Prenatal Exposure to Ecstasy Linked to Motor Dysfunction in Infants

Deborah Brauser

March 09, 2012

March 9, 2012 — Prenatal exposure to 3,4-methylenedioxymethamphetamine (MDMA), or "ecstasy," may lead to increased developmental difficulties, new research suggests.

In one of the first studies in humans to examine these risks, investigators found that infants of mothers who had used MDMA during pregnancy had significantly poorer motor quality and "lower milestone attainment" of coordinated movements at the age of 4 months than their unexposed peers.

"The findings suggest very specifically that there was something that affected the fetal neurologic system," principal investigator Lynn T. Singer, PhD, professor of environmental health sciences, pediatrics, psychiatry, and psychology at Case Western Reserve University in Cleveland, Ohio, told Medscape Medical News.

Dr. Lynn Singer

Interestingly, the MDMA-exposed infants were also significantly more likely to be male than were the nonexposed infants.

"That wasn't something we were expecting, although there's evidence that other toxins do have an influence on sex ratio. So this was another indicator that something is off, that something is being affected by this drug," said Dr. Singer.

"Doctors need to ask mothers what, if anything, they are taking during pregnancy. That really needs to become part of an open discussion that is not punitive to the mother."

The study was published online March 3 in Neurotoxicology and Teratology.

Lifetime Effects?

According to the researchers, MDMA "is one of the most widely used illicit recreational drugs among young adults" and is often associated with the dance club culture in the United States, Europe, and Australia.

In addition, roughly 500,000 MDMA tablets are taken each weekend in the United Kingdom; and in the United States, young women are more likely than young men to use the substance, report the investigators.

Previous animal research has shown links between prenatal exposure to MDMA and long-term memory and learning impairments. However, no prospective studies have examined the exposure in humans, "despite concerns about its potential for harmful effects to the fetus."

"In general, we're becoming cognizant of the fact that fetal exposures of multiple types can have long-lasting effects on a child up until adult life," said Dr. Singer.

She noted that known risk factors include exposure to maternal use of alcohol and cocaine.

"So as ecstasy has become a widely used drug among young people of childbearing age, we wanted to examine its effects."

For this study, Dr. Singer worked in collaboration with researchers from the University of East London in England and Swansea University in Wales. Together, they prospectively recruited 96 UK participants from the Drugs and Infancy Study (DAISY), which assessed recreational drug use among pregnant women.

An adaptation of the Maternal Post-Partum Interview was given by phone, in the home, or in the lab to assess substance use both before and during pregnancy. The Drug Abuse Screening Test was also administered to characterize self-reported levels of drug dependence.

At roughly 1 month of age, the participants' infants were examined using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS). At the age of 4 months, they were administered the Alberta Infant Motor Scale (AIMS) and 3 of the Bayley Scales of Infant Development: the Mental Development Index (MDI), the Psychomotor Index, and the Behavior Rating Scale (BRS).

The BRS was used to assess attention/arousal and motor quality, which included fine and gross motor movements.

Decreased Motor Quality

Although the majority of the participants reported having concurrently taken several illicit drugs before and during pregnancy, only 29% reported having used MDMA while pregnant.

"Women who used MDMA during pregnancy had fewer prior births and more negative sequelae associated with their drug use, including more health, work, and social problems," write the investigators.

Dr. Singer reported that many of these participants stopped using MDMA at some point during their pregnancy.

Nevertheless, the MDMA-exposed infants had significantly poorer motor quality at the age of 4 months, as shown in lower BRS scores, than did the infants not exposed to MDMA (unadjusted P = .009; adjusted P < .05).

They were also "rated as less coordinated and more likely to have slower and delayed movements," had significantly lower scores on the AIMS test, and demonstrated a trend toward significantly lower scores on the Psychomotor Index compared with the infants who were not exposed to MDMA.

In addition, 71% of the infants exposed to MDMA were male vs 31% of the non-MDA-exposed infants (adjusted odds ratio, 3.2; 95% confidence interval, 1.2 - 8.2; P < .02).

There were no significant between-group differences in birth weight, prematurity, length, or head circumference. There were also no significant differences in neonatal behavioral outcomes (as shown on the NNNS), in scores on the Bayley MDI, or in the attention/arousal measure of the BRS.

Troubling Findings

In further analyses, the investigators also found that higher neonatal exposure to alcohol, independent of MDMA effects, predicted significantly poorer motor quality (P < .005), and higher marijuana exposure predicted poorer attention on the NNNS (P < .02).

Still, the study's findings "suggest risk to the developing infant related to MDMA exposure and warrant continued follow-up to determine whether early motor delays persist or resolve," write the investigators.

Coinvestigator Andy Parrott, BSc, PhD, from Swansea University, said in a release that the results were troubling but not particularly surprising.

"Ecstasy can deplete the level of serotonin, which is an important neurotransmitter for many brain functions, including gross motor control," said Dr. Parrott.

Dr. Singer noted that a particular concern is with regard to women who use MDMA but may not realize that they are pregnant, especially because the first months of pregnancy are so important to fetal development.

"So I think clinicians really need to start educating women and cautioning them about potential harms prior to pregnancy. They need to be made aware that a lot of things can have an effect on the infant."

Timely Study

"This certainly is a timely study. As they point out, there's a dearth of information about the long-term effects of prenatal exposure to ecstasy," Mark L. Hudak, MD, professor of pediatrics and division chief of neonatology at the University of Florida College of Medicine in Jacksonville, told Medscape Medical News.

"Although the investigators didn't have a lot of patients to analyze, they did a good job in trying to control for confounding issues. And there is a suggestion that they found something by 4 months having to do with some subtle motor effects," added Dr. Hudak.

He noted that the study's sex ratio finding was also "intriguing but not inconsistent with the preclinical information that is available."

A limitation he cited included the fact that the fetuses exposed to MDMA were also exposed to other substances, and each of those substances could have their own effect.

As reported by Medscape Medical News, Dr. Hudak and colleagues recently published an American Academy of Pediatrics clinical report in Pediatrics on ways to identify and treat withdrawal and toxicity in infants after prenatal drug exposure.

"Overall, I'd say this was an interesting study and certainly worthy of more pursuit. I would be curious to see what their long-term follow-up with these children would be — and if there are any long-term effects on cognitive or other executive functions," he said.

"It would be fascinating to find out if it's preordained that the central nervous system is going to be limited because of this exposure."

The study was supported by a grant from the National Institute on Drug Abuse. The study authors and Dr. Hudak have disclosed no relevant financial relationships.

Neurotoxicol Teratol. Published online March 3, 2012. Abstract

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