Offspring Fat Mass Research Articles

Maternal adiposity and perinatal and offspring outcomes: an umbrella review.

Maternal adiposity deleteriously affects obstetrical health and has been associated with long-term adverse consequences in offspring. Here we conducted an umbrella review encompassing 194 observational meta-analyses, 10 Mendelian randomization studies and 748 interventional meta-analyses to appraise the published evidence on the associations between maternal adiposity and perinatal and offspring outcomes. Evidence grading suggested that 17 (8.8%) observational meta-analyses were supported by convincing evidence for 12 outcomes: maternal adiposity was associated with an increased risk of caesarean delivery following labour induction, infant mortality, Apgar score <7 at 1 min, antenatal depression, offspring overweight and obesity, early timing of puberty onset in daughters, attention deficit hyperactivity disorder, cerebral palsy, congenital heart disease and spina bifida (OR/RR ranging from 1.14 to 2.31), as well as increased offspring body fat percent and fat mass (SMD 0.31 and 0.35, respectively). Among these outcomes, interventional meta-analyses supported that maternal weight loss interventions significantly reduced the risk of antenatal depression but not low Apgar scores; these interventions also could not reduce offspring fat mass or body fat percent. Evidence from Mendelian randomization studies supported a causal relationship between maternal adiposity and gestational diabetes mellitus, preeclampsia, birth size and offspring adiposity. Our findings highlight that while observational meta-analyses reveal associations between maternal adiposity and various adverse perinatal and offspring outcomes, convincing, unbiased evidence or support from Mendelian randomization studies is limited. Maternal pre-conceptional and prenatal weight loss interventions can reduce some, but not all, of these adverse effects.

The Effect of Prenatal Docosahexaenoic Acid Supplementation on Offspring Fat Mass and Distribution at 24 Months Old

BackgroundExcessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. ObjectivesThis study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. MethodsInfants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. ResultsFor total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. ConclusionsGreater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

Associations between maternal overweight/obesity during pregnancy and body composition in young adult offspring.

Maternal obesity is associated with an increased risk of large-for-gestational-age births and childhood obesity. However, evidence on its potential associations with long-term offspring body composition remains limited. This prospective cohort study examined associations between maternal body mass index (BMI) during pregnancy and body composition in the young adult offspring. Participants were the offspring from a birth cohort in Chiang Mai (Thailand). Maternal BMI was assessed at the first antenatal clinic visit (≤24 weeks of gestation) in 1989-1990. In 2010-2011, we followed up the offspring at approximately 20 years of age, assessing their body composition using whole-body dual-energy X-ray absorptiometry (DXA) scans. Associations between maternal BMI and offspring body composition were explored using unadjusted and adjusted analyses. We assessed 391 young adults (55% were females). Higher maternal BMI was associated with increased offspring fat mass and lean mass. In adjusted analyses, offspring of mothers with overweight/obesity exhibited total body fat percentages 1.5 (95% CI 0.1, 2.9; p = 0.032) and 2.3 (95% CI 0.2, 4.5; p = 0.036) percentage points higher than offspring of normal-weight and underweight mothers, respectively. Fat mass index was similarly higher: 0.9 kg/m2 (95% CI 0.3, 1.5 kg/m2; p = 0.002) and 1.4 kg/m2 (95% CI 0.5, 2.3 kg/m2; p = 0.002), respectively. However, no differences in visceral adiposity were detected. Higher maternal BMI during pregnancy was associated with increased adiposity in young adult offspring. Our findings suggest that the cross-generational transmission of maternal obesity-related traits is associated with increased offspring adiposity in the long term.

P07-021-23 Prenatal Sugars Intake and Offspring Fat Mass in Early and Late Infancy

P07-021-23 Prenatal Sugars Intake and Offspring Fat Mass in Early and Late Infancy

Exposures during the prepuberty period and future offspring's health: evidence from human cohort studies†.

