Maternal Dietary Protein Intake Research Articles

Protein-Energy Malnutrition during Gestation and Lactation in Rats Affects Growth Rate, Brain Development and Essential Fatty Acid Metabolism

The influence of feeding a low protein diet to rat dams during gestation and lactation on lipid metabolism in pups was studied. Wistar rats were fed 5, 10, 15 and 25% dietary protein during gestation and lactation. Pup growth was monitored until weaning, and brain weight, protein concentration, proteolipid concentration and total lipid phosphorus concentration of brain were analyzed. The levels of fatty acids in dam milk as well as in pup liver phospholipids and brain prosphatidylcholine and phosphatidylethanolamine were determined. The progressive deprivation of maternal dietary protein produced a reduction in the total saturated fatty acid concentration of dam milk and an increment in the concentration of nonmetabolized linoleic acid. Pup body and brain weights as well as proteolipid, protein and total lipid phosphorus concentrations in brain were reduced in proportion to the degree of dietary protein deficiency. The products:precursor ratio of (n-6) fatty acids in liver phospholipids revealed an impairment in the elongation-desaturation pathway due to maternal protein deficiency. Both (n-6) and (n-3) polyunsaturated fatty acids within brain phosphatidylethanolamine were decreased by reduced maternal dietary protein intake, whereas only the linoleic acid-derived products were similarly affected in the corresponding phosphatidylcholine fraction. These results demonstrate the widespread and profound deleterious effects of low protein levels of maternal diet on the growth rate, brain development and fatty acid metabolism of rat pups.

Dietary protein intake during pregnancy and birth weight among Chinese pregnant women with low intake of protein

BackgroundPrevious studies have yielded inconsistent results on the association between maternal dietary protein intake and birth weight. Moreover, little is known about the effects of dietary protein intake from different sources on fetal growth. This study aimed to investigate the associations of different dietary protein sources (total protein, animal protein, plant protein, and major dietary protein sources) during pregnancy with birth weight and the related adverse birth outcomes.Methods7310 women were recruited using a stratified multistage random sampling method at 0–12 months (median: 3; 10–90th percentile: 0–7) after delivery in Shaanxi, China. Maternal diets were gathered by a validated FFQ and other characteristics were collected by a standard questionnaire. Multilevel linear or logistic regression models were used to estimate birth weight changes or ORs (95% CIs) for adverse birth outcomes associated with different dietary protein sources during pregnancy.ResultsThe mean percentage of energy from total protein was 11.4% (SD 2.2), with only 27.4% of total protein derived from animal protein. Per 3% increase in energy from total protein, animal protein, and dairy protein was associated with birth weight increases of 19.4 g (95% CI 6.0–32.9), 20.6 g (4.8–36.5), and 18.2 g (4.7–31.7), respectively. Per 3% increase in energy from total protein, animal protein, and dairy protein was also associated with lower risks of low birth weight (LBW) (total protein: OR = 0.78, 95% CI 0.64–0.94; animal protein: 0.79, 0.65–0.96; dairy protein: 0.71, 0.56–0.91), small for gestational age (SGA) (total protein: 0.88, 0.79–0.98; animal protein: 0.87, 0.78–0.97; dairy protein: 0.81, 0.68–0.96), and intrauterine growth retardation (IUGR) (total protein: 0.84, 0.72–0.98; animal protein: 0.86, 0.75–0.98; dairy protein: 0.78, 0.66–0.92). We observed no associations of plant protein and other major dietary protein sources with birth weight and the above birth outcomes. The results did not change when maternal protein was substituted for fat or carbohydrate.ConclusionsAmong Chinese pregnant women with low intake of protein, higher intake of dietary protein, in particular animal protein and dairy protein, is associated with higher birth weight and lower risks of LBW, SGA, and IUGR.

