Elevated serum squalene and cholesterol synthesis markers in pregnant obese women with gestational diabetes mellitus

We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus (GDM). Pregnant women at risk for GDM (BMI >30 kg/m²) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were collected at six time-points, one in each trimester of pregnancy, and at 6 weeks, 6 months, and 12 months postpartum. Analysis of serum squalene and noncholesterol sterols by gas-liquid chromatography revealed that in subjects with GDM (n = 22), the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher (P < 0.05) than in the controls (n = 30) in the first trimester, reflecting increased cholesterol synthesis. Also, subjects with GDM had an increased ratio of squalene to cholesterol (100 × μmol/mmol of cholesterol) in the second (11.5 ± 0.5 vs. 9.1 ± 0.5, P < 0.01) and third (12.1 ± 0.8 vs. 10.0 ± 0.7, P < 0.05) trimester. In GDM, the second trimester maternal serum squalene concentration correlated with neonatal birth weight (r = 0.70, P < 0.001). In conclusion, in obesity, GDM associated with elevated serum markers of cholesterol synthesis. Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM.     

Pre-Conception Dyslipidemia Is Associated with Development of Preeclampsia and Gestational Diabetes Mellitus

IntroductionThe association between glucose intolerance, elevated blood pressure and abnormal lipid levels is well established and comprises the basis of metabolic syndrome pathophysiology. We hypothesize that abnormal preconception lipid levels are associated with the increased risk of severe pregnancy complications such as preeclampsia and gestational diabetes mellitus.MethodsWe included all singleton deliveries (n = 27,721) of women without known cardiovascular morbidity and preeclampsia and gestational diabetes mellitus during previous pregnancies. Association between preconception low high density lipoprotein cholesterol (HDLc level≤50 mg/dL), high triglycerides (level≥150 mg/dL) and the primary outcome (composite of gestational diabetes mellitus/or preeclampsia) was assessed using Generalized Estimation Equations.ResultsPrimary outcome of preeclampsia and/or gestational diabetes was observed in a total of 3,243 subjects (11.7%). Elevated triglycerides and low HDLc were independently associated with the primary outcome: with odds ratio (OR) of 1.61 (95% CI 1.29–2.01) and OR = 1.33 (95% CI 1.09–1.63), respectively, after adjusting for maternal age, weight, blood pressure, repeated abortions, fertility treatments and fasting glucose. There was an interaction between the effects of HDLc≤50 mg/dL and triglycerides≥150 mg/dL with an OR of 2.69 (95% CI 1.73–4.19).ConclusionsOur analysis showed an increased rate of preeclampsia and/or gestational diabetes in women with low HDLc and high triglycerides values prior to conception. In view of the severity of these pregnancy complications, we believe this finding warrants a routine screening for the abnormal lipid profile among women of a child-bearing age.     

Prevalence of Gestational Diabetes Mellitus in Korea: A National Health Insurance Database Study

Aims/IntroductionThis study aimed to estimate the prevalence of gestational diabetes mellitus (GDM) and use of anti-diabetic medications for patients with GDM in Korea, using data of the period 2007–2011 from the Health Insurance Review and Assessment (HIRA) database, which includes the claims data of 97% of the Korean population.ResultsThe annual numbers of deliveries in 2009–2011 were 479,160 in 2009, 449,747 in 2010, and 377,374 in 2011. The prevalence of GDM during that period was 7.5% in 2009–2011: 5.7% in 2009, 7.8% in 2010, and 9.5% in 2011. The age-stratified analysis showed that the prevalence of GDM was highest in women aged 40–44 years, at 10.6% in 2009–2011, and that the annual prevalence significantly increased even in young women aged 20–29 years during that period (P < 0.05). More than 95% of the patients with GDM did not take any anti-diabetic medication. Among the anti-diabetic medications prescribed for patients with GDM, insulin was most commonly prescribed (for >98% of the patients with GDM on medication).ConclusionsThe prevalence of GDM in Korean women recently reached 5.7–9.5% in recent years. This represents a public health concern that warrants proper screening and medical care for GDM in women during the childbearing years.     

Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial

ObjectiveTo compare perinatal outcome and glycaemic control in two groups of pregnant diabetic patients receiving two insulin regimens.DesignRandomised controlled open label study.SettingUniversity affiliated hospital, Israel.Participants138 patients with gestational diabetes mellitus and 58 patients with pregestational diabetes mellitus received insulin four times daily, and 136 patients with gestational diabetes and 60 patients with pregestational diabetes received insulin twice daily.InterventionThree doses of regular insulin before meals and an intermediate insulin dose before bedtime (four times daily regimen), and a combination of regular and intermediate insulin in the morning and evening (twice daily regimen).ResultsMean daily insulin concentration before birth was higher in the women receiving insulin four times daily compared with twice daily: by 22 units (95% confidence interval 12 to 32) in patients with gestational diabetes and by 28 units (15 to 41) in patients with pregestational diabetes. Glycaemic control was better with the four times daily regimen than with the twice daily regimen: in patients with gestational diabetes mean blood glucose concentrations decreased by 0.19 mmol/l (0.13 to 0.25), HbA_1c by 0.3% (0.2% to 0.4%), and fructosamine by 41 μmol/l (37 to 45), and adequate glycaemic control (mean blood glucose concentration <5.8 mmol/l) was achieved in 17% (8% to 26%) more women; in patients with pregestational diabetes mean blood glucose concentration decreased by 0.44 mmol/l (0.28 to 0.60), HbA_1c by 0.5% (0.2% to 0.8%), and fructosamine by 51 μmol/l (45 to 57), and adequate glycaemic control was achieved in 31% (15% to 47%) more women. Maternal severe hypoglycaemic events, caesarean section, preterm birth, macrosomia, and low Apgar scores were similar in both dose groups. In women with gestational diabetes the four times daily regimen resulted in a lower rate of overall neonatal morbidity than the twice daily regimen (relative risk 0.59, 0.38 to 0.92), and the relative risk for hyperbilirubinaemia and hypoglycaemia was lower (0.51, 0.29 to 0.91 and 0.12, 0.02 to 0.97 respectively). The relative risk of hypoglycaemia in newborn infants to mothers with pregestational diabetes was 0.17 (0.04 to 0.74).ConclusionsGiving insulin four times rather than twice daily in pregnancy improved glycaemic control and perinatal outcome without further risking the mother.

Key messages

• Improving maternal glycaemic control during pregnancy is the key to better perinatal outcome
• In pregnant diabetic women insulin four times daily achieved better glycaemic control and lower rate of perinatal complications (hypoglycaemia, hyperbilirubinaemia) than insulin twice daily
• Better glycaemic control resulted from a larger total daily insulin dose
• The intensified regimen did not lead to higher rate of severe maternal hypoglycaemia

     

The Association of Gestational Weight Gain and Adverse Pregnancy Outcomes in Women with Gestational Diabetes Mellitus

Objective: To explore the association of excessive gestational weight gain (GWG) defined by the Institute of Medicine (IOM) targets and adverse perinatal outcomes in gestational diabetes mellitus (GDM) pregnancies, and whether a modified target might be related to a lower rate of adverse perinatal outcomes for GDM.Methods: This retrospective cohort study involved 1,138 women of normal glucose tolerance (NGT) and 1,200 women with GDM. Based on the IOM target, pregnancies were classified to appropriate GWG (aGWG), inadequate GWG, and excessive GWG (eGWG). Modified GWG targets included: upper limit of IOM target minus 1 kg (IOM-1) or 2 kg (IOM-2), both upper and lower targets minus 1 kg (IOM-1-1) or 2 kg (IOM-2-2).Results: The proportions of women achieving eGWG were 26.3% in NGT and 31.2% in GDM (P = .036); in comparison, for aGWG NGT, the risks of large for gestational age (LGA) were significantly higher in eGWG NGT (adjusted odds ratio &lsqb;OR] 1.47; 95% confidence interval &lsqb;CI] 1.02 to 2.13), aGWG GDM (adjusted OR 1.42; 95% CI 1.03 to 1.95), and eGWG GDM (adjusted OR 2.70; 95% CI 1.92 to 3.70). GDM pregnancies gaining aGWG based on the modified GWG targets (IOM-2, IOM-1-1, and IOM-2-2) had a lower prevalence of LGA and macrosomia delivery than that for similar pregnancies using the original IOM target (all P<.05).Conclusion: For aGWG GDM according to the IOM target, adhering to a more stringent weight control was associated with decreased adverse outcomes. A tighter IOM target might help to reduce the prevalence of adverse pregnancy outcomes.Abbreviations: aGWG = appropriate gestational weight gain; BG = blood glucose; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; GDM = gestational diabetes mellitus; GW = gestational weeks; GWG = gestational weight gain; HbA1c = hemoglobin A1c; iGWG = inadequate gestational weight gain; IOM = Institute of Medicine; LGA = large for gestational age; NGT = normal glucose tolerance; NICU = neonatal intensive care unit; OGTT = oral glucose tolerance test; OR = odds ratio; PARp = partial population attributable risks; SGA = small for gestational age     

Carotid artery plaque in women with rheumatoid arthritis and low estimated cardiovascular disease risk: a cross-sectional study