Emerging evidence suggests that exposures in prepuberty, particularly in fathers-to-be, may impact the phenotype of future offspring. Analyses of the RHINESSA cohort find that offspring of father’s exposed to tobacco smoking or overweight that started in prepuberty demonstrate poorer respiratory health in terms of more asthma and lower lung function. A role of prepuberty onset smoking for offspring fat mass is suggested in the RHINESSA and ALSPAC cohorts, and historic studies suggest that ancestral nutrition during prepuberty plays a role for grand-offspring’s health and morbidity. Support for causal relationships between ancestral exposures and (grand-)offspring’s health in humans has been enhanced by advancements in statistical analyses that optimize the gain while accounting for the many complexities and deficiencies in human multigeneration data. The biological mechanisms underlying such observations have been explored in experimental models. A role of sperm small RNA in the transmission of paternal exposures to offspring phenotypes has been established, and chemical exposures and overweight have been shown to influence epigenetic programming in germ cells. For example, exposure of adolescent male mice to smoking led to differences in offspring weight and alterations in small RNAs in the spermatozoa of the exposed fathers. It is plausible that male prepuberty may be a time window of particular susceptibility, given the extensive epigenetic reprogramming taking place in the spermatocyte precursors at this age. In conclusion, epidemiological studies in humans, mechanistic research, and biological plausibility, all support the notion that exposures in the prepuberty of males may influence the phenotype of future offspring.

Paternal Methyl Donor Supplementation in Rats Improves Fertility, Physiological Outcomes, Gut Microbial Signatures and Epigenetic Markers Altered by High Fat/High Sucrose Diet

Increased consumption of high fat/sucrose (HF/S) diets has contributed to rising rates of obesity and its co-morbidities globally, while also negatively impacting male reproductive health. Our objective was to examine whether adding a methyl donor cocktail to paternal HF/S diet (HF/S+M) improves health status in fathers and offspring. From 3–12 weeks of age, male Sprague Dawley rats consumed a HF/S or HF/S+M diet. Offspring were followed until 16 weeks of age. Body composition, metabolic markers, gut microbiota, DNA methyltransferase (DNMT) and microRNA expression were measured in fathers and offspring. Compared to HF/S, paternal HF/S+M diet reduced fat mass in offspring (p < 0.005). HF/S+M fathers consumed 16% fewer kcal/day, which persisted in HF/S+M female offspring and was explained in part by changes in serum glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels. Compared to HF/S, HF/S+M fathers had a 33% improvement in days until conception and 300% fewer stillbirths. In fathers, adipose tissue DNMT3a and hepatic miR-34a expression were reduced with HF/S+M. Adult male offspring showed upregulated miR-24, -33, -122a and -143 expression while females exhibited downregulated miR-33 expression. Fathers and offspring presented differences in gut microbial signatures. Supplementing a paternal HF/S diet with methyl-donors improved fertility, physiological outcomes, epigenetic and gut microbial signatures intergenerationally.

Parents' smoking onset before conception as related to body mass index and fat mass in adult offspring: Findings from the RHINESSA generation study.

Emerging evidence suggests that parents' preconception exposures may influence offspring health. We aimed to investigate maternal and paternal smoking onset in specific time windows in relation to offspring body mass index (BMI) and fat mass index (FMI). We investigated fathers (n = 2111) and mothers (n = 2569) aged 39-65 years, of the population based RHINE and ECRHS studies, and their offspring aged 18-49 years (n = 6487, mean age 29.6 years) who participated in the RHINESSA study. BMI was calculated from self-reported height and weight, and FMI was estimated from bioelectrical impedance measures in a subsample. Associations with parental smoking were analysed with generalized linear regression adjusting for parental education and clustering by study centre and family. Interactions between offspring sex were analysed, as was mediation by parental pack years, parental BMI, offspring smoking and offspring birthweight. Fathers' smoking onset before conception of the offspring (onset ≥15 years) was associated with higher BMI in the offspring when adult (β 0.551, 95%CI: 0.174-0.929, p = 0.004). Mothers' preconception and postnatal smoking onset was associated with higher offspring BMI (onset <15 years: β1.161, 95%CI 0.378-1.944; onset ≥15 years: β0.720, 95%CI 0.293-1.147; onset after offspring birth: β2.257, 95%CI 1.220-3.294). However, mediation analysis indicated that these effects were fully mediated by parents' postnatal pack years, and partially mediated by parents' BMI and offspring smoking. Regarding FMI, sons of smoking fathers also had higher fat mass (onset <15 years β1.604, 95%CI 0.269-2.939; onset ≥15 years β2.590, 95%CI 0.544-4.636; and onset after birth β2.736, 95%CI 0.621-4.851). There was no association between maternal smoking and offspring fat mass. We found that parents' smoking before conception was associated with higher BMI in offspring when they reached adulthood, but that these effects were mediated through parents' pack years, suggesting that cumulative smoking exposure during offspring's childhood may elicit long lasting effects on offspring BMI.

