Infant colic and HPA axis development across childhood.

This study examines the long-term impact of infant colic on Hypothalamic-Pituitary-Adrenal (HPA) axis development and the moderating role of attachment security, in a low-risk Dutch sample of 193 children. We assessed infant colic at 6 weeks, circadian cortisol concentrations at ages 1, 2.5, 6, and 10 years, and attachment security at 1 year. Findings indicated that infant colic was associated with steeper diurnal cortisol slopes and slightly higher cortisol concentrations throughout childhood. Attachment security did not moderate these associations. This is the first study to reveal a link between infant colic and the development of the HPA axis in healthy children beyond infancy. These findings have important implications for understanding early risk and protective factors in the stress system's development.

Implications of childhood adversity for women's perinatal sleep quality and depressive symptoms over time: A serial mediation model.

This study sought to examine the effects of childhood adversity on the longitudinal associations between perinatal sleep quality and depressive symptoms, and to determine the prospective associations between these constructs over time. A cross-lagged autoregressive model was used to examine the longitudinal association between sleep quality and depressive symptoms at four points during the perinatal period: 18 and 32 weeks of pregnancy, and 6 and 12 weeks postpartum. Longitudinal mediation models were used to examine whether sleep quality or depressive symptoms mediated the effects of childhood adversity on these symptoms. Most participants (86%) reported poor sleep quality during pregnancy. Significant cross-lagged effects of depressive symptoms on subsequent sleep quality were observed during pregnancy and postpartum. Depressive symptoms significantly mediated the effects of childhood trauma on sleep quality during pregnancy, but sleep quality did not significantly mediate the effects of childhood trauma on depressive symptoms. While sleep quality and depressive symptoms tend to co-occur, our analyses indicate that perinatal depressive symptoms work as the primary driver of sleep quality over time. Childhood adversity may have long-reaching effects in women as it was associated with more depressive symptoms in the perinatal period, which in turn appeared to undermine sleep quality.

Methodological recommendations for human microbiota-gut-brain axis research.

Observational studies have determined numerous correlations between sequence-based gut microbiota data and human mental traits. However, these associations are often inconsistent across studies. This inconsistency is one of the reasons that mechanistic validation studies of the observed correlations are lagging, making it difficult to establish causal associations. The absence of consistent study findings may partially be due to the lack of clear guidelines for identifying confounders of relations between complex microbial communities and mental conditions. Gut microbial complexity also impedes deciphering microbiota-host relations by using a single analytical approach. The aim of the current review is to help solve these problems by providing methodological recommendations for future human microbiota-gut-brain axis research on the selection of confounders, the use of integrative biostatistical methods, and the steps needed to translate correlative findings into causal conclusions.

Daily skin-to-skin contact alters microbiota development in healthy full-term infants.

The gut microbiota is vital for human body development and function. Its development in early life is influenced by various environmental factors. In this randomized controlled trial, the gut microbiota was obtained as a secondary outcome measure in a study on the effects of one hour of daily skin-to-skin contact (SSC) for five weeks in healthy full-term infants. Specifically, we studied the effects on alpha/beta diversity, volatility, microbiota maturation, and bacterial and gut-brain-axis-related functional abundances in microbiota assessed thrice in the first year. Pregnant Dutch women (n = 116) were randomly assigned to the SSC or care-as-usual groups. The SSC group participants engaged in one hour of daily SSC from birth to five weeks of age. Stool samples were collected at two, five, and 52 weeks and the V4 region was sequenced. We observed significant differences in the microbiota composition, bacterial abundances, and predicted functional pathways between the groups. The SSC group exhibited lower microbiota volatility during early infancy. Microbiota maturation was slower in the SSC group during the first year and our results suggested that breastfeeding duration may have partially mediated this relation. Our findings provide evidence that postpartum SSC may influence microbiota development. Replication is necessary to validate and generalize these results. Future studies should include direct stress measurements and extend microbiota sampling beyond the first year to investigate stress as a mechanism and research SSC's impact on long-term microbiota maturation trajectories.

Development of the gut microbiota in the first 14 years of life and its relations to internalizing and externalizing difficulties and social anxiety during puberty.

