aspirin and Placental Insufficiency studies

Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
acetylsalicylate : A benzoate that is the conjugate base of acetylsalicylic acid, arising from deprotonation of the carboxy group.
acetylsalicylic acid : A member of the class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group. A non-steroidal anti-inflammatory drug with cyclooxygenase inhibitor activity.

Placental Insufficiency: Failure of the PLACENTA to deliver an adequate supply of nutrients and OXYGEN to the FETUS.

Research Excerpts

Excerpt	Relevance	Reference
"To investigate the effect of low-dose, slow-release aspirin in reducing the incidence and/or severity of pregnancy complications in women identified as high risk of developing problems associated with uteroplacental insufficiency, namely pre-eclampsia or delivering a small-for-gestational age (SGA) baby."	9.09	A prospective management study of slow-release aspirin in the palliation of uteroplacental insufficiency predicted by uterine artery Doppler at 20 weeks. ( Aquilina, J; Campbell, S; England, P; Harrington, K; Kurdi, W, 2000)
"The purpose of this study was to investigate the hypothesis that maternal administration of 100mg aspirin each day will improve birth-weight and other measures of neonatal size when given as a treatment to pregnancies complicated by fetal growth restriction and umbilical-placental insufficiency."	9.08	Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. ( Evans, SF; Godfrey, M; Newnham, JP; Phillips, J; Walters, BJ, 1995)
"A randomized, placebo-controlled, double-blind trial was carried out to evaluate the fetal benefits of low-dose aspirin (150 mg/day) as a treatment of placental insufficiency during the last trimester of pregnancy."	9.06	Low-dose aspirin therapy improves fetal weight in umbilical placental insufficiency. ( Connelly, A; Cook, CM; Giles, WB; Thompson, RS; Trudinger, BJ, 1988)
"Aspirin use during pregnancy was associated with a reduced risk of hypoxia-related placental pathology in the high-risk population [the adjusted odds ratio and 95% confidence interval in the 1st, 2nd, and 3rd trimesters: 0."	7.88	Aspirin use during pregnancy and hypoxia-related placental pathology. ( Chen, C; Chen, Y; Feng, L; Ye, J; Ye, W; Zhang, J; Zhu, J; Zhu, X, 2018)
"To determine whether the beneficial effects of aspirin in the treatment of Doppler umbilical placental insufficiency correlate with the maternal pressor response to angiotensin infusion."	7.68	Angiotensin sensitivity predicts aspirin benefit in placental insufficiency. ( Cook, CM; Trudinger, BJ, 1993)
"Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth."	6.82	The role of melatonin in pregnancies complicated by placental insufficiency: A systematic review. ( Bussolaro, S; Fantasia, I; Rolnik, DL; Stampalija, T, 2022)
"For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0."	6.58	The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction. ( David, AL; Groom, KM, 2018)
"To investigate the effect of low-dose, slow-release aspirin in reducing the incidence and/or severity of pregnancy complications in women identified as high risk of developing problems associated with uteroplacental insufficiency, namely pre-eclampsia or delivering a small-for-gestational age (SGA) baby."	5.09	A prospective management study of slow-release aspirin in the palliation of uteroplacental insufficiency predicted by uterine artery Doppler at 20 weeks. ( Aquilina, J; Campbell, S; England, P; Harrington, K; Kurdi, W, 2000)
