Kenneth Kwek

Atopic Dermatitis in Early Life: Evidence for at Least Three Phenotypes? Results from the GUSTO Study.

Background: Atopic dermatitis (AD) has been highlighted as a likely first step in the ‘atopic march, emphasizing the need to define predisposing factors. Methods: We evaluated AD risk factors and phenotypes in an Asian mother-offspring cohort. We defined three phenotypes of doctor-diagnosed AD based on the time of onset of the disease: early AD occurring within the first 6 months of life, AD occurring between 6 and 12 months and late-onset AD starting after the age of 12 months. Results: Maternal allergic history was associated with an increased risk of developing early-onset AD (adjusted odds ratio (aOR) 20.46, 95% confidence interval (CI) 2.73-153.15, p < 0.01). Maternal allergic history and attendance at a daycare centre increased the odds of the development of AD between 6 and 12 months (aOR 4.19, 95% CI 1.01-17.45, p = 0.049 and aOR 11.42, 95% CI 1.49-87.50, p = 0.02, respectively). Risk factors associated with increased odds of late-onset AD from 12 months were the consumption of probiotics between the age of 9 and 12 months and antibiotic treatment in the first 6 months of life (aOR 4.32, 95% CI 1.07-17.45, p = 0.04 and aOR 3.11, 95% CI 1.10-8.76, p = 0.03, respectively). Early-onset AD was associated with an increased risk of developing allergic sensitization (aOR 46.51, 95% CI 3.44-628.81, p < 0.01). Conclusion: We found that early-onset AD was mainly associated with familial factors, while late-onset AD was associated with the consumption of antibiotics or probiotics. The findings support the concept that different phenotypes of AD exist in young children.

Long-chain polyunsaturated fatty acid status during pregnancy and maternal mental health in pregnancy and the postpartum period: results from the GUSTO study.

OBJECTIVEnStudies have demonstrated a relationship between lower omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) status and anxiety and depression. It is uncertain whether similar associations occur in pregnant women, when anxiety and depression could have long-term effects on the offspring. We examined the associations between plasma LC-PUFA status during pregnancy and perinatal mental health.nnnMETHODnAt 26-28 weeks gestation, plasma LC-PUFAs were measured in mothers of the Growing Up in Singapore Toward healthy Outcomes (GUSTO) mother-offspring cohort study, who were recruited between June 2009 and September 2010. Maternal symptoms of anxiety and depression were assessed with the State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) during the same period and at 3 months postpartum. The STAI-state subscale was used as a continuous measure of current anxiety, while EPDS scores ≥ 15 during pregnancy or ≥ 13 postpartum were indicative of symptoms of probable depression.nnnRESULTSnIn adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (β = -6.49 STAI-state subscale scores/unit increase of omega-3 fatty acid; 95% CI, -11.90 to -1.08) and higher plasma omega-6:omega-3 PUFA ratios (β = 6.58 scores/unit increase of fatty acid ratio; 95% CI, 1.19 to 12.66), specifically higher arachidonic acid (AA):docosahexaenoic acid, AA:eicosapentaenoic acid, and AA:docosapentaenoic acid ratios, were associated with increased antenatal anxiety (P < .05 for all), but not postpartum anxiety. There was no association between plasma PUFAs and perinatal probable depression.nnnCONCLUSIONSnNo association was found with probable depression in pregnancy or postpartum. Lower plasma omega-3 fatty acids and higher omega-6:omega-3 fatty acid ratios were associated with higher antenatal anxiety, but not postpartum anxiety. Replication in other studies is needed to confirm the findings and determine the direction of causality.nnnTRIAL REGISTRATIONnClinicalTrials.gov identifier: NCT01174875.

Association of maternal vitamin D status with glucose tolerance and caesarean section in a multi-ethnic Asian cohort: the growing up in Singapore towards healthy outcomes study

