Neuroimaging assessment of pediatric cerebral changes associated with SARS-CoV-2 infection during pregnancy.

Background: SARS-CoV-2 infection and perinatal neurologic outcomes are still not fully understood. However, there is recent evidence of white matter disease and impaired neurodevelopment in newborns following maternal SARS-CoV-2 infection. These appear to occur as a consequence of both direct viral effects and a systemic inflammatory response, with glial cell/myelin involvement and regional hypoxia/microvascular dysfunction. We sought to characterize the consequences of maternal and fetal inflammatory states in the central nervous system of newborns following maternal SARS-CoV-2 infection. Methods: We conducted a longitudinal prospective cohort study from June 2020 to December 2021, with follow-up of newborns born to mothers exposed or not exposed to SARS-CoV-2 infection during pregnancy. Brain analysis included data from cranial ultrasound scans (CUS) with grayscale, Doppler studies (color and spectral), and ultrasound-based brain elastography (shear-wave mode) in specific regions of interest (ROIs): deep white matter, superficial white matter, corpus callosum, basal ganglia, and cortical gray matter. Brain elastography was used to estimate brain parenchymal stiffness, which is an indirect quantifier of cerebral myelin tissue content. Results: A total of 219 single-pregnancy children were enrolled, including 201 born to mothers exposed to SARS-CoV-2 infection and 18 from unexposed controls. A neuroimaging evaluation was performed at 6 months of adjusted chronological age and revealed 18 grayscale and 21 Doppler abnormalities. Predominant findings were hyperechogenicity of deep brain white matter and basal ganglia (caudate nuclei/thalamus) and a reduction in the resistance and pulsatility indices of intracranial arterial flow. The anterior brain circulation (middle cerebral and pericallosal arteries) displayed a wider range of flow variation than the posterior circulation (basilar artery). Shear-wave US elastography analysis showed a reduction in stiffness values in the SARS-CoV-2 exposed group in all analyzed regions of interest, especially in the deep white matter elasticity coefficients (3.98 ± 0.62) compared to the control group (7.76 ± 0.77); p-value < 0.001. Conclusion: This study further characterizes pediatric structural encephalic changes associated with SARS-CoV-2 infection during pregnancy. The maternal infection has been shown to be related to cerebral deep white matter predominant involvement, with regional hyperechogenicity and reduction of elasticity coefficients, suggesting zonal impairment of myelin content. Morphologic findings may be subtle, and functional studies such as Doppler and elastography may be valuable tools to more accurately identify infants at risk of neurologic damage.

Panoramic snapshot of serum soluble mediator interplay in pregnant women with convalescent COVID-19: an exploratory study.

Introduction: SARS-CoV-2 infection during pregnancy can induce changes in the maternal immune response, with effects on pregnancy outcome and offspring. This is a cross-sectional observational study designed to characterize the immunological status of pregnant women with convalescent COVID-19 at distinct pregnancy trimesters. The study focused on providing a clear snapshot of the interplay among serum soluble mediators. Methods: A sample of 141 pregnant women from all prenatal periods (1st, 2nd and 3rd trimesters) comprised patients with convalescent SARS-CoV-2 infection at 3-20 weeks after symptoms onset (COVID, n=89) and a control group of pre-pandemic non-infected pregnant women (HC, n=52). Chemokine, pro-inflammatory/regulatory cytokine and growth factor levels were quantified by a high-throughput microbeads array. Results: In the HC group, most serum soluble mediators progressively decreased towards the 2nd and 3rd trimesters of pregnancy, while higher chemokine, cytokine and growth factor levels were observed in the COVID patient group. Serum soluble mediator signatures and heatmap analysis pointed out that the major increase observed in the COVID group related to pro-inflammatory cytokines (IL-6, TNF-α, IL-12, IFN-γ and IL-17). A larger set of biomarkers displayed an increased COVID/HC ratio towards the 2nd (3x increase) and the 3rd (3x to 15x increase) trimesters. Integrative network analysis demonstrated that HC pregnancy evolves with decreasing connectivity between pairs of serum soluble mediators towards the 3rd trimester. Although the COVID group exhibited a similar profile, the number of connections was remarkably lower throughout the pregnancy. Meanwhile, IL-1Ra, IL-10 and GM-CSF presented a preserved number of correlations (≥5 strong correlations in HC and COVID), IL-17, FGF-basic and VEGF lost connectivity throughout the pregnancy. IL-6 and CXCL8 were included in a set of acquired attributes, named COVID-selective (≥5 strong correlations in COVID and <5 in HC) observed at the 3rd pregnancy trimester. Discussion and conclusion: From an overall perspective, a pronounced increase in serum levels of soluble mediators with decreased network interplay between them demonstrated an imbalanced immune response in convalescent COVID-19 infection during pregnancy that may contribute to the management of, or indeed recovery from, late complications in the post-symptomatic phase of the SARS-CoV-2 infection in pregnant women.

