Chronotype changes after sex hormone use: A prospective cohort study in transgender users of gender-affirming hormones.

Chronotype, an individual's preferred sleep-wake timing, is influenced by sex and age. Men sometimes report a later chronotype than women and older age is associated with earlier chronotype. The sex-related changes in chronotype coincide with puberty and menopause. However, the effects of sex hormones on human chronotype remain unclear. To examine the impact of 3 months of gender-affirming hormone therapy (GAHT) on chronotype in transgender persons, this study used data from 93 participants from the prospective RESTED cohort, including 49 transmasculine (TM) participants starting testosterone and 44 transfeminine (TF) participants starting estrogens and antiandrogens. Midpoint of sleep and sleep duration were measured using the ultra-short Munich ChronoType Questionnaire (µMCTQ). After 3 months of GAHT, TM participants' midpoint of sleep increased by 24 minutes (95% CI: 3 to 45), whereas TF participants' midpoint of sleep decreased by 21 minutes (95% CI: -38 to -4). Total sleep duration did not change significantly in either group. This study provides the first prospective assessment of sex hormone use and chronotype in transgender persons, showing that GAHT can change chronotype in line with cisgender sex differences. These findings provide a basis for future studies on biological mechanisms and clinical consequences of chronotype changes.

The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

BACKGROUND/OBJECTIVES: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later. SUBJECTS/METHODS: Children (8.5 years-old) (N = 262, males = 50.4%; Chinese = 58.4%) completed a laboratory-based manipulation of social exclusion (the Cyberball task) prior to an ad-libitum snack. Heart rate variability (HRV) was measured during the inclusion and exclusion conditions and proportionate changes were calculated as a physiological measure of exclusion-related stress. Social anxiety and social-emotional assets were also measured as moderators. RESULTS: Greater stress (as measured physiologically or by self-report) did not directly, or indirectly via energy intake, predict later BMI (at 9- and 10-years). However, among children reporting higher social anxiety, greater stress as measured by proportionate changes in HRV was associated with increased energy intake (B = 532.88, SE = 226.49, t(255) = 2.35, [CI95 = 86.85,978.92]). A significant moderated mediation was also observed (index: (b = 0.01, bootSE = 0.01, [CI95 = 0.001, 0.036]), such that among children reporting higher social anxiety, greater stress from social exclusion predicted increased energy intake from a subsequent snack, which in turn predicted higher BMI 1.5 years later. CONCLUSION: This prospective study suggests that a pattern of greater snack intake in response to heightened vulnerability to the effects of ostracism may contribute to increases in child BMI scores.

Variations in Cortical Functional Gradients Relate to Dimensions of Psychopathology in Preschool Children.

OBJECTIVE: It is unclear how the functional brain hierarchy is organized in preschool-aged children, and whether alterations in the brain organization are linked to mental health in this age group. Here, we assessed whether preschool-aged children exhibit a brain organizational structure similar to that of older children, how this structure might change over time, and whether it might reflect mental health. METHOD: This study derived functional gradients using diffusion embedding from resting state functional magnetic resonance imaging data of 4.5-year-old children (N = 100, 42 male participants) and 6.0-year-old children (N = 133, 62 male participants) from the longitudinal Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. We then conducted partial least-squares correlation analyses to identify the association between the impairment ratings of different mental disorders and network gradient values. RESULTS: The main organizing axis of functional connectivity (ie, principal gradient) separated the visual and somatomotor regions (ie, unimodal) in preschool-aged children, whereas the second axis delineated the unimodal-transmodal gradient. This pattern of organization was stable from 4.5 to 6 years of age. The second gradient separating the high- and low-order networks exhibited a diverging pattern across mental health severity, differentiating dimensions related to attention-deficit/hyperactivity disorder and phobic disorders. CONCLUSION: This study characterized, for the first time, the functional brain hierarchy in preschool-aged children. A divergence in functional gradient pattern across different disease dimensions was found, highlighting how perturbations in functional brain organization can relate to the severity of different mental health disorders.

Pregnancy intention in relation to maternal and neonatal outcomes in women with versus without psychiatric diagnoses.

