NSIDRC Journal Article Alert — June 27, 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. Ferrante L, Opdal SH, Vege A, Rognum TO
TNF-alpha promoter polymorphisms in sudden infant death
Hum Immunol. 2008 Jun;69(6):368-73. Epub 2008 May 9

Institute of Forensic Medicine, University of Oslo, Norway.

Several studies indicate that the immune system is stimulated in sudden infant death syndrome (SIDS). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that strongly affects the cytokine cascade. A genetic variant associated with high production of TNF-alpha may thus be of significance in the pathogenesis of SIDS. The purpose of the current study was to investigate possible relationships among the promoter polymorphisms -1031T/C, -857C/T, -308G/A, -244G/A, and -238G/A in the TNF-alpha gene and SIDS. The subjects investigated consisted of 148 SIDS cases, 56 borderline SIDS cases, 41 cases of infectious death, and 131 adult controls. When investigating each single nuclear polymorphism (SNP) separately, associations between -238GG and SIDS (p = 0.022) and between -308GA and borderline SIDS (p = 0.005) were found. There were no associations between any of the other SNPs investigated. Furthermore, a SNP profile was constructed by creating a genotype pattern from the investigated SNPs. Fifteen gene combinations were obtained, and 4 profiles had significantly different frequencies in SIDS cases and controls. The two SNP profiles -1031CT, -238GG, -857CC, -308GG and -1031TT, -238GG, -857CC, -308AA were found more often in SIDS and may thus be unfavorable. The findings add evidence to the theory that an unfavorable genetic profile in the TNF-alpha gene may be involved in SIDS by exposing the infant to both a high level of and prolonged exposure to TNF-alpha.

2. Blood-Siegfried J, Rambaud C, Nyska A, Germolec DR
Evidence for infection, inflammation and shock in sudden infant death: parallels between a neonatal rat model of sudden death and infants who died of sudden infant death syndrome
Innate Immun. 2008 Jun;14(3):145-52

Duke University Medical Center, Durham, North Carolina, USA, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA. blood002@mc.duke.edu.

This study compared pathological findings from a neonatal rat model of sudden death with those from 40 sudden infant death syndrome (SIDS) infants collected at autopsy. In the rat model, influenza A virus was administered intranasally on postnatal day 10, and on day 12 a sublethal, intraperitoneal dose of Escherichia coli endotoxin; mortality was 80%. Tissue samples from the animals and infants were fixed in formaldehyde, embedded in paraffin, and sections stained with hematoxylin and eosin. Tissues from the SIDS specimens were additionally cultured for bacteria and viruses; post-mortem blood samples were evaluated for signs of inflammation. All sections were examined by a pediatric forensic pathologist familiar with SIDS pathology. Comparisons between the rat model and the human SIDS cases revealed that both exhibited gross and microscopic pathology related to organ shock, possibly associated with the presence of endotoxin. Uncompensated shock appeared to be a likely factor that caused death in both infants and rat pups. Response to a shock-inducing event might have played an important role in the events leading to death. The similarities between the neonatal rats and the human cases indicate that further research with the model might elucidate additional aspects of SIDS pathology.

Miscarriage/Stillbirth/Prenatal Issues

1. Ostojic? S, Pereza N, Volk M, Kapovic? M, Peterlin B
Genetic Predisposition to Idiopathic Recurrent Spontaneous Abortion: Contribution of Genetic Variations in IGF-2 and H19 Imprinted Genes
Am J Reprod Immunol. 2008 Jun 19. [Epub ahead of print]

Department of Biology and Medical Genetics, School of Medicine, University of Rijeka, Rijeka, Croatia.

