Effect of neurodevelopmental treatment in children with congenital Zika syndrome: A pilot study.

AIM: To evaluate the effects of neurodevelopmental treatment (NDT) in children with congenital Zika syndrome (CZS). METHODS: This prospective, interventional cohort study involved children with CZS undergoing follow-up at a specialist centre in northeastern Brazil. The duration of the proposed NDT protocol was 1 year, with 45-min sessions delivered one to five times weekly. Motor function, weight, height, head circumference and the incidence of comorbidities were evaluated in children before protocol initiation and then at 3, 6 and 12 months of treatment. RESULTS: Thirty children were evaluated (age mean 30.1 ± 3 months). Motor function improved from baseline to 6 months (P = 0.001). No difference in weight and head circumference z-score (P = 0.51 and P = 0.29, respectively), but an increase in height z-score (P < 0.001) was observed over the evaluation period. There was a reduction in the incidence of upper respiratory tract infections, pneumonia and urinary tract infections over the follow-up period. CONCLUSIONS: NDT proved to be a viable treatment approach that can improve motor function and reduce the incidence of comorbidities in children with CZS, while having no harmful effects on their growth.

Maternal mortality and COVID-19.

OBJECTIVE: The aim of this study was to collect and analyze data from different sources to have a general overview of COVID-19-related maternal deaths in Brazil, as well as to compare data with worldwide reports. STUDY DESIGN: We systematically searched data about COVID-19 maternal deaths from the Brazilian Ministry of Health surveillance system, State Departments of Health epidemiological reports, and media coverage. Data about timing of symptom onset and death (pregnancy or postpartum), gestational age, mode of birth, maternal age, comorbidities and/or risk factors, date of death, and place of death were retrieved when available. RESULTS: We identified 20 COVID-19-related maternal deaths, age range 20-43 years. Symptoms onset was reported as on pregnancy for 12 cases, postpartum for 3 cases, and during the cesarean section for 1 case (missing data for 4). In 16 cases, death occurred in the postpartum period. At least one comorbidity or risk factor was present in 11 cases (missing data for 4). Asthma was the most common risk factor (5/11). Ten cases occurred in the Northeast region, and nine cases occurred in the Southeast region (5 of them in São Paulo, the first epicenter of COVID-19 in the country). CONCLUSIONS: To the best of our knowledge, this is the largest available series of maternal deaths due to COVID-19. Barriers to access healthcare, differences in pandemic containment measures in the country and high prevalence of concomitant risk factors for COVID-19 severe disease may play a role in the observed disparity compared to worldwide reports on maternal outcomes.

COVID-19-related deaths among women of reproductive age in Brazil: The burden of postpartum.

OBJECTIVE: To compare risk of death due to COVID-19 among pregnant, postpartum, and non-pregnant women of reproductive age in Brazil, using the severe acute respiratory syndrome surveillance system (SARS-SS). METHODS: A secondary analysis was performed of the Brazilian official SARS-SS, with data retrieved up to August 17, 2020. Cases were stratified by pregnancy status, risk factors or co-morbidities, and outcome (death or recovery). Multiple logistic regression was employed to examine associations between independent variables and risk of death. RESULTS: A total of 24 805 cases were included, with 3129 deaths (12.6%), including 271 maternal deaths. Postpartum was associated with increased risk of death, admission to the intensive care unit (ICU), and mechanical ventilation. Co-morbidities with higher impact on case fatality rate among non-obstetric cases were cancer and neurological and kidney diseases. Among pregnant women, cancer, diabetes mellitus, obesity, and rheumatology diseases were associated with risk of death. In the postpartum subgroup, age over 35 years and diabetes mellitus were independently associated with higher chance of death. CONCLUSION: Postpartum was associated with worse outcomes among the obstetric population, despite lower risk of dying without accessing ICU care. Non-pregnant women with cancer, neurological diseases, and kidney diseases have a higher risk of death due to COVID-19.

