Preconception Low-Dose Aspirin Restores Diminished Pregnancy and Live Birth Rates in Women With Low-Grade Inflammation: A Secondary Analysis of a Randomized Trial

Abstract Context: Inflammation is linked to causes of infertility. Low-dose aspirin (LDA) may improve reproductive success in women with chronic, low-grade inflammation. Objective: To investigate the effect of preconception-initiated LDA on pregnancy rate, pregnancy loss, live birth rate, and inflammation during pregnancy. Design: Stratified secondary analysis of a multicenter, block-randomized, double-blind, placebo-controlled trial. Setting: Four US academic medical centers, 2007 to 2012. Participants: Healthy women aged 18 to 40 years (N = 1228) with one to two prior pregnancy losses actively attempting to conceive. Intervention: Preconception-initiated, daily LDA (81 mg) or matching placebo taken up to six menstrual cycles attempting pregnancy and through 36 weeks’ gestation in women who conceived. Main Outcome Measures: Confirmed pregnancy, live birth, and pregnancy loss were compared between LDA and placebo, stratified by tertile of preconception, preintervention serum high-sensitivity C-reactive protein (hsCRP) (low, <0.70 mg/L; middle, 0.70 to <1.95 mg/L; high, ≥1.95 mg/L). Results: Live birth occurred in 55% of women overall. The lowest pregnancy and live birth rates occurred among the highest hsCRP tertile receiving placebo (44% live birth). LDA increased live birth among high-hsCRP women to 59% (relative risk, 1.35; 95% confidence interval, 1.08 to 1.67), similar to rates in the lower and mid-CRP tertiles. LDA did not affect clinical pregnancy or live birth in the low (live birth: 59% LDA, 54% placebo) or midlevel hsCRP tertiles (live birth: 59% LDA, 59% placebo). Conclusions: In women attempting conception with elevated hsCRP and prior pregnancy loss, LDA may increase clinical pregnancy and live birth rates compared with women without inflammation and reduce hsCRP elevation during pregnancy.

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The Safety of Low-Dose Aspirin on the Mode of Delivery: Secondary Analysis of the Effect of Aspirin in Gestation and Reproduction Randomized Controlled Trial

American Journal of Perinatology ◽

10.1055/s-0040-1718581 ◽

2020 ◽

Author(s):

Allison A. Eubanks ◽

Carrie J. Nobles ◽

Sunni L. Mumford ◽

Keewan Kim ◽

Micah J. Hill ◽

...

Keyword(s):

Vaginal Delivery ◽

Live Birth ◽

Low Dose ◽

Controlled Trial ◽

Mode Of Delivery ◽

Secondary Analysis ◽

Clinical Effects ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Intent To Treat

Objective This study aimed to examine whether prenatal low-dose aspirin (LDA) therapy affects risk of cesarean versus vaginal delivery. Study Design This study is a secondary analysis of the randomized clinical effects of aspirin in gestation and reproduction (EAGeR) trial. Women received 81-mg daily aspirin or placebo from preconception to 36 weeks of gestation. Mode of delivery and obstetric complications were abstracted from records. Log-binomial regression models estimated relative risk (RR) of cesarean versus vaginal delivery. Data were analyzed among the total preconception cohort, as well as restricted to women who had a live birth. Results Among 1,228 women, 597 had a live birth. In the intent-to-treat analysis, preconception-initiated LDA was not associated with risk of cesarean (RR = 1.02; 95% confidence interval [CI]: 0.98–1.07) compared with placebo. Findings were similar in just women with a live birth and when accounting prior cesarean delivery and parity. Conclusion Preconception-initiated daily LDA was not associated with mode of delivery among women with one to two prior losses. Key Points

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Comparison of empirical use of low dose aspirin and enoxaprin in the treatment of unexplained recurrent pregnancy loss

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20200889 ◽

2020 ◽

Vol 9 (3) ◽

pp. 1138

Author(s):

Sunil Kumar Juneja ◽

Pooja Tandon ◽

Gagandeep Kaur ◽

Bakul Kapoor ◽

Guneet Singh Sidhu

Keyword(s):

Live Birth ◽

Pregnancy Loss ◽

Low Dose ◽

Recurrent Pregnancy Loss ◽

Chromosomal Anomalies ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Uterine Anomalies ◽

