scholarly journals Identifying Mediators Underlying the Intergenerational Cycle of Obesity: A Causal Mediation Analysis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1655-1655
Author(s):  
Tiange Liu ◽  
Noel Mueller ◽  
Sara Benjamin-Neelon
Keyword(s):  
Birth Weight ◽  
Gestational Age ◽  
Mediation Analysis ◽  
Mediation Effect ◽  
Delivery Mode ◽  
Z Score ◽  
Causal Mediation ◽  
Causal Mediation Analysis ◽  
Intergenerational Cycle ◽  
Infant Birth

Abstract Objectives To understand the mechanisms of the intergenerational cycle of obesity between women and offspring. Methods We recruited pregnant women into the Nurture study (North Carolina, US) and prospectively followed up their offspring until 1 year of age from 2013–2017. The exposure of this analysis was self-reported maternal pre-pregnancy body mass index (BMI) calculated using weight and height. The outcome was researcher-measured infant weight-for-length z-score (WFLZ) at 1 year, calculated based on the WHO Child Growth Standards. We conducted a causal mediation analysis to estimate the average mediation effect of each mediator, including gestational weight gain (GWG), delivery mode, infant birth weight-for-gestational age z-score, and duration of breastfeeding. We adjusted for maternal age, race, parity, smoking status prior to pregnancy, education, household income, food security, and gestational age (when not examining birth weight-for-gestational age z-score). Results We included 380 dyads. Among mothers, there were 65.5% black, 22.6% white, and 11.8% other/multiple race. Prior to pregnancy, 19.5% were overweight and 45.3% were obese. A 10 kg/m2 increment of pre-pregnancy BMI was associated with 0.16 (95% CI: 0.06, 0.27) higher infant WFLZ at 1 year. When examining mediators individually, birth weight-for-gestational age z-score had a statistically significant mediation effect (0.05, 95% CI: 0.02, 0.08), corresponding to 30.2% (95% CI: 20.0%, 62.9%) of the total effect of pre-pregnancy BMI on infant WFLZ. The average mediation effect by GWG was −0.04 (95% CI: −0.08, 0.00), by cesarean delivery was 0.01 (95% CI: −0.01, 0.04), and by breastfeeding duration was 0.02 (95% CI: −0.01, 0.06). Treating mediators as potential confounders for one another did not alter the results. Conclusions Infant birth weight-for-gestational age z-score mediated, in part (∼30%), the relation between maternal pre-pregnancy BMI and infant WFLZ at 1 year. In contrast, GWG, delivery mode, and breastfeeding were not mediators in our sample. This highlights the importance of primordial prevention of maternal obesity, ideally prior to conception, to mitigate the intergeneration cycle of obesity. Research exploring the potential mediating role of factors such as the gut microbiome is needed. Funding Sources The National Institutes of Health.

scholarly journals Micronutrient Supplementation During Pregnancy, Birth Weight and Neonatal Mortality in Uganda: A Causal Mediation Analysis

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 912-912
Author(s):  
Paddy Ssentongo ◽  
Djibril Ba ◽  
Claudio Fronterre ◽  
Jessica Ericson ◽  
Alison Gernand ◽  
...  
Keyword(s):  
Birth Weight ◽  
Neonatal Mortality ◽  
Mediation Analysis ◽  
Causal Effect ◽  
Significant Risk ◽  
Born Term ◽  
Deficiency Anemia ◽  
Term Infants ◽  
Causal Mediation ◽  
Causal Mediation Analysis

Abstract Objectives Low birth weight (LBW) is a significant risk factor for death in the first 30 days of life. Maternal iron-deficiency anemia during pregnancy increases the risk of LBW. We aimed to explore whether antenatal IFA supplementation reduces neonatal mortality in Uganda and to examine if the association of IFA supplementation with neonatal death is mediated through LBW. Methods We used a retrospective birth cohort from the 2016 population-based Uganda demographic and health survey. We examined information on neonatal survival, sociodemographic and intake of IFA supplementation of 9203 women and 17,202 live-born, term infants ≤ 5 y before the survey. Birth weight was categorized as very low (VLBW, defined as < 1500 g or very small baby as perceived by the mother), low (LBW, birth weight of < 2500 g or baby smaller than average as perceived by the mother), and normal (NBW, ≥ 2500 g or an average and larger baby as perceived by the mother). Causal mediation analysis (CMA) treating the birth weight as a mediator was conducted to measure the direct and indirect effects of IFA on neonatal mortality (death of a live-born infant during the first 30 d of life). Results IFA supplementation was reported in 89% of women. The prevalence of LBW and VLBW was 21% and 7% respectively. 474 (3%) babies died within the 30 d after birth, 320 (66%) died within the first 24 h and 469 (99%) died within the first week of life (early neonatal mortality). IFA supplementation during pregnancy was independently associated with a 56% reduction in neonatal mortality [(hazard ratio (HR): 0.44; 95% CI 0.31, 0.61); P < 0.0001] and 26% reduction in VLBW (Relative risk (RR): 0.74; 95% CI 0.60, 0.92, P = 0.007). There was a linear dose-response relationship between the category of birth weight and increased neonatal mortality (LBW versus NBW: RR: 1.39 95% CI: 1.05–1.81, P = 0.02, VLBW versus NBW: RR; 3.6: 95% CI: 2.83–4.53, P < 0.0001). CMA showed that 6% of the effect of IFA supplement on reducing neonatal mortality was meditated through reducing the risk of VLBW but not through LBW, and 94% of the causal effect was direct. Conclusions The use of antenatal iron/folic acid supplements during pregnancy is an important intervention to reduce neonatal mortality. These findings indicate that the association is weakly mediated through improved birth weight, and other mediators should be identified in future studies. Funding Sources NIH.