Successful pregnancy after ovulation induction with human chorionic gonadotropin in a woman with selective luteinising hormone deficiency.

Selective LH deficiency has been described in several men, but only in two women who presented normal pubertal development but secondary amenorrhoea due to anovulation. Despite its rarity, this condition represents a valuable model for studying the processes regulated by FSH or LH during late folliculogenesis and ovulation in humans. A woman previously diagnosed with selective LH deficiency due to a homozygous germline splice site mutation in LHB (IVS2 + 1G→C mutation) was submitted to an individualised ovarian induction protocol, first with recombinant LH and then with highly purified urinary hCG. Ovarian follicle growth and ovulation were achieved, and a healthy baby was born after an uneventful term pregnancy. The treatment described herein demonstrates that the clinical actions of exogenous LH or hCG in inducing late-stage follicular development in women with deficient LH production or performance might be interchangeable or inevitable, once FSH-dependent early follicular growth is assured.

Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection (PROUDEST Trial): Protocol for a Multicenter, Prospective Cohort Study.

BACKGROUND: A growing body of evidence suggests that SARS-COV-2 infection during pregnancy may affect maternal-fetal outcomes and possibly result in implications for the long-term development of SARS-CoV-2-exposed children. OBJECTIVE: The PROUDEST (Pregnancy Outcomes and Child Development Effects of SARS-CoV-2 Infection Study) is a multicenter, prospective cohort study designed to elucidate the repercussions of COVID-19 for the global health of mothers and their children. METHODS: The PROUDEST trial comprises 2 prospective, sequential substudies. The PREGNANT substudy will clinically assess the effects of SARS-CoV-2 infection on pregnancy, childbirth, and puerperium from a mechanistic standpoint to elucidate the pregnancy-related inflammatory and immunological phenomena underlying COVID-19. Pregnant women aged 18-40 years who have been exposed (proven with laboratory tests) to SARS-CoV-2 (group A; n=300) will be compared to control subjects with no laboratory evidence of in-pregnancy exposure to the virus (group B; n=300). Subjects exposed to other infections during pregnancy will be excluded. The BORN substudy is a long-term follow-up study that will assess the offspring of women who enrolled in the prior substudy. It will describe the effects of SARS-CoV-2 exposure during pregnancy on children's growth, neurodevelopment, and metabolism from birth up to 5 years of age. It includes two comparison groups; group A (exposed; n=300) comprises children born from SARS-CoV-2-exposed pregnancies, and group B (controls; n=300) comprises children born from nonexposed mothers. RESULTS: Recruitment began in July 2020, and as of January 2021, 260 pregnant women who were infected with SARS-CoV-2 during pregnancy and 160 newborns have been included in the study. Data analysis is scheduled to start after all data are collected. CONCLUSIONS: Upon completion of the study, we expect to have comprehensive data that will provide a better understanding of the effects of SARS-CoV-2 infection and related inflammatory and immunological processes on pregnancy, puerperium, and infancy. Our findings will inform clinical decisions regarding the care of SARS-CoV-2-exposed mothers and children and support the development of evidence-based public health policies. TRIAL REGISTRATION: Brazilian Register of Clinical Trials RBR65QXS2; https://ensaiosclinicos.gov.br/rg/RBR-65qxs2. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26477.

