A reduction in hospital length of stay reduces costs for colorectal surgery: an economic evaluation of the National Surgical Quality Improvement Program in Singapore.

PURPOSE: In 2017, the National Surgical Quality Improvement Program (NSQIP) was introduced in the Department of Colorectal Surgery at Singapore General Hospital as a pilot quality improvement initiative. This study aimed to examine the cost-effectiveness of NSQIP by evaluating its effects on surgical outcomes, length of stay (LOS), and costs. METHODS: We retrospectively reviewed patients undergoing colorectal surgery (2017-2020). Patients were divided into two cohorts: pre-NSQIP (2017-2018) and post-NSQIP (2019-2020). Outcomes evaluated were 30-day postoperative complications, LOS, and costs. Total cost-savings from NSQIP intervention's impact on LOS were estimated using a decision model with a one-way sensitivity analysis. Multivariate logistic regression was performed to identify factors for prolonged LOS. RESULTS: 1905 patients underwent colorectal surgery, with 996 in the pre-NSQIP cohort and 909 in the post-NSQIP cohort. A significant reduction in overall postoperative complications of 4.7% was observed in the post-NSQIP cohort (36.5% vs. 31.8%, p = 0.029). Patients in the post-NSQIP cohort had a shorter median LOS (8.0 vs. 6.0 days, p < 0.001). The implementation of NSQIP resulted in an 8.5% decrease in prolonged LOS > 6 days (p < 0.001), saving S$0.31 million on LOS. Total costs per case were reduced by 20.8% following NSQIP (S$39,539.05 vs. S$31,311.93, p < 0.001). CONCLUSION: Implementing NSQIP has significantly reduced overall postoperative complications, LOS, and costs and achieved cost savings following colorectal surgery.

Artificial intelligence education: An evidence-based medicine approach for consumers, translators, and developers.

Current and future healthcare professionals are generally not trained to cope with the proliferation of artificial intelligence (AI) technology in healthcare. To design a curriculum that caters to variable baseline knowledge and skills, clinicians may be conceptualized as "consumers", "translators", or "developers". The changes required of medical education because of AI innovation are linked to those brought about by evidence-based medicine (EBM). We outline a core curriculum for AI education of future consumers, translators, and developers, emphasizing the links between AI and EBM, with suggestions for how teaching may be integrated into existing curricula. We consider the key barriers to implementation of AI in the medical curriculum: time, resources, variable interest, and knowledge retention. By improving AI literacy rates and fostering a translator- and developer-enriched workforce, innovation may be accelerated for the benefit of patients and practitioners.

Development and testing of a multi-lingual Natural Language Processing-based deep learning system in 10 languages for COVID-19 pandemic crisis: A multi-center study.

Purpose: The COVID-19 pandemic has drastically disrupted global healthcare systems. With the higher demand for healthcare and misinformation related to COVID-19, there is a need to explore alternative models to improve communication. Artificial Intelligence (AI) and Natural Language Processing (NLP) have emerged as promising solutions to improve healthcare delivery. Chatbots could fill a pivotal role in the dissemination and easy accessibility of accurate information in a pandemic. In this study, we developed a multi-lingual NLP-based AI chatbot, DR-COVID, which responds accurately to open-ended, COVID-19 related questions. This was used to facilitate pandemic education and healthcare delivery. Methods: First, we developed DR-COVID with an ensemble NLP model on the Telegram platform (https://t.me/drcovid_nlp_chatbot). Second, we evaluated various performance metrics. Third, we evaluated multi-lingual text-to-text translation to Chinese, Malay, Tamil, Filipino, Thai, Japanese, French, Spanish, and Portuguese. We utilized 2,728 training questions and 821 test questions in English. Primary outcome measurements were (A) overall and top 3 accuracies; (B) Area Under the Curve (AUC), precision, recall, and F1 score. Overall accuracy referred to a correct response for the top answer, whereas top 3 accuracy referred to an appropriate response for any one answer amongst the top 3 answers. AUC and its relevant matrices were obtained from the Receiver Operation Characteristics (ROC) curve. Secondary outcomes were (A) multi-lingual accuracy; (B) comparison to enterprise-grade chatbot systems. The sharing of training and testing datasets on an open-source platform will also contribute to existing data. Results: Our NLP model, utilizing the ensemble architecture, achieved overall and top 3 accuracies of 0.838 [95% confidence interval (CI): 0.826-0.851] and 0.922 [95% CI: 0.913-0.932] respectively. For overall and top 3 results, AUC scores of 0.917 [95% CI: 0.911-0.925] and 0.960 [95% CI: 0.955-0.964] were achieved respectively. We achieved multi-linguicism with nine non-English languages, with Portuguese performing the best overall at 0.900. Lastly, DR-COVID generated answers more accurately and quickly than other chatbots, within 1.12-2.15 s across three devices tested. Conclusion: DR-COVID is a clinically effective NLP-based conversational AI chatbot, and a promising solution for healthcare delivery in the pandemic era.