BACKGROUND: Studies have identified adverse maternal and neonatal outcomes for women with psychiatric disorders. Additionally, psychiatric disorders may pose an increased risk for unintended pregnancies (UPs) which in turn may also impact negatively on outcomes. The present study aims to compare the incidence of UPs in women with versus without current/past psychiatric diagnoses and investigates whether psychiatric history modifies the relation between delivery outcomes in women with and without UPs. METHODS: A retrospective cohort was compiled of women who gave birth in a large hospital in Amsterdam, the Netherlands. Women ≥18 years old with singleton pregnancies and birth registrations in the electronic patient file during January 1, 2015 to March 1, 2020 were included. Patient characteristics (including pregnancy intention and psychiatric history), maternal (gestational diabetes, mode of delivery) and neonatal outcomes (e.g., gestational age [GA], birthweight and Apgar scores) were registered by health care providers in hospital charts. Incidence of UPs was compared between women with versus without current/past psychiatric diagnoses. Maternal and neonatal outcomes were compared between women with versus without UPs with linear or logistic regression models adjusted for relevant confounders with an interaction term for UP with current/past psychiatric diagnoses. RESULTS: We included 1219 women with and 1093 women without current/past psychiatric diagnoses. Current/past psychiatric diagnoses were significantly associated with UPs after adjustment for confounders (39.0% vs. 29.6%, OR 1.56, CI 1.23-2.00, p < 0.001). In sub-analyses, women with depressive (OR 1.67, CI 1.24-2.26, p = 0.001), personality (OR 2.64, CI 1.38-5.11, p = 0.004) and substance-related and addictive disorders (OR 4.29, CI 1.90-10.03, p = 0.001) had higher odds of UPs compared to women without current/past psychiatric diagnoses. Amongst women with UPs, current/past psychiatric diagnoses did not modify maternal or neonatal outcomes, except for GA at delivery as women with both UPs and current/past psychiatric diagnosis had a 2.21-day higher mean GA at delivery than women in the reference group (p-value interaction = 0.001). CONCLUSIONS: Current/past psychiatric diagnoses are associated with a higher odd of UPs. In our sample, maternal and neonatal outcomes were comparable for women with and without UPs and these results were similar for women with and without current/past psychiatric diagnoses, except for GA at delivery. Although our study is limited by several factors, we found that women with current/past psychiatric diagnoses, irrespective of pregnancy planning status, do not have more adverse maternal or pregnancy outcomes. Increased efforts are needed to ensure that psychoeducation and conversations about pregnancy planning and UPs are available for women with current/past psychiatric diagnoses.

Changes in depression symptom profile with gender-affirming hormone use in transgender persons.

BACKGROUND: Women show higher prevalence of depression and different symptomatology than men, possibly influenced by sex hormones. Many transgender persons, who face a high risk of depression, use Gender-Affirming Hormone Therapy (GAHT), but the impact of GAHT on depressive symptom profiles is unknown. METHODS: This study examined depressive symptoms in transgender persons before GAHT and after 3- and 12 months of GAHT. We used the Inventory of Depressive Symptomatology-Self Report to assess depressive symptoms, exploratory factor analysis (EFA) to assess symptom clusters, and linear mixed models to assess changes in symptom clusters. RESULTS: This study included 110 transmasculine (TM) and 89 transfeminine (TF) participants. EFA revealed four symptom clusters: mood, anxiety, lethargy, and somatic symptoms. Changes in total depressive symptoms significantly differed between TM and TF groups. After 3 months of GAHT, TM participants reported improvement in lethargy (-16 %; 95%CI: -29 %; -2 %), and after 12 months TF participants reported worsening in low mood (24 %; 95%CI: 3 %; 51 %), but absolute score changes were modest. Neither group showed changes in anxiety or somatic symptoms. LIMITATIONS: This study had limited sample sizes at 12 months follow-up and did not include relevant biological or psychosocial covariates. DISCUSSION: Changes in depressive symptoms after GAHT use differ in TM and TF persons: TM persons report slight improvements in lethargy, whereas TF persons report a slight increase in low mood. Starting GAHT represents a significant life event with profound social and physical effects, and further research should assess social and biological effects of GAHT on mood-related symptoms.

Influence of sex hormone use on sleep architecture in a transgender cohort.