Surgical treatment of tubal ectopic pregnancy through posterior colpotomy: experience from a Brazilian university hospital.

The objective of this study was to evaluate the feasibility of posterior colpotomy for the surgical treatment of tubal ectopic pregnancy in hemodynamically stable women. We performed a retrospective analysis of medical records obtained over a period of 18 months. Twelve cases were identified, with the following characteristics: mean gestational age, 7.7 weeks; mean serum ß-human chorionic gonadotropin level, 7,786 mIU/mL; and greater diameter of the mass, 15-69 mm. Treatment was successful in all cases. Salpingectomy was performed in 10 patients (83.3%) and salpingostomy, in 1 patient. The remaining patient only received peritoneal lavage, as the evidence of ectopic abortion with only a slightly dilated uterine tube was found during surgery. The mean surgical time was 42.5 minutes. In the analyzed cases, posterior colpotomy was found to be a feasible alternative method for the surgical treatment of tubal ectopic pregnancy in hemodynamically stable women.

Intrauterine Device Insertion during Cesarean Section in Women without Prenatal Contraception Counseling: Lessons from a Country with High Cesarean Rates.

OBJECTIVE: The moment of admission for delivery may be inappropriate for offering an intrauterine device (IUD) to women without prenatal contraception counseling. However, in countries with high cesarean rates and deficient prenatal contraception counseling, this strategy may reduce unexpected pregnancies and repeated cesarean sections. METHODS: This was a prospective cohort study involving 100 women without prenatal contraception counseling. Postplacental IUD was offered after admission for delivery and placed during cesarean. The rates of IUD continuation, uterine perforation, and endometritis were assessed at 6 weeks and 6 months, and the proportion of women continuing with IUD at 6 months was assessed with respect to the number of previous cesareans. RESULTS: Ninety-seven women completed the follow-up. The rate of IUD continuation was 91% at 6 weeks and 83.5% at 6 months. The expulsion/removal rate in the first 6 weeks was not different from that between 6 weeks and 6 months (9 vs 9.1%, respectively). There were 2 cases of endometritis (2.1%), and no case of uterine perforation. Among 81 women continuing with intrauterine device after 6-months, 31% had undergone only the cesarean section in which the IUD was inserted, 44% had undergone 2 and 25% had undergone 3 or more cesarean sections. CONCLUSION: Two thirds of the women who continued with IUD at 6 months had undergone 2 or more cesarean sections. Since offering trial of labor is unusual after 2 or more previous cesareans, we believe that offering IUD after admission for delivery may reduce the risk of repeated cesarean sections and its inherent risks.

OBJETIVO: O momento da admissão para o parto pode ser considerado inapropriado para oferecer o dispositivo intrauterino (DIU) para mulheres sem aconselhamento contraceptivo pré-natal. Entretanto, em países com elevadas taxas de cesáreas e aconselhamento contraceptivo deficiente, essa estratégia pode reduzir o risco de gestações não programadas e cesáreas repetidas. MéTODOS: Estudo de coorte envolvendo 100 mulheres sem aconselhamento contraceptivo pré-natal. A inserção de DIU pós-dequitação foi oferecida após a admissão para o parto e indicação de cesárea. As taxas de continuidade com o DIU, perfuração uterina e endometrite foram avaliadas após 6 semanas e 6 meses, e a proporção de mulheres que continuaram com o DIU após 6 meses foi analisada em relação ao número de cesáreas prévias. RESULTADOS: Noventa e sete mulheres completaram o seguimento. A taxa de permanência do DIU foi de 91% em 6 semanas e 83,5% em 6 meses. A taxa de expulsão/remoção nas primeiras 6 semanas foi não foi diferente daquela observada entre 6 emanas e 6 meses (9 vs 9,1%, respectivamente). Houve dois casos de endometrite (2,1%), e nenhum caso de perfuração uterina. Entre as 81 mulheres que permaneceram com o DIU após 6 meses, 31% haviam sido submetidas a apenas uma cesárea, em que o DIU foi inserido, 44% a 2, e 25% a 3 ou mais cesáreas. CONCLUSãO: Dois terços das mulheres que continuaram com o DIU após 6 meses haviam sido submetidas a 2 ou mais cesáreas. Considerando que oferecer a tentativa de parto vaginal após duas ou mais cesáreas prévias é incomum, é possível que a oferta do DIU na admissão para o parto possa reduzir o risco de cesáreas repetidas e de seus riscos associados.