Risk factors for adverse outcomes among pregnant and postpartum women with acute respiratory distress syndrome due to COVID-19 in Brazil.

OBJECTIVE: To evaluate whether clinical and social risk factors are associated with negative outcomes for COVID-19 disease among Brazilian pregnant and postpartum women. METHODS: A secondary analysis was conducted of the official Acute Respiratory Syndrome Surveillance System database. Pregnant and postpartum women diagnosed with COVID-19 ARDS until July 14, 2020, were included. Adverse outcomes were a composite endpoint of either death, admission to the intensive care unit (ICU), or mechanical ventilation. Risk factors were examined by multiple logistic regression. RESULTS: There were 2475 cases of COVID-19 ARDS. Among them, 23.8% of women had the composite endpoint and 8.2% died. Of those who died, 5.9% were not hospitalized, 39.7% were not admitted to the ICU, 42.6% did not receive mechanical ventilation, and 25.5% did not have access to respiratory support. Multivariate analysis showed that postpartum period, age over 35 years, obesity, diabetes, black ethnicity, living in a peri-urban area, no access to Family Health Strategy, or living more than 100 km from the notification hospital were associated with an increased risk of adverse outcomes. CONCLUSION: Clinical and social risk factors and barriers to access health care are associated with adverse outcomes among maternal cases of COVID-19 ARDS in Brazil.

Misoprostol administered sublingually at a dose of 12.5 µg versus vaginally at a dose of 25 µg for the induction of full-term labor: a randomized controlled trial.

BACKGROUND: Labor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25 µg. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5 µg versus vaginally at a dose of 25 µg to induce labor in a full-term pregnancy with a live fetus. METHODS: A randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score ≤ 6 and an indication for induction of labor were included. Following randomization, one group received 12.5 µg misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25 µg misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student's t-test, the chi-square test of association and Fisher's exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated. RESULTS: The frequency of tachysystole was lower in the group using 12.5 µg misoprostol sublingually compared to the group using 25 µg misoprostol vaginally (RR = 0.15; 95%CI: 0.02-0.97; p = 0.002). Failure to achieve vaginal delivery within 12 and 24 h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant. CONCLUSION: The effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative. TRIAL REGISTRATION: Registration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.

Motor function in children with congenital Zika syndrome.

AIM: To evaluate gross motor function and associated factors in children with congenital Zika syndrome (CZS). METHOD: Fifty-nine children (30 males, 29 females) with CZS at a mean (SD) age of 14.7 (3.9), months (range 5-29mo) were evaluated using the Gross Motor Function Measure (GMFM) and classified according to the Gross Motor Function Classification System (GMFCS). Neurological damage was evaluated by neuroimaging. The mothers' sociodemographic characteristics and general data on the children were obtained from interviews with the mothers and from the children's medical records. Correlational and multiple regression analyses were performed to identify factors associated with these children's motor function. RESULTS: In 81% of the children, motor function impairment was severe, classified as GMFCS level V. The overall GMFM score ranged from 5 to 210 (median 18; interquartile range 11), with only four children receiving scores in the D and E dimensions. The factors found to affect motor function were the presence of severe malformations of cortical development and small head circumference at birth. INTERPRETATION: Although motor impairment may be mild in some children, it is generally severe. Severe malformations of cortical development and small head circumference at birth were factors associated with poorer motor function, reflecting the greater severity of brain damage. WHAT THIS PAPER ADDS: Motor impairment is severe in most children with congenital Zika syndrome (CZS). Motor skills are adequate or close to adequate for age in 7% of children with CZS. Severe malformations of cortical development are associated with poor motor control. Small head circumference at birth is also associated with poor motor control.

