May 4th, 2010 
Women who use the antidepressant bupropion during early pregnancy may have an increased risk of having a baby with a particular type of heart defect, a new study suggests.
Researchers caution that it is not clear whether the medication, marketed as Wellbutrin, is the cause. And even if it is, they say, the absolute risk of the heart defect would be small — affecting just 2 out of every 1,000 infants born to women who used bupropion during the first trimester.
But the findings, published in the American Journal of Obstetrics & Gynecology, do add to questions about the risks of using antidepressants during early pregnancy.
Some studies have already linked other antidepressants — including some of the commonly used selective serotonin reuptake inhibitors (SSRIs) — to higher-than-average, though small, risks of certain birth defects.
A study last year, for example, found that among nearly half a million Danish children born between 1996 and 2003, the risk of heart defects was elevated among those whose mothers had used SSRIs such as fluoxetine (Prozac), sertraline (Zoloft) and citalopram (Celexa) during early pregnancy.
In this latest study, researchers found that among more than 12,700 U.S. infants born between 1997 and 2004, those whose mothers used bupropion during early pregnancy had more than double the risk of heart defects known as left outflow tract defects, compared with infants whose mothers had not used the drug.
Left outflow defects affect the flow of blood from the heart’s left chambers to the rest of the body. In this study, the most common type of this defect was coarctation of the aorta — a narrowing in the body’s main artery that, in children, typically requires surgical repair.
The findings do not mean, however, that depressed women on bupropion should stop taking it if they are planning a pregnancy, according to the researchers.
“I think it’s important that women understand that they should not just stop taking their medication,” said Dr. Jennita Reefhuis, a senior epidemiologist at the U.S. Centers for Disease Control and Prevention and one of the researchers on the study.
Instead, she told Reuters Health, women should talk with their doctors, ideally when they are planning a pregnancy rather than after they conceive.
The potential risk of birth defects from using antidepressants must be weighed against the risks of a woman stopping her current depression therapy, Reefhuis said.
“This study needs to be replicated before we can say anything conclusive,” Reefhuis said, noting that the findings point to an association between bupropion and left outflow defects, but cannot by itself prove cause-and-effect.
If the association is causal, she said, the absolute risk to any one woman would be small. For every 1,000 births, there are an estimated 0.8 cases of left outflow tract heart defects; based on the current findings, that rate would be 2 per 1,000 among women who use bupropion in the first trimester.
Reefhuis also pointed out that with any pregnancy, the overall risk of having a baby with some form of birth defect is 3 percent.
Guidelines released last year by the American Psychiatric Association and the American College of Obstetricians and Gynecologists state that psychotherapy may be an effective alternative to antidepressants for pregnant women with mild to moderate depression.
However, the guidelines say, women with a history of more severe depression, or other major psychiatric disorders, may need to continue with their medication.
Bupropion is also prescribed for smoking cessation, under the brand-name Zyban. In the case of smoking cessation, Reefhuis said, it may be easier for women to find an effective alternative to the drug.
Related
- Obesity in Pregnancy Ups Risk of Heart Defect in Baby
Obese pregnant women are at increased risk of having a baby with a congenital heart defect, a new study finds.
On average, obesity is associated with a 15 percent increased risk of having a baby with a heart defect. But the risk rises with the level of obesity. Compared to normal-weight women, the risk is 11 percent higher in moderately obese women and 33 percent higher in morbidly obese women.
In general, women who were overweight but not obese had no increased risk, said the researchers at the U.S. National Institute of Child Health and Human Development (NICHD) and the New York State Department of Health.
“The trend is unmistakable: the more obese a woman is, the more likely she is to have had a child with a heart defect,” study first author Dr. James L. Mills, of the NICHD’s Division of Epidemiology, Statistics and Prevention Research, said in a news release.
For this study, researchers compared the records of mothers of 7,392 children born with major heart defects and more than 56,000 mothers of infants born without birth defects. Because the study looked at the records of infants after they were born, it doesn’t conclusively prove that obese women who lose weight before becoming pregnant will reduce their risk of having a baby with a heart defect, the researchers noted.
