NSIDRC Journal Article Alert — November 14, 2008

Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss 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 Resource Center 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.

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Sudden Infant Death

1. Tiddens HA, Hofhuis W, Casotti V, Hop WC, Hulsmann AR, de Jongste JC Airway dimensions in bronchopulmonary dysplasia: Implications for airflow obstruction Pediatr Pulmonol. 2008 Nov 7. [Epub ahead of print]

Division of Respiratory Medicine and Allergology, Department of Pediatrics, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.

The cause of lung function abnormalities in bronchopulmonary dysplasia (BPD) is incompletely understood, even in the "new era" of this disease. Altered airway wall dimensions are important in the pathogenesis of airflow obstruction in diseases such as asthma and chronic bstructive pulmonary disease. Whether airway wall dimensions contribute to lung function abnormalities in BPD is unknown. The purpose of this study was to investigate airway wall dimensions in relation to airway size in BPD. Lung tissue of patients with BPD was obtained at autopsy, and lung tissue from children who died from sudden infant death syndrome (SIDS) served as control. Airway wall dimensions and epithelial loss were measured in 75 airways from 5 BPD patients and 176 airways from 11 SIDS patients. Repeated measures analysis of variance was used to assess the relationships between airway wall dimensions and airway size for BPD and SIDS patients. Little epithelial loss was present in the BPD patients while extensive loss was observed in some of the SIDS patients. The inner wall area, outer wall area, epithelium area and smooth muscle area were all substantially larger (all P < 0.001) in BPD than in SIDS patients. It is likely that the increased thickness of the airway wall components contributes to airflow obstruction in BPD patients. Pediatr. Pulmonol. (c) 2008 Wiley-Liss, Inc.

2. Duncan JR, Paterson DS, Kinney HC The development of nicotinic receptors in the human medulla oblongata: Inter-relationship with the serotonergic system Auton Neurosci. 2008 Nov 3. [Epub ahead of print]

Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, 02115, USA.

Maternal cigarette smoking during pregnancy adversely affects fetal development and increases the risk for the sudden infant death syndrome (SIDS). In SIDS we have reported abnormalities in the medullary serotonergic (5-HT) system, which is vital for homeostatic control. In this study we analyzed the inter-relationship between nicotinic receptors (nAChRs), to which nicotine in cigarette smoke bind, and the medullary 5-HT system in the human fetus and infant as a step towards determining the mechanisms whereby smoking increases SIDS risk in infants with 5-HT defects. Immunohistochemistry for the alpha4 nAChR subunit and 5-HT neurons was applied in fetal and infant medullae (15-92 postconceptional weeks, n=9). The distribution of different nAChRs was determined from 39-82 postconceptional weeks (n=5) using tissue autoradiography for (3)H-nicotine, (3)H-epibatidine, (3)H-cytisine, and (125)I-bungarotoxin; the findings were compared to laboratory 5-HT(1A) and 5-HT transporter binding data, and 5-HT neuronal density. Alpha4 immunoreactivity was ubiquitously expressed in medullary nuclei related to homeostatic functions from 15 weeks on, including rhombic lip germinal cells. At all ages, alpha4 co-localized with 5-HT neurons, indicating a potential site of interaction whereby exogenous nicotine may adversely affect 5-HT neuronal development and function. Binding for heteromeric nAChRs was highest in the inferior olive, and for homomeric nAChRs, in the vagal complex. In the paragigantocellularis lateralis, 5-HT(1A) receptor binding simultaneously increased as alpha7 binding decreased across infancy. This study indicates parallel dynamic and complex changes in the medullary nicotinic and 5-HT systems throughout early life, i.e., the period of risk for SIDS.

3. A, Vege A, Opdal SH, Moberg S, Rognum TO Surfactant protein A and D gene polymorphisms and protein expression in victims of sudden infant death Acta Paediatr. 2008 Oct 30. [Epub ahead of print]

Stray-Pedersen Institute of Forensic Medicine, University of Oslo, Norway.

