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.

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.

Medical conditions associated with recurrent miscarriage-Is BMI the tip of the iceberg?

BACKGROUND: In contrast to sporadic miscarriage, recurrent miscarriage (RM) is a rare entity which affects 1% of couples attempting conception. It is distressing for couples and healthcare professionals as the aetiology is unclear with limited treatment options. Apart from anti-phospholipid syndrome (APS), the strength of associations between RM and commonly investigated endocrine, autoimmune, thrombophilic and uterine structural abnormalities remains uncertain and variable. OBJECTIVES: To assess the prevalence of commonly investigated medical conditions associated with RM. STUDY DESIGN: A 9-year retrospective analysis of a prospectively collected database was conducted for 592 patients seen between 2008 and 2016, in tertiary level RM clinic in South Africa. RESULTS: In this period, 592 patients were assessed. The mean age was 29.73±5.46 (mean±SD), gravidity 4.6±1.82 and parity 0.98±1.05. The mean number of miscarriages per patient was 3.34±1.63, of which two-thirds (61.3%) were in the first trimester, a third (33%) in the second trimester and intrauterine fetal deaths (IUFDs) constituted 6% of total losses. Of the 50% of patients with no identified associated disorders, 15% were unexplained (investigations complete but no associations found), 10% became pregnant during investigation (investigations incomplete) and 25% were lost to follow-up (investigations incomplete). Nearly forty percent (38%) of patients had an associated endocrine disorder (22% PCOS, 11% IGT, 3% Diabetes Mellitus and 2% Thyroid Dysfunction) and 10% a uterine factor (4% Cervical Incompetence, 2% Fibroids, 2% Synechiae and 2% Anomalies). APS and Thrombophilias constituted 3% and 2% of patients respectively. The BMI (mean±SD) amongst patients with Unexplained RM, PCOS and IGT were 28.85±5.95, 30.86±7.79 and 33.40±6.47 respectively. Patients with IGT had significantly higher mean BMI in comparison to those with Unexplained RM (p<0.0001)*** and PCOS (p<0.001)**. CONCLUSION: PCOS, IGT and Type II Diabetes are all likely surrogates for elevated BMI and constitute 70% of those women with RM and identified associated medical disorders. In our population, BMI seems to have a substantial impact on recurrent pregnancy loss and future studies should interrogate its effect on recurrent miscarriage.