Reference Range for Glycated Haemoglobin in Full Term Antenatal Women- a Multicentric Cross Sectional Study

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Research Design and Methods : The study was conducted at three government hospitals in South India. Clinical data, maternal blood sample and foetal cord blood sample were collected from women admitted for safe confinement. Mean ( ± SD) of HbA1c in participants with no known diabetes (gestational or pregestational) or any complications (maternal or fetal) is described, 2.5 th to 97.5 th centile reference range was derived. Results : From 3 centres, 2004 women participated in the study. Data from 1039 participants who had no history of diabetes or any maternal or fetal complication were used to determine the reference range for HbA1c at term pregnancy. The mean HbA1c in subjects devoid of diabetes and its known complications was 5.0 (± 0.38) %. The reference range for normal HbA1c at term in these women was found to be 4.3 to 5.9 %. Maternal HbA1c at term pregnancy in non-diabetic pregnant women is associated with pre pregnancy BMI, maternal age and 2-hour plasma glucose level of 2 nd trimester oral glucose tolerance test (OGTT). Conclusions: The mean HbA1c at term pregnancy in non-diabetic women admitted for safe confinement is 5.00 (± 0.38) %. An HbA1c of 5.9 % or more at term should be considered abnormal and women with such a value may be kept at a close surveillance for development of diabetes. Type 2 Diabetes Gestational diabetes Glycated Haemoglobin Delivery Birth Weight What this study adds to the clinical work The normative values of HbA1c in full term antenatal women is defined for the first time. This will be useful in assessing the composite glycaemic environment faced by the mother and foetus in the final trimester of pregnancy and possibly to predict the risk of diabetes future diabetes in parous women. Introduction Gestational diabetes mellitus (GDM) is hyperglycemia first detected during pregnancy. It is the most common medical condition which complicates pregnancy ( 1 ). GDM not only increases the risk of complications in pregnancy for both the mother and the fetus, but also increases the risk of future metabolic syndrome and its complications for both mother and the child ( 2 ). The incidence of GDM has increased manifold owing to the raging pandemics of obesity and type 2 diabetes. ( 3 , 4 ) GDM prevalence ranged between 9 to 26% in the hyperglycemia and adverse pregnancy outcome (HAPO) study ( 5 ). A community-based study conducted in South India reported a prevalence of 17.5% among urban women,13.8% in semi urban, 9.9% in rural areas based on single two-hour 75-gram post glucose values ( 6 ). The fetal effects of GDM are mediated by transplacental passage of glucose and the consequent increased levels of fetal insulin. This results in fetal macrosomia, the chances of which are proportional to the duration and severity of maternal hyperglycaemia to which the foetus is exposed ( 7 , 8 ). Glycated Haemoglobin (HbA1c) is a composite marker of glycaemic levels of last 90–120 days in the non-pregnant state. In the pregnant state HbA1c levels fall due to a higher erythrocyte turnover, dilutional effect and lower blood glucose levels. HbA1c levels measured at the time of delivery represent the glycemia experienced by the mother and the foetus in the last trimester of pregnancy and may be useful in identifying women and babies who have been exposed to higher levels of blood glucose in the last trimester with or without the diagnosis of diabetes mellitus earlier. Screening programs for GDM involve evaluation of glycemia at 24–28 weeks’ gestation but gestational diabetes can develop even after this time ( 9 ). The normal values of HbA1c in the term pregnant women are not known. The current study was done to find the normative values of HbA1c at term pregnancy in women with no GDM or any of its known complications in the current pregnancy. Secondary objectives of the study were to find the determinants of HbA1c if any, in such women. Materials and Methods After obtaining the approval of the Human Ethics Committee, (HEC. GMCT/No 01/44/2018 dated 09/01/2018), the study was done over a period of 30 months starting in February 2018. The study was conducted at 3 tertiary care hospitals in two different districts of Kerala. Using the standard deviation of HbA1c of 0.4% from previous studies and a desired confidence interval of 0.05% the required sample size was calculated as 983 patients, assuming 80% power and alpha error fixed at 5%. Pregnant women admitted for safe confinement to these hospitals during the study period were consecutively included in the study. Patients on any type of steroid medication (systemic, topical or inhaled steroids etc), any other diseases complicating pregnancy were excluded from the study. After an informed written consent, demographic details of the mother, family history of diabetes, her previous obstetric history, mode of delivery, details of the new-born, complication in the new-born if any and comorbidities detected during current gestation (including diabetes and hypertension) were collected and entered in a predesigned proforma by trained nurses who were employed for the study. Hospital records were available to the research staff who collected the data. Maternal blood sample was collected for estimation of HbA1c, and random plasma glucose. Cord blood was also collected for estimation of foetal plasma glucose and insulin levels. All biochemical investigations were done using the same analysers for all subjects under a National Accreditation Board for Laboratories (NABL) certified quality control program. Plasma glucose estimation was done with the glucose oxidase- peroxidase method (GOD-POD). HbA1c was estimated using a National Glucose Standardization Program (NGSP) certified high performance liquid chromatography (HPLC) system (BIORAD-D10, USA). The demographic, anthropometric, clinical and biochemical data was tabulated in MS Excel 2017. Quantitative variables were summarized as mean ± SD. To find the normative value of HbA1c women with overt diabetes, GDM or any known complication in the current pregnancy were excluded from the analysis. Statistical analysis was done using SPSS version 28. Categorical variables are expressed as number and percentages and compared using chi-square test. To compare two independent groups of continuous variables, one way ANOVA was used. Post-hoc Bonferroni correction was employed to assess the differences within subgroups. Results Baseline parameters A total of 2004 subjects were enrolled in the study from the 3 different participating hospitals. Of these 1196 patients were from Thiruvananthapuram and the rest 808 women from Kottayam district. Mean age of included women was 25.15 ± 4.12 years (Table 1 ). Table 1 A- Clinical characteristics of participants without diagnosed GDM or maternal or fetal complications (n = 1039) Mean Std. Deviation Age (years) 25.15 4.12 Height (cm) 155.18 6.05 Maternal weight at term (Kg) 62.39 8.61 Pre-Pregnancy BMI (Kg/m 2 ) 21.70 3.47 HbA1c at term (%) 5.0 0.39 Haemoglobin level (g/dl) 11.68 1.01 Baby Birth Weight (Kg) 2.79 0.48 TSH (µIU/ml) 1.42 1.07 Ist trimester fasting PG (n = 547) 76.50 9.59 Ist trimester post prandial PG (n = 547) 90.35 15.64 2nd trimester Fasting PG (mg/dl) 80.77 10.55 2nd trimester OGTT 1 hr (mg/dl) 102.92 19.64 2nd trimester OGTT 2 hr (mg/dl) 98.42 19.63 PG- Plasma glucose, BMI- Body mass index, OGTT –oral glucose tolerance test (75 gram). Table 1 B- Frequency of categorical variables of study participants (n = 1196) Parameter Frequency (%) Primiparous 673 (64.3%) Vaginal Delivery 760 (72.9%) Caesarean 279 (27.1%) H/o abortion 87 (8.7%) Cephalic presentation 776 (74.8%) Breech Presentation 260 (24.9%) Transverse lie 3 (0.2%) 1 minute APGAR score < 8 26 (2.47%) Out of these participants, GDM was diagnosed in 552 and overt diabetes mellitus in 9 women. Patients with recurrent abortions (more than 2 abortions in past), past neonatal deaths, intra-uterine demise of fetus (IUD) preterm delivery (Gestational age < 37 weeks), premature rupture of membranes, antepartum haemorrhage, fever during pregnancy and macrosomia comprised 273 participants. For finding the normative values of HbA1c at the time of delivery, women with anaemia (Hb 30 Kg/m 2 , GDM, overt diabetes mellitus, history of recurrent abortions or neonatal deaths or intrauterine deaths, current preterm delivery i.e. Gestational age < 37 weeks, Premature rupture of membranes, Antepartum haemorrhage, fever, Macrosomia, were excluded. After excluding the above, data from 1039 subjects were available for assessing the normal values for HbA1c in pregnant women at term gestation. The mean HbA1c at term gestation was found to be 5.00 ± 0.38%. The reference 95 centiles (2.5th centile to 97.5th centile) for the HbA1c values in these complication free, non-diabetic, non-obese mothers was found to be 4.3–5.9% (Table 2 ). Table 2 Percentile of HbA1c at term in studied subjects HbA1c percentile HbA1c Value at delivery 2.5th 4.3% 25th 4.8% 50th (Median) 5.0% 75th 5.2% 97.5th 5.9% Among these non-diabetic, healthy, maternal and fetal complication free mothers, the HbA1c level at time of confinement was found to have a statistically significant correlation with 2 hour plasma glucose value of 2nd trimester (GTT), First trimester Post prandial glucose (PPG), Pre pregnancy BMI, Systolic BP, Diastolic BP and Maternal age (Table 3 ). On binary logistic regression done by dichotomising HbA1c at the median, only maternal pre pregnancy BMI (Pearson r = 0.22) and 2 Hr OGTT plasma glucose value of 2nd trimester (Pearson r = 0.26) were found to have an independent association. Birth weight and fetal insulin level were not found to have a significant correlation with the HbA1c levels among the apparently normal women. Table 3 Correlation between HbA1c and various other parameters at the time of delivery. Clinical Parameter Correlation with HbA1c (Pearson R) Age 0.07* Gestational Age -0.18** Prepregnancy Weight 0.13** Prepregnancy BMI 0.22** Haemoglobin -0.04 Birth Weight 0.06 Blood Loss 0.24** Maternal Plasma Glucose at delivery 0.12** Fetal Insulin 0.08 Fetal plasma glucose 0.08* Maternal Fasting PG 0.19** Maternal Post prandial PG 0.18** Serum Thyrotropin 0.00 Ist trimester Fasting PG 0.10* Ist trimester Post prandial PG -0.01 2nd trimester Fasting PG 0.07 2nd trimester OGTT (1hr) 0.07 2nd trimester OGTT (2 hr) 0.26** Systolic Blood pressure 0.11** Diastolic Blood Pressure 0.08** (* = P < 0.05, **= P < 0.01) PG- Plasma glucose, BMI- Body mass index, OGTT –oral glucose tolerance test (75 gram). Further the study participants were divided into 4 quartiles according to the HbA1c levels and the participants in the highest quartile (HbA1c > 5.2%) were compared to those in the lowest quartiles (HbA1c < 4.8%) with regard to relevant demographic, anthropometric obstetric and biochemical parameters (Table 4 ). Pre pregnancy BMI, maternal weight at term, Systolic blood pressure, second trimester 2-hour post glucose load plasma glucose values and maternal random plasma glucose at delivery were found to be significantly higher in the uppermost quartile when compared to the lowermost quartile. Women in the uppermost quartile of HbA1c were also at risk of an earlier termination of pregnancy compared to those with lesser HbA1c levels. Statistically significant difference was not found in the groups with regard to birth weight of the baby or placental weight. Table 4 Clinical parameters of participants in different HbA1c Quartiles Quartile 1 Mean (SD) Quartile 2 Mean (SD) Quartile 3 Mean (SD) Quartile 4 Mean (SD) Overall P Value Q1 Vs Q4 P value Age (years) 25.04 (3.86) 24.69 (3.97) 24.99 (4.22) 25.79 (4.30) 0.02 0.24 Gestational age (Weeks) 38.86 (1.91) 38.88 (2.01) 38.71 (1.60) 37.8 (1.95) < .001 < .001 Haemoglobin (g/dl) 11.67 (1.02) 11.77 (1.05) 11.67 (1.01) 11.61 (0.95) 0.38 1 1 min APGAR score 8.88 (0.56) 8.9 (0.53) 8.94 (0.40) 8.94 (0.33) 0.37 0.91 HbA1c (%) 4.49 (0.17) 4.85 (0.04) 5.06 (0.04) 5.45 (0.28) < .001 < .001 Fetal plasma glucose at delivery (mg/dl) 63.10 (19.32) 61.83 (17.12) 64.52 (25.82) 67.45 (24.88) 0.04 0.20 Maternal Plasma glucose at term (mg/dl) 89.07 (22.19) 90.80 (20.64) 92.54 (23.11) 96.34 (30.13) 0.01 0.01 Diastolic BP (mm of Hg) 73.06 (8.21) 74.81 (7.73) 75.09 (8.38) 74.81 (6.69) 0.01 0.01 Systolic BP (mm of Hg) 113.74 (10.64) 114.85 (11.73) 115.72 (12.27) 117.16 (9.51) 0.005 < 0.01 Pre pregnancy BMI (Kg/m 2 ) 21.10 (3.36) 21.10 (3.18) 21.45 (3.58) 23.19 (3.28) < .001 < .001 Weight at term (Kg) 60.65 (8.23) 60.89 (7.90) 61.81 (8.64) 65.72 (8.56) < .001 < .001 2nd trimester OGTT (2 hr) (mg/dl) 92.04 (17.04) 95.42 (17.83) 97.39 (17.33) 108.17 (22.15) < .001 < .001 2nd trimester OGTT (1 hr) (mg/dl) 102.51 (16.53) 100.39 (20.43) 103.77 (17.21) 107.44 (28.49) 0.12 0.64 2nd trimester FPG (mg/dl) 79.17 (10.42) 82.22 (10.94) 80.72 10.68) 81.3 (9.52) 0.06 0.67 1st trimester FPG (mg/dl) 75.62 (10.09) 76.99 (9.79) 76.54 (8.97) 77.54 (9.44) 0.50 1 1st trimester 2 hr PPPG (mg/dl) 91.6 (14.56) 89.34 (16.55) 88.19 (14.33) 94.20 (17.93) 0.03 1 TSH (mIU/ml) 1.45 (1.23) 1.38 (0.98) 1.37 (0.90) 1.45 (1.15) 0.77 1 Baby birth weight (Kg) 2.77 (0.50) 2.79 (0.49) 2.77 (0.46) 2.83 (0.44) 0.46 1 Discussion HbA1c is a measure of average glucose values in past 3–4 months. In pregnant women, the utility of HbA1c was earlier challenged due to the relatively faster erythrocyte turnover and hemodilution. Later as normative values for HbA1c for different trimesters became available, the guidelines have adopted trimester specific cutoffs for pregnant women. Although HbA1c level may not be reflective of the glycemic levels of last 3–4 months in pregnant women, it is certainly useful to assess the glycemic status of the last 1–2 months. ( 10 ) This physiological change may be useful in pregnancy because the follow up visits in pregnancy especially in those with diabetes are much more frequent than a non-pregnant patient and it becomes a more accurate indicator of glycemia in the near past without the confounding effect of remote hyperglycemia of 3 to 4 months back making it more relevant in the context of pregnancy where there can be relatively faster changes in the level of glycemia. HbA1c measured at term pregnancy reflects the average blood glucose values experienced by the mother and fetus after the 28–32 week of gestation. The importance of such a measurement in a patient not diagnosed to have diabetes till third trimester is to assess the glycemic exposure of the mother and the fetus in the last trimester. It may also help in determining the risk of future diabetes in the mother. In pregnant patients diagnosed to have diabetes, the HbA1c level can help in assessment of adequacy of glycemic control and of risk of maternal and fetal complications. Maternal hyperglycemia can occur any time during a pregnancy, the risk being higher in the later part of it. It has been shown that peripheral insulin sensitivity (defined as the ability of insulin to increase glucose uptake in skeletal muscle and adipose tissue) decreases by approximately 50% by late gestation and in women with normal glucose tolerance, there is a 2–3-fold increase in insulin secretion in response to the decreased insulin sensitivity that maintains euglycemia. ( 11 , 12 ) Despite this higher risk the screening programs do not assess for hyperglycemia after the 28th week of gestation ( 13 ). The current multicentric study was done to find the normative value of HbA1c at term pregnancy in healthy pregnant women admitted for safe confinement. The study determined the mean HbA1c value at delivery in previously normal women, admitted for safe confinement without any maternal or fetal complications to be 5.0 (± 0.38) %. As HbA1c levels decrease during pregnancy, in order to ensure optimal glycaemic control in pregnant woman with diabetes, it is necessary to use HbA1c reference values ​​specific for each trimester ( 14 ). With the current study normal value of HbA1c at the end of third trimester has been defined for the first time. Previously reference ranges have been studied for the 3rd trimester of pregnancy but the HbA1c estimation was done for different patients at different times during the third trimester ranging from 28th to 36th week of gestation. ( 15 , 16 ) Some investigation has previously been done on HbA1c at the time of delivery with pregnancy outcomes especially caesarean delivery, but again normal values in non-diabetic pregnant women has not been defined. ( 17 ) The current study finds that the upper limit of reference interval for HbA1c at full term pregnancy is 5.9%. It is in