NSIDRC Journal Article Alert — January 9, 2009
Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center at Georgetown University.
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Sudden Infant Death
1. Cummings KJ, Klotz C, Liu WQ, Weese-Mayer DE, Marazita ML, Cooper ME, Berry-Kravis EM, Tobias R, Goldie C, Bech-Hansen NT, Wilson RJ
Sudden infant death syndrome (SIDS) in African Americans: polymorphisms in the gene encoding the stress peptide pituitary adenylate cyclase-activating polypeptide (PACAP)
Acta Paediatr. 2008 Dec 17. [Epub ahead of print]
Department of Physiology and Biophysics, Hotchkiss Brain Institute and Institute of Maternal and Child Health, University of Calgary, AB, Canada.
Abstract Aims: Mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) are prone to sudden death in the second post-natal week, having respiratory and metabolic disturbances reminiscent of the human Sudden Infant Death Syndrome (SIDS). Here we test the hypothesis that the human PACAP gene is a site of genetic variance associated with SIDS in a cohort of 92 victims and 92 matched controls. Methods: Using polymerase chain reaction and sequencing, we examined the PACAP gene in 92 SIDS cases (46 Caucasians and 46 African Americans) and 92 race- and gender-matched controls. Results: We found no significant associations between PACAP and SIDS in Caucasians. However, in the African Americans, a non-synonymous single nucleotide polymorphism (i.e. an aspartic acid/glycine coding variant, rs2856966) within exon 2 of PACAP was significantly associated with SIDS (p = 0.004), as were haplotypes containing this polymorphism (p < 0.0001). Glycine was three times more likely at this location in the African-American SIDS victims (17 cases) than African-American controls (5 cases). Conclusion: These data are the first to suggest an association between a variant within the coding region of the PACAP gene and SIDS. Based on these findings, further investigations are warranted into the functional importance of PACAP signaling in neonatal survival and the role of PACAP-signaling abnormalities in SIDS.
2. Trotz M, Weber MA, Jacques TS, Malone M, Sebire NJ
Disseminated langerhans cell histiocytosis-related sudden unexpected death in infancy
Fetal Pediatr Pathol. 2009;28(1):39-44
Department of Histopathology, Great Ormond Street Hospital for Children, London, United Kingdom.
Sudden unexpected death in infancy (SUDI) is defined as the sudden and unexpected death of an infant aged less than 1 year and comprises a heterogeneous group of deaths; in around one-third of cases a definite cause of death is identified at autopsy, while almost two-thirds of such deaths will remain unexplained despite a careful review of the circumstances of death and a detailed postmortem examination. We report a case of SUDI due to previously undiagnosed disseminated Langerhans cell histiocytosis (LCH) in a 10-month-old male, a disease characterized by a clonal proliferation of dendritic Langerhans cells. The diagnosis was established on histological examination, which revealed extensive infiltration by LCH of the skin, lymph nodes, thymus, spleen, and lungs. Despite a high mortality in disseminated disease, to our knowledge, this is the first reported case in the English-language literature of disseminated multisystem Langerhans cell disease presenting as SUDI. Furthermore, this case demonstrates the importance of routine microscopic tissue sampling in all SUDI, as the diagnosis required histological examination of the organs and might have been missed had histology not been performed.
3. Blood-Siegfried J, Bowers M, Lorimer M
Is Shock a Key Element in the Pathology of Sudden Infant Death Syndrome (SIDS)?
Biol Res Nurs. 2008 Dec 28. [Epub ahead of print]
In developed countries, sudden infant death syndrome (SIDS) is the most common cause of death for infants between 1 month and 1 year of age. The etiology of SIDS is likely to be multifactorial, and current paradigms often describe three overlapping elements of risk. Those elements are a critical developmental period, a vulnerable infant, and one or more exogenous stressors. In the triple-risk model, SIDS infants are described as having an underlying vulnerability in cardiorespiratory control in the central nervous system during a critical period when autonomic control is developing. This vulnerability might affect the response to exogenous stressors, including prone sleeping position, hypoxia, and increased carbon dioxide. In the common bacterial hypothesis and fatal triangle, the focus is on the stressors. In the first, a combination of common respiratory infections can cause SIDS in an infant during a developmentally vulnerable period. This theory also includes 3 factors of vulnerability: a genetic predisposition, a vulnerable developmental age, and infectious stressors. In the fatal triangle theory, infection, inflammation, and genetics each play a role in triggering a SIDS fatality. From our work in an animal model, we have found that rat pups die from a combination of infectious insults during a critical time of development. This is exacerbated by perinatal nicotine exposure, a condition shown to alter the autonomic response in exposed offspring. We are proposing that shock and cardiovascular collapse is a key element that links these theories.