Problem Recurrent spontaneous abortion (RSA) is a common clinical problem with a complex etiology of genetic and non-genetic causes, which remains to be fully determined. IGF-2 stimulates trophoblast invasion, proliferation and maturation of placenta, while H19 RNA suppresses growth. As genomic imprinting plays a critical role in the development of placenta and embryo, our aim was to evaluate the possible role of variations in IGF-2 and H19 imprinted genes as factors of predisposition for RSA. Method of study A case-control study was conducted to determine the association between IGF-2 and H19 gene polymorphisms and the susceptibility to RSA in 113 couples with RSA and 226 controls. PCR/RFLP were performed to analyze IGF-2 ApaI and H19 HhaI polymorphisms. Results We found a statistically significant difference in the genotype frequency distribution of IGF-2 ApaI polymorphism between males from couples with RSA and healthy males (chi(2)(2) = 45.12; P < 0.0001). There were no differences in the genotype and allele distribution of H19 polymorphism frequencies, or for the IGF-2 ApaI polymorphism between female groups. Conclusion The presence of IGF-2 ApaI polymorphism in partners of RSA women could affect IGF-2 level of expression in placenta and embryo and represent a risk factor for RSA susceptibility.

2. Choi YK, Kwak-Kim J
Cytokine Gene Polymorphisms in Recurrent Spontaneous Abortions: A Comprehensive Review
Am J Reprod Immunol. 2008 Jun 19. [Epub ahead of print]

Reproductive Medicine, Department of Obstetrics and Gynecology, Rosalind Franklin University of Medicine and Science/The Chicago Medical School, North Chicago, IL, USA.

Problem Cytokine gene polymorphism studies in women with recurrent spontaneous abortion (RSA) are reviewed to provide comprehensive understanding and a direction for the future investigation. Method of study A search of PubMed was made to identify the published data between 2001 and 2007 regarding RSA and cytokine gene polymorphisms. Results Either allele and/or genotype frequencies of the following polymorphisms were reported to be significantly different between women with RSA and controls: IFN-gamma +874A-->T, TA (P = 0.01), AA (P = 0.04); IL-6, -634C-->G CG/GG (P = 0.026); IL-10, -592C-->A CC (P = 0.016); IL-1B -511C (P = 0.035), -31T (P = 0.029); IL-1RA, IL1RN*2 (P = 0.002), and IL1RN*3 (P = 0.002). None of these studies was repeatedly reported by others to be significantly different. Among these, four cytokine polymorphisms (IFN-gamma, +874A-->T; IL-1B -511C; IL-1RA, IL1RN*2, IL1RN*3) were refuted by others and rest of them were studied once. Conclusion Multiple cytokine polymorphisms were reported to be associated with RSA. However, a majority of studies were not confirmed by other investigators or refuted by others. Inconsistent study results might be related to: (i) the production of these cytokines is partly under genetic controls and other factors affect cytokine levels; (ii) ethnic background, environmental factors, and selection criteria for study populations are different and (iii) the possibilities exist that multiple cytokine gene polymorphisms or other genes in linkage disequilibrium may play a role in RSA.

3. Carp HJ, Meroni PL, Shoenfeld Y
Autoantibodies as predictors of pregnancy complications
Rheumatology (Oxford). 2008 Jun;47 Suppl 3:iii6-8

Department of Obstetrics & Gynecology, Sheba Medical Center, Tel Hashomer, Israel.

Certain autoantibodies which are found in autoimmune diseases including CTDs can impair fertility. Reproductive failure may present as pregnancy loss, either as miscarriage, intrauterine fetal death or stillbirth. There are also late obstetric complications such as intrauterine growth restriction, pre-eclampsia and pre-term birth. This review summarizes the possible influences of autoantibodies in reproductive failure, and particularly their predictive value (if available). The aPLs detectable by lupus anticoagulant, anti-cardiolipin or anti-beta2 glycoprotein I assays are associated with pregnancy loss and have a positive predictive value (PPV) of 75%. In spite of the general consensus on the management of pregnant aPL-positive women, few well-designed clinical trials have been reported and there is also insufficient data about the PPV of treatment. Anti-thyroid antibodies have been associated with pregnancy loss, and indeed have a PPV of 40%. However, no antibody is pathognomic for pregnancy loss. It may be more appropriate to assess a combination of antibodies rather than one antibody. However, a large meta-analysis of published trials is required in order to determine the prevalence of each particular autoantibody and different combinations of antibodies in different forms of reproductive failure.

