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Background

The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) showed that treatment of pregnant women with mild gestational diabetes mellitus is beneficial for both women and their infants. It is still uncertain whether there are benefits of similar treatment for women with borderline gestational diabetes.

This trial aims to assess whether dietary and lifestyle advice and treatment given to pregnant women who screen for borderline gestational diabetes reduces neonatal complications and maternal morbidities.

Methods/design

Design: Multicentre, randomised controlled trial.

Inclusion criteria: Women between 240 and 346 weeks gestation with a singleton pregnancy, a positive oral glucose challenge test (venous plasma glucose ≥7.8 mmol/L) and a normal oral 75 gram glucose tolerance test (fasting venous plasma glucose <5.5 mmol/L and a 2 hour glucose <7.8 mmol/L) with written, informed consent.

Trial entry and randomisation: Women with an abnormal oral glucose tolerance test (fasting venous plasma glucose ≥5.5 mmol/L or 2 hour glucose ≥7.8 mmol/L) will not be eligible and will be offered treatment for gestational diabetes, consistent with recommendations based on results of the ACHOIS trial. Eligible women will be randomised into either the ‘Routine Care Group’ or the ‘Intervention Group’.

Study groups: Women in the ‘Routine Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive obstetric care, which will include dietary and lifestyle advice, monitoring of blood glucose and further medical treatment for hyperglycaemia as appropriate.

Primary study outcome: Incidence of large for gestational age infants.

Sample size: A sample size of 682 women will be sufficient to show a 50% reduction in the risk of large for gestational age infants (alpha 0.05 two-tailed, 80% power, 4% loss to follow up) from 14% to 7% with dietary and lifestyle advice and treatment.

Discussion

A conclusive trial outcome will provide reliable evidence of relevance for the care of women with borderline glucose intolerance in pregnancy and their infants.

Trial registration

Australian New Zealand Clinical Trials Registry - ACTRN12607000174482

Background

Mild gestational diabetes is a common complication of pregnancy, affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries, such as shoulder dystocia, bone fractures and nerve palsies. This study aimed to compare the plasma glucose concentrations and serum insulin, leptin and adiponectin in cord blood of babies of women (a) without gestational diabetes mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with treatment.

Methods

95 women with mild GDM on oral glucose tolerance testing (OGTT) at one tertiary level maternity hospital who had been recruited to the ACHOIS trial at one of the collaborating hospitals and randomised to either Treatment (n = 46) or Routine Care (n = 49) and Control women with a normal OGTT (n = 133) were included in the study. Women with mild GDM (treatment or routine care group) and OGTT normal women received routine pregnancy care. In addition, women with treated mild GDM received dietary advice, blood glucose monitoring and insulin if necessary.

The primary outcome measures were cord blood concentrations of glucose, insulin, adiponectin and leptin.

Results

Cord plasma glucose was higher in women receiving routine care compared with control, but was normalized by treatment for mild GDM (p = 0.01). Cord serum insulin and insulin to glucose ratio were similar between the three groups. Leptin concentration in cord serum was lower in GDM treated women compared with routine care (p = 0.02) and not different to control (p = 0.11). Adiponectin was lower in both mild GDM groups compared with control (Treatment p = 0.02 and Routine Care p = 0.07), while the adiponectin to leptin ratio was lower for women receiving routine care compared with treatment (p = 0.08) and control (p = 0.05).

Conclusion

Treatment of women with mild GDM using diet, blood glucose monitoring and insulin if necessary, influences the altered fetal adipoinsular axis characteristic of mild GDM in pregnancy.

Background

The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM and the risks associated with GDM lead to increased health care costs and losses in productivity. The objective of this study is to evaluate whether the FitFor2 exercise program during pregnancy is cost-effective from a societal perspective as compared to standard care.

Methods

A randomised controlled trial (RCT) and simultaneous economic evaluation of the FitFor2 program were conducted. Pregnant women at risk for GDM were randomised to an exercise program to prevent high maternal blood glucose (n = 62) or to standard care (n = 59). The exercise program consisted of two sessions of aerobic and strengthening exercises per week. Clinical outcome measures were maternal fasting blood glucose levels, insulin sensitivity and infant birth weight. Quality of life was measured using the EuroQol 5-D and quality-adjusted life-years (QALYs) were calculated. Resource utilization and sick leave data were collected by questionnaires. Data were analysed according to the intention-to-treat principle. Missing data were imputed using multiple imputations. Bootstrapping techniques estimated the uncertainty surrounding the cost differences and incremental cost-effectiveness ratios.