Perception survey of crisis and emergency risk communication in an acute hospital in the management of COVID-19 pandemic in Singapore.

BACKGROUND: Emergency risk communication is a critical component in emergency planning and response. It has been recognised as significant for planning for and responding to public health emergencies. While there is a growing body of guidelines and frameworks on emergency risk communication, it remains a relatively new field. There has also been limited attention on how emergency risk communication is being performed in public health organisations, such as acute hospitals, and what the associated challenges are. This article seeks to examine the perception of crisis and emergency risk communication in an acute hospital in response to COVID-19 pandemic in Singapore and to identify its associated enablers and barriers. METHODS: A 13-item Crisis and Emergency Risk Communication (CERC) Survey, based on the US Centers for Disease and Control (CDC) CERC framework, was developed and administered to hospital staff during February 24-28, 2020. The survey also included an open-ended question to solicit feedback on areas of CERC in need of improvement. Chi-square test was used for analysis of survey data. Thematic analysis was performed on qualitative feedback. RESULTS: Of the 1154 participants who responded to the survey, most (94.1%) reported that regular hospital updates on COVID-19 were understandable and actionable. Many (92.5%) stated that accurate, concise and timely information helped to keep them safe. A majority (92.3%) of them were clear about the hospital's response to the COVID-19 situation, and 79.4% of the respondents reported that the hospital had been able to understand their challenges and address their concerns. Sociodemographic characteristics, such as occupation, age, marital status, work experience, gender, and staff's primary work location influenced the responses to hospital CERC. Local leaders within the hospital would need support to better communicate and translate hospital updates in response to COVID-19 to actionable plans for their staff. Better communication in executing resource utilization plans, expressing more empathy and care for their staff, and enhancing communication channels, such as through the use of secure text messaging rather than emails would be important. CONCLUSION: CERC is relevant and important in the hospital setting to managing COVID-19 and should be considered concurrently with hospital emergency response domains.

Spontaneous preterm birth and cervical length in a pregnant Asian population.

OBJECTIVE: Preterm birth (birth before 37 weeks of completed gestation) is the leading cause of neonatal death, and has an incidence of 5-13% which is believed to be on the rise. The objective of this study was to determine the rate of spontaneous preterm birth and investigate the relationship between preterm birth and cervical length in a pregnant Asian population. MATERIALS AND METHODS: A prospective observational study between September 2010 and November 2013 was performed at KK Women's and Children's Hospital, Singapore. 1013 women with single viable pregnancies were recruited at less than 14 weeks of gestation between September 2010 and November 2013, excluding those with multiple gestation, pre-existing autoimmune or renal disease or those with current pregnancies complicated by aneuploidy or fetal anomalies. Participant characteristics were obtained from an interviewer-administered questionnaire at the first recruitment visit. Cervical length was measured using ultrasound at each of the 4 antenatal visits (Visit 1: < 14 weeks, Visit 2: 18-22 weeks, Visit 3: 28-32 weeks and Visit 4: > 34 weeks) using the Fetal Medicine Foundation protocol. Data on pregnancy outcomes were obtained from obstetric case notes and records. The main outcome measure examined in this study was that of spontaneous preterm birth and its relationship to cervical length. RESULTS: There was a significantly shorter cervical length both in the 2nd trimester (18 to 22 weeks) and the 3rd trimester (28 to 32 weeks) in the preterm birth group compared to the term birth group (p = 0.028 and p < 0.001 respectively). In the first trimester (11 to 14 weeks), there was no statistically significant difference in cervical length between the two groups (p = 0.425). ROC curve analysis for cervical length in the preterm birth group for 18 to 22 weeks and 28 to 32 weeks showed an AUC of 0.605 and 0.725 respectively. At 28 to 32 weeks of gestation, a cut-off level at 2.49 cm has a sensitivity of 54.8%, specificity of 82.5%, negative predictive value of 97.9% and positive predictive value of 11.1%. CONCLUSION: There is a significantly shorter cervical length in the 2nd and 3rd trimester in the preterm birth group. Cervical length is a moderate predictor of preterm birth with good negative predictive value and a relatively good specificity. Ultrasound cervical length screening for pregnant Asian women between 18 and 22 weeks of gestation with a cutoff of ≥ 2.48cm can help to identify a group of women who are at risk for preterm birth.

Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome.

The amygdala and hippocampus undergo rapid development in early life. The relative contribution of genetic and environmental factors to the establishment of their developmental trajectories has yet to be examined. We performed imaging on neonates and examined how the observed variation in volume and microstructure of the amygdala and hippocampus varied by genotype, and compared with prenatal maternal mental health and socioeconomic status. Gene × Environment models outcompeted models containing genotype or environment only to best explain the majority of measures but some, especially of the amygdaloid microstructure, were best explained by genotype only. Models including DNA methylation measured in the neonate umbilical cords outcompeted the Gene and Gene × Environment models for the majority of amygdaloid measures and minority of hippocampal measures. This study identified brain region-specific gene networks associated with individual differences in fetal brain development. In particular, genetic and epigenetic variation within CUX1 was highlighted.

A sustainable model to improve maternal health and promote early obstetric care in resource-poor regions.

OBJECTIVE: To design and examine the feasibility of a sustainable training program to build local capacity and improve obstetric outcomes in Kampong Chhnang, Cambodia. METHODS: A "train-the-trainers" model was used to conduct an obstetrics course between 2012 and 2015, its aim to reduce maternal mortality and morbidity. All Cambodian healthcare providers trained by the program were included in the study. The obstetric outcomes of all patients under the care of the trained healthcare providers were analyzed retrospectively to assess the feasibility of the program. Data from all three hospitals and 42 health centers in the province that the trainees worked at were collected from case logs. RESULTS: There was a significant increased trend in recognition of cases of postpartum hemorrhage and pre-eclampsia, and occurrence of difficult deliveries and cesarean deliveries (P<0.001). The maternal mortality ratio decreased from 64.7 per 100 000 deliveries in 2012 to 40.8 per 100 000 deliveries in 2016. CONCLUSION: This sustainable model has the potential to positively impact obstetric education and maternal outcomes and could be adopted in other resource-poor countries, particularly in Southeast Asia.

Behavioral Heterogeneity in Relation with Brain Functional Networks in Young Children.

This study aimed to identify distinct behavioral profiles in a population-based sample of 654 4-year-old children and characterize their relationships with brain functional networks using resting-state functional magnetic resonance imaging data. Young children showed 7 behavioral profiles, including a super healthy behavioral profile with the lowest scores across all Child Behavior CheckList (CBCL) subscales (G1) and other 6 behavioral profiles, respectively with pronounced withdrawal (G2), somatic complaints (G3), anxiety and withdrawal (G4), somatic complaints and withdrawal (G5), the mixture of emotion, withdrawal, and aggression (G6), and attention (G7) problems. Compared with children in G1, children with withdrawal shared abnormal functional connectivities among the sensorimotor networks. Children in emotionally relevant problems shared the common pattern among the attentional and frontal networks. Nevertheless, children in sole withdrawal problems showed a unique pattern of connectivity alterations among the sensorimotor, cerebellar, and salience networks. Children with somatic complaints showed abnormal functional connectivities between the attentional and subcortical networks, and between the language and posterior default mode networks. This study provides novel evidence on the existence of behavioral heterogeneity in early childhood and its associations with specific functional networks that are clinically relevant phenotypes for mental illness and are apparent from early childhood.

The association between serum progesterone level and preterm delivery.

OBJECTIVE: To investigate the association of serum progesterone level and preterm delivery. METHODS: The present prospective cohort study enrolled women with singleton pregnancies attending their first prenatal visit at the outpatient specialist clinics at KK Women's and Children's Hospital, Singapore, between September 1, 2010, and August 31, 2014. Progesterone levels were measured at four clinical visits (visit 1: 9-14 weeks; visit 2: 18-22 weeks; visit 3: 28-32 weeks; visit 4: >34 weeks) and were compared (after adjusting for potential confounders) between patients who had term and preterm deliveries, and among subgroups of spontaneous preterm and iatrogenic preterm deliveries. RESULTS: There were 708 patients included. Serum progesterone levels at visit 3 were higher in the preterm delivery group than in the term delivery group (P=0.036). The levels did not differ between the two groups at other visits (all P>0.05). In the subgroup analysis, progesterone levels were higher in the iatrogenic preterm delivery subgroup than the term subgroup at visits 1 and 3. A progesterone cut-off level of 304.5 nmol/L demonstrated 81.8% sensitivity, 40.1% specificity, and negative and positive predictive values of 97.5% and 7.2%, respectively, as a predictor of preterm delivery. CONCLUSION: Higher serum progesterone levels at 28-32 weeks of pregnancy were observed in women who had preterm deliveries; it was weakly predictive of preterm delivery.

