Maternal anxiety-driven modulation of fetal limbic connectivity designs a backbone linking neonatal brain functional topology to socio-emotional development in early childhood.

A link between maternal anxiety during pregnancy and adverse socio-emotional outcomes in childhood has been consistently sustained on the very early neurodevelopmental alteration of structural pathways between fetal limbic and cortical brain regions. In this study, we provide follow-up evidence for a feed-forward model linking (i) maternal anxiety, (ii) fetal functional neurodevelopment, (iii) neonatal functional network organization with (iv) socio-emotional neurobehavioral development in early childhood. Namely, we investigate a sample of 16 mother-fetus dyads and show how a maternal state-trait anxiety profile with pregnancy-specific worries can significantly influence functional synchronization patterns between regions of the fetal limbic system (i.e., hippocampus and amygdala) and the neocortex, as assessed through resting-state functional magnetic resonance imaging. Generalization of the findings was supported by leave-one-out cross-validation. We further show how this maternal-fetal cross-talk propagates to functional network topology in the neonate, specifically targeting connector hubs, and further maps onto socio-emotional profiles, assessed through Bayley-III socio-emotional scale in early childhood (i.e., in the 12-24 months range). Based on this evidence, we put forward the hypothesis of a "Maternal-Fetal-Neonatal Anxiety Backbone", through which neurobiological changes driven by maternal anxiety could trigger a divergence in the establishment of a cognitive-emotional development blueprint, in terms of the nascent functional homeostasis between bottom-up limbic and top-down higher-order neuronal circuitry.

A hierarchical procedure to select intrauterine and extrauterine factors for methodological validation of preterm birth risk estimation.

BACKGROUND: Etiopathogenesis of preterm birth (PTB) is multifactorial, with a universe of risk factors interplaying between the mother and the environment. It is of utmost importance to identify the most informative factors in order to estimate the degree of PTB risk and trace an individualized profile. The aims of the present study were: 1) to identify all acknowledged risk factors for PTB and to select the most informative ones for defining an accurate model of risk prediction; 2) to verify predictive accuracy of the model and 3) to identify group profiles according to the degree of PTB risk based on the most informative factors. METHODS: The Maternal Frailty Inventory (MaFra) was created based on a systematic review of the literature including 174 identified intrauterine (IU) and extrauterine (EU) factors. A sample of 111 pregnant women previously categorized in low or high risk for PTB below 37 weeks, according to ACOG guidelines, underwent the MaFra Inventory. First, univariate logistic regression enabled p-value ordering and the Akaike Information Criterion (AIC) selected the model including the most informative MaFra factors. Second, random forest classifier verified the overall predictive accuracy of the model. Third, fuzzy c-means clustering assigned group membership based on the most informative MaFra factors. RESULTS: The most informative and parsimonious model selected through AIC included Placenta Previa, Pregnancy Induced Hypertension, Antibiotics, Cervix Length, Physical Exercise, Fetal Growth, Maternal Anxiety, Preeclampsia, Antihypertensives. The random forest classifier including only the most informative IU and EU factors achieved an overall accuracy of 81.08% and an AUC of 0.8122. The cluster analysis identified three groups of typical pregnant women, profiled on the basis of the most informative IU and EU risk factors from a lower to a higher degree of PTB risk, which paralleled time of birth delivery. CONCLUSIONS: This study establishes a generalized methodology for building-up an evidence-based holistic risk assessment for PTB to be used in clinical practice. Relevant and essential factors were selected and were able to provide an accurate estimation of degree of PTB risk based on the most informative constellation of IU and EU factors.

