Marian Willinger

The changing concept of sudden infant death syndrome: Diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk

There has been a major decrease in the incidence of sudden infant death syndrome (SIDS) since the American Academy of Pediatrics (AAP) released its recommendation in 1992 that infants be placed down for sleep in a nonprone position. Although the SIDS rate continues to fall, some of the recent decrease of the last several years may be a result of coding shifts to other causes of unexpected infant deaths. Since the AAP published its last statement on SIDS in 2000, several issues have become relevant, including the significant risk of side sleeping position; the AAP no longer recognizes side sleeping as a reasonable alternative to fully supine sleeping. The AAP also stresses the need to avoid redundant soft bedding and soft objects in the infants sleeping environment, the hazards of adults sleeping with an infant in the same bed, the SIDS risk reduction associated with having infants sleep in the same room as adults and with using pacifiers at the time of sleep, the importance of educating secondary caregivers and neonatology practitioners on the importance of “back to sleep,” and strategies to reduce the incidence of positional plagiocephaly associated with supine positioning. This statement reviews the evidence associated with these and other SIDS-related issues and proposes new recommendations for further reducing SIDS risk.

Gm1 ganglioside as a marker for neuronal differentiation in mouse cerebellum.

The distribution of GM1 ganglioside in developing mouse cerebellum was monitored by indirect immunofluorescent detection of choleragenoid receptors. In frozen sections of cerebellum from mice 5 to 10 days old, fluorescence is observed on granule cells in the inner rows of the external granular layer, in the growing molecular layer, the Purkinje cell layer, and the internal granular layer. In sections of adult mice, fluorescence is restricted to the bodies of Purkinje and internal granule neurons. The percentage of fluorescent dissociated or cultured cerebellar cells increases with the postnatal age of the mouse or the duration of time in vitro. No fluorescence is observed in the absence of choleragenoid or if the test material is extracted with chloroform:methanol. To determine whether the expression of surface GM1 ganglioside in culture is a reflection of a developmental program, mice are injected at particular times with [3H]thymidine and cerebellar cultures processed for simultaneous autoradiography and immunofluorescence. Granule cells from 8-day-old mice having cholera toxin receptors at 20 hr in vitro are a distinct population born 1 day or earlier prior to sacrifice. Cells synthesizing DNA on the day of sacrifice are not fluorescent at 20 hr in vitro. This observation correlates well with immunohistological results showing a lack of fluorescence in the outer proliferative rows of the external granular layer. Therefore GM1 ganglioside is not present on granule cell precursors but is expressed at some time after the cells become postmitotic. GM1 ganglioside is detected on growing parallel fibers in situ and neurites in vitro but not on adult axons, suggesting differential localization at a later stage of development.

Term Pregnancy: A Period of Heterogeneous Risk for Infant Mortality

OBJECTIVE: To estimate the trend of maternal racial and ethnic differences in mortality for early-term (37 0/7 to 38 6/7 weeks of gestation) compared with full-term births (39 0/7 to 41 6/7 weeks of gestation). METHODS: We analyzed 46,329,018 singleton live births using the National Center for Health Statistics U.S. period-linked birth and infant death data from 1995 to 2006. Infant mortality rates, neonatal mortality rates, and postneonatal mortality rates were calculated according to gestational age, race and ethnicity, and cause of death. RESULTS: Overall, infant mortality rates have decreased for early-term and full-term births between 1995 and 2006. At 37 weeks of gestation, Hispanics had the greatest decline in infant mortality rates (35.4%; 4.8 per 1,000 to 3.1 per 1,000) followed by 22.4% for whites (4.9 per 1,000 to 3.8 per 1,000); blacks had the smallest decline (6.8%; 5.9 per 1,000 to 5.5 per 1,000) as a result of a stagnant neonatal mortality rate. At 37 weeks compared with 40 weeks of gestation, neonatal mortality rates increase. For Hispanics, the relative risk is 2.6 (95% confidence interval [CI] 2.0–3.3); for whites, the relative risk is 2.6 (95% CI 2.2–3.1); and for blacks, the relative risk is 2.9 (95% CI 2.2–3.8). Neonatal mortality rates are still increased at 38 weeks of gestation. At both early- and full-term gestations, neonatal mortality rates for blacks are 40% higher than for whites and postneonatal mortality rates 80% higher, whereas Hispanics have a reduced postneonatal mortality rate when compared with whites. CONCLUSION: Early-term births are associated with higher neonatal, postneonatal, and infant mortality rates compared with full-term births with concerning racial and ethnic disparity in rates and trends. LEVEL OF EVIDENCE: II

