Adiponectin as a Potential Biomarker for Pregnancy Disorders.

Adiponectin is an adipocyte-derived hormone that plays a critical role in energy homeostasis, mainly attributed to its insulin-sensitizing properties. Accumulating studies have reported that adiponectin concentrations are decreased during metabolic diseases, such as obesity and type 2 diabetes, with an emerging body of evidence providing support for its use as a biomarker for pregnancy complications. The identification of maternal factors that could predict the outcome of compromised pregnancies could act as valuable tools that allow the early recognition of high-risk pregnancies, facilitating close follow-up and prevention of pregnancy complications in mother and child. In this review we consider the role of adiponectin as a potential biomarker of disorders associated with pregnancy. We discuss common disorders associated with pregnancy (gestational diabetes mellitus, preeclampsia, preterm birth and abnormal intrauterine growth) and highlight studies that have investigated the potential of adiponectin to serve as biomarkers for these disorders. We conclude the review by recommending strategies to consider for future research.

Global DNA methylation profiling in peripheral blood cells of South African women with gestational diabetes mellitus.

Background/Objective: Recently, several studies have reported that DNA methylation changes in tissue are reflected in blood, sparking interest in the potential use of global DNA methylation as a biomarker for gestational diabetes mellitus (GDM). This study investigated whether global DNA methylation is associated with GDM in South African women. Methods: Global DNA methylation was quantified in peripheral blood cells of women with (n = 63) or without (n = 138) GDM using the MDQ1 Imprint® DNA Quantification Kit. Results: Global DNA methylation levels were not different between women with or without GDM and were not associated with fasting glucose or insulin concentrations. However, levels were 18% (p = 0.012) higher in obese compared to non-obese pregnant women and inversely correlated with serum adiponectin concentrations (p = 0.005). Discussion: Contrary to our hypothesis, global DNA methylation was not associated with GDM in our population. These preliminary findings suggest that despite being a robust marker of overall genomic methylation that offers opportunities as a biomarker, global DNA methylation profiling may not offer the resolution required to detect methylation differences in the peripheral blood cells of women with GDM. Moreover, global DNA methylation in peripheral blood cells may not reflect changes in placental tissue. Further studies in a larger sample are required to explore the candidacy of a more targeted approach using gene-specific methylation as a biomarker for GDM in our population.

Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus.

Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM.

Association between gestational diabetes and biomarkers: a role in diagnosis.

BACKGROUND: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM. METHODS: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM. RESULTS: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p = 0.04) and had more clinical risk factors (p = 0.008). We found a significant difference in fasting insulin (p < 0.001), adiponectin (p = 0.046), HOMA (p < 0.001) and QUICKI (p < 0.001). HOMA (AUROC = 0.82) or QUICKI (AUROC = 0.82) improved the ability of risk factors to identify women at high risk of GDM. CONCLUSIONS: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.

Molecular Biomarkers for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included "gestational diabetes mellitus", "blood", "single-nucleotide polymorphism (SNP)", "DNA methylation", and "microRNAs", including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.

Autologous intrauterine transfusion in a case of anti-U.

BACKGROUND: Minor red blood cell antibodies are becoming a more common cause of hemolytic disease of the newborn. Anti-U are a rare alloantibody found almost exclusively in people of black descent. There is limited experience to guide the management of pregnancies complicated by anti-U. Furthermore, there is often no suitable cross-matched blood available for transfusion of a patient with anti-U. CASE REPORT: A 21-year-old P0G1 presented at 25 weeks' gestation with D- disease in pregnancy. She had a significant indirect antiglobulin test titer of 512. Anti-U were identified and no suitable cross-matched blood was available. Maternal blood was prepared for autologous intrauterine fetal transfusion. Two such transfusions were performed. RESULTS: A healthy fetus delivered at 32 weeks that did not require phototherapy or an exchange transfusion. CONCLUSION: Autologous transfusion of prepared maternal blood provides a safe option for intrauterine fetal therapy in pregnancies complicated by rare alloantibodies.

An audit of the initial resuscitation of severely ill patients presenting with septic incomplete miscarriages at a tertiary hospital in South Africa.