"The purpose of this study was to investigate the hypothesis that maternal administration of 100mg aspirin each day will improve birth-weight and other measures of neonatal size when given as a treatment to pregnancies complicated by fetal growth restriction and umbilical-placental insufficiency."	5.08	Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. ( Evans, SF; Godfrey, M; Newnham, JP; Phillips, J; Walters, BJ, 1995)
"A randomized, placebo-controlled, double-blind trial was carried out to evaluate the fetal benefits of low-dose aspirin (150 mg/day) as a treatment of placental insufficiency during the last trimester of pregnancy."	5.06	Low-dose aspirin therapy improves fetal weight in umbilical placental insufficiency. ( Connelly, A; Cook, CM; Giles, WB; Thompson, RS; Trudinger, BJ, 1988)
" There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency."	4.98	Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. ( Anderson, NH; Figueras, F; McCowan, LM, 2018)
"Aspirin use during pregnancy was associated with a reduced risk of hypoxia-related placental pathology in the high-risk population [the adjusted odds ratio and 95% confidence interval in the 1st, 2nd, and 3rd trimesters: 0."	3.88	Aspirin use during pregnancy and hypoxia-related placental pathology. ( Chen, C; Chen, Y; Feng, L; Ye, J; Ye, W; Zhang, J; Zhu, J; Zhu, X, 2018)
"To our knowledge, this is the first time that a combination of aspirin and glyceryl trinitrate (GTN) has been used in the prophylaxis of preeclampsia and fetal growth retardation, and their use associated with not only Doppler screening of the uterine arteries but also regular Doppler follow-up of the fetal arterial and venous circulation."	3.70	A novel approach to the management of pregnancies complicated by uteroplacental insufficiency and previous stillbirth. ( Black, RS; Campbell, S; Lees, CC; Oyelese, KO, 1998)
"To determine whether the beneficial effects of aspirin in the treatment of Doppler umbilical placental insufficiency correlate with the maternal pressor response to angiotensin infusion."	3.68	Angiotensin sensitivity predicts aspirin benefit in placental insufficiency. ( Cook, CM; Trudinger, BJ, 1993)
"Placental insufficiency affects about 10% of pregnancies and can lead to pre-eclampsia, fetal growth restriction, and preterm birth."	2.82	The role of melatonin in pregnancies complicated by placental insufficiency: A systematic review. ( Bussolaro, S; Fantasia, I; Rolnik, DL; Stampalija, T, 2022)
"For the prevention of fetal growth restriction, a recent large-study level meta-analysis and individual patient data meta-analysis confirm that aspirin modestly reduces small-for-gestational-age pregnancy in women at high risk (relative risk, 0."	2.58	The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction. ( David, AL; Groom, KM, 2018)
"Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings."	2.50	Antiphospholipid antibody syndrome. ( Hinote, CD; Kutteh, WH, 2014)
"Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings."	2.47	Obstetric antiphospholipid syndrome: an update on pathophysiology and management. ( Ernest, JM; Kutteh, WH; Marshburn, PB, 2011)
"Antiphospholipid syndrome is one of the few treatable causes of pregnancy loss, and successful pregnancy rates of 70% or more can be achieved with appropriate treatment."	2.44	[Pregnancy and antiphospholipid antibodies]. ( Goffinet, F; Le Guern, V, 2008)
"The risk of preeclampsia and placental insufficiency was substantial and occurred in 50% of patients."	2.42	Antiphospholipid syndrome in obstetrics. ( Heilmann, L; Pollow, K; von Tempelhoff, GF, 2003)

