Poor Maternal Diet Research Articles

Proportion of Low Birth Weight (LBW) Among Newborn Babies Delivered at Dhaka Medical College Hospital

<i>Background</i>: Low birth weight (LBW) remains a major public health problem especially in developing countries like Bangladesh. We assessed the proportion of LBW of the newborn babies delivered at DMCH and its associated maternal factors. <i>Methodology: </i>This cross-sectional descriptive study was conducted among 57 mother and newborn pairs delivered at Postnatal obstetrics wards of Dhaka Medical College Hospital (DMCH), Dhaka. Data was collected from each participants by face to-face interview using a semi-structured pre-tested questionnaire which included socio-demographic information and information about birth weight and its associated maternal factors. <i>Result: </i>This study involved 257 participants with a mean age of 25 years (±4.26), primarily aged 21 to 30 (64.97%). Approximately 38.13% had a monthly family income below 15,000 taka, and 10.98% of mothers were illiterate. One-third received 2 to 4 antenatal visits, with 8.56% having none. Delivery methods were nearly equal, with 49.02% vaginal and 50.97% cesarean. Common complications included PROM (14.39%), pre-term labor (11.67%), and GDM (10.89%). Term pregnancies accounted for 70%, while among preterm births, 20.23% were low birth weight (LBW) and 4.67% very low birth weight (VLBW), surpassing general population rates. <i>Conclusion: </i>Lack of regular antenatal care (ANC) visits and poor maternal diet significantly impact newborn birth weight. To reduce low birth weight (LBW), it is essential to monitor maternal diets and ensure at least four ANC visits for all mothers. LBW infants are at higher risk of mortality and chronic diseases, making its reduction vital for achieving Sustainable Development Goals (SDGs) on infant mortality. Further multi-center studies are needed to accurately assess LBW prevalence in Bangladesh.

PSIII-1 The effects of maternal diet on ram lamb reproductive characteristics

Abstract Maternal nutrition during gestation and resulting impacts on ram reproduction and epigenetics are poorly understood. We previously reported altered mRNA and epigenetic markers in F1 ram sperm due to poor maternal diet (restricted- and over-feeding) during gestation, yet the multigenerational effects on ram reproduction are unexplored. We hypothesized that F2 offspring born from restricted- and over-fed granddams would exhibit altered reproductive characteristics, and F1 and F2 offspring would display altered circulating concentrations of reproductive hormones. The objectives of this study were to determine the effects of poor maternal diet on 1) the reproductive function of F2 ram offspring, and 2) key reproductive hormones in F1 and F2 offspring. To evaluate these objectives, multiparous Dorset ewes (F0, n = 46) were fed 100% (CON), 60% (RES), or 140% (OVER) of National Research Council requirements from d 30 of gestation through parturition and a control diet during lactation. Offspring are identified as CON-F1 (n = 10 ewes; 12 rams), RES-F1 (n = 13 ewes; 21 rams), and OVER-F1 (n = 16 ewes; 15 rams). The F1 ewes (n = 37) were maintained on a control diet throughout and were bred between 16 and 19 mo of age to establish the F2 generation. Resulting male offspring are referred to as CON-F2 (n = 6 rams), RES-F2 (n = 13 rams), and OVER-F2 (n = 9 rams) in correspondence to the diets of the granddam. Semen samples of F2 rams were collected via electroejaculation at d 248.4 ± 0.36 (collection 1) and d 255.4 ± 0.36 (collection 2). Semen quality (volume, pH, sperm motility, and sperm concentration) was evaluated at both collections using mCASA; iSperm, Aidmics Biotechnology Co., LTD. Scrotal circumference was measured at collection 2. Sperm morphology was determined by contrast microscopy. Testosterone (T) and follicle stimulating hormone (FSH) were measured in F1 and F2 serum samples collected at d 256 ± 0.13 using commercially available kits. Data were analyzed using R Studio with P ≤ 0.05 considered significant and 0.05 < P ≤ 0.10 considered a tendency. An effect of granddam diet was not observed for F2 ram semen volume, pH, sperm motility, sperm concentration, scrotal circumference, nor histological sperm morphology (P ≥ 0.25). An effect of F0 diet was not observed for F1 or F2 offspring serum concentrations of T and FSH (P ≥ 0.28). In our model, F0 diet during gestation did not affect F2 male offspring sperm quality or circulating T and FSH in F1 and F2 generations. However, based on our previous reports that F0 diet altered F1 sperm epigenome, there may be an impact of maternal diet on epigenetic inheritance which warrants further exploration.