scholarly journals Maternal socioeconomic status and infant mortality with low birth weight as a mediator: an inter-country comparison between Scotland and Denmark using administrative data

2017 ◽  
Vol 1 (1) ◽  
Author(s):  
Yongfu Yu ◽  
Maximiliane Verfuerden ◽  
Pia Hardelid ◽  
Ania Zylbersztejn ◽  
Zeyan Liew ◽  
...  
Keyword(s):  
Socioeconomic Status ◽  
Birth Weight ◽  
Infant Mortality ◽  
Low Birth Weight ◽  
Mediation Analysis ◽  
Causal Mediation ◽  
Prenatal Factors ◽  
Causal Mediation Analysis ◽  
The Uk

ABSTRACT ObjectivesHigher rates of infant mortality in the UK than in the Nordic countries are partly explained by wider socio-economic disparities in the UK. We examined the extent to which low birth weight mediates the association between socioeconomic status (SES) and infant mortality using causal mediation analysis. We used cohorts of live births identified in administrative hospital data for the whole of Scotland and Denmark to explore the contribution of prenatal factors, represented by low birth weight, to differences in infant mortality between the two countries. ApproachWe included live-born children born in Denmark (n=1,432,205) and Scotland (n=1,427,163) from 1981-2004. Follow up was to 12 months of age. Information on deaths in first year of life was obtained through linkage with cause of death registers. We determined the effect of socioeconomic status on all cause infant mortality by comparing the highest and lowest quintiles of area-based deprivation (based on Carstairs score in Scotland) or level of maternal education in Denmark. Causal mediation analysis was used for survival outcomes with adjustment for maternal age at birth, sex, birth year of the child, and records indicating congenital malformation. ResultsDuring the follow-up, there were 8,158(0.57%) deaths in Denmark and 8,271(0.58%) deaths in Scotland. Comparing with the very high SES group, the overall hazard ratios of death for each SES quintile (starting with the lowest) compared with the highest SES quintile were 1.58(95% Confidence interval: 1.47-1.71), 1.40(1.32-1.49),1.25(1.20-1.30), 1.11(1.09-1.14) in Denmark, and 1.50(1.36-1.65),1.35(1.25-1.45),1.22(1.16-1.28),1.10(1.08-1.13) in Scotland. The proportions of excess infant deaths mediated through low birth weight (starting with the lowest) compared with the highest SES quintile were 54.7%, 52.1%, 49.5%, 46.9% in Denmark, and 26.0%, 23.9%, 22.0%, 20.1% in Scotland. ConclusionOur result suggests that SES has similar effects on infant mortality in Denmark and Scotland but more of the effect of SES on infant mortality is mediated through low birth weight in Denmark. Public health preventive strategies for infant mortality in both countries need to address prenatal risk factors for low birth weight. The substantial direct effects of SES on infant mortality seen in Scotland, which were not mediated through low birth weight, may be explained by other birth characteristics or could reflect persisting SES disparities in the care of infants after birth.

scholarly journals Mediation analysis of gestational age, congenital heart defects, and infant birth-weight

2014 ◽  
Vol 7 (1) ◽  
pp. 926 ◽  
Author(s):  
Adane F Wogu ◽  
Christopher A Loffredo ◽  
Ionut Bebu ◽  
George Luta
Keyword(s):  
Birth Weight ◽  
Congenital Heart Defects ◽  
Gestational Age ◽  
Mediation Analysis ◽  
Congenital Heart ◽  
Heart Defects ◽  
Infant Birth

scholarly journals Impact of size at birth and postnatal growth on metabolic and neurocognitive outcomes in prematurely born school-age children

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoo Jinie Kim ◽  
Seung Han Shin ◽  
Eun Sun Lee ◽  
Young Hwa Jung ◽  
Young Ah Lee ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Infants ◽  
Gestational Age ◽  
Growth Velocity ◽  
Postnatal Growth ◽  
School Age ◽  
Z Score ◽  
Neurodevelopmental Outcomes ◽  
Neurocognitive Outcomes ◽  
Size At Birth