IntroductionWe previously reported that most patients with rheumatoid arthritis (RA) and moderate cardiovascular disease (CVD) risk according to the Systematic COronary Evaluation score (SCORE) experience carotid artery plaque. In this study, we aimed to identify patient characteristics that can potentially predict carotid plaque presence in women with RA and a concurrent low CVD risk according to the SCORE.MethodsA cohort of 144 women with an evaluated low risk of CVD (SCORE value of zero) was assembled amongst 550 consecutive patients with RA that underwent CVD risk factor recording and carotid artery ultrasound. Participants had no established CVD, moderate or severe chronic kidney disease, or diabetes. We assessed carotid plaque(s) presence and its associated patient characteristics.ResultsCarotid artery plaque was present in 35 (24.3%) of women with RA. Age, the number of synthetic disease-modifying agents (DMARDs) and total cholesterol concentrations were independently associated with plaque in multivariable stepwise backward regression analysis (odds ratio (95% confidence interval) = 1.15 (1.07 to 1.24), P <0.0001, 1.51 (1.05 to 2.17), P = 0.03 and 1.66 (1.00 to 2.73) P = 0.04), respectively). The area under the curve (AUC) of the receiver operating curve (ROC) for the association with plaque was 0.807 (P <0.0001), 0.679 (P = 0.001) and 0.599 (P = 0.08) for age, total cholesterol concentrations and number of synthetic DMARDs used, respectively. The optimal cutoff value in predicting plaque presence for age was 49.5 years with a sensitivity and specificity of 74% and 75%, respectively, and for total cholesterol concentration, it was 5.4 mmol/l with a sensitivity and specificity of 63% and 70%, respectively. The plaque prevalence was 37.5% in patients (n = 80; 55.6%) with age >49.5 years or/and total cholesterol concentration of >5.4 mmol/l, respectively, compared to only 7.8% in those (n = 64; 44.4%) with age ≤49.5 years or/and total cholesterol concentration of ≤5.4 mmol/l, respectively.ConclusionsApproximately one-third of women with RA who experience a low SCORE value and are aged >49.5 years or/and have a total cholesterol concentration of >5.4 mmol/l, experience high-risk atherosclerosis, which requires intensive CVD risk management.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0576-7) contains supplementary material, which is available to authorized users.     

Hypofractionated radiotherapy in young versus older women with breast cancer: a retrospective study from India

BackgroundYoung women with breast cancer (BC) are not represented in the trials on hypofractionation. In this study we compared outcomes in young patients with BC to their older counterparts treated with hypofractionated radiotherapy (RT) in a regional cancer centre in India.Materials and methodsBetween January 1990 to December 2010, women with BC, treated with hypofractionated RT dose of 35–40 Gy/15#/3 weeks were divided into two groups, ≤ 35 years and > 35 years. Outcomes compared were locoregional recurrence rate (LRR), locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS) and toxicities. LRRFS, DFS and OS were estimated using the Kaplan-Meier method.ResultsOf total 2244 patients, 359 were ≤ 35 years of age and 1885 were > 35 years. Patient and disease characteristics were comparable between the two groups, except that comorbidities were significantly higher in the > 35 years age group, more patients aged ≤ 35 years had nodal N3 disease, received chemotherapy and RT to internal mammary nodes and more patients in the > 35 years group received hormonal therapy. Median follow up was 10 years (range 1–30 years). LRR and distant metastases were comparable between the two groups. However, synchronous LRR and distant metastases were significantly higher in the ≤ 35 years group 18 (5.1%) as compared to the > 35 years group 39 (2.1%) with p = 0.018. Estimated 10-year LRRFS, DFS and OS were 92% vs. 94% (p = 0.95), 68% vs. 73%(p = 0.058) and 78% vs. 76% (p = 0.10) in ≤ 35 years and > 35 years, respectively. OS for stage 1 was comparable between the two groups. However, for stage 2 and 3 it was 77% vs. 82% (p = 0.048) and 53% vs. 62% (p = 0.045) in the ≤ 35 years and > 35 years group, respectively. Acute and late toxicity were similar in the two groups.ConclusionYoung BC patients had higher LRR and distant metastases. LRRFS, DFS and toxicities were comparable between the two groups. However, OS was poorer in young BC patients with stage 2 and 3 disease.     

Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus

Aims

Serum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women.

Methods

This cross-sectional study consisted of 400 pregnant women including111 with GDM and 289 with normal glucose tolerance at 24–28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR).

Results

Serum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8–1.8) vs 0.7(0.6–1.0), P<0.01). The Spearman’s correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977–40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95mg/L.

Conclusions

Serum CysC is significantly and independently associated with insulin resistance and GDM. It may be a helpful biomarker to identify the risk of GDM in Chinese pregnant women.     

