Clinical characteristics, complications, and predictive model of histological chorioamnionitis in women with preterm premature rupture of membranes.

We aimed to analyze the impact of histological chorioamnionitis (HCA) in the presence of preterm premature rupture of the membranes (PPROM) on obstetric and neonatal outcomes, and its possible predictability. A retrospective cohort analysis of PPROM cases (20-37 weeks) was conducted comparing the patients with and without HCA, seeking a predictive model of HCA using logistic regression. A total of 295 cases of PPROM were selected, of which 72 (24.4%) had HCA. The group with HCA had a shorter latency period and a greater number of clinical and laboratory criteria in the evolution. The group with HCA had a worse comparative result and presented: lower gestational age at delivery, lower average birth weight, lower Apgar scores, longer neonatal hospitalization, worse maternal clinical conditions and, higher rates of stillbirth, low birth weight (LBW), very low birth weight (VLBW), complications in pregnancy and childbirth, and cesarean delivery due to fetal distress or chorioamnionitis. A predictive model for HCA was developed, with the following independent variables: abdominal pain (odds ratio [OR] = 11.61), uterine activity (noticeable contractions on physical exam) (OR = 5.97), fever (OR = 5.77), latency > 3 days (OR = 2.13), and C-reactive protein (OR = 1.01). With this model, an adequate receiver operating characteristic curve was found, with an area under the curve of 0.726, and some HCA probability curves were constructed for different clinical situations. In this novel study, we present a non-invasive predictive model, with clinical and laboratory variables, which may help in decision-making in a patient with PPROM.

Current evidence of SARS-CoV-2 vertical transmission: an integrative review.

OBJECTIVE: To review the current scientific evidence of vertical transmission related to coronavirus disease 2019 (COVID-19). METHODS: An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed) and LILACS databases, using the descriptors "pregnancy" AND "COVID-19" AND "vertical transmission". This search included case reports or case series published up until 17th June 2020 in English or Portuguese. After reading the articles available in their entirety, those related specifically to the potential risks of vertical transmission of COVID-19 during pregnancy were selected. We initially found a total of 57 articles; 26 were carefully screened and 15 were finally selected. RESULTS: Pregnancy can make women more susceptible to infections, especially by viral pathogens, given the various physiological and immunological changes that occur to maintain maternal-fetal balance. It is speculated that the fetus may be a possible target for COVID-19. Few studies (3 out of 15) in our analysis have found positive results for SARS-CoV-2 in fetal membranes, placenta, and in newborns right after birth. Additionally, no difference was noticed when comparing different modes of delivery, and seems reasonable to assume that pregnant women with stable clinical conditions can be encouraged for vaginal delivery. CONCLUSION: Further studies with a great number of cases are warranted to elucidate whether the virus may be vertically transmitted to the fetus and if any maternal conditions can influence that. Our findings seem to demonstrate that vertical transmission is possible but quite unusual.

Immunological aspects of coronavirus disease during pregnancy: an integrative review.

OBJECTIVE To review the immunological aspects of the 2019 coronavirus disease (COVID-19) in pregnancy, based on the scientific evidence currently available. METHODS An integrative review was performed by two independent researchers, based on the literature available in the MEDLINE (via PubMed) and LILACS databases, using the descriptors "pregnancy" and "COVID-19". This search included articles published up until 14th April 2020 published in English, Spanish or Portuguese. After reading the articles available in their entirety, those related specifically to the immunological aspects of the disease in pregnancy were selected. We initially found a total of 62 articles; 52 were accessed in full-text, and 5 were finally selected. RESULTS Pregnant women are more affected by respiratory diseases possibly because of physiological, immune, and anatomical changes. Some studies highlight the important shift to a T-helper lymphocyte type 2 (Th2) immune response in pregnancy, as a potential contributor to the severity in cases of COVID-19. Additionally, the cytokine storm present in severe cases leads to an increased inflammatory state, which may deteriorate the clinical prognosis in this population. Therefore, pregnant women may represent a vulnerable group to COVID-19 infection, primarily due to the immune imbalance in the maternal-fetal interface. CONCLUSION Maternal immune response probably plays an important role in the pathophysiology of this infection, although some details remain unsolved. Although further studies are needed to deeply investigate the immunological aspects of the disease in pregnancy, our findings may provide insights into the possible immune mechanisms involved in the pathophysiology of COVID-19 in pregnancy.

Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia.

OBJECTIVES: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia. METHODS: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins. RESULTS: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024). CONCLUSION: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

Epidemiological profile of patients with preterm premature rupture of membranes at a tertiary hospital in São Paulo, Brazil.

