• Users Online: 332
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 2  |  Page : 209-216

First trimester glycated hemoglobin in the prediction of gestational diabetes mellitus


1 Department of Obstetric and Gynecology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

Date of Submission17-Apr-2020
Date of Decision06-May-2020
Date of Acceptance02-Jun-2020
Date of Web Publication24-Jul-2020

Correspondence Address:
MBBCh Mahmoud A.G Ahmad
Cairo 11651
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_68_20

Rights and Permissions
  Abstract 


Background Gestational diabetes mellitus (GDM) is a serious disease, which may cause complications such as preeclampsia, increased cesarean rates, and macrosomia in mothers and neonates.
Objective The aim of the study was to examine whether women who have a first trimester prediabetes − glycated hemoglobin (HbA1C) range of 5.7–6.4% are more likely to have an abnormal second trimester oral glucose tolerance test (OGTT) compared with women who have a normal first trimester HbA1C.
Patients and methods The study was conducted at the Obstetrics and Gynecology Department of Sayed Galal University Hospital, Al-Azhar University, during the period between August 2018 and August 2019. The study included 121 pregnant women who regularly attended the outpatient clinic in the first trimester for antenatal care and who were subjected to personal, menstrual, obstetric, past, medical, and family history; general and abdominal examination; ultrasonography and measurement of HbA1C and OGTT.
Results The present study showed a statistically significant difference between women with HbA1C value in relation to prepregnancy BMI, pregnancy BMI, gestational age, method of screening, development of GDM, and at 0 h and after 1 h according to fasting value from OGTT result.
Conclusion HbA1C level is a good test for identifying patients at high risk of development of GDM. It has a prognostic value in the obese population. Its value has been demonstrated when it is done during the first trimester and up to 20 weeks of gestation. This information may help in GDM screening and treatment.

Keywords: diabetes, gestational, glycated, hemoglobin, mellitus


How to cite this article:
Fattah AT, Elboghdady AA, Abo-Ghabsha ME, Ahmad MA. First trimester glycated hemoglobin in the prediction of gestational diabetes mellitus. Al-Azhar Assiut Med J 2020;18:209-16

How to cite this URL:
Fattah AT, Elboghdady AA, Abo-Ghabsha ME, Ahmad MA. First trimester glycated hemoglobin in the prediction of gestational diabetes mellitus. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Aug 9];18:209-16. Available from: http://www.azmj.eg.net/text.asp?2020/18/2/209/290607




  Introduction Top


Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that may be first recognized during pregnancy [1].

GDM has a prevalence rate of ∼6–8%, and is higher in obese pregnancies, ranging from 7 to 14%. GDM has many fetal risks like fetal death, macrosomia, shoulder dystocia, neonatal hypoglycemia, respiratory distress syndrome, and childhood obesity [2].

Screening of diagnosis of GDM is frequently done at 24–28 weeks of pregnancy based on the fact that the diabetogenic effects of pregnancy increase as pregnancy advances. Glycated hemoglobin (HbA1C) is considered as a critical diabetes control measure through the findings of the landmark diabetes control and complications trial, which demonstrated that a sustained lowering of HbA1C was associated with fewer microvascular complications. HbA1C is formed when glucose in the blood reacts with amino groups of the hemoglobin protein [3].

HbA1C is a form of hemoglobin that characterizes plasma glucose over a prolonged period of time. It is used in the nonpregnant population as a screening tool for diabetes mellitus and as a tool for the assessment of glycemic control of known diabetic patients [4].

Normal values of HbA1C in pregnancy in nondiabetic women identified a normal reference interval of 4.3–5.4% in the first trimester.

In the nonobstetric population, it has been shown that an HbA1C value of 5.7–6.4% indicates impaired glucose tolerance and a high risk of future diabetes [5].

The purpose of this study was to examine whether women who have a first trimester prediabetes- HbA1C range of 5.7–6.4% is more likely to have an abnormal second trimester oral glucose tolerance test (OGTT) compared with women who have a normal first trimester HbA1C.