High fat diet consumption and social instability stress impair stress adaptation and maternal care in C57Bl/6 dams

Poor maternal diet and psychosocial stress represent two environmental factors that can significantly impact maternal health during pregnancy. While various mouse models have been developed to study the relationship between maternal and offspring health and behaviour, few incorporate multiple sources of stress that mirror the complexity of human experiences. Maternal high-fat diet (HF) models in rodents are well-established, whereas use of psychosocial stress interventions in female mice are still emerging. The social instability stress (SIS) paradigm, serves as a chronic and unpredictable form of social stress. To evaluate the combined effects of a poor maternal diet and intermittent social stress on maternal health and behaviour, we developed a novel maternal stress model using adult female C57Bl/6 mice. We observed that all HF+ mice demonstrated rapid weight gain, elevated fasting blood glucose levels and impaired glucose tolerance independent of the presence (+) or absence (-) of SIS. Behavioural testing output revealed anxiety-like behaviours remained similar across all groups prior to pregnancy. However, integrated anxiety z-scores revealed a mixed anxious profile amongst HF+/SIS+ females prior to pregnancy. HF+/SIS+ females also did not show reduced plasma ACTH and corticosterone levels that were observed in our other HF+ and HF- stress groups after SIS exposure. Further, HF+/SIS+ females demonstrated significant postpartum maternal neglect, resulting in fewer numbers of live offspring. These findings suggest that prolonged maternal HF diet consumption, coupled with previous exposure to SIS, places a significant burden on the maternal stress response system, resulting in reduced parental investment and negative postpartum behaviour towards offspring.

Sub-Optimal Paternal Diet at the Time of Mating Disrupts Maternal Adaptations to Pregnancy in the Late Gestation Mouse.

Pregnancy represents a stage during which maternal physiology and homeostatic regulation undergo dramatic change and adaptation. The fundamental purpose of these adaptations is to ensure the survival of her offspring through adequate nutrient provision and an environment that is tolerant to the semi-allogenic foetus. While poor maternal diet during pregnancy is associated with perturbed maternal adaptations during pregnancy, the influence of paternal diet on maternal well-being is less clearly defined. We fed C57BL/6 male mice either a control (CD), low protein diet (LPD), a high fat/sugar Western diet (WD) or the LPD or WD supplemented with methyl donors (MD-LPD and MD-WD, respectively) for a minimum of 8 weeks prior to mating with C57BL/6 females. Mated females were culled at day 17 of gestation for the analysis of maternal metabolic, gut, cardiac and bone health. Paternal diet had minimal influences on maternal serum and hepatic metabolite levels or gut microbiota diversity. However, analysis of the maternal hepatic transcriptome revealed distinct profiles of differential gene expression in response to the diet of the father. Paternal LPD and MD-LPD resulted in differential expression of genes associated with lipid metabolism, transcription, ubiquitin conjugation and immunity in dams, while paternal WD and MD-WD modified the expression of genes associated with ubiquitin conjugation and cardiac morphology. Finally, we observed changes in maternal femur length, volume of trabecular bone, trabecular connectivity, volume of the cortical medullar cavity and thickness of the cortical bone in response to the father's diets. Our current study demonstrates that poor paternal diet at the time of mating can influence the patterns of maternal metabolism and gestation-associated adaptations to her physiology.

Breastfeeding practices and social norms in Kinshasa, Democratic Republic of the Congo: A qualitative study.

