Armond S. Goldman (1930-2023) and the development of the immunobiology of human milk.

The understanding of the immunobiology of human milk is primarily a 20th-century phenomenon, but, even with our contemporary understanding, it remains a bit of a mystery. Breastfeeding of human milk, although the most obvious and natural form of nutrition for human infants, has been hindered by cultural and societal norms since ancient times. Thus, not all infants have experienced the advantages this form of nutrition may offer. Although these advantages have been anecdotally suggested since ancient times, it was only in the late 19th and early 20th centuries that the superiority of human milk was scientifically documented. The underlying immunobiological properties of human milk underpinning its observed superiority only became appreciated with advances in immunology that occurred in the mid to late 20th century. Armond S. Goldman (1930-2023) was in the vanguard of those promoting and developing an understanding of the immunobiology of human milk and its superiority in promoting the health of human infants.

The Osler Student Societies of the University of Texas medical branch: a medical professionalism translational tool.

This essay reviews some of the issues associated with the challenge of integrating the concepts of medical professionalism into the socialization and identity formation of the undergraduate medical student. A narrative-based approach to the integration of professionalism in medical education proposed by Coulehan (Acad Med 80(10):892-898, 2005) offers an appealing method to accomplish the task in a less didactic format and in a way that promotes more personal growth. In this essay, I review how the Osler Student Societies of the University of Texas Medical Branch developed and how they offer a convenient vehicle to carry out this narrative-based approach to professionalism. Through mentor-modeled professional behavior, opportunities for student self-reflection, the development of narrative skills through reflection on great literature, and opportunities for community service, the Osler Student Societies provide a ready-made narrative-based approach to medical professionalism education.

Chester R. Burns (1937-2006) and the origins of the American Osler Society.

The American Osler Society (AOS) traces its origin to a 1970 symposium on Humanism in Medicine in Galveston, Texas. Although John P. McGovern (1921-2007) receives credit for conceiving the symposium and spearheading formation of the AOS, Chester Ray Burns (1937-2006) played a key role that has not been sufficiently recognized. Burns, the first American-born physician to receive a doctorate in the history of medicine from the Johns Hopkins University, did much and perhaps most of the organizational work and brought to the symposium a perspective on the crossroads between medicine and the humanities that proved essential to the nascent organization's success. Burns went on to a productive career at the University of Texas Medical Branch (UTMB) in Galveston, became the 35th president of the AOS, and is among the relatively few physician-historians to have published scholarly articles in the history of medicine, medical biography, medical ethics, and philosophy as related to medicine.

Patrick Romanell, William Osler, and philosophy in medicine.

In 1974, Patrick Romanell (1912-2002) published a paper in the Bulletin of the New York Academy of Medicine taking William Osler (1849-1919) to task for dismissing philosophy as a distinguishing feature of the nature of medicine. Osler had expressed this thought in the Silliman Lectures given at Yale in 1913 on the Evolution of Modern Medicine. That the nature of medicine is underpinned by an understanding of the nature of man requires that the pedagogy and practice of medicine incorporate not only the empirical science that is the basis for clinical practice, but also the logical and metaphysical concepts of the nature of man. These concepts are informed by the humanities that include history, literature, and the arts. Despite Romanell's critique of Osler's statement, Romanell ultimately corroborates other statements made by Osler in the lecture series, substantiating Osler's deep appreciation for the nature of man and a philosophy of medicine that deserves emulation.

The limits of viability of extremely preterm infants.

Shaeffer and Avery's textbook, Diseases of the Newborn (1971), estimated the limit of viability to be around 28 weeks' gestation and/or 1000 g. Contemporarily, however, attempts are being made to resuscitate infants as early as 22 weeks' gestation. Clearly the "limit of viability" is a moving target, and the acceptable risk of intervening to attempt to "save" these small infants/fetuses is a value judgment and not one that can be answered by science. Even though the dilemma is not one that can be resolved empirically, the emphasis on resolution continues to be one of demands for "further research" by critics as well as advocates for the care of these small infants. Patrick Romanell (1912-2002) was a major philosopher in the critical naturalist movement in the United States and internationally. His observations on the tragic quality of human life and the dilemmas associated between the conflicts of good vs good rather than the epic quality of good vs evil lend themselves well to understanding the conflicts involved in determining the limits of viability of extremely preterm infants.

