Gestational diabetes mellitus (GDM) is characterised by carbohydrate intolerance that is recognised or begins during pregnancy, regardless of whether it is managed with diet or insulin/oral hypoglycemic agents1. It fails to acknowledge that unrecognised glucose intolerance may have preceded or commenced simultaneously with pregnancy. Pregnancies impacted by GDM are susceptible to many severe obstetric problems, including foetal growth abnormalities, shoulder dystocia, delivery injuries, prematurity, and an elevated rate of caesarean sections. The significance of GDM lies in the fact that it poses a threat of eventual diabetes for the next two generations. Women with a previous diagnosis of GDM face an elevated likelihood of developing diabetes, primarily type 2 diabetes mellitus (T2DM), as do their offspring2. Furthermore, any aberrant tolerance to glucose in pregnant women without GDM is linked to a progressive upsurge in negative maternal and foetal health outcomes. Consequently, GDM presents a substantial potential for the creation, evaluation, and execution of treatment tactics aimed at diabetes prevention. The ongoing global coronavirus epidemic has resulted in local lockdowns that have led to poor dietary habits, less physical activity, and heightened psychological stress. That is an even greater challenge for GDM management. Prompt intervention in screening all pregnant women for glucose intolerance, attaining euglycemia, and ensuring proper nutrition may likely avert the perpetuation of glucose intolerance throughout generations.

Screening programs combined with therapeutic measures (diet or diet plus insulin) have diminished the prenatal morbidity and death linked to GDM. Nevertheless, despite these efforts, the neonatal morbidity associated with GDM remains double that of moms with normal glucose tolerance during pregnancy3. A potential rationale for the sustained elevated perinatal morbidity associated with GDM could be attributed to delayed diagnosis. Despite reports indicating a 40-66 percent identification rate of impaired glucose tolerance when conducted early in pregnancy4, there have been contradictory findings about the efficacy of screening for GDM during the initial antenatal visit5. The primary concern in the effective management of GDM is the prompt identification and intervention, aimed at minimising maternal and foetal morbidity and preventing or postponing the onset of T2DM. The Oral Glucose Tolerance Test (OGTT) is a laborious procedure and sometimes poorly accepted by pregnant women. The patient must undergo fasting, remain seated for over two hours, and have a minimum of three venipunctures. The pregnant individual is susceptible to nausea and vomiting due to a delay in gastric emptying.

The necessity for a widely acceptable and straightforward exam is growing evident. Glycosylated HbA1c is presently the most recognised metric for chronic glycemia, excluding pregnancy. The 2009 guidelines of the National Health and Medical Research Council (NHMRC) advised that HbA1c should serve as the diagnostic criterion for T2DM, with a confirming value of 48 mmol/mol or 6.5% or higher6. The application of HbA1c for screening GDM is contentious. This investigation aims to assess the efficacy of HbA1c as a screening instrument for GDM.

A prospective research was undertaken among 141 consenting Singleton pregnant Women who attended the OPD in the Department of Obstetrics and Gynaecology of a tertiary care facility in Kerala, for their First antenatal visit (˂12 weeks). Those who were overtly diabetic, with any HB variant, multiple pregnancy, Chronic disease, cardiac, hepatic, or respiratory disease, under drugs that affect glucose metabolism, and with Haematological disorders, like Chronic anaemia, sickle cell disease, were excluded.  A detailed clinical assessment has been performed in the OPD.

Routine investigation during antenatal visits was done among patients, which included HbA1c. Informed consent has been obtained during the initial examination. HbA1c was determined in an EDTA whole blood sample, stored at ˂-70 °C and thawed immediately before the evaluation procedure. HbA1c was determined using a non-porous ion exchange HPLC array. The values were collected from EMR. All women were followed up till the second trimester (24-28 weeks) and underwent 75 75-gram OGTT, which was routinely done as a universal screening method. The values were collected from the Electronic Medical Record (EMR). The IADPSG (International Association of Diabetes and Pregnancy Study Groups) criteria7 were employed to detect GDM. The association of HbA1c with GDM has been looked for, and also the sensitivity of glycosylated HbA1c at various cut-off points was calculated. All the data collected was entered by the principal investigator in a structured proforma. The proforma contains relevant clinical history and investigation details.

Statistical Methods

All collected data were encoded and organised into a Microsoft Excel Spreadsheet, which was then re-validated and analysed using SPSS statistical software version 22. Categorical variables were represented by frequency and percentage. Quantitative variables were summarised utilising the mean and standard deviation. The Pearson Chi-square test was applied to compare categorical data among groups. An independent samples t-test was utilised to compare continuous variables between groups. A p-value below 0.05 was considered statistically significant.

In this study, of the 141 women tested, 69 were diagnosed with GDM. Our study identified a statistically significant connection between HbA1c levels in the first trimester and GDM.