Establishment of the nasal microbiota in the first 18 months of life: Correlation with early-onset rhinitis and wheezing.

BACKGROUND: Dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and susceptibility to childhood respiratory disorders. OBJECTIVE: The aim of this case-control study was to monitor, evaluate, and compare development of the nasal microbiota of infants with rhinitis and wheeze in the first 18 months of life with those of healthy control subjects. METHODS: Anterior nasal swabs of 122 subjects belonging to the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) birth cohort were collected longitudinally over 7 time points in the first 18 months of life. Nasal microbiota signatures were analyzed by using 16S rRNA multiplexed pair-end sequencing from 3 clinical groups: (1) patients with rhinitis alone (n = 28), (2) patients with rhinitis with concomitant wheeze (n = 34), and (3) healthy control subjects (n = 60). RESULTS: Maturation of the nasal microbiome followed distinctive patterns in infants from both rhinitis groups compared with control subjects. Bacterial diversity increased over the period of 18 months of life in control infants, whereas infants with rhinitis showed a decreasing trend (P < .05). An increase in abundance of the Oxalobacteraceae family (Proteobacteria phylum) and Aerococcaceae family (Firmicutes phylum) was associated with rhinitis and concomitant wheeze (adjusted P < .01), whereas the Corynebacteriaceae family (Actinobacteria phylum) and early colonization with the Staphylococcaceae family (Firmicutes phylum; 3 weeks until 9 months) were associated with control subjects (adjusted P < .05). The only difference between the rhinitis and control groups was a reduced abundance of the Corynebacteriaceae family (adjusted P < .05). Determinants of nasal microbiota succession included sex, mode of delivery, presence of siblings, and infant care attendance. CONCLUSION: Our results support the hypothesis that the nasal microbiome is involved in development of early-onset rhinitis and wheeze in infants.

Associations of physical activity and sedentary behavior during pregnancy with gestational diabetes mellitus among Asian women in Singapore.

BACKGROUND: Few studies have investigated physical activity (PA) and sedentary behavior (SB) in relation to fasting (FG) and 2-h postprandial plasma glucose (2hPG) levels and gestational diabetes mellitus (GDM); we investigated these associations among Asian pregnant women. METHODS: As part of the Growing Up in Singapore Towards healthy Outcomes cohort study, PA and SB (sitting and television times) were assessed by interviewer-administered questionnaire. During 75 g oral glucose tolerance tests at 26-28 weeks' gestation we measured FG, 2hPG levels and GDM (FG ≥ 7.0 mmol/L and/or 2hPG ≥ 7.8 mmol/L). Associations were analysed by multiple linear and logistic regression. RESULTS: Among the 1083 women studied, 18.6% had GDM. SB was not associated with FG, 2hPG and GDM. Higher categories of PA were associated with lower 2hPG and a lower likelihood of GDM (p-trend < 0.05), but not with FG levels. Compared to insufficiently active women, highly active women had lower 2hPG levels [ß (95% CI): -0.32 (-0.59, -0.05), p = 0.020) and were less likely to have GDM [OR: 0.56 (0.32-0.98), p = 0.040]. Stratified analysis revealed no associations among under/normal-weight women, but significant associations among overweight/obese women; in those with BMI ≥23 kg/m2, sufficiently active and highly active women were less likely to have GDM [OR: 0.52, (0.29-0.93), p = 0.028, and OR: 0.34, (0.15-0.77), p = 0.010, respectively]. CONCLUSION: Higher PA was associated with lower 2hPG levels and a lower prevalence of GDM, particularly in overweight/obese women. Further studies are warranted to confirm these findings, and to examine the effectiveness of PA promotion strategies for the prevention of gestational hyperglycemia.

Effect of Maternal Dietary Patterns during Pregnancy on Self-Reported Allergic Diseases in the First 3 Years of Life: Results from the GUSTO Study.

