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Cited by 359Gestational Diabetes Research and ManagementPregnancy and Medication ImpactDiabetes Management and Research

Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis

Open access
Horvath, K., Koch, K., Jeitler, K., Matyas, E., Bender, R., Bastian, H., Lange, S., Siebenhofer, A.·2010·BMJ
DOI 10.1136/bmj.c1395PMC PMC2848718
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Abstract

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).

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of randomised trials found that treating gestational diabetes lowers shoulder dystocia and large-for-gestational-age/macrosomia, but most other clinically important maternal and neonatal outcomes did not differ significantly. The evidence of benefit comes mainly from trials using a two-step screening strategy and is dominated by two large trials.

Key findings

  • In five trials of specific treatment versus usual care (2999 women), shoulder dystocia was significantly reduced (odds ratio 0.40, 95% CI 0.21 to 0.75), as were large-for-gestational-age infants (0.48, 0.38 to 0.62) and macrosomia (0.38, 0.30 to 0.49); one trial reported less pre-eclampsia (2.5% v 5.5%, P=0.02).
  • Most other single endpoints were not significantly different: caesarean section OR 0.86 (0.72 to 1.02), birth trauma OR 0.39 (0.13 to 1.15; P=0.088), neonatal intensive care admission OR 0.73 (0.50 to 1.06; P=0.098), and small for gestational age was not significant.
  • In 13 trials of intensive versus less intensive specific treatment, shoulder dystocia was significantly reduced (OR 0.31, 0.14 to 0.70), but caesarean section was not (OR 1.04, 0.80 to 1.34), and macrosomia/large for gestational age could not be pooled because of heterogeneity.
  • Long-term data were sparse: one trial reported diabetes later in life in 35% versus 36% (not significant), and no trials reported long-term effects in children.

Methods

  • Systematic review and meta-analysis of randomised controlled trials; searched multiple databases and reference lists up to October 2009. Trials were included if they compared specific treatment for gestational diabetes with usual care (pool A) or intensified with less intensified specific treatment (pool B), in pregnant women with impaired glucose tolerance based on an oral glucose tolerance test.
  • Pool A included 5 trials with 2999 women; all used a two-step approach with a 50 g glucose challenge test or risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Pool B included 14 eligible studies, of which 13 were analysed after excluding Yang et al because of publication discrepancies.
  • Meta-analysis used random-effects DerSimonian and Laird models with odds ratios; the Peto one-step method was used for rare events. Heterogeneity was assessed with χ² and I², and no pooled estimate was provided when heterogeneity was substantial (P<0.2).

Limitations

  • The paper states that evidence on beneficial effects remains unstable; major patient-important endpoints are infrequent and available from only a few studies, and two trials dominated the results. In Crowther et al, control women were told they did not have gestational diabetes and intervention women were not blinded, which could bias care; the combined endpoint was criticised because it depends heavily on subjective shoulder dystocia, and Landon et al’s composite endpoint included surrogate outcomes such as cord C peptide.
  • The paper states that pool B tested heterogeneous interventions and selection criteria, most pool B trials were at high risk of bias, and transferability is limited because most studies were conducted in North America, Europe, and Australia, with some ethnic groups underrepresented. Harms of treatment were not explicitly investigated, and long-term outcomes in mothers and children were sparse.
  • Evident from the text: many included trials were judged at high risk of bias, several meta-analyses were based on few trials, and no screening trials or direct comparisons of insulin with oral antidiabetic agents were included.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/bmj.c1395

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 98 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In three of the four studies that reported caesarean sections, there were no significant differences between specific treatment and usual care.

    “There were no significant differences between specific treatment and usual care in three17 19 22 of the four studies that reported caesarean sections (table 4).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [17] Bonomo M, Corica D, Mion E, Goncalves D, Motta G, Merati R, et al. Evaluating the therapeutic approach in pregnancies complicated by borderline glucose intolerance: a randomized clinical trial. Diabet Med 2005; 22: 1536-41. 16241919

      Not checked in the free run.

    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [22] Langer O, Levy J, Brustman L, Anyaegbunam A, Merkatz R, Divon M. Glycemic control in gestational diabetes mellitus: how tight is tight enough; small for gestational age versus large for gestational age? Am J Obstet Gynecol 1989; 161: 646-53. 2782347

      Not checked in the free run.

  • Findingown data

    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).

    “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).”
    Quote in the paperSubstantial claim
  • Findingcitation

    Bonomo et al included women with a positive result on the glucose challenge test but a negative result to the oral glucose tolerance test.

