Screen early in pregnancy for gestational diabetes, new Lancet series urges

Gestational diabetes affects one in seven expecting women globally and rates of this troubling condition are rising. Blood glucose levels that become elevated for the first time during pregnancy can lead to severe complications, such as preeclampsia, and increase the risk of stillbirth. And while the condition typically resolves after birth, it is linked to a tenfold increase in the risk of developing type 2 diabetes, along with risks for the child including obesity, cardiovascular disease, and neurodevelopmental disorders. 

Gestational diabetes has long been diagnosed between weeks 24 and 28 of pregnancy. But a recent randomized control study called Treatment of Booking Gestational Diabetes Mellitus, or TOBOGM, which was started in 2018 and whose results were published earlier this year, found that treating gestational diabetes before week 20 reduced the risk of severe perinatal complications, including preterm birth, low birthweight, stillbirth, and respiratory distress. The early treatment was most effective in women who had high blood glucose levels after an oral glucose tolerance test, which measures how well the body can metabolize the sugar in a very sweet, Gatorade-like drink. 

In some cases, women are tested early when they have risk factors such as high blood pressure, obesity, or previous gestational diabetes. But between 30% and 70% of all gestational diabetes cases could be detected much earlier — by the twentieth week of a pregnancy, according to a series published on Thursday in The Lancet by an international group of gestational diabetes researchers. 

The series comprises three papers: The first focuses on the physiological characteristics associated with gestational diabetes before, during, and after pregnancy; the second examines the prevalence of the condition; and the third calls for shifting the clinical perspective on gestational diabetes, thinking of it as a “life course” disease — one that will affect patients long term, rather than for the duration of a pregnancy.  

The authors, who are presenting their findings this week at the American Diabetes Association conference in Orlando, have specific recommendations for screening: They’re calling for early testing between10 and 14 weeks of pregnancy to catch cases of early gestational diabetes, followed by another screen at 24 to 28 weeks to identify cases that develop later. 

“At the moment, the perspective is very much that most gestational diabetes pops up at 24 to 28 weeks, and it goes away [after birth]. And then type 2 diabetes develops after that, and the baby is affected from 24 to 28 weeks until birth,” said David Simmons, an endocrinologist at Western Sydney University and the series’ lead author. “But the evidence is clear that even by 24 to 28 weeks, many babies are already large, and already affected by hyperglycemia,” said Simmons, who was also the lead author of the TOBOGM study.

This means thinking about gestational diabetes not only during pregnancy, but before and after. “It’s really important that we start thinking about how we prevent [gestational diabetes] before pregnancy, because actually that’s where a lot of the risk is,” said Simmons. After recommended screenings and treatment, “then we follow women and the offspring afterwards, forever trying to help them prevent their risk of type 2 diabetes,” he said. 

Better diagnosis is especially needed as rates of metabolic disease soar; many expectant women begin a pregnancy with undetected high glucose levels that can harm the baby as well as pose a risk to their pregnancy. Rates of detected gestational diabetes have gone up significantly in the last 20 years, doubling or more in a number of countries; rates range from 7% in North America to 28% in the Middle East and North Africa. 

Different detection methods make direct comparisons between countries challenging — which is why the series authors don’t  recommend earlier testing alone. They also propose bringing testing standards in line across the world. “The current difficulty is that many different screening and diagnostic approaches to detecting gestational diabetes exist — universal versus selective screening, one-step versus two-step testing, different glucose loads and duration of the oral glucose tolerance test,” said Arianne Sweeting, an endocrinologist at the University of Sydney and one of the series authors.

In some countries, including the U.S., pregnant people have their blood glucose measured without fasting, an hour after drinking 50 grams of glucose; they do a fasting test with 100g of glucose only if they first show signs of glucose resistance. Other countries, including Australia, do a single fasting test with 75g of glucose. This, Sweeting said, is due to the underlying intention of the test: In the U.S., the goal is to identify future risk of type 2 diabetes, while the WHO-recommended 75g test was based on a study that linked test results with perinatal outcomes.

The series authors recommend a universal fasting 75g test, twice in a pregnancy: The 50g test risks missing too many cases, they say, and the 100g test can be challenging for the patient, especially earlier in pregnancy when high levels of glucose can lead to vomiting. Further, said Simmons, studies have shown that many women simply don’t follow up for a second test. “Women would prefer a one-step test, and they want it early: It gets things done and then you know where you are,” he said. “The problem with that is some of the women will get a high glucose later on,” so a second test later in pregnancy would still be important to catch even more cases.

“I think the series [of papers] is timely. I think there’s a big interest for more precise identification and treatment for these complex conditions,” said Ellen Francis, an epidemiologist at Rutger University’s School of Public Health, who was not involved in the study. 

She agrees that adopting a 75g test would be preferable, as it gives more nuanced results that can help management and treatment. At the same time, she says, it’s important to keep in mind not all health systems may be equipped to take on more testing, or actually do more to support women with gestational diabetes. “Part of that precise approach is not just at the individual level but thinking at the systemic level and what the health care system can handle,” she said, “Because if you’re diagnosing a bunch of women, but you don’t have the infrastructure to treat all of them, then that’s not necessarily going to move the needle in a direction that we would be looking for.”

Clinicians aren’t all convinced. “It is definitely important to screen for overt diabetes in early pregnancy,” said Rebecca Reynolds, a professor of metabolic medicine at the University of Edinburgh, who was not involved in the study. “I think there is still uncertainty about whether we should be screening for early gestational diabetes and what glucose thresholds we should be using.”  

What’s especially important, added Reynolds, “is that we should be giving women really good advice about healthy diets and exercise, and even if they screen ‘negatively’ for early gestational diabetes, they should still receive this advice.” The series authors recommend the same guidelines for patients regardless of when they’re diagnosed: optimizing maternal diet and physical activity, regular self-monitoring of blood glucose levels and the addition of medication (insulin or metformin) when treatment targets are not achieved with lifestyle changes. 

Even if global clinicians can agree on new standards for gestational diabetes screening, there’s much more to learn, said Sweeting, and further research is necessary to determine the optimal maternal glucose target and safe thresholds for carbohydrate consumption in cases of gestational diabetes. “Further exploring a precision medicine approach that recognizes heterogeneity in gestational diabetes is also crucial,” she said. Reynolds points to the need for better testing to begin with: The oral glucose tolerance screen “is a clunky test, and not very repeatable,” she said. 

It’s also unclear whether earlier interventions in gestational diabetes have the potential to reduce the incidence of diabetes and other metabolic conditions at the population level. “There’s been a lot of studies in recent years showing an association between maternal hyperglycemia in pregnancy and the risk for the child to develop impaired glucose tolerance, excess adiposity, metabolic syndromes,” said Marie-France Hivert, a professor in the department of population health at Harvard and a co-author of the series. But existing research hasn’t shown that treating gestational diabetes after 24 weeks can prevent this kind of metabolic conditioning, she said.

The data on earlier treatment is still limited, as are long-term studies following children into their teenage years and after. “That’s one of the things we’re going to be looking at,” said Simmons, whose team plans to follow women and babies from the TOBOGM study that showed improved short-term outcomes with earlier diagnosis. They’ll be able to check on their health outcomes over time — approximately a five to seven year time span.