Intergenerational effects of maternal childhood maltreatment on newborns' stress regulation: The role of maternal depressive symptoms.

BACKGROUND: Maternal childhood maltreatment (CM) has been repeatedly associated with negative offspring's emotional outcomes. The dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis has emerged as the main underlying physiological mechanism. OBJECTIVE: To explore the association between maternal CM and newborns' physiological and neurobehavioral stress responses, considering the role of perinatal maternal depression and bonding. PARTICIPANTS AND SETTING: 150 healthy women were followed throughout pregnancy. 79 mother-infant dyads were included in the final analyses. Maternal CM was evaluated using the Childhood Trauma Questionnaire and depressive symptoms by the Edinburgh Postnatal Depression Scale (EPDS) at each trimester. At 7 weeks postpartum, the EPDS and the Postpartum Bonding Questionnaire were administered. Newborns' behavioral responses were assessed using "States Organization" (SO) and "States Regulation" (SR) subdomains of the Neonatal Behavioral Assessment Scale (NBAS). Newborns' salivary samples were collected before and after the NBAS to study cortisol reactivity. METHODS: A cross-lagged panel model was employed. RESULTS: Infants born to mothers with higher CM presented more optimal scores on SO (ß (0.635) = 0.216, p ã€ˆ001) and SR (ß (0.273) = 0.195, p = .006), and a higher cortisol reactivity after NBAS handling (ß(0.019) = 0.217, p = .009). Moreover, newborns of mothers with higher CM and postpartum depressive symptoms exhibited a poorer performance on SR (ß (0.156 = -0.288,p = .002). Analyses revealed non-significant relationships between mother-infant bonding, newborns' cortisol reactivity and SO. CONCLUSIONS: Newborns from mothers with greater CM present higher cortisol reactivity and more optimal behavioral responses, which may reflect a prenatal HPA axis sensitization. However, those exposed to maternal postnatal depressive symptoms present poorer stress recovery.

Effects of Mediterranean Diet or Mindfulness-Based Stress Reduction during pregnancy on fetal brain development detected by neurosonography. A secondary analysis of a Randomized Clinical Trial (IMPACT BCN).

INTRODUCTION: We investigated whether structured maternal lifestyle interventions based on Mediterranean diet or stress reduction influence fetal-infant neurodevelopment detected by detailed fetal neurosonography and Ages and Stages Questionnaires 3rd edition (ASQ) at 12months old. METHODS: This was a secondary analysis of a randomized clinical trial (2017-2020) including 1,221 singleton pregnancies at high-risk for small-for-gestational age. Participants were randomized into three groups at 19-23 weeks' gestation: Mediterranean diet intervention, stress reduction program or usual care. A detailed neurosonography was performed on 881 participants at mean(SD) 33.4(1.1) weeks' gestation. Neurosonographic measurements were done offline. ASQ was performed on 276 infants at one year of corrected age. RESULTS: Biparietal diameter were similar among study groups. Mediterranean diet group fetuses had deeper insula [26.80(1.68) vs. 26.63(1.75), mm, p=0.02] and longer corpus callosum [42.98 (2.44) vs. 42.62(2.27), mm, p=0.04], with lower rate of suboptimal score infants in ASQ problem-solving domain (6.2% vs. 16.3%, p=0.03); Stress reduction group fetuses had deeper insula [26.90(1.75) vs. 26.63(1.75), mm, p=0.04] and lower rates of suboptimal score infants in ASQ fine motor domain (4.3% vs. 12.8%, p=0.04), compared to usual care group fetuses. CONCLUSION: Maternal structured intervention during pregnancy of the trial has the potential to modify offspring's neurodevelopment.

FetMRQC: A robust quality control system for multi-centric fetal brain MRI.