Results

There were no statistically significant differences in any outcome measure. During pregnancy, total health care costs and costs of productivity losses were statistically non-significant (mean difference €1308; 95%CI €-229 - €3204). The cost-effectiveness analyses showed that the exercise program was not cost-effective in comparison to the control group for blood glucose levels, insulin sensitivity, infant birth weight or QALYs.

Conclusion

The twice-weekly exercise program for pregnant women at risk for GDM evaluated in the present study was not cost-effective compared to standard care. Based on these results, implementation of this exercise program for the prevention of GDM cannot be recommended.

Trial registration

NTR1139

Background

The costs of gestational diabetes mellitus (GDM) screening have been frequently reported, but total GDM-related health care costs compared to the health care costs of women without GDM have not been reported. The aim of this study was to analyse GDM-related health care costs among women with an elevated risk of GDM.

Methods

The study was based on a cluster-randomised GDM prevention trial (N = 848) carried out at maternity clinics, combined with data from the Finnish Medical Birth Register and Care Registers for Social Welfare and Health Care. Costs of outpatient visits to primary and secondary care, cost of inpatient hospital care before and after delivery, the use of insulin, delivery costs and babies’ stay in the neonatal intensive care unit were analysed. Women who developed GDM were compared to those who were not diagnosed with GDM.

Results

Total mean health care costs adjusted for age, body mass index and education were 25.1% higher among women diagnosed with GDM (€6,432 vs. €5,143, p < 0.001) than among women without GDM. The cost of inpatient visits was 44% higher and neonatal intensive care unit use was 49% higher in the GDM group than among women without GDM. The delivery costs were the largest single component in both groups.

Conclusions

A confirmed GDM diagnosis was associated with a significant increase in total health care costs. Effective lifestyle counselling by primary health care providers may offer a means of reducing the high costs of secondary care.

Background

There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time.

The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications.

Methods/Design

Design: Multicentred randomised trial.

Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy.

Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care.

Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible).

Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity.

Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power).

Discussion

This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.

Clinical Trial Registration

Current Controlled Trials ISRCTN15761056

Background

Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes.

The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes.

Methods/Design

Design: Multicentred randomised, controlled trial.

Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit.

Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth.

Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies.

Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice.

Outcome assessors will be blinded to the allocated treatment group.

Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age).

Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed).

Discussion

This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.

Trial Registration

Australian and New Zealand Clinical Trials Registry ACTRN12607000161426

Objective

To examine prenatal, maternal, and infant outcomes and costs through 1 year after delivery using a model of prenatal care for women at high risk of delivering low-birth-weight infants in which half of the prenatal care was provided in women’s homes by nurse specialists with master’s degrees.

Study Design

Randomized clinical trial.

Patients and Methods

A sample of 173 women (and 194 infants) with high-risk pregnancies (gestational or pregestational diabetes mellitus, chronic hypertension, preterm labor, or high risk of preterm labor) were randomly assigned to the intervention group (85 women and 94 infants) or the control group (88 women and 100 infants). Control women received usual prenatal care. Intervention women received half of their prenatal care in their homes, with teaching, counseling, telephone outreach, daily telephone availability, and a postpartum home visit by nurse specialists with physician backup.

Results

For the full sample, mean maternal age was 27 years; 85.5% of women were single mothers, 36.4% had less than a high school education, 93.6% were African American, and 93.6% had public health insurance, with no differences between groups on these variables. The intervention group had lower fetal/infant mortality vs the control group (2 vs 9), 11 fewer preterm infants, more twin pregnancies carried to term (77.7% vs 33.3%), fewer prenatal hospitalizations (41 vs 49), fewer infant rehospitalizations (18 vs 24), and a savings of more than 750 total hospital days and $2,880,000.

Conclusion

This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs.

Aims

The aim was to evaluate the cost-effectiveness of primary prevention of gestational diabetes mellitus (GDM) through intensified counselling on physical activity, diet, and appropriate weight gain among the risk group.

Materials and Methods

The cost-effectiveness analysis was based on data from a cluster-randomised controlled GDM prevention trial carried out in primary health-care maternity clinics in Finland. Women (n = 399) with at least one risk factor for GDM were included. The incremental cost-effectiveness ratio (ICER) was calculated in terms of birth weight, 15D, and perceived health as measured with a visual analogue scale (VAS). A bootstrap technique for cluster-randomised samples was used to estimate uncertainty around a cost-effectiveness acceptability curve.

