NSIDRC Journal Article Alert — June 20, 2008

Prepared by the National Sudden Infant Death 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 NSIDRC 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. Turillazzi E, La Rocca G, Anzalone R, Corrao S, Neri M, Pomara C, Riezzo I, Karch SB, Fineschi V
Heterozygous nonsense SCN5A mutation W822X explains a simultaneous sudden infant death syndrome
Virchows Arch. 2008 Jun 13. [Epub ahead of print]

Department of Forensic Pathology, University of Foggia, Ospedale Colonnello D’Avanzo, Viale degli Aviatori 1, 71100, Foggia, Italy.

The sudden, unexpected, and unexplained death of both members of a set of healthy twins (simultaneous sudden infant death syndrome (SSIDS)) is defined as a case in which both infants meet the definition of sudden infant death syndrome individually. A search of the world medical literature resulted in only 42 reported cases of SSIDS. We report the case of a pair of identical, male, monozygotic twins, 138 days old, who suddenly died, meeting the full criteria of SSIDS and where a genetic screen was performed, resulting in a heterozygous nonsense SCN5A mutation (W822X) in both twins. Immunohistochemistry was performed on cardiac tissue samples utilizing polyclonal antibodies anti-Na(+) CP type Valpha (C-20) and a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay. The cellular localization of the Na(+) CP type Valpha (C-20) demonstrated by confocal microscopy on staining pattern of myocytes was concentrated in the intercalated disks of ventricular myocytes. These findings suggest that defective ion channels represent viable candidates for the pathogenesis of SIDS and, obviously, of SSIDS, supporting a link between sudden infant death syndrome and cardiac channelopathies.

Other Infant Death

1. Paintlia MK, Paintlia AS, Singh AK, Singh I
Attenuation of Lipopolysaccharide Induced Inflammatory Response and Phospholipids Metabolism at the Feto-Maternal Interface by N-Acetyl-Cysteine
Pediatr Res. 2008 Jun 11. [Epub ahead of print]

Department of Pediatrics [M.K.P., A.S.P., I.S.]; Department of Pathology and Laboratory Medicine [A.K.S.], Medical University of South Carolina, Charleston, South Carolina 29425.

Maternal microbial infections cause adverse fetal developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Recent studies demonstrated that oxidative-stress plays an important role in chorioamniotitis pathogenesis. Herein we investigated the effect of N-acetyl cysteine (NAC) on lipopolysaccharide-induced preterm labor and fetal demise in murine model. Lipopolysaccharide exposure at embryonic day 18 demonstrated an increase in the abortion rate and fetal demise in pregnant dams. This was associated with increase in an inflammatory response (cytokines, chemokines and iNOS expression) and infiltration of leukocytes (monocytes and polymorphonuclear cells) in the placenta. There was increased expression of cytosolic and secretary phospholipase A2 with increased secretion of prostaglandin-2 and leukotriene B4 in the placenta, suggestive of increased metabolism of phospholipids. In addition, expression of cycloxygenase-2 and malondialdehyde production (oxidative-stress marker) was increased in the placenta. Conversely, NAC pretreatment abolished these effects of lipopolysaccharide in the placenta. Collectively, these data provide evidence that LPS-induced increased inflammation and metabolism of phospholipids at the feto-maternal interface (placenta) is critical for preterm labor and fetal demise during maternal microbial infections which could be blocked by antioxidant-based therapies.

Bereavement

1. Engelkemeyer SM, Marwit SJ
Posttraumatic growth in bereaved parents
J Trauma Stress. 2008 Jun 13;21(3):344-346. [Epub ahead of print]

University of Missouri-St. Louis, St. Louis, MO.

The Posttraumatic Growth Inventory (PTGI), Revised Grief Experience Inventory, and World Assumptions Scale were administered to 111 bereaved parents. The PTGI scores indicate that many bereaved parents report personal growth in domains outlined by L.G. Calhoun and R. G. Tedeschi (2001). Grief intensity was inversely correlated with growth scores. Self-worth was a strong predictor of growth scores, whereas assumptions about the benevolence and meaningfulness of the world were not correlated with growth.