BACKGROUND: Septic incomplete miscarriages remain a cause of maternal deaths in South Africa. There was an initial decline in mortality when a strict protocol based approach and the Choice of Termination of Pregnancy Act in South Africa were implemented in this country. However, a recent unpublished audit at the Pretoria Academic Complex (Kalafong and Steve Biko Academic Hospitals) suggested that maternal mortality due to this condition is increasing. The objective of this investigation is to do a retrospective audit with the purpose of identifying the reasons for the deteriorating mortality index attributed to septic incomplete miscarriage at Steve Biko Academic Hospital. METHODS: A retrospective audit was performed on all patients who presented to Steve Biko Academic Hospital with a septic incomplete miscarriage from 1(st) January 2008 to 31(st) December 2010. Data regarding patient demographics, initial presentation, resuscitation and disease severity was collected from the "maternal near-miss"/SAMM database and the patient's medical record. The shock index was calculated for each patient retrospectively. RESULTS: There were 38 SAMM and 9 maternal deaths during the study period. In the SAMM group 86.8% and in the maternal death group 77.8% had 2 intravenous lines for resuscitation. There was no significant improvement in the mean blood pressure following resuscitation in the SAMM group (p 0.67), nor in the maternal death group (p 0.883). The shock index before resuscitation was similar in the two groups but improved significantly following resuscitation in the SAMM group (p 0.002). Only 31.6% in the SAMM group and 11.1% in the maternal death group had a complete clinical examination, including a speculum examination of the cervix on admission. No antibiotics were administered to 21.1% in the SAMM group and to 33.3% in the maternal death group. CONCLUSION: The strict protocol management for patients with septic incomplete miscarriage was not adhered to. Physicians should be trained to recognise and react to the seriously ill patient. The use of the shock index in the identification and management of the critically ill pregnant patient needs to be investigated.

Gestational Diabetes and the Gut Microbiota: Fibre and Polyphenol Supplementation as a Therapeutic Strategy.

Gestational diabetes mellitus (GDM) is an escalating public health concern due to its association with short- and long-term adverse maternal and child health outcomes. Dysbiosis of microbiota within the gastrointestinal tract has been linked to the development of GDM. Modification of microbiota dysbiosis through dietary adjustments has attracted considerable attention as adjunct strategies to improve metabolic disease. Diets high in fibre and polyphenol content are associated with increased gut microbiota alpha diversity, reduced inflammation and oxidative processes and improved intestinal barrier function. This review explores the potential of fibre and polyphenol supplementation to prevent GDM by investigating their impact on gut microbiota composition and function.

Pregnant women's dietary patterns and knowledge of gestational weight gain: A cross-sectional study.

OBJECTIVE: Excess gestational weight gain (GWG) is a risk factor for various unfavorable maternal and neonatal outcomes that may be preventable. Maintaining a healthy lifestyle while pregnant can help prevent uncontrollable weight gain. The aim of this study was to assess pregnant women's knowledge on weight, GWG, diet, and knowledge of obesity-related complications among women who seek care at our semi-urban, regional setting. METHODS: A prospective observational study was conducted at the prenatal clinic at Kalafong Academic Hospital. Prospective participants completed a questionnaire on their perception of GWG, attitudes toward GWG, knowledge of GWG, associated complications of obesity, and food choices. Data analysis was performed using SAS version 9.4. RESULTS: The majority of the 500 individuals were overweight or obese prior to pregnancy. By the end of the third trimester, this increased by 10.1% (n = 420; 86.1%). Nearly half (n = 240; 48.78%) of the overweight and obese women underestimated their weight. Only 26.53% (n = 26) of women who checked their body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) gained weight according to recommendations. However, less than half (n = 96; 30.5%) gained weight within the recommended range, despite the fact that the majority of them (n = 315; 64%) were aware of the harmful effects of obesity on the cardiovascular system and the effects of high calories on weight gain (n = 321; 65%). CONCLUSION: Despite basic knowledge of the impact of high-caloric intake on weight gain and cardiovascular complications, less than half of the study population gained weight within the recommended range.

The Maternal Microbiome and Gestational Diabetes Mellitus: Cause and Effect.