Karyotype versus Microarray Testing for Genetic Abnormalities after Stillbirth

BACKGROUND Genetic abnormalities have been associated with 6 to 13% of stillbirths, but the true prevalence may be higher. Unlike karyotype analysis, microarray analysis does not require live cells, and it detects small deletions and duplications called copy-number variants. METHODS The Stillbirth Collaborative Research Network conducted a population-based study of stillbirth in five geographic catchment areas. Standardized postmortem examinations and karyotype analyses were performed. A single-nucleotide polymorphism array was used to detect copy-number variants of at least 500 kb in placental or fetal tissue. Variants that were not identified in any of three databases of apparently unaffected persons were then classified into three groups: probably benign, clinical significance unknown, or pathogenic. We compared the results of karyotype and microarray analyses of samples obtained after delivery. RESULTS In our analysis of samples from 532 stillbirths, microarray analysis yielded results more often than did karyotype analysis (87.4% vs. 70.5%, P<0.001) and provided better detection of genetic abnormalities (aneuploidy or pathogenic copy-number variants, 8.3% vs. 5.8%; P=0.007). Microarray analysis also identified more genetic abnormalities among 443 antepartum stillbirths (8.8% vs. 6.5%, P=0.02) and 67 stillbirths with congenital anomalies (29.9% vs. 19.4%, P=0.008). As compared with karyotype analysis, microarray analysis provided a relative increase in the diagnosis of genetic abnormalities of 41.9% in all stillbirths, 34.5% in antepartum stillbirths, and 53.8% in stillbirths with anomalies. CONCLUSIONS Microarray analysis is more likely than karyotype analysis to provide a genetic diagnosis, primarily because of its success with nonviable tissue, and is especially valuable in analyses of stillbirths with congenital anomalies or in cases in which karyotype results cannot be obtained. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.).

Use of a dummy (pacifier) during sleep and risk of sudden infant death syndrome (SIDS) : population based case-control study

Abstract Objectives To examine the association between use of a dummy (pacifier) during sleep and the risk of sudden infant death syndrome (SIDS) in relation to other risk factors. Design Population based case-control study. Setting Eleven counties in California. Participants Mothers or carers of 185 infants whose deaths were attributed to SIDS and 312 randomly selected controls matched for race or ethnicity and age. Main outcome measure Use of a dummy during sleep determined through interviews. Results The adjusted odds ratio for SIDS associated with using a dummy during the last sleep was 0.08 (95% confidence interval 0.03 to 0.21). Use was associated with a reduction in risk in every category of sociodemographic characteristics and risk factors examined. The reduced risk associated with use seemed to be greater with adverse sleep conditions (such as sleeping prone or on side and sleeping with a mother who smoked), although the observed interactions were not significant. In addition, use of a dummy may reduce the impact of other risk factors for SIDS, especially those related to adverse sleep environment. For example, infants who did not use a dummy and slept prone or on their sides (v on their back) had an increased risk of SIDS (2.61, 1.56 to 4.38). In infants who used dummies, there was no increased risk associated with sleeping position (0.66, 0.12 to 3.59). While cosleeping with a mother who smoked was also associated with increased risk of SIDS among infants who did not use a dummy (4.5, 1.3 to 15.1), there was no such association among those who did (1.1, 0.1 to 13.4). Conclusions Use of a dummy seems to reduce the risk of SIDS and possibly reduces the influence of known risk factors in the sleep environment.

Trends and Factors Associated With Infant Bed Sharing, 1993-2010: The National Infant Sleep Position Study

IMPORTANCE A strong association between infant bed sharing and sudden infant death syndrome or unintentional sleep-related death in infants has been established. Occurrences of unintentional sleep-related deaths among infants appear to be increasing. OBJECTIVES To determine the trends and factors associated with infant bed sharing from 1993 through 2010, including the association of physician advice on bed sharing. DESIGN National Infant Sleep Position study conducted with annual telephone surveys. SETTING The 48 contiguous states. PARTICIPANTS Nighttime caregivers of infants born within 7 months of each survey administration. Approximately 1000 interviews were completed annually. MAIN OUTCOMES AND MEASURES Infant bed sharing as a usual practice. RESULTS Of 18 986 participants, 11.2% reported an infant sharing a bed as a usual practice. Bed sharing increased from 1993 (6.5%) to 2010 (13.5%). Although bed sharing increased significantly among white respondents from 1993 to 2000 (P < .001), the increase from 2001 to 2010 was not significant (P = .48). Black and Hispanic respondents reported an increase in bed sharing throughout the study period, with no difference between the earlier and later periods (P = .63 and P = .77, respectively). After accounting for the study year, factors associated with increase in infant bed sharing as a usual practice included maternal educational level of less than high school compared with college or greater (adjusted odds ratio, 1.42 [95% CI, 1.12-1.79]); black (3.47 [2.97-4.05]), Hispanic (1.33 [1.10-1.61]), and other (2.46 [2.03-2.97]) maternal race or ethnicity compared with white race; household income of less than

Prepregnancy risk factors for antepartum stillbirth in the United States.

20,000 (1.69 [1.44-1.99]) and

Stillbirth classification-developing an international consensus for research: Executive summary of a national institute of child health and human development workshop

20,000 to

Frequency of bed sharing and its relationship to breastfeeding

50,000 (1.29 [1.14-1.45]) compared with greater than

Racial disparities in stillbirth risk across gestation in the United States.

50,000; living in the West (1.61 [1.38-1.88]) or the South (1.47 [1.30-1.66]) compared with the Midwest; infants younger than 8 weeks (1.45 [1.21-1.73]) or ages 8 to 15 weeks (1.31 [1.17-1.45]) compared with 16 weeks or older; and being born prematurely compared with full-term (1.41 [1.22-1.62]). Almost 46% of the participants reported talking to a physician about bed sharing. Compared with those who did not receive advice from a physician, those who reported their physicians had a negative attitude were less likely to have the infant share a bed (adjusted odds ratio, 0.66 [95% CI, 0.53-0.82]), whereas a neutral attitude was associated with increased bed sharing (1.38 [1.05-1.80]). CONCLUSIONS AND RELEVANCE Our finding of a continual increase in bed sharing throughout the study period among black and Hispanic infants suggests that the current American Academy of Pediatrics recommendation about bed sharing is not universally followed. The factors associated with infant bed sharing may be useful in evaluating the impact of a broad intervention to change behavior.