Prenatal stress is associated with child behavioral outcomes increasing susceptibility for psychiatric disorders in later life. Altered fetal brain development might partly mediate this association, as some studies suggest. With this study, we investigated the relation between prenatal stress, child’s brain structure and behavioral problems. The association between self-reported maternal pregnancy-related anxiety (PRAQ-R2 questionnaire, second and third trimester) and brain gray matter volume was probed in 27 4-year-old children (13 female). Voxel based morphometry was applied with an age-matched template in SPM for the whole-brain analyses, and amygdala volume was assessed with manual segmentation. Possible pre- and postnatal confounders, such as maternal depression and anxiety among others, were controlled for. Child behavioral problems were assessed with the Strength and Difficulties Questionnaire by maternal report. We found a significant interaction effect of pregnancy-related anxiety and child’s sex on child’s amygdala volume, i.e., higher pregnancy-related anxiety in the second trimester was related to significantly greater left relative amygdala volume in girls compared to boys. Further exploratory analyses yielded that both maternal pregnancy-related anxiety and child’s amygdala volume are related to child emotional and behavioral difficulties: While higher pregnancy-related anxiety was associated with more emotional symptoms, peer relationship problems and overall child difficulties, greater left amygdala volume was related to less of these child difficulties and might partly mediate sex-specific associations between pregnancy-related anxiety and child behavioral difficulties. Our data suggest that maternal prenatal distress leads to sexually dimorphic structural changes in the offspring’s limbic system and that these changes are also linked to behavioral difficulties. Our results provide further support for the notion that prenatal stress impacts child development.
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.
Information on normal brain structure and development facilitates the recognition of abnormal developmental trajectories and thus needs to be studied in more detail. We imaged 68 healthy infants aged 2–5 weeks with high-resolution structural MRI (magnetic resonance imaging) and investigated hemispheric asymmetry as well as the associations of various total and lobar brain volumes with infant age and sex. We found similar hemispheric asymmetry in both sexes, seen as larger volumes of the right temporal lobe, and of the left parietal and occipital lobes. The degree of asymmetry did not vary with age. Regardless of controlling for gestational age, gray and white matter had different age-related growth patterns. This is a reflection of gray matter growth being greater in the first years, while white matter growth extends into early adulthood. Sex-dependent differences were seen in gray matter as larger regional absolute volumes in males and as larger regional relative volumes in females. Our results are in line with previous studies and expand our understanding of infant brain development.
Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother–infant dyads (44 female, 11–54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.
Brain development is most rapid during the fetal period and the first years of life. This process can be affected by many in utero factors, such as chemical exposures and maternal health characteristics. The goal of this review is twofold: to review the most recent findings on the effects of these prenatal factors on the developing brain and to qualitatively assess how those factors were generally reported in studies on infants up to 2 years of age. To capture the latest findings in the field, we searched articles from PubMed 2012 onward with search terms referring to magnetic resonance imaging (MRI), brain development, and infancy. We identified 19 MRI studies focusing on the effects of prenatal environment and summarized them to highlight the recent advances in the field. We assessed population descriptions in a representative sample of 67 studies and conclude that prenatal factors that have been shown to affect brain metrics are not generally reported comprehensively. Based on our findings, we propose some improvements for population descriptions to account for plausible confounders and in time enable reliable meta‐analyses to be performed. This could help the pediatric neuroimaging field move toward more reliable identification of biomarkers for developmental outcomes and to better decipher the nuances of normal and abnormal brain development.
Highlights Assessed relation of maternal prenatal distress to amygdalae and hippocampi volumes. Newborn amygdalar volumes negatively related to maternal prenatal distress in males. No association between maternal prenatal distress and newborn hippocampal volumes. Prenatal maternal distress seems to affect newborn brain in a sex-dependent way.
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.
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