Preeclampsia in pregnant women with COVID-19: a prospective cohort study from two tertiary hospitals in Southern Brazil.

Background: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia. Methods: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed. Results: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant. Conclusions: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.

Performance of a local reference curve for predicting small for gestational age fetuses in pregnant women with HIV/AIDS.

PURPOSE: To compare the performance of a local estimated fetal weight curve with curves established for other populations to predict small for gestational age (SGA) fetuses. METHODS: A retrospective and cross-sectional study involving 231 fetuses in which the performance of a local curve (proposed model) was compared with the Hadlock and Intergrowth-21st curves in the prediction of SGA fetuses, by applying them to a population of high-risk pregnant woman with HIV/AIDS. For each model, a receiver operating characteristic curve was adjusted, considering the SGA classification by the neonatal Intergrowth method as the gold standard, and the area under the curve (AUC) was calculated. RESULTS: The models presented linear correlations with each other. The agreement of the proposed model with Hadlock was very good (kappa = 0.83), whereas the proposed model and Intergrowth-21st had moderate agreement (kappa = 0.44). The SGA fetus detection sensitivities of the proposed model and Hadlock were 61.9% and 57.1%, with specificity of 84.1% and 86.2% and accuracy of 80.1% and 81%, respectively, without statistical difference. The sensitivity of the Intergrowth-21st model was 33.3%, while the accuracy was 85.7% and the specificity was 97.4%. The AUC estimated values for the Hadlock, proposed, and Intergrowth-21st models were 0.834, 0.832, and 0.835, respectively. CONCLUSION: The proposed model and Hadlock were interchangeable in the prediction of SGA fetuses and superior to the Intergrowth-21st model.

Urinary bladder agenesis and renal hypoplasia potentially related to in utero Zika virus infection.

This case report describes the clinical findings of a 22-year-old pregnant woman with confirmed Zika virus infection, at 16 weeks of gestation, in Sucre, Colombia. Her ultrasound revealed severe oligohydramnios, intrauterine growth restriction, and a complete absence of the urinary bladder of the fetus. The poor prognosis led to the decision to terminate the pregnancy. Autopsy of the fetus revealed severe bilateral renal hypoplasia.

Effects of Zika infection on growth.

OBJECTIVES: To present the currently available evidence of the effects of congenital Zika virus infection on infant growth, to discuss possible intervening factors, and to describe preliminary data on this growth in a cohort of exposed children. SOURCE OF DATA: Non-systematic review in PubMed, BVS, CAPES, Scopus, Web of Science, Cochrane and Google Scholar databases in the last 5 years, using the terms infection/disease by Zika virus and growth/nutrition/nutritional status/infant nutrition and nutritional needs. Additionally, the anthropometric data of the first 2.5 years of a cohort of children exposed to the Zika virus during pregnancy were reviewed. SYNTHESIS OF DATA: Both intrauterine growth restriction and low birth weight were reported in series of cases of children with congenital Zika syndrome. The postnatal growth deficit of these children appears to be directly proportional to the degree of neurological impairment. The etiology is multifactorial, and nutritional and non-nutritional factors are probably involved. The data from the present cohort show that the head circumference evolution depends on this measurement at birth and that weight-height growth has a trend toward lower weight and length in children with congenital microcephaly and normocephalic at birth who develop some neurological abnormality. CONCLUSIONS: The few existing data suggest that, in children with congenital Zika, the greater the degree of neurological impairment, the greater the impact on growth, whether or not associated with microcephaly at birth.

Prospective Cohort Study of Congenital Cytomegalovirus Infection during Pregnancy with Fetal Growth Restriction: Serologic Analysis and Placental Pathology.

OBJECTIVE: To investigate prospectively the prevalence of congenital cytomegalovirus (CMV) infection and the pathologic features of the placenta in cases of fetal growth restriction (FGR). STUDY DESIGN: Forty-eight pregnant women who were diagnosed with FGR during pregnancy were enrolled for 15 months. Maternal CMV serologic tests, pathologic examinations of the placenta, and newborn urinary CMV-DNA polymerase chain reaction tests were performed in all the cases. The clinical characteristics and laboratory findings of the pregnant women and their newborns were collected. Biomarkers for inflammation, angiogenesis, and placental hormones were measured in the maternal serum at FGR diagnosis or in the neonatal urine at birth. RESULTS: One of the 48 cases with FGR was a congenital CMV infection. CMV antigen was detected in the placenta of 7 cases with FGR. The change rate of the estimated fetal body weight was significantly lower in FGR cases with placental CMV detection. Placental villitis was observed more frequently in FGR cases with placental CMV detection. Human placental lactogen was significantly decreased in FGR cases with placental CMV detection. Increased C-reactive protein and serum amyloid A levels in the maternal serum were observed more frequently in FGR cases with placental CMV detection. Newborn urine ß-2 microglobulin levels were significantly higher in FGR cases with placental CMV detection. CONCLUSIONS: Serologic tests for maternal CMV, the change rate of the estimated fetal body weight, analysis of several biomarkers, and placental pathologic examinations might be helpful in comprehensively predicting the possibility of congenital CMV infection.