    “Bonomo et al included women with a positive result on the glucose challenge test but a negative result to the oral glucose tolerance test17; all other studies required a positive glucose challenge test and a positive oral glucose tolerance test for inclusion.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Bonomo M, Corica D, Mion E, Goncalves D, Motta G, Merati R, et al. Evaluating the therapeutic approach in pregnancies complicated by borderline glucose intolerance: a randomized clinical trial. Diabet Med 2005; 22: 1536-41. 16241919

      Not checked in the free run.

  • Findingnone given

    None of the trials specifically reported on maternal deaths.

    “None of the trial specifically reported on maternal deaths.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Five randomised controlled trials matched the inclusion criteria for specific treatment for gestational diabetes compared with usual care.

    “Five randomised trials matched the inclusion criteria for specific treatment for gestational diabetes compared with usual care (table 1).17 18 19 20 21 22 23”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 17 18 19 20 21 22 23

      Not checked in the free run.

  • Classified as probably not a substantial claim. 23
  • May combine two claims. 30
  • The quote only partly states this claim. 2

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the intervention groups all pregnant women measured their own glucose concentrations and were treated with diet alone or additional insulin treatment if blood glucose concentrations exceeded prespecified targets.

    “In the intervention groups all pregnant women measured their own glucose concentrations and were treated with diet alone or additional insulin treatment if blood glucose concentrations exceeded prespecified targets.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    All studies in pool A 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.

    “All studies used a two step approach with a 50 g glucose challenge test or check of risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Thirteen trials were left to include in the different meta-analyses.

    “This left 13 trials to include in the different meta-analyses.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    We found no information on possible adverse effects of false positive or false negative test results and labelling and on behavioural changes postpartum.

    “We found no information on possible adverse effects of false positive or false negative test results and labelling and on behavioural changes postpartum.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Five trials provided information on pre-eclampsia.

    “Five trials provided information on pre-eclampsia.26 30 34 35 39”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [26] Bevier WC, Fischer R, Jovanovic L. Treatment of women with an abnormal glucose challenge test (but a normal oral glucose tolerance test) decreases the prevalence of macrosomia. Am J Perinatol 1999; 16: 269-75. 10586979

      Not checked in the free run.

    • cites [30] Elnour AA, El Mugammar I, Jaber T, Revel T, McElnay JC. Pharmaceutical care of patients with gestational diabetes mellitus. J Eval Clin Pract 2008; 14: 131-40. 18211656

      Not checked in the free run.

    • cites [34] Homko CJ, Sivan E, Reece EA. The impact of self-monitoring of blood glucose on self-efficacy and pregnancy outcomes in women with diet-controlled gestational diabetes. Diabetes Educ 2002; 28: 435-43. 12073958

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Eight studies reported on perinatal mortality, with four perinatal deaths in 1380 pregnant women.

    “Eight studies reported on perinatal mortality,24 25 31 32 33 34 35 36 37 38 40 with four perinatal deaths in 1380 pregnant women.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [24] Bancroft K, Tuffnell DJ, Mason GC, Rogerson LJ, Mansfield M. A randomised controlled pilot study of the management of gestational impaired glucose tolerance. BJOG 2000; 107: 959-63. 10955425

      Not checked in the free run.

    • cites [25] Lao T, Ho LF. A randomised controlled pilot study of the management of gestational impaired glucose tolerance. BJOG 2001; 108: 769. 11467709

      Not checked in the free run.

    • cites [31] Garner P, Okun N, Keely E, Wells G, Perkins S, Sylvain J, et al. A randomized controlled trial of strict glycemic control and tertiary level obstetric care versus routine obstetric care in the management of gestational diabetes: a pilot study. Am J Obstet Gynecol 1997; 177: 190-5. 9240606

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The meta-analysis on birth trauma showed a lower number of events in the intervention group than in the usual care group, but the difference was not significant (0.39, 0.13 to 1.15; P=0.088).

    “The meta-analysis on birth trauma, which included data from Crowther et al19 and Landon et al,21 showed a lower number of such events in the intervention group than in the usual care group, but the difference was not significant (0.39, 0.13 to 1.15; P=0.088; fig 3).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [21] Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 1339-48. 19797280 PMC2804874

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    The review found no information on neonatal hypoglycaemia necessitating glucose infusion or on the necessity of breathing support in babies with respiratory distress syndrome.

