title: Course of HbA1c in non-diabetic pregnancy related to birth weight.
abstract: BACKGROUND
  Despite good glycaemic control (according to the internationally accepted level of HbA1c < 7% (53.0 mmol/mol)) the incidence of macrosomia in pregnant women with diabetes is still very high. We measured HbA1c levels in each of the three trimesters of pregnancy in a cohort of healthy women to determine whether the upper reference level for good glycaemic control in diabetic pregnant females should be lower than the internationally accepted level. Secondly we investigated whether changes in HbA1c values in the course of pregnancy are associated with birth weight.
  
  
  METHODS
  We determined HbA1c by high-performance liquid chromatography in 103 healthy pregnant women. The results were corrected with a method which was certified by the National Glycohaemoglobin Standardisation Program (NGSP) and standardised to the Diabetes Control and Complication trial reference assay. All women had a body mass index (BMI) < 30, none of the women had diabetes in the family in the first and/or second degree. The multiparous women had no history of macrosomia or small for gestational age infants.
  
  
  RESULTS
  In the first trimester mean ± SD (range) HbA1c (n=93) was 4.7 ± 1.25% (27.9 ± 13.7 mmol/mol) (3.9-5.4% (19.1-35.5 mmol/mol)), in the second trimester (n=86) 4.6 ± 1.33% (26.8 ± 14.6 mmol/mol) (3.7-5.7% (16.9-38.8 mmol/mol)) and in the third trimester (n=71) 4.9 ± 1.39% (30.1 ± 15.2 mmol/mol) (4.0-6.0% (20.2-42.1 mmol/mol)). The calculated upper reference HbA1c values for the three trimesters were 5.4, 5.5 and 5.8% (35.5, 36.6 and 39.9 mmol/mol), respectively, compared with 6.5% (47.5 mmol/mol) in non-pregnant women in our hospital. We found a significant correlation between the differences of the first and second trimester HbA1c values and the birth weight percentiles (r=-0.251; p=0.032). All 44 women with a decrease in the HbA1c value from the first to the second trimester had a birth weight percentile ≤ 90. In the 30 women with no change or an increase in the HbA1c value from the first to the second trimester there was no relation between HbA1c values and birth weight percentiles, but seven of the 30 (23.3%) had a birth weight percentile of > 90.
  
  
  CONCLUSIONS
  HbA1c is lower in all three trimesters of normal pregnancy compared with the level in non-pregnant women, and the change in HbA1c from the first to the second trimester predicts (the percentile of) birth weight. This could implicate that in order to prevent macrosomia in pregnant women with diabetes one should aim at lower HbA1c levels than the internationally accepted level, and at a decrease in HbA1c from the first to the second trimester.
authors: Department of Obstetrics, Leiden University Medical Centre, Leiden, the Netherlands.
authors: A R E
authors: AR
authors: Versantvoort
authors: J
authors: J
authors: van Roosmalen
authors: J K
authors: JK
authors: Radder
mesh_terms: D000328:Adult; D001724:Birth Weight; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy / Q000378:metabolism*; D011264:Pregnancy Trimesters / Q000378:metabolism; D012016:Reference Values
chemical_list: D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human