1. Research With Pregnant Women Permissible Regulations, Cautious Practice: A US Perspective
Anna C. Mastroianni, JD, MPH
Professor of Law, University of Washington School of Law
Associate Director, Institute for Public Health Genetics
Seattle, USA
Leslie Meltzer Henry, JD, PhD
Professor of Law, University of Maryland Carey School of Law
Core Faculty, Johns Hopkins Berman Institute of Bioethics
Baltimore, USA

2. Orientation
United States permits pregnant women’s participation in research under conditions specified in regulations and official guidances
Facilitated through local IRB review with national oversight
“Subpart B” [Additional Protections for Pregnant Women, Human Fetuses and Neonates Involved in Research] regulations set up ethical framework, with extensive reach and international influence
Permissibility stymied by regulatory and other legal obstacles

3. The Reach of Subpart B Subpart B Applies NIH-Funded Research
Conducted Inside or Outside of the United States
Research Funded by U.S. Agency that Follows Subpart B
Any Funder
Research Conducted at an FWA Institution Inside or Outside of the United States
Any Funder
Research Team Member Affiliated with FWA Institution Inside or Outside of the United States

4. US Regulatory Approach to Common Ethical Issues
Presumption of Inclusion
“Pregnant women or fetuses may be involved in research if all of the following conditions are met…” (2001)
Contrast ICH “ In general, pregnant women should be excluded …where drug not intended for use in pregnancy”
Population Classified as Vulnerable
“IRB…should be particularly cognizant of the special problems of research involving vulnerable populations, such as…pregnant women…..”
Contrast ICH: “special population” with “unique risk/benefit considerations “ or “modification of use of the dose or schedule of a drug “ and “attention… to informed consent.”

5. US Regulatory Approach to Common Ethical Issues Benefit-Risk
Prospect of direct benefit to woman or fetus
“risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the woman or the fetus”
No prospect of direct benefit to woman or fetus
Where “no such prospect of benefit, the risk to the fetus is not greater than minimal” and research purpose is “development of important biomedical knowledge which cannot be obtained by any other means”

6. Additional Mechanism for Approving Research with Pregnant Women
Standard: “reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant women [or] fetuses …”
Process: Decision by Secretary of Health and Human Services, after consultation with expert panel, public comment, and public meeting

7. US Regulatory Approach to Common Ethical Issues: Paternal Consent
Inform of “reasonably foreseeable impact of the research on the fetus”
Additional consent of father required if research holds out prospect of direct benefit solely to the fetus
Exceptions: unavailability, incompetence, temporary incapacity, pregnancy resulted from rape or incest.

8. Default Approach  De Facto Exclusion of Pregnant Women
Many researchers and institutional review boards (IRBs) continue to regard pregnancy as a near-automatic cause for exclusion, regardless of the costs of exclusion or the magnitude or likelihood of the risks of participation.
A. Lyerly, M. Little & R. Faden. The second wave: toward responsible inclusion of pregnant women in research.
Real-Life Implications
Fewer than 20 FDA-approved drugs are approved for use during pregnancy
Mean time for determining risk of medication in pregnancy: 27 years post-drug approval

9. Legal Obstacles Lawyers are active and influential participants in decisionmaking throughout the research process
Regulatory Ambiguity and Inconsistency
Legal Risk Management
Litigation Climate and “Long Tail” Liability Concerns
Insurance Availability
Compensation Availability
Venue-Specific Laws
International Complexity
Fetal Protection Laws

10. Acknowledgments