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1.
Pediatr Dev Pathol ; 23(3): 177-180, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32397896

RESUMO

This study describes the pathology and clinical information on 20 placentas whose mother tested positive for the novel Coronovirus (2019-nCoV) cases. Ten of the 20 cases showed some evidence of fetal vascular malperfusion or fetal vascular thrombosis. The significance of these findings is unclear and needs further study.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Doenças Placentárias/etiologia , Doenças Placentárias/patologia , Placenta/patologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Complicações Infecciosas na Gravidez/patologia , Trombose/etiologia , Adolescente , Adulto , Feminino , Doenças Fetais/etiologia , Doenças Fetais/patologia , Humanos , Recém-Nascido , New York , Pandemias , Gravidez , Trombose/patologia , Adulto Jovem
2.
Am J Obstet Gynecol ; 223(5): 753.e1-753.e14, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32416155

RESUMO

BACKGROUND: Autophagy is highly active in neuroepithelial cells of the developing neuroepithelium, and impairment of autophagy leads to neural tube defects. In this study, we have found that maternal diabetes suppresses autophagy that leads to neural tube defects and consequent cellular imbalance in the endoplasmic reticulum where critical events occur, leading to the induction of diabetic embryopathy. Because the mammalian target of rapamycin pathway suppresses autophagy, we hypothesized that 70 kDa ribosomal protein S6 kinase 1 (p70S6K1), a major downstream effector of mammalian target of rapamycin, mediates the inhibitory effect of maternal diabetes on autophagy in the developing neuroepithelium. OBJECTIVE: We investigated whether p70S6K1 mediates the inhibitory effect of maternal diabetes on autophagy during neurulation. We also examined whether p70S6K1 deficiency restores autophagy and therefore relieves endoplasmic reticulum stress and inhibits maternal diabetes-induced apoptosis, which leads to reduction in neural tube defect incidence in diabetic embryopathy. STUDY DESIGN: Female p70S6K1 heterogeneous knockout (p70S6K1+/-) mice were bred with male p70S6K1 heterogeneous knockout (p70S6K1+/-) mice to generate wild-type (WT), p70S6K1+/- and p70S6K1 knockout (p70S6K1-/-) embryos. Embryos at embryonic day 8.5 were harvested for the assessment of indices of autophagy, endoplasmic reticulum stress, and apoptosis. Neural tube defect incidence in embryos was determined at embryonic day 10.5. For in vitro studies, small interfering RNA knockdown of p70S6K1 in C17.2 mouse neural stem cells was used to determine the effect of p70S6K1 deficiency on autophagy impairment and endoplasmic reticulum stress under high glucose conditions. RESULTS: Knockout of the Rps6kb1 gene, which encodes for p70S6K1, ameliorated maternal diabetes-induced NTDs and restored autophagosome formation in neuroepithelial cells suppressed by maternal diabetes. Maternal diabetes-suppressed conversion of LC3-I (microtubule-associated protein 1A/1B-light chain 3) to LC3-II, an index of autophagic activity, in neurulation stage embryos was abrogated in the absence of p70S6K1. p70S6K1 knockdown in neural stem cells also restored autophagosome formation and the conversion of LC3-I to LC3-II. The activation of the major unfolded protein response, indicated by phosphorylation of inositol-requiring enzyme 1 alpha, and protein kinase R-like endoplasmic reticulum kinase, and eukaryotic translation initiation factor 2α, and the increase of the endoplasmic reticulum stress marker, C/EBP homologous protein, were induced by maternal diabetes in vivo and high glucose in vitro. Unfolded protein response and endoplasmic reticulum stress induced by maternal diabetes or high glucose were reduced by Rps6kb1 deletion or p70S6K1 knockdown, respectively. Rps6kb1 knockout blocked maternal diabetes-induced caspase cleavage and neuroepithelial cell apoptosis. The superoxide dismutase mimetic Tempol abolished high glucose-induced p70S6K1 activation. CONCLUSION: The study revealed the critical involvement of p70S6K1 in the pathogenesis of diabetic embryopathy.


