Female adiposity and time-to-pregnancy: a multiethnic prospective cohort.

STUDY QUESTION: Are higher overall and central adiposity associated with reduced fecundability, measured by time-to-pregnancy (TTP), in Asian women? SUMMARY ANSWER: Higher overall adiposity, but not central adiposity, was associated with longer TTP in Asian women. WHAT IS KNOWN ALREADY: High body mass index (BMI) has been associated with a longer TTP, although the associations of body composition and distribution with TTP are less clear. There are no previous studies of TTP in Asian women, who have a relatively higher percentage of body fat and abdominal fat at relatively lower BMI. STUDY DESIGN, SIZE, DURATION: Prospective preconception cohort using data from 477 Asian (Chinese, Malay and Indian) women who were planning to conceive and enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) study, 2015-2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women's mean age was 30.7 years. Overall adiposity was assessed by BMI, sum of 4-site skinfold thicknesses (SFT) and total body fat percentage (TBF%, measured using air displacement plethysmography); central adiposity was assessed by waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and A body Shape Index (ABSI). Pregnancy occurring within one year from recruitment was ascertained by ultrasonography. Those who did not conceive within one year of recruitment, were lost to follow-up, or initiated fertility treatment were censored. TTP was measured in cycles. Discrete-time proportional hazards models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) for each anthropometric measure in association with fecundability, adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to women with a normal BMI of 18.5-22.9 kg/m2, women with higher BMI of 23-27.4 and ≥27.5 kg/m2 showed lower FR of 0.66 (95% CI 0.45, 0.97) and 0.53 (0.31, 0.89), respectively. Compared to women in the lowest quartile of SFT (25-52.9 mm), those in the highest quartile of ≥90.1 mm showed lower FR of 0.58 (95% CI 0.36, 0.95). Compared to women in the lowest quartile of TBF% (13.6-27.2%), those in the upper two quartiles of 33.0-39.7% and ≥39.8% showed lower FR of 0.56 (95% CI 0.32, 0.98) and 0.43 (0.24, 0.80), respectively. Association of high BMI with reduced fecundability was particularly evident among nulliparous women. Measures of central adiposity (WC, WHR, WHtR, ABSI) were not associated with fecundability. LIMITATIONS REASONS FOR CAUTION: Small sample size could restrict power of analysis.The analysis was confined to planned pregnancies, which could limit generalizability of findings to non-planned pregnancies, estimated at around 44% in Singapore. Information on the date of last menstrual period for each month was not available, hence the accuracy of self-reported menstrual cycle length could not be validated, potentially introducing error into TTP estimation. Measures of exposures and covariates such as cycle length were not performed repeatedly over time; cycle length might have changed during the period before getting pregnant. WIDER IMPLICATIONS OF THE FINDINGS: Other than using BMI as the surrogate measure of body fat, we provide additional evidence showing that higher amounts of subcutaneous fat that based on the measure of SFT at the sites of biceps, triceps, suprailiac and subscapular, and TBF% are associated with longer TTP. Achieving optimal weight and reducing total percentage body fat may be a potential intervention target to improve female fertility. The null results observed between central adiposity and TTP requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S): This research is supported by Singapore National Research Foundation under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health's National Medical Research Council, (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore. Y.S.C., K.M.G., F.Y. and Y.S.L. have received reimbursement to speak at conferences sponsored by companies selling nutritional products. Y.S.C., K.M.G. and S.Y.C. are part of an academic consortium that has received research funding from Abbott, Nutrition, Nestle and Danone. Other authors declared no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Effect of 12-month intervention with lipid-based nutrient supplement on the physical activity of Malawian toddlers: a randomised, controlled trial.