consistence with the American Diabetes association target for HbA1c which recommend a level of < 6% to be optimal during pregnancy if it can be achieved without hypoglycemic episodes ( 18 ). In the 2nd and 3rd trimesters, HbA1c < 6% has been proposed to have lowest risk of large for gestational age infants, preterm delivery, and preeclampsia ( 19 ). It is also recommended that HbA1c should be monitored more frequently i.e., monthly, during pregnancy ( 19 ). Regarding the determinants of HbA1c at full term gestation, the current study found that 2nd trimester GTT, 2 hour glucose value, FPG and PPG of first trimester, Pre-pregnancy BMI, Systolic BP, Diastolic BP, and Maternal age have significant correlation with HbA1c levels at term. As only women with normal BMI, without GDM or overt diabetes and those without any fetal and maternal complications were included in the analysis the relation between HbA1c and the birthweight and fetal insulin levels may have been masked as those with high BMI, diagnosed GDM or overt diabetes. Pre-pregnancy BMI exerts its influence on HbA1c even in the third trimester of pregnancy highlighting the importance of adiposity in the pathogenesis of GDM. This association has been consistently observed in many previous studies on HbA1c in all trimesters of pregnancy. This highlights the importance of normalizing BMI, prior to conception for possible prevention of GDM. 2nd trimester OGTT 2 Hour glucose value association with HbA1c is important as it may be evaluated as a sensitive predictor of hyperglycemia in the third trimester of pregnancy. Intrauterine hyperglycaemia through its effects on fetal β-cells and adipose tissue can lead to late development of metabolic complications in the offspring. In a follow- up study ( 20 ) from Denmark, offspring’s (18–27 years of age) of women with GDM, 21% of the offspring had pre- diabetes or diabetes accounting for an eight-fold increased risk compared with the background population. Furthermore, the risk of overweight and the metabolic syndrome was higher (twofold and fourfold, respectively) and insulin sensitivity and secretion were reduced. The ‘HAPO- Follow up study’ confirmed these findings but suggests that although maternal adiposity is a strong risk factor for offspring obesity, GDM remains a significant risk factor, even after adjustment for maternal BMI ( 21 ). Further studies correlating the effects of sustained third trimester hyperglycaemia (as reflected by HbA1c at term) in offspring are needed. The current study had a strength of multicentric data collection and a large sample size. The study had the novelty of defining HbA1c levels at term in normal pregnant women for the first time. The limitations of the study included lack of fetal C peptide level estimation which would have been a better marker for fetal endogenous insulin secretion. Conclusions The mean HbA1c at term pregnancy in normal women, without any maternal or fetal complications admitted for safe confinement is 5.00 (± 0.38) %. The 95% reference range for HbA1c at term is 4.3–5.9%. Pre pregnancy BMI and 2nd trimester GTT 2-hour glucose value, are independently associated with the HbA1c levels at term. Declarations Disclosures: The authors have nothing to disclose and there are no conflicts of interest. Acknowledgement: Government of Kerala State (Health Department) and The Indian Institute of Diabetes, Thiruvananthapuram are acknowledged for funding the study. The authors hereby acknowledge the support extended by Dr. Remla A, Senior Scientific Officer, Indian Institute of Diabetes, Trivandrum, in supervision of biochemical measurements and biochemical data management. Mr. Sajeev S, Ms. Arya Suresh, Mrs. Divya, Mrs. Jessy Sam, Mrs. Archana Nibu and Mr. Sudi Sisupalan (Research Assistants, Department of Endocrinology, Govt. Medical College, Thiruvananthapuram) are acknowledged for their role in clinical data acquisition, entry, and tabulation. Author contributions Authors RVJ conceived the project and reviewed the manuscript. AN, CJ and PKJ conducted the study. AN and JC analyzed the data. AG reviewed the literature and prepared the manuscript. CN, CPV, AB contributed to data acquisition, discussion and reviewed the manuscript. Guarantor statement Dr. Abilash Nair, and Dr. Jayakumari C are the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of interest: None. References Metzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 1998 21 (Suppl 2) B161–B167. Farahvar S, Walfisch A, Sheiner E. Gestational diabetes risk factors and long-term consequences for both mother and offspring: a literature review. Expert Rev Endocrinol Metab. 2019 Jan;14(1):63-74. doi: 10.1080/17446651.2018.1476135. Epub 2018 Jun 5. PMID: 30063409 Li G, Wei T, Ni W, Zhang A, Zhang J, Xing Y, Xing Q. Incidence and Risk Factors of Gestational Diabetes Mellitus: A Prospective Cohort Study in Qingdao, China. Front Endocrinol (Lausanne). 2020 Sep 11;11:636. doi: 10.3389/fendo.2020.00636. 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Lurie S, Danon D. Life span of erythrocytes in late pregnancy. Obstet Gynecol. 1992;80(1):123–6. Ku¨hl C, Holst J. Plasma glucagon and the insulin: glucagon ratio in gestational diabetes. Diabetes 1976;25(1):16–23. Damm, P., Kuhl, C., Bertelsen, A. & Molsted- Pedersen, L. Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus. Am. J. Obstet. Gynecol. 167, 607–616 (1992). Lowe WL Jr, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, McCance D, Hamilton J, Nodzenski M, Talbot O, Brickman WJ, Clayton P, Ma RC, Tam WH, Dyer AR, Catalano PM, Lowe LP, Metzger BE; HAPO Follow-up Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care. 2019 Mar;42(3):372-380. doi: 10.2337/dc18-1646. Epub 2019 Jan 17. PMID: 30655380; PMCID: PMC6385693. Cite Share Download PDF Status: Published Journal Publication published 04 Oct, 2023 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Reviewers agreed at journal 18 Jun, 2023 Reviewers invited by journal 06 Jun, 2023 Editor invited by journal 05 Jun, 2023 Editor assigned by journal 01 Jun, 2023 First submitted to journal 31 May, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2998652","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":207477300,"identity":"64bc8e75-819a-4e4e-b36f-85a1db6889e0","order_by":0,"name":"Jayakumari Chellamma","email":"","orcid":"","institution":"Government Medical College Kottayam","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jayakumari","middleName":"","lastName":"Chellamma","suffix":""},{"id":207477301,"identity":"ee98473c-19c1-4d1c-9a8a-6056a0268a2f","order_by":1,"name":"Jayakumar R V","email":"","orcid":"","institution":"Indian Institute of Diabetes, Thiruvananthapuram","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jayakumar","middleName":"R","lastName":"V","suffix":""},{"id":207477302,"identity":"9b778548-3953-4acc-b3e5-62f62459f41e","order_by":2,"name":"Abilash Nair","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvklEQVRIiWNgGAWjYDACCR6GAwwMCXIg9oEHpGgxBmtJIFYLECQkNoApYnTwz+49eOhGTVr6/LDDD4G22MnpNhCy5M65hMM5x3JyN95OMwBqSTY2O0DImhs5BodzGypyN85OAGk5kLiNkBZ5qJZ0w9npH4jTYgDRkpMgL51DpC2Gd84YAP2SZrhBOqfgQIIBEX6Ru91j/DmnJllefnb65g8fKuzkCHsf7kKwSgNilYOAfAMpqkfBKBgFo2BEAQAJaUtpXaSqhAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6776-1582","institution":"Government Medical College Thiruvananthapuram","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Abilash","middleName":"","lastName":"Nair","suffix":""},{"id":207477303,"identity":"26d315c6-0751-4c83-9c2a-3b6a02062836","order_by":3,"name":"Nirmala C","email":"","orcid":"","institution":"Government Medical College Thiruvananthapuram","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nirmala","middleName":"","lastName":"C","suffix":""},{"id":207477304,"identity":"c65f132c-aafb-48fd-a588-83babc0c4281","order_by":4,"name":"Puthiyaveettil Khadar Jabbar","email":"","orcid":"","institution":"Government Medical College Thiruvananthapuram","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Puthiyaveettil","middleName":"Khadar","lastName":"Jabbar","suffix":""},{"id":207477305,"identity":"9c7403c9-9671-4266-bd2d-4c22bc932764","order_by":5,"name":"Vijayan C P","email":"","orcid":"","institution":"Government Medical College Kottayam","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Vijayan","middleName":"C","lastName":"P","suffix":""},{"id":207477306,"identity":"3498c6b3-c4a3-4abe-8a44-5a7d85a49a2d","order_by":6,"name":"Asha Babu","email":"","orcid":"","institution":"W\u0026C Hospital, Thycaud, Thiruvananthapuram","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Asha","middleName":"","lastName":"Babu","suffix":""},{"id":207477307,"identity":"a3b10184-6e92-4755-a56d-2d6830ecbadb","order_by":7,"name":"Anjana Gopi","email":"","orcid":"","institution":"ESIC Model and Super specialty Hospital, Asramam, Kollam","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anjana","middleName":"","lastName":"Gopi","suffix":""}],"badges":[],"createdAt":"2023-05-30 07:30:40","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2998652/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2998652/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-023-07231-1","type":"published","date":"2023-10-04T15:02:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":44302242,"identity":"474e11cd-44d6-485f-8e23-b1bc35c56bd5","added_by":"auto","created_at":"2023-10-09 15:09:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":401982,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2998652/v1/c7fe8e32-557f-4ee4-9e09-bf424c7915ff.