STUDY DESIGN: Retrospective review of VLBW infants cared for at a single level III NICU during a two year period, n = 199.

RESULTS: Overall transfusion requirement was 4.6 +/- 6.2 transfusions/infant/hospital course. Length of hospital stay, days of mechanical ventilation, requirement for dopamine support, birth weight, initial hematocrit, periventricular leukomalacia and necrotizing enterocolitis all independently correlated with number of transfusions and donors. Bronchopulmonary dysplasia and patent ductus arteriosus were associated with donor but not transfusion number.

CONCLUSIONS: Our data characterize the population of VLBW infants with the greatest blood transfusion and donor requirement. Further investigation is needed to target this population for interventions to reduce blood exposure.

METHODS: We conducted a prospective, community-based survey of women receiving prenatal care at Philadelphia community health centers. We conducted surveys at the first prenatal visit and at a mean age +/- standard deviation of 3 +/-1, 11 +/- 1, and 24 +/- 2 months postpartum, obtaining information on sociodemographic and health characteristics, child's health care provider, and 6 parenting practices. Group differences were tested between those with and without a CSOC by using the chi-square test for categorical variables and the Student's t test for continuous variables. Logistic regression analysis was conducted to adjust for potential confounding variables.

RESULTS: Our sample consisted of 894 mostly young, African American, single women and their children. In the adjusted analysis, mothers of children with a CSOC, when compared with those without a CSOC, were more likely to have a high school education or less, be born in the United States, have a postpartum checkup, have stable child health insurance, and initiate care for their child at a site other than a community-based health center. Use of parenting practices was similar for children with and without a CSOC.

CONCLUSIONS: Maternal nativity, postpartum care, child health insurance, and initial site of infant care were associated with CSOC, but infant health characteristics were not. Use of parenting practices did not differ for those with and without a CSOC.

METHODS: In-person group interviews were conducted to obtain a composite picture of actual breastfeeding policies and practices. One questionnaire per hospital was completed based on responses from group consensus. Twenty-five hospitals providing maternity care were contacted. Information was obtained from personnel representing different areas of maternity services. Hospitals were classified according to the degree to which they were implementing the Ten Steps to Successful Breastfeeding.

RESULTS: Mean breastfeeding rates at suburban hospitals were significantly higher than urban hospitals (72% vs. 49%, p = 0.015). Most hospitals were classified as high or moderately high implementers on six of the Ten Steps, including staff training (67%), printed information distributed to breastfeeding mothers (94%), breastfeeding initiation (61%), oral breastfeeding instruction given to mothers (83%), infant feeding schedules (89%), and hospital postpartum support (83%). Most hospitals reported partial or low implementation on two maternity practices: infant formula supplementation (61%) and rooming-in (72%).

CONCLUSIONS: In the past 15 years, hospitals in the Philadelphia area have an increased awareness about breastfeeding and enhanced support of breastfeeding by healthcare professionals. In spite of an increase in overall breastfeeding rates, formula supplementation in hospitals and contact time between mothers and their newborns continue to be areas of concern.

OBJECTIVE: To identify factors associated with growth in children on growth hormone (GH) therapy using data from the American Norditropin Studies: Web-enabled Research (ANSWER) Program® registry.

METHODS: GH-naïve children with GH deficiency, multiple pituitary hormone deficiency, idiopathic short stature, Turner syndrome, or a history of small for gestational age were eligible (N = 1,002). Using a longitudinal statistical approach, predictive factors were identified in patients with GHD for change from baseline in height standard deviation score (ΔHSDS) following 2 years of treatment.

RESULTS: Gradual increases in ΔHSDS over time were observed for all diagnostic categories. Significant predictive factors of ΔHSDS, ranked by significance were: height velocity (HV) at 4 months > baseline age > baseline HSDS > baseline body mass index (BMI) SDS > baseline insulin-like growth factor I (IGF-I) SDS; gender was not significant. HV at 4 months and baseline BMI SDS were positively correlated, whereas baseline age, HSDS, and IGF-I SDS were negatively correlated with ΔHSDS.

CONCLUSIONS: These results may help guide GH therapy based on pretreatment characteristics and early growth response.

