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Anti-Inflammatory Drugs Taken in Early Pregnancy More Than Double Risk of Miscarriage, Study Finds

ScienceDaily (Sep. 6, 2011) The risk of miscarriage is 2.4 times greater for women who took any type and dosage of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in early pregnancy, according to a study in CMAJ (Canadian Medical Association Journal).
Nonaspirin NSAIDs are a class of drugs that include naproxen, ibuprofen, diclofenac, and celecoxib, and are one of the most common medications used during pregnancy. However, there are concerns about use of these drugs in pregnancy, although studies on the risks have been inconsistent. Researchers from the University of Montreal, CHU Ste-Justine, Quebec, and cole Nationale de la Statistique et de l'Analyse de l'Information, Rennes, France, undertook a study to determine the risk of miscarriage associated with the types and dosages of nonaspirin NSAIDs. They looked at a total of 4705 cases of miscarriage up to the 20th week of gestation, 352 (7.5%) of whom took nonaspirin NSAIDs. Of the 47 050 women in the control group who did not miscarry, 1213 (2.6%) had been exposed to nonaspirin NSAIDs. The data came from the Quebec Pregnancy Registry, which provides information on filled prescriptions, physician visits and diagnoses, and hospitalisations during pregnancy. Women ranged in age from 15 to 45 years old on the first day of gestation and were insured by the Rgie de l'Assurance Maladie du Qubec (RAMQ) for their medications for at least one year prior to and during pregnancy. Exposure to nonaspirin NSAIDs was defined as having filled at least one prescription for any type of the drug during the first 20 weeks of pregnancy or in the two weeks prior to the start of the pregnancy. Ibuprofen is the only nonaspirin NSAID available over the counter in Quebec, and women in the RAMQ drug plan can have that prescribed as a prescription. Naproxen was the most commonly used nonaspirin NSAID followed by ibuprofen. "The use of nonaspirin NSAIDs during early pregnancy is associated with statistically significant risk (2.4-fold increase) of having a spontaneous abortion," writes Dr. Anick Brard, from the University of Montreal and the Director of the Research Unit on Medications and Pregnancy at CHU Ste-Justine. "We consistently saw that the risk of having a spontaneous abortion was associated with gestational use of diclofenac, naproxen, celecoxib, ibuprofen and rofecoxib alone or in combination, suggesting a class effect." The highest risk was associated with diclofenac alone and the lowest risk was in users of rofecoxib alone. However, dosage of nonaspirin NSAIDs did not appear to affect risk. These findings are consistent with other studies but are novel with regards to the nonaspirin NSAIDs types and dosages. "Given that the use of nonaspirin NSAIDs during early pregnancy has been shown to increase the risk of major congenital malformations and that our results suggest a class effect on the risk of clinically detected spontaneous abortion, nonaspirin NSAIDs should be used with caution during pregnancy.," the authors conclude. Source: http://www.sciencedaily.com/releases/2011/09/110906121225.htm

Prenatal Use of Newer Antiepileptic Drugs Not Associated With Increased Risk of Major Birth Defects, Study Finds
ScienceDaily (May 17, 2011) Use of newer-generation antiepileptic drugs, which are also prescribed for bipolar mood disorders and migraine headaches, during the first trimester of pregnancy was not associated with an increased risk of major birth defects in the first year of life among infants in Denmark, according to a study in the May 18 issue ofJAMA. Older-generation antiepileptic drugs are associated with an increased risk of birth defects.
"Epilepsy during pregnancy is a therapeutic challenge. Since the 1990s, the number of licensed antiepileptic drugs has substantially increased, but safety data on first-trimester use of newergeneration antiepileptic drugs and birth defects are limited," according to background information in the article. Ditte Molgaard-Nielsen, M.Sc., and Anders Hviid, M.Sc., Dr.Med.Sci., of the Statens Serum Institut, Copenhagen, Denmark, conducted a study to analyze the association between the use of lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam (newer-generation antiepileptic drugs) during the first trimester of pregnancy and the risk of any major birth defects. The study included data on 837,795 live-born infants in Denmark from January 1996 through September 2008. Individual-level information on dispensed antiepileptic drugs to mothers, birth defect diagnoses, and potential confounders (factors that can influence outcomes) were ascertained from nationwide health registries. Among the live births included in the study (837,795), 19,960 were diagnosed with a major birth defect (2.4 percent) during the first year of life. Among 1,532 pregnancies exposed to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam at any time during the first trimester, 49 infants were diagnosed with a major birth defect (3.2 percent) compared with 19,911 infants (2.4 percent) among 836,263 unexposed pregnancies. After adjusting for various factors, the authors found that exposure to lamotrigine, oxcarbazepine, topiramate, gabapentin, or levetiracetam at any time during the first trimester was not associated with an increased risk of major birth defects. Gabapentin and levetiracetam exposure during the first trimester was uncommon. The prevalence odds ratios for any major birth defects after exposure to any newer-generation antiepileptic drugs during the first trimester were not statistically different for mothers with epilepsy, mood affective disorder or migraine, or without a diagnosis. "Our study, to our knowledge, is the largest analytic cohort study on this topic and provides comprehensive safety information on a class of drugs commonly used during pregnancy. The use of lamotrigine and oxcarbazepine during the first trimester was not associated with moderate or greater risks of major birth defects like the older-generation antiepileptic drugs, but our study cannot exclude a minor excess in risk of major birth defects or risks of specific birth defects. Topiramate, gabapentin, and levetiracetam do not appear to be major teratogens [an agent that can cause malformations in an embryo or fetus], but our study cannot exclude minor to moderate risks of major birth defects," the authors conclude.
Source: http://www.sciencedaily.com/releases/2011/05/110517162026.htm

Prenatal Exposure to Nicotine Affects Stem Cells in Hippocampus


ScienceDaily (Nov. 15, 2010) Prolonged prenatal exposure to nicotine decreases the number of newborn cells in the hippocampus, a brain area important in learning and memory, according to preliminary research presented at Neuroscience 2010, the annual meeting of the Society for Neuroscience, held in San Diego. The study offers a neurobiological explanation for why the children of women who smoke during pregnancy are at an increased risk of developing learning disabilities.
"Previous research has shown that nicotine, cocaine, and other addictive drugs decrease the number of newborn cells in adults. Our research suggests that these effects may be even more dramatic in newborn animals," said Robin Lester, PhD, of the University of Alabama at Birmingham, who directed the study. "These findings provide further warnings to expectant mothers that they should seek help in refraining from smoking during pregnancy," Lester said. To mimic the conditions of moderate to heavy smoking in a pregnant mother, Lester and his colleagues treated pregnant rats with nicotine through an implanted mini-pump, which acts similarly to a nicotine patch. The researchers then counted the number of newborn cells in the offsprings' dentate gyrus, a section of the hippocampus known to contain neuronal stem cells. They also monitored synaptic plasticity -- the reorganization of neural pathways considered essential to learning. "We found a reduced number of dividing stem cells and altered plasticity in the newborn animals exposed to nicotine," Lester said. These findings may lead to new approaches to treating learning disabilities and other behavior deficits associated with prenatal nicotine exposure. Research was supported by a United States Public Service Grant and the Evelyn F. McKnight Brain Institute.
Source: http://www.sciencedaily.com/releases/2010/11/101115155215.htm

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