FUNCIÓN MOTORA EN NIÑOS CON SÍNDROME DE ZIKA CONGÉNITO: OBJETIVO: Evaluar la función motora gruesa y los factores asociados en niños con síndrome de Zika congénito (CZS). MÉTODO: Cincuenta y nueve niños (30 varones, 29 mujeres) con CZS a una edad media (DE) de 14,7 (3,9), meses (rango 5-29 meses) se evaluaron utilizando la Medida de la función motora gruesa (GMFM) y se clasificaron de acuerdo con el Sistema de Clasificación de la Función Motora Gruesa (GMFCS). El impacto estructural neurológico se evaluó mediante neuroimagen. Las características sociodemográficas de las madres y los datos generales de los niños se obtuvieron en entrevistas con las madres y de los registros médicos de los niños. Se realizaron análisis de regresión correlacional y múltiple para identificar los factores asociados con la función motora de estos niños. RESULTADOS: En el 81% de los niños, el deterioro de la función motora fue grave, clasificado como nivel V de GMFCS. El puntaje general de GMFM varió de 5 a 210 (mediana 18; rango intercuartil 11), y solo cuatro niños recibieron puntajes en las dimensiones D y E. Los factores que afectaron la función motora fueron la presencia de malformaciones graves del desarrollo cortical y la circunferencia de la cabeza (microcefalia) al nacer. INTERPRETACIÓN: Aunque el deterioro motor puede ser leve en algunos niños, generalmente el impacto de CZS es grave. Las malformaciones graves del desarrollo cortical y la microcefalia al nacer fueron factores asociados con una función motora más limitada, lo que refleja la mayor gravedad del daño cerebral.

FUNÇÃO MOTORA EM CRIANÇAS COM SÍNDROME CONGÊNITA DE ZIKA: OBJETIVO: Avaliar a função motora grossa e fatores associados em crianças com síndrome congênita de Zika (SCZ). MÉTODO: Cinquenta e nove crianas (30 do sexo masculino, 29 do sexo feminino) com SCZ com uma média (DP) de idade de 14,7 (3,9) meses (variação 5-29m) foram avaliadas usando a Medida da Função Motora Grossa (GMFM) e classificadas de acordo com o Sistema de Classificação da Função Motora Grossa (GMFCS). O dano neurológico foi avaliado por neuroimagem. As características sócio-demográficas da mãe e dados gerais sobre as crianças foram obtidos em entrevistas com as mães e a partir dos prontuários medicos. Análises de correlação e de regressão múltipla foram realizadas para identificar fatores associados com a função motora destas crianças. RESULTADOS: Em 81% das crianças, o comprometimento da função motora era severo, classificao como nível GMFCS V. O escore geral da GMFM various de 5 a 210 (mediana 18; intervalo interquartil 11), com apenas quatro crianças recebendo pontuações nas dimensões D e E. Os fatores que afetaram a função motora grossa foram a presença de malformações severas no desenvolvimento cortical, e o pequeno perímetro cefálico ao nascimento. INTERPRETAÇÃO: Embora a deficiência motora possa ser leve em algumas crianças, em geral ela é severa. Malformações severas no desenvolvimento cortical e o pequeno perímetro cefálico foram fatores associados com pior função motora, refletindo a maior severidade do dano cerebral.

Effectiveness of an oral versus sublingual loading dose of nifedipine for tocolysis.

