NSIDRC Journal Article Alert — August 14, 2009

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

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.

Sudden Infant Death

1. Rouleau C, Bongrand AF, Pidoux O Dr, Roustan E, Martrille L, Costes-Martineau V, Cambonie G

Sudden Infant Death Syndrome (SIDS): characteristics of deaths since the fall in SIDS in the French region of Languedoc-Roussillon

Arch Dis Child. 2009 Aug 6. [Epub ahead of print]

Department of Pathology, Lapeyronie Hospital, France.

The aim of this retrospective study was to report the characteristics of SIDS deaths in the French region of Languedoc-Roussillon from 2003-2008. In order to estimate more accurately the time at which infant deaths occurred, we evaluated the time interval between when the baby was last observed alive, taken as the time of last feeding, and the discovery of death. It was conducted in 2 groups of sudden unexpected death of infants (SUDI), classified as unexplained SUDI (SIDS, N=27) or explained SUDI (N=22), following post mortem procedures. In SIDS, 67% (18/27) of deaths were discovered in the wakeful day (09:00h to 21:00h) and most deaths occurred within the first 4 hours after feeding (66%). In explained SUDI, 68.2% of deaths were discovered at night and time intervals between last feeding and discovery of death were longer than in SIDS (mean: 7.1hr, p<0.01). In the Languedoc-Roussillon, in which SIDS death rate remains relatively high, SIDS deaths were discovered mostly in the wakeful day and explained SUDI mostly at night. Variations in the time interval between the last feed and discovery of death in the two groups may result from differences in parental attentiveness during the day and night time periods.

2. Toruner GA, Kurvathi R, Sugalski R, Shulman L, Twersky S, Pearson PG, Tozzi R, Schwalb MN, Wallerstein R

Copy number variations in three children with sudden infant death

Clin Genet. 2009 Jul;76(1):63-8

The Genetics and Genetics Counseling Program, The Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, NJ, USA. torunega@umdnj.edu

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 x 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an approximately 3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death.

Bereavement

1. Swanson PB, Kane RT, Pearsall-Jones JG, Swanson CF, Croft ML

How couples cope with the death of a twin or higher order multiple

Twin Res Hum Genet. 2009 Aug;12(4):392-402

School of Psychology, Curtin University of Technology, Australia.

Fifty-two Australian couples who had experienced the death of at least one member of a multiple birth (twin or higher order), with at least one survivor of that birth, were interviewed about their experiences at the time of the death, and since. This study compared parents' coping after the twins' deaths using the Beck Depression Inventory II, Perinatal Grief Scale, and unstructured interviews with some structured queries. Parents provided information on the influence of family, community and medical staff. According to retrospective reports, mothers experienced significantly more depression and grief than fathers at the time of loss. Both parents found the death of their twins grievous, but fathers, unlike mothers, were not encouraged to express their emotions. Although parents generally agreed about what helped them cope, fathers believed that they should be able to cope regardless of their grief. The strength of parents' spiritual beliefs had increased significantly since their loss, and there was some evidence that depressed and grieving mothers turned to spiritual support. Parents whose children died earlier reported levels of depression similar to those reported by parents whose children died later. To date, this is the largest study of grief in couples who have experienced the death of a twin and who have a surviving twin or higher order multiple.

Miscarriage/Stillbirth/Prenatal Issues

1. Chaiworapongsa T, Romero R, Tarca A, Kusanovic JP, Mittal P, Kim SK, Gotsch F, Erez O, Vaisbuch E, Mazaki-Tovi S, Pacora P, Ogge G, Dong Z, Kim CJ, Yeo L, Hassan SS.J

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study

Matern Fetal Neonatal Med. 2009 Aug 6:1-18. [Epub ahead of print]

Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, Michigan, USA.