Significant Difference ◽

Recurrent Pregnancy Losses

Background: Recurrent pregnancy losses have commonly been defined as three or more consecutive spontaneous pregnancy losses. About 1-2% of women suffer from recurrent miscarriages. The cause is multifactorial such as uterine anomalies, endocrine disorders, immunological causes, infections, chromosomal anomalies and maternal autoimmune diseases. In 50-60% of cases recurrent pregnancy losses, the cause remains unclear. Objective of this study was to compare the maternal and fetal outcome in patients with unexplained recurrent pregnancy loss treated with LMWH (Enoxaparin) vs Aspirin during pregnancy.Methods: Women with 3 or more pregnancy losses, aged between 18-40 years, booked for antenatal care and delivery in our hospital between January 2012 and December 2016 were followed till 6 months after delivery.Results: A total number of 146 women were assessed for eligibility. We had 62 women in Group A (aspirin group) and 84 women in Group E (enoxaparin group). Enoxaparin was given to all those ladies who had taken aspirin in previous pregnancies with no live outcome. Good neonatal outcome was observed with Enoxaparin.Conclusions: Live birth rates did not show significant difference between the two study groups. But empirical use of enoxaparin in patients with no live birth who have taken low dose aspirin in previous pregnancy had shown improved results, so enoxaparin should be used empirically as a first line agent in such cases.

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Summary for Patients: The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin–Detected Pregnancy, Pregnancy Loss, and Live Birth

Annals of Internal Medicine ◽

10.7326/p20-0016 ◽

2021 ◽

Keyword(s):

Live Birth ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Pregnancy Loss ◽

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin

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The effect of low dose aspirin and low molecular weight heparin (enoxaparin) in recurrent pregnancy loss associated with antiphospholipid antibody syndrome

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20174652 ◽

2017 ◽

Vol 6 (11) ◽

pp. 4830 ◽

Cited By ~ 1

Author(s):

Sasmita Swain ◽

Sujata Singh

Keyword(s):

Antiphospholipid Syndrome ◽

Live Birth ◽

Antiphospholipid Antibodies ◽

Pregnancy Loss ◽

Low Dose ◽

Recurrent Pregnancy Loss ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Dose Aspirin ◽

Low Dose Aspirin

Background: Recurrent miscarriage affects 1–2% of women. Recurrent pregnancy loss (RPL) is the loss of three or more consecutive pregnancies before or during the 20th week of gestation. The most important association between gestational loss and autoimmune phenomena is the presence of antiphospholipid antibodies represented by the lupus anticoagulants and or anticardiolipin antibodies (Antiphospholipid Antibody Syndrome). The antiphospholipid syndrome is an acquired autoimmune. The clinical features are thrombosis (venous, arterial and microvascular) and/or pregnancy complications; the most prominent of which is recurrent abortion.Methods: Twenty-two selected patients during pregnancy with clinical and/or serological findings of antiphospholipid syndrome had received low dose aspirin (75 mg once daily orally) plus LMWH enoxaparin (40 mg subcutaneously/day).Results: There are live born in 86% cases compared to abortion (< 20 weeks gestational age) in 14 % cases. From 19 liveborn babies the mother having normotensive in 79% and preeclampsia 21%, 85% babies having normal growth and 15% are IUGR. 36% cases are at term (>37 weeks) and 50% cases are at preterm (<37 week) on which 9%) is spontaneous preterm and 41% is iatrogenic preterm due to preeclampsia, IUGR, PPROM and APH.Conclusions: Use of low dose aspirin (75mg) and enoxaparin 40 mg subcutaneously daily in patients with RPL due to antiphospholipid syndrome resulted in higher live birth rates. Combination treatment with aspirin and LMWH leads to a high live birth rate among women with recurrent abortion and antiphospholipid antibodies.

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Prevention of Fetal Death in the Antiphospholipid Antibody Syndrome

Lupus ◽

10.1177/096120339600500528 ◽

1996 ◽

Vol 5 (5) ◽

pp. 467-472 ◽

Cited By ~ 22

Author(s):

S Cowchock

Keyword(s):

Pregnant Women ◽

Live Birth ◽

Low Dose ◽

Fetal Death ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Live Birth Rates ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Plasma Heparin