Relations between the gut microbiota and host mental health have been suggested by a growing number of case-control and cross-sectional studies, while supporting evidence is limited in large community samples followed during an extended period. Therefore, the current preregistered study ( https://osf.io/8ymav , September 7, 2022) described child gut microbiota development in the first 14 years of life and explored its relations to internalizing and externalizing difficulties and social anxiety in puberty, a period of high relevance for the development of mental health problems. Fecal microbiota composition was analysed by 16S ribosomal RNA gene amplicon sequencing in a total of 1003 samples from 193 children. Through a clustering method, four distinct microbial clusters were newly identified in puberty. Most children within three of these clusters remained in the same clusters from the age of 12 to 14 years, suggesting stability in microbial development and transition during this period. These three clusters were compositionally similar to enterotypes (i.e., a robust classification of the gut microbiota based on its composition across different populations) enriched in Bacteroides, Prevotella, and Ruminococcus, respectively. Two Prevotella 9-predominated clusters, including one reported by us earlier in middle childhood and the other one in puberty, were associated with more externalizing behavior at age 14. One Faecalibacterium-depleted pubertal cluster was related to more social anxiety at age 14. This finding was confirmed by a negative cross-sectional relation between Faecalibacterium and social anxiety in the 14-year-olds. The findings of this study continue to map gut microbiota development in a relatively large community sample followed from birth onwards, importantly extending our knowledge to puberty. Results indicate that Prevotella 9 and Faecalibacterium may be relevant microbial taxa in relation to externalizing behavior and social anxiety, respectively. These correlational findings need validations from other similar cohort studies, as well as well-designed mechanistic pre-clinical investigations before inferring cause and effect.

Individual differences in processing speed and curiosity explain infant habituation and dishabituation performance.

Habituation and dishabituation are the most prevalent measures of infant cognitive functioning, and they have reliably been shown to predict later cognitive outcomes. Yet, the exact mechanisms underlying infant habituation and dishabituation are still unclear. To investigate them, we tested 106 8-month-old infants on a classic habituation task and a novel visual learning task. We used a hierarchical Bayesian model to identify individual differences in sustained attention, learning performance, processing speed and curiosity from the visual learning task. These factors were then related to habituation and dishabituation. We found that habituation time was related to individual differences in processing speed, while dishabituation was related to curiosity, but only for infants who did not habituate. These results offer novel insights in the mechanisms underlying habituation and serve as proof of concept for hierarchical models as an effective tool to measure individual differences in infant cognitive functioning. RESEARCH HIGHLIGHTS: We used a hierarchical Bayesian model to measure individual differences in infants' processing speed, learning performance, sustained attention, and curiosity. Faster processing speed was related to shorter habituation time. High curiosity was related to stronger dishabituation responses, but only for infants who did not habituate.

Prenatal anticipatory stress: Baby preparation and worry scale-revised in the Dutch context.

BACKGROUND: Prenatal distress encompasses a range of different emotions, worries, and experiences of stress. The Baby Preparation and Worry Scale (Baby-PAWS) was recently developed to target anticipatory worries during pregnancy about the postnatal period. However, the Baby-PAWS questionnaire was only examined in the United States of America, limiting the questionnaire's generalizability to different countries. To address this issue, we performed a psychometric evaluation of the questionnaire in a Dutch sample and examined associations between the Baby-PAWS questionnaire and established measures of maternal distress (i.e., EPDS, STAI, PRAQ-R) and infant temperament (i.e., IBQ-R). METHODS: Healthy pregnant women (N = 521) completed questionnaires during their third trimester and postnatally, including the Baby-PAWS and distress measures. A subsample of mothers (N = 194) also reported on infant temperament at 12 weeks postpartum. RESULTS: Exploratory factor analysis suggested a four-factor structure for the 16-item questionnaire in our Dutch sample, as compared to the expected three-factor structure found in the original psychometric evaluation with the American sample. The total Baby-PAWS score was related to pre-and postnatal depression, anxiety, stress, and specific scales of infant temperament. American women scored higher on the Baby-PAWS items than Dutch women. LIMITATIONS: Our participants had higher-than-average socioeconomic status, limiting the generalizability of the findings. CONCLUSION: The current analyses indicate good validity of the Baby-PAWS in a Dutch sample. Furthermore, our results highlight cross-cultural differences in perinatal mental health and show the importance of examining instrument structure of context-dependent constructs, such as prenatal worries.

