Thesis (MPH.) -- University of Limpopo, 2020 / The purpose of this study was to determine the prevalence of gestational diabetes mellitus (GDM) and the associated risk factors in the Greater Giyani Area, Mopani District. Quantitative cross-sectional descriptive study was conducted to determine the prevalence rate and risk factors of GDM. Data was collected using questionnaire and data entry form. One hundred and one (101) pregnant women who were attending antenatal clinic visits at Nkhensani Hospital, Nkhensani Gateway Clinic and Giyani Healthcare Centre participated in the study. The SPSS programme was used and p-value of <0.05 was considered significant. The study found that the prevalence of GDM in the area was 1.9%. Pregnant women above 30 years with secondary education, employed, obese and at gestational age of 31-35 weeks were more likely to present with GDM. A family history of diabetes was significantly associated with development of GDM. In conclusion, the universal screening approach for GDM needs to be adopted by all health institutions.

Gestational diabetes mellitus (GDM ) is a disease that appears during pregnancy due to an insulin resistance. GDM is associated with increased risks for complications both to the mother and the child during pregnancy. These risks include conditions such as neonatal macrosomi and hypoglycemia for the child. This leads to increased risk for cesarean section and birth injuries. GDM can be treated with a changed diet supported with exercise. If the blood glucose levels still remain high, insulin or metformin medication can be introduced to treat the patient. Metformin is a safe and effective anti-diabetic drug and it is used as a treatment for GDM. Since the treatment during GDM varies, the effect of insulin versus metformin was examined. The aim of this litterature study was to compare the treatment with metformin versus insulin and to investigate the differences between the two drugs in the treatment of GDM. The medical databases PubMed and Google Scholar were used to search for clinical studies that compare the effects of the two treatments. Four studies were selected for this litterature study. The results in this study indicated that both insulin and metformin are effective as  glucose lowering drugs in the treatment of GDM. All patients do not respond to metformin and therefore insulin may be preferable in the treatment of some patient. Both insulin and metformin lead to better glycemic control in GDM patients. Both drugs are safe and effective but metformin has several advantages. The cost is low, it is easier to use and leads to fewer cases of hypoglycemia compared to insulin, even though all patients do not respond to metformin, it is considered a good alternative.

Background: Gestational Diabetes Mellitus (GDM) has been linked with later metabolic abnormalities in offspring due to subsequent overweight and obesity. In Sub-Saharan Africa, there is a paucity of data on the outcomes of children exposed to GDM in utero. Aims: The primary aim of this sub-study was to investigate the prevalence of overweight and obesity in 5 and 6-year-old children from GDM complicated pregnancies and macrosomia at birth in the same cohort. The secondary aim was to identify risk factors associated with overweight and obesity in these 5 and 6-year-old children. Outcome measures: The main outcome was the prevalence of overweight and obesity in these children as measured by their age-specific body mass index (BMI) and Z-scores. Additionally, the association between other risk factors, overweight and obesity was investigated. Methods: A cross-sectional sub-study design was employed nested within a larger study that is investigating the progression to type 2 diabetes in women managed for GDM during 2010 and 2011. Mothers who participated in the larger study were informed about the sub-study and invited to allow their children to participate in the sub-study. Written informed consent was obtained from the mothers for the sub-study. The following data were collected: anthropometric data at birth and pregnancy related information from the mothers’ hospital record, additional demographic, social and medical information by questionnaire from the mother and at the research center. In addition, the children were weighed and had their height measured using standardized methods. Anthropometry was standardized using WHO standards. Risk factors for overweight and obesity were tested using a BMI>1 Z-score cut-off, (as a binary variable) in a manual multivariate logistic regression model. Results: The sub-study recruited 176 participants; 78 boys (44.3%) and 98 girls (55.7%). The mean (SD) Z-scores for the children’s anthropometry at ages 5 to 6 years were 0.28 (1.40) for weight, 0.01 (1.07) for height and 0.37 (1.63) for BMI. The overall prevalence of macrosomia at birth (birth weight>4000 gm) was 12.3 % (95% CI 8.2-9.1). The overall prevalence of overweight in the 5 and 6-year-old children was 13.4% (95% CI 8.6-20.4), while the prevalence of obesity was 14.2% (95% CI 9.2-21.2). The combined prevalence of overweight and obesity was 27.6% (95% CI 20.6-35.9). The prevalence of macrosomia (P=0.53) or overweight/obesity proportions (P=0.37) at ages 5 to 6 years did not differ by gender. In multivariate logistic regression analysis, factors independently associated with the risk of overweight and obesity were: mothers’ oral glucose tolerance test 2-hour blood glucose level during pregnancy (AOR=2.06, 95% CI 1.14-3.74, P=0.02), birth weight (AOR=1.00, 95% CI 1.00-1.00, P=0.01), child’s age in years (AOR=0.03, 95% CI 0.002-0.29, P=0.004) and number of adults in the house (AOR=0.38, 95% CI 0.17-0.86, P=0.02). Conclusion: This is the first study to report the prevalence of overweight and obesity in children born from GDM complicated pregnancies, in the Western Cape, South Africa. The combined prevalence of overweight and obesity found in 5 and 6-year-old children exposed to GDM in the Western Cape is higher than overweight and obesity in children reported in other South African studies. This can imply a higher tendency towards overweight and obesity in children exposed to GDM which needs further exploration.