Aim: To investigate the innate immune components surfactant protein A (SP-A) and D (SP-D) in victims of sudden infant death syndrome (SIDS). Methods: Ten common single nucleotide polymorphisms (SNPs) in the exons of SP-A1, SP-A2 and SP-D genes were analysed in 42 cases of SIDS and 46 explained sudden infant deaths. SP-A and SP-D protein expression in tissue from the aerodigestive tract was semi-quantitatively evaluated by immunohistochemistry. Results: SP-D immunoreactivity was found in lungs and tissue from submandibular gland, palatine tonsils and duodenum. Positive SP-A immune staining was found exclusively in lung tissue. Neither the allele nor the haplotype distribution of the SP-A and SP-D genes was significantly different in SIDS compared to explained deaths. The most common SP-A haplotype, 6A2/1A0, tended to be overrepresented in the cases with low immunohistochemical SP-A expression (61%) compared to cases with high expression (49%), p = 0.08. The SP-D expression was not influenced by the 11 C/T or 160 A/G polymorphisms. Conclusion: No significant association between the common genetic variants of SP-A and SP-D and SIDS is disclosed by the present study. However, low SP-A protein expression may possibly be determined by the 6A2/1A0 SP-A haplotype, this should be subject for further investigation.

Miscarriage/Stillbirth/Prenatal Issues

1. Chrus´ciel M, Andronowska A, Postek A Expression Patterns of Endothelial and Inducible Nitric Oxide Isoforms in the Porcine Umbilical Cord Reprod Domest Anim. 2008 Oct 30. [Epub ahead of print]

Department of Reproductive Histophysiology, Division of Reproductive Endocrinology and Pathophysiology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Poland.

Stable fetal-placental blood pressure and flow are extremely important in fetal growth and development. Uncontrolled and long-standing increased or decreased vascular blood pressure in the umbilical cord (UC) affects hyperaemia or ischaemia and consequently causes fetal death. Nitric oxide (NO) is one of the most active factors controlling blood flow through relaxation of the vascular smooth muscle. In this study, we investigated endothelial (eNOS) and inducible (iNOS) nitric oxide synthase expression and NADPH-diaphorase activity (NADPH-d) in the porcine UC at various stages of pregnancy. The UCs were collected from pigs on days 40, 60, 75 and 90 of pregnancy and postpartum. Western blot analysis as well as immunohistchemical staining revealed protein presence for eNOS and iNOS in the UC of the pig. The eNOS expression was maintained at a significantly higher level in all analysed days of pregnancy when compared with postnatal stage. Additionally, a significant protein increase for eNOS was observed in a periplacental part of UC on day 90. There were no obvious differences in iNOS protein level in UC samples derived from different stages of pregnancy. NADPH-diaphorase histochemical activity was correlated with NOS immunoreactivity during all analysed days of pregnancy. These results suggest that NOS isoforms are responsible for regulation of blood circulation in UC and immune responses.

2. Riipinen A, Väisänen E, Nuutila M, Sallmen M, Karikoski R, Lindbohm ML K, Taskinen H, Söderlund-Venermo M Parvovirus B19 Infection in Fetal Deaths Clin Infect Dis. 2008 Nov 7. [Epub ahead of print]

1Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, 2Department of Virology, Haartman Institute, and 3Central Pathology Laboratory, Helsinki University Central Hospital Laboratory Division, and 4School of Public Health, University of Helsinki, and 5Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.

Parvovirus B19 infection during pregnancy can lead to nonimmune fetal hydrops, miscarriage, and intrauterine fetal death (IUFD). Some studies have suggested that parvovirus B19 infection may surprisingly often result in nonhydropic fetal death during the third trimester, in the absence of maternal serological evidence of acute infection. This study was conducted to investigate the prevalence of parvovirus B19 DNA among fetuses from miscarriages and IUFDs. Methods. @nbsp; We retrospectively studied 535 unborn fetuses, including 120 fetuses from miscarriages and 169 from IUFDs. The control fetuses were 246 fetuses from induced abortions. All fetuses were autopsied from July 1992 through December 1995 and from January 2003 through December 2005 in Helsinki, Finland. The period included a major epidemic of parvovirus B19 infection in 1993. Formalin-fixed, paraffin-embedded fetal tissues were studied with use of a highly sensitive and specific PCR that was capable of detecting all 3 parvovirus B19 genotypes and by histologic examination. In addition, maternal parvovirus B19 serological status was determined. Results. @nbsp; Parvovirus B19 DNA was detected in 5 fetuses with gestational ages of 14, 22, 23, 30, and 39 weeks; these included fetuses from 4 (2.4%) of the 169 IUFDs and 1 (0.8%) of the 120 miscarriages. During the epidemic year 1993, the prevalence of parvovirus B19 DNA-positive fetal deaths was 6 times the prevalence during nonepidemic years. All 5 mothers of the parvovirus B19 DNA-positive fetuses had serological signs of acute parvovirus B19 infection close to the time of fetal death. The only nonhydropic fetus was full-term. Conclusions. @nbsp; Our findings indicate that the prevalence of parvovirus B19 infection among fetuses from IUFDs is low. In particular, our findings did not verify the claimed high prevalence of third-trimester nonhydropic IUFDs associated with parvovirus B19.