The Born-Alive Infant Protection Act: impact on fetal and live birth mortality.

The Born-Alive Infant Protection Act (BAIPA) of 2002 defined a live birth in the United States without regard to gestation. The objective of this analysis was to determine if a significant decline in the fetal death rate or an increase in the live born death rate at previable gestational ages of 17 to 22 weeks has occurred. U.S. public use fetal death files and linked birth and infant death files were obtained for the years 2000 to 2005 for gestations of 17 to 22 weeks. The fetal death rate declined from 53.8% in the 2000 to 2002 period to 52.6% for the period 2003 to 2005 and the live birth mortality rate increased from 46.2 to 47.4% ( P < 0.02). The average annual live birth death rate increased significantly only at 17 weeks gestation ( P < 0.02). Although there was a small but statistically significant change in the fetal and live birth death rates for infants considered to be previable for the period following the passage of the BAIPA, the change appears to be isolated to only the most immature at 17 weeks gestation.

Images, science, and rights of the early modern fetus.

How do we define the beginnings of human life? Images, science, and culture have offered insight into this question. The early modern period (1500-1800) is particularly rich for examining the understanding of the human fetus. Using the 1712 Essay on the Possibility and Probability of a Child's Being Born Alive, and Live, in the Latter End of the Fifth Solar, or in the Beginning of the Sixth Lunar Month, this paper argues that evolving knowledge of the fetus failed to modify cultural norms for defining the beginning of human life. This compares with contemporary 21st century observations and how our definition of the beginning of human life has not been modified.

Urinary NT-proBNP as a potential noninvasive biomarker for screening of pulmonary hypertension in preterm infants: a pilot study.

OBJECTIVE: This pilot study aimed to determine the feasibility of urinary NT-proBNP (NT-proBNP) as a potential noninvasive screening marker for pulmonary hypertension (PH). STUDY DESIGN: A prospective cross-sectional study was conducted. Preterm infants (PI) (birthweight <1500 gm and <30 weeks gestational age (GA)) were enrolled. Serial urinary NT-proBNP measurements and echocardiograms (ECHO) were performed at 28, 32, and 36 weeks. RESULTS: Thirty-six patients were included in the final analysis (BPD-PH group = 6, BPD group = 20, control = 10). Urinary NT-proBNP levels were higher in the BPD-PH group compared with BPD and control groups at all study intervals. A urine NT-proBNP cutoff level of 2345 pg/ml at 28 weeks of GA had a sensitivity and specificity of 83.3% and 84.2%, respectively, for detection of BPD-PH (AUC 0.816, p = 0.022). CONCLUSION: Urinary NT-proBNP measurement is feasible in preterm infants and appears to be a good noninvasive screening tool for PH.

Impact of cesarean section on intermediate and late preterm births: United States, 2000-2003.

BACKGROUND: Cesarean section appears to be associated with increased risk of neonatal mortality among infants of low-risk term pregnancies, but it may offer some survival advantage among the most extremely preterm infants. The impact on intermediate (32-33 wk) and late preterm (34-36 wk) deliveries remains uncertain. The objective of this analysis was to compare the neonatal mortality rate (death at 0-27 days), the mechanical ventilation usage rate, and the incidence of hyaline membrane disease among intermediate and late preterm infants delivered by primary cesarean section compared with those delivered vaginally. METHODS: United States Linked Birth and Infant Death Certificate files from the years 2000 to 2003 were used. Maternal demographic characteristics, medical complications, and labor and delivery complications were abstracted from the files along with infant information. Because of concern for misclassification of gestational age, a procedure was used to trim away births in which the birthweight of an infant for a specific gestational age was inconsistent. Adjusted odds ratios were calculated using logistic regression for the risk of the three outcomes of interest relative to the mode of delivery. RESULTS: A total of 422,001 live births were available with complete data from the trimmed data set (60% of untrimmed data). After adjustment by logistic regression for infant size at birth, birthweight, sex, Apgar score at 5 minutes less than 4, multiple births, breech presentation, presence of an anomaly, the presence of any maternal medical condition or complication of labor and delivery, labor induction, maternal race, age, education, and gravidity, the adjusted odds ratios (95% CI for neonatal mortality at gestational ages of 32, 33, 34, 35, and 36 wk) were, respectively, 1.69 (1.31-2.20), 1.79 (1.40-2.29), 1.08 (0.83-1.40), 2.31 (1.78-3.00), and 1.98 (1.50-2.62). CONCLUSIONS: These data suggest that for low-risk preterm infants at 32 to 36 weeks' gestation, independent of any reported risk factors, primary cesarean section may pose an increased risk of neonatal mortality and morbidity.

