Newborn brain structural characteristics and their relationships with maternal prenatal distress : Findings from the FinnBrain Birth Cohort MRI Study

Plasticity renders the brain sensitive to its intrauterine environment and susceptible to alterations during early brain development. The amygdala and hippocampus, structures key in socioemotional functions, are susceptible to these alterations. Understanding the normal variation in the newborn brain facilitates the recognition of such aberrant developmental trajectories, which may occur after exposure to maternal prenatal psychological distress (PPD) and result in a predisposition to psychopathology. This study aimed to 1) describe the normal variation of newborn brain volumetric measures in relation to newborn characteristics; 2) assess the prevalence and risk factors of incidental findings in newborn brain magnetic resonance imaging (MRI); 3) investigate how different types and timings of maternal PPD associate with newborn amygdalar and hippocampal volumes, and whether this association is modified by newborn sex. Information on maternal depressive and anxiety symptoms was gathered at gestational weeks (GW) 14, 24 and 34, and pregnancy¬specific anxiety (PSA) symptoms at GW24. Newborns were imaged with MRI at two to five weeks of postnatal age (n=175). The sub studies constituted variant samples sizes from the total population. Newborn brain lobar volumes were similarly asymmetric in both sexes. Modest sex differences were observed in regional brain volumes. Newborn age predicted larger volumes of gray and white matter. The prevalence of incidental findings in brain MRI was 7.4 % and that of hemorrhages 6.9 %. Risk factors for hemorrhages were vaginal and vacuum-assisted deliveries. All the different types of PPD associated with the left newborn amygdalar volume at GW24 in a sex-specific manner. In males, PPD predicted smaller amygdalar volumes, while in females larger amygdalar volumes. Further analyses suggested a negative association between PSA and the right hippocampal volume in females. Newborn sex appears to be a significant factor moderating the relationship between PPD and newborn brain structures, suggesting sex-specific susceptibility to psychopathologies.Vastasyntyneen aivojen rakenteelliset ominaisuudet ja niiden yhteydet äidin raskaudenaikaiseen stressiin – tuloksia FinnBrain syntymäkohortin MRI-tutkimuksesta Aivojen muovautuvuus herkistää aivot kohdunsisäiselle ympäristölle ja lisää alttiutta muutoksille niiden kehityksessä. Muutoksille herkkiä rakenteita ovat mantelitumake ja aivoturso, jotka ovat tärkeitä sosioemotionaalisissa toiminnoissa. Aivorakenteiden normaalivaihtelun ymmärtäminen helpottaa poikkeavien kehityssuuntien havait¬semista, jollaisia voi kehittyä äidin raskaudenaikaiselle psykologiselle stressille (RPS) altistumisen jälkeen ja jotka voivat altistaa psykiatrisille häiriöille. Tutkimuksen tavoitteena oli 1) kuvata vastasyntyneiden aivorakenteiden tilavuuksien normaalivaihtelua suhteessa vastasyntyneen ominaisuuksiin; 2) kartoittaa vastasyntyneiden aivojen magneettikuvantamisen sattumalöydösten esiin¬tyvyys ja riskitekijät; 3) tutkia äidin RPS:n eri tyyppien ja ajoituksen yhteyttä vastasyntyneen mantelitumakkeen ja aivoturson tilavuuksiin, sekä vaikuttaako vastasyntyneen sukupuoli yhteyteen. Raskaana olevien äitien masennus-ja ahdistuneisuusoireita mitattiin raskausviikoilla (RV) 14, 24, 34 ja