Assuntos
Autofagia/genética , Estresse do Retículo Endoplasmático/genética , Doenças Fetais/genética , Células-Tronco Neurais/metabolismo , Defeitos do Tubo Neural/genética , Gravidez em Diabéticas/genética , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Resposta a Proteínas não Dobradas/genética , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Autofagossomos/efeitos dos fármacos , Autofagossomos/metabolismo , Glicemia/metabolismo , Óxidos N-Cíclicos/farmacologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Doenças Fetais/etiologia , Doenças Fetais/metabolismo , Glucose/farmacologia , Técnicas In Vitro , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Células-Tronco Neurais/efeitos dos fármacos , Defeitos do Tubo Neural/embriologia , Defeitos do Tubo Neural/metabolismo , Células Neuroepiteliais/efeitos dos fármacos , Células Neuroepiteliais/metabolismo , Neurulação/genética , Estresse Oxidativo , Gravidez , Gravidez em Diabéticas/metabolismo , Marcadores de Spin , Resposta a Proteínas não Dobradas/efeitos dos fármacos
3.
Int J Gynaecol Obstet ; 149(3): 347-353, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32115707

RESUMO

OBJECTIVE: To evaluate risk factors associated with fetal gastroschisis. METHODS: As a secondary aim of a larger case-control study, pregnant women attending the Fetal Medicine Unit at the Department of Obstetrics and Gynecology at Hospital das Clinicas, Sao Paulo University Medical School between July 1, 2013, and July 31, 2015, were allocated into either the gastroschisis group, where the woman was carrying a fetus with gastroschisis, or the control group, where the fetus was normal. Patients in the control group were matched at study entry for maternal age, preconception body mass index and weeks of gestation. In-person interviews were conducted during pregnancy to obtain data on demographic, medical, and social characteristics; exposure to substances; pregnancy history; the presence of chronic disease, urinary tract infections (UTIs), influenza, and fever; and the occurrence of stress events between the month before the last menstrual period and the first trimester of pregnancy. RESULTS: Of 171 women included in the study, 57 were allocated to the gastroschisis group and 114 to the control group. There were significant associations between gastroschisis and maternal UTI (P=0.011), tobacco use (P=0.001), alcohol consumption (P≤0.001), and illicit drug use (P=0.012). After analysis by standard logistic regression, the remaining significant factors were UTI, tobacco use, and alcohol consumption. CONCLUSION: UTI and exposure to tobacco or alcohol just before conception and during early pregnancy were associated with an increase in the likelihood of fetal gastroschisis.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Gastrosquise/epidemiologia , Fumar/epidemiologia , Infecções Urinárias/epidemiologia , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Doenças Fetais/etiologia , Gastrosquise/etiologia , Humanos , Modelos Logísticos , Gravidez , Primeiro Trimestre da Gravidez , Fatores de Risco , Adulto Jovem
4.
BJOG ; 127(3): 355-362, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31505103

RESUMO

OBJECTIVE: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT). DESIGN: A retrospective study. SETTING: Reference fetal medicine unit. POPULATION: Sixty-two fetuses infected <14 weeks of gestation. METHODS: We defined second-trimester assessment (STA) as the combination of ultrasound findings <28 weeks of gestation and fetal platelet count at cordocentesis. Three groups were defined: normal, extracerebral, and cerebral STA. MAIN OUTCOME MEASURES: For each group, the PV of STA alone, STA + MRI, and STA + US3rdT were assessed retrospectively. Outcome at birth and at follow-up were reported. RESULTS: The STA was normal, and with extracerebral and cerebral features, in 43.5, 42.0, and 14.5%, respectively. The negative PV of normal STA and MRI for moderate to severe sequelae was 100%. The residual risk was unilateral hearing loss in 16.7% of cases. Of pregnancies with cerebral STA, 44% were terminated. Following extracerebral STA, 48% of neonates were symptomatic and 30% had moderate to severe sequelae. In those cases, the positive and negative PV of MRI for sequelae were 33 and 73%, respectively. STA + US3rdT had a lower negative PV than MRI for symptoms at birth and for moderate to severe sequelae. Any false-positive findings at MRI were mostly the result of hypersignals of white matter. CONCLUSIONS: Serial assessment in the second and third trimesters by ultrasound and MRI is necessary to predict the risk of sequelae occurring in 35% of pregnancies following fetal infection in the first trimester of pregnancy. TWEETABLE ABSTRACT: Serial ultrasound prognostic assessment following fetal CMV infection in the 1st trimester is improved by MRI at 32 weeks.


Assuntos
Encéfalo/diagnóstico por imagem , Infecções por Citomegalovirus , Citomegalovirus/isolamento & purificação , Doenças Fetais , Imagem por Ressonância Magnética/métodos , Polimicrogiria , Complicações Infecciosas na Gravidez , Ultrassonografia Pré-Natal/métodos , Aborto Eugênico/estatística & dados numéricos , Adulto , Autopsia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/epidemiologia , Feminino , Doenças Fetais/etiologia , Doenças Fetais/patologia , França , Humanos , Lactente , Recém-Nascido , Masculino , Polimicrogiria/etiologia , Polimicrogiria/patologia , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Trimestres da Gravidez , Prognóstico
5.
Fetal Diagn Ther ; 47(2): 156-164, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31505487

RESUMO

BACKGROUND: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists. OBJECTIVES: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies. METHOD: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d'Hémobiologie Périnatale) and born between 2010 and 2017. RESULTS: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21-33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18-0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death. CONCLUSIONS: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.