Fetal brain MRI is becoming an increasingly relevant complement to neurosonography for perinatal diagnosis, allowing fundamental insights into fetal brain development throughout gestation. However, uncontrolled fetal motion and heterogeneity in acquisition protocols lead to data of variable quality, potentially biasing the outcome of subsequent studies. We present FetMRQC, an open-source machine-learning framework for automated image quality assessment and quality control that is robust to domain shifts induced by the heterogeneity of clinical data. FetMRQC extracts an ensemble of quality metrics from unprocessed anatomical MRI and combines them to predict experts' ratings using random forests. We validate our framework on a pioneeringly large and diverse dataset of more than 1600 manually rated fetal brain T2-weighted images from four clinical centers and 13 different scanners. Our study shows that FetMRQC's predictions generalize well to unseen data while being interpretable. FetMRQC is a step towards more robust fetal brain neuroimaging, which has the potential to shed new insights on the developing human brain.

Robust tracking of deformable anatomical structures with severe occlusions using deformable geometrical primitives.

BACKGROUND AND OBJECTIVE: Surgical robotics tends to develop cognitive control architectures to provide certain degree of autonomy to improve patient safety and surgery outcomes, while decreasing the required surgeons' cognitive load dedicated to low level decisions. Cognition needs workspace perception, which is an essential step towards automatic decision-making and task planning capabilities. Robust and accurate detection and tracking in minimally invasive surgery suffers from limited visibility, occlusions, anatomy deformations and camera movements. METHOD: This paper develops a robust methodology to detect and track anatomical structures in real time to be used in automatic control of robotic systems and augmented reality. The work focuses on the experimental validation in highly challenging surgery: fetoscopic repair of Open Spina Bifida. The proposed method is based on two sequential steps: first, selection of relevant points (contour) using a Convolutional Neural Network and, second, reconstruction of the anatomical shape by means of deformable geometric primitives. RESULTS: The methodology performance was validated with different scenarios. Synthetic scenario tests, designed for extreme validation conditions, demonstrate the safety margin offered by the methodology with respect to the nominal conditions during surgery. Real scenario experiments have demonstrated the validity of the method in terms of accuracy, robustness and computational efficiency. CONCLUSIONS: This paper presents a robust anatomical structure detection in present of abrupt camera movements, severe occlusions and deformations. Even though the paper focuses on a case study, Open Spina Bifida, the methodology is applicable in all anatomies which contours can be approximated by geometric primitives. The methodology is designed to provide effective inputs to cognitive robotic control and augmented reality systems that require accurate tracking of sensitive anatomies.

Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm premature rupture of membranes.

