NSIDRC Journal Article Alert — June 13, 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. D'Errico S, Neri M, Riezzo I, Rossi G, Pomara C, Turillazzi E, Fineschi V
beta-Tryptase and quantitative mast-cell increase in a sudden infant death following hexavalent immunization
Forensic Sci Int. 2008 Jun 5. [Epub ahead of print]

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

The association between sudden infant death syndrome and immunization is frequently discussed. Serious adverse events following vaccination have generally been defined as those adverse events that result in permanent disability, hospitalization or prolongation of hospitalization, life threatening illness, congenital anomaly or death. They are generally referred to the inherent properties of the vaccine (vaccine reaction) or some error in the immunization process (programme error).The event could also be totally unrelated but only temporally linked to immunization (coincidental event). A fatal case of a 3-month-old female infant, who died within 24h of vaccination with hexavalent vaccine is presented. Clinical data, post-mortem findings (acute pulmonary oedema, acute pulmonary emphysema), quali-quantitative data collected from immunohistochemical staining (degranulating mast cells) and laboratory analysis with a high level of beta-tryptase in serum, 43.3mug/l, allows us to conclude that acute respiratory failure likely due to post hexavalent immunization-related shock was the cause of death.

2. Stray-Pedersen A, Vege A, Rognum TO
Helicobacter pylori antigen in stool is associated with SIDS and sudden infant deaths due to infectious disease
Pediatr Res. 2008 Jun 4. [Epub ahead of print]

Institute of Forensic Medicine, University of Oslo, N-0027 Oslo, Norway.

Infection with Helicobacter pylori has been proposed to be a common cause of Sudden Infant Death Syndrome, SIDS. We investigated the frequency of H. pylori infection in 160 infant deaths and 156 live controls by means of the HpSA immunoassay. Histology was performed in 26 randomly selected cases. H. pylori antigen was detected in 8% (12/156) of the live controls compared to 25% (30/122) of SIDS cases (p<0.001), 53% (9/17) of deaths due to infection (p<0.001) and 9% (1/11) of accidental/violent deaths (p=0.60). In the classic age peak for SIDS, 1-5 months, 31 % (21/67) of SIDS cases were HpSA positive compared to 1.5 % (1/68) of live controls (p<0.001). Rod-like immunoperoxidase positive H. pylori organisms were identified in 7/12 HpSA positive gastric antrum sections compared to 2/14 HpSA negative (p=0.038). Significantly elevated IL-6 levels in cerebrospinal fluid representing signs of central immune stimulation were demonstrated in HpSA positive SIDS victims compared to HpSA negative victims (p=0.045). Detection of H. pylori antigen in stool is associated with SIDS and deaths due to infections. We hypothesize that H. pylori infection in infancy may be involved as the triggering pathogen for sudden death during the first five months after birth.

3. Klintschar M, Reichenpfader B, Saternus KS
A Functional Polymorphism in the Tyrosine Hydroxylase Gene Indicates a Role of Noradrenalinergic Signaling in Sudden Infant Death Syndrome
J Pediatr. 2008 Apr 2. [Epub ahead of print]

Institute of Legal Medicine, Georg August University Göttingen, Austria; the Institute of Legal Medicine, Martin Luther-University Halle-Wittenberg, Austria.

OBJECTIVES: Catecholamines may contribute to the cause of sudden infant death syndrome (SIDS). TH01, a tetrameric short tandem repeat marker in the tyrosine hydroxylase gene, regulates gene expression and catecholamine production. STUDY DESIGN: We investigated TH01 in 172 German Caucasian SIDS cases and 390 sex- and age-matched control subjects. RESULTS: The *9.3 alleles were more frequent in patients with SIDS than in control subjects (40.12% vs 31.15%; P = .006). For homozygotes the odds ratio was 1.83 (95% confidence interval: 1.09-3.05), for carriers 1.58 (1.09-2.28). Moreover, *9.3 alleles were significantly more frequent during the winter (47.73% vs 35.38% in the warmer seasons), and the frequency of *9.3 alleles varied significantly with the age at death (weeks 7 to 12: 49.04% vs 29.63% within the first 6 weeks). Other risk factors (sleeping position, gestation, smoking) had no significant impact on the frequency of *9.3. CONCLUSIONS: Our results indicate a relationship between SIDS and TH01 genotype, presumably caused by an impairment of breathing regulation or arousal. We propose that noradrenalinergic neuronal activity contributes to the cause of a major subset of SIDS victims. Moreover, the results further stress that SIDS is a highly heterogenic group.