Introduction: Gestational diabetes mellitus (GDM) is a significant public health concern, due to its association with short- and long-term complications in both mothers and offspring. DNA methylation and single nucleotide polymorphisms (SNPs) offer potential to serve as molecular biomarkers, which may lead to improved detection of GDM with positive effects on health outcomes. Aim: The aim of this study was to investigate whether DNA methylation and SNPs are associated with GDM and may offer potential as molecular biomarkers for GDM in South Africa (SA). Methods: This study followed a two-pronged approach. Firstly, literature searches were conducted to collate and synthesise all published articles reporting on the prevalence of GDM in SA, the screening and diagnostic strategies used, and the current status of DNA methylation and SNPs as biomarkers for GDM. Secondly, we conducted experiments to investigate global (n=201), genome-wide (n=24) and gene-specific DNA methylation (n=286) of the adiponectin gene (ADIPOQ) in whole blood of women with and without GDM, using an Enzyme-Linked Immunosorbent Assay, a methylationEPIC BeadChip Array and pyrosequencing, respectively. In addition, genotype and allele frequencies of ADIPOQ rs266729 and rs17300539, and methylenetetrahydrofolate reductase (MTHFR) rs1801133 were determined, using quantitative real-time PCR (n=449) and DNA sequencing for validation. Results: The literature search showed that the prevalence of GDM in SA has increased over the years. Furthermore, it showed that the lack of uniformity in screening and diagnosis between and within countries hamper the accurate detection of GDM. Lastly, the literature search identified several studies that support the use of DNA methylation and SNPs as potential biomarkers for GDM. Experimentally, we showed no differences in global DNA methylation between GDM and non-GDM groups. Interestingly, global DNA methylation levels were 18% (p=0.012) higher in obese compared to non-obese pregnant women. Genome-wide methylation analysis identified 1046 differentially methylated CpG sites (associated with 939 genes) (Cut-off threshold: M>0.06 and p<0.01). Among the top five CpG sites identified, one CpG mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which has been shown to regulate insulin production and secretion. Two CpG sites (-3410: p=0.048 and -3400: p=0.004) in the ADIPOQ promoter were hypomethylated during GDM in HIV negative, but not in HIV positive women. Lastly, no association between the ADIPOQ and MTHFR polymorphisms and GDM was observed in our population. Conclusion: To our knowledge, this is the first study to investigate the association between DNA methylation or ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms and GDM in SA. Findings suggest that gene-specific, but not global methylation nor SNPs rs266729, rs17300539 and rs1801133, may offer potential as molecular biomarkers of GDM in this population. Future longitudinal studies in larger samples that include both HIV negative and positive pregnant women are warranted to explore the candidacy of DNA methylation as molecular biomarkers for GDM. / Thesis (PhD)--University of Pretoria, 2019. / National Research Foundation (NRF) of South Africa, Thuthuka Grant (unique grant no. 99391). / South African Medical Research Council (SAMRC) / Obstetrics and Gynaecology / PhD / Unrestricted