Physical activity is beneficial for children's well-being. The effect of dietary supplementation on children's physical activity in food-insecure areas remains little studied. We examined the effects of a lipid-based nutrient supplement (LNS) on children's objectively measured physical activity in a randomised, controlled, outcome-assessor-blinded trial. Mothers of the children received one capsule daily of Fe-folic acid (IFA), one capsule containing eighteen micronutrients (MMN) or one 20 g sachet of LNS (containing twenty-two MMN, protein, carbohydrates, essential fatty acids and 494 kJ (118 kcal)) during pregnancy and for 6 months thereafter. Children in the IFA and MMN groups received no supplementation, and these groups were collapsed into a single control group; children in the LNS group received 20 g LNS from 6 to 18 months. We measured physical activity with accelerometers over 1 week at 18 months. The main outcome was mean vector magnitude counts/15 s. Of the 728 children at the beginning of child intervention at 6 months, 570 (78 %) provided sufficient data for analysis. The mean accelerometer counts for the 190 children in the LNS group and for the 380 children in the control group were 303 (sd 59) and 301 (sd 56), respectively (P for difference=0·65). LNS, given to mothers during pregnancy and 6 months postpartum and to their infants from 6 to 18 months of age, did not increase physical activity among 18-month-old children.

Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

PURPOSE: Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. METHODS: English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. RESULTS: Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. CONCLUSION: Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

Effect of 12-month intervention with lipid-based nutrient supplements on physical activity of 18-month-old Malawian children: a randomised, controlled trial.

BACKGROUND/OBJECTIVES: This study measured the effects of dietary supplementation with lipid-based nutrient supplements (LNSs) on 18-month-old children's physical activity. SUBJECTS/METHODS: In a randomised, controlled, outcome-assessor blinded trial 1932 six-month-old children from Malawi received one of five interventions daily from 6-18 months of age: 10-g milk-LNS, 20-g milk-LNS, 20-g non-milk-LNS, 40-g milk-LNS or 40-g non-milk-LNS, or received no intervention in the same period (control). The control group received delayed intervention with corn-soy blend from 18-30 months. Physical activity was measured over 1 week by ActiGraph GT3X+ accelerometer at 18 months. Main outcome was mean vector magnitude accelerometer counts/15 s. Analyses were restricted to children with valid accelerometer data on at least 4 days with minimum 6 h of wearing time per day. RESULTS: Of the 1435 children recruited to this substudy, 1053 provided sufficient data for analysis. The mean (s.d.) vector magnitude accelerometer counts in the total sample were 307 (64). The difference (95% CI) in mean accelerometer counts, compared with the control group, was 8 (-6 to 21, P=0.258) in 10-g milk-LNS, 3 (-11 to 17, P=0.715) in 20-g milk-LNS, 5 (-8 to 19, P=0.445) in 20-g non-milk-LNS, 10 (-3 to 23, P=0.148) in 40-g milk-LNS and 2 (-12 to 16, P=0.760) in 40-g non-milk-LNS groups. CONCLUSIONS: Provision of 10-40 g doses of LNS daily for 12 months did not increase physical activity of Malawian toddlers.

The Functional Living Index-Cancer is a reliable and valid instrument in Chinese cancer patients.

PURPOSE: To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients. METHODS: The English FLIC was translated into Traditional Chinese by the standard forward-backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample. RESULTS: We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy. CONCLUSIONS: The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.

Feasibility and validity of the ActiGraph GT3X accelerometer in measuring physical activity of Malawian toddlers.

AIM: To test the feasibility and validity of the ActiGraph GT3X accelerometer in measuring physical activity of rural Malawian toddlers. METHODS: Fifty-six children aged 16.0-18.5 months wore the accelerometer on their right hip for 7 days. We analysed days with a minimum of 600 min of wear time, excluding night time and periods when the unit registered zero for 20 consecutive minutes. The first and last days were excluded as they were incomplete. Accelerometer counts were compared with coded free play video recordings to define median accelerometer counts for sedentary, light, moderate and vigorous activity. Count cut points were defined for moderate to vigorous physical activity, with predictive validity assessed using a second set of video recordings. RESULTS: Median wear time was 797 min/day, with 79% of participants completing at least four eligible days. Accelerometer counts were significantly higher for observed moderate to vigorous physical activity, than lighter activity, with cut points of 208 counts/15 sec for vector magnitude and 35 counts/15 sec for vertical axis, showing sensitivity of 94.2% and 84.1% and specificity of 90.9% and 84.6%, respectively. CONCLUSION: The accelerometer proved a feasible and valid method of assessing physical activity among Malawian toddlers.

