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Abstract Context Gestational diabetes mellitus (GDM) diagnosed in early pregnancy is a health care challenge because it increases the risk of adverse outcomes. Plasma-glycated CD59 (pGCD59) is an emerging biomarker for diabetes and GDM. The aim of this study was to assess the performance of pGCD59 as a biomarker of early GDM and its association with delivering a large for gestational age (LGA) infant. Objectives To assess the performance of pGCD59 to identify women with GDM in early pregnancy (GDM < 20) and assess the association of pGCD59 with LGA and potentially others adverse neonatal outcomes linked to GDM. Methods Blood levels of pGCD59 were measured in samples from 693 obese women (body mass index > 29) undergoing a 75-g, 2-hour oral glucose tolerance test (OGTT) at <20 weeks’ gestation in the Vitamin D and Lifestyle Intervention study: the main analyses included 486 subjects who had normal glucose tolerance throughout the pregnancy, 207 who met criteria for GDM at <20 weeks, and 77 diagnosed with GDM at pregnancy weeks 24 through 28. Reference tests were 75-g, 2-hour OGTT adjudicated based on International Association of Diabetes and Pregnancy Study Group criteria. The index test was a pGCD59 ELISA. Results Mean pGCD59 levels were significantly higher (P < 0.001) in women with GDM < 20 (3.9 ± 1.1 standard peptide units [SPU]) than in those without (2.7 ± 0.7 SPU). pGCD59 accurately identified GDM in early pregnancy with an area under the curve receiver operating characteristic curves of 0.86 (95% confidence interval [CI], 0.83-0.90). One-unit increase in maternal pGCD59 level was associated with 36% increased odds of delivering an LGA infant (odds ratio for LGA vs non-LGA infant: 1.4; 95% CI, 1.1-1.8; P = 0.016). Conclusion Our results indicate that pGCD59 is a simple and accurate biomarker for detection of GDM in early pregnancy and risk assessment of LGA.

In this pragmatic, randomized trial comparing one-step screening for gestational diabetes mellitus with two-step screening, one-step screening resulted in more diagnoses of gestational diabetes mellitus but did not affect the incidence of adverse perinatal and maternal outcomes.

Objective To determine if a low glycaemic index diet in pregnancy could reduce the incidence of macrosomia in an at risk group.Design Randomised controlled trial.Setting Maternity hospital in Dublin, Ireland.Participants 800 women without diabetes, all in their second pregnancy between January 2007 to January 2011, having previously delivered an infant weighing greater than 4 kg. Intervention Women were randomised to receive no dietary intervention or start on a low glycaemic index diet from early pregnancy.Main outcomes The primary outcome measure was difference in birth weight. The secondary outcome measure was difference in gestational weight gain.Results No significant difference was seen between the two groups in absolute birth weight, birthweight centile, or ponderal index. Significantly less gestational weight gain occurred in women in the intervention arm (12.2 v 13.7 kg; mean difference −1.3, 95% confidence interval −2.4 to −0.2; P=0.01). The rate of glucose intolerance was also lower in the intervention arm: 21% (67/320) compared with 28% (100/352) of controls had a fasting glucose of 5.1 mmol/L or greater or a 1 hour glucose challenge test result of greater than 7.8 mmol/L (P=0.02).Conclusion A low glycaemic index diet in pregnancy did not reduce the incidence of large for gestational age infants in a group at risk of fetal macrosomia. It did, however, have a significant positive effect on gestational weight gain and maternal glucose intolerance.Trial registration Current Controlled Trials ISRCTN54392969.

Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are found in the most frequent pathology of pregnancy: gestational diabetes, where leptin may mediate the increased size of the placenta and the fetus, which becomes macrosomic. In fact, leptin mediates the increased protein synthesis, as observed in trophoblasts from gestational diabetic subjects. In addition, leptin seems to facilitate nutrients transport to the fetus in gestational diabetes by increasing the expression of the glycerol transporter aquaporin-9. The high plasma leptin levels found in gestational diabetes may be potentiated by leptin resistance at a central level, and obesity-associated inflammation plays a role in this leptin resistance. Therefore, the importance of anti-inflammatory nutrients to modify the pathology of pregnancy is clear. In fact, nutritional intervention is the first-line approach for the treatment of gestational diabetes mellitus. However, more nutritional intervention studies with nutraceuticals, such as polyphenols or polyunsaturated fatty acids, or nutritional supplementation with micronutrients or probiotics in pregnant women, are needed in order to achieve a high level of evidence. In this context, the Mediterranean diet has been recently found to reduce the risk of gestational diabetes in a multicenter randomized trial. This review will focus on the impact of maternal obesity on placental inflammation and nutrients transport, considering the mechanisms by which leptin may influence maternal and fetal health in this setting, as well as its role in pregnancy pathologies.