  Patients and methods Top


This prospective cohort study was conducted at the Obstetrics and Gynecology Department of Sayed Galal University Hospital, Al-Azhar University during the period between August 2018 and August 2019. The study is approved by the ethical committee of faculty of medicine, Al-Azhar University, Cairo, Egypt and an informed consent was taken from each participant. The study included 121 pregnant women who regularly attended the outpatient clinic in the first trimester for antenatal care.

Inclusion criteria

Women during the childbearing period (18–45 years old) and singleton pregnancies.

Exclusion criteria

Multiple gestations, pregestational known diabetes (types 1 and 2), glucose intolerance, and fasting plasma glucose (FPG) levels more than or equal to 126 or HbA1C more than 6.5. Past history of GDM in previous pregnancy. Hemoglobin variant/hemoglobinopathy or if hemoglobin level less than 10 g/dl at the first visit. Medical conditions that influence HbA1C and its measurement including conditions which lead to false positive results, such as decreased erythropoiesis (as in iron or vitamin B12 deficiency anemia), decreased erythrocyte destruction rate (as in splenectomy, drugs, for example large doses of aspirin and chronic opiate use), conditions which lead to false negative results such as increased erythropoiesis (as in the administration of erythropoietin, vitamin B12), reticulocytosis, increased erythrocyte destruction rate (as in hemoglobinopathies and splenomegaly, rheumatoid arthritis) or antiretroviral drugs such as ribavirin.

All individuals were subjected to full personal, menstrual, obstetric, past medical, and family history; general and abdominal examination; ultrasonography and measurement of HbA1C and OGTT.

Statistical analysis

Recorded data were analyzed using the Statistical Package for the Social Sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). Quantitative data were expressed as mean±SD. Qualitative data were expressed as frequency and percentage.

The following tests were done: independent samples t test of significance was used when comparing between two means. c2 test of significance was used in order to compare proportions between qualitative parameters. The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the P value was considered significant as the following: a P value of less than 0.05 was considered significant; P value less than 0.001 was considered as highly significant; and P value more than 0.05 was considered insignificant.


  Results Top


The results of the present study are demonstrated in the following tables and figures.

[Table 1] shows no statistically significant difference between women with a HbA1C value (<5.7% vs. 5.7–6.4%) according to age (years) ([Figure 1]).
Table 1 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to age (years)

Click here to view
Figure 1 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to age (years).

Click here to view


[Table 2] shows highly statistically significant decrease mean of HbA1C value less than 5.7% compared with HbA1C value 5.7–6.4% according to prepregnancy BMI ([Figure 2]).
Table 2 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to prepregnancy BMI (kg/m2)

Click here to view
Figure 2 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to prepregnancy BMI (kg/m2).

Click here to view


[Table 3] shows statistically significant difference between women with a HbA1C value of less than 5.7% versus 5.7–6.4% according BMI ([Figure 3]).
Table 3 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to BMI (kg/m2)

Click here to view
Figure 3 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to BMI (kg/m2).

Click here to view


[Table 4] shows statistically significant increase in mean of HbA1C value less than 5.7% compared with HbA1C value 5.7–6.4% according to gestational age at HbA1C testing (weeks) ([Figure 4]).
Table 4 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to gestational age at glycated hemoglobin testing (weeks)

Click here to view
Figure 4 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to gestational age at glycated hemoglobin testing (weeks).

Click here to view


[Table 5] shows no statistically significant difference between women with a HbA1C value (<5.7% vs. 5.7–6.4%) according to gestational age at diabetes screen/diagnosis ([Figure 5]).
Table 5 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to gestational age at diabetes screen/diagnosis (weeks)

Click here to view
Figure 5 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to gestational age at diabetes screen/diagnosis (weeks).

Click here to view


[Table 6] shows no statistically significant difference between women with a HbA1C value (<5.7% vs. 5.7–6.4%) according to parity ([Figure 6]).
Table 6 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to parity

Click here to view
Figure 6 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to parity.