raskausspesifistä ahdistuneisuutta (RSA) RV:lla 24. Vastasyntyneet (n=175) kuvattiin magneetti¬kameralla kahden-viiden viikon ikäisinä syntymän jälkeen. Osatutkimuksien otoskoot koostuivat vaihtelevista osista koko tutkimuspopulaatiota. Vastasyntyneen aivolohkojen asymmetriassa ei ollut eroa sukupuolten välillä. Maltillisia sukupuolieroja havaittiin aivotilavuuksissa rajatuilla alueilla. Vasta¬syntyneen ikä ennusti suurempia harmaan ja valkean aineen tilavuuksia. Sattuma¬löydösten esiintyvyys aivokuvissa oli 7.4 % ja verenvuotojen 6.9 %. Verenvuotojen riskitekijät olivat alatie-ja imukuppisynnytykset. RPS:n eri tyypit olivat vahvimmin yhteydessä vastasyntyneiden vasemman mantelitumaketilavuuden kanssa RV:lla 24 sukupuoliriippuvaisella tavalla, mikä ilmeni pienempinä tilavuuksina poikavauvoilla ja suurempina tilavuuksina tyttövauvoilla. Lisäanalyysit viittasivat negatiiviseen yhteyteen RPS:n ja tyttöjen oikean aivotursotilavuuden välillä. Sukupuoli vaikuttaisi säätelevän RPS:n vaikutuksia vastasyntyneen aivoihin mahdollisesti lisäten alttiutta tietyllä sukupuolella toista useammin esiintyville psykiatrisille häiriöille.Vastasyntyneen aivojen rakenteelliset ominaisuudet ja niiden yhteydet äidin raskaudenaikaiseen stressiin – tuloksia FinnBrain syntymäkohortin MRI-tutkimuksesta Aivojen muovautuvuus herkistää aivot kohdunsisäiselle ympäristölle ja lisää alttiutta muutoksille niiden kehityksessä. Muutoksille herkkiä rakenteita ovat mantelitumake ja aivoturso, jotka ovat tärkeitä sosioemotionaalisissa toiminnoissa. Aivorakenteiden normaalivaihtelun ymmärtäminen helpottaa poikkeavien kehityssuuntien havait¬semista, jollaisia voi kehittyä äidin raskaudenaikaiselle psykologiselle stressille (RPS) altistumisen jälkeen ja jotka voivat altistaa psykiatrisille häiriöille. Tutkimuksen tavoitteena oli 1) kuvata vastasyntyneiden aivorakenteiden tilavuuksien normaalivaihtelua suhteessa vastasyntyneen ominaisuuksiin; 2) kartoittaa vastasyntyneiden aivojen magneettikuvantamisen sattumalöydösten esiin¬tyvyys ja riskitekijät; 3) tutkia äidin RPS:n eri tyyppien ja ajoituksen yhteyttä vastasyntyneen mantelitumakkeen ja aivoturson tilavuuksiin, sekä vaikuttaako vastasyntyneen sukupuoli yhteyteen. Raskaana olevien äitien masennus-ja ahdistuneisuusoireita mitattiin raskausviikoilla (RV) 14, 24, 34 ja raskausspesifistä ahdistuneisuutta (RSA) RV:lla 24. Vastasyntyneet (n=175) kuvattiin magneetti¬kameralla kahden-viiden viikon ikäisinä syntymän jälkeen. Osatutkimuksien otoskoot koostuivat vaihtelevista osista koko tutkimuspopulaatiota. Vastasyntyneen aivolohkojen asymmetriassa ei ollut eroa sukupuolten välillä. Maltillisia sukupuolieroja havaittiin aivotilavuuksissa rajatuilla alueilla. Vasta¬syntyneen ikä ennusti suurempia harmaan ja valkean aineen tilavuuksia. Sattuma¬löydösten esiintyvyys aivokuvissa oli 7.4 % ja verenvuotojen 6.9 %. Verenvuotojen riskitekijät olivat alatie-ja imukuppisynnytykset. RPS:n eri tyypit olivat vahvimmin yhteydessä vastasyntyneiden vasemman mantelitumaketilavuuden kanssa RV:lla 24 sukupuoliriippuvaisella tavalla, mikä ilmeni pienempinä tilavuuksina poikavauvoilla ja suurempina tilavuuksina tyttövauvoilla. Lisäanalyysit viittasivat negatiiviseen yhteyteen RPS:n ja tyttöjen oikean aivotursotilavuuden välillä. Sukupuoli vaikuttaisi säätelevän RPS:n vaikutuksia vastasyntyneen aivoihin mahdollisesti lisäten alttiutta tietyllä sukupuolella toista useammin esiintyville psykiatrisille häiriöille