However, “if a woman is obese, it makes sense for her to try to lose weight before becoming pregnant,” Mills said. “Not only will weight loss improve her own health and that of her infant, it is likely to have the added benefit of reducing the infant’s risk for heart defects.”
- Antiseizure Drug Increases Birth Defect Risk
Using the antiseizure medication valproic acid (Depakote) in the first trimester of pregnancy significantly increased the risk of six types of birth defect, European researchers found.
In an analysis of more than 98,000 pregnancies, the risk of the serious spinal defect known as spina bifida was increased more than 12 times for children of mothers on the drug, according to Lolkje T.W. de Jong-van den Berg, of the University of Groningen in the Netherlands and colleagues.
The risks of another five defects were increased between two and seven times, the researchers reported in the June 10 issue of the New England Journal of Medicine.
Those findings support recommendations by the American Academy of Neurology to avoid the use of the drug in pregnancy, the researchers wrote. In the clinic, they continued, the risks of birth defects associated with valproic acid should be routinely considered in women of childbearing age.
Looking at past studies and comparing them against an antiepileptic-study database set up by the European Surveillance of Congenital Anomalies (EUROCAT), the researchers found that six malformations were significantly linked to a woman’s valproic acid use in her first trimester of pregnancy. In addition to spina bifida, the children of these women faced a more than doubled risk of a heart condition known as an atrial septal defect and a five-fold risk of cleft palate.
The risk of hypospadias — a condition in which the opening of the urethra in boys is on the underside of the penis rather than the end — went up nearly five times with a mother’s use of the drug. Craniosynostosis, a condition in which the bones of the skull close too early, was nearly seven times as common in these children, and polydactyly, a condition in which a child has more than five fingers per hand, was more than twice as common.
On the other hand, the researchers found, absolute risks of malformations remained low, ranging from 0.1 percent for craniosynostosis to 0.7 percent for hypospadias. The absolute risk for spina bifida associated with valproic acid was 0.6 percent, they found.
The researchers also cautioned that the study was observational, so it could not indicate anything about cause and effect. They were also unable to say anything about possible confounding by indication, since the drug is used for several clinical indications, or the effects of varying dosages.
- Common antidepressants ‘increase miscarriage risk’
Taking common antidepressants while pregnant significantly increases the chances of suffering a miscarriage, a new study warns.
The risk rose by more than two thirds if expectant mothers were taking the drugs, researchers found.
Previous studies have also found a link between antidepressants and birth defects.
Experts warned that doctors should discuss the possible risks with pregnant women.
Depression is a very common illness, and an estimated more than one in 30 women take antidepressants while expecting a baby.
However, there are fears that coming off the drugs can lead patients to a relapse into depression, potentially putting both mother and baby at risk.
Researchers found a link between miscarriage and a type of antidepressants, Selective serotonin re-uptake inhibitors (SSRIs), a class of drugs which includes Prozac.
A combination of different antidepressants could up to double the risk of miscarriage, the study also found.
Dr. Anick Berard, from the University of Montreal, who led the research, said: “These results, which suggest an overall class effect of selective serotonin re-uptake inhibitors, are highly robust given the large number of users studied.
“Physicians who have patients of child-bearing age taking antidepressants or have pregnant patients who require antidepressant therapy early in pregnancy discuss the risks and benefits with them.”
The study looked at 5,124 women who had suffered miscarriages.
They found an increased risk associated with SSRIs, especially Seroxat (also called paroxetine) and Efexor (also called venlafaxine).
Overall, the increased risk was 68 per cent.
The findings were published in the Canadian Medical Association Journal.
Last year a study found that expectant mothers who took Seroxat were three times as likely to have a baby with a heart abnormality and those who took Prozac were four times as likely as other women.
A spokesman for Pfizer, which makes venlafaxine, said: “Pfizer will need to review this study in detail until we can provide any further comment.”
- Migraine drugs don’t up birth defect risk: study
A study in nearly 70,000 pregnant women has found no link between migraine drugs called triptans and the risk of birth defects.
