Unsupervised Segmentation of Fetal Brain MRI using Deep Learning Cascaded Registration

Accurate segmentation of fetal brain magnetic resonance images is crucial for analyzing fetal brain development and detecting potential neurodevelopmental abnormalities. Traditional deep learning-based automatic segmentation, although effective, requires extensive training data with ground-truth labels, typically produced by clinicians through a time-consuming annotation process. To overcome this challenge, we propose a novel unsupervised segmentation method based on multi-atlas segmentation, that accurately segments multiple tissues without relying on labeled data for training. Our method employs a cascaded deep learning network for 3D image registration, which computes small, incremental deformations to the moving image to align it precisely with the fixed image. This cascaded network can then be used to register multiple annotated images with the image to be segmented, and combine the propagated labels to form a refined segmentation. Our experiments demonstrate that the proposed cascaded architecture outperforms the state-of-the-art registration methods that were tested. Furthermore, the derived segmentation method achieves similar performance and inference time to nnU-Net while only using a small subset of annotated data for the multi-atlas segmentation task and none for training the network. Our pipeline for registration and multi-atlas segmentation is publicly available at https://github.com/ValBcn/CasReg.Comment: 17 pages, 8 figures, 5 tables, paper submitted to IEEE transaction on medical imagin

Fetal Liver Volume Assessment Using Magnetic Resonance Imaging in Fetuses With Cytomegalovirus Infection

Objective: To assess fetal liver volume (FLV) by magnetic resonance imaging (MRI) in cytomegalovirus (CMV)-infected fetuses compared to a group of healthy fetuses. Method: Most infected cases were diagnosed by the evidence of ultrasound abnormalities during routine scans and in some after maternal CMV screening. CMV-infected fetuses were considered severely or mildly affected according to prenatal brain lesions identified by ultrasound (US)/MRI. We assessed FLV, the FLV to abdominal circumference (AC) ratio (FLV/AC-ratio), and the FLV to fetal body volume (FBV) ratio (FLV/FBV-ratio). As controls, we included 33 healthy fetuses. Hepatomegaly was evaluated post-mortem in 11 cases of congenital CMV infection. Parametric trend and intraclass correlation analyses were performed. Results: There were no significant differences in FLV between infected (n = 32) and healthy fetuses. On correcting the FLV for AC and FBV, we observed a significantly higher FLV in CMV-infected fetuses. There were no significant differences in the FLV, or the FLV/AC or FLV/FBV-ratios according to the severity of brain abnormalities. There was excellent concordance between the fetal liver weight estimated by MRI and liver weight obtained post-mortem. Hepatomegaly was not detected in any CMV-infected fetus. Conclusion: In CMV-infected fetuses, FLV corrected for AC and FBV was higher compared to healthy controls, indicating relative hepatomegaly. These parameters could potentially be used as surrogate markers of liver enlargement. Keywords: fetal brain abnormalities; fetal cytomegalovirus infection; fetal liver; magnetic resonance imaging; pregnancy

Maternal Dietary Inflammatory Index during Pregnancy Is Associated with Perinatal Outcomes: Results from the IMPACT BCN Trial

The information available on the effects of maternal dietary habits on systemic inflammation and adverse maternal outcomes is limited. We aimed to evaluate whether Dietary Inflammatory Index (DII) score during pregnancy is associated with maternal body mass index (BMI), Mediterranean diet (MD) adherence, and perinatal outcomes. At 19-23 weeks' gestation, 1028 pregnant women were recruited. Dietary information was assessed using a 17-item dietary score to evaluate MD adherence and a validated 151-item food frequency questionnaire. DII score was established according to 33 food and nutritional proinflammatory and anti-inflammatory items. Participants were distributed into tertiles according to the DII score, where a lower DII score (first tertile) represented an anti-inflammatory diet and the third tertile represented the more proinflammatory diet. Maternal characteristics and perinatal outcomes were collected, and newborns' birthweight percentiles were calculated. Adjusted logistic regression models were used to assess the association of the DII score with maternal and perinatal characteristics, setting the third tertile as the reference group. Women in the third tertile showed lower adherence to MD score compared to the first tertile: median (25th to 75th percentile) 9 (7 to 11) vs. 6 (4.25 to 8), p < 0.001. The proinflammatory diet was significantly associated with a higher maternal pre-pregnancy BMI (adjusted β = 0.88; 95% CI: 0.31 to 1.45) and lower newborn's birthweight percentile (adjusted β = −9.84th; 95% CI: −19.6 to −0.12). These data show that a proinflammatory diet profile may be associated with maternal overweight and fetal undergrowth

