Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes

ACHOIS showed that treatment did not reduce rates of symptomatic neonatal hypoglycemia or jaundice requiring phototherapy.

“The results of the ACHOIS trial showed that treatment did not reduce the rates of symptomatic neonatal hypoglycemia or jaundice requiring phototherapy.8”

In the MFMU study, no changes were noted in the composite endpoint, but the incidence of LGA and shoulder dystocia decreased significantly.

“In the MFMU study, no changes were noted in the composite endpoint, but the incidence of LGA and shoulder dystocia decreased significantly [2,29,30].”

In the ACHOIS study, the composite endpoint was significantly reduced with antihyperglycemic intervention, and there was lower weight gain by 1.7 kg on average and lower incidence of LGA.

“In the ACHOIS study, the composite endpoint (neonatal death, perinatal injury, hyperbilirubinemia, neonatal hypoglycemia and hyperinsulinemia) was significantly reduced with antihyperglycemic intervention, and there was also a lower weight gain (by 1.7 kg on average) and a lower incidence of LGA.”

The expected benefits of using IADPSG criteria to the offspring are inferred from intervention trials that focused on individuals with lower levels of hyperglycemia than those identified using older GDM diagnostic criteria; those trials found modest benefits, including reduced rates of large-for-gestational-age births and preeclampsia.

“The expected bene fi ts of using IADPSG criteria to the offspring are inferred from intervention trials that focused on individuals with lower levels of hyperglycemia than those identi fi ed using older GDM diagnostic criteria. Those trials found modest bene fi ts, including reduced rates of largefor-gestational-age births and preeclampsia (211,212).”

80-90% of participants being treated for mild GDM in these two randomized controlled trials could be managed with lifestyle therapy alone.

“Of note, 80-90% of participants being treated for mild GDM in these two randomized controlled trials could be managed with lifestyle therapy alone.”

Several randomized controlled trials (RCTs) have provided evidence of improved perinatal outcomes of GDM in the second half of pregnancy.

“Although the diagnostic criteria for GDM differ, several randomized controlled trials (RCTs) have provided evidence of improved perinatal outcomes of GDM in the second half of pregnancy.”

For some women, the diagnosis is a catalyst for positive behavioural change and improved quality of life.

“For some women, the diagnosis is a catalyst for positive behavioural change 36 and improved quality of life. 15”

The recommended approach to screening and diagnosis of gestational diabetes mellitus is based on available trial evidence.

“This approach is based on available trial evidence, 15 , 16”

The trial findings confirm a modest benefit from identifying and treating women with mild carbohydrate intolerance during pregnancy.

“Overall, consistent with findings from the ACHOIS trial, the findings from our trial confirm a modest benefit from the identification and treatment of women with mild carbohydrate intolerance during pregnancy.8”

ACHOIS concluded that treatment reduces serious perinatal complications and may improve health-related quality of life.

“The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS), a large, randomized trial of treatment for gestational diabetes mellitus, concluded that treatment reduces serious perinatal complications and may also improve health-related quality of life.8”

ACHOIS also showed a reduction in shoulder dystocia when women with mild gestational diabetes received treatment (1% vs 3% untreated).

“Consistent with the results of our trial, the ACHOIS trial also showed a reduction in the rate of shoulder dystocia when women with mild gestational diabetes mellitus received treatment (1%, vs. 3% in the untreated group).8”

Two randomized clinical trials in women with GDM demonstrated improvement of pregnancy outcomes in women identified with and treated for GDM compared with women left untreated.

“Two randomized clinical trials (RCTs) in women with GDM demonstrated the improvement of these pregnancy outcomes in women identified with and treated for GDM compared with women left untreated [6,7].”

Treatment of even mild forms of glucose intolerance in GDM offers an added benefit.

“The treatment of even mild forms of glucose intolerance in GDM offers an added benefit, as demonstrated by the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) and Maternal-Fetal Medicine Units Network (MFMU).”

Although two RCTs found that treatment of GDM can reduce perinatal morbidity, it is not known whether treatment reduces long-term risks in children.

“Although two RCTs found that treatment of GDM can reduce perinatal morbidity (264,265), it is not known whether treatment reduces long-term risks in children.”

80-90% of participants being treated for mild GDM in two randomized controlled trials could be managed with lifestyle therapy alone.

“It is important to note that 80 -90% of participants being treated for mild GDM in these two randomized controlled trials could be managed with lifestyle therapy alone.”

The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial the 2-h PG threshold (140 mg/dL) was lower than the IADPSG cutoff (153 mg/dL).

“The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial (212), the 2-h PG threshold (140 mg/dL [7.8 mmol/L]) was lower than the cutoff recommended by the IADPSG (153 mg/dL [8.5 mmol/L]).”

The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial the 2-h PG threshold (140 mg/dL [7.8 mmol/L]) was lower than the cutoff recommended by the IADPSG (153 mg/dL [8.5 mmol/L]).

