Volume 36, Issue 8 pp. 1046-1053

Research: Pregnancy

Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial

J. M. Yamamoto,

J. M. Yamamoto

orcid.org/0000-0002-3556-0820

Departments of Medicine and Obstetrics and Gynaecology, University of Calgary, Calgary, Canada

Alberta Children's Hospital Research Institute, Calgary, Canada

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R. Corcoy,

R. Corcoy

orcid.org/0000-0001-5055-6814

Servei d'Endocrinologia i Nutrició, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

CIBER-BBN, Madrid, Spain

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L. E. Donovan,

L. E. Donovan

Departments of Medicine and Obstetrics and Gynaecology, University of Calgary, Calgary, Canada

Alberta Children's Hospital Research Institute, Calgary, Canada

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Z. A. Stewart,

Z. A. Stewart

Wellcome Trust–Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK

Department of Cardiovascular Sciences, University of Leicester, UK

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G. Tomlinson,

G. Tomlinson

Department of Medicine, University Health Network, Toronto, Canada

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K. Beardsall,

K. Beardsall

Department of Paediatrics, University of Cambridge, Cambridge, UK

Neonatal Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

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D. S. Feig,

D. S. Feig

orcid.org/0000-0001-8561-7584

Department of Medicine, University of Toronto, Toronto, Canada

Mount Sinai Hospital, Sinai Health System, Toronto, Canada

Lunenfeld-Tanenbaum Research Institute, Toronto, Canada

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H. R. Murphy,

Corresponding Author

H. R. Murphy

[email protected]

orcid.org/0000-0001-6876-8727

Wellcome Trust–Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK

Women's Health Academic Centre, Division of Women's and Children's Health, King's College London, London, UK

Norwich Medical School, Floor 2, Bob Champion Research and Education Building, James Watson Road, University of East Anglia, Norwich Research Park, Norwich, UK

Correspondenceto: H. R. Murphy.

E-mail: [email protected]

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on behalf of the CONCEPTT Collaborative Group*,

the CONCEPTT Collaborative Group*

"A complete list of the members of the CONCEPTT Collaborative Group can be found in the supporting material”Search for more papers by this author

J. M. Yamamoto,

J. M. Yamamoto

orcid.org/0000-0002-3556-0820

Departments of Medicine and Obstetrics and Gynaecology, University of Calgary, Calgary, Canada

Alberta Children's Hospital Research Institute, Calgary, Canada

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R. Corcoy,

R. Corcoy

orcid.org/0000-0001-5055-6814

Servei d'Endocrinologia i Nutrició, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

CIBER-BBN, Madrid, Spain

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L. E. Donovan,

L. E. Donovan

Departments of Medicine and Obstetrics and Gynaecology, University of Calgary, Calgary, Canada

Alberta Children's Hospital Research Institute, Calgary, Canada

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Z. A. Stewart,

Z. A. Stewart

Wellcome Trust–Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK

Department of Cardiovascular Sciences, University of Leicester, UK

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G. Tomlinson,

G. Tomlinson

Department of Medicine, University Health Network, Toronto, Canada

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K. Beardsall,

K. Beardsall

Department of Paediatrics, University of Cambridge, Cambridge, UK

Neonatal Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

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D. S. Feig,

D. S. Feig

orcid.org/0000-0001-8561-7584

Department of Medicine, University of Toronto, Toronto, Canada

Mount Sinai Hospital, Sinai Health System, Toronto, Canada

Lunenfeld-Tanenbaum Research Institute, Toronto, Canada

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H. R. Murphy,

Corresponding Author

H. R. Murphy

[email protected]

orcid.org/0000-0001-6876-8727

Wellcome Trust–Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK

Women's Health Academic Centre, Division of Women's and Children's Health, King's College London, London, UK

Norwich Medical School, Floor 2, Bob Champion Research and Education Building, James Watson Road, University of East Anglia, Norwich Research Park, Norwich, UK

Correspondenceto: H. R. Murphy.

E-mail: [email protected]

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on behalf of the CONCEPTT Collaborative Group*,

the CONCEPTT Collaborative Group*

"A complete list of the members of the CONCEPTT Collaborative Group can be found in the supporting material”Search for more papers by this author

First published: 20 May 2019

https://doi.org/10.1111/dme.13988

Citations: 55

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Abstract

Aims

To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants.

Methods

A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by continuous glucose monitoring measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration < 2.6 mmol/l and requiring intravenous dextrose.

