NSIDRC Journal Article Alert — March 13, 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. Baruteau AE, Baruteau J, Joomye R, Martins R, Treguer F, Baruteau R, Daubert JC, Mabo P, Roussey M

Role of congenital long-QT syndrome in unexplained sudden infant death: proposal for an electrocardiographic screening in relatives

Eur J Pediatr. 2009 Mar 6 [Epub ahead of print]

CHU Rennes, Service de Cardiologie et Maladies Vasculaires, Rennes, 35000, France, alban.baruteau@wanadoo.fr.

INTRODUCTION: Congenital long-QT syndrome (LQTS) is a sporadic or familial inherited arrhythmia. It can lead to sudden death by ventricular fibrillation which occurs at any age but particularly during infancy. Recent studies of postmortem molecular analysis in infants who died of unexplained sudden infant death syndrome (SIDS) showed abnormal mutations to LQTS in 10% to 12%. Current methods of etiologic investigation of sudden infant death syndrome do not allow the diagnosis of LQTS. A targeted anamnesis together with systematic electrocardiograms of first- and second-degree relatives could be an efficient LQTS diagnostic tool. Therefore, we propose to include them in screening procedures for SIDS etiologies. CONCLUSION: LQTS accounts for a significant number of unexplained SIDS. We suggest adding a systematic familial electrocardiographic screening to the current etiologic investigations in order to track congenital LQTS in relatives.

2. Audero E, Gross C

Could serotonin play a role in sudden infant death?

Pediatr Res. 2009 Feb;65(2):131

3. Haas C, Braun J, Bär W, Bartsch C

No association of serotonin transporter gene variation with sudden infant death syndrome (SIDS) in Caucasians

Leg Med (Tokyo). 2009 Mar 2. [Epub ahead of print]

Institute of Legal Medicine, University Zurich, Winterthurerstrasse 190/52, 8057 Zurich, Switzerland.

Genetic studies on SIDS have been motivated by clinical, epidemiological, and/or neuropathological observations made of SIDS victims. One of the candidate genes is the serotonin transporter (5-HTT) gene, based on decreased serotonergic receptor binding observed in the brain-stems of SIDS victims. Two polymorphisms in the regulatory region of the 5-HTT gene differentially modulate gene expression (promoter, intron 2). The promoter allelic variants long (L) and extra long (XL) and the intron 2 12-repeat allele seem to be associated with SIDS; however, the 5-HTT promoter allele distribution varies widely by ethnicity. We investigated the DNA of 145 Caucasian SIDS cases and 58 controls and could find no significant association between our Caucasian SIDS cases and controls either for the promoter L allele and the intron 2 12-repeat allele, or for the combined L-12 haplotype as well as the L- or 12-containing genotypes.

Miscarriage/Stillbirth/Prenatal Issues

1. Benhadi N, Wiersinga W, Reitsma J, Vrijkotte T, Bonsel G

Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death

Eur J Endocrinol. 2009 Mar 9. [Epub ahead of print]

N Benhadi, endocrinology, Academic Medical Centre of the university of Amsterdam, Amsterdam, 1105 AZ, Netherlands.

Background: To examine the relationship between maternal Thyroid Stimulating Hormones (TSH) and free thyroxine (T4) concentrations in pregnancy and the risk of miscarriage, fetal or neonatal death. Method: Cohort study of 2497 Dutch pregnant women. TSH, free T4 and Thyroid Peroxidase Antibodies (TPO-Ab) concentrations were determined at first booking. Child loss was operationalised as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded. Results: 27 cases of child loss were observed. The mean TSH and free T4 level in the women with child loss was 1.48 mU/L and 9.82 pmol/L compared to 1.11 mU/L and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60 (95%CI: 1.04-2.47; p= 0.033) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, DM, Hypertension, previous preterm and previous stillbirth/miscarriage (AOR=1.80; 95%CI: 1.07-3.03; p=0.027). This was not true for FT4 concentrations (OR= 1.41; 95%CI; 0.21 to 9.40; P= 0.724). Conclusion: In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal free T4 concentations and child loss was not associated.