4. Richardson HL, Walker AM, Horne RS
Sleep position alters arousal processes maximally at the high-risk age for sudden infant death syndrome
J Sleep Res. 2008 Dec;17(4):450-7
Pediatric Sleep Unit, Hôpital M&re-Enfant & INSERM-U628, University Lyon, Lyon, France. pfranco@univ-lyon1.fr
OBJECTIVE: Previous data have suggested that a prolonged QTc interval during the first days of life can be associated with some cases of sudden infant death syndrome (SIDS). Analysis of heart rate variability during sleep in future SIDS victims has shown findings compatible with an imbalance in autonomic tone. We hypothesized that some future SIDS infants could have longer QTc intervals during sleep, compared with healthy control infants, and that this difference would correlate with the autonomic imbalance already found in these infants. METHODS: QTc intervals and a heart rate autoregressive power spectral analysis were calculated during the same periods in the polysomnographic sleep recordings of 18 infants who eventually died of SIDS and of 18 control infants. The control infants were matched for sex, gestational age, postnatal age, birth weight, and sleep position. The median postnatal age was 8 weeks. RESULTS: Compared with control infants, future SIDS victims were characterized by having longer QTc intervals during total sleep (P = 0.019), rapid eye movement sleep (P = 0.045) and non-rapid eye movement sleep (P = 0.029). When the night was divided into 3 equal parts, this difference was always present but was most marked during the last part of the night. There was, respectively, a negative and a positive correlation between parasympathetic activity and sympathovagal balance and median and maximum QTc interval values. CONCLUSION: Compared with QTc intervals in matched control infants, QTc intervals were increased in future SIDS victims. Such a prolongation could be related to the autonomic dysfunction already reported in these patients.
5. Franco P, Groswasser J, Scaillet S, Lanquart JP, Benatar A, Sastre JP, Chevalier P, Kugener B, Kahn A, Lin JS
QT interval prolongation in future SIDS victims: a polysomnographic study
Sleep. 2008 Dec 1;31(12):1691-9
Ritchie Centre for Baby Health Research, Monash Institute of Medical Research, Monash University, Melbourne, Australia.
An impaired ability to arouse from sleep may play an important role in the pathogenesis of sudden infant death syndrome (SIDS). This study aimed to investigate the effects of prone sleeping on the nature of both induced and spontaneous arousal responses in infants. Thirteen healthy term infants were studied longitudinally at 2-4 weeks, 2-3 months and 5-6 months postnatal age. A pulsatile jet of air to the nostrils was used to induce arousal from both active sleep and quiet sleep in both prone and supine positions. For each stimulus, arousals were classified as sub-cortical activations and cortical arousals, scored using physiological and electroencephalogram changes and expressed as a percentage of the total number of arousals. Spontaneous arousals were similarly analysed. Increased proportions of cortical arousals, hence decreased proportions of sub-cortical activations, were observed in the prone position at 2-3 months. This distinct peak in the proportion of cortical arousals occurred regardless of sleep state and regardless of whether the arousal occurred spontaneously or was induced by air-jet stimulation. The nature of arousal responses in healthy term infants is altered in the prone sleeping position at 2-3 months after birth, the age where SIDS incidence is highest. We postulate that a greater propensity for cortical arousal may be a protective mechanism to promote complete arousal in a vulnerable sleeping position and/or a vulnerable period of maturation. Inadequate or incomplete cortical arousals may explain the increased risk of SIDS associated with the prone position at this age.