No Association Between Maternal Dietary Protein Intake and Offspring Insulin Sensitivity Measures in the First Two Years of Life

Abstract Objectives Findings of an association between maternal dietary protein intake (1.1–1.7 g·kg−1·day−1) close to requirements for pregnant women throughout gestation (1.22–1.52 g·kg−1·day−1) and offspring insulin sensitivity are mixed, perhaps as a result of the small spread in protein intake and the large gap between measurements (∼9–40 years). Therefore, our objective was to evaluate the association between a wider spread of dietary protein intake during pregnancy and measurements of insulin sensitivity in the offspring in early life. Methods Healthy women (n = 182, mean ± SD; BMI: 26.2 ± 4.2 kg/m2) were recruited early in pregnancy (<10 weeks). Dietary protein intake was assessed using a 3-day food record in early (∼10 weeks, EP) and late (∼30 weeks, LP) pregnancy. Offspring blood was sampled at 12 and 24 months, and the updated homeostatic model assessment of insulin resistance (HOMA2-IR) was computed using fasting glucose and insulin. Body composition was measured using nuclear magnetic resonance. Two linear models were fitted to the data to estimate: 1) the unadjusted relationship of maternal protein intake to offspring HOMA2-IR and 2) the relationship of maternal protein intake to offspring HOMA2-IR adjusted for maternal plant protein intake and BMI, and offspring sex and body fat percentage. Values are mean ± SD. Results Habitual protein intake (average of early and late pregnancy measurements range: 0.5–1.9 g·kg−1·day−1) decreased throughout pregnancy (EP: 1.09 ± 0.36; vs. LP: 0.97 ± 0.28 g·kg−1·day−1, P = 0.0003). Offspring HOMA2-IR did not change from 12 (0.8 ± 0.8) to 24 (0.8 ± 0.9) months. Simple regression analysis: EP dietary protein intake did not associate with HOMA2-IR at 12 (β = 0.153, P = 0.429) and 24 (β = −0.349, P = 0.098) months. Similarly, LP dietary protein intake did not associate with offspring HOMA2-IR at 12 (β = 0.023, P = 0.916) and 24 (β = −0.442, P = 0.085) months. Results remained unchanged after multiple regression analyses were conducted. Conclusions Maternal dietary protein intake (amount or type) during pregnancy is not associated with indirect measurements of insulin sensitivity in offspring during the first two years of life. Funding Sources United States Department of Agriculture Agricultural Research Service Project 6026-51,000-012-06S, and NIH/NIDDK R01 DK107516.

Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene

PurposeThe aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring.MethodsFourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP).ResultsHigh-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed.ConclusionsTaken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.

Epigenetic Mechanisms of Maternal Dietary Protein and Amino Acids Affecting Growth and Development of Offspring.

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring's later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body's one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

The Association between Maternal Dietary Protein Intake and Risk of Gestational Diabetes Mellitus.

Background:The amount and type of dietary protein affect glucose metabolism. However, the association between dietary protein intake and gestational diabetes mellitus (GDM) risk is vague. We examined this association. Methods: We included 152 GDM and 168 non-GDM participants (total 320), age 18–45 years from Arash Women's Hospital, Tehran, Iran. Protein intake was ascertained from 168-item Food Frequency Questionnaire at 24–40 weeks’ gestation. GDM was defined as fasting blood sugar >95 mg/dL and/or oral glucose tolerance test >155 mg/dL. Dietary data were assessed using N4 software and statistical analysis was performed using SPSS 21. We tested the association between the amount of protein consumed from red and processed meat, poultry, dairy, egg, seafood, and vegetable plus sociodemographic and lifestyle covariates and GDM risk using multivariate logistic regression analysis.Results:There was a significant association between the physical activity (P < 0.035), socioeconomic status (P < 0.013), body mass index, age, and each trimester's weight (P < 0.001), and risk of GDM. No significant association was observed between the intake of protein from major protein sources and risk of GDM. The only significant association was observed for egg consumption which was lower in GDM participants (P = 0.004), yet this association turned nonsignificant after adjustment for confounders, except for the fourth quartile (odds ratio: 0.43, 95% confidence interval: 0.208, 0.893).Conclusions:According to our findings, dietary intake of total and major protein sources could not affect the GDM risk. Differences between Iranian and Western population and the reverse causality might be the main reasons for this nonsignificant association.

Impacts of maternal dietary protein intake on fetal survival, growth, and development.

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H2S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new, effective means to improve embryonic/fetal survival and growth in mammals.

Maternal Macronutrient Intake and Offspring Blood Pressure 20Years Later.

