Hyperemesis Gravidarum Linked to Increased Autism Risk

By Anne Harding

October 19, 2019

NEW YORK (Reuters Health) - Children exposed to hyperemesis gravidarum (HG) in utero are more likely to be diagnosed with autism spectrum disorders (ASDs) than those whose mothers did not suffer from HG, according to a new retrospective cohort study.

"Our findings provide additional evidence that the intrauterine environment has a significant impact on ASD risk," Dr. Darios Getahun of Kaiser Permanente Southern California (KPSC) in Pasadena and colleagues note in their report, published online October 3 in the American Journal of Perinatology.

Given that metabolic problems in early pregnancy have been linked to neurodevelopmental conditions in offspring, the authors hypothesized that exposure to HG—severe nausea and vomiting in pregnancy that can lead to maternal malnutrition and dehydration—would also be associated with increased ASD risk in children.

To investigate, they looked at 469,789 children born in 1991-2014 at KPSC hospitals, 1.8% of whom were diagnosed with ASD.

The incidence of ASD among unexposed children was 1.71/1,000 person-years, while it was 2.87/1,000 person-years for HG-exposed children. HG diagnosis in the first (hazard ratio 1.58) and second (HR 1.36) trimesters were both associated with increased ASD risk.

HG-exposed children with ASD were diagnosed at younger ages than unexposed children with autism, the researchers found. The association was seen in both sexes, but was stronger in girls than boys (HRs 1.62 and 1.50, respectively).

Drugs for treating mild HSG were not associated with ASD risk.

HG exposure was significantly associated with ASD risk in white children (HR 1.70) and Hispanic children (HR 1.76), but not in black children or Asian/Pacific Islanders.

"HG, as a cause of maternal malnutrition in early pregnancy, may have a profound effect on fetal brain development either (i) directly, through metabolic imbalances resulted from maternal malnutrition and dehydration, or (ii) indirectly, through hypoxemia and reduced nutritional supply to the fetus by compromising placental function," Dr. Getahun and colleagues write.

They conclude: "HG diagnosis is associated with ASD risk and may be helpful in identifying at-risk children who could benefit from enhanced surveillance and earlier diagnosis and intervention."

Dr. Patrick Mullin, an associate professor of maternal-fetal medicine at the Keck School of Medicine at the University of Southern California who has studied HG, reviewed the research for Reuters Health.

"Recently, research has been identifying maternal medical conditions that create in-utero environments that may lead to the development of not only fetal complications but also medical problems for the exposed individual later in life," Dr. Mullin noted in an email. "The Barker Hypothesis talks about how the fetal response to in-utero stresses leads to conditions such as chronic hypertension and diabetes as that individual gets older. Evidence is developing of a similar effect associated with HG leading to conditions including ASD and neuro-developmental delay."

Clinicians providing prenatal care need to identify and treat HG earlier, he added, noting that the condition has always been underdiagnosed and undertreated.

"While we don't yet have definitive data on whether earlier treatment of HG can minimize the development of potential medical problems for the exposed individual later in life, we do know early and appropriate treatment of a patient with HG will decrease her need for hospitalization and will decrease her development of complications during her pregnancy," Dr. Mullin said.

Most women with HG first have less severe symptoms known as nausea and vomiting of pregnancy (NVP), he added. "Providing women with support and effective therapy when they have NVP may prevent some from having their condition worsen to HG."

Dr. Getahun was not available for an interview by press time.

SOURCE: http://bit.ly/2VO0kUY

Am J Perinatol 2019.