Research

Studies (21)

Authors

Clinical Trials (4)

Trial Overview

Trial Outcomes

Fetal Outcome 1 - Incidence of Early Preterm Delivery (<34 Weeks)

Fetal Outcome 2 - Incidence of Actual Birth Weight <2500g

Fetal Outcome 3 - Incidence of Actual Birth Weight <1500g

Fetal Outcome 4 - Incidence of Fetal Loss

Fetal Outcome 5 - Incidence of Spontaneous Abortion

Fetal Outcome 6 - Incidence of All Stillbirth

Fetal Outcome 7 - Incidence of Medical Termination of Pregnancy

Timeframe	Studies, this research(%)	All Research%
pre-1990	3 (14.29)	18.7374
1990's	7 (33.33)	18.2507
2000's	3 (14.29)	29.6817
2010's	7 (33.33)	24.3611
2020's	1 (4.76)	2.80

Authors	Studies
Fantasia, I	1
Bussolaro, S	1
Stampalija, T	1
Rolnik, DL	1
Groom, KM	1
David, AL	1
McCowan, LM	1
Figueras, F	1
Anderson, NH	1
Ye, J	1
Chen, Y	1
Zhu, J	1
Chen, C	1
Zhu, X	1
Feng, L	1
Ye, W	1
Zhang, J	1
Kutteh, WH	2
Hinote, CD	1
Abheiden, C	1
Van Hoorn, ME	1
Hague, WM	1
Kostense, PJ	1
van Pampus, MG	1
de Vries, J	1
Le Guern, V	1
Goffinet, F	1
Ernest, JM	1
Marshburn, PB	1
Patrono, C	1
Rocca, B	1
Heilmann, L	1
von Tempelhoff, GF	1
Pollow, K	1
Beaufils, M	2
Uzan, S	2
Bréart, G	1
Cook, CM	3
Trudinger, BJ	2
Newnham, JP	1
Godfrey, M	1
Walters, BJ	1
Phillips, J	1
Evans, SF	1
Oyelese, KO	1
Black, RS	1
Lees, CC	1
Campbell, S	2
Vikhliaeva, EM	1
Harrington, K	1
Kurdi, W	1
Aquilina, J	1
England, P	1
Shuev, BV	1
Dotts, IB	1
Trudinger, B	1
Thompson, R	1
Giles, W	1
Connelly, A	2
Thompson, RS	1
Giles, WB	1
Köpernick, H	1
Mest, HJ	1
Schwarz, B	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Correlation Between Pulmonary Artery Doppler And Other Ultrasonographic Markers With Neonatal Outcome In Placenta Accreta Spectrum Patients[NCT04911322]		71 participants (Actual)	Observational	2021-08-15	Completed
Correlation Between Pulmonary Artery Doppler And Neonatal Outcome In Hypertensive Disorders Of Pregnancy[NCT05793125]		72 participants (Anticipated)	Observational	2023-04-03	Recruiting
A Randomized Trial of Transplacental Aspirin Therapy for Early Onset Fetal Growth[NCT04557475]	Phase 3	0 participants (Actual)	Interventional	2022-06-11	Withdrawn (stopped due to We are modifying this trial's protocol and will resubmit a new application at a later date.)
Aspirin Supplementation for Pregnancy Indicated Risk Reduction In Nulliparas (ASPIRIN)[NCT02409680]		11,976 participants (Actual)	Interventional	2016-03-23	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Intervention	Participants (Count of Participants)
Intervention Arm	189
Placebo Arm	230

Intervention	Participants (Count of Participants)
Intervention Arm	1078
Placebo Arm	1153

Intervention	Participants (Count of Participants)
Intervention Arm	78
Placebo Arm	101

Intervention	Participants (Count of Participants)
Intervention Arm	303
Placebo Arm	353

Intervention	Participants (Count of Participants)
Intervention Arm	134
Placebo Arm	152

Intervention	Participants (Count of Participants)
Intervention Arm	141
Placebo Arm	166

- Incidence of Medical Termination of Pregnancy (NCT02409680)
Timeframe: At delivery

Incidence of Hypertensive Disorders of Pregnancy

Intervention	Participants (Count of Participants)
Intervention Arm	42
Placebo Arm	30

- Hypertensive disorders of pregnancy is defined by the characterization of evidence of a hypertensive disorder, including either preeclampsia or eclampsia occurring during the pregnancy. (NCT02409680)
Timeframe: Evidence of hypertensive disorder during the pregnancy (prior to delivery/birth)

Incidence of Perinatal Mortality

Intervention	Participants (Count of Participants)
Intervention Arm	352
Placebo Arm	325

- Incidence of Perinatal Mortality (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Incidence of Preterm Birth

Intervention	Participants (Count of Participants)
Intervention Arm	264
Placebo Arm	309

The primary outcome of this study is incidence of preterm birth, which will be defined as delivery at or after 20 0/7 weeks and prior to 37 0/7 weeks. This will be determined based on actual date of delivery in comparison to the projected estimated due date (EDD), independent of whether or not the preterm delivery is indicated or spontaneous. (NCT02409680)
Timeframe: At delivery

Incidence of Small for Gestational Age (SGA)

Intervention	Participants (Count of Participants)
Intervention Arm	668
Placebo Arm	754

- Small for gestational age (SGA) as defined by the INTERGROWTH-21st standard (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Maternal Outcome 1 - Incidence of Vaginal Bleeding

Intervention	Participants (Count of Participants)
Intervention Arm	1506
Placebo Arm	1564

- Vaginal bleeding (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Maternal Outcome 2 - Incidence of Antepartum Hemorrhage

Intervention	Participants (Count of Participants)
Intervention Arm	214
Placebo Arm	246

- Antepartum hemorrhage (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Maternal Outcome 3 - Incidence of Postpartum Hemorrhage

Intervention	Participants (Count of Participants)
Intervention Arm	26
Placebo Arm	25

- Postpartum hemorrhage (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Maternal Outcome 4 - Incidence of Maternal Mortality