Breastfeeding has many benefits for both mothers and children. The World Health Organization recommends exclusive breastfeeding for the first six months of life. However, in the Democratic Republic of the Congo, slightly under half of children under six months are exclusively breastfed. This study aimed to describe breastfeeding practices and to explore perceived social norms regarding breastfeeding among mothers in Kinshasa. A qualitative descriptive study was conducted in Kinshasa from June to July 2013. This study purposively sampled 54 mothers of infants aged 6 to 12 months, who participated in six focus group discussions. Based on the Theory of Planned Behaviour, the discussion guide explored infant feeding in the first six months, knowledge of breastfeeding, perception of the feasibility of exclusive breastfeeding, and perception of the social norms with regard to exclusive breastfeeding. The content analysis approach was used to analyse data. Mothers had good breastfeeding knowledge; however, few of them had practised exclusive breastfeeding as recommended during the first six months. Exclusive breastfeeding was considered unfeasible in their context. Barriers to exclusive breastfeeding were reported as baby's cries, social pressure, warm climate, and poor maternal diet. Social norms were supportive of breastfeeding but unfavourable to exclusive breastfeeding. In Kinshasa, mothers have a good knowledge of breastfeeding. However, few practise exclusive breastfeeding. Social pressure plays an important role in the cessation of exclusive breastfeeding before six months. In order to improve the practice of exclusive breastfeeding in this context, social and behaviour change programmes should target the entire population rather than mothers only.

Effects of poor maternal diet during gestation are detected in F2 offspring.

Poor maternal nutrition of F0 ewes impairs F1 offspring growth, with minimal differences in glucose tolerance or select metabolic circulating factors, and independent of differences in residual feed intake (RFI). To determine if poor maternal nutrition in F0 ewes alters F2 offspring growth, circulating leptin, feed efficiency, or glucose tolerance, F0 ewes (n = 46) pregnant with twins were fed 100% (control), 60% (restricted), or 140% (over) of National Research Council requirements from days 30 ± 0.02 of gestation until parturition. At 16 to 19 mo of age, female F1 (n = 36) offspring were bred to generate F2 offspring [CON-F2 (n = 12 ewes; 6 rams), RES-F2 (n = 7 ewes; 13 rams), or OVER-F2 (n = 13 ewes; 9 rams) corresponding to diets of the granddam (F0)]. Lamb body weights (BW) and blood samples were collected weekly from days 0 to 28 and every 14 d until day 252 of age. Circulating leptin was measured in serum at days 0, 7, 14, 56, 210, and 252. An intravenous glucose tolerance test was performed at days 133 ± 0.28. At days 167 ± 0.33, individual daily intake was recorded over a 77-d feeding period to determine RFI. Rams were euthanized at days 285 ± 0.93, and body morphometrics, loin eye area (LEA), back fat thickness, and organ weights were collected and bone mineral density (BMD) and length were determined in the right hind leg. During gestation, OVER-F1 ewes tended to be 8.6% smaller than CON-F1 ewes (P ≤ 0.06). F2 offspring were of similar BW from birth to day 70 (P ≥ 0.20). However, from days 84 to 252, RES-F2 offspring tended to be 7.3% smaller than CON-F2 (P ≤ 0.10). Granddam diet did not influence F2 ram body morphometrics, organ or muscle weights, LEA, adipose deposition, or leg BMD (P ≥ 0.84). RES-F2 (-0.20) and CON-F2 (-0.45) rams tended to be more feed efficient than CON-F2 ewes (0.31; P ≤ 0.08). No effects of granddam diet were observed on glucose or insulin average or baseline concentrations, area under the curve, first-phase response, or ratio (P ≥ 0.52). However, CON-F2 rams (297mg/dL ± 16.5) had a greater glucose peak compared with RES-F2 rams (239mg/dL ± 11.2; P = 0.05). Peak insulin concentrations were not influenced by granddam diet (P = 0.75). At d 56, RES-F2 and OVER-F2 offspring had 53.5% and 61.8% less leptin compared with CON-F2 offspring, respectively (P ≤ 0.02). These data indicate that poor maternal nutrition impacts offspring growth into the second generation with minimal impacts on offspring RFI, glucose tolerance, and circulating leptin.