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eReference Range for Glycated Haemoglobin in Full Term Antenatal Women- a Multicentric Cross Sectional Study\u003c/p\u003e","fulltext":[{"header":"What this study adds to the clinical work","content":"\u003cp\u003eThe normative values of HbA1c in full term antenatal women is defined for the first time. This will be useful in assessing the composite glycaemic environment faced by the mother and foetus in the final trimester of pregnancy and possibly to predict the risk of diabetes future diabetes in parous women.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eGestational diabetes mellitus (GDM) is hyperglycemia first detected during pregnancy. It is the most common medical condition which complicates pregnancy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). GDM not only increases the risk of complications in pregnancy for both the mother and the fetus, but also increases the risk of future metabolic syndrome and its complications for both mother and the child (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The incidence of GDM has increased manifold owing to the raging pandemics of obesity and type 2 diabetes. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) GDM prevalence ranged between 9 to 26% in the hyperglycemia and adverse pregnancy outcome (HAPO) study (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). A community-based study conducted in South India reported a prevalence of 17.5% among urban women,13.8% in semi urban, 9.9% in rural areas based on single two-hour 75-gram post glucose values (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe fetal effects of GDM are mediated by transplacental passage of glucose and the consequent increased levels of fetal insulin. This results in fetal macrosomia, the chances of which are proportional to the duration and severity of maternal hyperglycaemia to which the foetus is exposed (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Glycated Haemoglobin (HbA1c) is a composite marker of glycaemic levels of last 90\u0026ndash;120 days in the non-pregnant state. In the pregnant state HbA1c levels fall due to a higher erythrocyte turnover, dilutional effect and lower blood glucose levels. HbA1c levels measured at the time of delivery represent the glycemia experienced by the mother and the foetus in the last trimester of pregnancy and may be useful in identifying women and babies who have been exposed to higher levels of blood glucose in the last trimester with or without the diagnosis of diabetes mellitus earlier. Screening programs for GDM involve evaluation of glycemia at 24\u0026ndash;28 weeks\u0026rsquo; gestation but gestational diabetes can develop even after this time (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). The normal values of HbA1c in the term pregnant women are not known. The current study was done to find the normative values of HbA1c at term pregnancy in women with no GDM or any of its known complications in the current pregnancy. Secondary objectives of the study were to find the determinants of HbA1c if any, in such women.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eAfter obtaining the approval of the Human Ethics Committee, (HEC. GMCT/No 01/44/2018 dated 09/01/2018), the study was done over a period of 30 months starting in February 2018. The study was conducted at 3 tertiary care hospitals in two different districts of Kerala. Using the standard deviation of HbA1c of 0.4% from previous studies and a desired confidence interval of 0.05% the required sample size was calculated as 983 patients, assuming 80% power and alpha error fixed at 5%.\u003c/p\u003e \u003cp\u003ePregnant women admitted for safe confinement to these hospitals during the study period were consecutively included in the study. Patients on any type of steroid medication (systemic, topical or inhaled steroids etc), any other diseases complicating pregnancy were excluded from the study. After an informed written consent, demographic details of the mother, family history of diabetes, her previous obstetric history, mode of delivery, details of the new-born, complication in the new-born if any and comorbidities detected during current gestation (including diabetes and hypertension) were collected and entered in a predesigned proforma by trained nurses who were employed for the study. Hospital records were available to the research staff who collected the data. Maternal blood sample was collected for estimation of HbA1c, and random plasma glucose. Cord blood was also collected for estimation of foetal plasma glucose and insulin levels. All biochemical investigations were done using the same analysers for all subjects under a National Accreditation Board for Laboratories (NABL) certified quality control program. Plasma glucose estimation was done with the glucose oxidase- peroxidase method (GOD-POD). HbA1c was estimated using a National Glucose Standardization Program (NGSP) certified high performance liquid chromatography (HPLC) system (BIORAD-D10, USA). The demographic, anthropometric, clinical and biochemical data was tabulated in MS Excel 2017. Quantitative variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. To find the normative value of HbA1c women with overt diabetes, GDM or any known complication in the current pregnancy were excluded from the analysis. Statistical analysis was done using SPSS version 28. Categorical variables are expressed as number and percentages and compared using chi-square test. To compare two independent groups of continuous variables, one way ANOVA was used. Post-hoc Bonferroni correction was employed to assess the differences within subgroups.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cstrong\u003eBaseline parameters\u003c/strong\u003e \u003cp\u003eA total of 2004 subjects were enrolled in the study from the 3 different participating hospitals. Of these 1196 patients were from Thiruvananthapuram and the rest 808 women from Kottayam district. Mean age of included women was 25.15\u0026thinsp;\u0026plusmn;\u0026thinsp;4.12 years (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eA- Clinical characteristics of participants without diagnosed GDM or maternal or fetal complications (n\u0026thinsp;=\u0026thinsp;1039)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStd. Deviation\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e155.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal weight at term (Kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8.61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-Pregnancy BMI (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c at term (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin level (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaby Birth Weight (Kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH (\u0026micro;IU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIst trimester fasting PG (n\u0026thinsp;=\u0026thinsp;547)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e76.