Update on: Firsttrimester Diagnosis and Therapy @ 11 – 13 ⁺⁶ weeksʼ gestation

1  Introduction: First-trimester screening for abnormal glucose metabolism

A summary of the guideline (LL) was published in 2 parts in “Ultraschall in der Medizin” 1 ,  2 . The full version has been published at https://register.awmf.org/de/leitlinien/detail/085-002 . Amendment 1.3 to Chapter 11 of the full version, published on 20 June 2025, replaces the previous version of Chapter 11 of the guideline.

Amendment 1.3 had become necessary because a Trilogy in “Lancet” 3 ,  4 ,  5 had published evidence requesting a change in paradigm of screening and prevention for GDM from 24 – 28 weeks of gestation to the 11 – 13 ⁺⁶ weeks of gestation.

The rationale for an amendment for chapter 11 is new evidence that early screening at 11 – 13 ⁺⁶ weeks and early intervention in high risk groups halves macrosomia and respiratory distress in neonates. There are additional non-significant positive effects.

The guideline groups AWMF 085-002 S2e LL “First trimester diagnosis and therapy at the 11 – 13 ⁺⁶ weeks of pregnancy” and AWMF 057 – 008 S3 LL “Gestational diabetes mellitus (GDM): diagnosis, therapy and follow-up” have independently adopted recommendations on GDM screening in the first trimester, subsequently harmonizing them for both guidelines. The 2 groups also refer to each otherʼs guidelines.

The following information is based on the short version of Amendment 1.3.

For the full version both in English and German, please go to the link above on the AWMF website.

2  Screening for diabetes mellitus and LGA @ 11 – 13 ⁺⁶ weeks of gestation

2.1  Screening for GDM/iGDM @ 11 – 13 ⁺⁶ weeks of gestation

Indications for GDM screening include a previous pregnancy with GDM, obesity, or any of the factors listed in Fig. 1 .

Fig. 1.

 Risk factors for gestational diabetes with odds ratios from meta-analyses 4 . Yellow boxes: modifiable risk factors, all other boxes: non-modifiable risk factors. [rerif]

The risk factors are approximately the same in all countries, in some cases slightly different, probably due to measurement heterogeneity rather than real differences 4 .

Pre-Screening for GDM: Risk factors ( Fig. 1 ), HbA1c, fasting glucose.