STUDY OBJECTIVES: Sex differences in sleep architecture are well-documented, with females experiencing longer total sleep time, more slow wave sleep (SWS), and shorter Rapid Eye Movement (REM) sleep duration than males. Although studies imply that sex hormones could affect sleep, research on exogenous sex hormones on sleep architecture is still inconclusive. This study examined sleep architecture changes in transgender individuals after 3 months of gender-affirming hormone therapy (GAHT). METHODS: We assessed sleep architecture in 73 transgender individuals: 38 transmasculine participants who started using testosterone and 35 transfeminine participants who started using estrogens and antiandrogens. Sleep architecture was measured before GAHT and after 3 months of GAHT for 7 nights using an ambulatory single-electrode sleep EEG device. Changes in sleep architecture were analyzed using linear mixed models, and non-normally distributed outcomes were log-transformed and reported as percentages. RESULTS: In transmasculine participants, SWS decreased by 7 minutes (95% CI: -12; -3) and 1.7% (95% CI: -3%; -0.5%), REM sleep latency decreased by 39% (95% CI: -52%; -22%) and REM sleep duration increased by 17 minutes (95% CI: 7; 26) after 3 months of GAHT. In transfeminine participants, sleep architecture showed no significant changes after 3 months of GAHT. CONCLUSIONS: Sleep architecture changes after 3 months of masculinizing GAHT in line with sleep in cisgender males, while it shows no changes after feminizing GAHT. The sex-specific nature of these changes raises new questions about sex hormones and sleep. Future research should focus on studying possible underlying neural mechanisms and clinical consequences of these changes.

Allostatic load in children: The cost of empathic concern.

Early-life adversity affects long-term health outcomes but there is considerable interindividual variability in susceptibility to environmental influences. We proposed that positive psychological characteristics that reflect engagement with context, such as being concerned about people or performance on tasks (i.e., empathic concern), could moderate the interindividual variation in sensitivity to the quality of the early environment. We studied 526 children of various Asian nationalities in Singapore (46.6% female, 13.4% below the poverty line) with longitudinal data on perinatal and childhood experiences, maternal report on empathic concern of the child, and a comprehensive set of physiological measures reflecting pediatric allostatic load assessed at 6 y of age. The perinatal and childhood experiences included adversities and positive experiences. We found that cumulative adverse childhood experience was positively associated with allostatic load of children at 6 y of age at higher levels of empathic concern but not significantly associated at lower levels of empathic concern. This finding reveals evidence for the importance of empathic concern as a psychological characteristic that moderates the developmental impact of environmental influences, serving as a source for vulnerability to adversities in children.

The Modified Tampa-Scale of Kinesiophobia for Anterior Shoulder Instability.

Purpose: To assess content validity and to modify the Tampa Scale of Kinesiophobia (TSK) to make it suitable for application in patients with anterior shoulder instability. Methods: A four-round Delphi method was performed to establish expert consensus on developing the Tampa Scale of Kinesiophobia for patients with anterior shoulder instability (TSK-SI) using an expert group of Dutch shoulder-specialized orthopedic surgeons and physiotherapists. During round 1, experts were asked to score the 17 items of the original TSK on relevance and construction using the COSMIN guidelines. With this feedback, questions were reviewed and modified. During round 2, experts were asked to score the modified items. This process was repeated until consensus was established. Then, patients were asked to participate in a moderator-guided, three-step-test interview using a Web-based platform to assess the modified scale. Sessions were recorded and evaluated by the working group. The modified scale was finally adjusted on the basis of the input of these patients. Results: Thirty Dutch shoulder experts were included, of which 25 completed all 4 rounds, after which consensus was established. One question was added to the modified scale based on feedback in round 1, establishing the 18-item TSK-SI. Sixteen patients with shoulder instability were included, which all completed the three-step test interview. Following this, question 4 (changed to present tense) and question 7 (hypothetical component added) were adjusted, resulting in the final TSK-SI. Conclusions: This consensus modification of the TSK to TSK-SI can support the content validity of the instrument to assess kinesiophobia in patients with anterior shoulder instability. These modifications may improve the responsiveness and validity of the TSK-SI, as it does not match all the items of the original TSK. Level of evidence: Level V, consensus statement.

Dialysis withdrawal and symptoms of anxiety and depression: a prospective cohort study.

BACKGROUND: An important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The. METHODS: A prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities. RESULTS: A total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities. DISCUSSION: Withdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines.

Neonatal admission after lithium use in pregnant women with bipolar disorders: a retrospective cohort study.