1245-P: Maternal HbA1c Is Related to Childhood Fat Mass and Only Partially Mediated by Neonatal Fat Mass

Maternal diabetes during pregnancy impacts offspring body composition and has been associated with greater offspring adiposity across the life course. However, the extent to which the relationship between maternal glycemia and offspring adiposity during later life is independent of neonatal adiposity is unclear. In a prospective study of 544 mother-child pairs in the Healthy Start Study, we estimated the total effect of maternal HbA1c on childhood fat mass (FM) %, and the direct effect independent of neonatal FM %. We measured maternal fasting HbA1c at a gestational age of 20-34 weeks, and offspring FM % using air displacement plethysmography at birth and during childhood (age 4-7 y). We used multivariable linear regression with HbA1c tertiles (T1 [reference], T2, T3) as the exposure, neonatal FM % as the mediator, and childhood FM % as the outcome. A counterfactual-based approach was used to estimate total and direct effects, while also accounting for exposure-mediator interaction. Covariates were maternal race, education, gestational weight gain and smoking, and offspring sex and age. The medians (interquartile ranges) of the HbA1c tertiles were T1: 4.80 (3.70, 4.90), T2: 5.05 (5.00, 5.10), and T3: 5.30 (5.20, 6.30). The estimated total effect on child FM % was 1.27 (95% CI: 0.00, 2.54) units higher for T2 vs. T1, and 1.53 (0.23, 2.82) units higher for T3 vs. T1 (P-trend=0.02). After adjusting for pre-pregnancy BMI, the total effect was 1.18 (-0.09, 2.44) and 1.31 (0.00, 2.62) units higher for T2 vs. T1 and T3 vs. T1, respectively (P-trend=0.04). The direct effect after accounting for neonatal FM % was slightly attenuated (T2 vs. T1: 1.14 [-0.11, 2.39], T3 vs. T1: 1.20 [-0.11, 2.51]; P-trend=0.07). Excluding women with gestational diabetes mellitus (n=27) did not substantially impact the results. Our data suggest that maternal glycemia during pregnancy, even within normal levels, may influence childhood adiposity through pathways that are in part mediated by programming of neonatal adiposity. Disclosure E.C. Francis: None. B. Ringham: None. D.H. Glueck: None. W. Perng: None. D. Dabelea: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK076648-10)

Gestational diabetes mellitus, pre-pregnancy body mass index, and gestational weight gain as risk factors for increased fat mass in Brazilian newborns.