3. Pazarbas¸i A, Demirhan O, Turgut M, Güzel I, Tas¸temir D Inheritance of a translocation between chromosomes 12 and 16 in a family with recurrent miscarriages and a newborn with Down syndrome carrying the same translocation Genet Couns. 2008;19(3):301-8

Department of Medical Biology and Genetics, Faculty of Medicine, University of Cukurova, Turkey. payfer@cu.edu.tr

Reciprocal translocation carriers have reduced fertility, increased risk of spontaneous abortion or unbalanced karyotype in their offspring. Here, we report the inheritance of a translocation between chromosomes 12 and 16 in a family with recurrent miscarriages and a newborn with Down syndrome carrying the same translocation. Chromosomal analysis from fetal amniotic fluid and peripheral blood lymphocytes from the family were performed at the Cukurova university hospital in Turkey. We assessed a family in which the translocation between chromosomes 12 and 16 segregates; one of the eight progenies with the karyotype 47,XY,+21,t(12;16)(q24;q24) was heterozygote for the translocation and presented with Down syndrome. His mother is phenotypically normal, one brother and one sister were also carrying the same translocation. Apparently, this rearrangement occurred due to the unbalanced chromosome segregation of the mother [t(12;16)(q24;q24)mat]. This case will enable us to explain the behavior of segregation patterns and the mechanism for each type oftranslocation from carrier to carrier and their effects on reproduction and numerical aberrations. The t(12;16) is also associated with fetal wastage and may play a role in the etiology of the family's miscarriages. These findings can be used in clinical genetics and may be used as an effective tool for reproductive guidance and genetic counseling.

4. Bae J, Choi DH, Kang MS, Cha SH, Oh D, Kim NK Effect of methylenetetrahydrofolate reductase and enhancer region polymorphisms on the risk of idiopathic recurrent spontaneous abortion in a Korean population Fertil Steril. 2008 Nov 4. [Epub ahead of print]

Institute for Clinical Research, Bundang CHA General Hospital, College of Medicine, Pochon CHA University, Seongnam, South Korea; Graduate School of Life Science and Biotechnology, College of Medicine, Pochon CHA University, Seongnam, South Korea.

Previous studies reported an association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms and recurrent spontaneous abortion, whereas no studies are available for the association with thymidylate synthase enhancer region (TSER) genotypes. Mutations of MTHFR and TSER are not likely significant risk factors of idiopathic recurrent spontaneous abortion in Korean women.

5. Ilhan F, Yener Z Immunohistochemical detection of Brucella melitensis antigens in cases of naturally occurring abortions in sheep J Vet Diagn Invest. 2008 Nov;20(6):803-6

Department of Pathology, Veterinary Faculty, Yuzuncu Yil University, 6500, Kampus, Van, Turkey. fatmasayn@hotmail.com or fatmasayn@yahoo.com.

Brucella melitensis, a worldwide zoonotic pathogen, is a significant cause of abortion in sheep and goats in some countries. The present study was carried out to determine, by immunohistochemistry, the presence of B. melitensis antigens in 110 naturally occurring aborted sheep fetuses. Sections of lung, liver, kidney, and spleen of each fetus were stained with immunoperoxidase to detect Brucella antigens. Brucella melitensis antigens were detected in 33 of 110 fetuses (30%). In the 33 positive cases, Brucella antigens were found in lung (25 [22.7%]), liver (21 [19%]), spleen (13 [11.8%]), and kidney (6 [5.4%]). Microscopic studies demonstrated that Brucella antigens were mainly located in the cytoplasm of macrophages and neutrophils of the lung, and in the cytoplasm of macrophages in the portal infiltrates and Kupffer cells of the liver. It was concluded that immunohistochemistry in formalin-fixed, paraffin-embedded tissues is a useful tool for the diagnosis of spontaneous ovine abortion caused by B. melitensis.

