H. David McIntyre

The Hyperglycemia and Adverse Pregnancy Outcome Study: Associations of GDM and obesity with pregnancy outcomes

OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m2), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93–2.47), for obesity alone 1.73 (1.50–2.00), and for both GDM and obesity 3.62 (3.04–4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

Inflammatory mediators and glucose in pregnancy: results from a subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.

CONTEXT Inflammatory mediators are associated with type 2 and gestational diabetes. It is unknown whether there are associations with glucose in pregnant women with lesser degrees of hyperglycemia. OBJECTIVE The objective of the study was to examine associations of inflammatory mediators with maternal glucose levels and neonatal size in a subset of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. DESIGN Eligible pregnant women underwent a 75-g oral glucose tolerance test between 24 and 32 wk gestation, and levels of C-peptide, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), and resistin were measured in fasting serum samples. Associations of inflammatory mediators with maternal glucose and with birth size were assessed using multiple linear regression analyses, adjusting for maternal body mass index (BMI), fasting C-peptide, and other potential confounders. RESULTS Mean levels of adiponectin declined, and PAI-1 and CRP increased across increasing levels of maternal glucose, BMI, and C-peptide. For example, for fasting plasma glucose less than 75 mg/dl and fasting plasma glucose of 90 mg/dl or greater, adiponectin was 22.5 and 17.4 μg/ml and PAI-1 was 30.9 and 34.2 ng/ml, respectively. Associations with 1- and 2-h plasma glucose remained significant for adiponectin (P<0.001), PAI-1 (P<0.05), and CRP (P<0.01) after adjustment for BMI and C-peptide. Adiponectin and CRP were inversely associated with birth weight, sum of skinfolds and percent body fat, and PAI-1 with sum of skinfolds (all P<0.05) after adjustment for confounders. Resistin was not associated with 1- or 2-h glucose or birth size. CONCLUSION Levels of inflammatory mediators are associated with levels of maternal glucose in pregnant women without overt diabetes.

Overweight and obesity in Australian mothers: epidemic or endemic?

Objectives: To document temporal trends in maternal overweight and obesity in Australian women and to examine associations with pregnancy outcomes.

Pregnancy outcomes in women of very advanced maternal age

Objective:  To assess outcomes for pregnancies progressing beyond 20 weeks’ gestation in women of very advanced maternal age.

SPRING: an RCT study of probiotics in the prevention of gestational diabetes mellitus in overweight and obese women

BackgroundObesity is increasing in the child-bearing population as are the rates of gestational diabetes. Gestational diabetes is associated with higher rates of Cesarean Section for the mother and increased risks of macrosomia, higher body fat mass, respiratory distress and hypoglycemia for the infant. Prevention of gestational diabetes through life style intervention has proven to be difficult. A Finnish study showed that ingestion of specific probiotics altered the composition of the gut microbiome and thereby metabolism from early gestation and decreased rates of gestational diabetes in normal weight women. In SPRING (the Study of Probiotics IN the prevention of Gestational diabetes), the effectiveness of probiotics ingestion for the prevention of gestational diabetes will be assessed in overweight and obese women.Methods/designSPRING is a multi-center, prospective, double-blind randomized controlled trial run at two tertiary maternity hospitals in Brisbane, Australia. Five hundred and forty (540) women with a BMI > 25.0 kg/m2 will be recruited over 2 years and receive either probiotics or placebo capsules from 16 weeks gestation until delivery. The probiotics capsules contain > 1x109 cfu each of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB-12 per capsule. The primary outcome is diagnosis of gestational diabetes at 28 weeks gestation. Secondary outcomes include rates of other pregnancy complications, gestational weight gain, mode of delivery, change in gut microbiome, preterm birth, macrosomia, and infant body composition. The trial has 80% power at a 5% 2-sided significance level to detect a >50% change in the rates of gestational diabetes in this high-risk group of pregnant women.DiscussionSPRING will show if probiotics can be used as an easily implementable method of preventing gestational diabetes in the high-risk group of overweight and obese pregnant women.

Normalizing metabolism in diabetic pregnancy: Is it time to target lipids?

