NSIDRC Journal Article Alert — July 25, 2008

Prepared by the National Sudden Infant Death Resource Center at Georgetown University.

This journal article alert provides selected items added to the National Library of Medicine’s PubMed database in the last week.

Past issues of NSIDRC journal alerts are available at http://www.sidscenter.org.
Availability of full-text journal articles is often limited to subscribers or through inter-library loan. Please see your local library for copies of these articles, or view PubMed's How to Get the Journal Article for more details.

1. Byard RW, Jensen LL
How Reliable is Reported Sleeping Position in Cases of Unexpected Infant Death?
J Forensic Sci. 2008 Jul 14. [Epub ahead of print]

Discipline of Pathology, The University of Adelaide, Frome Rd, Adelaide, SA 5005, Australia.

Examination of sudden infant death syndrome (SIDS) deaths in South Australia over a 7-year period from 2000 to 2006 was undertaken. There were 32 out of 35 cases where details of position when found were known. The data confirmed a marked decline in deaths in the prone position over the past decade, but showed no significant decline in cases reportedly found dead in the supine position. Posterior lividity was present in most cases (n = 30), 10 of whom also had anterior lividity. Posterior lividity was attributable either to the position of the body after death or to the effect of supine postmortem storage. In six cases, however, fixed anterior lividity indicated that death had occurred in the prone position despite statements that the infants had been found on the side (n = 1) and in the supine position (n = 5). This contradiction indicates that caregivers' descriptions of terminal sleeping positions may not be supported by autopsy findings. The numbers of SIDS deaths reported in the supine position in South Australia may not, therefore, represent a genuine tally, but instead may be a function of inaccurate reporting. This may act as a confounding factor in studies attempting to link sleeping position with other risk factors.

2. Viemari JC
Noradrenergic modulation of the respiratory neural network
Respir Physiol Neurobiol. 2008 Jun 27. [Epub ahead of print]

Laboratoire Plasticité et Physio-Pathologie de la Motricité (P3M), UMR 6196-CNRS, Aix-Marseille Université, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille Cedex 20, France.

Noradrenergic dysregulation has been reported in human pathologies affecting the control of breathing, such as sudden infant death syndrome, congenital central hypoventilation syndrome and Rett syndrome. Noradrenergic neurons, located predominantly in pontine nuclei, are among the earliest to arise within the hindbrain and play an essential role in the maturation of the respiratory network. Noradrenergic neurons also play a major role in the modulation of the respiratory motor pattern from birth through adulthood. The critical importance of this signaling system in respiratory control is illustrated by the severe respiratory disturbances associated with gene mutations affecting noradrenergic neurons (Phox2 and Mecp2). Here, the role of catecholaminergic pontine nuclei in the control of breathing, the cellular effects of norepinephrine on the respiratory network and the pathological consequence to breathing of abnormalities in this signaling system will be discussed.

3. Perskvist N, Skoglund K, Edston E, Bäckström G, Lodestad I, Palm U
TNF-alpha and IL-10 gene polymorphisms versus cardioimmunological responses in sudden infant death
Fetal Pediatr Pathol. 2008 Oct;27(3):149-65

National Board of Forensic Medicine, Department of Forensic Medicine, Linköping Division, Linköping , Sweden.

We hypothesized that genetic variations of cytokines could contribute to the risk of developing a fatal immunological reaction in the heart of infants. Thus, tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 gene polymorphisms versus induction of cardioimmunologxical responses in victims of sudden infant death syndrome (SIDS) were explored. We genotyped 35 infants (23 cases of SIDS and 12 infants with a known cause of death), and 100 healthy adult controls for IL-10 -1082 G/A, -592 C/A and TNF-alpha-238 G/A, -308 G/A. We found a higher frequency of the ATA haplotype and ATA/ATA genotype of IL-10 associated with SIDS (13%). The frequency of homozygote infants for IL-10 haplotypes in SIDS was higher (52%) than the control group (34%). All SIDS cases were homozygotice for the TNF-alpha-238 G allele and 20 infants were homozygous for the TNF-alpha-308 G allele in the same group. None of the infants with higher levels of infiltrated T-cells (n=8) was homozygous for IL-10 gene polymorphisms, whereas in contrast 3 cases of the 6 that displayed higher levels of cardiac mast cells were homozygous. In this study, the increased number of interstitial T-cells, mast cells, and macrophages in the myocardial interstitium demonstrated no correlation with the genotype for either cytokines.

