The association of maternal vitamin D status with infant birth outcomes, postnatal growth and adiposity in the first 2 years of life in a multi-ethnic Asian population: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population.

Caffeine intake interacts with Asian gene variants in Parkinson's disease: a study in 4488 subjects.

Background: Caffeine intake reduces risk of Parkinson's disease (PD), but the interaction with genes is unclear. The interaction of caffeine with genetic variants in those at high PD risk has healthcare importance. We investigate interactions of caffeine intake with risk variants found in Asians, and determine PD risk estimates in caffeine-drinkers carrying these variants. Methods: PD patients and controls without neurological disorders were included. Caffeine intake was assessed using a validated evaluation tool. Leucine rich repeat kinase 2 (LRRK2) risk variants were genotyped. Statistical analysis was conducted with logistic regression models. Gene-caffeine interactions were quantified using attributable proportion (AP) due to interaction (positive interaction defined as AP >0). Findings: 5100 subjects were screened and 4488 subjects (1790 PD, 2698 controls) with genetic data of at least one LRRK2 variant were included. Risk-variant-carriers who were non-caffeine-drinkers had increased PD odds compared to wildtype carriers who were caffeine-drinkers for G2385R [OR 8.6 (2.6-28.1) p < 0.001; AP = 0.71], R1628P [OR 4.6 (1.6-12.8) p = 0.004; AP = 0.50] and S1647T [OR 4.0 (2.0-8.1) p < 0.001; AP = 0.55] variants. Interpretation: Caffeine intake interacts with LRRK2 risk variants across three different groups of gene carriers. Asymptomatic risk-variant-carriers who are non-caffeine-drinkers have four to eight times greater PD risk compared to wildtype-caffeine-drinkers. Lifestyle modifications to mitigate PD risk in asymptomatic healthy risk variant carriers have potential roles in our Asian cohort. Funding: This study was supported by the National Medical Research Council (STaR and PD OF LCG 000207 grants) and Duke-NUS Medical School.

Multiple System Atrophy (MSA) and smoking: a meta-analysis and mechanistic insights.

BACKGROUND: The association between cigarette smoking and multiple system atrophy (MSA) has been debated. We conducted a systematic review and a meta-analysis to investigate this link. RESULTS: We identified 161 articles from database searching and bibliographic review. Five case-control studies satisfied the inclusion and exclusion criteria, and 435 and 352 healthy controls and MSA patients were examined. The prevalence of MSA amongst ever smokers was lower compared to never smokers (aOR=0.57; 95% CI, 0.29-1.14), although this result did not reach statistical significance. This was also observed for current and former smokers, with a stronger association for current smokers (aOR=0.63 vs aOR=0.96). CONCLUSIONS: There is a suggestion that smoking protects against MSA. Prospective studies in larger patient cohorts are required to further evaluate the cause-effect relationship and functional studies in cellular and animal models will provide mechanistic insights on their potential etiologic links. METHODS: PubMed and Cochrane Library were searched from inception to July 7, 2019 to identify case-control studies that analyzed smoking as an environmental risk or protective factor for MSA. Two authors independently extracted data and performed risk-of-bias and quality assessment. The random-effects model was assumed to account for between-study variance when pooling the crude and adjusted odds ratios.

Etiologic links between environmental and lifestyle factors and Essential tremor.

Essential tremor (ET) is one of the most common adult movement disorders, characterized by clinical tremor and other nonmotor symptoms. It is a progressive disease that shares features with other neurodegenerative diseases. ET is a complex disease with both genetic and environmental underpinnings. While genetic forms of ET are well recognized, the role of environmental and lifestyle factors in ET has been debated. Studies suggest that exposure to neurotoxic compounds such as ß-carboline alkaloids and ethanol are potential risk factors for ET, while antioxidant intake may be protective. In addition, smoking acts as a protective factor in ET, parallel to its effects in other neurological diseases. New evidence points to pesticide and lead exposure as potential risk factors. There is growing evidence to suggest that environmental and lifestyle factors play a role in ET but additional research is needed in order to completely understand their cause and effect association. There is also a need for larger case-control and prospective cohort studies across different populations to further evaluate the etiological importance of these factors in ET.

Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with emerging evidence that it is associated with retinal ganglion cell loss; however, few data exist to establish this association. OBJECTIVE: To determine whether macular ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL), as quantitatively measured by non-invasive in vivo spectral-domain optical coherence tomography (SD-OCT), are altered in patients with AD and mild cognitive impairment (MCI). METHODS: Patients with AD and MCI were recruited from dementia/memory clinics, and cognitively normal controls were selected from the Singapore Epidemiology of Eye Disease program. SD-OCT (Cirrus HD-OCT, software version 6.0.2, Carl Zeiss Meditec Inc, Dublin, CA) was used to measure the GC-IPL and RNFL thicknesses. RESULTS: Compared with cognitively normal controls (n = 123), patients with AD (n = 100) had significantly reduced GC-IPL thicknesses in all six (superior, superonasal, inferonasal, inferior, inferotemporal, and superotemporal) sectors (mean differences from -3.42 to -4.99 µm, all p < 0.05) and reduced RNFL thickness in superior quadrant (-6.04 µm, p = 0.039). Patients with MCI (n = 41) also had significantly reduced GC-IPL thicknesses compared with controls (mean differences from -3.62 to -5.83 µm, all p < 0.05). Area under receiver operating characteristic curves of GC-IPL were generally higher than that of RNFL to discriminate AD and MCI from the controls. CONCLUSIONS: Our data strengthens the link between retinal ganglion cell neuronal and optic nerve axonal loss with AD, and suggest that assessment of macular GC-IPL can be a test to detect neuronal injury in early AD and MCI.

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

OBJECTIVE: Studies 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. METHOD: At 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. RESULTS: In adjusted regression analyses (n = 698), lower plasma total omega-3 PUFA concentrations (ß = -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 (ß = 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. CONCLUSIONS: No 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01174875.