NSIDRC Journal Article Alert — November 6, 2009

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

These articles have been selected from PubMed, a service of the National Library of Medicine that includes over 19 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources.

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Sudden Infant Death

1. Chugh SS, Reinier K, Balaji S, Uy-Evanado A, Vickers C, Mariani R, Gunson K, Jui J
Population-based analysis of sudden death in children: The Oregon Sudden Unexpected Death Study
Heart Rhythm. 2009 Nov;6(11):1618-22. Epub 2009 Jul 29.

Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048 sumeet.chugh@cshs.org

Comment in Heart Rhythm. 2009 Nov;6(11):1623-4

BACKGROUND: There is a lack of prospective population-based data regarding sudden death in children. OBJECTIVE: The purpose of this study was to assess the burden of sudden cardiac arrest (SCA) in the pediatric population in a 3-year community-wide study. METHODS: During 2002-2005, all residents of Multnomah County, Oregon (population 660,486) who underwent SCA were ascertained from emergency medical services, the medical examiner, and emergency rooms of 16 area hospitals. A comprehensive evaluation was performed, including analysis of circumstances of death, medical records, and available autopsy data. Annual incidence rates were calculated for all residents age <18 years using the 2000 U.S. Census data. RESULTS: A total of 33 children met the criteria for SCA (58% female, median age 0.37 years, range 0.03-12.3 years). The majority of SCAs (76%) occurred in children age <1 year. At least 90% of this subgroup also met the criteria for the sudden infant death syndrome (SIDS). Pediatric SCAs constituted 2.8% of all SCAs. The pediatric annual incidence rate per 100,000 population was 1.7 (95% confidence interval [CI] 1.1-2.3), compared with 60/100,000 for all ages. The pediatric annual incidence rate per 100,000 children was 7.5 (95% CI 5.1-10.5). The annual incidence rate of SIDS was 0.8/1000 live births. In contrast to an adult survival rate of 8%, none of the children survived to be discharged from the hospital. CONCLUSIONS: The burden of pediatric sudden death was low (3% of all sudden deaths), but 90% occurred before the age of 1 year, and the majority were diagnosed as SIDS (70% of overall sudden deaths in children). Population education to prevent SIDS and enhanced postnatal diagnosis of occult heart disease are likely to have the greatest impact on the prevention of pediatric sudden death.

2. Möllborg P, Alm B
Sudden infant death syndrome during low incidence in Sweden 1997-2005
Acta Paediatr. 2009 Oct 29. [Epub ahead of print]

Central Infant Welfare Unit, Primary Health Care, FyrBoDal, Uddevalla, Sweden.

Abstract Background: Following the change from prone to supine in preferred sleeping position, the incidence of Sudden Infant Death Syndrome (SIDS) in Sweden fell from 1.1 per 1000 live births in 1992 to 0.41 in 1995. After a further small decline, we have been experiencing a plateau at around 0.25 since 2000. Aim: To identify the changes that have occurred in the epidemiology of SIDS since the end of the Nordic Epidemiological SIDS Study in 1995. Methods: Data from the Medical Birth Register of Sweden, covering the years 1995-2005, were used. Sleeping position is not included in the register. Results: The incidence of SIDS has remained low in Sweden. Independent risk factors were smoking during early pregnancy, parents not living together, low maternal age, high parity and short gestational age. The odds ratio for smoking has continued to increase and the median age of death has continued to decrease since the previous study. We found no signs of seasonality in the current material. Conclusions: Age at death continued to decrease. The high incidence during weekends persisted. Seasonality was not significant. There was no evidence of a changing effect from risk factors in the studied period.

3. Blood-Siegfried J
The role of infection and inflammation in sudden infant death syndrome
Immunopharmacol Immunotoxicol. 2009;31(4):516-23

Duke University, School of Nursing, box 3322, Durham, NC 27710, USA. blood002@mc.duke.edu

Sudden Infant Death Syndrome (SIDS) is the most common cause of post-neonatal mortality in the developed world. The exact cause of SIDS is likely to be multifactorial involving a critical developmental period, a vulnerable infant, and one or more triggers. Many SIDS infants have a history of viral illness preceding death. Prone sleep position, one of the leading risk factors, can increase airway temperature, as well as stimulate bacterial colonization and bacterial toxin production. Markers of infection and inflammation are often found on autopsy along with microbial isolates. Although the causal link between infection and SIDS is not conclusive, there is evidence that an infectious insult could be a likely trigger of SIDS in some infants.