Varhaisen stressin vaikutukset lasten aivojen kehitykseen

Stressi saa elimistössä aikaan monia muutoksia, jotka näkyvät muun muassa eri elinjärjestelmien aktivoitumisena stressivasteiden herätessä puolustamaan kehoa mahdollista uhkaa vastaan. Stressin vaikutukset yksilöön alkavat jo kohdussa ja jatkuvat läpi elämän. Raskauden aikaisen ja jälkeisen stressin asema tutkimusten kohteena onkin vahvistunut ja samalla on paljastunut yhteyksiä myöhemmän iän sairastavuuden lisääntymiseen. Raskausajan ja syntymän jälkeisen varhaisen stressin vaikutuksia aivojen kehitykseen tutkitaan soveltamalla erilaisia MRI-kuvantamistekniikoita, joilla saadaan tarkasti tietoa mahdollisista muutoksista aivojen harmaassa ja valkeassa aineessa. Tämän kirjallisuuskatsauksen tarkoituksena on tuoda esille kuvantamismenetelmän haasteita ja mahdollisuuksia sekä uusimpia tutkimustuloksia kriittisesti tarkasteltuina. Työssä keskitytään lähinnä löydöksiin mantelitumakkeen, aivoturson, aivokuoren ja valkean aineen radastojen alueilla. Tarkastelussa on myös mm. ainutlaatuinen äiti-lapsi-vuorovaikutus, joka näyttäisi olevan avainasemassa stressin aiheuttamille muutoksille lasten aivojen kehityksessä. Aineistona on käytetty lähinnä aiheeseen liittyviä kansainvälisissä julkaisusarjoissa julkaistuja prospektiivisista ja retrospektiivisistä eläin- ja ihmistutkimuksista laadittuja artikkeleita, jotka on haettu PubMed –viitetietokannasta. Varhaisen stressin vaikutukset lasten aivojen kehitykseen ovat oleellisia selvittää, jotta voidaan paremmin varautua stressistä mahdollisesti seuraaviin kehityksellisiin ja terveydellisiin ongelmiin. MRI-kuvaustekniikat antavat yksityiskohtaista tietoa kehittyvien aivojen rakenteesta ja soveltuvat turvallisuutensa ja nopean kehityksensä ansiosta näiden mekanismien tutkimiseen.Siirretty Doriast

Neural correlates of gentle skin stroking in early infancy

Physical expressions of affection play a foundational role in early brain development, but the neural correlates of affective touch processing in infancy remain unclear. We examined brain responses to gentle skin stroking, a type of tactile stimulus associated with affectionate touch, in young infants. Thirteen term-born infants aged 11–36 days, recruited through the FinnBrain Birth Cohort Study, were included in the study. Soft brush strokes, which activate brain regions linked to somatosensory as well as socio-affective processing in children and adults, were applied to the skin of the right leg during functional magnetic resonance imaging. We examined infant brain responses in two regions-of-interest (ROIs) known to process gentle skin stroking – the postcentral gyrus and posterior insular cortex – and found significant responses in both ROIs. These results suggest that the neonate brain is responsive to gentle skin stroking within the first weeks of age, and that regions linked to primary somatosensory as well as socio-affective processing are activated. Our findings support the notion that social touch may play an important role in early life sensory processing. Future research will elucidate the significance of these findings for human brain development.</p

Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder

Polygenic risk scores for major depressive disorder (PRS-MDD) have been identified in large genome-wide association studies, and recent findings suggest that PRS-MDD might interact with environmental risk factors to shape human limbic brain development as early as in the prenatal period. Striatal structures are crucially involved in depression; however, the association of PRS-MDD with infant striatal volumes is yet unknown. In this study, 105 Finnish mother-infant dyads (44 female, 11-54 days old) were investigated to reveal how infant PRS-MDD is associated with infant dorsal striatal volumes (caudate, putamen) and whether PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant striatal volumes. A robust sex-specific main effect of PRS-MDD on bilateral infant caudate volumes was observed. PRS-MDD were more positively associated with caudate volumes in boys compared to girls. No significant interaction effects of genotype PRS-MDD with the environmental risk factor "prenatal maternal depressive symptoms" (genotype-by-environment interaction) nor significant interaction effects of genotype with prenatal maternal depressive symptoms and sex (genotype-by-environment-by-sex interaction) were found for infant dorsal striatal volumes. Our study showed that a higher PRS-MDD irrespective of prenatal exposure to maternal depressive symptoms is associated with smaller bilateral caudate volumes, an indicator of greater susceptibility to major depressive disorder, in female compared to male infants. This sex-specific polygenic effect might lay the ground for the higher prevalence of depression in women compared to men.Peer reviewe

Maternal pre-pregnancy BMI associates with neonate local and distal functional connectivity of the left superior frontal gyrus