Assuntos
Anemia/terapia , Transfusão de Sangue Intrauterina , Doenças Fetais/terapia , Aborto Induzido , Anemia/sangue , Anemia/diagnóstico , Anemia/etiologia , Biomarcadores/sangue , Transfusão de Sangue Intrauterina/efeitos adversos , Feminino , Morte Fetal/etiologia , Doenças Fetais/sangue , Doenças Fetais/diagnóstico , Doenças Fetais/etiologia , Hemoglobina Fetal/metabolismo , Idade Gestacional , Humanos , Nascimento Vivo , Gravidez , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
6.
J Matern Fetal Neonatal Med ; 33(3): 482-492, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29947269

RESUMO

The global incidence of diabetes mellitus, including diabetes in pregnant women, is on the rise. Diabetes mellitus in a pregnant woman jeopardizes not only maternal health but can also have significant implications on the child to be born. Therefore, timely diagnosis and strict glycemic control are of utmost importance in achieving a safe outcome for both the mother and fetus. The treating physician should be aware of the complications that can arise due to poor glycemic control during pregnancy. The objective of this article is to discuss the key concerns in a neonate born to diabetic mother, the underlying pathogenesis, and the screening schedule during pregnancy.


Assuntos
Diabetes Gestacional , Doenças Fetais/etiologia , Doenças do Recém-Nascido/etiologia , Gravidez em Diabéticas , Glicemia , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/terapia , Homeostase , Humanos , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Doenças do Recém-Nascido/terapia , Programas de Rastreamento , Gravidez
7.
Semin Pediatr Neurol ; 32: 100767, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31813521

RESUMO

Perinatal strokes are a diverse but specific group of focal cerebrovascular injuries that occur early in brain development and affect an estimated 5 million people worldwide. The objective of this review is to describe the epidemiology, clinical presentations, pathophysiology, outcomes, and management for the 6 subtypes of perinatal stroke. Some perinatal strokes are symptomatic in the first days of life, typically with seizures, including neonatal arterial ischemic stroke, neonatal hemorrhagic stroke, and cerebral sinovenous thrombosis. The remaining subtypes present in the first year of life or later, usually with motor asymmetry and include arterial presumed perinatal ischemic stroke, presumed perinatal hemorrhagic stroke, and in utero periventricular venous infarction. The consequences of these injuries include cerebral palsy, epilepsy, and cognitive and behavioral challenges, in addition to the psychosocial impact on families. While there have been significant advances in understanding mechanisms of both injury and recovery, there is still a great deal to learn regarding causation and the optimization of outcomes.


Assuntos
Doenças Fetais , Acidente Vascular Cerebral , Animais , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/etiologia , Doenças Fetais/fisiopatologia , Doenças Fetais/terapia , Humanos , Recém-Nascido , Gravidez , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia
8.
Obstet Gynecol Surv ; 74(10): 611-622, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31670834

RESUMO

Objective: To review what is currently known about placental mesenchymal dysplasia (PMD) including imaging techniques for diagnosis and differentiation from a molar pregnancy, genetics, maternal/fetal effects, and management. Evidence Acquisition: A literature search by research librarians at 2 universities was undertaken using the search engines PubMed and Web of Science. The search terms used were "etiology" OR "cause" OR "risk" OR "risks" OR "epidemiology" OR "diagnosis" OR "therapy" OR "prognosis" OR "management" AND "placental mesenchymal dysplasia" OR "placenta" AND "mesenchymal dysplasia." No limit was put on the number of years searched. Results: The etiology of PMD remains uncertain, although there are a number of theories on causation. An elevated maternal serum α-fetoprotein level, slightly elevated human chorionic gonadotropin level, normal karyotype, multicystic lesions on ultrasound, and varying degrees of flow within cysts using color Doppler (stained-glass appearance) are helpful in making the diagnosis. On pathologic examination of the placenta, PMD is differentiated from molar pregnancy by the absence of trophoblastic hyperplasia. Fetal complications of PMD include hematologic disorders, Beckwith-Wiedemann syndrome, liver tumors, fetal growth restriction, preterm delivery, and intrauterine fetal demise. Maternal complications include gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver function tests, low platelets) syndrome, and eclampsia. Conclusions: Accurate diagnosis of PMD is imperative for appropriate management and surveillance to minimize adverse maternal and fetal outcomes. Relevance: The importance of a correct diagnosis of PMD is important because it can be misdiagnosed as a partial molar pregnancy or a complete mole with coexisting normal fetus, and this can result in inappropriate management.