PSIV-1 Effects of Poor Maternal Nutrition During Gestation on F0 and F1 Ewe Colostrum and Milk Composition and Colostrum Igg

Abstract High-quality colostrum and milk are critical for proper neonatal growth and immune system development. Immunoglobulin G (IgG) is the predominant antibody class in colostrum and is vital for passive immune transfer in sheep. There is limited understanding of how poor maternal nutrition during gestation (restricted- and over-feeding) might influence colostrum and milk composition and colostrum IgG concentrations and how F1 offspring colostrum and milk are impacted as a result of F0 maternal diet. The objective of this experiment was to determine if poor maternal nutrition during gestation impacts F0 and F1 colostrum and milk composition, including IgG concentrations. We hypothesized that maternal restricted-feeding would decrease, and maternal over-feeding would increase total solids, fat, and protein during early and transitional lactation and that restricted-feeding would increase IgG concentrations and over-feeding would decrease IgG concentrations in F0 and F1 ewe colostrum. Multiparous Dorset ewes pregnant (n = 46) with twins were fed 100% (control; n = 13), 60% (restricted; n = 17) or 140% (over; n = 16) of National Research Council (NRC) requirements. After birth and during lactation, dams were fed 100% NRC for lactating ewes, so the nutritional insult only occurred during gestation. Resulting ewe offspring (n = 32) were raised on control diets and were bred between 16 and 19 mo of age. Colostrum samples were collected within 24 h of parturition and milk samples were collected at d 3 and d 21 postpartum. Colostrum and milk composition were evaluated using Brix Refractometry (total solids, g/dL) and spectrophotometry (crude fat, %; crude protein, %). Additionally, a radial immunodiffusion assay was used to determine IgG concentrations (mg/dL) in colostrum. A treatment by time interaction was observed for F0 colostrum crude fat where restricted-fed ewes had less fat than control-fed ewes (P ≤ 0.024). No interaction was detected for all other F0 and F1 composition variables (P ≥ 0.16). We did not detect a main effect of diet on F0 or F1 total solids, crude fat, and crude protein of colostrum nor milk (P ≥ 0.24). A main effect of time was observed for all variables where colostrum had greater total solids, crude fat, and crude protein compared with milk at d 3 and d 21 (P ≤ 0.0001). No effect of maternal diet on IgG concentrations were detected in F0 or F1 ewe colostrum (P ≥ 0.46). These data indicate that poor maternal diet has minimal effects on F0 and F1 ewe colostrum composition and IgG concentrations, and d 3 and d 21 milk composition. In addition, the impact of F0 diet on colostrum fat composition did not persist into the F1 generation.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory Tcell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

Restricted- and over-feeding during gestation decreases growth of offspring throughout maturity.

To determine the effects of poor maternal nutrition on the growth and metabolism of offspring into maturity, multiparous Dorset ewes pregnant with twins (n = 46) were fed to either 100% (control; n = 13), 60% (restricted; n = 17), or 140% (over; n = 16) of National Research Council requirements from day 30 ± 0.02 of gestation until parturition. Offspring of these ewes are referred to as CON (n = 10 ewes; 12 rams), RES (n = 13 ewes; 21 rams), or OVER (n = 16 ewes; 13 rams), respectively. Lamb body weights (BW) and blood samples were collected weekly from birth (day 0) to day 28 and then every 14 d until day 252. Intravenous glucose tolerance test (infusion of 0.25 g dextrose/kg BW) was performed at day 133 ± 0.25. At day 167 ± 1.42, individual daily intake was recorded over a 77 d feeding period to determine residual feed intake (RFI). Rams were euthanized at day 282 ± 1.82 and body morphometrics, loin eye area (LEA), back fat thickness, and organ weights were collected. The right leg was collected from rams at necropsy and dual-energy x-ray absorptiometry was used to determine bone mineral density (BMD) and length. Averaged from day 0 until day 252, RES and OVER offspring weighed 10.8% and 6.8% less than CON offspring, respectively (P ≤ 0.02). When adjusted for BW, liver and testes weights tended to be increased and decreased, respectively, in RES rams compared with CON rams (P ≤ 0.08). Additionally, RES BMD and bone length were less than CON rams (P ≤ 0.06). Treatment did not influence muscle mass, LEA, or adipose deposition (P ≥ 0.41). Rams (-0.17) were more feed efficient than ewes (0.23; P < 0.01); however, no effect of maternal diet was observed (P ≥ 0.57). At 2 min post glucose infusion, glucose concentrations in OVER offspring were greater than CON and RES offspring (P = 0.04). Concentrations of insulin in CON rams tended to be greater than OVER and RES ewes at 5 min (P ≤ 0.07). No differences were detected in insulin:glucose or area under the curve (AUC) for glucose or insulin (P ≤ 0.29). Maternal diet did not impact offspring triglycerides or cholesterol (P ≤ 0.35). Pre-weaning leptin tended to be 70% greater in OVER offspring than CON (P ≤ 0.07). These data indicate that poor maternal nutrition impairs offspring growth throughout maturity but does not affect RFI. Changes in metabolic factors and glucose tolerance are minimal, highlighting the need to investigate other mechanisms that may contribute to negative impacts of poor maternal diet.