Objective. An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women. Study Design. This longitudinal nested case-control study included normal pregnant women (n = 208) and patients with PTL leading to preterm delivery (n = 52). Maternal blood samples were collected at 6 gestational age intervals from 6 to36.9 weeks of gestation. The end point (time of diagnosis) of the study, 'True PTL', was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. Results. (1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women since 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of 'true PTL'. (2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of 'true PTL'; and (3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patients diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. Conclusion. The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition.

2. Gallicchio L, Flaws JA

No interaction between smoking and working as a hairdresser with respect to miscarriage and infertility

J Occup Environ Med. 2009 Aug;51(8):868-9

Comment on J Occup Environ Med. 2008 Dec;50(12):1371-7.

3. Bobadilla-Morales L, Cervantes-Luna MI, García-Cobián TA, Gómez-Meda BC, de la Torre CO,Corona-Rivera JR, Corona-Rivera A

Chromosome instability in a patient with recurrent abortions

Genet Couns. 2009;20(2):153-9

Laboratorio de Citogenética Genotoxicidad y Biomonitoreo y Clínica de Asesoramiento Genético, Instituto de Genética Humana Dr. Enrique Corona Rivera, Departamento de Biología Molecular y Genómica, División de Disciplinas Básicas, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México. lucinabo@cucs.udg.mx

Chromosomal aberrations are one of the recognized possible etiologic genetic causes of recurrent spontaneous abortions. Increased chromosome instability without constitutional chromosome abnormalities is uncommon in these couples. In this work we present a non consanguineous healthy couple with recurrent abortions without constitutional chromosome aberrations in which spontaneous and induced chromosome aberrations were observed in the female. Chromosome analysis was performed in the presence of different chromosome damage inductors such as gamma radiation, Uv light, and mitomycin-C. Alterations observed only in the female were: spontaneous and induced tetraradial chromosomes and increased chromosomal damage induced only by gamma radiation. Oral mucosa micronuclei were moderately increased in the female. Chromosome instability associated to abortion is proposed.

4. Inkster ME, Fahey TP, Donnan PT, Leese GP, Mires GJ, Murphy DJ

The role of modifiable pre-pregnancy risk factors in preventing adverse fetal outcomes among women with type 1 and type 2 diabetes

Acta Obstet Gynecol Scand. 2009 Aug 4:1-5. [Epub ahead of print]

Division of Community Health Sciences, University of Dundee, Dundee, UK.

We investigated the fetal outcomes of pregnancy in women with pre-existing diabetes in relation to pre-pregnancy risk factors using a community-based cohort of women in Tayside, Scotland. There were 211 pregnancies in 132 women with insulin-requiring type 1 and 2 diabetes between January 1993 and December 2005. Adverse fetal outcome was classified as spontaneous miscarriage, termination for medical reasons, stillbirth, neonatal death, or congenital malformation and occurred in 61 (29%) pregnancies. Mothers with poor glycemic control pre-conceptually and at booking (HbA(1c)>/=7.5%) had almost a three-fold increase in adverse fetal outcome compared with mothers having fair control, odds ratio (OR) 2.59 (95% CI 1.11-6.03), and 2.71 (95% CI 1.39-5.28), respectively. Mothers who were still smoking at the booking visit had a two-fold increase in adverse fetal outcome (OR 2.12, 95% CI 1.09-4.10). Further improvement in the management of diabetes and pregnancy is needed through enhanced preconception services addressing the full spectrum of modifiable risk factors.

