Minimal Risk in Research Involving Pregnant Women and Fetuses

45 C.F.R. § 46.102(i) (2005).

45 C.F.R. § 46.110(b)(1) (2005).

45 C.F.R. § 46.116(d) (2005).

45 C.F.R. § 46.117(c)(2) (2005).

45 C.F.R. § 46.204(b) (2005).

45 C.F.R. § 46.204(d) (2005).

Department of Health and Human Services, Office for Human Research Protections, “Categories of Research That May Be Reviewed by the Institutional Review Board (IRB) through an Expedited Review Procedure,” November 9, 1998, available at <http://www.hhs.gov/ohrp/policy/expedited98.html> (last visited May 18, 2011).

Coutelle C. Rodeck C. , “On the Scientific and Ethical Issues of Fetal Somatic Gene Therapy,” Gene Therapy 9, no. 11 (2002): 670–673.

Waddington S. N. Kramer M. G. Hernandez-Alcoceba R. , “In Utero Gene Therapy: Current Challenges and Perspectives,” Molecular Therapy 11, no. 5 (2005): 661–676.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research Involving Children: Report and Recommendations, DHEW Publication No. (OS) 77–0004 (Washington, D.C.: U.S. Government Printing Office, 1977), at xx (emphasis added).

Freedman B. Fuks A. Weijer C. , “In Loco Parentis: Minimal Risk as an Ethical Threshold for Research upon Children,” Hastings Center Report 23, no. 2 (1993): 13–19. For a commentary that agrees with the position and argument of Freedman et al.,

See Weijer C. , “The Ethical Analysis of Risk,” Journal of Law, Medicine & Ethics 28, no. 4 (2000): 344–361

see also Miller P. B. Weijer C. , “Moral Solutions in Assessing Research Risk,” IRB 22, no. 5 (2000): 6–10.

National Bioethics Advisory Commission, Ethical and Policy Issues in Research Involving Human Participants, August 2001, at 83, available at <http://bioethics.georgetown.edu/nbac/human/overvol1.pdf> (last visited May 25, 2011). For an earlier statement of an argument based on justice,

See Kopelman L. , “Estimating Risk in Human Research,” Clinical Research 29, no. 1 (1981): 1–8.

Department of Health and Human Services, National Human Research Protections Advisory Committee, Children's Workgroup Report, April 2001, at 5, available at <http://www.hhs.gov/ohrp/archive/nhrpac/mtg04–01/child-workgroup4-5-01.pdf> (last visited May 25, 2011).

Institute of Medicine, Committee on Clinical Research Involving Children, Ethical Conduct of Clinical Research Involving Children (Washington, D.C.: National Academies Press, 2004): At 121–122.

Department of Health and Human Services, Secretary's Advisory Committee on Human Research Protections, “SACHRP Chair Letter to HHS Secretary Regarding Recommendations,” July 28, 2005, available at <http://www.hhs.gov/ohrp/sachrp/sachrpltrtohhssec.html> (, 2011).

Kopelman L. M. , “Minimal Risk as an International Ethical Standard in Research,” Journal of Medicine and Philosophy 29, no. 3 (2004): 351–378, at 363.

Id., at 366.

Department of Health and Human Services, Secretary's Advisory Committee on Human Research Protections, “SACHRP Chair Letter to HHS Secretary Regarding Recommendations,” July 28, 2005, Appendix B, available at <http://www.hhs.gov/ohrp/sachrp/sachrpltrtohhssecapdb.html> (last visited March 23, 2011).

See Kopelman , supra note 12, at2.

Id., at 4.

See Freedman Fuks Weijer , supra note 11

Department of Health and Human Services, supra note 13.

See Kopelman , supra note 12, at 4.

See Kopelman , supra note 16, at 364.

See Institute of Medicine, supra note 14, at 123.

See National Bioethics Advisory Commission, supra note 12, at 83.

Id.

See Department of Health and Human Services, supra note 13, at 1.

See Institute of Medicine, supra note 14, at 122

Department of Health and Human Services, supra note 15. For an example of an age-indexed approach,

See Wendler D. , “Minimal Risk in Pediatric Research as a Function of Age,” Archives of Pediatric and Adolescent Medicine 163, no. 2 (2009): 115–118.

See id. (Department of Health and Human Services).

See Freedman Fuks Weijer , supra note 11.

Kopelman L. M. , “Children as Research Subjects: A Dilemma,” Journal of Medicine and Philosophy 25, no. 6 (2000): 745–764, at 757.

The studies include: Janofsky J. Starfield B. , “Assessment of Risk in Research on Children,” Journal of Pediatrics 98, no. 5 (1981): 842–846

Shah S. Whittle A. Wilfond B. Gensler G. Wendler D. , “How Do Institutional Review Boards Apply the Federal Risk and Benefit Standards for Pediatric Research?” JAMA 291, no. 4 (2004): 476–482.

See National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, supra note 10, at xx–xxi.