Gestational diabetes mellitus (GDM) is a growing public health concern that affects many pregnancies globally. The condition is associated with adverse maternal and neonatal outcomes including gestational hypertension, preeclampsia, placental abruption, preterm birth, stillbirth, and fetal growth restriction. In the long-term, mothers and children have an increased risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease. Accumulating evidence suggest that alterations in the maternal microbiome may play a role in the pathogenesis of GDM and adverse pregnancy outcomes. This review describes changes in the maternal microbiome during the physiological adaptations of pregnancy, GDM and adverse maternal and neonatal outcomes. Findings from this review highlight the importance of understanding the link between the maternal microbiome and GDM. Furthermore, new therapeutic approaches to prevent or better manage GDM are discussed. Further research and clinical trials are necessary to fully realize the therapeutic potential of the maternal microbiome and translate these findings into clinical practice.

Hypertensive disorders of pregnancy and long-term cardiovascular health: FIGO Best Practice Advice.

Hypertensive disorders of pregnancy (HDP) are the most common causes of maternal and perinatal morbidity and mortality. They are responsible for 16% of maternal deaths in high-income countries and approximately 25% in low- and middle-income countries. The impact of HDP can be lifelong as they are a recognized risk factor for future cardiovascular disease. During pregnancy, the cardiovascular system undergoes significant adaptive changes that ensure adequate uteroplacental blood flow and exchange of oxygen and nutrients to nurture and accommodate the developing fetus. Failure to achieve normal cardiovascular adaptation is associated with the development of HDP. Hemodynamic alterations in women with a history of HDP can persist for years and predispose to long-term cardiovascular morbidity and mortality. Therefore, pregnancy and the postpartum period are an opportunity to identify women with underlying, often unrecognized, cardiovascular risk factors. It is important to develop strategies with lifestyle and therapeutic interventions to reduce the risk of future cardiovascular disease in those who have a history of HDP.

Management of obesity across women's life course: FIGO Best Practice Advice.

Obesity is a chronic, progressive, relapsing, and treatable multifactorial, neurobehavioral disease. According to the World Health Organization, obesity affects 15% of women and has long-term effects on women's health. The focus of care in patients with obesity should be on optimizing health outcomes rather than on weight loss. Appropriate and common language, considering cultural sensitivity and trauma-informed care, is needed to discuss obesity. Pregnancy is a time of significant physiological change. Pre-, ante-, and postpartum clinical encounters provide opportunities for health optimization for parents with obesity in terms of, but not limited to, fertility and breastfeeding. Pre-existing conditions may also be identified and managed. Beyond pregnancy, women with obesity are at an increased risk for gastrointestinal and liver diseases, impaired kidney function, obstructive sleep apnea, and venous thromboembolism. Gynecological and reproductive health of women living with obesity cannot be dismissed, with accommodations needed for preventive health screenings and consideration of increased risk for gynecologic malignancies. Mental wellness, specifically depression, should be screened and managed appropriately. Obesity is a complex condition and is increasing in prevalence with failure of public health interventions to achieve significant decrease. Future research efforts should focus on interprofessional care and discovering effective interventions for health optimization.

Using FIGO Nutrition Checklist counselling in pregnancy: A review to support healthcare professionals.

The period before and during pregnancy is increasingly recognized as an important stage for addressing malnutrition. This can help to reduce the risk of noncommunicable diseases in mothers and passage of risk to their infants. The FIGO Nutrition Checklist is a tool designed to address these issues. The checklist contains questions on specific dietary requirements, body mass index, diet quality, and micronutrients. Through answering these questions, awareness is generated, potential risks are identified, and information is collected that can inform health-promoting conversations between women and their healthcare professionals. The tool can be used across a range of health settings, regions, and life stages. The aim of this review is to summarize nutritional recommendations related to the FIGO Nutrition Checklist to support healthcare providers using it in practice. Included is a selection of global dietary recommendations for each of the components of the checklist and practical insights from countries that have used it. Implementation of the FIGO Nutrition Checklist will help identify potential nutritional deficiencies in women so that they can be addressed by healthcare providers. This has potential longstanding benefits for mothers and their children, across generations.

Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice.

Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.