Assuntos
Doenças Fetais/etiologia , Doenças Placentárias/diagnóstico , Placenta/patologia , Adulto , Vilosidades Coriônicas/diagnóstico por imagem , Vilosidades Coriônicas/patologia , Diagnóstico Diferencial , Feminino , Doenças Fetais/diagnóstico , Humanos , Imageamento Tridimensional , Placenta/diagnóstico por imagem , Doenças Placentárias/etiologia , Doenças Placentárias/patologia , Gravidez , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal
9.
J Nippon Med Sch ; 86(4): 192-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31484880

RESUMO

Twin to twin transfusion syndrome (TTTS) is a major complication of monochorionic diamniotic (MD) twins, and its onset is known to be associated with placental vascular anastomoses and blood flow imbalance. In a typical case of TTTS, the recipient develops polyhydramnios, weight gain, cardiomegaly and hydrops fetalis in the uterus. In contrast, the donor develops oligohydramnios and intrauterine growth restriction. Recently, the significance of the renin-angiotensin-aldosterone system (RAAS) that transfers from the donor to the recipient has attracted interest in the fetal circulation of TTTS. The donor has decreased renal blood flow due to decreased circulating blood volume. For this reason, the secretion of RAAS hormones is augmented in the fetal kidneys of the donor. In TTTS, these RAAS hormones from the donor transfer to the recipient through the anastomosed vessels. In addition to excess preload, the recipient heart is exposed to excess afterload due to systemic vasoconstriction through RAAS hormones. Commonly occurring complications in the recipient include myocardial hypertrophy, atrioventricular valve regurgitation, and pulmonary valve stenosis or pulmonary atresia. Fetoscopic laser photocoagulation (FLP) has been introduced recently because neither mortality nor neurological morbidity have been satisfactorily improved with conventional treatment. FLP is a curative method that may improve the prognosis of TTTS. In Japan, this procedure has been performed frequently, and positive neurological outcomes have been achieved.


Assuntos
Transfusão Feto-Fetal , Feto/irrigação sanguínea , Volume Sanguíneo , Cardiomegalia/embriologia , Cardiomegalia/etiologia , Feminino , Doenças Fetais/etiologia , Doenças Fetais/fisiopatologia , Retardo do Crescimento Fetal/etiologia , Transfusão Feto-Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/etiologia , Transfusão Feto-Fetal/patologia , Transfusão Feto-Fetal/terapia , Fetoscopia , Humanos , Terapia com Luz de Baixa Intensidade , Poli-Hidrâmnios/etiologia , Gravidez , Prognóstico , Estenose da Valva Pulmonar/embriologia , Estenose da Valva Pulmonar/etiologia , Circulação Renal , Sistema Renina-Angiotensina/fisiologia
10.
Int J Pediatr Otorhinolaryngol ; 127: 109642, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31479918

RESUMO

OBJECTIVE: Currently no established criteria exist to guide use of ex utero intrapartum treatment (EXIT) for fetal neck mass management. This study aims to correlate prenatal radiographic findings with incidence of ex utero intrapartum treatment and necessity of airway intervention at delivery. METHODS: We reviewed our EXIT experience between 2012 and 17. Furthermore, we performed a literature review of articles reporting incidences of fetal neck masses considered for EXIT. Articles that were included (1) discussed prenatal radiographic findings such as size, features, and evidence of compression and (2) reported extractable data on delivery outcomes and airway status. RESULTS: Ten cases at our institution were reviewed. Another 137 cases across 81 studies met inclusion criteria. These studies showed aerodigestive tract compression to be significantly associated with neck masses undergoing EXIT. Additionally, there was significantly higher incidence of airway intervention in cases where polyhydramnios, anatomic compression, and solid masses were seen on prenatal diagnostic imaging, while mass location and size did not correlate with airway intervention. CONCLUSION: With this data, we propose that any neck mass with anatomic compression on fetal imaging in the 3rd trimester should be considered for EXIT. When radiographic findings do not show compression but do display polyhydramnios or a solid neck mass (regardless of polyhydramnios), an airway surgeon should be available for perinatal airway assistance.


