Burden, risk factors and outcomes associated with gestational diabetes in a population-based cohort of pregnant women from North India

Background The burden of gestational diabetes mellitus (GDM) appears to be increasing in India and may be related to the double burden of malnutrition. The population-based incidence and risk factors of GDM, particularly in lower socio-economic populations, are not known. We conducted analyses on data from a population-based cohort of pregnant women in South Delhi, India, to determine the incidence of GDM, its risk factors and association with adverse pregnancy outcomes (stillbirth, preterm birth, large for gestational age babies) and need for caesarean section. Methods We analyzed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. An oral glucose tolerance test (OGTT) was performed at the time of confirmation of pregnancy, and for those who had a normal test (≤140 mg), it was repeated at 24–28 and at 34–36 weeks. Logistic regression was performed to ascertain risk factors associated with GDM. Risk ratios (RR) were calculated to find association between GDM and adverse pregnancy outcomes and need for caesarean section. Results 19.2% (95% CI: 17.6 to 20.9) pregnant women who had at least one OGTT were diagnosed to have GDM. Women who had prediabetes at the time of confirmation of pregnancy had a significantly higher risk of developing GDM (RR 2.08, 95%CI 1.45 to 2.97). Other risk factors independently associated with GDM were woman’s age (adjusted OR (AOR) 1.10, 95% CI 1.06 to 1.15) and BMI (AOR 1.04, 95% CI 1.01 to 1.07). Higher maternal height was found to be protective factor for GDM (AOR 0.98, 95% CI 0.96 to 1.00). Women with GDM, received appropriate treatment did not have an increase in adverse outcomes and no increased need for caesarean section Conclusions A substantial proportion of pregnant women from a low to mid socio-economic population in Delhi had GDM, with older age, higher BMI and pre-diabetes as important risk factors. These findings highlight the need for interventions for prevention and provision of appropriate management of GDM in antenatal programmes. Clinical trial registration Clinical Trial Registry – India, #CTRI/2017/06/008908 (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

Co-Administration of Clomiphene Citrate and Letrozole in Mild Ovarian Stimulation Versus Conventional Controlled Ovarian Stimulation Among POSEIDON Group 4 Patients

This retrospective study assessed the effect of the co-administration of clomiphene citrate (CC) and letrozole in mild ovarian stimulation, compared to conventional regimens, among Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 4 patients. There were 114 POSEIDON Group 4 patients undergoing in vitro fertilization treatments with 216 stimulation cycles recruited from a Taiwan’s reproductive center during 2016-2020. Main outcomes were the numbers, quality of retrieved oocytes and embryo development. Pregnancy outcomes were assessed after embryo transfers. Per stimulation cycle, patients receiving mild stimulation with a combination of CC and letrozole (study group) versus those with COS (control group) had lower numbers of pre-ovulatory follicles (2.00 ± 1.23 vs. 2.37 ± 1.23, p=0.0066) and oocytes retrieved (1.83 ± 1.17 vs. 2.37 ± 1.23, p=0.0017), and lower follicular output rate (58.6% vs. 68.38%, p=0.0093) and mature oocyte output rate (44.29% vs. 52.88%, p=0.0386) but a higher top-quality metaphase II oocyte ratio (66.7% vs. 54.59%, p=0.0444) and a similar fertilization rate (91.67% vs. 89.04%, p=0.4660). With adjustment for significant between-group baseline differences using multivariable logistic generalized estimating equation model analyses, there was no statistical difference in oocytes retrieved and embryo development between the study and control groups, and insignificant increases in successful pregnancies in the study group were found compared to the control group (i.e., odds ratios [95% CIs]: 1.13 [0.55, 232] and 1.50 [0.65, 3.49] for ongoing pregnancy and live birth, respectively). For POSEIDON Group 4 patients, cotreatment of CC and letrozole in mild stimulation may increase the high-quality oocyte ratio and yield comparable fertilization rate and pregnancy outcomes.

Maternal Pre-Pregnancy Obesity Combined With Abnormal Glucose Metabolism Further Increases Adverse Pregnancy Outcomes in Chinese Pregnant Women

AimsOur aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes.MethodsA total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups.ResultsCompared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286–7.156]; 1.993 [1.171–3.393]; 8.495 [4.982–14.485]), preeclampsia (2.649 [1.224–5.735]; 2.129 [1.128–4.017]; 4.643 [2.217–9.727]), cesarean delivery (1.589 [1.212–2.083]; 1.328 [1.095–1.611]; 2.627 [1.908–3.617]), preterm delivery (1.899 [1.205–2.993]; 1.358 [0.937–1.968]; 2.301 [1.423–3.720]), macrosomia (2.449 [1.517–3.954]; 1.966 [1.356–2.851]; 4.576 [2.895–7.233]), and total adverse maternal outcomes (1.762 [1.331–2.332]; 1.365 [1.122–1.659]; 3.228 [2.272–4.587]) and neonatal outcomes (1.951 [1.361–2.798]; 1.547 [1.170–2.046]; 3.557 [2.471–5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone.ConclusionsMaternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.

