Diabetes 'increases birth defect risk'

“Diabetic mothers-to-be have high risk of giving birth to children with congenital abnormality,” The Guardian said today.

The news is based on UK research that compared the rates of birth defects in women with and without diabetes. It found that about 7% of pregnancies in women with diabetes were affected by birth defects that were not caused by problems with the number or structure of the chromosomes. This was 3.8 times higher than the rate in women without diabetes. The study also found that women who have worse control over their blood sugar around the time of conception were at greater risk.

It has been known for some time that diabetes in pregnancy is associated with a higher risk of various complications, and this large study provides further evidence on the link between diabetes and birth defects. UK medical guidance already addresses this risk, and recommends that from adolescence onwards, women with diabetes should be routinely given information on the importance of planning any future pregnancies and on getting specialist care and advice when they decide to have a baby. Women with very poor control of their diabetes are also advised not to become pregnant until their blood sugar control has improved.

Women with diabetes are likely to already be aware of these risks. However, this study provides another reminder that diabetic women who are thinking about becoming pregnant should discuss their options with their doctor first.

Where did the story come from?

The study was carried out by researchers from Newcastle University, the Regional Maternity Survey Office in Newcastle, and the South Tees NHS Trust. It was funded by Diabetes UK, the Department of Health, the Healthcare Quality Improvement Partnership, and the four primary care trusts in northeast England. The study was published in the peer-reviewed medical journal Diabetologica.

The Guardian provided good coverage of this story, and put it into context of what is already known about how a woman’s diabetes can affect her pregnancy. The shorter news article in The Independent covered the basics of the story, but could be taken to suggest that the study was the first to discover the risk. In fact, this risk has been known for some time.

What kind of research was this?

Pregnancies in women with diabetes are already known to be at increased risk of various complications, including stillbirth and birth abnormalities. This cohort study aimed to clarify the extent to which diabetes increases the risk of major birth defects, and how this risk is affected by other factors such as maternal age, smoking and socioeconomic status.

A cohort study is the best way to assess this type of question, which could not be answered by a randomised controlled trial. Clearly, women with diabetes differ from women without diabetes in terms of their medical condition, but the two groups may also vary in other ways. It is important that researchers take such differences into account during their analyses.

What did the research involve?

The researchers used data collected on approximately 401,000 pregnancies that occurred between 1996 and 2008. They looked at whether mothers had diabetes, and if their babies had birth defects. The researchers then looked at whether birth defects were more common in babies born to mothers with diabetes.

The researchers obtained their data from the north of England, collected by the Northern Diabetes in Pregnancy Survey (NorDIP) and the Northern Congenital Abnormality Survey (NorCAS). NorDIP contains data on pregnancies in women diagnosed with diabetes at least six months before conception. It does not include women with gestational diabetes (diabetes that only occurs in pregnancy).

The study excluded multiple pregnancies (twins or triplets) and included pregnancies where the baby died at or before 20 weeks of pregnancy, or where the pregnancy was terminated due to a foetal abnormality. It included all eligible births in the study region in the study period. Abnormalities were classified according to standard definitions, and could be recorded up to the age of 12 years. Some birth abnormalities are caused by problems with the number or structure of chromosomes (the structures in the cell that contain our DNA). These abnormalities were looked at separately.

The researchers looked at the effect of various diabetes-related factors including how well the woman’s blood sugar was controlled at around the time of conception, whether she had type 1 or type 2 diabetes, and diabetes complications diagnosed before pregnancy (such as kidney or eye problems). They also looked at the effect of maternal age at the time of delivery, gestational age at time of delivery, folic acid intake before conception, foetal gender, number of previous babies, pre-pregnancy care, and smoking during pregnancy. Any significant factors were taken into account in the analyses to determine the effect of the individual factors.

What were the basic results?

Among the 401,149 pregnancies, 1,677 were in women with pre-existing diabetes. Most of these women (78.4%) had type 1 diabetes. Overall, 9,488 pregnancies were affected by at least one major birth defect, and 129 of these were in women with diabetes.

In women with diabetes, 71.6 per 1,000 pregnancies were affected by non-chromosomal major birth defects. This was 3.8 times higher than the rate in women without diabetes. Women with diabetes did not have an increased risk of having a baby with birth defects caused by chromosomal abnormalities.

When looking at specific factors linked to the risk of birth defects, the researchers found that women who had worse blood sugar control at around the time of conception were at increased risk of having babies with birth defects. Blood sugar control is often calculated using a measure called HbA1c level. This represents the levels of haemoglobin in the blood with a sugar molecule attached.

Doctors generally try to keep HbA1c levels below 7%. In this study, each increase of 1% in HbA1c over 6.3% was associated with a 30% increase in the odds of birth defects (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.2 to 1.4). Women who already had kidney problems as a result of their diabetes also had an increased risk of having babies with birth defects (OR 2.5, 95% CI 1.1 to 5.3).

Some other factors were associated with an increased risk of birth abnormalities when looked at in isolation, such as low intake of folic acid and lower socioeconomic status. However, once all other factors were taken into account, these were no longer statistically significant.

How did the researchers interpret the results?

The researchers concluded that the main modifiable factor associated with birth defects in women with diabetes is their blood sugar control at around the time of conception. They say that the association with diabetes-related kidney problems needs to be studied further.

Conclusion

This study supports the existence of an association between maternal diabetes and increased risk of birth abnormalities, and helps quantify the size of the association. The study’s strengths include its large size and ability to include the entire population in the study area. However, there are a number of points to note:

• The researchers took into account various factors that could influence the results. However, as with all studies of this type, it is possible that unknown or unmeasured factors, other than maternal diabetes, could have affected the risk of birth defects.
• From this study we cannot say what effect diabetes arising in pregnancy (gestational diabetes) might have on risk of birth defects, as these women were not included in this analysis.
• The study relied on registry-recorded data, and there may be some omissions or inaccuracies in this data. That said, the registries used standard systems for recording data that should increase the reliability of their records.

The link between maternal diabetes and an increased risk of birth defects is already established. Better blood sugar control can help reduce this risk, although it cannot eliminate the risk completely. The National Institute for Health and Clinical Excellence (NICE) recommends that women with diabetes who are trying to conceive should aim for an HbA1c of less than 6.1%, if this can be achieved safely. It also suggests that women with an HbA1c of over 10% should avoid becoming pregnant.

NICE also recommends that:

• Women with diabetes who are planning to become pregnant should be informed of the need to establish good blood sugar control before conception, and that maintaining it throughout pregnancy will reduce the risk of miscarriage, birth defects, stillbirth and neonatal death. They also say that it is important for healthcare providers to explain that these risks can be reduced, but not eliminated entirely.
• The importance of avoiding unplanned pregnancy should be an essential component of diabetes education from adolescence onwards for women with diabetes.
• Women with diabetes who are planning to become pregnant should be offered pre-conception care and advice before they stop using contraception.

This study supports the need for specialist information and planning for pregnancy in women with diabetes. Women with diabetes who are thinking about becoming pregnant should discuss this with their doctor if they have not already done so.