Review of studies finds lower preeclampsia risk with prenatal aspirin

The use of low-dose aspirin during pregnancy was associated with a reduced risk of preeclampsia in women at high risk, and did not appear to be associated with harmful effects, in a systematic review of 23 studies of low-dose aspirin in women at high or average risk of preeclampsia, the authors reported.

In women at high risk for preeclampsia, "available evidence indicates modest effects but important benefits of daily low-dose aspirin for prevention of the condition and consequent illness," concluded Jillian Henderson, Ph.D., of Kaiser Permanente Northwest, Portland, Ore., and her associates.

However, the review had limitations and could not rule out rare or long-term risks of treatment, they said. In addition, more studies are needed, including more in black women, who are disproportionately affected by preeclampsia in the United States.

The study of the effects of low-dose aspirin on the risk of preeclampsia and other maternal and fetal outcomes is being published online April 8 in Annals of Internal Medicine (www.annals.org).

The review, funded by the Agency for Healthcare Research and Quality (AHRQ), was conducted for the U.S. Preventive Services Task Force. The USPSTF will post a draft recommendation, based on this review, as an update to the USPSTF 1996 recommendation (which is not active).

The authors reviewed 23 studies of low-dose aspirin in women at high or average risk of preeclampsia with a mean age of 20-31 years; these included randomized controlled studies and observational studies. Treatment was not started before 12 weeks in any of the studies, but was started before 16 weeks in 8 studies. With the exception of six studies, treatment was continued until delivery. In most of the studies, daily aspirin doses ranged from 60 to 100 mg.

The use of aspirin was associated with a 24% reduced risk of preeclampsia in the studies of high-risk women. The dosage or timing (started before or after 16 weeks) did not have an effect on risk. The reduced risk was greater in the studies that used doses higher than 75 mg, but this difference was not significant, the authors reported.

The use of aspirin was associated with a 20% reduced risk of intrauterine growth restriction (IUGR) and a 14% reduced risk of preterm birth, they reported, adding that the addition of negative studies could make these associations nonsignificant.

In the discussion, the authors said that their confidence in the magnitude of these results was "tempered by evidence of small-study effects and modest findings" in the two largest studies. Therefore, a more conservative estimate for the reduced risk of these outcomes – preeclampsia, IUGR, and preterm birth – was "closer to 10%," they wrote.

They did not identify any harmful effects of aspirin to the baby or mother, but "potential rare or long-term harms could not be ruled out," they concluded. There was some evidence of a possible increased risk in placental abruption, but the associations were not statistically significant. There was no evidence that perinatal mortality was increased, and the data suggested there was "possibly a benefit" on mortality favoring low-dose aspirin.

Their analyses also did not find evidence that low-dose aspirin increased the risk of postpartum hemorrhage or increased mean blood loss or the risk of intracranial hemorrhage in newborns.

The long-term follow-up data on infants (up to age 18 months) available in one study did not show differences in hospital visits, gross motor development, or height and weight between infants exposed to aspirin and those not exposed to aspirin.

Among the limitations of the study was the fact that only studies considered "fair to good quality" were included, and that the smaller studies did not capture any rare events such as perinatal death or placental abruption.

The review was conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center, under a contract to the AHRQ. One author was paid by the USPSTF to conduct the review; two authors reported receiving AHRQ grants during this study (one author) or outside of the study (one author); the rest had no disclosures.

emechcatie@frontlinemedcom.com

The use of low-dose aspirin during pregnancy was associated with a reduced risk of preeclampsia in women at high risk, and did not appear to be associated with harmful effects, in a systematic review of 23 studies of low-dose aspirin in women at high or average risk of preeclampsia, the authors reported.

In women at high risk for preeclampsia, "available evidence indicates modest effects but important benefits of daily low-dose aspirin for prevention of the condition and consequent illness," concluded Jillian Henderson, Ph.D., of Kaiser Permanente Northwest, Portland, Ore., and her associates.

However, the review had limitations and could not rule out rare or long-term risks of treatment, they said. In addition, more studies are needed, including more in black women, who are disproportionately affected by preeclampsia in the United States.

The study of the effects of low-dose aspirin on the risk of preeclampsia and other maternal and fetal outcomes is being published online April 8 in Annals of Internal Medicine (www.annals.org).

The review, funded by the Agency for Healthcare Research and Quality (AHRQ), was conducted for the U.S. Preventive Services Task Force. The USPSTF will post a draft recommendation, based on this review, as an update to the USPSTF 1996 recommendation (which is not active).

The authors reviewed 23 studies of low-dose aspirin in women at high or average risk of preeclampsia with a mean age of 20-31 years; these included randomized controlled studies and observational studies. Treatment was not started before 12 weeks in any of the studies, but was started before 16 weeks in 8 studies. With the exception of six studies, treatment was continued until delivery. In most of the studies, daily aspirin doses ranged from 60 to 100 mg.

The use of aspirin was associated with a 24% reduced risk of preeclampsia in the studies of high-risk women. The dosage or timing (started before or after 16 weeks) did not have an effect on risk. The reduced risk was greater in the studies that used doses higher than 75 mg, but this difference was not significant, the authors reported.

