Screening

Screening

Screening determines who should undergo an oral glucose tolerance test (OGTT), the definitive diagnostic test for gestational diabetes mellitus (GDM). Screening may be accomplished using clinical risk factors, biochemical testing with a glucose challenge test (two-step testing), or a combination of both. Positive screening is followed by a diagnostic OGTT.[56]​ Guidelines and expert consensus variously recommend screening for GDM in pregnant women at both high and usual risk; however, screening strategies have not been compared in randomised trials.[57]

UK recommendations

In the UK, the National Institute for Health and Care Excellence (NICE) recommends offering diagnostic testing with a 75 g 2-hour OGTT at 24-28 weeks’ gestation to high-risk women with any one or more of the following risk factors for GDM:[4]

  • BMI >30 kg/m²

  • A previous baby weighing ≥4.5 kg

  • Family history of diabetes mellitus (first-degree relative with diabetes mellitus)

  • Family origin in an area with high prevalence of diabetes mellitus. NICE no longer specifies which family origins this includes, leaving this to be decided at a local level or by individual clinicians.

Women who have had GDM in a previous pregnancy should be offered early self-monitoring of blood glucose or a 2-hour 75 g OGTT as soon as possible after booking (whether in the first or second trimester), and a further 2-hour 75 g OGTT at 24-28 weeks if the results of the first OGTT are normal.[4]

GDM should be diagnosed if a pregnant woman has either:

  • A fasting plasma glucose (FPG) ≥5.6 mmol/L (≥100 mg/dL), or

  • A 2-hour plasma glucose ≥7.8 mmol/L (≥140 mg/dL).

NICE does not recommend assessing the risk of developing GDM with FPG, random blood glucose, haemoglobin A1c (HbA1c), glucose challenge test, or urinalysis for glycosuria.[4]

It is important to take steps to encourage all pregnant women with risk factors to attend for an OGTT test. A prospective case-control study, performed before the current NICE guidelines were in place, found that without FPG screening, women ‘at risk’ of GDM (as per the NICE criteria above) experienced 47% greater risk of late stillbirth. For those who were screened, this excess was essentially eliminated. Similarly, without GDM diagnosis, women with raised FPG experienced a fourfold greater risk of late stillbirth. For those who were diagnosed, this excess was no longer apparent.[58]

Other guidelines

The criteria and approach for diagnosis of GDM are not universally accepted and screening protocols vary between countries.[2]

Timing of screening

Guidelines concur in their recommendation that screening should be undertaken from 24 weeks; this is because treatment of GDM at or after 24 weeks of gestation has been shown to be significantly associated with improved health outcomes (decreased risk of primary caesarean deliveries, shoulder dystocia, macrosomia, large for gestational age, birth injuries, and neonatal intensive care unit admissions).[59] One randomised controlled trial (RCT) found that early GDM diagnosis (prior to 24 weeks of gestation) and immediate treatment demonstrated a modest decrease in a primary composite neonatal outcome that was primarily driven by a reduction in neonatal respiratory distress.[60]​ Another RCT, however, found that early screening for GDM (at 14-20 weeks’ gestation) in obese women did not improve perinatal outcomes.[61]​ Due to the lack of consistent evidence to indicate neonatal and maternal benefit from early diagnosis and treatment, the American College of Obstetricians and Gynecologists (ACOG) does not recommend routine screening for GDM before 24 weeks of gestation.[62] If women enter antenatal care after 28 weeks’, screening should be performed as soon as possible.[53]

Universal versus risk factor-based screening

The American Diabetes Association (ADA), American Association of Clinical Endocrinology (AACE) and International Federation of Gynecology and Obstetrics (FIGO) endorse universal screening for GDM in later pregnancy.[54][63]​ This means that at 24-28 weeks' gestation, all women not known to have diabetes (including high-risk women if earlier testing was normal) should undergo screening with a glucose tolerance test.[3][54]​​ US Preventive Services Task Force (USPSTF) guidelines note that testing can occur later if women enter antenatal care after 28 weeks’ gestation.[53]

Other guidelines use risk factor-based screening to inform the need for OGTT at 24-28 weeks’ gestation.​[56] The World Health Organization (WHO) leaves the decision on universal or targeted screening to local health authorities according to local burden of GDM, resource availability, and priorities, although it suggests first-trimester screening of high-risk women and universal screening at 24-28 weeks’ gestation as possible approaches.[2]

Testing strategies

Testing strategies adopt either a one-step method using the 75 g OGTT or a two-step method using a 50 g (non-fasting) glucose load to screen, followed by a 100 g OGTT for those who screen positive.[3] There is no consensus among national and international organisations for the optimal approach, and the choice generally depends on local customs.

One-step strategy:[1][3]

  • Perform a 75 g OGTT, with plasma glucose measurement fasting and at 1 and 2 hours, at 24-28 weeks of gestation in all women not previously diagnosed with overt diabetes.