4. Miniati I, Guiducci S, Mecacci F, Mello G, Matucci-Cerinic M
Pregnancy in systemic sclerosis
Rheumatology (Oxford). 2008 Jun;47 Suppl 3:iii16-8

Department of Biomedicine, Section of Rheumatology, AOUC Florence, viale Pieraccini 18, 50139 Florence, Italy. irene.miniati@unifi.it

While in the past, pregnant SSc patients were thought to be at high risk for poor fetal and maternal outcome, at present, careful planning, close monitoring and appropriate therapy allows these patients to have a successful pregnancy. Retrospective studies clearly show an increased frequency of pre-term births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis: despite the fact that ACE inhibitors are associated with congenital abnormalities and are relatively contraindicated in pregnancy, in this case their use is recommended. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc as such patients are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. HCQ, intravenous immunoglobulins (if blood pressure is not high and renal function is normal) and low doses of steroids may be safely used. In case of rapid worsening of disease activity, elective termination in the first trimester and an induced pre-term birth in the last trimester may be suggested. In order to minimize risks, a multidisciplinary team should assist scleroderma patients to suggest the best timing for a pregnancy and to tailor adequate supportive treatment during the pregnancy.

5. Hong Y, Wang X, Lu P, Song Y, Lin Q
Killer immunoglobulin-like receptor repertoire on uterine natural killer cell subsets in women with recurrent spontaneous abortions
Eur J Obstet Gynecol Reprod Biol. 2008 Jun 20. [Epub ahead of print]

Department of Obstetrics and Gynecology, Renji Hospital, Shanghai Jiao Tong University, 145 Shandong Mid Road, Shanghai 200001, PR China.

OBJECTIVE: The objective of this study is to investigate the distribution of inhibitory and activating killer immunoglobulin-like receptors (KIRs) on uterine natural killer (uNK) cells and the compatibility of KIR/HLA-C at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (RSA) in the Chinese population. STUDY DESIGN: Sixteen patients with unexplained recurrent spontaneous abortion were enrolled in this study. The PCR sequence-specific primers (SSP) method was used to detect the inhibitory/activating KIRs in uterine NK cells and the HLA-C gene polymorphism expressed on the trophoblast. RESULTS: The frequencies of inhibitory KIR2DL2 in the RSA group were increased significantly compared with those of the controls. The other inhibitory KIR2DL families did not show significantly different frequencies in the RSA group. No difference in numbers of inhibitory KIR genes with statistical significance was observed between the RSA group and the controls. When analyzing activating KIRs, none of the KIR2DS1-5 family showed statistically different frequencies in the RSA group compared with the controls. Similarly, there was no statistically significant difference between the numbers of activating KIR genes in the RSA group and the controls. Finally, the matching of the inhibitory or activating KIRs/HLA combination at the maternal-fetal interface did not play a dominant role in the pathogenesis of pregnancy loss. CONCLUSIONS: This study suggests that the imbalance of inhibitory and activating KIRs in uterine NKs might confer susceptibility to the occurrence of pregnancy loss. The maternal inhibitory/activating KIRs-HLA-C polymorphism expressed on trophoblast cells from decidual tissues seems to play a limited role in abortion.