See Department of Health and Human Services, supra note 18.

See Institute of Medicine, supra note 14, at 126.

See Department of Health and Human Services, supra note 18.

See National Bioethics Advisory Commission, supra note 12, at 80–85.

See Kopelman , supra note 16, at 375.

Id., at 365.

Council for International Organizations of Medical Sciences, International Ethical Guidelines for Biomedical Research Involving Human Subjects, Geneva, 2002, at 49, available at <http://www.cioms.ch/publications/layout_guide2002.pdf> (last visited May 25, 2011).

See Kopelman , supra note 12, at 4.

See Kopelman , supra note 16, at 361.

Resnik D. B. , “Eliminating the Daily Life Risks Standard from the Definition of Minimal Risk,” Journal of Medical Ethics 31, no. 1 (2005): 35–38.

See Freedman Fuks Weijer , supra note 11, at 16.

Wendler D. Belsky L. Thompson K. M. Emanuel E. J. , “Quantifying the Federal Minimal Risk Standard,” JAMA 294, no. 7 (2005): 826–832.

See Kopelman , supra note 16, at 361.

Fisher C. B. Kornetsky S. Z. Prentice E. D. , “Determining Risk in Pediatric Research with No Prospect of Direct Benefit: Time for a National Consensus on the Interpretation of Federal Regulations,” American Journal of Bioethics 7, no. 3 (2007): 5–10.

Id., at 7.

Wendler D. , “Protecting Subjects Who Cannot Give Consent,” Hastings Center Report 35, no. 5 (2005): 37–43, at 38

see also Wendler , supra note 45, at 831.

Id. ( Wendler )

supra note 45.

Id., at 830–831.

See Wendler (2005), supra note 49, at 40.

American College of Obstetricians and Gynecologists, Routine Tests in Pregnancy, available at <http://www.acog.org/publications/patient_education/bp133.cfm?printerFriendly=yes> (last visited May 18, 2011).

American Institute of Ultrasound in Medicine, Prudent Use and Clinical Safety, available at <http://www.aium.org/publications/statements.aspx> (last visited January 1, 2011)

American College of Obstetricians and Gynecologists, Committee on Ethics, “Nonmedical Use of Obstetric Ultrasonography,” Obstetrics and Gynecology 104, no. 2 (2004): 423–424.

Simpson J. L. Elias S. , Genetics in Obstetrics and Gynecology, 3rd ed. (Philadelphia: Elsevier, 2003) at 101–102.

Id., at 101–113.

Michels T. C. Tiu A. Y. , “Second Trimester Pregnancy Loss,” American Family Physician 76, no. 9 (2007): 1341–1346.

Wyatt P. R. Owolabi T. Meier C. Huang T , “Age-Specific Risk of Fetal Loss Observed in a Second Trimester Serum Screening Population,” American Journal of Obstetrics and Gynecology 192, no. 1 (2005): 240–246, at 241. This study might underestimate the post-first-trimester mortality rate because it involved pregnancies at 15 weeks gestational age onward.

Dugoff L. Cuckle H. S. Hobbins J. C. , “Prediction of Patient-Specific Risk for Fetal Loss Using Maternal Characteristics and First- and Second-Trimester Maternal Serum Down Syndrome Markers,” American Journal of Obstetrics and Gynecology 199, no. 3 (2008): 290e1–290e6, at 290e3–290e4. This study reports early and late fetal loss rates that, when combined, yield the percentage stated in the text.

Cunningham F. G. Hauth J. C. Leveno K. J. , Williams Obstetrics, 22nd ed. (New York: McGraw-Hill, 2005): Chap. 27, “Abnormalities of the Placenta, Umbilical Cord, and Membranes,” at 619–630. “Nuchal cord” refers to the umbilical cord being wrapped around the fetal neck. This can cause cord compression and associated decrease in oxygenation leading to fetal brain injury or death.

Clapp J. F. Stepanchak W. Hashimoto K. Ehrenberg H. Lopez B. , “The Natural History of Antenatal Nuchal Cords,” American Journal of Obstetrics and Gynecology 189, no. 2 (2003): 488–493.

Burton D. J. Filly R. A. , “Sonographic Diagnosis of the Amniotic Band Syndrome,” American Journal of Roentgenology 156, no. 3 (1991): 555–558, at 555. Amniotic band syndrome is believed to be caused when disruption of the amniotic membrane leads to fetal parts entering the space between the amniotic and chorionic membranes and becoming entangled with fibrous septa, disrupting normal development.

Osterman M. J. K. Martin J. A. Menacker F. , “Expanded Health Data from the New Birth Certificate, 2006,” National Vital Statistics Reports 58, no. 5 (2009): 1–24, at 4.

Id., at 19, 20. An estimate of those with pathologies throughout gestation would be those born with congenital anomalies. The total number of reported births, excluding infants with congenital anomalies, was 2,066,433. The number of NICU admissions, excluding infants with congenital anomalies, is estimated to be 116,987.