PSXV-10 Poor Maternal Nutrition Impacts Mrna Expression of Epigenetic Factors in ram Offspring Liver

Abstract Poor maternal nutrition (over- and restricted-feeding) alters growth and metabolism in offspring after birth; however, the mechanisms are not well understood. Epigenetics, the heritable changes in gene expression without altering the DNA sequence, is a possible mechanism. We hypothesized that mRNA expression of epigenetic factors in livers of male offspring would be altered as a result of poor maternal diet during gestation. Multiparous Dorset ewes (n = 46) pregnant with twins were fed 100%, 60% or 140% of NRC requirements from d 30 ± 0.02 of gestation until parturition. Male offspring are referred to as CON (n=12), RES (n=21), and OVER (n=13), respectively. Ram lambs were euthanized at d 284±1.82, and liver tissue was immediately snap-frozen. RNA was isolated from liver and gene expression was quantified using real-time (RT)-PCR. Epigenetic factors of interest included DNA methyltransferases (DNMT; DNMT1, DNMT3B), ten eleven translocation enzyme 2 (TET2), lysine acetyltransferases (KAT; KAT1, KAT2B, KAT6A, KAT8), histone deacetylases (HDAC; HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC8, HDAC11, sirtuin1), and histone methyltransferases [ASH1 like histone lysine methyltransferase (ASH1L), euchromatic histone lysine methyltransferase (EHMT)1, EHMT2, SET domain bifurcated histone lysine methyltransferase 2 (SETDB2)]. Gene expression of ASH1L and KAT6A were decreased in liver tissue of RES compared with OVER by 42.8% and 59.7%, respectively (P≤0.017). Gene expression of DNMT1 and HDAC3 were decreased in RES compared with CON by 38.3% and 35.0%, respectively (P≤0.045). Gene expression of EHMT1 and HDAC8 were increased in OVER compared with CON by 19.3% and 37.4%, respectively (P≤0.045). There were no differences detected in expression of other genes (P≥0.060). Thus, maternal diet affects hepatic mRNA expression of specific epigenetic factors which may contribute to altered metabolism and liver function. Further investigation is warranted to determine how epigenetic modifications impact offspring growth and metabolism long-term.

Poor maternal diet during gestation alters offspring muscle proteome in sheep.