4. McKinney CM, Holt VL, Cunningham ML, Leroux BG, Starr JR
Maternal and Infant Characteristics Associated with Prone and Lateral Infant Sleep Positioning in Washington State, 1996-2002
J Pediatr. 2008 Mar 26. [Epub ahead of print]

Dallas Regional Campus, University of Texas Houston School of Public Health (C.M.), Houston, TX.

OBJECTIVE: To identify factors predictive of either lateral or prone infant sleep positioning. STUDY DESIGN: We used data for 11340 mother-infant pairs from the Pregnancy Risk Assessment Monitoring System for infants born in Washington State, 1996 to 2002. We used predictive modeling to identify statistically significant (P < .05) predictors of lateral and prone sleep positioning. RESULTS: Factors associated with both high-risk sleep positions included infant's year of birth, maternal race and ethnicity, maternal county of residence, and maternal parity. Mother's being US-born (versus foreign-born) and male infant sex were predictive only of prone sleep positioning. Having Medicaid as primary insurance, receipt of government benefits, low infant gestational age, and low birth weight were predictive only of lateral sleep positioning. CONCLUSIONS: Factors predictive of either high-risk sleep position should be considered when devising public health intervention strategies for the prevention of SIDS.

5. Chang RK, Keens TG, Rodriguez S, Chen AY
Sudden Infant Death Syndrome: Changing Epidemiologic Patterns in California 1989-2004
J Pediatr. 2008 May 24. [Epub ahead of print]

Division of Cardiology (R.C., S.R.), Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA.

OBJECTIVE: To evaluate the changes of sudden infant death syndrome (SIDS) epidemiology in California. STUDY DESIGN: We used 1989 to 2004 California statewide death registry data. SIDS cases were selected by "age of decedent" <1 year and "cause of death" listed as SIDS. RESULTS: We identified 6303 cases (61% males) of SIDS. SIDS incidence rate decreased by 77%, from 1.38 per 1000 births in 1989 to 0.31 per 1000 births in 2004. No further decrease in SIDS incidence was noted from 2002 to 2004. The incidence rate was highest among blacks (2.02 per 1000 births) and lowest in Asian/Pacific Islanders (0.46 per 1000 births). The overall median age at death was 82 days, with no significant change over time. However, the peak age at death shifted from 2 months of age in 1989 to 2001 to 3 months of age in 2002 to 2004. Seasonal variation in the incidence of SIDS was attenuated. The difference in incidence rates between weekdays and weekends increased over the study period. CONCLUSIONS: The incidence rate of SIDS declined in California from 1989 to 2001, with no further decline after 2002. Several epidemiologic changes were noted: The peak age of SIDS death shifted from 2 months to 3 months of age; seasonal variation diminished; and weekday to weekend difference became more pronounced.

Miscarriage/Stillbirth/Prenatal Issues

1. 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.

2. 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 7. [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.

3. Mehta S, Manji KP, Young AM, Brown ER, Chasela C, Taha TE, Read JS, Goldenberg RL, Fawzi WW
Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women
Am J Clin Nutr. 2008 Jun;87(6):1639-49

Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. smehta@hsph.harvard.edu

BACKGROUND: Poor nutrition may be associated with mother-to-child transmission (MTCT) of HIV and other adverse pregnancy outcomes. OBJECTIVE: The objective was to examine the relation of nutritional indicators with adverse pregnancy outcomes among HIV-infected women in Tanzania, Zambia, and Malawi. DESIGN: Body mass index (BMI; in kg/m(2)) and hemoglobin concentrations at enrollment and weight change during pregnancy were prospectively related to fetal loss, neonatal death, low birth weight, preterm birth, and MTCT of HIV. RESULTS: In a multivariate analysis, having a BMI < 21.8 was significantly associated with preterm birth [odds ratio (OR): 1.82; 95% CI: 1.34, 2.46] and low birth weight (OR: 2.09; 95% CI: 1.41, 3.08). A U-shaped relation between weight change during pregnancy and preterm birth was observed. Severe anemia was significantly associated with fetal loss or stillbirth (OR: 3.67; 95% CI: 1.16, 11.66), preterm birth (OR: 2.08; 95% CI: 1.39, 3.10), low birth weight (OR: 1.76; 95% CI: 1.07, 2.90), and MTCT of HIV by the time of birth (OR: 2.26; 95% CI: 1.18, 4.34) and by 4-6 wk among those negative at birth (OR: 2.33; 95% CI: 1.15, 4.73). CONCLUSIONS: Anemia, poor weight gain during pregnancy, and low BMI in HIV-infected pregnant women are associated with increased risks of adverse infant outcomes and MTCT of HIV. Interventions that reduce the risk of wasting or anemia during pregnancy should be evaluated to determine their possible effect on the incidence of adverse pregnancy outcomes and MTCT of HIV.