Neonatal mortality for primary cesarean and vaginal births to low-risk women: application of an "intention-to-treat" model.

BACKGROUND: The percentage of United States births delivered by cesarean section continues to increase, even for women considered to be at low risk for the procedure. The purpose of this study was to use an "intention-to-treat" methodology, as recommended by a National Institutes of Health conference, to examine neonatal mortality risk by method of delivery for low-risk women. METHODS: Low-risk births were singleton, term (37-41 weeks' gestation), vertex births, with no reported medical risk factors or placenta previa and with no prior cesarean section. All U.S. live births and infant deaths for the 1999 to 2002 birth cohorts (8,026,415 births and 17,412 infant deaths) were examined. Using the intention-to-treat methodology, a "planned vaginal delivery" category was formed by combining vaginal births and cesareans with labor complications or procedures since the original intention in both cases was presumably a vaginal delivery. This group was compared with cesareans with no labor complications or procedures, which is the closest approximation to a "planned cesarean delivery" category possible, given data limitations. Multivariable logistic regression was used to model neonatal mortality as a function of delivery method, adjusting for sociodemographic and medical risk factors. RESULTS: The unadjusted neonatal mortality rate for cesarean deliveries with no labor complications or procedures was 2.4 times that for planned vaginal deliveries. In the most conservative model, the adjusted odds ratio for neonatal mortality was 1.69 (95% CI 1.35-2.11) for cesareans with no labor complications or procedures, compared with planned vaginal deliveries. CONCLUSIONS: The finding that cesarean deliveries with no labor complications or procedures remained at a 69 percent higher risk of neonatal mortality than planned vaginal deliveries is important, given the rapid increase in the number of primary cesarean deliveries without a reported medical indication.

Cesarean section and the outcome of very preterm and very low-birthweight infants.

Births of extremely preterm infants, less than 26 weeks' gestation, by cesarean section have increased significantly in the United States over the past decade. The justification for this increase is not well supported in the literature. This review examines recent analyses that suggest there may be some survival advantage for infants less than 26 weeks delivered by cesarean section. The appropriateness of intervening with cesarean sections for these very immature infants, however, remains uncertain.

Hyaline membrane disease (HMD): an historical and Oslerian perspective.

Hyaline membrane disease (HMD) offers an illustration of a disease discovered during the lifetime of William Osler and effectively treated in the twentieth century-the perspective that suggests that there was a straightforward progressive identification of the disease process, a discovery of the underlying biochemical agent responsible for the pathophysiology, and the pharmacological refinement of that agent to be used to treat the disease is illusory. By reviewing the timeline from the earliest pathological description of what was to be later termed HMD to the discovery of surfactant and its impact on infant mortality, this narrative will demonstrate how various random historical events served to affect the progress of developing a treatment for HMD; how the marked reduction in deaths due to HMD may have set the stage for unrealistic expectations; and how the humanities have warned us of the potential for excessive optimism in our understanding of nature.

NTproBNP as a surrogate biomarker for early screening of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia.