6. Walsh CA, Vallerie AM, Baxi LV
Etiology of stillbirth at term: a 10-year cohort study
J Matern Fetal Neonatal Med. 2008 Jul;21(7):493-501

Obstetrics and Gynecology, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA. Objective. To examine etiological factors contributing to cases of intrauterine fetal demise in term pregnancies over a 10-year period. Methods. This was a retrospective cohort analysis of 29 908 term (37(+0) to 41(+6) weeks gestation) infants delivering in a single tertiary-referral university institution over the 10-year period from 1996 to 2005. Cases of stillbirth were identified from a computerized hospital database, and pathological, clinical, and biochemical data were reviewed for all cases. Trends were analyzed using the Cusick test for trend. Categorical data were analyzed using the Fisher's exact test, with the 5% level considered significant. Results. The incidence of intrauterine fetal demise at term was 1.8 per 1000 at-risk pregnancies. There was no significant downward trend in the rate of term stillbirth between 1996 and 2005 (p = 0.0808). Stillbirths were unexplained in 51% of cases, although in many cases a possible etiological factor was identified but not necessarily proven. There was a significant downward trend in the incidence of unexplained term stillbirths at our institution over the 10-year study period (p = 0.0105). Placental/cord factors accounted for 25% of term stillbirths and did not decrease significantly over the study period (p = 0.0953). Almost 50% of term stillbirths occurred in women who registered late or had no antenatal care. However, suboptimal antenatal care was not predictive of differences in either acceptance of perinatal postmortem or successful identification of stillbirth etiology. Conclusions. The incidence of stillbirth at term is 2 per 1000 term pregnancies and has not changed significantly in the past 10 years. Almost 50% of term stillbirths occurred in women with suboptimal antenatal care. More than half of cases are unexplained, often resulting from an incomplete diagnostic work-up. Despite this, there has been a significant downward trend in the rates of unexplained stillbirth at term. It is imperative that a complete diagnostic work-up is performed in cases of term stillbirth, to minimize the incidence of unexplained stillbirth.

7. Facchinetti F, Reddy U, Stray-Pedersen B, Baronciani D, Requejo JH
International issues in stillbirth
J Matern Fetal Neonatal Med. 2008 Jun;21(6):425-8

Mother-Infant Department, Unit of Obstetrics and Gynecology, University of Modena and Reggio Emilia, Modena, Italy.

The phenomenon of stillbirth has been poorly addressed in terms of reported statistics and as a clinical issue. A Study Group of the European Association of Perinatal Medicine reviewed the topic and highlighted specific issues. Such proposal was discussed in an open workshop held in Modena, Italy last year and this paper reports the final recommendations. Briefly, at least 22 completed weeks of gestation was endorsed as definition for including SB in statistics and for clinical studies. A minimum diagnostic work-up was suggested together with the emphasis toward a local, multidisciplinary audit process, in order to comprehend causality. Attention for parents emotional support and appropriate counselling was believed as essential part of the clinical process. Finally, the need for funding comprehensive research programs in SB through international, multidisciplinary involvement was believed mandatory for developing effective preventative strategies to avert the devastating occurrence of stillbirth.

8. Badawy AM, Khiary M, Sherif LS, Hassan M, Ragab A, Abdelall I
Low-molecular weight heparin in patients with recurrent early miscarriages of unknown aetiology
J Obstet Gynaecol. 2008 Apr;28(3):280-4

Department of Obstetrics and Gynecology, Mansoura University Hospitals, Mansoura, Gomhoreya St, 5544, Egypt. ambadawy@yahoo.com The aim of this randomised prospective study was to assess the efficacy of early thromboprophylaxis with low-molecular weight heparin (LMWH) in women with a history of recurrent first trimester spontaneous abortion or miscarriages without identifiable causes vs no treatment. The study comprised of 340 women with unexplained spontaneous recurrent miscarriages. Patients in group A were prescribed LMWH (Enoxaparin sodium 0.2 ml, 20 mg, once daily subcutaneously) from the time of confirmation of fetal viability by ultrasonography until 34 weeks' gestation, and folic acid tablets 0.5 mg daily until 13 weeks' gestation. Patients in group B were given folic acid tablets 0.5 mg daily until 13 weeks' gestation. Termination of pregnancy was the primary outcome. There was a significant difference in the incidence of both early (4.1% vs 8.8%) and late miscarriages (1.1% vs 2.3%) in group A than in group B, respectively. There were no differences between both groups as regards the occurrence of pre-eclampsia, placental abruption, caesarean delivery, intra-partum bleeding or ecchymosis at operative wounds. There were no differences in most of the neonatal values between both groups. However, the mean birth weight was significantly higher in group A. LMWH seems to be a safe drug and effective in significantly reducing the incidence of recurrent miscarriages of unknown aetiology when given in the first trimester and continued throughout pregnancy.