OBJECTIVE: To perform a descriptive analysis of preterm premature rupture of membranes (PPROM) cases attended in a tertiary hospital. METHOD: Retrospective analysis of medical records and laboratory tests of patients admitted to a Brazilian tertiary hospital between 2006 and 2011, with a confirmed diagnosis of PPROM and gestational age (GA) at delivery <37 weeks. RESULTS: A total of 299 pregnant women were included in the study. Nine patients evolved to abortion, and 290 pregnant women remained for the final analysis. There was initial diagnostic doubt in 17.6% of the cases. The oligohydramnios rate [amniotic fluid index (AFI) <5] was 27.9% on admission. Chorioamnionitis was initially diagnosed in 10.8% of the patients and was retrospectively confirmed in 22.9% of the samples. The latency period had a mean of 9.1 days. The main reasons for interruption were premature labor (55.2%), GA ≥36 weeks (27.2%), and fetal distress (6.9%). The delivery method was cesarean section in 55% of cases. The mean birth weight was 2,124 grams, and 67% of the neonates had a low birth weight (<2500 g). The GA at delivery averaged 33.5 weeks. The stillbirth rate was 5.3%, and the early neonatal mortality rate was 5.6%. There were complications at delivery in 18% of mothers. CONCLUSION: In one of the few Brazilian reports on the epidemiological profile of PPROM, with GA until 37 weeks and intercurrences generally excluded from assessments (such as twinning and fetal malformations), there is a favorable evolution, with an acceptable rate of complications.

The effect of prenatal vaginal progesterone on cervical length in nonselected twin pregnancies.

PURPOSE: The aim of this study was to investigate the influence of vaginal progesterone on cervical length (CL) in asymptomatic nonselected twin gestations. METHODS: This was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. The CL was examined at six different time periods: 18-21+6 weeks (T1), 21-23+6 weeks (T2), 24-26+6 weeks (T3), 27-29+6 weeks (T4), 30-32+6 weeks (T5) and 33-34+6 weeks (T6). The rate of cervical shortening per week and the percent cervical shortening were compared between the groups, with analyses of the entire cohort and of those who delivered spontaneously according to gestational age at birth. RESULTS: The final analysis included 184 women in the progesterone group and 188 women in the placebo group. The baseline characteristics were similar in both groups. No differences in cervical shortening in terms of absolute value or percent shortening were observed between the groups at each time period or throughout gestation. Furthermore, no difference was found in cervical shortening for those who delivered spontaneously. CONCLUSION: Cervical shortening in asymptomatic nonselected twin pregnancies occurred at a similar rate, regardless of vaginal progesterone treatment.

Expression of dNK cells and their cytokines in twin pregnancies with preeclampsia

OBJECTIVES: To assess the expression of decidual natural killer (dNK) cells and their cytokines in twin pregnancies with preeclampsia. METHODS: This was a prospective case-control study. The inclusion criteria were diamniotic (monochorionic or dichorionic) twin pregnancies in the third trimester with negative serological results for infectious diseases; absence of major fetal abnormalities or twin-twin transfusion syndrome; and no history of administration of corticosteroids in this pregnancy. The control group (CG) included uncomplicated twin pregnancies, and the preeclampsia group (PEG) included twin gestations with clinical and laboratory confirmation of the disease according to well-established criteria. Samples of the decidua were obtained and analyzed by immunohistochemistry for the expression of dNK cells and interleukins (ILs) 10, 12 and 15. In addition, maternal serum samples were collected to determine the levels of these interleukins. RESULTS: Thirty twin pregnancies were selected: 20 in the control group (CG) and 10 in the preeclampsia group (PEG). The PEG showed strong placental immunostaining for IL-15 (p=0.001) and high maternal serum levels of IL-10 (22.7 vs. 11.9 pg/mL, p=0.024) and IL-15 (15.9 vs. 7.4 pg/mL, p=0.024). CONCLUSION: A higher maternal serum concentration of both pro- and anti-inflammatory factors was observed in the twin pregnancies in the PEG. However, no difference in placental expression of IL-10 was found between the groups. These findings may suggest that maternal attempts to balance these interleukins were not sufficient to cause a placental response, and this failure may contribute to the development of preeclampsia.