BackgroundGestational diabetes mellitus (GDM) is a common complication of pregnancy. It may predispose offspring to increased fat mass (FM) and the development of obesity, however few data from Latin America exist.ObjectiveTo investigate the influence of GDM on newborn FM in mother-newborn pairs recruited from a public maternity care center in São Paulo, Brazil.MethodsData were collected cross-sectionally in 2013–2014 from 72 mothers diagnosed with GDM, and 211 mothers with normal glucose tolerance (NGT). Newborn FM was evaluated by air-displacement plethysmography (PEA POD), and relevant demographic and obstetric data were collected from hospital records. Associations between maternal GDM status and newborn FM were investigated by multiple linear regression analysis, with adjustment for maternal age, pre-pregnancy BMI, gestational weight gain, type of delivery, sex of the child, and gestational age.ResultsFM was greater in GDM versus NGT newborns in a bivariable model (Median (IQR), GDM: 0.35 (0.3) kg vs. NGT: 0.27 (0.2) kg, p = 0.02), however GDM status was not a significant predictor of FM with adjustment for other variables. Rather, pre-pregnancy BMI (coefficient (β) 1.46; 95% confidence interval (CI) 0.66, 2.27), gestational weight gain (β 1.32; 95% CI 0.49, 2.15), and male sex (β -17.8; 95% CI -27.2, -8.29) predicted newborn FM. Analyzing GDM and NGT groups separately, pre-pregnancy BMI (β 6.75; 95% CI 2.36, 11.1) and gestational weight gain (β 5.64; 95% CI 1.16, 10.1) predicted FM in the GDM group, while male sex alone predicted FM in the NGT group (β -12.3; 95% CI -18.3, -6.34).ConclusionsCombined model results suggest that in our cohort, pre-pregnancy BMI and gestational weight gain are more important risk factors for increased neonatal FM than GDM. However, group-specific model results suggest that GDM status may contribute to variation in the relationship between maternal/offspring factors and FM. Our use of a binary GDM variable in the combined model may have precluded clearer results on this point. Prospective cohort studies including data on maternal pre-pregnancy BMI, GWG, and glycemic profile are needed to better understand associations among these variables and their relative influence on offspring FM.

Impact of maternal obesity on body weight regulation and sleep time in offspring

Mississippi Center for Obesity Research, University of Mississippi Medical Center – Jackson, MS. There is limited understanding of the mechanisms that link parental obesity to adverse metabolic outcomes in their offspring. In this study we examined factors that influence body weight regulation and sleep time in mice fed a high fat diet after weaning (HFD, n=5) that were offspring of dams also fed a HFD (45% fat) and compared them to HFD fed mice (n=5) from dams on a control diet. Food intake was measured daily and body weight and body composition (EchoMRI) were measured weekly. Energy expenditure (EE), oxygen consumption (VO2), motor activity (MA) and sleep time (Sable System 40 sec criterion) were monitored for 5 consecutive days at 22 weeks of age. There were no significant differences in calorie intake (17.3±0.7 vs. 16.2±0.8 kcal/day), fasting blood glucose (170±13 vs. 187±16 mg/dL), total EE (5.7±0.6 vs. 5.7±0.2 kcal/hr), VO2 (1.5±0.1 vs. 1.7±0.1 ml/min) or MA (57±6 vs. 65±5 m/day) in offspring from dams fed a HFD compared to offspring from dams fed a control diet. However, there were significant increases in body weight (47.3±1.5 vs. 42.4±1.1 g) and fat mass (19.8±0.6 vs. 15.7±1.6 g), and decreased sleep time (8.6±0.2 vs. 9.7±0.2 hr/day, p=0.005) in offspring of dams fed a HFD. These results suggest that maternal obesity increases body weight and fat mass in offspring fed a HFD, and reduces sleep time without altering food intake, VO2, EE, MA, or fasting glucose levels in adult mice (NHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428)Support or Funding InformationNHLBI PO1HL51971, NIGMS P20GM104357 and NIGMS U54GM115428This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Relation of placental alkaline phosphatase expression in human term placenta with maternal and offspring fat mass.

