One peer-reviewed scientific paper does not truth make. We know this from the poorly conceived study that was published in the Lancet about autism and childhood immunization shots. It was a significantly flawed study with just a few children in it; yet, it's conclusions affected many parents' decision-making, unfortunately. It is with skepticism that I read all scientific papers, even those published in highly respected journals. Follow me below the fold as I describe the findings of one brand new study that links lower IQ in toddlers who were exposed in utero to a widely used drug to control epilepsy, and why I think the researchers might be on to something.
Today, the New England Journal of Medicine published a study by a team of a dozen researchers from a number of respected institutions (e.g., Emory University in Atlanta; the Medical College of Georgia in Augusta; the University of Liverpool; and, USC) titled, "Cognitive Function at 3 Years of Age after Fetal Exposure to Antiepileptic Drugs." As a matter of truth-in-disclosure, I am not affiliated with any of the researchers, their institutions, or the NEJM. You should also know this: about a million American females suffer from a seizure disorder; 25,000 children are born in the United States per year to mothers with a seizure disorder; and, according to the Epilepsy Foundation:
Women with epilepsy face epilepsy-related reproductive difficulties throughout their lives, including increased rates of sexual dysfunction, infertility and seizures related to the menstrual cycle.
and,
Despite risks, successful pregnancy is possible, but often inappropriately discouraged by health care providers.
For women who suffer from epilepsy, both the condition of epilepsy and pregnancy are not things to be taken lightly. There are commonly prescribed drugs (carbamazepine [Tegretol], lamotrigine [Lamictal], phenytoin [Dilantin], and valproate [Valproic Acid]) to treat a seizure disorder, but all drugs can have side effects. In animal studies, fetal exposure to these types of drugs can produce cognitive and behavioral abnormalities in the offspring, a finding that warrants the examination of possible similar effects in children. Today's reported study suggests that one thing a woman who suffers from epilepsy would want to consider is whether or not the medication she takes to control her seizure disorder could adversely affect her fetus. If this study's findings are replicated, it will provoke neurologists and their child-bearing aged epileptic patients to have discussions about what medication would be best for both the patient and the patient's baby.
Here's what the researchers did, and what they've reported.
Between 1999 and 2004, pregnant women with epilepsy in the United States and the United Kingdom participated in a study that examined the effects of anti-convulsive medication taken during their pregnancies on the cognitive functioning of their children. The researchers plan to follow the children through the age of six which in my opinion is a smart thing to do since children's relative cognitive functioning (relative to other children, that is) can be affected by a number of environmental factors (e.g., lead exposure), and because if one really wants to examine a drug's long-term effect on childhood cognitive functioning, then one really has to examine the children when they are children, not merely when they are babies or toddlers. As the title of the NEJM article suggests, the study published today represents the findings from the first phase of the study. The study examined the IQs of 309 three-year-old children of women who took one (and only one) anti-convulsive medication when pregnant: Dilantin; Lamictal; Tegretol; or, Valproic Acid. From the study's abstract, this is what the researchers found (emphasis mine):
At 3 years of age, children who had been exposed to valproate in utero had significantly lower IQ scores than those who had been exposed to other antiepileptic drugs. After adjustment for maternal IQ, maternal age, antiepileptic-drug dose, gestational age at birth, and maternal preconception use of folate, the mean IQ was 101 for children exposed to lamotrigine, 99 for those exposed to phenytoin, 98 for those exposed to carbamazepine, and 92 for those exposed to valproate. On average, children exposed to valproate had an IQ score 9 points lower than the score of those exposed to lamotrigine (95% confidence interval [CI], 3.1 to 14.6; P=0.009), 7 points lower than the score of those exposed to phenytoin (95% CI, 0.2 to 14.0; P=0.04), and 6 points lower than the score of those exposed to carbamazepine (95% CI, 0.6 to 12.0; P=0.04). The association between valproate use and IQ was dose dependent. Children's IQs were significantly related to maternal IQs among children exposed to carbamazepine, lamotrigine, or phenytoin but not among those exposed to valproate.
For those unfamiliar with IQ, 100 is considered spot-on average (the 50th percentile), and scores from 90 to 109 (16th percentile to the 84th percentile) are considered in the average range of intellectual functioning. The good news for the children in this study is obvious: anti-convulsant medication was not correlated with significantly impaired cognitive functioning at age three. In my opinion, just as important is the finding that Valproic Acid—which is increasingly being used in psychiatry to treat Bipolar Disorder and those who suffer from chronic emotional, ideational, and relational instability (Borderline Personality Disorder)—is associated with a six- to nine-point lower IQ in children exposed in utero, on average.
Also in my opinion, that IQ was Valproic Acid-dose dependent is an important finding. Why? Because researchers have found a similar association between blood lead levels in 3- to 5-year old children and IQ (the higher the lead level, the lower the IQ score):
The blood lead concentration was inversely and significantly associated with IQ. In the linear model, each increase of 10 µg per deciliter in the lifetime average blood lead concentration was associated with a 4.6-point decrease in IQ (P=0.004), whereas for the subsample of 101 children whose maximal lead concentrations remained below 10 µg per deciliter, the change in IQ associated with a given change in lead concentration was greater. When estimated in a nonlinear model with the full sample, IQ declined by 7.4 points as lifetime average blood lead concentrations increased from 1 to 10 µg per deciliter.
I also think the fact that the study did not examine a group of children whose epileptic mothers took no anti-seizure medication during pregnancy is not a significant flaw. Why not? Because intelligence tests are, as I've said, designed to have average scores that cluster around 100, and the average IQs of the children in this study clustered around 100, which is to be expected.
Today's published study is just one that I know of that has linked the use of a specific anti-seizure medication to lowered intellectual functioning. It will take results from the researchers' follow-up study in a few years and it will take more studies, by other researchers, to know whether or not women who take anti-convulsive medication should be speaking to their doctors about what medication is likely to have the least adverse effect on their to-be-born child and the most effect in treating whatever it is they are taking anti-convulsant medication for.