11.1	Recommendation	New Amendment of 2025
Level of Recommendation: A	Screening for GDM should be carried out @ 11 – 13 +6 weeks of gestation (Saravanan 2024, Hivert 2024, Sweeting 2024, Simmons 2023, Bhattacharya 2024). Risk factors for GDM should be assessed in every pregnant woman @ 11 – 13 +6 weeks of gestation ( Fig. 1 ) (Sweeting et al., 2024). A 75 g oGTT should be performed for all pregnant women with risk factors (Sweeting et al., 2024, Yeral et al., 2013, Benhalima et al., 2024). If the 75 g oGTT is rejected or is not feasible, risk factors and an HbA1c > 5.7%/fasting glucose > 95 mg/dl (> 5.27 mmol/l) should be determined (Sweeting et al., 2024, Kattini et al., 2020, Benhalima et al., 2024).
Level of Evidence 1a	Saravanan P, Deepa M, Ahmed Z, Ram U, Surapaneni T, Kallur SD, Desari P, Suresh S, Anjana RM, Hannah W, Shivashri C, Hemavathy S, Sukumar N, Kosgei WK, Christoffersen-Deb A, Kibet V, Hector JN, Anusu G, Stallard N, Ghebremichael-Weldeselassie Y, Waugh N, Pastakia SD, Mohan V. Early pregnancy HbA1c as the first screening test for gestational diabetes: results from three prospective cohorts. Lancet Diabetes Endocrinol. 2024 Aug;12(8):535 – 544. doi:10.1016/S2213-8587(24)00151-7 . Epub 2024 Jun 24. PMID: 38936371 ( LoE 1b ). Hivert MF, Backman H, Benhalima K, Catalano P, Desoye G, Immanuel J, McKinlay CJD, Meek CL, Nolan CJ, Ram U, Sweeting A, Simmons D, Jawerbaum A. Pathophysiology from preconception, during pregnancy, and beyond. Lancet. 2024 Jul 13;404(10448):158 – 174. doi:10.1016/S0140-6736(24)00 827 – 4. Epub 2024 Jun 20. PMID: 38909619 ( LoE 5 ). Sweeting A, Hannah W, Backman H, Catalano P, Feghali M, Herman WH, Hivert MF, Immanuel J, Meek C, Oppermann ML, Nolan CJ, Ram U, Schmidt MI, Simmons D, Chivese T, Benhalima K. Epidemiology and management of gestational diabetes. Lancet. 2024 Jul 13;404(10448):175 – 192. doi:10.1016/S0140-6736(24)00825-0 . Epub 2024 Jun 20. PMID: 38909620 ( LoE 1a ).
	Simmons D, Immanuel J, Hague WM, Teede H, Nolan CJ, Peek MJ, Flack JR, McLean M, Wong V, Hibbert E, Kautzky-Willer A, Harreiter J, Backman H, Gianatti E, Mohan V, Enticott J, Cheung NW. On behalf of the TOBOGM Research Group. Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy. New Engl J Med. 2023; 388: 2132 – 2144 ( LoE 1b ). Bhattacharya S, Nagendra L, Dutta D, Kamrul-Hasan ABM. Treatment Versus Observation in Early Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2024 Dec 17: dgae878. doi:10.1210/clinem/dgae878 . Epub ahead of print. PMID: 39689014 ( LoE 1a ). Yeral MI, Ozgu-Erdinc AS, Uygur D, Doga Seckin K, Fatih Karsli M, Nuri Danisman A. Prediction of gestational diabetes mellitus in the first trimester, comparison of fasting plasma glucose, two-step and one-step methods: a prospective randomized controlled trial. Endocrine. 2013. DOI doi:10.1007/s12020-013-0111-z ( LoE 1b ). Kattini R, Hummelen R, Kelly L. Early Gestational Diabetes Mellitus Screening With Glycated Hemoglobin: A Systematic Review. J Obstet Gynaecol Can. 2020 Nov;42(11):1379 – 1384. doi:10.1016/j.jogc.2019.12.015 . Epub 2020 Apr 6. PMID: 32268994 ( LoE 2a ). Benhalima K, Geerts I, Calewaert P, Van Rijsselberghe M, Lee D, Bochanen N, Verstraete S, Buyse L, Lewi L, Caron R, Tency I, Staquet M, Vermeersch P, Wens J. The 2024 Flemish consensus on screening for gestational diabetes mellitus early and later in pregnancy. Acta Clin Belg. 2024 Jun;79(3):217 – 224. doi:10.1080/17843 286.2024.2384 258. Epub 2024 Jul 27. PMID: 39 068 500 ( LoE 5 ).
	strong consensus (10/10)

Definitions and Criteria

Gestational diabetes mellitus (GDM) refers to hyperglycaemia first diagnosed in pregnancy.

It can be divided into early ( 11 – 13 ⁺⁶ wks) and late GDM ( 24 – 28  wks).

• Hivert et al., 2024: overt Diabetes /Typ-2-Diabetes: glycated haemoglobin ≥6.5% , fasting glucose ≥7.0 mmol/l (126 mg%) and/or 2 h ≥11.1 mmol/l (200 mg%) on a 75 g oGTT 3

• Yeral et al., 2013. RCT GDM @ 11 – 13 ⁺⁶ wks gestation, 75 g GTT fasting for 8 – 14 h, GDM: one or more abnormal glucose values using the ADA and IADPSG criteria: fasting glucose ≥5.1 mmol/l (92%), 1 h glucose ≥10.0 mmol/l (180 mg%), 2 h glucose ≥8.5 mmol/L (153 mg%) 6 ,  7 ,  8

• IADPSG, Metzger et al., 2010: GDM 24 – 28 wks gestation: fasting glucose ≥5.1 mmol/l (92 mg%) and/or 1 h ≥10.0 mmol/l (180 mg%) and/or 2 h ≥8.5 mmol/l (153 mg%) 8

• TOBOGM 2018 criteria (= WHO 2014), GDM any time in pregnancy, one-step, 2 h 75 g OGTT, fasting glucose ≥5.1 mmol/l (92%), 1 h glucose ≥10.0 mmol/l (180 mg%), 2 h glucose ≥8.5 mmol/L (153 mg%) 9 ,  10