Results

The mean total cost in the intervention group was €7,763 (standard deviation (SD): €4,511) and in the usual-care group was €6,994 (SD: €4,326, p = 0.14). The mean intervention cost was €141. The difference for costs in the birth-weight group was €753 (95% CI: −250 to 1,818) and in effects for birth weight was 115 g (95% CI: 15 to 222). The ICER for birth weight was almost €7, with 86.7% of bootstrap pairs located in the north-east quadrant, indicating that the intervention was more effective and more expensive in birth weight terms than the usual care was. The data show an 86.7% probability that each gram of birth weight avoided requires an additional cost of €7.

Conclusions

Intervention was effective for birth weight but was not cost-effective for birth weight, 15D, or VAS when compared to the usual care.

Trial Registration

ISRCTN 33885819.

Objective

To investigate the possible association between total daily iron intake during pregnancy, haemoglobin in early pregnancy and the risk of gestational diabetes mellitus (GDM) in women at increased risk of GDM.

Design

A prospective cohort study (based on a cluster-randomised controlled trial, where the intervention and the usual care groups were combined).

Setting

Primary healthcare maternity clinics in 14 municipalities in south-western Finland.

Participants

399 Pregnant women who were at increased risk of GDM participated in a GDM prevention trial and were followed throughout pregnancy.

Main outcome measurements

The main outcome was GDM diagnosed with oral glucose tolerance test at 26–28 weeks’ gestation or based on a diagnosis recorded in the Finnish Medical Birth registry. Data on iron intake was collected using a 181-item food frequency questionnaire and separate questions for supplement use at 26–28 weeks’ gestation.

Results

GDM was diagnosed in 72 women (18.1%) in the study population. The OR for total iron intake as a continuous variable was 1.006 (95% CI 1.000 to 1.011; p=0.038) after adjustment for body mass index, age, diabetes in first-degree or second-degree relatives, GDM or macrosomia in earlier pregnancy, total energy intake, dietary fibre, saturated fatty acids and total gestational weight gain. Women in the highest fifth of total daily iron intake had an adjusted OR of 1.66 (95% CI 0.84 to 3.30; p=0.15) for GDM. After excluding participants with low haemoglobin levels (≤120 g/l) already in early pregnancy the adjusted OR was 2.35 (95% CI 1.13 to 4.92; p=0.023).

Conclusions

Our results suggest that high iron intake during pregnancy increases the risk of GDM especially in women who are not anaemic in early pregnancy and who are at increased risk of GDM. These findings suggest that routine iron supplementation should be reconsidered in this risk group of women.

Background

Pregnancy is a period in the life of women that is often associated with decreased daily physical activity and/or exercise. However, maintaining adequate levels of daily physical activity during pregnancy is important for mother and child. Studies suggest that moderate daily physical activity and exercise during pregnancy are associated with reductions in the risk of gestational diabetes mellitus (GDM). However, at present, physical activity is not routinely advised to pregnant women at risk for gestational diabetes in the Netherlands. In FitFor2-study we aim to assess whether an exercise program can improve insulin sensitivity and fasting plasma glucose levels of women at high risk for gestational diabetes, assuming that this will lower their risk of gestational diabetes.

Methods

The FitFor2-study is a randomised controlled trial. Women who visit one of the participating hospitals or midwifery practices and who are at risk for gestational diabetes are eligible to participate. After baseline measurement they are randomly allocated to in the intervention or control group. The intervention group receives an exercise program twice a week in addition to usual care. The exercise program consist of aerobic and strength exercises and takes place under close supervision of a physiotherapist. Data are collected at 15, 24 and 32 weeks of pregnancy and 12 weeks after delivery. Primary maternal outcome measures are fasting plasma glucose and relative increase in insulin resistance. Primary neonatal outcome is birth weight. Secondary outcome measures are: maternal serum triglycerides, HDL, cholesterol, HbA1c, maternal weight gain during pregnancy, maternal physical activity level, foetal growth.

Discussion

If the FitFor2 intervention program proves to be effective, obstetricians and midwives should refer women at risk for GDM to a special exercise program. Exercise programs for pregnant women under supervision of an experienced trainer are already available in the Netherlands, and these programs could be adjusted easily for this target group. Furthermore, the costs of these programs should be refunded by including them in the basic health care cost reimbursement schemes.

