Should you take aspirin during pregnancy?
Posted by Andrew Price on
Disclaimer: I am a medical professional, but I am not your medical professional. When making decisions about your or your baby’s medical health you should do your own research and/or consult with your medical provider or obstetrician.
The most common reason your obstetrician wants you to take low dose aspirin is to reduce your risk of developing preeclampsia. In this article I hope to help you understand the differences between gestational hypertension, preeclampsia and eclampsia; how each is diagnosed; and help you decide if taking a baby aspirin (81-mg per day) is right for you.
Preeclampsia is a rare and severe form of high blood pressure occurring during pregnancy, usually after 20 weeks gestation. It has been found that nearly half of women with gestational hypertension (new-onset of blood pressure being measured greater than 140/90 mm Hg after 20 weeks gestation) develop preeclampsia. The annual incidence of preeclampsia in the U.S. is 3.9%. Preeclampsia is a syndrome specific to pregnancy that can affect the function of every organ in the body. The difference between severe gestational hypertension and preeclampsia can be subtle, because severe gestational hypertension can quickly progress to severe preeclampsia and eclampsia.
Gestational hypertension is diagnosed when your blood pressure reaches 140/90 mm Hg or greater for the first time after 20 weeks of pregnancy, but without protein in your urine. In women who’s blood pressure was greater than 140/90 mm Hg for the first time after 20 weeks, half of those developed preeclampsia syndrome. Preeclampsia syndrome has symptoms such as headaches and stomach pain or indigestion. In severe cases of preeclampsia syndrome, convulsions and seizures may occur in the mother and/or fetal growth may be restricted.
Preeclampsia is diagnosed* when the mother has gestational hypertension with one or more of the following:
- protein excretion greater than 300 mg/dL in her urine over a 24-hour collection period
- urine protein:creatinine ratio (greater/equal to) 0.3
- persistent 30 mg/dL (1+ on dipstick) protein in random urine sample
*It is up to the discretion of the provider to make the diagnosis of preeclampsia
Eclampsia is diagnosed when a mother, diagnosed with preeclampsia, experiences convulsions (uncontrolled muscle spasms) and/or epileptic seizures before, during or after labor. These seizures may occur even beyond 48 hours postpartum, however, this is less common. (Alexander et al 2006; Brown et al 1987). According to the 1998 National Vital Statistics report (Ventura et al, 2000) the incidence of Eclampsia in the U.S. in 1998 was 0.32% or 1 in 3,250 deliveries.
The most severe forms of preeclampsia are HELLP syndrome, hypertensive brain hemorrhaging and severe pulmonary edema. HELLP stands for Hemolysis, Elevated Liver enzymes and Low Platelet count. Symptoms include moderate to severe right-upper pain and tenderness. Lab tests showing elevated aminotransferase levels of aspartate transferase (AST) or alanine transferase (ALT) greater than 70 U/L are considered markers for severe preeclampsia at risk for developing HELLP.
Brain hemorrhaging lesions have been visualized in up to 60% of women with eclampsia, however, only half of these cases proved to be fatal. (Melrose, 1984; Richards, et al 1988; Sheehan and Lynch 1973).
Pulmonary edema occurs when excessive fluids accumulate in the lungs and suppress gas exchange resulting in decreased oxygen availability to body tissues and brain. This can occur in a mild form due to normal childbirth but can be exacerbated if preeclampsia is diagnosed.
Your doctor’s goal is to help ensure your health and the health of your baby. So before we look at aspirin specifically, here are some suggestions to help you reduce your risk of preeclampsia and the worsening conditions related to it.
- 1. Monitor your health and blood pressure early in pregnancy and throughout pregnancy.
- 2. Communicate frequently with your obstetrician regarding new pain, spotting, or changes in blood pressure.
- 3. If you are calcium deficient, talk with your obstetrician about healthy methods to increase your blood calcium levels, possibly with dietary supplementation
- If severe preeclampsia occurs prior to 23 weeks, most doctors will recommend pregnancy termination, as there were no infant survivors prior to 23 weeks gestation at time of delivery. Bombrys et al; 2008)
- Prior to delivery, talk with your doctor about their opinion on prophylactic magnesium sulfate for eclampsia prevention.
- Low-dose aspirin after 12 weeks gestation.
