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Glycosylated haemoglobin as an indicator of diabetes control in pregnancy: A 10-year review of the relationship between HbA1c trends and delivery outcome in type I and type II diabetes

Published:December 07, 2022DOI:https://doi.org/10.1016/j.ejogrb.2022.12.007

      Abstract

      Background

      Pregestational diabetes mellitus (PGDM) confers an increased risk of adverse maternal and neonatal outcomes [1,2]. Glycaemic control in the medium and long term is commonly evaluated by examining glycosylated haemoglobin (HbA1c) levels. However, the value of HbA1c in pregnancy may be diminished by increased level of red cell turnover characteristic of pregnancy [
      • Lurie S.
      • Mamet Y.
      Red blood cell survival and kinetics during pregnancy.
      ,
      • Lurie S.
      Age distribution of erythrocyte population in late pregnancy.
      ]. We sought to examine the impact of HbA1c in the first trimester and pre-delivery, and the within-patient change throughout gestation on mode of delivery and birthweight in pregnancies complicated by a pre-pregnancy diagnosis of type I or type II diabetes.

      Methods

      A 10-year consecutive cohort of pregnancies complicated by PGDM, from Jan 2010 until Dec 2019, was examined for HbA1c data in the first trimester and within 6 weeks of delivery. Perinatal outcome data, including gestational age at delivery, mode of delivery and birthweight centile, were obtained from hospital records. The Spearman Rank correlation was used to correlate HcA1c levels in the first trimester with birthweight centiles. Non-parametric summaries and rank-based tests, Signed-rank test and Kruskal-Wallis test, were used to compare Hba1c levels.

      Results

      During the 10-year study period, a consecutive cohort of 396 pregnancies that attained a viable gestational age (>24 weeks’ gestation) and complicated by pregestational diabetes was identified; representing 81 % of the population of pregestational diabetic pregnancies managed by this service during the study period. The median [IQR] HbA1c levels (mmol/mol) in the first trimester, pre-delivery and the differential across gestation were 51 [19] mmol/mol, 43 [11] mmol/mol and −8 [13] mmol/mol, respectively. A statistically significant reduction in HbA1c levels throughout gestation was observed (p < 0.001). The median [IQR] birthweight centile was 69 [50 – 96]. The distributions in HbA1c levels and birthweight centiles were heavily skewed. No correlation was identified between HbA1c levels and mode of delivery.

      Conclusion

      Neither baseline HbA1c levels, pre-delivery values, nor trends across gestation appear to impact birthweight centile or mode of delivery in PGDM. While optimising glycaemic control can affect the long term health of the mother, these indices cannot be relied upon to reflect the impact of glycaemic control on fetal growth aberrations that influence mode of delivery.

      Abbreviations:

      ACOG (American College of Obstetricians and Gynecologists), HbA1c (glycosylated haemoglobin), ICU (intensive care unit), IQR (interquartile range), NICE (National Institute for Health and Care Excellence), PGDM (pregestational diabetes mellitus), WHO (World Health Organization)

      Keywords

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      References:

        • McCance D.R.
        • Casey C.
        Type 1 Diabetes in Pregnancy.
        Endocrinol Metab Clin North Am. 2019; 48: 495-509
        • Kapur A.
        • McIntyre H.D.
        • Hod M.
        Type 2 Diabetes in Pregnancy.
        Endocrinol Metab Clin North Am. 2019; 48: 511-531
        • Lurie S.
        • Mamet Y.
        Red blood cell survival and kinetics during pregnancy.
        Eur J Obstet Gynecol Reprod Biol. 2000; 93: 185-192
        • Lurie S.
        Age distribution of erythrocyte population in late pregnancy.
        Gynecol Obstet Invest. 1990; 30: 147-149
        • Murphy H.R.
        • Howgate C.
        • O'Keefe J.
        • Myers J.
        • Morgan M.
        • Coleman M.A.
        • et al.
        Characteristics and outcomes of pregnant women with type 1 or type 2 diabetes: a 5-year national population-based cohort study.
        Lancet Diabetes Endocrinol. 2021; 9: 153-164
      1. Federational ID. 1. International Diabetes Federational : IDF Atlas.9th Edition2019. IDF; 2019.

      2. Excellence NNIfHaC. Diabetes in Pregnancy: Management of Diabetes and Its Complications from Preconception to the Postnatal Period. London: National Collaborating Centre for Ws, Children's H. National Institute for Health and Care Excellence; 2015 2015. Contract No.: NG63.

        • Lowe L.P.
        • Metzger B.E.
        • Dyer A.R.
        • Lowe J.
        • McCance D.R.
        • Lappin T.R.
        • et al.
        Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes.
        Diabetes Care. 2012; 35: 574-580
        • Inkster M.E.
        • Fahey T.P.
        • Donnan P.T.
        • Leese G.P.
        • Mires G.J.
        • Murphy D.J.
        Poor glycated haemoglobin control and adverse pregnancy outcomes in type 1 and type 2 diabetes mellitus: Systematic review of observational studies.
        BMC Pregnancy Childbirth. 2006; 6: 30
      3. WHO Guidelines Approved by the Guidelines Review Committee. Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus: Abbreviated Report of a WHO Consultation. Geneva: World Health Organization Copyright © World Health Organization 2011.; 2011.

        • English E.
        • Idris I.
        • Smith G.
        • Dhatariya K.
        • Kilpatrick E.S.
        • John W.G.
        The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review.
        Diabetologia. 2015; 58: 1409-1421
        • Paliogiannis P.
        • Zinellu A.
        • Mangoni A.A.
        • Capobianco G.
        • Dessole S.
        • Cherchi P.L.
        • et al.
        Red blood cell distribution width in pregnancy: a systematic review.
        Biochem Med (Zagreb). 2018; 28030502
      4. Organization WH. https://srhr.org [Website]. WHO; 2022 [cited 2022 7/6/22]. Available from: https://srhr.org.