BACKGROUND: Lithium is the preferred treatment for pregnant women with bipolar disorders (BD), as it is most effective in preventing postpartum relapse. Although it has been prescribed during pregnancy for decades, the safety for neonates and obstetric outcomes are a topic of ongoing scientific debate as previous research has yielded contradicting outcomes. Our study aims to compare (re)admission rates and reasons for admissions in neonates born to women with bipolar disorders (BD) with and without lithium exposure. METHODS: A retrospective observational cohort study was conducted in a Dutch secondary hospital (two locations in Amsterdam). Women with BD who gave birth after a singleton pregnancy between January 2011 and March 2021 and their neonates were included. Outcomes were obtained by medical chart review of mothers and neonates and compared between neonates with and without lithium exposure. The primary outcome was admission to a neonatal ward with monitoring, preterm birth, small for gestational age (SGA), 5-minute Apgar scores, neonatal asphyxia, and readmission ≤ 28 days. RESULTS: We included 93 women with BD, who gave birth to 117 live-born neonates: 42 (36%) exposed and 75 (64%) non-exposed to lithium. There were no significant differences in neonatal admission with monitoring (16.7 vs. 20.0%, p = 0.844). Additionally, preterm birth (7.1 vs. 5.3%), SGA (0.0 vs. 8.0%), 5-minute Apgar scores (means 9.50 vs. 9.51), neonatal asphyxia (4.8 vs. 2.7%) and readmission (4.8 vs. 5.3%) were comparable. Overall, 18.8% of BD offspring was admitted. Women with BD had high rates of caesarean section (29.1%), gestational diabetes (12.8%) and hypertensive disorders of pregnancy (8.5%). CONCLUSIONS: In a sample of neonates all born to women with BD using various other psychotropic drugs, exposure to lithium was not associated with greater risk of neonatal admission to a ward with monitoring compared to non-exposure to lithium, questioning the necessity for special measures after lithium exposure. However, offspring of women with BD was admitted regularly and women with BD have high obstetric risk which require clinical and scientific attention.

Sex hormones, insomnia, and sleep quality: Subjective sleep in the first year of hormone use in transgender persons.

STUDY OBJECTIVES: Transgender persons can use gender-affirming hormone therapy (GAHT) to align their physical appearance with their identified gender. Many transgender persons report poor sleep, but the effects of GAHT on sleep are unknown. This study examined the effects of a 12 months of GAHT use on self-reported sleep quality and insomnia severity. METHODS: A sample of 262 transgender men (assigned female at birth, started masculinizing hormone use) and 183 transgender women (assigned male at birth, started feminizing hormone use), completed self-report questionnaires on insomnia (range 0-28), sleep quality (range 0-21) and sleep onset latency, total sleep time and sleep efficiency before start of GAHT and after 3, 6, 9, and 12 months of GAHT. RESULTS: Reported sleep quality showed no clinically significant changes after GAHT. Insomnia showed significant but small decreases after 3 and 9 months of GAHT in trans men (-1.11; 95%CI: -1.82; -0.40 and -0.97; 95%CI: -1.81; -0.13, respectively) but no changes in trans women. In trans men, reported sleep efficiency decreased by 2.8% (95%CI: -5.5%; -0.2%) after 12 months of GAHT. In trans women, reported sleep onset latency decreased by 9 min (95%CI: -15; -3) after 12 months of GAHT. CONCLUSIONS: These findings show that 12 months of GAHT use did not result in clinically significant changes in insomnia or sleep quality. Reported sleep onset latency and reported sleep efficiency showed small to modest changes after 12 months of GAHT. Further studies should focus on underlying mechanisms by which GAHT could affect sleep quality.

Association between maternal labour epidural analgesia and autistic traits in offspring.