Pregnancy-induced growth of a spinal hemangioblastoma: presumed mechanisms and their implications for therapeutic approaches.

Hemangioblastomas are benign tumors of the central nervous system (CNS) that may occur either sporadically or as part of von Hippel-Lindau (VHL) disease, in which they coexist with a series of other tumors outside the CNS. Because of their low mitosis rate, hemangioblastomas usually have slow-growing and late manifestations, but may cause sudden neurological symptoms if tumor hemorrhage occurs. Few studies have evaluated the impact of pregnancy on the evolution of hemangioblastomas. Some authors have reported tumor growth in women with VHL disease, but no such association was observed by others. The influence of pregnancy on sporadic hemangioblastomas remains largely unexplored. We report here the case of a pregnant woman whose first manifestation of sporadic spinal hemangioblastoma was life-threatening, rapidly progressive dysautonomia. In addition, we discuss the role of pregnancy in the triggering of symptoms, as well as the possibility of medically indicated delivery for the management of these tumors.

Lactation Induction in a Commissioned Mother by Surrogacy: Effects on Prolactin Levels, Milk Secretion and Mother Satisfaction.

Case report of a 39-year-old intended mother of a surrogate pregnancy who underwent induction of lactation by sequential exposure to galactagogue drugs (metoclopramide and domperidone), nipple mechanical stimulation with an electric pump, and suction by the newborn. The study aimed to analyze the effect of each step of the protocol on serum prolactin levels, milk secretion and mother satisfaction, in the set of surrogacy. Serum prolactin levels and milk production had no significant changes. Nevertheless, the mother was able to breastfeed for four weeks, and expressed great satisfaction with the experience. As a conclusion, within the context of a surrogate pregnancy, breastfeeding seems to bring emotional benefits not necessarily related to an increase in milk production.

Lactation Induction in a Commissioned Mother by Surrogacy: Effects on Prolactin Levels, Milk Secretion and Mother Satisfaction / Indução da lactação em mãe por útero de substituição: efeitos na concentração de prolactina, produção láctea e satisfação materna

Abstract Case report of a 39-year-old intended mother of a surrogate pregnancy who underwent induction of lactation by sequential exposure to galactagogue drugs (metoclopramide and domperidone), nipple mechanical stimulation with an electric pump, and suction by the newborn. The study aimed to analyze the effect of each step of the protocol on serum prolactin levels, milk secretion and mother satisfaction, in the set of surrogacy. Serum prolactin levels and milk production had no significant changes. Nevertheless, themother was able to breastfeed for four weeks, and expressed great satisfaction with the experience. As a conclusion, within the context of a surrogate pregnancy, breastfeeding seems to bring emotional benefits not necessarily related to an increase in milk production.

Resumo Relato de caso de mãe por útero de substituição, de 39 anos de idade, submetida a indução da lactação por exposição sequencial a drogas galactogogas (metoclopramida e domperidona), estimulação mamilar mecânica com bomba elétrica, e sucção pelo recém-nascido. O estudo teve como objetivo analisar os efeitos de cada etapa do protocolo na concentração sérica de prolactina, no volume de secreção láctea e na satisfação materna. A concentração sérica de prolactina e a produção láctea não apresentaram mudanças significativas. Entretanto, a mãe foi capaz de amamentar a criança por quatro semanas, e manifestou grande satisfação com a experiência. Como conclusão, no contexto de maternidade por útero de substituição, o aleitamento materno parece promover benefícios emocionais, não necessariamente relacionados ao aumento do volume de leite.

Cerebrospinal Fluid CRH Levels in Late Pregnancy Are Not Associated With New-Onset Postpartum Depressive Symptoms.

