Federal regulations have additional requirements to protect pregnant women, human fetuses and neonates involved in human subjects research under 45 CFR 46 Subpart B. See answers to key questions below.

Pregnancy is defined under 45 CFR 46.202(f) as a period of time from implantation until delivery. A woman shall be assumed to be pregnant if she exhibits any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.

If your study will target pregnant women or is a treatment-intervention study (i.e., drug/device) that will not exclude pregnant women/fetus then you should complete the Pregnant Women Subform with your IRB application.

Pregnant women and fetuses may be involved in research if the IRB determines all of the following conditions are met (45 CFR 46.204):

  • Where scientifically appropriate, preclinical studies (including studies on pregnant animals) and clinical studies (including studies on nonpregnant women) have been conducted and provide data for assessing potential risks to pregnant women and fetuses.
  • There is a prospect of direct benefit for the woman or the fetus, and the risk to the fetus is caused solely by interventions or procedures; or, if there is no prospect of direct benefit, the risk to the fetus is minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means.
  • Any risk is the least possible for achieving the objectives of the research.
  • No inducements, monetary or otherwise, will be offered to terminate a pregnancy.
  • Individuals engaged in the research will have no part in any decisions as to the timing, method or procedures used to terminate the pregnancy.
  • Investigators engaged in the research will have no part in determining the viability of a neonate.

Viable neonates are considered children, and 45 CFR 46 Subpart D applies. You must complete the Children Subform with your application. Please see our Research Involving Children FAQ for additional guidance. 

Neonates of uncertain viability (ability to survive independently) and nonviable neonates may be involved in research if the IRB determines the specific conditions required on 45 CFR 46 Subpart B are met. You must complete the Nonviable Neonates or Neonates of Uncertain Viability Subform with your application. Conditions:

  • Where scientifically appropriate, preclinical and clinical studies have been conducted and provide data for assessing potential risks to neonates.
  • Each individual providing consent under paragraph 45 CFR 205(b)(2) and c(5) of this section is fully informed regarding the reasonably foreseeable impact of the research on the neonate.
  • Individuals engaged in the research will have no part in determining the viability of a neonate.

Neonates of uncertain viability:

  • The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective; or the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means and there will be no added risk to the neonate resulting from the research.
  • The legally effective informed consent of either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, the legally effective informed consent of either parent’s legally authorized representative is obtained in accord with Subpart A of 45 CFR 46, except that the consent of the father or his legally authorized representative need not be obtained if the pregnancy resulted from rape or incest.

Nonviable neonates:

  • Vital functions of the neonate will not be artificially maintained.
  • The research will not terminate the heartbeat or respiration of the neonate.
  • There will be no added risk to the neonate resulting from the research.
  • The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means.
  • The legally effective informed consent of both parents of the neonate is obtained in accord with Subpart A of 45 CFR 46, except that a waiver and alteration provisions of 46.116(c) and (d) do not apply. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent of a nonviable neonate will suffice to meet the requirements, except that the consent of the father need not be obtained if the pregnancy resulted from rape or incest. The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice to meet the requirements.

Yes. Minimal risk research involving pregnant women and fetuses or their records, which also meet other required exemption criteria, may qualify as exempt. However, observational research involving pregnant women cannot be exempt if funded by the Environmental Protection Agency.

Informed consent must disclose the reasonably foreseeable impact of the research on the pregnant woman, fetus or neonate and fit into one of the options below under 45 CFR46.204:

  • The research holds out the prospect of direct benefit to the pregnant woman and consent will be obtained from the woman or the woman's legally authorized representative.
  • The research holds out the prospect of direct benefit to the pregnant woman and the fetus, and consent will be obtained from the woman or the woman's legally authorized representative.
  • The research does NOT hold out the prospect of direct benefit for the woman or fetus, but the risk to the fetus is minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained from any other means, and consent will be obtained from the woman or the woman's legally authorized representative.
  • The research holds out the prospect of direct benefit solely to the fetus and consent will be obtained from the pregnant woman and the father. (The father's consent does not need to be obtained if he is unable to consent because of unavailability, incompetence or temporary incapacity or the pregnancy resulted from rape or incest).