STUDY OBJECTIVE: Studies investigating associations between maternal epidural analgesia (MEA) and autism spectrum disorder (ASD) in the offspring are conflicting and lack prospective neurobehavioral follow-up assessments for autistic traits. We aim to prospectively investigate associations between MEA and autistic traits in the offspring. DESIGN: Prospective neurobehavioral observational cohort study. SETTING: Singaporean tertiary healthcare institutions. PATIENTS: Participants recruited were singleton non-IVF children, >36 weeks gestation, delivered via normal vaginal delivery by mothers >18 years of age, delivered in Singapore from June 2009-September 2010 and followed up over 7 years. INTERVENTIONS: Exposure to maternal epidural analgesia during delivery. MEASUREMENTS: The primary outcome is an abnormal Social Responsiveness Scale (SRS) T score at 7 years (≥60 points). Secondary outcomes include the diagnosis of ASD and abnormal scores for autistic traits assessed via a neurobehavioral battery comprising: CBCL (child behavioural checklist), Q-CHAT (Quantitative Checklist for Autism in Toddlers), and Bayley-III. Multivariable analyses adjusting for maternal and offspring characteristics were performed. MAIN RESULTS: 704 out of 769 mother-child dyads recruited fulfilled the criteria for analysis. 365/704 mothers received MEA. The incidence of an abnormal SRS score at 7 years in offspring exposed to MEA was 19.9%, and 26.1% in non-exposed offspring (p = 0.154). Multivariable analysis did not demonstrate a significant association between MEA and abnormal SRS scores at 7 years (O.R.0.726, 95% C·I. 0.394-1.34, p = 0.305). After adjustment for maternal and fetal demographics, exposure to MEA was not significantly associated with an abnormal screen in all other tests for autistic traits. The clinical incidence of ASD was 1.76% in children without exposure to MEA, and 2.32% in children with MEA exposure (p = 0.506). CONCLUSIONS: MEA is not significantly associated with the development of ASD and autistic traits in offspring, assessed over 7 years. Results should be taken into perspective given our wide confidence intervals and small cohort size.

Preconception sleep quality moderates the association between preconception hair cortisol levels and mental health in pregnant women.

BACKGROUND: Poor sleep quality may elevate cortisol levels and affect prenatal mental health through altered HPA axis functioning. This study aims to examine whether subjective sleep quality during preconception moderates the association between preconception hair cortisol levels and mental health from preconception to pregnancy trimesters. METHODS: Women from a prospective cohort study completed the Pittsburgh Sleep Quality Index (PSQI), the Edinburgh Postnatal Depression Scale (EPDS), and the State-Trait Anxiety Inventory (STAI) questionnaires during preconception (T0) and at each pregnancy trimesters (T1, T2, and T3). We analyzed 266 of these women who conceived and had fully completed measures at preconception for hair cortisol, sleep quality and either EPDS or STAI-state. Changes in EPDS and STAI-state scores were derived (i.e., T1-T0, T2-T0, T3-T0). Johnson-Neyman technique identified PSQI scores with significant moderation of cortisol on mental health. RESULTS: After adjusting for potential covariates, there was a significant positive correlation between preconception hair cortisol levels and depressive symptom at the second trimester (rs (144) = 0.22, p = 0.008), but not the first and third trimesters (all ps > 0.05). The positive association between preconception hair cortisol and change in depressive symptoms between third trimester and preconception was significant only among women with poor preconception sleep quality (PSQI ≥ 7). LIMITATIONS: Sleep quality and prenatal mood were derived from self-reported questionnaires, which may be more susceptible to bias. CONCLUSIONS: The positive association between preconception hair cortisol and change in prenatal depressive symptoms is significant among women who reported poor sleep quality during preconception. Improving preconception sleep quality can potentially mitigate the association between preconception hair cortisol and depressive symptoms during pregnancy.

Chronotype and time-of-day effects on spatial working memory in preschool children.

STUDY OBJECTIVES: Spatial working memory (SWM) capacity subserves complex cognitive functions, yet it is unclear whether individual diurnal preferences and time-of-day influence SWM in preschool children. The main and interaction effects of chronotype and time-of-day on SWM and SWM differences in preschoolers with different chronotypes within each time-of-day group will be examined. METHODS: We studied a subset of typically developing 4.5-year-olds taking part in a birth cohort study (n = 359). The Children's Chronotype Questionnaire categorized children into morning-, intermediate-, and evening-types. Using a computerized neuropsychological test (Cambridge Neuropsychological Test Automated Battery), SWM was determined from the total number of between-search errors (ie, between search-total errors) and Strategy scores. Higher between search-total errors or lower Strategy scores indicated worse SWM. Time-of-day was categorized into late morning (10:00 am to 11:59 am), afternoon (12:00 pm to 3:59 pm), and late afternoon (4:00 pm to 6:30 pm). In a subsample (n = 199), caregiver-reported chronotype was validated using actigraphy-measured sleep midpoint. RESULTS: After controlling for ethnicity, no significant main and interaction effects of chronotype and time-of-day on between search-total errors and Strategy scores were seen (all P > .05). However, evening-types outperformed morning-types (ie, lower mean between search-total errors) in the late afternoon (P = .013) but not in the late morning and afternoon (all P > .05). Actigraphy data in the subsample confirmed that evening-types had later sleep midpoints during weekdays and weekends (P < .001). CONCLUSIONS: Since evening-type preschoolers had better SWM in the late afternoon compared to morning-type preschoolers, this gives insights into optimal learning opportunities in early childhood education. CITATION: Abdul Jafar NK, Tham EKH, Eng DZH, et al. Chronotype and time-of-day effects on spatial working memory in preschool children. J Clin Sleep Med. 2023;19(10):1717-1726.

