Obstetrics and Gynaecology - Research Publications
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ItemThe effect of breastfeeding on postpartum glucose tolerance and lipid profiles in women with gestational diabetes mellitus(BMC, 2019-11-04)Background: We aimed to investigate the association of breastfeeding on postpartum glucose levels and lipid profiles in women diagnosed with gestational diabetes mellitus (GDM) and women without GDM. Methods: We performed a secondary analysis of a cohort study of 243 women, 159 women with GDM and 84 normally glucose tolerant women between 2012 and 2017. At approximately 6–10 weeks postpartum, we measured fasting blood glucose and plasma lipid levels. Breastfeeding behaviour was self-defined as exclusive breastfeeding or not exclusive breastfeeding. Results: The mean (SD) glucose in the group of women who breastfed exclusively was 4.6 (0.49) mmol/L, compared to 4.9 (0.58) mmol/L (95% CI 0.45, 0.15, p < 0.001) among women who did not exclusively breastfeed. Among women with GDM, the reduction in fasting glucose in women who were breastfeeding was 0.22 mmol/L (95% CI 0.39, 0.05, p = 0.004), and in women who were not GDM, the reduction was 0.14 mmol/L (95% CI 0.37, 0.09, p = 0.24,). After adjustment for GDM status in pregnancy, maternal body mass index (BMI), maternal age and ethnicity, and exclusive breastfeeding was associated with a decreased fasting glucose of 0.19 (95% CI 0.318, 0.061, p = 0.004). After similar adjustment, there was no significant difference in triglycerides, high density lipoprotein cholesterol or low-density lipoprotein cholesterol between women who were breastfeeding and women who were not breastfeeding. Conclusions: Breastfeeding is associated with a reduction in fasting glucose levels postpartum, but not maternal lipid profile. Breastfeeding may play a role in reducing glucose intolerance in women who have had GDM.
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ItemPostpartum circulating cell-free insulin DNA levels are higher in women with previous gestational diabetes mellitus who develop type 2 diabetes in later life(Hindawi Publishing Corporation, 2019)Background. Women with previous gestational diabetes mellitus (GDM) have evidence of postpartum β-cell dysfunction, which increases their risk of developing type 2 diabetes (T2DM) later in life. Elevated levels of circulating cell-free preproinsulin (INS) DNA correlate with dying β-cells in both mice and humans. The aim of this study was to determine if cell-free circulating INS DNA levels are higher in women with previous GDM who develop T2DM. Methods. We used droplet digital (dd) PCR to measure the levels of cell-free circulating methylated and unmethylated INS DNA in plasma from 97 women with normal glucose tolerance (NGT), 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of T2DM. Results. In the follow-up period, 22% of women developed T2DM. Compared with NGT women, total cell-free INS DNA levels were significantly higher in women who developed T2DM (P = 0.02). There was no difference in cell-free circulating unmethylated and methylated INS DNA levels between NGT women and women who developed T2DM (P = 0.09 and P = 0.07, respectively). Conclusions. In women with a previous index GDM pregnancy, postpartum levels of cell-free circulating INS DNA are significantly higher in those women who later developed T2DM.
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ItemPlacental Vitamin D-Binding Protein Expression in Human Idiopathic Fetal Growth Restriction(HINDAWI LTD, 2017)Vitamin D-binding protein is a multifunctional serum protein with multiple actions related to normal health. Vitamin D-binding protein transports vitamin D and influences the metabolism of this key hormone but it also has additional immunomodulatory and actin-clearing properties. We investigated whether vitamin D-binding protein expression is altered in fetal growth restriction-associated placental dysfunction. Protein was extracted from 35 placentae derived from 17 healthy control subjects and 18 gestation-matched subjects with fetal growth restriction (FGR). FGR subjects were further subdivided as idiopathic (n = 9) and nonidiopathic (n = 9). Vitamin D-binding protein and 25(OH) vitamin D were measured by ELISA and normalized to protein concentration. The results showed significantly reduced levels of placental vitamin D-binding protein (control versus FGR, p < 0.05, Student's t-test) that were strongly associated with idiopathic fetal growth restriction (p < 0.01, Kruskal-Wallis), whereas levels of vitamin D-binding protein were not associated with placental 25(OH) vitamin D stores (p = 0.295, Pearson's correlation). As such, vitamin D-binding protein may be a factor in unexplained placental dysfunction associated with idiopathic fetal growth restriction and may potentially serve as a biomarker of this disease.