• new: Flemish Consensus Benhalima et al., 2024: higher cut-offs for 1st trimester

  • GDM@ 11 – 13 ⁺⁶ wks gestation, fasting ≥5.3 mmol/l (≥ 95%), 1 h ≥10.6 mmol/l (≥ 191%) and/or 2 h ≥9.0 mmol/l (≥ 162%) 11

  • GDM @ 24 – 28 wks gestation (IADPSG 2010, unchanged), fasting glucose ≥5.1 mmol/l (92 mg%) and/or 1 h ≥10.0 mmol/l (180 mg%) and/or 2 h ≥8.5 mmol/l (153 mg%) 8

All figures in mmol/L were also converted to mg% and vice versa:

www.diabsite.de/diabetes/labor/umrechnung.html

mg = 92&mmol = &berechne = ausrechnen

mg% tommol: mg/dl × 0,0555 = mmol/l,

mmol to mg%:mmol/l × 18.02 = mg/dl).

Rationale for higher cut-off values in the first vs. second trimester:

TheWHO 2014 criteria showed a higher rate of growth retarded fetuses in the first trimester and were less predictive 9 ,  10 .

In the TOBOGM pilot trial ( T reatment O f B ooking O f G estational Diabetes M ellitus, in the treatment group 36% vs. 0% (p = 0.043) were admitted to the neonatal intensive care unit due to FGR . In the untreated group , 0% vs. 33% (p = 0.030) had LGA (LoE 1b) 12 .

Thus, there were some FGRs in the early treatment group and some LGAs in the control group .

A subgroup analysis of the TOBOGM trial also showed that an intervention has a greater impact on the composite adverse neonatal outcome, if a population with higher cut-off values in the oGTT and oGTT below 14 + 0 week of gestation was selected beforehand. If the oGTT was repeated at 24 ⁺⁰ -28 ⁺⁰ weeks of gestation, it was positive in 78% of women with increased levels in the first trimester and in only 51.4% of those with lower values (LoE 1b) 13 .

The Flemish criteria (Benhalima et al., 2024) define a population with higher glucose levels in the first trimester in a better way and can therefore effectively avoid FGR and reduce LGA – and they provide a higher prediction for a follow-up oGTT to also be positive at 24 – 28 weeks of gestation. These slightly higher cutoffs were therefore used for recommendation 11.1 (LoE 5) 11 . Glucose monitoring and growth checks should be carried out at regular intervals, which enables monitoring of under- and overtherapy (macrosomia, growth restriction).

2.2  Screening for pre-diabetes and type 1 diabetes mellitus @ 11 – 13 ⁺⁶ weeks of gestation

11.2	Recommendation	New Amendment of 2025
Level of Recommendation EC EC A	The diagnosis of pre-diabetes outside the pregnancy is made when HbA1c is 5.7–<6.5% (40 – 48 mmol/mol Hb), (American Diabetes Association 2019). At 11 – 13 +6 weeks of gestation, a 75 g oGTT should be performed to verify gestational diabetes (fasting BG: 95 mg/dl [5.3 mmol/l], 1 h: 191 mg/dl [10.6 mmol/l], 2 h: 162 mg/dl [9.0 mmol/l]; Benhalima et al., 2024). If one of these limits is exceeded, counselling on blood glucose self-monitoring, dietary advice and guidance on physical activity and, if necessary, insulin therapy should be provided (Simmons et al., 2023, Bhattacharya et al., 2024).
Level of Evidence 5 5 1b 1a	American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S13 – S28. doi:10.2337/dc19-S002 . PMID: 30559228 ( LoE 5 ). Benhalima K, Geerts I, Calewaert P, Van Rijsselberghe M, Lee D, Bochanen N, Verstraete S, Buyse L, Lewi L, Caron R, Tency I, Staquet M, Vermeersch P, Wens J. The 2024 Flemish consensus on screening for gestational diabetes mellitus early and later in pregnancy. Acta Clin Belg. 2024 Jun;79(3):217 – 224. doi:10.1080/17843286.2024.2384258 . Epub 2024 Jul 27. PMID: 39068500 ( LoE 5 ). Simmons D, Immanuel J, Hague WM, Teede H, Nolan CJ, Peek MJ, Flack JR, McLean M, Wong V, Hibbert E, Kautzky-Willer A, Harreiter J, Backman H, Gianatti E, Sweeting A, Mohan V, Enticott J, Cheung NW; TOBOGM Research Group. Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy. N Engl J Med. 2023 Jun 8;388(23): 2132 – 2144. doi:10.1056/NEJMoa2214956 . Epub 2023 May 5. PMID: 37144983 ( LoE 1b ). Bhattacharya S, Nagendra L, Dutta D, Kamrul-Hasan ABM. Treatment Versus Observation in Early Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2024 Dec 17:dgae878. doi:10.1210/clinem/dgae878 . Epub ahead of print. PMID: 39689014 ( LoE 1a ). strong consensus (10/10)