Miscarriage/Stillbirth/Prenatal Issues

1. Kaptan K, Beyan C, Ifran A, Pekel A
Platelet-derived microparticle levels in women with recurrent spontaneous abortion
Int J Gynaecol Obstet. 2008 Jun 10. [Epub ahead of print]

Department of Hematology, Gülhane Military Medical Academy, Ankara, Turkey.

OBJECTIVE: To investigate the significance of platelet-derived microparticles (PMPs) in women with recurrent spontaneous abortion. METHODS: We measured platelet P-selectin (CD62P) as a platelet activation marker and CD42b(+) microparticles as PMPs by flow cytometry in whole blood of 20 women with recurrent spontaneous abortion and 20 age-matched healthy controls with no previous history of spontaneous abortion. RESULTS: PMP levels in women with recurrent spontaneous abortion were higher than in women in the control group (4.79+/-1.18% vs 3.06+/-0.92%; P<0.000). CD62P levels were not significantly higher in the study group compared with the control group (13.78+/-8.62% vs 10.78+/-7.35%; P>0.05). CONCLUSION: Our findings suggest that PMPs may have a role in the pathogenesis of recurrent spontaneous abortion.

2. Antinori M, Licata E, Dani G, Cerusico F, Versaci C, d'Angelo D, Antinori S
Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial
Reprod Biomed Online. 2008 Jun;16(6):835-41

RAPRUI Day Hospital (International Associated Research Institute for Human Reproduction), Via Timavo 2, Rome, Italy. monica.antinori@raprui.com.

The aim of this prospective randomized study was to assess the advantages of a new modified intracytoplasmic sperm injection (ICSI) technique called intracytoplasmic morphologically selected sperm injection (IMSI) over the conventional ICSI procedure in the treatment of patients with severe oligoasthenoteratozoospermia. The new procedure consisted of IMSI based on a preliminary motile sperm organellar morphology examination under x6600 high magnification. A total of 446 couples with at least two previous diagnoses of severe oligoasthenoteratozoospermia, 3 years of primary infertility, the woman aged 35 years or younger, and an undetected female factor were randomized to IVF micro-insemination treatments: ICSI (n = 219; group 1) and IMSI (n = 227; group 2). A comparison between the two different techniques was made in terms of pregnancy, miscarriage and implantation rates. The data showed that IMSI resulted in a higher clinical pregnancy rate (39.2% versus 26.5%; P = 0.004) than ICSI when applied to severe male infertility cases. Despite their initial poor reproductive prognosis, patients with two or more previous failed attempts benefited the most from IMSI in terms of pregnancy (29.8% versus 12.9%; P = 0.017) and miscarriage rates (17.4% versus 37.5%). At present, 35 healthy babies have been born following the introduction of this promising technique in daily IVF practice.

3. Matalliotakis I, Cakmak H, Sakkas D, Mahutte N, Koumantakis G, Arici A
Impact of body mass index on IVF and ICSI outcome: a retrospective study
Reprod Biomed Online. 2008 Jun;16(6):778-83

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA. matakgr@yahoo.com.

A group of 140 women with a body mass index (BMI) < or = 24 kg/m(2) undergoing 291 cycles was compared with a group of 138 women with a BMI >24 kg/m(2) in 291 cycles, with respect to duration of ovarian stimulation and dose of gonadotrophin, number of oocytes collected, cleavage and implantation rate, clinical pregnancy, miscarriage and delivery rates. Patients with a BMI > 24 kg/m(2) demonstrated a significant decrease in the number of follicles after stimulation (P = 0.01), a comparative increase in the number ampoules of gonadotrophin used (P = 0.03) and a lower number of eggs collected (P = 0.05). The mean number of embryos on days 1, 2 and 3 was significantly lower in the group with BMI > 24 kg/m(2) (P < 0.001). No significant difference was found in clinical pregnancy and miscarriage rates between the two groups. In spite of the lower response in women with BMI > 24 kg/m(2), the delivery rate per retrieval was not different (24.6 versus 24.8%). These results indicate a lower stimulation response in women with elevated BMI, but no adverse effect on IVF outcome. In relation to wellbeing, however, it is recommended that patients with a high BMI reduce their weight before IVF treatment.