A 10-year audit of pregnancies affected by diabetic ketoacidosis at the Pretoria Academic Complex.

BACKGROUND: Diabetic ketoacidosis (DKA) during pregnancy is associated with increased rates of maternal and perinatal mortality and morbidity. DKA management guidelines are designed to ensure optimal management and minimize adverse outcomes. OBJECTIVE: To determine the level of adherence to DKA management guidelines at a tertiary center in Pretoria, South Africa and report on maternal and perinatal outcomes of the pregnancies complicated by DKA. METHODS: This was a retrospective clinical record audit using the Society for Endocrinology, Metabolism and Diabetes of South Africa guidelines against documented management. Adherence to three cornerstones of therapy was measured: intravenous fluids, insulin therapy, and management of electrolytes. RESULTS: Fifty-six records of pregnancies that were complicated with DKA over a 10-year period were reviewed. Mean age was 29.6 years (range 20-43 years). Thirty-six (64.3%) women had type 1 diabetes mellitus. DKA was categorized into mild (n = 26, 46.4%), moderate (n = 22, 39.3%), and severe (n = 8, 14.3%). The study demonstrated lack of adherence to the three cornerstones of therapy. Of the 49 (85.7%) women with recorded perinatal outcomes, 30.6% had stillbirths. Severe maternal DKA (pH <7.0) demonstrated adverse perinatal outcomes (P = 0.005). CONCLUSION: Despite the availability of guidelines, DKA is sub-optimally managed in pregnancy, which may contribute to adverse maternal and perinatal outcomes.

The role of maternal DNA methylation in pregnancies complicated by gestational diabetes.

Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been suggested that the frequency and severity of pregnancy complications are linked to the degree of hyperglycemia. Epigenetic mechanisms reflect gene-environment interactions and have emerged as key players in metabolic adaptation to pregnancy and the development of complications. DNA methylation, the best characterized epigenetic mechanism, has been reported to be dysregulated during various pregnancy complications, including pre-eclampsia, hypertension, diabetes, early pregnancy loss and preterm birth. The identification of altered DNA methylation patterns may serve to elucidate the pathophysiological mechanisms that underlie the different types of maternal diabetes during pregnancy. This review aims to provide a summary of existing knowledge on DNA methylation patterns in pregnancies complicated by pregestational type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Four databases, CINAHL, Scopus, PubMed and Google Scholar, were searched for studies on DNA methylation profiling in pregnancies complicated with diabetes. A total of 1985 articles were identified, of which 32 met the inclusion criteria and are included in this review. All studies profiled DNA methylation during GDM or impaired glucose tolerance (IGT), while no studies investigated T1DM or T2DM. We highlight the increased methylation of two genes, Hypoxia-inducible Factor-3α (HIF3α) and Peroxisome Proliferator-activated Receptor Gamma-coactivator-Alpha (PGC1-α), and the decreased methylation of one gene, Peroxisome Proliferator Activated Receptor Alpha (PPARα), in women with GDM compared to pregnant women with normoglycemia that were consistently methylated across diverse populations with varying pregnancy durations, and using different diagnostic criteria, methodologies and biological sources. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. Furthermore, these genes may provide insight into the pathways that are epigenetically influenced during maternal diabetes and which should be prioritized and replicated in longitudinal studies and in larger populations to ensure their clinical applicability. Finally, we discuss the challenges and limitations of DNA methylation analysis, and the need for DNA methylation profiling to be conducted in different types of maternal diabetes in pregnancy.

A Big Role for microRNAs in Gestational Diabetes Mellitus.