Maternal Age at First Delivery Is Associated with the Risk of Metabolic Syndrome in Postmenopausal Women: From 2008–2010 Korean National Health and Nutrition Examination Survey

BackgroundRecent cross-sectional studies demonstrated that earlier maternal age at first childbirth is correlated with a higher risk of diabetes in postmenopausal women. In this study, we evaluated whether the age at first delivery is associated with the risk of metabolic syndrome (MetS) in postmenopausal women.MethodsA total of 4,261 postmenopausal women aged 45 years or older were analyzed using data generated from Korea National Health and Nutrition Examination Surveys (2008–2010). Subjects were divided into three groups according to the maternal age at first delivery as follows: ≤ 20 years (n=878), 21-25 years (n=2314), and ≥ 26 years (n=1069).ResultsApproximately 37% of subjects had MetS. The prevalence of MetS showed a gradual increase as maternal age at first delivery decreased (≥ 26 years = 30.9% vs. 21-25 years = 39.9% vs. ≤ 20 years = 50.8%, respectively, p < 0.001). Central obesity indices such as trunk fat mass and waist circumference were significantly higher in the group aged ≤ 20 years than other groups. After adjustments for confounding factors, the odds ratios (ORs) for predicting the presence of MetS increased gradually as first delivery age decreased (≥ 26 years vs. 21-25 years vs. ≤ 20 years: OR [95% CI] = 1 vs. 1.324 [1.118-1.567] vs. 1.641 [1.322-2.036], respectively). Among components of MetS, younger maternal age at first delivery (≤ 20 years) was significantly associated with increased waist circumference (OR [95% CI] = 1.735 [1.41-2.13]), elevated blood pressure (1.261 [1.02-1.57]), high triglyceride (1.333 [1.072-1.659]), and low HDL-cholesterol (1.335[1.084-1.643]).ConclusionsOur findings suggest that younger maternal age at first delivery is independently associated with a higher risk of central obesity and MetS in postmenopausal women.     

Association of Maternal Vitamin D Status with Glucose Tolerance and Caesarean Section in a Multi-Ethnic Asian Cohort: The Growing Up in Singapore Towards Healthy Outcomes Study

Objective

Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study.

Methods

Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26–28 weeks’ gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section.

Results

In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73).

Conclusions

25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women.     

Early Predictors of Gestational Diabetes Mellitus in IVF-Conceived Pregnancies

ObjectiveGestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcomes. This study aimed to identify early and reliable GDM predictors that would enable implementation of preventive and management measures.MethodsThe participants were a 28-week prospective cohort of in vitro fertilization (IVF)-conceived pregnant women (≤39 years, body mass index [BMI] 18.5-38 kg/m²) without a known history of diabetes mellitus. Fasting blood samples were analyzed at baseline (pre-IVF) and 12 weeks’ gestation for reproductive hormones, glucose, serum insulin, lipids, thyroid function, adiponectin, and lipopolysaccharide-binding protein. At 28 weeks, a 75-g oral glucose tolerance test was used to screen for GDM.ResultsFor the overall group at baseline, 22% had BMI ≥30 kg/m², 45% had polycystic ovary syndrome, 16% had hemoglobin A1C of 5.7% to 6.1%, and 14% had a past history of GDM. At 28 weeks of gestation (n = 158), 34 women had developed GDM and 124 had not. Significant baseline predictors of GDM onset included greater BMI (29.0 vs 25.8 kg/m²), older age (34 vs 32 years), higher levels of follicle-stimulating hormone/luteinizing hormone ratio (1.2 vs 1.0), hemoglobin A1C (5.5 vs 5.2%), insulin (10.6 vs 7.1 μIU/mL), homeostatic model assessment of insulin resistance (2.2 vs 1.7), total cholesterol (199 vs 171 mg/dL), and low-density lipoprotein cholesterol (123 vs 105 mg/dL), and lower triglyceride levels (74 vs 76 mg/dL). Significant 12-week GDM predictors included greater maternal weight gain (delta: 3.4 vs 1.5 kg) and higher levels of insulin (11.3 vs 7.6 μIU/mL), triglycerides (178 vs 120 mg/dL), and homeostatic model assessment of insulin resistance (2.3 vs 1.5). Twelve-week BMI is a predictor of GDM following adjustment for polycystic ovary syndrome status and maternal age.ConclusionWhile preconception maternal BMI, age, and follicle-stimulating hormone/luteinizing hormone ratio are predictors of subsequent development of GDM, early IVF-conceived gestational weight gain is the best predictor of GDM onset.     