BackgroundResults from 2 cohort studies in Scotland established in the 1940s and 1950s (Aberdeen and Motherwell) suggested that a high protein diet during pregnancy might adversely influence offspring blood pressure at adult age. Our objective was to examine this association in the Danish Fetal Origins Cohort (DaFO88).Methods and ResultsThis was a prospective birth cohort of 965 women who gave birth in 1988–1989 in Aarhus, Denmark, and whose offspring (n=434) participated in a clinical examination ≈20 years later. Macronutrient intake was assessed in gestational week 30. Multivariable adjusted linear regression was used to examine the relation between higher maternal protein intake, at the expense of carbohydrates, and offspring blood pressure (isocaloric substitution). Main analyses were adjusted for mother's age during pregnancy, prepregnancy body mass index, parity, smoking during pregnancy, educational level, and offspring's sex. The mean total energy intake was 8.7 MJ/day (SD 2.3 MJ/day). The mean energy from carbohydrate, fat, and protein intake was 51, 31, and 16 of total energy, respectively. The results showed that after adjustment, higher maternal protein intake was associated with slightly higher offspring diastolic blood pressure (highest compared with the lowest quintile of protein intake: ∆=2.4 mm Hg; 95% CI 0.4–4.4; P=0.03 for trend). Similar differences, although not significant, were found for systolic blood pressure (∆=2.6 mm Hg; 95% CI −0.0 to 5.3; P=0.08 for trend).ConclusionsHigher maternal dietary protein intake at the expense of carbohydrates was associated with a modest increase in offspring blood pressure in young adulthood.

Higher Maternal Dietary Protein Intake Is Associated with a Higher Risk of Gestational Diabetes Mellitus in a Multiethnic Asian Cohort

BackgroundDietary protein may affect glucose metabolism through several mechanisms, but results from studies on dietary protein intake and risk of gestational diabetes mellitus (GDM) have been inconsistent. ObjectiveWe examined the cross-sectional associations of dietary protein intake from different food sources during pregnancy with the risk of GDM in a multiethnic Asian population. MethodsWe included 980 participants with singleton pregnancies from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. Protein intake was ascertained from 24-h dietary recall and 3-d food diaries at 26–28 wk gestation. GDM was defined as fasting glucose ≥7.0 mmol/L and/or 2-h postload glucose ≥7.8 mmol/L at 26–28 wk gestation. We evaluated the association of dietary protein intake with GDM risk by substituting carbohydrate with protein in an isocaloric model with the use of multivariable logistic regression analysis. ResultsThe prevalence of GDM was 17.9% among our participants. After adjustment for potential confounders, a higher total dietary protein intake was associated with a higher risk of GDM; the OR comparing the highest with the lowest quartile of intake was 2.15 (95% CI: 1.27, 3.62; P-trend = 0.016). Higher intake levels of both animal protein (OR: 2.87; 95% CI: 1.58, 5.20; P-trend = 0.001) and vegetable protein (OR: 1.78; 95% CI: 0.99, 3.20; P-trend = 0.009) were associated with a higher risk of GDM. Among the animal protein sources, higher intake levels of seafood protein (OR: 2.17; 95% CI: 1.26, 3.72; P-trend = 0.023) and dairy protein (OR: 1.87; 95% CI: 1.11, 3.15; P-trend = 0.017) were significantly associated with a higher GDM risk. ConclusionHigher intake levels of both animal and vegetable protein were associated with a higher risk of GDM in Asian women. This trial was registered at clinicaltrials.gov as NCT01174875.

First-trimester maternal protein intake and childhood kidney outcomes: the Generation R Study

Nutritional exposures during in utero development may have long-lasting consequences for postnatal renal health. Animal studies suggest that specifically maternal dietary protein intake during pregnancy influences childhood kidney function. We examined the associations of total, animal, and vegetable maternal protein intake during pregnancy with kidney volume and function in school-aged children. This study was conducted in 3650 pregnant women and their children who were participating in a population-based cohort study from early life onward. First-trimester energy-adjusted maternal protein intake was assessed with a food-frequency questionnaire. At the child's age of 6 y, we assessed kidney volume, estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C concentrations, and microalbuminuria using urine albumin:creatinine ratios. First-trimester maternal total protein intake was associated with a higher childhood creatinine-based eGFR (difference: 0.06 mL × min(-1) × 1.73 m(-2); 95% CI: 0.01, 0.12 mL · min(-1) · 1.73 m(-2) per gram of protein intake). This association was mainly driven by vegetable protein intake (0.22 mL × min(-1) × 1.73 m(-2); 95% CI: 0.10, 0.35 mL · min(-1) · 1.73 m(-2) per gram of vegetable protein intake). These associations were not explained by protein intake in early childhood. First-trimester maternal protein intake was not significantly associated with childhood kidney volume, cystatin C-based eGFR, or the risk of microalbuminuria. Our findings suggest that higher total and vegetable, but not animal, maternal protein intake during the first trimester of pregnancy is associated with a higher eGFR in childhood. Further follow-up studies are needed to investigate whether maternal protein intake in early pregnancy also affects the risk of kidney diseases in later life.