OBJECTIVE: Pulmonary hypertension (PH) is a known complication of bronchopulmonary dysplasia (BPD). This study aimed to determine the utility of serial N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) levels in the screening of BPD associated PH (BPD-PH) in preterm infants. STUDY DESIGN: Infants with birth weight <1500 g and <30 week corrected gestational age (CGA) were followed with serial NTproBNP levels and echocardiograms (ECHO). They were divided into control, BPD and BPD-PH groups. Statistical analyses included repeated measures analysis of variance and receiver operator curve (ROC) generation. RESULTS: Infants in the BPD-PH and BPD group had significantly elevated NTproBNP levels as compared to the control group. ROC curves for NTproBNP at 28 weeks CGA provided a cut-point of 2329 pg/ml and 578.1 pg/ml for detection of BPD-PH and BPD, respectively. CONCLUSIONS: NTproBNP appears to be a good screening tool to determine the onset of BPD-PH as early as 28 weeks CGA.

Age at death, season, and day of death as indicators of the effect of the back to sleep program on sudden infant death syndrome in the United States, 1992-1999.

BACKGROUND: In June 1992, the American Academy of Pediatrics Task Force on Infant Positioning and Sudden Infant Death Syndrome (SIDS) made its first recommendation concerning placing infants in a supine position. Since the publication of this recommendation, SIDS rates in the United States have declined 44%. Before this recommendation, SIDS had a marked seasonal pattern and was noted to occur more frequently on weekends. OBJECTIVE: The objective of this study was to determine if significant changes in SIDS rates have occurred in age at death (0-27 days vs 1-6 months vs 7-11 months), season of death, and weekday of death since the implementation of the recommendations for supine positioning of infants for sleep. DESIGN: United States natality and mortality data were used for the years 1992 through 1994. United States linked infant birth and death certificate files were used for the years 1995 through 1999. Season of death was calculated from month of death and was ordered for analysis from winter to fall to spring to summer; day of death was ordered from Monday to Sunday and additionally analyzed as weekend (Saturday and Sunday) vs weekday (Monday through Friday). RESULTS: During the 8 years, 28 548 deaths were attributed to SIDS among residents of the United States. The average annual decrease in the SIDS rate for neonates aged 0 to 27 days was 6.6%; for infants aged 1 to 6 months, 9.0%; and for infants aged 7 to 11 months, 6.1%. The average decline in seasonal rates from winter to summer was 11.2% per season. A significant interaction between year of death and season indicated a diminishing rate of seasonal variation. The odds ratio for weekend vs weekday SIDS deaths was 0.98 (95% confidence interval, 0.96-1.01). There was no significant interaction between year of death and weekday of death, which indicates no change in the relationship since the implementation of the supine sleeping recommendations. CONCLUSIONS: These data provide insights into the effect of the supine sleep recommendations on SIDS. The reduction in seasonal variation of SIDS suggests advantages conferred by supine sleeping in colder seasons.

Sudden infant death syndrome among extremely preterm infants: United States 1997-1999.

BACKGROUND: Preterm infants have been reported to be at higher risk than term infants for sudden infant death syndrome (SIDS). Reasons for this higher risk are not clear. OBJECTIVE: The objective of this study was to analyze medical and demographic characteristics among infants 24 to 32 weeks gestation to identify characteristics more prevalent among infants dying of SIDS in the postneonatal period than among infants of similar gestation who survived or who died of other causes in the postneonatal period. DESIGN/METHODS: United States linked birth and death certificate period data for 1997 to 1999 were used for this analysis. The population used was limited to infants 24 to 32 weeks gestation weighing 500 to 2500 g. SIDS deaths were limited to the postneonatal period and compared to survivors and infants dying in the postneonatal period of other causes. RESULTS: There were 469 postneonatal SIDS deaths with complete data (rate=2.2/1000 live births surviving > or =28 days); 3950 other postneonatal deaths (rate=18.7/1000) and 206,640 survivors. Compared with survivors, infants dying of SIDS were more likely to be born to mothers with <12 years of education (odds ratio=2.5, 95% confidence interval (95% CI=1.8, 3.3); be born to mothers < or =17 years of age (OR=2.0, 95% CI=1.4, 2.8); and be born to mothers with >3 previous pregnancies (OR=2.6, 95% CI=1.9, 3.5). Compared with infants dying in the postneonatal period of other causes, these same demographic factors continued to be significant risk factors for SIDS. There were no medical risk factors such as breech presentation, abruptio placenta, Apgar score <4 at 5 minutes, or mechanical ventilation for >30 minutes after birth, for which infants dying of SIDS were at greater risk than survivors or infants dying of other causes. CONCLUSIONS: Risk factors for SIDS among infants 24 to 32 weeks gestation appear to be more associated with sociodemographic characteristics than medical characteristics. This suggests that for the immediate future, the risk for SIDS among very preterm infants will be best addressed through further modification of the environment and parent behavior.