Intervention	Participants (Count of Participants)
Intervention Arm	54
Placebo Arm	43

- Incidence of Maternal Mortality (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Maternal Outcome 5 - Incidence of Late Abortion

Intervention	Participants (Count of Participants)
Intervention Arm	9
Placebo Arm	12

- Incidence of Late Abortion (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Maternal Outcome 6 - Change in Maternal Hemoglobin

Intervention	Participants (Count of Participants)
Intervention Arm	23
Placebo Arm	30

Hemoglobin < 7.0 gm/dl at 26-30 weeks gestation or a drop of 3.5+ gm/dl from screening to 26-30 weeks gestation (NCT02409680)
Timeframe: At enrollment, 4 weeks post enrollment, and 26-30 weeks GA.

Maternal Outcome 7 - Incidence of Preterm, Preeclampsia

Intervention	Participants (Count of Participants)
Intervention Arm	290
Placebo Arm	333

Early preterm delivery (<34 weeks) and hypertensive disorders (i.e.: preeclampsia) (NCT02409680)
Timeframe: At delivery or at Day 42 after delivery

Article	Year
The role of melatonin in pregnancies complicated by placental insufficiency: A systematic review. European journal of obstetrics, gynecology, and reproductive biology, 2022, Volume: 278 Topics: Antioxidants; Aspirin; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Melatonin; Placent	2022
The role of aspirin, heparin, and other interventions in the prevention and treatment of fetal growth restriction. American journal of obstetrics and gynecology, 2018, Volume: 218, Issue:2S Topics: Anticoagulants; Aspirin; Female; Fetal Growth Retardation; Genetic Therapy; Heparin; Heparin, Low-Mo	2018
Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. American journal of obstetrics and gynecology, 2018, Volume: 218, Issue:2S Topics: Aspirin; Biomarkers; Canada; Consensus; Evidence-Based Medicine; Female; Fetal Growth Retardation; F	2018
Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. American journal of obstetrics and gynecology, 2018, Volume: 218, Issue:2S Topics: Aspirin; Biomarkers; Canada; Consensus; Evidence-Based Medicine; Female; Fetal Growth Retardation; F	2018
Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. American journal of obstetrics and gynecology, 2018, Volume: 218, Issue:2S Topics: Aspirin; Biomarkers; Canada; Consensus; Evidence-Based Medicine; Female; Fetal Growth Retardation; F	2018
Evidence-based national guidelines for the management of suspected fetal growth restriction: comparison, consensus, and controversy. American journal of obstetrics and gynecology, 2018, Volume: 218, Issue:2S Topics: Aspirin; Biomarkers; Canada; Consensus; Evidence-Based Medicine; Female; Fetal Growth Retardation; F	2018
Antiphospholipid antibody syndrome. Obstetrics and gynecology clinics of North America, 2014, Volume: 41, Issue:1 Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Aspirin; Female; Fibrin	2014
[Pregnancy and antiphospholipid antibodies]. Presse medicale (Paris, France : 1983), 2008, Volume: 37, Issue:11 Topics: Animals; Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Complemen	2008
Obstetric antiphospholipid syndrome: an update on pathophysiology and management. Seminars in reproductive medicine, 2011, Volume: 29, Issue:6 Topics: Abortion, Habitual; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Aspirin; Female; Hepari	2011
Aspirin and Other COX-1 inhibitors. Handbook of experimental pharmacology, 2012, Issue:210 Topics: Animals; Aspirin; Atherosclerosis; Atrial Fibrillation; Cyclooxygenase 1; Cyclooxygenase Inhibitors;	2012
Antiphospholipid syndrome in obstetrics. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, 2003, Volume: 9, Issue:2 Topics: Abortion, Habitual; Abortion, Spontaneous; Adult; Annexin A5; Antibodies, Anticardiolipin; Anticoagu	2003
[Aspirin and pregnancy: present data and future perspectives]. Contraception, fertilite, sexualite (1992), 1995, Volume: 23, Issue:3 Topics: Aspirin; Controlled Clinical Trials as Topic; Drug Evaluation; Female; Humans; Hypertension; Placent	1995
[Pregnancy nephropathies]. Presse medicale (Paris, France : 1983), 1993, Dec-04, Volume: 22, Issue:38 Topics: Adult; Antihypertensive Agents; Aspirin; Epoprostenol; Female; Hemostasis; Humans; Hypertension; Kid	1993
[Pharmacological prevention of gestation complications]. Terapevticheskii arkhiv, 1999, Volume: 71, Issue:10 Topics: Aspirin; Calcium, Dietary; Fatty Acids, Unsaturated; Female; Humans; Hypertension; Placental Insuffi	1999
[Aspirin as a cyclooxygenase inhibitor in various complications of the gestational period]. Akusherstvo i ginekologiia, 1992, Issue:3-7 Topics: Aspirin; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Epoprostenol; Female; Fetal Gr	1992

