Multigenerational adversity impacts on human gut microbiome composition and socioemotional functioning in early childhood.

Adversity exposures in the prenatal and postnatal period are associated with an increased risk for psychopathology, which can be perpetuated across generations. Nonhuman animal research highlights the gut microbiome as a putative biological mechanism underlying such generational risks. In a sample of 450 mother-child dyads living in Singapore, we examined associations between three distinct adversity exposures experienced across two generations-maternal childhood maltreatment, maternal prenatal anxiety, and second-generation children's exposure to stressful life events-and the gut microbiome composition of second-generation children at 2 y of age. We found distinct differences in gut microbiome profiles linked to each adversity exposure, as well as some nonaffected microbiome features (e.g., beta diversity). Remarkably, some of the microbial taxa associated with concurrent and prospective child socioemotional functioning shared overlapping putative functions with those affected by adversity, suggesting that the intergenerational transmission of adversity may have a lasting impact on children's mental health via alterations to gut microbiome functions. Our findings open up a new avenue of research into the underlying mechanisms of intergenerational transmission of mental health risks and the potential of the gut microbiome as a target for intervention.

Toddler disorganized attachment in relation to cortical thickness and socioemotional problems in late childhood.

Disorganized attachment is a risk for mental health problems, with increasing work focused on understanding biological mechanisms. Examining late childhood brain morphology may be informative - this stage coincides with the onset of many mental health problems. Past late childhood research reveals promising candidates, including frontal lobe cortical thickness and hippocampal volume. However, work has been limited to Western samples and has not investigated mediation or moderation by brain morphology. Furthermore, past cortical thickness research included only 33 participants. The current study utilized data from 166 children from the GUSTO Asian cohort, who participated in strange situations at 18 months and MRI brain imaging at 10.5 years, with 124 administered the Child Behaviour Checklist at 10.5 years. Results demonstrated disorganization liked to internalizing problems, but no mediation or moderation by brain morphology. The association to internalizing (but not externalizing) problems is discussed with reference to the comparatively higher prevalence of internalizing problems in Singapore.

Is there a link between passive smoke exposure and early-onset myopia in preschool Asian children?

PURPOSE: To investigate the association of passive tobacco smoke exposure with early-onset myopia among three-year-old children in Singapore. METHODS: Pregnant mothers who attended their first trimester clinic at two major maternity units were recruited into the GUSTO birth cohort. The current analysis comprised 572 three-year-old children, who underwent cycloplegic autorefraction and axial length (AL) measurements. Myopia was defined as spherical equivalent (SE) of ≤-0.50 dioptres (D). Either parent completed questionnaires describing their child's exposure to passive smoke at six months, one and two years of age. RESULTS: There were 197 children (36.2%) who were exposed to passive smoke from birth to before six months. Compared to non-exposed children, children exposed to any passive smoke from birth to before six months experienced greater myopia prevalence (adjusted OR = 2.79; 95% CI: 1.24-6.29; p = 0.01). The odds of myopia in a child was greater if a smoker smokes at home, in the family car, or in the presence of the child (adjusted OR = 3.95; 95% CI: 1.41-11.09; p < 0.01) compared to non-exposed child. In contrast to myopia, childhood exposure to passive smoke did not systematically shift mean values for SE or AL. CONCLUSIONS: In this prospective birth cohort study, we found that childhood exposure to passive smoke from birth to before six months slightly increased the risk of early-onset myopia. This may indicate a delayed response to passive smoke exposure before six months and the development of myopia at three years of age. Our study is limited by the small number of myopic children at this young age. Thus, larger prospective studies using more objective cotinine level measures are required to fully establish and understand the influence of tobacco smoke on refractive development in older children.

Prevalence, risk factors and parental perceptions of gastroesophageal reflux disease in Asian infants in Singapore

INTRODUCTION@#Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents.@*METHODS@#Mother-infant dyads in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort were prospectively followed from preconception to 12 months post-delivery. GERD diagnosis was ascertained through the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) administered at 4 time points during infancy. Data on parental perceptions and lifestyle modifications were also collected.@*RESULTS@#The prevalence of infant GERD peaked at 26.5% at age 6 weeks, decreasing to 1.1% by 12 months. Infants exclusively breastfed at 3 weeks of life had reduced odds of GERD by 1 year (adjusted odds ratio 0.43, 95% confidence interval 0.19-0.97, P=0.04). Elimination of "cold or heaty food" and "gas producing" vegetables, massaging the infant's abdomen and application of medicated oil to the infant's abdomen were quoted as major lifestyle modifications in response to GERD symptoms.@*CONCLUSION@#Prevalence of GERD in infants is highest in the first 3 months of life, and the majority outgrow it by 1 year of age. Infants exclusively breastfed at 3 weeks had reduced odds of GERD. Cultural-based changes such as elimination of "heaty or cold" food influence parental perceptions in GERD, which are unique to the Asian population. Understanding the cultural basis for parental perceptions and health-seeking behaviours is crucial in tailoring patient education appropriately for optimal management of infant GERD.

