Background It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes Methods A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (58 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (111 mmol per liter) or less Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia Results For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (69 mg per deciliter [04 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (309 mg per deciliter [17 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (235 mg per deciliter [13 mmol per liter]) For birth weight above the 90th percentile, the odds ratios were 138 (95% confidence interval [CI], 132 to 144), 146 (139 to 153), and 138 (132 to 144), respectively; for cord-blood serum C-peptide level above the 90th percentile, 155 (95% CI, 147 to 164), 146 (138 to 154), and 137 (130 to 144); for primary cesarean delivery, 111 (95% CI, 106 to 115), 110 (106 to 115), and 108 (103 to 112); and for neonatal hypoglycemia, 108 (95% CI, 098 to 119), 113 (103 to 126), and 110 (100 to 112) There were no obvious thresholds at which risks increased Significant associations were also observed for secondary outcomes, although these tended to be weaker Conclusions Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels

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Hyperglycemia and adverse pregnancy outcomes

In the accompanying comment letter (1), Weinert summarizes published data from the Brazilian Gestational Diabetes Study (2) and comments on applying International Association of Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommendations (3) for the diagnosis of gestational diabetes mellitus (GDM) to that cohort

The Brazilian study provided evidence that adverse perinatal outcomes are associated with levels of maternal glycemia below those diagnostic of GDM by American Diabetes Association or World Health Organization criteria However, the results were potentially confounded by the treatment of GDM It did find that women with GDM were at increased risk for some …

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International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy.

OBJECTIVE —To examine factors associated with variation in the risk for type 2 diabetes in women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS —We conducted a systematic literature review of articles published between January 1965 and August 2001, in which subjects underwent testing for GDM and then testing for type 2 diabetes after delivery. We abstracted diagnostic criteria for GDM and type 2 diabetes, cumulative incidence of type 2 diabetes, and factors that predicted incidence of type 2 diabetes. RESULTS —A total of 28 studies were examined. After the index pregnancy, the cumulative incidence of diabetes ranged from 2.6% to over 70% in studies that examined women 6 weeks postpartum to 28 years postpartum. Differences in rates of progression between ethnic groups was reduced by adjustment for various lengths of follow-up and testing rates, so that women appeared to progress to type 2 diabetes at similar rates after a diagnosis of GDM. Cumulative incidence of type 2 diabetes increased markedly in the first 5 years after delivery and appeared to plateau after 10 years. An elevated fasting glucose level during pregnancy was the risk factor most commonly associated with future risk of type 2 diabetes. CONCLUSIONS —Conversion of GDM to type 2 diabetes varies with the length of follow-up and cohort retention. Adjustment for these differences reveals rapid increases in the cumulative incidence occurring in the first 5 years after delivery for different racial groups. Targeting women with elevated fasting glucose levels during pregnancy may prove to have the greatest effect for the effort required.

https://care.diabetesjournals.org/content/diacare/25/10/1862.full.pdf

Gestational diabetes and the incidence of type 2 diabetes: a systematic review.

Sponsors asked the IOM's Food and Nutrition Board and the Division of Behavioral and Social Sciences and Education Board on Children, Youth, and Families to review and update the IOM (1990) recommendations for weight gain during pregnancy and recommend ways to encourage their adoption through consumer education, strategies to assist practitioners, and public health strategies.The committee was asked to address the following tasks: 1. Review evidence on the relationship between weight gain patterns before, during, and after pregnancy and maternal and child health outcomes, with particular attention to the prevalence of maternal obesity racial/ethnic and age differences, components of GWG, and implications of weight during pregnancy on postpartum weight retention, maternal and child obesity, and later child health. 2. Within a life-stage framework consider factors in relation to GWG that are associated with maternal health outcomes such as lactation performance, postpartum weight retention, cardiovascular disease, metabolic processes including glucose and insulin-related issues, and risk of other chronic diseases; for infants and children, in addition to low birth weight, consider early developmental impacts and obesity-related consequences (e.g., mental health, diabetes). 3. Recommend revisions to the existing guidelines, where necessary, including the need for specific pregnancy weight guidelines for underweight, normal weight, and overweight and obese women and adolescents and women carrying twins or higher-order multiples. 4. Consider a range of approaches to promote appropriate weight gain, including: individual (behavior), psychosocial, community, health care, and health systems; timing and components of interventions; and ways to enhance awareness and adoption of the guidelines, including interdisciplinary approaches, consumer education to men and women, strategies to assist practitioners to use the guidelines, and public health strategies. 5. Identify gaps in knowledge and recommend research priorities.