RESULTS: When ES cells were primed with Noggin/fibroblast growth factors (bFGF and FGF-8) in a more robust neural differentiation medium for 2 days before differentiation induction, the efficiency of in vitro motor neuron differentiation was improved from ~25% to ~50%. The differentiated ES cells expressed a pan-neuronal marker (neurofilament) and motor neuron markers (Hb9, Islet-1, and ChAT). Even though SMN-deficient ES cells had marked reduced levels of SMN (~20% of that in control ES cells), the morphology and differentiation efficiency for these cells are comparable to those for control samples. However, proteomics in conjunction with western blot analyses revealed 6 down-regulated and 14 up-regulated proteins with most of them involved in energy metabolism, cell stress-response, protein degradation, and cytoskeleton stability. Some of these activated cellular pathways showed specificity for either undifferentiated or differentiated cells. Increased p21 protein expression indicated that SMA ES cells were responding to cellular stress. Up-regulation of p21 was confirmed in spinal cord tissues from the same SMA mouse model from which the ES cells were derived.

CONCLUSION: SMN-deficient ES cells provide a cell-culture model for SMA. SMN deficiency activates cellular stress pathways, causing a dysregulation of energy metabolism, protein degradation, and cytoskeleton stability.

The program, now in its eighth year, is run by the Disaster Management Division of Israel's Ministry of Health in collaboration with the Israel Defense Forces' Surgeon General and American Physicians and Friends for Medicine in Israel.

METHODS: A year-by-year description of the events is given, including the scientific and social content of the annual meetings and changes in the business of the society, in many cases using comments from the past presidents. The valuable and unique diversity of the members is discussed and illustrated, presenting the disciplines and main research areas of the presidents. The number of submitted abstracts and the various categories are tabulated, averaging the number and type over successive periods. A significant increase in the number of abstracts dealing with epidemiology and developmental biology is evident. The society's development is compared to that of a human, and the question was asked by Shephard et al. (2000): Have we reached the maturational stage of old age or senescence, or is the society still maturing gracefully? This question needs further discussion by all the members. By 2010, many positive changes are happening to revitalize the society.

RESULTS: During the past 50 years, we have developed the scientific basis to prevent birth defects caused by rubella, alcoholism, and folate deficiency, as well as other prenatal exposures. We are now taking advantage of advances in many fields to begin shaping the Teratology Society of the 21st century.

CONCLUSIONS: We must now engage in political battles to obtain the resources needed to conduct further research and to implement prevention programs, as well as to provide care and rehabilitation for persons with birth defects.

What is Teratology?

“What a piece of work is an embryo!” as Hamlet might have said. “In form and moving how express and admirable! In complexity how infinite!” It starts as a single cell, which by repeated divisions gives rise to many genetically identical cells. These cells receive signals from their surroundings and from one another as to where they are in this ball of cells —front or back, right or left, headwards or tailwards, and what they are destined to become. Each cell commits itself to being one of many types; the cells migrate, combine into tissues, or get out of the way by dying at predetermined times and places. The tissues signal one another to take their own pathways; they bend, twist, and form organs. An organism emerges. This wondrous transformation from single celled simplicity to myriad-celled complexity is programmed by genes that, in the greatest mystery of all, are turned on and off at specified times and places to coordinate the process. It is a wonder that this marvelously emergent operation, where there are so many opportunities for mistakes, ever produces a well-formed and functional organism.

And sometimes it doesn’t. Mistakes occur. Defective genes may disturb development in ways that lead to death or to malformations. Extrinsic factors may do the same. “Teratogenic” refers to factors that cause malformations, whether they be genes or environmental agents. The word comes from the Greek “teras,” for “monster,” a term applied in ancient times to babies with severe malformations, which were considered portents or, in the Latin, “monstra.”

Malformations can happen in many ways. For example, when the neural plate rolls up to form the neural tube, it may not close completely, resulting in a neural tube defect—anencephaly if the opening is in the head region, or spina bifida if it is lower down. The embryonic processes that form the face may fail to fuse, resulting in a cleft lip. Later, the shelves that will form the palate may fail to move from the vertical to the horizontal, where they should meet in the midline and fuse, resulting in a cleft palate. Or they may meet, but fail to fuse, with the same result. The forebrain may fail to induce the overlying tissue to form the eye, so there is no eye (anophthalmia). The tissues between the toes may fail to break down as they should, and the toes remain webbed.

Experimental teratology flourished in the 19th century, and embryologists knew well that the development of bird and frog embryos could be deranged by environmental “insults,” such as lack of oxygen (hypoxia). But the mammalian uterus was thought to be an impregnable barrier that would protect the embryo from such threats. By exclusion, mammalian malformations must be genetic, it was thought.