Poor maternal nutrition during gestation can result in reduced offspring muscle growth and altered muscle metabolism. We hypothesized that over- or restricted-nutrition during gestation would alter the longissimus dorsi muscle (LM) proteome of offspring. Pregnant ewes were fed 60% (restricted), 100% (control), or 140% (over) of National Research Council requirements for total digestible nutrients from day 30 of gestation until parturition. Fetal (RES, CON, OVER) LM were collected at days 90 and 135 of gestation, or from offspring within 24 h of birth. Sarcoplasmic proteins were isolated, trypsin digested, and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating tandem mass tag technology. Differential expression of proteins was identified by ANOVA followed by Tukey's HSD post hoc tests, and regularized regression via the elastic net. Significance was set at P < 0.05. Over-represented pathways containing differentially expressed proteins were identified by Reactome and included metabolism of proteins, immune system, cellular response to stress/external stimuli, developmental biology, and infectious disease. As a result of maternal diet, a total of 312 proteins were differentially expressed (day 90 = 89 proteins; day 135 = 115 proteins; birth = 131 proteins). Expression of eukaryotic initiation factor (EIF) 2S3, EIF3L, and EIF4G2 was lower in OVER fetuses at day 90 of gestation (P < 0.05). Calcineurin A and mitogen-activated protein kinase 1 were greater in RES fetuses at day 90 (P < 0.04). At day 135 of gestation, pyruvate kinase and lactate dehydrogenase A expression were greater in OVER fetuses than CON (P < 0.04). Thioredoxin expression was greater in RES fetuses relative to CON at day 135 (P = 0.05). At birth, proteins of the COP9 signalosome complex were greater in RES offspring relative to OVER (P < 0.05). Together, these data indicate that protein degradation and synthesis, metabolism, and oxidative stress are altered in a time and diet-specific manner, which may contribute to the phenotypic and metabolic changes observed during fetal development and postnatal growth.

Maternal nutrient restriction and over-feeding during gestation alter expression of key factors involved in placental development and vascularization.

Poor maternal nutrition can negatively affect fetal and placental growth and development. However, the mechanism(s) that contribute to altered placenta growth and function are not well understood. We hypothesized that poor maternal diet would impact signaling through the C-X-C motif chemokine ligand (CXCL) 12-CXCL4 axis and/or placental expression of the insulin-like growth factor (IGF) axis. Using our established sheep model of poor maternal nutrition, we examined the effects of restricted- and over-feeding on ewe placentome gene and protein expression. Specifically, ewes were fed a control (CON; 100%), restricted (RES; 60%), or over (OVER; 140%) diet beginning at day 30.2 ± 0.02 of gestation, and samples were collected at days 45, 90, and 135 of gestation, representing periods of active placentation, peak placental growth, and near term, respectively. Placentomes were separated into cotyledon and caruncle, and samples snap frozen. Protein was determined by western blot and mRNA expression by real-time PCR. Data were analyzed by ANOVA and significance determined at P ≤ 0.05. Ewes fed a RES diet had decreased CXCL12 and vascular endothelial growth factor (VEGF), and increased tumor necrosis factor (TNF)α protein compared with CON ewes in caruncle at day 45 (P ≤0.05). In day 45 cotyledon, CXCR7 protein was increased and mTOR was decreased in RES relative to CON (P ≤0.05). At day 90, CXCR4 and CXCR7 were reduced in RES caruncle compared with CON, whereas VEGF was reduced and mTOR increased in cotyledon of RES ewes relative to CON (P ≤0.05). In OVER caruncle, at day 45 CXCR4 and VEGF were reduced and at day 90 CXCR4, CXCR7, and TNFα were reduced in caruncle compared with CON (P ≤0.05). There was no observed effect of OVER diet on protein abundance in the cotyledon (P > 0.05). Expression of IGF-II mRNA was increased in OVER at day 45 and IGFBP-3 was reduced in RES at day 90 in caruncle relative to CON (P ≤0.05). Maternal diet did not alter placentome diameter or weight (P > 0.05). These findings suggest that restricted- and over-feeding negatively impact protein and mRNA expression of key chemokines and growth factors implicated in proper placenta development and function.

Evaluation of multiple micronutrient supplementation and medium-quantity lipid-based nutrient supplementation in pregnancy on child development in rural Niger: A secondary analysis of a cluster randomized controlled trial.

BackgroundIt is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.Methods and findingsWe conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron–folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: −0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: −0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: −0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: −0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: −0.22, 0.44; p = 0.53) or motor scores (SMD: −0.04; 95% CI: −0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.ConclusionsThere was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.Trial registrationClinicalTrials.gov NCT02145000.

Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences.