Other Infant Death

1. Ishikawa T, Zhu BL, Li DR, Zhao D, Michiue T, Maeda H
An autopsy case of an infant with Joubert syndrome who died unexpectedly and a review of the literature
Forensic Sci Int. 2008 Jul 16. [Epub ahead of print]

Department of Legal Medicine, Osaka City University Medical School, Asahi-machi 1-4-3, Abeno, Osaka, 545-8585, Japan.

2. Jahan S
Poverty and infant mortality in the Eastern Mediterranean region: a meta-analysis
J Epidemiol Community Health. 2008 Aug;62(8):745-51

Health Education and Training Department, Primary Health Care Administration, Qassim, Saudi Arabia. saulatjahan@hotmail.com

OBJECTIVES: To test the hypothesis that poverty is associated with infant mortality in Eastern Mediterranean countries and to measure the strength of the association. METHODS: A bibliographic search was conducted. The studies including data regarding deaths during the first year of life, socioeconomic status of the household and/or maternal literacy were selected. Nine studies, conducted in the Eastern Mediterranean region, fulfilled the inclusion criteria. These included seven cross-sectional surveys and two case-control studies. Maternal illiteracy and low socioeconomic status were used to show the level of poverty in each household. Risk estimates for low socioeconomic status and maternal illiteracy were extracted from each study. Meta-analysis was performed for the association between exposure groups of low socioeconomic status and maternal illiteracy and the outcome of death within the first year of life. MAIN RESULTS: Poverty was associated with an increased risk of infant death (pooled OR 1.52, 95% CI 1.38 to 1.67), significant at p<0.0001. There was a significantly increased risk of infant death among illiterate mothers (OR 1.72, 95% CI 1.42 to 2.08) compared with literate mothers. The meta-analysis OR for an association between low socioeconomic status subgroup and infant death was 1.37 (95% CI 1.25 to 1.49), significant at p<0.0001. CONCLUSIONS: This meta-analysis indicates that there is a significantly increased mortality risk in infants born in poor households. The results suggest that policies aimed at poverty alleviation and female literacy will substantially contribute to a decrease in infant mortality.

The present report describes the unexpected death of a 6-month-old female infant who had been clinically diagnosed with Joubert syndrome. This is a relatively rare congenital neurological disorder characterized by hypoplasia/aplasia of cerebellar vermis, which transmits information from the body to the cerebellum, and is associated with respiratory dysfunction, abnormal eye movements, and developmental delay. The infant was found dead in bed and the immediate cause of death was determined as aspiration of vomit which may have been induced by a neurological disorder related to hypoplasia of the cerebellar vermis. These findings, together with a review of previous clinical case reports, suggest that Joubert syndrome should be considered as a predisposition to sudden unexpected death in infants mainly due to aspiration or complicated infection.

Miscarriage/Stillbirth/Prenatal Issues

1. Ambartsumyan G, Clark AT
Aneuploidy and early human embryo development
Hum Mol Genet. 2008 Apr 15;17(R1):R10-5

Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.

Human embryo development occurs through a process that encompasses reprogramming, sequential cleavage divisions and mitotic chromosome segregation and embryonic genome activation. Chromosomal abnormalities may arise during germ cell and/or pre-implantation embryo development, and are a major cause of spontaneous miscarriage or birth defects. Nonetheless, model systems suitable for the study of human germ cell and embryo development have been limited until recently. We suggest that human embryonic stem cells may provide a valuable human cell-based model for genetic studies of human pre-implantation pluripotent cells. Here, we review the current literature on diagnosing chromosomal abnormalities in the pre-implantation embryo, and the importance of provisions from the human oocyte in establishing and maintaining the human embryonic genome during the first 3 days post-conception. We focus on transcriptional analysis of human oocytes and embryos and the unique cell cycle and checkpoint requirements in the early embryo. Taken together, data suggest that the unique programs of the early human embryo, including management of aneuploid cells, may paradoxically promote embryo development but contribute to the high rate of spontaneous miscarriages in human pregnancies.