4. Bersinger NA, Wunder DM, Birkhäuser MH, Mueller MD
Gene expression in cultured endometrium from women with different outcomes following IVF
Mol Hum Reprod. 2008 Jun 6. [Epub ahead of print]

Department of Obstetrics and Gynaecology, Inselspital, Berne University Hospital, and University of Berne, Switzerland.

Estradiol and progesterone are crucial for the acquisition of receptivity and the change in transcriptional activity of target genes in the implantation window. The aim of this study was to differentiate the regulation of genes in the endometrium of patients with recurrent implantation failure (IF) versus those who became pregnant after IVF treatment. Moreover, the effect of embryo-derived factors on endometrial transcriptional activity was studied. Nine women with known IVF outcome (IF, M=Miscarriage, OP=ongoing pregnancy) and undergoing hysteroscopy with endometrial biopsy were enrolled. Biopsies were taken during the midluteal phase. After culture in presence of embryo-conditioned IVF media, total RNA was extracted and submitted to reverse transcription, target cDNA synthesis, biotin labelling, fragmentation, and hybridisation using the Affymetrix Human Genome U133A 2.0 Chip. Differential expression of selected genes was re-analysed by quantitative PCR, in which the results were calculated as threshold cycle differences between the groups and normalised to GAPDH and beta-actin. Differences were seen for several genes from endometrial tissue between the IF and the pregnancy groups, and when comparing OP with M, 1875 up- and 1807 downregulated genes were returned. Real-time PCR analysis confirmed upregulation for somatostatin, PLAP-2, mucin 4, and CD163, and downregulation of glycodelin, IL-24, CD69, leukaemia inhibitory factor, and prolactin receptor between Op and M. When the different embryo conditioned media were compared, no significant differential regulation could be demonstrated. Although microarray profiling may currently not be sensitive enough for studying the effects of embryo-derived factors on the endometrium, the observed differences in gene expression between M and OP, suggest that it will become an interesting tool for the identification of fertility relevant markers produced by the endometrium.

5. Saravelos SH, Cocksedge KA, Li TC
Prevalence and diagnosis of congenital uterine anomalies in women with reproductive failure: a critical appraisal
Hum Reprod Update. 2008 Jun 6. [Epub ahead of print]

Reproductive Medicine and Surgery Unit, University of Sheffield, Sheffield Teaching Hospitals, Jessop Wing, Tree Root Walk, Sheffield S10 2SF, UK.

BACKGROUND The prevalence of congenital uterine anomalies in women with reproductive failure remains unclear, largely due to methodological bias. The aim of this review is to assess the diagnostic accuracy of different methodologies and estimate the prevalence of congenital uterine anomalies in women with infertility and recurrent miscarriage (RM). METHODS Studies from 1950 to 2007 were identified through a MEDLINE search; all relevant references were further reviewed. RESULTS The most accurate diagnostic procedures are combined hysteroscopy and laparoscopy, sonohysterography (SHG) and possibly three-dimensional ultrasound (3D US). Two-dimensional ultrasound (2D US) and hysterosalpingography (HSG) are less accurate and are thus inadequate for diagnostic purposes. Preliminary studies (n = 24) suggest magnetic resonance imaging (MRI) is a relatively sensitive tool. A critical analysis of studies suggests that the prevalence of congenital uterine anomalies is approximately 6.7% [95% confidence interval (CI), 6.0-7.4] in the general population, approximately 7.3% (95% CI, 6.7-7.9) in the infertile population and approximately 16.7% (95% CI, 14.8-18.6) in the RM population. The arcuate uterus is the commonest anomaly in the general and RM population. In contrast, the septate uterus is the commonest anomaly in the infertile population, suggesting a possible association. CONCLUSIONS Women with RM have a high prevalence of congenital uterine anomalies and should be thoroughly investigated. HSG and/or 2D US can be used as an initial screening tool. Combined hysteroscopy and laparoscopy, SHG and 3D US can be used for a definitive diagnosis. The accuracy and practicality of MRI remains unclear.