Protein Requirements of Healthy Pregnant Women during Early and Late Gestation Are Higher than Current Recommendations1–4

Background: Adequate maternal dietary protein intake is necessary for healthy pregnancy. However, current protein intake recommendations for healthy pregnant women are based on factorial calculations of nitrogen balance data derived from nonpregnant adults. Thus, an estimate of protein requirements based on pregnancy-specific data is needed.Objective: The objective of this study was to determine protein requirements of healthy pregnant women at 11–20 (early) and 31–38 (late) wk of gestation through use of the indicator amino acid oxidation method.Methods: Twenty-nine healthy women (24–37 y) each randomly received a different test protein intake (range: 0.22–2.56 g · kg−1 · d−1) during each study day in early (n = 35 observations in 17 women) and late (n = 43 observations in 19 women) gestation; 7 women participated in both early and late gestation studies. The diets were isocaloric and provided energy at 1.7 × resting energy expenditure. Protein was given as a crystalline amino acid mixture based on egg protein composition, except phenylalanine and tyrosine, which were maintained constant across intakes. Protein requirements were determined by measuring the oxidation rate of L-[1-13C]phenylalanine to 13CO2 (F13CO2). Breath and urine samples were collected at baseline and isotopic steady state. Linear regression crossover analysis identified a breakpoint (requirement) at minimal F13CO2 in response to different protein intakes.Results: The estimated average requirement (EAR) for protein in early and late gestation was determined to be 1.22 (R2 = 0.60; 95% CI: 0.79, 1.66 g · kg-1 · d-1) and 1.52 g · kg−1 · d−1 (R2 = 0.63; 95% CI: 1.28, 1.77 g · kg-1 · d-1), respectively.Conclusions: These estimates are considerably higher than the EAR of 0.88 g · kg−1 · d−1 currently recommended by the Dietary Reference Intakes. To our knowledge, this study is the first to directly estimate gestational stage–specific protein requirements in healthy pregnant women and suggests that current recommendations based on factorial calculations underestimate requirements. This trial was registered at clinicaltrials.gov as NCT01784198.

Maternal protein intake during pregnancy and offspring overweight 20 y later

Animal studies have shown that protein intake in pregnancy may influence offspring fat metabolism and adiposity. The macronutrient ratio in human pregnancy appears to be important for offspring glucose tolerance; however, less is known about the influence on offspring adiposity. We examined the relation between maternal dietary protein intake during pregnancy and offspring anthropometric measures and biomarkers of adiposity and glucose metabolism. We used a prospective cohort of 965 Danish pregnant women recruited in 1988-1989 with offspring follow-up at 19-21 y. Macronutrient intake was collected in gestational week 30, and we divided protein according to its source (animal and vegetable including cereals). Offspring body mass index (BMI; in kg/m(2)) and waist circumference were recorded at follow-up (n = 695-697), and biomarkers were quantified in a subset (n = 443) of participants. We used multivariable linear and log-binomial regression to calculate effect estimates and 95% CIs for a 1:1-g substitution of carbohydrates for protein. Offspring mean (±SD) BMI was 22.1 ± 3.3 and 22.8 ± 2.9 for women and men, respectively. The prevalence of overweight (BMI ≥25) was 16.9% for women and 19.1% for men. We showed that a 1:1-g substitution of animal protein for carbohydrates increased risk of BMI ≥25 in female [quartile 4 compared with quartile 1: risk ratio (RR): 3.36; 95% CI: 1.52, 7.42] and male (quartile 4 compared with quartile 1: RR: 2.22; 95% CI: 0.92, 5.35) offspring. These results appeared to be accounted for by protein from meat sources. The results could not be explained by postnatal risk factors. Protein from animal sources, primarily meat products, consumed during pregnancy may increase risk of overweight in offspring; this association appeared to be stronger for female offspring. Because of the lack of information on postnatal exposure in this cohort, these results are hypothesis-generating and need to be replicated in other cohorts.

