Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium.

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Acquired Hip Dysplasia in Children with Congenital Zika Virus Infection in the First Four Years of Life.

Acquired hip dysplasia has been described in children with cerebral palsy (CP); periodic surveillance is recommended in this population to prevent hip displacement and dislocation. Children with congenital zika syndrome (CZS) may present a spectrum of neurological impairments with changes in tonus, posture, and movement similar to children with CP. However, the relationship between CZS and hip dysplasia has not been characterized. In this prospective cohort study, we aimed to describe the occurrence of hip dysplasia in patients with CZS. Sixty-four children with CZS from 6 to 48 months of age were included and followed at a tertiary referral center in Rio de Janeiro, Brazil, with periodic radiologic and clinical hip assessments. Twenty-six (41%) patients were diagnosed with hip dysplasia during follow-up; mean age at diagnosis was 23 months. According to the Gross Motor Function Classification System (GMFCS), 58 (91%) patients had severe impairment (GMFCS IV and V) at the first evaluation. All patients with progression to hip dysplasia had microcephaly and were classified as GMFCS IV or V. Pain and functional limitation were reported by 22 (84%) caregivers of children with hip dysplasia. All patients were referred to specialized orthopedic care; eight (31%) underwent surgical treatment during follow-up. Our findings highlight the importance of implementing a hip surveillance program and improving access to orthopedic treatment for children with CZS in order to decrease the chances of dysplasia-related complications and improve quality of life.

Anthropometric Parameters of Children with Congenital Zika Virus Exposure in the First Three Years of Life.

Little is known about the impact of congenital Zika virus (ZIKV) exposure on growth in the first years of life. In this prospective cohort study,201 ZIKV antenatally-exposed children were followed at a tertiary referral center in Rio de Janeiro, Brazil. Eighty-seven were classified as congenital Zika syndrome (CZS) patients and 114 as not congenital Zika syndrome (NCZS); growth parameters were described and compared between groups and with WHO standard growth curves. Thirty-four (39%) newborns with CZS and seven (6%) NCZS were small for gestational age (p < 0.001). NCZS mean weight measures ranged from −0.45 ± 0.1 to 0.27 ± 0.2 standard deviations (SD) from the WHO growth curve median during follow-up, versus −1.84 ± 0.2 to −2.15 ± 0.2 SD for the CZS group (p < 0.001). Length mean z-scores varied from −0.3 ± 0.1 at 1 month to 0.17 ± 0.2 SD between 31 and 36 months in the NCZS group, versus −2.3 ± 0.3 to −2.0 ± 0.17 SD in the CZS group (p < 0.001). Weight/height (W/H) and BMI z-scores reached -1.45 ± 0.2 SD in CZS patients between 31 and 36 months, versus 0.23 ± 0.2 SD in the NCZS group (p < 0.01). Between 25 and 36 months of age, more than 50% of the 70 evaluated CZS children were below weight and height limits; 36 (37.1%) were below the W/H cut-off. Gastrostomy was performed in 23 (26%) children with CZS. During the first three years of life, CZS patients had severe and early growth deficits, while growth of NCZS children was normal by WHO standards.

Adverse fetal and neonatal outcomes in pregnancies with confirmed Zika Virus infection in Rio de Janeiro, Brazil: A cohort study.

OBJECTIVE: To analyze adverse fetal and neonatal outcomes of Zika virus infection by the timing of infection during pregnancy. Method: Cohort study of 190 pregnancies with 193 offspring with a positive RT-PCR test for Zika virus (March/2016 to April/2017). RESULTS: Death or defects related to congenital Zika virus infection were identified in 37.3% of fetuses and newborns, and microcephaly in 21.4% of the newborns. The proportion of small for gestational age newborns was 21.9%. Maternal symptoms in the first trimester were significantly associated with the birth of newborns with microcephaly/cerebral atrophy, small for gestational age and with the deaths (one abortion, one stillbirth and the two neonatal deaths). Maternal infection during the second trimester was further associated with asymptomatic newborns at birth. The study showed that 58.5% of the offspring with microcephaly and / or cortical atrophy were small for gestational age, with an evident decrease in symptomatic offspring without microcephaly, 24.1%, and with only 9.1% in the asymptomatic group. CONCLUSION: This study showed that the earlier the symptoms appear during gestation, the more severe the endpoints. We found a higher percentage of small for gestational age newborns exposed to Zika virus early in gestation. We also found a group of apparently asymptomatic newborns with proven Zika infection, which highlights the importance of follow up studies in this population.