Porphyromonas gingivalis Administration Induces Gestational Obesity, Alters Gene Expression in the Liver and Brown Adipose Tissue in Pregnant Mice, and Causes Underweight in Fetuses

Preventing adverse pregnancy outcomes is crucial for maternal and child health. Periodontal disease is a risk factor for many systemic diseases including adverse pregnancy outcomes, such as preterm birth and low birth weight. In addition, the administration of the periodontopathic bacterium Porphyromonas gingivalis exacerbates obesity, glucose tolerance, and hepatic steatosis and alters endocrine function in the brown adipose tissue (BAT). However, the effects of having periodontal disease during pregnancy remain unclear. Thus, this study investigates the effect of P. gingivalis administration on obesity, liver, and BAT during pregnancy. Sonicated P. gingivalis (Pg) or saline (Co) was injected intravenously and administered orally to pregnant C57BL/6J mice three times per week. Maternal body weight and fetal body weight on embryonic day (ED) 18 were evaluated. Microarray analysis and qPCR in the liver and BAT and hepatic and plasma triglyceride quantification were performed on dams at ED 18. The body weight of Pg dams was heavier than that of Co dams; however, the fetal body weight was decreased in the offspring of Pg dams. Microarray analysis revealed 254 and 53 differentially expressed genes in the liver and BAT, respectively. Gene set enrichment analysis exhibited the downregulation of fatty acid metabolism gene set in the liver and estrogen response early/late gene sets in the BAT, whereas inflammatory response and IL6/JAK/STAT3 signaling gene sets were upregulated both in the liver and BAT. The downregulation of expression levels of Lpin1, Lpin2, and Lxra in the liver, which are associated with triglyceride synthesis, and a decreasing trend in hepatic triglyceride of Pg dams were observed. P. gingivalis administration may alter lipid metabolism in the liver. Overall, the intravenous and oral administration of sonicated P. gingivalis-induced obesity and modified gene expression in the liver and BAT in pregnant mice and caused fetuses to be underweight.

Graft function and pregnancy outcomes after kidney transplantation

Background After kidney transplantation, pregnancy and graft function may have a reciprocal interaction. We evaluated the influence of graft function on the course of pregnancy and vice versa. Methods We performed a retrospective observational study of 92 pregnancies beyond the first trimester in 67 women after renal transplantation from 1972 to 2019. Pre-pregnancy eGFR was correlated with outcome parameters; graft function was evaluated by Kaplan Meier analysis. The course of graft function in 28 women who became pregnant after kidney transplantation with an eGFR of < 50 mL/min/1.73m2 was compared to a control group of 79 non-pregnant women after kidney transplantation during a comparable time period and with a matched basal graft function. Results Live births were 90.5% (fetal death n = 9). Maternal complications of pregnancy were preeclampsia 24% (graft loss 1, fetal death 3), graft rejection 5.4% (graft loss 1), hemolytic uremic syndrome 2% (graft loss 1, fetal death 1), maternal hemorrhage 2% (fetal death 1), urinary obstruction 10%, and cesarian section. (76%). Fetal complications were low gestational age (34.44 ± 5.02 weeks) and low birth weight (2322.26 ± 781.98 g). Mean pre-pregnancy eGFR was 59.39 ± 17.62 mL/min/1.73m2 (15% of cases < 40 mL/min/1.73m2). Pre-pregnancy eGFR correlated with gestation week at delivery (R = 0.393, p = 0.01) and with percent eGFR decline during pregnancy (R = 0.243, p = 0.04). Pregnancy-related eGFR decline was inversely correlated with the time from end of pregnancy to chronic graft failure or maternal death (R = -0.47, p = 0.001). Kaplan Meier curves comparing women with pre-pregnancy eGFR of ≥ 50 to < 50 mL/min showed a significantly longer post-pregnancy graft survival in the higher eGFR group (p = 0.04). Women after kidney transplantation who became pregnant with a low eGFR of > 25 to < 50 mL/min/1.73m2 had a marked decline of renal function compared to a matched non-pregnant control group (eGFR decline in percent of basal eGFR 19.34 ± 22.10%, n = 28, versus 2.61 ± 10.95%, n = 79, p < 0.0001). Conclusions After renal transplantation, pre-pregnancy graft function has a key role for pregnancy outcomes and graft function. In women with a low pre-pregnancy eGFR, pregnancy per se has a deleterious influence on graft function. Trial registration Since this was a retrospective observational case series and written consent of the patients was obtained for publication, according to our ethics’ board the analysis was exempt from IRB approval. Clinical Trial Registration was not done. The study protocol was approved by the Ethics Committee of Hannover Medical School, Chairman Prof. Dr. H. D. Troeger, Hannover, December 12, 2015 (IRB No. 2995–2015).