Objective Epidemiological studies relating maternal 25-hydroxyvitamin D (25OHD) with gestational diabetes mellitus (GDM) and mode of delivery have shown controversial results. We examined if maternal 25OHD status was associated with plasma glucose concentrations, risks of GDM and caesarean section in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Methods Plasma 25OHD concentrations, fasting glucose (FG) and 2-hour postprandial glucose (2HPPG) concentrations were measured in 940 women from a Singapore mother-offspring cohort study at 26–28 weeks’ gestation. 25OHD inadequacy and adequacy were defined based on concentrations of 25OHD ≤75nmol/l and >75nmol/l respectively. Mode of delivery was obtained from hospital records. Multiple linear regression was performed to examine the association between 25OHD status and glucose concentrations, while multiple logistic regression was performed to examine the association of 25OHD status with risks of GDM and caesarean section. Results In total, 388 (41.3%) women had 25OHD inadequacy. Of these, 131 (33.8%), 155 (39.9%) and 102 (26.3%) were Chinese, Malay and Indian respectively. After adjustment for confounders, maternal 25OHD inadequacy was associated with higher FG concentrations (β = 0.08mmol/l, 95% Confidence Interval (CI) = 0.01, 0.14), but not 2HPPG concentrations and risk of GDM. A trend between 25OHD inadequacy and higher likelihood of emergency caesarean section (Odds Ratio (OR) = 1.39, 95% CI = 0.95, 2.05) was observed. On stratification by ethnicity, the association with higher FG concentrations was significant in Malay women (β = 0.19mmol/l, 95% CI = 0.04, 0.33), while risk of emergency caesarean section was greater in Chinese (OR = 1.90, 95% CI = 1.06, 3.43) and Indian women (OR = 2.41, 95% CI = 1.01, 5.73). Conclusions 25OHD inadequacy is prevalent in pregnant Singaporean women, particularly among the Malay and Indian women. This is associated with higher FG concentrations in Malay women, and increased risk of emergency caesarean section in Chinese and Indian women.

Maternal Dietary Patterns and Gestational Diabetes Mellitus in a Multi-Ethnic Asian Cohort: The GUSTO Study

Gestational Diabetes Mellitus (GDM) is associated with an increased risk of perinatal morbidity and long term health issues for both the mother and offspring. Previous research has demonstrated associations between maternal diet and GDM development, but evidence in Asian populations is limited. The objective of our study was to examine the cross-sectional relationship between maternal dietary patterns during pregnancy and the risk of GDM in a multi-ethnic Asian cohort. Maternal diet was ascertained using 24-h dietary recalls from participants in the Growing up in Singapore towards healthy outcomes (GUSTO) study—a prospective mother-offspring cohort, and GDM was diagnosed according to 1999 World Health Organisation guidelines. Dietary patterns were identified using factor analysis, and multivariate regression analyses performed to assess the association with GDM. Of 909 participants, 17.6% were diagnosed with GDM. Three dietary patterns were identified: a vegetable-fruit-rice-based-diet, a seafood-noodle-based-diet and a pasta-cheese-processed-meat-diet. After adjusting for confounding variables, the seafood-noodle-based-diet was associated with a lower likelihood of GDM (Odds Ratio (95% Confidence Interval)) = 0.74 (0.59, 0.93). The dietary pattern found to be associated with GDM in our study was substantially different to those reported previously in Western populations.

Determinants of Breastfeeding Practices and Success in a Multi-Ethnic Asian Population.

BACKGROUNDnMany countries in Asia report low breastfeeding rates and the risk factors for early weaning are not well studied. We assessed the prevalence, duration, and mode of breastfeeding (direct or expressed) among mothers of three Asian ethnic groups.nnnMETHODSnParticipants were 1,030 Singaporean women recruited during early pregnancy. Data collected included early breastfeeding experiences, breastfeeding duration, and mode of breastfeeding. Full breastfeeding was defined as the intake of breast milk, with or without water. Cox regression models were used to identify factors associated with discontinuation of any and full breastfeeding. Logistic regression analyses assessed the association of ethnicity with mode of breastfeeding.nnnRESULTSnAt 6xa0months postpartum, the prevalence of any breastfeeding was 46 percent for Chinese mothers, 22 percent for Malay mothers, and 41 percent for Indian mothers; prevalence of full breastfeeding was 11, 2, and 5 percent, respectively. More Chinese mothers fed their infants expressed breast milk, instead of directly breastfeeding them, compared with the other two ethnic groups. Duration of any and full breastfeeding were positively associated with breastfeeding a few hours after birth, higher maternal age and education, and negatively associated with irregular breastfeeding frequency and being shown how to breastfeed. Adjusting for maternal education, breastfeeding duration was similar in the three ethnic groups, but ethnicity remained a significant predictor of mode of breastfeeding.nnnCONCLUSIONSnThe low rates and duration of breastfeeding in this population may be improved with breastfeeding education and support, especially in mothers with lower education. Further work is needed to understand the cultural differences in mode of feeding and its implications for maternal and infant health.

Pre- and Post-Natal Maternal Depressive Symptoms in Relation with Infant Frontal Function, Connectivity, and Behaviors.