Assisted reproductive technology (ART) is an infertility treatment used to assist women to become pregnant. Although the procedure is safe, there are gaps in understanding the association between treatment and adverse pregnancy outcomes (e.g., stillbirth) in the United States. The purpose of this study was to investigate the relationship between stillbirth delivery and ART. The 2 research questions addressed the association between methods of conception (ART versus non-ART) and the delivery of a stillbirth, and the association between multiple gestation pregnancy and risk of stillbirths. Retrospective cohort data from the States Monitoring ART collaborative were analyzed using Pearson's chi squared tests and log binominal regression models. Findings indicated that from 2006 to 2011, the average stillbirth rates were lower among ART-conceived pregnancies than non-ART conceived pregnancies. After controlling for confounding factors, ART-conceived pregnancies did not show increased risks of stillbirths compared to non-ART conceived pregnancies regardless of plurality. This lower risk of stillbirth was particularly significant during early pregnancies, before 28 weeks of gestation. Findings may be used to improve understanding of the use of ART treatment and its associated pregnancy outcomes. Findings may also be used to prevent stillbirths and to improve prenatal care, early stillbirth detection, and effective clinical management of fetal and maternal conditions during pregnancy.

A healthy in utero environment is essential for achieving optimal outcomes for women and their children. Gestational weight gain (GWG) has been shown to impact current and future maternal-infant health outcomes. Suboptimal weight gain during pregnancy (defined by the Institute of Medicine GWG guidelines) has been linked to several complications and is implicated in the inter-general cycle of obesity. Understanding contributors to GWG and intervening during pregnancy with healthy behaviour strategies may have a multi-generational effect for chronic disease prevention. The objective of the first study of this thesis was to examine the association between i) eating habits during pregnancy, ii) advice from family or friends about GWG, and iii) personal effort to stay within weight gain limits, and meeting GWG recommendations. Cross-sectional data were collected from pregnant and postpartum women who responded to the validated electronic maternal (EMat) health survey. Regardless of receiving advice about GWG, women self-reporting less healthy eating habits in pregnancy than before pregnancy, receiving advice from family/friends about GWG, and lower personal effort to stay within guidelines, had an increased odds of weight gain discordant with recommendations. The objective of the second study was to assess the short-term effect of the SmartMoms Canada application (app) usage on promoting adequate GWG and healthy behaviours. SmartMoms Canada is an app-based intervention designed to help pregnant women adhere to GWG guidelines and improve healthful behaviours. Pregnant women using the SmartMoms Canada app more frequently had a higher moderate-to-vigorous physical activity daily average when compared with women with a lower usage. Together, the EMat and SmartMoms results from this thesis contribute to identifying and mitigating potential factors associated with discordant GWG and healthy behaviours.

Background: In the pregnant population, being physical active and meeting gestational weight gain (GWG) guidelines have numerous health benefits for both mother and infant. Markers of lipid metabolism are known to be influenced by these two variables in the non-pregnant population. However, the relationship between physical activity (PA) and GWG on lipid markers has yet to be assessed during pregnancy. My thesis aims to address this gap in the literature. Methods: The first objective of my thesis was to examine the relationship between maternal PA and GWG on gross measurements of fetal and placental development (n=40). Specifically, three markers of placental efficiency (Pl-E) were examined (birthweight [BW], BW-to-placenta weight ratio, and residual BW). The second objective of my thesis was to analyze maternal serum lipid and glucose markers (n=40), in mid (24-28 weeks) and late (34-38 weeks) gestation as well as from the umbilical cord (UC) as they relate to both PA and GWG. The third objective of my thesis was to explore how PA level and GWG status affect markers of lipid metabolism in term placenta (n=31). Markers of placental lipid transport (FATP1, FABP4, FAT/CD36) were assessed at the protein level, and enzymatic activity of placental lipoprotein lipase was also measured. Lastly, placental lipid storage was assessed by examining triglyceride content, paired with lipid droplet staining. Results: There was no relationship between PA independently or in combination with GWG on any Pl-E markers. A significant association was found between GWG and BW in women who gained weight excessively compared to insufficiently. Neither PA nor GWG categorization was associated with maternal lipid and glucose markers. Total cholesterol levels measured in UC serum were significantly lower in women categorized as active throughout pregnancy (p<0.0001) or whose activity dropped in late gestation (p<0.0001) compared to those who were inactive v throughout gestation. Glucose levels were lower in UC blood of women who gained weight appropriately in mid-gestation compared to those who gained insufficient (p=0.040) or excessive (p=0.021) weight. In terms of placental fatty acid transport, there was a significant interaction between PA status and GWG categorization and placental FATP1 protein expression (F=14.62, p<0.0001). Finally, while no differences were found in placental lipid droplet staining, the droplets were more likely to be clustered within the syncytiotrophoblast border. Conclusion: In conclusion, maternal PA had no association with Pl-E, while GWG was only associated with BW. My thesis work found that while maternal serum lipid markers were not associated with PA and GWG, both maternal PA and GWG status were related to changes in UC and placental lipid markers throughout pregnancy. In combination with previous research from our lab, it is suggested that women who are physically active during pregnancy, and gain weight appropriately may be transporting fewer nutrients (i.e. fatty acid, glucose, cholesterol) to the placenta than those who are inactive, yet simultaneously increasing metabolization. Future research should further investigate these findings by performing functional experiments.