        • McLeod L.
        • Ray J.G.
        Prevention and detection of diabetic embryopathy.
        Community Genet. 2002; 5: 33-39
        • Macintosh M.C.
        • Fleming K.M.
        • Bailey J.A.
        • Doyle P.
        • Modder J.
        • Acolet D.
        • et al.
        Perinatal mortality and congenital anomalies in babies of women with type 1 or type 2 diabetes in England, Wales, and Northern Ireland: population based study.
        BMJ. 2006; 333: 177
        • Kallem V.R.
        • Pandita A.
        • Pillai A.
        Infant of diabetic mother: what one needs to know?.
        J Matern Fetal Neonatal Med. 2020; 33: 482-492
        • Hanson U.
        • Persson B.
        Outcome of pregnancies complicated by type 1 insulin-dependent diabetes in Sweden: acute pregnancy complications, neonatal mortality and morbidity.
        Am J Perinatol. 1993; 10: 330-333
        • Dunne F.P.
        • Avalos G.
        • Durkan M.
        • Mitchell Y.
        • Gallacher T.
        • Keenan M.
        • et al.
        ATLANTIC DIP: pregnancy outcome for women with pregestational diabetes along the Irish Atlantic seaboard.
        Diabetes Care. 2009; 32: 1205-1206
        • Colstrup M.
        • Mathiesen E.R.
        • Damm P.
        • Jensen D.M.
        • Ringholm L.
        Pregnancy in women with type 1 diabetes: have the goals of St. Vincent declaration been met concerning foetal and neonatal complications?.
        J Matern Fetal Neonatal Med. 2013; 26: 1682-1686
        • Balsells M.
        • García-Patterson A.
        • Gich I.
        • Corcoy R.
        Maternal and fetal outcome in women with type 2 versus type 1 diabetes mellitus: a systematic review and metaanalysis.
        J Clin Endocrinol Metab. 2009; 94: 4284-4291
        • Middleton P.
        • Crowther C.A.
        • Simmonds L.
        Different intensities of glycaemic control for pregnant women with pre-existing diabetes.
        Cochrane Database Syst Rev. 2012; 8 (Cd008540)
        • Bashir M.
        • Dabbous Z.
        • Baagar K.
        • Elkhatib F.
        • Ibrahim A.
        • Brich S.A.
        • et al.
        Type 2 diabetes mellitus in pregnancy: The impact of maternal weight and early glycaemic control on outcomes.
        Eur J Obstet Gynecol Reprod Biol. 2019; 233: 53-57
        • Ladfors L.
        • Shaat N.
        • Wiberg N.
        • Katasarou A.
        • Berntorp K.
        • Kristensen K.
        Fetal overgrowth in women with type 1 and type 2 diabetes mellitus.
        PLoS One. 2017; 12: e0187917
        • Tennant P.W.
        • Glinianaia S.V.
        • Bilous R.W.
        • Rankin J.
        • Bell R.
        Pre-existing diabetes, maternal glycated haemoglobin, and the risks of fetal and infant death: a population-based study.
        Diabetologia. 2014; 57: 285-294
        • Sibai B.M.
        • Caritis S.N.
        • Hauth J.C.
        • MacPherson C.
        • VanDorsten J.P.
        • Klebanoff M.
        • et al.
        Preterm delivery in women with pregestational diabetes mellitus or chronic hypertension relative to women with uncomplicated pregnancies. The National institute of Child health and Human Development Maternal- Fetal Medicine Units Network.
        Am J Obstet Gynecol. 2000; 183: 1520-1524
        • Garner P.
        Type I diabetes mellitus and pregnancy.
        Lancet. 1995; 346: 157-161
      5. EA Reece DC SG. Diabetes in women: adolescence, pregnancy, and menopause. 3rd ed: Wolters Kluwer; 2004 2004.

        • Penno G.
        • Solini A.
        • Bonora E.
        • Fondelli C.
        • Orsi E.
        • Zerbini G.
        • et al.
        HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study.
        Diabetes Care. 2013; 36: 2301-2310
        • Lepercq J.
        • Coste J.
        • Theau A.
        • Dubois-Laforgue D.
        • Timsit J.
        Factors associated with preterm delivery in women with type 1 diabetes: a cohort study.
        Diabetes Care. 2004; 27: 2824-2828
        • Spotti D.
        Pregnancy in women with diabetic nephropathy.
        J Nephrol. 2019; 32: 379-388
      6. ACOG Practice Bulletin No. 201: Pregestational Diabetes Mellitus. Obstetrics and gynecology. 2018;132(6):e228-e48.

        • Lurie S.
        Changes in age distribution of erythrocytes during pregnancy: a longitudinal study.
        Gynecol Obstet Invest. 1993; 36: 141-144
        • Howells M.R.
        • Jones S.E.
        • Napier J.A.
        • Saunders K.
        • Cavill I.
        Erythropoiesis in pregnancy.
        Br J Haematol. 1986; 64: 595-599
        • Stohlman Jr., F.
        Humoral regulation of erythropoiesis. VII. Shortened survival of erythrocytes produced by erythropoietine or severe anemia.
        Proc Soc Exp Biol Med. 1961; 107: 884-887
        • Peck T.M.
        • Arias F.
        Hematologic changes associated with pregnancy.
        Clin Obstet Gynecol. 1979; 22: 785-798