9. Friebe A, Arck P
Causes for spontaneous abortion: What the bugs 'gut' to do with it?
Int J Biochem Cell Biol. 2008 May 18. [Epub ahead of print]

Charite?, University Medicine, Berlin, Germany; Brain Body Institute, McMaster University, Hamilton, Canada.

Spontaneous miscarriage is the most common adverse pregnancy outcome in humans and occurs in 15-20% of all recognized pregnancies. High psychosocial stress perception has long been recognized as a threat to pregnancy maintenance and accumulating evidence supports that stress affects maternal adaptation to pregnancy and subsequently impedes fetomaternal tolerance. This review strongly focuses on the role of microbial products within the stress-induced signalling cascade, linking the disequilibrium of the endogenous microflora to immune activation and pregnancy loss. The stress signalling cascade utilizes the presence of lipopolysaccharide (LPS), which acts as a danger signal via Toll like receptor 4. Physiologically, the intestinal microflora provides a source for endogenous LPS, i.e. during the stress response, and psychosocial stress challenge in mice enhances the gastrointestinal permeability and bacterial uptake from the gut. Clearly, these novel insights not only deepen our understanding of mechanisms involved in the stress response cascade, but also initiate a renaissance of therapeutic intervention strategies, aiming to modulate the intestinal flora by probiotic bacteria. In turn, intestinal barrier function may be enhanced and mediators of immune tolerance may be restored, i.e. in the context of reproduction.

10. Imbasciati E, Tincani A, Gregorini G, Doria A, Moroni G, Cabiddu G, Marcelli D
Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome
Nephrol Dial Transplant. 2008 Jun 18. [Epub ahead of print]

1Scuola di Specialita? in Nefrologia, Universita? Milano Bicocca.

BACKGROUND: Only few data are available on pregnancy in patients with lupus nephritis (LN) diagnosed before conception. The aim of this study was to identify the risk factors for complicated pregnancy in women with pre-existing LN. METHODS: In a multicentre study, we collected data on 113 pregnancies occurring in 81 women with pre-existing biopsy-proven LN. Primary outcomes were fetal loss including perinatal death and renal flares during and 12 months after pregnancy. Univariate and logistic regression analyses were used to identify predictors of outcomes. RESULTS: Renal biopsy performed 7.2 +/- 4.9 years before pregnancy showed the following WHO classes: 6 patients in II, 8 in III, 48 in IV and 19 in V. At conception, most patients were in complete (49%) or partial (27%) remission. There were nine spontaneous abortions, one stillbirth and five neonatal deaths. Thirty-one deliveries were preterm. Birth weight was <2500 g in 34 newborns. During pregnancy or after delivery, there were 34 renal flares, most of which (20) were reversible. Three patients had a progressive decline of glomerular filtration rate (one on dialysis). At logistic regression analysis, the pregnancy outcome was predicted by hypocomplementaemia at conception (RR 19.02; 90% CI 4.58-78.96) and aspirin during pregnancy (RR 0.11; 90% CI 0.03-0.38). Renal flare was predicted by renal status (partial remission RR 3.0; 90% CI 1.23-7.34, nonremission RR 9.0; 90% CI 3.59-22.57). CONCLUSIONS: Pregnancy can be successful in most women with pre-existing LN, even for those with a severe renal involvement at onset. Renal flares during and after pregnancy are not uncommon and can be predicted by renal status assessed before pregnancy. Normocomplementaemia and low-dose aspirin therapy during pregnancy are independent predictors of a favourable fetal outcome.