CONTEXT: CRH participates in the hypothalamic-pituitary-adrenal axis and in neural circuits involved in the pathophysiology of depression. During pregnancy, the placenta produces large amounts of CRH, and production ceases abruptly after delivery. The relationship between CRH in the cerebrospinal fluid (CSF) during pregnancy and peripartum mood disorders has not been investigated. OBJECTIVES: The objectives were to determine whether there are differences in CSF CRH concentrations of pregnant and nonpregnant women and whether CSF CRH concentrations in late pregnancy are associated with the presence of depressive symptoms during pregnancy and in the early postpartum period. DESIGN: This was a prospective cohort study conducted from January to April, 2011. SETTING: The study was conducted in one public and two private hospitals in Brasilia, Brazil. PATIENTS: Patients included 107 healthy pregnant women who underwent elective cesarean delivery and 22 nonpregnant healthy women who underwent spinal anesthesia for elective surgical sterilization. INTERVENTION: CRH in CSF was measured in pregnant and nonpregnant women by ELISA. MAIN OUTCOME MEASURE: The association between CSF CRH concentration at delivery and maternal depression assessed before cesarean section and postpartum (4 to 8 wk) with the Edinburgh Postnatal Depression Scale (EPDS), with a cutoff of ≥ 13. RESULTS: CRH concentration in the CSF was significantly higher in pregnant (4.1 ± 0.51 log CRH) than in nonpregnant women (3.6 ± 0.26 log CRH) (P < .001). Depressive symptoms starting after delivery occurred in 5.6% of women. CRH concentration in CSF was not different between women without depressive symptoms and women showing such symptoms during pregnancy or in the postpartum period. CONCLUSION: CRH concentration in the CSF was higher in pregnant women than in nonpregnant women. However, in this sample, CSF CRH in late pregnancy was not associated with new-onset depressive symptoms in the early postpartum period.

Depression with postpartum onset: a prospective cohort study in women undergoing elective cesarean section in Brasilia, Brazil.

PURPOSE: It was to determine the prevalence of depressive symptoms in a sample of puerperal women from Brasília, Brazil, distinguishing cases with onset after delivery from those already present during pregnancy. METHODS: A prospective cohort study with convenience sampling of patients submitted to elective cesarean section at two private hospitals. As an instrument for assessing depressive symptoms, the Edinburgh Postnatal Depression Scale with cutoff >13 was applied shortly before delivery and four to eight weeks after childbirth. RESULTS: Among the 107 women who completed the study, 11 (10.3%) had significant depressive symptoms during pregnancy and 12 (11.2%) during the postpartum period. Among the 12 patients with postpartum symptoms, 6 had symptoms during pregnancy, so that 5.6% of the sample had postpartum onset of depression. The higher overall frequency of depression was significantly among single women than among married women (p=0.04), a fact mainly due to a higher frequency of single women experiencing persistent depressive symptoms both before and after delivery (p=0.002). The risk of depression was not influenced by age, parity or educational level. CONCLUSION: Women with depression identified during the postpartum period comprise a heterogeneous group, in which symptoms may have started before pregnancy, during pregnancy or after childbirth. In this sample, half of the postpartum depression cases already presented symptoms during late pregnancy. Since depression can arise before and after childbirth, it may have different etiologies and, therefore, a different response to treatment, a possibility that should be considered by clinicians and researchers.

Depression with postpartum onset: a prospective cohort study in women undergoing elective cesarean section in Brasilia, Brazil / Depressão com início após o parto: estudo de corte prospectivo em mulheres submetidas à cesárea eletiva em Brasília, Brasil

