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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Association of poverty with sudden infant death syndrome in metropolitan counties of the United States in the years 1990 and 2000.

BACKGROUND: Sudden infant death syndrome (SIDS) has been associated with poverty indirectly in the United States with the use of vital statistics data by using proxies of socioeconomic status such as maternal education. OBJECTIVES: The objective of this analysis was to examine the relationship of poverty to SIDS at an ecologic level, by examining the association between poverty within metropolitan counties of the United States and the occurrence of SIDS within those metropolitan counties. METHODS: The percentage of each US county's population below established federal poverty guidelines (poverty index) was obtained from US Census data for 1990 and 2000 by race (Hispanic-HISP, non-Hispanic white-NHW, and non-Hispanic black-NHB). These data were merged by year of birth, county, and race with US Vital Statistics Linked Birth and Infant Death Certificate data. RESULTS: Fourth (highest poverty quartile) versus first quartile poverty odds ratios (OR) were significantly increased in 1990 and 2000 for NHB (OR1990 = 1.84, OR2000 = 2.29) and NHW (OR1990 = 1.87, OR2000 = 2.17), but not for HISP (OR1990 = 0.64, OR2000 = 0.59). CONCLUSIONS: There is a significant association between poverty and SIDS at the metropolitan county level for NHB and NHW. Hispanics do not demonstrate this association.

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.

Infant and neonatal mortality for primary cesarean and vaginal births to women with "no indicated risk," United States, 1998-2001 birth cohorts.

BACKGROUND: The percentage of United States' births delivered by cesarean section has increased rapidly in recent years, even for women considered to be at low risk for a cesarean section. The purpose of this paper is to examine infant and neonatal mortality risks associated with primary cesarean section compared with vaginal delivery for singleton full-term (37-41 weeks' gestation) women with no indicated medical risks or complications. METHODS: National linked birth and infant death data for the 1998-2001 birth cohorts (5,762,037 live births and 11,897 infant deaths) were analyzed to assess the risk of infant and neonatal mortality for women with no indicated risk by method of delivery and cause of death. Multivariable logistic regression was used to model neonatal survival probabilities as a function of delivery method, and sociodemographic and medical risk factors. RESULTS: Neonatal mortality rates were higher among infants delivered by cesarean section (1.77 per 1,000 live births) than for those delivered vaginally (0.62). The magnitude of this difference was reduced only moderately on statistical adjustment for demographic and medical factors, and when deaths due to congenital malformations and events with Apgar scores less than 4 were excluded. The cesarean/vaginal mortality differential was widespread, and not confined to a few causes of death. CONCLUSIONS: Understanding the causes of these differentials is important, given the rapid growth in the number of primary cesareans without a reported medical indication.

Outcome of gastroschisis: a 20-year case review of infants with gastroschisis born in Galveston, Texas.

BACKGROUND/PURPOSE: In the past decade, the preferred method of closure of gastroschisis at our institution has been staged reduction using a silo with repair on an elective basis (SR) rather than primary surgical closure (PC). We performed a 20-year case review of infants with gastroschisis at a university hospital to compare these shifts in management and to determine factors affecting outcome. METHODS: Seventy-two cases were reviewed from 1983 to 2003. Times to first and full feeds were outcome variables for statistical analysis. RESULTS: The prevalence of gastroschisis increased from 0.03% to 0.1% since 1983. Patients had low birth weights (mean = 2294 g) and were borderline premature (mean = 35.8 weeks). Only 3% of the infants were African American. There was a high rate of cesarean deliveries (57%). Ten patients (15%) had gastroschisis complicated by liver herniation, intestinal atresia(s), and/or necrosis/perforation. Most patients were managed by SR (67%). Eight percent of the infants died, 9% developed necrotizing enterocolitis, and 50% had other gastrointestinal complications. Twenty-seven percent of the infants managed with SR did not need initial mechanical ventilation. However, the patients who underwent SR were ventilated longer after birth as compared with those who underwent PC (P < .08). Infants with a complicated gastroschisis had significantly longer times to first and full feeds (P < .001). Patients managed with SR took significantly longer to reach full feeds (P = .001), and there was a trend of starting feeds later (P = .06). When patients with a complicated gastroschisis were excluded, the differences between the SR and PC groups were even greater (P = .01; P < .001). CONCLUSIONS: In our patient population, the prevalence of gastroschisis increased by more than 400% since 1983. The defect was rare in African-American infants. Management by SR was associated with longer ventilation times and longer times to first and full feeds for both uncomplicated and complicated gastroschisis cases.

Changes in the classification of sudden unexpected infant deaths: United States, 1992-2001.

BACKGROUND: Sudden infant death syndrome (SIDS) makes up the largest component of sudden unexpected infant death in the United States. Since the first recommendations for supine placement of infants to prevent SIDS in 1992, SIDS postneonatal mortality rates declined 55% between 1992 and 2001. OBJECTIVE: The objective of this analysis was to examine changes in postneonatal mortality rates from 1992 to 2001 to determine if the decline in SIDS was due in part to a shift in certification of deaths from SIDS to other causes of sudden unexpected infant death. In addition, the analysis reviews the change in mortality rates attributed to the broad category of sudden unexpected infant death in the United States since 1950. METHODS: US mortality data were used. The International Classification of Diseases (ICD) chapters "Symptoms, Signs, and Ill-Defined Conditions" and "External Causes of Injury" were considered to contain all causes of sudden unexpected infant death. The following specific ICD (ninth and tenth revisions) underlying-cause-of-death categories were examined: "SIDS," "other unknown and unspecified causes," "suffocation in bed," "suffocation-other," "aspiration," "homicide," and "injury by undetermined intent." The average annual percentage change in rates was determined by Poisson regression. An analysis was performed that adjusted mortality rates for changes in classification between ICD revisions. RESULTS: The all-cause postneonatal mortality rate declined 27% and the postneonatal SIDS rate declined 55% between 1992 and 2001. However, for the period from 1999 to 2001 there was no significant change in the overall postneonatal mortality rate, whereas the postneonatal SIDS rate declined by 17.4%. Concurrent increases in postneonatal mortality rates for unknown and unspecified causes and suffocation account for 90% of the decrease in the SIDS rate between 1999 and 2001. CONCLUSIONS: The failure of the overall postneonatal mortality rate to decline in the face of a declining SIDS rate in 1999-2001 raises the question of whether the falling SIDS rate is a result of changes in certifier practices such that deaths that in previous years might have been certified as SIDS are now certified to other non-SIDS causes. The observation that the increase in the rates of non-SIDS causes of sudden unexpected infant death could account for >90% of the drop in the SIDS rates suggests that a change in classification may be occurring.