Alkaline phosphatase is implicated in intestinal lipid transport and in the development of obesity. Placental alkaline phosphatase is localised to the microvillous plasma membrane of the placental syncytiotrophoblast at the maternal-fetal interface, but its role is unclear. We investigated the relations of placental alkaline phosphatase activity and mRNA expression with maternal body composition and offspring fat mass in humans. Term human placentas from the UK Birthright cohort (n = 52) and the Southampton Women's Survey (SWS) (n = 95) were studied. In the Birthright cohort, alkaline phosphatase activity was measured in placental microvillous plasma membrane vesicles. In the SWS, alkaline phosphatase mRNA was measured using Nanostring. Alkaline phosphatase gene expression was compared to other lipid-related genes. In Birthright samples placental microvillous plasma membrane alkaline phosphatase activity was positively associated with maternal triceps skinfold thickness and BMI (β = 0.04 (95% CI: 0.01-0.06) and β = 0.02 (0.00-0.03) µmol/mg protein/min per SD, P = 0.002 and P = 0.05, respectively) after adjusting for potential confounders. In SWS samples placental alkaline phosphatase mRNA expression in term placenta was positively associated with maternal triceps skinfold (β = 0.24 (0.04, 0.44) SD/SD, P = 0.02), had no association with neonatal %fat mass (β = 0.01 (-0.20 to 0.21) SD/SD, P = 0.93) and was negatively correlated with %fat mass at ages 4 (β = -0.28 (-0.52 to -0.04) SD/SD, P = 0.02), 6-7 (β = -0.25 (-0.49 to -0.02) SD/SD, P = 0.03) years. When compared with placental expression of other genes, alkaline phosphatase expression was positively related to genes including the lysophosphatidylcholine transporter MFSD2A (major facilitator superfamily domain containing 2A, P < 0.001) and negatively related to genes including the fatty acid transport proteins 2 and 3 (P = 0.001, P < 0.001). Our findings suggest relationships between placental alkaline phosphatase and both maternal and childhood adiposity. The inverse relationship between placental alkaline phosphatase gene expression and childhood %fat mass suggests that placental alkaline phosphatase may help to protect the foetus from the adverse effects of maternal obesity.

Vitamin D during pregnancy and offspring body composition: a prospective cohort study.

Evidence regarding the association between gestational vitamin D status and offspring body composition during childhood is inconsistent. Therefore, we aimed to determine the association between maternal vitamin D and offspring lean and fat mass in the Vitamin D in Pregnancy birth cohort. Subjects were mother-child pairs recruited from the Australian-based Vitamin D in Pregnancy cohort study. Mothers were recruited before 16weeks' gestation and provided a blood sample at both recruitment and at 28-32weeks' gestation. Serum vitamin D [25(OH)D] was measured by radioimmunoassay (Tyne and Wear, UK). Offspring lean and fat mass were quantified by using dual-energy X-ray absorptiometry (GE Lunar Prodigy, Madison, WI, USA) at 11years of age. Median maternal 25(OH)D levels were 55.9 (42.2-73.3) and 56.1 (43.6-73.9) at recruitment and 28-32weeks' gestation, respectively. Maternal smoking was identified as an effect modifier in the association between maternal vitamin D status at recruitment and offspring body composition. In smokers, but not non-smokers, serum 25(OH)D status at recruitment was negatively associated with offspring fat mass percentage and positively associated with lean mass (both p<0.05). There was no association with 25(OH)D status at 28-32weeks' gestation. Maternal vitamin D status in early pregnancy, in smokers, is associated with offspring body composition. These important findings warrant confirmation in larger studies and trials.

Disentangling the associations between parental BMI and offspring body composition using the four-component model.

ABSTRACTObjectivesThis study sets out to investigate the intergenerational associations between the body mass index (BMI) of parents and the body composition of their offspring.MethodsThe cross‐sectional data were analyzed for 511 parent–offspring trios from London and south‐east England. The offspring were aged 5–21 years. Parental BMI was obtained by recall and offspring fat mass and lean mass were obtained using the four‐component model. Multivariable regression analysis, with multiple imputation for missing paternal values was used. Sensitivity analyses for levels of non‐paternity were conducted.ResultsA positive association was seen between parental BMI and offspring BMI, fat mass index (FMI), and lean mass index (LMI). The mother's BMI was positively associated with the BMI, FMI, and LMI z‐scores of both daughters and sons and of a similar magnitude for both sexes. The father's BMI showed similar associations to the mother's BMI, with his son's BMI, FMI, and LMI z‐scores, but no association with his daughter. Sensitivity tests for non‐paternity showed that maternal coefficients remained greater than paternal coefficients throughout but there was no statistical difference at greater levels of non‐paternity.ConclusionsWe found variable associations between parental BMI and offspring body composition. Associations were generally stronger for maternal than paternal BMI, and paternal associations appeared to differ between sons and daughters. In this cohort, the mother's BMI was statistically significantly associated with her child's body composition but the father's BMI was only associated with the body composition of his sons. Am. J. Hum. Biol. 28:524–533, 2016. © 2016 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc.