Effects of Zika infection on growth / Repercussões da infecção por Zika sobre o crescimento

Abstract Objectives: To present the currently available evidence of the effects of congenital Zika virus infection on infant growth, to discuss possible intervening factors, and to describe preliminary data on this growth in a cohort of exposed children. Source of data: Non-systematic review in PubMed, BVS, CAPES, Scopus, Web of Science, Cochrane and Google Scholar databases in the last 5 years, using the terms infection/disease by Zika virus and growth/nutrition/nutritional status/infant nutrition and nutritional needs. Additionally, the anthropometric data of the first 2.5 years of a cohort of children exposed to the Zika virus during pregnancy were reviewed. Synthesis of data: Both intrauterine growth restriction and low birth weight were reported in series of cases of children with congenital Zika syndrome. The postnatal growth deficit of these children appears to be directly proportional to the degree of neurological impairment. The etiology is multifactorial, and nutritional and non-nutritional factors are probably involved. The data from the present cohort show that the head circumference evolution depends on this measurement at birth and that weight-height growth has a trend toward lower weight and length in children with congenital microcephaly and normocephalic at birth who develop some neurological abnormality. Conclusions: The few existing data suggest that, in children with congenital Zika, the greater the degree of neurological impairment, the greater the impact on growth, whether or not associated with microcephaly at birth.

Resumo Objetivos: Apresentar as evidências atualmente disponíveis das repercussões da infecção congênita pelo vírus Zika no crescimento infantil, discutir possíveis fatores intervenientes e descrever dados preliminares desse crescimento em uma coorte de crianças expostas. Fonte dos dados: Revisão não sistemática nos portais de banco de dados PubMed, BVS, Capes, Scopus, Web of Science, Cochrane e Google Scholar nos últimos cinco anos, com o uso dos termos infecção/doença pelo vírus Zika e crescimento/nutrição/status nutricional/nutrição infantil e necessidades nutricionais. Além disso, foram revistos os dados antropométricos dos primeiros dois anos e meio de uma coorte de crianças expostas ao vírus Zika durante a gestação. Síntese dos dados: Tanto a restrição do crescimento intrauterino como o baixo peso ao nascer têm sido relatados em séries de casos de crianças com síndrome de Zika congênita. O déficit de crescimento pós-natal dessas crianças parece ser diretamente proporcional ao grau de comprometimento neurológico. A etiologia é multifatorial, com fatores nutricionais e não nutricionais provavelmente envolvidos. Os dados de nossa coorte mostram que a evolução do perímetro cefálico é dependente do valor dessa medida ao nascimento e que o crescimento pondero-estatural apresenta uma tendência de menor peso e comprimento em crianças com microcefalia congênita e normocefálicas ao nascimento, mas com alguma anormalidade neurológica evolutiva. Conclusões: Os poucos dados existentes sugerem que em crianças com Zika congênita, o impacto sobre o crescimento será tanto maior quanto maior for o grau de comprometimento neurológico, associado ou não à microcefalia ao nascimento.

Specific Biomarkers Associated With Neurological Complications and Congenital Central Nervous System Abnormalities From Zika Virus-Infected Patients in Brazil.

Background: Zika virus (ZIKV) infections have been linked to different levels of clinical outcomes, ranging from mild rash and fever to severe neurological complications and congenital malformations. Methods: We investigated the clinical and immunological response, focusing on the immune mediators profile in 95 acute ZIKV-infected adult patients from Campinas, Brazil. These patients included 6 pregnant women who later delivered during the course of this study. Clinical observations were recorded during hospitalization. Levels of 45 immune mediators were quantified using multiplex microbead-based immunoassays. Results: Whereas 11.6% of patients had neurological complications, 88.4% displayed mild disease of rash and fever. Several immune mediators were specifically higher in ZIKV-infected patients, and levels of interleukin 10, interferon gamma-induced protein 10 (IP-10), and hepatocyte growth factor differentiated between patients with or without neurological complications. Interestingly, higher levels of interleukin 22, monocyte chemoattractant protein 1, TNF-α, and IP-10 were observed in ZIKV-infected pregnant women carrying fetuses with fetal growth-associated malformations. Notably, infants with congenital central nervous system deformities had significantly higher levels of interleukin 18 and IP-10 but lower levels of hepatocyte growth factor than those without such abnormalities born to ZIKV-infected mothers. Conclusions: This study identified several key markers for the control of ZIKV pathogenesis. This will allow a better understanding of the molecular mechanisms of ZIKV infection in patients.

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

Zika Virus Infection in Pregnant Women in Rio de Janeiro.

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).