Obstetrical outcomes and maternal morbidities associated with COVID-19 in pregnant women in France: A national retrospective cohort study

BackgroundTo the best of our knowledge, no study has exhaustively evaluated the association between maternal morbidities and Coronavirus Disease 2019 (COVID-19) during the first wave of the pandemic in pregnant women. We investigated, in natural conceptions and assisted reproductive technique (ART) pregnancies, whether maternal morbidities were more frequent in pregnant women with COVID-19 diagnosis compared to pregnant women without COVID-19 diagnosis during the first wave of the COVID-19 pandemic.Methods and findingsWe conducted a retrospective analysis of prospectively collected data in a national cohort of all hospitalizations for births ≥22 weeks of gestation in France from January to June 2020 using the French national hospitalization database (PMSI). Pregnant women with COVID-19 were identified if they had been recorded in the database using the ICD-10 (International Classification of Disease) code for presence of a hospitalization for COVID-19. A total of 244,645 births were included, of which 874 (0.36%) in the COVID-19 group. Maternal morbidities and adverse obstetrical outcomes among those with or without COVID-19 were analyzed with a multivariable logistic regression model adjusted on patient characteristics. Among pregnant women, older age (31.1 (±5.9) years old versus 30.5 (±5.4) years old, respectively, p < 0.001), obesity (0.7% versus 0.3%, respectively, p < 0.001), multiple pregnancy (0.7% versus 0.4%, respectively, p < 0.001), and history of hypertension (0.9% versus 0.3%, respectively, p < 0.001) were more frequent with COVID-19 diagnosis. Active smoking (0.2% versus 0.4%, respectively, p < 0.001) and primiparity (0.3% versus 0.4%, respectively, p < 0.03) were less frequent with COVID-19 diagnosis. Frequency of ART conception was not different between those with and without COVID-19 diagnosis (p = 0.28).When compared to the non-COVID-19 group, women in the COVID-19 group had a higher frequency of admission to ICU (5.9% versus 0.1%, p < 0.001), mortality (0.2% versus 0.005%, p < 0.001), preeclampsia/eclampsia (4.8% versus 2.2%, p < 0.001), gestational hypertension (2.3% versus 1.3%, p < 0.03), postpartum hemorrhage (10.0% versus 5.7%, p < 0.001), preterm birth at <37 weeks of gestation (16.7% versus 7.1%, p < 0.001), <32 weeks of gestation (2.2% versus 0.8%, p < 0.001), <28 weeks of gestation (2.4% versus 0.8%, p < 0.001), induced preterm birth (5.4% versus 1.4%, p < 0.001), spontaneous preterm birth (11.3% versus 5.7%, p < 0.001), fetal distress (33.0% versus 26.0%, p < 0.001), and cesarean section (33.0% versus 20.2%, p < 0.001). Rates of pregnancy terminations ≥22 weeks of gestation, stillbirths, gestational diabetes, placenta praevia, and placenta abruption were not significantly different between the COVID-19 and non-COVID-19 groups. The number of venous thromboembolic events was too low to perform statistical analysis. A limitation of this study relies in the possibility that asymptomatic infected women were not systematically detected.ConclusionsWe observed an increased frequency of pregnant women with maternal morbidities and diagnosis of COVID-19 compared to pregnant women without COVID-19. It appears essential to be aware of this, notably in populations at known risk of developing a more severe form of infection or obstetrical morbidities and in order for obstetrical units to better inform pregnant women and provide the best care. Although causality cannot be determined from these associations, these results may be in line with recent recommendations in favor of vaccination for pregnant women.

In a national retrospective study, Sylvie Epelboin and colleagues investigate obstetrical outcomes and maternal morbidities among pregnant women with a COVID-19 diagnosis in France.     

Lower Cerebrospinal Fluid/Plasma Fibroblast Growth Factor 21 (FGF21) Ratios and Placental FGF21 Production in Gestational Diabetes

Objectives

Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants.

Design

CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m²) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m²)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA.

Results

Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05).

Conclusions

The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points.     

Clinical Markers Implying the Need for Treatment in Women with Gestational Diabetes Mellitus

ObjectiveTo assess the association of the point-of-care hemoglobin A_1c (POC A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for medication in women with gestational diabetes (GDM).MethodsPOC A1C, FBG, and BMI values at GDM diagnosis and fetal weight at delivery were obtained for women identified from a prospective patient registry. These outcomes were compared between women who did not require medication for GDM and women who did require medication.ResultsMean values of POC A1C, FBG, and BMI in 67 patients who required medication were higher than those in 71 patients who did not require medication (POC A1C: 5.72 ± 0.45% vs 5.35 ± 0.46% [P < .001]; FBG: 97.4 ± 12.3 mg/dL vs 86.4 ± 9.5 mg/dL [P < .001]; BMI: 35.4 ± 6.4 kg/m2 vs 30.4 ± 6.2 kg/m2 [P < .001]). There was a modest correlation between POC A1C and FBG (Spearman rho 0.4, P < .001) and between POC A1C and BMI (Spearman rho 0.366, P < .001). Maternal POC A1C was not correlated with fetal weight at delivery (Spearman rho –0.010, P = .915).ConclusionsHigher POC A1C, FBG, and BMI values were associated with the need for medication in women with GDM. The use of clinical markers to assess glycemic control sooner in pregnancy may lead to the earlier identification of women at risk for GDM and earlier intervention to decrease the risk for complications. (Endocr Pract. 2012;18:62-65)     