Assuntos
Obstrução das Vias Respiratórias/cirurgia , Doenças Fetais/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/etiologia , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Período Periparto , Gravidez , Centros de Atenção Terciária , Ultrassonografia Pré-Natal
11.
Proc Natl Acad Sci U S A ; 116(40): 20190-20200, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31527230

RESUMO

Maternal infections during pregnancy are associated with increased risk of neurodevelopmental disorders, although the precise mechanisms remain to be elucidated. Previously, we established a maternal immune activation (MIA) model using swine, which results in altered social behaviors of piglet offspring. These behavioral abnormalities occurred in the absence of microglia priming. Thus, we examined fetal microglial activity during prenatal development in response to maternal infection with live porcine reproductive and respiratory syndrome virus. Fetuses were obtained by cesarean sections performed 7 and 21 d postinoculation (dpi). MIA fetuses had reduced brain weights at 21 dpi compared to controls. Furthermore, MIA microglia increased expression of major histocompatibility complex class II that was coupled with reduced phagocytic and chemotactic activity compared to controls. High-throughput gene-expression analysis of microglial-enriched genes involved in neurodevelopment, the microglia sensome, and inflammation revealed differential regulation in primary microglia and in whole amygdala tissue. Microglia density was increased in the fetal amygdala at 7 dpi. Our data also reveal widespread sexual dimorphisms in microglial gene expression and demonstrate that the consequences of MIA are sex dependent. Overall, these results indicate that fetal microglia are significantly altered by maternal viral infection, presenting a potential mechanism through which MIA impacts prenatal brain development and function.


Assuntos
Doenças Fetais/etiologia , Complicações Infecciosas na Gravidez/veterinária , Doenças dos Suínos/virologia , Viroses/veterinária , Animais , Comportamento Animal , Modelos Animais de Doenças , Feminino , Doenças Fetais/metabolismo , Neurônios/metabolismo , Neurotransmissores/metabolismo , Gravidez , Suínos
12.
Placenta ; 86: 28-34, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31401007

RESUMO

AIMS: The aims of this study were to explore factors that associated with gestational diabetes mellitus (GDM), and to determine the relationship between early maternal HbA1c levels and adverse fetal or neonatal events, and to determine an optimal maternal glucose testing method in order to decrease the potential health risk for their offspring. METHODS: From December 2015 to May 2016, a total of 6744 pregnant women were enrolled from Shanghai First Maternal and Infant Hospital affiliated to Tongji University prospectively in the nested case-control study. Each GDM case was matched with a healthy pregnant woman and followed up. Outcome analyses were conducted between GDM case and control groups, as well as elevated and normal maternal HbA1c levels, respectively. RESULTS: A total of 1836 women were included in the adverse fetal and neonatal events examination. For pregnant women with early HbA1c ≥ 5.2%, the adjusted risk ratios (RR) of respiratory distress syndrome (RDS), pneumonia and jaundice were 4.37 (95%CI 1.54-12.35), 2.03 (95%CI 1.24-3.33) and 1.49 (95%CI 1.01-2.20), respectively. After treatments, the frequency for the majority of events in GDM group was similar to that of healthy pregnant women. Moreover, the area under the curve (AUC) of early maternal HbA1c in predicting potential RDS is 0.734. HbA1c ≤ 4.9% excluded for RDS. CONCLUSIONS: Compared with women with normal HbA1c, those with an early elevated HbA1c level were more likely to develop adverse events, including RDS, pneumonia and jaundice. Early HbA1c testing can be used as an auxiliary method identifying potential RDS.


Assuntos
Diabetes Gestacional/sangue , Doenças Fetais/etiologia , Hemoglobina A Glicada/metabolismo , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Doenças Fetais/sangue , Humanos , Recém-Nascido , Gravidez
13.
Medicine (Baltimore) ; 98(28): e16282, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305411

