Associations of maternal caffeine intake during pregnancy with abdominal and liver fat deposition in childhood

Background: Maternal caffeine intake during pregnancy is associated with an increased risk of childhood obesity. Studies in adults suggest that caffeine intake might also directly affect visceral and liver fat deposition, which are strong risk factors for cardio-metabolic disease. Objective: To assess the associations of maternal caffeine intake during pregnancy with childhood general, abdominal, and liver fat mass at 10 years of age. Methods: In a population-based cohort from early pregnancy onwards among 4770 mothers and children, we assessed maternal caffeine intake during pregnancy and childhood fat mass at age 10 years. Results: Compared with children whose mothers consumed <2 units of caffeine per day during pregnancy, those whose mothers consumed 4-5.9 and ≥6 units of caffeine per day had a higher body mass index, total body fat mass index, android/gynoid fat mass ratio, and abdominal subcutaneous and visceral fat mass indices. Children whose mothers consumed 4-5.9 units of caffeine per day had a higher liver fat fraction. The associations with abdominal visceral fat and liver fat persisted after taking childhood total body fat mass into account. Conclusions: High maternal caffeine intake during pregnancy was associated with higher childhood body mass index, total body fat, abdominal visceral fat, and liver fat. The associations with childhood abdominal visceral fat and liver fat fraction were independent of childhood total body fat. This suggests differential fat accumulation in these depots, which may increase susceptibility to cardio-metabolic disease in later life

Maternal Glucose Concentrations in Early Pregnancy and Cardiometabolic Risk Factors in Childhood

Objective: This study aimed to examine the associations of maternal early-pregnancy glucose and insulin concentrations with offspring cardiometabolic risk factors and fat distribution. Methods: In a population-based prospective cohort study among 3,737 mothers and their children, random maternal glucose and insulin concentrations were measured at a median gestational age of 13.2 (95% range 10.5-17.1) weeks. Childhood fat, blood pressure, and blood concentrations of lipids, glucose, and insulin at the age of 10 years were measured. Results: Higher maternal early-pregnancy glucose and insulin concentrations were associated with a higher risk of childhood overweight, and higher maternal early-pregnancy insulin concentrations were associated with an increased childhood risk of clustering of cardiometabolic risk factors (all P < 0.05). These associations were explained by maternal prepregnancy BMI. Independent of maternal prepregnancy BMI, one SD score (SDS) higher maternal early-pregnancy glucose and insulin concentrations were associated with higher childhood glucose (0.08 SDS, 95% CI: 0.04-0.11) and insulin concentrations (0.07 SDS, 95% CI: 0.03-0.10), but not with childhood blood pressure, lipids, and fat measures. Conclusions: These results suggest that maternal early-pregnancy random glucose and insulin concentrations are associated with childhood glucose a

Second and third trimester fetal ultrasound population screening for risks of preterm birth and small-size and large-size for gestational age at birth: a population-based prospective cohort study

BACKGROUND: Preterm birth, small size for gestational age (SGA) and large size for gestational age (LGA) at birth are major risk factors for neonatal and long-term morbidity and mortality. It is unclear which periods of pregnancy are optimal for ultrasound screening to identify fetuses at risk of preterm birth, SGA or LGA at birth. We aimed to examine whether single or combined second and third trimes

A population-based resource for intergenerational metabolomics analyses in pregnant women and their children: the Generation R Study

INTRODUCTION: Adverse exposures in early life may predispose children to cardio-metabolic disease in later life. Metabolomics may serve as a valuable tool to disentangle the metabolic adaptations and mechanisms that potentially underlie these associations. OBJECTIVES: T

PDT in the Thoracic Cavity: Spectroscopic Methods and Fluence Modeling for Treatment Planning