Toxoplasmosis in pregnancy: a clinical, diagnostic, and epidemiological study in a referral hospital in Rio de Janeiro, Brazil

ABSTRACT Toxoplasmosis in pregnant women can cause significant morbidity and mortality in the fetus, which may be mitigated by early diagnosis and treatment. Social factors have also been related to the risk of developing the congenital form of toxoplasmosis, since some of these factors interfere directly in the quality of prenatal care. This study aimed to describe the clinical, laboratory, and epidemiological data of pregnant women diagnosed with toxoplasmosis and their newborns followed up at a referral hospital in Rio de Janeiro, Brazil. This was descriptive cohort study of 334 pregnant women with toxoplasmosis followed from May 2014 to December 2017. We conducted interviews to assess knowledge about the disease and its preventive measures, analyzed clinical and laboratory data during antenatal visits, and collected data from the newborns' medical charts. Results: This was a predominantly low-income women cohort study, with little schooling, mainly referred from public health services late in pregnancy (178; 53.3%), in the second and third trimesters (286; 85.6%). Diagnosis of acute toxoplasmosis had not been confirmed in 171 cases (51.2%). Out of 183 (54.9%) women who had initiated treatment at the original health services, 45 (24.6%) received an incorrect prescription. Seventy-two amniocenteses were performed, with positive real-time polymerase chain reaction (qPCR) in the amniotic fluid in two cases (2.8%). Congenital toxoplasmosis at birth was identified in eight newborns (5.4%). Conclusion: Late referral to specialized medical services, inadequate toxoplasmosis management at the original prenatal care services, and social vulnerabilities are contributing factors to the persistent occurrence of congenital toxoplasmosis cases.

Zika vírus e gravidez: achados fetais avaliados pelo ultrassom e doppler e sua associação com o desfecho perinatal / Zika virus and pregnancy: fetal findings assessed by ultrasound and doppler and their association with perinatal outcome

A infecção congênita pelo vírus Zika (ICZ) produz um amplo espectro de complicações perinatais, destacando-se as anomalias estruturais. A associação de achados ultrassonográficos pré-natais (USO) com outros desfechos perinatais adversos, não foi descrita até o momento. Identificamos também um grupo de gestantes cujos conceptos apresentam anomalias estruturais suspeitas de ICZ, porém sem diagnóstico etiológico. Desenvolvemos duas linhas de trabalho. O primeiro trabalho teve como objetivo determinar se os resultados dos exames de ultrassom (USO) e dopplervelocimetria (doppler) realizados durante o pré-natal estavam associados a desfechos neonatais anormais em gestações afetadas pelo ZIKV. Desenho: recorte de um estudo de coorte prospectiva realizado em um único centro de referência no Rio de Janeiro, entre 01 de setembro de 2015 a 31 de maio de 2016, envolvendo 92 gestantes, portadoras de fetos únicos, infectadas pelo vírus ZIKV, com diagnóstico confirmado por exame de transcriptidase reversa aplicada à reação em cadeia da polimerase (RT-PCR). Medidas: como desfecho primário, utilizamos o resultado neonatal adverso composto (RNAC) (morte perinatal, achados anormais no exame neonatal ou achados anormais na neuroimagem pós-natal). Os desfechos secundários incluíram a associação de achados específicos com desfechos neonatais. Resultados: Entre as 92 gestantes e seus conceptos, 55 (60%) apresentaram resultados normais e 37 (40%) resultados anormais nos exames USO. Dos 45 recém-nascidos (RN) com RNAC, 23 (51%) apresentaram resultados normais ao USO. Onze gestantes (12%) apresentaram resultados anormais no exame neonatal (odds ratio ajustado [aOR], 11,6; IC 95%, 1,8-72,8), na neuroimagem pós-natal (aOR, 6,7, IC 95%, 1,1-38,9) e RNAC (aOR, 27,2; IC 95%, 2,5-296,6). Resultados anormais no doppler da artéria cerebral média foram associados a anormalidades do exame neonatal (aOR, 12,8; 95% CI, 2,6-63,2), na neuroimagem pós-natal (aOR, 8,8; IC 95%, 1,7-45,9) e no RNAC (aOR, 20,5; 95% CI, 3,2-132,6). Houve 2 mortes perinatais. Achados anormais no USO pré-natal tiveram uma sensibilidade de 48,9% (IC95%, 33,7%-64,2%) e uma especificidade de 68,1% (IC95%, 52,9%-80,1%) quando associados com os RNAC. Para um resultado normal no USO pré-natal, a sensibilidade foi menor (22,2%; IC95%, 11,2%-37,1%), mas a especificidade foi maior (97,9%; IC95%, 88,7%-99,9%). Conclusão: Resultados anormais nos exames de USO e doppler em gestantes infectadas pelo ZIKV, foram associados a RNAC. Resultados normais no USO pré-natal não estiveram associadas a um desfecho neonatal normal. Frente aos resultados encontrados, recomendamos avaliação completa para todos os RNs expostos ao ZIKV. O segundo trabalho objetivou analisar o comprometimento fetal, utilizando a amniocentese, em gestantes portadoras de fetos com alterações estruturais suspeitas ao USO de ICZ, sem diagnóstico prévio da etiologia. Desenho: estudo de casos que incluiu 16 pacientes. A exposição: amniocentese para realização de RT-PCR para toxoplasmose, ZIKV e citomegalovírus; foi também oferecido cariótipo fetal. Resultados: o exame detectou 7/9 (78%) casos de ICZ; 2 RNs foram diagnosticados após o nascimento. O diagnóstico etiológico foi realizado em 63% dos casos (10/16). Conclusão: a amniocentese foi uma importante ferramenta para diagnosticar ICZ, TORCH e aneuploidias, permitindo o aconselhamento parental adequado, e a programação da assistência perinatal.