Prepared by the
National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center
Georgetown University
2115 Wisconsin Avenue, N.W., Suite 601
Washington, DC 20007
(866) 866-7437 toll free
(202) 687-7466 local
(202) 784-9777 fax
info@sidscenter.org
http://www.sidscenter.org


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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. Sudden Infant Death 1. Rouleau C, Bongrand AF, Pidoux O Dr, Roustan E, Martrille L, Costes-Martineau V, Cambonie G Sudden Infant Death Syndrome (SIDS): characteristics of deaths since the fall in SIDS in the French region of Languedoc-Roussillon Arch Dis Child. 2009 Aug 6. [Epub ahead of print] Department of Pathology, Lapeyronie Hospital, France. The aim of this retrospective study was to report the characteristics of SIDS deaths in the French region of Languedoc-Roussillon from 2003-2008. In order to estimate more accurately the time at which infant deaths occurred, we evaluated the time interval between when the baby was last observed alive, taken as the time of last feeding, and the discovery of death. It was conducted in 2 groups of sudden unexpected death of infants (SUDI), classified as unexplained SUDI (SIDS, N=27) or explained SUDI (N=22), following post mortem procedures. In SIDS, 67% (18/27) of deaths were discovered in the wakeful day (09:00h to 21:00h) and most deaths occurred within the first 4 hours after feeding (66%). In explained SUDI, 68.2% of deaths were discovered at night and time intervals between last feeding and discovery of death were longer than in SIDS (mean: 7.1hr, p<0.01). In the Languedoc-Roussillon, in which SIDS death rate remains relatively high, SIDS deaths were discovered mostly in the wakeful day and explained SUDI mostly at night. Variations in the time interval between the last feed and discovery of death in the two groups may result from differences in parental attentiveness during the day and night time periods. 2. Toruner GA, Kurvathi R, Sugalski R, Shulman L, Twersky S, Pearson PG, Tozzi R, Schwalb MN, Wallerstein R Copy number variations in three children with sudden infant death Clin Genet. 2009 Jul;76(1):63-8 The Genetics and Genetics Counseling Program, The Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, NJ, USA. torunega@umdnj.edu Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty-seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array-based comparative genomic hybridization (array-CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 x 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an approximately 3-Mb (chr 8: 143,211,215-qter) duplication on 8q24.3-qter and a 4.4-Mb deletion on the 22q13.3-qter (chr 22: 45,047,068-qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240-kb (chr 6: 26,139,810-26,380,787) duplication and a 1.9-Mb deletion (chr 6: 26,085,971-27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array-CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array-CGH analysis may be beneficial during the investigations after sudden infant death. Bereavement 1. Swanson PB, Kane RT, Pearsall-Jones JG, Swanson CF, Croft ML How couples cope with the death of a twin or higher order multiple Twin Res Hum Genet. 2009 Aug;12(4):392-402 School of Psychology, Curtin University of Technology, Australia. Fifty-two Australian couples who had experienced the death of at least one member of a multiple birth (twin or higher order), with at least one survivor of that birth, were interviewed about their experiences at the time of the death, and since. This study compared parents' coping after the twins' deaths using the Beck Depression Inventory II, Perinatal Grief Scale, and unstructured interviews with some structured queries. Parents provided information on the influence of family, community and medical staff. According to retrospective reports, mothers experienced significantly more depression and grief than fathers at the time of loss. Both parents found the death of their twins grievous, but fathers, unlike mothers, were not encouraged to express their emotions. Although parents generally agreed about what helped them cope, fathers believed that they should be able to cope regardless of their grief. The strength of parents' spiritual beliefs had increased significantly since their loss, and there was some evidence that depressed and grieving mothers turned to spiritual support. Parents whose children died earlier reported levels of depression similar to those reported by parents whose children died later. To date, this is the largest study of grief in couples who have experienced the death of a twin and who have a surviving twin or higher order multiple. Miscarriage/Stillbirth/Prenatal Issues 