2. van Oppenraaij RH, Jauniaux E, Christiansen OB, Horcajadas JA, Farquharson RG, Exalto N; On Behalf of ESHRE Special Interest Group for Early Pregnancy (SIGEP)

Predicting adverse obstetric outcome after early pregnancy events and complications: a review

Hum Reprod Update. 2009 Mar 7. [Epub ahead of print]

Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Room Ba-226, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited orsmall uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care.

3. Gómez Ponce de León R, Wing DA

Misoprostol for termination of pregnancy with intrauterine fetal demise in the second and third trimester of pregnancy - a systematic review

Contraception. 2009 Apr;79(4):259-71. Epub 2008 Dec 9

IPAS and School of Public Health, University of North Carolina at Chapel Hill, NC 28516, USA. gomezr@ipas.org

BACKGROUND: A systematic review was conducted to compare with other methods, using the best available evidence, the benefits and risks associated with the administration of misoprostol to terminate pregnancy with fetal demise in the second and third trimesters (defined as gestational age of more than 14 weeks). STUDY DESIGN: We assessed all published randomized controlled trials identified from the Cochrane Pregnancy and Childbirth Group Trials Register, MEDLINE, POPLINE, LILACS and CINHAL from 1987 to 2008 comparing misoprostol alone (vaginal, oral or sublingual administration) with placebo or no treatment or any other method of uterine evacuation (including cervical ripening with other prostaglandins administered vaginally or extra-amniotically, oxytocin, as well as mechanical methods of evacuation including extra-amniotic Foley catheter or laminaria placement) in women with diagnosis of intrauterine fetal death in the second and third trimester of pregnancy. We also evaluated the use of misoprostol alone with misoprostol plus other adjuncts such as intravenous oxytocin. Meta-analyses were performed using relative risks (RRs) as the measure of effect size for binary outcomes and weighted mean differences for continuous outcome measures. For all data, 95% confidence intervals (CIs) were also computed. RESULTS: Fourteen studies comparing different interventions were included. The induction regimens varied considerably in the number of applications of medication, dosages and time intervals between doses. The main outcome was uterine evacuation at 48 h. In all studies evaluated, both vaginal and oral misoprostol showed 100% success rate in achieving uterine evacuation at 48 h. We also evaluated the success at achieving uterine evacuation at 24 h. Although the differences were not statistically significant and heterogeneity was observed, vaginal misoprostol was as effective as oral administration, achieving uterine evacuation within 48 h (RR=0.96, 95% CI=0.85 to 1.09). Oral administration was associated with more side effects than vaginal administration. The mean time intervals from induction to delivery were not significantly different between the vaginal and oral treatment groups [-1.97 (95% CI=-3.22 to 0.72)], so that the clinical benefit of oral administration and avoidance of repeated vaginal administration is probably marginal. Vaginal misoprostol alone was less effective in achieving uterine evacuation at 24 h compared with vaginal misoprostol plus oxytocin. However, there was no statistically significant difference (RR=1.00, 95% CI=0.89 to 1.12) in uterine evacuation at 48 h for vaginal misoprostol either with or without oxytocin administration. CONCLUSIONS: Overall, the body of evidence regarding induction of labor and delivery for second and third trimester of pregnancy is limited and the studies vary in methodology and selected outcome measures, making direct comparisons difficult. Vaginal misoprostol was less effective than oral misoprostol for effecting delivery within 24 h, but not within 48 h.