Does Adding Adverse Pregnancy Outcomes Improve the Framingham Cardiovascular Risk Score in Women? Data from the Tehran Lipid and Glucose Study

Background Limited and conflicting evidence is available regarding the predictive value of adding adverse pregnancy outcomes (APOs) to established cardiovascular disease (CVD) risk factors. Hence, the objective of this study was to determine whether adding APOs to the Framingham risk score improves the prediction of CVD events in women. Methods and Results Out of 5413 women who participated in the Tehran Lipid and Glucose Study, 4013 women met the eligibility criteria included for the present study. The exposure and the outcome variables were collected based on the standard protocol. Cox proportional hazard model was used to evaluate the association of APOs and CVDs. The variant of C‐statistic for survivals and reclassification of subjects into Framingham risk score categories after adding APOs was reported. Out of the 4013 eligible subjects, a total of 1484 (36.98%) women reported 1 APO, while 395 (9.84%) of the cases reported multiple APOs. Univariate proportional hazard Cox models showed the significant relations between CVD events and APOs. The enhanced model had a higher C‐statistic indicating more acceptable discrimination as well as a slight improvement in discrimination (C‐statistic differences: 0.0053). Moreover, we observed a greater risk of experiencing a CVD event in women with a history of multiple APOs compared with cases with only 1 APO (1 APO: hazard ratio [HR] = 1.22; 2 APOs: HR; 1.94; ≥3 APOs: HR = 2.48). Conclusions Beyond the established risk factors, re‐estimated CVDs risk by adding APOs to the Framingham risk score may improve the accurate risk estimation of CVD. Further observational studies are needed to confirm our findings.

Independent effect of gestational weight gain and prepregnancy obesity on pregnancy outcomes among Saudi women: A sub-cohort analysis from Riyadh mother and baby cohort study (RAHMA)

Background Gestational weight gain (GWG) and prepregnancy obesity are garnering more attention as determining factors of pregnancy outcomes when it comes to the wellbeing of both the mother and her baby. This study was conducted to describe the pattern of GWG among participants of Riyadh Mother and Baby Multicenter Cohort Study (RAHMA) and to investigate the detrimental effects of excessive GWG and prepregnancy obesity on pregnancy outcomes. Methods RAHMA is a multicentre cohort study conducted in three hospitals in Riyadh, Saudi Arabia. Participants were categorized according to the Institute of Medicine into inadequate, adequate, and excessive GWG, and stratified by body mass index (BMI) into under/normal weight, overweight, and obese. To examine the independent effect of maternal prepregnancy obesity and GWG, a multivariate regression model was used and adjusted odds ratio (AOR) and 95% Confidence Interval (CI) for each outcome were calculated. Results A total of 7029 participants were included in this study; 31.8% had adequate GWG, 25.9% had excessive GWG and 42.3% had inadequate GWG, while 29.7% had normal BMI, 33.3% were overweight, 34.8% were obese, and 2.2% were underweight. Excessive GWG was independently associated with increased risk of hypertensive events, (AOR = 1.77, 95% CI 1.20–2.63). Obesity was associated with higher risk of gestational diabetes (AOR 2.11, 95% CI 1.76–2.53), hypertensive events (AOR 2.06, 95% CI 1.48–3.01), and delivery by emergency caesarean section (AOR = 1.63, 95% CI 1.35–1.97). Infants of obese women had increased odds of macrosomia (AOR 3.11, 95% CI 1.94–4.99) and lower odds of low birth weight (AOR = 0.68, 95% CI 0.53–0.88). Conclusion In comparison to excessive GWG, which increases the risk of hypertensive events during pregnancy, prepregnancy obesity is associated with more adverse outcomes including GDM, hypertensive events in pregnancy and emergency CS.