1. Chaiworapongsa T, Romero R, Tarca A, Kusanovic JP, Mittal P, Kim SK, Gotsch F, Erez O, Vaisbuch E, Mazaki-Tovi S, Pacora P, Ogge G, Dong Z, Kim CJ, Yeo L, Hassan SS.J A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: Evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study Matern Fetal Neonatal Med. 2009 Aug 6:1-18. [Epub ahead of print] Perinatology Research Branch, NICHD/NIH/DHHS, Detroit, Michigan, USA. Objective. An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women. Study Design. This longitudinal nested case-control study included normal pregnant women (n = 208) and patients with PTL leading to preterm delivery (n = 52). Maternal blood samples were collected at 6 gestational age intervals from 6 to36.9 weeks of gestation. The end point (time of diagnosis) of the study, 'True PTL', was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches. Results. (1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women since 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of 'true PTL'. (2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of 'true PTL'; and (3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patients diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term. Conclusion. The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition. 2. Gallicchio L, Flaws JA No interaction between smoking and working as a hairdresser with respect to miscarriage and infertility J Occup Environ Med. 2009 Aug;51(8):868-9 Comment on J Occup Environ Med. 2008 Dec;50(12):1371-7. 3. Bobadilla-Morales L, Cervantes-Luna MI, García-Cobián TA, Gómez-Meda BC, de la Torre CO,Corona-Rivera JR, Corona-Rivera A Chromosome instability in a patient with recurrent abortions Genet Couns. 2009;20(2):153-9 Laboratorio de Citogenética Genotoxicidad y Biomonitoreo y Clínica de Asesoramiento Genético, Instituto de Genética Humana Dr. Enrique Corona Rivera, Departamento de Biología Molecular y Genómica, División de Disciplinas Básicas, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México. lucinabo@cucs.udg.mx Chromosomal aberrations are one of the recognized possible etiologic genetic causes of recurrent spontaneous abortions. Increased chromosome instability without constitutional chromosome abnormalities is uncommon in these couples. In this work we present a non consanguineous healthy couple with recurrent abortions without constitutional chromosome aberrations in which spontaneous and induced chromosome aberrations were observed in the female. Chromosome analysis was performed in the presence of different chromosome damage inductors such as gamma radiation, Uv light, and mitomycin-C. Alterations observed only in the female were: spontaneous and induced tetraradial chromosomes and increased chromosomal damage induced only by gamma radiation. Oral mucosa micronuclei were moderately increased in the female. Chromosome instability associated to abortion is proposed. 4. Inkster ME, Fahey TP, Donnan PT, Leese GP, Mires GJ, Murphy DJ The role of modifiable pre-pregnancy risk factors in preventing adverse fetal outcomes among women with type 1 and type 2 diabetes Acta Obstet Gynecol Scand. 2009 Aug 4:1-5. [Epub ahead of print] Division of Community Health Sciences, University of Dundee, Dundee, UK. We investigated the fetal outcomes of pregnancy in women with pre-existing diabetes in relation to pre-pregnancy risk factors using a community-based cohort of women in Tayside, Scotland. There were 211 pregnancies in 132 women with insulin-requiring type 1 and 2 diabetes between January 1993 and December 2005. Adverse fetal outcome was classified as spontaneous miscarriage, termination for medical reasons, stillbirth, neonatal death, or congenital malformation and occurred in 61 (29%) pregnancies. Mothers with poor glycemic control pre-conceptually and at booking (HbA(1c)>/=7.5%) had almost a three-fold increase in adverse fetal outcome compared with mothers having fair control, odds ratio (OR) 2.59 (95% CI 1.11-6.03), and 2.71 (95% CI 1.39-5.28), respectively. Mothers who were still smoking at the booking visit had a two-fold increase in adverse fetal outcome (OR 2.12, 95% CI 1.09-4.10). Further improvement in the management of diabetes and pregnancy is needed through enhanced preconception services addressing the full spectrum of modifiable risk factors. Prepared by the National Sudden and Unexpected Infant/Child Death and Pregnancy Loss Resource Center Georgetown University 2115 Wisconsin Avenue, N.W., Suite 601 Washington, DC 20007 (866) 866-7437 toll free (202) 687-7466 local (202) 784-9777 fax info@sidscenter.org http://www.sidscenter.org
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NSIDRC Journal Article Alert — August 14, 2009