6. Feki M, Omar S, Menif O, Tanfous NB, Slimane H, Zouari F, Rezigua H, Chelly H, Kaabachi N
Thyroid disorders in pregnancy: Frequency and association with selected diseases and obstetrical complications in Tunisian women
Clin Biochem. 2008 May 24. [Epub ahead of print]

Laboratory of Biochemistry and Service of Endocrinology, Rabta Hospital, Tunis, Tunisia

OBJECTIVE: To determine the prevalence of thyroid disorders (TDs) and identify groups at risk for TDs in Tunisian pregnant women. METHODS: Thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase antibodies (TPO-Ab) were determined in 1519 pregnant women. Thyroid disorder was defined as hyperthyroidism (TSH</=0.10 mIU/L) or hypothyroidism (TSH>4.5 mIU/L), and/or positive TPO-Ab (>12 IU/L). RESULTS: TDs were observed in 147 women (9.7%). The prevalence was 6.5%, 3.2% and 1.3% for positive anti-TPO, hypothyroidism and hyperthyroidism, respectively. According to a trimester of gestation (first, second, and third, respectively), the prevalence decreases for positive TPO-Ab (7.7%, 7.5% and 4.7%) and for hyperthyroidism (2.7%, 0.7% and 0.5%), but increases for hypothyroidism (2.2%, 3.3% and 3.7%). TDs were more frequent in women with non-thyroid autoimmune disease [25% vs 9.6%; odds ratio (OR), 95% confidence interval (95% CI), 3.16 (1.01-11.8); p=0.05]. Women with positive TPO-Ab showed higher prevalence of non-thyroid autoimmune disease [25% vs 6.4%; OR (95% CI), 4.90 (1.31-18.4); p=0.04] and a trend toward increase of past gestational hypertension (p=0.09), late abortion (p=0.09), and fetal death (p=0.09). Hypothyroidism was more frequent in women with non-thyroid autoimmune disease and those with past pregnancy loss. CONCLUSIONS: TDs are common in Tunisian pregnant women and are associated with autoimmune diseases and poor gestational outcomes. These data support the benefit of thyroid testing in pregnant women, especially those with these conditions.

7. Chen XK, Wen SW, Fleming N, Yang Q, Walker MC
Increased risks of neonatal and postneonatal mortality associated with teenage pregnancy had different explanations
J Clin Epidemiol. 2008 Jul;61(7):688-94. Epub 2008 Mar 10

OMNI Research Group, Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6; Clinical Epidemiology Program, Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada K1H 8L6.

OBJECTIVE: To determine the potential pathway of the association between teenage pregnancy and neonatal and postneonatal mortality. STUDY DESIGN AND SETTING: We carried out a retrospective cohort study of 4,037,009 nulliparous pregnant women under 25 years old who had a live singleton birth during 1995 to 2000, based on linked birth and infant death data set of the United States. RESULTS: Teenage pregnancy (10-19 years old) was associated with increased neonatal mortality (odds ratio [OR]: 1.20, 95% confidence interval [CI]=1.16-1.24) and postneonatal mortality (OR: 1.47, 95% CI=1.41-1.54) after adjustment for potential confounders. With further adjustment for weight gain during pregnancy, teenage pregnancy was still associated with increased risk of neonatal (OR: 1.23, 95% CI=1.19-1.28) and postneonatal mortality (OR: 1.48, 95% CI=1.42-1.55). When adjustment was made for gestational age at birth, there was no association of teenage pregnancy with neonatal mortality (OR: 0.98, 95% CI=0.95-1.02), whereas there was significant association with postneonatal mortality (OR: 1.40, 95% CI=1.34-1.46). CONCLUSION: The increased risk of neonatal death associated with teenage pregnancy is largely attributable to higher risk of preterm births, whereas increased postneonatal mortality is independent of the known confounders and gestational age at birth.

8. Towers CV, Carr MH
Antenatal fetal surveillance in pregnancies complicated by fetal gastroschisis
Am J Obstet Gynecol. 2008 Jun;198(6):686.e1-5; discussion 686.e5

Division of Maternal-Fetal Medicine, Long Beach Memorial Women's Hospital, Long Beach, CA, USA. drtowers@rbcpress.com

