decreased weight (392 vs. 422 g, P = 0.09). MVM risk was twice as high [risk ratios 2.03 (95% confidence interval: 1.16-3.57); P = 0.01] in the stable group; the increased risk remaining significant when adjusting for maternal age [risk ratios 2.04 (95% confidence interval: 1.12-3.72); P = 0.02]. Furthermore, MVM was significantly associated with preterm delivery and low birth weight (P = 0.002 and <0.0001, respectively). CONCLUSION: Preconception initiation of ART was associated with an increased MVM risk, and may contribute to placental dysfunction. The association between MVM with preterm delivery and low birth weight suggests that a placenta-mediated mechanism likely links the putative association between long-term use of ART and adverse birth outcomes.

Maternal characteristics and pregnancy outcomes of hospitalized pregnant women with SARS-CoV-2 infection in South Africa: An International Network of Obstetric Survey Systems-based cohort study.

OBJECTIVE: To describe risk factors and outcomes of pregnant women infected with SARS-CoV-2 admitted to South African healthcare facilities. METHODS: A population-based cohort study was conducted utilizing an amended International Obstetric Surveillance System protocol. Data on pregnant women with SARS-CoV-2 infection, hospitalized between April 14, 2020, and November 24, 2020, were analyzed. RESULTS: A total of 36 hospitals submitted data on 673 infected hospitalized pregnant women; 217 (32.2%) were admitted for COVID-19 illness and 456 for other indications. There were 39 deaths with a case fatality rate of 6.3%: 32 (14.7%) deaths occurred in women admitted for COVID-19 illness compared to 7 (1.8%) in women admitted for other indications. Of the women, 106 (15.9%) required critical care. Maternal tuberculosis, but not HIV co-infection or other co-morbidities, was associated with admission for COVID-19 illness. Rates of cesarean delivery did not differ significantly between women admitted for COVID-19 and those admitted for other indications. There were 179 (35.4%) preterm births, 25 (4.7%) stillbirths, 12 (2.3%) neonatal deaths, and 162 (30.8%) neonatal admissions. Neonatal outcomes did not differ significantly from those of infected women admitted for other indications. CONCLUSION: The maternal mortality rate was high among women admitted with SARS-CoV-2 infection and higher in women admitted primarily for COVID-19 illness with tuberculosis being the only co-morbidity associated with admission.

Preeclampsia in 2017: Obstetric and Anaesthesia Management.

In many centres, anaesthesia now incorporates perioperative medicine. Preeclampsia is a perioperative medical challenge requiring a multi-disciplinary team. New definitions stress the rapid progression of the disease and highlight the importance of early detection. Anaesthesiologists should understand the pathophysiology of the disease and develop the ultrasound skills required to assist in the assessment of disease severity. This facilitates the choice of anaesthesia method and perioperative management in complicated cases. Regional anaesthesia remains central, but there are important developments in the practice of general anaesthesia, if indicated. Appropriate haemodynamic monitoring should be established. Anaesthesiologists should also lead the resuscitation team in the management of cardiorespiratory failure and coagulopathy.