OBJECTIVE: To determine the effectiveness of an oral versus sublingual loading dose of nifedipine for tocolysis. METHODS: An open, randomized clinical trial conducted between March 1, 2013, and April 31, 2014. Participants were pregnant women with a diagnosis of premature labor, single live fetus, topical pregnancy, gestational age 24-36 weeks, normal fetal vitality, cervical dilatation less than or equal to 4 cm, cervical effacement less than or equal to 80%, and intact amniotic membranes. They were randomized into two groups, oral and sublingual nifedipine, 20 mg loading dose, repeated every 30 minutes (maximum dose of 60 mg). The primary endpoint was the time until tocolysis and the secondary endpoints were the effectiveness of tocolysis within 90 minutes, 12 hours, and 48 hours; premature delivery within 48 hours; and maternal hemodynamic parameters and side effects. RESULTS: There were 80 patients randomized to oral (n=40) and sublingual (n=40) nifedipine. The time required for tocolysis was significantly less with sublingual nifedipine (160 minutes vs 340 minutes; P=0.0003). Sublingual nifedipine was also more successful than oral nifedipine at inhibiting premature labor within 90 minutes (n=8 [20.0%] vs n=1 [2.5%], P=0.014). There was no statistically significant difference between the groups for the other secondary endpoints. CONCLUSION: Compared with oral administration, a sublingual loading dose of nifedipine resulted in faster tocolysis in patients with premature labor. Brazilian Clinical Trials Registry (ReBEC): U1111-11566186.

The tragedy of COVID-19 in Brazil: 124 maternal deaths and counting

Relatórios iniciais no início da pandemia de COVID-19 indicaram que a população obstétrica não parecia estar em maior risco de desenvolver sintomas graves de COVID-19 do que a população em geral. [1] No entanto, após publicações recentes que mostram que a gravidez e o período pós-parto podem realmente representar riscos adicionais para mulheres e bebês, essas observações preliminares requerem urgentemente revisão. [2] Explicações para risco aumentado podem incluir imunodeficiência relativa associada a adaptações fisiológicas maternas, bem como resposta orgânica a infecções por vírus.

Serum magnesium levels during magnesium sulfate infusion at 1 gram/hour versus 2 grams/hour as a maintenance dose to prevent eclampsia in women with severe preeclampsia: A randomized clinical trial.

BACKGROUND: Magnesium sulfate is the ideal drug for the prevention and treatment of eclampsia. Nevertheless, the best regimen for protection against eclampsia with minimal side effects remains to be established. This study aimed to compare serum magnesium levels during intravenous infusion of magnesium sulfate at 1 gram/hour versus 2 grams/hour as a maintenance dose to prevent eclampsia in pregnant and postpartum women with severe preeclampsia. METHODS: A randomized, triple-blind clinical trial was conducted, comparing serum magnesium levels during the intravenous infusion of magnesium sulfate at 1 gram/hour versus 2 grams/hour as a maintenance dose for the prevention of eclampsia in 62 pregnant and postpartum women with severe preeclampsia, 31 in each group. An intravenous loading dose of 6 grams of magnesium sulfate was administered over 30 minutes in both groups. The patients were then randomized to receive a maintenance dose of either 1 or 2 grams/hour for 24 hours. Primary outcomes consisted of serum magnesium levels at the following time points: baseline, 30 minutes, every 2 hours until the end of the first 6 hours, and every 6 hours thereafter until the termination of magnesium sulfate infusion. Side effects, maternal complications, and neonatal outcomes were the secondary outcomes. RESULTS: Serum magnesium levels were higher in the 2-gram/hour group, with a statistically significant difference from 2 hours after the beginning of the magnesium sulfate infusion (P <.05). Oliguria was the most common complication recorded in both groups, with no significant difference between the 2 regimens (RR 0.88; 95% CI: 0.49-1.56; P = .65). No cases of eclampsia occurred. Side effects were more common in the 2-gram/hour group (RR 1.89; 95% CI: 1.04-3.41; P = .02); however, all were mild. There were no differences between the 2 groups regarding neonatal outcomes, except for admission to neonatal intensive care, which was more frequent in the 1-gram/hour group (25% vs 6.3%; P = .04). CONCLUSION: Magnesium sulfate therapy at the maintenance dose of 1 gram/hour was just as effective as the 2-gram maintenance dose, with fewer side effects.

Anal prevalence of HPV in women with pre-malignant lesion or cancer in the cervix and anal canal simultaneously: cross-sectional study.

