Friday, March 31, 2023
Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™
ABIM Diplomates - maximum of 0.25 ABIM MOC points
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Pharmacists - 0.25 Knowledge-based ACPE (0.025 CEUs)
Physician Assistant - 0.25 AAPA hour(s) of Category I credit
IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit
This activity is intended for diabetologists/endocrinologists, family medicine/primary care physicians, internists, obstetricians/gynecologists/women's health physicians, pediatricians, public health and prevention officials, nurses/nurse practitioners, pharmacists, physician assistants, and other members of the healthcare team for pregnant women and their offspring.
The goal of this activity is for members of the healthcare team to be better able to describe the joint effect of maternal weight and excessive weight gain (EWG) as defined by National Academy of Medicine recommendations on risk for attention-deficit/hyperactivity disorder (ADHD) in offspring of mothers with gestational diabetes mellitus (GDM), according to a cohort study of singleton births greater than 2 weeks of gestation among women with GDM between 1991 and 2008.
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CME / ABIM MOC / CE Released: 2/3/2023
Valid for credit through: 2/3/2024
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Gestational diabetes mellitus (GDM) has been linked to greater risk for attention-deficit/hyperactivity disorder (ADHD) and other neuropsychiatric disorders in offspring. Hyperglycemia may interfere with fetal brain development via chronic inflammation, hypoxia, and fetal hyperinsulinemia, causing neurobehavioral disorders later in life.
Maternal obesity is a leading risk factor for neonatal complications (macrosomia, large for gestational age [LGA], prematurity, and perinatal mortality) and for adverse long-term mental health outcomes. Despite strategies to prevent maternal obesity, approximately 30% of reproductive-age women and 47% of women with GDM are obese at the first antenatal visit.
Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder (ADHD).
Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now an observational study of 1036 singleton births at one hospital between 1991 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain (EWG) during pregnancy may be jointly associated with an increased risk for offspring ADHD. The median follow-up was 17.7 years.
Maternal obesity was independently associated with ADHD (adjusted HR [aHR] 1.66 [95% CI: 1.1, 2.67]), but EWG during pregnancy and maternal overweight were not, reported Verónica Perea, MD, PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, Spain, and colleagues in the September 28, 2022 issue of the Journal of Clinical Endocrinology & Metabolism.[1]
Still, in women with pregestational obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk for offspring ADHD was higher compared with women of normal weight whose pregnancy weight stayed within NAM guidelines[2] (aHR 2.13 [95% CI: 1.14, 4.01]).
"The results of this study suggest that the negative repercussions of [EWG] on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD," the researchers wrote.
The study[1] also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR 1.36 [95% CI: 0.78, 2.37]). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study[3] in newborns showed an increased long-term risk for ADHD in infants born to women with GDM compared with the nondiabetic population. This long-term risk for ADHD increased in the presence of pregestational obesity (HR 1.64 [95% CI: 1.42, 1.88]).
Similarly, evidence from systematic reviews and meta-analyses[4] has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes; however, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.
Although causal inferences cannot be drawn from the current observational study, "it seems that the higher risk [for ADHD] observed would be explained by the role of gestational weight gain [(GWG)] during the antenatal period," Perea said in an interview.
Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Perea said. "This should be a priority in the current management of gestation."
Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, Massachusetts, agreed.
"I think one of the key issues is that there's very little attention paid to how weight gain is regulated during pregnancy," she said in an interview.
On many other points, however, Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, Boston, Massachusetts, did not agree.
The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years,[5] she emphasized. "These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences."
The current study[1] does not say "anything new or novel," Stanford added. "Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don't think there was any appreciable increase when weight gain during pregnancy was factored in. It's mild at best."
Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, New York, expressed a similar point of view. Although the study findings "add to the current literature," they should be interpreted "cautiously," Bornstein said in an interview.
The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy "was not clear," he said. "Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn't demonstrate a cause and effect or a magnitude for this effect."
The healthcare team should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Bornstein suggested. "Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes."
Treating obesity before conception mitigates GDM risk, agreed Stanford.
"The issue," she explained, "is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy."
Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. "Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus."
This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Perea and study coauthors reporting have no conflicts of interest. Stanford disclosed relationships with Boehringer Ingelheim Pharmaceuticals, Inc.; Currax; Gelesis; Lilly USA, LLC; Novo Nordisk; Pfizer Inc.; and Rhythm Pharmaceuticals. Bornstein reported having no conflicts of interest.
