Prenatal Tobacco Exposure Linked to Multiple Neurodevelopmental Problems

Deborah Brauser

November 10, 2009

November 9, 2009 (Honolulu, Hawaii) — Prenatal tobacco exposure (TE) has been linked to irritability in neonates, poor attention and information processing in infants, and impulsivity in preschool children," according to new research presented here at the American Academy of Child & Adolescent Psychiatry 56th Annual Meeting.

"We found that even in the first year of life, we can see differences in attention and irritability and in regulation of emotions," lead investigator Sandra A. Wiebe, PhD, assistant professor in the Department of Psychology at the University of Alberta, Canada, told Medscape Psychiatry.

"Then at age 3, we saw that kids with prenatal [TE] seem to have trouble waiting for an award, which ties in with findings that smoking during pregnancy can have specific impact on the parts of the brain that are involved in regulating behavior," she added.

It is estimated 10% to 30% of women in the United States still smoke while pregnant. However, many past studies that looked at the effects of prenatal TE were often retrospective and had bias recall and underreporting, said Dr. Wiebe.

The investigators sought to examine "the neurocognitive effects of prenatal TE in the first 3 years of life by prospectively assessing the regulation of behavior in the neonatal, infant, and preschool periods."

More Irritable, Less Attentive

In the first study, 304 women were enrolled before their fourth month of pregnancy. Both biological verifications and self-reports were used to assess smoking. Overall, the patients who smoked averaged 4 cigarettes per day during pregnancy.

All mothers were interviewed about smoking during pregnancy and completed the Child Behavior Checklist (CBCL).

Using the Neonatal Temperament Assessment, the investigators examined the women's newborns 1 to 3 days after birth and at weeks 2 and 4. These standardized tests included reflex assessments, orientation to audio and visual stimuli, and response to stressors.

Results showed that birth outcomes were "very similar" between the 2 groups for head circumference, length, and birth weight.

However, the TE infants were less attentive shortly after birth (catching up by 4 weeks) and exhibited consistently more irritability across all time points.

In a second study, 207 of the infants from study 1 (TE, n = 95; non-TE, n = 112) were evaluated again at 6 months of age, this time with "an object recognition task to assess attention and habituation," reported Dr. Wiebe.

Preliminary results from this study showed that the distribution of attention for TE infants differed from the nonexposed infants.

Although both groups had the same pattern of habituation/distribution, there was a trend for the TE infants to have more casual (and less focused) attention (P < .01).

"There's the possibility that this could point to poor information processing," said Dr. Wiebe.

Self-Regulation Problems

In the third study, which is an ongoing pilot trial, the same investigators evaluated self-regulation and executive control in a different population, conducting a snack delay task in a sample of 237 typically developing 3-year-olds (120 were male). Of these, 22% of mothers reported smoking while pregnant.

"ADHD is not typically diagnosed in preschoolers," explained Dr. Wiebe. "So in this study, we wanted to find out whether prenatal [TE] and non-TE children differ in their ability to wait for a reward and to regulate motor behavior during a delay of gratification task?"

During the task, all the children were told to keep their hands face down on a table until a bell sounded, which was their cue that they could then take a snack.

Results showed that more of the TE preschoolers ate the snack before their cue and ate it earlier than the nonexposed children. In addition, the mothers of the TE children reported more ADHD symptoms on the CBCL.

No differences were found in hand and body movements.

"Overall, these findings were consistent with preclinical animal models," said Dr. Wiebe. "Across all our studies, smoking during pregnancy was related to attention and self-regulatory problems at multiple points in development.

"These differences between the groups may be subtle, but the effects of maternal smoking could have a large impact and lead to a snowball effect later on. So it's definitely something clinicians should consider," she added.

Dr. Wiebe said she understands that it's hard for mothers to give up smoking. "But if they can realize that their baby or child might have specific problems, not just in health but in other important areas, that might be just that one little additional incentive that might help the mom to finally quit [smoking]. We need to explain that it can affect how well a baby learns about the world, as well as how well they're able to behave adaptively in various situations once they start preschool or kindergarten."

In future research the investigators plan to conduct a longitudinal follow-up study that includes a snack test on the participants in the first 2 studies.

"We're also interested in looking at how these measures may relate more directly to ADHD and how parenting may influence these neurodevelopment effects. Are there things that these women are doing that add an additional risk factor, and if there are subgroups that smoke due to being depressed, what effect might that have on their children? It's just getting more of the big picture of how children develop," concluded Dr. Wiebe.

Early Indicators of Later Problems

"What's interesting in these studies is that the investigators were assuming from the start that there's some effect [of TE] and were then trying to tease apart the very beginnings of it," said session moderator Nicolette Borek, PhD, deputy branch chief in the Behavioral and Brain Development Branch, Division of Clinical Neuroscience and Behavioral Research at the National Institute on Drug Abuse, Bethesda, Maryland.

"So in trying to understand the different effects, they were breaking down the various neurobehavioral outcomes in terms of looking at the very early indicators of potential problem behaviors, such as lack of attention or self-regulation, later on. Ideally, it would be great to find a way to then intervene on those behaviors early on to possibly prevent them from turning into long-term effects," said Dr. Borek.

In another prenatal TE study presented during the same session, investigational team member Helen J. Leffers, MSc, project director in the Department of Psychiatry and Human Behavior at Brown University, Providence, Rhode Island, reported on possible exposure-induced neurobehavioral symptoms in the womb and during the first 30 days of life.

"This presentation focused on maternal smoking and its potential effects on fetal and infant neurobehavioral development," said Ms. Leffers.

Preliminary results from this prospective study of 78 pairs of infants and mothers (39 smokers, 40% Latino, 36% white) showed that smoking exposure and higher levels of cotinine at birth were associated with increased signs of stress and abstinence in the early days of life, increased arousal in the first days of life and at the end of the first month, and increased hypertoxicity in the early days of life.

"Exposed infants showed worse orientation and worse self-regulation across the first month and more nonoptimal reflexes in the first days of life. And greater birth cotinine was associated with increased cortisol reactivity in a period consistent with withdrawal from nicotine," according to the presentation. "These results support the possibility of a withdrawal process in prenatal [TE] exposed infants and suggest at least immediate, if not persistent, neurobehavioral alterations."

This study is "very preliminary," said Dr. Borek. "This is the first time that we're aware of a team looking at what's happening at the very beginning of life. So we're trying to figure out what it all means, and their evaluation of all the data will be interesting. We're very curious to see further analysis, as well as the follow-up on these newborns.

"What I liked about both Dr. Wiebe's and Ms. Leffers' studies, and what is so intriguing, was their looking at the subtle, early potential differences that may then become part of the trajectory towards greater behavior problems," Dr. Borek added.

"The question that will need to be answered in all, though, is, 'Are there other things that are different about the mothers in the exposed vs the nonexposed groups that we might not be measuring, such as environmental or biological factors?' Both of the presentations are coming from different perspectives and have scads of data that need to be analyzed. And I'm excited to see more in the future," she said.

Dr. Wiebe, Dr. Borek, and Mrs. Leffers have disclosed no relevant financial relationships.

American Academy of Child & Adolescent Psychiatry (AACAP) 56th Annual Meeting: Abstracts 18.2 and 18.1. Presented October 31, 2009.

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