Gut microbiota and child behavior in early puberty: does child sex play a role?

A growing number of studies have indicated relations between the gut microbiota and mental health. However, to date, there is a scarcity of microbiota studies in community samples in early puberty. The current preregistered study (https://osf.io/wu2vt) investigated gut microbiota composition in relation to sex in low-risk children and explored behavioral associations with gut microbiota composition and metabolites in the same samples, together with the potential role of sex. Fecal microbiota composition was analyzed in 12-year-old children (N = 137) by 16S rRNA gene sequencing and quantitative PCR. Modest sex differences were observed in beta diversity. Generalized linear models showed consistent behavioral relations to both relative and absolute abundances of individual taxa, including positive associations between Parasutterella and mother-reported internalizing behavior, and negative associations between Odoribacter and mother-reported externalizing behavior. Additionally, Prevotella 9 was positively related to mother-reported externalizing behavior, confirming earlier findings on the same cohort at 5 years of age. Sex-related differences were found in behavioral relations to Ruminiclostridium 5, Alistipes, Streptococcus, Ruminiclostridium 9, Ruminococcaceae UCG-5, and Dialister, for relative abundances, as well as to Family XIII AD3011 group and an unidentified bacterium within the Tenericutes, for absolute abundances. Limited behavioral relations were observed regarding alpha diversity and fecal metabolites. Our findings describe links between the gut microbiota and child behavior, together with differences between child sexes in these relations, in low-risk early pubertal children. Importantly, this study confirmed earlier findings in this cohort of positive relations between Prevotella 9 and externalizing behavior at age 10 years. Results also show the merit of including absolute abundances in microbiota studies.

Adolescents' hair cortisol concentrations during COVID-19: Evidence from two longitudinal studies in the Netherlands and the United States.

BACKGROUND: Prolonged stress exposure is associated with alterations in cortisol output. The COVID-19 pandemic represented a stressor for many, including children. However, a high-quality caregiving environment may protect against psychological problems and possibly against elevations in cortisol. We examined adolescents' physiological stress responses to the pandemic and the role of attachment in two longitudinal samples from the Netherlands and the United States (https://aspredicted.org/HHY_8MK). METHODS: Cortisol was assessed from hair samples before and during the pandemic, while attachment was self-reported prepandemic. Study 1 included a Dutch sample (N = 158; examined at ages 10 and later at 14 years old), whereas Study 2 included a US sample (N = 153; examined at ages 9-11 and again 2 years later) and an age-matched prepandemic sample (N = 29, 10-13 years old). Repeated-measures analyses of variance examined changes in cortisol from prepandemic to during the pandemic and the effect of attachment in each sample separately. RESULTS: After accounting for age, both studies revealed nonsignificant changes in hair cortisol and a nonsignificant effect of attachment. A significant effect of sex emerged in Study 1, with Dutch girls showing a significant cortisol increase during the pandemic, which was not explained by puberty. CONCLUSION: These findings suggest differential associations of the pandemic with hair cortisol increases by sex and country.

A longitudinal study of the gut microbiota during the first three years of life: Links with problem behavior and executive functions at preschool age.

Early life is a sensitive period when microbiota-gut-brain interactions may have important impact on development. This study investigated the associations of the gut microbiota in the first three years of life (two, six, and 12 weeks, and one and three years) with problem behavior and executive functions in N = 64 three-year-old children. Higher relative abundance of Streptococcus at the age of two weeks, as well as its trajectory over time (including ages two, six and 12 weeks, and one and three years), was related to worse executive functions. Higher relative abundance of [Ruminococcus] torques group at the age of three years, as well as its trajectory from one to three years, was associated with less internalizing behavior. Besides, several robust age-specific associations were identified: higher Bifidobacterium relative abundance (age three years) was associated with more internalizing and externalizing issues; higher Blautia relative abundance (age three years) was linked to less internalizing behavior; and increased relative abundance of an unidentified Enterobacteriaceae genus (age two weeks) was related to more externalizing behavior. Our findings provide important longitudinal evidence that early-life gut microbiota may be linked to behavioral and cognitive development in low-risk children.