OBJECTIVE: To determine the prevalence of anal HPV genotypes and associated factors in women with pre-malignant lesion or cancer in the cervix and anal canal. METHODS: A prospective, cross-sectional study analyzed DNA samples taken from women with cervical pre-malignant lesions or cancer to identify anal HPV by polymerase chain reaction (PCR). The prevalence of high-risk HPV (HR-HPV) in women with intraepithelial neoplasia and anal cancer was calculated; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS: A total of 152 patients were included (mean age 37.8 ± 10.01 years), of whom 101 (66.4%) had anal HR-HPV. Fourteen different anal HPV types were identified. HPV 16 and 18 were found in 30 (52.6%) anal high-grade squamous intraepithelial lesions (HSIL), and HPV 31 and 33 in 21 (36.8%) lesions. In the logistic regression analysis, the factors that remained associated with HR-HPV types were: an anal histopathology report of HSIL or invasive carcinoma (odds ratio [OR] 8.96, 95% confidence interval [CI] 3.40-23.57; P<0.0001) and alcohol consumption (OR 2.20, 95% CI 1.01-4.80; P=0.04). CONCLUSION: Prevalence of HR-HPV is high in the anal canal of women with cervical and anal pre-malignant lesions simultaneously or cancer of the cervix and/or anal canal. HPV 16, 31, 33, and 18 were the four major genotypes identified.

Acute pulmonary edema in an obstetric intensive care unit: A case series study.

Acute pulmonary edema (PE) affects 0.08% to 1.5% of women during pregnancy and in the postpartum. At the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), acute PE accounts for 1.5% of admissions to the obstetric intensive care unit (ICU) and occurs in 9.3% of the patients admitted with near miss criteria. This study was conducted to describe the clinical/epidemiological profile of patients with acute PE in IMIP's obstetric ICU.A case series of 50 patients with acute PE in an obstetric ICU in northeastern Brazil between August 2012 and March 2015. Frequency distribution and measures of central tendency/dispersion were calculated using Epi Info, version 7.1.5.The mean age of the women was 27.2 years; 60% were from Recife; 50% had 8 to 11 years of schooling; 54.0% were primigravidas. Acute PE occurred antepartum (58%), postpartum (38%), or intrapartum (4.0%). Overall, 8% had had previous episodes; 6% relapsed during hospitalization; 4% died. Caesarean sections were common (78.0%), with 73.3% delivering at <37 weeks and 39.0% at <34 weeks. Etiologies were hypertensive (62%), cardiogenic (16.0%), both hypertensive and cardiogenic (20.0%) or due to fluid overload (2.0%). Irrespective of etiology, in the 24 hours preceding acute PE, fluid overload was present in 34.0%. Median time from diagnosis until resuscitation maneuvers was 5 minutes (within 30 minutes of diagnosis in 75.0% of patients). Mean ICU time was 5 days and mean hospitalization time 11 days.Acute PE is a severe disease resulting in high maternal/perinatal morbidity/mortality rates. Most commonly, it occurred antepartum and associated with hypertension. Fluid overload appears to constitute an important trigger.

Correlation between electromyography and perineometry in evaluating pelvic floor muscle function in nulligravidas: A cross-sectional study.

OBJECTIVE: To correlate the results of electromyography and perineometry in the assessment of PFM function in nulligravidas. METHODS: The cross-sectional observational study was approved by the internal review board of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) and was conducted in the Instituto Paraibano de Pesquisa Professor Joaquim Amorim Neto (IPESQ). Thirty-eight nulligravidas aged 18-39 years of age, who had already initiated their sexual life, participated in the study. Exclusion criteria consisted of the presence of genital prolapse, a history of pelvic or urogenital surgery and the presence of neurological disease producing muscle disorders. For the evaluation procedure, the women were submitted to a clinical evaluation of the pelvic floor muscles followed by electromyography. Perineometry was performed 72 h later. Prior to electromyography and perineometry, the women were given standardized training with electromyographic biofeedback to teach them to contract only their pelvic floor muscles. RESULTS: A highly positive, statistically significant correlation (r = 0.968; P < 0.001) was found between the electromyographic and perineometric findings. CONCLUSIONS: A strong correlation was found between perineometric and electromyographic findings of pelvic floor muscle function.