Objective: To examine differences in the antenatal detection rate of small for gestational age (SGA) infants among several race-ethnicity groups and determine whether perinatal outcomes differ in antenatally detected versus undetected SGA infants according to race-ethnicity. Methods: A retrospective cohort study was conducted at a single tertiary care center that evaluated all deliveries of SGA infants >23 weeks gestation between January 2016-January 2020. Race and ethnicity were self-reported and categorized as non-Hispanic White, non-Hispanic Black, Hispanic, or Asian. The medical charts of those eligible were reviewed and the primary study outcomes were analyzed using multivariable logistic regression analyses with accompanying point estimates and 95% confidence intervals. Results: A total of 526 childbearing persons satisfied our predefined inclusion criteria. The predominant race-ethnicity group was non-Hispanic White who comprised 50% of the study population. Antenatal detection rate of SGA was found to be 38%. The detection rate, while not statistically different, ranged from 28-40% according to race-ethnicity with Asians having the lowest detection rates. Higher rates of preterm birth, labor induction, and lower median birthweights were observed in antenatally detected versus undetected SGA pregnancies. However, no significant differences were observed with regards to perinatal outcomes when antenatally detected versus undetected SGA was compared according to race-ethnicity. Conclusions: Antenatal detection may not be the primary solution to improving racial and ethnic disparities among SGA infants. Additional investigation to identify, address, and improve disparities in other areas of perinatal medicine is necessary to provide more equitable care. Further work to investigate the barriers to antenatal detection of SGA is warranted as an avenue for improving perinatal outcomes.

Prolonged second stage of labor, excessive gestational weight gain and cesarean delivery has been associated with adverse maternal and fetal outcomes. Physical activity during pregnancy is a modifiable risk factor which has never been studied among Hispanic women. Gestational weight gain, another modifiable risk factor has only been evaluated as a risk factor for cesarean delivery in two studies among women induced for labor. To date, no study has examined the effect of duration of second stage of labor on intra-ventricular hemorrhage in very preterm births. We examined these maternal risk factors for prolonged second stage of labor, rate of cesarean delivery and fetal outcomes. The first study evaluated the association between physical activity and duration of second stage of labor. Prior studies regarding physical activity and duration of second stage of labor have been conflicting and none have examined the Hispanic population. During pregnancy, activities such as household chores, childcare, sports and women's occupation constitute a significant proportion of physical activity but have not been considered in prior studies. We examined the association between total physical activity (occupational, sport/exercise, household/care giving, and active living) during pre, early and mid-pregnancy and duration of second stage of labor in a prospective cohort of 1,231 Hispanic participants. Physical activity was quantified using the Kaiser Physical Activity Survey administered during pregnancy. Using multivariate linear regression we did not find statistically significant association between pre, early and mid-pregnancy physical activity and duration of second stage of labor. The second study focused on the effect of gestational weight gain on the cesarean delivery rate after induction of labor. The rate of induction of labor (IOL) has more than doubled from 9.5% in 1990 to 22.5% in 2006. Cesarean delivery usually follows a failed IOL and is associated with maternal and fetal morbidity. One of the two studies evaluating the effect of gestational weight gain on the rate of cesarean section in patients undergoing IOL was restricted to women with normal Body Mass Index (BMI) and the other was subjected to bias because more than half of the patients were missing BMI data. Therefore, we evaluated the effect of gestational weight gain on the rate of cesarean delivery after labor induction. In a retrospective cohort study design, using data from May 2005 to June 2008 and a multivariate logistic regression we found a 13% increase in risk of cesarean delivery with 5 kg increase in gestational weight gain. Finally, we evaluated the effect of mode of delivery and duration of second stage of labor on intra-ventricular hemorrhage (IVH) among early preterm births. IVH is a serious complication associated with preterm birth and important predictors of cerebral palsy and neurodevelopmental delays. Prior studies on this relationship in early preterm births are sparse. In a retrospective cohort study of newborns born less than 30 weeks or less than 1500 g between May 2003 and August 2008, we found an increase in risk of IVH after vaginal delivery. However, duration of second stage of labor had no significant effect on risk of IVH.