Association of Cord Blood Thyroid-Stimulating Hormone Levels with Maternal, Delivery and Infant Factors

INTRODUCTION@#This study examined maternal, delivery and infant factors associated with cord thyroid-stimulating hormone (TSH) concentrations in an Asian population.@*METHODS@#The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study is a mother-offspring birth cohort from 2 major hospitals in Singapore. Cord serum TSH was measured using the Abbott ARCHITECT TSH Chemiluminescent Microparticle Immunoassay and the ADVIA Centaur TSH-3 Immunoassay. After excluding infants with a maternal history of thyroid disease, screening cord TSH results from 604 infants were available for multivariable regression analysis in relation to the factors of interest.@*RESULTS@#Babies born by vaginal delivery had significantly higher cord serum TSH concentrations than babies born by caesarean section. Cord serum TSH concentrations differed significantly by measurement method. There was no association of cord TSH concentrations with ethnicity, sex, birth weight, gestational age, maternal body mass index, gestational weight gain, gestational diabetes mellitus status and other maternal, delivery and infant factors studied.@*CONCLUSION@#Interpretation of cord serum TSH results may need to take into account mode of delivery and measurement method.

Early initiation and regular breast milk expression reduces risk of lactogenesis II delay in at-risk Singaporean mothers in a randomised trial

INTRODUCTION@#Lactogenesis II (LaII) failure can be prevented in at-risk mothers with simple proactive interventions. In a randomised trial, we investigated the efficacy of early and regular breast milk expression in establishing LaII, using an electric double-breast pump.@*METHODS@#Mothers with uncomplicated singleton deliveries were randomised to intervention (n = 31) or control (n = 29) groups. The former commenced breast milk expression with an electric pump within one hour of delivery and maintained regular expression with direct breastfeeding. Control mothers directly breastfed without regular pump expression. Expressed milk volumes were analysed for citrate, lactose, sodium and protein.@*RESULTS@#Median time of LaII was Day 3 (interquartile range [IQR] 1 day) with intervention and on Day 4 (IQR 1 day) among controls (p = 0.03). Biochemical steady-state concentrations were achieved around early Day 4 (sodium, total protein) and Days 4-5 (citrate, lactose). Sodium, protein and lactose levels were similar in both groups over seven days, at 5.80 mM, 0.68 mM and -13.38 mM, respectively. Mean daily milk volume with intervention was 73.9 mL on Day 3 and 225.2 mL on Day 7, greater than controls (25.4 mL on Day 3 and 69.2 mL on Day 7; p < 0.2). Mean infant weights were similar on Day 8 at 3,477 g with intervention and 3,479 g among controls.@*CONCLUSION@#LaII is established by postnatal Day 3 with early initiation of regular breast milk expression, a useful intervention for mothers at risk of early-onset breastfeeding failure.

Relationship between all fevers or fever after vaccination, and atopy and atopic disorders at 18 and 36 months

BACKGROUND: Studies have reported that early febrile episodes and febrile episodes with infections are associated with a decreased risk of developing atopy. OBJECTIVE: To examine further the association between presence of and number of febrile episodes are with atopy and atopic diseases and if there was a difference between all fevers and fever after vaccination. METHODS: We studied 448 infants in a Singapore mother-offspring cohort study (Growing Up in Singapore Towards Healthy Outcomes) which had complete data for the exposures and outcomes of interest. Fever was defined as more than 38.0℃ and was self-reported. The presence of and number of febrile episodes were examined for association with outcome measures, namely parental reports of doctor-diagnosed asthma and eczema, and rhinitis, which was evaluated by doctors involved in the study at 18 and 36 months. These outcomes were considered atopic if there were 1 or more positive skin prick tests. RESULTS: The presence of all fevers from 0–6 months of age was associated with reduced odds of having atopy at 36 months of age (unadjusted odds ratio [OR], 0.628; 95% confidence interval [CI], 0.396–0.995). The presence of fever after vaccination from 0–24 months of age was associated with reduced odds of having atopy at 36 months of age (OR, 0.566; 95% CI, 0.350–0.915). The presence of all fevers from 0–6 months of age was associated with reduced odds of having atopic eczema at 36 months (OR, 0.430; 95% CI, 0.191–0.970). Fever was associated with increased odds of having doctor-diagnosed asthma and rhinitis. CONCLUSION: There was an inverse relationship between the presence of all fevers from 0–6 months of age and the development of atopy and eczema at 36 months of age. Fever after vaccination might be considered a subclinical infection that did not show the same effect in early life.