Impact of cesarean section on neonatal mortality rates among very preterm infants in the United States, 2000-2003.

OBJECTIVE: The objective of this analysis was to compare the neonatal mortality rates for infants delivered through primary cesarean section versus vaginal delivery, taking into consideration a number of potentially risk-modifying conditions. METHODS: US linked birth and infant death certificate files for 2000-2003 were used. Demographic, medical, and labor and delivery complications were abstracted from the files with infant information. The primary outcome examined was neonatal death (death at 0-27 days of age). Because of concern regarding misclassification of gestational age, a procedure was used to trim away births for which the birth weight for a specific gestational age was incongruous. Adjusted odds ratios were calculated for the risk of neonatal death relative to the mode of delivery (primary cesarean section versus vaginal delivery), using logistic regression analysis. RESULTS: There were data for 13,733 neonatal deaths and 106,809 survivors available from the trimmed data set for analysis for the 4-year period. More than 80% of pregnancies with delivery between 22 and 31 weeks of gestation experienced >or=1 risk factor. Adjusted odds ratios demonstrated significantly reduced risk of neonatal death for infants delivered through cesarean section at 22 to 25 weeks of gestation (adjusted odds ratios of 0.58, 0.52, 0.72, and 0.81 for 22, 23, 24, and 25 weeks, respectively). CONCLUSION: Cesarean section does seem to provide survival advantages for the most immature infants delivered at 22 to 25 weeks of gestation, independent of maternal risk factors for cesarean section.

Size for gestational age at birth: impact on risk for sudden infant death and other causes of death, USA 2002.

BACKGROUND: Small for gestational age (SGA) infants have been reported to be at higher risk for sudden infant death syndrome (SIDS). OBJECTIVE: To compare the risk of SIDS among SGA and large for gestational age (LGA) infants with that of death from other causes of sudden unexpected deaths in infancy (SUDI) and the residual "other" causes of infant death. METHODS: The 2002 US period infant birth and death certificate linked file was used to identify infant deaths classified as SIDS (ICD-10 code R95), SUDI (ICD-10 codes R00-Y84 excluding R95) or all other residual codes. The 2002 race and sex-specific birth cohorts were used to generate the 10th and 90th percentiles of birth weight for each gestational age week from 24 to 42 weeks' gestation. Demographic variables previously identified as associated with SIDS were used in multiple logistic regression equations to determine the risk for death among SGA and LGA infants (birth weight <10th percentile and >90th percentile, respectively) independent of other potentially confounding variables. RESULTS: Complete data on 1956 SIDS deaths, 2012 SUDI, and 11 592 other deaths were available. The adjusted OR for SIDS, SUDI and "other" causes for SGA infants was 1.65 (95% CI 1.47 to 1.85), 1.78 (1.59 to 2.00) and 4.68 (4.49 to 4.88), respectively. The adjusted OR for LGA infants was reduced for SIDS (0.73 (0.60 to 0.89)), SUDI (0.81 (0.68 to 0.98)) and "other" (0.42 (0.38 to 0.46)). CONCLUSION: Although SGA infants seem to be at slightly increased risk for SIDS or SUDI their risk for "other" residual causes is about 2.5 times higher. LGA infants seem to be at reduced risk of mortality for all causes. The mechanisms by which restricted intrauterine growth increases risk of mortality and excessive intrauterine growth offers protective effects are uncertain.