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A new study involving thousands of Boston families found that children exposed to multiple drugs in the womb are more likely to face physical and mental difficulties as they grow up.

The study, published Friday in the online journal JAMA Network Open, is the first to examine a large group of opioid-exposed children over many years and seek to identify the developmental consequences. Yet the research fails to untangle the host of factors that affect how children fare, and several specialists in newborn medicine said it does little more than point to avenues for future research.

Lead author Romuladus E. Azuine, director of epidemiology research at the US Health Resources and Services Administration, said the study provides “very shocking and troubling” insights into the potential aftereffects of the opioid crisis.

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“The opioid epidemic is not an epidemic of the present. It is an epidemic of the future,” Azuine said. “We have shown long-term consequences for children.”

The study found that drug-exposed youngsters were more likely than their peers to be born small or premature, have growth problems and conduct disorders as preschoolers, and suffer from attention deficit hyperactivity disorder when they get to school.

All the women took opioids (heroin, oxycodone, or methadone) while pregnant — but most also smoked, drank alcohol, and used other illicit substances. The analysis did not tease out the effects of the different substances. It also provided no information about the children’s home environment, which research has shown to be at least as influential as drug exposure during pregnancy.

Significantly, the study does not reveal the number of children who suffered bad outcomes. It shows that the drug-exposed children had higher odds of having certain problems, but not how prevalent those problems were.

The questions the study raises are critical because increasing numbers of babies have been born dependent on opioids in recent years. The number of women who were addicted to opioids when they delivered babies quadrupled across the nation from 1999 to 2014, according to a federal study last year. In Massachusetts, one of the states hardest hit by the opioid crisis, the increase was even greater: more than sixfold from 1999 to 2013, the most recent year measured.

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To better understand the effects of such trends, researchers from the Health Resources and Services Administration, Johns Hopkins University, and Boston Medical Center delved into the medical records of 8,509 mother-infant pairs who agreed to participate in a study starting in 1998. Called the Boston Birth Cohort, the group consists of low-income urban mothers who delivered babies at Boston Medical Center. Of them, 454 children, about 5 percent, were exposed to opioids in the womb.

The authors acknowledge that their work doesn’t separate the effects of opioids from the alcohol, tobacco, cocaine, and other illicit substances the women also took.

For example, it’s already well-known that babies born to smokers are more likely to be undersized or premature. Because the mothers who took opioids were also more likely to smoke, it’s not clear whether the opioid exposure made any difference.

Dr. Stephen W. Patrick, a Vanderbilt University specialist in newborn medicine who has studied opioid-exposed babies, said the study fails to answer the burning questions about the long-term effects of opioid exposure in the womb.

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“What the study shows us is that polysubstance exposure can be associated with adverse outcomes,” he said. “It highlights the need for close follow-up for substance-exposed newborns.”

Dr. Barry Zuckerman, a Boston Medical Center pediatrician and one of the study’s authors, acknowledged the study’s limitations. How each substance contributes to the bad effects remains an unanswered question, he said.

“Any implications for prevention have to go beyond just stopping opioids,” he said. “In the real world, we need interventions to address all substances and risk factors.”

Decades of research into the lives of children exposed to cocaine and methamphetamine in the womb has shown that it’s not the drugs alone that affect how the children fare — it’s the environment where they grow up and the stresses they endure. Poverty, violence, and trauma have at least as much influence on a child’s future as the chemicals the child was exposed to during gestation, said Barry M. Lester, director of Brown University’s Center for the Study of Children at Risk.

Are opioids somehow worse for babies than cocaine and methamphetamine? Lester said it remains unknown, and the recent study, in his opinion, sheds no new light.

But Zuckerman, while acknowledging that the study is “flawed,” said opioid use may amplify the negative effects of a person’s life circumstances. It’s known that they affect the brain because opioid-exposed infants suffer from withdrawal at birth, something not seen with cocaine, he said.

The study, he said, provides “documentation of what we clinically have always seen,” he said. “It adds evidence to the concern that all of us clinicians have had for these mothers and babies.”

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Dr. Jonathan M. Davis, chief of Tufts Medical Center’s division of newborn medicine, said the study provides “important information” about the complexities of patients’ lives.

Opioid use, he said, occurs amid a web of social, emotional, and economic factors. It can be a sign of a troubled life across generations, starting with childhood trauma — which leads many women into addiction — and continuing into adult lives afflicted with poverty, violence, and stress.

The new research points to the importance of taking care of the children after they leave the hospital, he said.

“We’re sending them home and wishing them good luck,” Davis said. “Every one of these opioid-exposed babies should be referred for early intervention and tracked and followed.”

Dr. Munish Gupta, a pediatrician specializing in newborns at Beth Israel Deaconess Medical Center, reacted to the study with alarm, saying he feared it would scare pregnant women away from necessary treatment because it doesn’t distinguish between women who used illicit opioids and those who took prescribed opioids to treat their addiction.

Doctors strongly recommend that pregnant women who are addicted to opioids, rather than simply stopping all drugs, take a different type of opioid, either methadone or buprenorphine. These drugs control cravings and prevent overdoses, enabling women to stabilize their lives, focus on health and nutrition, and deliver healthier babies.

But inevitably the fetus is exposed to the drugs and often will undergo withdrawal at birth. That’s considered better than the alternative: Some 90 percent of pregnant women who stop heroin use will relapse, exposing the fetus to high and irregular doses of opioids and risking overdose and death.

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Dr. Davida M. Schiff, medical director of a Massachusetts General Hospital clinic for women with opioid use disorder and their children, says her patients are often reluctant to take the recommended medications because they fear the effects on their babies. She worries this latest study will make it even harder to persuade them.

“We know that these families are very high risk,” she said. “Can we pour the resources into actually supporting them as opposed to providing more judgment and stigma and shame?”


Felice J. Freyer can be reached at felice.freyer@globe.com. Follow her on Twitter @felicejfreyer.