RESUMO

RATIONALE: Pain management is an essential part of good obstetrical care. The rapid onset of pain relief after combined spinal-epidural (CSE) analgesia may cause a transient imbalance in maternal catecholamine level, leading to uterine hyperactivity and fetal heart rate (FHR) abnormalities. How to manage the uterine basal tone and FHR abnormalities after labor analgesia still remains controversial. PATIENT CONCERNS: A 33-year-old nulliparous woman at 40 weeks' gestation underwent induction of labor after premature rupture of membranes. CSE analgesia was provided when the patient described her pain as the top on a scale of 10 during induction of labor with oxytocin infusion. DIAGNOSES: Uterine hypertonus and fetal bradycardia were diagnosed within 10 minutes after CSE analgesia. INTERVENTIONS: Oxytocin infusion and CSE analgesia were immediately suspended, and measures of staying in left lateral decubitus position and giving supplemental oxygen were attempted to resuscitating the baby. Because of suspicious fetal distress, the baby was rapidly delivered by emergency cesarean section. OUTCOMES: The Apgar score of the baby was 8 and 10 at 1 and 5 minutes after birth. Subsequent follow-up confirmed that both mother and baby were in good condition. LESSONS: The loss of the tocolytic effect of epinephrine after CSE analgesia and continuous oxytocin infusion may work together to form a totally synergistic function, finally leading to inevitable uterine hypertonus and fetal bradycardia. Both the obstetrical provider and anesthesiologist should carefully monitor all patients in the first 15 minutes after CES analgesia induction. Oxytocin administration in this critical period deserves attention. Additionally, intraprofessional collaboration is also necessary to ensure high quality and safe delivery for all childbearing women.


Assuntos
Analgesia Obstétrica , Bradicardia/etiologia , Doenças Fetais/etiologia , Trabalho de Parto Induzido , Hipertonia Muscular/etiologia , Doenças Uterinas/etiologia , Adulto , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Feminino , Humanos , Recém-Nascido , Ocitócicos , Ocitocina
14.
Am J Med Genet A ; 179(8): 1535-1542, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31215128

RESUMO

Fetal gastroschisis is a paraumbilical abdominal wall defect with herniation of the abdominal organs. This multifactorial malformation occurs in young pregnant women, and the underlying cause of the disease remains unknown; however, nutritional factors may play a role in its development. This case-control study explored the association of maternal nutrient intake with the occurrence of gastroschisis. The gastroschisis group (GG) comprised 57 pregnant women with fetuses with gastroschisis, and the control group (CG) comprised 114 pregnant women with normal fetuses matched for maternal age, gestational age, and preconception body mass index classification. Nutritional assessments related to the preconception period were obtained using the food consumption frequency questionnaire, and nutrient intakes were calculated using nutrition programs. The median daily calorie intake was higher (2,382.43 vs. 2,198.81; p = .041) in the GG than in the CG. The median intake of methionine (763.89 vs. 906.34; p = .036) and threonine (1,248.34 vs. 1,437.01; p = .018) was lower in the GG than in the CG. Pregnant women with fetuses with gastroschisis have a diet characterized by higher calorie intake and lower levels of essential amino acids (methionine and threonine) during the preconception period than pregnant women with normal fetuses.


Assuntos
Ingestão de Energia , Doenças Fetais/epidemiologia , Doenças Fetais/etiologia , Gastrosquise/epidemiologia , Gastrosquise/etiologia , Exposição Materna , Nutrientes , Adulto , Estudos de Casos e Controles , Feminino , Feto , Gastrosquise/diagnóstico , Idade Gestacional , Humanos , Micronutrientes , Nutrientes/administração & dosagem , Razão de Chances , Gravidez , Adulto Jovem
15.
Curr Opin Anaesthesiol ; 32(3): 291-297, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31045636

RESUMO

PURPOSE OF REVIEW: The aim of this study was to review the current literature on anesthesia for predelivery procedures and to summarize recent findings on anesthesiological methods used. RECENT FINDINGS: Ex-utero intrapartum treatment (EXIT)-procedures are performed to secure the newborn's oxygenation in case of severe airway obstruction due to multiple conditions. A key feature of EXIT is continued intactness of the maternofetal circulation by uterine relaxation achieved by general anesthesia with high doses of anesthetic gases. A dose reduction may be achieved by combining inhaled anesthesia with propofol. After intrauterine transfusion the anesthesia team needs to be prepared for a potential need of emergency cesarean section. Temporary fetal endoluminal tracheal occlusion and laser coagulation for twin-to-twin transfusion syndrome may be either performed in monitored anesthesia care or neuraxial anesthesia. Neuraxial anesthesia also is a method of choice for fetal valvuloplasty and amniotic band release. Fetal myelomenigocele repair requires general anesthesia with tocolysis. SUMMARY: Predelivery procedures require a differentiated anesthesia approach depending on the invasiveness of the intervention. Anesthesia ranges from monitored care to neuraxial anesthesia and general anesthesia. Depending on the procedure uterine relaxation and fetal immobilization are crucial for technical success. Interdisciplinary consultation optimizes the anesthesia plan for complex procedures.