Trial registration

NTR1139

Background

Hyperglycemia in pregnancy is associated with poor perinatal outcome. Even if pregnant women with diabetes are monitored according to current guidelines, they do much worse than their normoglycaemic counterparts, marked by increased risks of pre-eclampsia, macrosomia, and caesarean section amongst others. Continuous Glucose Monitoring (CGM) is a new method providing detailed information on daily fluctuations, used to optimize glucose control. Whether this tool improves pregnancy outcome remains unclear. In the present protocol, we aim to assess the effect of CGM use in diabetic pregnancies on pregnancy outcome.

Methods/design

The GlucoMOMS trial is a multicenter open label randomized clinical trial with a decision and cost-effectiveness study alongside. Pregnant women aged 18 and over with either diabetes mellitus type 1 or 2 on insulin therapy or with gestational diabetes requiring insulin therapy before 30 weeks of gestation will be asked to participate. Consenting women will be randomly allocated to either usual care or complementary CGM. All women will determine their glycaemic control by self-monitoring of blood glucose levels and HbA1c. In addition, women allocated to CGM will use it for 5–7 days every six weeks. Based on their CGM profiles they receive dietary advice and insulin therapy adjustments if necessary. The primary outcome measure is rate of macrosomia, defined as a birth weight above the 90th centile. Secondary outcome measures will be birth weight, composite neonatal morbidity, maternal outcome and costs. The analyses will be according to the intention to treat principle.

Discussion

With this trial we aim at clarifying whether the CGM improves pregnancy outcome when used during diabetic pregnancies.

Trial registration

Nederlands Trial Register: NTR2996

Background

Prevention of preterm birth remains one of the most important challenges in maternity care. We propose a randomised trial with: a simple Candida testing protocol that can be easily incorporated into usual antenatal care; a simple, well accepted, treatment intervention; and assessment of outcomes from validated, routinely-collected, computerised databases.

Methods/Design

Using a prospective, randomised, open-label, blinded-endpoint (PROBE) study design, we aim to evaluate whether treating women with asymptomatic vaginal candidiasis early in pregnancy is effective in preventing spontaneous preterm birth. Pregnant women presenting for antenatal care <20 weeks gestation with singleton pregnancies are eligible for inclusion. The intervention is a 6-day course of clotrimazole vaginal pessaries (100 mg) and the primary outcome is spontaneous preterm birth <37 weeks gestation.

The study protocol draws on the usual antenatal care schedule, has been pilot-tested and the intervention involves only a minor modification of current practice. Women who agree to participate will self-collect a vaginal swab and those who are culture positive for Candida will be randomised (central, telephone) to open-label treatment or usual care (screening result is not revealed, no treatment, routine antenatal care). Outcomes will be obtained from population databases.

A sample size of 3,208 women with Candida colonisation (1,604 per arm) is required to detect a 40% reduction in the spontaneous preterm birth rate among women with asymptomatic candidiasis from 5.0% in the control group to 3.0% in women treated with clotrimazole (significance 0.05, power 0.8). Analyses will be by intention to treat.

Discussion

For our hypothesis, a placebo-controlled trial had major disadvantages: a placebo arm would not represent current clinical practice; knowledge of vaginal colonisation with Candida may change participants' behaviour; and a placebo with an alcohol preservative may have an independent affect on vaginal flora. These disadvantages can be overcome by the PROBE study design.

This trial will provide definitive evidence on whether screening for and treating asymptomatic candidiasis in pregnancy significantly reduces the rate of spontaneous preterm birth. If it can be demonstrated that treating asymptomatic candidiasis reduces preterm births this will change current practice and would directly impact the management of every pregnant woman.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12610000607077

Summary

Background

Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes.

Methods

We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (α-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045.

Findings

Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0·81, 95% CI 0·59–1·12). No adverse maternal or neonatal outcomes were reported.

Interpretation

Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing.

Funding

The Wellcome Trust.

Background

The impact of borderline gestational diabetes mellitus (BGDM), defined as a positive oral glucose challenge test (OGCT) and normal oral glucose tolerance test (OGTT), on maternal and infant health is unclear. We assessed maternal and infant health outcomes in women with BGDM and compared these to women who had a normal OGCT screen for gestational diabetes.