BACKGROUND: Brain injury and poor neurodevelopment have been consistently reported in infants and adults born before term. These changes occur, at least in part, prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not by neurosonography along with amniotic fluid brain injury biomarkers. OBJECTIVE: This study aimed to evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm premature rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a risk mediator. STUDY DESIGN: In this prospective cohort study, fetal brain remodeling and injury were evaluated using neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm premature rupture of membranes between 24.0 and 34.0 weeks of gestation, with (n=41) and without (n=54) intra-amniotic inflammation. The controls for neurosonography were outpatient pregnant patients without preterm labor or preterm premature rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm premature rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin 6 concentrations of >13.4 ng/mL in preterm labor and >1.43 ng/mL in preterm premature rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. Neuron-specific enolase, protein S100B, and glial fibrillary acidic protein were selected as amniotic fluid brain injury biomarkers. Data were adjusted for cephalic biometrics, fetal growth percentile, fetal sex, noncephalic presentation, and preterm premature rupture of membranes at admission. RESULTS: Fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes showed signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in the intra-amniotic inflammation, non-intra-amniotic inflammation, and control groups, the transcerebellar diameter measurements were 32.7 mm (interquartile range, 29.8-37.6), 35.3 mm (interquartile range, 31.2-39.6), and 35.0 mm (interquartile range, 31.3-38.3), respectively (P=.019), and the vermian height measurements were 16.9 mm (interquartile range, 15.5-19.6), 17.2 mm (interquartile range, 16.0-18.9), and 17.1 mm (interquartile range, 15.7-19.0), respectively (P=.041). Second, they presented a lower corpus callosum area (0.72 mm2 [interquartile range, 0.59-0.81], 0.71 mm2 [interquartile range, 0.63-0.82], and 0.78 mm2 [interquartile range, 0.71-0.91], respectively; P=.006). Third, they showed delayed cortical maturation (the Sylvian fissure depth-to-biparietal diameter ratios were 0.14 [interquartile range, 0.12-0.16], 0.14 [interquartile range, 0.13-0.16], and 0.16 [interquartile range, 0.15-0.17], respectively [P<.001], and the right parieto-occipital sulci depth ratios were 0.09 [interquartile range, 0.07-0.12], 0.11 [interquartile range, 0.09-0.14], and 0.11 [interquartile range, 0.09-0.14], respectively [P=.012]). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm premature rupture of membranes had higher concentrations of neuron-specific enolase (11,804.6 pg/mL [interquartile range, 6213.4-21,098.8], 8397.7 pg/mL [interquartile range, 3682.1-17,398.3], and 2393.7 pg/mL [interquartile range, 1717.1-3209.3], respectively; P<.001), protein S100B (2030.6 pg/mL [interquartile range, 993.0-4883.5], 1070.3 pg/mL [interquartile range, 365.1-1463.2], and 74.8 pg/mL [interquartile range, 44.7-93.7], respectively; P<.001), and glial fibrillary acidic protein (1.01 ng/mL [interquartile range, 0.54-3.88], 0.965 ng/mL [interquartile range, 0.59-2.07], and 0.24 mg/mL [interquartile range, 0.20-0.28], respectively; P=.002). CONCLUSION: Fetuses with preterm labor with intact membranes or preterm premature rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in fetuses with intra-amniotic inflammation.

Robot assisted Fetoscopic Laser Coagulation: Improvements in navigation, re-location and coagulation.

Fetoscopic Laser Coagulation (FLC) for Twin to Twin Transfusion Syndrome is a challenging intervention due to the working conditions: low quality images acquired from a 3 mm fetoscope inside a turbid liquid environment, local view of the placental surface, unstable surgical field and delicate tissue layers. FLC is based on locating, coagulating and reviewing anastomoses over the placenta's surface. The procedure demands the surgeons to generate a mental map of the placenta with the distribution of the anastomoses, maintaining, at the same time, precision in coagulation and protecting the placenta and amniotic sac from potential damages. This paper describes a teleoperated platform with a cognitive-based control that provides assistance to improve patient safety and surgery performance during fetoscope navigation, target re-location and coagulation processes. A comparative study between manual and teleoperated operation, executed in dry laboratory conditions, analyzes basic fetoscopic skills: fetoscope navigation and laser coagulation. Two exercises are proposed: first, fetoscope guidance and precise coagulation. Second, a resolved placenta (all anastomoses are indicated) to evaluate navigation, re-location and coagulation. The results are analyzed in terms of economy of movement, execution time, coagulation accuracy, amount of coagulated placental surface and risk of placenta puncture. In addition, new metrics, based on navigation and coagulation maps evaluate robotic performance. The results validate the developed platform, showing noticeable improvements in all the metrics.

Diurnal cortisol throughout pregnancy and its association with maternal depressive symptoms and birth outcomes.