4. Wicherek L, Basta P, Pitynski K, Marianowski P, Kijowski J, Wiatr J, Majka M

The characterization of the subpopulation of suppressive B7H4(+) macrophages and the subpopulation of CD25(+) CD4(+) and FOXP3(+) regulatory T-cells in decidua during the secretory cycle phase, Arias Stella reaction, and spontaneous abortion - a preliminary report

Am J Reprod Immunol. 2009 Apr;61(4):303-12

Department of Gynecology and Oncology, Jagiellonian University, Krakow, Poland. mowicher@cyf-kr.edu.pl

PROBLEM: The presence of immunosuppressive cells within the endometrium and decidua is crucial for establishing maternal immune tolerance against fetal antigens. We decided to evaluate the subpopulations of Treg cells and B7H4 macrophages in eutopic endometrium typified by Arias Stella reaction during the development of Fallopian tube pregnancy as well as in decidua at the time of spontaneous abortion (SA), and to compare these findings to those observed in the endometrium during the secretory cycle phase of healthy women. METHOD OF STUDY: The decidual tissue samples evaluated in our study were obtained from 26 women who underwent curettage as a result of the following circumstances: five of the women because of a laparoscopic procedure necessitated by Fallopian tube pregnancy, and 11 of them because of SA. The control group consisted of 10 patients on whom curettage was preformed as an additional procedure during laparoscopic myomectomy. The presence of regulatory T-cells and B7H4-positive macrophages in the samples was analysed by fluorescence-activated cell sorter (FAC-Scan). RESULTS: Both the percentages of FOXP3(+) cells in the subpopulation of CD25(+) CD4(+) T lymphocytes and the percentage of B7H4-positive cells in the macrophage subpopulation found in the deciduae of patients suffering SA were higher than those found in eutopic endometrium with Arias Stella reaction. No such differences in the percentages of these cells were observed when the tissue samples from patients with SA were compared with those from the control group. The percentage of B7H4-positive macrophages, however, was found to be significantly lower in endometrium with Arias Stella reaction in comparison to that observed in secretory endometrium. CONCLUSION: The alterations in both the Treg cell and suppressive B7H4(+) macrophage subpopulations would seem to be related to the suppression of maternal immune cells in the endometrium at the beginning of decidualization.

