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.

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.

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.

Reasons given by pregnant women for participating in a clinical trial aimed at preventing premature delivery: a qualitative analysis.

BACKGROUND: In clinical trials, pregnant women are potentially vulnerable, and the fetus is exposed to the intervention. This study aimed to identify the reasons that led pregnant women at a high risk of premature delivery to participate in a randomized clinical trial. METHODS: The women participating in the main trial were contacted by telephone postpartum and invited to answer an open questionnaire in a cross-sectional study. Data were collected by telephone and analyzed using thematic analysis. After the analysis categories were defined, all the answers were reviewed, categorized and grouped. A descriptive summary of the content of each category was then made. RESULTS: Overall, 208 women from different geographical regions of the country agreed to participate. Four categories were identified: 1) The risk of losing the baby; 2) A previous experience of premature delivery; 3) The role of the doctor and other health professionals, and 4) The availability of quality medical care and free medication. The main reason given for agreeing to participate was to reduce the risks associated with the baby being born prematurely, particularly when the woman herself or someone close to her had already experienced premature delivery. Other reasons were having received clear guidance and explanations from the doctor regarding prematurity and about the study and being given the opportunity to receive free treatment with greater access to the public healthcare system. CONCLUSIONS: The decision to participate in a clinical trial is not easy, particularly when the individual is vulnerable and in a critical situation as in the case of a pregnant woman at a high risk of delivering prematurely. Fears and uncertainties regarding the pregnancy outcome, as well as the woman's previous experiences and her awareness of the actual risks she faces will affect her decision regarding whether or not to participate. Recruitment challenges could be overcome by ensuring that the research team provides adequate information and support, thus creating a bond with participants that would foster a sense of safety and trust in the study proposals.

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.

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.

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.

Tumor necrosis factor (TNF) alpha and interleukin (IL) 18 genes polymorphisms are correlated with susceptibility to HPV infection in patients with and without cervical intraepithelial lesion.

BACKGROUND: The Human Papillomavirus (HPV) predisposes 500 000 women to cervical cancer. Host genetic background may facilitate virus persistence in the uterine cervix. Polymorphisms in regulatory and coding regions of cytokine genes have been associated with susceptibility to some human diseases. AIM: This study aims at investigating whether TNFA -308 G/A and IL18 -137 G/C and -607 C/A polymorphisms are associated with susceptibility to HPV infection/progression to high-grade squamous intraepithelial lesion (HSIL). SUBJECTS AND METHODS: One hundred and twenty-two HPV infected and 132 HPV negative women (the latter used as healthy controls) were analysed. TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were analysed using specific sequence polymorphism PCR (SSP-PCR). Univariate statistical analysis and a logistic regression were performed. RESULTS: The TNFA -308A allele was associated with susceptibility to HPV infection (p = 0.0008), while the IL18 -607A allele conferred protection against HPV infection (p = 0.0043). TNFA -308 G/A and IL18 (-137G/C and -607 C/A) polymorphisms were not associated with development of cervical lesions (p > 0.05). An association was also observed between smoking and susceptibility to the development of HSIL. CONCLUSION: The findings suggest an association between two TNFA SNPs and susceptibility to HPV infection in women from Northeast Brazil. The results need to be functionally validated and replicated in other populations with different ethnic backgrounds.

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.

Prevalence of post-mastectomy pain syndrome and associated risk factors: a cross-sectional cohort study.