Fig. 2.

 Screening for pre-diabetes @ 11 – 13 ⁺⁶ weeks of gestation. ¹ 75 g oGTT fasting: 95 mg/dl (5.3 mmol/l), 1 h: 191 mg/dl (10.6 mmol/l), 2 h: 162 mg/dl (9.0 mmol/l) 11 . [rerif]

2.3  Early intervention for GDM < 20 weeks of gestation

In summary, a series of RCTs 14 and the TOBOGM trial 2023 13 show robust evidence for a benefit of early oGTT screening and therapy, in particular for non-obese pregnant women.

Essentially, the incidence of macrosomia and respiratory distress syndrome is both reduced by half 14 ,  15 (LoE 1a, 2a). Screening and Prevention of GDM @ 11 – 13 ⁺⁶ weeks of gestation.

11.3	Recommendation	New Amendment of 2025
Level of Recommendation A	To define a high-risk population for which significant neonatal outcome improvements can be achieved (halving of macrosomia and respiratory distress syndrome ), the following limits should be used for the 75 g oGTT @ 11 – 13 +6  wks of gestation: fasting BG: 95 mg/dl (5.3 mmol/l), 1 h: 191 mg/dl (10.6 mmol/l), 2 h: 162 mg/dl (9.0 mmol/l); (Benhalima 2024). If one of these limits is exceeded, counselling on blood glucose self-monitoring, dietary advice, guidance on physical activity and – if necessary – insulin therapy should be provided (Simmons et al., 2023; Bhattacharya et al., 2024). If the oGTT is negative @ 11 – 13 +6 weeks of gestation, GDM screening should be offered @ 24 +0 -28 +0 weeks of gestation: fasting blood glucose (BG): 92 mg/dL (5.1 mmol/L), 1 h: 180 mg/dL (10 mmol/L), 2 h: 153 mg/dL (8.5 mmol/L); (Metzger, IADPSG 2010/Colagiuri, WHO 2014). If the oGTT is positive @ 11 – 13 +6 weeks of gestation, and if blood glucose self-monitoring and therapy are established, no further GDM screening should be offered @ 24 +0 -28 +0 weeks of gestation.
Level of Evidence 1b	Benhalima K, Geerts I, Calewaert P, Van Rijsselberghe M, Lee D, Bochanen N, Verstraete S, Buyse L, Lewi L, Caron R, Tency I, Staquet M, Vermeersch P, Wens J. The 2024 Flemish Consensus on screening for gestational diabetes mellitus early and later in pregnancy. Acta Clin Belg. 2024 Jun;79(3):217 – 224. doi:10.1080/17843286.2024.2384258 . Epub 2024 Jul 27. PMID: 39068500 ( LoE 5 ). Simmons D, Immanuel J, Hague WM, Teede H, Nolan CJ, Peek MJ, Flack JR, McLean M, Wong V, Hibbert E, Kautzky-Willer A, Harreiter J, Backman H, Gianatti E, Sweeting A, Mohan V, Enticott J, Cheung NW; TOBOGM Research Group. Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy. N Engl J Med. 2023 Jun 8;388(23):2132 – 2144. doi:10.1056/NEJMoa2214956 . Epub 2023 May 5. PMID: 37144983 ( LoE 1b ). Bhattacharya S, Nagendra L, Dutta D, Kamrul-Hasan ABM. Treatment Versus Observation in Early Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials. J Clin Endocrinol Metab. 2024 Dec 17: dgae878. doi:10.1210/clinem/dgae878 . Epub ahead of print. PMID: 39689014 ( LoE 1a ). International Association of Diabetes and Pregnancy Study Groups Consensus Panel; Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano PA, Damm P, Dyer AR, Leiva Ad, Hod M, Kitzmiler JL, Lowe LP, McIntyre HD, Oats JJ, Omori Y, Schmidt MI. International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care. 2010 Mar;33(3):676 – 82. doi:10.2337/dc09-1848 . PMID: 20190296; PMCID: PMC2827530 ( LoE 5 ). Colagiuri S, Falavigna M, Agarwal MM, Boulvain M, Coetzee E, Hod M, Meltzer SJ, Metzger B, Omori Y, Rasa I, Schmidt MI, Seshiah V, Simmons D, Sobngwi E, Torloni MR, Yang HX. Strategies for implementing the WHO diagnostic criteria and classification of hyperglycaemia first detected in pregnancy. Diabetes Res Clin Pract. 2014 Mar;103(3):364 – 72. doi:10.1016/j.diabres.2014.02.012 . Epub 2014 Feb 25. PMID: 24731475 ( LoE 5 ).
	strong consensus (10/10)