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can affect embryonic development. This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA. These epigenetic changes can compromise the health of the offspring later in life. We discuss different types of nutritional stressors in human and animal models, such as maternal undernutrition, seasonal diets, low-protein diet, high-fat diet, and synthetic folic acid supplement use, and how these nutritional exposures epigenetically affect target genes and their outcomes. In addition, we review the concept of thrifty genes during the preimplantation period, and some examples that relate to epigenetic change and diet. Finally, we discuss different examples of maternal diets, their effect on outcomes, and their relationship with assisted reproductive technology (ART), including their implications on epigenetic modifications.

PSIII-24 Poor gestational nutrition impacts sheep offspring growth but not feed efficiency

Abstract The objective was to determine the effects of poor maternal nutrition during gestation on growth and feed efficiency of offspring. We hypothesized that body weights (BW) would decrease and residual feed intake (RFI) would increase (reduced feed efficiency) in offspring of restricted- and over-fed ewes. Forty-six multiparous Dorset ewes pregnant with twins were fed 100%, 60% or 140% of NRC requirements from d 30 of gestation until parturition. Offspring are referred to as CON (n = 10 ewes; 12 rams), RES (n = 13 ewes; 21 rams), and OVER (n = 16 ewes; 13 rams), respectively. Lamb BW were measured weekly from birth to d 28 and biweekly until d 252 of age. Starting at d 167±13.6, daily intake of a complete pelleted feed was recorded using a Super SmartFeed (C-lock Inc., Rapid City, SD) over a 77 d- feeding period. Average BW were taken two days before, at mid-point, and two days after the feeding trial period and RFI was calculated for each animal. Rams were euthanized at d 284±12 and body morphometrics, loin eye area (LEA), back fat thickness, and organ weights were collected. From birth to d 252, ram lambs were 5.4 kg heavier (P &amp;lt; 0.001) than ewe lambs. Control ewe lambs were 4.3 kg heavier than RES and OVER (P &amp;lt; 0.05) from birth to 9 months and CON rams were 4.7 kg heavier (P &amp;lt; 0.01) than RES. Rams (-0.17) were more efficient than ewes (0.23; P &amp;lt; 0.01); however, no dietary treatment difference was observed (P ≥ 0.57). No differences in muscle mass, LEA, and adipose deposition were observed (P ≥ 0.41). These data indicate that poor maternal diet during gestation impacts offspring growth but not RFI. Further investigation is warranted to determine if differences in BW are a result of metabolic alterations impacted by poor maternal nutrition during gestation.

526 Late-Breaking: Poor Maternal Diet Alters the Muscle Proteome at Mid-gestation in Sheep

Abstract Maternal diet during gestation can negatively impact fetal development and postnatal growth and body composition. We hypothesized that poor maternal nutrition during gestation would alter protein expression in muscle at day 90 of gestation in sheep. Pregnant ewes (n = 24) were fed a control, restricted, or over-fed diet (100, 60, or 140% of NRC requirements for total digestible nutrients, respectively; n = 8 per treatment) starting at day 30 of gestation. At day 90 of gestation, fetal longissimus dorsi samples were collected (CON, RES, and OVER, respectively). Sarcoplasmic proteins were trypsin digested and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Differential expression of proteins was identified via two statistical techniques: ANOVA followed by Tukey’s HSD post-hoc tests, and regularized regression via elastic net. Significance was set at P &amp;lt; 0.05. Over-represented pathways containing differentially expressed proteins were identified by Reactome and included metabolism of proteins, immune system, cellular response to stress/external stimuli, developmental biology, and infectious disease. Within these pathways, 26S proteasome non-ATPase regulatory subunit (PSMD) 1, PSMD6, and PSMD14, components of the 26 S proteasome, were reduced 6 to 10% in OVER relative to CON offspring. Proteins involved in elongation and initiation, including eukaryotic initiation factor (EIF) 2 subunit 3, EIF 4 gamma 2, and EIF 3 subunit B were reduced 8 to 15% in OVER relative to CON offspring. Mitogen-activated protein kinase (MAPK) 1 and dual-specificity MAPK kinase (MEKK) 1 were increased by 12% in RES relative to OVER and CON offspring. Together, these data indicate that protein degradation and synthesis are altered in mid-gestation muscle development in OVER offspring, and that cell signaling related to cell proliferation is affected in RES offspring. These changes may contribute to the phenotypic and metabolic changes observed during fetal development and postnatal growth.