BACKGROUND: Depression during pregnancy is a common complication that can negatively affect fetal health and birth outcomes. Cortisol is believed to be a key mediator of this association. Although pregnancy entails a natural increase in cortisol levels, preclinical depression could alter its circadian rhythm, producing excessively high overall diurnal cortisol levels that might be harmful for the fetus and future offspring development. OBJECTIVES: Using a prospective longitudinal design, we aimed to study (i) trimestral cortisol circadian rhythm and its overall levels throughout pregnancy in healthy women, (ii) the extent to which maternal depressive symptoms influence both cortisol rhythmicity and overall levels, and (iii) the possible adverse consequences of elevated maternal cortisol on the offspring's weight and gestational age at birth. STUDY DESIGN: 112 healthy pregnant women from the general Spanish population were recruited before their first pregnancy. To assess cortisol circadian rhythm, participants provided four saliva samples at each trimester of pregnancy (at awakening, 30 min after awakening, before lunch and before going to bed). Overall cortisol levels were calculated with AUCg approximation. Depressive symptoms were evaluated in each trimester and defined according to EPDS cut-off values (1st trimester, EPDS ≥ 11; 2nd and 3rd trimesters, EPDS ≥ 10). At birth, the risk for low weight, prematurity and weight birth percentile was retrieved for 100 infants. Mixed models and simple effects were employed to study changes of maternal cortisol circadian rhythm and overall levels throughout pregnancy and the possible influence of maternal depressive symptoms. Finally, logistic regressions were performed to assess the associations between maternal overall cortisol levels in each trimester of pregnancy and birth anthropometrics. RESULTS: Although overall diurnal cortisol levels increase throughout pregnancy, cortisol circadian rhythm is preserved in all trimesters [1st (F(3110)= 92.565, p < .001), 2nd (F(3,85)= 46.828, p < .001) and 3rd (F(3,90)= 65.555, p < .001)]. However, women with depressive symptoms showed a flattened cortisol circadian pattern only during the second trimester, characterized by a blunted awakening peak and reduced evening decline (F(3,85)= 4.136, p = .009), but not during the first (F(3,11)= 1.676, p = .176) or the third (F(3,90)= 1.089, p = .358) trimesters. Additionally, they did not show a cortisol increase from second to third trimester (p = .636). Finally, higher maternal cortisol levels in second and third trimesters seemed to be associated with increased risk of prematurity (adjusted OR -0.371, 95% CI 0.490-0.972, p = .034) and low birth weight percentile (adjusted OR -0.612, 95% CI 0.348-0.846, p = .007) respectively. CONCLUSION: Maternal cortisol levels increased throughout pregnancy, although cortisol circadian rhythm was preserved in all trimesters of pregnancy. However, prenatal depressive symptoms were associated with flattened maternal cortisol circadian rhythm in mid-pregnancy. Therefore, it seems that women with depressive symptoms tended to increase less gradually their cortisol levels from mid to late pregnancy. Finally, higher maternal cortisol levels in mid and late-pregnancy seem to be associated with poorer birth anthropometrics Early detection of depressive symptoms in general population could help to prevent putative obstetrical and birth adverse outcomes.

Complicaciones del embarazo gemelar monocorial: claves para el diagnóstico y tratamiento / Complications of monochorionic twin pregnancies: Key concepts for the diagnosis and management

El embarazo gemelar monocorial (MC) se presenta en uno de cada 250 embarazos y representa una proporción significativa de morbi mortalidad perinatal en los embarazos gemelares y en general. El manejo óptimo de los MC se basa en 2 aspectos fundamentales: clasificación temprana de la corionicidad y seguimiento estricto. El diagnóstico diferencial de las complicaciones del MC sigue siendo todavía un reto para el especialista de medicina fetal. Esto se debe a la frecuente superposición de signos clínicos y a las relaciones complejas entre las potenciales complicaciones. La experiencia clínica demuestra que en la mayoría de los casos la clasificación y el manejo adecuado se pueden lograr mediante la aplicación sistemática de conceptos sencillos. Esta revisión proporciona una visión global que permite una compresión integral de los embarazos gemelares MC, sus posibles complicaciones y los conceptos claves que permiten un diagnóstico diferencial adecuado y un manejo específico(AU)