Methods

We compared demographic, obstetric and neonatal outcomes between women participating in the Australian Collaborative Trial of Supplements with antioxidants Vitamin C and Vitamin E to pregnant women for the prevention of pre-eclampsia (ACTS) who had BGDM and who screened negative on OGCT.

Results

Women who had BGDM were older (mean difference 1.3 years, [95% confidence interval (CI) 0.3, 2.2], p = 0.01) and more likely to be obese (27.1% vs 14.1%, relative risk (RR) 1.92, [95% CI 1.41, 2.62], p < 0.0001) than women who screened negative on OGCT. The risk of adverse maternal outcome overall was higher (12.9% vs 8.1%, RR 1.59, [95% CI 1.00, 2.52], p = 0.05) in women with BGDM compared with women with a normal OGCT. Women with BGDM were more likely to develop pregnancy induced hypertension (17.9% vs 11.8%, RR 1.51, [95% CI 1.03, 2.20], p = 0.03), have a caesarean for fetal distress (17.1% vs 10.5%, RR 1.63, [95% CI 1.10, 2.41], p = 0.01), and require a longer postnatal hospital stay (mean difference 0.4 day, [95% CI 0.1, 0.7], p = 0.01) than those with a normal glucose tolerance.

Infants born to BGDM mothers were more likely to be born preterm (10.7% vs 6.4%, RR 1.68, [95% CI 1.00, 2.80], p = 0.05), have macrosomia (birthweight ≥4.5 kg) (4.3% vs 1.7%, RR 2.53, [95% CI 1.06, 6.03], p = 0.04), be admitted to the neonatal intensive care unit (NICU) (6.5% vs 3.0%, RR 2.18, [95% CI 1.09, 4.36], p = 0.03) or the neonatal nursery (40.3% vs 28.4%, RR 1.42, [95% CI 1.14, 1.76], p = 0.002), and have a longer hospital stay (p = 0.001). More infants in the BGDM group had Sarnat stage 2 or 3 neonatal encephalopathy (12.9% vs 7.8%, RR 1.65, [95% CI 1.04, 2.63], p = 0.03).

Conclusion

Women with BGDM and their infants had an increased risk of adverse health outcomes compared with women with a negative OGCT. Intervention strategies to reduce the risks for these women and their infants need evaluation.

Trial registration

Current Controlled Trials ISRCTN00416244

BACKGROUND

It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes.

METHODS

Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma.

RESULTS

A total of 958 women were randomly assigned to a study group — 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P = 0.14). There were no perinatal deaths. However, there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes, including mean birth weight (3302 vs. 3408 g), neonatal fat mass (427 vs. 464 g), the frequency of large-for-gestational-age infants (7.1% vs. 14.5%), birth weight greater than 4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs. 4.0%), and cesarean delivery (26.9% vs. 33.8%). Treatment of gestational diabetes mellitus, as compared with usual care, was also associated with reduced rates of preeclampsia and gestational hypertension (combined rates for the two conditions, 8.6% vs. 13.6%; P = 0.01).

CONCLUSIONS

Although treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications, it did reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders.

Background

Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes.

Methods

A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively.

Results

After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m2) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (≥ 25 kg/m2). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6).

Conclusions

These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.

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.

Objective To summarise the benefits and harms of treatments for women with gestational diabetes mellitus.

Design Systematic review and meta-analysis of randomised controlled trials.

Data sources Embase, Medline, AMED, BIOSIS, CCMed, CDMS, CDSR, CENTRAL, CINAHL, DARE, HTA, NHS EED, Heclinet, SciSearch, several publishers’ databases, and reference lists of relevant secondary literature up to October 2009.

Review methods Included studies were randomised controlled trials of specific treatment for gestational diabetes compared with usual care or “intensified” compared with “less intensified” specific treatment.

Results Five randomised controlled trials matched the inclusion criteria for specific versus usual treatment. All studies used a two step approach with a 50 g glucose challenge test or screening for risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Meta-analyses did not show significant differences for most single end points judged to be of direct clinical importance. In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common (odds ratio 0.40, 95% confidence interval 0.21 to 0.75), and one randomised controlled trial reported a significant reduction of pre-eclampsia (2.5 v 5.5%, P=0.02). For the surrogate end point of large for gestational age infants, the odds ratio was 0.48 (0.38 to 0.62). In the 13 randomised controlled trials of different intensities of specific treatments, meta-analysis showed a significant reduction of shoulder dystocia in women with more intensive treatment (0.31, 0.14 to 0.70).