11. Andrade R, Sanchez ML, Alarco?n GS, Fessler BJ, Ferna?ndez M, Bertoli AM, Apte M, Vila? LM Reveille JD
Adverse pregnancy outcomes in women with systemic lupus erythematosus from a multiethnic US cohort: LUMINA (LVI)
Clin Exp Rheumatol. 2008 Mar-Apr;26(2):268-74

LUMINA Study Group. Department of Medicine (Division of Clinical Immunology and Rheumatology), School of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, USA.

OBJECTIVE: To study the factors associated with an adverse pregnancy outcome in women with systemic lupus erythematosus (SLE). METHODS: SLE women from LUMINA of Hispanic, African American and Caucasian ethnicity were studied. Adverse pregnancy outcome was a miscarriage or abortion (<20 weeks), a stillbirth (> or = 20) and/or a moderate to severe preterm-baby (<34 weeks); good outcome was either a mild preterm-baby (> or = 34 weeks) or a full-term baby [C-section or vaginal delivery (38-42 weeks)]. Pregnancies occurring after SLE diagnosis (TD) were included; pregnancy outcome was the unit of analyses. The relationship between selected variables and pregnancy outcomes was examined by univariable and multivariable analyses. RESULTS: Adverse outcomes occurred in 63.7% of 102 pregnancies. In the univariable analyses, Texan Hispanic and African American ethnicities, fewer years of education, higher number of ACR criteria, renal involvement, glucocorticoid exposure and the maximum dose of glucocorticoids used prior to the pregnancy outcome were associated with an adverse pregnancy outcome. Renal involvement was independently associated with an adverse pregnancy outcome [Odds ratio (OR)=5.219 (95% Confidence Interval (CI) 1.416-19.239, p=0.0131] as were the maximum dose of glucocorticoids used prior to the pregnancy outcome (OR=1.028; CI:1.002-1.054; p=0.0315) and fewer years of education (OR=1.204; CI:1.006-1.472; p=0.0437). Ethnicity was not retained in the multivariable model. CONCLUSION: Renal involvement, the maximum dose of glucocorticoids used prior to pregnancy and fewer years of education were associated with adverse pregnancy outcomes. These data have implications for the management of women with lupus planning to become pregnant. Publication Types: Research Support, N.I.H., Extramural Research Support,

12. Aliyu MH, Wilson RE, Zoorob R, Chakrabarty S, Alio AP, Kirby RS, Salihu HM
Alcohol consumption during pregnancy and the risk of early stillbirth among singletons
Alcohol. 2008 Jun 16. [Epub ahead of print]

Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA

The purpose of this study is to investigate the association between maternal alcohol intake in pregnancy and the occurrence of early stillbirth using a retrospective cohort analysis of singleton births in Missouri that occurred in the period 1989 through 1997 (N=655,979). We used Cox proportional hazards regression to generate adjusted risk estimates for total, early, and late stillbirth associated with maternal alcohol intake and used the Robust Sandwich Estimator to adjust for intracluster correlations among sibships. Overall, a total of 3,508 counts of stillbirth were identified, yielding a stillbirth rate of 5.3 per 1,000. Among mothers who consumed alcohol during pregnancy, the stillbirth rate was 8.3 per 1,000. Mothers who consumed alcohol while pregnant were 40% more likely to experience stillbirth as compared with nondrinking mothers (adjusted hazards ratio=1.4, 95% confidence interval: 1.2-1.7). A dose-response relationship was evident; mothers who consumed five or more drinks per week during pregnancy experienced a 70% elevated risk of stillbirth compared with nondrinking mothers (adjusted hazards ratio=1.7; 95% confidence interval: 1.0-3.0). The risk of early stillbirth was 80% higher among drinking mothers compared with abstainers (adjusted hazards ratio=1.8; 95% confidence interval: 1.3-2.3). The elevated risks for both early and late stillbirth did not reach statistical significance when broken down by level of alcohol intake. In conclusion, maternal drinking during pregnancy is associated with an increased risk of early stillbirth. These findings underscore the need to reinforce current counseling strategies toward pregnant women and women who intend to conceive on the detrimental effects of alcohol use in pregnancy.