The first treatment of pregnant women with antiphospholipid antibody syndrome (APLS) employed high doses of corticosteroids, plus low dose aspirin, with the goal of suppressing production of the autoantibody. Corticosteroids (usually prednisone), even when much lower doses are used, and even when tapered after midpregnancy, have been associated with significant maternal and obstetric risks and side effects: the most important are osteomalacia and preterm delivery (often precipitated by premature rupture of the membranes). Since the publication of a randomized trial demonstrating equivalent live birth rates of about 75% whether heparin or prednisone was used for treatment (plus low dose aspirin), the use of adjusted doses of heparin, together with low dose aspirin, has replaced prednisone for treatment of pregnant women; although prednisone may still be needed to treat manifestations of associated autoimmune disorders. A recent randomized trial has shown that the addition of heparin to aspirin is probably superior to treatment with aspirin alone. To achieve prophylactic levels of plasma heparin equivalent to those measured in patients who are not pregnant and are treated with the usual dose of standard heparin of 5000 IU every 12 h, the heparin dose required for treatment of pregnant women is usually higher. For that reason, heparin doses should be adjusted using the nadir APTT, or better plasma heparin measured by a factor Xa inhibition assay at the 2 h post-injection peak. Although low molecular weight heparin has been shown to be useful in prevention of fetal resorption in a mouse model, and appears to be equally safe for treatment of pregnant women, we still have no published data to show therapeutic equivalency, with respect to treatment of APLS-complicated pregnancy, to standard heparin preparations, and none that demonstrate any lower risk for the complication of most concern when heparin is given to pregnant women—osteopenia. Similarly, intravenous infusion of gamma globulins (IVG) appears on the basis of case reports to be effective additional treatment in cases where standard therapy has failed. Gamma globulin preparations contain anti-idiotypic antibodies that have been shown to bind to patient antiphospholipid antibodies. The place for the addition of IVG to standard therapy has not been defined, but clinically significant and corticosteroid-resistant thrombocytopenia complicating antiphospholipid antibody syndrome might be one indication for primary treatment with IVG ± low dose aspirin. Overall, live birth rates in most treatment studies are in the range of 70–80%. The reported birth rate information, however, cannot be compared between studies. None of the studies reported have used tools such as logistic regression analysis to allow for such significant predictors of live birth as the number of prior miscarriages, maternal age, medical history, or a history of fetal death (loss of a viable and chromosomally normal fetus after the 10th gestational week).

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The Effect of Preconception-Initiated Low-Dose Aspirin on Human Chorionic Gonadotropin–Detected Pregnancy, Pregnancy Loss, and Live Birth

Annals of Internal Medicine ◽

10.7326/m20-0469 ◽

2021 ◽

Author(s):

Ashley I. Naimi ◽

Neil J. Perkins ◽

Lindsey A. Sjaarda ◽

Sunni L. Mumford ◽

Robert W. Platt ◽

...

Keyword(s):

Live Birth ◽

Chorionic Gonadotropin ◽

Human Chorionic Gonadotropin ◽

Pregnancy Loss ◽

Low Dose ◽

Dose Aspirin ◽

Low Dose Aspirin

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The role of aspirin and inflammation on reproduction: the EAGeR trial

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2018-0368 ◽

2019 ◽

Vol 97 (3) ◽

pp. 187-192

Author(s):

Lindsay D. Levine ◽

Tiffany L. Holland ◽

Keewan Kim ◽

Lindsey A. Sjaarda ◽

Sunni L. Mumford ◽

...

Keyword(s):

Live Birth ◽

Birth Rate ◽

Low Dose ◽

Live Birth Rate ◽

Low Grade ◽

Negative Effects ◽

Offspring Sex Ratio ◽

Reactive Protein ◽

Dose Aspirin ◽

Low Dose Aspirin

Inflammation has been linked to several complications in pregnancy, including pregnancy loss. Due to its anti-inflammatory properties, aspirin, a widely available and inexpensive therapy, has potential to help mitigate the negative effects of inflammation along the reproductive pathway. Therefore, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was designed to elucidate whether preconception-initiated daily low-dose aspirin would increase the live birth rate in women with 1–2 prior pregnancy losses and no infertility diagnosis and attempting unassisted conception. Here, we present an overview of the collected findings. Low-dose aspirin was associated with an increased live birth rate among women with a single loss at <20 weeks gestation within the past year. When stratified by tertile of C-reactive protein (CRP), a biomarker of inflammation, treatment with aspirin restored a decrement in the live birth rate in women in the highest CRP tertile (relative risk 1.35, 95% confidence interval 1.08–1.67), increasing to similar rates as women of the lower and mid-CRP tertiles. The same effect modification by inflammation status was observed when examining the effect of low-dose aspirin on offspring sex ratio. These results suggest that inflammation plays an important role in reproduction, and that chronic, low-grade inflammation may be amenable to aspirin treatment.

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