Conclusions Treatment for gestational diabetes, consisting of treatment to lower blood glucose concentration alone or with special obstetric care, seems to lower the risk for some perinatal complications. Decisions regarding treatment should take into account that the evidence of benefit is derived from trials for which women were selected with a two step strategy (glucose challenge test/screening for risk factors and oral glucose tolerance test).

Objective

To analyze the association of hemoglobin A1c (HbA1c) at gestational diabetes mellitus (GDM) diagnosis with postpartum abnormal glucose in a cohort of women with GDM.

Methods

Women with singleton pregnancies managed for GDM at a large diabetes and pregnancy program located in Charlotte, North Carolina who completed a postpartum 2-hour oral glucose tolerance test were eligible for inclusion in this retrospective cohort study. Clinical information, including maternal HbA1c at diagnosis was abstracted from medical records. A parametric survival model was used to assess the association of HbA1c at GDM diagnosis with postpartum maternal abnormal glucose including impaired fasting glucose, impaired glucose tolerance, and any postpartum abnormal glucose.

Results

Of the 277 postpartum women with GDM 75 (32%) had impaired fasting glucose, 61 (28%) had impaired glucose tolerance, and 15 (9%) were diagnosed with type 2 diabetes after delivery. After adjustment for clinic, maternal age, parity, prepregnancy BMI 25 kg/m2 or higher, non-white race or ethnicity, and gestational week at first HbA1c we detected a trend of increased risk for impaired fasting glucose (p=0.01), impaired glucose tolerance (p=0.002), and any glucose abnormality (p <0.001) associated with increased quartile of HbA1c at GDM diagnosis.

Conclusion

HbA1c measured at GDM diagnosis may be a useful tool for identifying GDM patients at highest risk of developing postpartum abnormal glucose.

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.

Overview

The proportion of preterm and low-birth-weight infants has been growing steadily for two decades. Most of the more than $10 billion spent on neonatal care in the United States in 2003 was spent on the 12.3% of infants who were born preterm. Research has shown higher initial hospital costs and a higher rate of acute care visits and rehospitalization for preterm and low-birth-weight infants, but only a limited number of studies of the cost of prematurity that follow infants through the first year of life have been conducted.

This study is a secondary analysis of data on a subset of infants drawn from a randomized clinical trial that examined health outcomes and health care costs in women with high-risk pregnancies and their infants. For the current study, a sample of 84 singleton infants was chosen. Forty-three infants (51 %) were full term (37 weeks’ gestation or more) and 41 (49%) were born preterm (less than 37 weeks’ gestation). Fifty-five infants (65.5%) were born at normal birth weights (2,500 g or greater), 24 (28.5%) were born at low birth weights (1,501 to 2,499 g), and five (6%) were born at very low birth weights (less than 1,500 g).

Data on the initial hospital charges and the rates of rehospitalization and acute care visits in the first year of life in relation to gestational age and birth weight were collected. The results clearly demonstrated that the charges for initial hospitalizations increased as birth weights and gestational ages decreased. Low-birth-weight infants were less likely to have unscheduled acute care visits than normal-birth-weight infants.

Interventions to improve prenatal care targeted to women at high risk for delivering preterm or low-birth-weight infants would reduce health care costs and improve health outcomes of infants as well.

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.

Background

This abandoned randomised controlled trial assessed the effects of hospitalisation from 24 to 30 weeks gestation for women with a triplet pregnancy on the risk of preterm birth.

Methods

Women with a triplet pregnancy and no other condition necessitating hospital admission were approached for participation in the study, and randomised to either antenatal hospitalisation (hospitalised group), or to routine antenatal care (control group). The randomisation schedule used variable blocks with stratification by parity, and a researcher not involved with clinical care contacted by telephone to determine treatment allocation by opening the next in a series of consecutively numbered, opaque, sealed envelopes. Primary study outcomes were preterm birth (defined as birth less than 37 weeks gestation) and very preterm birth (defined as birth less than 34 weeks gestation), and the development of maternal pregnancy induced hypertension. The trial was ceased prior to achieving the calculated sample size due to difficulties in recruitment. The results of this randomised controlled trial were then combined with the results of another comparing bed rest in women with a triplet pregnancy.