Validation of a pregnancy-adapted Mediterranean Diet Adherence Screener (preg-MEDAS): a validation study nested in the Improving Mothers for a better PrenAtal Care Trial BarCeloNa (IMPACT BCN) trial

Background: Non-time-consuming and easy-to-administer dietary assessment tools specific for pregnancy are needed. Objectives: The aim of this validation study nested in the IMPACT BCN (Improving Mothers for a better PrenAtal Care Trial BarCeloNa) trial is to determine the concurrent validity of the 17-item pregnancy-adapted Mediterranean diet score (preg-MEDAS) and to analyze whether changes in the preg-MEDAS score were associated with maternal favorable dietary and cardiometabolic changes after 3 mo of intervention in pregnant women. Methods: Dietary data was collected in 812 participants using the preg-MEDAS and a 151-item validated food frequency questionnaire (FFQ) at baseline (19-23 wk gestation) and final visit (31-34 wk gestation). Concurrent preg-MEDAS validity was evaluated by Pearson and intraclass correlation coefficients, κ statistic, and Bland-Altman methods. Results: The preg-MEDAS had a good correlation with the FFQ (r = 0.76 and intraclass correlation coefficient 0.75). The agreement of each of the preg-MEDAS items ranged from 40.9% to 93.8% with a substantial agreement mean concordance (κ = 0.61). A 2-point increase in preg-MEDAS was associated with a decrease in maternal mean and systolic blood pressure (β: -0.51 mmHg; 95% confidence interval [CI]: -0.97, -0.04 mmHg and -0.87 mmHg; 95% CI: -1.48, -0.26 mmHg, respectively). Conclusions: The preg-MEDAS displays good validity for assessing adherence to the Mediterranean diet, allowing detection of dietary changes over time. In addition, changes observed in preg-MEDAS are significantly associated with a decrease in maternal blood pressure. Therefore, we propose preg-MEDAS as a rapid and simple dietary assessment tool during pregnancy. This trial was registered at clinicaltrials.gov as NCT03166332

Effects of a Mediterranean Diet Intervention on Maternal Stress, Well-Being, and Sleep Quality throughout Gestation-The IMPACT-BCN Trial

Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation. Keywords: Mediterranean diet; pregnancy; anxiety; well-being; sleep qualit

Effects of Mediterranean diet or mindfulness-based stress reduction on fetal and neonatal brain development: a secondary analysis of a randomized clinical trial

