Preeclampsia and IUGR are important causes of maternal and perinatal mortality and morbidity. Preeclampsia affects 2% to 5% of pregnancies, leading to more than 100,000 maternal deaths worldwide each year. Previous studies have indicated a risk reduction of 20% for preeclampsia with low-dose aspirin started any time during pregnancy.
This is a systematic review and meta-analysis of studies examining the use of low-dose aspirin, started at 16 weeks or earlier or later than 16 weeks of gestation, on maternal and neonatal outcomes of preeclampsia or IUGR and other neonatal outcomes in women at risk for preeclampsia.
- Included were prospective randomized controlled trials extracted from EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials from 1965 to 2008, which examined the effect of low-dose aspirin on pregnant women at risk for preeclampsia.
- Excluded were quasi-randomized trials or studies in which 20% or more women were lost to follow-up.
- Women in the treatment group had to be treated with low-dose aspirin (50 – 150 mg daily, alone or in combination with dipyridamole < 300 mg). The control group had to be allocated to placebo or to no treatment.
- The primary outcome was the occurrence of preeclampsia.
- Secondary outcomes included IUGR, severe preeclampsia, gestational hypertension, placental abruption, preterm birth, low birth weight, and gestational age at delivery.
- Outcomes were stratified by gestational age at which aspirin was started: 16 weeks of gestation or less or more than 16 weeks of gestation.
- Of 773 articles initially identified, 34 were selected for analysis, including 27 articles for the primary outcome of preeclampsia.
- 11,348 women were analyzed.
- 12 studies had women starting aspirin at 16 weeks of gestation or earlier, and 22 studies reported data on women starting aspirin after 16 weeks of gestation.
- Risk for preeclampsia was defined in different ways, including nulliparity and a history of preeclampsia or other hypertensive disorders.
- Women who began aspirin at 16 weeks of gestation or less had a significantly reduced risk for preeclampsia (RR, 0.47; prevalence 9.3% vs 21.3% in the control group).
- They also had a significantly reduced risk for IUGR as defined by the various meta-analysis studies (RR, 0.44; prevalence 7% vs 16.3% in the control group).
- Low-dose aspirin started at 16 weeks of gestation or earlier was also associated with a reduction in severe preeclampsia (RR, 0.09; prevalence 0.7% vs 15.0% in the control group), gestational hypertension (RR, 0.62; prevalence 16.7% vs 29.7% in the control group), and preterm birth (RR, 0.22; prevalence 3.5% vs 16.9% in the control group).
- All studies involving starting aspirin at 16 weeks of gestation or earlier included women at moderate or high risk for preeclampsia.
- The birth weight increase in women starting aspirin at 16 weeks of gestation or earlier was 196 g vs 70 g in women starting aspirin later than 16 weeks.
- The rate of preterm birth was lower for aspirin started earlier than 16 weeks (weighted mean difference, 1.4 weeks).
- Starting low-dose aspirin later than 16 weeks of gestation was not associated with a significant reduction in preeclampsia, IUGR, preterm birth, or gestational hypertension.
- The authors concluded that low-dose aspirin started at 16 weeks of gestation or earlier, but not started at later than 16 weeks, was associated with improved maternal and neonatal outcomes in women at risk for preeclampsia.
- Low-dose aspirin started at 16 weeks of gestation or earlier in women at risk for preeclampsia is associated with a reduction in the risk for preeclampsia, IUGR, preterm birth, low birth weight, and gestational hypertension.
- Low-dose aspirin started later than 16 weeks of gestation in women at risk for preeclampsia is not associated with a reduction in the risk for preeclampsia, IUGR, preterm birth, and gestational hypertension