Epidemiological profile of patients with preterm premature rupture of membranes at a tertiary hospital in São Paulo, Brazil

OBJECTIVE: To perform a descriptive analysis of preterm premature rupture of membranes (PPROM) cases attended in a tertiary hospital. METHOD: Retrospective analysis of medical records and laboratory tests of patients admitted to a Brazilian tertiary hospital between 2006 and 2011, with a confirmed diagnosis of PPROM and gestational age (GA) at delivery <37 weeks. RESULTS: A total of 299 pregnant women were included in the study. Nine patients evolved to abortion, and 290 pregnant women remained for the final analysis. There was initial diagnostic doubt in 17.6% of the cases. The oligohydramnios rate [amniotic fluid index (AFI) <5] was 27.9% on admission. Chorioamnionitis was initially diagnosed in 10.8% of the patients and was retrospectively confirmed in 22.9% of the samples. The latency period had a mean of 9.1 days. The main reasons for interruption were premature labor (55.2%), GA ≥36 weeks (27.2%), and fetal distress (6.9%). The delivery method was cesarean section in 55% of cases. The mean birth weight was 2,124 grams, and 67% of the neonates had a low birth weight (<2500 g). The GA at delivery averaged 33.5 weeks. The stillbirth rate was 5.3%, and the early neonatal mortality rate was 5.6%. There were complications at delivery in 18% of mothers. CONCLUSION: In one of the few Brazilian reports on the epidemiological profile of PPROM, with GA until 37 weeks and intercurrences generally excluded from assessments (such as twinning and fetal malformations), there is a favorable evolution, with an acceptable rate of complications.

Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection / Parâmetros associados a desfechos fetais adversos na infecção congênita pelo parvovírus B19

Abstract Objective To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered nonrecovery and categorized as an adverse outcome. Results The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the nonrecovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study.

Resumo Objetivo Investigar os parâmetros clínicos e ultrassonográficos associados ao desfecho fetal adverso em pacientes com infecção congênita por parvovírus B19 manejada por meio de transfusão intrauterina. Métodos Trata-se de um estudo retrospectivo de um único centro realizado entre janeiro de 2005 e dezembro de 2016, que avaliou pacientes com gestação única com infecção fetal por parvovírus confirmada por reação em cadeia da polimerase de líquido amniótico ou amostras de sangue fetal submetidas a pelo menos uma transfusão intrauterina. As características maternas, os achados ultrassonográficos e os parâmetros relacionados à transfusão intrauterina foram comparados entre os dois grupos (recuperação/não recuperação), que foram categorizados com base na resposta fetal após transfusão intrauterina. A progressão para morte fetal ou parto sem recuperação fetal após transfusões foi considerada não recuperação, e categorizada como um desfecho adverso. Resultados A análise final incluiu dez gravidezes únicas: sete foram categorizadas no grupo de recuperação, e três, no grupo de não recuperação. As características basais foram semelhantes entre os grupos. Todos os fetos estavam hidrópicos no momento do diagnóstico. Não foram identificadas diferenças significativas entre os grupos em relação aos parâmetros ultrassonográficos ou os das transfusões intrauterinas; Entretanto, o grupo de não recuperação tendeu a ter um número aumentado demarcadores ultrassonográficos e níveis mais baixos de hemoglobina e plaquetas fetais antes da transfusão. Conclusão Não foi possível estabelecer firmemente os parâmetros clínicos ou ultrassonográficos associados ao desfecho fetal adverso em pacientes com infecção por parvovírus manejada por meio de transfusões intrauterinas. Entretanto, edema de pele, espessamento placentário e oligoidrâmnio podem indicar maior comprometimento fetal e, posteriormente, desfechos fetais adversos. No entanto, estudos adicionais são necessários, principalmente devido ao pequeno número de casos analisados neste estudo.

Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.

Objective To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study.

Objetivo Investigar os parâmetros clínicos e ultrassonográficos associados ao desfecho fetal adverso em pacientes com infecção congênita por parvovírus B19 manejada por meio de transfusão intrauterina. Métodos Trata-se de um estudo retrospectivo de um único centro realizado entre janeiro de 2005 e dezembro de 2016, que avaliou pacientes com gestação única com infecção fetal por parvovírus confirmada por reação em cadeia da polimerase de líquido amniótico ou amostras de sangue fetal submetidas a pelo menos uma transfusão intrauterina. As características maternas, os achados ultrassonográficos e os parâmetros relacionados à transfusão intrauterina foram comparados entre os dois grupos (recuperação/não recuperação), que foram categorizados com base na resposta fetal após transfusão intrauterina. A progressão para morte fetal ou parto sem recuperação fetal após transfusões foi considerada não recuperação, e categorizada como um desfecho adverso. Resultados A análise final incluiu dez gravidezes únicas: sete foram categorizadas no grupo de recuperação, e três, no grupo de não recuperação. As características basais foram semelhantes entre os grupos. Todos os fetos estavam hidrópicos no momento do diagnóstico. Não foram identificadas diferenças significativas entre os grupos em relação aos parâmetros ultrassonográficos ou os das transfusões intrauterinas; Entretanto, o grupo de não recuperação tendeu a ter um número aumentado de marcadores ultrassonográficos e níveis mais baixos de hemoglobina e plaquetas fetais antes da transfusão. Conclusão Não foi possível estabelecer firmemente os parâmetros clínicos ou ultrassonográficos associados ao desfecho fetal adverso em pacientes com infecção por parvovírus manejada por meio de transfusões intrauterinas. Entretanto, edema de pele, espessamento placentário e oligoidrâmnio podem indicar maior comprometimento fetal e, posteriormente, desfechos fetais adversos. No entanto, estudos adicionais são necessários, principalmente devido ao pequeno número de casos analisados neste estudo.