Serotype-specific avidity is achieved following a single dose of the 7-valent pneumococcal conjugate vaccine, and is enhanced by 23-valent pneumococcal polysaccharide booster at 12 months.

AIM: To evaluate whether the avidity of serotype-specific IgG to pneumococcal serotypes is enhanced by an increased number of doses of the 7-valent pneumococcal conjugate vaccine (PCV) in infancy or by a 12 month 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster, and/or subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. METHODS: Fijian infants aged 6 weeks were recruited, stratified by ethnicity and randomized to 8 groups to receive 0, 1, 2, or 3 doses of PCV, with or without 23vPPS at 12 months. All children received mPPS at 17 months of age. Avidity of serotype-specific IgG for PCV serotypes in the first 12 months and for all 23vPPS serotypes thereafter was assessed by EIA after sodium thiocyanate elution. RESULTS: At one month post primary series, the 2 and 3 PCV dose groups demonstrated similar avidity, with the single dose group tending to have lower avidity. However, by age 9 months, the single dose group had similar avidity to the 2 and 3 PCV groups for most serotypes. The 23vPPS booster enhanced affinity maturation for most serotypes and this was most marked in those groups that received a single PCV dose. There was little further increase following the mPPS. CONCLUSIONS: By 9 months of age, similar avidity can be induced following one, 2 or 3 doses of PCV. A 23vPPS booster at 12 months enhanced affinity maturation with an increase in antibody avidity for most serotypes. Subsequent re-challenge with mPPS at 17 months did not further enhance the avidity of serotype-specific response in the 12 month 23vPPS groups.

Opsonophagocytic activity following a reduced dose 7-valent pneumococcal conjugate vaccine infant primary series and 23-valent pneumococcal polysaccharide vaccine at 12 months of age.

Opsonophagocytic activity (OPA) was measured following reduced infant doses of 7-valent pneumococcal conjugate vaccine (PCV-7) with or without 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months, and subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. Fijian infants were randomized to receive 0, 1, 2, or 3 PCV-7 doses. Half received PPV-23 at 12 months and all received mPPS at 17 months. OPA was performed on up to 14 serotypes. Three and 2 PCV-7 doses resulted in similar OPA for most PCV-7 serotypes up to 9 months and for half of the serotypes at 12 months. A single dose improved OPA compared with the unvaccinated group. PPV-23 significantly improved OPA for all serotypes tested but in general, was associated with diminished responses following re-challenge.

Pneumococcal nasopharyngeal carriage following reduced doses of a 7-valent pneumococcal conjugate vaccine and a 23-valent pneumococcal polysaccharide vaccine booster.

This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.

A simple approach to the estimation of incidence rate difference.

The incidence rate difference (IRD) is a parameter of interest in many medical studies. For example, in vaccine studies, it is interpreted as the vaccine-attributable reduction in disease incidence. This is an important parameter, because it shows the public health impact of an intervention. The IRD is difficult to estimate for various reasons, especially when there are quantitative covariates or the duration of follow-up is variable. In this paper, the authors propose an approach based on weighted least-squares regression for estimating the IRD. It is very easy to implement because it boils down to performing ordinary least-squares regression analysis of transformed variables. Furthermore, if the outcome events are repeatable, the authors propose that data on all events be analyzed instead of first events only. Four versions of the Huber-White robust standard error are considered for statistical inference. Simulation studies are used to examine the performance of the proposed method. In a variety of scenarios simulated, the method provides an unbiased estimate for the IRD, and the empirical coverage proportion of the 95% confidence interval is very close to the nominal level. The method is illustrated with data from a vaccine trial carried out in the Gambia in 2001-2004.

Spatial analysis of tuberculosis in an urban west African setting: is there evidence of clustering?