Cross-sectional study of anal intraepithelial lesions in women with cervical neoplasia without HIV.

OBJECTIVE: To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia. METHODS: The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS: There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (P<0.001); subclinical HPV lesions on vulvoscopy (P=0.057) were not associated with anal intraepithelial neoplasia. CONCLUSION: The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years.

Validation of fullPIERS model for prediction of adverse outcomes among women with severe pre-eclampsia.

OBJECTIVE: To evaluate the accuracy of the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) model for the prediction of complications among patients with severe pre-eclampsia in northeastern Brazil. METHODS: A retrospective study was conducted of data for all patients with severe pre-eclampsia admitted to a center in Recife in 2014. The fullPIERS model was applied to calculate the predicted probability of complications. A receiver operating characteristic curve was constructed to determine the accuracy of the model, and the area under the curve was calculated. Multiple logistic regression analysis was performed. RESULTS: Among 325 included women, 55 (16.9%) had one or more complication before discharge. The area under the curve was 0.72 (P<0.001), determining a cutoff point for fullPIERS probability of 1.7%. Sensitivity was 60.0% and specificity was 65.1%; the positive likelihood ratio was 1.72 and the negative likelihood ratio was 0.61. In multivariate analysis, the only variable that remained significantly associated with complications was a fullPIERS probability of more than 1.7% (odds ratio 5.87, 95% confidence interval 3.16-10.89; P<0.001). CONCLUSION: The fullPIERS model is a useful tool for predicting complications in women with severe pre-eclampsia, with the cutoff point of 1.7%.

The spectrum of neuropathological changes associated with congenital Zika virus infection.

A major concern associated with ZIKV infection is the increased incidence of microcephaly with frequent calcifications in infants born from infected mothers. To date, postmortem analysis of the central nervous system (CNS) in congenital infection is limited to individual reports or small series. We report a comprehensive neuropathological study in ten newborn babies infected with ZIKV during pregnancy, including the spinal cords and dorsal root ganglia (DRG), and also muscle, pituitaries, eye, systemic organs, and placentas. Using in situ hybridization (ISH) and electron microscopy, we investigated the role of direct viral infection in the pathogenesis of the lesions. Nine women had Zika symptoms between the 4th and 18th and one in the 28th gestational week. Two babies were born at 32, one at 34 and 36 weeks each and six at term. The cephalic perimeter was reduced in four, and normal or enlarged in six patients, although the brain weights were lower than expected. All had arthrogryposis, except the patient infected at 28 weeks gestation. We defined three patterns of CNS lesions, with different patterns of destructive, calcification, hypoplasia, and migration disturbances. Ventriculomegaly was severe in the first pattern due to midbrain damage with aqueduct stenosis/distortion. The second pattern had small brains and mild/moderate (ex-vacuo) ventriculomegaly. The third pattern, a well-formed brain with mild calcification, coincided with late infection. The absence of descending fibres resulted in hypoplastic basis pontis, pyramids, and cortico-spinal tracts. Spinal motor cell loss explained the intrauterine akinesia, arthrogryposis, and neurogenic muscle atrophy. DRG, dorsal nerve roots, and columns were normal. Lympho-histiocytic inflammation was mild. ISH showed meningeal, germinal matrix, and neocortical infection, consistent with neural progenitors death leading to proliferation and migration disorders. A secondary ischemic process may explain the destructive lesions. In conclusion, we characterized the destructive and malformative consequences of ZIKV in the nervous system, as reflected in the topography and severity of lesions, anatomic localization of the virus, and timing of infection during gestation. Our findings indicate a developmental vulnerability of the immature CNS, and shed light on possible mechanisms of brain injury of this newly recognized public health threat.

Immune activation in amniotic fluid from Zika virus-associated microcephaly.

Recent advances in the understanding of neuropathogenesis associated with Zika virus (ZIKV) infection has led to descriptions of neonatal microcephaly cases. However, none of these reports have evaluated the humoral response during ZIKV infection. We report here polyfunctional immune activation associated with increased interferon-gamma-inducible protein 10, interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), monocyte chemoattractive protein 1 (MCP-1), and granulocyte colony-stimulating factor (G-CSF) levels in the amniotic fluid of ZIKV-positive pregnant women with neonatal microcephaly. These cytokines have been associated not only with neuronal damage, but also with differentiation and proliferation of neural progenitor cells. Our results suggested that the immune activation caused by ZIKV infection in the uterine environment could also interfere with fetal development. ANN NEUROL 2017;81:152-156.

Pushing/bearing down methods for the second stage of labour.

BACKGROUND: Maternal pushing during the second stage of labour is an important and indispensable contributor to the involuntary expulsive force developed by uterus contraction. Currently, there is no consensus on an ideal strategy to facilitate these expulsive efforts and there are contradictory results about the influence on mother and fetus. OBJECTIVES: To evaluate the benefits and possible disadvantages of different kinds of techniques regarding maternal pushing/breathing during the expulsive stage of labour on maternal and fetal outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 January 2015) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and quasi-randomised assessing the effects of pushing/bearing down techniques (type and/or timing) performed during the second stage of labour on maternal and neonatal outcomes. Cluster-RCTs were eligible for inclusion but none were identified. Studies using a cross-over design and those published in abstract form only were not eligible for inclusion.We considered the following comparisons.Timing of pushing: to compare pushing, which begins as soon as full dilatation has been determined versus pushing which begins after the urge to push is felt.Type of pushing: to compare pushing techniques that involve the 'Valsalva Manoeuvre' versus all other pushing techniques. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We included 20 studies in total, seven studies (815 women) comparing spontaneous pushing versus directed pushing, with or without epidural analgesia and 13 studies (2879 women) comparing delayed pushing versus immediate pushing with epidural analgesia. The results come from studies with a high or unclear risk of bias, especially selection bias and selective reporting bias. Comparison 1: types of pushing: spontaneous pushing versus directed pushingOverall, for this comparison there was no difference in the duration of the second stage (mean difference (MD) 11.60 minutes; 95% confidence interval (CI) -4.37 to 27.57, five studies, 598 women, random-effects, I(2): 82%; T(2): 220.06). There was no clear difference in perineal laceration (risk ratio (RR) 0.87; 95% CI 0.45 to 1.66, one study, 320 women) and episiotomy (average RR 1.05 ; 95% CI 0.60 to 1.85, two studies, 420 women, random-effects, I(2) = 81%; T(2) = 0.14). The primary neonatal outcomes such as five-minute Apgar score less than seven was no different between groups (RR 0.35; 95% CI 0.01 to 8.43, one study, 320 infants), and the number of admissions to neonatal intensive care (RR 1.08; 95% CI 0.30 to 3.79, two studies, n = 393) also showed no difference between spontaneous and directed pushing and no data were available on hypoxic ischaemic encephalopathy.The duration of pushing (secondary maternal outcome) was five minutes less for the spontaneous group (MD -5.20 minutes; 95% CI -7.78 to -2.62, one study, 100 women). Comparison 2: timing of pushing: delayed pushing versus immediate pushing (all women with epidural)For the primary maternal outcomes, delayed pushing was associated with an increase of 54 minutes in the duration of the second stage of labour (MD 54.29 minutes; 95% CI 38.14 to 70.43; 10 studies, 2797 women, random-effects; I(2) = 91%; T(2) = 543.38), and there was no difference in perineal laceration (RR 0.94; 95% CI 0.78 to 1.14, seven studies. 2775 women) and episiotomy (RR 0.95; 95% CI 0.87 to 1.04, five studies, 2320 women). Delayed pushing was also associated with a 20-minute decrease in the duration of pushing (MD - 20.10; 95% CI -36.19 to -4.02, 10 studies, 2680 women, random-effects, I(2) = 96%; T(2) = 604.37) and an increase in spontaneous vaginal delivery (RR 1.07; 95% CI 1.03 to 1.11, 12 studies, 3114 women).For the primary neonatal outcomes, there was no difference between groups in admission to neonatal intensive care (RR 0.98; 95% CI 0.67 to 1.41, three studies, n = 2197) and five-minute Apgar score less than seven (RR 0.15; 95% CI 0.01 to 3.00, three studies, n = 413). There were no data on hypoxic ischaemic encephalopathy. Delayed pushing was associated with a greater incidence of low umbilical cord blood pH (RR 2.24; 95% CI 1.37 to 3.68) and increased the cost of intrapartum care by CDN$ 68.22 (MD 68.22, 95% CI 55.37, 81.07, one study, 1862 women). AUTHORS' CONCLUSIONS: This review is based on a total of 20 included studies that were of a mixed methodological quality.Timing of pushing with epidural is consistent in that delayed pushing leads to a shortening of the actual time pushing and increase of spontaneous vaginal delivery at the expense of an overall longer duration of the second stage of labour and double the risk of a low umbilical cord pH (based only on one study). Nevertheless, there was no difference in the caesarean and instrumental deliveries, perineal laceration and episiotomy, and in the other neonatal outcomes (admission to neonatal intensive care, five-minute Apgar score less than seven and delivery room resuscitation) between delayed and immediate pushing. Futhermore, the adverse effects on maternal pelvic floor is still unclear.Therefore, there is insufficient evidence to justify routine use of any specific timing of pushing since the maternal and neonatal benefits and adverse effects of delayed and immediate pushing are not well established.For the type of pushing, with or without epidural, there is no conclusive evidence to support or refute any specific style or recommendation as part of routine clinical practice. Women should be encouraged to bear down based on their preferences and comfort.In the absence of strong evidence supporting a specific method or timing of pushing, patient preference and clinical situations should guide decisions.Further properly well-designed randomised controlled trials are required to add evidence-based information to the current knowledge. These trials should address clinically important maternal and neonatal outcomes and will provide more complete data to be incorporated into a future update of this review.