The effect of prenatally administered vaginal progesterone on uterine artery Doppler in asymptomatic twin pregnancies.

OBJECTIVES: This study investigated the influence of vaginal progesterone on uterine circulation in asymptomatic twin gestations. STUDY DESIGN: This study was a secondary analysis of a randomized, double-blind, placebo-controlled trial of twin pregnancies exposed to vaginal progesterone or placebo. We included all trial participants who had undergone uterine artery pulsatility index evaluation at the time of randomization. During each ultrasound examination, the uterine artery pulsatility index was evaluated transabdominally. The mean uterine artery pulsatility index between the progesterone and placebo groups were compared for each gestational age, starting between 18 to 34 weeks and 6days and were analyzed at three (Time 1), six (Time 2) and nine (Time 3) weeks after randomization. RESULTS: The final analysis included 128 women in the progesterone group and 122 women in the placebo group. The baseline characteristics were similar in both groups. No difference in the mean uterine artery pulsatility index was observed between the progesterone and placebo groups at each week of gestation or throughout gestation. CONCLUSIONS: In twin pregnancies, the use of vaginal progesterone in the second half of pregnancy does not influence uterine circulation.

Evaluation of wound healing and antimicrobial properties of aqueous extract from Bowdichia virgilioides stem barks in mice.

The decoction of the stem barks from Bowdichia virgilioides KUNTH is a folk remedy used to treat inflammatory disorders in Latin American and Brazil. In the present study, the wound healing activity of aqueous extract of the stem bark from B. virgilioides, called AEBv, was evaluated by the rate of healing by wound contraction and period of epithelization at different days post-wound using the wound excisional model. On day 9, the AEBv-treated animals exhibited significative reduction in the wound area when compared with controls. In wound infected with S. aureus, the AEBv significantly improved the wound contraction when compared to the saline-treated mice. The histological analysis showed that AEBv induced a collagen deposition, increase in the fibroblast count and few inflammatory cells than compared to saline-treated group. The expression of collagen type I was increased in the group treated with AEBv as indicated by immunohistochemical staining. In vitro, the AEBv was effective only against S. aureus but not against P. aeruginosa. Together, the results of this study demonstrate, for the first time, the healing and antimicrobiological effects of aqueous extract of the stem bark from B. virgilioides in the therapy of skin wounds.

Modulation of inflammatory processes by leaves extract from Clusia nemorosa both in vitro and in vivo animal models.

The present study was carried out to investigate the anti-inflammatory effect of the hexane extract of the leaves from Clusia nemorosa G. Mey, called HECn, using carrageenan-induced mice pleurisy and cotton pellet-induced mice granuloma. Additionally, the ability of HECn to affect both neutrophil migration as viability was investigated by use of the Boyden chamber assay and flow cytometry, respectively. The HECn significantly inhibited exudation, total leukocytes and neutrophils influx, as well as TNFα levels in carrageenan-induced pleurisy. However, the extract not suppressed the granulomatous tissue formation in the cotton pellet-induced granuloma test. Experiments performed in vitro revealed that HECn on human neutrophils inhibited a dose-dependent manner the CXCL1-induced neutrophil chemotaxis. Furthermore, HECn also inhibited the chemoattraction of human neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4) and platelet activating factor (PAF) in a Boyden chamber. However, this same treatment not was able to induce apoptosis. The results obtained in this study showed that the extract from leaves of C. nemorosa possess a potent inhibitory activity in acute model of inflammation, being the effects mediated, in part, by inhibition of neutrophil responsiveness. These results indicate that C. nemorosa could be a good source for anti-inflammatory compounds.

Methanol extract from mycelium of endophytic fungus Rhizoctonia sp. induces antinociceptive and anti-inflammatory activities in mice.

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.