A new population-based reference for gestational age-specific size-at-birth of Singapore infants

<p><b>INTRODUCTION</b>There is currently a lack of representative data for local gestational age-specific size-at- birth percentile charts. Existing charts also suffer from limitations relating to the measurement of gestational age (GA) and an outdated population. We aim to construct reference values and charts for size-at-birth from 35 to 41 weeks, based on the healthy local population.</p><p><b>MATERIALS AND METHODS</b>Prospective observational birth cohort study which recruited pregnant mothers from the 2 major public hospitals with obstetric service in Singapore, at <14 weeks gestation and data was collected for birth weight, length and head circumference of infants born from November 2009 to May 2011. Percentile curves were created separately for male and female infants using the lambda-mu-sigma (LMS) method. The new percentile curves were then compared with other internationally published growth charts.</p><p><b>RESULTS</b>Smoothened curves for birth weight, length and head circumference centiles were created from 863 infants (460 males, 403 females). Male infants consistently exceeded female infants in all 3 variables at each GA. For a male and female Singapore infant at 38 weeks gestation, the 10-50-90th centile values for weight would be 2663-3096-3597 vs. 2571-2966-3417 grams, for length 46.4-48.6-51.1 vs. 45.6-48.0-50.4 cm, and for head circumference 32.0-33.5-35.2 vs. 31.4-32.9-34.6 cm. There was no statistically significant difference between ethnic groups. On comparing our birth weight curves with data from Finland across all gestations, birth weights in our term infants (GA ≥37 weeks) were found to be lower across the 10-50-90th percentiles.</p><p><b>CONCLUSION</b>The new centile charts in this study may be used as reference charts for size-at-birth for a subgroup of near-term and term infants. The use of foreign charts may lead to misclassification of small for gestational age (SGA) or large for gestational age (LGA) infants.</p>

The methodology of the GUSTO cohort study: a novel approach in studying pediatric allergy

Growing Up in Singapore Towards healthy Outcomes (GUSTO) is Singapore's largest birth cohort study to date. The main aim of GUSTO is to evaluate the role of developmental factors in the early pathways to metabolic compromise. Detailed data is collected for a range of environmental exposures in the parents and offspring, and allergic disorders are among a number of outcomes assessed in infancy and childhood. Under the Allergy domain of GUSTO, this integrated study will describe the epidemiology of allergic manifestations and different phenotypes in the Asian context and help shed light on the association of metabolic disease to allergy. Epigenetic mechanisms and associations with other childhood disorders will also be explored. The aim of this report is to focus on methodology of GUSTO, and to suggest similar approaches (i.e., integrated cohort studies on pediatric allergy) worldwide. Recruitment commenced in 2009 with a cohort of 1,163 pregnant mothers in their first trimester. The mothers and children were followed throughout pregnancy and follow-up will continue until the child reaches 3 years of age. Preliminary results showed that 39.8% of the mothers had a personal history of having at least one allergic disease, which included asthma, eczema and allergic rhinitis. Further data collection and analyses are still ongoing. Allergy is a complex spectrum of disorders with numerous poorly-understood aspects. The ongoing GUSTO cohort study, with its longitudinal design and multi-disciplinary nature, may provide new insights into developmental influences on allergy. As a Singapore-based study, it will be the first integrated allergy cohort in Southeast Asia, of which recruitment started during pregnancy.

Emerging trends in breastfeeding practices in Singaporean Chinese women: findings from a population-based study

<p><b>INTRODUCTION</b>This study records the prevalence and patterns of breastfeeding in Singaporean Chinese mothers who gave birth between 2000 and 2008.</p><p><b>MATERIALS AND METHODS</b>The Strabismus, Amblyopia and Refractive Error in Singaporean Children (STARS) study is a population-based survey conducted in South-Western Singapore. Disproportionate random sampling by 6-month age groups of Chinese children born from 2000 to 2008 was performed. The mothers (n = 3009) completed a standard questionnaire which recorded the initiation, content, method and duration of breastfeeding. World Health Organization (WHO) definitions for feeding content were used: Replacement (exclusive commercial formula or any liquid or solid/semi-solid food, excluding breast milk), Complementary (breast milk, solid/semi-solid foods, and any non-human liquid), and Exclusive (breast milk only, without additional food, drink or water). STARS-specific definitions for feeding method were used: Expressed (breast milk only fed via bottle, with no additional food or non-human liquid), Combination (breast milk and non-breast milk, fed via bottle and breast), and Direct (breast milk only fed via breast).</p><p><b>RESULTS</b>Breastfeeding initiation (overall prevalence 77.0%) and duration increased over time, and were independently associated with higher maternal education: in 2000 and 2001, 68.6% of mothers initiated breastfeeding and 12.9% breast fed for <or=6 months, versus 82.0% and 26.7%, respectively, from 2006 to 2008; 47.4% of primary-school-educated women initiated breastfeeding, and 11.1% fed for >or=6 months, vs 90.9% and 35.3%, respectively, of university-educated women (P <0.001). Expressed, Combination and Complementary feeding also increased, while Replacement feeding decreased (P <0.001). There was no difference in breastfeeding patterns by the child's gender.</p><p><b>CONCLUSIONS</b>In a population-based sample of Singaporean Chinese mothers giving birth from 2000 to 2008, breastfeeding initiation and duration increased over time and were independently associated with higher maternal education. This increase was associated with increased milk expression and complementary feeding. Thus awareness of breastfeeding benefits is rising in Singapore, but future health policies may need to target less-educated mothers.</p>