BACKGROUND: Maternal diet during pregnancy has been suggested to be an important early-life exposure that influences immune tolerance and the development of allergic diseases in offspring. METHODS: We examined the relationship between maternal dietary patterns assessed using 24-h recalls and food diaries at 26-28 weeks of pregnancy and the subsequent development of allergic outcomes in the offspring in the Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort. Exploratory factor analysis was used to characterize maternal dietary patterns during pregnancy. During repeated visits in the first 36 months of life, questionnaires were administered to ascertain allergic symptoms, namely, eczema, rhinitis, and wheeze. At ages 18 and 36 months, we administered skin-prick testing to inhalant and food allergens. RESULTS: Of the 3 maternal dietary patterns that emerged, the seafood and noodles pattern was associated with a reduced risk of developing allergen sensitization at both 18 months (odds ratio [95% confidence interval]: 0.7 [0.5-0.9]) and 36 months (0.7 [0.6-0.9]) after adjustment for a family history of allergy, and ethnicity, sex, and maternal education levels. No associations between the patterns vegetables, fruit, and white rice or pasta, cheese, and processed meat were observed with any of the allergic outcomes in the first 18 and 36 months of life. CONCLUSION: Maternal diet during pregnancy can influence the subsequent development of allergic outcomes in offspring.

The influence of CHRNA4, COMT, and maternal sensitivity on orienting and executive attention in 6-month-old infants.

Despite claims concerning biological mechanisms sub-serving infant attention, little experimental work examines its underpinnings. This study examines how candidate polymorphisms from the cholinergic (CHRNA4 rs1044396) and dopaminergic (COMT rs4680) systems, respectively indicative of parietal and prefrontal/anterior cingulate involvement, are related to 6-month-olds' (n=217) performance during a visual expectation eye-tracking paradigm. As previous studies suggest that both cholinergic and dopaminergic genes may influence susceptibility to the influence of other genetic and environmental factors, we further examined whether these candidate genes interact with one another and/or with early caregiving experience in predicting infants' visual attention. We detected an interaction between CHRNA4 genotype and observed maternal sensitivity upon infants' orienting to random stimuli and a CHRNA4-COMT interaction effect upon infants' orienting to patterned stimuli. Consistent with adult research, we observed a direct effect of COMT genotype on anticipatory looking to patterned stimuli. Findings suggest that CHRNA4 genotype may influence susceptibility to other attention-related factors in infancy. These interactions may account for the inability to establish a link between CHRNA4 and orienting in infant research to date, despite developmental theorizing suggesting otherwise. Moreover, findings suggest that by 6months, dopamine, and relatedly, the prefrontal cortex/anterior cingulate, may be important to infant attention.

Gestational age-specific reference intervals for serum thyroid hormone levels in a multi-ethnic population.

BACKGROUND: Thyroid disorders are common during pregnancy. To date, a limited number of studies have reported differences in serum thyroid hormone concentrations between different ethnic groups. We sought to establish gestational age-specific reference intervals for serum levels of thyroid hormones in a multi-ethnic population and investigate whether separate reference intervals should be used for different ethnic groups. METHODS: A total of 926 pregnant women from multiple ethnic groups attended four separate study visits spanning the three trimesters. Venous blood samples were taken at 9 to 14 weeks, 18 to 22 weeks, 28 to 32 weeks, and 34 to 39 weeks of gestation. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4), free triiodothyronine (T3), total T4, total T3, thyroid peroxidase antibody and thyroglobulin antibody were measured using Abbott Architect immunoassays. A total of 562 women with singleton pregnancies were found to be negative for both thyroid autoantibodies at all four study visits and thus included in the reference sample group for the establishment of reference intervals (2.5th to 97.5th percentiles). RESULTS: Reference intervals for serum thyroid hormones at 9-14 weeks of gestation derived from the combined group of pregnant women are as follows: TSH, 0.01-2.39 mIU/L; free T4, 11.4-19.5 pmol/L; free T3, 4.23-6.69 pmol/L; total T4, 77.8-182.4 nmol/L; total T3, 1.39-2.97 nmol/L. No differences in the five thyroid parameters' reference intervals are detectable among the ethnic groups except that at study visit 3 (28-32 weeks of gestation), the upper reference limit of total T3 in Malays (3.20 nmol/L; 90% CI, 2.99-3.76 nmol/L) is slightly higher than that in Chinese (2.86 nmol/L; 90% CI, 2.70-2.98 nmol/L). CONCLUSIONS: The findings from this study on a multi-ethnic cohort highlight the importance of establishing locally derived and gestational age-specific reference intervals for the five thyroid hormone parameters.