Click here to view


[Table 7] shows statistically significant difference between women with a HbA1C value [<5.7% (79.6%) vs. 5.7–6.4% (53.8%)] according to the method of screening ([Figure 7]).
Table 7 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according method of screening

Click here to view
Figure 7 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to the method of screening.

Click here to view


[Table 8] shows statistically significant difference between women with a HbA1C value [<5.7% (11.1%) vs. 5.7–6.4% (30.8%)] according to the development of GDM ([Figure 8]).
Table 8 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according development of gestational diabetes mellitus

Click here to view
Figure 8 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to development of gestational diabetes mellitus.

Click here to view


[Table 9] shows statistically significant decrease in mean of HbA1C value less than 5.7% compared with HbA1C value 5.7–6.4% at 0 h according to fasting value from glucose tolerance test results ([Figure 9]).
Table 9 Comparison between women with a glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according fasting value from glucose tolerance test results at first trimester

Click here to view
Figure 9 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to fasting value from glucose tolerance test results at first trimester.

Click here to view


[Table 10] shows statistically significant decrease mean of HbA1C value less than 5.7% compared with HbA1C value 5.7–6.4% at 0 h and after 1 h according to fasting value from glucose tolerance test results ([Figure 10]).
Table 10 Comparison between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to fasting value from glucose tolerance test results at second trimester

Click here to view
Figure 10 Bar chart between women with glycated hemoglobin value (<5.7% vs. 5.7–6.4%) according to fasting value from glucose tolerance test results.

Click here to view



  Discussion Top


GDM is defined as carbohydrate intolerance that may be first recognized during pregnancy. GDM has maternal and fetal complications such as preeclampsia, polyhydramnios, preterm labor, cesarean delivery, shoulder dystocia, birth injury, and neonatal hyperbilirubinemia [6].

Studies have demonstrated early detection and treatment of GDM decreases many of these complications and improves perinatal outcome [7].

The landmark Hyperglycemia and Adverse Pregnancy Outcome study of ∼25 000 pregnant women showed a strong relationship between maternal glycemia and adverse pregnancy outcomes [8].

Complications associated with GDM do not end with pregnancy, and GDM identifies a group of women at risk for the development of type 2 diabetes, impaired glucose tolerance, and metabolic syndrome in the future.

In addition, GDM has an economic burden that results in an increase of 25–34% in maternity care costs and a 49% increase in neonatal ICU costs, compared with those pregnancies without GDM [9].

The OGTT is the established modality of screening for GDM [10]. Women with GDM should be subjected to an OGTT at or after 6 weeks postpartum [11].

However, the routine application of OGTT is not preferred due to its high cost, lengthy procedure, need for fasting, and patient’s noncompliance. More convenient and simple approaches minimize the use of OGTT, without affecting the likelihood of diagnosing GDM. Many studies have assessed the use of FPG both alone and in combination with glucose challenge test for the diagnosis of GDM; however, both had lower sensitivity than OGTT. HbA1C is an alternative test for the screening of GDM. Compared with OGTT, HbA1C is preferred because it does not require fasting, consumption of a concentrated glucose beverage, or multiple blood draws. The intraindividual coefficient of variation of HbA1C (3.6%) is lesser than both fasting (5.7%) and 2-h glucose (16.6%) [12]. In addition, HbA1C has low interindividual variability (<1%) compared with FPG (4%).

The interindividual and intraindividual variabilities of fasting glucose and 2-h glucose are higher during pregnancy compared with the nonpregnant state; however, the literature is silent regarding the variability of HbA1C during pregnancy. HbA1C has shown fair correlation with OGTT for the screening and diagnosis of GDM, with lower sensitivity and specificity [13].

HbA1C has also shown to have reasonable correlation with OGTT results in the postpartum period, but as an independent test, it performed poorly compared with OGTT. Here, the present study evaluated the role of HbA1C in screening and diagnosis of GDM and its correlation with adverse pregnancy outcomes [14].

