Prophylactic use of aspirin can considerably bring down the incidence of preterm SGA

Use of prophylactic aspirin in high-risk group identified by first trimester screening for preeclampsia would considerably lower the incidence of preterm and early SGA by about 20% and 40%, respectively report the results of a data analysis published July 2018 in ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) journal Ultrasound in Obstetrics and Gynecology.

The researchers analyzed the data from two multicentric trials: Screening program for pre-eclampsia (SPREE) study and the Aspirin for Evidence-Based Preeclampsia Prevention trial (ASPRE). SPREE is a prospective multicenter cohort study that screened women for PE during 11-13 weeks by measuring Mean arterial pressure (MAP), Uterine artery pulsatility index (UtA‐PI), Serum placental growth factor (PlGF), and Serum pregnancy‐associated plasma protein‐A (PAPP‐A).

ASPRE trial examined the prophylactic effect of low-dose aspirin started at 11-14 weeks for prevention of PE in women at increased risk for preterm PE.  The results demonstrated that aspirin reduces the incidence of early-PE by 89% and pre-term PE by 62% but does not much reduce the incidence of term PE.

The combined use of maternal factors mean arterial pressure, uterine artery pulsatility index and serum placental growth factor for the screening for preterm preeclampsia identifies a high proportion of patients who will develop small for gestational age (SGA) babies.

Screening in SPREE trial identified 46% of SGA <10th Percentile neonate born before 37 weeks and 56% of those born before 32 weeks with a screen positive rate of 12.2%. Analysis of data from ASPRE trial showed that aspirin reduced the rate of SGA <10th Percentile by 40% in babies born at or before 37 weeks and by 73% in babies born before 32 weeks.

The decrease in the incidence of SGA infants was mainly due to a substantial decrease in the incidence of PE to the amount of 90% in babies born before 32 weeks and 70% in babies born at or before 37 weeks.

Hence, the authors concluded that first-trimester screening of PE identifies a high proportion of patients with who will develop preterm-SGA as the pregnancy progresses further and the prophylactic use of aspirin can prevent that.

Here is a Video abstract of the above study

Abstract

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News from ACOG 2018: Aspirin cuts down the risk of superimposed preeclampsia in women with chronic hypertension

Keeping up with the American College of Obstetricians and Gynecologists (ACOG) 2016 practice guideline of supplementing low-dose aspirin to pregnant women with chronic hypertension was associated with a 57% decrease in superimposed preeclampsia.

Investigators at Thomas Jefferson University presented the results of this retrospective study in a poster presentation at the ACOG 2018 annual meeting (April 27–30, 2018, Austin, Texas).

The study participants included 715 women with chronic hypertension carrying singleton pregnancy, who delivered at Thomas Jefferson University Hospital between January 2008 to July 2017.

The women were divided into 2 groups based on whether they delivered before and after ACOG recommendations. The pre-ACOG group included 635 women while the post-ACOG group had 80 women.

The cohort was further stratified based on additional risk factor for the development of superimposed preeclampsia (SIP) like a previous history of preeclampsia or pregestational diabetes. The primary outcome of interest was the development of preeclampsia, while the secondary outcomes studied were the incidence of SIP with severe features (SIPSF), small for gestational age, and preterm birth was also studied.

The incidence of SIP was dramatically reduced by 57% in women with chronic HT who received low dose aspirin (OR 0.43 (95% CI 0.26-0.73).

Women who had no other risk factor for the development of SIP, the incidence of SIP and SIP with severe features decreased by 75% and 77% respectively.

The incidence of secondary outcomes did not show any significant changes. Aspirin showed the highest benefits in women with chronic hypertension who did not have any additional risk factor for preeclampsia.

Hence the authors concluded that this study showed that ACOG guidelines have a significant positive impact on bringing down the incidence of superimposed preeclampsia in patients with chronic hypertension.

Abstract

ACOG Practice Advisory on Low-Dose Aspirin and Prevention of Preeclampsia

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Daily low dose aspirin brings down rates of preterm preeclampsia in high risk women.

Courtesy: Preeclampsia Foundation

Women who received 150 mg of aspirin daily had 62% reduced risk of developing preterm preeclampsia (resulting in delivery before 37 weeks) and an 82% reduction in the rate of early preeclampsia (resulting in delivery before 34 weeks) as compared to women who received placebo reports the result of small randomized trial.  

The results of this Fetal Medicine Foundation’s (FMF’s) Project “ASPRE” was presented at the 16th World Congress in Fetal Medicine, 25-29th June 2017, Ljubljana, Slovenia as well as published online simultaneously in the New England Journal of Medicine.