Intake of carbohydrates during pregnancy in obese women is associated with fat mass in the newborn offspring

Transmission of obesity across generations is of concern. Offspring of obese women have short- and long-term increased morbidities. A high intake of carbohydrate during pregnancy combined with impaired glucose tolerance is postulated to result in high birth weight, which is linked to subsequent metabolic disease. The objective was to examine the association between carbohydrate intake in obese pregnant women and their offspring's body composition. Secondary analyses were performed in an observational setting of 222 pregnant women with a pregestational BMI (in kg/m(2)) ≥30 participating in a randomized controlled trial. Diet was assessed at gestational weeks 11-14 and 36-37 by using a semiquantitative food-frequency questionnaire. Body composition in the offspring was assessed at birth by dual-energy X-ray absorptiometry. Relative fat mass (%) was the primary outcome. Absolute measures (total fat, abdominal fat, and lean body mass) were secondary outcomes. Mean ± SD weight and absolute and relative fat mass in the offspring at birth were 3769 ± 542 g, 436 ± 214 g, and 11% ± 4%, respectively. Maternal intake of digestible carbohydrates was associated with the offspring's relative fat mass in late (P-trend = 0.006) but not early (P-trend = 0.15) pregnancy. A comparison of mothers in the highest (median: 238 g/d) compared with the lowest (median: 188 g/d) quartile of digestible carbohydrate intake showed a mean adjusted higher value in the offspring's relative fat mass of 2.1% (95% CI: 0.6%, 3.7%), which corresponded in absolute terms to a 103-g (95% CI: 27, 179-g) higher fat mass. Abdominal fat mass was also higher. In a strata of women with well-controlled glucose (2-h glucose values ≤6.6 mmol/L), no association between carbohydrate intake and offspring fat mass was observed, but the associations became significant and increased in strength with higher intolerance (strata with 2-h glucose values between 6.7-7.7 and ≥7.8 mmol/L). In obese women, even those without gestational diabetes but with impaired glucose tolerance, a lower carbohydrate intake at moderate levels in late gestation is associated with a lower fat mass in their offspring at birth. The TOP study was registered at clinicaltrials.gov as NCT01345149.

Relationship between maternal pre-pregnancy body mass index, gestational weight gain and childhood fatness at 6-7 years by air displacement plethysmography.

This study aims to investigate the effect of maternal pre‐pregnancy body mass index (BMI) and gestational weight gain (GWG) on offspring body composition. In this prospective cohort study, offspring body composition at 6 years of age was obtained through air displacement plethysmography. Linear regression was used to obtain crude and adjusted coefficients. Information regarding offspring body composition and maternal pre‐pregnancy BMI was available for 3156 children and on offspring body composition and GWG for 3129 children. There was a direct association of maternal pre‐pregnancy BMI and GWG with offspring's fat mass (FM), fat‐free mass (FFM), fat mass index (FMI), fat‐free mass index (FFMI) and body fat percent (BF%) in crude and adjusted analyses. After adjustment for co‐variables, for each kg m−2 of maternal pre‐pregnancy BMI increase, there was a mean increment of 0.13 kg in the offspring FFM, 0.06 kg m−2 in FFMI, 0.11 kg in FM, 0.07 kg m−2 in FMI and 0.18% in BF%. For each kilogram of maternal GWG increase, there was a mean increment of 0.08 kg in offspring's FM, 0.05 kg m−2 in FMI, 0.04 kg in FFM, 0.01 kg m−2 in FFMI and 0.18 % in BF%. Mothers with a higher pre‐pregnancy BMI or GWG tend to have children with greater adiposity at age 6 years. Fetal overnutrition is more likely among mothers with greater BMI during pregnancy; as a consequence, it can accelerate the childhood obesity epidemic.

Perinatal maternal feeding with an energy dense diet and/or micronutrient mixture drives offspring fat distribution depending on the sex and growth stage.

Maternal nutrition during pregnancy and lactation influences offspring development and health. Novel studies have described the effects on next generation obesity-related features depending on maternal macro- and micro-nutrient perinatal feeding. We hypothesized that the maternal obesogenic diet during pregnancy and lactation programs an obese phenotype, while maternal micronutrient supplementation at these stages could partially prevent these features. Thus, the aim was to assess the influence of a perinatal maternal feeding with an obesogenic diet enriched in fat and sucrose and a micronutrient supplementation during pregnancy and lactation on offspring growth and obese phenotypical features during life course. Female Wistar rats were assigned to four dietary groups during pregnancy and lactation: control, control supplemented with micronutrients (choline, betaine, folic acid and vitamin B12 ), high-fat sucrose (HFS) and HFS supplemented. At weaning, the offspring were transferred to a chow diet, and weight and fat mass were measured at weeks 3, 12 and 20. At birth, both male and female offspring from mothers fed the obesogenic diet showed lower body weight (-5 and -6%, respectively), while only female offspring weight decreased by maternal micronutrient supplementation (-5%). During lactation, maternal HFS diet was associated with increased body weight, while micronutrient supplementation protected against body weight gain. Whole body fat mass content increased at weeks 3, 12 and 20 (from 16 to 65%) due to maternal HFS diet. Maternal micronutrient supplementation decreased offspring fat mass content at week 3 (-8%). Male offspring showed higher adiposity than females at weeks 12 and 20. In conclusion, maternal HFS feeding during pregnancy and lactation was associated with a low offspring weight at birth and obese phenotypical features during adult life in a sex- and time-dependent manner. Furthermore, maternal methyl donor supplementation protected against body weight gain in male offspring during lactation and in female offspring also during juvenile period.

Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) γ methylation in offspring, grand-offspring mice.

RationaleGreater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH) have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear.ObjectivesWe hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected.Materials and MethodsPregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND) 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding proteins (C/EBP) α, cyclooxygenase (Cox)-2, fatty acid synthase (FAS) and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue.FindingsOffspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice.ConclusionsGreater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.

Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy.

BackgroundPreviously we have examined the effect of maternal dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring fat mass. Considering the involvement of the placenta in fetal programming, we aimed to analyze the sex-specific gene expression in human term placenta and its response to the n-3 LCPUFA intervention, as well as their correlations to offspring adiposity.ResultsPlacental gene expression was assessed in a control and n-3 LCPUFA intervention group by DNA microarrays, biological pathway analyses and RT-qPCR validation. Expression data were correlated with sex steroid hormone levels in placenta and cord plasma, and offspring anthropometric data. Transcriptome data revealed sexually dimorphic gene expression in control placentas per se, whereas in intervention placentas sex-specific expression changed, and more n-3 LCPUFA-regulated genes were found in female than male placentas. Sexually dimorphic gene expression and n-3 LCPUFA-responsive genes were enriched in the pathway for cell cycle and its associated modulator pathways. Significant mRNA expression changes for CDK6, PCNA, and TGFB1 were confirmed by RT-qPCR. CDK6 and PCNA mRNA levels correlated with offspring birth weight and birth weight percentiles. Significantly reduced placental estradiol-17β/testosterone ratio upon intervention found in female offspring correlated with mRNA levels for the 'Wnt signaling' genes DVL1 and LRP6.ConclusionsOverall, human placentas show sexually dimorphic gene expression and responsiveness to maternal n-3 LCPUFA intervention during pregnancy with more pronounced effects in female placentas. The absence of correlations of analyzed placental gene expression with offspring adipose tissue growth in the first year is not mutually exclusive with programming effects, which may manifest later in life, or in other physiological processes.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-941) contains supplementary material, which is available to authorized users.

Maternal dietary glycemic index and glycemic load in early pregnancy are associated with offspring adiposity in childhood: the Southampton Women’s Survey

Maternal hyperglycemia in pregnancy is associated with greater adiposity in offspring. The glycemic index (GI) and glycemic load (GL) describe the glycemic response to carbohydrate ingestion. However, the influence of maternal dietary GI and GL in pregnancy on childhood adiposity is unknown. We examined relations of maternal dietary GI and GL in early and late pregnancy with offspring body composition. A total of 906 mother-child pairs from the prospective cohort the Southampton Women's Survey were included. Children underwent dual-energy X-ray absorptiometry measurements of body composition at birth and 4 and 6 y of age. Log-transformed fat mass and lean mass were standardized with a mean (±SD) of 0 ± 1. Maternal dietary GI and GL were assessed at 11 and 34 wk of gestation by using an administered food-frequency questionnaire. After control for potential confounders, both maternal dietary GI and GL in early pregnancy were positively associated with fat mass at 4 and 6 y of age [fat mass SDs per 10-unit GI increase: β = 0.43 (95% CI: 0.06, 0.80), P = 0.02 at 4 y of age; β = 0.40 (95% CI: 0.10, 0.70), P = 0.01 at 6 y of age; fat mass SDs per 50-unit GL increase: β = 0.43 (95% CI: 0.19, 0.67), P < 0.001 at 4 y of age; β = 0.27 (95% CI: 0.07, 0.47), P = 0.007 at 6 y of age]. In contrast, there were no associations between maternal dietary GI or GL in late pregnancy and offspring fat mass at these ages. Maternal dietary GI and GL were not associated with fat mass at birth or offspring lean mass at any of the ages studied. Higher maternal dietary GI and GL in early pregnancy are associated with greater adiposity in childhood.

Effect of maternal obesity with and without gestational diabetes on offspring subcutaneous and preperitoneal adipose tissue development from birth up to year-1

BackgroundMaternal obesity and gestational diabetes mellitus (GDM) may independently influence offspring fat mass and metabolic disease susceptibility. In this pilot study, body composition and fat distribution in offspring from obese women with and without GDM and lean women were assessed within the 1st year of life, and maternal and newborn plasma factors were related to offspring adipose tissue distribution.MethodsSerum and plasma samples from pregnant obese women with (n = 16) or without (n = 13) GDM and normoglycemic lean women (n = 15) at 3rd trimester and offspring cord plasma were used for analyzing lipid profiles, insulin and adipokine levels. At week-1 and 6, month-4 and year-1, offspring anthropometrics and skinfold thickness (SFT) were measured and abdominal subcutaneous (SCA) and preperitoneal adipose tissue (PPA) were determined by ultrasonography.ResultsCord insulin was significantly increased in the GDM group, whereas levels of cord leptin, total and high molecular weight (HMW) adiponectin were similar between the groups. Neonates of the GDM group showed significantly higher SFT and fat mass until week-6 and significantly increased SCA at week-1 compared to the lean group that persisted as strong trend at week-6. Interestingly, PPA in neonates of the GDM group was significantly elevated at week-1 compared to both the lean and obese group. At month-4 and year-1, significant differences in adipose tissue growth between the groups were not observed. Multiple linear regression analyses revealed that cord insulin levels are independently related to neonatal PPA that showed significant relation to PPA development at year-1. Maternal fasted C-peptide and HMW adiponectin levels at 3rd trimester emerged to be determinants for PPA at week-1.ConclusionMaternal pregravid obesity combined with GDM leads to newborn hyperinsulinemia and increased offspring fat mass until week-6, whereas pregravid obesity without GDM does not. This strongly suggests the pivotal role of GDM in the adverse offspring outcome. Maternal C-peptide and HMW adiponectin levels in pregnancy emerge to be predictive for elevated PPA in newborns and might be indicative for the obesity risk at later life. Altogether, the findings from our pilot study warrant evaluation in long-term studies.Trial registrationGerman Clinical Trials Register DRKS00004370