13. Pedersen LM, Pedersen TA, Ravn HB, Hjortdal VE
Outcomes of pregnancy in women with tetralogy of Fallot
Cardiol Young. 2008 Jun 18:1-7. [Epub ahead of print]

Department of Cardiothoracic Surgery, Skejby Hospital, Aarhus University Hospital, Aarhus, Denmark.

BACKGROUND: Surgical results after repair of tetralogy of Fallot have remained excellent for the last decades, with current long-term rates of survival over 95%. Since functional capacity, quality of life, and social interactions are basically normal in this large group of patients, pregnancy obviously becomes a relevant issue for the female subgroup. In consequence, adequate obstetrical and cardiological management of pregnancy is particularly important. OBJECTIVE: To describe the outcomes of pregnancy, and fertility, in a series of women who underwent surgery for tetralogy of Fallot in a single centre.Methods and results. We obtained data from hospital records, national registries, and questionnaires on 78 women who underwent surgical correction of tetralogy of Fallot between 1972 and 1992. Of 58 women who reached an age of at least 18 years, with 45 of this cohort currently surviving, 13 having died as adults, there were 54 pregnancies in 25 women. The recorded rate of spontaneous abortion was 15%, and infertility rate was 3.4%. There have been 41 life births, with a median weight at birth of 3.2 kg. Only 1 newborn was small for gestational age, and no one was born before the 36th week. The recurrence rate of congenital heart disease was high, at 9.8%. Cardiac complications during or after pregnancy were not observed, and only one woman had pre-eclampsia.

CONCLUSIONS: Pregnancy is well tolerated in women with tetralogy of Fallot, and an excellent neonatal outcome is expected. The recurrence risk of congenital cardiac disease, most often tetralogy of Fallot, is high.

14. Iravani AT, Saeedi MM, Pakravesh J, Hamidi S, Abbasi M
Thyroid autoimmunity and recurrent spontaneous abortion in Iran: a case-control study
Endocr Pract. 2008 May-Jun;14(4):458-64
.
School of Medicine, Medical Sciences/University of Tehran, Tehran, Iran. Iravani_amir@yahoo.com

OBJECTIVE: To determine the association of thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab) with recurrent spontaneous abortion in a euthyroid, nonpregnant population of women in Iran. METHODS: In this case-control study conducted between November 2003 and September 2006 in Tehran, Iran, nonpregnant women with a history of 3 or more consecutive pregnancy losses and age-matched, healthy parous women without a history of reproductive problems were assessed. Thyroid function tests were performed, which included assessment of thyroid-stimulating hormone, triiodothyronine, thyroxine, and the presence of TG-Ab and TPO-Ab. RESULTS: A total of 641 patients and 269 controls were included. Mean age (+/- SD) was 30.6 +/- 6.4 years (range, 16-51 years) in the patient group and 30.05 +/- 6.6 years (range, 18-48 years) in the control group. Thyroid antibodies were present in 157 of 641 patients (24.5%) and in 34 of 269 controls (12.6%) (P<.001). The presence of thyroid antibodies was significantly associated with recurrent abortion independent of the impact of age with an odds ratio of 2.24 (95% confidence interval, 1.5-3.35). CONCLUSIONS: In this population of women in Iran, TG-Ab and TPO-Ab were identified more frequently in women with recurrent abortions compared with controls, and thyroid autoimmunity was independently associated with a higher risk of recurrent abortion.

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