Determinants of maternal breast milk cortisol increase: Examining dispositional and situational factors.

BACKGROUND: Breast milk is a rich nutritional source, containing numerous proteins, carbohydrates, and hormones that impact long-term offspring development. Strikingly, predictors and correlates of breast milk composition remain largely unknown. Building on a previously discovered increase in breast milk cortisol concentration from 2 to 12 weeks postpartum, we investigated potential predictors of maternal breast milk cortisol in the first three months post-delivery by examining a suite of maternal dispositional (e.g., attachment, adverse childhood experiences or ACEs) and situational factors (e.g., partner support, self-efficacy). METHODS: Data from 73 mothers were collected prenatally, at birth, and 2-, 6- and 12 weeks postpartum. The analyses, which sought to predict postnatal changes in breast milk cortisol, included a pool of theoretically-sound constructs (Table 1) and an exploratory data-driven approach. We fit models differing in complexity as preregistered: 1) Random Forest models, capable of modeling interactions and non-linear relationships, and 2) Bayesian linear models, allowing to model change over time while less prone to overfitting. RESULTS: Overall, we found that no single variable had strong predictive value beyond the known predictors of cortisol, such as time since awakening and time of collection. However, results from both models suggest that ACEs carry information that warrants future investigations, pointing towards a negative relationship with cortisol concentration in breast milk, albeit with a minimal effect size. CONCLUSION: Using sophisticated models, we found that early life stress may play a role in physiological stress markers in breast milk in the first three months postpartum, with potential implications for offspring development.

Are adolescent diet quality and emotional eating predicted by history of maternal caregiving quality and concurrent inhibitory control?

The risk for unhealthy eating behaviour, including poor diet quality and emotional eating, is heightened in adolescence and could result in profound and long-lasting psychological and physical implications. Caregiving quality and adolescents' regulatory skills, such as inhibitory control, may play an essential role in the development of adolescent eating behaviour. This preregistered study investigated whether maternal caregiving throughout the first 14 years of life predicts adolescent diet quality and emotional eating and whether potential associations are mediated by adolescents' inhibitory control. In this low-risk community cohort, maternal caregiving quality was observed at child ages five weeks, 12 months, 2.5, 10, and 14 years. At age 14, diet quality and emotional eating were assessed through self-report. Adolescent inhibitory control was assessed with three behavioural tasks and a maternal report. Mediation analyses were performed with structural equation modelling in R. No evidence was found for links between maternal caregiving quality and adolescent diet quality and emotional eating. Higher levels of adolescent inhibitory control predicted better adolescent diet quality. Longitudinal and experimental studies are needed to investigate directionality, and replication studies are needed in more representative samples (e.g. including high-risk families). Such studies will shed further light on potential links between the history of caregiving behaviour and adolescent regulatory and eating behaviour.

The effects and process of the intervention "Individual Shantala Infant Massage" in preventive child healthcare to improve parent-child interaction: study protocol for a quasi-experimental study.