4. Drago F, Broccolo F, Zaccaria E, Malnati M, Cocuzza C, Lusso P, Rebora A
Pregnancy outcome in patients with pityriasis rosea
J Am Acad Dermatol. 2008 May;58(5 Suppl 1):S78-83

Department of Endocrinological and Metabolic Sciences, Section of Dermatology, University of Genoa, Genoa, Milan. rebdermo@unige.it.

BACKGROUND: The effect of pityriasis rosea (PR) on the outcome of pregnancy has not been previously reported. OBJECTIVE: We sought to investigate the possible impact of PR in pregnant women. METHODS: In all, 38 women who developed PR during pregnancy were observed. In one of them, who developed PR at 10 weeks' gestation and aborted 2 weeks later, plasma, peripheral blood mononuclear cells, maternal skin, and placental and embryonic tissues were studied by quantitative calibrated real-time polymerase chain reaction for human herpesviruses (HHV)-6 and -7. Controls included plasma from 36 healthy blood donors, plasma and paraffin-embedded tissue sections from 12 patients with other dermatitides, and from placental and embryonic tissues from one woman who presented with a 19-week intrauterine fetal death. RESULTS: Of the 38 women, 9 had a premature delivery and 5 miscarried. In particular, 62% of the women who developed PR within 15 weeks' gestation aborted. Neonatal hypotonia, weak motility, and hyporeactivity were noted in 6 cases. In the patient studied in detail, HHV-6 DNA was detected in plasma, peripheral blood mononuclear cells, skin, and placenta and embryonic tissues, whereas HHV-7 DNA was absent. HHV-6 p41 antigen was detected by immunohistochemistry in skin lesions, placenta, and embryonic tissues. No herpesvirus DNA was detected in plasma and tissues from control subjects. LIMITATIONS: This is a case series study with a small number of patients. CONCLUSION: PR may be associated with an active HHV-6 infection. In pregnancy, PR may foreshadow premature delivery with neonatal hypotonia and even fetal demise especially if it develops within 15 weeks' gestation.

5. Bombrys AE, Neiger R, Hawkins S, Sonek J, Croom C, McKenna D, Ventolini G, Habli M, How H, Sibai B
Pregnancy outcome in isolated single umbilical artery
Am J Perinatol. 2008 Apr;25(4):239-42

Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, Ohio 45267-0526, USA.

Our objective was to determine whether the rate of small for gestational age (SGA) infants and adverse perinatal outcome are increased in pregnancies diagnosed with an isolated single umbilical artery (SUA). We compared 297 pregnancies with a SUA diagnosed on routine obstetrical ultrasound with 297 pregnancies with a three-vessel cord control. Pregnancies complicated by major fetal anomalies were excluded. The rate of SGA, fetal death, and neonatal outcomes were compared between the two groups. Data analysis were performed using the T-test and chi-square test. The sample size had 80% power to detect a 50% difference between groups assuming a SGA rate of 20% in the SUA group and 10% in the control, alpha = 0.05. Among the SUA group, in 21 neonates (7.1%) the presence of a SUA could not be confirmed by postnatal examination, and 21 (7.1%) had major congenital anomalies, leaving 255 for final analysis. In the control group, 8 of the 297 (2.7%) had major congenital anomalies, leaving 289 for final analysis. The incidence of SGA neonates was 35 of 255 (13.7%) in the isolated SUA group compared with 38 of 289 (13.1%) in the control group ( P = 0.93). The composite perinatal outcomes (fetal death and/or SGA) were also similar between the groups (16.1% versus 14.5%; P = 0.72). We concluded that pregnancies with isolated SUA have a similar rate of SGA to those with 3VC.When a SUA is identified antenatally, a targeted ultrasound is warranted to rule out associated anomalies. Serial antepartum ultrasound for fetal growth is not necessary in managing pregnancies complicated by isolated SUA.

6. Khaund A, Lumsden MA
Impact of fibroids on reproductive function
Best Pract Res Clin Obstet Gynaecol. 2008 Aug;22(4):749-60. Epub 2008 Jun 10

North Glasgow University Hospitals, Glasgow Royal and Princess Royal Maternity Hospitals, 10 Alexandra Parade, Glasgow G31 2ER, UK.