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIst trimester post prandial PG (n\u0026thinsp;=\u0026thinsp;547)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester Fasting PG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e80.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester OGTT 1 hr (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester OGTT 2 hr (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e98.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003ePG- Plasma glucose, BMI- Body mass index, OGTT \u0026ndash;oral glucose tolerance test (75 gram).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eB- Frequency of categorical variables of study participants (n\u0026thinsp;=\u0026thinsp;1196)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFrequency (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimiparous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e673 (64.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e760 (72.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaesarean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e279 (27.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH/o abortion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCephalic presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e776 (74.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreech Presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e260 (24.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTransverse lie\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (0.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 minute APGAR score\u0026thinsp;\u0026lt;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (2.47%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/p\u003e \u003cp\u003eOut of these participants, GDM was diagnosed in 552 and overt diabetes mellitus in 9 women. Patients with recurrent abortions (more than 2 abortions in past), past neonatal deaths, intra-uterine demise of fetus (IUD) preterm delivery (Gestational age\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks), premature rupture of membranes, antepartum haemorrhage, fever during pregnancy and macrosomia comprised 273 participants. For finding the normative values of HbA1c at the time of delivery, women with anaemia (Hb\u0026thinsp;\u0026lt;\u0026thinsp;10 gm %), pregestational BMI\u0026thinsp;\u0026gt;\u0026thinsp;30 Kg/m\u003csup\u003e2\u003c/sup\u003e, GDM, overt diabetes mellitus, history of recurrent abortions or neonatal deaths or intrauterine deaths, current preterm delivery i.e. Gestational age\u0026thinsp;\u0026lt;\u0026thinsp;37 weeks, Premature rupture of membranes, Antepartum haemorrhage, fever, Macrosomia, were excluded. After excluding the above, data from 1039 subjects were available for assessing the normal values for HbA1c in pregnant women at term gestation.\u003c/p\u003e \u003cp\u003eThe mean HbA1c at term gestation was found to be 5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38%. The reference 95 centiles (2.5th centile to 97.5th centile) for the HbA1c values in these complication free, non-diabetic, non-obese mothers was found to be 4.3\u0026ndash;5.9% (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePercentile of HbA1c at term in studied subjects\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c percentile\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHbA1c Value at delivery\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2.5th\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.3%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e25th\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50th (Median)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.0%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e75th\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.2%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e97.5th\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.9%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong these non-diabetic, healthy, maternal and fetal complication free mothers, the HbA1c level at time of confinement was found to have a statistically significant correlation with 2 hour plasma glucose value of 2nd trimester (GTT), First trimester Post prandial glucose (PPG), Pre pregnancy BMI, Systolic BP, Diastolic BP and Maternal age (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). On binary logistic regression done by dichotomising HbA1c at the median, only maternal pre pregnancy BMI (Pearson r\u0026thinsp;=\u0026thinsp;0.22) and 2 Hr OGTT plasma glucose value of 2nd trimester (Pearson r\u0026thinsp;=\u0026thinsp;0.26) were found to have an independent association. Birth weight and fetal insulin level were not found to have a significant correlation with the HbA1c levels among the apparently normal women.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between HbA1c and various other parameters at the time of delivery.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCorrelation with HbA1c (Pearson R)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.07*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGestational Age\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.18**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrepregnancy Weight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.13**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrepregnancy BMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.22**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHaemoglobin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth Weight\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBlood Loss\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.24**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal Plasma Glucose at delivery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.12**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFetal Insulin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFetal plasma glucose\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.08*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal Fasting PG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.19**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMaternal Post prandial PG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSerum Thyrotropin\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIst trimester Fasting PG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.10*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIst trimester Post prandial PG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2nd trimester Fasting PG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2nd trimester OGTT (1hr)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2nd trimester OGTT (2 hr)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.26**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystolic Blood pressure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.11**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiastolic Blood Pressure\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.08**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e(* = P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **= P\u0026thinsp;\u0026lt;\u0026thinsp;0.01)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003ePG- Plasma glucose, BMI- Body mass index, OGTT \u0026ndash;oral glucose tolerance test (75 gram).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFurther the study participants were divided into 4 quartiles according to the HbA1c levels and the participants in the highest quartile (HbA1c\u0026thinsp;\u0026gt;\u0026thinsp;5.2%) were compared to those in the lowest quartiles (HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;4.8%) with regard to relevant demographic, anthropometric obstetric and biochemical parameters (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Pre pregnancy BMI, maternal weight at term, Systolic blood pressure, second trimester 2-hour post glucose load plasma glucose values and maternal random plasma glucose at delivery were found to be significantly higher in the uppermost quartile when compared to the lowermost quartile. Women in the uppermost quartile of HbA1c were also at risk of an earlier termination of pregnancy compared to those with lesser HbA1c levels. Statistically significant difference was not found in the groups with regard to birth weight of the baby or placental weight.