OBJECTIVES: To describe the pattern of tuberculosis (TB) occurrence in Greater Banjul, The Gambia with Geographical Information Systems (GIS) and Spatial Scan Statistics (SaTScan) and to determine whether there is significant TB case clustering. METHODS: In Greater Banjul, where 80% of all Gambian TB cases arise, all patients with TB registered at chest clinics between March 2007 and February 2008 were asked to participate. Demographic, clinical characteristics and GPS co-ordinates for the residence of each consenting TB case were recorded. A spatial scan statistic was used to identify purely spatial and space-time clusters of tuberculosis among permanent residents. RESULTS: Of 1145 recruited patients with TB, 84% were permanent residents with 88% living in 37 settlements that had complete maps available down to settlement level. Significant high- and low-rate spatial and space-time clusters were identified in two districts. The most likely cluster of high rate from both the purely spatial analysis and the retrospective space-time analysis were from the same geographical area. A significant secondary cluster was also identified in one of the densely populated areas of the study region. CONCLUSIONS: There is evidence of significant clustering of TB cases in Greater Banjul, The Gambia. Systematic use of cluster detection techniques for regular TB surveillance in The Gambia may aid effective deployment of resources. However, passive case detection dictates that community-based active case detection and risk factor surveys would help confirm the presence of true clusters and their causes.

Safety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy.

Fijian infants aged 6 weeks were stratified by ethnicity and randomized to receive 0, 1, 2, or 3 PCV-7 doses with or without the 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months. Strong booster effects for all 7 PCV-7 serotypes were elicited, and for 4/7 serotypes these responses were highest in the single PCV-7 group. There were fourfold rises in GMC for all non-PCV-7 serotypes. By 17 months the PPV-23 group still had significantly higher GMC (each p<0.001) for all serotypes. The PPV-23 was well tolerated and induced excellent responses for all serotypes which were greatest in the single PCV-7 group.

Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age, a randomized controlled trial.

BACKGROUND: To evaluate the immunological impact of the 23-valent pneumococcal polysaccharide vaccine (23vPPS) at 12 months, for children who have received zero to three infant doses of seven-valent pneumococcal conjugate vaccine (PCV), on responses to a subsequent exposure to a small dose of 23vPPS (mPPS). METHODS: Five hundred and fifty-two Fijian infants were stratified by ethnicity and randomized into eight groups to receive zero, one, two, or three PCV doses at 14 weeks, six and 14 weeks, or six, ten, and 14 weeks. Within each group, half received 23vPPS at 12 months and all received mPPS at 17 months. Sera were taken prior and one month post-mPPS. FINDINGS: By 17 months, geometric mean antibody concentrations (GMC) to all 23 serotypes in 23vPPS were significantly higher in children who had received 23vPPS at 12 months compared to those who had not. Post-mPPS, children who had not received the 12 month 23vPPS had a significantly higher GMC for all PCV serotypes compared with those who had (each p<0.02). For the non-PCV serotypes, children who had not received the 12 month 23vPPS had significantly higher GMC for six of 16 non-PCV serotypes (7F, 9N, 12F, 19A, 22F, 33F) than those who did (each p<0.02). After adjusting for the pre-mPPS level, exposure to 23vPPS was associated with a lower response to mPPS for all serotypes (each p<0.001). INTERPRETATION: Despite higher antibody concentrations at 17 months in children who had received 23vPPS at 12 months, the response to a re-challenge was poor for all 23 serotypes compared to children who had not received the 12 month 23vPPS.

Continuation of linear growth failure and its association with cognitive ability are not dependent on initial length-for-age: a longitudinal study from 6 months to 11 years of age.

