February 16th, 2010 
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.
Related
- Drugs for depression, anxiety tied to preterm birth
Pregnant women who take certain drugs for depression or anxiety may have heightened risks of preterm delivery or other birth complications, according to a new study.
Researchers found that among nearly 3,000 women who gave birth in Washington State, those who started taking antidepressants known as selective serotonin reuptake inhibitors (SSRIs) in the second or third trimester had a higher risk of preterm birth.
Compared with their counterparts not on the medications, these women were nearly five times more likely to deliver prematurely.
The same risk was not seen, however, among women who started on an SSRI before pregnancy or during the first trimester. SSRIs include drugs like sertraline (Zoloft), paroxetine (Paxil) and fluoxetine (Prozac).
The researchers also found a higher risk of preterm delivery among women who took anti-anxiety drugs known as benzodiazepines, regardless of when they began treatment.
Those drugs, which include medications like lorazepam (Ativan) and alprazolam (Xanax), were linked to higher risks of other complications as well – including low birth weight, newborn respiratory distress and a low Apgar score, a standard measure of newborn health.
The findings of the study are published in the American Journal of Obstetrics & Gynecology.
Exactly what the study means for women on SSRIs or benzodiazepines is not entirely clear. A major limitation is that it could not estimate the benefits of treatment, lead researcher Dr. Ronit Calderon-Margalit, of the Hebrew University-Hadassah School of Public Health in Jerusalem, noted in an email to Reuters Health.
Any risks of using the medications during pregnancy need to be balanced against the risks of leaving depression and anxiety disorders untreated.
“It is very important to have other studies of the risks associated with (these) drugs, but also of benefits associated with treating mothers,” said Calderon-Margalit, who was at the University of Washington in Seattle at the time of the study.
In addition, SSRIs did not appear to present equal risks for all women. Calderon-Margalit described the antidepressant findings as “mostly reassuring” for women who start the drugs before pregnancy or in the first trimester — as most SSRI users in the study had.
The study included 2,793 pregnant women, 11 percent of whom used a psychiatric medication during pregnancy. Of these, 138 were on an SSRI, while 85 used a benzodiazepine.
Among women who were not on any medication, 9 percent gave birth prematurely, versus nearly half of women on benzodiazepines.
Meanwhile, 14 percent of women on SSRIs had a preterm birth, but the elevated risk turned out to be concentrated among those who started an antidepressant after the first trimester. Of those 21 women, 16 delivered prematurely.
Several other birth complications, often related to preterm birth, were also higher-than-average among women on benzodiazepines.
Seventeen percent of their newborns suffered respiratory distress syndrome and one-third ended up in the neonatal intensive care unit. Those figures were 3 percent and 6 percent, respectively, among newborns whose mothers had not used psychiatric medications during pregnancy.
Calderon-Margalit pointed out that most women on benzodiazepines used lorazepam (Ativan), so it is possible that the risks are associated mainly with that drug. However, further research is needed to determine whether any particular medications carry particular risks.
- Antidepressants Raise Risk of Pre-Term Birth: Study
Danish women who took antidepressants during pregnancy had twice the risk of pre-term delivery as other women, and their babies were more likely to be admitted to an intensive care unit than those of women who did not take the drugs, researchers reported on Monday.
They said antidepressants, known as selective serotonin reuptake inhibitors or SSRIs, which affect a message-carrying brain chemical called serotonin, may raise the risk of pre-term delivery and affect a baby’s health at birth.
Some prior studies have found that drugs in this class can cross the placenta and appear in the umbilical cord blood of babies whose mothers have taken them.
“The study justifies increased awareness to the possible effects of intrauterine exposure to antidepressants,” Dr. Najaaraq Lund of the Bandim Health Project in Guinea-Bissau, and colleagues wrote in the Archives of Pediatrics and Adolescent Medicine.
About one in 10 pregnant women experience depression during pregnancy. Because depression can jeopardize a pregnant woman’s health, doctors often prescribe antidepressants, but it is not yet clear how these drugs affect a baby’s health.
