Egle Couto

Quality of life, depression and anxiety among pregnant women with previous adverse pregnancy outcomes

CONTEXT AND OBJECTIVE Previous adverse pregnancy outcomes (recurrent spontaneous abortion, fetal death, preterm birth or early neonatal death) can affect the quality of life of pregnant women. The objective of this study was to compare the quality of life and the prevalence of symptoms of anxiety and depression among pregnant women with and without these antecedents. DESIGN AND SETTING An analytical cross-sectional study was performed in four settings (two high-risk and two low-risk prenatal clinics) in the city of Campinas, São Paulo, Brazil. METHODS A total of 240 women were interviewed by a single investigator between the 18th and 24th weeks of gestation: 120 women with prior adverse pregnancy outcomes (group 1) and 120 women with no such history (group 2), matched according to their numbers of living children. Sociodemographic variables were collected and two questionnaires were used: the Short Form-36 quality-of-life questionnaire and the Depression and Anxiety Scale. RESULTS The women in group 1 had lower scores in all the items on the quality-of-life questionnaire. Depression and anxiety were more frequent in group 1 (P < 0.0001). An inverse correlation was found between the Short Form-36 domains and anxiety and depression. CONCLUSIONS Women with histories of recurrent spontaneous abortion, fetal death, preterm birth or early neonatal death seem to have poorer quality of life and more symptoms of anxiety and depression during their subsequent pregnancy, compared with those without such antecedents.

Gestational prognostic factors in women with recurrent spontaneous abortion

CONTEXT AND OBJECTIVE Recurrent spontaneous abortion (RSA) is defined as three or more consecutive pregnancy losses before 20 weeks and is associated with several etiological factors related to genetics, anatomy, hormones, infections and immunology, for example. Many cases of RSA remain unclear. New factors or their associations may influence gestational results. The aim was to identify possible single or associated causes of RSA that could predict gestational prognosis for women undergoing investigation and treatment. DESIGN AND SETTING Case-control study, at the Recurrent Abortion Outpatient Clinic, Department of Obstetrics and Gynecology School of Medicine, Universidade Estadual de Campinas (Unicamp). METHODS Two hundred and forty-six medical records of women with RSA seen at the Recurrent Abortion Outpatient Clinic, Department of Obstetrics and Gynecology School of Medicine, Universidade Estadual de Campinas (Unicamp), between 1994 and 2003, were evaluated. Data on age, obstetric history, possible etiological factors, treatment and pregnancy outcomes were evaluated. Statistical analysis was performed using odds ratios (OR), logistic regression analysis and decision trees. RESULTS Two hundred and twenty-nine women were included in the study. The most frequently found etiological factors were immunological, particularly alloimmune factors (93.9%). Women with a single alloimmune factor had better gestational results (77.7% deliveries) than those with other associated factors. Autoimmune factors were associated with a higher abortion rate (OR: 4.30; 95% confidence interval, CI: 1.36-13.63). No association was found between the number of abortions prior to treatment and pregnancy results. Women aged 40 or over presented the highest rate of spontaneous abortion (OR: 5.83; 95% CI: 1.12-30.40). CONCLUSION Age over 40 years old, immunological factors and two or more concomitant factors were associated with poor gestational outcomes among the women studied.

Association of anticardiolipin antibody and C677T in methylenetetrahydrofolate reductase mutation in women with recurrent spontaneous abortions: a new path to thrombophilia?

CONTEXT Recurrent spontaneous abortion (RSA) has been associated with venous thrombosis in the mother. Acquired and inherited thrombophilia factors are possible causes. OBJECTIVE To evaluate the association between thrombogenic factors and recurrent spontaneous abortion. TYPE OF STUDY Case-control study. SETTING Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas. METHODS 40 ml of blood was collected from 88 women attending an RSA clinic and 88 fertile women attending a family planning clinic, to evaluate the presence of acquired and inherited thrombophilia factors. Anticardiolipin antibodies (ACA), lupus anticoagulant and deficiencies of proteins C and S and antithrombin III were evaluated by enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. DNA was amplified by the polymerase chain reaction (PCR) to study factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Data were analyzed using odds ratios and a regression model for age adjustment. Fishers exact test was used to evaluate statistical relationships between associated factors and RSA. RESULTS ACA was detected in 11 women with RSA and one fertile woman. Heterozygous C677T was detected in 59 women with RSA and 35 fertile women. Concomitant presence of ACA and C677T was found in eight women with RSA and no fertile women (p < 0.01). DISCUSSION The meaning of the association between C677T mutation in the MTHFR gene and ACA is still not clear. It is possible that an inherited factor that alone would not strongly predispose a woman to thrombosis could, when associated with an acquired factor, start the process and increase the likelihood of thrombosis expression. CONCLUSIONS ACA and C677T in the MTHFR gene are statistically associated with RSA. The association of these two conditions is a new finding in thrombogenic factors and RSA.