Results

Neonatal hypoglycaemia occurred in 57/225 (25.3%) infants, 21 (15%) term and 36 (40%) preterm neonates. During the second and third trimesters, mothers of infants with neonatal hypoglycaemia had higher HbA_1c [48 ± 7 (6.6 ± 0.6) vs. 45 ± 7 (6.2 ± 0.6); P = 0.0009 and 50 ± 7 (6.7 ± 0.6) vs. 46 ± 7 (6.3 ± 0.6); P = 0.0001] and lower continuous glucose monitoring time-in-range (46% vs. 53%; P = 0.004 and 60% vs. 66%; P = 0.03). Neonates with hypoglycaemia had higher cord blood C-peptide concentrations [1416 (834, 2757) vs. 662 (417, 1086) pmol/l; P < 0.00001], birthweight > 97.7th centile (63% vs. 34%; P < 0.0001) and skinfold thickness (P ≤ 0.02). Intrapartum continuous glucose monitoring was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia.

Conclusions

Modest increments in continuous glucose monitoring time-in-target (5–7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum continuous glucose monitoring data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period.

Supporting Information

References

1Yamamoto JM, Benham J, Mohammad K, Donovan LE, Wood S. Intrapartum glycaemic control and neonatal hypoglycaemia in pregnancies complicated by diabetes: a systematic review. Diabet Med 2018; 35: 173–183.
10.1111/dme.13546
CAS PubMed Web of Science® Google Scholar
2Shah R, Harding J, Brown J, McKinlay C. Neonatal glycaemia and neurodevelopmental outcomes: a systematic review and meta-analysis. Neonatology 2018; 115: 116–126.
10.1159/000492859
PubMed Web of Science® Google Scholar
3Evers IM, de Valk HW, Visser GH. Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ 2004; 328: 915.
10.1136/bmj.38043.583160.EE
PubMed Web of Science® Google Scholar
4Dashora U, Murphy HR, Temple RC, Stanley KP, Castro E, George S et al. Managing hyperglycaemia during antenatal steroid administration, labour and birth in pregnant women with diabetes. Diabet Med 2018; 35: 1005–1010.
10.1111/dme.13674
CAS PubMed Web of Science® Google Scholar
5 National Institute for Health and Care Excellence. Diabetes in pregnancy: management from preconception to the postnatal period 25 February 2015. Available at https://www.nice.org.uk/guidance/ng3.
Google Scholar
6 Diabetes Canada Clinical Practice Guidelines Expert Committee, Feig DS, Berger H, Donovan L, Godbout A, Kader T et al. Diabetes and Pregnancy. Can J Diabetes 2018; 42(Suppl 1): S255–S282.
PubMed Web of Science® Google Scholar
7Levy N, Hall GM. National guidance contributes to the high incidence of inpatient hypoglycaemia. Diabet Med 2019; 36: 120–121.
10.1111/dme.13795
CAS PubMed Web of Science® Google Scholar
8Modi A, Levy N, Hall GM. ‘Primum non nocere’ (first do no harm). Intrapartum glycaemic control and neonatal hypoglycaemia. Diabet Med 2018; 35: 1130–1131.
10.1111/dme.13659
CAS PubMed Web of Science® Google Scholar
9Yamamoto JM, Murphy HR. Inpatient hypoglycaemia; should we should we focus on the guidelines, the targets or our tools? Diabet Med 2019; 36: 122–123.
10.1111/dme.13814
CAS PubMed Web of Science® Google Scholar
10Metzger BE, Persson B, Lowe LP, Dyer AR, Cruickshank JK, Deerochanawong C et al. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics 2010; 126: e1545–e1552.
10.1542/peds.2009-2257
PubMed Web of Science® Google Scholar
11Maresh MJ, Holmes VA, Patterson CC, Young IS, Pearson DW, Walker JD et al. Glycemic targets in the second and third trimester of pregnancy for women with type 1 diabetes. Diabetes Care 2015; 38: 34–42.
10.2337/dc14-1755
PubMed Web of Science® Google Scholar
12Feig DS, Donovan LE, Corcoy R, Murphy KE, Amiel SA, Hunt KF et al. Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet 2017; 390: 2347–2359.
10.1016/S0140-6736(17)32400-5
CAS PubMed Web of Science® Google Scholar
13Stewart ZA, Yamamoto JM, Wilinska ME, Hartnell S, Farrington C, Hovorka R et al. Adaptability of closed loop during labor, delivery, and postpartum: a secondary analysis of data from two randomized crossover trials in type 1 diabetes pregnancy. Diabetes Technol Ther 2018; 20: 501–505.
10.1089/dia.2018.0060
CAS PubMed Web of Science® Google Scholar
14Stewart ZA, Thomson L, Murphy HR, Beardsall K. A feasibility study of paired continuous glucose monitoring intrapartum and in the newborn in pregnancies complicated by type 1 diabetes. Diabetes Technol Ther 2019; 21: 20–27.