Note: For children/minors who are pregnant, assent and permission are obtained in accord with Subpart D. The Children Subform should be completed as well as the Pregnant Women Subform, with your application.

For additional guidance, please see:

If the study will specifically exclude pregnant women, the consent form may need to address the reason why with instructions to inform study investigators if they become pregnant or their partner becomes pregnant (for example, studies involving drugs, biologics or medical devices). If your study is greater than minimal risk, routine pregnancy testing may be required. In minimal risk studies, self-report of pregnancy status may be acceptable. Please see our Example Consent Text for Study-Specific Activities template located on our researcher resources page for specific verbiage to include in the consent form.

Missouri law related to pregnancy testing minors:

If circumstances lead to a suspicion of abuse (including sexual abuse) or neglect of the minor involved in the research, the mandatory reporting law must be followed. Abuse is not limited to abuse inflicted by the parent/guardian but includes abuse inflicted by any other person (210.115, Revised Statutes of Missouri). Statutory rape in Missouri is committed if the victim is “less than fourteen years of age.”

  • Ages 0-13: Child assent and parental/guardian consent will include language that a positive pregnancy result in a child under age 14 will be reported to both the child and parent/guardian.
  • Ages 14-17: Minors aged 14 and older will authorize the pregnancy test and will authorize whether the parent/guardian may be informed of the results. The minor needs to be informed of the result, then the minor needs to determine whether the parent/guardian will be informed as well.

Note: A provider/practitioner must be listed on the study to help ensure standard clinical practices are followed for mandatory reporting and discussing pregnancy with minors and parents/guardians when necessary.

If a subject becomes pregnant while participating in a study where pregnancy is an exclusion criterion, the investigator must either:

  • Terminate enrollment (considering the risks associated with terminating) and consult the IRB.
  • Submit an amendment form to either:
    • Include pregnant women (if it’s feasible for the participant to remain in the study and it meets the requirements under 45 CFR 46 Subpart B).
    • Add the individual as a new participant of the study.

In some drug trials, the risk of paternal transmission to the fetus is unknown. In those cases, contraception is required for enrolled male research participants. Please see our Example Consent Text for Study-Specific Activities template located on our researcher resources page for specific verbiage to include in the consent form related to risks of fathering a child and acceptable birth control for male and female participants.

If the partner becomes unexpectedly pregnant, the investigator must promptly notify the IRB. If not already approved by the IRB and the pregnancy will be followed, a separate Pregnant Partner Release for the unintended pregnant partner must be submitted to the IRB as an amendment.

There are no explicit FDA regulations regarding pregnant participants in research. The FDA states that “in general, pregnant women are excluded from drug development clinical trials” but concedes that it may be “scientifically and ethically appropriate to include pregnant women in a clinical trial.” 

The FDA published draft guidance in April 2018: Pregnant Women: Scientific and Ethical Considerations for Inclusion in Clinical Trials Guidance for Industry. 

Research done as an Investigational New Drug (IND) in pregnant participants still needs to follow the FDA preclinical animal requirements. These animal requirements include female reproduction toxicity and genotoxicity studies. Any research done with FDA-approved products must meet Subpart B requirements of preliminary animal studies because this is already an FDA requirement with application for drug approval.
 

For research subject to requirements of the Environmental Protection Agency (EPA): 

  • The EPA prohibits research involving the intentional exposure of pregnant participants, nursing participants or children to any substance (40 CFR 26).

For research subject to requirements of the Department of Defense (DoD):

  • The DOD applies Subpart B only to research involving pregnant participants that is greater than minimal risk and includes interventions or invasive procedures involving the woman, fetus or neonate (DOD Instruction 3216.02).