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Relationship between impaired glucose tolerance during pregnancy and poor outcomes



Twenty studies (one randomized clinical trial, sixteen cohort studies, one case-control study, one cross-sectional study, and a Cochrane systematic review) were evaluated to investigate the relationship between impaired glucose tolerance during pregnancy and poor outcomes.

In these studies, definitions of impaired glucose tolerance (IGT) during pregnancy were not standardized. Definitions used included:

  • One hour abnormal glucose challenge test
  • One abnormal value on the 2-hour or 3-hour oral glucose tolerance test
Similarities Between IGT and GDM

In a neutral-quality case-control study by Ergin et al (2002) of 110 women with uncomplicated pregnancies, the fasting insulin levels of patients with normal oral glucose tolerance tests were significantly lower than those patients with GDM (P < 0.001) and a single value abnormality (P < 0.005). Values for total insulin secretion were highest in GDM (P < 0.001), followed by the single value abnormality group (P < 0.005), both significantly differing from the values of patients with normal oral glucose tolerance test results.

In a neutral-quality cross-sectional study by Retnakaran et al (2006) of 179 pregnant women, the metabolic implications of IGT in pregnancy were found to vary in relation to the timing of the abnormal glucose values from the diagnostic oral glucose tolerance tests. The metabolic phenotype associated with 1-hour IGT resembles that of GDM, whereas the metabolic phenotype associated with 2-hour/3-hour IGT exhibits similarity to that of normal glucose tolerance.

Macrosomia and Large for Gestational Age Newborns

A positive-quality randomized clinical trial by Bonomo et al (2005) evaluated the consequences of very mild forms of gestational glucose intolerance in 300 women. Fourteen percent of neonates in the untreated borderline glucose intolerance group were Large for Gestational age (LGA) compared to 6% of the treated borderline glucose intolerance group and 9.1% in the control group (P= 0.046). The researchers concluded that even very mild alterations in glucose intolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures.

In a positive-quality historical cohort study by Jensen et al (2001) of 2,904 singleton pregnancies, both fasting and 2-hour glucose values were significantly associated with macrosomia, whereas only the 2-hour value was associated with assisted delivery, emergency cesarean section, and shoulder dystocia. When corrected for other risk factors, hypertension and induction of labor were marginally associated with glucose levels.

In a positive-quality historical cohort study by Jimenez-Moleon et al (2002) of 1962 pregnant women, both maternal gestational diabetes risk factors and greater carbohydrate intolerance in gravidae were associated with an increase in adverse newborn outcomes. Regardless of carbohydrate intolerance, macrosomia was always higher among gravidae with gestational diabetes risk factors than among women without them. A clear association was seen between the degree of carbohydrate intolerance and the frequency of macrosomia, from 4.0% in the negative screen group to 50.0% among those diagnosed with GDM and classified under non-optimal metabolic control (p <0.001 for trend). Results were similar when weight was analyzed as LGA and were significantly more frequent in newborns of the GDM group.

In a positive-quality historical cohort study by Ostlund et al (2003) of 1,141 women (812 controls, 213 with untreated IGT and 116 with GDM/DM), the proportion of infants who were large for gestational age was independently significantly associated with untreated IGT during pregnancy (odds ratio 7.3, 95% confidence interval 4.1 to 12.7).

In a positive-quality cohort study by Bo et al (2004) of 700 pregnant women, metabolic syndrome was the best predictor of presence of large-for-gestational age babies in patients with an abnormal challenge and normal tolerance test (odds ratio 3.15), one abnormal value (odds ratio 3.53) and gestational diabetes (odds ratio 4.15). Offspring birth weights, prevalence of large-for-gestational age babies, and icterus were significantly higher in women with an abnormal challenge test.

In a positive-quality cohort study by Gruendhammer et al (2003) of 456 pregnant women, the percent of large-for gestational-age and macrosomic infants was significantly increased only in women with three abnormal GTT values. Women with one, two or three abnormal GTT values revealed an increased percentage of cesarean section compared to the age and BMI-matched control group; even women with one abnormal value were at an increased risk of hypertension and higher rate of cesarean section.