Miscarriage/Stillbirth/Prenatal Issues
1. Mercé LT, Barco MJ, Alcázar JL, Sabatel R, Troyano J
Intervillous and uteroplacental circulation in normal early pregnancy and early pregnancy loss assessed by 3-dimensional power Doppler angiography
Am J Obstet Gynecol. 2008 Dec 27. [Epub ahead of print]
Department of Obstetrics and Gynecology, International Ruber Hospital, Madrid.
OBJECTIVE: To assess intervillous and uteroplacental circulation in early normal pregnancies and miscarriages. STUDY DESIGN: One hundred normal pregnancies and 46 delayed miscarriages were evaluated by 3-dimensional vaginal ultrasound and power Doppler angiography. Volumes of the early placenta and the subplacental area were obtained between 5 and 12.6 weeks' gestation. The placental volume, vascularization index, flow index, and vascularization flow index was calculated. RESULTS: Intraclass correlation coefficients ranged from 0.961 for placental volume to 0.885 for intervillous flow index. Intervillous power Doppler signals were not detected before the sixth week. Placental volume (R(2) = 0.68), intervillous vascularization index (R(2) = 0.30), flow index (R(2) = 0.33) and vascularization flow index (R(2) = 0.35), uteroplacental flow index (R(2) = 0.34), and vascularization flow index (R(2) = 0.17) increase significantly (P < .001) throughout the first trimester of normal pregnancies. Uteroplacental vascularization index was not significantly related to gestational age. Intervillous vasculariztion index, flow index, and vascularization flow index were significantly raised in miscarriages, but there were no significant differences for uteroplacental vascularization index, flow index, or vascularization flow index. CONCLUSION: Intervillous and uteroplacental blood flow increases throughout the first trimester of normal pregnancies. Intervillous circulation is abnormally increased when a miscarriage is diagnosed.
2. Bolor H, Mori T, Nishiyama S, Ito Y, Hosoba E, Inagaki H, Kogo H, Ohye T, Tsutsumi M, Kato T, Tong M, Nishizawa H, Pryor-Koishi K, Kitaoka E, Sawada T, Nishiyama Y, Udagawa Y, Kurahashi H
Mutations of the SYCP3 Gene in Women with Recurrent Pregnancy Loss
Am J Hum Genet. 2009 Jan;84(1):14-20. Epub 2008 Dec 24
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Aneuploidy, a chromosomal numerical abnormality in the conceptus or fetus, occurs in at least 5% of all pregnancies and is the leading cause of early pregnancy loss in humans. Accumulating evidence now suggests that the correct segregation of chromosomes is affected by events occurring in prophase during meiosis I. These events include homologous chromosome pairing, sister-chromatid cohesion, and meiotic recombination. In our current study, we show that mutations in SYCP3, a gene encoding an essential component of the synaptonemal complex that is central to the interaction of homologous chromosomes, are associated with recurrent pregnancy loss. Two out of 26 women with recurrent pregnancy loss of unknown cause were found to carry independent heterozygous nucleotide alterations in this gene, neither of which was present among a group of 150 fertile women. Analysis of transcripts from minigenes harboring each of these two mutations revealed that both affected normal splicing, possibly resulting in the production of C-terminally mutated proteins. The mutant proteins were found to interact with their wild-type counterpart in vitro and inhibit the normal fiber formation of the SYCP3 protein when coexpressed in a heterologous system. These data suggest that these mutations are likely to generate an aberrant synaptonemal complex in a dominant-negative manner and contribute to abnormal chromosomal behavior that might lead to recurrent miscarriage. Combined with the fact that similar mutations have been previously identified in two males with azoospermia, our current data suggest that sexual dimorphism in response to meiotic disruption occurs even in humans.
3. Bhattacharya S, Bhattacharya S
Effect of miscarriage on future pregnancies
Womens Health (Lond Engl). 2009 Jan;5(1):5-8
Editorial
4. Gissler M, Alexander S, Macfarlane A, Small R, Stray-Pedersen B, Zeitlin J, Zimbeck M, Gagnon A
Stillbirths and infant deaths among migrants in industrialized countries
Acta Obstet Gynecol Scand. 2008 Dec 19:1-15. [Epub ahead of print]
STAKES National Research and Development Centre for Welfare and Health, Helsinki, Finland.