Maternal obesity/overweight during pregnancy has reached epidemic proportions and has been linked with adverse outcomes for the offspring, including cognitive impairment and increased risk for neuropsychiatric disorders. Prior neuroimaging investigations have reported widespread aberrant functional connectivity and white matter tract abnormalities in neonates born to obese mothers. Here we explored whether maternal pre-pregnancy adiposity is associated with alterations in local neuronal synchrony and distal connectivity in the neonate brain. 21 healthy mother-neonate dyads from uncomplicated pregnancies were included in this study (age at scanning 26.14 +/- 6.28 days, 12 male). The neonates were scanned with a 6-min resting-state functional magnetic resonance imaging (rs-fMRI) during natural sleep. Regional homogeneity (ReHo) maps were computed from obtained rs-fMRI data. Multiple regression analysis was performed to assess the association of pre-pregnancy maternal body-mass-index (BMI) and ReHo. Seed-based connectivity analysis with multiple regression was subsequently performed with seed-ROI derived from ReHo analysis. Maternal adiposity measured by pre-pregnancy BMI was positively associated with neonate ReHo values within the left superior frontal gyrus (SFG) (FWE-corrected p < 0.005). Additionally, we found both positive and negative associations (p < 0.05, FWE-corrected) for maternal pre-pregnancy BMI and seed-based connectivity between left SFG and prefrontal, amygdalae, basal ganglia and insular regions. Our results imply that maternal pre-pregnancy BMI associates with local and distal functional connectivity within the neonate left superior frontal gyrus. These findings add to the evidence that increased maternal pre-pregnancy BMI has a programming influence on the developing neonate brain functional networks

Prevalence and Risk Factors of Incidental Findings in Brain MRIs of Healthy Neonates — The FinnBrain Birth Cohort Study

Background: Birth is a traumatic event with molding forces directed to the fetal skull, which may result in intracranial hemorrhages. However, the knowledge on prevalence and risk factors of incidental brain magnetic resonance imaging (MRI) findings in infants is still inconclusive.Methods: The prevalence and nature of incidental MRI findings were assessed in a birth cohort of 175 asymptomatic infants. The role of delivery method as well as other potential risk factors for intracranial hemorrhages were evaluated. The infants underwent 3T MRI at the age of 2–5 weeks, and the neurological status of the infants with an incidental finding was evaluated by a pediatric neurologist. Information on the delivery method, duration of delivery, parity, used anesthesia, oxytocin induction, and Apgar score was gathered to evaluate their association with the prevalence of hemorrhages.Results: Incidental intracranial hemorrhages were detected in 12 infants (6.9%), all following spontaneous or assisted vaginal delivery. Vacuum-assistance was found to be a risk factor for subdural hemorrhages with an odds ratio (OR) of 4.7 (95% CI [1.18; 18.9], p = 0.032). All infants were evaluated to develop normally by their clinical status.Conclusions: Incidental intracranial hemorrhages are relatively common among infants born by vaginal delivery. They are often of little clinical significance within the first years of life and have unlikely consequences for later neurodevelopment either. Despite their benign character, investigators should be prepared to share this information with parents competently as the findings can cause parental anxiety, and especially as the popularity of MRI as a research tool is increasing.</p

Association of Cumulative Paternal Early Life Stress With White Matter Maturation in Newborns

This cohort study examines infants and parents in the FinnBrain Birth Cohort to assess the association between paternal cumulative early life stress and offspring brain development.Question Is there an association between paternal early life stress exposure and newborn offspring brain development? Findings In the FinnBrain Birth Cohort study, among 72 trios of infants and their parents, a statistically significant association was found between paternal cumulative early life stress and child brain development, which persisted after controlling for several maternal variables. Meaning These data suggest an intergenerational mode of inheritance of offspring brain development; this finding may have implications for pediatric neuropsychiatric disorders.Importance Early life stress (ELS) has been shown to affect brain development and health outcomes. Recent animal studies have linked paternal early stress exposures with next-generation outcomes. Epigenetic inheritance through the male germline has been suggested to be one of the mechanisms. Objectives To test whether paternal ELS, as measured using the Trauma and Distress Scale, is associated with neonate brain development. Design, Setting, and Participants This cohort study included data from participants from the prospective 2-generation FinnBrain Birth Cohort, which was collected from 2011 to 2015. Pregnant women and the fathers were consecutively recruited at gestational week 12 from maternity clinics in Finland. Magnetic resonance imaging data were analyzed in 2019. Participants in this study were 72 families (infant, father, mother). Exposure Paternal exposure to ELS. Main Outcomes and Measures Fractional anisotropy (FA) values in the major white-matter tracts of the newborn brain. Results A total of 72 trios (infant, mother, and father) were analyzed. At the time of delivery, the mean (SD) age was 31.0 (4.4) years for fathers and 30.3 (4.5) years for mothers. Forty-one infants (57%) were boys; mean (SD) child age at inclusion was 26.9 (7.2) days from birth and 205 (8) days from estimated conception. Increasing levels of paternal ELS were associated with higher FA values in the newborn brain in the body of the corpus callosum, right superior corona radiata, and retrolenticular parts of the internal capsule. This association persisted after controlling for maternal ELS, maternal socioeconomic status (SES), maternal body mass index, maternal depressive symptoms during pregnancy, child sex, and child age from birth and gestation corrected age when imaged. In additional region-of-interest analyses, the association between FA values and paternal Trauma and Distress Scale sum scores remained statistically significant in the earliest maturing regions of the brain, eg, the genu of the corpus callosum (in the regression models, beta = 0.00096; 95% CI, 0.00034-0.00158; P = .003) and the splenium (beta = 0.00090; 95% CI, 0.00000-0.00180; P = .049). Conclusions and Relevance This cohort study found a statistically significant association between paternal ELS and offspring brain development. This finding may have far-reaching implications in pediatrics, as it suggests the possibility of a novel route of intergenerational inheritance of ELS on next-generation brain development