This study was designed to determine the prevalence of post-mastectomy pain and its associated risk factors in women submitted to surgical treatment for breast cancer. A cross-sectional cohort study was conducted involving 250 women treated surgically for breast cancer. The variables evaluated were (a) post-mastectomy pain syndrome (PMPS) (as a dependent variable or outcome) and (b) the patients' social characteristics (schooling, marital status), biological characteristics (body mass index, skin color, age), prior history of headache and dysmenorrhea, occurrence of acute postoperative pain, and type of surgery (mastectomy or quadrantectomy) (as independent or predictive variables). The prevalence ratios (PR) and their respective 95% confidence intervals (95% CI) were calculated as a measure of the risk of PMPS. Multivariate analysis was performed using a hierarchical model of stepwise logistic regression that included possible explanatory variables, calculating the adjusted risk of PMPS from the odds ratio (OR) and the 95% CI at a significance level of 5%. PMPS was found in 44.4% of patients. The variables that remained strongly associated with PMPS following multiple logistic regression analysis were quadrantectomy with axillary lymphadenectomy (OR = 2.83; 95% CI: 1.60-5.02), prior history of headache (OR = 1.92; 95% CI: 1.10-3.34), and age <50 years (OR = 4.37; 95% CI: 2.43-7.86). PMPS is a common condition, particularly in women submitted to quadrantectomy with axillary lymphadenectomy, those under 50 years of age, and those with a prior history of headache. Attention should be paid to these factors at preoperative evaluation and counseling, and they should be taken into consideration in postoperative management.

Active pelvic movements on a Swiss ball reduced labour duration, pain, fatigue and anxiety in parturient women: a randomised trial.

QUESTION: How much do active pelvic movements on a Swiss ball during labour affect maternal and neonatal outcomes? METHOD: A randomised trial with concealed allocation, blinded assessors and intention-to-treat analysis. PARTICIPANTS: Two-hundred parturient women. INTERVENTION: The experimental group performed pelvic anteversion and retroversion, lateral pelvic tilts and circular hip movements according to individual obstetric evaluation (foetal station and position, cervical dilatation and the presence of early pushing urge) on a Swiss ball. The control group received usual care. Both groups were permitted to walk and shower. OUTCOME MEASURES: The primary outcome was the duration of the first stage of labour. The secondary outcomes were the duration of the second stage of labour, pain intensity, delivery mode, medication use, local swelling, fatigue, anxiety, satisfaction and neonatal outcomes. RESULTS: The experimental intervention reduced the duration of labour by 179 minutes (95% CI 146 to 213) in stage one and 19 minutes (95% CI 13 to 25) in stage two. It decreased pain by approximately 2 points (95% CI 2 to 2) on a 0-to-10 scale at 30, 60 and 90 minutes. It reduced the risk of a caesarean section (ARR 0.14, 95% CI 0.03 to 0.25; NNT 7, 95% CI 4 to 32) and vulvar swelling (ARR 0.11, 95% CI 0.03 to 0.19; NNT 9, 95% CI 5 to 31). It reduced fatigue by 18 points (95% CI 16 to 21) on a 15-to-75-point scale and anxiety by 9 points (95% CI 8 to 11) on an 18-to-72-point scale. Other effects were negligible or unclear. CONCLUSION: Active pelvic movements on a Swiss ball during labour reduced the duration of labour, pain intensity, and maternal fatigue and anxiety; they also lowered the risk of caesarean section and vulvar swelling. Several effects exceeded the smallest worthwhile effect. REGISTRATION: NCT04124835.

Misoprostol prior to inserting an intrauterine device in nulligravidas: a randomized clinical trial.