Maternal outcomes according to mode of delivery in women with severe preeclampsia: a cohort study.

OBJECTIVE: To determine the association between mode of delivery and maternal complications in patients with severe preeclampsia. METHODS: A prospective cohort study was conducted with 500 pregnant women with severe preeclampsia. The mode of delivery, vaginal or caesarean section, was considered the exposure, while the postpartum maternal complications and severe maternal morbidity were the outcomes. Logistic regression analysis was performed to determine the adjusted risk and 95% confidence intervals (95% CI) of maternal morbidity. RESULTS: Labour was spontaneous in 22.0% and induced in 28.2%, while 49.8% had an elective caesarean section. Ninety-five (67.4%) of the patients in whom labour was induced delivered vaginally. Total Caesarean rate was 68.2%. The risk of severe maternal morbidity was significantly greater in patients submitted to Caesarean section (54.0% versus 32.7%) irrespective of the presence of labour. Factors that remained associated with severe maternal morbidity following multivariate analysis were a diagnosis of HELLP syndrome after delivery (OR = 3.73; 95% CI: 1.55-9.88) and having a caesarean (OR = 1.91; 95% CI: 1.52-4.57). CONCLUSIONS: Caesareans are often performed in patients with severe preeclampsia and are associated with significant postpartum maternal morbidity. Induction of labour should be considered a feasible option in these patients.