Associations between sleep trajectories up to 54 months and cognitive school readiness in 4 year old preschool children.

Purpose: This study explores the association between the duration and variation of infant sleep trajectories and subsequent cognitive school readiness at 48-50 months. Methods: Participants were 288 multi-ethnic children, within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Caregiver-reported total, night and day sleep durations were obtained at 3, 6, 9, 12, 18, 24 using the Brief Infant Sleep Questionnaire and 54 months using the Child Sleep Habits Questionnaire. Total, night and day sleep trajectories with varying durations (short, moderate, or long) and variability (consistent or variable; defined by standard errors) were identified. The cognitive school readiness test battery was administered when the children were between 48 and 50 months old. Both unadjusted adjusted analysis of variance models and adjusted analysis of covariance models (for confounders) were performed to assess associations between sleep trajectories and individual school readiness tests in the domains of language, numeracy, general cognition and memory. Results: In the unadjusted models, children with short variable total sleep trajectories had poorer performance on language tests compared to those with longer and more consistent trajectories. In both unadjusted and adjusted models, children with short variable night sleep trajectories had poorer numeracy knowledge compared to their counterparts with long consistent night sleep trajectories. There were no equivalent associations between sleep trajectories and school readiness performance for tests in the general cognition or memory domains. There were no significant findings for day sleep trajectories. Conclusion: Findings suggest that individual differences in longitudinal sleep duration patterns from as early as 3 months of age may be associated with language and numeracy aspects of school readiness at 48-50 months of age. This is important, as early school readiness, particularly the domains of language and mathematics, is a key predictor of subsequent academic achievement.

Nutrient trajectories during infancy and their associations with childhood neurodevelopment.

PURPOSE: To examine the associations between infants' dietary nutrient trajectories and subsequent neurodevelopment during childhood in the Growing Up in Singapore Towards healthy Outcomes study. METHODS: One-day food records were collected at ages 6, 9 and 12 months, whilst Bayley Scales of Infant and Toddler Development-III and Kaufman Brief Intelligence Test-2 were conducted at ages 24 and 54 months respectively. Nutrient trajectories were constructed using multi-level mixed modelling and associations with neurodevelopment (24 months: n = 484; 54 months: n = 444) were examined using adjusted multivariable linear regression. RESULTS: At age 24 months, higher protein intake (at 6 months) and increasing rate of intake (from 6 to 12 months) were associated with higher fine motor score [ß = 0.17 SD (95% CI 0.03, 0.31) and 0.62 SD (0.10, 1.14) respectively]. Higher fat intake was associated with higher receptive language score [0.04 SD (0.003, 0.07)], but increasing rate of intake was associated with lower expressive language [- 0.20 SD (- 0.39, - 0.01)] and fine motor [- 0.29 SD (- 0.48, - 0.10)] scores. Higher carbohydrate intake was associated with lower gross motor score [- 0.07 SD (- 0.14, - 0.005)], but increasing rate of intake was associated with higher receptive language [0.44 SD (0.08, 0.81)] and fine motor [0.56 SD (0.18, 0.93)] scores. Increasing rate of dietary fibre intake was associated with higher fine motor scores [0.63 SD (0.16, 1.10)]. No significant associations were observed with neurodevelopment at 54 months. CONCLUSION: Our findings provide greater understanding of how nutrition over time could have varying effects on child neurodevelopment.

Experiences with Family Planning amongst Persons with Mental Health Problems: A Nationwide Patient Survey.