Article	Year
Does low-molecular-weight heparin influence fetal growth or uterine and umbilical arterial Doppler in women with a history of early-onset uteroplacental insufficiency and an inheritable thrombophilia? Secondary randomised controlled trial results. BJOG : an international journal of obstetrics and gynaecology, 2016, Volume: 123, Issue:5 Topics: Adult; Anticoagulants; Aspirin; Birth Weight; Blood Flow Velocity; Drug Therapy, Combination; Female	2016
Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. The Australian & New Zealand journal of obstetrics & gynaecology, 1995, Volume: 35, Issue:4 Topics: Adult; Aspirin; Birth Weight; Double-Blind Method; Female; Fetal Growth Retardation; Humans; Placent	1995
Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. The Australian & New Zealand journal of obstetrics & gynaecology, 1995, Volume: 35, Issue:4 Topics: Adult; Aspirin; Birth Weight; Double-Blind Method; Female; Fetal Growth Retardation; Humans; Placent	1995
Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. The Australian & New Zealand journal of obstetrics & gynaecology, 1995, Volume: 35, Issue:4 Topics: Adult; Aspirin; Birth Weight; Double-Blind Method; Female; Fetal Growth Retardation; Humans; Placent	1995
Low dose aspirin for the treatment of fetal growth restriction: a randomized controlled trial. The Australian & New Zealand journal of obstetrics & gynaecology, 1995, Volume: 35, Issue:4 Topics: Adult; Aspirin; Birth Weight; Double-Blind Method; Female; Fetal Growth Retardation; Humans; Placent	1995
A prospective management study of slow-release aspirin in the palliation of uteroplacental insufficiency predicted by uterine artery Doppler at 20 weeks. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2000, Volume: 15, Issue:1 Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arteries; Aspirin; Delayed-Action Preparations; Fema	2000
Low-dose aspirin improves fetal weight in umbilical placental insufficiency. Lancet (London, England), 1988, Jul-23, Volume: 2, Issue:8604 Topics: Aspirin; Female; Fetus; Humans; Placenta Diseases; Placental Insufficiency; Pregnancy	1988
Low-dose aspirin therapy improves fetal weight in umbilical placental insufficiency. American journal of obstetrics and gynecology, 1988, Volume: 159, Issue:3 Topics: Adult; Aspirin; Birth Weight; Blood Flow Velocity; Clinical Trials as Topic; Double-Blind Method; Fe	1988

Article	Year
Aspirin use during pregnancy and hypoxia-related placental pathology. Pregnancy hypertension, 2018, Volume: 14 Topics: Adult; Aspirin; Case-Control Studies; Female; Humans; Hypoxia; Middle Aged; Placenta; Placental Insu	2018
Angiotensin sensitivity predicts aspirin benefit in placental insufficiency. British journal of obstetrics and gynaecology, 1993, Volume: 100, Issue:1 Topics: Angiotensins; Aspirin; Female; Fetal Growth Retardation; Humans; Placental Insufficiency; Pregnancy;	1993
A novel approach to the management of pregnancies complicated by uteroplacental insufficiency and previous stillbirth. The Australian & New Zealand journal of obstetrics & gynaecology, 1998, Volume: 38, Issue:4 Topics: Adult; Aspirin; Drug Therapy, Combination; Female; Fetal Death; Fetal Growth Retardation; Fetal Moni	1998
Pharmacological management of an impending placental insufficiency. Prostaglandins, leukotrienes, and essential fatty acids, 1988, Volume: 33, Issue:3 Topics: Aspirin; Epoprostenol; Female; Gestational Age; Humans; Microcirculation; Placenta Diseases; Placent	1988

aspirin and Placental Insufficiency