    “We found no information on neonatal hypoglycaemia necessitating glucose infusion or on the necessity of breathing support in babies with respiratory distress syndrome.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Information on birth weight was available from all but two studies; in only one study was it significantly lower in babies from women receiving intensified treatment.

    “Information on birth weight was available from all but two studies30 41; in only one study26 was it significantly lower in babies from women receiving intensified treatment (table 7).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [30] Elnour AA, El Mugammar I, Jaber T, Revel T, McElnay JC. Pharmaceutical care of patients with gestational diabetes mellitus. J Eval Clin Pract 2008; 14: 131-40. 18211656

      Not checked in the free run.

    • cites [41] Rossi G, Somigliana E, Moschetta M, Bottani B, Barbieri M, Vignali M. Adequate timing of fetal ultrasound to guide metabolic therapy in mild gestational diabetes mellitus: results from a randomized study. Acta Obstet Gynecol Scand 2000; 79: 649-54. 10949229

      Not checked in the free run.

    • cites [26] Bevier WC, Fischer R, Jovanovic L. Treatment of women with an abnormal glucose challenge test (but a normal oral glucose tolerance test) decreases the prevalence of macrosomia. Am J Perinatol 1999; 16: 269-75. 10586979

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In each of the three studies, a smaller proportion of infants from mothers in the specific treatment group had to be transferred to an intensive care unit, but in none was the difference significant.

    “In each of these studies, a smaller proportion of infants from mothers in the specific treatment group had to be transferred to an intensive care unit (table 5), but in none was the difference significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The review found no information on possible behavioural changes in women to prevent diabetes and insufficient data on long term outcomes in the children.

    “We also found no information on possible behavioural changes in women to prevent diabetes and insufficient data on long term outcomes in the children.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    Adverse effects from treatment were not reported.

    “Adverse effects from treatment were not reported.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    These complications are infrequent and information is available from only a few of the included studies.

    “These complications are infrequent and information is available from only a few of the included studies.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Findingreasoning

    It is not known if screening has harms serious enough to counterbalance the possible benefits of treatment.

    “It is not known if screening has harms serious enough to counterbalance the possible benefits of treatment.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingnone given

    All studies in pool A recruited women with gestational diabetes based on a two step strategy (positive glucose challenge test or risk factors, then oral glucose tolerance test).

    “All studies in pool A recruited women with gestational diabetes based on a two step strategy.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    Crowther et al reported that women in the intervention group did not worry more or less than women in the control group but did significantly better in regard to depression after birth, physical functioning, and health state utility.

    “Crowther et al reported that women in the intervention group did not worry more or less than women in the control group but did significantly better in regard to depression after birth, physical functioning, and health state utility.19”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

  • May combine two claims.

    Findingnone given

    Compared with routine care, this management is associated with a reduction in the incidence of shoulder dystocia and macrosomia.

    “Compared with routine care this management is associated with a reduction in the incidence of shoulder dystocia and macrosomia.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Rates of caesarean section, proportion of small for gestational age babies, and gestational age at birth were not significantly different between interventions, so no indication of labelling or other harmful effects was found for these outcomes.

    “Rates of caesarean section, proportion of small for gestational age babies, and gestational age at birth were not significantly different between interventions so no indication of labelling or other harmful effects was found for these outcomes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Women in all interventional studies in pool A were selected in a two step process (50 g glucose challenge test or risk factors, then 75 g or 100 g oral glucose tolerance test), whereas women in HAPO underwent only a one step 75 g oral glucose tolerance test.

    “while women in all the interventional studies in pool A were selected in a two step process consisting of a 50 g glucose challenge test (or screening for risk factors, or both) and a second 75 g or 100 g oral glucose tolerance test, women in HAPO2 underwent only a one step 75 g oral glucose tolerance test.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002. 18463375

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    Induction of labour and transfer of newborns to a neonatal nursery were higher in the intervention group in Crowther et al.

    “Induction of labour and transfer of newborns to a neonatal nursery were higher in the intervention group.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

  • The quote only partly states this claim.

    Findingnone given

    Two studies (Crowther et al and Landon et al) dominated the results.

    “Two studies19 21 dominated the results, so the limitations of these trials must be considered.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [21] Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 1339-48. 19797280 PMC2804874

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The mean fasting blood glucose concentrations in Crowther et al and Landon et al were similar (86.5 mg/dl and 86.6 mg/dl) and not that different from HAPO (80.9 mg/dl), but the incidence of large for gestational age babies in the control groups was rather different (22%, 15%, 9.5%).