However, the researchers did find a “slight increase” in the risk of excessive bleeding during labor, and the failure of the uterus to contract normally after delivery, for women who used the drugs while pregnant.
Triptans are among the most powerful drugs used for migraine; others include aspirin, Excedrin, and ibuprofen.
While as many as three in 10 women may develop migraines during their childbearing years, women often shy away from using such drugs during pregnancy because of safety concerns, according to study co-author Katerina Nezvalova-Henriksen of the University of Oslo in Norway and her colleagues.
However, the authors of the study in Headache note, untreated migraine may itself carry risks for mother and child; some studies have linked it to pre-eclampsia, a potentially deadly pregnancy complication.
“While it is important to exert caution when using any medications during pregnancy, this study indicates” that pregnant women can either start or continue taking triptans without “any major risk” of miscarriage, premature delivery, or other bad outcomes, the authors conclude.
Nezvalova-Henriksen and her team studied nearly 70,000 women. Two percent, or 1,535, had used sumatriptan (Imitrex), rizatriptan (Maxalt), zolmitriptan (Zomig), or eletriptan (Relpax) in pregnancy.
Less than one percent — 373 women — had used the drugs before getting pregnant but not during pregnancy.
The overall birth defect rate, which encompasses everything from large birthmarks to serious heart problems, was the same among women who had taken triptans during pregnancy and those who didn’t have migraines: 5 percent. Among those who had used triptans in the past but not during pregnancy, it was slightly higher: 6 percent.
The women who used triptans were also more likely than non-triptan users to take other drugs during pregnancy, including acetaminophen (Tylenol) with codeine and non-steroidal anti-inflammatory drugs such as ibuprofen.
However, the rate of major birth defects – such as serious problems of the limbs or internal organs — was 3 percent for all three groups. That rate – about one in 33 births – is about what would be expected for all birth defects in the general population.
The researchers did find that women who used triptans in their second or third trimester were more likely to develop a condition called atonic uterus, in which the uterus fails to contract back to its normal size after delivery. This is the leading cause of excessive bleeding after delivery. They were also more likely to lose significant amounts of blood during labor and delivery.
And during pregnancy, they were more likely to suffer from vomiting than women who had never used the drug; they were also more likely to develop pre-eclampsia or eclampsia, and more likely to have deficiencies in the B-vitamin folate.
While many women who suffer migraines will experience improvements in their symptoms after their first trimester, Nezvalova-Henriksen and her team note, those whose symptoms don’t improve by then aren’t likely to get better.
- Agricultural Chemical Spray Linked to Birth Defect Risk
There’s a link between a birth defect called gastroschisis and the agricultural chemical atrazine, a new study has found.
Gastroschisis is an abdominal wall defect in which the intestines, and sometimes other organs, develop outside the abdomen through an opening in the abdominal wall. The incidence of this birth defect, also called infant abdominal hernia, has doubled to quadrupled over the past 30 years.
In the new study, researchers at the University of Washington in Seattle investigated whether environmental exposures were a factor in a higher than normal number of cases in the eastern part of the state.
“Our state has about two times the national average number of cases of gastroschisis,” study co-author Dr. Sarah Waller said in a news release. “The life expectancy for fetuses with this diagnosis is better than 90 percent; however it requires delivery at a tertiary care center with immediate neonatal intervention, which often separates families and can cause serious financial and emotional stress.”
Waller and colleagues analyzed 805 cases of live-born infants with gastroschisis between 1987 and 2006, along with 3,616 normal infants who acted as controls. The researchers matched birth certificates with U.S. Geological Survey databases of agricultural spraying of atrazine, nitrates, and 2,4-dichlorophenoxyacetic acid.
Gastroschisis occurred more often among infants born to mothers who lived less than 25 kilometers (or about 15.5 miles) from the site of high surface water contamination with atrazine. There was no increased risk associated with the other chemicals. The study authors also found that the risk of gastroschisis was higher for women who conceived in the spring (March through May), when agricultural chemical use is more prevalent.
