Does aspirin (acetylsalicylic acid) use in the first trimester increase the risk of neural tube defects?

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Does Aspirin in First Trimester Cause Neural Tube Defects?

No, aspirin use in the first trimester does not cause neural tube defects. Multiple high-quality sources confirm that low-dose aspirin is not associated with increased risk of structural malformations, including neural tube defects, when used during early pregnancy.

Evidence for Safety

The most recent and comprehensive evidence demonstrates no teratogenic risk with first-trimester aspirin exposure:

  • A 2023 meta-analysis of 8 randomized controlled trials including 15,234 participants found no significant difference in congenital anomalies with low-dose aspirin started before 14 weeks (OR 0.87,95% CI 0.62-1.23) 1

  • The American College of Physicians confirms that low-dose aspirin (81-100 mg daily) during pregnancy carries minimal maternal or fetal risks when used appropriately, with no increased risk of congenital anomalies 2

  • A 1992 comprehensive review explicitly stated that "the use of aspirin in the first trimester is not associated with increased risk of structural malformations" 3

Important Distinction: Gastroschisis vs Neural Tube Defects

One specific anomaly warrants mention, though it is NOT a neural tube defect:

  • There is a possible increased risk of gastroschisis (a different type of abdominal wall defect) with first trimester aspirin exposure (OR 2.37,95% CI 1.44-3.88), though the American College of Chest Physicians notes this estimate has "questionable validity" due to significant bias in contributing studies 2

  • Gastroschisis is an abdominal wall defect where intestines protrude through the abdominal wall—this is completely distinct from neural tube defects like spina bifida or anencephaly 2

Neural Tube Defects: Actual Risk Factors

The established risk factors for neural tube defects do NOT include aspirin:

  • History of a previous fetus or child with a neural tube defect 4
  • First-, second-, or third-degree relative with a neural tube defect 4
  • Maternal diabetes or obesity 4
  • Antiepileptic medications such as valproic acid or carbamazepine 4
  • Inadequate folic acid supplementation 4

Clinical Context for Aspirin Use

Low-dose aspirin is actually recommended in early pregnancy for high-risk women:

  • The U.S. Preventive Services Task Force and American College of Obstetricians and Gynecologists recommend starting low-dose aspirin between 12-16 weeks of gestation for women at high risk of preeclampsia 5

  • For maximum effectiveness in preventing preeclampsia, aspirin should ideally be initiated before 16 weeks of gestation 5

  • The safety profile is well-established: no increased risk of placental abruption, postpartum hemorrhage, fetal intracranial bleeding, perinatal mortality, or congenital anomalies 2, 5

Long-Term Developmental Safety

Follow-up studies confirm no adverse developmental effects:

  • The largest trial follow-up at 18 months showed no differences in physical or mental developmental outcomes (gross motor development, height, weight, hospital visits) in children exposed to aspirin in utero 2

  • A comprehensive follow-up study of 4,365 children at 18 months found no clear differences in congenital malformations, major motor deficit, or severe neuromotor or developmental delay 6

References

Research

Low-dose aspirin use in the first trimester of pregnancy and odds of congenital anomalies: A meta-analysis of randomized controlled trials.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics, 2023

Guideline

Risk of Baby Aspirin in Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The use of low dose aspirin in pregnancy.

American journal of reproductive immunology (New York, N.Y. : 1989), 1992

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Aspirin Prophylaxis in Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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