    “although the mean fasting blood glucose concentrations in the studies of Crowther et al19 and Landon et al21 were similar (86.5 mg/dl (4.76 mmol/l) and 86.6 mg/dl (4.77 mmol/l), respectively) and not that different from that in HAPO2 (80.9 mg/dl (4.46 mmol/l)), the incidence of large for gestational age babies in the control groups was rather different (22%,19 15%,21 9.5%2).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [21] Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 1339-48. 19797280 PMC2804874

      Not checked in the free run.

    • cites [2] Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002. 18463375

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Most of the included studies were conducted in North America, Europe, and Australia, so not all ethnic groups were sufficiently represented.

    “As most of the included studies were conducted in North America, Europe, and Australia not all ethnic groups were sufficiently represented.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Epidemiological research suggests that women who have gestational diabetes have an increased risk of type 2 diabetes later in life.

    “Epidemiological research suggests that women who have gestational diabetes have an increased risk of type 2 diabetes later in life.3”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 2009; 373: 1773-9. 19465232

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The methods, inclusion and exclusion criteria, and outcomes of interest were described in a pre-published protocol.

    “The methods, the inclusion and exclusion criteria, and the outcomes of interest were described in a pre-published protocol.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen. Screening auf Gestationsdiabetes. Berichtsplan S07-01. Version 1.0. IQWIG, 2007.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Assessment of risk of bias was based on adequacy of randomisation, allocation concealment, blinding of outcome assessors, comparability of women in the different intervention groups for prognostically relevant factors at baseline, and handling of missing values.

    “Assessment of risk of bias was based on the adequacy of randomisation, allocation concealment, blinding of outcome assessors, comparability of women in the different intervention groups for prognostically relevant factors at baseline, and handling of missing values (such as withdrawals and drop outs).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Complications associated with gestational diabetes include shoulder dystocia and birth injuries, neonatal hyperbilirubinaemia, hypoglycaemia, respiratory distress syndrome, caesarean section, and pre-eclampsia.

    “Among those complications are shoulder dystocia and birth injuries, neonatal hyperbilirubinaemia, hypoglycaemia, respiratory distress syndrome, caesarean section, and pre-eclampsia.2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002. 18463375

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Crowther et al, there were no neonatal or perinatal deaths in the intervention group and five such events in the control group.

    “While there were no neonatal or perinatal deaths reported by Landon et al21 and in the intervention group in Crowther et al,19 five such events occurred in the control group of Crowther et al19 (table 5).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [21] Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 1339-48. 19797280 PMC2804874

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Various screening strategies and diagnostic criteria are used to identify women with gestational diabetes mellitus.

    “This uncertainty is reflected in the fact that various screening strategies and diagnostic criteria are used to identify women with gestational diabetes mellitus.6 7 8 9 10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 6 7 8 9 10

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Data on quality, patients' characteristics, interventions, and relevant outcomes were independently abstracted by two reviewers.

    “Data on quality, patients’ characteristics, interventions, and relevant outcomes were independently abstracted by two reviewers (AS, KH, KJ, EM, UP, and/or KK).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Lack of blinding of patients and study staff was not considered a major flaw because gestational diabetes is treated by complex interventions that are not amenable to blinding.

    “As gestational diabetes is treated by complex interventions that are not amenable to blinding, we did not consider lack of blinding of patients and study staff to be a major flaw.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    In pool A the risk for bias was judged to be low for Crowther et al and Landon et al and high for the three remaining trials.

    “In pool A the risk for bias was judged to be low for Crowther et al19 and Landon et al21 and high for the three remaining trials (table 3).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [21] Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 1339-48. 19797280 PMC2804874

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    The comparison with usual care enabled direct inferences and effect sizes to be drawn.

    “The comparison with usual care enabled direct inferences and effect sizes to be drawn.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Pool B allowed for indirect conclusions, including the evaluation of dose-response relations.

    “Pool B allowed for indirect conclusions, including the evaluation of dose-response relations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    In pool B, the risk for bias was judged to be low in two studies and high for the remaining trials.

    “In pool B, the risk for bias was judged to be low in two studies,37 39 and high for the remaining trials (table 3).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Nachum Z, Ben-Shlomo I, Weiner E, Shalev E. Twice daily versus four times daily insulin dose regimens for diabetes in pregnancy: randomised controlled trial. BMJ 1999; 319: 1223-7. 10550081 PMC28269

      Not checked in the free run.