Monochorionic twin pregnancy (MC) occurs in one in 250 pregnancies and represents a significant proportion of perinatal morbidity and mortality in twin pregnancies, and in general. The optimal management of MC is based on two fundamental aspects: early classification of chorionicity and close monitoring. The differential diagnosis of the complications of MC is still a challenge to the fetal medicine specialist. This is due to the frequent overlap of clinical signs and the complex relationships between the potential complications. However, the differential diagnosis and subsequent decisions are based on relatively simple rules. While some cases can be really complicated, clinical experience shows that in most cases proper classification and management can be achieved through the consistent use of simple concepts. This review provides an overview that allows a comprehensive understanding of MC twin pregnancies, the typical complications and the key concepts that allow an appropriate differential diagnosis and specific management(AU)

Tratamiento por fetoscopia de la transfusión feto-fetal: resultados en 500 casos consecutivos / Fetoscopic laser surgery for twin-to-twin transfusion syndrome: Outcome of 500 consecutive cases

Objetivos. Evaluar los resultados perinatales de 500 casos consecutivos de transfusión feto-fetal (TFF) tratados en nuestro Hospital mediante fetoscopia láser. Material y métodos. Estudio prospectivo con 500 casos de TFF grave tratadas con fetoscopia láser como primera opción. Evaluamos la supervivencia, evolución perinatal, complicaciones obstétricas y tasa de lesión neurológica a los 6 meses de vida. Resultados. La edad gestacional media al tratamiento fue 19,4 semanas (rango 15,0-31,4). La placenta fue anterior en el 48% (n=240). La tasa de conversión a oclusión de cordón fue del 1,2% (6/500). La supervivencia neonatal global fue del 74,8% (748/1.000), con un superviviente al menos en el 91,6% (458/500). La duración media del procedimiento fue de 29,4min (9-64). No se observó ningún caso de corioamnionitis o desprendimiento de placenta asociado al procedimiento. Se observó persistencia de TFF en 2 casos (0,4%) y TAPS en 8 (1,6%). Se produjo rotura prematura de membranas (RPM) antes de las 32 semanas en 32 casos (6,4%). La edad gestacional media al parto fue de 33,6 semanas (26,4-38,5), con un 92% después de las 28 semanas. El peso medio en receptores fue 1.920 g (rango 680-3.660) y en donantes 1.615 g (rango 440-2.530). La tasa de anomalías severas del neurodesarrollo fue del 6,4%. Conclusión. En una de las mayores series consecutivas de TFF en el mismo centro, los resultados se sitúan en rango alto de las series publicadas. La coagulación fetoscópica láser de las anastomosis vasculares es segura para la madre y presenta resultados consistentes en centros con experiencia(AU)

Objective. To evaluate the perinatal outcome in the 500 consecutive cases of severe twin-twin transfusion syndrome (TTTS) treated in a single centre with fetoscopic laser coagulation. Material and methods. A prospective study including 500 cases of severe TTS treated with laser therapy as a first option. Main outcome measures were survival, perinatal outcome, obstetrical complications and rate of neurological damage at 6-12 months of life. Results. Mean gestational age at therapy was 19.4 weeks (range 15.0-31.4). The placenta was anterior in 48% (n=240) of the cases. The rate of conversion to cord occlusion was 1.2% (6/500). Overall neonatal survival was 74.8% (748/1,000), with at least one survivor in 91.6% (458/500). Mean duration of surgery was 29.4min (range 9-64). There were no cases of intra- or post-operative abruptio placenta or chorioamnionitis. TTTS persisted in 2 cases (0.4%) and TAPS occurred in 8 (1.6%). Premature rupture of membranes (PROM) at <32 weeks occurred in 32 cases (6.4%). Mean gestational age at delivery was 33.6 weeks (26.4-38.5), with 92% beyond 28 weeks. Mean birth-weight was 1,920 g (range 680-3,660) in recipients and 1,615 g (range 440-2,530) in donors. Severe neurological damage was observed in 6.4%. Conclusions. In this large consecutive series of TTTS treated by fetoscopy in the same centre, results lie in the high range of those previously reported. Fetoscopic laser coagulation of the placental anastomosis is a safe therapy and offers consistent results in centres with experience(AU)