In a positive-quality prospective cohort study by Parretti et al (2003) of 189 pregnant women, fetal fat and lean mass measurements were sonographically determined. With respect to fetal fat body mass, all measurements were significantly higher in the 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test and without gestational diabetes, compared to the 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values. In all instances, the significantly contributing factors were gestational age and maternal 1-hour postprandial glucose values; another frequent contributor was prepregnancy BMI.

In a positive-quality prospective cohort study by Saldana et al (2003) of 2,055 pregnant women, black women with IGT had higher rates of both macrosomia (38.5% vs 10.0%) and LGA (53.9% vs 13.2%) compared with white women, independent of maternal prepregnancy weight.

In a positive-quality prospective cohort study by Vambergue et al (2000) of 239 pregnant women, an increased rate of adverse maternal and fetal outcomes was associated with untreated mild gestational hyperglycemia compared to controls; the rate of large for gestational age infants was significantly higher (22.1% vs 11.4%, P < 0.05). After adjustment for confounders, the relationship between LGA and mild gestational hyperglycemia persisted (odds ratio 2.50, 95% confidence interval 1.16 to 5.40, P < 0.05).

In a neutral-quality historical cohort study by Nordin et al (2006) of 298 pregnant women (78 with IGT, 57 with GDM, 14 with IFG, and 149 controls with normal OGTT), there was an increased risk of pre-eclampsia and macrosomia in both the GDM and impaired fasting glucose subjects, but impaired glucose tolerance was not associated with adverse fetal or maternal outcomes.

In a neutral-quality cohort study by Aberg et al (2001) of 14,078 women with singleton pregnancies, advanced maternal age and high BMI were risk factors for increased oral glucose tolerance values. Increased rates of cesarean delivery and infant macrosomia were observed in subjects with glucose tolerance values of 7.8 to 8.9 mmol/L (140-162 mg/dl) and in subjects with GDM.

In a neutral-quality cohort study by Schaefer-Graf et al (2003) of 368 women (280 with GDM and 88 with IGT), maternal weight, glycemia after therapy, rates of fetal macrosomia and LGA were not significantly different between subjects with GDM and IGT.

Incidence of Preterm Birth

In a positive-quality historical cohort study by Lao and Ho (2003) of 2,168 women with singleton pregnancies, the incidence of preterm birth correlated significantly with increasing glucose tolerance. Incidence of spontaneous birth before 37 weeks in the lowest to the highest 2-hour value groups was 5.5%, 2.6%, 3.7%, 4.9%, 8.5% and 10.3% (P = 0.015); before 32 weeks was 0.4%, 0.3%, 0.8%, 0.4%, 2.2%, and 3.4% (P = 0.018).

In a neutral-quality historical cohort study by Hedderson et al (2003) of 46,230 pregnancies, the risk of spontaneous preterm birth increased with increasing levels of pregnancy glycemia, and this association was independent of perinatal complications that could have triggered early delivery. After adjustment for confounding variables, pregnancies with abnormal screening (relative risk 1.23, 95% confidence interval 1.08 to 1.41), Carpenter-Coustan (relative risk 1.53, 95% confidence interval 1.16 to 2.03) and GDM (relative risk 1.42, 95% confidence interval 1.15 to 1.77) had a significantly higher risk of spontaneous preterm birth than pregnancies with normal screening.

In a neutral-quality cohort study by Yang et al (2002) of 9,471 pregnant women, after adjusting for confounding variables, women with IGT were at increased risk for premature rupture of membranes (odds ratio 10.07, 95% confidence interval 2.90 to 34.93), preterm birth (odds ratio 6.42, 95% confidence interval 1.46 to 28.34), breech presentation (odds ratio 3.47, 95% confidence interval 1.11 to 10.84), and high birth weight (90th percentile or 4,000 g, odds ratio 2.42, 95% confidence interval 1.07 to 5.46).

Increased Perinatal Morbidity

In a positive-quality historical cohort study by Lao and Ho (2001) of 1,472 singleton pregnancies with gestational IGT, the placental ratio in pregnancies complicated by IGT was unrelated to maternal characteristics or glycemic parameters, but a high placental ratio was associated with increased morbidity. After adjusting for the effects of preterm birth and vaginal delivery, a high placental ratio was associated with low 1-minute Apgar score, respiratory complications, and treatment for infection.

In a positive-quality historical cohort study by Lao and Wong (2002) of 461 singleton pregnancies, maternal IGT was associated with increased overall prenatal morbidity as well as specific complications in LGA infants. After adjusting for confounding factors, the IGT group had an increased incidence of Erb's palsy (odds ratio 7.81), meconium aspiration syndrome (odds ratio 5.29), phototherapy (odds ratio 2.10), sepsis (odds ratio 2.90), and shoulder dystocia (odds ratio 5.64).

Neonatal Hypoglycemia

A positive-quality systematic review of three studies from the Cochrane Collaboration by Tuffnell et al (2003) examined alternative policies of care for women with gestational diabetes and impaired glucose tolerance (IGT) in pregnancy. Studies reviewed were not included in this Evidence Summary. The difference in abdominal operative delivery rates was not statistically significant (RR 0.86, 95% CI 0.51 to 1.45) and the effect of special care baby unit admission was also not significant (RR 0.49, 95% CI 0.19 to 1.24). Reduction in birth weight greater than 90th centile (RR 0.55, 95% CI 0.19 to 1.61) was not found to be significant. This review suggests that an interventionist policy of treatment may be associated with a reduced risk of neonatal hypoglycemia (RR 0.25, 95% CI 0.07 to 0.86). The reviewers concluded there are insufficient data for any reliable conclusions about the effects of treatments for impaired glucose tolerance on perinatal outcome.

Summary of research regarding treatment of women with impaired glucose tolerance during pregnancy
listed in order of study type and rating

Author/Year Rating Study Type Intervention Duration of intervention Population Outcomes Limitations
Bonomo et al, 2005

A, +

Randomized clinical trial Women in the intervention group were immediately given dietary advice providing 24-30 kcal/kg per day, based on prepregnancy body weight; caloric intake was divided into three meals and two or three snacks, and distributed as 50-55% carbohydrate; 25-30% protein, 20-25% fat. They then entered an outpatient management protocol, which involved visits every 2 weeks, when the main clinical parameters (weight, blood pressure) were recorded, discussion of dietary habits with evaluation of therapeutic compliance, and measurement of fasting and 2 hour postprandial blood glucose, of HBA1C, and fructosamine. Blood glucose targets <5 mmol/ fasting and <6.7 mmol/l 2 hour postprandial. Urine was tested every morning at home for ketone bodies. Diagnosis until postpartum 300 women 14% of neonates in the untreated borderline glucose intolerance group were LGA compared to 6% of the treated borderline glucose intolerance group and 9.1% in the control group (P= 0.046). The researchers concluded that even very mild alterations in glucose intolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures. None.
Jensen et al, 2001 B, + Historical cohort

Patients with GDM were treated with diet, insulin, or both and kept under special obstetric surveillance. These patients were excluded from the study. The nondiabetic women were referred to routine obstetric care.

Diagnosis until postpartum 2,904 nondiabetic women referred to routine obstetric care were eligible for the analysis

Both fasting and 2-hour glucose values were significantly associated with macrosomia, whereas only the-2-hour value was associated with assisted delivery, emergency cesarean section, and shoulder dystocia.

When corrected for other risk factors, hypertension and induction of labor were marginally associated with glucose levels.

The results of the multivariate analysis support the contention that the adverse outcomes associated with gestational diabetes are not entirely explained by the presence of various risk factors but are to some extent attributable to the carbohydrate disorder itself.

It remains to be seen whether there is a relationship between more severe perinatal complications and glucose levels in this range.