Background: Fetal macrosomia, defined as a birth weight ≥4,000 g, may affect 12% of newborns of normal women and 15-45% of newborns of women with gestational diabetes mellitus (GDM). The increased risk of macrosomia in GDM is mainly due to the increased insulin resistance of the mother. In GDM, a higher amount of blood glucose passes through the placenta into the fetal circulation. As a result, extra glucose in the fetus is stored as body fat causing macrosomia, which is also called ‘large for gestational age'. This paper reviews studies that explored the impact of GDM and fetal macrosomia as well as macrosomia-related complications on birth outcomes and offers an evaluation of maternal and fetal health. Summary: Fetal macrosomia is a common adverse infant outcome of GDM if unrecognized and untreated in time. For the infant, macrosomia increases the risk of shoulder dystocia, clavicle fractures and brachial plexus injury and increases the rate of admissions to the neonatal intensive care unit. For the mother, the risks associated with macrosomia are cesarean delivery, postpartum hemorrhage and vaginal lacerations. Infants of women with GDM are at an increased risk of becoming overweight or obese at a young age (during adolescence) and are more likely to develop type II diabetes later in life. Besides, the findings of several studies that epigenetic alterations of different genes of the fetus of a GDM mother in utero could result in the transgenerational transmission of GDM and type II diabetes are of concern.

AbstractObjectiveTo investigate the association between gestational diabetes mellitus and adverse outcomes of pregnancy after adjustment for at least minimal confounding factors.DesignSystematic review and meta-analysis.Data sourcesWeb of Science, PubMed, Medline, and Cochrane Database of Systematic Reviews, from 1 January 1990 to 1 November 2021.Review methodsCohort studies and control arms of trials reporting complications of pregnancy in women with gestational diabetes mellitus were eligible for inclusion. Based on the use of insulin, studies were divided into three subgroups: no insulin use (patients never used insulin during the course of the disease), insulin use (different proportions of patients were treated with insulin), and insulin use not reported. Subgroup analyses were performed based on the status of the country (developed or developing), quality of the study, diagnostic criteria, and screening method. Meta-regression models were applied based on the proportion of patients who had received insulin.Results156 studies with 7 506 061 pregnancies were included, and 50 (32.1%) showed a low or medium risk of bias. In studies with no insulin use, when adjusted for confounders, women with gestational diabetes mellitus had increased odds of caesarean section (odds ratio 1.16, 95% confidence interval 1.03 to 1.32), preterm delivery (1.51, 1.26 to 1.80), low one minute Apgar score (1.43, 1.01 to 2.03), macrosomia (1.70, 1.23 to 2.36), and infant born large for gestational age (1.57, 1.25 to 1.97). In studies with insulin use, when adjusted for confounders, the odds of having an infant large for gestational age (odds ratio 1.61, 1.09 to 2.37), or with respiratory distress syndrome (1.57, 1.19 to 2.08) or neonatal jaundice (1.28, 1.02 to 1.62), or requiring admission to the neonatal intensive care unit (2.29, 1.59 to 3.31), were higher in women with gestational diabetes mellitus than in those without diabetes. No clear evidence was found for differences in the odds of instrumental delivery, shoulder dystocia, postpartum haemorrhage, stillbirth, neonatal death, low five minute Apgar score, low birth weight, and small for gestational age between women with and without gestational diabetes mellitus after adjusting for confounders. Country status, adjustment for body mass index, and screening methods significantly contributed to heterogeneity between studies for several adverse outcomes of pregnancy.ConclusionsWhen adjusted for confounders, gestational diabetes mellitus was significantly associated with pregnancy complications. The findings contribute to a more comprehensive understanding of the adverse outcomes of pregnancy related to gestational diabetes mellitus. Future primary studies should routinely consider adjusting for a more complete set of prognostic factors.Review registrationPROSPERO CRD42021265837.