Infant and Child MRI: A Review of Scanning Procedures

Magnetic resonance imaging (MRI) is a safe method to examine human brain. However, a typical MR scan is very sensitive to motion, and it requires the subject to lie still during the acquisition, which is a major challenge for pediatric scans. Consequently, in a clinical setting, sedation or general anesthesia is often used. In the research setting including healthy subjects anesthetics are not recommended for ethical reasons and potential longer-term harm. Here we review the methods used to prepare a child for an MRI scan, but also on the techniques and tools used during the scanning to enable a successful scan. Additionally, we critically evaluate how studies have reported the scanning procedure and success of scanning. We searched articles based on special subject headings from PubMed and identified 86 studies using brain MRI in healthy subjects between 0 and 6 years of age. Scan preparations expectedly depended on subject's age; infants and young children were scanned asleep after feeding and swaddling and older children were scanned awake. Comparing the efficiency of different procedures was difficult because of the heterogeneous reporting of the used methods and the success rates. Based on this review, we recommend more detailed reporting of scanning procedure to help find out which are the factors affecting the success of scanning. In the long term, this could help the research field to get high quality data, but also the clinical field to reduce the use of anesthetics. Finally, we introduce the protocol used in scanning 2 to 5-week-old infants in the FinnBrain Birth Cohort Study, and tips for calming neonates during the scans

Sex-specific associations between maternal pregnancy-specific anxiety and newborn amygdalar volumes-preliminary findings from the FinnBrain Birth Cohort Study

Previous literature links maternal pregnancy-specific anxiety (PSA) with later difficulties in child emotional and social cognition as well as memory, functions closely related to the amygdala and the hippocampus. Some evidence also suggests that PSA affects child amygdalar volumes in a sex-dependent way. However, no studies investigating the associations between PSA and newborn amygdalar and hippocampal volumes have been reported. We investigated the associations between PSA and newborn amygdalar and hippocampal volumes and whether associations are sex-specific in 122 healthy newborns (68 males/54 females) scanned at 2-5 weeks postpartum. PSA was measured at gestational week 24 with the Pregnancy-Related Anxiety Questionnaire Revised 2 (PRAQ-R2). The associations were analyzed with linear regression controlling for confounding variables. PSA was associated positively with left amygdalar volume in girls, but no significant main effect was found in the whole group or in boys. No significant main or sex-specific effect was found for hippocampal volumes. Although this was an exploratory study, the findings suggest a sexually dimorphic association of mid-pregnancy PSA with newborn amygdalar volumes

Newborn white matter microstructure moderates the association between maternal postpartum depressive symptoms and infant negative reactivity

Maternal postpartum depression is a prominent risk factor for aberrant child socioemotional development, but there is little understanding about the neural phenotypes that underlie infant sensitivity to maternal depression. We examined whether newborn white matter fractional anisotropy (FA), a measure of white matter maturity, moderates the association between maternal postpartum depressive symptoms and infant negative reactivity at 6 months. Participants were 80 mother–infant dyads participating in a prospective population-based cohort, and included families whose newborns underwent a magnetic resonance/diffusion tensor imaging scan at 2–5 weeks of age and whose mothers reported their own depressive symptoms at 3 and 6 months postpartum and infant negative emotional reactivity at 6 months. The whole-brain FA moderated the association between maternal depressive symptoms and mother-reported infant negative reactivity at 6 months after adjusting for the covariates. Maternal depressive symptoms were positively related to infant negative reactivity among infants with high or average FA in the whole brain and in corpus callosum and cingulum, but not among those with low FA. The link between maternal depressive symptoms and infant negative reactivity was moderated by newborn FA. The variation in white matter microstructure might play a role in child susceptibility to parental distress.</p