Anxiety and Depression in Early Gestation and the Association with Subsequent Gestational Diabetes Mellitus in a Disadvantaged Population

Published online: 12 October 2023Objectives: Evaluate the association between poor mental health and risk of developing gestational diabetes mellitus (GDM) in a cohort of women from a socioeconomically disadvantaged community. Methods: A total of 1363 nulliparous women with singleton pregnancies recruited to the Screening Tests to Predict Poor Outcomes of Pregnancy study in Adelaide, Australia. Women were assessed for mental health in the first trimester, including likelihood of depression, high functioning anxiety, perceived stress and risk of developing a mental health disorder. GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria. Socioeconomic status was measured using the New Zealand Socioeconomic Index (NZSEI). Results: Complete mental health data was available for 1281 participants. There was no statistically significant difference in SEI, depression, risk of mental health issues, high functioning anxiety and perceived stress between women who developed GDM and those who did not. There was no difference in history of depression nor risk of developing a high mental health disorder in first trimester after adjusting for SEI, BMI in first trimester, smoking status in first trimester and maternal age between women with a GDM pregnancy and those who did not. Conclusions for Practice: There was no difference in markers of poor mental health in early pregnancy between women who subsequently did or did not develop GDM. Cohort participants were socioeconomically disadvantaged, potentially contributing to the lack of apparent differences in depression observed between groups. Socioeconomically disadvantaged women should be targeted in pre-conception planning to reduce risk of GDM.Maleesa M. Pathirana, Prabha H. Andraweera, Shalem Leemaqz, Emily Aldridge, Margaret A. Arstall, Gustaaf A. Dekker, Claire T. Robert

Early pregnancy cardio metabolic risk factors and the prevalence of metabolic syndrome 10 years after the first pregnancy

Background We aimed to compare risk factors for CVD 10 years postpartum among women who had ≥ 1 compared to no cardio metabolic risk factor in early first pregnancy. Methods Women of the SCOPE (Screening fOr Pregnancy Endpoints) study from Adelaide, South Australia were invited to participate in a cardiovascular risk assessment 10 years after the delivery of the first child. Data from 141 women who completed all the assessments are included in the analyses. Result Compared to women who did not have any cardio metabolic risk factor at 15 ± 1 weeks’ gestation during the first pregnancy, those who had ≥ 1 risk factor were 5.5 times more likely to have metabolic syndrome 10 years postpartum (aOR = 5.5, 95% CI 1.8–17.3, p = 0.004). Women who had ≥ 1cardio metabolic risk factor during the first pregnancy were more likely to be obese (p = 0.001), have high total cholesterol levels (p <0.001) or have increased insulin resistance (p <0.001) 10 years later compared to women who had no risk factor during the first pregnancy. 63.5% of the women with no cardio metabolic risk factor compared to 39% of women who had ≥ 1 risk factor in first pregnancy, had neither a complicated first pregnancy nor was diagnosed with MetS 10 years postpartum (p = 0.023). Conclusion Cardio metabolic risk factors at the booking visit in the first pregnancy may be useful in identifying young women at risk of future CVD.Prabha H. Andraweera, Michelle D. Plummer, Amy Garrett, Shalem Leemaqz, Melanie R. Wittwer, Emily Aldridge, Maleesa M. Pathirana, Gus A. Dekker, Claire T. Roberts, Margaret A. Arstal

Gestational diabetes mellitus and cardio-metabolic risk factors in women and children at 3 years postpartum

Introduction: Gestational diabetes mellitus (GDM) is thought to be associated with cardio-metabolic risk factor development in women and their children during the early postpartum period and early childhood. We hypothesized that these women and their children would exhibit increased abnormal cardio-metabolic risk factors three years after pregnancy. Methods: Women from the Screening Tests to Predict Poor Outcomes of Pregnancy study were invited to attend a followup with the child from their index pregnancy at 3 years postpartum. Women and children were assessed for anthropometric measures and haemodynamic function. Fasting blood samples were obtained from women to assess lipid and glucose status. Results: A total of 281 woman-child dyads participated in the 3-year follow-up, with 40 women developing GDM during their index pregnancy. Fasting serum insulin was higher in women with GDM in index pregnancy compared to those with an uncomplicated pregnancy. However, this association was mediated by early pregnancy BMI and socioeconomic index (SEI). The rate of metabolic syndrome was higher in the GDM group than the uncomplicated pregnancy group. Maternal GDM was associated with elevated maternal fasting serum triglycerides at 3 years after adjustment for early pregnancy BMI and SEI. Children exposed to GDM in utero had higher waist circumference compared to children born after an uncomplicated pregnancy, but this is mediated the above covariates. Conclusion: Exposure to GDM is associated with elevated serum triglycerides in women at 3 years postpartum but other cardiometabolic outcomes in women and children appear to be mediated by early pregnancy BMI and SEI.Maleesa M. Pathirana, Prabha H. Andraweera, Emily Aldridge, Shalem Y. Leemaqz, Madeline Harrison, Jade Harrison, Petra E. Verburg, Margaret A. Arstall, Gustaaf A. Dekker, Claire T. Robert

Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2

Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis

Published online by Cambridge University Press: 06 January 2020Gestational diabetes mellitus (GDM) is a pregnancy complication that affects one in seven pregnancies. Emerging evidence demonstrates that children born of pregnancies complicated by GDM may be at increased risk of cardiovascular disease (CVD) in adulthood. Therefore, the aim of this study was to determine cardiovascular risk factors in offspring exposed to GDM in utero. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Information was extracted on established CVD risk factors including blood pressure, lipids, blood glucose, fasting insulin, body mass index (BMI), and endothelial/microvascular function. The review protocol is registered in PROSPERO (CRD42018094983). Prospective and retrospective studies comparing offspring exposed to GDM compared to controls (non-GDM pregnancies) were considered. We included studies that defined GDM based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) definition, or prior definitions. The PRISMA guidelines were followed in conducting this systematic review. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Study selection, data extraction, and quality assessment were done by two independent reviewers. The data were pooled using a random-effects model. Of 59 eligible studies, 24 were included in the meta-analysis. Offspring exposed to GDM had higher systolic blood pressure (mean difference (MD): 1.75 mmHg, 95% CI 0.57-2.94; eight studies, 7264 participants), BMI z-score (MD 0.11, 95% CI 0.02-0.20; nine studies, 8759 participants), and glucose (standard MD 0.43, 95% CI 0.08-0.77; 11 studies, 6423 participants) than control participants. In conclusion, offspring exposed to GDM have elevated systolic blood pressure, BMI, and glucose. Those exposed to GDM in utero may benefit from early childhood blood pressure measurements.Maleesa M. Pathirana, Zohra S. Lassi, Claire T. Roberts and Prabha H. Andraweer

Author response to: Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis

Letter to the EditorThis commentary is an author response to Yu and colleagues regarding the manuscript entitled ‘Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: Systematic review and meta-analysis’. We address their concern regarding minor errors in our manuscript, our search strategy and assessment of heterogeneity.Maleesa M. Pathirana, Zohra S. Lassi, Claire T. Roberts, and Prabha H. Andraweer

Association between metabolic syndrome and gestational diabetes mellitus in women and their children: a systematic review and meta-analysis

Published: 15 September 2020PURPOSE:The primary aim of this systematic review and meta-analysis was to determine the association between gestational diabetes mellitus (GDM) and metabolic syndrome (MetS) in women and children. Our secondary aim was to assess the development of MetS with respect to the elapsed time postpartum at which MetS was diagnosed. METHODS:This review is registered with PROSPERO (CRD42020173319). PubMed, CINHAL, SCOPUS, and EMBASE databases were searched. Studies reporting on the rate of MetS in pregnant women with GDM, the rate of MetS in women with a history of GDM, and the rate of MetS in offspring exposed to GDM in utero compared to healthy controls were selected. RESULTS:We identified 588 articles from the literature search. Fifty-one studies were included in the review and of those 35 were included in the meta-analysis. Quantitative summary measures showed that women with a history of GDM had an increased risk of developing MetS compared to those without a history of GDM (RR 2.36, 95% CI 1.77-3.14, 29 studies, 13,390 participants; heterogeneity: χ2 p < 0.00001; I2 = 93%). Offspring exposed to GDM in utero have an increased risk of developing MetS compared to those not exposed to GDM in utero. (RR 2.07, 95% CI 1.26-3.42, three studies, 4,421 participants; heterogeneity: χ2 p = 0.33; I2 = 12%). Women diagnosed with GDM have an increased risk of developing MetS during pregnancy (RR 20.51, 95% CI 5.04-83.55; three studies, 406 participants; heterogeneity: χ2 p = 0.96; I2 = 0%). Subgroup analysis revealed that MetS is diagnosed as early as <1 year postpartum in women with a history of GDM. CONCLUSIONS/INTERPRETATION:Women with GDM have an increased risk of developing MetS during pregnancy. Women with a history of GDM and offspring exposed to GDM in utero have higher risks of developing MetS compared to those with no history of GDM. Metabolic syndrome in women with a history of GDM is seen as early as <1 year postpartum.Maleesa M. Pathirana, Zohra S. Lassi, Anna Ali, Margaret A. Arstall, Claire T. Roberts and Prabha H. Andraweer