    • cites [39] Rae A, Bond D, Evans S, North F, Roberman B, Walters B. A randomised controlled trial of dietary energy restriction in the management of obese women with gestational diabetes. Aust N Z J Obstet Gyanecol 2000; 40: 416-22. 11194427

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fetal macrosomia is associated with gestational diabetes and is a surrogate for many of the complications.

    “Fetal macrosomia is associated with gestational diabetes2 and is a surrogate for many of the complications.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002. 18463375

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Multiple teams of two reviewers independently screened the title, abstract, and key words of each reference and applied the inclusion and exclusion criteria.

    “Multiple teams of two reviewers (AS, KH, KJ, EM, and/or additional researchers) independently screened the title, abstract, and key words of each reference identified by the search and applied the inclusion and exclusion criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    Benefit from treatment in women with gestational diabetes is a prerequisite for effectiveness of a screening programme for gestational diabetes.

    “Benefit from treatment in these women is a prerequisite for effectiveness of a screening programme for gestational diabetes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premiseown data

    In Crowther et al, neonatal hypoglycaemia treated with glucose infusion occurred more often in the intervention group, while in Landon et al it occurred less often.

    “While in the study of Crowther et al19 these events occurred more often in the intervention group, in Landon et al21 they occurred less often (fig 3).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

    • cites [21] Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361: 1339-48. 19797280 PMC2804874

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Crowther et al reported a combined end point of perinatal death, shoulder dystocia, bone fracture, or nerve palsy; such complications were seen in 1% of babies from intervention group and 4% from usual care group (P=0.01).

    “Crowther et al reported a combined end point, which consisted of any of perinatal death, shoulder dystocia, bone fracture, or nerve palsy.19 Such complications were seen in 1% of all babies from mothers in the intervention group and 4% of babies born to mothers in the usual care group (P=0.01 for difference).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med 2005; 352: 2477-86. 15951574

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In that trial, no women in the intensified treatment group developed diabetes, while two women (7%) in the control group did.

    “While no women in the intensified treatment group developed diabetes, this was the case for two women (7%) in the control group.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [24] Bancroft K, Tuffnell DJ, Mason GC, Rogerson LJ, Mansfield M. A randomised controlled pilot study of the management of gestational impaired glucose tolerance. BJOG 2000; 107: 959-63. 10955425

      Not checked in the free run.

    • cites [25] Lao T, Ho LF. A randomised controlled pilot study of the management of gestational impaired glucose tolerance. BJOG 2001; 108: 769. 11467709

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    It remains unclear how long after giving birth the women were tested.

    “It remains unclear how long after giving birth the women were tested.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    In usual care, "telling" is part of the intervention, so this is likely to reflect what happens when labelling a pregnant woman with the diagnosis of gestational diabetes.

    “In usual care “telling” is part of the intervention, so this is likely to reflect what happens when labelling a pregnant woman with the diagnosis of gestational diabetes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Although many studies investigating effects of treatment were identified, effects on major end points important to patients remain uncertain.

    “Although we identified many studies investigating the effects of treatment, effects on major end points important to patients remain uncertain.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    Effects can be fully judged only by screening trials, which follow up women with negative screening results.

    “Effects can be fully judged only by screening trials, which follow up women with negative screening results.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Transferability is hampered by the fact that the studies applied different inclusion and exclusion criteria, recruited different ethnic groups, and defined outcomes differently.

    “Transferability is also hampered by the fact that the studies applied different inclusion and exclusion criteria, recruited different ethnic groups, and defined outcomes differently.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The higher perinatal death in one older study probably reflects advances in pregnancy and neonatal care from the 1960s to today.

    “probably reflecting the advances in pregnancy and neonatal care from the 1960s to today.”
    Quote in the paperNot a substantial claim
47 of 47

  • The paper relies on this without support.

    It remains controversial which outcomes can be influenced by specific treatment for gestational diabetes.

    “But it remains controversial which outcomes can be influenced.”

  • The paper relies on this without support.

    It is still unclear which affected women, and their offspring, with what degree of maternal carbohydrate intolerance, will benefit from treatment.

    “Also, it is still unclear which affected women, and their offspring, with what degree of maternal carbohydrate intolerance, will benefit from treatment.”

  • The authors state this as an assumption.

    In studies that included all randomised women in analyses but did not specifically report maternal mortality, maternal mortality was assumed to be zero.

    “Assumed to be zero in those studies that included all randomised women in analyses but not specifically reported.”

  • The paper relies on this without support.

    It is unclear which outcomes can be influenced and which women with gestational diabetes and their babies will benefit from treatment, depending on the mother’s degree of carbohydrate intolerance.