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Weight Gain During Pregnancy: Reexamining the Guidelines

Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees that is first detected during pregnancy. GDM is detected through the screening of pregnant women for clinical risk factors and, among at-risk women, testing for abnormal glucose tolerance that is usually, but not invariably, mild and asymptomatic. GDM appears to result from the same broad spectrum of physiological and genetic abnormalities that characterize diabetes outside of pregnancy. Indeed, women with GDM are at high risk for having or developing diabetes when they are not pregnant. Thus, GDM provides a unique opportunity to study the early pathogenesis of diabetes and to develop interventions to prevent the disease.

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Gestational Diabetes Mellitus

Pregnancy outcome and prepregnancy body mass index in 2459 glucose-tolerant Danish women

Ninety nine consecutive insulin dependent and 101 non-diabetic pregnant women were examined by ultrasonograph to assess early fetal growth. In 42 of the diabetic mothers and three of the non-diabetic mothers the scan showed early intrauterine growth delay. At 4-5 years of age all children available for study were evaluated by the Denver developmental screening test. Only 23 of the 34 children of diabetic mothers with early intrauterine growth delay had normal test scores compared with 46 of the 50 children of diabetic mothers with normal intrauterine growth. The children failed in personal-social development, gross motor development, and particularly in language and speech development. Children of diabetic mothers with normal early fetal growth had scores very similar to those of the children of non-diabetic mothers, of whom 76 of the 86 tested had normal scores. This study suggests that children with a history of growth delay in early diabetic pregnancy should be screened for possible developmental impairment.

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Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4.

SUMMARY



Aims To assess maternal and neonatal complications in pregnancies of diabetic women treated with oral hypoglycaemic agents during pregnancy.



Methods  A cohort study including all consecutively registered, orally treated pregnant diabetic patients set in a diabetic obstetrical service at a university hospital: 50 women treated with metformin, 68 women treated with sulphonylurea during pregnancy and a reference group of 42 diabetic women treated with insulin during pregnancy.



Results  The prevalence of pre-eclampsia was significantly increased in the group of women treated with metformin compared to women treated with sulphonylurea or insulin (32 vs. 7 vs. 10%, P < 0.001). No difference in neonatal morbidity was observed between the orally treated and insulin-treated group; no cases of severe hypoglycaemia or jaundice were seen in the orally treated groups. However, in the group of women treated with metformin in the third trimester, the perinatal mortality was significantly increased compared to women not treated with metformin (11.6 vs. 1.3%, P < 0.02).



Conclusion  Treatment with metformin during pregnancy was associated with increased prevalence of pre-eclampsia and a high perinatal mortality.

Oral hypoglycaemic agents in 118 diabetic pregnancies.

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.

OBJECTIVE —To investigate the effect of gestational weight gain in obese glucose-tolerant women.

RESEARCH DESIGN AND METHODS —We performed a historical cohort study of 481 women with prepregnancy BMI ≥30 kg/m2 and a normal 2-h 75-g oral glucose tolerance test (OGTT) during the third trimester (according to World Health Organization criteria). Data on OGTT results and clinical outcomes were collected from medical records. Four groups were defined according to weight gain: group 1, <5.0 kg ( n = 93); group 2, 5.0–9.9 kg ( n = 134); group 3, 10.0–14.9 kg ( n = 132); and group 4, ≥15.0 kg ( n = 122).

RESULTS —Birth weight increased significantly with increasing weight gain (mean grams ± SD): group 1, 3,456 ± 620; group 2, 3,624 ± 675; group 3, 3,757 ± 582; and group 4, 3,784 ± 597 ( P < 0.001). The birth weight in group 1 was similar to that of the background population of primarily normal-weight women (3,478 g). In multivariate analyses, increasing weight gain was associated with significantly higher rates of hypertension (OR 4.8 [95% CI for group 4 vs. group 1: 1.7–13.1]), cesarean section (3.5 [1.6–7.8]), induction of labor (3.7 [1.7–8.0]), and large-for-gestational-age infants (4.7 [2.0–11.0]). There was no difference in rates of small-for-gestational-age infants. Significant predictors for birth weight (determined by multiple linear regression) were gestational weight gain, 2-h OGTT result, pregestational BMI, maternal age, gestational age, and smoking.

CONCLUSIONS —Increasing weight gain in obese women is associated with increasing pregnancy complications. Our data suggest that minimal gestational weight gain might normalize birth weight. Prospective studies should be performed to clarify the safety of recommending limited gestational weight gain.

https://care.diabetesjournals.org/content/diacare/28/9/2118.full.pdf

Lars Mølsted-Pedersen

Papers

Pregnancy outcome and prepregnancy body mass index in 2459 glucose-tolerant Danish women

Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4.

Oral hypoglycaemic agents in 118 diabetic pregnancies.

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus.

Gestational Weight Gain and Pregnancy Outcomes in 481 Obese Glucose-Tolerant Women