Issues With the Diagnosis and Classification of Hyperglycemia in Early Pregnancy

Abstract

In 2010, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) panel published consensus-based recommendations on the diagnosis and classification of hyperglycemia in pregnancy (1). Within that document, the recommendations regarding early pregnancy testing were designed to facilitate early detection and treatment of hyperglycemia (HbA 1c $6.5% [48 mmol/mol], fasting venous plasma glucose $7.0 mmol/L, random plasma glucose $11.1 mmol/L with confirmation) that, outside pregnancy, would be classified as diabetes. The term "overt diabetes" was suggested to describe these women. Subsequently, the World Health Organization (WHO) adopted the IADPSG criteria with some modifications and promoted the use of the term "diabetes in pregnancy" (2) for this group.Cognizant that milder degrees of hyperglycemia would also be detected by early pregnancy testing, the IADPSG also recommended that fasting plasma glucose (FPG) in the range 5.1-6.9 mmol/L should be considered diagnostic of gestational diabetes mellitus (GDM) if noted at any time during pregnancy. More recent data from Italy (3) and China (4), where IADPSG diagnostic criteria were applied, have strongly challenged this recommendation, demonstrating a clear fall in FPG in early pregnancy and showing that early FPG $5.1 mmol/L is poorly predictive of later GDM at 24-28 weeks' gestation. Zhu et al. (4) suggested using FPG 6.1-6.9 mmol/L "at the time of booking and the first prenatal visit" as a pragmatic criterion for GDM diagnosis in China. To date, similar data have not been reported in other populations.We note that no randomized controlled trial data exist regarding the balance between additional benefits and costs of detecting and treating degrees of hyperglycemia less severe than "overt" diabetes from early pregnancy.The potential utility of HbA 1c in early pregnancy has also been addressed. In particular, a large cohort study from New Zealand (5) noted that HbA 1c $5.9% (41 mmol/mol) identified all cases of WHO diabetes in pregnancy and was associated with a twofold risk of congenital anomalies, preeclampsia, and shoulder dystocia and a threefold risk of perinatal deaths. The use of HbA 1c in this context is not currently endorsed by major national bodies and must carry some caveats because of the known limitations of the test. However, despite its poor sensitivity for impaired fasting glucose and impaired glucose tolerance, HbA 1c may offer a pragmatic means of identifying women at high risk of serious pregnancy complications and warrants further detailed evaluation.In conclusion, we suggest that the use of the IADPSG fasting glucose threshold of $5.1 mmol/L for the identification of GDM in early pregnancy is not justified by current evidence and that an early HbA 1c $5.9% (41 mmol/mol) may identify women at higher risk for adverse pregnancy outcomes. In contrast to "standard" GDM testing at 24-32 weeks' gestation, insufficient data exist to confidently recommend cutoff points for oral glucose tolerance testing in early pregnancy (e.g....

Effect of physical activity and/or healthy eating on GDM risk: The DALI Lifestyle Study

“…Conversion rates were still very high (19% by 24-28 weeks and 37% by 35-37 weeks), even after excluding approximately 20% of women with 'hyperglycaemia' in early pregnancy. As the criteria for GDM diagnosis early in pregnancy may need to be higher (32), it could be argued that some women who would have benefited from the DALI intervention were excluded. However, it has made DALI one of the few true trials for the prevention of incident GDM, rather than intervening among a group where a proportion at least had pre-existing GDM.…”

Modification of WHO diagnostic criteria for gestational diabetes: implications for classification of hyperglycemia in pregnancy

“…7,26 The fasting glucose alone contributed to 32.2% and 42.2% of the diagnosis of GDM by the IADPSG and the WHO 2013 criteria respectively. By contrast a high fasting glucose cut-off of 7.0 mmol/L did not contribute at all to the diagnosis of GDM by WHO criteria.…”

“…This suggest that although a fasting value of 7.0 mmol/L may be too high, 5.1 mmol/L should be considered too low with a tendency to high false positive rate. 7,26 In a recent publication, we canvassed for a combination of WHO (1999) and IADPSG criteria as a risk stratification tool for predicting adverse pregnancy outcome due to hyperglycemia in pregnancy. 27 We showed that women who met both criteria were more likely to have adverse pregnancy outcome than women who met only one of either criteria.…”

2. Classification and Diagnosis of Diabetes:Standards of Medical Care in Diabetes—2018

“…GDM is diabetes that is first diagnosed in the second or third trimester of pregnancy that is not clearly either preexisting type 1 or type 2 diabetes (see Section 13 "Management of Diabetes in Pregnancy"). The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) GDM diagnostic criteria for the 75-g OGTT as well as the GDM screening and diagnostic criteria used in the twostep approach were not derived from data in the first half of pregnancy, so the diagnosis of GDM in early pregnancy by either FPG or OGTT values is not evidence based (57).…”