Influence of the Time of Day and Fasting Duration on Glucose Level following a 1-Hour, 50-Gram Glucose Challenge Test in Pregnant Women

Background

Previous studies have shown that the time of day (TD) of glucose measurement and the fasting duration (FD) influence the glucose levels in adults. Few studies have examined the effects of the TD and FD on the glucose level following a 1-hour, 50-gram glucose challenge test (GCT) in pregnant women in screening for or diagnosing gestational diabetes mellitus (GDM). The objective of this study was to investigate the influence of the TD (morning, afternoon, night) and the FD (the time of the last food ingestion as follows: ≤1 hour, 1–2 hours, and >2 hours) by examining their combined effects on the glucose levels following a 50-gram GCT in pregnant women.

Methods and Results

We analyzed the data of 1,454 non-diabetic pregnant Taiwanese women in a prospective study. Multiple linear regression and multiple logistic regression were used to estimate the relationships between the 9 TD-FD groups and the continuous and binary glucose levels (cut-off at 140 mg/dL) following a 50-gram GCT, after adjusting for maternal age, nulliparity, pre-pregnancy body mass index, and weight gain. Different TD and FD groups were associated with variable glucose responses to the 50-gram GCT, some of which were significant. The estimate coefficients (β) of the TD-FD groups “night, ≤1 hr” and “night, 1–2 hr” revealed significantly lower glucose concentrations [β (95% confidence interval [CI]): −6.46 (−12.53, −0.38) and −6.85 (−12.50, −1.20)] compared with the “morning, >2 hr” group. The TD-FD groups “afternoon, ≤1 hr” and “afternoon, 1–2 hr” showed significantly lower odds ratios (OR) of a positive GCT; the adjusted ORs (95% CI) were 0.54 (0.31–0.95) and 0.58 (0.35–0.96), respectively.

Conclusions

Our findings demonstrate the importance of standardizing the TD and FD for the 1-hour, 50-gram GCT. In screening for and diagnosing GDM, the TD and FD are modifiable factors that should be considered in clinical practice and epidemiological studies.     

Correlation of viral load of Hepatitis B with the gestation period and the development of diabetes mellitus

ObjectiveTo elaborate how the viral load of HBV affects the gestational diabetes mellitus (GDM).MethodsWe enrolled 196 chronic HBV-infected pregnant patients in this hospital between January 2012 and December 2017 for delivery in this study. According to the viral load of HBV-DNA, these patients were divided into the HBV-DNA negative group (n = 107, <1 × 10³ copies/mL) and HBV-DNA positive group (n = 89, ≥1 × 10³ copies/mL). Simultaneously, 100 HBV-free pregnant women who were admitted to the hospital for delivery were included in the control group. Before delivery, fasting venous blood was drawn from the pregnant women to perform the HBV-DNA quantification through qRT-PCR; from the 24th to 28th gestation week, all pregnant women underwent OGTT, with the third-trimester-of-pregnancy as the endpoint. Besides, we also measured the FBG, 2hPG and hemoglobin A1c (HbAIc).ResultsAmong 168 pregnant patients carrying chronic HBV, viral load of 107 patients was less than 1 × 10³ copies/mL (54.6%), and 89 not less than 1 × 10³ copies/mL (45.4%). The incidence rates of GDM in the HBV-DNA negative group and HBV-DNA positive group were 18.7% and 19.1%, respectively, significantly higher than that in the control group (p < 0.05), while the difference of the incidence rates of GDM between two HBV-DNA groups were not significant (p > 0.05). In HBV-DNA negative group and HBV-DNA positive group, FBGs, 2hPGs and HbAIcs were respectively (6.96 ± 0.36) mmol/L and (7.04 ± 0.37) mmol/L, (10.26 ± 1.29) mmol/L and (10.16 ± 1.12) mmol/L, and (8.66 ± 0.97) % and (8.91 ± 0.90) %, significantly higher than (4.57 ± 0.34) mmol/L, (6.16 ± 0.86) mmol/L and (5.13 ± 0.57) % (p < 0.05); however, between two HBV-DNA groups, comparisons of the FBG, 2hPG and HbAIc suggested no significant differences (p > 0.05). In 196 patients carrying chronic HBV, positive correlations were identified between the viral load of HBV-DNA, and FBG, 2hPG and HbAIc (p < 0.01).ConclusionHBV infection can increase the incidence rate of GDM, and the viral load of HBV-DNA is correlated with the glucose level of pregnant patients.     

