RESUMO
Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis "functioning". The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning.
Assuntos
Glucocorticoides , Sistema Hipotálamo-Hipofisário , Adolescente , Criança , Estudos Transversais , Metilação de DNA , Epigênese Genética , Feminino , Glucocorticoides/metabolismo , Humanos , Hidrocortisona , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Gravidez , Receptores de Glucocorticoides/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Estresse Psicológico/metabolismoRESUMO
The abilities to monitor one's actions and novel information in the environment are crucial for behavioural and cognitive control. This study investigated the development of error and novelty monitoring and their electrophysiological correlates by using a combined flanker with novelty-oddball task in children (7-12 years) and adolescents (14-18 years). Potential moderating influences of prenatal perturbation of steroid hormones on these performance monitoring processes were explored by comparing individuals who were prenatally exposed and who were not prenatally exposed to synthetic glucocorticoids (sGC). Generally, adolescents performed more accurately and faster than children. However, behavioural adaptations to error or novelty, as reflected in post-error or post-novelty slowing, showed different developmental patterns. Whereas post-novelty slowing could be observed in children and adolescents, error-related slowing was absent in children and was marginally significant in adolescents. Furthermore, the amplitude of error-related negativity was larger in adolescents, whereas the amplitude of novelty-related N2 was larger in children. These age differences suggest that processes involving top-down processing of task-relevant information (for instance, error monitoring) mature later than processes implicating bottom-up processing of salient novel stimuli (for instance, novelty monitoring). Prenatal exposure to sGC did not directly affect performance monitoring but initial findings suggest that it might alter brain-behaviour relation, especially for novelty monitoring.
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Desenvolvimento do Adolescente , Desenvolvimento Infantil , Cognição , Adolescente , Encéfalo/fisiologia , Criança , Potenciais Evocados , Feminino , Humanos , Masculino , Desempenho Psicomotor , Tempo de ReaçãoRESUMO
PURPOSE: Placenta accreta spectrum (PAS) disorders can cause major intrapartum haemorrhage. The optimal management approach is not yet defined. We analysed available cases from a tertiary perinatal centre to compare the outcome of different individual management strategies. METHODS: A monocentric retrospective analysis was performed in patients with clinically confirmed diagnosis of PAS between 07/2012 and 12/2019. Electronic patient and ultrasound databases were examined for perinatal findings, peripartum morbidity including blood loss and management approaches such as (1) vaginal delivery and curettage, (2) caesarean section with placental removal versus left in situ and (3) planned, immediate or delayed hysterectomy. RESULTS: 46 cases were identified with an incidence of 2.49 per 1000 births. Median diagnosis of placenta accreta (56%), increta (39%) or percreta (4%) was made in 35 weeks of gestation. Prenatal detection rate was 33% for all cases and 78% for placenta increta. 33% showed an association with placenta praevia, 41% with previous caesarean section and 52% with previous curettage. Caesarean section rate was 65% and hysterectomy rate 39%. In 9% of the cases, the placenta primarily remained in situ. 54% of patients required blood transfusion. Blood loss did not differ between cases with versus without prenatal diagnosis (p = 0.327). In known cases, an attempt to remove the placenta did not show impact on blood loss (p = 0.417). CONCLUSION: PAS should be managed in an optimal setting and with a well-coordinated team. Experience with different approaches should be proven in prospective multicentre studies to prepare recommendations for expected and unexpected need for management.
Assuntos
Cesárea , Histerectomia , Placenta Acreta/terapia , Hemorragia Pós-Parto/prevenção & controle , Adulto , Cesárea/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Placenta , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/epidemiologia , Gravidez , Cuidado Pré-Natal , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
: The aim of this study was to find a prenatal parameter to be able to predict possible prenatal complications or postnatal surgical options, thus allowing the fetal medicine specialist, together with pediatric surgeons and neonatologists, to improve the counseling of the parents and to determine the timing of delivery and therapy. This was a retrospective analysis of prenatal diagnosis and outcome of fetuses with 34 cases of gastroschisis between the years 2007 and 2017. A total of 34 fetuses with gastroschisis were examined and 33 outcomes registered: 22 cases of simple gastroschisis (66.7%) and 11 cases of complex gastroschisis (33.3%). A cut-off value of 18 mm for intraabdominal bowel dilatation (IABD) showed a positive predictive value (PPV) of 100% for predicting simple gastroschisis. IABD gives the best prediction for simple versus complex gastroschisis (cut-off of 18 mm). Extra-abdominal bowel dilatation (EABD) cut-off values of 10 mm and 18 mm showed low sensitivity and specificity to predict complex gastroschisis.