Cardiovascular risk factors in women with previous gestational diabetes mellitus: a systematic review and meta-analysis

Published: 27 October 2020 OnlinePublThis systematic review and meta-analysis aimed to synthesize evidence on conventional cardiovascular disease (CVD) risk factors among women with previous Gestational Diabetes Mellitus (GDM). The review protocol is registered with PROSPERO (CRD42019118149). PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Studies reporting on CVD risk factors in women with previous GDM compared to women without previous GDM were selected. A total of 139 studies were eligible, of which 93 were included in the meta-analysis. Women with previous GDM have significantly higher systolic blood pressure (2.47 mmHg 95% CI 1.74 to 3.40, n = 48, 50,118 participants) diastolic blood pressure (1.89 mmHg 95% CI 1.32 to 2.46, n = 48, 49,495 participants), BMI (1.54 kg/m2 95% CI 1.32 to 2.46, n = 78, 255,308 participants), total cholesterol (0.26 SMD 95% CI 0.15 to 0.37, n = 48, 38,561 participants), LDL cholesterol (0.19 SMD 95% CI 0.08 to 0.30, n = 44, 16,980 participants), triglycerides (0.56 SMD 95% CI 0.42 to 0.70, n = 46, 13,175 participants), glucose (0.69 SMD 95% CI 0.56 to 0.81, n = 55, 127,900 participants), insulin (0.41 SMD 95% CI 0.23 to 0.59, n = 32, 8881 participants) and significantly lower HDL cholesterol (-0.28 SMD 95% CI -0.39 to -0.16, n = 56, 35,882 participants), compared to women without previous GDM. The increased blood pressure, total cholesterol, triglycerides and glucose are seen as early as <1 year post-partum.Women with previous GDM have a higher risk of CVD based on significant increases in conventional risk factors. Some risk factors are seen as early as <1 year post-partum. Women with GDM may benefit from early screening to identify modifiable CVD risk factors.Maleesa M. Pathirana, Zohra Lassi, Anna Ali, Margaret Arstall, Claire T. Roberts, Prabha H. Andraweer

Pregnancy complications and cardiovascular disease risk perception: A qualitative study

Objectives: We aimed to assess women’s perceptions on the long-term risks for cardiovascular disease (CVD) after major pregnancy complications. Methods: Women who experienced major pregnancy complications and those who experienced uncomplicated pregnancies were invited to participate in a qualitative study. Focus group discussions (FGDs) and self-administered questionnaires were used to explore: The knowledge of long-term sequelae after experiencing a major pregnancy complication; Importance of education on heart health; The practicality of referral to a clinic after pregnancy complications; Willingness for regular postpartum clinic visits after pregnancy complications. A thematic qualitative analysis was undertaken. Results: 26 women participated in four FGDs. The majority of women did not know of the association between major pregnancy complications and CVD. The main views expressed were: Women who experience pregnancy complications should receive education on improving heart health; An appointment for the first CVD risk screening visit needs to be made prior to discharge from the delivery suite; Women will benefit by having the option to select between a hospital and a general-practitioner based model of follow up. Conclusions: These views are important in developing postpartum strategies to reduce CVD risk among women who experience pregnancy complications.Prabha H. Andraweera, Zohra S. Lassi, Maleesa M. Pathirana, Michelle D. Plummer, Gus A. Dekker, Claire T. Roberts, Margaret A. Arstal

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95–1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91–1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71–1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70–0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89–1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events.Madeleine N Jones, Kirsten R Palmer, Maleesa M Pathirana, Jose Guilherme Cecatti, Olimpio B Moraes Filho, Lena Marions, Måns Edlund, Martina Prager, Craig Pennell, Jan E Dickinson, Nelson Sass, Marta Jozwiak, Mieke Ten Eikelder, Katrien Oude Rengerink, Kitty W M Bloemenkamp, Amanda Henry, Ellen C L Løkkegaard, Ib Jarle Christensen, Jeff M Szychowski, Rodney K Edwards, Michael Beckmann, Caroline Diguisto, Amélie Le Gouge, Franck Perrotin, Ian Symonds, Sean O, Leary, Daniel L Rolnik, Ben W Mol, Wentao L