Resumo Objetivo Descrever uma população de pacientes diagnosticadas com toxoplasmose na gestação e seus respectivos recém-nascidos, relatando o protocolo do hospital durante o tratamento e seguimento. Métodos Coorte retrospectiva de gestantes com infecção aguda por toxoplasmose e risco de transmissão transplacentária, encaminhadas para acompanhamento pelo Grupo deMedicina Fetal doHospital de Clínicas de Porto Alegre (HCPA) entre 1o de janeiro de 2006 e 31 de dezembro de 2016. Todas as pacientes comdoença confirmada foram incluídas. O protocolo de diagnóstico e tratamento foi aplicado; uma análise da reação em cadeia da polimerase (RCP) no líquido amniótico foi utilizada para diagnosticar a toxoplasmose e determinar o tratamento. Os recém-nascidos foram acompanhados no ambulatório de pediatria especializadoeminfecções congênitas. Pacientes que não foramseguidas ou cujo parto não foi feito no hospital foram excluídas. Resultados A toxoplasmose gestacional foi confirmada em 65 pacientes; 40 realizaram amniocentese, e 6 (15%) foram identificadas com RCP positiva no líquido amniótico. Este resultado associado à idade gestacional definiu a terapia tríplice durante a gestação em 5 casos, e a monoterapia em 1 caso (por idade gestacional avançada). Quatro destas crianças foram tratadas desde o nascimento com terapia tríplice por 12 meses, 1 não foi tratada (por recusa materna), e 1 evoluiu com óbito dentro das primeiras 54 horas de vida devido a complicações da toxoplasmose congênita. Dos 34 casos remanescentes com RCP negativa, 33 foram tratados com monoterapia, e 1 foi tratado com terapia tríplice (por achados ultrassonográficos); destes recém-nascidos, 9 (26,5%) tiveram imunoglobulina G (IgG) negativa, 24 (70,6%) tiveram IgG positiva, mas nenhum apresentou imunoglobulina M (IgM) positiva, e 1 (2,9%) apresentou alterações compatíveis comdoença congênita e iniciou a terapia tríplice logo após o nascimento. Entre as 25 pacientes que não fizeram RCP no líquido amniótico, 5 foram tratadas com terapia tríplice (por achados ultrassonográficos/ tratamento prévio) e 20 receberam monoterapia; somente 2 recém-nascidos receberam tratamento para toxoplasmose congênita. Entre os 65 casos de toxoplasmose gestacional, 6 (9,2%) recém-nascidos tiveram o diagnóstico de toxoplasmose congênita. Um total de 2 pacientes submetidas à terapia tríplice apresentaram efeitos adversos severos das medicações utilizadas. Conclusão Este estudo sugere que a triagem da RCP para toxoplasmose do líquido amniótico pode ser útil no rastreamento de pacientes com maior potencial para complicações fetais, que podem se beneficiar do tratamento poli antimicrobiano. Pacientes com RCP negativa devem continuar a prevenir a infecção fetal com monoterapia, sem risco de comprometimento fetal ou materno.

Abstract Objective To describe a population of pregnant women diagnosed with toxoplasmosis and their respective newborns, describing the hospital protocol for treatment and follow-up. Methods Retrospective cohort of pregnant women with acute toxoplasmosis infection and risk of transplacental transmission who were sent to the Fetal Medicine Group of Hospital de Clínicas de Porto Alegre (HCPA) between - January 1, 2006 and December 31, 2016. All patients with confirmed disease were included. The diagnostic protocol and treatment were applied; a polymerase chain reaction (PCR) analysis of the amniotic fluid was used to diagnose toxoplasmosis and determine the treatment. The newborns were followed up at the pediatric outpatient clinic specializing in congenital infection. The patients who were not followed up or were not born in the HCPA were excluded. Results A total of 65 patients were confirmed to have gestational toxoplasmosis; 40 performed amniocentesis, and 6 (15%) were identified as having positive PCR in the amniotic fluid. In five of those cases, this result associated with the gestational age defined the triple therapy during pregnancy, and in one case, it defined the monotherapy (advanced gestational age). A total of 4 of these newborns were treated from birth with triple therapy for 10months, 1 was not treated (due to maternal refusal), and 1 progressed to death within the first 54 hours of life due to complications of congenital toxoplasmosis. Of the 34 remaining cases with a negative PCR, 33 were treated with monotherapy and 1 was treated with triple therapy (ultrasound findings); of these children, 9 (26.5%) presented negative immunoglobulin G (IgG), 24 (70.6%) presented positive IgG (but none presented positive immunoglobulin M [IgM]), and 1 (2,9%) presented alterations compatible with congenital disease and started treatment with the triple therapy soon after birth. Out of the total sample of 60 patients, among the 25 who did not perform amniotic fluid PCR, 5 were treated with triple therapy (ultrasound findings/prior treatment) and 20 patients were submitted to monotherapy; only two newborns underwent treatment for congenital toxoplasmosis. Among the 65 cases of gestational toxoplasmosis, 6 (9,2%) children had a diagnosis of congenital toxoplasmosis, and 2 patients with triple therapy felt severe adverse effects of the medications. Conclusions The present study suggests that research on PCR screening of the amniotic fluid may be useful to identify patients with a higher potential for fetal complications, who may benefit from the poly-antimicrobial treatment. Patients with negative PCR results must continue to prevent fetal infection with monotherapy, without risk of fetal or maternal impairment.