AbstractPrematurity, size at birth, and postnatal growth are important factors that determine cardiometabolic and neurodevelopmental outcomes later in life. In the present study, we aimed to investigate the associations between the size at birth and growth velocity after birth with cardiometabolic and neurodevelopmental outcomes in preterm infants. Fifty-six preterm infants born at < 32 weeks of gestation or having a birth weight of < 1500 g were enrolled and categorized into small for gestational age (SGA) and appropriate for gestational age (AGA) groups. Anthropometric and cardiometabolic parameters were assessed at school-age, and the Korean Wechsler Intelligence Scale for Children, fourth edition (K-WISC-IV) was used for assessing the intellectual abilities. The growth velocity was calculated by changes in the weight z-score at each time period. Multivariate analysis was conducted to investigate the associations of growth velocity at different periods with cardiometabolic and neurodevelopmental outcomes. Forty-two (75%) were classified as AGA and 25% as SGA. At school-age, despite the SGA children showing significantly lower body weight, lean mass index, and body mass index, there were no differences in the cardiometabolic parameters between SGA and AGA groups. After adjusting for gestational age, birth weight z-score, weight z-score change from birth to discharge and sex, change in weight z-score beyond 12 months were associated with a higher systolic blood pressure, waist circumference, and insulin resistance. Full-scale intelligent quotient (β = 0.314, p = 0.036) and perceptional reasoning index (β = 0.456, p = 0.003) of K-WISC-IV were positively correlated with postnatal weight gain in the neonatal intensive care unit. Although cardiometabolic outcomes were comparable in preterm SGA and AGA infants, the growth velocity at different time periods resulted in different cardiometabolic and neurocognitive outcomes. Thus, ensuring an optimal growth velocity at early neonatal period could promote good neurocognitive outcomes, while adequate growth after 1 year could prevent adverse cardiometabolic outcomes in preterm infants.

scholarly journals Exact parametric causal mediation analysis for a binary outcome with a binary mediator

2021 ◽  
Author(s):  
Marco Doretti ◽  
Martina Raggi ◽  
Elena Stanghellini
Keyword(s):  
Logistic Regression ◽  
Direct Effect ◽  
Mediation Analysis ◽  
Delta Method ◽  
Binary Outcome ◽  
Effect Decomposition ◽  
Causal Mediation ◽  
Regression Parameters ◽  
Causal Mediation Analysis ◽  
Parametric Expression

AbstractWith reference to causal mediation analysis, a parametric expression for natural direct and indirect effects is derived for the setting of a binary outcome with a binary mediator, both modelled via a logistic regression. The proposed effect decomposition operates on the odds ratio scale and does not require the outcome to be rare. It generalizes the existing ones, allowing for interactions between both the exposure and the mediator and the confounding covariates. The derived parametric formulae are flexible, in that they readily adapt to the two different natural effect decompositions defined in the mediation literature. In parallel with results derived under the rare outcome assumption, they also outline the relationship between the causal effects and the correspondent pathway-specific logistic regression parameters, isolating the controlled direct effect in the natural direct effect expressions. Formulae for standard errors, obtained via the delta method, are also given. An empirical application to data coming from a microfinance experiment performed in Bosnia and Herzegovina is illustrated.

scholarly journals Variable selection for causal mediation analysis using LASSO-based methods

2021 ◽  
pp. 096228022199750
Author(s):  
Zhaoxin Ye ◽  
Yeying Zhu ◽  
Donna L Coffman
Keyword(s):  
Propensity Score ◽  
Indirect Effect ◽  
Adaptive Lasso ◽  
Mediation Effect ◽  
Regularization Methods ◽  
Causal Mediation ◽  
Outcome Information ◽  
Causal Mediation Analysis ◽  
Selection For ◽  
Mimic Iii

Causal mediation effect estimates can be obtained from marginal structural models using inverse probability weighting with appropriate weights. In order to compute weights, treatment and mediator propensity score models need to be fitted first. If the covariates are high-dimensional, parsimonious propensity score models can be developed by regularization methods including LASSO and its variants. Furthermore, in a mediation setup, more efficient direct or indirect effect estimators can be obtained by using outcome-adaptive LASSO to select variables for propensity score models by incorporating the outcome information. A simulation study is conducted to assess how different regularization methods can affect the performance of estimated natural direct and indirect effect odds ratios. Our simulation results show that regularizing propensity score models by outcome-adaptive LASSO can improve the efficiency of the natural effect estimators and by optimizing balance in the covariates, bias can be reduced in most cases. The regularization methods are then applied to MIMIC-III database, an ICU database developed by MIT.

Sign in / Sign up

Export Citation Format

Share Document