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk.

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.

A bilingual advantage in 54-month-olds' use of referential cues in fast mapping.

Research has demonstrated a bilingual advantage in how young children use referential cues such as eye gaze and pointing gesture to locate an object or to categorize objects. This study investigated the use of referential cues (i.e. eye gaze) in fast mapping in three groups of children that differed in their language exposure. One hundred and seven 54-month-old children who were English monolinguals (n = 28), English-Mandarin bilinguals (n = 48), and English-Mandarin bilinguals with exposure to a third language (i.e. trilinguals, n = 31) were assessed with a word learning task using two types of test - a referent test and a mutual exclusivity test. During the task, following the gaze of an adult speaker was needed to be able to indicate the correct referent of a novel word at test. All three groups of children demonstrated successful word learning in explicit selection of and implicit looking time toward the target object during testing. However, bilingual and trilingual children outperformed their monolingual peers in both types of test when they were asked to explicitly select the correct objects. These findings suggest positive effects of bilingualism on children's use of referential cues in fast mapping.

Neonatal neural networks predict children behavioral profiles later in life.

This study aimed to examine heterogeneity of neonatal brain network and its prediction to child behaviors at 24 and 48 months of age. Diffusion tensor imaging (DTI) tractography was employed to construct brain anatomical network for 120 neonates. Clustering coefficients of individual structures were computed and used to classify neonates with similar brain anatomical networks into one group. Internalizing and externalizing behavioral problems were assessed using maternal reports of the Child Behavior Checklist (CBCL) at 24 and 48 months of age. The profile of CBCL externalizing and internalizing behaviors was then examined in the groups identified based on the neonatal brain network. Finally, support vector machine and canonical correlation analysis were used to identify brain structures whose clustering coefficients together significantly contribute the variation of the behaviors at 24 and 48 months of age. Four meaningful groups were revealed based on the brain anatomical networks at birth. Moreover, the clustering coefficients of the brain regions that most contributed to this grouping of neonates were significantly associated with childhood internalizing and externalizing behaviors assessed at 24 and 48 months of age. Specially, the clustering coefficient of the right amygdala was associated with both internalizing and externalizing behaviors at 24 months of age, while the clustering coefficients of the right inferior frontal cortex and insula were associated with externalizing behaviors at 48 months of age. Our findings suggested that neural organization established during fetal development could to some extent predict individual differences in behavioral-emotional problems in early childhood. Hum Brain Mapp 38:1362-1373, 2017. © 2016 Wiley Periodicals, Inc.

Maternal Circadian Eating Time and Frequency Are Associated with Blood Glucose Concentrations during Pregnancy.

BACKGROUND: Synchronizing eating schedules to daily circadian rhythms may improve metabolic health, but its association with gestational glycemia is unknown. OBJECTIVE: This study examined the association of maternal night-fasting intervals and eating episodes with blood glucose concentrations during pregnancy. METHODS: This was a cross-sectional study within a prospective cohort in Singapore. Maternal 24-h dietary recalls, fasting glucose, and 2-h glucose concentrations were ascertained at 26-28 wk gestation for 1061 women (aged 30.7 ± 5.1 y). Night-fasting intervals were based on the longest fasting duration during the night (1900-0659). Eating episodes were defined as events that provided >50 kcal, with a time interval between eating episodes of ≥15 min. Multiple linear regressions with adjustment for confounders were conducted. RESULTS: Mean ± SD night-fasting intervals and eating episodes per day were 9.9 ± 1.6 h and 4.2 ± 1.3 times/d, respectively; fasting and 2-h glucose concentrations were 4.4 ± 0.5 and 6.6 ± 1.5 mmol/L, respectively. In adjusted models, each hourly increase in night-fasting intervals was associated with a 0.03 mmol/L decrease in fasting glucose (95% CI: -0.06, -0.01 mmol/L), whereas each additional daily eating episode was associated with a 0.15 mmol/L increase in 2-h glucose (95% CI: 0.03, 0.28 mmol/L). Conversely, night-fasting intervals and daily eating episodes were not associated with 2-h and fasting glucose, respectively. CONCLUSIONS: Increased maternal night-fasting intervals and reduced eating episodes per day were associated with decreased fasting glucose and 2-h glucose, respectively, in the late-second trimester of pregnancy. This points to potential alternative strategies to improve glycemic control in pregnant women. This study was registered at www.clinicaltrials.gov as NCT01174875.