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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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. Baruteau AE, Baruteau J, Joomye R, Martins R, Treguer F, Baruteau R, Daubert JC, Mabo P, Roussey M Role of congenital long-QT syndrome in unexplained sudden infant death: proposal for an electrocardiographic screening in relatives Eur J Pediatr. 2009 Mar 6 [Epub ahead of print] CHU Rennes, Service de Cardiologie et Maladies Vasculaires, Rennes, 35000, France, alban.baruteau@wanadoo.fr. INTRODUCTION: Congenital long-QT syndrome (LQTS) is a sporadic or familial inherited arrhythmia. It can lead to sudden death by ventricular fibrillation which occurs at any age but particularly during infancy. Recent studies of postmortem molecular analysis in infants who died of unexplained sudden infant death syndrome (SIDS) showed abnormal mutations to LQTS in 10% to 12%. Current methods of etiologic investigation of sudden infant death syndrome do not allow the diagnosis of LQTS. A targeted anamnesis together with systematic electrocardiograms of first- and second-degree relatives could be an efficient LQTS diagnostic tool. Therefore, we propose to include them in screening procedures for SIDS etiologies. CONCLUSION: LQTS accounts for a significant number of unexplained SIDS. We suggest adding a systematic familial electrocardiographic screening to the current etiologic investigations in order to track congenital LQTS in relatives. 2. Audero E, Gross C Could serotonin play a role in sudden infant death? Pediatr Res. 2009 Feb;65(2):131 3. Haas C, Braun J, Bär W, Bartsch C No association of serotonin transporter gene variation with sudden infant death syndrome (SIDS) in Caucasians Leg Med (Tokyo). 2009 Mar 2. [Epub ahead of print] Institute of Legal Medicine, University Zurich, Winterthurerstrasse 190/52, 8057 Zurich, Switzerland. Genetic studies on SIDS have been motivated by clinical, epidemiological, and/or neuropathological observations made of SIDS victims. One of the candidate genes is the serotonin transporter (5-HTT) gene, based on decreased serotonergic receptor binding observed in the brain-stems of SIDS victims. Two polymorphisms in the regulatory region of the 5-HTT gene differentially modulate gene expression (promoter, intron 2). The promoter allelic variants long (L) and extra long (XL) and the intron 2 12-repeat allele seem to be associated with SIDS; however, the 5-HTT promoter allele distribution varies widely by ethnicity. We investigated the DNA of 145 Caucasian SIDS cases and 58 controls and could find no significant association between our Caucasian SIDS cases and controls either for the promoter L allele and the intron 2 12-repeat allele, or for the combined L-12 haplotype as well as the L- or 12-containing genotypes. Miscarriage/Stillbirth/Prenatal Issues 1. Benhadi N, Wiersinga W, Reitsma J, Vrijkotte T, Bonsel G Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death Eur J Endocrinol. 2009 Mar 9. [Epub ahead of print] N Benhadi, endocrinology, Academic Medical Centre of the university of Amsterdam, Amsterdam, 1105 AZ, Netherlands. Background: To examine the relationship between maternal Thyroid Stimulating Hormones (TSH) and free thyroxine (T4) concentrations in pregnancy and the risk of miscarriage, fetal or neonatal death. Method: Cohort study of 2497 Dutch pregnant women. TSH, free T4 and Thyroid Peroxidase Antibodies (TPO-Ab) concentrations were determined at first booking. Child loss was operationalised as miscarriage, fetal or neonatal death. Women with overt thyroid dysfunction were excluded. Results: 27 cases of child loss were observed. The mean TSH and free T4 level in the women with child loss was 1.48 mU/L and 9.82 pmol/L compared to 1.11 mU/L and 9.58 pmol/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60 (95%CI: 1.04-2.47; p= 0.033) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, DM, Hypertension, previous preterm and previous stillbirth/miscarriage (AOR=1.80; 95%CI: 1.07-3.03; p=0.027). This was not true for FT4 concentrations (OR= 1.41; 95%CI; 0.21 to 9.40; P= 0.724). Conclusion: In a cohort of pregnant women without overt thyroid dysfunction, the risk of child loss increased with higher levels of maternal TSH. Maternal free T4 concentations and child loss was not associated. 2. van Oppenraaij RH, Jauniaux E, Christiansen OB, Horcajadas JA, Farquharson RG, Exalto N; On Behalf of ESHRE Special Interest Group for Early Pregnancy (SIGEP) Predicting adverse obstetric outcome after early pregnancy events and complications: a review Hum Reprod Update. 2009 Mar 7. [Epub ahead of print] Division of Obstetrics and Prenatal Medicine, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Room Ba-226, PO Box 2040, 3000 CA Rotterdam, The Netherlands. BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited orsmall uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care. 3. Gómez Ponce de León R, Wing DA Misoprostol for termination of pregnancy with intrauterine fetal demise in the second and third trimester of pregnancy - a systematic review Contraception. 