STUDY QUESTION: How effective is the vaginal administration of misoprostol in dilating the cervix prior to inserting an intrauterine device (IUD) in nulligravidas? SUMMARY ANSWER: The use of misoprostol at a dose of 400 µg administered vaginally 4 h prior to IUD insertion increased the ease of insertion and reduced the incidence of pain during the procedure, although the frequency of cramps increased following misoprostol use. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Misoprostol has been widely used in Obstetrics and Gynecology; however, its usefulness and efficacy in facilitating IUD insertion in nulligravidas have yet to be established. The present study shows that the benefits of misoprostol use prior to IUD insertion include facilitating insertion and reducing pain during the procedure; therefore, weighing up the benefits encountered against the only negative side effect (cramps prior to insertion), these results suggest that misoprostol use should become standard practice to facilitate IUD insertion in nulligravidas. STUDY DESIGN, SIZE DURATION: A randomized, double-blind clinical trial was conducted. PARTICIPANTS/MATERIALS, SETTING METHODS: Nulligravid women of reproductive age were submitted to IUD insertion between July 2009 and November 2011 at the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, Brazil. A total of 179 women were randomly allocated to two groups: 86 to receive 400 µg of misoprostol vaginally 4 h prior to IUD insertion and 93 to receive placebo. Risk ratios (RRs) were calculated as measures of relative risk, together with their 95% confidence intervals (95% CI). The number needed to treat (NNT) and the number needed to harm (NNH) were also calculated. MAIN RESULTS AND THE ROLE OF CHANCE: Significant differences were found between the groups for all the immediate end points studied, with less difficulty in inserting the IUD [RR = 0.49 (23/86 versus 51/93); 95% CI: 0.33-0.72; P = 0.00005], a lower risk of dilatation <4 mm [RR = 0.48 (24/86 versus 54/93); 95% CI: 0.33-0.70; P = 0.0001], a reduction in moderate-to-severe pain at IUD insertion [RR = 0.56 (32/86 versus 62/93]; 95% CI: 0.41-0.76; P = 0.00008), as well as a lesser likelihood of experiencing a disagreeable or very disagreeable sensation [RR = 0.49(29/86 versus 64/93); 95% CI: 0.35-0.68; P = 0.000004] in the group that was given misoprostol compared with the group that received placebo. There was no significant difference between the groups in relation to complications during IUD insertion. There were no cases of uterine perforation in either group. The frequency of cramps was 40% higher in the misoprostol group. LIMITATIONS, REASONS FOR CAUTION: The present study showed a positive balance between the benefits and risks of the use of misoprostol; however, it is not feasible to conclude that its use is imperative prior to IUD insertion in nulligravidas and IUD insertion should not be canceled when the medication is unavailable. WINDER IMPLICATIONS OF THE FINDINGS: In view of its effect in promoting cervical dilatation, misoprostol may be used prior to IUD insertion both in nulligravidas and in any women with cervical stenosis irrespective of parity. STUDY FUNDING: This study was funded by the Instituto de Medicina Integral Prof Fernando Figueira. COMPETING INTERESTS: None.

Visceral adiposity in the first half of pregnancy predicts newborn weight among adolescent mothers.

OBJECTIVE: Maternal obesity is a strong risk factor for gestational diabetes mellitus and fetal macrosomia. We assessed the association between maternal visceral adiposity tissue (VAT) depth in the first half of pregnancy and both glucose tolerance in late pregnancy and newborn weight in pregnant adolescents. METHODS: We completed a prospective cohort study of 73 pregnant adolescents aged 10 to 19 years, without pre-pregnancy diabetes. VAT depth was measured by ultrasound at 12 to 20 weeks' gestation, followed by a two-hour 75-g oral glucose tolerance test at 36 to 39 weeks' gestation, to determine the glucose area under the curve (AUC glucose0-120). The association between VAT depth and newborn weight was evaluated by multiple linear regression analysis, controlling for maternal age, parity, smoking, gestational age at delivery, infant sex, pre-pregnancy BMI, weight gain in pregnancy, and fasting serum glucose at 36 to 39 weeks' gestation. The relation between VAT depth and AUC glucose0-120 was assessed by linear regression analysis, adjusting for maternal age, parity, smoking, pre-pregnancy BMI, and weight gain in pregnancy. RESULTS: A 1 cm increase in VAT depth was associated with a 206 g (95% CI 101 to 311) adjusted increase in mean birth weight. VAT depth and the other model covariates together explained more of the variance in birth weight (r(2) = 0.282; P < 0.001) than pre-pregnancy BMI with the other covariates in the same model (r(2) = 0.081; P = 0.076). All three glucose tolerance test measures were performed at 36 to 39 weeks' gestation in 51 of the 73 participants. The relationship between VAT depth and AUC glucose0-120 was not significant (P = 0.43). CONCLUSION: VAT depth in the first half of pregnancy predicts newborn weight better than BMI, but is not associated with glucose tolerance in late pregnancy.