Maternal animal protein intake during pregnancy and risk of overweight in offspring 20 years later: a prospective cohort study

BackgroundDevelopment of excess adiposity has been hypothesised to originate in early life. Animal studies have shown that protein intake in pregnancy might influence offspring fat metabolism and adiposity. Macronutrient ratio in human pregnancy seems to be important for child blood pressure and glucose tolerance; less is known about the influence on offspring adiposity. We investigated the relation between maternal dietary protein intake during pregnancy and child anthropometric measures and biomarkers of adiposity and glucose metabolism. MethodsWe used a prospective cohort of 965 Danish pregnant women recruited in 1988–89 with offspring followed up at 20 years. This population was 80% of a consecutive sample of 1212 women carrying singletons and attending prenatal care in the city of Aarhus, Denmark. For the follow-up study, mothers were first informed about the study by mail and then the offspring were asked to fill out a web-based questionnaire and attend a clinical examination. Almost 95% (n=915) of mother–child pairs could be identified in the central registration. 690 of the offspring filled out the questionnaire and 443 participated in the clinical examination. Macronutrient intake was collected in gestational week 30, and we divided protein according to source (animal, vegetable including cereals). Offspring body-mass index (BMI) and waist circumference were recorded at follow-up (n=696), and biomarkers were quantified in a subset (n=443) of participants. We used multivariable linear and logistic regression to calculate effect estimates and 95% CIs for a 1:1 substitution of protein for carbohydrates in percent energy. All models were adjusted for maternal energy intake, maternal age, maternal education, parity, maternal pre-pregnancy BMI, maternal smoking during pregnancy, and sibling overweight. We accounted for missing data by the missing indicator method because the covariates were poorly correlated with the exposure and were therefore weak confounders. The study was approved by the Danish Data Protection Agency and the Danish Council of Ethics. FindingsAt baseline, mean maternal age was 29·1 years (SD 4·1), 373 (54%) of 695 women reported higher academic or university education, and 411 (59%) were nulliparous. Mean pre-pregnancy BMI was 21·3 kg/m2 (SD 2·9) and 242 women (35%) reported smoking during pregnancy. Offspring mean BMI was 22·4 kg/m2 (SD 3·1) and waist circumference was 79·8 cm (9·3) for women and 84·3 cm (9·3) for men; 124 (18%) of 695 participants had a BMI of at least 25 kg/m2. We found that a 1:1 substitution of animal protein for carbohydrates increased the risk of a BMI of at least 25 kg/m2 among female (quartile 4 vs quartile 1 risk ratio 3·36, 95% CI 1·52–7·42) and male (2·24, 0·93–5·40) offspring in a multivariable model that adjusted for covariates including maternal pre-pregnancy BMI and smoking, and sibling overweight. These results seemed to be accounted for by protein from meat sources. Consumption of vegetable protein in the highest quartile was not associated with overweight but was related to reduced LDL cholesterol in male offspring. InterpretationProtein intake from animal sources, primarily meat products, consumed during pregnancy seems to increase the risk of overweight in offspring; this association seemed to be stronger for female offspring. Although we cannot exclude potential residual confounding and selection bias, we adjusted for important and relevant confounders. In a subanalysis on selection bias, we found no significant differences for maternal age and BMI, parity, birthweight, gestational age, and maternal protein intake during pregnancy among those with and without outcome data. We were unable to estimate whether part of the association was accounted for by postnatal diet. FundingThe Danish Agency for Science, Technology and Innovation (DSF: 09-067124, DSF: 09-063072, DFS: 2101-06-0005, FSS: 09-065631).

Folic Acid and Protein Content in Maternal Diet and Postnatal High-Fat Feeding Affect the Tissue Levels of Iron, Zinc, and Copper in the Rat