Introduction. The relation of migration to infant outcomes is unclear. There are studies which show that some migrant groups have similar or even better outcomes than those from the receiving country. Equally, raised risk of adverse outcomes for other migrant groups has been reported. Objective. We sought to determine (1) if migrants in western industrialized countries have consistently higher risks of stillbirth, neonatal mortality, or infant mortality, (2) if there are migrant sub-groups at potentially higher risk, and (3) what might be the explanations for any risk differences found. Design and Setting. Systematic review of the literature on perinatal health outcomes among migrants in western industrialized countries. Methods and Main outcome measures. Drawing on a larger systematic review of perinatal outcomes and migration, we reviewed studies including mortality outcomes (stillbirths and infant deaths). Results. Eligible studies gave conflicting results. Half (53%) reported worse mortality outcomes, one third (35%) reported no differences and a few (13%) reported better outcomes for births to migrants compared to the receiving country population. Refugees were the most vulnerable group. For non-refugees, non-European migrants in Europe and foreign-born blacks in the United States had the highest excess mortality. In general, adjustment of background factors did not explain the increased mortality rate among migrants. Regarding causes of death, higher preterm birth rates explained the increased mortality figures among some migrant groups. The increased mortality from congenital anomalies may be related to restricted access to screening, but also to differing attitudes to screening and termination of pregnancy. Conclusions. Mortality risk among babies born to migrants is not consistently higher, but appears to be greatest among refugees, non-European migrants to Europe, and foreign-born blacks in the US. To understand this variation better, more information is needed about migrant background, such as length of time in receiving country and receiving country language fluency. Additional data on demographic, health care, biological, medical, and socioeconomic risk factors should be gathered and analyzed in greater detail.
5. Baste V, Moen BE, Riise T, Hollund BE, Oyen N
Infertility and Spontaneous Abortion Among Female Hairdressers: The Hordaland Health Study
J Occup Environ Med. 2008 Dec;50(12):1371-1377
From the Research Group for Occupational and Environmental Medicine (Ms Baste), UNIFOB, Bergen, Norway; Research Group for Occupational and Environmental Medicine, Department of Public Health and Primary Health Care (Dr Moen), University of Bergen, Norway; Research Group for Epidemiology, Lifestyle and Chronic Disease, Department of Public Health and Primary Health Care (Dr Riise), University of Bergen, Norway; Department of Occupational Medicine (Dr Hollund), Haukeland University Hospital, Norway; Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care (Dr Øyen), University of Bergen, Norway; and Department of Epidemiology Research (Dr Øyen), Statens Serum Institut, Copenhagen, Denmark.
OBJECTIVES:: The authors investigated the risks of negative reproductive outcome among female hairdressers. METHODS:: A cross-sectional study was conducted in 1997-1999, and 16,907 women in their forties were invited (response 71%). Information on infertility, delayed conception, spontaneous abortions, smoking, education, and occupation was collected. RESULTS:: Infertility and spontaneous abortion were higher among female hairdressers than among women in other occupations (adjusted relative risks = 1.30; 95% confidence intervals = 1.08 to 1.55 and 1.31; 1.07 to 1.60, respectively). There was a significant interaction between work and smoking habits. Smoking increased the risk of infertility among women in other occupations, but this was not found among hairdressers. CONCLUSIONS:: Female hairdressers have an increased risk of infertility and spontaneous abortions that might be due to their occupational chemical exposure. The risk was primarily found among never smokers.
6. McClure EM, Saleem S, Pasha O, Goldenberg RL
Stillbirth in developing countries: a review of causes, risk factors and prevention strategies
J Matern Fetal Neonatal Med. 2008 Dec 16:1-8. [Epub ahead of print]
Research Triangle Institute, Durham, NC, USA.
