Children exposed to opioids in the womb may have heightened risks of long-term mental and physical health issues, a new study suggests.

The findings, published online June 28 in JAMA Network Open, dovetail with an opioid epidemic that has taken a widespread toll in the United States—pregnant women and newborns included.

Opioid use has been rising among pregnant women nationally. A study last year found that in 2014–2015, just over 6 out of every 1,000 births were to women using opioids. That was up from 1.5 per 1,000 a decade before.

The immediate risks have been known: Babies can be born addicted to opioids and go through withdrawal—a condition known as neonatal abstinence syndrome (NAS). It causes breathing problems, tremors, fever and other symptoms that can last for up to 6 months, according to the March of Dimes. Opioid use during pregnancy also raises the risk of preterm birth or low birth weight.

Less has been known, though, about children's longer-term outlook. That's where the new study comes in, the researchers said.

On average, the investigators found, children exposed to opioids in the womb had roughly twice the risk of being diagnosed with conduct disorder, emotional disturbances, or attention-deficit/hyperactivity disorder (ADHD). And as preschoolers, those children were also more likely to show slower-than-normal physical development.

The opioid epidemic is more than a problem of "now," said lead researcher Romuladus Azuine of the US Health Resources and Services Administration.

"The consequences are intergenerational, and that's very concerning to us," he said.

What's not clear, though, is the extent to which moms' opioid use is directly responsible for the longer-term problems. Women who abused the drugs during pregnancy often used other substances, too—including alcohol, cocaine, and tobacco.

And then there's the home environment where a child is raised. A range of factors—from stress to poor nutrition—could be at work, experts said.

Dr. Ruth Landau, of NewYork-Presbyterian/Columbia University Medical Center in New York, NY, said that it's difficult to "disentangle the societal and environmental circumstances from the opioid exposure."

Azuine agreed that a "holistic" view of the opioid epidemic is necessary. People need access to treatment for various types of substance abuse, while efforts to prevent opioid abuse should confront the social and economic factors that help fuel it.

More than 130 Americans die every day from an opioid overdose, according to the US National Institute on Drug Abuse (NIDA). Illegal opioids, like heroin and illicitly manufactured fentanyl, have become the biggest concern in recent years. Still, prescription opioids—like OxyContin, Vicodin, and Percocet—were involved in 35% of opioid overdose deaths in 2017, government figures show. And most heroin abusers started out with prescription opioids, NIDA says.

The new findings are based on more than 8,500 mothers who gave birth at Boston Medical Center between 1998 and 2016. Just over 5% of babies were exposed to opioids in the womb. Over time, the number of newborns with NAS rose from 2% of births in 2004 to 6% in 2008—and hovered above 3% by 2016.

Around preschool age, children who had been exposed to opioids (and born with NAS or not) had twice the risk of conduct disorder or emotional disturbances, and were 80% more likely to be slow in reaching physical development milestones, the study found. At school age, they had twice the risk of being diagnosed with ADHD.

Dr. Rahul Gupta is chief medical officer for the March of Dimes. He said the findings are important because they begin to get at the longer-term impact of prenatal opioid exposure.

"The consequences are not just during pregnancy and childbirth," he said, adding that opioid abuse is not an isolated problem.

"Addiction to (multiple substances) is an issue, societal conditions are an issue," Gupta said. Ideally, he said, opioid abuse should be caught and treated before pregnancy. But doctors should also screen pregnant women for substance abuse, he said.

The "gold standard" treatment for opioid abuse involves medications, including methadone and buprenorphine. Babies can still be born with NAS when mothers take those medications, Gupta said. But, he added, treatment should still improve their outcomes—in part, by improving the mothers' health and ability to make "better decisions for their baby."