10.1089/dia.2018.0221
CAS PubMed Web of Science® Google Scholar
15Gardosi J, Francis A. Gestation network. Customised weight centile calculator. GROW v 8.1 UK. Available at http://www.gestation.net/birthweightcentiles/centile_object.htm. Last accessed 7 July 2017.
Google Scholar
16 Institute of Medicine and National Research Council of the National Academies. Weight gain during pregnancy: reexamining the guidelines 2009. Available at http://www.nationalacademies.org/hmd/~/media/Files/Report Files/2009/Weight-Gain-During-Pregnancy-Reexamining-the-Guidelines/Report Brief - Weight Gain During Pregnancy.pdf. Last accessed 11 January 2019.
Google Scholar
17Joshi T, Oldmeadow C, Attia J, Wynne K. The duration of intrapartum maternal hyperglycaemia predicts neonatal hypoglycaemia in women with pre-existing diabetes. Diabet Med 2017; 34: 725–731.
10.1111/dme.13337
CAS PubMed Web of Science® Google Scholar
18Stewart ZA, Wilinska ME, Hartnell S, Temple RC, Rayman G, Stanley KP et al. Closed-loop insulin delivery during pregnancy in women with type 1 diabetes. N Engl J Med 2016; 375: 644–654.
10.1056/NEJMoa1602494
CAS PubMed Web of Science® Google Scholar
19Stewart ZA, Wilinska ME, Hartnell S, O'Neil LK, Rayman G, Scott EM et al. Day-and-night closed-loop insulin delivery in a broad population of pregnant women with type 1 diabetes: a randomized controlled crossover trial. Diabetes Care 2018; 41: 1391–1399.
10.2337/dc17-2534
CAS PubMed Web of Science® Google Scholar
20Drever E, Tomlinson G, Bai AD, Feig DS. Insulin pump use compared with intravenous insulin during labour and delivery: the INSPIRED observational cohort study. Diabet Med 2016; 33: 1253–1259.
10.1111/dme.13106
CAS PubMed Web of Science® Google Scholar
21Yamamoto JM, Kallas-Koeman MM, Butalia S, Lodha AK, Donovan LE. Large-for-gestational-age (LGA) neonate predicts a 2.5-fold increased odds of neonatal hypoglycaemia in women with type 1 diabetes. Diabetes Metab Res Rev 2017; 33. https://doi.org/10.1002/dmrr.2824
10.1002/dmrr.2824
PubMed Web of Science® Google Scholar
22Cordua S, Secher AL, Ringholm L, Damm P, Mathiesen ER. Real-time continuous glucose monitoring during labour and delivery in women with Type 1 diabetes - observations from a randomized controlled trial. Diabet Med 2013; 30: 1374–1381.
10.1111/dme.12246
CAS PubMed Web of Science® Google Scholar
23 Group HSCR, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991–2002.
10.1056/NEJMoa0707943
PubMed Web of Science® Google Scholar
24Hegarty JE, Harding JE, Gamble GD, Crowther CA, Edlin R, Alsweiler JM. Prophylactic oral dextrose gel for newborn babies at risk of neonatal hypoglycaemia: a randomised controlled dose-finding trial (the Pre-hPOD Study). PLoS Med 2016; 13: e1002155.
10.1371/journal.pmed.1002155
PubMed Web of Science® Google Scholar
25Stenninger E, Lindqvist A, Aman J, Ostlund I, Schvarcz E. Continuous subcutaneous glucose monitoring system in diabetic mothers during labour and postnatal glucose adaptation of their infants. Diabet Med 2008; 25: 450–454.
10.1111/j.1464-5491.2008.02416.x
CAS PubMed Web of Science® Google Scholar
26Feig DS, Corcoy R, Donovan LE, Murphy KE, Barrett JFR, Sanchez JJ et al. Pumps or multiple daily injections in pregnancy involving type 1 diabetes: a prespecified analysis of the CONCEPTT randomized trial. Diabetes Care 2018; 41: 2471–2479.
10.2337/dc18-1437
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume36, Issue8

Special issue on Health Economics

August 2019

Pages 1046-1053

Filename	Description
dme13988-sup-0001-TableS1-S2.docxWord document, 18.7 KB	Table S1. Differences in cord blood C-peptide concentration (pmol/l) by neonatal and maternal characteristics. Table S2. Results of univariate logistic regression for neonatal hypoglycaemia.
dme13988-sup-0002-Supinfo.docxWord document, 21.1 KB

Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial

Abstract

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Supporting Information

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Citing Literature

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Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial

Abstract

Aims

Methods

Results

Conclusions

Supporting Information

References

Citing Literature

References

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