Sumner J. Yaffe

The use of pharmacotherapies for smoking cessation during pregnancy

A workshop entitled “The use of pharmacotherapies for smoking cessation during pregnancy”, sponsored by the National Institute of Child Health and Human Development (NICHD) and the Robert Wood Johnson Foundation (RWJF), was held in Rockville, Maryland, on 19 May 1999. The goals of the workshop were: (1) to determine the current state of knowledge related to the use of pharmacotherapies for smoking cessation during pregnancy; and (2) to outline a research agenda to determine the effectiveness and safety of these pharmacotherapies. Attending the workshop were many of the academic experts working in this area in the USA and representatives from NICHD, RWJF, the National Cancer Institute (NCI), the National Institute of Drug Abuse (NIDA), the Food and Drug Administration (FDA), the Centers for Disease Control and Prevention (CDC), the American College of Obstetrics and Gynecology (ACOG), the Society for Research on Nicotine and Tobacco (SRNT), and several pharmaceutical companies. In the USA, of the four million women who deliver babies each year, approximately 0.8–1 million smoke during their pregnancies. Smoking has a substantial adverse impact on pregnancy outcomes including growth retardation, preterm birth, perinatal mortality, sudden infant death syndrome (SIDS), and childhood behavioural problems. In developed countries, more than a third of all cases of growth retardation is caused by maternal smoking, and the more a woman smokes, the larger the effect on fetal growth. Stopping smoking is one of the major preventive measures likely to have a substantial impact on improving pregnancy outcome. Smoking most likely achieves its negative impact on pregnancy outcome through a number of mechanisms. These include the following: (1) nicotine is a toxin at the cellular level and also may act through its vasoconstrictive properties; (2) carbon monoxide—a major byproduct of cigarette smoking—binds to haemoglobin, resulting in a functional maternal anaemia; (3) carbon monoxide also …

Paediatric Labelling Requirements

SummaryThe US Food and Drug Administration (FDA) has proposed new labelling regulations that describe alternative approaches for providing additional information to support labelling a drug, already approved for use in adults, for use in children. Therefore, the study of drugs in paediatric populations may now be encouraged. Paediatric pharmacokinetic studies are an important part of these trials. This action by the FDA may help resolve the ethical and technological concerns about the performance of clinical trials in children, and may render paediatric clinical trials more feasible. Most investigations in children are opportunistic in nature and their design is often constrained by a requisite noninvasive approach.Appropriately applied population-based techniques for both pharmacokinetic and pharmacodynamic data analysis may represent the most robust approach for generating a sufficiently large and accurate database for the use of new or old drugs in paediatric patients. Accordingly, this information, which is crucial for paediatric labelling of any drug product, must be obtained in infants and children if we are to truly individualise therapy for paediatric patients.The funding of 6 Pediatric Pharmacology Research Units by the US National Institutes of Health, and guidelines for application of pharmacokinetic methods to children may further contribute to the performance of paediatric clinical trials.

Studies on renal enzymes in a patient with renal tubular acidosis

Abstract A metabolic case study of a four year old girl with renal tubular acidosis is presented. Renal function was normal except for inability to maintain a hydrogen gradient across the tubular epithelium. There was minimal limitation in total transfer of hydrogen ions into the urine, as expressed by titratable acidity, ammonia and reabsorbed bicarbonate. Histologic examination of a renal biopsy specimen disclosed dilatation of the tubules with some alteration in cellular surface. Enzyme assays for carbonic anhydrase and glutaminase activities were normal. Histochemical assay showed deficient staining for TPN diaphorase, but this was not corroborated by direct biochemical assay. No adequate explanation for the disorder was obtained, but it is suggested that a quantitative defect in energy production might have limited the renal secretion of free hydrogen ions.