Objective. To understand the rates, causes and risk factors for stillbirth in developing countries as well as the strategies that have been evaluated to reduce stillbirth. Methods. We searched the English literature for 2003-2008 for all articles related to stillbirth and perinatal mortality in developing countries and reviewed all related publications. Results. Despite the large number of stillbirths worldwide, the topic of stillbirths in developing countries has received very little research, programmatic or policy attention. In many developing countries, almost half of the deliveries occur at home, and under-reporting of stillbirths is a significant problem. Reliable data about rates and causes are unavailable in many areas of the world. Nevertheless, of the estimated 3.2 million stillbirths that occur yearly world-wide, the vast majority occur in developing countries. Rates in many developing countries are 10-fold greater or more than in developed countries. There is not a standard international classification system that defines cause of death, nor is there agreement about the lower limits of birthweight or gestational age that define stillbirth, making comparisons of causes of stillbirth or rates over time or between sites problematic. From available data, prolonged and obstructed labour, pre-eclampsia and various infections, all without adequate treatment, appear to account for the majority of stillbirths in developing countries. Identification and treatment of maternal syphilis has been effective in reducing stillbirth risk, as has improvements in access to emergency obstetrical services and particularly caesarean section. Conclusions. Further research is needed to understand the causes and the best preventive strategies for stillbirth specific to geographic areas. However, based on current data, better access to appropriate obstetric care, particularly during labour and delivery and better screening and treatment of syphilis should reduce developing country stillbirth rates dramatically.
7. Trogstad L, Magnus P, Moffett A, Stoltenberg C
The effect of recurrent miscarriage and infertility on the risk of pre-eclampsia
BJOG. 2009 Jan;116(1):108-13
Division of Epidemiology, Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. lill.trogstad@fhi.no
OBJECTIVE: Pre-eclampsia, recurrent miscarriage and infertility may all partly be caused by unsuccessful placentation early in pregnancy. If so, one will expect these disorders to be associated in population studies. The aim of the present investigation was to estimate the risk of pre-eclampsia in women with recurrent miscarriage and infertility. DESIGN: Cohort study. SETTING: The Norwegian Mother and Child Cohort Study (MoBa), a large population-based pregnancy cohort. SAMPLE: The sample consisted of 20,846 singleton pregnancies to nulliparous women participating in the MoBa, 1999-2005. METHODS: Information on miscarriage, infertility and potential confounders was self-reported in postal questionnaires, whereas the diagnosis of pre-eclampsia was retrieved from the Medical Birth Registry of Norway. Risk estimation and confounder control was performed with multiple logistic regression. MAIN OUTCOME MEASURES: Pre-eclampsia according to history of miscarriage and infertility. RESULTS: An increased risk of pre-eclampsia, although not statistically significant, was found for women with recurrent miscarriages (adjusted OR 1.51, 95% CI 0.80-2.83). Women who had ever been treated for infertility also had increased risk (adjusted OR 1.29, 95% CI 1.05-1.60). When these two risk factors were combined, the adjusted odds ratio for pre-eclampsia was 2.40 (95% CI 1.11-5.18). CONCLUSIONS: The study supports the hypothesis that infertility, recurrent miscarriage and pre-eclampsia share elements of the same aetiological factors.
8. Goodman C, Goodman CS, Hur J, Jeyendran RS, Coulam C
The association of Apoprotien E polymorphisms with recurrent pregnancy loss
Am J Reprod Immunol. 2009 Jan;61(1):34-8
CARI Reproductive Institute, Chicago, IL, USA.
PROBLEM: We have previously reported the role of polymorphisms of thrombogenic genes involved in coagulation and fibrinolysis as risk factors for recurrent pregnancy loss. Thrombophilia has been viewed as a multigenic disorder rather than a monogenetic clinical phenotype and Apo E has been shown to play an important role in lipid metabolism in pregnancy. As individuals carrying the E4 allele of the ApoE gene have the highest risk for thrombosis, we evaluated the frequency of the Apo E4 genotype among women suffering from recurrent pregnancy loss. METHOD OF STUDY: Buccal swabs were obtained from 69 women with a history of two or more consecutive spontaneous abortions and 37 women with at least two live births and not more than one miscarriage. DNA was extracted from the buccal swabs and PCR amplification of Apo E2, E3, and E4 was performed. RESULTS: Women experiencing recurrent pregnancy loss had a significantly higher prevalence of Apo E3/4, E4/4 genotypes (21.7%) compared with control women (5.4%) (P = 0.036). CONCLUSION: Apo E4 polymorphism may contribute to the thrombophilic risk factors contributing to recurrent pregnancy loss.
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