Tight controls lower birth defects for diabetic women
Undiagnosed GD may also play a role
A few weeks ago, a woman with a 22-year history of Type 1 diabetes and serious diabetic retinopathy gave birth to a healthy baby girl at Temple University Medical Center in Philadelphia.
Mom and baby are doing fine, thanks to the efforts of reproductive specialists there who helped the mother gain perfect glycemic control before she became pregnant and helped her to maintain that control along the rocky hormonal road of pregnancy.
Without such unrelenting attention, her chances of giving birth to a baby with a major birth defect were about one in 10. The experts have no wiggle room on this one: Pregnancy must be a carefully planned and orchestrated event for diabetic women.
"Hyperglycemia causes birth defects, so it’s critical, it’s pivotal, it’s absolutely essential that every diabetic woman of reproductive age must achieve excellent control," says fertility specialist E. Albert Reece, MD, Abraham Roth professor and chairman of the department of obstetrics, gynecology and reproductive sciences at Temple University in Philadelphia.
One in every 30 to 50 women of reproductive age has diabetes. National Diabetes Education Initiative figures released in 1995 said approximately 75% of them have Type 1 diabetes, but experts say those numbers may have changed with the rising rate of Type 2 diabetes in young people.
And major birth defects occur in 8% to 12% of women with either type of diabetes who do not participate in special preconception plans. This is four to six times the rate of nondiabetic populations. "That’s why clinicians must make it abundantly clear to women with diabetes: Do not become pregnant without careful advance planning," says Reece. When blood glucose is in normal ranges, birth defects are almost as rare as they are in the general population, so the bedrock of a planned pregnancy for a diabetic woman is glycemic control.
Tight control is de rigueur in disease management since the Diabetes Control and Complica tions Trial and the United Kingdom Prospective Diabetes Study, but for pregnant women, says Reece, it isn’t optional.
All diabetic women should be in excellent control, with fasting blood glucose from 70 mg/dL to 100 mg/dL. In addition, they should take 0.4 mg of folic acid a day, exercise regularly, and have retinopathy exams, according to guidelines from the American Diabetes Association. (See preconception planning outline, p. 17.)
If they are obese, the experts recommend delaying pregnancy until they have lost some weight. Women with impaired glucose tolerance (IGT) should also be counseled and their sugars aggressively treated, says Reece. "You never know when they go from IGT to diabetes. It could happen in a month or even less, and that could be the critical month for the fetus."
Need to get control before pregnancy
A woman with diabetes who becomes pregnant without excellent control poses enormous risks to her child. That’s because the most serious birth defects are genetically in place during the first seven to 10 weeks of pregnancy, often before a woman even knows she is pregnant.
"That’s when the embryo is most vulnerable," says Boris Kousseff, MD, professor of pediatrics, genetics and pathology at the University of South Florida in Tampa.
"Understanding helps you prevent birth defects," adds Reece.
The litany of possibilities for first trimester birth defects is grim. Kousseff’s studies have found the risks include:
• Central nervous system disorders:
— open neural tube defects;
— absent corpus callosum;
— microcephaly;
— macrocephaly;
— hydrocephaly.
• Cardiovascular system disorders:
— transposition of great vessels;
— cardiomegaly;
— hypoplastic left heart.
• Gastrointestinal malformations:
— pyloric stenosis;
— microcolon;
— duodenal and/or anorectal atresia;
— omphalo-enteric cyst/fistula.
• Urogenital malformations:
— renal agenesis;
— renal cysts;
— duplication of ureter;
— uterine agenesis;
— hypoplastic vagina;
— micropenis;
— ambiguous genitals.
• Musculoskeletal abnormalities:
— caudal dysgenesis/deficiency;
— craniosynostosis;
— costovertebral anomalies;
— limb reduction;
— cleft palate;
— club foot;
— polysyndactyly.
• Other abnormalities:
— sinus inversus;
— microphthalmia;
— colobomas of iris or chorioretina;
— cutaneous vascular dysplasia.
Poor control is also the cause of most stillbirths, Kousseff theorizes. "Pregnancy is a diabetogenic state, so we have to be very, very careful," he says to clinicians. "It’s a time of hormonal fluctuations that make control much more difficult. Your ears should perk up when you hear a patient has diabetes. . . . Adjust medications and act according to do whatever it takes to get her under better control."
A larger problem, Kousseff and Reece agree, is diabetic women who have unplanned pregnancies.
The solution: "Get them into the office and get them under control as quickly as possible," says Kousseff.
"Clinicians need to bring home to their patients the message of planned pregnancies and preconception counseling over and over," adds Reece.
Kousseff’s research has turned up some surprising evidence that runs counter to current medical opinion. His study, published in the American Journal of Medical Genetics (1999; 83:402-408), suggests that undiagnosed gestational diabetes may be the cause of many common idiopathic birth defects.
His 11-year study examined records of 22,100 families and evaluated 152 children of mothers with GD. Of those, 24 had no anomalies, 41 had another primary diagnosis to account for their malformations, and 87 had classic anomalies or structural defects seen in diabetic embryopathy.
Those abnormalities matched those seen in the children of diabetic mothers and, Kousseff says, corroborate animal studies that indicate the embryopathy seen in GD is similar to the complications children develop whose mothers had diabetes.
"Now we have to figure out a way to catch gestational diabetes in the first trimester before the embryopathy occurs," says Kousseff.
"We don’t look for it, so we don’t find it. What we are saying here is that the entire practice of obstetrics needs to be changed. Imagine how much flack we are going to get," he adds.
[Contact E. Albert Reece at (215) 707-3002 and Boris Kousseff at (813) 975-6900.]
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