Results

Seven women with a triplet pregnancy were recruited to the trial, with three randomised to the hospitalisation group, and four to the control group. There were no statistically significant differences between the two groups for the primary outcomes birth before 37 weeks (3/3 hospitalisation group versus 4/4 control group; relative risk (RR) not estimable), birth before 34 weeks (3/3 hospitalisation group versus 2/4 control group; RR 2.00 95% Confidence Intervals (CI) 0.75–5.33) and pregnancy induced hypertension (1/3 hospitalisation group versus 1/4 control group; RR 1.33 95%CI 0.13–13.74).

When the results of this trial were incorporated into a meta-analysis with the previous randomised controlled trial assessing hospitalisation and bed rest for women with a triplet pregnancy, (total sample size 26 women and 78 infants), there were no statistically significant differences identified between the two groups.

Conclusion

The results of this trial and meta-analysis suggest no benefit of routine hospitalisation and bed rest for women with a triplet pregnancy to reduce the risk of preterm birth. The adoption or continuation of a policy of routine hospitalisation and bed rest for women with an uncomplicated triplet pregnancy cannot be recommended.

Background

Pregnant women commonly receive screening for gestational diabetes mellitus by use of a 50 g glucose challenge test, followed by a diagnostic oral glucose tolerance test for those whose glucose challenge test result is abnormal. Although women with gestational diabetes have an increased risk of cardiovascular disease, it is not known whether mild glucose intolerance during pregnancy is also associated with cardiovascular disease. Thus, we sought to determine whether pregnant women with an abnormal glucose challenge test result but without gestational diabetes have an increased risk of cardiovascular disease.

Methods

We conducted a retrospective population-based cohort study that included all women in Ontario aged 20–49 years with live deliveries between April 1994 and March 1998. We excluded women with pregestational diabetes. The population was stratified into 3 cohorts: women with gestational diabetes (n = 13 888); women who received an antepartum oral glucose tolerance test (suggestive of an abnormal result of the glucose challenge test) but who did not have gestational diabetes (n = 71 831); and women who did not receive an oral glucose tolerance test (suggestive of a normal result of the glucose challenge test) (n = 349 977). The primary outcome was cardiovascular disease (admission to hospital for acute myocardial infarction, coronary bypass, coronary angioplasty, stroke or carotid endarterectomy).

Results

Compared with women who did not receive an oral glucose tolerance test, women with gestational diabetes and women who received an oral glucose tolerance test but did not have gestational diabetes had a higher risk of cardiovascular disease over 12.3 years of median follow-up (adjusted hazard ratio [HR] for women with gestational diabetes 1.66, 95% confidence interval [CI] 1.30–2.13, p < 0.001; adjusted HR for those with an oral glucose test but not gestational diabetes 1.19, 95% CI 1.02–1.39, p = 0.03).

Interpretation

Mild glucose intolerance in pregnancy may be associated with an increased risk of cardiovascular disease.

Objective

To estimate the incremental cost of implementing policies for intensive control of blood glucose concentration and blood pressure for all patients with type 2 diabetes in England.

Design

Extrapolation of resource use and cost data derived from a randomised controlled trial.

Setting

General practice, outpatient care, and inpatient care.

Population

Trial population with diagnosed type 2 diabetes in England extrapolated to the population of England.

Main outcome measures

Total costs based on use of healthcare resources including costs of management, treatment, and hospitalisation.

Results

The incremental net annual cost of implementing intensive control of blood glucose and blood pressure to all people with diagnosed type 2 diabetes in England is estimated to be £100.5m ($156m; €159m), which is equivalent to less than 1% of the proposed additional annual expenditure on the NHS in 2001-5. This estimate varied in sensitivity analyses from £67m to £121m.

Conclusions

Policies to improve control of blood glucose and blood pressure of people with type 2 diabetes are effective in reducing complications associated with the disease and are also cost effective. The total cost represents a small fraction of the NHS's spending plans.

What is already known on this topicThe United Kingdom Prospective Diabetes Study (UKPDS) has shown that policies of intensive control of blood glucose concentration and blood pressure for people with type 2 diabetes are cost effective interventionsCurrent levels of diabetes care in England need to be improved, but the total cost and the implications for NHS staffing are unknownWhat this study addsImplementing the main findings of the UKPDS to all people with diagnosed type 2 diabetes in England would have a net annual cost of around £100m, which equates to 1% of the planned increase in annual expenditure on the NHS over the period 2001-5About 720 additional staff would be required to implement these control policies, especially specialist nurses and practice nursesThe advent of primary care trusts and the national service framework for diabetes should create new incentives and mechanisms to adopt these improved standards