This study investigated the relationships between pre- and early post-natal maternal depression and their changes with frontal electroencephalogram (EEG) activity and functional connectivity in 6- and 18-month olds, as well as externalizing and internalizing behaviors in 24-month olds (n = 258). Neither prenatal nor postnatal maternal depressive symptoms independently predicted neither the frontal EEG activity nor functional connectivity in 6- and 18-month infants. However, increasing maternal depressive symptoms from the prenatal to postnatal period predicted greater right frontal activity and relative right frontal asymmetry amongst 6-month infants but these finding were not observed amongst 18-month infants after adjusted for post-conceptual age on the EEG visit day. Subsequently increasing maternal depressive symptoms from the prenatal to postnatal period predicted lower right frontal connectivity within 18-month infants but not among 6-month infants after controlling for post-conceptual age on the EEG visit day. These findings were observed in the full sample and the female sample but not in the male sample. Moreover, both prenatal and early postnatal maternal depressive symptoms independently predicted children’s externalizing and internalizing behaviors at 24 months of age. This suggests that the altered frontal functional connectivity in infants born to mothers whose depressive symptomatology increases in the early postnatal period compared to that during pregnancy may reflect a neural basis for the familial transmission of phenotypes associated with mood disorders, particularly in girls.

Eye size and shape in newborn children and their relation to axial length and refraction at 3 years

To determine if eye size and shape at birth are associated with eye size and refractive error 3 years later.

A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

BackgroundHypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy.MethodsA cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2.DiscussionThe proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders.

ANXIETY AND DEPRESSION DURING PREGNANCY AND TEMPERAMENT IN EARLY INFANCY: FINDINGS FROM A MULTI-ETHNIC, ASIAN, PROSPECTIVE BIRTH COHORT STUDY

Maternal antenatal mood is associated with negative infant temperament. This link has not been substantiated in Asian populations. We evaluated the association between antenatal maternal mood and infant temperament among Asian mother-infant pairs. Antenatal maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale (J. Cox, J. Holden, & R. Sagovsky, 1987) and the State-Trait Anxiety Inventory (C. Spielberger, R. Gorsuch, R. Lushene, P. Vagg, & G. Jacobs, 1983), respectively, at 26 weeks of pregnancy and 3 months postnatally. Infant temperament was evaluated with the Early Infant Temperament Questionnaire (B. Medoff-Cooper, W.B. Carey, & S.C. McDevitt, 1993) at 3 months. Factor analysis was performed to extract culturally relevant categories of temperamental traits. Linear regression was performed to examine the influences of antenatal maternal mood on the factor-model-derived infant temperament. Of the 609 mothers, 11% met risk criteria for depression, 17% for state-anxiety, and 19% for trait-anxiety during pregnancy. Factor analysis yielded three infant temperament factors: Emotionality and Attentional Regulation, Sensory Reactivity, and Regularity and Motor Expression, Cronbachs αs = 0.613, 0.712, and 0.752, respectively. Maternal antenatal state-anxiety, p < .001, and trait anxiety, p = .005, were associated with negative emotionality and poor attentional regulation, especially among Chinese, whereas depression was not, p = .090. There was an association between maternal antenatal anxiety and negative infant temperamental traits in this Asian sample.

Demographic Characteristics, Health Behaviors Before and During Pregnancy, and Pregnancy and Birth Outcomes in Mothers with Different Pregnancy Planning Status

Studies on pregnancy intentions and their consequences have yielded mixed results. Here, we comprehensively analyzed the maternal characteristics, health behaviors before and during pregnancy, as well as pregnancy and birth outcomes, across three different pregnancy planning status in 861 women participating in an ongoing Asian mother-offspring cohort study. At 26–28xa0weeks’ gestation, the women’s intention and enthusiasm toward their pregnancy were used to classify their pregnancy into planned or unplanned, and unplanned pregnancy was further subdivided into mistimed or unintended. Data on maternal characteristics, health behaviors, and pregnancy outcomes up to that stage were recorded. After delivery, birth outcomes of the offspring were recorded. Linear and logistic regression analyses were performed. Overall, 56xa0% had a planned pregnancy, 39xa0% mistimed, and 5xa0% unintended. Compared to women who planned their pregnancy, women with mistimed pregnancy had higher body mass index and were more likely to have cigarette smoke exposure and less likely to have folic acid supplementation. At 26–28xa0weeks’ gestation, unintended pregnancy was associated with increased anxiety. Neonates of mistimed pregnancy had shorter birth length compared to those of planned pregnancy, even after adjustment for maternal baseline demographics. These findings suggest that mothers who did not plan their pregnancy had less desirable characteristics or health behaviors before and during pregnancy and poorer pregnancy and birth outcomes. Shorter birth length in mistimed pregnancy may be attributed to maternal behaviors before or in the early stages of pregnancy, therefore highlighting the importance of preconception health promotion and screening for women of child-bearing age.