Clinical characteristics of participants

The age group-wise distribution of study subjects shows that the maximum number of women (48.2 %) belonged to the age group 26-30 years, followed by 26.2% in the 31-35 years age group. Distribution of study subjects according to obstetric score showed that the maximum number of women (43.3 %) were G1, followed by 37.6% who were G2. 65.9% of women belonging to the upper class (according to the modified Kuppuswamy scale) developed GDM, followed by 56.1% of women belonging to the upper middle class. These indicate a significant association between socioeconomic status and the development of GDM in pregnancy, with a p-value of <0.001. A significant association was found between Body Mass Index (BMI) and the development of GDM in pregnancy, as 66.7% of overweight women developed GDM and 95% of obese women also had GDM, with a p value of <0.001. 88.9% of women in the study group who developed GDM had a history of GDM, which showed a significant association between history of GDM and development of GDM in current pregnancy, with a p value of 0.016. 81.5% of Women with a history of Polycystic Ovarian Syndrome (PCOS) developed GDM, while only 18.5% of women with a history of PCOS did not have GDM. These indicate a significant association between history of PCOS and GDM, with a p-value of <0.001. 80% of Women in the study who developed GDM had a history of infertility, which showed a significant association between history of infertility and GDM, with a p value of 0.003. A history of hypothyroidism and hypertension was found not to have any significant association with GDM status in the prospective study.

Table 1: Association of HbA1c with GDM

                      *statistically significant

Table 1 indicates that the highest number of cases, 33 out of 69 diagnosed with GDM, exhibited HbA1c between 5.1 and 5.5, which was statistically significant (p = 0.001).

Table 2: Diagnostic characteristics of HbA1C for predicting GDM

Table 2 shows that the cut off value of HbA1c was 5.15%. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 72.5, 58.3, 62.5, 68.9, and 65.2% respectively.

GDM is linked to obstetric problems that impact the maternal and newborn health outcomes. Complications encompass macrosomia, caesarean section, shoulder dystocia, birth trauma, preeclampsia, postpartum mother onset of T2DM, and heightened obesity and T2DM in the progeny later in life. Additionally, newborn metabolic problems may occur due to inadequately managed maternal diabetes during pregnancy including hypoglycemia, hyperbilirubinemia, hypocalcaemia, and polycythaemia8.

Despite numerous studies questioning the diagnostic efficacy of the HbA1c test for GDM, its comparatively simple execution has led to its continued use for pregnant individuals in various institutions, including our outpatient department. The inconclusive information about several appropriate cut-off values for HbA1c further exacerbates confusion in its implementation. This study examined the diagnostic efficacy of HbA1c and its connection with standard OGTT in a diverse cohort of pregnant individuals.

Association of HbA1c and GDM

This study identified an appropriate cutoff for HbA1c at ≥5.15, with a sensitivity of 72.5%, specificity of 58.3%, positive predictive value (PPV) of 62.5%, negative predictive value (NPV) of 68.9%, and an accuracy of 65.2%.  This study demonstrates that GDM exhibit upsurge of HbA1c concentrations throughout the first trimester. This indicates a considerable sensitivity of HbA1c as a predictor of GDM. Research indicates that a HbA1c level exceeding 6.0 is a significant indicator for GDM. Nevertheless, the American Diabetes Association defines the threshold for GDM as greater than 6.5.

Obesity is a recognised risk variable for the onset of GDM, and suggests that obese individuals have 2 - 4-fold greater risk of development of GDM than non-obese patients12. This study shows that overweight and obese women are more prone for GDM (p <0.001).

Association of PCOD and GDM

This study showed that 81.5% women with history of PCOD developed GDM and 46.2% developed GDM who doesn't had any history of PCOD. Which shows a significant association between PCOD and development of GDM. In all pregnancies, women with PCOS were more inclined to develop GDM (aOR 2.19, 95% CI 2.02–2.37)13, 14. This finding indicates that PCOS continues to be a clinically relevant independent risk factor for GDM, even when other potentially larger independent risk factors are present.

A notable correlation exists between BMI and the onset of GDM during pregnancy, with 66.7% of overweight women and 95% of obese women developing GDM, yielding a p-value of <0.001. Comparable findings were reported in a retrospective cohort study involving 24,324 pregnant women at the University of California, San Francisco. Research indicates that women with diabetes are more prone to being overweight, and a BMI exceeding 25 during the initial half of pregnancy markedly elevates the risk of impaired glucose tolerance in screenings conducted after 24 weeks and GDM. Research indicates that elevated BMI during pregnancy correlates with GDM and constitutes a risk factor for its development. Excess weight, particularly obesity (BMI ⩾ 25) and morbid obesity (BMI ⩾ 50), elevates the risk of GDM in the first trimester of pregnancy15.

Women in the study who developed GDM had a history of infertility, which showed a significant association between Past history of infertility and GDM, with a p value of 0.003. In an analysis of Pregnancies conducted by Deirdre K. Tobias and Reyes-Munoz E, their research study indicated, a history of infertility was markedly linked to a heightened risk of GDM. In the age-adjusted model, pregnancies in women with a history of infertility exhibited a statistically significant 50% increased risk of GDM compared to those without such a history (RR = 1.50, 95% CI: 1.34, 1.69). P < 0.00116,17.

DM can cause many pregnancy complications. Multiple glucose intolerance screening tests exist. The OGTT was used to screen for GDM in this investigation. In 141 prenatal cases, most gestational diabetes patients had HbA1c levels between 5.1% and 5.5%. According to the evidence, HbA1c may predict GDM. Future research with an increased sample size should confirm the association between HbA1c levels and GDM screening tests. An accurate predictor will help detect and control GDM early, reducing pregnant complications.

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