Consensus is lacking as to whether routine screening and treatment for gestational diabetes mellitus is warranted. This large randomized trial of the treatment of gestational diabetes demonstrated that serious perinatal complications were significantly less common among the offspring of women who received dietary advice, blood glucose monitoring, and insulin therapy as needed to maintain glycemic control than among the offspring of women who received routine care. This trial demonstrated that serious perinatal complications were significantly less common among the offspring of women who received screening and treatment for gestational diabetes mellitus than among the offspring of women who received routine care. Gestational diabetes mellitus occurs in 2 to 9 percent of all pregnancies 1 , 2 and is associated with substantial rates of maternal and perinatal complications. The risk of perinatal mortality is not increased, 3 but the risk of macrosomia is. Other perinatal risks include shoulder dystocia, birth injuries such as bone fractures and nerve palsies, and hypoglycemia. Long-term adverse health outcomes reported among infants born to mothers with gestational diabetes include sustained impairment of glucose tolerance, 4 subsequent obesity 5 (although not when adjusted for size 6 ), and impaired intellectual achievement. 7 For women, gestational diabetes is a strong risk factor for diabetes. 8 Although the . . .

Metformin improves insulin sensitivity and was compared with placebo in this study involving obese pregnant women without diabetes. Antenatal administration of metformin was associated with lower maternal weight gain but not in lower birth weight of the baby. The prevalence of obesity is increasing both in developed countries and in developing countries, and obesity is considered to be a global pandemic. 1 An estimated one fifth of pregnant women in the United Kingdom and one third of those in the United States are obese. 2 , 3 Obesity during pregnancy is associated with an increased risk of adverse short-term and long-term consequences for both mother and baby. 4 – 11 Attempts at reducing the incidence of pregnancy complications associated with obesity have focused on dietary and lifestyle interventions, but these have generally been unsuccessful. 12 – 17 An alternative strategy is the use of metformin, . . .

OBJECTIVE: Gestational diabetes mellitus (GDM) may cause obesity in the offspring. The objective was to assess the effect of treatment for mild GDM on the BMI of 4- to 5-year-old children. RESEARCH DESIGN AND METHODS: Participants were 199 mothers who participated in a randomized controlled trial of the treatment of mild GDM during pregnancy and their children. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance program in the state of South Australia. The main outcome measure was age- and sex-specific BMI Z score based on standards of the International Obesity Task Force. RESULTS: At birth, prevalence of macrosomia (birth weight ≥4,000 g) was 5.3% among the 94 children whose mothers were in the intervention group, and 21.9% among the 105 children in the routine care control group. At 4- to 5-years-old, mean (SD) BMI Z score was 0.49 (1.20) in intervention children and 0.41 (1.40) among controls. The difference between treatment groups was 0.08 (95% CI -0.29 to 0.44), an estimate minimally changed by adjustment for maternal race, parity, age, and socio-economic index (0.08 [-0.29 to 0.45]). Evaluating BMI ≥85th percentile rather than continuous BMI Z score gave similarly null results. CONCLUSIONS: Although treatment of GDM substantially reduced macrosomia at birth, it did not result in a change in BMI at age 4- to 5-years-old.

Objective To evaluate the effectiveness of continuous glucose monitoring during pregnancy on maternal glycaemic control, infant birth weight, and risk of macrosomia in women with type 1 and type 2 diabetes.Design Prospective, open label randomised controlled trial.Setting Two secondary care multidisciplinary obstetric clinics for diabetes in the United Kingdom.Participants 71 women with type 1 diabetes (n=46) or type 2 diabetes (n=25) allocated to antenatal care plus continuous glucose monitoring (n=38) or to standard antenatal care (n=33).Intervention Continuous glucose monitoring was used as an educational tool to inform shared decision making and future therapeutic changes at intervals of 4-6 weeks during pregnancy. All other aspects of antenatal care were equal between the groups.Main outcome measures The primary outcome was maternal glycaemic control during the second and third trimesters from measurements of HbA1c levels every four weeks. Secondary outcomes were birth weight and risk of macrosomia using birthweight standard deviation scores and customised birthweight centiles. Statistical analyses were done on an intention to treat basis.Results Women randomised to continuous glucose monitoring had lower mean HbA1c levels from 32 to 36 weeks’ gestation compared with women randomised to standard antenatal care: 5.8% (SD 0.6) v 6.4% (SD 0.7). Compared with infants of mothers in the control arm those of mothers in the intervention arm had decreased mean birthweight standard deviation scores (0.9 v 1.6; effect size 0.7 SD, 95% confidence interval 0.0 to 1.3), decreased median customised birthweight centiles (69% v 93%), and a reduced risk of macrosomia (odds ratio 0.36, 95% confidence interval 0.13 to 0.98).Conclusion Continuous glucose monitoring during pregnancy is associated with improved glycaemic control in the third trimester, lower birth weight, and reduced risk of macrosomia.Trial registration Current Controlled Trials ISRCTN84461581.