Mindfulness-Based Interventions During Pregnancy and Long-Term Effects on Postpartum Depression and Maternal Mental Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objectives: Preventing postpartum depression (PPD) is a public health goal. The scientific literature has demonstrated the short-term efficacy of Mindfulness-Based Interventions (MBIs) delivered during pregnancy on PPD. Nevertheless, the long-term outcomes of MBIs are still unclear. Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). Four databases were searched to identify RCTs focused on describing the efficacy of MBIs on PPD and published in English up to February 2022. Settings/Location: The study was conducted globally. Subjects: Pregnant women who received MBIs. Interventions: MBIs were delivered during pregnancy in the included RCTs. Outcome Measures: Data collection and analysis effect size were combined using a random-effects model. The reporting in this study was consistent with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: Six studies were included. The overall effect size significantly reduced PPD symptoms severity in the MBI group versus the control group in the first 3 months after childbirth (standardized mean difference = -0.26; 95% confidence interval = -0.51 to -0.01; I2 = 30.65%). The effects of MBIs were significant in women who started MBIs with a low risk of developing PPD. Conclusions: MBIs delivered during pregnancy have long-term benefits for PPD. Implications for Practice: Further studies focused on testing MBIs starting during pregnancy and lasting over the postpartum and modulating the intensity of delivering MBIs based on the risk for developing PPD are needed to inform the practice with solid evidence.

Effects of flexible sacrum position at birth on maternal and neonatal outcomes: A retrospective cohort study.

OBJECTIVE: To examine the differences in both maternal and neonatal outcomes between flexible and non-flexible sacrum positions at birth. METHODS: A descriptive, cross-sectional, retrospective study was carried out on a sample of low-risk pregnant women. Univariate and multivariate logistic regressions and multivariate linear regressions were conducted to estimate the association between our discrete or continuous variables of interest. Maternal outcomes were perineal tear, maternal blood loss, second stage length; neonatal outcomes were Apgar scores and neonatal asphyxia. Results were adjusted for maternal age, neonatal birth weight, and epidural analgesia. RESULTS: We considered for final analysis 2198 women. In primiparous women, women giving birth in the all-fours position were significantly more likely to have an intact perineum (P = 0.011) and a shorter length of the second stage of labor (P = 0.022). Maternal age (P = 0.005) and neonatal weight (P = 0.013) significantly increased perineal tearing; maternal age (P = 0.004) and neonatal birth weight (P < 0.001) were significantly associated with a higher amount of blood loss. Maternal age (P = 0.002) and neonatal weight (P < 0.001) significantly increased the length of the second stage of labor. For multiparous women, the side-lying position was significantly correlated with an intact perineum (P = 0.031); maternal age and intact perineum were statistically inversely associated. Epidural analgesia significantly increased the length of the second stage of labor in both nulliparous (P < 0.001) and pluriparous women (P < 0.001). No significant differences were found in neonatal outcomes. CONCLUSION: Women with a low-risk labor should be free to choose their birth position as flexible sacrum positions are shown to increase maternal well-being and do not affect neonatal health.

RS-FetMRI: a MATLAB-SPM Based Tool for Pre-processing Fetal Resting-State fMRI Data.

Resting-state functional magnetic resonance imaging (rs-fMRI) most recently has proved to open a measureless window on functional neurodevelopment in utero. Fetal brain activation and connectivity maps can be heavily influenced by 1) fetal-specific motion effects on the time-series and 2) the accuracy of time-series spatial normalization to a standardized gestational-week (GW) specific fetal template space.Due to the absence of a standardized and generalizable image processing protocol, the objective of the present work was to implement a validated fetal rs-fMRI preprocessing pipeline (RS-FetMRI) divided into 6 inter-dependent preprocessing modules (i.e., M1 to M6) and designed to work entirely as an extension for Statistical Parametric Mapping (SPM).RS-FetMRI pipeline output analyses on rs-fMRI time-series sampled from a cohort of fetuses acquired on both 1.5 T and 3 T MRI scanning systems showed increased efficacy of estimation of the degree of movement coupled with an efficient motion censoring procedure, resulting in increased number of motion-uncorrupted volumes and temporal continuity in fetal rs-fMRI time-series data. Moreover, a "structural-free" SPM-based spatial normalization procedure granted a high degree of spatial overlap with high reproducibility and a significant improvement in whole-brain and parcellation-specific Temporal Signal-to-Noise Ratio (TSNR) mirrored by functional connectivity analysis.To our knowledge, the RS-FetMRI pipeline is the first semi-automatic and easy-to-use standardized fetal rs-fMRI preprocessing pipeline completely integrated in MATLAB-SPM able to remove entry barriers for new research groups into the field of fetal rs-fMRI, for both research or clinical purposes, and ultimately to make future fetal brain connectivity investigations more suitable for comparison and cross-validation.