OBJECTIVE: The purpose of this study was to determine if antenatal fetal surveillance should be considered in pregnancies complicated by fetal gastroschisis, and if so, what gestational age should testing begin. STUDY DESIGN: During an 18-year period, all pregnancies delivered of a newborn that had gastroschisis were identified. Numerous data parameters were collected, including gestational age at delivery, birthweight, indication for delivery, antenatal testing results if performed, and neonatal outcome. Fetal compromise was defined as stillbirth or moderate to severe arterial cord blood gas acidosis at the time of delivery (pH < 7.10). RESULTS: During the study period, 84 pregnancies complicated by fetal gastroschisis were delivered from 117,564 gestations. Antenatal testing was performed in 58 cases (69%). Of the 26 (31%) without antenatal testing, 17 had an antenatal diagnosis of gastroschisis and in 9, the diagnosis was made on the day of delivery. In the 17 with an antenatal diagnosis, there were 2 stillbirths (29(4/7) and 31(3/7) weeks' gestation) and 1 was delivered with a moderate to severe arterial cord blood gas acidosis at 29(5/7) weeks' gestation. An additional case of moderate to severe arterial cord blood gas acidosis occurred in the 9 cases where the diagnosis was made on the day of delivery. Of the 58 pregnancies with antenatal surveillance, there were no stillbirths and no cases with a moderate to severe arterial cord blood gas acidosis. Of these 58 cases, 22 (38%) were delivered based on an abnormal testing result. Of the 84 total cases, 32 (38%) had birthweights < 10th percentile, and of these, 16 (19%) had birthweights < 3rd percentile. CONCLUSION: Based on these data, antenatal fetal surveillance may be warranted in pregnancies complicated by fetal gastroschisis beginning at a gestational age of 28 to 29 weeks. Fetal testing between the thresholds of viability up to 28 weeks' gestation would be controversial.

9. Ban-Frangež H, Tomaževic( T, Virant-Klun I, Verdenik I, Ribic(-Pucelj M, -Bokal EV
The outcome of singleton pregnancies after IVF/ICSI in women before and after hysteroscopic resection of a uterine septum compared to normal controls
Eur J Obstet Gynecol Reprod Biol. 2008 Jun 2. [Epub ahead of print]

Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Šlajmerjeva 3, SI-1000 Ljubljana, Slovenia.

OBJECTIVE(S): To evaluate the effect of hysteroscopic resection of a large uterine septum (Class V according to the American Fertility Society (AFS) classification) and of a small partial uterine septum (Class VI according to AFS classification or arcuate uterus) on the abortion rate in pregnancies after IVF and ICSI. STUDY DESIGN: The retrospective matched control study included 31 women who conceived following IVF or ICSI before hysteroscopic resection of a large (12 women) or small partial (19 women) uterine septum and 106 women who conceived following IVF or ICSI after hysteroscopic resection of a large (49 women) or small partial (57 women) uterine septum. For each pregnancy in the study group, we found two consecutive pregnant control women from the IVF/ICSI registry who had a normal uterus and were matched for age, BMI, stimulation protocol and the use of IVF or ICSI and for various infertility causes. The abortion/pregnancy rate was the main outcome measure. Data on the septum length were obtained during hysteroscopic resection by comparing the length of the 1.4cm long yellow tip of the electric knife to the length of the resected septum. RESULTS: The abortion rate before hysteroscopic metroplasty was significantly higher, both in women with a small partial septum (78.9% before resection vs. 23.7% in the normal controls, OR 12.08) and a large septum (83.3% before resection vs. 16.7% in normal controls, OR 25.00) compared to women with a normal uterus. After the surgery, the abortion rate was comparable to the abortion rate in women with normal uterus: in both women with a small partial and women with a larger septum. CONCLUSION(S): Similar to a large uterine septum, a small partial uterine septum is an important and hysteroscopically preventable risk factor for spontaneous abortion in pregnancies after IVF and ICSI.

10. Salmon JE, Girardi G
Theodore E. Woodward Award: antiphospholipid syndrome revisited: a disorder initiated by inflammation
Trans Am Clin Climatol Assoc. 2007;118:99-114

Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. salmonj@hss.edu.

The antiphospholipid syndrome (APS), characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies, is a leading cause of miscarriage and maternal and fetal morbidity. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Given that the primary treatment for APS patients is anticoagulation throughout pregnancy, usually with sub-anticoagulant doses of heparin, we considered the possibility that heparin prevents pregnancy loss by inhibiting complement. We found that heparin inhibits activation of complement on trophoblasts in vivo and in vitro and that anticoagulation, in and of itself, is not sufficient to prevent pregnancy complications in our experimental model of APS. Our studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and emphasize the importance of developing and testing targeted complement inhibitory therapy for patients with APS.

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