Bakgrund: Diagnosen graviditetsdiabetes innebär en glukosintolerans vilket kan ge stora konsekvensersom komplikationer vid födsel, makrosomi eller diabetes typ 2. Riskfaktorerna för att fådiagnosen är bland annat högt BMI, ålder &gt;35 år samt låg fysisk aktivitetsnivå. Behandlingensom ges idag är råd om kost och träning, vid behov kan även läkemedel förskrivas. Syfte: Att sammanställa det nuvarande vetenskapliga underlaget vad gäller fysisk aktivitet för attförebygga uppkomst av diabetes hos gravida kvinnor i riskzonen för att utvecklagraviditetsdiabetes. Metod: Detta arbete är en systematisk litteraturstudie av randomiserade kontrollerade studier, somidentifierades via databaserna PubMed och Scopus. Granskning av risk för snedvridningbedömdes med TESTEX och tillförlitligheten för det sammanvägda resultatet bedömdes meden lokal mall från Uppsala universitet. Resultat: Åtta artiklar inkluderades i litteraturöversikten. Sju artiklar fick mellan 10-13 poäng efterTESTEX granskningen. En artikel uppnådde inte gränsvärdet för tillräcklig kvalité för attinkluderas i det sammanvägda resultatet. De sju artiklar med lägst risk för snedvridningvisade att träning inte hade någon signifikant effekt för att kunna förebygga uppkomsten avgraviditetsdiabetes. Tillförlitligheten till det sammanvägda resultatet bedömdes som låg. Slutsats: Baserat på resultaten från denna översikt konstateras att träning inte har en signifikant effektpå att förebygga graviditetsdiabetes för kvinnor med högt BMI alternativt låg fysiskaktivitetsnivå. Dock, på grund av den låga tillförlitligheten i de sammanvägda resultaten,behövs mer forskning inom detta område. / Background: The diagnosis of gestational diabetes implies glucose intolerance, which can have significantconsequences such as birth complications, macrosomia, or type 2 diabetes. Risk factors fordeveloping gestational diabetes include a high BMI, age &gt;35 years and low physical activitylevels. The current treatment provided involves advice on diet and exercise, and if necessary,medication can also be prescribed. Objective: To gather the current scientific evidence regarding the prevention of gestational diabetes withphysical activity for women at risk of developing gestational diabetes. Methods: This work was a systematic literature review of randomized controlled trials obtained throughthe databases PubMed and Scopus. Review of the risk of bias was assessed using TESTEX,and the reliability of the aggregated result was evaluated using a local template from UppsalaUniversity.  Results: Eight articles were included in the literature review. Seven articles scored between 10-13points after the TESTEX evaluation. One article did not reach the threshold for sufficientquality to be included in the combined results. The seven articles with the lowest risk of biasindicated that exercise did not have a significant effect in preventing the onset of gestationaldiabetes. However, the reliability of the aggregated result was assessed as low. Conclusions: Based on the findings from this review, it is observed that exercise does not have a significanteffect in preventing gestational diabetes for women with either high BMI or low physicalactivity levels. However, due to the low reliability of the combined results, more research isneeded in this area.