Fig. 3.

 Screening and Prevention for GDM @ 11 – 13 ⁺⁶ weeks of gestation. ve+ = Screening-positive; ve- = Screening-negative. ¹ 75 g oGTT fasting: 95 mg/dl (5.3 mmol/l), 1 h: 191 mg/dl (10.6 mmol/l), 2 h: 162 mg/dl (9.0 mmol/l) 11 , ⁽²⁾ if rejected/not feasible: HbA1c >5.7% 11 / fasting Glc >95 mg/dl (> 5.27 mmol/l) 11 , ³ fasting: 92 mg/dl (5.1 mmol/l), 1 h: 180 mg/dl (10 mmol/l), 2 h: 153 mg/dl (8.5 mmol/l) 8 ,  10 . [rerif]

2.4  Screening for LGA fetuses (no diabetes) @ 11 – 13 ⁺⁶ weeks of gestation

11.4	Recommendation
Level of Recommendation: EC	LGA screening (macrosomia screening) in the first trimester should be carried out if a child has already been born with macrosomia other risk factors for LGA are present.
Level of Evidence	strong consensus (10/10)

11.5	Recommendation	2011
Level of Recommendation: B	If LGA (macrosomia) screening is carried out in the first trimester, it should be based on maternal characteristics, NT, free beta-hCG and PAPP-A. This will detect approximately 35% of LGA fetuses for an FPR of 10% .
Level of Evidence 1b	Poon LC, Karagiannis G, Stratieva V, Syngelaki A, Nicolaides KH. First-trimester prediction of macrosomia. Fetal Diagn Ther 2011;29: 139 – 47.
	strong consensus (9/9)

11.6	Recommendation
Level of Recommendation B	LGA (macrosomia) screening starting in the first trimester can be performed by maternal factors and serial biometry . The inclusion of biomarkers does not increase the DR. Screening based on maternal factors has a DR of 44% for a FPR of 10% . If additional biometry is performed @ 19 – 24, 30 – 34 and 35 – 37 weeks of gestation, the corresponding DRs are 51%, 56% and 73% for a FPR of 10% .
Level of Evidence: 2b	Frick AP, Syngelaki A, Zheng M, Poon LC, Nicolaides KH. Prediction of large-for-gestational-age neonates: screening by maternal factors and biomarkers in the three trimesters of pregnancy. Ultrasound Obstet Gynecol 2016;47: 332 – 9.
	Strong consensus (10/10)

2.5  Important research questions

Gestational Diabetes mellitus

As there is a high probability of benefit from an early treatment, there is an urgent need for randomized controlled trials to further investigate the potential benefits or harms of treating early onset GDM in the first trimester. First and foremost, this requires detailed studies on first trimester markers for GDM, the level of cut-off values to identify a high-risk population and the benefit of early intervention.

Zitierweise für diesen Artikel.

Ultraschall in Med 2025; 46: 428 – 439 doi:10.1055/a-2679-1034