There is debate regarding whether fibroids cause infertility or if they are simply an association. However, it is possible that fibroids are responsible for 2-3% of cases of infertility. The mechanisms by which these benign tumours could cause impaired reproductive function, both in terms of difficulty conceiving and early pregnancy loss, remain unclear. Myomectomy facilitates removal of a fibroid with preservation of reproductive potential. The procedure is associated with significant risks but, overall, some studies have suggested that this surgical option increases pregnancy rates significantly in women with fibroid-associated infertility. Miscarriage rates in women with fibroids and those who have undergone myomectomy vary considerably. It appears that miscarriage rates fall after myomectomy, although the overall rates of pregnancy loss remain higher than those seen in the general population. Fibroids affect 0.1-3.9% of pregnancies, and a number of complications encountered antenatally and post partum are thought to be directly related to the presence of these benign tumours. A number of contraceptive options exist for women with fibroids, with the choice depending on patient preference and both fibroid and patient characteristics.

7. Koivunen R, Pouta A, Franks S, Martikainen H, Sovio U, Hartikainen AL, McCarthy MI, Ruokonen A, Bloigu A, Järvelin MR, Morin-Papunen L
Fecundability and spontaneous abortions in women with self-reported oligo-amenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study
Hum Reprod. 2008 Jun 10. [Epub ahead of print]

Family Federation of Finland, 90220 Oulu, Finland.

BACKGROUND Women with polycystic ovary syndrome (PCOS) suffer from anovulatory infertility and hospital-based studies suggest that they have an increased risk of spontaneous abortion. Our aim was to investigate the proportion of women, with self-reported oligo-amenorrhea and/or hirsutism in a general population, who had suffered from infertility, the percentage of them managing to conceive and their rate of spontaneous abortion. METHODS At age 31, a postal questionnaire including questions about hirsutism and oligo-amenorrhea was sent to all women from the population-based Northern Finland Birth Cohort 1966 (total n = 5889). Of these, 4535 (79.5%) answered the questionnaire, 1103 reported hirsutism and/or oligo/amenorrhea (symptomatic women) and 3420 were non-symptomatic. The fecundability ratio (FR) was defined as the probability of conception of a clinically detectable pregnancy within 12 months. RESULTS The overall pregnancy (77.7% versus 75.6%) and spontaneous abortion (19.3% versus 18.6%) rates did not differ between the two groups and the risk of spontaneous abortion was not associated with body mass index (BMI), waist-to-hip ratio (WHR) or waist circumference. Symptomatic women had suffered more often from infertility than non-symptomatic women (19.4% versus 11.1%, P < 0.01). Oligo-amenorrhea and/or hirsutism (FR = 0.74, P < 0.001) and obesity (FR = 0.68, P = 0.002) were both independently associated with decreased fecundability, but symptomatic women had become pregnant and had one or two successful deliveries as often as non-symptomatic women. CONCLUSIONS Women with self-reported oligo-amenorrhea and/or hirsutism had lower fecundability and suffered more often from infertility, but had at least one delivery as often as non-symptomatic women, and did not exhibit an increased risk of spontaneous abortion.

8. Li L, Shoji W, Oshima H, Obinata M, Fukumoto M, Kanno N
Crucial role of peroxiredoxin III in placental antioxidant defense of mice
FEBS Lett. 2008 Jun 9. [Epub ahead of print]

Department of Cell Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai 980-8575, Japan; Department of Obstetrics and Gynecology, Peking University First Hospital, 1 Xi’anmen Dajie, Xicheng District, Beijing 100034, China.

We observed frequent stillbirth in peroxiredoxin III (PrxIII) knockout maternal mice. Quantitative real time PCR (qRT-PCR) and Western-blot analysis revealed increased oxidative stress in placentas that were deficient in PrxIII. We did not find significant difference between PrxIII knockout maternal mice and wild-type littermates in hematological parameters, fetal number, and embryonic development. Nevertheless, we noticed enhanced expression of PrxI in erythrocytes of pregnant knockout mice. Our results provided in vivo evidence that PrxIII played a crucial role in placental antioxidant defense. Up-regulation of PrxI might provide a compensation that protected erythrocytes against oxidative damage.

Prepared by the
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