6. Duke W, Williams L, Correa A Using active birth defects surveillance programs to supplement data on fetal death reports: Improving surveillance data on stillbirths Birth Defects Res A Clin Mol Teratol. 2008 Nov 4. [Epub ahead of print]

Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.

BACKGROUND: Surveillance of stillbirths using fetal death reports (FDRs) has been challenging because of under-reporting of fetal deaths and missing data on the FDRs. Using active case finding and chart abstraction within the infrastructure of established birth defect surveillance programs could potentially enhance the data from FDRs. The data collection form for the Metropolitan Atlanta Congenital Defects Program, an active, population-based birth defects surveillance system, was modified to collect additional information on stillbirths from medical records. METHODS: The study population was a 25% simple random sample of stillbirths recorded on FDRs in 2004 (n = 125) by residents in the five central counties of metropolitan Atlanta. Stillbirth was defined as a fetal death at >/=20 weeks gestation or >/=350 g if age was unknown. Data on demographic characteristics and risk factors collected from the two sources were compared for completeness and agreement, as well as causes of and conditions associated with the fetal death. RESULTS: Combining data sources provided more information. Demographic and risk factor variables in the two data sources showed strong agreement (categorical variable, kappa range = 0.79-1.00; continuous variable, correlation coefficient range = 0.61-1.00). The actively ascertained data provided more complete information for causes and conditions of fetal death. Data from the FDRs yielded 42% of cases with no listed cause of death or associated condition compared with 10% using Metropolitan Atlanta Congenital Defects Program data. CONCLUSIONS: Expanding the potential of existing active birth defects surveillance programs to include stillbirth surveillance could potentially improve the quantity and quality of available data on fetal deaths. Ongoing studies are needed to corroborate these findings and to assess completeness of case ascertainment. Birth Defects Research (Part A), 2008. Published 2008 Wiley-Liss, Inc.

7. Lopez de Maturana E, Wu XL, Gianola D, Wigel KA, Rosa GJ Exploring Biological Relationships between Calving Traits in Primiparous Cattle with a Bayesian Recursive Model Genetics. 2008 Nov 3. [Epub ahead of print]

University of Wisconsin-Madison.

Structural equation models (SEM) of a recursive type with heterogeneous structural coefficients were used to explore biological relationships between gestation length (GL), calving difficulty (CD) and perinatal mortality, also known as stillbirth (SB), in cattle, with the last two traits having categorical expression. An acyclic model was assumed, where recursive effects existed from the GL phenotype to the liabilities (latent variables) to CD and SB, and from the liability to CD to that of SB considering four periods regarding GL. The data contained GL, CD and SB records from 90,393 primiparous cows, sired by 1,122 bulls, distributed over 935 herd-calving year classes. Low genetic correlations between GL and the other calving traits were found, whereas the liabilities to CD and SB were high and positively correlated, genetically. The model indicated that gestations of around 274 days of length (3 days shorter than the average) would lead to the lowest CD and SB, and confirmed the existence of an intermediate optimum of GL with respect to these traits.

8. Bellver J, Garrido N, Remohí J, Pellicer A, Meseguer M Influence of paternal age on assisted reproduction outcome Reprod Biomed Online. 2008 Nov;17(5):595-604

Instituto Valenciano de Infertilidad, Plaza de la Policía Local, 3, Valencia 46015, Spain. jbellver@ivi.es

There has been an increasing tendency to delay parenthood in developed countries in recent years, and there is not enough information available regarding the effect of this on fertility. The aim of this work was to determine the role of paternal age on the outcome of assisted reproduction. A retrospective study was designed comprising a total of 2204 intrauterine insemination (IUI) cycles, 1286 IVF cycles and 1412 IVF cycles with donated oocytes during the period 2000 to 2006. Male mean age was 34.3 years (range 25-56) for IUI, 34.8 years (range 19-62) for IVF and 41.10 years (range 25-71) for ovum donation cycles. Statistics revealed no differences regarding pregnancy and miscarriage rates when the results were compared among age groups. In standard IVF and ovum donation cycles there was no clear association between embryo quality and paternal age. There was no significant relationship between male age and implantation rate. So far this is the largest study concerning the relevance of male age in assisted reproduction. As confirmed by the present data, the effect of the age of the male in the range studied is irrelevant. This finding contributes to the information that can be provided to infertile couples.

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