2. Singhal S, Prasad S, Singh B, Prasad JK, Gupta HP
Effect of including growth factors and antioxidants in maturation medium used for in vitro culture of buffalo oocytes recovered in vivo
Anim Reprod Sci. 2008 Jun 5. [Epub ahead of print]

Department of Animal Reproduction, Gynaecology & Obstetrics, College of Veterinary and Animal Sciences, G.B. Pant University of Agriculture & Technology, Pantnagar 263145, Uttarakhand, India.

This study examined the effect of including one of two growth factors (100ng/ml IGF-1 or 20ng/ml EGF) in combination with one of two antioxidants (50muM cysteamine or 50muM beta-mercaptoethanol) in maturation, fertilization and subsequent development of buffalo oocytes. The oocytes were recovered by in vivo ovum pick-up technique from six Murrah buffalo heifers twice a week over a period of 16 weeks. Immediately after ovum pick-up oocytes recovered from six donors were allocated randomly to five different maturation treatments. The control treatment was the basic maturation medium (MM; TCM-199 supplemented with 10% FBS, 10IU/ml LH, 0.5mug/ml FSH, 1mug/ml estradiol-17beta and 50mug/ml gentamicin). The other four treatments consisted of the control maturation medium (MM) plus one combination of a growth factor and an antioxidant viz. IGF-1+cysteamine; IGF-1+beta-ME; EGF+cysteamine or EGF+beta-ME. The total number of oocytes assigned to each maturation treatment ranged from 31 to 66. After maturation in different maturation medium, media used for in vitro fertilization and subsequent development of embryo was same for all groups. Data were analysed using Chi-square test. The maturation rate observed for the growth factor plus antioxidant treatments was similar to that for the control (90.4%). The highest cleavage rate recorded in the IGF-1+cysteamine treatment (71.9%) which was significantly higher (P<0.05) than the IGF-1+beta-ME (45.2%) and EGF+beta-ME (46.4%) treatments, but not significantly differ from the control (63.8%) and EGF+cysteamine treatment (60.7%). The proportion of cleaved oocytes those developed to blastocyst stage was significantly higher in the IGF-1+cysteamine treatment (52.2%; P<0.05) than in the control (23.3%), the EGF+cysteamine (13.5%) or the EGF+beta-ME (7.7%) treatments, but did not differ significantly from the IGF-1+beta-ME (28.6%) treatment. Following non-surgical transfer of 15 embryos to 14 synchronized recipients, four became pregnant and only one recipient sustained the pregnancy as long as 4.5 months when spontaneous abortion occurred. It was concluded that supplementing the maturation medium with IGF-1+cysteamine improved the production of buffalo embryos significantly in vitro culture.

3. Meister R, Schaefer C
Statistical methods for estimating the probability of spontaneous abortion in observational studies-Analyzing pregnancies exposed to coumarin derivatives
Reprod Toxicol. 2008 Jun 26. [Epub ahead of print]

Department II, Mathematics, Physics, Chemistry, University of Applied Sciences, Technische Fachhochschule Berlin, Luxemburger Strasse 10, 13353 Berlin, Germany.

BACKGROUND: Spontaneous abortion rates are of general interest when investigating pregnancy outcome. In most studies observations are left truncated as pregnant women enter with a delay of several weeks after conception. Apart from spontaneous abortion pregnancy may end in induced abortion or live birth. These outcomes are considered as competing events (risks). Although statistical methods for handling this setting are available since more than 10 years, studies on pregnancy outcome after drug exposure usually report crude rates of spontaneous abortions, ignoring left truncation and competing risks. METHODS: The authors propose simple methods which remove bias inherent to crude rates. The probability of spontaneous abortion is estimated using an event-history based approach for the subdistribution of competing risks that handles left truncation appropriately. Variance estimation enables the construction of approximate confidence intervals and of a simple test-statistic for comparing rates between different cohorts. The proposed methods are applied to a comparative prospective study on the association of spontaneous abortion and exposure to coumarin derivatives. RESULTS: The naive analysis using crude rates gives substantially different results than those based on the proposed methods, with up to a twofold change. Correctly incorporating left truncation into the analysis may increase the variance of the estimators, relative to an ideal sample where all pregnancies are followed from the time of conception. The consequences of such truncation for study design are discussed. CONCLUSION: Combining corrections for left truncation and competing risks offers a powerful method for analyzing miscarriage risk.

Prepared by the
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