Bereavement

1. Kersting A, Ohrmann P, Pedersen A, Kroker K, Samberg D, Bauer J, Kugel H, Koelkebeck K, Steinhard J, Heindel W, Arolt V, Suslow T
Neural Activation Underlying Acute Grief in Women After the Loss of an Unborn Child
Am J Psychiatry. 2009 Nov 2. [Epub ahead of print]

Objective The traumatic loss of an unborn child by induced termination of pregnancy because of fetal malformation is a major life event that causes intense maternal grief. Increasing evidence supports the hypothesis that the same neural structures involved in the experience of physical pain are involved in the experience of social pain and loss. Method To investigate neural activation patterns related to acute grief, the authors conducted a functional MRI study of 12 post-termination women and 12 noninduced women who delivered a healthy child. Brain activation was measured while participants viewed pictures of happy baby, happy adult, and neutral adult faces. Results Relative to comparison women, post-termination women showed greater activation in the middle and posterior cingulate gyrus, the inferior frontal gyrus, the middle temporal gyrus, the thalamus, and the brainstem in response to viewing happy baby faces. Functional connectivity between the cingulate gyrus and the thalamus during the processing of happy baby faces was significantly stronger in post-termination women. Conclusions Overall, acute grief after the loss of an unborn child was closely related to the activation of the physical pain network encompassing the cingulate gyrus, the inferior frontal gyrus, the thalamus, and the brainstem. To the authors' knowledge, the stronger functional thalamocingulate connectivity in post-termination women is the first in vivo demonstration of an involvement of the neural maternal attachment network in grief after the loss of an unborn child.

2. [No authors listed]
Coping with loss. A look at grief and the grieving process
Mayo Clin Womens Healthsource. 2009 Dec;13(12):1-2

Miscarriage/Stillbirth/Prenatal Issues

1. Heuser C, Manuck T, Hossain S, Silver R, Varner M
Non-anomalous stillbirth by gestational age: Trends differ based on method of epidemiologic calculation
J Matern Fetal Neonatal Med. 2009 Nov 3. [Epub ahead of print]

Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah, USA.

Objective. The objective of the study is to compare gestational age specific rates, risks and prospective risks of stillbirth. Methods. A retrospective cohort study of women with a singleton non-anomalous pregnancy was conducted. Definitions were chosen to maintain consistency with previous literature. Results. Rate was highest at 20 weeks, nadired at 41 weeks and rose thereafter. Risk was low earlier in gestation, nadired at 29 weeks and rose with increasing gestational age. Prospective risk was highest at 20 weeks, nadired at 40 weeks and rose at 42 weeks. Conclusions. Differences in trends of stillbirth are noted depending on the calculation. All of these calculations are useful in clinical practice.

2. Fretts RC
The study of stillbirth
Am J Obstet Gynecol. 2009 Nov;201(5):429-30

Comment on Am J Obstet Gynecol. 2009 Nov;201(5):469.e1-8.

3. Holm Tveit JV, Saastad E, Stray-Pedersen B, Børdahl PE, Frøen JF
Maternal characteristics and pregnancy outcomes in women presenting with decreased fetal movements in late pregnancy
Acta Obstet Gynecol Scand. 2009 Nov 2. [Epub ahead of print]

Division of Obstetrics and Gynecology, and Centre for Perinatal Research, Rikshospitalet University Hospital, and University of Oslo, Medical Faculty, Norway.

Abstract Objective. 'Normal' fetal activity is recognized as a sign of fetal well-being and concerns for decreased fetal movements is a frequent cause of non-scheduled antenatal visits. The aim of this study was to identify maternal characteristics in women presenting decreased fetal movements in a total population, to identify the risk of adverse outcomes and assess the management provided. Design. Prospective population-based cohort. Setting. Fourteen delivery units in Norway. Population. A total of 2,374 pregnancies presenting with a perception of decreased fetal movements and 614 control/referent cases. Methods. All singleton third trimester pregnancies presenting with a perception of decreased fetal movements were registered from June 2004 through October 2005. Pregnancies never examined for this condition were collected as a cross-sectional sample from the same population. Main outcome measures. Fetal growth restriction, preterm birth and stillbirth. Results. Mothers with decreased fetal movements were more often smokers, overweight and primiparous. Of the women, 32% presented with perceived absence of fetal movements, of whom 25% waited for more than 24 hours without any movements. Abnormal findings were identified in 16% of examinations. Decreased fetal movements were associated with adverse pregnancy outcome in 26%, including preterm birth and fetal growth restriction. An intervention or repeated consultations were performed in 41% of cases, including 14% admissions to maternity ward. None of the included hospitals had written guidelines for management. Conclusions. A perception of decreased fetal movements is significantly associated with adverse pregnancy outcome such as preterm birth, fetal growth restriction and stillbirth. Guidelines for management and information to pregnant women are needed.