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ItemOmentin-1 Is Decreased in Maternal Plasma, Placenta and Adipose Tissue of Women with Pre-Existing Obesity(PUBLIC LIBRARY SCIENCE, 2012-08-28)OBJECTIVE: The aim of this study was to determine (i) the effect of maternal obesity and gestational diabetes mellitus (GDM) on (i) the circulating levels of omentin-1 in cord and maternal plasma, and (ii) gene expression and release of omentin-1 from human placenta and adipose tissue. The effect of pregnancy on circulating omentin-1 levels was also determined. DESIGN: Omentin-1 levels were measured in maternal and cord plasma from obese and non-obese normal glucose tolerant women (NGT; n = 44) and women with GDM (n = 39) at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of omentin-1 was measured from 22 NGT and 22 GDM women collected at the time of term elective Caesarean section. Omentin-1 levels were also measured in maternal plasma from 13 NGT women at 11 and 28 weeks gestation and 7 weeks postpartum. RESULTS: Maternal obesity was associated with significantly lower omentin-1 levels in maternal plasma; however, there was no effect of maternal obesity on cord omentin levels. Omentin-1 gene expression was lower in placenta and adipose tissue obtained from women with pre-existing obesity. In addition to this, adipose tissue release of omentin-1 was significantly lower from obese pregnant women. Omentin-1 levels were significantly lower in non-obese GDM compared to non-obese NGT women. However, there was no difference in omentin-1 levels between obese NGT and obese GDM women. There was no effect of GDM on cord omentin levels, and placental and adipose tissue omentin-1 expression. Maternal omentin-1 levels were negatively correlated with fetal birthweight and fetal ponderal index. CONCLUSIONS: The data presented in this study demonstrate that pre-existing maternal obesity is associated with lower omentin-1 expression in placenta, adipose tissue and maternal plasma. Alteration in omentin-1 in pregnancy may influence the development of metabolic disorders in offspring later in life.
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ItemIs Vitamin D Binding Protein a Novel Predictor of Labour?(PUBLIC LIBRARY SCIENCE, 2013-10-04)Vitamin D binding protein (VDBP) has previously been identified in the amniotic fluid and cervicovaginal fluid (CVF) of pregnant women. The biological functions of VDBP include acting as a carrier protein for vitamin D metabolites, the clearance of actin that is released during tissue injury and the augmentation of the pro-inflammatory response. This longitudinal observational study was conducted on 221 healthy pregnant women who spontaneously laboured and delivered either at term or preterm. Serial CVF samples were collected and VDBP was measured by ELISA. Binary logistic regression analysis was performed to assess the utility of VDBP as a predictor of labour. VDBP in the CVF did not change between 20 and 35 weeks' gestation. VDBP measured in-labour was significantly increased 4.2 to 7.4-fold compared to 4-7, 8-14 and 15-28 days before labour (P<0.05). VDBP concentration was 4.3-fold significantly higher at 0-3 days compared to 15-28 days pre-labour (P<0.05). The efficacy of VDBP to predict spontaneous labour onset within 3 days provided a positive and negative predictive value of 82.8% and 95.3% respectively (area under receiver operator characteristic curve = 0.974). This longitudinal study of pregnant women suggests that VDBP in the CVF may be a useful predictor of labour.
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ItemHuman cervicovaginal fluid biomarkers to predict term and preterm labor(FRONTIERS MEDIA SA, 2015-05-13)Preterm birth (PTB; birth before 37 completed weeks of gestation) remains the major cause of neonatal morbidity and mortality. The current generation of biomarkers predictive of PTB have limited utility. In pregnancy, the human cervicovaginal fluid (CVF) proteome is a reflection of the local biochemical milieu and is influenced by the physical changes occurring in the vagina, cervix and adjacent overlying fetal membranes. Term and preterm labor (PTL) share common pathways of cervical ripening, myometrial activation and fetal membranes rupture leading to birth. We therefore hypothesize that CVF biomarkers predictive of labor may be similar in both the term and preterm labor setting. In this review, we summarize some of the existing published literature as well as our team's breadth of work utilizing the CVF for the discovery and validation of putative CVF biomarkers predictive of human labor. Our team established an efficient method for collecting serial CVF samples for optimal 2-dimensional gel electrophoresis resolution and analysis. We first embarked on CVF biomarker discovery for the prediction of spontaneous onset of term labor using 2D-electrophoresis and solution array multiple analyte profiling. 2D-electrophoretic analyses were subsequently performed on CVF samples associated with PTB. Several proteins have been successfully validated and demonstrate that these biomarkers are associated with term and PTL and may be predictive of both term and PTL. In addition, the measurement of these putative biomarkers was found to be robust to the influences of vaginal microflora and/or semen. The future development of a multiple biomarker bed-side test would help improve the prediction of PTB and the clinical management of patients.
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ItemPredicting Preterm Labour: Current Status and Future Prospects(HINDAWI LTD, 2015)Preterm labour and birth are a major cause of perinatal morbidity and mortality. Despite modern advances in obstetric and neonatal management, the rate of preterm birth in the developed world is increasing. Yet even though numerous risk factors associated with preterm birth have been identified, the ability to accurately predict when labour will occur remains elusive, whether it is at a term or preterm gestation. In the latter case, this is likely due to the multifactorial aetiology of preterm labour wherein women may display different clinical presentations that lead to preterm birth. The discovery of novel biomarkers that could reliably identify women who will subsequently deliver preterm may allow for timely medical intervention and targeted therapeutic treatments aimed at improving maternal and fetal outcomes. Various body fluids including amniotic fluid, urine, saliva, blood (serum/plasma), and cervicovaginal fluid all provide a rich protein source of putative biochemical markers that may be causative or reflective of the various pathophysiological disorders of pregnancy, including preterm labour. This short review will highlight recent advances in the field of biomarker discovery and the utility of single and multiple biomarkers for the prediction of preterm birth in the absence of intra-amniotic infection.