Jimenez-Moleon et al, 2001 B, + Historical cohort

All GDM women were tested with diet, 5 of them (7.7%) under treatment of diet plus insulin

In GDM gravidae, the metabolic control was considered “non-optimal” when the woman presented a fasting plasma glucose >105 mg/dl and /or a 2 h postprandial >120 mg/dl on two or more occasions or the patient’s obstetric or endocrinological record specified that the response to treatment was poor.

Metabolic control was considered “non-optimal" in 12 GDM women (18.5%).

Diagnosis until postpartum 1,962 women

Both maternal gestational diabetes risk factors and greater carbohydrate intolerance in gravidae are associated with an increase in adverse newborn outcomes.

Gestational diabetes was associated with a greater incidence of high birth weight, hypoglycemia and hypocalcemia.

Adequate metabolic control of the illness reduced the risk of adverse outcome.

Birth weight traced a positive slope with respect to the degree of carbohydrate intolerance. Regardless of carbohydrate intolerance, macrosomia was always higher among gravidae with gestational diabetes risk factors than among women without them.

A clear association was seen between the degree of carbohydrate intolerance and the frequency of macrosomia, from 4.0% in the negative screen group to 50.0% among those diagnosed with GDM and classified under non-optimal metabolic control (p <0.001 for trend). Results were similar when weight was analyzed as LGA and were significantly more frequent in newborns of the GDM group.

Other factors commonly associated with the development of a macrosomic fetus are advanced maternal age, obesity, weight gain during pregnancy, prolonged gestation and multiparity; some of these are known to be associated with GDM as well. The researchers attempted to eliminate the possible bias introduced by these risk factors by stratifying data as the presence or absence of advanced maternal age (30 years or older) and obesity (BMI >27).

Lao and Ho, 2003 B, + Historical cohort

Women with GDM were referred to a dietitian and put on diet control (30 kcal/kg of ideal weight) and then assessed with pre- and 2-hour postprandial blood glucose profiles.

Insulin therapy was started for inadequate control (fasting plasma glucose >5.9 mmol/L or postprandial glucose >7mmol/L) if dietary readjustment failed to normalize the blood glucose profile.

Obstetrical intervention was based on clear-cut-clinical indications only, and labor induction or elective cesarean section was not performed for suspected large for gestational age (LGA) fetuses in pregnancies complicated by GDM unless other complications, such as malpresentations, were also present.

Diagnosis to postpartum 2,168 women delivering in the hospital with complete records, including 1,169 women with GDM treated with diet restriction only.

Incidence of spontaneous birth before 37 weeks in the lowest to the highest 2-hour value groups was 5.5%, 2.6%, 3.7%, 4.9%, 8.5% and 10.3% (P = 0.015); before 32 weeks was 0.4%, 0.3%, 0.8%, 0.4%, 2.2%, and 3.4% (P = 0.018).

There was no information on the incidence of previous preterm birth in the database and thus there was no examination of the contribution of this factor to the outcome of the index pregnancy.

Lao and Ho, 2001 B, + Historical cohort

Patients with GDM were referred to a dietitian and put on dietary control (30 kcal/kg) initially.

Insulin therapy was given if dietary readjustment failed to maintain the fasting glucose level less than 6.0 mmol/L or postprandial glucose less than 7.1 mmol/L.

HbA1c level was measured after diagnosis to exclude preexisting but undiagnosed diabetes mellitus.

During pregnancy all obstetric patients were treated according to established departmental protocols.

Routine ultrasound examination was done at 18-20 weeks to confirm the maturity and to exclude fetal anomalies.

A proprietary preparation of multivitamins and iron supplements (with 29 mg of elemental iron) was given to all patients.

Labor induction and cesarean delivery were performed based on medical indications.

High-risk pregnancies received regular fetal monitoring with the nonstress test and ultrasound assessment, and intrapartum electronic fetal heart rate monitoring was applied to all patients.

After delivery, for all complicated pregnancies or cases of suspected fetal distress, pediatricians attended the delivery.

In all cases, infants were examined after delivery and the maturity confirmed by the pediatricians.

After delivery of the placenta, it was washed in a sink to clear away any blood and meconium before it was examined on a corrugated board besides the sink.

