Ibuprofen may harm fertility of female child

Pregnant women who take the pain killer ibuprofen in the first trimester of their pregnancy may be reducing the store of eggs in the ovaries of their daughters. Researchers have found the first evidence in human ovarian tissue that exposure to ibuprofen during the crucial first three months of fetal development results in a loss of the germ cells that go into making the follicles from which female eggs develop. The germ cells either died or failed to grow and multiply at the usual rate.

Female children are born with a finite number of follicles in their ovaries and this defines their future reproductive capacity as adults," explained Dr Séverine Mazaud-Guittot, a researcher at INSERM in Rennes, France, who led the study. "A poorly stocked initial reserve will result in a shortened reproductive life span, early menopause or infertility-events that occur later in life.

The development of the follicles in the fetus has not been completed by the end of the first trimester, so if the ibuprofen treatment is short then the ovarian reserve may recover to some extent. However,  two to seven days of exposure to ibuprofen dramatically reduced the germ cell stockpile in human fetal ovaries during the first trimester of pregnancy and the ovaries did not recover fully from this damage.

This suggests that prolonged exposure to ibuprofen during fetal life may lead to long-term effects on women's fertility and raises concern about ibuprofen consumption by women during the first trimester of pregnancy. Researcher obtained human fetuses between 7-12 weeks of development from legally induced terminations of pregnancy and with the mothers' consent.

Then they cultured the ovarian tissue in the laboratory; part of the tissue from each fetus was exposed to ibuprofen and a second part (the control) was not. Samples from 185 fetuses were analysed. They measured the quantity of ibuprofen in the blood in the umbilical cord in order to analyse how much the fetus would have been exposed to.

They found that ibuprofen crosses the placental barrier. The concentration in the umbilical cords of fetuses from mothers who ingested 800 mg (four pills of 200 mg) two to four hours before surgery is similar to the concentration that can be found in adult's blood for the same treatment. This shows that the fetus is exposed to the same concentration as the mother. In contrast to the fetal tissue that was not exposed to ibuprofen, the tissue that was exposed to concentrations of 10 μM (micromolar) of ibuprofen for a week had approximately half the number of ovarian germ cells 2.

There were fewer cells growing and dividing, more cells dying and a dramatic loss of germ cell numbers, regardless of the gestational age of the fetus. There were significant effects after seven days of exposure to 10 μM of ibuprofen, cell death occurred after two days of treatment. Five days after withdrawing ibuprofen, these harmful effects of ibuprofen were not fully reversed. Ibuprofen use should be restricted to the shortest duration and at the lowest dose necessary to achieve pain or fever relief, especially during pregnancy.
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Acetaminophen in pregnancy may cause language delays

According to new study, children whose mothers used acetaminophen-known as Tylenol early in pregnancy may have an increased risk of language delays. Researchers found that when pregnant women used the painkiller during the first trimester, their daughters were more likely to have language delays, such link was not  seen among boys.

A "language delay" meant the child was using fewer than 50 words, according to the report. This medication should probably be used only with caution, and limited to absolute need," said Christina Chambers, a pediatrics professor at the University of California, San Diego. Chambers, who also co-directs the university's Center for Better Beginnings.

Doctors consider its pain and fever reliever of choice during pregnancy. That's because nonsteroidal anti-inflammatory drugs-including aspirin, ibuprofen and naproxen haverisks, particularly later in pregnancy, according to the Organization of Teratology Information Specialists. The group tracks research on medication and other exposures during pregnancy.

There is no good alternative to acetaminophen, evidence is growing that there can be risks from taking the drug during pregnancy, especially more than occasionally. One recent study found that when women used acetaminophen for more than a month during pregnancy, their children had a higher risk of being diagnosed with attention deficit hyperactivity disorder ADHD.

It's not clear that the drug causes developmental problems, but researchers have speculated that it might interfere with hormones that are important in fetal brain development. Acetaminophen is hormonally active, any hormonal effects might affect girls and boys differently. The findings are based on Swedish women who enrolled in a long-term health study during their first trimester. Overall, 59 percent said they'd taken acetaminophen since becoming pregnant.

Their children had their language development assessed at 30 months of age. Roughly 4 percent of girls and 13 percent of boys were found to have a delay. Among girls, the study found, the risk of language delay rose in accordance with mothers' prenatal acetaminophen use. If a pregnant woman had taken more than six tablets in the first trimester, her daughter's risk of language delay was about six times higher, versus girls whose mothers did not use the drug.
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Fever in early pregnancy causes facial birth defects

Researchers have known for decades that fevers in the first trimester of pregnancy increase the risk for some heart defects and facial deformities such as cleft lip or palate in developing fetus. Researchers now have evidence indicating that fever is responsible for interferes with the development of the heart and jaw during the first three to eight weeks of pregnancy.

The results suggest a portion of congenital birth defects could be prevented by lowering the mother's fever with the use of acetaminophen during the first trimester. Women who are planning to become pregnant are advise to start taking prenatal vitamins and folic acid, they should take drug that can reduce the effects of fever if they have fever during the first trimester

Acetaminophen (Tylenol), which has been studied extensively and determined to be safe during the first trimester is recommended. The use of nonsteroidal anti-inflammatory drugs NSAIDs such as ibuprofen and aspirin also reduce fevers, but some NSAIDs are not safe to use during the later stages of pregnancy.

To observe how fever impacts a developing fetus, the researchers studied zebra embryo. Among their discoveries, they found that neural crest cells, the cells that are critical building blocks for the heart, face and jaw - contain temperature-sensitive properties. These neural crest cells contain temperature-sensitive ion channels that typically are found in the sensory neurons. They're the channels that, when you stick your hand in a hot cup of water, tell your body the temperature has changed.

The researchers engineered a noninvasive magnet-based technology to create fever-like conditions in two specific temperature-sensitive ion channels called TRPV1 and TRPV4 in the neural crest cells involved in developing the heart and face. When those neural crest cells were subjected to conditions mimicking a transient fever, the embryos developed craniofacial irregularities and heart defects, including double outlet right ventricle, Tetralogy of Fallot and other outflow obstructions. The type of defect depends on whether the fever occurs during heart development or head and face development.
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