Although maternal, fetal, and placental mechanisms compensate for disturbances in the fetal environment, any nutritional inadequacies present during pregnancy may affect fetal metabolism, and their consequences may appear in later life. The aim of the present study is to investigate the influence of maternal diet during gestation on Fe, Zn, and Cu levels in the livers and kidneys of adult rats. The study was carried out on the offspring (n = 48) of mothers fed either a protein-balanced or a protein-restricted diet (18% vs. 9% casein) during pregnancy, with or without folic acid supplementation (0.005- vs. 0.002-g folic acid/kg diet). At 10 weeks of age, the offspring of each maternal group were randomly assigned to groups fed either the AIN-93G diet or a high-fat diet for 6 weeks, until the end of the experiment. The levels of Fe, Zn, and Cu in the livers and kidneys were determined by the F-AAS method. It was found that postnatal exposure to the high-fat diet was associated with increased hepatic Fe levels (p < 0.001), and with decreased liver Zn and Cu contents (p < 0.01 and p < 0.05, respectively), as well as with decreased renal Cu contents (p < 0.001). Moreover, the offspring’s tissue mineral levels were also affected by protein and folic acid content in the maternal diet. Both prenatal protein restriction and folic acid supplementation increased the liver Zn content (p < 0.05) and the kidney Zn content (p < 0.001; p < 0.05, respectively), while folic acid supplementation resulted in a reduction in renal Cu level (p < 0.05). Summarizing, the results of this study show that maternal dietary folic acid and protein intake during pregnancy, as well as the type of postweaning diet, affect Fe, Zn, and Cu levels in the offspring of the rat. However, the mechanisms responsible for this phenomenon are unclear, and warrant further investigation.

Decreased maternal dietary protein intake during pregnancy alters large conductance, calcium‐activated K channel (BKCa) function in fetal coronary artery smooth muscle cells

We have shown that maternal nutrient restriction during pregnancy impairs an EDHF‐like pathway that is mediated via BKCa activation in fetal coronary arteries (CA). We hypothesized that BKCa activity is altered in CA of fetuses from malnourished ewes. Pregnant ewes were fed diets that differed only in metabolizable protein levels (control = 100% vs low protein = 80% of NRC recommendation) from day 100 – 130 of gestation. Fetal CA were then harvested and whole‐cell K currents (−70 to +50mV, 200 ms duration) were obtained in freshly isolated smooth muscle cells (n = 5–6 cells/fetus). In fetal CA smooth muscle cells from ewes fed a low protein diet, the I‐V curve was shifted to the left and peak current density was increased by 31% (low protein = 92.3 ± 7.5 vs. control = 70.5 ± 6.8 pA/pF; n=14). Iberiotoxin (100 nM) almost completely inhibited the K current in cells from the low protein group (72.3 ± 4.8% inhibition), but only partially inhibited this current in controls (31.5 ± 6.2% inhibition). Expression and localization of BKCa α‐ and β1‐subunits was similar in CA from both groups. Restricted maternal protein intake during late pregnancy enhances BKCa activity in fetal CA, without altering BKCa expression or localization, and may represent an adaptation to the dysfunction in the coronary arterial EDHF‐like pathway previously observed in offspring of ewes subjected to decreased nutrient intake during pregnancy (NIH R03HD061532).

High and low maternal protein intake of pregnant rats reduces incorporation of food derived amino acids into fetal protein

It has been shown that maternal dietary protein (P) intake affects fetal and post weaning growth (Daenzer et al., J. Nutr. 132: 142, 2002). We studied amino acid (AA) metabolism of pregnant mothers and their fetuses. Female rats were pair‐fed isocaloric diets of either low (LP, 10%), adequate (control, CP, 20%) or high casein content (HP, 40%) from start of mating throughout gestation. On gestation d 14 and 19 the plasma AA concentrations and relative incorporation (RI) of orally administered 13C‐lysine (Lys) and 13C‐leucine (Leu) in placental and fetal P based on product/precursor relationships was measured. Placental and fetal weights were not different. Maternal plasma AA showed higher concentrations of branched chain AA in HP, whereas taurine concentrations were increased in LP and CP, but not in HP (P &lt; 0.05). Maternal plasma P 13C‐enrichment decreased with increasing maternal P intake. On d 14 and 19 RILys and RILeu in placental and fetal P were significantly lower (P &lt; 0.05; except P &gt; 0.05 for HP on day 19) in LP and HP fed rats as compared to CP. The data suggest that oxidative losses of AA induced by HP feeding may have consequences for placental and fetal P synthesis. An inadequate maternal P intake alters intrauterine AA metabolism which underlies fetal growth retardation.

Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth

A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry. We analyzed data on 1040 mother-infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988-1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference -to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index. In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: -32.7, -3.0; P=0.02). Protein intake was also associated negatively with ponderal index (beta=-0.01; 95% CI: -0.02, -0.00; P=0.01). A 1 % increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants. This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.