Relationship between Polycystic Ovarian Syndrome and Subsequent Gestational Diabetes Mellitus: A Nationwide Population-Based Study

Objective

This nationwide population-based study aims to explore the relationship between polycystic ovarian syndrome (PCOS) and subsequent gestational diabetes mellitus (GDM).

Methods

Data from 1998–2012 Taiwan National Health Insurance Research Database were used for this study. ICD9-CM codes 256.4X and 648.X were used separately for the diagnoses of PCOS and GDM, which were further confirmed by records of blood tests or ultrasonography to ensure the accuracy of the diagnoses. Women diagnosed at < 15 or > 45 years of age, and those diagnosed with overt diabetes mellitus or GDM prior to PCOS were excluded. During pregnancy, each woman with a previous diagnosis of PCOS was age-matched to 10 women without PCOS. Odds ratios (ORs) for risk of GDM were calculated by logistic regression analysis with adjustment for economic status and co-morbidities.

Results

Among 7,629 eligible women with a valid PCOS diagnosis, 3,109 (42.87%) had subsequent pregnancies. GDM occurred frequently among women with a history of PCOS as compared to those without PCOS (20.46% vs. 10.54%, p<0.0001). Logistic regression analysis revealed that PCOS was associated with GDM (adjusted OR = 2.15; 95% CI:1.96–2.37). Among 3,109 affected patients, 1,160 (37.31%) had used medications for PCOS and 261 (8.39%) were treated with an oral hypoglycemic agent (OHA). There was no significant difference in development of GDM between the medication and no medication sub-groups (p>0.05). If not used after conception, OHAs did not reduce the risk of GDM (adjusted OR = 1.20; 95% CI:0.88–1.62).

Conclusions

A history of PCOS is a significant and independent risk factor for development of GDM. Medication for PCOS or pre-pregnancy use of OHAs does not reduce the risk of GDM. When at-risk women become pregnant, they require closer surveillance for maternal and fetal well-being, and should follow a strict diet and adhere to weight gain control to avoid obstetric complications due to GDM.     

Serum Phosphorus Concentration and Coronary Artery Calcification in Subjects without Renal Dysfunction

Serum phosphorus (P) concentration is associated with coronary artery calcification (CAC) as well as cardiovascular events in patients with chronic kidney disease. It has been suggested that this relationship is extended to subjects without renal dysfunction, but further explorations in diverse races and regions are still needed. We performed a cross-sectional study of 2,509 Korean subjects (Far Eastern Asian) with an estimated glomerular filtration rate of ≥60 ml/min/1.73m² and who underwent coronary computerized tomography. Serum P concentration was divided into pre-determined 4 categories: ≤3.2, 3.2< to ≤3.6, 3.6< to ≤4.0 and >4.0 mg/dL. Agatston score (AS), an index of CAC, was divided into 3 categories: 0, 0< to ≤100, and >100. A multinomial logit model (baseline outcome: AS = 0) was applied to estimate the odds ratio (OR) for each serum P category (reference: ≤3.2mg/dL). Mean age of subjects was 53.5±9.1 years and 36.9% were female. In the adjusted model, serum P concentration of 3.6< to ≤4.0 mg/dL and >4.0 mg/dL showed high ORs for AS of >100 [OR: 1.58, 95% confidence interval (CI): 1.04–2.40 and OR: 2.11, 95% CI: 1.34–3.32, respectively]. A unit (mg/dL) increase in serum P concentration was associated with 50% increase in risk of AS >100 (OR: 1.50, 95% CI: 1.16–1.94). A higher serum P concentration, even within a normal range, may be associated with a higher CAC in subjects with normal renal function.     

Gestational Weight Gain as an Independent Risk Factor for Macrosomia in Women with Intermediate State Gestational Blood Glucose

