aspirin and Neural Tube Defects 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class of benzoic acids that is salicylic acid in which the hydrogen that is attached to the phenolic hydroxy group has been replaced by an acetoxy group.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.

Neural Tube Defects: Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)

Research Excerpts

Excerpt	Relevance	Reference
"It is still controversial whether aspirin use during pregnancy increases the risk of certain congenital abnormalities (in particular, neural tube defects, gastroschisis, and cleft lip +/- palate)."	7.73	Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. ( Czeizel, AE; Nørgård, B; Puhó, E; Skriver, MV; Sørensen, HT, 2005)
"Pre-treatment with aspirin (both 150 and 200 mg/kg) on day 8 of gestation resulted in a numerical, though not statistically significant increase in alcohol-induced exencephaly."	5.29	Effect of pre-treatment with aspirin on alcohol-induced neural tube defects in the TO mouse fetuses. ( Craigmyle, MB; Padmanabhan, R; Wasfi, IA, 1994)
" Some are beginning to broaden prenatal screening to include pregnancy complications such as pre-eclampsia that can be prevented using soluble low-dose aspirin treatment started before 16 weeks of gestation."	4.93	Development of prenatal screening--A historical overview. ( Cuckle, H; Maymon, R, 2016)
"It is still controversial whether aspirin use during pregnancy increases the risk of certain congenital abnormalities (in particular, neural tube defects, gastroschisis, and cleft lip +/- palate)."	3.73	Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. ( Czeizel, AE; Nørgård, B; Puhó, E; Skriver, MV; Sørensen, HT, 2005)
"Pre-treatment with aspirin (both 150 and 200 mg/kg) on day 8 of gestation resulted in a numerical, though not statistically significant increase in alcohol-induced exencephaly."	1.29	Effect of pre-treatment with aspirin on alcohol-induced neural tube defects in the TO mouse fetuses. ( Craigmyle, MB; Padmanabhan, R; Wasfi, IA, 1994)
"Aspirin was injected in four different doses sub-blastodermally into fresh embryonated eggs."	1.29	Mechanism of aspirin induced neural tube defect in chick embryo. ( Iyengar, B; Kotwani, A; Mehta, VL, 1994)

Research

Studies (8)

Authors

Clinical Trials (1)

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	0 (0.00)	18.7374
1990's	5 (62.50)	18.2507
2000's	1 (12.50)	29.6817
2010's	2 (25.00)	24.3611
2020's	0 (0.00)	2.80

Authors	Studies
Campos-Outcalt, D	1
Cuckle, H	1
Maymon, R	1
Nørgård, B	1
Puhó, E	1
Czeizel, AE	1
Skriver, MV	1
Sørensen, HT	1
Kotwani, A	2
Mehta, VL	2
Iyengar, B	2
Padmanabhan, R	1
Wasfi, IA	1
Craigmyle, MB	1
Kubow, S	1
Yaylayan, V	1
Mandeville, S	1
Cohen, AW	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
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
Development of prenatal screening--A historical overview. Seminars in perinatology, 2016, Volume: 40, Issue:1 Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Biomarkers; Cell-Free System; DNA; Down Syndrome;	2016
Prenatal care, screening, and complications. Current opinion in obstetrics & gynecology, 1991, Volume: 3, Issue:6 Topics: alpha-Fetoproteins; Aspirin; Blood Transfusion, Autologous; Female; Humans; Mass Screening; Neural T	1991

Article	Year
USPSTF recommendations: A 2017 roundup. The Journal of family practice, 2017, Volume: 66, Issue:5 Topics: Advisory Committees; Aspirin; Breast Feeding; Cardiovascular Diseases; Colorectal Neoplasms; Dose-Re	2017
Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study. American journal of obstetrics and gynecology, 2005, Volume: 192, Issue:3 Topics: Abnormalities, Drug-Induced; Aspirin; Case-Control Studies; Cleft Lip; Cleft Palate; Female; Fetus;	2005
Aspirin by virtue of its acidic property may act as teratogen in early chick embryo. Indian journal of physiology and pharmacology, 1995, Volume: 39, Issue:2 Topics: Abnormalities, Drug-Induced; Animals; Aspirin; Blastoderm; Buffers; Chick Embryo; Dose-Response Rela	1995
Effect of pre-treatment with aspirin on alcohol-induced neural tube defects in the TO mouse fetuses. Drug and alcohol dependence, 1994, Volume: 36, Issue:3 Topics: Anencephaly; Animals; Aspirin; Brain; Dose-Response Relationship, Drug; Embryonic and Fetal Developm	1994
Protection by acetylsalicylic acid against hyperglycemia-induced glycation and neural tube defects in cultured early somite mouse embryos. Diabetes research (Edinburgh, Scotland), 1993, Volume: 22, Issue:4 Topics: Animals; Aspirin; Embryo, Mammalian; Female; Glucose; Glycosylation; Hyperglycemia; Male; Mice; Mice	1993
Mechanism of aspirin induced neural tube defect in chick embryo. The Indian journal of medical research, 1994, Volume: 99 Topics: Alprostadil; Animals; Aspirin; Chick Embryo; Dinoprost; Neural Tube Defects	1994

aspirin and Neural Tube Defects