In the early 1940s, several events changed this view. In Australia an astute ophthalmologist, Norman Gregg, established a connection between maternal rubella (German measles) and the triad of cataracts, heart malformations, and deafness. In Cincinnati Josef Warkany, an Austrian pediatrician showed that depriving female rats of vitamin B (riboflavin) could cause malformations in their offspring— one of the early experimental demonstrations of a teratogen. Warkany was trying to produce congenital cretinism by putting the rats on an iodine deficient diet. The diet did indeed cause malformations, but not because of the iodine deficiency; depleting the diet of iodine had also depleted it of riboflavin!

Several other teratogens were found in experimental animals, including nitrogen mustard (an anti cancer drug), trypan blue (a dye), and hypoxia (lack of oxygen). The pendulum was swinging back; it seemed that malformations were not genetically, but environmentally caused.

In Montreal, in the early 1950s, Clarke Fraser’s group wanted to bring genetics back into the picture. They had found that treating pregnant mice with cortisone caused cleft palate in the offspring, and showed that the frequency was high in some strains and low in others. The only difference was in the genes. So began “teratogenetics,” the study of how genes influence the embryo’s susceptibility to teratogens.

The McGill group went on to develop the idea that an embryo’s genetically determined, normal, pattern of development could influence its susceptibility to a teratogen— the multifactorial threshold concept. For instance, an embryo must move its palate shelves from vertical to horizontal before a certain critical point or they will not meet and fuse. A teratogen that causes cleft palate by delaying shelf movement beyond this point is more likely to do so in an embryo whose genes normally move its shelves late.

As studies of the basis for abnormal development progressed, patterns began to appear, and the principles of teratology were developed. These stated, in summary, that the probability of a malformation being produced by a teratogen depends on the dose of the agent, the stage at which the embryo is exposed, and the genotype of the embryo and mother.

The number of mammalian teratogens grew, and those who worked with them began to meet from time to time, to talk about what they were finding, leading, in 1960, to the formation of the Teratology Society. There were, of course, concerns about whether these experimental teratogens would be a threat to human embryos, but it was thought, by me at least, that they were all “sledgehammer blows,” that would be teratogenic in people only at doses far above those to which human embryos would be exposed. So not to worry, or so we thought.

Then came thalidomide, a totally unexpected catastrophe. The discovery that ordinary doses of this supposedly “harmless” sleeping pill and anti-nauseant could cause severe malformations in human babies galvanized this new field of teratology. Scientists who had been quietly working in their laboratories suddenly found themselves spending much of their time in conferences and workshops, sitting on advisory committees, acting as consultants for pharmaceutical companies, regulatory agencies, and lawyers, as well as redesigning their research plans.

The field of teratology and developmental toxicology expanded rapidly. The following pages will show how far we have come, and how many important questions still remain to be answered. A lot of effort has gone into developing ways to predict how much of a hazard a particular experimental teratogen would be to the human embryo (chapters 9–19). It was recognized that animal studies might not prove a drug was “safe” for the human embryo (in spite of great pressure from legislators and the public to do so), since species can vary in their responses to teratogenic exposures. A number of human teratogens have been identified, and some, suspected of teratogenicity, have been exonerated—at least of a detectable risk (chapters 21–32). Regulations for testing drugs before market release have greatly improved (chapter 14). Other chapters deal with how much such things as population studies (chapter 11), post-marketing surveillance (chapter 13), and systems biology (chapter 16) add to our understanding. And, in a major advance, the maternal role of folate in preventing neural tube defects and other birth defects is being exploited (chapter 32). Encouraging women to take folic acid supplements and adding folate to flour have produced dramatic falls in the frequency of neural tube defects in many parts of the world.

Progress has been made not only in the use of animal studies to predict human risks, but also to illumine how, and under what circumstances, teratogens act to produce malformations (chapters 2–8). These studies have contributed greatly to our knowledge of abnormal and also normal development. Now we are beginning to see exactly when and where the genes turn on and off in the embryo, to appreciate how they guide development and to gain exciting new insights into how genes and teratogens interact. The prospects for progress in the war on birth defects were never brighter.

F. Clarke Fraser McGill University (Emeritus) Montreal, Quebec, Canada

1. As a result of this activity, the audience will be able to identify the risk factors associated with pediatric drowning scenarios.

2. As a result of this activity, the audience will be able to educate the parent’s of their pediatric patients about effective drowning prevention strategies.

Educational Objectives

1. To recognize that drowning and near drowning represent very significant tragedies in the United States.

2. To learn the components of a behavioral approach for a more effective drowning prevention strategy.

3. To recognize the role of health care providers in drowning prevention.

4. To understand the “best practices” for existing comprehensive drowning prevention strategy efforts.

5. To be able to identify a local program of instruction within the six current types of aquatic educational exposures for infants and young children in the United States.