January 21st, 2010 
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.
Related
- 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.
- 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.
- Many Pregnant Women Take Drugs Harmful to Baby
With the help of their doctors, women planning to become pregnant should take an inventory of the medications they take, researchers from Canada advise.
In a study, they found that many pregnant women still take medications long known to cause birth defects.
Some medications with known fetal risk, such as drugs that control epilepsy, are essential during pregnancy, Dr. Anick Berard, at the University of Montreal in Quebec, noted in an email correspondence to Reuters Health.
Other medications, such as those that treat severe acne, anxiety and psychiatric drugs, antibiotics, and many drugs prescribed for heart disease and medical conditions, “can and should be avoided,” according to Berard.
Women should understand the side effects of any drug they are taking — especially drugs treating a chronic condition — and plan pregnancies to avoid or minimize risks such drugs pose to babies, Berard added.
For the 5 years between January 1998 and the last day of 2002, Berard and colleagues analyzed the prescriptions filled by pregnant women for drugs available at the time and known to pose fetal risks.
Their report, in BJOG: An International Journal of Obstetrics and Gynecology, shows 56 percent of 109,344 pregnant women filled at least one medication prescription. A total of 6.3 percent (6,871 women) did so for at least one medication known to pose a risk to the fetus.
“These pregnancies were associated with an elevated number of (pregnancy terminations) and babies born with major (birth defects) in comparison with the expected numbers in the population,” they note.
Specifically, terminations occurred in 47 percent of the pregnancies exposed to drugs with known fetal risks. Six percent of these pregnancies ended in miscarriage.
By contrast, in the much larger non-exposed group about 36 percent of the pregnancies had been terminated and fewer than 5 percent ended in miscarriage.
Berard’s team further identified birth defects in 8.2 percent of 2,842 infants exposed to risky drugs during gestation and available for assessment, compared with 7.1 percent of the 59,287 infants not exposed. This is “a statistically significant difference,” they note.
They emphasize, however, that it cannot be concluded that the drug exposure caused the birth defects. These pregnancies may have also been exposed to other harmful agents or maternal health conditions, they point out.
- Rheumatoid arthritis tied to pregnancy complications
Pregnant women with rheumatoid arthritis may have increased risks of high blood pressure, having an underweight baby or needing a cesarean section, a new study suggests.
Rheumatoid arthritis (RA) arises when the immune system mistakenly attacks tissue in the joints, leading to inflammation, pain and progressive joint damage. The disease is more common in women than men, and frequently develops during the childbearing years.
So far, studies have come to conflicting findings as to the potential effects of RA on pregnancy. Some, for example, have found that women with RA have higher risks of preterm delivery and having an underweight newborn, while others have found no such link.
For the new study, researchers used records from Taiwan’s national health system to compare 1,912 new mothers with RA with 9,560 new mothers without the disease.
They found that women with RA had a two-fold higher risk of pre-eclampsia — a potentially dangerous condition, marked by high blood pressure and protein in the urine, that develops in the second or third trimester.
Women with RA were also 47 percent more likely to have a low-birth-weight baby and 19 percent more likely to require a C-section, according to findings published in the Annals of Rheumatic Diseases.
Still, with the exception of C-section — reported for 42 percent of women with RA and 38 percent of those without RA — the large majority of women did not have these pregnancy complications.
Just under 3 percent of women with RA developed pre-eclampsia, compared with just over 1 percent of women in the comparison group. Eight percent of new moms with RA had a baby weighing less than 5.5 pounds, versus 5.5 percent of the comparison group.
Women with RA were also more likely to have a newborn who was “small for gestational age,” a sign of restricted growth in the womb. The problem was seen in 17 percent of women with RA, and 15 percent of women without the condition.
It is not clear why there is an association between RA and certain problems of pregnancy, according to Dr. Herng-Ching Lin and colleagues at Taipei Medical University.
Although the current study was large and allowed the researchers to account for a number of factors in the odds of pregnancy complications — like the women’s age and family income — it also lacked some important information.
The researchers had no information on the severity of each woman’s RA or medication use during pregnancy. So it’s not possible to tell how those factors might have affected the odds of complications, Lin’s team notes.
A number of RA medications, like methotrexate and leflunomide, may be harmful to the fetus and must be stopped before a woman conceives. But certain other medications, like prednisone and non-steroidal anti-inflammatory drugs such as ibuprofen, may still be used during pregnancy.
Future studies, Lin’s team writes, should try to determine the roles of RA severity and medication use in the pregnancy complications seen in this study. For now, the findings reinforce the recommendation that women with RA get good prenatal care, with regular visits to their obstetrician and rheumatologist.
- Omega-3 Supplements Don’t Reduce Risk of Preterm Birth
Omega-3 fatty acid supplements are believed to have many health benefits, but the one thing they can’t do is help women with a history of delivering their babies early carry their next child to full term, new research finds.
“The omega-3 did not add any benefit,” said study author Dr. Margaret Harper, an associate professor of obstetrics and gynecology at Wake Forest University School of Medicine, Winston-Salem, NC. The study appears in the February issue of Obstetrics & Gynecology.
Harper and her colleagues randomly assigned 852 pregnant women with a history of a preterm birth either to get a daily omega-3 supplement or a placebo beginning about week 16 to 22 and continuing through week 36 of gestation.
All women also received weekly intramuscular hormone injections of hydroxyprogesterone caproate, which has been shown to improve the chances of carrying a baby to term, Harper said.
Her team followed up to see which women delivered before 37 weeks. Full-term is defined as 37 weeks of completed gestation.
Delivery before 37 weeks occurred in 37.8 percent of those taking omega-3, and 41.6 percent of those in the placebo group, a small difference.
Prematurity is the leading cause of newborn death, the authors write in the report, and it is increasing in the United States. A woman who delivers one baby before term is more likely to deliver future babies early.
Harper’s team decided to study the value of the omega-3 supplements after conflicting findings about the value of the supplements for women at high risk of premature delivery. For those at low-risk, she said, the findings seem to agree that omega-3 supplements don’t further reduce the risk of preterm birth.
A recent large review of published studies found only one that showed benefit of the supplements in high-risk women, she said.
According to Harper, omega-3 fatty acids, when metabolized, are converted to much less potent biochemicals called prostaglandins, which make the uterus contract, than are omega-6 fatty acids — also essential fatty acids but typically over-eaten in Western diets. Adding omega-3s to an omega-6-heavy diet, so the thinking went, might result in better chances of carrying the baby to term.
Omega-3 supplements, in other research, have been found to help heart health, to lower blood pressure and to reduce the risk of abnormal heartbeats.
But in Harper’s study, she also noted that women getting omega-3 supplements were more likely to give birth to a baby with respiratory distress syndrome (RDS). While 59 babies (13.9 percent) of those in the omega-3 group had RDS, only 35 (8.7 percent) of those in the placebo group did. In other words, the omega-3 mothers’ babies were 1.6 times more likely to get RDS than infants born to mothers taking placebo. It’s the first time such a finding has been reported in clinical trials, the authors wrote.
“While the study’s results showed no difference, there is early evidence that omega-3 fatty acids are beneficial for fetal brain development, so women should still consider taking them, in conjunction with their doctor’s advice, despite what seems to be little benefit for the reduction of spontaneous preterm birth.”