After examination, the entire placenta, including the membranes and the attached segment of cord, was placed in a plastic container for weighing in on an electronic scale, with the weight of the container calibrated beforehand.

Diagnosis to postpartum 1,472 pregnant women

The placental ratio in pregnancies complicated by IGT was unrelated to maternal characteristics or glycemic parameters, but a high placental ratio was associated with increased morbidity.

After adjusting for the effects of preterm birth and vaginal delivery, a high placental ratio was associated with low 1-minute Apgar score, respiratory complications, and treatment for infection.

There is controversy about the association between GDM and increased placental ratio. It is likely that GDM is only one of the conditions that can result in a disproportionably large placenta.

Lao and Wong, 2002 B, + Historical cohort

Women diagnosed as having IGT or DM were placed on dietary control (30 kcal/kg) initially.

They were then assessed with a two-hour postprandial blood sugar profile.

Insulin therapy was started for inadequate control (postprandial glucose >7 mmol/L) if dietary adjustments failed to normalize the blood glucose profile.

Routine multivitamin and iron supplements (with 29 mg of elemental iron in a proprietary preparation) were given to all women.

Every woman received electronic fetal monitoring during labor.

Pediatricians attended the delivery for resuscitation in all cases of suspected fetal distress, preterm delivery and other potential neonatal complications.

Within 30 minutes after birth, heel prick was performed for blood glucose estimation with hemoglucostix and was repeated every two hours for three times, then every six hours for one more day.

If hypoglycemia was detected (<2.5 mmol/L), a blood sample was sent to the laboratory for repeat glucose measurement.

If the newborn exhibited such signs as jitteriness, blood calcium and magnesium levels were estimated.

Feeding with breast milk or formula was done within two hours of birth.

Diagnosis to postpartum

461 Large for Gestational Age newborns

Despite dietary treatment, maternal IGT was associated with increased perinatal morbidity independent of its effect on fetal size.

After adjusting for confounding factors, the IGT group had an increased incidence of Erb's palsy (odds ratio 7.81), meconium aspiration syndrome (odds ratio 5.29), phototherapy (odds ratio 2.10), sepsis (odds ratio 2.90), and shoulder dystocia (odds ratio 5.64).

Although IGT was found in this study to be a significant risk factor for neonatal sepsis, the cause was not apparent, as there was no difference in the incidence of prelabor rupture of the membranes or mode of delivery. Further studies are necessary to elucidate the mechanism of this complication.

Ostland et al, 2003 B, + Historical cohort

Women diagnosed with GDM or diabetes were referred to special antenatal clinics.

Women with OGTT results below the diagnostic criteria for diabetes were considered normal (non-GDM) and were treated in the routine antenatal clinics by midwives.

No extra control subjects were suggested.

Diagnosis to postpartum 1,141 women (812 controls, 213 with untreated IGT, 116 with GDM/DM)

There was an increased independent association between cesarean section rate, prematurity, LGA, and macrosomic infants born to mothers with untreated IGT.

A significantly higher number of children in IGT group were admitted to and treated for 2 days or longer at a NICU.

The proportion of infants who were large for gestational age was independently significantly associated with untreated IGT during pregnancy (odds ratio 7.3, 95% confidence interval 4.1 to 12.7).

Most of the children were healthy, but there was still increased morbidity.

The outcome in the diabetes group could be due to either difficulties to influence the outcome by treatment, or the fact that treatment could have stopped the increased complications noted in this group with greater deterioration in glucose tolerance.

Bo et al, 2004 B, + Cohort

OGTT negative (normal), n = 100

OGTT positive, OGTT negative, n = 350, received no diet counseling or treatment

OGTT only one abnormal value, n = 100, and GDM positive, n = 150, both received a diet plan, and about 10% of GDM patients placed on insulin

Diagnosis to postpartum 700 pregnant Caucasian women

Metabolic syndrome was the best predictor of presence of large-for-gestational age babies in patients with an abnormal challenge and normal tolerance test (odds ratio 3.15), one abnormal value (odds ratio 3.53) and gestational diabetes (odds ratio 4.15).

