Lithium and Heart Defects (backstory for Lithium and Pregnancy: Second Opinion)
If there is one factoid that physicians and other health care providers tend to take away from preclinical pharmacology class it might be “Lithium during pregnancy equals Ebstein’s anomaly, whatever that might be.” As usual the more accurate picture behind the facile factoid is a lot more complicated. There is some background necessary to better understand this issue.
Firstly, the baseline rate of birth defects in humans is about 2.5%, meaning about 25 babies out of a thousand will be born with some significant error of development. About a third of these defects will involve the heart, for a rate of about 8 congenital heart defects per 1000 babies born. Ebstein’s anomaly is a rare form of heart defect in which the tricuspid valve does not develop normally leading to artialization of the right ventricle and a variety of leaflet defects. Ebstein’s anomaly can be treated, but it is a very serious illness when it is severe enough to show up at birth. The incidence of Ebstein’s is estimated to be about 1 in 2000 congenital heart defects although there may be more people who have mild forms that are not diagnosed until later in life , if at all. What this means is that the baseline incidence of Ebstein’s anomaly is thought to be around 1 in 250,000 births.
The second prong of our background information begins with an entity called the Lithium Baby Register. This was a voluntary register to which people could report births to mothers on lithium and their outcomes. This started in 1969 and when the data was reviewed in 1980 there were 225 babies reported -18 had cardiac defects, 6 of which were Ebstein’s anomaly. Given that we have established that it was supposed to take 1.5 million babies to get 6 cases of this disorder, these numbers really caught people’s attention.
However, there are problems with interpreting this data. It turned out that people were a lot more likely to report interesting birth defects than boring normal babies to the registry, so it really didn’t help clarify what the real incidences might be. Remember 2-3 babies out of a hundred have serious birth defects anyway, so just the presence of birth defects doesn’t mean anything special.
In the past 20 years or so researchers have attempted to clarify this issue and answer the question – does lithium cause an increased incidence of heart defects and/or Ebstein’s anomaly? To sum up, their answer is basically maybe a little bit for Ebstein’s and little bit more than that for heart defects, but nobody’s totally sure. Glad we cleared that up! The positive take home message is that the risk is not really that large, definitely not the way it originally was postulated; and it is reasonable, with proper medical follow-up, for women to have babies while on lithium.
A couple of addenda – why would someone have to stay on lithium and what is the period of concern during the pregnancy? The heart develops in the first trimester, so after that there is no issue with lithium from a heart birth defect. A woman may need to remain on lithium throughout her pregnancy because the risk to her and her fetus can be much greater if she becomes manic (which can lead to risk taking behaviors, lack of sleep, dehydration, drug and alcohol abuse, and poor nutrition)or depressed (and does not take care of herself or commits suicide) than from the lithium. Unfortunately, all the other drugs for treating mania are also implicated in birth defects.
If you are uncomfortable with risk analysis and pregnancy, ask yourself this – assuming that you or your close associates had no particular health concerns, what did you do about the risk you were assuming in getting pregnant? Did you even think about the 2-3% chance of having a seriously affected baby? Did you try to find out if there were lifestyle issues or family history that put you at specific risk? For those that can manage it, Ignorance can truly be bliss.