BACKGROUND: Individual Shantala Infant Massage is an intervention that is offered by several Dutch Preventive Child Healthcare (PCH) organizations as optional preventive support, in addition to basic care as offered to all children. It targets vulnerable families and aims to enhance sensitive parenting and to reduce (effects of) parental stress. The intervention is carried out by a certified nurse. It consists of three structured home visits. Parents learn to massage their infant and receive parenting support. This study aims to investigate the effectiveness and the process of the intervention. The main hypothesis is that Individual Shantala Infant Massage leads to increased parental sensitive responsiveness, lower perceived and physiological parental stress, and improved child growth and development in the intervention group, compared to a control group where this intervention is not offered by PCH. Secondary research questions address effects on parenting confidence and parental concerns regarding the infant, the influence of background characteristics and the intervention process. METHODS: The study is a quasi-experimental non-randomized trial. The aim is to include 150 infant-parent dyads in both the intervention and the control group. This takes into account possible attrition and missing data as 105 dyads with complete data per group are sufficient for analysis. All participants complete questionnaires at T0 (pre-test, child age between six-sixteen weeks), T1 (post-intervention, or ± four weeks after T0), and T2 (follow-up at five months). At T2, a hair tuft is cut from the parents' head to measure hair cortisol levels. Data on infant growth and development is obtained from PCH files. In the intervention group, additional data is collected to evaluate the intervention process: parents complete an evaluation questionnaire at T1, nurses keep semi-structured logbooks of intervention sessions and interviews are conducted with parents and professionals. DISCUSSION: Study results can contribute to the evidence base of infant massage as applied in Dutch PCH, and can inform parents, PCH practitioners, policy makers and researchers both inside and outside the Netherlands on feasibility and effectiveness of the infant massage intervention as applied in this format and setting. TRIAL REGISTRATION: ISRCTN registry: ISRCTN16929184. Date (retrospectively) registered: 29/03/2022.

Breastfeeding and room-sharing during COVID-19 in the Netherlands: The impact of perinatal healthcare support.

AIM: The recommendations of 6 months of exclusive breastfeeding (EBF) and parent-infant room-sharing (RS) are often not followed. As these early caregiving practices may have been affected by the COVID-19-related restrictions, we documented BF and RS practices in the Netherlands (2020-2021) and the effects of perceived perinatal healthcare support. METHODS: Pregnant women and mothers of an infant younger than 6 months (N = 784) completed online questionnaires (e.g., demographic information, the impact of COVID-19 on their lives aspects, infant childcare practices) twice: at the beginning of the pandemic and when the infant reached 6 months of age. RESULTS: The pandemic EBF practices mirrored pre-pandemic Dutch reports (17.8 %; Mduration = 3.4 months), while RS rates and duration seemingly doubled (30.6 %; Mduration = 3.98 months). Higher maternal education (r = 0.18) and multiparity (r = 0.08) were significantly associated with longer EBF, and similarly for education (r = 0.17) and multiparity (r = 0.11) with RS durations. Higher perceived perinatal healthcare support predicted shorter RS duration [ß = -0.509, t(5,596) = -2.27, p = .023]. CONCLUSION: While the COVID-19 pandemic did not impact EBF, it may have promoted RS. The negative association between perinatal healthcare support and RS may suggest that parents who need more support from their providers also experience more challenges adhering to RS recommendations, yet this hypothesis remains to be corroborated.

Maternal sensitivity and child internalizing and externalizing behavior: a mediating role for glucocorticoid receptor gene (NR3C1) methylation?

The early caregiving environment can have lasting effects on child mental health. Animal models suggest that glucocorticoid receptor gene (NR3C1) DNA methylation plays a mediating role in linking more responsive caregiving to improved behavioral outcomes by its impact on the stress regulatory system. In this longitudinal study, we examined whether children's NR3C1 methylation levels mediate an effect of maternal sensitivity in infancy on levels of child internalizing and externalizing behavior in a community sample. Maternal sensitivity of 145 mothers was rated at infant age 5 weeks, 12 months, and 30 months by observing mother-infant interactions. Buccal DNA methylation was assessed in the same children at age 6 years and maternal-reported internalizing and externalizing behavior was assessed at age 6 and 10 years. Higher sensitivity at age 5 weeks significantly predicted lower DNA methylation levels at two NR3C1 CpG loci, although methylation levels at these loci did not mediate an effect of maternal sensitivity on levels of child internalizing and externalizing behavior. Overall, the study provides evidence that maternal sensitivity in early infancy is associated with DNA methylation levels at loci involved in stress regulation, but the significance of this finding for child mental health remains unclear.

Fucosylated Human Milk Oligosaccharides during the First 12 Postnatal Weeks Are Associated with Better Executive Functions in Toddlers.