In 2018, the American College of Obstetricians and Gynecologists (ACOG) submitted an opinion paper on the use of Low-Dose Aspirin use during pregnancy. In the consensus statement they made the following recommendations:
- Low-dose aspirin (81 mg/day) prophylaxis is recommended in women at high risk of preeclampsia and should be initiated between 12 weeks and 28 weeks of gestation (optimally before 16 weeks) and continued daily until delivery
- Low-dose aspirin prophylaxis should be considered for women with more than one of several moderate risk factors for preeclampsia
- Low-dose aspirin prophylaxis is not recommended solely for the indication of prior unexplained stillbirth, in the absence of risk factors for preeclampsia
- Low-dose aspirin prophylaxis is not recommended for prevention of fetal growth restriction, in the absence of risk factors for preeclampsia
- Low-dose aspirin prophylaxis is not recommended for prevention of early pregnancy loss.
The 2018 recommendations by ACOG for the use of low-dose aspirin to prevent preeclampsia were based on the recommendations by the United States Preventive Services Task Force (USPSTF) in their statement. Since the recommendations were adopted by the ACOG, the USPSTF has issued an updated statement in 2021.
Aspirin is a non-steroidal anti-inflammatory drug (NSAID) that non-selectively inhibits the COX inflammatory pathways. At low doses, aspirin has been shown to decrease a product of the COX-1 pathway, thromboxane A2 (TXA2). TXA2 is a potent vasoconstrictor and also promotes platelet aggregation (stickiness/coagulation). Initial studies of low-dose aspirin for preeclampsia prevention was suggested due to the evidence suggestion that an imbalance of the metabolism of TXA2 and prostacyclin were involved in the development of preeclampsia and low-dose aspirin inhibits the production of TXA2. However, other studies suggest that preeclampsia is a result of poor implantation of the placenta into the uterus, likely due to various causes.
In other words, preeclampsia is likely due to early structural malformations of the placenta and uterus which manifest later in pregnancy as an imbalance of prostacyclin and TXA2, however, this theory has not been scientifically proven.
However, is unknown if low-dose aspirin improves early placental blood perfusion and current research has not determined the precise mechanism by which low-dose aspirin prevents preeclampsia in some women, leaving us with uncertainty as to why the USPSTF and ACOG are recommending its use.
What are the risks of taking low-dose aspirin while pregnant?
Very few and/or mild risks to the mother have been reported for those taking low-dose aspirin during pregnancy. In one random control study (16) it was found that there was a slight increase in need for transfusion in women taking low dose aspirin, but the difference was small, 4.0% of those taking low-dose aspirin needed a transfusion whereas 3.2% not taking aspirin needed a transfusion. This equates to a Number Needed to Harm of 1 out of 125 patients taking aspirin had an increased need for a transfusion.
For the baby, there have been no studies have shown an increased risk for the baby when the the mother takes low-dose aspirin after 12 weeks gestation. There was a meta-analysis of 5 observational studies which found an increase in infants being born with gastroschisis in those whose mother had been taking aspirin. However, those mothers had been taking aspirin (and possibly other licit and illicit drugs in the first trimester). Observational studies are also subject to recall bias, where people are more likely to return if there is a problem and less likely to return if there is not a problem. (22) Low-dose aspirin has not been found to be associated with gastroschisis or ductal closure in the third trimester. No increase in fetal brain hemorrhages has been found to be associated with low-dose aspirin usage either.
Are there contraindications to taking low-dose aspirin?
If you have a history of aspirin allergy, or hypersensitivity to other salicylates, you may be at risk of anaphylaxis and you should consult with your doctor or not take low-dose aspirin. There is also a high risk for cross-sensitivity between other NSAIDs and aspirin, so low-dose aspirin is also contraindicated in women who have a hypersensitivity to NSAIDs. If you have nasal polyps, taking low-dose aspirin may cause life-threatening broncho-constriction and you should avoid taking low-dose aspirin. If you have asthma and have a history of aspirin-induced bronchospasm, you should also avoid taking low-dose aspirin.
Relative contraindications include: active peptic ulcer disease, gastrointestinal bleeding, and severe liver dysfunction. If you are under 18, Reye syndrome has been reported (less than 1%) in children who have taking aspirin while recovering from a viral illness, such as the flu and chicken pox.
Other factors such as those that may increase your risk for obstetric bleeding should be discussed with your obstetrician as to whether or not low-dose aspirin is something you should take.
When should I start taking Low-Dose Aspirin?
The consensus statement suggests to begin treatment after 12 weeks, but before 16 weeks for greatest risk reduction in maternal preeclampsia and fetal growth restriction. Earlier use, such as in first trimester, has not been shown to be beneficial or cause adverse effects in mother or child.
When should I stop taking Low-Dose Aspirin?