Offspring birth weights, prevalence of large-for-gestational age babies, and icterus were significantly higher in women with an abnormal challenge test.

Considering the potential limit of the weight circumference measurements during pregnancy, the prevalence of the metabolic syndrome was assessed without considering waist values.

As no definition of the metabolic syndrome in pregnancy exists, the researchers noted that their definition was arbitrary, though based on recent consensus.

If studies on larger sample sizes provide support for these presumptions, the follow-up of all women with OGTT+ and the research of the components of the metabolic syndrome, to identify higher risk subjects for adverse neonatal outcomes, might be warranted.

Gruendhammer et al, 2003 B, + Cohort

Therapy was based on dietary recommendations when the 2 h pp glucose levels exceeded 6.6 mmol/l insulin therapy was started.

Insulin was administered as an intermediate insulin once or twice daily.

Treatment targets were: Fasting glucose values lower than 5.0 mmol/l and 2h pp glucose values lower than 6.6 mmol/l.

Fasting and pp glucose controls, as well as clinical controls, were performed at weekly intervals or, in women under insulin therapy, by glucose-self-monitoring.

Women with one increased glucose value at the GTT underwent weekly controls and obtained the same dietary instructions as well as insulin administration procedures as women with two or more abnormal glucose values and thus manifested GDM.

Diagnosis to postpartum

456 pregnant women

The percent of large-for gestational-age and macrosomic infants was significantly increased only in women with three abnormal GTT values.

Women with one, two or three abnormal GTT values revealed an increased percentage of cesarean section compared to the age and BMI-matched control group; even women with one abnormal value were at an increased risk of hypertension and higher rate of cesarean section.

The increased rate of LGA infants in the Control group could be due to the fact that the assignment to this non-diabetic group was based on normal glucose values in the oral glucose tolerance test. The determination of cord blood insulin levels might help to perform a stricter risk stratification.

Because perinatal and long-term health risks of mother and child increased in relation to the severity of maternal hyperglycemia also women with only one abnormal GTT value seemed to need further control and treatment procedures. Larger clinical trials will be necessary to improve and confirm the value of the diagnostic criteria, including “gestational impaired glucose tolerance”, and to optimize therapeutic and control regimes.

Parretti et al, 2003 B, + Cohort Not applicable Not applicable 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test and without gestational diabetes, and 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values.

With respect to fetal fat body mass, all measurements were significantly higher in the 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test and without gestational diabetes, compared to the 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values. In all instances, the significantly contributing factors were gestational age and maternal 1-hour postprandial glucose values; another frequent contributor was prepregnancy BMI.

The results need confirmation and verification in glucose intolerant pregnant women to legitimize possible clinical use.

The lack of fat mass measurement in the neonate does not allow comparison between sonographic findings and those obtained postnatally.

Standard curves lean and fat mass should be defined in a large normal population.

Saldana et al, 2003 B, + Cohort Women with GDM received both diet and or insulin treatment at both clinics and women with IGT were not treated at either clinic. Diagnosis to postpartum 2,055 pregnant women

Black women with IGT had higher rates of both macrosomia (38.5% vs 10.0%) and LGA (53.9% vs 13.2%) compared with white women, independent of maternal prepregnancy weight.

Sample size for the analysis was small.

It is possible that more proximate etiological factors, which were not measured in the study, may account for the relationships observed.

Residual confounding associated with the measured variables may be influencing the relationship.

The small number of IGT cases among black women (n=13), limited the precision of the estimated risk.

Vambergue et al, 2000 B, + Cohort Systematic screening by 50-g glucose challenge test offered to all women between 24 and 28 weeks of gestation. At the time of diagnosis 239 pregnant women, 131 with mild gestational hyperglycemia, 108 controls

An increased rate of adverse maternal and fetal outcomes was associated with untreated mild gestational hyperglycemia compared to controls; the rate of large for gestational age infants was significantly higher (22.1% vs 11.4%, P < 0.05).