Background: Maternal suboptimal nutrition and high stress levels are associated with adverse fetal and infant neurodevelopment. Objective: This study aimed to investigate if structured lifestyle interventions involving a Mediterranean diet or mindfulness-based stress reduction during pregnancy are associated with differences in fetal and neonatal brain development. Study design: This was a secondary analysis of the randomized clinical trial Improving Mothers for a Better Prenatal Care Trial Barcelona that was conducted in Barcelona, Spain, from 2017 to 2020. Participants with singleton pregnancies were randomly allocated into 3 groups, namely Mediterranean diet intervention, stress reduction program, or usual care. Participants in the Mediterranean diet group received monthly individual sessions and free provision of extra-virgin olive oil and walnuts. Pregnant women in the stress reduction group underwent an 8-week mindfulness-based stress reduction program adapted for pregnancy. Magnetic resonance imaging of 90 fetal brains was performed at 36 to 39 weeks of gestation and the Neonatal Neurobehavioral Assessment Scale was completed for 692 newborns at 1 to 3 months. Fetal outcomes were the total brain volume and lobular or regional volumes obtained from a 3-dimensional reconstruction and semiautomatic segmentation of magnetic resonance images. Neonatal outcomes were the 6 clusters scores of the Neonatal Neurobehavioral Assessment Scale. Multiple regression analyses were conducted to assess the association between the interventions and the fetal and neonatal outcomes. Results: When compared with the usual care group, the offspring exposed to a maternal Mediterranean diet had a larger total fetal brain volume (mean, 284.11 cm3; standard deviation, 23.92 cm3 vs 294.01 cm3; standard deviation, 26.29 cm3; P=.04), corpus callosum (mean, 1.16 cm3; standard deviation, 0.19 cm3 vs 1.26 cm3; standard deviation, 0.22 cm3; P=.03), and right frontal lobe (44.20; standard deviation, 4.09 cm3 vs 46.60; standard deviation, 4.69 cm3; P=.02) volumes based on magnetic resonance imaging measures and higher scores in the Neonatal Neurobehavioral Assessment Scale clusters of autonomic stability (mean, 7.4; standard deviation, 0.9 vs 7.6; standard deviation, 0.7; P=.04), social interaction (mean, 7.5; standard deviation, 1.5 vs 7.8; standard deviation, 1.3; P=.03), and range of state (mean, 4.3; standard deviation, 1.3 vs 4.5; standard deviation, 1.0; P=.04). When compared with the usual care group, offspring from the stress reduction group had larger fetal left anterior cingulate gyri volume (1.63; standard deviation, 0.32 m3 vs 1.79; standard deviation, 0.30 cm3; P=.03) based on magnetic resonance imaging and higher scores in the Neonatal Neurobehavioral Assessment Scale for regulation of state (mean, 6.0; standard deviation, 1.8 vs 6.5; standard deviation, 1.5; P<.01). Conclusion: Maternal structured lifestyle interventions involving the promotion of a Mediterranean diet or stress reduction during pregnancy were associated with changes in fetal and neonatal brain development. Trial registration: ClinicalTrials.gov NCT03166332

Diet quality and nutrient density in pregnant women according to adherence to Mediterranean diet