2009 Apr;79(4):259-71. Epub 2008 Dec 9 IPAS and School of Public Health, University of North Carolina at Chapel Hill, NC 28516, USA. gomezr@ipas.org BACKGROUND: A systematic review was conducted to compare with other methods, using the best available evidence, the benefits and risks associated with the administration of misoprostol to terminate pregnancy with fetal demise in the second and third trimesters (defined as gestational age of more than 14 weeks). STUDY DESIGN: We assessed all published randomized controlled trials identified from the Cochrane Pregnancy and Childbirth Group Trials Register, MEDLINE, POPLINE, LILACS and CINHAL from 1987 to 2008 comparing misoprostol alone (vaginal, oral or sublingual administration) with placebo or no treatment or any other method of uterine evacuation (including cervical ripening with other prostaglandins administered vaginally or extra-amniotically, oxytocin, as well as mechanical methods of evacuation including extra-amniotic Foley catheter or laminaria placement) in women with diagnosis of intrauterine fetal death in the second and third trimester of pregnancy. We also evaluated the use of misoprostol alone with misoprostol plus other adjuncts such as intravenous oxytocin. Meta-analyses were performed using relative risks (RRs) as the measure of effect size for binary outcomes and weighted mean differences for continuous outcome measures. For all data, 95% confidence intervals (CIs) were also computed. RESULTS: Fourteen studies comparing different interventions were included. The induction regimens varied considerably in the number of applications of medication, dosages and time intervals between doses. The main outcome was uterine evacuation at 48 h. In all studies evaluated, both vaginal and oral misoprostol showed 100% success rate in achieving uterine evacuation at 48 h. We also evaluated the success at achieving uterine evacuation at 24 h. Although the differences were not statistically significant and heterogeneity was observed, vaginal misoprostol was as effective as oral administration, achieving uterine evacuation within 48 h (RR=0.96, 95% CI=0.85 to 1.09). Oral administration was associated with more side effects than vaginal administration. The mean time intervals from induction to delivery were not significantly different between the vaginal and oral treatment groups [-1.97 (95% CI=-3.22 to 0.72)], so that the clinical benefit of oral administration and avoidance of repeated vaginal administration is probably marginal. Vaginal misoprostol alone was less effective in achieving uterine evacuation at 24 h compared with vaginal misoprostol plus oxytocin. However, there was no statistically significant difference (RR=1.00, 95% CI=0.89 to 1.12) in uterine evacuation at 48 h for vaginal misoprostol either with or without oxytocin administration. CONCLUSIONS: Overall, the body of evidence regarding induction of labor and delivery for second and third trimester of pregnancy is limited and the studies vary in methodology and selected outcome measures, making direct comparisons difficult. Vaginal misoprostol was less effective than oral misoprostol for effecting delivery within 24 h, but not within 48 h. 4. Wicherek L, Basta P, Pitynski K, Marianowski P, Kijowski J, Wiatr J, Majka M The characterization of the subpopulation of suppressive B7H4(+) macrophages and the subpopulation of CD25(+) CD4(+) and FOXP3(+) regulatory T-cells in decidua during the secretory cycle phase, Arias Stella reaction, and spontaneous abortion - a preliminary report Am J Reprod Immunol. 2009 Apr;61(4):303-12 Department of Gynecology and Oncology, Jagiellonian University, Krakow, Poland. mowicher@cyf-kr.edu.pl PROBLEM: The presence of immunosuppressive cells within the endometrium and decidua is crucial for establishing maternal immune tolerance against fetal antigens. We decided to evaluate the subpopulations of Treg cells and B7H4 macrophages in eutopic endometrium typified by Arias Stella reaction during the development of Fallopian tube pregnancy as well as in decidua at the time of spontaneous abortion (SA), and to compare these findings to those observed in the endometrium during the secretory cycle phase of healthy women. METHOD OF STUDY: The decidual tissue samples evaluated in our study were obtained from 26 women who underwent curettage as a result of the following circumstances: five of the women because of a laparoscopic procedure necessitated by Fallopian tube pregnancy, and 11 of them because of SA. The control group consisted of 10 patients on whom curettage was preformed as an additional procedure during laparoscopic myomectomy. The presence of regulatory T-cells and B7H4-positive macrophages in the samples was analysed by fluorescence-activated cell sorter (FAC-Scan). RESULTS: Both the percentages of FOXP3(+) cells in the subpopulation of CD25(+) CD4(+) T lymphocytes and the percentage of B7H4-positive cells in the macrophage subpopulation found in the deciduae of patients suffering SA were higher than those found in eutopic endometrium with Arias Stella reaction. No such differences in the percentages of these cells were observed when the tissue samples from patients with SA were compared with those from the control group. The percentage of B7H4-positive macrophages, however, was found to be significantly lower in endometrium with Arias Stella reaction in comparison to that observed in secretory endometrium. CONCLUSION: The alterations in both the Treg cell and suppressive B7H4(+) macrophage subpopulations would seem to be related to the suppression of maternal immune cells in the endometrium at the beginning of decidualization. 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 — March 13, 2009

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