Papers

Association between outcome of pregnancy and glycaemic control in early pregnancy in type 1 diabetes: population based study

Rosemary Temple, consultant physicican ^a, Vivien Aldridge, diabetes nurse specialist ^a, Richard Greenwood, consultant physician ^a, Philip Heyburn, consultant physician ^a, Michael Sampson, consultant physician ^a, Katharine Stanley, consultant obstetrician ^b. 

^a Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospital NHS Trust, Norwich NR4 7UY, ^b East Anglia Centre for Fetal and Maternal Medicine, Norfolk and Norwich University Hospital NHS Trust

Correspondence to: R Temple rosemary.temple{at}Norfolk-norwich.thenhs.com

Recent studies of pregnancy in women in the United Kingdom with type 1 diabetes have shown a fourfold to tenfold increased risk of congenital malformation and a fivefold increased risk of perinatal mortality compared with non-diabetic women. ^{1 2} These studies used different measures of glycaemic control (concentrations of glycated haemoglobin and fructosamine) both within and between centres so no conclusions were reached about the relation between outcome and glycaemic control. We conducted a population study examining the relation between glycaemic control in early pregnancy and outcome of pregnancy in women with type 1 diabetes.

	Participants, methods, and results

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This observational study was carried out in a single centre in Norwich from January 1991 to December 2000. The resident population is 510 000 and mainly white. We defined adverse pregnancy outcome as spontaneous abortion (first or second trimester), major congenital malformation (potentially life threatening or associated with serious long term disability), stillbirth, or neonatal death. We measured glycated haemoglobin concentration at booking for prenatal care and then monthly using the Biomen 8140 method.

Women were divided into two groups according to their glycated haemoglobin concentration at booking; women with values <7.5% (mean of normal range plus 5 standard deviations) were defined as having fair control and those with values 7.5% were defined as having poor control. The study was approved by the local ethics committee.

We included only the first pregnancy for each woman during the study in the statistical analyses to avoid possible biases. We analysed data with SPSS software using Student's t test, Mann-Whitney U test, and ² test as appropriate. Fisher's exact test was used for small numbers.

There were 242 pregnancies in 158 women. Thirty two pregnancies had an adverse outcome, with 18 (7%) spontaneous abortions, eight (3%) major congenital malformations (six neural tube defects), four stillbirths, and two neonatal deaths.

We studied the relation between glycated haemoglobin concentration at booking and adverse outcome in the 158 first pregnancies. The table shows the patient characteristics and pregnancy outcomes. Adverse outcome was significantly higher in the poor control group than the fair control group (relative risk 4.3, 95% confidence interval 1.8 to 10). Compared with the fair control group, the poor control group had a fourfold increase in the spontaneous abortion rate (relative risk 4.0, 1.2 to 13.1) and ninefold increase in the congenital malformation rate (relative risk 9.2, 1.1 to 79.9). Perinatal mortality was higher in the poor control group than the fair control group (54/1000 births v 19/1000, relative risk 2.8, 0.41 to 19.4) but with the small numbers the difference was not significant. Perinatal mortality in the background population is 7.8/1000.

	Comment

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We found a significant relation between adverse outcome of pregnancy and poor glycaemic control in early pregnancy in women with type 1 diabetes. There was a fourfold increase in adverse outcome, a fourfold increase in spontaneous abortion, and a ninefold increase in major congenital malformation in women with a glycated haemoglobin concentration above 7.5% at booking. Our study has substantial advantages over earlier studies, being a complete, prospective, population based, single centre study analysing only one pregnancy per woman. It confirms earlier reports of increased risk of spontaneous abortion and malformation with poor glycaemic control in early pregnancy in women with type 1 diabetes.^3-5 Our findings suggest that good glycaemic control around the time of conception is necessary to optimise outcome of pregnancy in diabetic women. Diabetic women and their carers need to be advised of the risks and encouraged to optimise glycaemic control before and during pregnancy.

	Acknowledgments

Contributors: RCT had the key idea for the study. All authors contributed to development of the study. RCT and VJA collected data for the study and RCT did the data entry and statistical analysis and compiled the first draft of the manuscript. All authors contributed to interpretation of results and revised critically and approved the final report. We thank Moira Kelly and Lynettte Yaxley for help in initial development of the study and Michael Grande for statistical advice. RCT is guarantor for the study.

	Footnotes

Funding: None.

Competing interests: None declared.

	References

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1.	Casson IF, Clarke CA, Howard CV, McKendrick O, Pennycook S, Pharoah POD, et al. Outcomes of pregnancy in insulin dependent women: results of a five year cohort study. BMJ 1997; 315: 275-278[Abstract/Free Full Text].
2.	Hawthorne G, Robson S, Ryall EA, Sen D, Roberts SH, Ward Platt MP. Prospective population based survey of outcome of pregnancy in diabetic women: results of the northern diabetic pregnancy audit, 1994. BMJ 1997; 315: 279-281[Abstract/Free Full Text].
3.	Hanson U, Persson B, Thurnell S. Relationship between haemoglobin A1c in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden. Diabetologia 1990; 33: 100-104[CrossRef][Web of Science][Medline].
4.	Nielson GL, Sorensen PH, Nielson PH, Sabroe S, Olsen J. Glycosylated hemoglobin as predictor of adverse fetal outcome in type 1 diabetic pregnancies. Acta Diabetol 1997; 34: 217-222[CrossRef][Web of Science][Medline].
5.	Rosenn B, Miodovnik M, Combs CA, Khoury J, Siddiqi TA. Glycaemic thresholds for spontaneous abortions and congenital malformations in insulin-dependent diabetes mellitus. Obstet Gynecol 1994; 84: 515-520[Web of Science][Medline].

(Accepted 22 April 2002)