Assuntos
Anestesia Geral/métodos , Anestésicos Inalatórios/administração & dosagem , Doenças Fetais/terapia , Terapias Fetais/métodos , Bloqueio Nervoso/métodos , Obstrução das Vias Respiratórias/complicações , Anestesia Geral/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Doenças Fetais/etiologia , Terapias Fetais/efeitos adversos , Humanos , Planejamento de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Circulação Placentária , Gravidez
16.
Biochem Biophys Res Commun ; 514(3): 960-966, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-31092336

RESUMO

Pregnancies complicated by preexisting maternal diabetes mellitus are associated with a higher risk of birth defects in infants, known as diabetic embryopathy. The common defects seen in the central nervous system result from failure of neural tube closure. The formation of neural tube defects (NTDs) is associated with excessive programmed cell death (apoptosis) in the neuroepithelium under hyperglycemia-induced intracellular stress conditions. The early cellular response to hyperglycemia remains to be identified. We hypothesize that hyperglycemia may disturb intracellular calcium (Ca2+) homeostasis, which perturbs organelle function and apoptotic regulation, resulting in increased apoptosis and embryonic NTDs. In an animal model of diabetic embryopathy, we performed Ca2+ imaging and observed significant increases in intracellular Ca2+ ([Ca2+]i) in the embryonic neural epithelium. Blocking T-type Ca2+ channels with mibefradil, but not L-type with verapamil, significantly blunted the increases in [Ca2+]i, implicating an involvement of channel type-dependent Ca2+ influx in hyperglycemia-perturbed Ca2+ homeostasis. Treatment of diabetic pregnant mice with mibefradil during neurulation significantly reduced NTD rates in the embryos. This effect was associated with decreases in apoptosis, alleviation of endoplasmic reticulum stress, and increases of anti-apoptotic factors. Taken together, our data suggest an important role of Ca2+ influx in hyperglycemia-induced NTDs and of T-type Ca2+ channels as a potential target to prevent birth defects in diabetic pregnancies.


Assuntos
Cálcio/metabolismo , Hiperglicemia/complicações , Defeitos do Tubo Neural/etiologia , Gravidez em Diabéticas/metabolismo , Animais , Apoptose , Modelos Animais de Doenças , Feminino , Doenças Fetais/etiologia , Doenças Fetais/metabolismo , Glucose/metabolismo , Hiperglicemia/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Defeitos do Tubo Neural/metabolismo , Gravidez
17.
J Perinatol ; 39(7): 920-926, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31073147

RESUMO

OBJECTIVE: To estimate the prevalence and characteristics of fetal thrombocytopenia at the time of percutaneous umbilical cord sampling (PUBS) in pregnancies complicated by alloimmunization and to conduct a systematic review on fetal thrombocytopenia in these pregnancies. STUDY DESIGN: Retrospective cohort study of all patients undergoing PUBS at our institution from 2000-2017. Clinical data, including fetal platelet counts, were abstracted from the medical record and analyzed with routine statistical procedures. A systematic review and meta-analysis were also conducted according to standard procedures. RESULT: At first procedure, prior to any transfusion, 13/36 fetuses (36%) had thrombocytopenia: 11/36 (31%) had moderate thrombocytopenia and 2/36 (6%) had severe thrombocytopenia (14 patients had no platelet count at first procedure). The systematic review identified six studies, and the prevalence of fetal thrombocytopenia at the time of PUBS for alloimmunization was 18% (95% confidence interval 11%, 26%). CONCLUSION: Thrombocytopenia is common and underappreciated in fetuses undergoing PUBS for alloimmunization.


Assuntos
Incompatibilidade de Grupos Sanguíneos/complicações , Sangue Fetal , Doenças Fetais/etiologia , Trombocitopenia/etiologia , Anemia/diagnóstico , Anemia/etiologia , Antígenos de Plaquetas Humanas/imunologia , Feminino , Sangue Fetal/citologia , Fetoscopia , Idade Gestacional , Humanos , Contagem de Plaquetas , Gravidez , Complicações Hematológicas na Gravidez , Estudos Retrospectivos , Trombocitopenia/diagnóstico , Trombocitopenia/imunologia
18.
BMC Pediatr ; 19(1): 79, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885166