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PURPOSE: Pregnancy complications (PC) with signs of threatened preterm birth are often associated with lengthy hospital stays, which have been shown to be accompanied by anxiety, depressive symptoms, and increased stress level. It remains unclear, whether the perinatal course of mental health of these women differs from women without PC and whether there may be differences in the postpartum mother-infant bonding. METHODS: In a naturalistic longitudinal study with two measurements (24-36th weeks of gestation and 6 weeks postpartum), we investigated depression (EPDS), anxiety (STAI-T), stress (PSS), and postpartum mother-infant bonding (PBQ) in women with threatened preterm birth (N = 75) and women without PC (N = 70). For data evaluation, we used means of frequency analysis, analysis of variance with repeated measurements, and t-tests for independent samples. RESULTS: The patient group showed significantly higher rates of depression, anxiety, and stress during inpatient treatment in pregnancy, as well as 6 weeks postpartum compared to the control group. While depression and anxiety decreased over time in both groups, stress remained at the same level 6 weeks postpartum as in pregnancy. We found no significant differences in mother-infant bonding between the two groups at all considered PBQ scales. CONCLUSION: It is recommended to pay attention to the psychological burden of all obstetric patients as a routine to capture a psychosomatic treatment indication. A general bonding problem in women with threatened preterm birth was not found. Nevertheless, increased maternal stress, anxiety, and depressiveness levels during pregnancy may have a negative impact on the development of the fetus.
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Relações Mãe-Filho/psicologia , Mães/psicologia , Complicações na Gravidez/psicologia , Nascimento Prematuro/psicologia , Adulto , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Saúde Mental , Gravidez , Inquéritos e QuestionáriosRESUMO
CONTEXT: Antenatal synthetic glucocorticoid (sGC) treatment constitutes a potent programming factor of the hypothalamic-pituitary-adrenal (HPA) axis. Previous findings from our group revealed long-term changes in cortisol stress reactivity following antenatal sGC therapy. However, the few prior studies exclusively relied on spot measurements of phasic HPA axis activity, which may not adequately capture cortisol output over prolonged periods of time. OBJECTIVE: To address this gap, the current study utilized hair steroid concentrations, a valid marker of integrated long-term HPA-axis activity, to investigate endocrine changes in individuals treated with antenatal sGC. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study comprised 76 term-born children (7-12 years) and 58 adolescents (14-18 years). Cumulated hormonal secretion in scalp hair over a 3-month period was determined for different biomarkers of tonic HPA axis activity by liquid chromatography coupled with tandem mass spectrometry. Hair steroid levels were compared between participants with antenatal sGC therapy (dexamethasone or betamethasone) and different control groups. RESULTS: Findings from this study provide no evidence for a significant effect of antenatal sGCs on long-term hair steroid concentrations. Participants treated with antenatal sGC exhibited comparable levels of hair cortisol, cortisone, dehydroepiandrosterone, and cortisol/dehydroepiandrosterone ratios compared to those of mothers who had been admitted to hospital for pregnancy complications but had never received sGC therapy and controls from physiological pregnancies. CONCLUSION: In conjunction with data from previous studies, it is thus tempting to speculate that sGC may affect the capacity of dynamic changes and flexible adaption of an individual's HPA axis rather than changes in tonic steroid output.
Assuntos
Glucocorticoides/uso terapêutico , Cabelo/química , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Esteroides/análise , Adolescente , Betametasona/análise , Betametasona/uso terapêutico , Criança , Cortisona/análise , Estudos Transversais , Dexametasona/análise , Dexametasona/uso terapêutico , Feminino , Glucocorticoides/análise , Humanos , Hidrocortisona/análise , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Recém-Nascido , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Gravidez , Complicações na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Medicamentos Sintéticos/análise , Medicamentos Sintéticos/uso terapêuticoRESUMO
INTRODUCTION: It can be observed that there is an increase in the methamphetamine (MA) consumption in Saxony (Federal Republic of Germany). There is so far no data available in German speaking countries about the risk of MA consumption in pregnancy or delivery. METHODS: The data from all pregnant women who were examined or delivered at the Clinic for Obstetrics and Gynaecology between 2010-2015 were retrospectively searched for MA consumption. 119 pregnancies with 113 deliveries of 115 women consuming MA could be evaluated. 88 women admitted the consumption according to the history, 28 women denied it and there was no information available in the records of 3 cases. 113 women agreed to test MA in blood and 93 cases were positive (28 cases of them with low-dose consumption). The statistical analysis was performed by the Institute for Medical Informatics and Biometry. The data driven from the quality control report of the department of Gynaecology in 2015 was used as a control group. RESULTS: MA-consumers are significantly younger, without a permanent relationship, without a job and have a low education level. The first detection of the pregnancy was late and the number of performed routine examinations including ultrasound assessment was lower compared to the controls. 7 women had no routine examination. The number of premature contractions, cervical insufficiency and gestational diabetes were significantly higher. The number of patients needing tocolysis, antenatal glucocorticoid treatment for prevention of neonatal respiratory distress syndrome or in-patient care was significantly higher in patients consuming MA. The number of amniotic infection syndrome and premature rupture of membranes were higher. The rate of intrauterine fetal death was 3,5% which was much higher than the rate of control group (0,2%). DISCUSSION: The MA-consumption increases the risk for mother and child significantly during the pregnancy and delivery (pregnancy complications, premature delivery, increased rate of abortion, intrauterine death). A special attention must be taken for the young pregnant, non-working women without a partner who do not take the routine examinations in account or start having them late.