There does not seem to be a benefit to stopping low-dose aspirin use prior to delivery. Timing of stopping the use of low-dose aspirin has not been related to excessive maternal or fetal bleeding. You can take the aspirin up to, and after birth. However, keep in mind, long-term daily aspirin use in non-pregnant adults (less than 300 mg/day for more than 5 years) has an increased associated risk of major gastrointestinal and cerebral bleeding episodes. As well as, the childhood exposure to aspirin during recovery from a viral infection has resulted in Reye syndrome in 1% of children.
What are the risk factors for preeclampsia?
The more recent USPSTF recommendations for low-dose aspirin use for prevention of preeclampsia define risks for preeclampsia in 3 categories: High, Moderate and Low in the table below.
Table 1. Risk factors for developing preeclampsia
Each of the single high-risk factors have at least an 8% incidence of preeclampsia (double the relative-risk compared to the overall population). The moderate risk factors are independently associated with a moderate-risk for preeclampsia, some more than others. The authors do not discuss the absolute risk of each factor. Black ethnicity is not associated as a biological or genetic risk, this risk factor is a result of increased risk due to historic social, medical, educational and environmental inequality shaping long term risks to health, access to health care and the unequal distribution of resources necessary for a value-added life.
Does Low-dose aspirin reduce the risk for developing preeclampsia?
The 2017 Aspirin for Evidence-Based Preeclampsia Prevention trial randomized 1,776 women at high risk for preeclampsia to 150-mg dose aspirin or to placebo. The authors found a statistically significant decrease in rate of preterm preeclampsia (4.3% vs. 1.6%). But let’s look carefully at these numbers. A common statistical method to assess drug effectiveness is the Number Needed to Treat (NNT) calculation. Take the inverse of the difference between the non-treated group and treated group and you get your number of treatments needed in order to prevent preeclampsia in 1 individual. The lower the NNT, the more effective the drug is at treatment/prevention. The inverse of (4.3%-1.6%) is about 37. In other words, you have to give 37 women with high risk for developing preeclampsia the low-dose aspirin treatment (150-mg in this case) to prevent 1 woman from developing preeclampsia. Besides, the recommendation by ACOG and USPSTF is 81-mg aspirin. Presumably the 81-mg dose would have an even smaller effect than the 150-mg dose and an even larger NNT. It is unlikely that prophylaxis, low-dose aspirin, alone, is effective at preventing preeclampsia in high risk women.
Okay, so if aspirin doesn’t reduce my risk for developing preeclampsia should I still take it?
Thankfully, the risk of developing preeclampsia is low. However, if you have one or more of the risk factors listed in the table above, you should definitely discuss it with your obstetrician. However, there are other benefits to taking aspirin during the second trimester of pregnancy. Around 12-24 weeks and beyond, many women report round ligament pain as the baby grows. As an analgesic, aspirin is great at reducing pain! Since the risks for taking daily, low-dose aspirin are minimal, this is probably a good reason to take low-dose aspirin as well.
For me, my wife has a couple of the moderate risk factors listed in the table above and, after consulting with our obstetrician, decided that the benefits outweigh the risks when it comes to including low-dose aspirin in her prenatal care. But that was our decision. Your medical decision should be made with your healthcare team, significant other and obstetrician. It is always your choice.
ACOG Committee Opinion No. 743: Low-Dose Aspirin Use During Pregnancy. Obstetrics & Gynecology 132(1):p e44-e52, July 2018. | DOI: 10.1097/AOG.0000000000002708
US Preventive Services Task Force. Aspirin Use to Prevent Preeclampsia and Related Morbidity and Mortality: US Preventive Services Task Force Recommendation Statement. JAMA. 2021;326(12):1186–1191. doi:10.1001/jama.2021.14781
Alexander JM, McIntire DD, Leveno KJ, Cunningham FG. Selective magnesium sulfate prophylaxis for the prevention of eclampsia in women with gestational hypertension. Obstet Gynecol. 2006 Oct;108(4):826-32. doi: 10.1097/01.AOG.0000235721.88349.80. PMID: 17012442.
Brown CE, Cunningham FG, Pritchard JA. Convulsions in hypertensive, proteinuric primiparas more than 24 hours after delivery. Eclampsia or some other cause? J Reprod Med. 1987 Jul;32(7):499-503. PMID: 3625613.
Ventura SJ, Martin JA, Curtin SC, Mathews TJ, Park MM. Births: final data for 1998. Natl Vital Stat Rep. 2000 Mar 28;48(3):1-100. PMID: 10761414.