During the last three decades, a few initial reports have given way to the recent well-conducted studies [15]. The current study was conducted to examine whether women with a first trimester prediabetes HbA1C range of 5.7–6.4% are more likely to have an abnormal second trimester OGTT compared with women with a normal first trimester HbA1C.

The current study showed a statistically significant difference between women with a HbA1C value of less than 5.7% versus 5.7–6.4% according to pregnancy BMI and prepregnancy BMI. And there was a negative relation between HbA1C value and pregnancy BMI and a positive relation between HbA1C value and prepregnancy BMI. These findings were in agreement with a study by Huh et al. [16] in which they revealed an inverse association between HbA1C and BMI due to the result of different mechanisms according to glucose tolerance status.

Also, these findings were in agreement with a study by Fong et al. [2], which revealed that women in the high hemoglobin value group (HbA1C 5.7–6.4%) trended to have a higher prepregnancy BMI and generally have higher HbgA1C values.

In this study, there was a negative relationship between gestational age and hemoglobin levels as women at earlier gestational age have higher HbA1C values (5.7–6.4%). The same finding was confirmed by Fong et al. [2].

This study revealed a positive correlation between HbA1C level and development of GDM as women with less than 5.7% HbA1C values have lower risks of developing GDM than women with higher levels of HbA1C. This finding is similar to the results obtained by Fong et al.

[2], where more than 10% of the women had an early HbA1C level of 5.7–6.4%. These patients ultimately had a nearly one in three chance of the development of GDM compared with less than one-tenth of patients with HbA1C levels of less than 5.7%. This result remained significant even after adjustment for a number of confounders.It is well known that fasting glucose tolerance test is the simplest and fastest way to measure blood glucose and diagnose diabetes (after fasting for 6–8 h before the test). The current study showed a significantly higher value in the HbA1C 5.7–6.4% group compared with the HbA1C less than 5.7% (with mean±SD 90.92±11.36 vs. 83.64±8.71, respectively, in the 0 h) and (mean±SD 173.36±9.11 vs. 167.21±8.65, respectively, after 1 h) and (mean±SD 143.06±6.51 vs. 141.22±10.42, respectively, after 2 h). These findings go in the same line with Wang et al. [17] as the mean 1 h 75-g glucose tolerance value was significantly higher in the HbA1C 5.7–6.4% group (150.6 vs. 133.6 mg/dl; P<0.001), and the fasting glucose tolerance value was 82.6 vs. 79.0 mg/dl (P<0.001).

Furthermore, the predictive effects and cutoff values for these factors varied according to prepregnancy BMI. Thus, p-BMI should be a consideration for the risk assessment of pregnant patients for GDM development [17].

FPG and BMI levels of women before pregnancy are valuable predictors for early diagnosis of GDM [18].


  Conclusion Top


An HbA1C level of 5.7–6.4% is a good method for identifying patients at the highest risk of development of GDM. It may be most prognostic in an obese population. Its efficacy has been demonstrated when the sample is drawn during the first trimester and up to 20 weeks of gestation. This information may help in the screening and treatment of GDM. HbA1C is better than FPG in early detection and diagnosis of GDM as it does not require a fasting state, requires only a single blood draw, and is interpreted by a single value. Conversely, HbA1C is more expensive to analyze than plasma glucose. Recent technological advances have made HbA1C a more standardized and user-friendly test with wide availability. This study evaluated HbA1C as a screening test for GDM in a high-risk population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
American College of Obstetricians and Gynecologists Committee on Practice Bulletins Obstetrics. ACOG Practice Bulletin: clinical management guidelines for obstetrician gynecologists. Number 30 (replaces Technical Bulletin Number 200, 1994). Gestational diabetes. Obstetr Gynecol 2010; 98:525–538.  Back to cited text no. 1
    
2.
Fong A, Serra AE, Gabby L, Wing DA, Berkowitz KM. Use of hemoglobin A1C as an early predictor of gestational diabetes mellitus. Am J Obstetr Gynecol 2014; 211:641.el–7.  Back to cited text no. 2
    
