Bethesda, Maryland
August 27 & 28, 2003

NIDA Organizer(s): Pushpa V. Thadani, Ph.D. & Rao Rapaka, Ph.D.

Meeting Purpose and Intent

Use of drugs of abuse during pregnancy is a major public health concern because of potential adverse effects on the fetus and the risk to maternal health. Since the placenta is the primary link between the mother and the conceptus and is essential for fetal growth and development, abnormalities in placental formation and function resulting from drug use and abuse could have a major influence on pregnancy outcome. Pregnancy complications such as preeclampsia, placenta previa and placental abruption seen in the general population, which are associated with adverse or poor fetal outcomes, frequently occur in women who abuse drugs during pregnancy, which represents a major public health concern. The clinical literature to date reports that infants born of mothers who used drugs, licit and illicit, have impaired somatic growth and development as well as neurobehavioral deficits. Other studies show that cocaine, marijuana, heroin and other abused drugs can cross the placental barrier. However, at present little information is available on the impact of abused drugs on placental biology alone or in combination with other 'host' factors such as poor prenatal care, stress, infection, and poor maternal nutrition, which are common co-morbid factors in drug abusing women.

Recent advances in the field of placental biology and the limited investigation of drugs of abuse related to placental development prompted the National Institute on Drug Abuse (NIDA) to assemble a group of biomedical researchers to discuss cutting-edge research with the mission of translating these findings to clinical application and to identify technologies that could facilitate research on the effects of drugs of abuse on placental function. The research areas covered in the conference included the development of the placenta, its role in immune-endocrine interactions during pregnancy, its function in the transfer of molecules (transporter systems), and the influence of infectious agents and xenobiotics on placental biology.

Brief Discussion of Meeting Outcome

Since the objective of this workshop was to identify gaps in our knowledge and topics for future research and how current technology could advance NIDA's mission, the discussion centered on emerging research in the drug abuse field related to placental physiology. Although existing data clearly suggest that drugs of abuse do produce alterations in placental function that can adversely affect the fetus, a number of key issues require attention. Workshop participants identified the following deficiencies in our knowledge base and made recommendations for a research agenda to address these deficiencies. Additional studies were recommended to:

1. Gain information as to how 'host' factors including genetic variation, recreational drug use, infection and malnutrition influence the placental barrier and its function;
2. Determine how the embryo/fetus is protected in different compartments;
3. Characterize the cellular and molecular processes involved in the transport of drugs and other molecules by various transport systems;
4. Study interactions of the endocrine and immune systems, both from a maternal and fetal perspective, as well as related to placental development and the impact of drugs of abuse;
5. Elucidate the effects of drugs of abuse on growth and angiogenic factors using animal and model cell systems;
6. Develop new technology to examine drug distribution and pharmacokinetics in vivo in small animals;
7. Identify biomarkers in biological fluids (serum, urine, saliva) and placental tissue that can be used to assess drug exposure in pregnant women using newer tools of genomics and proteomics.

It was believed that ultimately, studies addressing these needs would generate information that would advance our understanding as to how the development of the placenta is affected by drugs of abuse alone or in combination with other host factors, and how these effects relate to the growth and development of the fetus and postnatal health.

Expected Follow-up

Publicize the report and encourage researchers to submit proposals.

Brief Description of Resulting Publications

The conference report was published in Am. J. Obstet. Gynecol. in 2004, volume 191(6): 1858-1862. "National Institute on Drug Abuse Conference Report on Placental Proteins, Drug Transport, and Fetal Development" Pushpa V. Thadani, Jerome F. Strauss, Sudhansu K. Dey, et al.

Agenda

August 27, 2003

August 28, 2003

Participants List