“The OGTT glucose cutoffs in these two trials overlapped the thresholds recommended by the IADPSG, and in one trial (195), the 2-h PG threshold (140 mg/dL [7.8 mmol/L]) was lower than the cutoff recommended by the IADPSG (153 mg/dL [8.5 mmol/L]).”

Intervention trials focusing on individuals with lower levels of hyperglycemia than those identified using older GDM diagnostic criteria found modest benefits, including reduced rates of large-for-gestational-age births and preeclampsia.

“Those trials found modest benefits, including reduced rates of largefor-gestational-age births and preeclampsia (194,195).”

The ACHOIS trial was not based on the IADPSG criteria for GDM.

“However, that RCT study was not based on the IADPSG criteria for GDM.”

In the ACHOIS trial, the intervention group had a significantly lower risk of neonatal complications than the non-intervention group among GDM cases.

“In the GDM cases in ACHOIS, the intervention group had a significantly lower risk of neonatal complications than the non‐intervention group 13 .”

Identification and treatment of gestational diabetes mellitus defined by elevated glucose concentrations following a glucose load is supported by high quality evidence.

“women should be counselled that identification and treatment of gestational diabetes mellitus defined by elevated glucose concentrations following a glucose load is supported by high quality evidence, 15 , 16”

Follow-up of the children in both these studies at 4 to 5 and 7 years of age, respectively, failed to observe differences in limited indicators of child adiposity between children of mothers with treated GDM and those with untreated GDM.

“Follow-up of the children in both these studies at 4 to 5 (264-266) and 7 years of age (267), respectively, failed to observe differences in limited indicators of child adiposity between children of mothers with treated GDM and those with untreated GDM.”

Blood glucose-lowering pharmacological therapy is effective at improving outcomes in women with gestational diabetes whose hyperglycemia does not respond sufficiently to lifestyle therapy.

“Blood glucose-lowering pharmacological therapy is effective at improving outcomes in women with gestational diabetes whose hyperglycemia does not respond sufficiently to lifestyle therapy (71, 82, 88–90).”

Despite improvements in maternal glycemic control and reduced perinatal complications, the prevalence of adverse pregnancy outcomes remains higher than in the general population.

“Despite recent improvements in maternal glycemic control and a reduction in the frequency of perinatal complications, the prevalence of adverse pregnancy outcomes continues to be higher than the general population.12,23”

The ACHOIS and MFMU RCTs, despite using different diagnostic tests and criteria, produced quite similar treatment outcomes.

“Although the diagnostic tests and criteria used in the 2 RCTs differed substantially, treatment outcomes were quite similar (Table 1)”

MNT is a cornerstone of therapy for all women with GDM, and approximately 80% to 90% of women meet therapeutic targets with MNT alone.

“Medical nutrition therapy (MNT) is a cornerstone of therapy for all women with GDM, and approximately 80% to 90% of women are able to meet therapeutic targets with MNT alone.12,13”

Lifestyle interventions have been attributed with decreased risk of macrosomia, decreased neonatal adiposity, and increased likelihood of achieving postpartum weight goals.

“Multiple benefits have been attributed to lifestyle interventions, including decreased risk of macrosomia, decreased neonatal adiposity, and increased likelihood to achieve postpartum weight goals.12,13,50”

Maternal glycemia relates to birth weight.

“which fits with other data showing that maternal glycemia relates to birth weight.21–23”

Two randomized trials showed that treatment of mild gestational diabetes, predominantly with diet, compared with standard pregnancy care was associated with improved pregnancy outcomes.

“There are two randomized trials showing that treatment of mild GDM (predominantly with diet) compared with standard pregnancy care was associated with improved pregnancy outcomes (22,23)”

In ACHOIS, the large-for-gestational-age rate was reduced from 21.95% to 13.44%, a 38.8% reduction, in women identified and treated compared with those whose gestational diabetes was not identified.

“For example, in ACHOIS, 28 the rate of LGA was reduced from 21.95% to 13.44%, a 38.8% reduction, in the women who were identified and treated compared with the women whose GDM was not identified.”

The trial's incidence estimates were based on the Australian Carbohydrate Intolerance Study, a randomized trial of high-risk women with mild gestational diabetes.

“The incidence estimates, as stated in the online appendix (Supplemental Table 2 1 ), were based on reported outcomes in the Australian Carbohydrate Intolerance Study (ACHOIS) study, 28 an RCT that comprised high-risk women diagnosed as having mild GDM”

Applying ACHOIS's 35% preeclampsia reduction to the additional 12% undiagnosed mild gestational diabetes cases in group 2 yields a relative risk estimate of 1.107, again lower than 1.2.

