Original researchRole of HbA1c in predicting risk for congenital malformations
Introduction
Association between pre-existing and gestational diabetes and rates of congenital abnormalities is well known [1], [2], [3], [4], [5] and among persons with known diabetes or GDM, role of good glycemic control in preventing birth defects is well documented [6], [7]. Utilization of these research observations in prevention of hyperglycemia-related negative outcomes of pregnancy is limited due to variability in diagnostic criteria and practical difficulties in implementation of those criteria.
Traditionally GDM used to be defined as any degree of glucose intolerance with onset or first recognition during pregnancy [8]. This definition did not differentiate between pre-existing diabetes diagnosed during pregnancy and the one that is developed during pregnancy. Its limitations were recognized for many years and in 2008–2009, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG), that represents many relevant organizations, including the American Diabetes Association (ADA), recommended that diabetes diagnosed at initial prenatal visit, using standard criteria, should be categorized as overt and not gestational, diabetes [9].
Diagnosis of GMD has always been variable and still is. After several international workshops and many decades of research, in practice, there is still no unified global approach to GDM. IADPSG recommends “One-step” approach that requires performing a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 h, at 24–28 weeks of gestation in women not previously diagnosed with overt diabetes. NIH recommends the “Two-step” approach (NIH consensus) that requires performing a 50-g GLT (non-fasting), with plasma glucose measurement at 1 h (Step 1), at 24–28 weeks of gestation in women not previously diagnosed with overt diabetes. If the plasma glucose level measured 1 h after the load is $140 mg/dL × (7.8 mmol/L), proceed to 100-g OGTT (Step 2). The 100-g OGTT should be performed when the patient is fasting. The reason for difference in recommendations is that glycemic dysregulation exists on a continuum and the differences in decision reflect the different views while balancing the harms and benefits [10]. Experts agree that there are insufficient data to strongly demonstrate the superiority of one strategy over the other in diagnosis of GDM [10].
Any of the abovementioned recommendations, if universally applied, could be of great help in decreasing maternal hyperglycemia-related risk, but there have been reservations about its implementation by clinicians and hindrances in application due to logistic reasons. Regardless of superiority of one method over the other for the diagnosis of GDM for a large number of pregnant mothers in Asian countries compliance to these recommendations is restricted by economic and cultural constraints. In many cultures, delays in registration of pregnancy and regularity in antenatal visits are very common [11]. For example in Saudi Arabia, testing of HbA1c is not routinely done in antennal clinics, most of the women do not attend antennal clinics as per schedule for various personal and practical reasons and they find it difficult to come to the health care facility in fasting state. Testing of fasting blood sugar is not feasible in many cases as women do not come prepared for it and physicians usually depend on random blood sugar for initial assessment. As the time and size of last meal and activity prior to the test varies, a large number of potential cases of hyperglycemia are likely to be missed out. For many women, their first antenatal visit to the health care facility is the only pre-delivery visit they make. This makes diagnosis of both overt and gestational diabetes difficult. As postprandial hyperglycemia precedes fasting hyperglycemia many cases existing or gestation pre-diabetes may remain undiagnosed when identified on the basis of FBS alone [12]. At present, there is limited information about role of using other methods for identifying maternal hyperglycemia and its association with risk of congenital abnormalities.
Performing HbA1c test at first antenatal visit could identify a large proportion of unknown pre-existing overt diabetes and may also help in better identification of women who are at high risk of maternal hyperglycemia during later stages of pregnancy and subsequent higher risk of negative birth outcomes. Use of HbA1c in postpartum screening of women with GDM detected an additional 10.6% of patients with pre-diabetes but observations are limited and controversial in relation to use of HbA1c at first antennal visit [13], [14] and are rare about its association with pregnancy outcomes. It has also been noticed that normal OGTT does not always exclude GDM. One group of researcher suggest that women with above normal hab1c and normal OGTT needs to be considered as a separate group of hyperglycemic pregnant women [15]. Authors suggest further research for determining benefits of measuring HbA1c and establishing thresholds keeping mind differences in ethnicity and iron status or any other factors the a may affect glycosylation or red cell turnover [15].
In this study, we tried to explore the association of HbA1c at first antenatal visit and diagnosis of GDM with presence of congenital malformations in live births.
Section snippets
Study design
Prospective observational study.
Subjects and sampling
Subjects were recruited from the outpatient clinics of Ohoud hospital (governmental), Al-Safa hospital (private) and 21 primary health care centers.
Eleven hundred and eighty (1180), native Saudi pregnant women were randomly chosen from those attending the antenatal care clinics.
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The criteria for eligibility were: Willing to participate and attend for follow-up.
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In the first trimester.
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Exclusion criteria: Presence of systemic diseases that are known to cause birth
Characteristics of the subjects
Eleven hundred and eighty (1180), native Saudi pregnant women, were enrolled in the study. Seventy-four cases (6.3%) dropped out for different reasons and a total of 1106 were followed till the end of pregnancy. Mean age of the participants was 27.9 years (range 15–52). More than half (56.0%) of the studied couples were unrelated while (44%) were first-degree cousins. There was no significant difference between both groups.
Outcome of pregnancy
Outcome of pregnancy in 1106 recruited women is shown in Fig. 1. A total
Discussion
This study has evidenced association between HbA1c at first parental visit and risk for congenital malformations. According to guidelines, these women would be labeled as having overt diabetes pre-diabetes [10]. However, as there are controversies about using HbA1c for diagnosis of diabetes, they were not categorizes as diabetics by the healthcare facilities. The results of this paper highlight the fact that in spite of limitations in using HbA1c as a diagnostic criterion in certain groups it
Conclusion
We observed that estimating HbA1c at first antenatal visit can be used as a screening test to identify women at high risk of delivering babies with CM. The observations made in this study provide strong support to the suggestion that “HbA1c be used universally to identify women requiring specialized care for avoiding and detecting gestational hyperglycemia”. This suggestion is particularly relevant for communities where irregularity in antenatal visits is a common practice and feasibility of
Conflict of interest
The authors state that they have no conflict of interest.
Acknowledgement
Funding for this project was provided by King Abdulaziz City for Science and Technology (KACST), Saudi Arabia by grant number AT-28-113.
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