To study this, Lund and colleagues analyzed data on 57,000 pregnancies and deliveries at Aarhus University Hospital in Skejby, Denmark, between 1989 to 2006.
They identified 329 pregnancies in which the mothers took an SSRI medication, another 4,902 with a history of psychiatric illness not treated with an antidepressant, and 51,700 with no history of psychiatric illness.
Women who took antidepressants while pregnant delivered their babies five days earlier than other women in the study, and had twice the risk of pre-term delivery than women with no history of psychiatric illness.
Babies exposed to antidepressants during pregnancy were far more likely than those in the other two groups to have a five-minute Apgar score — a measure of a newborn’s health — of seven or below. Seven is typically an indicator of a healthy baby.
They were also more likely to be admitted to the neonatal intensive care unit, and some of these babies showed signs of withdrawal, such as jitters, seizures, respiratory problems, infections and jaundice.
The team found no differences in the babies’ head size or birth weight among the three groups.
Antidepressants used by women in the study included Pfizer Inc’s Zoloft, known generically as sertraline; Forest Laboratories Inc’s Celexa, or citalopram, and Lexapro, or escitalopram; Eli Lilly and Co’s Prozac or fluoxetine; and GlaxoSmithKline’s Paxil or paroxetine.
- 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.
- Infertility treatments may raise preterm birth risk
Couples who conceive through certain types of infertility treatment may have a higher-than-normal likelihood of having a premature baby, a new study suggests.
Danish researchers found that among more than 20,000 women who gave birth at their hospital between 1989 and 2006, those who had conceived through in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) had a higher risk of preterm delivery.
Of the 730 babies born to women who underwent IVF or ICSI, nearly 8 percent were premature and 1.5 percent were very premature — born before the 32nd week of pregnancy. A normal pregnancy lasts 40 weeks.
In comparison, roughly 5 percent of babies born to fertile mothers were premature, and 0.6 percent were born very preterm, the researchers report in the journal Fertility and Sterility.
When the researchers accounted for factors like the mother’s age, weight and exposure to cigarette smoking, the IVF and ICSI procedures were still linked to a 53 percent greater risk of preterm delivery and a doubling in the odds of very premature birth.
Other forms of fertility treatment — namely, fertility drugs and insemination — were not related to the risk of preterm delivery.
Nor was the higher risk with IVF and ICSI explained by elevated rates of twin or higher-order births. The study included only singleton births.
Together, the researchers say, the findings suggest that something about the IVF and ICSI procedures themselves might raise the odds of preterm birth.
Both IVF and ICSI involve joining a woman’s egg and a man’s sperm in a lab dish, then — if fertilization is successful — transferring one or more embryos to the woman’s uterus. ICSI is typically used for male fertility problems, including a low sperm count or poor sperm quality. It involves isolating a single sperm and injecting it directly into the egg.
“The IVF/ICSI procedures include hormone stimulation and mechanical procedures. Both of these factors may influence the risk of preterm delivery,” lead researcher Dr. Kirsten Wisborg, of Aarhus University Hospital in Denmark, told Reuters Health in an email.
The fact that other forms of fertility treatment were not linked to preterm delivery suggests that infertility itself is not to blame, according to Wisborg. However, she pointed out, couples who undergo IVF or ICSI may have a different “reproductive pathology” than those who conceive via fertility drugs or insemination, as they frequently have been infertile for a longer period and have failed to conceive through those “low-tech” fertility treatments.
There may also be other factors, unmeasured in this study, that put women who undergo IVF or ICSI at greater risk of preterm delivery, Wisborg said.
Another possibility, Wisborg said, has to do with the “vanishing twin” phenomenon. Some of the singleton births to women who underwent IVF or ICSI may have begun as a twin pregnancy, with only one fetus surviving beyond the early stages. Research suggests that these surviving fetuses are at increased risk of preterm delivery and low birth weight.
The most important factor in reducing preterm birth risk with IVF or ICSI is to avoid higher-order pregnancies, according to Wisborg. But women can also lower the risk, she said, by not smoking and avoiding alcohol during pregnancy.
- 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.