Human milk oligosaccharides (HMOs) are one of the most abundant solid components in a mother's milk. Animal studies have confirmed a link between early life exposure to HMOs and better cognitive outcomes in the offspring. Human studies on HMOs and associations with later child cognition are scarce. In this preregistered longitudinal study, we investigated whether human milk 2'-fucosyllactose, 3'-sialyllactose, 6'-sialyllactose, grouped fucosylated HMOs, and grouped sialylated HMOs, assessed during the first twelve postnatal weeks, are associated with better child executive functions at age three years. At infant age two, six, and twelve weeks, a sample of human milk was collected by mothers who were exclusively (n = 45) or partially breastfeeding (n = 18). HMO composition was analysed by use of porous graphitized carbon-ultra high-performance liquid chromatography-mass spectrometry. Executive functions were assessed at age three years with two executive function questionnaires independently filled in by mothers and their partners, and four behavioural tasks. Multiple regression analyses were performed in R. Results indicated that concentrations of 2'-fucosyllactose and grouped fucosylated HMOs were associated with better executive functions, while concentrations of grouped sialylated HMOs were associated with worse executive functions at age three years. Future studies on HMOs that sample frequently during the first months of life and experimental HMO administration studies in exclusively formula-fed infants can further reveal associations with child cognitive development and uncover potential causality and sensitive periods.

Commentary: Natural disaster studies on prenatal stress - moving forward - a commentary/reflection on Nomura et al. (2023).

This commentary is based on the premise that the goal of scientific publications is to advance knowledge and inspire scientific discussion. First, the Nomura et al. paper is briefly summarized and shortly discussed to illustrate some of the challenges faced in this field, and suggestions for improvement are made. Then, the reader is invited to take a step back and reflect on how to continue investigating the effects of natural disasters on pregnant women and their children in the best possible manner. Additional suggestions are made for much-needed research on other types of severe maternal prenatal stress and on high-quality interventions for natural disasters. The goal is to stimulate reflection and exchange so that future choices made by researchers, funding bodies, and policymakers lead to substantial advances in the field of prenatal stress.

Maternal anxiety forecasts shorter prolongation of pregnancies complicated by early-onset preeclampsia.

PURPOSE: In early-onset preeclampsia, each additional day of pregnancy prolongation reduces offspring infant mortality about 9%. We evaluated if maternal stress at admission to hospital for early-onset preeclampsia predicted admission-to-delivery intervals in days. METHODS: This prospective, longitudinal cohort-study involved 15 singleton pregnancies with a diagnosis of preeclampsia before 34 weeks gestation with intended expectant management. Upon hospital admission, maternal psychological stress was assessed with questionnaires and physiological stress with hair cortisol. Hair samples were analyzed in three hair segments representing the preconception period, and the first and second trimester of pregnancy. RESULTS: Mean pregnancy prolongation was 16.2 days. Higher maternal anxiety at hospital admission significantly correlated with shorter admission-to-delivery intervals (r = - 0.54, p = 0.04). Chronically increased hair cortisol concentrations (i.e. from preconception through the second trimester) of pregnancy tended to be related to shorter admission-to-delivery intervals (p <. 10). CONCLUSION: Higher reported anxiety is, and chronically high hair cortisol tended to be, related with fewer days of prolongation from admission to delivery in women with early-onset preeclampsia. These findings suggest that maternal stress might be a potential determinant of disease progression. Future research into early innovative stress-reducing interventions for early-onset preeclampsia may shed more light on the etiology and treatment of this disease.

Cumulative risk exposure and child cellular aging in a Dutch low-risk community sample.

One of the proposed mechanisms linking childhood stressor exposure to negative mental and physical health outcomes in later life is cellular aging. In this prospective, longitudinal, and pre-registered study, we examined the association between a cumulative pattern of childhood risk exposure from age 6 to age 10 (i.e., poor maternal mental health, parental relationship problems, family/friend death, bullying victimization, poor quality friendships) and change in two biomarkers of cellular aging (i.e., telomere length, epigenetic age) from age 6 to age 10 in a Dutch low-risk community sample (n = 193). We further examined the moderating effect of cortisol reactivity at age 6. Ordinary Least Squares regression analyses revealed no significant main effects of childhood risk exposure on change in cellular aging, nor a moderation effect of child cortisol reactivity. Secondary findings showed a positive correlation between telomere length and cortisol reactivity at age 6, warranting further investigation. More research in similar communities is needed before drawing strong conclusions based on the null results.