  • The OGTT should be performed in the morning after an overnight fast of at least 8-hours.

  • The diagnosis of GDM is made when any one of the following plasma glucose values are exceeded (International Association of Diabetes and Pregnancy Study Groups [IADPSG] criteria, endorsed by the ADA):

    • Fasting: ≥5.1 mmol/L (≥92 mg/dL)

    • 1 hour: ≥10.0 mmol/L (≥180 mg/dL)

    • 2 hours: ≥8.5 mmol/L (≥153 mg/dL).

  • These criteria differ from those of NICE, with a substantially lower fasting glucose (5.1 mmol/L [92 mg/dL] versus 5.6 mmol/L [100 mg/dL] for NICE), a higher 2-hour glucose (8.5 mmol/L [153 mg/dL] versus 7.8 mmol/L [140 mg/dL] for NICE), and an additional 1-hour glucose level.

Two-step strategy:[3][51][52][64]

  • Perform a 1-hour 50 g glucose load test (GLT) which does not have to be fasting.​

  • Glucose thresholds of ≥7.2, 7.5, or 7.8 mmol/L (≥130, 135, or 140 mg/dL) on the GLT can be considered abnormal (ACOG recommends that any of these thresholds can be used).​​ Lower thresholds are more sensitive, but less specific and more prone to false-positives. There are no RCTs of differing thresholds; therefore, it is reasonable for institutions to consider the tradeoffs specific to the population served when determining a cut-off.​

  • If glucose levels are greater than the chosen cut-off value on the GLT, a 3-hour 100 g fasting OGTT should be performed.

  • According to the Carpenter and Coustan criteria (endorsed by the ADA and ACOG), two or more plasma glucose levels at or above the following thresholds establish diagnosis:[3][51]

    • Fasting: ≥5.3 mmol/L (≥95 mg/dL)

    • 1 hour: ≥10.0 mmol/L (≥180 mg/dL)

    • 2 hours: ≥8.6 mmol/L (≥155 mg/dL)

    • 3 hours: ≥7.8 mmol/L (≥140 mg/dL).

  • The older National Diabetes Data Group criteria are stricter and can be used as an alternative to the Carpenter and Coustan criteria. Two or more plasma glucose levels at or above the following thresholds establish diagnosis:[65]

    • Fasting: ≥5.8 mmol/L (≥105 mg/dL)

    • 1 hour: ≥10.6 mmol/L (≥190 mg/dL)

    • 2 hours: ≥9.2 mmol/L (≥165 mg/dL)

    • 3 hours: ≥8.0 mmol/L (≥145 mg/dL).

The IADPSG and FIGO recommend the one-step approach.[1][63] The US National Institutes of Health and ACOG recommend the older two-step test (although ACOG notes that one raised value, as opposed to two, may be used for the diagnosis of GDM).[1][51]​​​[52]​​​[62]​​ The ADA, USPSTF, and AACE recognise that there are data to support both approaches, with the ADA noting that the one-step strategy has been adopted internationally as the preferred approach.[3][53]​​[54]​​

Different diagnostic criteria will identify different degrees of maternal hyperglycaemia and maternal/fetal risk, leading some experts to debate, and disagree on, optimal strategies for the diagnosis of GDM.[3]​ One randomised trial which compared the two testing strategies identified twice as many individuals with GDM using the one-step method compared with the two-step method; however, despite more individuals ending up being treated for GDM using the one-step method, there was no difference in pregnancy and perinatal complications (though concerns were raised about sample size estimates and suboptimal engagement with the screening and treatment protocol).[66]​ A 2021 USPST systematic review concluded that one-step versus two-step screening is associated with increased likelihood of GDM (11.5% vs. 4.9%) but without improved health outcomes.[67] The ADA comments that data comparing population-wide outcomes with one-step versus two-step approaches have been inconsistent to date, but that longer-term outcome studies are currently underway.[3]

The World Health Organization (WHO) recommends a one-step strategy but uses its own glucose thresholds to distinguish between GDM and overt diabetes (termed “diabetes in pregnancy” in the guideline).[2] GDM is defined as hyperglycaemia at any point in pregnancy that fails to meet the non-pregnant adult diagnostic thresholds for diabetes, whereas overt diabetes is diagnosed when these thresholds are met.[2] Based on this definition, WHO guidelines advise that diagnosis of GDM should be made at any time in pregnancy if one or more of the following criteria are met:[2]

  • Fasting plasma glucose 5.1-6.9 mmol/L (92-125 mg/dL)

  • 1-hour plasma glucose ≥10.0 mmol/L (≥180 mg/dL) following a 75 g oral glucose load

  • 2-hour plasma glucose 8.5-11.0 mmol/L (153-199 mg/dL) following a 75 g oral glucose load.

Fasting and 2-hour plasma glucose levels above these values would indicate overt (rather than gestational) diabetes.[2] There are no established criteria for the diagnosis of overt diabetes based on the 1-hour post-load value.[2]

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