Congenital infection with the Zika virus (ICZ) produces a broad spectrum of perinatal abnormalities, including structural defects. The association of prenatal ultrasonographic findings (USO) with adverse perinatal outcomes has not been described so far. We also identified a group of pregnant women whose concepts have structural abnormalities suspected of having ICZ, but without an etiological diagnosis. We have developed two lines of work: The aim of the first study was to determine if the results of ultrasound and Doppler examinations performed during prenatal care were associated with abnormal neonatal outcomes in pregnancies affected by ZIKV. Design: a prospective cohort study conducted in a single referral center in Rio de Janeiro, between September 1, 2015 and May 31, 2016, involving 92 pregnant women with single fetuses infected with the ZIKV virus, diagnosed confirmed by reverse transcriptase examination applied to the polymerase chain reaction (RT-PCR). Measurements: As a primary endpoint, we used composite adverse neonatal outcome (RNAC) (perinatal death, abnormal findings on neonatal examination or abnormal findings in postnatal neuroimaging). Secondary outcomes included the association of specific findings with neonatal outcomes. Results: Among the 92 pregnant women and their concepts, 55 (60%) presented normal results and 37 (40%) had abnormal results in USO exams. Of the 45 newborns (NB) with RNAC, 23 (51%) presented normal results to the USO. Eleven pregnant women (12%) presented abnormal results in the neonatal exam (adjusted odds ratio [aOR], 11.6, 95% CI, 1.8-72.8), postnatal neuroimaging (aOR, 6.7, CI 95%, 1,1-38,9) and RNAC (aOR, 27.2, 95% CI, 2.5-296.6). Doppler abnormalities of the middle cerebral artery were associated with abnormalities of the neonatal examination (aOR, 12.8, 95% CI, 2.6-63.2), postnatal neuroimaging (aOR, 8.8, 95% CI, , 1.7-45.9) and RNAC (aOR, 20.5, 95% CI, 3.2-132.6). There were 2 perinatal deaths. Abnormal findings in prenatal USO had a sensitivity of 48.9% (95% CI, 33.7% - 64.2%) and a specificity of 68.1% (95% CI, 52.9% - 80.1%) when associated with RNACs. For a normal result in prenatal USO, the sensitivity was lower (22.2%, 95% CI, 11.2% -37.1%), but the specificity was higher (97.9%, 95% CI, 88, 7% -99.9%), in relation to RNAC. Conclusion: Abnormal results in USO and Doppler tests in pregnant women infected with ZIKV were associated with neonatal adverse outcomes. Normal results in prenatal USO were not associated with a normal neonatal outcome. In view of the results found, we recommend a complete evaluation for all NBs exposed to ZIKV. The second study aimed to analyze the fetal impairment, using amniocentesis, in pregnant women with fetuses with structural alterations suspected by USO, without previous diagnosis of the etiology. Design: case study involving 16 patients. Exposure: amniocentesis for the realization of RT-PCR for toxoplasmosis, ZIKV and cytomegalovirus; fetal karyotype was also offered. Results: the examination detected 7/9 (78%) cases of ICZ; 2 RNs were diagnosed after birth. The etiological diagnosis was performed in 63% of the cases (10/16). Conclusion: amniocentesis was an important tool to diagnose ICZ, TORCH and aneuploidies, allowing adequate parental counseling, and programming perinatal care.