Body stalk anomaly: adverse maternal outcomes in a series of 21 cases

To evaluate the demographic characteristics of cases with body stalk anomaly (BSA) and describe the obstetric outcome.

Pregnancy-associated venous thromboembolism in combined heterozygous factor V Leiden and prothrombin G20210A mutations

CONTEXT Pregnancy and puerperium raise the risk of thromboembolic events, and these risks are increased in women who are carriers of thrombophilia factors. Prothrombin (FII) G20210A and factor V Leiden heterozygous mutations are associated with moderate risk of thrombosis. The association of these thrombophilic conditions is very rare in pregnancy, and the real risk of thrombosis is unknown. CASE REPORT We describe a case of a pregnant woman who was found to be carrier of heterozygous factor V Leiden and prothrombin (FII) G20210A mutations. Five years before pregnancy she had had an episode of extensive deep venous thrombosis in the ileofemoral region, while using hormonal contraceptives. Anticardiolipin antibody (ACA), lupus anticoagulant and deficiencies of protein C, protein S and antithrombin III were evaluated by means of enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. Deoxyribonucleic acid (DNA) was amplified using the polymerase chain reaction (PCR) to study the factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene. In the sixth week of her first pregnancy, she developed another episode of deep venous thrombosis in the femoropopliteal veins of the right leg. She was treated with low-molecular weight heparin (nadroparin) until parturition (0.3 ml or 2,850 UI/day). The pregnancy evolved without any significant obstetric morbidity. The patient delivered a healthy baby by cesarean section. During the puerperium, she used prophylactic doses of nadroparin for (0.3 ml or 2,850 UI/day) six weeks and had no complications. We suggest that women who have an association of thrombophilia factors and a prior episode of venous thromboembolism must have antepartum anticoagulation management using unfractioned or low-molecular weight heparin and postpartum management using low-molecular weight heparin or oral anticoagulants. Anticoagulation is recommended during pregnancy because the real magnitude of the risk of major and life-threatening thromboembolic events in these women is unknown.

Fenótipo de subfertilidade, polimorfismos cromossômicos e falhas de concepção

PURPOSE To evaluate the prevalence of cytogenetic alterations and chromosomic polymorphism in couples with a subfertility phenotype in a Brazilian population. METHODS Karyotype analysis through G and C banding of 1,236 individuals who presented the subfertility phenotype, from two different centers (public and private) were included in the study. These patients were classified in two sub-groups: one with two or more gestational consecutive losses or not and the o with, at least, one gestacional loss or absence of conception. Karyotype results were evaluated in different groups and frequencies were calculated. Statistical analyses were carried out through Fishers exact test and Odds Ratio analysis. RESULTS Approximately 25% of the cases presented abnormal karyotype results, including numerical and structural alterations and also polymorphic variants. In both centers, the prevalence of polymorphic variants was 8.9 and 3.8%, respectively. CONCLUSIONS There was no significant difference between the prevalence of polymorphic variants and other abnormalities in individuals with or without previous history of reproductive loss. The results of the present study reinforce the need of adequate disclosure of complete cytogenetic information in the karyotype results, with specific attention in relation to the polymorphic variants.

Fetal genotyping for platelets antigens: a precise tool for alloimmune thrombocytopenia: case report and literature review

IntroductionMaternal–fetal alloimmune thrombocytopenia complicates about 0.1% of all pregnancies and is associated with major fetal and neonatal morbidity and mortality, especially spontaneous central nervous system bleeding leading to death and neurological handicaps. Successful prevention and treatment depend on the identification of at-risk possible carriers of anti-platelet antibodies.Case report We report a case of a mother with a previous child that developed neonatal hemorrhage; HPA-5b anti-platelet antibodies were detected post-natally. During the next pregnancy, fetal genotyping confirmed the presence of HPA-5b antigen; she was treated with weekly intravenous human immunoglobulin and oral prednisone. Pregnancy evolved without remarkable features and a full-term baby was delivered, with normal platelet counts.ConclusionFetal alloimmune thrombocytopenia is a potentially lethal condition, but early detection and prevention lead to successful outcome in most cases.