Outcomes in pregnancies complicated by preexisting diabetes (type 1 and type 2) and gestational diabetes mellitus have improved, but there is still excess morbidity compared with normal pregnancy. Management strategies appropriately focus on maternal glycemia, which demonstrably improves pregnancy outcomes for mother and infant. However, we may be reaching the boundaries of obtainable glycemic control for many women. It has been acknowledged that maternal lipids are important in pregnancies complicated by diabetes. Elevated maternal lipids are associated with preeclampsia, preterm delivery, and large-for-gestational-age infants. Despite this understanding, assessment of management strategies targeting maternal lipids has been neglected to date. Consideration needs to be given to whether normalizing maternal lipids would further improve pregnancy outcomes. This review examines the dyslipidemia associated with pregnancy complicated by diabetes, reviews possible therapies, and considers whether it is time to start actively managing this aspect of maternal metabolism.

Obesity in pregnancy: outcomes and economics

Maternal obesity is an important aspect of reproductive care. It is the commonest risk factor for maternal mortality in developed countries and is also associated with a wide spectrum of adverse pregnancy outcomes. Maternal obesity may have longer-term implications for the health of the mother and infant, which in turn will have economic implications. Efforts to prevent, manage and treat obesity in pregnancy will be costly, but may pay dividends from reduced future economic costs, and subsequent improvements to maternal and infant health. Decision-makers working in this area of health services should understand whether the problem can be reduced, at what cost; and then, what cost savings and health benefits will accrue in the future from a reduction of the problem.

Issues With the Diagnosis and Classification of Hyperglycemia in Early Pregnancy

In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) panel published consensus-based recommendations on the diagnosis and classification of hyperglycemia in pregnancy (1). Within that document, the recommendations regarding early pregnancy testing were designed to facilitate early detection and treatment of hyperglycemia (HbA1c ≥6.5% [48 mmol/mol], fasting venous plasma glucose ≥7.0 mmol/L, random plasma glucose ≥11.1 mmol/L with confirmation) that, outside pregnancy, would be classified as diabetes. The term “overt diabetes” was suggested to describe these women. Subsequently, the World Health Organization (WHO) adopted the IADPSG criteria with some modifications and promoted the use of the term “diabetes in pregnancy” (2) for this group. Cognizant that milder degrees of hyperglycemia would also be detected by early pregnancy testing, the IADPSG also recommended that fasting …

Audit of maternal and fetal outcomes in women treated for glucose intolerance during pregnancy

To determine whether one should aim for glycaemia that is statistically ‘normal’ or for levels of glycaemia low enough to prevent macrosomia (if such a threshold exists) when glucose intolerance is detected during pregnancy

Overweight and obesity knowledge prior to pregnancy: A survey study

BackgroundOverweight and obesity are associated with increased risk for pregnancy complications. Knowledge about increased risks in overweight and obese women could contribute to successful prevention strategies and the aim of this study is to assess current levels of knowledge in a pregnant population.MethodsCross sectional survey of 412 consecutive unselected women in early pregnancy in Brisbane, Australia: 255 public women attending their first antenatal clinic visit and 157 women at private maternal fetal medicine clinics undergoing a routine ultrasound evaluation prior to 20 weeks gestation. The cohort was stratified according to pre pregnancy BMI (< 25.0 or ≥ 25.0). The main outcome measure was knowledge regarding the risks of overweight and obesity in pregnancy.ResultsOver 75% of respondents identified that obese women have an increased risk of overall complications, including gestational diabetes and hypertensive disorders of pregnancy compared to women of normal weight. More than 60% of women asserted that obesity would increase the risk of caesarean section and less than half identified an increased risk of adverse neonatal outcomes. Women were less likely to know about neonatal complications (19.7% did not know about the effect of obesity on these) than maternal complications (7.4%). Knowledge was similar amongst women recruited at the public hospital and those recruited whilst attending for an ultrasound scan at a private clinic. For most areas they were also similar between women of lower and higher BMI, but women with BMI < 25.0 were less likely to know that obesity was associated with increased rate of Caesarean section than those with higher BMI (16.8% versus 4.5%, P < 0.001). Higher educational status was associated with more knowledge of the risks of overweight and obesity in pregnancy.ConclusionsMany women correctly identify that overweight and obesity increases the overall risk of complications of pregnancy and childbirth. The increased risks of maternal complications associated with being obese are better known than the increased risk of neonatal complications. Maternal education status is a main determinant of the extent of knowledge and this should be considered when designing education campaigns.