RE reports grants from the Fundación Dieta Mediterránea (Spain), and Cerveza y Salud (Spain), and personal fees for given lectures from Brewers of Europe (Belgium), the Fundación Cerveza y Salud (Spain), Pernaud-Ricard (Mexico), Instituto Cervantes (Alburquerque, United States), Instituto Cervantes (Milan, Italy), Instituto Cervantes (Tokyo, Japan), Lilly Laboratories (Spain), and the Wine and Culinary International Forum (Spain), as well as nonfinancial support for the organization of a National Congress on Nutrition and feeding trials with products from Grand Fountain and Uriach Laboratories (Spain). EG reports, during the conduct of the study, grants from La Caixa Foundation, grants from Cerebra Foundation for the Brain Injured Child, and grants from AGAUR. AN reports personal fees from La Caixa Foundation (Doctoral INPhINIT - RETAINING, fellowship LCF/BQ/DR19/11740018), during the conduct of the study.We thank the study participants for their personal time and commitment to this trial. We also thank all the medical staff, residents, midwives and nurses of BCNatal, especially Laura Segales, Marta Dacal, Maria Laura Boutet, Annachiara Basso, Marta Camacho, Marta Garcia, Mireia Pascual, and Alba Camacho from BCNatal Fetal Medicine Research Center, Barcelona, Spain, for their support in the recruitment, interventions and data collection of the trial; Carlos Galante from the Department of Internal Medicine, Hospital Clinic, Barcelona, Spain, for his support in the Mediterranean diet intervention; and Julian Lozano-Castellon, Anallely Lopez-Yerena, Ines Dominguez-Lopez, and Maria Marhuenda-Munoz from School of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain for their support in the biomarkers analysis of Mediterranean diet compliance. Finally, we thank the Clinic-IDIBAPS Biobank for valuable management of samples.The project was partially funded by: a grant from "la Caixa" Foundation (LCF/PR/GN18/10310003); Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); and AGAUR under grant 2017 SGR no. 1531. SC-B has received support from Universitat de Barcelona (Margarita Salas postdoctoral fellowship). ML has received support from Hospital Clínic i Provincial de Barcelona (Contractes Clínic de Recerca Emili Letang-Josep Font 2020). INSA-Ma María de Maeztu Unit of Excellence (grant CEX2021-001234-M funded by MICIN/AEI/FEDER, UE). RE has received support from the Instituto de Salud Carlos III (AC19/00100), as part of the FoodPhyt project, under the umbrella of the European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL) (2019-02201). FrC was supported by a research grant from the Instituto de Salud Carlos III (PI22/00684). AN has received support from a fellowship from "la Caixa" Foundation, Doctoral INPhINIT - RETAINING (LCF/BQ/DR19/11740018). CP was supported by a research grant from the Instituto de Salud Carlos III (JR19/00006). FáC has received support from Fundació Jesus Serra, Instituto de Salud Carlos III (Instituto de Salud Carlos III (INT21/00027), and Fundació Mutua Madrileña (Spain).Background and aims: The dietary pattern followed during pregnancy, specifically healthy dietary patterns such as the Mediterranean diet, is a key factor in the mother's and the offspring's health. Pregnant women dietary intake is not enough to cover the micronutrient requirements of pregnancy, and higher adherence to the Mediterranean diet may improve dietary quality and nutritional density. The aim of the present study was to describe the dietary nutrient intake and diet quality during pregnancy and to evaluate whether a high adherence to Mediterranean diet was associated with a more adequate intake of micronutrients. Methods: This was a cross-sectional study with 1,356 pregnant women selected during the routine second trimester ultrasound scan (19-23 weeks' gestation). Energy and nutrient intake were calculated using a validated 151-item semi-quantitative food frequency questionnaire and nutrient density was estimated dividing the absolute nutrient intake by total energy intake. Adherence to the Mediterranean diet was evaluated with a 17-item Mediterranean diet adherence score. The criterion used for risk of inadequate nutrient intake has been set below two thirds (2/3) of the dietary reference intakes. The differences were assessed by multivariate linear regression models adjusted for confounders. Results: A significant proportion of pregnant women had an inadequate intake of macro and micronutrient that was lower in those with high adherence to the Mediterranean diet (≥12 points, n = 122, 19%), including calcium (the Mediterranean diet high adherence 2.5% vs. low adherence 26.7%, p < 0.001), magnesium (0% vs. 7.6%, p = 0.001), iron (24.5% vs. 74.1%, p < 0.001), and vitamin B9 (0% vs. 29.8%, p < 0.001), vitamin C (0% vs. 1.9%, p = 0.033), and vitamin D (61.5% vs. 92.8%, p < 0.001) intake. High adherence to Mediterranean diet was associated with higher intake of protein, monounsaturated fatty acids, fiber, vitamins (B1, B9, C, D), calcium, magnesium, iron, zinc, phosphor, potassium, essential fatty acids, and α-linolenic acid, and with a lower intake of α-linoleic acid and trans fatty acids as compared to low adherence to Mediterranean diet. Conclusion: High adherence to Mediterranean diet was associated with higher diet quality and lower proportion of inadequate micro and macronutrient intake. The Mediterranean diet promotion, particularly among pregnant women, may be a useful and public health strategy to avoid overweight and nutrient deficiencies

Maternal Stress, Anxiety, Well-Being, and Sleep Quality in Pregnant Women throughout Gestation