Abortamento recorrente de causa imunológica: avaliação de um protocolo de investigação e tratamento

Results on investigation and immune treatment for recurrent abortion are presented. Up to 60% of patients who are free of any clinical identifiable cause for abortion are believed to have alloimmune abnormalities. One of the suggested therapies for this condition is paternal lymphocyte immunization. We present the result of 116 pregnancies followed at the Departamento de Tocoginecologia UNICAMP. Patients were thoroughly evaluated for causes of recurrent abortion mentioned in the literature (genetics, hormones, uterine abnormalities and infections), for autoimmune (antiphospholipid syndrome, abnormal autoantibodies) and for alloimmune causes (crossmatch by microlymphocytotoxicity and mixed lymphocyte culture). Patients who presented negative crossmatch and lower than 50% inhibition in mixed lymphocyte culture were treated with two concentrated intradermal paternal lymphocyte immunizations. Women were stimulated to attempt pregnancy with a positive crossmatch and higher than 50% inhibition in mixed lymphocyte culture. Women whose immune status did not change with this treatment were immunized again with paternal lymphocytes associated or not to a third party donor. We report that 81% of the women treated with this protocol had good pregnancy outcome.

Prevalência de anticorpos antifosfolípides em diabéticas gestacionais e pré-gestacionais

OBJETIVO: identificar e descrever a prevalencia de anticorpos antifosfolipides (anticorpo anticardiolipina e anticoagulante lupico) em gestantes diabeticas. METODOS: estudo prospectivo de prevalencia, realizado no periodo de julho de 2003 a marco de 2004. Foram estudadas 56 gestantes diabeticas gestacionais e pre-gestacionais que ingressaram ao pre-natal e aceitaram participar do estudo. Nenhuma gestante foi excluida. Se um ou outro anticorpo estivesse presente, a gestante seria tratada com heparina e acido acetilsalicilico. Foram caracterizados os perfis da gestante, a evolucao da gestacao e o recem-nascido. RESULTADOS: foram diagnosticados anticorpos antifosfolipides em apenas quatro gestantes das 56 estudadas, o que representou prevalencia de 7% (IC 95% - 0,1-13,9). Nas gestantes diabeticas com anticorpos antifosfolipides a duracao do diabetes foi de cinco anos ou mais. A idade variou de 27 a 38 anos, sendo uma primigesta, outra secundigesta e as outras duas multiparas. As gestantes com anticorpos antifosfolipides, que foram tratadas, tiveram recem-nascidos vivos, de termo, cujos pesos variaram entre 2.650 g e 4.000 g. CONCLUSAO: a prevalencia de anticorpos antifosfolipides em gestantes diabeticas gestacionais e baixa, e similar a populacao geral de gravidas. Esta prevalencia aumenta quando a gestante e diabetica pre-gestacional.

Malformações do sistema nervoso central e a presença da mutação C677T-MTHFR no sangue fetal

PURPOSE To evaluate the association between central nervous system (CNS) malformations and the C677T-MTHFR mutation in fetal blood. METHODS A case-control study was conducted to compare the MTHFR-C677T mutation detected in 78 fetuses with CNS malformations and with 100 morphologically normal fetuses. Genomic DNA was extracted and purified from fetal blood using the Wizard® Genomic DNA Purification Kit (Promega Corp., Madison, WI, USA) according to manufacturers protocol. The polymerase chain reaction (PCR) was used to assay the thermolabile MTHFR-C677T mutation. The γ² and the Fishers exact tests were used for descriptive analysis and the Wilcoxon test was used for univariate analysis. Logistic regression analysis was performed to identify which variables were predictors of CNS malformation. RESULTS Cases and controls were similar regarding maternal characteristics such as age and number of deliveries and abortions. The MTHFR-C677T mutation was detected in 20 cases (25.6%) and in 6 controls in its heterozygous form (OR 10.3; 95%CI 3.3-32.2) and in 6 cases (7.7%) and in 1 control in its homozygous form (OR 12.3; 95%CI 1.3-111.1), and the differences were statistically significant. CONCLUSION The presence of the MTHFR-C677T mutation in fetal blood was consistent with a higher risk of CNS malformations, both in the heterozygous and homozygous forms.