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Transtornos Relacionados ao Uso de Anfetaminas/epidemiologia , Metanfetamina/efeitos adversos , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Criança , Feminino , Morte Fetal , Alemanha/epidemiologia , Humanos , Recém-Nascido , Metanfetamina/administração & dosagem , Gravidez , Complicações na Gravidez/diagnóstico , Estudos Retrospectivos , Natimorto/epidemiologia , TocóliseRESUMO
An increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.
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Diabetes Mellitus Tipo 1/diagnóstico , Programas de Rastreamento , Efeitos Psicossociais da Doença , Humanos , Recém-Nascido , Pais/psicologia , Projetos Piloto , Fatores de RiscoRESUMO
Preterm birth is a highly prevalent phenomenon that was shown to be associated with mental stress during pregnancy (Rich-Edwards and Grizzard in Am J Obstet Gynecol 192(5 Suppl):S30-S35, 2005). We aimed to assess the effects of heart rate variability (HRV)-biofeedback in patients with preterm labour. Therefore, we conducted a controlled randomized parallel group study in 48 female patients aged 19-38 years (median = 29) with preterm labour at gestational week 24th-32nd (median = 29th). In this study, one group (n = 24) attended six sessions of HRV-biofeedback over 2 weeks whereas patients of the other group (n = 24) were assigned to control sessions. In the HRV-biofeedback treated group, perception of chronic stress was decreased 4 weeks after completion of training compared to baseline (p < 0.05) but there was no change in the control group. In the HRV-biofeedback group, preterm birth was seen in 3 patients (13 %) whereas in the control group, preterm delivery occurred in 8 patients (33 %, p = n.s.). There was no difference in birth weight between groups and HRV remained unchanged. In conclusion, our study demonstrates that HRV-biofeedback can reduce chronic stress in patients with preterm labour when administered as an adjunct to routine care. However, it remains unclear whether stress reduction through HRV-biofeedback has a beneficial effect on preterm birth.
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Biorretroalimentação Psicológica , Frequência Cardíaca/fisiologia , Trabalho de Parto Prematuro/terapia , Estresse Psicológico/terapia , Adulto , Feminino , Humanos , Trabalho de Parto Prematuro/fisiopatologia , Gravidez , Psicometria , Estresse Psicológico/fisiopatologia , Resultado do Tratamento , Adulto JovemRESUMO
Studies in non-human mammals have identified olfactory signals as prime mediators of mother-infant bonding and they have been linked with maternal attitudes and behavior in our own species as well. However, although the neuronal network processing infant cues has been studied for visual and auditory signals; to date, no such information exists for chemosensory signals. We contrasted the cerebral activity underlying the processing of infant odor properties in 15 women newly given birth for the first time and 15 women not given birth while smelling the body odor of unfamiliar 2 day-old newborn infants. Maternal status-dependent activity was demonstrated in the thalamus when exposed to the body odor of a newly born infant. Subsequent regions of interest analyses indicated that dopaminergic neostriatal areas are active in maternal-dependent responses. Taken together, these data suggests that body odors from 2 day-old newborns elicit activation in reward-related cerebral areas in women, regardless of their maternal status. These tentative data suggests that certain body odors might act as a catalyst for bonding mechanisms and highlights the need for future research on odor-dependent mother-infant bonding using parametric designs controlling for biological saliency and general odor perception effects.
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Absence of the ductus venosus (ADV) is a rare vascular anomaly. Its prognosis depends on the pathway of the umbilical flow to the systemic venous circulation, and the presence or absence of associated structural or chromosomal anomalies, sometimes resulting in hydrops fetalis. In cases with isolated ADV in the absence of associated anomalies, survival rates are as high as 85%, depending on the shunt situation. Here, we report a patient with ADV and extrahepatic umbilical vein drainage with favorable outcome after intrauterine reversal of early signs of cardiac failure. Diagnosis was made after the appearance of moderate cardiomegaly in the 25th gestational week. Thus, in the case of cardiomegaly with or without further signs of cardiac failure, ultrasound imaging of the venous duct should be considered.
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Cardiomegalia/etiologia , Insuficiência Cardíaca/etiologia , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Veias Umbilicais/anormalidades , Malformações Vasculares/diagnóstico por imagem , Adulto , Cardiomegalia/diagnóstico por imagem , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Recém-Nascido , Masculino , Gravidez , Remissão Espontânea , Veias Umbilicais/diagnóstico por imagem , Malformações Vasculares/complicaçõesRESUMO
Congenital arteriovenous malformations are rare causes of congestive cardiac failure in neonates. The most common sites are in the head and liver, but other sites include the thorax, the abdomen and the limbs. The onset of failure is usually not in the immediate neonatal period, but later on in life, albeit that lesions such as the arteriovenous malformation of the vein of Galen, and other arteriovenous malformations in different locations which produce high flow can present early. We describe here the first case, to the best of our knowledge, of prenatal detection of an intrathoracic arteriovenous malformation producing neonatal cardiac failure, which was successfully treated by surgery postnatally.