Diagnóstico de malformações congênitas: impactos sobre a saúde mental de gestantes / Diagnosis of congenital malformations: Impact on the mental health of pregnant women

Resumo Malformação congênita, segunda maior causa de mortalidade infantil, constitui condição de vulnerabilidade importante na gravidez, que repercute desfavoravelmente na saúde mental da gestante. Objetivou-se estudar o impacto do momento do diagnóstico de malformação congênita sobre a saúde mental de 66 gestantes em atendimento pré-natal. Para isso, as participantes responderam ao Questionário "Momento da notícia", o qual identifica variáveis psicossociais relativas ao momento do diagnóstico da deficiência, e as Escalas Beck, para avaliar sinais e sintomas de ansiedade (Beck Anxiety Inventory) e depressão (Beck Depression Inventory). Todas receberam a notícia através de um médico, sendo 19 no segundo trimestre gestacional. Quatorze consideraram a transmissão do diagnóstico apropriada. No entanto, quando a notícia ocorreu no primeiro trimestre, tanto indicadores de ansiedade (p = 0,0009) quanto de depressão (p = 0,000004) se associaram ao momento da comunicação do diagnóstico; diferente de quando a gestante era comunicada no segundo trimestre, ao qual esteve associado somente os indicadores de depressão (p = 0,0462). Discute-se indicadores de ansiedade e depressão na gestação relacionados ao diagnóstico de malformação congênita como agravantes da vulnerabilidade física e psíquica durante a gestação.

Abstract Congenital malformation, the second largest cause of infant mortality, is an important cause of vulnerability during pregnancy, and it has an unfavorable effect on the mental health of pregnant woman. The objective of this study was to investigate the impact of the moment of diagnosis of congenital malformation on the mental health of 66 pregnant women receiving prenatal care. The participants answered the questionnaire "Momento da notícia" (Moment of diagnosis), which identifies psychosocial variables related to the moment of diagnosis. The Beck Scales were also used to assess signs and symptoms of anxiety (Beck Anxiety Inventory) and depression (Beck Depression Inventory). All participants were given the diagnosis by a physician, and 19 were notified during the second trimester of pregnancy. The diagnosis communication was considered adequate by fourteen participants. However, when the diagnosis was notified during the first trimester of pregnancy it was associated with indicators of anxiety (p = 0.0009) and depression (p = 0.000004). Different results were found when the mother was notified during the second trimester, when only the indicators of depression were associated to the diagnosis received (p = 0.0462). The present study addressed the indicators of anxiety and depression during pregnancy associated to the diagnosis of congenital malformation as risk factors for the physical and psychological vulnerability during this period.

Fumo e gravidez: repercussöes hemodinâmicas materna e fetal / Smoking and pregnancy: hemodynmics repercussions maternal and fetal

Apesar das campanhas esclarecedoras, o hábito de fumar durante a gestaçäo ainda majora as estatísticas das populaçöes de pré-natal. As repercussöes atribuídas ao hábito de fumar estäo bem documentadas e seräo minudenciadas no presente trabalho, que visa analisar as possíveis repercussöes hemodinâmicas materna e fetal do fumo

Dopplerfluxometria das artérias uterinas e umbilical na avaliaçåo do prognóstico materno e fetal / Uterine and umbilical doppler velocimetry in the evaluation of materno and fetal outcome

Foram acompanhadas 180 gestantes portadoras de gestaçöes únicas através da dopplerfluxometria das artérias uterinas e umbilical. Utilizamos um aparelho duplex, composto pela unidade de Doppler UGR-34, acoplado ao ultra-som SSD-280LS, ambos da marca ALOKA, Japåo. Para a avaliaçåo da artéria uterina, calculamos inicialmente a relaçåo A/B de cada artéria, e, em seguida, a média e a diferença entre as artérias direita e esquerda. Anotamos ainda a presença ou ausência de incisuras. O estudo da artéria umbilical considerou a relaçåo A/B normal e anormal, destacando-se um subgrupo que apresentou diástole-zero. Correlacionamos esses achados com a presença ou posterior desenvolvimento de hipertensåo arterial e o resultado perinatal, avaliado pelo peso do neonato, índice de Apgar de 5 minutos, natimortalidade, neomortalidade precoce e ausência de anomalias congênitas. Observamos que a dopplerfluxometria das artérias uterinas, avaliadas pela média e diferença da relaçåo A/B, e principalmente pela presença de incisura, associa-se significativamente com o prognóstico materno, nåo aguardando associaçåo com o prognóstico fetal. Por outro lado, o doppler da artéria umbilical, avaliado pela relaçåo A/B anormal e principalmente peo achado de diástole-zero, associa-se significativamente com o mau prognóstico fetal, nåo se asociando com o prognóstico materno

Conduta obstétrica na gestante diabética / Obstetrical management of diabetes in pregnancy

Os autores comentam sobre o acompanhamento e a conduta, sob o ponto de vista obstétrico, da gestaçäo em paciente diabética. É considerada a utilizaçäo da ultra-sonografia, da dopplerfluxometria, da biópsia de vilo corial, da ecocardiografia, da cardiotocografia, da amniocentese e da alfafetoprote­na. Por fim, säo discutidos os critérios de interrupçäo das gestaçöoes nessa populaçäo.