The influence of maternal ethnic group and diet on breast milk fatty acid composition

<p><b>INTRODUCTION</b>Breast milk fatty acids play a major role in infant development. However, no data have compared the breast milk composition of different ethnic groups living in the same environment. We aimed to (i) investigate breast milk fatty acid composition of three ethnic groups in Singapore and (ii) determine dietary fatty acid patterns in these groups and any association with breast milk fatty acid composition.</p><p><b>MATERIALS AND METHODS</b>This was a prospective study conducted at a tertiary hospital in Singapore. Healthy pregnant women with the intention to breastfeed were recruited. Diet profile was studied using a standard validated 3-day food diary. Breast milk was collected from mothers at 1 to 2 weeks and 6 to 8 weeks postnatally. Agilent gas chromatograph (6870N) equipped with a mass spectrometer (5975) and an automatic liquid sampler (ALS) system with a split mode was used for analysis.</p><p><b>RESULTS</b>Seventy-two breast milk samples were obtained from 52 subjects. Analysis showed that breast milk ETA (Eicosatetraenoic acid) and ETA:EA (Eicosatrienoic acid) ratio were significantly different among the races (P = 0.031 and P = 0.020), with ETA being the highest among Indians and the lowest among Malays. Docosahexaenoic acid was significantly higher among Chinese compared to Indians and Malays. No difference was demonstrated in n3 and n6 levels in the food diet analysis among the 3 ethnic groups.</p><p><b>CONCLUSIONS</b>Differences exist in breast milk fatty acid composition in different ethnic groups in the same region, although no difference was demonstrated in the diet analysis. Factors other than maternal diet may play a role in breast milk fatty acid composition.</p>

Care of women in menopause: sexual function, dysfunction and therapeutic modalities

<p><b>INTRODUCTION</b>The physiological changes that occur in menopause alter sexual function and affect well-being. Hormonal changes contribute significantly to reduced sexual function in older women and sexual dysfunction may well be amenable to treatment with exogenous hormones or other agents.</p><p><b>MATERIALS AND METHODS</b>Relevant clinical studies were identified by a computerised literature search. The collated data were presented to fellow gynaecologists for review, analysis of results and discussion in a series of meetings dedicated to finding the best evidence in menopause management. The evidence was assessed and used to prepare guidelines around the management of women who are affected by sexual dysfunction in menopause.</p><p><b>RESULTS</b>Hormone therapy benefits many women who have dyspareunia related to vaginal atrophy, reduced libido and decreased satisfaction, particularly if these symptoms adversely affect their quality of life. Alternative agents such as tibolone and sildenafil citrate can be useful adjuncts.</p><p><b>CONCLUSIONS</b>It is increasingly important to recognise postmenopausal sexual dysfunction. Treatment of this syndrome must be individualised to the specific complaints of each woman. Hormones and other agents are relevant treatment options for properly-selected women.</p>

Use of fetal electrocardiogram for intrapartum monitoring

<p><b>INTRODUCTION</b>Intrapartum fetal monitoring is essential for the identification of fetal hypoxia to reduce perinatal morbidity and mortality. Cardiotocography is associated with low specificity for fetal acidosis and poor perinatal outcome leading to unnecessary operative deliveries. ST waveform analysis of the fetal electrocardiogram has been shown to be a promising adjunctive intrapartum assessment tool. We aim to present the pathophysiology, the role of intrapartum monitoring and the practical usage of this relatively new technology in our review.</p><p><b>METHODS</b>An electronic search of Medline and OVID was carried out, followed by a manual search of the references identified by the electronic search.</p><p><b>RESULTS</b>The incorporation of ST waveform analysis to cardiotocography has been shown to reduce the rates of neonatal metabolic acidosis, moderate and severe neonatal encephalopathy, thus improving perinatal outcome. The reduction in operative delivery rates due to fetal distress is also significant. The pathophysiology and practical usage of this technology were discussed.</p><p><b>CONCLUSIONS</b>With more accurate identification of fetal hypoxia and reduction of unnecessary intervention rates, incorporation of ST waveform analysis of fetal electrocardiography into cardiotocography can improve the standard of intrapartum fetal monitoring.</p>