PURPOSE: It was to determine the prevalence of depressive symptoms in a sample of puerperal women from Brasília, Brazil, distinguishing cases with onset after delivery from those already present during pregnancy. METHODS: A prospective cohort study with convenience sampling of patients submitted to elective cesarean section at two private hospitals. As an instrument for assessing depressive symptoms, the Edinburgh Postnatal Depression Scale with cutoff >13 was applied shortly before delivery and four to eight weeks after childbirth. RESULTS: Among the 107 women who completed the study, 11 (10.3%) had significant depressive symptoms during pregnancy and 12 (11.2%) during the postpartum period. Among the 12 patients with postpartum symptoms, 6 had symptoms during pregnancy, so that 5.6% of the sample had postpartum onset of depression. The higher overall frequency of depression was significantly among single women than among married women (p=0.04), a fact mainly due to a higher frequency of single women experiencing persistent depressive symptoms both before and after delivery (p=0.002). The risk of depression was not influenced by age, parity or educational level. CONCLUSION: Women with depression identified during the postpartum period comprise a heterogeneous group, in which symptoms may have started before pregnancy, during pregnancy or after childbirth. In this sample, half of the postpartum depression cases already presented symptoms during late pregnancy. Since depression can arise before and after childbirth, it may have different etiologies and, therefore, a different response to treatment, a possibility that should be considered by clinicians and researchers.

OBJETIVO: Foi determinar a prevalência de sintomas depressivos em uma amostra de puérperas da cidade de Brasília, Brasil, discriminando os casos com surgimento após o parto daqueles já presentes durante a gestação. MÉTODOS: Estudo de corte prospectivo. Amostragem por conveniência de pacientes que seriam submetidas à cesariana eletiva em dois hospitais privados. Como instrumento para avaliar os sintomas depressivos, foi utilizada a Escala de Depressão Pós-natal de Edimburgo, com ponto de corte >13, aplicada momentos antes do parto e quatro a oito semanas após o nascimento da criança. RESULTADOS: Das 107 mulheres que completaram o estudo, 11 (10,3%) apresentaram sintomas depressivos significativos na gestação e 12 (11,2%) no período pós-parto. Das 12 pacientes com sintomas no pós-parto, 6 já tinham os sintomas durante a gestação, de modo que 5,6% da amostra teve depressão com início após o parto. A frequência global de depressão foi significativamente maior entre as mulheres solteiras em comparação com mulheres casadas (p=0,04) por causa principalmente da maior frequência de mulheres solteiras apresentando sintomas depressivos persistentes, antes e depois do parto (p=0,002). O risco de depressão não foi influenciado pela idade, paridade e escolaridade. CONCLUSÃO: As mulheres com depressão reconhecida no período pós-parto compõem um grupo heterogêneo, no qual o quadro pode ter tido início antes da gestação, durante a gestação ou após o parto. Na amostra estudada, metade dos casos de depressão reconhecida após o parto já apresentava os sintomas no final da gestação. Uma vez que a depressão que surge antes e após o parto pode ter etiologia diferente e, portanto, apresentar resposta ao tratamento diferente, os clínicos e pesquisadores devem estar atentos a essa possibilidade.

Infecção por citomegalovírus na gestação: rastrear ou não rastrear? / Cytomegalovirus infection in pregnancy: to screen or not to screen?

Um dos mais polêmicos exames de triagem neonatal para detecção de casos de citomegalovírus é a sorologia. O fato de as sorologias serem falhas no diagnóstico de infecção aguda e a falta de tratamento específico durante a gestação levou a questionar a utilidade da sua triagem. Os autores relatam um caso de infecção por citomegalovírus causadora de malformação cardíaca e óbito fetal, em gestante com sorologia indicativa de infecção pregressa. Avaliaram-se os benefícios dessa triagem em detrimento à sua possível ineficácia. Provavelmente, pela natureza da enfermidade, a solução só poderá ser alcançada com o desenvolvimento de vacinas que confiram proteção, aplicadas antes da fase reprodutiva.

One of the most controversial exams in the neonatal period is the trial for cytomegalovirus. The flaws in sorology for the diagnosis of current infection and the lack of specific treatment during pregnancy arrises questions about the usefulness of such investigation. We present a case of cytomegalovirus infection causing heart malformation and fetal death in a pregnant woman with positive sorology for past infection. We evaluated the benefits of the cytomegalovírus investigation opposed to its possible inefficacy. Probably, the solution will only be reached with the development of protective vaccines, given before the reproductive age.