AIM: To examine linear growth and its association with cognitive ability at age 11 years among full-term singletons with varying degree of stunting or without stunting at age 6 months. METHODS: A total of 1516 Filipino term-born singletons were followed bimonthly from age 6 to 24 months and took cognitive and academic achievement tests at 11 years. The tests were factor-analysed to give a summary cognitive ability score. Linear regression was used to examine associations and adjust for covariates. RESULTS: Mean height-for-age Z-score (HAZ) was -1.0 at age 6 months and -2.4 at 24 months. HAZ at 6 months, change in HAZ from 6 to 24 months and change in HAZ from 24 months to 11 years were positively associated with cognitive ability at 11 years (each p < 0.001). The association was seen in all categories of HAZ at 6 months. CONCLUSION: In this setting where linear growth retardation was common, association between linear growth after age 6 months and cognitive ability in adolescence was not dependent on initial HAZ. Prevention of growth stunting may benefit all children regardless of their initial HAZ.

Prevalent infectious tuberculosis in Harare, Zimbabwe: burden, risk factors and implications for control.

SETTING: Harare's high density suburbs. OBJECTIVES: To investigate the burden, duration and risk factors for prevalent tuberculosis (TB) and explore potential control strategies. METHODS: Randomly selected adults had TB culture, symptom screen and human immunodeficiency virus (HIV) serology. Prevalent TB was defined as undiagnosed or still culture-positive. Notification data and HIV prevalence in TB out-patients were used to estimate duration of infectiousness (prevalence/estimated incidence). RESULTS: Among 10 092 participants, 40 (0.40%, 95%CI 0.28-0.54) had prevalent smear-positive TB. HIV (adjusted odds ratio [aOR] 3.1, 95%CI 1.6-6.3, population attributable fraction [PAF] 33%), male sex (aOR 3.1, 95%CI 1.5-6.4, PAF 40%), and overcrowding (PAF 34%) were significant risk factors, with past TB treatment significant for HIV-negative participants only (PAF 7%). Recent household TB contact was not significant (PAF 10%). HIV prevalence was 21.1%; 76.9% of HIV-positive participants were previously untested. Duration of infectiousness was at least 18 weeks in HIV-positive and approximately 1 year in HIV-negative patients. CONCLUSIONS: Overcrowding, male sex and HIV infection were major risk factors for prevalent smear-positive TB. Reducing diagnostic delay may have greater potential to improve the control of prevalent TB than interventions targeted at household contacts, TB treatment outcomes, or TB-HIV interventions under current levels of awareness of HIV status.

Immunogenicity following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine.

The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received zero, one, two, or three doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following three PCV doses, geometric mean concentration (GMC) to all seven serotypes were > or = 1.0 microg/mL, and >85% of children achieved antibody levels > or = 0.35 microg/mL at 18 weeks. Following two doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with three doses. Following a single dose, significant responses were seen for all serotypes post-primary series compared with the unvaccinated. By 12 months, differences between two and three doses persisted for serotype 14 only. Although GMC following three doses are higher than after two doses, the differences were small. A single dose may offer some protection for most serotypes.

Three estimates of the association between linear growth failure and cognitive ability.

OBJECTIVES: To compare three estimators of association between growth stunting as measured by height-for-age Z-score and cognitive ability in children, and to examine the extent statistical adjustment for covariates is useful for removing confounding due to socio-economic status. METHODS: Three estimators, namely random-effects, within- and between-cluster estimators, for panel data were used to estimate the association in a survey of 1105 pairs of siblings who were assessed for anthropometry and cognition. Furthermore, a 'combined' model was formulated to simultaneously provide the within- and between-cluster estimates. RESULTS: Random-effects and between-cluster estimators showed strong association between linear growth and cognitive ability, even after adjustment for a range of socio-economic variables. In contrast, the within-cluster estimator showed a much more modest association: For every increase of one Z-score in linear growth, cognitive ability increased by about 0.08 standard deviation (P < 0.001). The combined model verified that the between-cluster estimate was significantly larger than the within-cluster estimate (P = 0.004). CONCLUSION: Residual confounding by socio-economic situations may explain a substantial proportion of the observed association between linear growth and cognition in studies that attempt to control the confounding by means of multivariable regression analysis. The within-cluster estimator provides more convincing and modest results about the strength of association.