Objectif : L'obésité maternelle constitue un solide facteur de risque en ce qui concerne le diabète sucré gestationnel et la macrosomie fœtale. Nous avons évalué, chez des adolescentes enceintes, l'association entre, d'une part, la profondeur du tissu adipeux viscéral (TAV) maternel au cours de la première moitié de la grossesse et, d'autre part, la tolérance au glucose aux derniers moments de la grossesse et le poids du nouveau-né. Méthodes : Nous avons mené une étude de cohorte prospective auprès de 73 adolescentes enceintes âgées de 10 à 19 ans qui ne présentaient pas un diabète prégrossesse. La profondeur du TAV a été mesurée par échographie à 12 - 20 semaines de gestation; par la suite, nous avons mené une épreuve d'hyperglycémie provoquée par voie orale (deux heures, 75 g) à 36 - 39 semaines de gestation, en vue de déterminer la surface sous la courbe du glucose (SSC glucose0­120). L'association entre la profondeur du TAV et le poids du nouveau-né a été évaluée au moyen d'une analyse de régression linéaire multiple, en neutralisant l'effet de l'âge maternel, de la parité, du tabagisme, de l'âge gestationnel au moment de l'accouchement, du sexe du nouveau-né, de l'IMC prégrossesse, du gain pondéral pendant la grossesse et de la glycémie à jeun à 36 - 39 semaines de gestation. La relation entre la profondeur du TAV et la SSC glucose0­120 a été évaluée au moyen d'une analyse de régression linéaire, en neutralisant l'effet de l'âge maternel, de la parité, du tabagisme, de l'IMC prégrossesse et du gain pondéral pendant la grossesse. Résultats : L'augmentation de la profondeur du TAV d'un centimètre a été associée à une hausse corrigée du poids moyen de naissance de 206 g (IC à 95 %, 101 - 311). La profondeur du TAV (prise en considération conjointement avec les autres covariables du modèle) a mieux permis d'expliquer la variance du poids de naissance (r2 = 0,282; P < 0,001) que l'IMC prégrossesse (prise en considération conjointement avec les autres covariables du même modèle) (r2 = 0,081; P = 0,076). Les trois épreuves d'hyperglycémie ont été menées à 36 - 39 semaines de gestation chez 51 des 73 participantes. La relation entre la profondeur du TAV et la SSC glucose0­120 ne s'est pas révélée être significative (P = 0,43). Conclusion : Bien que la profondeur du TAV au cours de la première moitié de la grossesse permette de mieux prédire le poids du nouveau-né que l'IMC, elle n'est pas associée à la tolérance au glucose aux derniers moments de la grossesse.

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%.

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.

Role of fetal sex in the outcome of antenatal glucocorticoid treatment to prevent respiratory distress syndrome: systematic review and meta-analysis.

BACKGROUND: Antenatal glucocorticoid (AGC) therapy has been associated with a decrease in respiratory distress syndrome (RDS). While preterm males remain at greater risk of RDS than females, the role of fetal sex in AGC response is not well known. OBJECTIVES: To review the available evidence regarding the effect of fetal sex in the prevention of RDS using AGC. METHOD: We conducted a systematic review and meta-analysis of RCTs to compare the effect of AGC in male and female infants with regard to the rates of RDS, intra-ventricular hemorrhage (IVH) grades III and IV, and neonatal mortality. Random effects with 95% confidence intervals were assessed in both groups and relative risks were compared using mixed regression. RESULTS: From 248 potentially eligible articles, we included eight in the analysis for a total of 1109 male and 968 female infants. Both male and female infants had a significant decrease in the risks, but no difference between the sexes was observed in terms of reduction in RDS (RR 0.50; 95% CI 0.33 to 0.77 for males, and RR 0.57; 95% CI 0.43 to 0.75 for females, P = 0.99), reduction in IVH (P = 0.98), and reduction in neonatal mortality (P = 0.43). In a sub-analysis, use of betamethasone was associated with a significant decrease in the rate of RDS in males (RR 0.29; 95% CI 0.15 to 0.57) but dexamethasone was not (RR 0.78; 95% CI 0.57 to 1.07). Conversely, dexamethasone use was significantly helpful in females (RR 0.51; 95% CI 0.32 to 0.81) but betamethasone was not (RR 0.62; 95% CI 0.38 to 1.00). CONCLUSION: The effect of AGC for prevention of RDS is similar in females and males. However, futures studies should investigate the type of AGC according to fetal/neonatal sex.

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.