Maternal diabetes is associated with pregnancy complications and poses a serious health risk to both mother and child. Growing evidence suggests that pregnancy complications are more frequent and severe in pregnant women with pregestational type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) compared to women with gestational diabetes mellitus (GDM). Elucidating the pathophysiological mechanisms that underlie the different types of maternal diabetes may lead to targeted strategies to prevent or reduce pregnancy complications. In recent years, microRNAs (miRNAs), one of the most common epigenetic mechanisms, have emerged as key players in the pathophysiology of pregnancy-related disorders including diabetes. This review aims to provide an update on the status of miRNA profiling in pregnancies complicated by maternal diabetes. Four databases, Pubmed, Web of Science, EBSCOhost, and Scopus were searched to identify studies that profiled miRNAs during maternal diabetes. A total of 1800 articles were identified, of which 53 are included in this review. All studies profiled miRNAs during GDM, with no studies on miRNA profiling during pregestational T1DM and T2DM identified. Studies on GDM were mainly focused on the potential of miRNAs to serve as predictive or diagnostic biomarkers. This review highlights the lack of miRNA profiling in pregnancies complicated by T1DM and T2DM and identifies the need for miRNA profiling in all types of maternal diabetes. Such studies could contribute to our understanding of the mechanisms that link maternal diabetes type with pregnancy complications.

Coronavirus and Pregnancy: The Challenges of the 21st Century: A Review.

Despite many advances in medicine we are still faced with emerging pathogens. Pregnant women have been disproportionately affected by previous coronavirus outbreaks. The COVID-19 pandemic has not affected pregnant women as greatly as SARS-CoV and MERS, but has posed other challenges such as the need for quarantine and isolation, limited access to antenatal care, use of personal protective equipment (PPE), vaccine hesitancy and inequities in vaccine access and therapeutics between rich countries and the global south. This review will describe the impact of the significant coronaviruses on pregnancy, with special focus on the challenges being encountered by the SARS-CoV-2 global pandemic.

A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes.

Pregestational type 1 (T1DM) and type 2 (T2DM) diabetes mellitus and gestational diabetes mellitus (GDM) are associated with increased rates of adverse maternal and neonatal outcomes. Adverse outcomes are more common in women with pregestational diabetes compared to GDM; although, conflicting results have been reported. This systematic review aims to summarise and synthesise studies that have compared adverse pregnancy outcomes in pregnancies complicated by pregestational diabetes and GDM. Three databases, Pubmed, EBSCOhost and Scopus were searched to identify studies that compared adverse outcomes in pregnancies complicated by pregestational T1DM and T2DM, and GDM. A total of 20 studies met the inclusion criteria and are included in this systematic review. Thirteen pregnancy outcomes including caesarean section, preterm birth, congenital anomalies, pre-eclampsia, neonatal hypoglycaemia, macrosomia, neonatal intensive care unit admission, stillbirth, Apgar score, large for gestational age, induction of labour, respiratory distress syndrome and miscarriages were compared. Findings from this review confirm that pregestational diabetes is associated with more frequent pregnancy complications than GDM. Taken together, this review highlights the risks posed by all types of maternal diabetes and the need to improve care and educate women on the importance of maintaining optimal glycaemic control to mitigate these risks.

No Association Between ADIPOQ or MTHFR Polymorphisms and Gestational Diabetes Mellitus in South African Women.

PURPOSE: Gestational diabetes mellitus (GDM) is a growing public health concern. GDM affects approximately 14% of pregnancies globally, and without effective treatment, is associated with short- and long-term complications in mother and child. Lower serum adiponectin (ADIPOQ) concentrations and aberrant DNA methylation have been reported during GDM. The aim of this study was to investigate the association between the ADIPOQ -11377C>G and -11391G>A, and methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphisms and GDM in a population of black South African women. MATERIALS AND METHODS: DNA was isolated from the peripheral blood of 447 pregnant women with (n=116) or without (n=331) GDM, where after ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms were genotyped using TaqMan Quantitative Real-Time PCR analysis. RESULTS: Women with GDM had a higher body mass index (p=0.012), were more insulin resistant (p<0.001) and had lower adiponectin levels (p=0.013) compared to pregnant women with normoglycemia. Genotypic, dominant and recessive genetic models showed no association between ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms and GDM. Intriguingly, the risk G allele of ADIPOQ rs266729 was associated with higher fasting glucose and insulin concentrations, while the T allele in MTHFR rs1801133 was associated with higher fasting insulin concentrations only. CONCLUSION: ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms are not associated with GDM in a population of black South African women. These findings suggest that these single nucleotide polymorphisms (SNPs) do not individually increase GDM risk in the African population. However, the role of these SNPs in possible gene-gene or gene-environment interactions remain to be established.