Appendix I: National Children’s Study Advisory Committee 8th Meeting
Thematic Group Breakout Meeting Summary: Pregnancy Outcome
December 15, 2003
Sheraton Atlanta Hotel
Chair: Donald J. Dudley, M.D., NCSAC Member, University of Texas Health Science Center at San Antonio
Dr. Dudley called the meeting to order, asked the observers in attendance to introduce themselves and identify the organizations they represented.
The group first discussed whether there were any gaps in the hypotheses. They noted that nothing in the pregnancy outcome group addresses exposures from chemicals and physical environment. This might not be part of a core hypothesis but certainly needs to be addressed in the National Children’s Study. There was broad agreement that maternal stress needed to be evaluated. A hypothesis on this topic would involve pregnancy, asthma, development and behavior, birth defects, injury, and social environment.
The group discussed the well-developed hypothesis on intrauterine infections and preterm birth. They reviewed the exposures and outcomes, including the most appropriate times to sample. Dr. Dudley pointed out that this hypothesis is directly related to two from the Development and Behavior Group (infection/cerebral palsy and infection/schizophrenia). Because this is a life course Study, these three hypotheses all are related to what happens during pregnancy. This highlights the need for a standardized neurodevelopmental protocol that looks at cerebral palsy. It was noted that this would not be easy to do at 40 different sites.
Psychosocial Stress and Pregnancy and Infancy Workshop
The group discussed the Psychosocial Stress and Pregnancy and Infancy Workshop, which had not yet released a final document for NCSAC to review. That should be available by the March meeting and it will contain very detailed exposure and outcome measures. The Workshop determined that:
- Stress can be defined.
- Stress can be measured.
- Measures are relatively straightforward and not too burdensome to subjects.
- The Study should include preconception and postpartum measures.
Exposures and Outcomes
Core exposures and outcomes that might not be addressed by specific hypotheses were discussed. The Study shouldn’t forget obvious things, such as birth weight, stillbirth, method of conception (for example, in vitro fertilization), or if the mother had a spontaneous or induced abortion.
The group discussed preconceptional sampling and paternal exposures, which have not been discussed in any great detail. The ICC subcommittee draft contains the hypothesis dealing with the risk of birth defects in women with impaired glucose tolerance. Drs. Erickson and Jones of the Birth Defects Working Group advanced this hypothesis. Exposures and outcomes for this hypothesis were discussed in detail, including:
- Glucose testing
- Hemoglobin testing preconceptionally, and at 6, 12, and 18 weeks.
Outcomes included birth defects that will be evaluated by growth measures and dysmorphology. The group agreed that the Study needs a standardized protocol for neonatal evaluation including photos of head, face, and hands, and renal and cardiac ultrasounds.
A discussion was then held on healthy outcomes. Both of the hypotheses discussed could be turned around and considered from a health perspective. For example, why do women with impaired glucose tolerance have normal children? Why do women with intrauterine infections not deliver preterm or have babies with cerebral palsy? The group discussed different effect modifiers such as gene-environment interactions, nutrition, folate, and antioxidants.
Adequacy of Thematic Areas
The adequacy of the thematic areas was discussed. Group members pointed out that there is no thematic area that looks at reproductive development, but one participant commented that this is included in the obesity and physical development. They thought that this thematic area should consider a name change to Obesity, Growth, and Pubertal Development or something more descriptive of the range of issues they are looking at.
- Gestational diabetes
- Type 2 diabetes
- Fasting blood sugar.
Could diabetes result in birth defects?
- Diabetes-related defects
- Defective chromosomes.
When is glucose intolerance tested?
- 28th week of gestation
- Should be tested once every trimester.
Were mothers with children born with birth defects taking a substance?
How can researchers find out if the was mother taking a substance?
- Abstracting medical records
- Asking mother/not dependable
- Pharmaceutical databases.
How are birth defects identified?
- Three-dimensional ultrasound
- Renal ultrasound
- Cardiac ultrasound
- Head ultrasound.
What are the risk factors of a mother having a child with a birth defect?
- Impaired glucose.
Collect and bank for testing:
- Cervical mucous at initial visit and repeated at 18, 24, and 34 weeks
- Maternal blood
- Maternal saliva.
- Gross exam of the placenta-cord, membranes, staining
- Photographs of both maternal and fetal sides of placenta.
- Pregnancy wastage
- Pregnancy loss
- Growth restrictions.
- Standard follow up of neurological developments (one year and three years)
- Cerebral palsy is not visible until down the line.
Are there drugs that mediate and modify infections? Yes, there are dozens of mediators of inflammation:
- Treat infection (preterm labor still does not go away)
What are the two standard barrels for pregnancy outcomes?
- Birth defects
- More prevalent than preterm labor
- Does not result in children.
How to measure early loss:
- Collecting tissue for first trimester.
When looking back at childhood, doctors found that schizophrenia was a problem but not recognized until adulthood.
Obesity insulin resistance:
- Two ultrasounds to screen for growth development
- Three-dimensional ultrasounds, once every trimester.
Testing gestational age exposures:
- Meconium has been used for research
Doctors suggested that during the postpartum stage they maybe able to tell what happened during pregnancy if mother is:
Why do most mothers with infection go on to have healthy children whereas others do not?
What type of chemicals?
- Folic acid
What are some other hypotheses that should be addressed?
- Reproductive development
- Obesity and growth
- Pubertal development.
Dr. Dudley suggested that there is not enough communication between different Working Groups and that they should get in touch with the following groups:
- Nutrition, Growth, and Pubertal Development
- Exposure to Chemical Agents
- Physical Exposures.
Members of the National Children’s Study need to follow up with glucose geneticists and nutritionists.
Thematic Group Members
Chair: Donald J. Dudley, M.D., University of Texas Health Science Center at San Antonio
Tye E. Arbuckle, Ph.D., Environmental Health Science Bureau, Heath Canada
Christine A. Bachrach, Ph.D., Center for Population Research, NICHD, NIH, DHHS
Amy Branum, M.S.P.H., National Center for Health Statistics, CDC, DHHS
Adolfo Correa, M.D., Ph.D., M.P.H., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS
Mark Cosentino, D.P.M., Ph.D., Science Applications International Corporation
Dave Erickson, D.D.S., Ph.D., M.P., National Center on Birth Defects and Developmental Disabilities, CDC, DHHS
Judith A. Graham, Ph.D., American Chemistry Council
Gary D. V. Hankins, M.D., Department of Obstetrics and Gynecology, University of Texas Medical, Galveston
Kenneth Lyons Jones, M.D., University of California, San Diego
Carole A. Kimmel, Ph.D., Office of Research and Development, EPA
Mark A. Klebanoff, M.D., M.P.H., NICHD, NIH, DHHS
Larry L. Needham, Ph.D., National Center for Environmental Health, CDC, DHHS
Paul J. Seligman, M.D., M.P.H., Center for Drug Evaluation and Research, FDA, DHHS
Lucina Suarez, Ph.D., State of Texas Department of Health
Observers and Other Participants
Leni Buff, National Children’s Study Program Office, NICHD, NIH, DHHS
Jan L. Leahey, NICHD, NIH, DHHS
William Lyman, Ph.D., Department of Pediatrics, Wayne State University
Tracey W. Thomas, Ph.D., Office of Research and Development, EPA