PDT for the thoracic cavity provides a promising cancer treatment modality, but improvements in treatment planning, particularly in PDT dosimetry, can be made to improve uniformity of light delivery. When a cavity of arbitrary geometry is illuminated, the fluence increases due to multiple-scattered photons, referred to as the Integrating Sphere Effect (ISE). Current pleural PDT treatment protocol at the University of Pennsylvania monitors light fluence (hereafter simply fluence, measured in W/cm2) via seven isotropic detectors sutured at different locations in thoracic cavity of a patient. This protocol monitors light at discrete locations, but does not provide a measurement of fluence for the thoracic cavity as a whole. Current calculation of light fluence includes direct light only and thus does not account for the unique optical properties of each tissue type present, which in turn affects the accuracy of the calculated light distribution in the surrounding tissue and, in turn, the overall cell death and treatment efficacy. Treatment planning for pleural PDT can be improved, in part, by considering the contribution of scattered light, which is affected by the two factors of geometry and in vivo optical properties. We expanded the work by Willem Star in regards to the ISE in a spherical cavity. A series of Monte Carlo (MC) simulations were run for semi-infinite planar, spherical, and ellipsoidal geometries for a range of optical properties. The results of these simulations are compared to theory and numerical solutions for fluence in the cavity and at the cavity-medium boundary. The development via MC simulations offers a general method of calculating the required light fluence specialized to each patient, based on the treatment surface area. The scattered fluence calculation is dependent on in vivo optical properties (μa and μs\u27) of the tissues treated. Diffuse reflectance and fluorescence spectroscopy methods are used to determine the optical properties and oxygenation (reflectance measurements) and drug concentration (fluorescence measurements) of different tissues in vivo, before and after treatment, in patients enrolled the Phase I HPPH study ongoing at the University of Pennsylvania. This work aims to provide the building blocks essential to pleural PDT treatment planning by more accurately calculating the required fluence using a model that accounts for the effects of treatment geometry and optical properties measured in vivo

Critical periods and growth patterns from fetal life onwards associated with childhood insulin levels

Aims/hypothesis: We aimed to identify critical periods and specific longitudinal growth patterns from fetal life onwards associated with childhood insulin and C-peptide levels. Methods: In a prospective population-based cohort study of 4328 children, we repeatedly measured (femur) length and (estimated fetal) weight from the second trimester of fetal life until 6 years of age. BMI was calculated from 6 months onwards. Insulin and C-peptide levels were measured at 6 years of age. Results: Preterm birth and small or large size for gestational age at birth were not associated with childhood insulin levels. Conditional growth modelling showed that, independent of growth in other time intervals, weight growth in each time interval from birth onwards, length growth from 6 months onwards and BMI growth from 12 months onwards were positively associated with childhood insulin levels. The strongest associations were present for weight and BMI growth between 48 and 72 months of age. Repeated measurement analyses showed that, compared with children in the lowest quartile of childhood insulin, those in the highest quartile had a higher length from birth onwards and a higher weight and BMI from 24 months onwards. These differences increased with age. No associations were observed for fetal growth characteristics. Similar results were observed for C-peptide levels. Conclusions/interpretation: Our results suggest that rapid length, weight and BMI growth from birth onwards, but not during fetal life, is associated with higher insulin levels in childhood

High maternal early-pregnancy blood glucose levels are associated with altered fetal growth and increased risk of adverse birth outcomes

Aims/hypothesis: The study aimed to assess the associations of maternal early-pregnancy blood glucose levels with fetal growth throughout pregnancy and the risks of adverse birth outcomes. Methods: In a population-based prospective cohort study among 6116 pregnant women, maternal non-fasting glucose levels were measured in blood plasma at a median 13.2 weeks of gestation (95% range 9.6–17.6). We measured fetal growth by ultrasound in each pregnancy period. We obtained information about birth outcomes from medical records and maternal sociodemographic and lifestyle factors from questionnaires. Results: Higher maternal early-pregnancy non-fasting glucose levels were associated with altered fetal growth patterns, characterised by decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, resulting in an increased length and weight at birth (p ≤0.05 for all). A weaker association of maternal early-pregnancy non-fasting glucose levels with fetal head circumference growth rates was present. Higher maternal early-pregnancy non-fasting glucose levels were also associated with an increased risk of delivering a large-for-gestational-age infant, but decreased risk of delivering a small-for-gestational-age infant (OR 1.28 [95% CI 1.16, 1.41], OR 0.88 [95% CI 0.79, 0.98] per mmol/l increase in maternal early-pregnancy non-fasting glucose levels, respectively). These associations were not explained by maternal sociodemographic factors, lifestyle factors or BMI. Maternal early-pregnancy non-fasting glucose levels were not associated with preterm birth or delivery complications. Conclusions/interpretation: Higher maternal early-pregnancy non-fasting glucose levels are associated with decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, and an increased risk of delivering a large-for-gestational-age infant. Future preventive strategies need to focus on screening for an impaired maternal glucose metabolism from preconception and early pregnancy onwards to improve birth outcomes