The use of aspirin was associated with a 20% reduced risk of intrauterine growth restriction (IUGR) and a 14% reduced risk of preterm birth, they reported, adding that the addition of negative studies could make these associations nonsignificant.

In the discussion, the authors said that their confidence in the magnitude of these results was "tempered by evidence of small-study effects and modest findings" in the two largest studies. Therefore, a more conservative estimate for the reduced risk of these outcomes – preeclampsia, IUGR, and preterm birth – was "closer to 10%," they wrote.

They did not identify any harmful effects of aspirin to the baby or mother, but "potential rare or long-term harms could not be ruled out," they concluded. There was some evidence of a possible increased risk in placental abruption, but the associations were not statistically significant. There was no evidence that perinatal mortality was increased, and the data suggested there was "possibly a benefit" on mortality favoring low-dose aspirin.

Their analyses also did not find evidence that low-dose aspirin increased the risk of postpartum hemorrhage or increased mean blood loss or the risk of intracranial hemorrhage in newborns.

The long-term follow-up data on infants (up to age 18 months) available in one study did not show differences in hospital visits, gross motor development, or height and weight between infants exposed to aspirin and those not exposed to aspirin.

Among the limitations of the study was the fact that only studies considered "fair to good quality" were included, and that the smaller studies did not capture any rare events such as perinatal death or placental abruption.

The review was conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center, under a contract to the AHRQ. One author was paid by the USPSTF to conduct the review; two authors reported receiving AHRQ grants during this study (one author) or outside of the study (one author); the rest had no disclosures.

emechcatie@frontlinemedcom.com

The use of low-dose aspirin during pregnancy was associated with a reduced risk of preeclampsia in women at high risk, and did not appear to be associated with harmful effects, in a systematic review of 23 studies of low-dose aspirin in women at high or average risk of preeclampsia, the authors reported.

In women at high risk for preeclampsia, "available evidence indicates modest effects but important benefits of daily low-dose aspirin for prevention of the condition and consequent illness," concluded Jillian Henderson, Ph.D., of Kaiser Permanente Northwest, Portland, Ore., and her associates.

However, the review had limitations and could not rule out rare or long-term risks of treatment, they said. In addition, more studies are needed, including more in black women, who are disproportionately affected by preeclampsia in the United States.

The study of the effects of low-dose aspirin on the risk of preeclampsia and other maternal and fetal outcomes is being published online April 8 in Annals of Internal Medicine (www.annals.org).

The review, funded by the Agency for Healthcare Research and Quality (AHRQ), was conducted for the U.S. Preventive Services Task Force. The USPSTF will post a draft recommendation, based on this review, as an update to the USPSTF 1996 recommendation (which is not active).

The authors reviewed 23 studies of low-dose aspirin in women at high or average risk of preeclampsia with a mean age of 20-31 years; these included randomized controlled studies and observational studies. Treatment was not started before 12 weeks in any of the studies, but was started before 16 weeks in 8 studies. With the exception of six studies, treatment was continued until delivery. In most of the studies, daily aspirin doses ranged from 60 to 100 mg.

The use of aspirin was associated with a 24% reduced risk of preeclampsia in the studies of high-risk women. The dosage or timing (started before or after 16 weeks) did not have an effect on risk. The reduced risk was greater in the studies that used doses higher than 75 mg, but this difference was not significant, the authors reported.

The use of aspirin was associated with a 20% reduced risk of intrauterine growth restriction (IUGR) and a 14% reduced risk of preterm birth, they reported, adding that the addition of negative studies could make these associations nonsignificant.

In the discussion, the authors said that their confidence in the magnitude of these results was "tempered by evidence of small-study effects and modest findings" in the two largest studies. Therefore, a more conservative estimate for the reduced risk of these outcomes – preeclampsia, IUGR, and preterm birth – was "closer to 10%," they wrote.

They did not identify any harmful effects of aspirin to the baby or mother, but "potential rare or long-term harms could not be ruled out," they concluded. There was some evidence of a possible increased risk in placental abruption, but the associations were not statistically significant. There was no evidence that perinatal mortality was increased, and the data suggested there was "possibly a benefit" on mortality favoring low-dose aspirin.

Their analyses also did not find evidence that low-dose aspirin increased the risk of postpartum hemorrhage or increased mean blood loss or the risk of intracranial hemorrhage in newborns.

The long-term follow-up data on infants (up to age 18 months) available in one study did not show differences in hospital visits, gross motor development, or height and weight between infants exposed to aspirin and those not exposed to aspirin.

Among the limitations of the study was the fact that only studies considered "fair to good quality" were included, and that the smaller studies did not capture any rare events such as perinatal death or placental abruption.

The review was conducted by the Kaiser Permanente Research Affiliates Evidence-based Practice Center, under a contract to the AHRQ. One author was paid by the USPSTF to conduct the review; two authors reported receiving AHRQ grants during this study (one author) or outside of the study (one author); the rest had no disclosures.

emechcatie@frontlinemedcom.com