4. Surkan PJ, Rådestad I, Cnattingius S, Steineck G, Dickman PW
Social support after stillbirth for prevention of maternal depression
Acta Obstet Gynecol Scand. 2009 Nov 2. [Epub ahead of print]

Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.

Abstract Objective. To study how social support is associated with ensuing maternal depression following stillbirth. Design. Data from a population-based national postal questionnaire. Setting. Sweden. Population. A total of 314 (83%) of all 380 Swedish-speaking women who gave birth to singleton stillborn infants in Sweden during 1991, identified through the Swedish Medical Birth Register. Methods. Postal questionnaires addressing maternal social support and demographics were completed three years following the stillbirth. The association between support-related factors and later maternal depression was assessed using multivariable regression models. Main outcome measure. The Center for Epidemiologic Studies Depression Scale. Results. In adjusted analyses, a father's refusal to talk about a stillborn baby with the mother was associated with an almost five-fold risk of later maternal depressive symptoms [adjusted risk ratio (RR) 4.6, 95% confidence interval (CI) 1.5-14.5]. The mother's belief that she could talk with the infant's father about the child was associated with a reduced risk (adjusted RR 0.5, 95% CI 0.1-0.9). Conclusions. Unwillingness of the father to discuss a stillborn infant with the mother was related to subsequent maternal depressive symptomatology.

5. Raca G, Artzer A, Thorson L, Huber S, Modaff P, Laffin J, Pauli RM
Array-based comparative genomic hybridization (aCGH) in the genetic evaluation of stillbirth
Am J Med Genet A. 2009 Oct 28;149A(11):2437-2443. [Epub ahead of print]

UW Cytogenetic Services, Wisconsin State Laboratory of Hygiene, Madison, Wisconsin.

This study examined the utility of array-based comparative genomic hybridization (aCGH) in detecting genetic abnormalities associated with late pregnancy loss. Comparisons were made with classic cytogenetics to test whether aCGH represents a superior methodology for the clinical evaluation of stillbirth. Stillborn infants were selected for aCGH testing from the Wisconsin Stillbirth Service Program (WiSSP) database and tissue bank, based on abnormal clinical findings (presence of at least two abnormalities of two different organs or parts of the body). aCGH analysis was successfully completed in 15 cases which met the clinical criteria and for which sufficient amount of high quality DNA was recovered from archival material. The testing was performed using commercially available 1 Mb BAC arrays. Among 15 tested stillborns, aCGH detected two abnormalities (trisomy 21 and an unbalanced translocation between chromosomes 3 and 10), for an overall detection rate of 13% in stillborns with malformations who had normal or unobtainable cytogenetic results. This preliminary study supports the clinical value of aCGH testing in diagnostic evaluation of stillborns with congenital anomalies. (c) 2009 Wiley-Liss, Inc.

6. Nowak I, Malinowski A, Tchorzewski H, Barcz E, Wilczynski JR, Grybos M, Kurpisz M, Luszczek W, Banasik M, Reszczynska-Slezak D, Majorczyk E, Wisniewski A, Senitzer D, Sun J Yao, Kusnierczyk P.
Frequencies of killer immunoglobulin-like receptor genotypes influence susceptibility to spontaneous abortion
J Appl Genet. 2009;50(4):391-398

Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.

Natural killer (NK) cells are the most abundant lymphocyte population in the decidua. These cells express killer immunoglobulin-like receptors (KIRs), which upon recognition of HLA class I molecules on trophoblasts may either stimulate NK cells (activating KIRs) or inhibit them (inhibitory KIRs) to produce soluble factors necessary for the maintenance of pregnancy. KIR genes exhibit extensive haplotype polymorphism; individuals differ in both the number and kind (activating vs. inhibitory) of KIR genes. This polymorphism affects NK cell reactivity and susceptibility to diseases, including gynecological disorders. Therefore we KIR-genotyped 149 spontaneously aborting women and 117 control multiparae (at least 2 healthy-born children). Several genotypes (i.e. combinations of various KIR genes) were differently distributed among the patients and control subjects. Differences were observed in the numbers and the ratios of activating to inhibitory KIRs between patients and healthy women: (i) genotypes containing 6 activating KIR genes were less frequent and those containing 6 inhibitory KIR genes were more frequent in patients than in control subjects, and (ii) an excess of inhibitory KIRs (activating-to-inhibitory KIR gene ratios of 0.33 to 0.83) was associated with miscarriage, whereas ratios close to equilibrium (0.86-1.25) seemed to be protective. In addition, the results suggest for the first time that sporadic and recurrent spontaneous abortions as well as miscarriage in the presence or absence of autoantibodies may have different KIR genotypic backgrounds.

7. Pearce MS, Glinianaia SV, Rankin J, Rushton S, Charlton M, Parker L, Pless-Mulloli T
No association between ambient particulate matter exposure during pregnancy and stillbirth risk in the north of England, 1962-1992
Environ Res. 2009 Oct 26. [Epub ahead of print]

Institute of Health and Society, Newcastle University, Sir James Spence Institute, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK.

OBJECTIVES: Research evidence suggests that exposure to ambient air pollutants can adversely affect the growth and development of the foetus and infant survival. Much less is known regarding the potential for an association between black smoke air pollution and stillbirth risk. This potential association was examined using data from the historical cohort UK Particulate Matter and Perinatal Events Research (PAMPER) study. METHODS: Using data from paper-based neonatal records from the two major maternity hospitals in Newcastle upon Tyne (UK), a birth record database of all singletons born during 1961-1992 to mothers resident in the city was constructed. Weekly black smoke levels were obtained from routine data recorded at 20 air pollution monitoring stations over the study period. A two-stage statistical modelling strategy was used, incorporating temporally and spatially varying covariates to estimate black smoke exposure during each trimester and for the whole pregnancy period for each individual pregnancy. Conditional logistic regression models, with stratification on year of birth, were used to assess potential associations between black smoke exposures in pregnancy and stillbirth risk. RESULTS: The PAMPER database consists of 90,537 births, between 1962 and 1992, with complete gestational age and residential address information, of which 812 were stillborn. There was no association between black smoke exposures in any trimester or across whole pregnancy and risk of stillbirth. Adjustment for potential confounders did not alter these results. CONCLUSIONS: While black smoke in pregnancy is likely to be related to other pregnancy outcomes, our findings do not suggest that black smoke air pollution exposure during pregnancy increases the risk of stillbirth.

8. Broy P, Bérard A
Gestational Exposure to Antidepressants and the Risk of Spontaneous Abortion: A Review
Curr Drug Deliv. 2009 Oct 29. [Epub ahead of print]

Sainte-Justine Hospital, Research Center, 3175, chemin de la Côte-Ste-Catherine, Montreal (Quebec) H3T 1C5, Canada. anick.berard@umontreal.ca.

Background. Although the relationship between antidepressant use during pregnancy and its adverse effects has been widely investigated, very few studies have evaluated the impact of antidepressant use during pregnancy on the risk of spontaneous abortion. We present an overview of the evidence relating to the association between antidepressant use during gestation and the risk of spontaneous abortion. Methods. We systematically searched PubMed and the reference lists of all relevant articles, including reviews, published in English or French from 1975 through 2009 for studies that examined the association between adverse pregnancy outcomes and gestational exposure to antidepressants with data on spontaneous abortions. Only etiologic studies were considered. Results. Fifteen studies met inclusion criteria. The majority of these were prospective cohort studies on tricyclics antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs) use during pregnancy. Overall, in unadjusted analyses, fluoxetine (OR = 2.0; 95% CI = 1.4 - 3.0) and bupropion (OR = 4.1; 95% CI = 1.5 - 11.1) were significantly associated with the risk of spontaneous abortion. However, in adjusted analyses, only paroxetine (OR = 1.7; 95% CI = 1.3 - 2.3) and venlafaxine (OR = 2.1; 95% CI = 1.3 - 3.3) were significantly associated with the risk of spontaneous abortion. Conclusions. This review suggests that gestational exposure to antidepressants, especially paroxetine and venlafaxine, can lead to spontaneous abortion.

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Prepared by the
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