Abstract Trisomy 18 (T18) and trisomy 13 (T13) are polymalformative syndromes associated with a high rate of spontaneous abortions, intrauterine death, and short postnatal life. This study describes the overall outcome in a country where the therapeutic interruption of pregnancy is not available. The medical records of women with prenatal diagnosis of full trisomy of T13 or T18 between October 1994 and October 2017 were analyzed in order to describe their natural outcomes. Thirteen cases of T13 and 29 cases of T18 were included. The miscarriage rate was 9% for T18 and no cases for T13. Intrauterine fetal death occurred in 46% and 52% of cases for T13 and T18, respectively. The rate of live births for T13 was 54%, and the median survival was one day (95% CI -33.55 - 90.40) and 71% died in the first 24 hours of life. The rate of live births for T18 was 37% and the median survival was two days (95% CI -1.89 - 13.17); 90% of the affected babies died within first week of life. For the affected babies reaching the first year of life and for those who lived longer, multiple invasive and expensive procedures were required, without success in prolonging life beyond 180 days. This large series provides information for professionals and women regarding the natural histories of T13 and T18. Results of this study are consistent with those referenced in the literature, emphasizing the need of structured protocols and guidelines aiming early T13 and T18 diagnosis, prenatal care, gestation/parents follow-up, and counseling processes. For those couples with earlier diagnosis, a better follow-up and counseling during the prenatal care lead to the option for a support or palliative management of the newborn. Finally, when the counseling process is appropriate, it becomes easier to take decisions respecting the parent’s autonomy and to look for better outcomes for both, the mother and the fetus.

Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46, XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.

OBJETIVOS: comparar os efeitos endometriais e no padrão de sangramento uterino de tratamento com (1) sistema intrauterine com levonorgestrel (SIU-LNG) e estradiol (1 mg/dia, v.o.) ou (2) associação oral de drospirenona (DRSP) (2 mg/dia) e estradiol (1 mg/dia). MÉTODOS: trinta e quatro pacientes (idade 52,53 ± 4,44 grupo SIU-LNG e 53,15 ± 4,018 grupo DRSP)foram randomizadas. A gravidade dos sintomas menopausais foi avaliado pelo índice de Kupperman a cada três meses. Ultrassom transvaginal, histeroscopia e avaliação histológica foram repetidos após 12 meses. Durante este período, as pacientes fizeram registros em calendários menstruais. Todas as variáveis categóricas foram descritas como porcentagens. Variáveis foram testadas para distribuição normal e teste t de Student para amostras independents e ANOVA para medidas repetidas foram utilizados quando apropriado. Significância estatística foi considerada para p<0.05. RESULTADOS: leve sangramento vaginal foi relatado no primeiro mês de tratamento por 53,3% das pacientes do grupo SIU-LNG/estradiol vs. 7,7% das pacientes do grupo drospirenona/estradiol. Não houve diferença na espessura endometrial entre os grupos durante o periodo do estudo. Os achados histológicos ao final do estudo motraram endométrio atrófico em 53,3% das pacientes no grupo SIU-LNG/estradiol vs. 76,9% das pacientes no grupo drospirenona/estradiol. CONCLUSÕES: nossos resultados sugerem boa proteção endometrial com ambos os tratamentos de terapia hormonal.

OBJECTIVES: to compare the endometrial effects and uterine bleeding patterns associated with treatment using (1) levonorgestrel-releasing intrauterine system (LNG-IUS) and estradiol (1 mg/day, p.o.) or (2) orally administered drospirenone (2 mg/day) andestradiol (1 mg/day). METHODS: thirty-four patients (aged 52.53 ± 4.44 in the LNG-IUS group and 53.15 ± 4.018 in the DRSP group) were randomized. The severity of menopausal symptoms was evaluated using the Kupperman index every three months. Transvaginal ultrasound, hysteroscopy and histological evaluation were repeated after 12 months. During this period, patients kept menstrual calendars. All categorical variables were described as percentages. Variables were tested for normal distribution and Student's t test was applied for independent samples and ANOVA forrepeated measures when appropriate. Data were considered to be significant when p<0.05. RESULTS: slight vaginal bleeding was reported in the first month of treatment by 53.3% of patients from the LNG-IUS/estradiol group compared with 7.7% of patients from the drospirenone/estradiol group. There were no differences in endometrial thickness between the two groups throughout the study period. End-of-study histological findings showed atrophic endometrium in 53.3% of patients in the LNG-IUS/estradiol group compared with 76.9% of patients in the drospirenone/estradiol group. CONCLUSIONS: our results suggest good endometrial protection with both HT regimens.