    “It is unclear which outcomes can be influenced and which women with gestational diabetes and their babies will benefit from treatment, depending on the mother’s degree of carbohydrate intolerance”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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.”

    From Gestational Diabetes Mellitus—Recent Literature Review (2022) · cites this paper as [30]

    The Discussion (Main findings; page unavailable) reports a significant reduction in the ACHOIS/Crowther composite endpoint, but defines it as perinatal death, shoulder dystocia, bone fracture, or nerve palsy—not the listed outcomes. That section associates the listed metabolic outcomes with a different trial, whose composite was not significantly reduced. The Results (Specific treatment versus usual care: pool A; page unavailable) report lower LGA incidence with treatment, but the searched passages do not substantiate 1.7 kg less maternal weight gain. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • 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].”

    From Gestational Diabetes Mellitus—Recent Literature Review (2022) · cites this paper as [30]

    The Discussion (Main findings; page unavailable) says the composite endpoint in Landon et al.’s study was not significantly different between groups. The Results (pool A; page unavailable) include that study among those with significantly fewer LGA infants, but report a significant reduction in shoulder dystocia only for the pooled analysis of Landon and Crowther, not for the MFMU study alone. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Gestational diabetes mellitus is associated with neonatal hyperinsulinemia and shoulder dystocia.

    “neonatal hyperinsulinemia and shoulder dystocia”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [65]

    The Introduction identifies shoulder dystocia as a complication associated with gestational diabetes mellitus. It lists neonatal hypoglycaemia, but not neonatal hyperinsulinemia; the Discussion mentions cord-blood C-peptide only as a surrogate endpoint in a trial, without stating the claimed association. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Gestational diabetes mellitus is associated with greater incidence of large-for-gestational-age infants, fetal adiposity and macrosomia.

    “GDM is associated with greater incidence of large-for-gestational-age infants, fetal adiposity and macrosomia”

    From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [65]

    The Introduction states that fetal macrosomia is associated with gestational diabetes. The Results (Specific treatment versus usual care, pool A) report fewer large-for-gestational-age infants and fewer cases of macrosomia with treatment. Our copy does not report an association with fetal adiposity, so that part of the claim is unsupported. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 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).”

    From Gestational Diabetes Mellitus—Recent Literature Review (2022) · cites this paper as [30]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Langer control macrosomia percentage does not match group size

    Minor

    Table 5 reports 40 cases as 13%, but the Langer control group has 63 women in table 1; 40 of 63 is about 63%.

    Reported 13 · recomputed 63.492063

  • Langer intervention macrosomia percentage does not match group size

    Minor

    Table 5 reports 13 cases as 4%, but the Langer intervention group has 63 women in table 1; 13 of 63 is about 21%.

    Reported 4 · recomputed 20.634921

  • Not every other pool A trial required a positive glucose challenge test

    Minor

    The text says every trial other than Bonomo required a positive glucose challenge test, but Crowther's eligibility criteria also allowed entry on the basis of risk factors instead.

3 of 3

Cites

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Cited by

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Related

Authors
Horvath, K., Koch, K., Jeitler, K., Matyas, E., Bender, R., Bastian, H., Lange, S., & Siebenhofer, A.
Affiliations
  • Medical University of Graz (AT)
  • Institute for Quality and Efficiency in Health Care (DE)
  • Goethe University Frankfurt (DE)
Corresponding author
Horvath, K.
ORCID
Venue
BMJ
Publisher
BMJ
Published
2010-04-01
Volume
340
Issue
apr01 1
Pages
c1395-c1395
ISSN
  • 0007-1447 (ISSN-L)
  • 0959-8138
  • 1468-5833
DOI
10.1136/bmj.c1395
PMC
PMC2848718
OpenAlex
W1993777011
Cited by
359
References
62
Citations by year
2026: 2 · 2025: 10 · 2024: 18 · 2023: 23 · 2022: 18 · 2021: 11 · 2020: 20 · 2019: 15 · 2018: 26 · 2017: 26 · 2016: 33 · 2015: 29 · 2014: 21 · 2013: 28 · 2012: 34
FWCI
5.14
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
gestational diabetes mellitus, treatment intensity, glycemic control, shoulder dystocia, preeclampsia, large for gestational age, perinatal complications, glucose challenge test, oral glucose tolerance test, obstetric care
MeSH terms
Critical Care, Female, Humans, Pregnancy, Pregnancy Outcome, Prenatal Care, Bias, Randomized Controlled Trials as Topic, Diabetes, Gestational

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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