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical parameters of participants in different HbA1c Quartiles\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuartile 1 Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eQuartile 2 Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eQuartile 3 Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eQuartile 4 Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eOverall P Value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eQ1 Vs Q4 P value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.04 (3.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.69\u003c/p\u003e \u003cp\u003e(3.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.99\u003c/p\u003e \u003cp\u003e(4.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.79\u003c/p\u003e \u003cp\u003e(4.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age (Weeks)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38.86\u003c/p\u003e \u003cp\u003e(1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.88\u003c/p\u003e \u003cp\u003e(2.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.71\u003c/p\u003e \u003cp\u003e(1.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.8\u003c/p\u003e \u003cp\u003e(1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.67\u003c/p\u003e \u003cp\u003e(1.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.77\u003c/p\u003e \u003cp\u003e(1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.67\u003c/p\u003e \u003cp\u003e(1.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.61\u003c/p\u003e \u003cp\u003e(0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1 min APGAR score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.88\u003c/p\u003e \u003cp\u003e(0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.9\u003c/p\u003e \u003cp\u003e(0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.94\u003c/p\u003e \u003cp\u003e(0.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.94\u003c/p\u003e \u003cp\u003e(0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHbA1c (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.49\u003c/p\u003e \u003cp\u003e(0.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.85\u003c/p\u003e \u003cp\u003e(0.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.06\u003c/p\u003e \u003cp\u003e(0.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.45\u003c/p\u003e \u003cp\u003e(0.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFetal plasma glucose at delivery (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.10 (19.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.83\u003c/p\u003e \u003cp\u003e(17.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e64.52\u003c/p\u003e \u003cp\u003e(25.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.45\u003c/p\u003e \u003cp\u003e(24.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal Plasma glucose at term (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e89.07\u003c/p\u003e \u003cp\u003e(22.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90.80\u003c/p\u003e \u003cp\u003e(20.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92.54\u003c/p\u003e \u003cp\u003e(23.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96.34\u003c/p\u003e \u003cp\u003e(30.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic BP (mm of Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e73.06\u003c/p\u003e \u003cp\u003e(8.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74.81\u003c/p\u003e \u003cp\u003e(7.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.09\u003c/p\u003e \u003cp\u003e(8.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e74.81\u003c/p\u003e \u003cp\u003e(6.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP (mm of Hg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e113.74\u003c/p\u003e \u003cp\u003e(10.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114.85\u003c/p\u003e \u003cp\u003e(11.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115.72\u003c/p\u003e \u003cp\u003e(12.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e117.16\u003c/p\u003e \u003cp\u003e(9.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre pregnancy BMI (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21.10\u003c/p\u003e \u003cp\u003e(3.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.10\u003c/p\u003e \u003cp\u003e(3.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.45\u003c/p\u003e \u003cp\u003e(3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.19\u003c/p\u003e \u003cp\u003e(3.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight at term (Kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60.65\u003c/p\u003e \u003cp\u003e(8.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60.89\u003c/p\u003e \u003cp\u003e(7.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.81\u003c/p\u003e \u003cp\u003e(8.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e65.72\u003c/p\u003e \u003cp\u003e(8.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester OGTT (2 hr) (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92.04\u003c/p\u003e \u003cp\u003e(17.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.42\u003c/p\u003e \u003cp\u003e(17.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e97.39\u003c/p\u003e \u003cp\u003e(17.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e108.17\u003c/p\u003e \u003cp\u003e(22.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester OGTT (1 hr) (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e102.51\u003c/p\u003e \u003cp\u003e(16.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.39\u003c/p\u003e \u003cp\u003e(20.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e103.77\u003c/p\u003e \u003cp\u003e(17.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e107.44 (28.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2nd trimester FPG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e79.17\u003c/p\u003e \u003cp\u003e(10.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.22\u003c/p\u003e \u003cp\u003e(10.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80.72\u003c/p\u003e \u003cp\u003e10.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81.3\u003c/p\u003e \u003cp\u003e(9.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st trimester FPG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e75.62\u003c/p\u003e \u003cp\u003e(10.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.99\u003c/p\u003e \u003cp\u003e(9.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76.54\u003c/p\u003e \u003cp\u003e(8.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77.54\u003c/p\u003e \u003cp\u003e(9.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1st trimester 2 hr PPPG (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e91.6\u003c/p\u003e \u003cp\u003e(14.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.34\u003c/p\u003e \u003cp\u003e(16.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88.19\u003c/p\u003e \u003cp\u003e(14.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.20\u003c/p\u003e \u003cp\u003e(17.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH (mIU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.45\u003c/p\u003e \u003cp\u003e(1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.38\u003c/p\u003e \u003cp\u003e(0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.37\u003c/p\u003e \u003cp\u003e(0.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.45\u003c/p\u003e \u003cp\u003e(1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaby birth weight (Kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.77\u003c/p\u003e \u003cp\u003e(0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.79\u003c/p\u003e \u003cp\u003e(0.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.77\u003c/p\u003e \u003cp\u003e(0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.83\u003c/p\u003e \u003cp\u003e(0.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eHbA1c is a measure of average glucose values in past 3\u0026ndash;4 months. In pregnant women, the utility of HbA1c was earlier challenged due to the relatively faster erythrocyte turnover and hemodilution. Later as normative values for HbA1c for different trimesters became available, the guidelines have adopted trimester specific cutoffs for pregnant women. Although HbA1c level may not be reflective of the glycemic levels of last 3\u0026ndash;4 months in pregnant women, it is certainly useful to assess the glycemic status of the last 1\u0026ndash;2 months. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) This physiological change may be useful in pregnancy because the follow up visits in pregnancy especially in those with diabetes are much more frequent than a non-pregnant patient and it becomes a more accurate indicator of glycemia in the near past without the confounding effect of remote hyperglycemia of 3 to 4 months back making it more relevant in the context of pregnancy where there can be relatively faster changes in the level of glycemia.\u003c/p\u003e \u003cp\u003eHbA1c measured at term pregnancy reflects the average blood glucose values experienced by the mother and fetus after the 28\u0026ndash;32 week of gestation. The importance of such a measurement in a patient not diagnosed to have diabetes till third trimester is to assess the glycemic exposure of the mother and the fetus in the last trimester. It may also help in determining the risk of future diabetes in the mother. In pregnant patients diagnosed to have diabetes, the HbA1c level can help in assessment of adequacy of glycemic control and of risk of maternal and fetal complications.\u003c/p\u003e \u003cp\u003eMaternal hyperglycemia can occur any time during a pregnancy, the risk being higher in the later part of it. It has been shown that peripheral insulin sensitivity (defined as the ability of insulin to increase glucose uptake in skeletal muscle and adipose tissue) decreases by approximately 50% by late gestation and in women with normal glucose tolerance, there is a 2\u0026ndash;3-fold increase in insulin secretion in response to the decreased insulin sensitivity that maintains euglycemia. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) Despite this higher risk the screening programs do not assess for hyperglycemia after the 28th week of gestation (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe current multicentric study was done to find the normative value of HbA1c at term pregnancy in healthy pregnant women admitted for safe confinement. The study determined the mean HbA1c value at delivery in previously normal women, admitted for safe confinement without any maternal or fetal complications to be 5.0 (\u0026plusmn;\u0026thinsp;0.38) %. As HbA1c levels decrease during pregnancy, in order to ensure optimal glycaemic control in pregnant woman with diabetes, it is necessary to use HbA1c reference values ​​specific for each trimester (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). With the current study normal value of HbA1c at the end of third trimester has been defined for the first time. Previously reference ranges have been studied for the 3rd trimester of pregnancy but the HbA1c estimation was done for different patients at different times during the third trimester ranging from 28th to 36th week of gestation. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSome investigation has previously been done on HbA1c at the time of delivery with pregnancy outcomes especially caesarean delivery, but again normal values in non-diabetic pregnant women has not been defined. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThe current study finds that the upper limit of reference interval for HbA1c at full term pregnancy is 5.9%. It is in consistence with the American Diabetes association target for HbA1c which recommend a level of \u0026lt;\u0026thinsp;6% to be optimal during pregnancy if it can be achieved without hypoglycemic episodes (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). In the 2nd and 3rd trimesters, HbA1c\u0026thinsp;\u0026lt;\u0026thinsp;6% has been proposed to have lowest risk of large for gestational age infants, preterm delivery, and preeclampsia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). It is also recommended that HbA1c should be monitored more frequently i.e., monthly, during pregnancy (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRegarding the determinants of HbA1c at full term gestation, the current study found that 2nd trimester GTT, 2 hour glucose value, FPG and PPG of first trimester, Pre-pregnancy BMI, Systolic BP, Diastolic BP, and Maternal age have significant correlation with HbA1c levels at term. As only women with normal BMI, without GDM or overt diabetes and those without any fetal and maternal complications were included in the analysis the relation between HbA1c and the birthweight and fetal insulin levels may have been masked as those with high BMI, diagnosed GDM or overt diabetes. Pre-pregnancy BMI exerts its influence on HbA1c even in the third trimester of pregnancy highlighting the importance of adiposity in the pathogenesis of GDM. This association has been consistently observed in many previous studies on HbA1c in all trimesters of pregnancy. This highlights the importance of normalizing BMI, prior to conception for possible prevention of GDM. 2nd trimester OGTT 2 Hour glucose value association with HbA1c is important as it may be evaluated as a sensitive predictor of hyperglycemia in the third trimester of pregnancy.\u003c/p\u003e \u003cp\u003eIntrauterine hyperglycaemia through its effects on fetal β-cells and adipose tissue can lead to late development of metabolic complications in the offspring. In a follow- up study (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) from Denmark, offspring\u0026rsquo;s (18\u0026ndash;27 years of age) of women with GDM, 21% of the offspring had pre- diabetes or diabetes accounting for an eight-fold increased risk compared with the background population. Furthermore, the risk of overweight and the metabolic syndrome was higher (twofold and fourfold, respectively) and insulin sensitivity and secretion were reduced. The \u0026lsquo;HAPO- Follow up study\u0026rsquo; confirmed these findings but suggests that although maternal adiposity is a strong risk factor for offspring obesity, GDM remains a significant risk factor, even after adjustment for maternal BMI (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Further studies correlating the effects of sustained third trimester hyperglycaemia (as reflected by HbA1c at term) in offspring are needed.\u003c/p\u003e \u003cp\u003eThe current study had a strength of multicentric data collection and a large sample size. The study had the novelty of defining HbA1c levels at term in normal pregnant women for the first time. The limitations of the study included lack of fetal C peptide level estimation which would have been a better marker for fetal endogenous insulin secretion.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe mean HbA1c at term pregnancy in normal women, without any maternal or fetal complications admitted for safe confinement is 5.00 (\u0026plusmn;\u0026thinsp;0.38) %. The 95% reference range for HbA1c at term is 4.3\u0026ndash;5.9%. Pre pregnancy BMI and 2nd trimester GTT 2-hour glucose value, are independently associated with the HbA1c levels at term.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosures:\u0026nbsp;\u003c/strong\u003eThe authors have nothing to disclose and there are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u003c/strong\u003e Government of Kerala State (Health Department) and The Indian Institute of Diabetes, Thiruvananthapuram are acknowledged for funding the study.\u0026nbsp;The authors hereby acknowledge the support extended by Dr. Remla A, Senior Scientific Officer, Indian Institute of Diabetes, Trivandrum, in supervision of biochemical measurements and biochemical data management. Mr. Sajeev S, Ms. Arya Suresh, Mrs. Divya, Mrs. Jessy Sam, Mrs. Archana Nibu and Mr. Sudi Sisupalan (Research Assistants, Department of Endocrinology, Govt. Medical College, Thiruvananthapuram) are acknowledged for their role in clinical data acquisition, entry, and tabulation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors RVJ conceived the project and reviewed the manuscript. AN, CJ and PKJ conducted the study. AN and JC analyzed the data. AG reviewed the literature and prepared the manuscript. CN, CPV, AB contributed to data acquisition, discussion and reviewed the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGuarantor statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Abilash Nair, and Dr. Jayakumari C are the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e None.