This study was partially funded by the "LaCaixa" Foundation under grant agreements LCF/PR/GN14/10270005 and LCF/PR/GN18/10310003, the CEREBRA Foundation for the Brain Injured Child (Carmarthen, Wales, UK) and the Departament de Recerca i Universitats de la Generalitat de Catalunya 2021-SGR-01422. LB and FC have received funding from the Instituto de Salud Carlos III (ISCIII) through the projects CM21/00058 and INT21/00027 which are co-funded by the European Union. Funders played no role in the study's design, data collection, data analysis, data interpretation, or the writing of the manuscript.Background: Maternal stress, anxiety, well-being, and sleep quality during pregnancy have been described as influencing factors during pregnancy. Aim: We aimed to describe maternal stress, anxiety, well-being, and sleep quality in pregnant women throughout gestation and their related factors. Methods: A prospective study including pregnant women attending BCNatal, in Barcelona, Spain (n = 630). Maternal stress and anxiety were assessed by the Perceived Stress Scale (PSS) and State-Trait Anxiety Inventory (STAI)-validated questionnaires. Maternal well-being was assessed using the World Health Organization Well-Being Index Questionnaire (WHO-5), and sleep quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). All questionnaires were obtained twice during the second and third trimester of pregnancy. A multivariate analysis was conducted to assess factors related to higher maternal stress and anxiety and worse well-being and sleep quality. Results: High levels of maternal stress were reported in 23.1% of participants at the end of pregnancy, with maternal age <40 years (OR 2.02; 95% CI 1.08-3.81, p = 0.03), non-white ethnicity (OR 2.09; 95% CI 1.19-4.02, p = 0.01), and non-university studies (OR 1.86; 95% CI 1.08-3.19, p = 0.02) being the parameters mostly associated with it. A total of 20.7% of women had high levels of anxiety in the third trimester and the presence of psychiatric disorders (OR 3.62; 95% CI 1.34-9.78, p = 0.01) and non-university studies (OR 1.70; 95% CI 1.11-2.59, p = 0.01) provided a significant contribution to high anxiety at multivariate analysis. Poor maternal well-being was observed in 26.5% of women and a significant contribution was provided by the presence of psychiatric disorders (OR 2.96; 95% CI 1.07-8.25, p = 0.04) and non-university studies (OR 1.74; 95% CI 1.10-2.74, p = 0.02). Finally, less sleep quality was observed at the end of pregnancy (p < 0.001), with 81.1% of women reporting poor sleep quality. Conclusion: Maternal stress and anxiety, compromised maternal well-being, and sleep quality disturbances are prevalent throughout pregnancy. Anxiety and compromised sleep quality may increase over gestation. The screening of these conditions at different stages of pregnancy and awareness of the associated risk factors can help to identify women at potential risk

Fetal neurosonography and infant neurobehavior in assisted reproductive technologies following fresh and frozen embryo transfer

Objective: We aimed to explore fetal cortical brain development by neurosonography in fetuses conceived by assisted reproductive technology (ART), including frozen and fresh embryo transfer (ET), compared with those conceived spontaneously (SC), and to investigate its association with infant neurobehavior at 12 months of age. Methods: This was a prospective cohort study of 210 singleton pregnancies, including 70 SC pregnancies, 70 conceived by in-vitro fertilization (IVF) following frozen ET and 70 conceived by IVF after fresh ET. Fetal neurosonography was performed at 32 ± 2 gestational weeks to assess cortical development. Sulci depths were measured offline and normalized by biparietal diameter (BPD). Ages and Stages Questionnaires (ASQ) were completed postnatally, at 12 ± 1 months of corrected age. Neurosonographic findings were adjusted by regression analysis for maternal age, ethnicity, parity, fetal sex and fetal-weight centile and gestational age at scan, and ASQ scores were adjusted for maternal age, ethnicity, parity, educational level and employment status, gestational age at birth, breastfeeding, infant sex and infant age at the ASQ evaluation. Results: Overall, in comparison to the SC fetuses, fetuses conceived by ART showed statistically significant differences in cortical development, with reduced parieto-occipital sulci depth adjusted for BPD (mean ± SD: fresh ET, 12.5 ± 2.5 vs frozen ET, 13.4 ± 2.6 vs SC, 13.4 ± 2.6, P < 0.001), cingulate sulci depth adjusted for BPD (median (interquartile range (IQR)): fresh ET, 5.8 (4.2-7.4) vs frozen ET, 5.8 (4.1-7.5) vs SC, 6.5 (4.8-7.8), P = 0.001) and calcarine sulci depth adjusted for BPD (median (IQR): fresh ET, 13.5 (10.1-16.1) vs frozen ET, 14.5 (12.1-15.8) vs SC, 16.4 (14.3-17.9), P < 0.001), together with lower Sylvian fissure grading score. Changes in cortical development were more pronounced in the fresh ET than in the frozen ET group. ART infants showed lower ASQ scores as compared to SC infants, particularly in the fresh ET group (mean ± SD global ASQ Z-score: fresh ET, -0.3 ± 0.4 vs frozen ET, -0.2 ± 0.4 vs SC, 0 ± 0.4, P < 0.001). Conclusions: Fetuses conceived by ART show a distinctive pattern of cortical development and suboptimal infant neurodevelopment, with more pronounced changes in those conceived following fresh ET. These findings support the existence of in-utero brain reorganization associated with ART and warrant follow-up studies to assess its long-term persistence. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology