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In utero diet may be directly related to the risk of fetal hyperinsulinaemia and offspring metabolic health. This review examines the relationship between maternal dietary exposures and sub-clinical fetal hyperinsulinaemia and neonatal adiposity. Articles were identified in MEDLINE, Web of Science, Cochrane Controlled Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, SCOPUS, and SPORTDiscus (September 2019–March 2021) using the preferred reporting items for systematic reviews and meta-analyses guidelines. PROSPERO registration ID CRD42020146453. Studies were selected by two independent reviewers. Randomised controlled trials (RCT) involving a dietary intervention with pregnant women (healthy pregnancy, gestational diabetes mellitus and obesity) and reporting fetal cord-blood insulin, c-peptide, glucose or adiposity estimates were included. One author extracted all information on main study characteristics and outcomes. Risk of bias was assessed using the Cochrane Collaboration’s bias risk assessment tool. A total of 733 articles were identified. Fourteen articles from 11 RCTs (3614 participants) were included. Studies reviewed showed no specific effect of maternal diet on neonatal cord blood insulin, c-peptide or glucose levels. Infants born to mothers who followed a low glycaemic load (GL) had lower skin fold thickness compared to controls. Interventions that provided individualised nutrition counselling to women with obesity or previous infant born > 4 kg were also associated with lower adiposity. The studies reviewed suggest that lifestyle-based dietary interventions to improve glycaemia (low GL) have a protective effect against excess adiposity. Future studies should incorporate multi-modal interventions with dietary counselling to support lifestyle changes throughout gestation and include assessments of maternal insulin resistance at recruitment.
Obesity rates among children are rapidly rising internationally and have been linked to noncommunicable diseases in adulthood. Individual preventive strategies have not effectively reduced global obesity rates, leading to a gap in clinical services regarding the development of early perinatal interventions. The objective of this scoping review is to explore the relationship between maternal BMI and breastfeeding behaviors on child growth trajectories to determine their relevance in developing interventions aimed at preventing childhood obesity.
The scoping review was guided and informed by the Arksey and O’Malley (2005) framework. A systematic search was performed in four databases. Studies included in the final review were collated and sorted into relevant themes. A systematic search yielded a total of 5831 records (MEDLINE: 1242, EMBASE: 2629, CINAHL: 820, PubMed: 1140). Results without duplicates (n = 4190) were screened based on relevancy of which 197 relevant-full-text articles were retrieved and assessed for eligibility resulting in 14 studies meeting the inclusion criteria. Data were extracted and charted for the studies and six themes were identified: (1) healthy behaviors, lifestyle, and social economic status; (2) parental anthropometrics and perinatal weight status; (3) genetics, epigenetics, and fetal programming; (4) early infant feeding; (5) infant growth trajectories; and (6) targeted prevention and interventions. Early life risk factors for child obesity are multifactorial and potentially modifiable. Several at-risk groups were identified who would benefit from early preventative interventions targeting the importance of healthy weight gain, exclusive breastfeeding to 6 months, and healthy lifestyle behaviors.
The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02–9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02–0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.
The crosstalk between maternal stress exposure and fetal development may be mediated by epigenetic mechanisms, including DNA methylation (DNAm). To address this matter, we collect 32 cord blood samples from low-income Brazilian pregnant adolescents participants of a pilot randomized clinical intervention study (ClinicalTrials.gov, Identifier: NCT02807818). We hypothesized that the association between the intervention and infant neurodevelopmental outcomes at 12 months of age would be mediated by DNAm. First, we searched genome methylation differences between cases and controls using different approaches, as well as differences in age acceleration (AA), represented by the difference of methylation age and birth age. According to an adjusted p-value ≤ 0.05 we identified 3090 differentially methylated positions- CpG sites (DMPs), 21 differentially methylated regions (DMRs) and one comethylated module weakly preserved between groups. The intervention group presented a smaller AA compared to the control group (p = 0.025). A logistic regression controlled by sex and with gestational age indicated a coefficient of −0.35 towards intervention group (p = 0.016) considering AA. A higher cognitive domain score from Bayley III scale was observed in the intervention group at 12 months of age. Then, we performed a potential causal mediation analysis selecting only DMPs highly associated with the cognitive domain (adj. R2 > 0.4), DMRs and CpGs of hub genes from the weakly preserved comethylated module and epigenetic clock as raw values. DMPs in STXBP6, and PF4 DMR, mediated the association between the maternal intervention and the cognitive domain at 12 months of age. In conclusion, DNAm in different sites and regions mediated the association between intervention and cognitive outcome.
Accumulating evidence suggests that in utero exposures can influence the development of the immune system. Few studies have investigated whether prenatal exposure to persistent organic pollutants (POPs) is associated with allergy-related phenotypes in childhood, nor explored sex differences. We examined the association between prenatal exposure to POPs and offspring allergic outcomes in early and mid-childhood. We included 682 mother–child pairs from the prospective birth cohort Rhea. We measured dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and 6 polychlorinated biphenyl (PCB) congeners in maternal first trimester serum. Parents completed the questionnaires adapted from the International Study on Asthma and Allergy in Childhood (ISAAC) for allergy-related phenotypes when their children were 4 and 6 years old. We used Poisson regression models to estimate Risk Ratios. Prenatal HCB was associated with increased risk for rhinoconjunctivitis at 6 years (RR (95% CI): 2.5; (1.3, 4.8) for a doubling in the exposure). Among girls, prenatal DDE was associated with increased risk for current wheeze, current asthma and current rhinoconjunctivitis at 4 years (RR (95%CI): 1.4 (0.8, 2.6), 1.6 (1.1, 2.4) and 1.8 (1.0, 3.3) and p-interaction = 0.035, 0.027 and 0.059, respectively), with increased risk for current rhinoconjunctivitis at 6 years (RR (95%CI): 1.7 (0.7, 3.8) and p-interaction = 0.028) and total PCBs were associated with increased risk for current eczema at 4 years (RR (95%CI): 2.1 (1.1, 4.2) and p-interaction = 0.028). In boys, prenatal DDE was associated with decreased risk for current wheeze and current asthma at 4 years. Our findings suggest that even low levels of exposure to POPs prenatally may affect the development of childhood allergy-related outcomes in a sex and age-specific manner.
In the last decades, obesity and nonalcoholic fatty liver disease (NAFLD) have become increasingly prevalent in wide world. Fatty liver can be detrimental to liver regeneration (LR) and offspring of obese dams (HFD-O) are susceptible to NAFLD development. Here we evaluated LR capacity in HFD-O after partial hepatectomy (PHx). HFD-O re-exposed or not to HFD in later life were evaluated for metabolic parameters, inflammation, proliferation, tissue repair markers and survival rate after PHx. Increasing adiposity and fatty liver were observed in HFD-O. Despite lower IL-6 levels, Ki67 labeling, cells in S phase and Ciclin D1/PCNA protein content, a lower impact on survival rate was found after PHx, even when re-exposed to HFD. However, no difference was observed between offspring of control dams (SC-O) and HFD-O after surgery. Although LR impairment is dependent of steatosis development, offspring of obese dams are programmed to be protected from the damage promoted by HFD.
Studies on childhood feeding and current food consumption, according to the NOVA classification, in adults are scarce. The objective of this study was to evaluate the relationship between childhood dietary practices and the current consumption of different categories of processed foods in young adults using data from the Nutritionists’ Health Study (NutriHS) cohort. A cross-sectional analysis was performed using data of 392 on nutrition undergraduate students or nutritionists aged ≥18 years. Current food consumption was assessed using a food frequency questionnaire and the NOVA classification. The investigated childhood eating practices included fruit and vegetable intake, exclusive breastfeeding, and other breastfeeding practices. Participants breastfed with introduction of solid, semi-solid or soft foods before 6 months had higher current consumption of processed foods than those who were not breastfed (β = 4.30; 95% confidence interval [CI] = 0.56–8.04) and those who did not have the habits of eating fruits and vegetables during childhood consumed less unprocessed and minimally processed foods in adulthood than those who ate fruits and vegetables during infancy (β = −3.76; 95% CI = −0.82 to −6.70). Further, later introduction of infant formula or other types of milk between 3 and 5 months of age had a lower current consumption of ultra-processed foods than those fed infant formula or other types of milk before 1 month age of life (β = −3.09; 95% CI = −6.12 to −0.06). In conclusion, childhood feeding practices were linked to food consumption in adult life in NutriHS cohort, highlighting that the first 1000 days of life seems to impact on food choices during adulthood, with potential to protect against nutrition-related diseases later in life.
The addition of reproductive fluids (RF) to the culture media has shown benefits in different embryonic traits but its long-term effects on the offspring phenotype are still unknown. We aimed to describe such effects in pigs. Blood samples and growth parameters were collected from piglets derived from in vitro-produced embryos (IVP) with or without RF added in the culture media versus those artificially inseminated (AI), from day 0 to month 6 of life. An oral glucose tolerance test was performed on day 45 of life. We show here the first comparative data of the growth of animals produced through different assisted reproductive techniques, demonstrating differences between groups. Overall, there was a tendency to have a larger size at birth and faster growth in animals derived from in vitro fertilization and embryo culture versus AI, although this trend was diminished by the addition of RFs to the culture media. Similarly, small differences in hematological indices and glucose tolerance between animals derived from AI and those derived from IVP, with a sex-dependent effect, tended to fade in the presence of RF. The addition of RF to the culture media could contribute to minimizing the phenotypical differences between the in vitro-derived and AI offspring, particularly in males.
Increased population longevity could be influenced by early life factors. Some areas have long-lived populations, also in a historical perspective. We aimed to study these factors in Halland, an area with the highest life expectancy in Sweden. We collected archival data on gestational age and birth characteristics from 995 live singleton full-term births at the Halmstad Hospital, Halland, from the period 1936 to 1938 and compared these to 3364 births from three hospitals in nearby Scania for the period 1935–1945. In addition, data were obtained on maternal and offspring characteristics from the national Swedish Medical Birth Register during 1973–2013. The results show that when controlling for background maternal and offspring characteristics, mean birth weight (BW) and mean birth length were higher in Halland than in Scania, but the proportion of low birth weight (LBW) and small for gestational age (SGA) was lower. However, mean BW for Halland did not differ from the rest of Sweden in recent years 2004–2013. We also conducted a mortality follow-up for children born in Scania, which showed that LBW, being born SGA, or short birth length reduced survival. In conclusion, the high mean life expectancy in Halland compared to the rest of Sweden could have been associated with beneficial early life factors influencing birth size in the past. In more recent decades the mean BW of Halland is not different from the national mean. Thus, longevity could be expected to become more equal to the national mean in the future.
This work aimed to investigate the effects of early progeny exposure to methylglyoxal (MG), programming for metabolic dysfunction and diabetes-like complications later in life. At delivery (PN1), the animals were separated into two groups: control group (CO), treated with saline, and MG group, treated with MG (20 mg/kg of BW; i.p.) during the first 2 weeks of the lactation period. In vivo experiments and tissue collection were done at PN90. Early MG exposure decreased body weight, adipose tissue, liver and kidney weight at adulthood. On the other hand, MG group showed increased relative food intake, blood fructosamine, blood insulin and HOMA-IR, which is correlated with insulin resistance. Besides, MG-treated animals presented dyslipidaemia, increased oxidative stress and inflammation. Likewise, MG group showed steatosis and perivascular fibrosis in the liver, pancreatic islet hypertrophy, increased glomerular area and pericapsular fibrosis, but reduced capsular space. This study shows that early postnatal exposure to MG induces oxidative stress, inflammation and fibrosis markers in pancreas, liver and kidney, which are related to metabolic dysfunction features. Thus, nutritional disruptors during lactation period may be an important risk factor for metabolic alterations at adulthood.
Previous studies have suggested that maternal active smoking can increase the risk of birth defects, but evidence on second-hand tobacco smoke (SHS) is limited. We aimed to assess the association between maternal exposure to SHS and birth defects in a Chinese population. The data were based on a large-scale cross-sectional survey conducted in Shaanxi Province, China. Considering the characteristics of survey design and the potential impact of confounding factors, we adopted propensity score matching (PSM) to match the SHS exposure group and the non-exposure group to attain a balance of the confounders between the two groups. Subsequently, conditional logistic regression was employed to estimate the effect of SHS exposure on birth defects. Furthermore, sensitivity analyses were conducted to verify the key findings. After nearest neighbor matching of PSM with a ratio of 2 and a caliper width of 0.03, there were 6,205 and 12,410 participants in the exposure and control group, respectively. Pregnant women exposed to SHS were estimated to be 58% more likely to have infants with overall birth defects (OR = 1.58, 95% CI: 1.30–1.91) and 75% more likely to have infants with circulatory system defects (OR = 1.75, 95% CI: 1.26–2.44). We also observed that the risk effect of overall birth defects had an increasing trend as the frequency of exposure increased. Additionally, sensitivity analyses suggested that our results had good robustness. These results indicate that maternal exposure to SHS likely increases the risk of overall birth defects, especially circulatory system defects, in Chinese offspring.
Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.
As rates of obesity, diabetes, and related comorbidities have increased, the consumption of artificial sweeteners (ASs) as sugar substitutes has also risen in popularity as they are perceived as a healthier alternative to sugar sweetened products. However, there is conflicting evidence regarding the impact of AS intake on metabolic and reproductive health. Glucose intolerance during pregnancy due to intake of sugar sweetened foods can result in an increased risk for the development of type 2 diabetes post-pregnancy. However, limited information exists on the impact of AS intake during pregnancy and lactation on the mother’s health in later life. We hypothesised both AS and fructose would impair metabolic health post-partum (PP) following maternal consumption during pregnancy and lactation. Female C57Bl/6 mice received a standard control diet ad libitum with either water (CD), fructose (Fr; 34.7 mm intake), or AS (AS;12.5 mm Acesulfame-K) throughout pregnancy and lactation. Post-weaning, AS and Fr dams were fed the CD diet for the remainder of the experiment. Oral glucose tolerance tests were undertaken 8 weeks PP and dams were humanely killed at 9 weeks PP, with adipose tissue and ovaries collected for analysis. Experimental diets did not influence maternal bodyweight. At 8 weeks PP, increased glucose intolerance was evident in both AS and Fr dams. Adipocyte size was significantly increased in both the AS and Fr groups PP. Further, in the ovary, AS increased expression of genes associated with follicular development and ovulation. Therefore, ASs may not represent beneficial substitutes to fructose during pregnancy, with the potential to increase the risk of T2DM in later life in mothers.
This study aimed to investigate how maternal birthweight is related to early pregnancy obesity, gestational diabetes mellitus (GDM), and offspring birthweight. Females born term and singleton in Sweden between 1973 and 1995 (N = 305,893) were studied at their first pregnancy. Information regarding their birthweight, early pregnancy body mass index, and pregnancy complications was retrieved from the Swedish Medical Birth Register, as were data on their mothers and offspring. High maternal birthweights (2–3 standard deviation scores (SDS) and >3 SDS) were associated with greater odds of early pregnancy obesity, odds ratio (OR) 1.52 (95% confidence interval (CI) 1.42–1.63) and OR 2.06 (CI 1.71–2.49), respectively. A low maternal birthweight (<2 SDS) was associated with greater odds of GDM (OR 2.49, CI 2.00–3.12). No association was found between high maternal birthweight and GDM. A maternal birthweight 2–3 SDS was associated with offspring birthweight 2–3 SDS (OR 3.83, CI 3.44–4.26), and >3 SDS (OR 3.55, CI 2.54–4.97). Corresponding ORs for a maternal birthweight >3 SDS were 5.38 (CI 4.12–7.01) and 6.98 (CI 3.57–13.65), respectively. In conclusion, a high maternal birthweight was positively associated with early pregnancy obesity and offspring macrosomia. A low, but not a high maternal birthweight, was associated with GDM.
Our primary objectives are to empirically identify distinct childhood groups based on trajectories of waist circumference (WC) and waist circumference index measurements, and then to estimate associations between these groups and adult diabetes incidence, as well as other outcomes, including blood pressure, body size, body composition, and hemoglobin levels. Childhood WC and height measurements as well as various adult measurements are taken from participants in the Fels Longitudinal Study. Childhood groups are identified using group-based trajectory modeling. Associations between the resulting group probabilities and adult outcomes are examined using mixed models. Our results show that distinct childhood groups are identifiable for both waist size measurements, with growth curves exhibited by these groups becoming distinguishably separate at around 4 years of age. Higher probabilities for groups exhibiting the larger waist size for either measurement were estimated to have higher risks of developing diabetes in adulthood. Associations were also observed between group probabilities and systolic blood pressure, diastolic blood pressure, and various anthropomorphic measurements, with most associations consistently occurring in early adulthood. These findings expand upon the existing literature, showing that childhood trends in waist size, distinguishable at ages as early as 4 years, are associated with adult Type-2 diabetes.