RESUMO

BACKGROUND: Maternofetal carnitine transport through the placenta is the main route of fetal carnitine uptake. Decreased free carnitine levels discovered by newborn screening has identified many asymptomatic adult women with systemic primary carnitine deficiency (PCD). Here, we presented amplitude integrated electroencephalogram (aEEG) and magnetic resonance imaging (MRI) findings from a neonate with epilepsy whose mother was carnitine deficient. CASE PRESENTATION: A one-day-old female newborn was admitted after experiencing seizures for half a day; status epilepticus was found on the continuous normal voltage background pattern with immature sleep-wake cycling during aEEG monitoring. On T1-weighted, T2-weighted, FLAIR, and DWI head MRI, there were various degrees of hyperintense signals and diffusion restrictions in the deep white matter of the right hemisphere. Tandem mass spectrometry discovered carnitine deficiency on the second day, which elevated to normal by the 9th day before L-carnitine supplementation was started. The patient was treated with phenobarbital after admission. No further seizures were noted by day 5. It was confirmed that the patient's mother had a low level of serum-free carnitine. Gene analyses revealed that the newborn had heterozygote mutations on c.1400C > G of the SLC22A5 gene, and her mother had homozygous mutations on c.1400C > G. The patient had a good outcome at the 8-month follow up. CONCLUSIONS: Maternal carnitine deficiency that occurs during the perinatal period may manifest as secondary epilepsy with cerebral injury in neonates. The short-term neurodevelopmental outcomes were good. Early diagnosis of asymptomatic PCD in female patients can provide guidance for future pregnancies.


Assuntos
Cardiomiopatias/complicações , Carnitina/deficiência , Hiperamonemia/complicações , Doenças Musculares/complicações , Convulsões/etiologia , Encéfalo/diagnóstico por imagem , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Carnitina/sangue , Carnitina/genética , Eletroencefalografia , Feminino , Doenças Fetais/etiologia , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/genética , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Imagem por Ressonância Magnética , Mães , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Mutação
19.
Physiol Rep ; 7(4): e13973, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30785235

RESUMO

As the comparative pathophysiology of perinatal infection in the fetus and newborn is uncertain, this study contrasted the cerebral effects of endotoxemia in conscious fetal sheep and newborn lambs. Responses to intravenous bacterial endotoxin (lipopolysaccharide, LPS) or normal saline were studied on three consecutive days in fetal sheep (LPS 1 µg/kg, n = 5; normal saline n = 5) and newborn lambs (LPS 2 µg/kg, n = 10; normal saline n = 5). Cerebro-vascular function was assessed by monitoring cerebral blood flow (CBF) and cerebral vascular resistance (CVR) over 12 h each day, and inflammatory responses were assessed by plasma TNF alpha (TNF-α), nitrate and nitrite concentrations. Brain injury was quantified by counting both resting and active macrophages in the caudate nucleus and periventricular white matter (PVWM). An acute cerebral vasoconstriction (within 1 h of LPS injection) occurred in both the fetus (ΔCVR +53%) and newborn (ΔCVR +63%); subsequently prolonged cerebral vasodilatation occurred in the fetus (ΔCVR -33%) in association with double plasma nitrate/nitrite concentrations, but not in the newborn. Abundant infiltration of activated macrophages was observed in both CN and PVWM at each age, with the extent being 2-3 times greater in the fetus (P < 0.001). In conclusion, while the fetus and newborn experience a similar acute disruption of the cerebral circulation after LPS, the fetus suffers a more prolonged circulatory disruption, a greater infiltration of activated macrophages, and an exaggerated susceptibility to brain injury.


Assuntos
Encéfalo/embriologia , Encefalite/fisiopatologia , Doenças Fetais/fisiopatologia , Lipopolissacarídeos/toxicidade , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiopatologia , Circulação Cerebrovascular , Encefalite/etiologia , Feminino , Doenças Fetais/etiologia , Macrófagos/patologia , Masculino , Nitratos/sangue , Nitritos/sangue , Ovinos , Fator de Necrose Tumoral alfa/sangue , Vasoconstrição , Vasodilatação
20.
Kobe J Med Sci ; 64(4): E157-E159, 2019 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-30728342

RESUMO

Fetal intestinal volvulus is a rare condition, and fetal diagnosis of this disease is still challenging, especially in primary cases not accompanied by other comorbidities, such as intestinal malformations. Herein, we report a case of fetal primary small bowel volvulus associated with acute gastric dilatation detected by ultrasonography. We speculate that the mechanism of acute gastric dilatation in our case was peristatic malfunction of the whole intestine caused by a strangulated ileus resulting from fetal intestinal volvulus. In conclusion, acute gastric dilatation detected by fetal ultrasound can indicate the fetal intestinal volvulus.


Assuntos
Doenças Fetais/etiologia , Dilatação Gástrica/complicações , Volvo Intestinal/etiologia , Ultrassonografia Pré-Natal , Doença Aguda , Adulto , Feminino , Doenças Fetais/diagnóstico por imagem , Humanos , Volvo Intestinal/diagnóstico por imagem , Masculino , Gravidez
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