Developmental Immunotoxicity of Lead in the Rat: Influence of Maternal Diet

The effect of maternal dietary protein intake on lead-induced developmental immunotoxicity was studied in female Fischer 344 rats receiving lead acetate (250 ppm) or sodium acetate (control) in the drinking water during breeding and pregnancy until parturition. Dams were fed isocaloric diets (either 20% casein or 10% casein) from 2 wk prior to mating until the end of lactation. After weaning, dams and female offspring were given the 20% casein diet and regular water. Immune function was assessed in dams at 8 wk postpartum and in offspring at 13 wk of age. Dams showed no marked difference in any of the immune endpoints examined, regardless of diet or lead treatment. In contrast, lead exposure during early development produced a subsequent significant reduction of both the delayed-type hypersensitivity response and interferon γ production in adult offspring independent of maternal diet. Lead-exposed offspring from the high-dietary-protein group had significantly elevated production of both interleukin-4 and tumor necrosis factor α(TNF-α) with increased relative spleen weight and a decreased body weight compared to offspring in the lead control group. In contrast, lead-exposed offspring from dams receiving the low-protein diet had no marked change in TNF-α levels, relative spleen weight, or body weight, while interleukin-4 levels were significantly reduced compared with the lead control group. In conclusion, maternal dietary protein intake can modulate the immunotoxic effects of lead exposure during early development. This occurred at levels of protein intake and doses of lead exposure that produced no detectable effect on the maternal immune system.

Maternal dietary protein intake and sex‐specific investment in Mastomys coucha (Rodentia: Muridae)

AbstractWe examined data on captive multi‐mammate mice (Mastomys coucha) to assess differential maternal investment, and sex‐specific resource allocation. Differences in maternal size were induced through manipulation of dietary protein in three treatment groups: low (10%), medium (15%) and high (20%) protein diets. Mothers on the 20% protein diet were significantly larger than those on the lower protein diets, and produced significantly more male than female offspring. Mothers on the lower protein diets did not produce sex‐biased litters. There were no sex‐specific differences in body size or body tissue composition of pups at birth or at weaning within each treatment group. At weaning, pups in the 20% protein treatment group had proportionately greater amounts of lean tissue and less body lipid reserves than pups in the 10% protein treatment group. Pups in the 20% protein treatment group were also larger, and had faster growth rates, than those in the 10% protein treatment group. Weaned pups in the 15% protein treatment group had the fastest growth rates and greatest energetic reserves of all of the treatment groups. Our results suggest that larger mothers on the high (20%) protein diet show differential investment in the sexes, not by allocating more resources to individuals of that sex, but by producing more male than female offspring.

Differential hepatic lobar gene expression in offspring exposed to altered maternal dietary protein intake.

Increased plasma fibrinogen concentrations are a recognized risk factor for coronary heart disease, and increased fibrinogen levels in adults are associated with parameters of reduced early growth. We studied fibrinogen gene expression in adult offspring of dams fed either a 20% (control) or an 8% protein diet [maternal low-protein (MLP) rats] during pregnancy and lactation and determined whether any effects were consistent between left and right liver lobes, since the fetal liver has a unique blood supply that produces differential stimuli to the left and right lobes. In MLP offspring, there was a reduction in all three fibrinogen mRNA copy numbers in the left liver lobe [left vs. right lobes for alpha-, beta-, and gamma-fibrinogen (x10(6) copies/ng total RNA): 8.04 vs. 23.16, P<0.001; 4.74 vs. 13.07, P<0.001; and 4.61 vs. 16.38, P = 0.007, respectively], with a parallel reduction in fibrinogen concentration in the left liver lobe (8.53+/-0.33 vs. 10.41 +/-0.65 arbitrary units, P = 0.014, left and right lobes, respectively). No such effect was observed in offspring of control dams. To investigate the underlying mechanism, glucocorticoid receptor function and mRNA levels were studied, since expression of fibrinogen genes is regulated by glucocorticoid hormones. The binding affinity of the high-affinity glucocorticoid receptor was reduced only in the left liver lobe of the MLP offspring (P = 0.02, left. vs. right), with a parallel reduction in this lobe in glucocorticoid receptor mRNA level (P = 0.006, left vs. right). In conclusion, maternal dietary protein restriction reduces fibrinogen gene expression, fibrinogen protein, and mRNA level and binding affinity of glucocorticoid receptors only in the left liver lobe of the adult offspring.