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMetzger BE, Coustan DR. Summary and recommendations of the Fourth International Workshop-Conference on Gestational Diabetes Mellitus. The Organizing Committee. Diabetes Care 1998 21 (Suppl 2) B161\u0026ndash;B167.\u003c/li\u003e\n\u003cli\u003eFarahvar S, Walfisch A, Sheiner E. Gestational diabetes risk factors and long-term consequences for both mother and offspring: a literature review. Expert Rev Endocrinol Metab. 2019 Jan;14(1):63-74. doi: 10.1080/17446651.2018.1476135. Epub 2018 Jun 5. PMID: 30063409\u003c/li\u003e\n\u003cli\u003eLi G, Wei T, Ni W, Zhang A, Zhang J, Xing Y, Xing Q. Incidence and Risk Factors of Gestational Diabetes Mellitus: A Prospective Cohort Study in Qingdao, China. Front Endocrinol (Lausanne). 2020 Sep 11;11:636. doi: 10.3389/fendo.2020.00636. PMID: 33042010; PMCID: PMC7516372.\u003c/li\u003e\n\u003cli\u003eKampmann U, Madsen LR, Skajaa GO, Iversen DS, Moeller N, Ovesen P. Gestational diabetes: A clinical update. World J Diabetes. 2015 Jul 25;6(8):1065-72. doi: 10.4239/wjd.v6.i8.1065. PMID: 26240703; PMCID: PMC4515446.\u003c/li\u003e\n\u003cli\u003eHyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: preeclampsia. Am J Obstet Gynecol 2010; 202: 255.e1-255.e7.\u003c/li\u003e\n\u003cli\u003eSeshiah V, Balaji V, Balaji MS, Paneerselvam A, Arthi T, Thamizharasi M, Datta M. Prevalence of gestational diabetes mellitus in South India (Tamil Nadu)\u0026mdash;a community based study. J Assoc Physicians India. 2008 May;56:329-33.\u003c/li\u003e\n\u003cli\u003ePedersen J. Weight and length at birth of infants of diabetic mothers. Acta Endocrinologica (Copenh) 1954; 16:330\u0026ndash;342.\u003c/li\u003e\n\u003cli\u003eAkanmode AM, Mahdy H. Macrosomia. [Updated 2022 Sep 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557577/?report=classic\u003c/li\u003e\n\u003cli\u003eAmerican Diabetes Association Professional Practice Committee. 15. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022 Jan 1;45(Suppl 1):S232-S243. doi: 10.2337/dc22-S015. PMID: 34964864.\u003c/li\u003e\n\u003cli\u003eWarner EA.,. Herold AH, Chapter 15 - Interpreting Laboratory Tests, Editor(s): Robert E. Rakel, David P. Rakel, Textbook of Family Medicine (Eighth Edition), W.B. Saunders, 2012, Pages 176-204, ISBN 9781437711608, https://doi.org/10.1016/B978-1-4377-1160-8.10015-6).\u003c/li\u003e\n\u003cli\u003eCatalano, P. M., Tyzbir, E. D., Roman, N. M., Amini, S. B. \u0026amp; Sims, E. A. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. Am. J. Obstet. Gynecol. 165, 1667\u0026ndash;1672 (1991).\u003c/li\u003e\n\u003cli\u003eCavaghan MK, Ehrmann DA, Polonsky KS. Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J Clin Invest. 2000 Aug;106(3):329-33. doi: 10.1172/JCI10761. PMID: 10930434; PMCID: PMC314336.).\u003c/li\u003e\n\u003cli\u003eMinschart C, Beunen K, Benhalima K. An Update on Screening Strategies for Gestational Diabetes Mellitus: A Narrative Review. Diabetes Metab Syndr Obes. 2021 Jul 5;14:3047-3076. doi: 10.2147/DMSO.S287121. PMID: 34262311; PMCID: PMC8273744.)\u003c/li\u003e\n\u003cli\u003eLurie S, Blickstein I. Age distribution of erythrocyte population in late pregnancy. Gynecol Obstet Investig. 1993;36(3):163\u0026ndash;5.\u003c/li\u003e\n\u003cli\u003eS\u0026aacute;nchez-Gonz\u0026aacute;lez, C.M., Castillo-Mora, A., Alvarado-Maldonado, I.N. et al. Reference intervals for hemoglobin A1c (HbA1c) in healthy Mexican pregnant women: a cross-sectional study. BMC Pregnancy Childbirth 18, 424 (2018). ( https://doi.org/10.1186/s12884-018-2057-x\u003c/li\u003e\n\u003cli\u003eP. Shobha,1 Sherly Mathen,1 and Joison Abraham1J Family Med Prim Care. 2016 Jul-Sep; 5(3): 646\u0026ndash;651. doi: 10.4103/2249 4863.197313)\u003c/li\u003e\n\u003cli\u003e(Hong JGS, Fadzleeyanna MYN, Omar SZ, Tan PC. HbA1c at term delivery and adverse pregnancy outcome. BMC Pregnancy Childbirth. 2022 Sep 3;22(1):679. doi: 10.1186/s12884-022-05000-7.)\u003c/li\u003e\n\u003cli\u003eLurie S, Danon D. Life span of erythrocytes in late pregnancy. Obstet Gynecol. 1992;80(1):123\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eKu\u0026uml;hl C, Holst J. Plasma glucagon and the insulin: glucagon ratio in gestational diabetes. Diabetes 1976;25(1):16\u0026ndash;23.\u003c/li\u003e\n\u003cli\u003eDamm, P., Kuhl, C., Bertelsen, A. \u0026amp; Molsted- Pedersen, L. Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus. Am. J. Obstet. Gynecol. 167, 607\u0026ndash;616 (1992).\u003c/li\u003e\n\u003cli\u003eLowe WL Jr, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, McCance D, Hamilton J, Nodzenski M, Talbot O, Brickman WJ, Clayton P, Ma RC, Tam WH, Dyer AR, Catalano PM, Lowe LP, Metzger BE; HAPO Follow-up Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care. 2019 Mar;42(3):372-380. doi: 10.2337/dc18-1646. Epub 2019 Jan 17. PMID: 30655380; PMCID: PMC6385693.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Type 2 Diabetes, Gestational diabetes, Glycated Haemoglobin, Delivery, Birth Weight","lastPublishedDoi":"10.21203/rs.3.rs-2998652/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2998652/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e:\u003c/strong\u003e There are no large studies to define the normal value of Glycated haemoglobin (HbA1c) measured in full term pregnant women.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResearch Design and Methods\u003c/strong\u003e\u003c/em\u003e: The study was conducted at three government hospitals in South India. Clinical data, maternal blood sample and foetal cord blood sample were collected from women admitted for safe confinement. Mean (\u003cstrong\u003e± \u003c/strong\u003eSD) of HbA1c in participants with no known diabetes (gestational or pregestational) or any complications (maternal or fetal) is described, 2.5\u003csup\u003eth\u003c/sup\u003e to 97.5\u003csup\u003eth\u003c/sup\u003e centile reference range was derived.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e:\u003c/strong\u003e\u0026nbsp; From 3 centres, 2004 women participated in the study. Data from 1039 participants who had no history of diabetes or any maternal or fetal complication were used to determine the reference range for HbA1c at term pregnancy. The mean HbA1c in subjects devoid of diabetes and its known complications was 5.0 (± 0.38) %.\u0026nbsp; The reference range for normal HbA1c at term in these women was found to be 4.3 to 5.9 %. Maternal HbA1c at term pregnancy in non-diabetic pregnant women is associated with pre pregnancy BMI, maternal age and 2-hour plasma glucose level of 2\u003csup\u003end\u003c/sup\u003e trimester oral glucose tolerance test (OGTT).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e \u003c/em\u003eThe mean HbA1c at term pregnancy in non-diabetic women admitted for safe confinement is 5.00 (± 0.38) %. An HbA1c of 5.9 % or more at term should be considered abnormal and women with such a value may be kept at a close surveillance for development of diabetes.\u003c/p\u003e","manuscriptTitle":"Reference Range for Glycated Haemoglobin in Full Term Antenatal Women- a Multicentric Cross Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-06-08 09:11:00","doi":"10.21203/rs.3.rs-2998652/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2023-06-18T18:07:04+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-06-06T20:04:03+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Archives of Gynecology and Obstetrics","date":"2023-06-05T19:44:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-06-01T14:02:06+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2023-05-31T07:55:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"f93565b0-955c-4677-ac1a-fd8ec5645829","owner":[],"postedDate":"June 8th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2023-10-09T15:08:03+00:00","versionOfRecord":{"articleIdentity":"rs-2998652","link":"https://doi.org/10.1007/s00404-023-07231-1","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2023-10-04 15:02:11","publishedOnDateReadable":"October 4th, 2023"},"versionCreatedAt":"2023-06-08 09:11:00","video":"","vorDoi":"10.1007/s00404-023-07231-1","vorDoiUrl":"https://doi.org/10.1007/s00404-023-07231-1","workflowStages":[]},"version":"v1","identity":"rs-2998652","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2998652","identity":"rs-2998652","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}