3.
Ozgu-Erdinc AS, Yilmaz S, Yeral MI, Seckin KD, Erkaya S, Danisman AN. Prediction of gestational diabetes mellitus in the first trimester: comparison of C-reactive protein, fasting plasma glucose, insulin and insulin sensitivity indices. J Matern Fetal Neonatal Med 2014; 28:1957–1962.  Back to cited text no. 3
    
4.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2012; 35:64–71.  Back to cited text no. 4
    
5.
O’Connor C, O’Shea PM, Owens LA, Carmody L, Avalos G, Nestor L et al. Trimester − specific reference intervals for hemoglobin A1C (HbA1c) in pregnancy. Clin Chem Lab Med 2012; 50:905–909.  Back to cited text no. 5
    
6.
Soumya S, Rohilla M, Chopra S, Dutta S, Bhansali A, Parthan G et al. HbA1c: a useful screening test for gestational diabetes mellitus. Diabetes Technol Ther 2015; 17:904.  Back to cited text no. 6
    
7.
Alwan N, Tuffnell DJ, West J. Treatments for gestational diabetes. Cochrane Database Syst Rev 2009; 3:CD003395.  Back to cited text no. 7
    
8.
Metzger BE, Lowe LP, Dyer AR, Trimble ER, Contreras M, Sacks DA et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002.  Back to cited text no. 8
    
9.
Gillespie P, Cullinan J, O’Neill C, Dunne F, ATLANTIC DIP Collaborators. Modeling the independent effects of gestational diabetes mellitus on maternity care and costs. Diabetes Care 2013; 36:1111–1116.  Back to cited text no. 9
    
10.
American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2014; 37(Suppl 1):S44.  Back to cited text no. 10
    
11.
Metzger BE, Buchanan TA, Coustan DR, De Leiva A, Dunger DB, Hadden DR et al. Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care 2007; 30(Suppl 2):251–260.  Back to cited text no. 11
    
12.
Selvin E, Crainiceanu CM, Brancati FL, Coresh J. Short-term variability in measures of glycemia and implications for the classification of diabetes. Arch Intern Med 2007; 167:1545–1551.  Back to cited text no. 12
    
13.
Aldasouqi SA, Solomon DJ, Bokhari S, Khan PM, Muneera S, Gossain VV. Glycohemoglobin A1C: a promising screening tool in gestational diabetes mellitus. Int J Diabetes Dev Ctries 2008; 28:121–124.  Back to cited text no. 13
    
14.
Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 2002; 25:1862–1868.  Back to cited text no. 14
    
15.
Agarwal MM. Gestational diabetes mellitus: screening with fasting plasma glucose. World J Diabetes 2016; 7:279–289.  Back to cited text no. 15
    
16.
Huh JH, Kim KJ, Lee BW, Kim DW, Kang ES, Cha BS, Lee HC. The relationship between BMI and glycated albumin to glycated hemoglobin (GA/A1c) ratio according to glucose tolerance status. PLoS One 2014; 9:e89478.  Back to cited text no. 16
    
17.
Wang C, Zhu W, Wei Y, Su R, Feng H, Lin L, Yang H. The predictive effects of early pregnancy lipid profiles and fasting glucose on the risk of gestational diabetes mellitus stratified by body mass index. J Diabetes Res 2016; 2:1–15.  Back to cited text no. 17
    
18.
Zhang L, Wang Q, Qu Y, Zhang W, Zhang Y, Jiang B, Ding H. Predictive value of fasting plasma glucose and body mass index of pre-pregnancy women for gestational diabetes mellitus. Zhonghua Yi Xue Za Zhi 2015; 95:2695–2697.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

Top
 
 
  Search
 
Similar in PUBMED
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
   Abstract
  Introduction
  Patients and methods
  Results
  Discussion
  Conclusion
   References
   Article Figures
   Article Tables

 Article Access Statistics
    Viewed67    
    Printed0    
    Emailed0    
    PDF Downloaded18    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]