After adjustment for confounders, the relationship between LGA and mild gestational hyperglycemia persisted (odds ratio 2.50, 95% confidence interval 1.16 to 5.40, P < 0.05).

The study confirmed the increased rate of adverse maternal and fetal outcome associated with untreated mild gestational hyperglycaemic women.

The complications seen were probably a result of the metabolic status; it is tempting to postulate that the mechanism of fetal macrosomia in the study group may be maternal hyperglycaemia leading to fetal hyperinsulinism.

Hedderson et al, 2003 B, ø Historical cohort Not applicable Not applicable 46,230 pregnancies

The risk of spontaneous preterm birth increased with increasing levels of pregnancy glycemia, and this association was independent of perinatal complications that could have triggered early delivery.

After adjustment for confounding variables, pregnancies with abnormal screening (relative risk 1.23, 95% confidence interval 1.08 to 1.41), Carpenter-Coustan (relative risk 1.53, 95% confidence interval 1.16 to 2.03) and GDM (relative risk 1.42, 95% confidence interval 1.15 to 1.77) had a significantly higher risk of spontaneous preterm birth than pregnancies with normal screening.

This study was limited to recorded data, and therefore we were unable to control for other potential confounding variables of the association between preterm birth and maternal glycemia such as prepregnancy weight and parity which have previously been reported to be associated with both preterm birth and GDM.

The Kaiser Permanente Medical Care program of Northern California membership represents approximately 30% of the surrounding population and is representative of the population living in the same geographical area demographically, ethnically, and socioeconomically, except the membership under-represents the very poor and the very wealthy.

Nordin et al, 2006 B, ø Historical cohort Not applicable Not applicable 149 patients (78 with IGT, 57 with GDM and 14 with IFG) were included. 149 patients with normal OGTT were chosen as controls. There was an increased risk of pre-eclampsia and macrosomia in both the GDM and impaired fasting glucose subjects, but impaired glucose tolerance was not associated with adverse fetal or maternal outcomes.

The prepregnancy BMI was unavailable; therefore, the BMI at 32 weeks period of amenorrhea (POA) was used, as by this time the diabetogenic stress had usually manifested in patients with glucose intolerance. In addition, detection and treatment after 32 weeks POA did not improve fetal outcome.

Small numbers in groups.

Yang et al, 2002 B, ø Cohort Screening program as part of the care from antenatal care base units in the Tianjin Antenatal Care Network Not applicable 9,471 pregnant women

After adjusting for confounding variables, women with IGT were at increased risk for premature rupture of membranes (odds ratio 10.07, 95% CI 2.90 to 34.93), preterm birth (odds ratio 6.42, 95% CI 1.46 to 28.34), breech presentation (odds ratio 3.47, 95% CI 1.11 to 10.84), and high birth weight (90th percentile or 4,000 g, odds ratio 2.42, 95% CI 1.07 to 5.46).

Technical, as well as logistic, difficulties were potential barriers to scientific data collection that is considered fundamental to future policy decisions.

Despite careful planning in hospital selection to obtain a representative NGT sample, the researchers found that the sampling distribution for age, BMI, blood pressure(SBP and DBP), and gestational weeks at the initial screening for the 302 control subjects shifted to the right-hand side of the general obstetric population of Tianjin City. The bias appeared systematic and was in part removed through statistical adjustments.

As a comparison group, a higher rather than a lower reading on age, BMI, blood pressure, and gestational weeks at the initial screening was likely to contribute to an underestimation of poor pregnancy outcomes that were reported.

Missing medical records, in particular maternal body weight when admitted for delivery (IGT: 19 and NGT: 12), may also contribute to a reduced predictive power and further underestimate poor perinatal outcomes.

Aberg et al, 2001 B, ø Cohort In the clinical care of the pregnant woman, the control and the sub-GDM groups were treated in the same way, without an consideration of the glucose level.

All women with identified GDM were treated at the center for antenatal care in Lund University Hospital.

All were given a device for home blood glucose monitoring.

Blood glucose was tested 6 times daily if the woman was insulin treated and 6 times every other day if not.