High rates of unintended pregnancies in patients with mental health problems reflect the unmet need for tailored family planning. This study aims to explore aspects of family planning that are especially challenging for patients experiencing health problems by obtaining the perspective of (former) patients and those with close relationships with the (former) patients. In August 2021, members of a Dutch national mental health panel, consisting of (former) patients and close ones, were invited to respond to a 34-question online survey that included questions on four domains: reproductive history, decision making, parenting, and sexuality. This study has revealed the severe and adverse impact of mental health problems across all of the four domains of reproductive health and family planning, which the questions specifically targeted. Based on these results, we recommend discussing family planning with all patients experiencing or at risk for mental health problems and their partners. These discussions should address a desire to have children, (involuntary) childlessness, uncertainties about parenting and sexuality, while remaining considerate of experienced taboos.

Mid-pregnancy and postpartum maternal mental health and infant sleep in the first year of life.

Perinatal depression and anxiety are common and associated with sleep problems in the offspring. Depression and anxiety are commonly comorbid, yet often studied independently. Our study used an integrative measure of anxiety and depressive symptoms to examine the associations of maternal mental health (mid-pregnancy and postnatal) with infant sleep during the first year of life. A total of 797 mother-child dyads from the 'Growing Up in Singapore Towards healthy Outcome' cohort study provided infant sleep data at 3, 6, 9 and 12 months of age, using the caregiver reported Brief Infant Sleep Questionnaire. Maternal mental health was assessed at 26-28 weeks gestation and 3 months postpartum using the Edinburgh Postnatal Depression Scale, Beck Depression Inventory and State-Trait Anxiety Inventory. Bifactor modelling with the individual questionnaire items produced a general affect factor score that provided an integrated measure of anxiety and depressive symptoms. Linear mixed models were used to model the sleep outcomes, with adjustment for maternal age, education, parity, ethnicity, sex of the child and maternal sleep quality concurrent with maternal mental health assessment. We found that poorer mid-pregnancy, but not postpartum, maternal mental health was associated with longer wake after sleep onset duration across the first year of life (ß = 49, 95% confidence interval 13-85 min). Poor maternal mental health during mid-pregnancy is linked to longer period of night awakening in the offspring during infancy. Interventions that aim to improve maternal antenatal mental health should examine infant sleep outcomes.

Trajectories of reported sleep duration associate with early childhood cognitive development.

STUDY OBJECTIVES: Examine how different trajectories of reported sleep duration associate with early childhood cognition. METHODS: Caregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children's Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived-each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively. RESULTS: Compared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory. CONCLUSIONS: Longer and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years.

Early Neurodevelopmental Outcomes Following Exposure to General Anesthesia in Infancy: EGAIN, a Prospective Cohort Study.

BACKGROUND: General anesthesia (GA) is known to worsen neural outcomes in animals, but human research assessing early-life GA exposure and neurodevelopment show inconsistent findings. We investigated the effects of a single GA exposure for minor surgery on the neurodevelopment of healthy children at multiple time-points, using clinical assessments along with behavioral and neurophysiological measures rarely used in human research. METHODS: GA-exposed children were a prospective cohort of 250 full-term, healthy infants who underwent GA for minor surgery before 15 months. Nonexposed children were from a separate cohort of similar age, sex, ethnicity, and maternal education. In both cohorts, clinical measures (Bayley Scales of Infant and Toddler Development-III [BSID-III] and Child Behavior Checklist [CBCL1½-5]) were assessed at 24 months, and experimental tests (memory and attentional) and neurophysiology (event-related potentials) at 6 and 18 months. RESULTS: At 24 months, there were no differences between GA-exposed and nonexposed children in the cognitive, language, motor, and socioemotional domains of the BSDI-III; however, GA-exposed children had poorer parental-reported scores in BSID-III general adaptability (94.2 vs. 99.0 [mean difference, 4.77; 97.3% confidence interval, -9.29, -0.24]; P =0.020) and poorer internalizing behavior scores on CBCL1½-5 (52.8 vs. 49.4 [mean difference, 3.35; 97.3% confidence interval, 0.15-6.55]; P =0.021). For experimental measures, GA-exposed children showed differences in 4 tests at 6 and 18 months. CONCLUSIONS: GA-exposed children did not differ from unexposed children in cognitive, language or motor outcomes at 24 months, but exhibited poorer parent-reported behavior scores. Differences in infant behavior and neurophysiology were detected at 6 and 18 months. Neurophysiological assessments may complement clinically relevant assessments to provide greater insights into neurodevelopment following early GA exposure.