Women with high levels of free triiodothyronine (fT3)—a thyroid hormone—early in pregnancy face an increased risk of developing gestational diabetes, according to researchers at the National Institutes of Health (NIH). 1
The study, which looked at a subset of women involved in a landmark NIH trial of 2,802 pregnant women of diverse ethnicities at 12 clinical centers across the US, casts doubt on the longstanding practice that discourages routine screening of pregnant women for thyroid disorders.1
“Our findings, in conjunction with previous evidence of thyroid-related adverse pregnancy outcomes, support the potential benefits of thyroid screening among pregnant women,” conclude the authors of the study, which was published in The Journal of Clinical Endocrinology & Metabolism.
Although thyroid problems are relatively common during pregnancy, their effects can be substantial. Risks include increased odds of miscarriage and preterm delivery, as well as adverse health outcomes for babies and children that range from thyroid disorders to issues with neurocognitive development.
And, as demonstrated by the NIH report, maternal thyroid dysfunction may also increase the likelihood of gestational diabetes (GDM), a condition that can cause significant and lasting harm to mother and child, and whose prevalence is rising steadily in the US and around the world.2
In this study, researchers at the National Institute of Child Health and Human Development (NICHD) compared the medical records of 107 women with GDM to those of 214 pregnant women without the condition. They found that women with the highest levels of free triiodothyronine (fT3) were more than four times as likely to develop GDM as those with the lowest levels of the thyroid hormone.3
And women with the highest fT3:fT4 ratios had a nearly 14-fold increased risk of GDM compared to those with the lowest ratios.1 “Higher fT3 levels may be an indicator of gestational diabetes risk starting early in pregnancy,” said Cuilin Zhang, MD, PhD, lead author of the study and senior investigator in the epidemiology branch at NICHD in Rockville, Maryland.
Still, Dr. Zhang acknowledges that more research on the connection between thyroid dysfunction and GDM is needed. “Data from more studies are needed to confirm our findings before routine, universal screening is recommended,” she said, adding that additional research on the effects in children is also warranted: “We need data on screening and offspring outcomes as well.”
To date, despite the possible harm to mothers and their children—and even in the midst of a burgeoning GDM epidemic— scant research has been carried out on the subject. “Although thyroid dysfunction in early pregnancy may have adverse effects on pregnancy outcome and offspring, few prospective studies have evaluated these effects,” wrote the authors of a separate 2016 study appearing in The Journal of Clinical Endocrinology and Metabolism, which found that low thyroid hormone levels in early pregnancy are a risk factor for GDM.4
Gestational diabetes, the most common obstetric metabolic disease, is generally defined as a glucose tolerance disorder that arises during pregnancy. It is estimated to affect 2-10% of pregnancies each year in the US, according to the Centers for Disease Control and Prevention; some estimates have put the number as high as 14% or more.5,6
GDM can have transient as well as lasting effects on both mother and child. Pregnant women who develop the condition are at elevated risk for high blood pressure, preeclampsia, preterm birth and delivery by C-section, often because of infant macrosomia, a condition in which the baby grows to be significantly larger than average. Babies born to mothers with GDM are prone to a variety of health problems including respiratory distress and neonatal hypoglycemia.5,7,8
Even after delivery, a GDM diagnosis may set mother and child on a path toward diabetes: Women whose pregnancies have been affected by GDM are more than 7 times as likely to develop type 2 diabetes (T2D) in the future, according to the American Diabetes Association. Once a woman has had gestational diabetes, the chances are 2 in 3 that the condition will return in future pregnancies. Babies subject to GDM go on to face increased risks of obesity, impaired glucose intolerance, T2D and other problems such as heart disease.9
Data have shown that the frequency of GDM often reflects the frequency of T2D in the underlying population and that the two are, in effect, fueling each other. “The prevalence of GDM is increasing alongside rising levels of obesity and inactivity, which can increase insulin resistance, mirroring the increasing rate of type 2 diabetes in the non-pregnant population,” noted a research review on the prevalence of GDM in the UK and Ireland published in 2016 by the National Institute for Health Research.10
Established risk factors for gestational diabetes include: Being overweight or gaining a lot of weight during pregnancy; having a family history of diabetes; being African American, Native American, Asian, Hispanic or Pacific Islander; having had gestational diabetes in the past; and being older than 25, according to the American Diabetes Association, although data have shown that in the US, rates of GDM are climbing more quickly among younger women than among older women.9,11
While those in the recent NIH study who went on to develop GDM after displaying thyroid dysfunction early in pregnancy were said to be generally healthy, with neither a high pre-pregnancy BMI nor a family or personal history of diabetes, thyroid dysfunction and GDM can be connected, and thyroid hormones are known to play an important role in glucose metabolism and homeostasis.
It can be difficult to predict who will develop thyroid disorders in pregnancy, but previous or current thyroid abnormalities, as well as a family history of thyroid problems, are known risk factors, Dr. Zhang said, adding that symptoms such as the following could indicate thyroid trouble: increased heart rate, high blood pressure, increased body temperature or feeling unusually warm with increased sweating, feeling agitated or nervous, feeling restless but also tired or weak, and having increased appetite accompanied by weight loss.
At the same time, though, symptoms of thyroid dysfunction can be similar to those seen in pregnancy. “Hypothyroidism is not always clear-cut, and many of the symptoms are associated with being pregnant, such as fatigue and weight gain,” said Amy Hess Fischl, MS, RDN, CDE, diabetes educator at the University of Chicago’s Kovler Diabetes Center. A blood test measuring thyroid hormone levels including TSH, free T4 and fT3, which isn’t always checked, is a more reliable indicator, she said.
In the absence of routine thyroid screening during pregnancy, the question of whether a woman should be tested early in pregnancy is an individual one. “This is really a discussion women should have with their healthcare provider,” Hess Fischl said, adding, however, that it's important to keep in mind that obesity, along with a history of prediabetes, high blood pressure, gestational diabetes, or a family history of type 2 diabetes, is fueling the bulk of the GDM epidemic, not thyroid problems.
If a thyroid screen performed early in the pregnancy shows dysfunction, it provides justification to test earlier than usual for gestational diabetes, Dr. Zhang said. GDM tests are typically performed at 24-28 weeks.
Seen from a broader perspective, the study’s evaluation of women early in pregnancy could have useful and important implications. “As a clinician, it raises an interesting concept by moving testing and evaluation into the first trimester,” said Alissa Dangel, MD, Obstetrician and Gynecologist at Tufts Medical Center in Boston. “Many diseases happen long before we see the impact, and this raises additional support for investigating things during the first trimester and addressing issues sooner.”
Treatment for gestational diabetes, which should begin as soon as the condition is diagnosed, aims to keep blood glucose levels equal to those of pregnant women without the condition, according to the American Diabetes Association. While many women are able to keep GDM in check through healthy eating and physical activity, those who have trouble may need insulin injections to help control blood sugar levels.6,7
It’s important to keep in mind that GDM is largely preventable. Experts say there are three things women can do to lessen their chances of developing the disease: maintain a healthy weight; follow the right diet, and stay active.
Finally, women who have had a pregnancy complicated by GDM should remain vigilant, taking steps to prevent T2D in themselves and their children. The National Institute of Diabetes and Digestive and Kidney Diseases recommends that women be tested for diabetes 6 to 12 weeks after delivery; provided blood glucose is shown to be normal, women should be checked every three years thereafter. Maintaining a healthy weight is paramount, ideally through regular physical activity (at least 30 minutes a day, five days a week) and healthy food choices. Breastfeeding is a great way to begin—it gives babies the right balance of nutrients and helps mothers to burn calories.12