Combined Multi-Marker Screening and Randomised Patient Treatment with Aspirin for Evidence-Based Pre-Eclampsia Prevention (ASPRE) is a multicentre collaboration on the prediction and prevention of preeclampsia sponsored by the Seventh Framework Programme of the European Union.

The FMF combined PerkinElmer’s highly sensitive DELFIA® Xpress PlGF 1-2-3™ assay, which is optimized for first trimester prediction of preeclampsia with mean arterial pressure, uterine-artery pulsatility index, to identify 1776 women with singleton pregnancies who were at high risk of developing preeclampsia.

The women were randomized at 11 to 14 weeks of gestation to receive either aspirin 150 mg per day, or placebo until 36 weeks of gestation and followed for delivery with preeclampsia before 37 weeks of gestation.

After randomization, 152 women did not want to participate and 4 were lost to follow-up, so the aspirin group has 798 women and the placebo group has 822 women.  

In an intent to treat analysis it was seen that preterm preeclampsia occurred in 13 women (1.6%) in aspirin group versus 35 women (4.3%) in the placebo group (P=0.004).

Other pregnancy complications like miscarriages, still births, pregnancy termination and neonatal deaths were comparable in both the groups, but the study was not designed to test secondary outcomes.

The authors concluded , “ This randomized trial showed that among women with singleton pregnancies who were identified by means of first-trimester screening as being at high risk for preterm preeclampsia, the administration of aspirin at a dose of 150 mg per day from 11 to 14 weeks of gestation until 36 weeks of gestation resulted in a significantly lower incidence of preterm preeclampsia than that with placebo.”

Full Text of the article in NEJM can be accessed here. 

ACOG supports the USPSTF’s broader list of risk factors for supplementing low dose aspirin in preeclampsia risk reduction.

low dose aspirin 

The current ACOG recommendation for supplementing low dose aspirin for reducing the risk of developing preeclampsia is based on report by Task Force on Hypertension in Pregnancy in 2013.

The task force recommended 60-80 mg of aspirin started late first trimester for all women who are at risk by their obstetric history:

• history of preeclampsia in more than one prior pregnancy.
• history of early onset preeclampsia with preterm delivery at <34 weeks' gestation.

The U.S.Preventive Services Task Force (USPSTF) conducted a systematic review and meta-analysis of several good quality RCTs and published the results as clinical guidelines. It expanded its list of high risk pregnancies at risk for developing preeclampsia in 2014.[1]  The list was divided into 3 categories: high, medium and low risk for developing preeclampsia.

1) Women are considered at high risk if one or more of the following factors are present:

• History of preeclampsia, especially when accompanied by an adverse outcome
• Multifetal gestation
• Chronic hypertension
• Type 1 or 2 diabetes
• Renal disease
• Autoimmune disease such as systemic lupus erythematous, antiphospholipid syndrome.

2) Women are considered at moderate risk if they have several of these moderate-risk factors:

• Nulliparity
• Obesity (body mass index >30 kg/m²)
• Family history of preeclampsia (mother or sister)
• Sociodemographic characteristics (African American race, low socioeconomic status)
• Age ≥35 years
• Personal history factors (e.g., low birthweight or small for gestational age, previous adverse pregnancy outcome, >10-year pregnancy interval)

3) Women are considered at low risk if they have:

• A history of uneventful term delivery.

ACOG issued a practice advisory in July 2016[2] supporting  the recommendation by USPSTF to consider the use of low-dose aspirin (81 mg/day), initiated between 12 and 28 weeks of gestation, for the prevention of preeclampsia, and recommends using the high-risk factors as recommended by the USPSTF and listed above.

Supplementing the low dose aspirin reduced the reduced the risk for preeclampsia by 24% in clinical trials and reduced the risk for preterm birth by 14% and IUGR by 20%.

In a meta-analysis of RCTs and observational studies, USPSTF did found any evidence of increased risk of placental abruption, postpartum hemorrhage, or fetal intracranial bleeding even in moderate to low risk patients.

It is estimated that ten million women develop preeclampsia each year around the world, with 76,000 deaths due preeclampsia and related hypertensive disorders.  It is also responsible for 50,000 stillbirths and early neonatal deaths in developing nations.

A woman in developing country is seven times more likely to develop preeclampsia than a woman in a developed country, contributing to 10-25% of all Maternal mortality.

In the United States, it affects 5-8% of all pregnancies.

Establishing casualty, early detection and prevention of preeclampsia along with identifying the women at risk has been the mainstay of preeclampsia research in the last decade.

Link to USPSTF complete final recommendation  can be found here. 

Link to ACOG practice advisory can be found here. 

  

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[1] https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication

[2] http://www.acog.org/About-ACOG/News-Room/Practice-Advisories/Practice-Advisory-Low-Dose-Aspirin-and-Prevention-of-Preeclampsia-Updated-Recommendations