Objective: Macrosomia is closely associated with gestational diabetes mellitus (GDM) but its relationship with maternal intermediate state gestational blood glucose (ISGBG; normal fasting blood glucose and 7.8 mmol/L <1 hour blood glucose &lsqb;BG] <10 mmol/L or 6.7 mmol/L <2 hour BG <8.5 mmol/L) is unclear. Here, we analyzed the clinical characteristics and pregnancy outcomes and explored risk factors for macrosomia in women with ISGBG.Methods: A total of 847 women with normal glucose tolerance gestation, 330 with ISGBG, and 99 with GDM were included. Maternal and fetal clinical data were collected and 3-point BG following oral glucose tolerance test, fasting insulin, glycated hemoglobin, and blood lipids profile were measured.Results: The incidence rate of macrosomia among the neonates of women with ISGBG was as high as 10.9%. In the ISGBG group, prepregnancy body mass index (BMI), gestational weight gain (GWG) and the proportion of women with excessive GWG (eGWG) were significantly higher in women with macrosomia compared with those who delivered a normal weight neonate. In women with ISGBG, neonate weight was positively correlated with maternal prepregnancy weight (r = 0.183, P<.01), prepregnancy BMI (r = 0.135, P<.01), and GWG (r = 0.255, P<.01), and negatively correlated with high-density lipoprotein cholesterol (r = -0.172, P<.01). Nonetheless, only eGWG was an independent risk factor (odds ratio = 3.18, 95% confidence interval = 1.26 to 7.88, P<.05) for macrosomia. The risk of macrosomia in pregnant women with prepregnancy BMI <25 kg/m² or BMI ≥25 kg/m² and eGWG was 3.39 and 3.27 times, respectively.Conclusion: The incidence rate of macrosomia is increased in women with ISGBG and eGWG is the strongest independent risk factor. In order to reduce the risk for macrosomia, timely lifestyle intervention to promote appropriate weight gain during pregnancy deserves evaluation.Abbreviations: AUC = area under the curve; BG = blood glucose; 1 hour BG = 1 hour blood glucose after OGTT; 2 hour BG = 2 hour blood glucose after OGTT; BMI = body mass index; CI = confidence interval; eGWG = excessive gestational weight gain; FBG = fasting blood glucose; FINS = fasting insulin; GDM = gestational diabetes mellitus; HbA1c = glycated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance index; ISGBG = intermediate state gestation blood glucose; LDL-C = low-density lipoprotein cholesterol; Ln = natural logarithm; MLBW = mature low birth weight; NGTG = normal glucose tolerance gestation; OGTT = oral glucose tolerance test; OR = odds ratio; SD = standard deviation     

Joint and Independent Associations of Gestational Weight Gain and Pre-Pregnancy Body Mass Index with Outcomes of Pregnancy in Chinese Women: A Retrospective Cohort Study

Objective

To explore the joint and independent effects of gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) on pregnancy outcomes in a population of Chinese Han women and to evaluate pregnant women’s adherence to the 2009 Institute of Medicine (IOM) gestational weight gain guidelines.

Methods

This was a multicenter, retrospective cohort study of 48,867 primiparous women from mainland China who had a full-term singleton birth between January 1, 2011 and December 30, 2011. The independent associations of pre-pregnancy BMI, GWG and categories of combined pre-pregnancy BMI and GWG with outcomes of interest were examined using an adjusted multivariate regression model. In addition, women with pre-pregnancy hypertension were excluded from the analysis of the relationship between GWG and delivery of small-for-gestational-age (SGA) infants, and women with gestational diabetes (GDM) were excluded from the analysis of the relationship between GWG and delivery of large-for-gestational-age (LGA) infants.

Results

Only 36.8% of the women had a weight gain that was within the recommended range; 25% and 38.2% had weight gains that were below and above the recommended range, respectively. The contribution of GWG to the risk of adverse maternal and fetal outcomes was modest. Women with excessive GWG had an increased likelihood of gestational hypertension (adjusted OR 2.55; 95% CI = 1.92–2.80), postpartum hemorrhage (adjusted OR 1.30; 95% CI = 1.17–1.45), cesarean section (adjusted OR 1.31; 95% CI = 1.18–1.36) and delivery of an LGA infant (adjusted OR 2.1; 95% CI = 1.76–2.26) compared with women with normal weight gain. Conversely, the incidence of GDM (adjusted OR 1.64; 95% CI = 1.20–1.85) and SGA infants (adjusted OR 1.51; 95% CI = 1.32–1.72) was increased in the group of women with inadequate GWG. Moreover, in the obese women, excessive GWG was associated with an apparent increased risk of delivering an LGA infant. In the women who were underweight, poor weight gain was associated with an increased likelihood of delivering an SGA infant. After excluding the mothers with GDM or gestational hypertension, the ORs for delivery of LGA and SGA infants decreased for women with high GWG and increased for women with low GWG.

Conclusions

GWG above the recommended range is common in this population and is associated with multiple unfavorable outcomes independent of pre-pregnancy BMI. Obese women may benefit from avoiding weight gain above the range recommended by the 2009 IOM. Underweight women should avoid low GWG to prevent delivering an SGA infant. Pregnant women should therefore be monitored to comply with the IOM recommendations and should have a balanced weight gain that is within a range based on their pre-pregnancy BMI.