All women with GDM had telephone contact with a diabetologist every week or every second week. Approxmately 40% of the women were treated with insulin.

Diagnosis to postpartum

14,078 pregnant women

Advanced maternal age and high BMI were risk factors for increased oral glucose tolerance values.

Increased rates of cesarean delivery and infant macrosomia were observed in subjects with glucose tolerance values of 7.8 to 8.9 mmol/L (140-162 mg/dl) and in subjects with GDM.

Limitations were noted related to the "smoking" variable.

After stratification for smoking the difference in birthweight increased. One explanation could be that smoking increases insulin resistance. On the other hand, women with gestational diabetes smoked significantly less than the control group. The researchers noted that is was difficult to explain the decreased frequency of smoking in women with GDM.

Schaefer-Graf et al, 2003 B, ø Cohort

Women had ultrasound examinations at entry to and during diabetic care.

Both GDM and IGT groups were managed comparably.

Diagnosis to postpartum. 368 women (280 with GDM and 88 with IGT). Maternal weight, glycemia after therapy, rates of fetal macrosomia and LGA were not significantly different between subjects with GDM and IGT. Authors note limitations of bias in selection of the different cohorts, as well as a high rate of obese women compared to the average German population.
Ergin et al, 2002 C, ø Case- Control To assure consistency in testing procedures, all women instructed to add 150 g of carbohydrate to their usual meals for each 3 days before the the OGTT. 3 days before OGTT 110 pregnant women

Fasting insulin levels of patients with normal oral glucose tolerance tests were significantly lower than those patients with GDM (P < 0.001) and a single value abnormality (P < 0.005).

Values for total insulin secretion were highest in GDM (P < 0.001), followed by the single value abnormality group (P < 0.005), both significantly differing from the values of patients with normal oral glucose tolerance test results.

Patients with single value abnormalities were indistinguishable from patients with GDM and significantly different from the values for the normal OGTT group, by means of the fasting insulin levels and the insulin resistance.

Retnakaran et al, 2006 D, ø Cross-sectional Not applicable Not applicable 179 pregnant women

The metabolic implications of IGT in pregnancy were found to vary in relation to the timing of the abnormal glucose values from the diagnostic oral glucose tolerance tests.

The metabolic phenotype associated with 1-hour IGT resembles that of GDM, whereas the metabolic phenotype associated with 2-hour/3-hour IGT exhibits similarity to that of normal glucose tolerance.

The cross-sectional nature of this study precluded inference on causal relationship. In particular, the researchers were unable to address the relationship between the timing of IGT on an OGT and either pregnancy outcome or postpartum diabetes.

Due to the absence of data on maternal diet in the days preceding the OGTT, the researchers noted that it was conceivable that differences in carbohydrate intake on those days could have affected findings in women with IGT.

It should also be noted that almost all study participants, including those comprising the NGT group, had a positive GCT result before recruitment. Thus, findings with this NGT group may not reflect a truly normal patient population (i.e., with normal screening GCT and normal results on a diagnostic OGTT).

Tuffnell et al, 2003 M, + Systematic review 3 studies which provided alternative policies of care for women with gestational diabetes and impaired glucose tolerance (IGT) in pregnancy were reviewed. Not applicable Three studies with 233 women The difference in abdominal operative delivery rates was not statistically significant (RR 0.86, 95% CI 0.51 to 1.45) and the effect of special care baby unit admission was also not significant (RR 0.49, 95% CI 0.19 to 1.24). Reduction in birth weight greater than 90th centile (RR 0.55, 95% CI 0.19 to 1.61) was not found to be significant. This review suggests that an interventionist policy of treatment may be associated with a reduced risk of neonatal hypoglycemia (RR 0.25, 95% CI 0.07 to 0.86). None. Studies reviewed were not included in this Evidence Summary.




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Worksheets
Aberg A, Rydhstroem H, Frid A. Impaired glucose tolerance associated with adverse pregnancy outcome: A population-based study in southern Sweden. Am J Obstet Gynecol 2001;184:77-83.

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