Protein/Amino Acid Metabolism and Nutrition in Very Low Birth Weight Infants

A large number of studies in recent years have described protein and nitrogen metabolism in the neonate. However, the majority of these data are difficult to interpret because of a number of confounding variables, particularly in very low birth weight (VLBW) infants. In contrast, application of state-of-the-art tracer isotopic and molecular biology methods in isolated cell system and whole animals has resulted in major advances in our understanding of the regulation of protein breakdown, synthesis, and protein accretion. The following workshop summary reviews the recent developments in basic physiology of protein metabolism in cellular and animal models in relation to human preterm infants, and identifies the important areas toward which future basic and clinical research should be directed to provide for optimal nitrogen accretion and growth of the VLBW infant.

Maternal and pediatric AIDS in the United States: the current situation and future research directions

The epidemic of HIV infection and disease in women, adolescents and children represents a complexly intertwined biological and social challenge to health care workers and researchers alike. When considering various issues in confronting this epidemic, women must be viewed as individuals important in their own right, as the primary caretaker of their family members (both infected and uninfected), and as the sexual partners of men who may or may not be infected. Of the myriad of compelling biological questions facing AIDS researchers today, two of the most interesting involve the timing and determinants of vertical transmission and the natural history of HIV infection and disease in women. Scientifically, confronting this epidemic involves research into pathogenesis, epidemiology, natural history, treatment, and prevention of HIV infection. Primary emphasis in the research arena in HIV/AIDS in the United States is focused on therapeutic and prophylactic research. Other research issues are very important, including studies of early diagnostic techniques, behavioral research concerning reproductive choices, the role of breastfeeding in HIV transmission, HIV‐specific adolescent issues, and surrogate markers of disease progression.

Critical Periods of Neuroendocrine Development: Effects of Prenatal Xenobiotics

Phenobarbital, when administered prenatally in a small dose to animals, produced profound, and permanent effects on reproductive function in the offspring. Preliminary analysis of a unique cohort of adolescents who were exposed to phenobarbital in utero, suggests that long-term effects are also evident in the human. The precise nature of these effects is currently being determined and will be reported separately. These effects may be qualitatively and quantitatively different from effects seen in animals because of species difference in the timing or neuroendocrine differentiation. Of greater importance, however, is the fact that biologic and pharmacologic effects can be seen in the human following exposure to xenobiotics perinatally. Implications for other pharmacologic agents await further investigation. The rat model appears to have validity for extrapolation to man.

Mental Retardation and Developmental Disabilities: Research, Education, and Technology Transfer An Overview

“It has long been recognized that the prevalence of mental retardation is significantly higher in those population groups where maternal care is frequently inadequate,” and “The hazards of premature birth result in a significantly higher incidence of death and damage, including mental retardation, than occurs among full-term infants”: These two statements are quoted from the Prevention Section of the President’s Panel on Mental Retardation, which developed a national plan in 1962 to combat mental retardation. Although we will hear from others in the program about the epidemiology of mental retardation, I wish to emphasize in my presentation and overview the importance that prenatal care and low birth weight have made and continue to make toward the problem of the mentally retarded and the developmentally disabled. As you are aware, the mission given to the National Institute of Child Health and Human Development (NICHD) is to ensure through research the birth of healthy babies, the birth of wanted babies, and the opportunity of each infant to reach adulthood unimpaired by physical or mental handicap, and thus able to achieve his or her full potential. No mission could coincide more closely with the dreams and aspirations of the American people, and indeed the whole human family. This is what we want for all our children. The promotion of the healthy development of children, from prenatal life to adulthood, through research presents a unique but challenging opportunity to NICHD. Although this dream is closer to realization today than 22 years ago when Congress established this institute, we still have a long way to go. The infant mortality rate has been cut by more than half in the United States during this time, due in large part to advances from research supported by this institute. Much of this research has focused on the development of neonatal intensive care and the physiologic measures employed in supporting sick newborn infants. As a consequence birth-weight-specific mortality is lowest in the United States. Nonetheless, eleven countries in the developed world have a lower overall rate; in part because their burden of low-birth-weight infants is low. The infant mortality rate among blacks in the United States is still double that among whites, and the rate of low birth weight has not changed significantly over the years since the institute was created. Although 95% of sexually active American women use some form of fertility regulation at some time, surveys indicate that more than half (52%) of the six million pregnancies each year are not wanted at all, or not wanted at the time they occur. Unwanted pregnancy warrants discussion because these women are