“A similar analysis applies to the 35% reduction in preeclampsia, reported with diagnosis and treatment in ACHOIS, 28 to the additional 12% undiagnosed cases of mild GDM in group 2. The reported rate of preeclampsia or gestational hypertension in the treated GDM women in group 2 was 20.3%.Based on these values and calculations similar to those above for LGA, we obtain a relative risk estimate of 1.”

ACHOIS incidence figures for adverse outcomes included only pregnancies with gestational diabetes, whereas the current trial examined outcomes in the overall screened groups.

“Of importance, the incidence figures for adverse outcomes in ACHOIS 28 included only pregnancies with GDM.It is not clear how these ACHOIS figures factored into the sample size estimates, because the current study looked at the outcomes in the overall screened groups, rather than only in those with GDM.”

ACHOIS compared a group identified and treated for mild gestational diabetes with a group blinded to the diagnosis.

“ACHOIS compared 1 group (N¼506) identified and treated for their mild GDM and the other group (N¼524) blinded, along with their caregivers, to the diagnosis.”

The perinatal composite outcome occurred in 4% of untreated gestational diabetes cases in ACHOIS, yet the current trial estimated its incidence as 4% in the entire sample.

“For example, the perinatal composite outcomes occurred in 4% of the untreated GDMs in ACHOIS yet the current study estimated its incidence as 4% in the entire sample.”

In the ACHOIS study, participants had 75 g 2-hour OGTT plasma glucose values between 140 and 198 mg/dL, which indicates a milder form of gestational diabetes than IADPSG criteria identify.

“Participants in the ACHOIS study 28 had 75 g, 2-hour OGTT plasma glucose between 140 mg/dL and 198 mg/dL, indicating milder GDM than those diagnosed by IADPSG criteria.17”

When mild gestational diabetes was recognized and treated, relative risks for some major immediate adverse outcomes were significantly reduced by similar proportions: 40% to 60% for large-for-gestational-age and macrosomic babies and 30% to 40% for hypertensive disorders of pregnancy.

“As shown in Table 3, the relative risk for some of the main adverse immediate outcomes were significantly reduced, by similar proportions of 40% to 60% for LGA and macrosomic babies and 30% to 40% for hypertensive disorders of pregnancy, when mild GDM was recognized and treated.”

In the two trials of mild gestational diabetes, 10% to 20% of patients required pharmacologic treatment in addition to medical nutritional therapy.

“the two trials that focused on the treatment of”

Treatment of gestational diabetes mellitus reduces serious adverse outcomes.

“Both studies found that treatment of GDM can reduce both serious adverse outcomes and the frequency of large babies (macrosomia) (174,175).”

Two randomized clinical trials showed that treating mild gestational diabetes mellitus provides benefit.

“Two randomized clinical trials have now demonstrated a benefit from the treatment of”

Treatment of gestational diabetes mellitus reduces the frequency of macrosomia.

“Both studies found that treatment of GDM can reduce both serious adverse outcomes and the frequency of large babies (macrosomia) (174,175).”

The prevalence of maternal adverse events in this study is similar to the routine care groups in the Crowther et al. and Landon et al. studies.

“Considering this, the prevalence of the various maternal adverse events is similar to the 'routine care' groups in the Crowther et al. [10] and Landon et al. [11] studies.”

Unlike this study, the studies by Metzger et al., Crowther et al., and Landon et al. excluded women with greater degrees of hyperglycaemia.

“Unlike our study, Metzger et al. [2], Crowther et al. [10] and Landon et al. [11] excluded women with greater degrees of hyperglycaemia.”

80-90% of women in both mild GDM studies could be managed with lifestyle therapy alone.

“It is important to note that 80–90% of women in both of the mild GDM studies (whose glucose values overlapped with the thresholds recommended herein) could be managed with lifestyle therapy alone.”

Expected benefits to pregnancies and offspring of women diagnosed with GDM by the new criteria are inferred from intervention trials that focused on women with more mild hyperglycemia than identified using older GDM diagnostic criteria and that found modest benefits.

“Expected benefits to their pregnancies and offspring is inferred from intervention trials that focused on women with more mild hyperglycemia than identified using older GDM diagnostic criteria and that found modest benefits (15,16).”

Two randomized controlled trials comparing active treatment versus standard obstetric care for mild GDM have been conducted.

“Two randomized controlled trials comparing active treatment versus standard obstetric care for mild GDM have been conducted during the years in which the HAPO study was carried out (47,48).”

Results of the two randomized controlled trials and HAPO are highly complementary.

“Although not directly comparable, it was concluded that results of the two randomized controlled trials (47,48) and HAPO (25,26) are highly complementary.”

In both randomized controlled trials, treatment, achieved primarily by diet/lifestyle modification, resulted in reduced birth weight and frequency of LGA births and preeclampsia.

“In both randomized controlled trials, treatment, achieved primarily by diet/lifestyle modification, resulted in reduced birth weight and frequency of LGA births and preeclampsia.”