Maternal diet before and during pregnancy modulates microglial activation and neurogenesis in the postpartum rat brain

The implications of poor maternal diet on offspring metabolic and neuroimmune development are well established. Increasing evidence now suggests that maternal obesity and poor diet can also increase the risk of postpartum mood disorders, but the mechanisms are unknown. Here we investigated the effects of a poor, high-fat-high-sugar diet (HFSD) on peripheral and central inflammation, neurogenesis and postpartum anxiety-like behaviours. We hypothesised that long-term consumption of a HFSD pre- and post-conception would increase the levels of circulating cytokines and induce microglial activation, particularly in the arcuate nucleus of the hypothalamus (ARC), as the primary brain region involved in the integration of satiety signalling; and this would lead to increased anxiety, stress responsivity and disrupted neurogenesis. We further hypothesised that these effects would be ameliorated by consumption of a healthier diet during pregnancy – specifically a diet high in omega-3 polyunsaturated fatty acids (PUFAs). As expected, the HFSD significantly increased pre-conception body weight, elevated circulating cytokines and activated microglia in the ARC, as well as in the basolateral amygdala. The HFSD also significantly increased the numbers of immature (doublecortin (DCX)-positive) neurons in the subgranular/granular region of the hippocampus, a neurogenic response that was, surprisingly, mimicked by consumption of a diet high in omega-3 PUFAs. Despite these effects of peri-pregnancy dietary imbalance, we detected no differences in anxiety-like behaviours or hypothalamic-pituitary-adrenal (HPA) axis reactivity between the groups. A shift to a healthier diet post-conception reversed the peripheral inflammation and alleviated the microglial activation. These novel data indicate the importance of a balanced peri-pregnancy diet and highlight the need for future research into key triggers that alter the neuroimmune balance in the maternal brain.

Association between Maternal Dietary Diversity and Low Birth Weight in Central India: A Case-Control Study.

Low birth weight (LBW) is one of the major public health challenges in India. LBW etiology is multifactorial and linked to multiple determinants, including maternal undernutrition and sociodemographic characteristics. The objective of the present endeavor was to assess how maternal dietary diversity and other sociodemographic factors among marginalized populations are associated with the incidence of LBW. The study was a part of the community-based intervention that aimed to improve maternal and child health in the Morena district of Madhya Pradesh, a state in central India. In this case-control study, cases were defined as mothers with an LBW child (<2500 grams) and controls as mothers without an LBW child. A quantitative survey was done with women of reproductive age, having at least one child aged 0–24 months. We calculated the dietary diversity based on the number of food groups consumed during pregnancy by women on a daily basis. Stepwise logistic regression models were built to test for associations between sociodemographic and dietary diversity variables and LBW incidence. There were 157 mothers with and 214 without an LBW child. Women's diets mainly consisted of grains, such as wheat, rice, maize, and roots and tubers. Eggs and meat were consumed by less than 1% of the women. There were 20% lesser chances of an LBW child with increasing maternal dietary diversity scores (odds ratio: 0.79; 95% CI: 0.65, 0.96). The poor maternal diet quality during pregnancy may result in adverse birth outcomes with long-term consequences in a child.

Personalized Nutrition Approach in Pregnancy and Early Life to Tackle Childhood and Adult Non-Communicable Diseases.

The development of childhood and adult non-communicable diseases (NCD) is associated with environmental factors, starting from intrauterine life. A new theory finds the roots of epigenetic programming in parental gametogenesis, continuing during embryo development, fetal life, and finally in post-natal life. Maternal health status and poor nutrition are widely recognized as implications in the onset of childhood and adult diseases. Early nutrition, particularly breastfeeding, also plays a primary role in affecting the health status of an individual later in life. A poor maternal diet during pregnancy and lack of breastfeeding can cause a nutrient deficiency that affects the gut microbiota, and acts as a cofactor for many pathways, impacting the epigenetic controls and transcription of genes involved in the metabolism, angiogenesis, and other pathways, leading to NCDs in adult life. Both maternal and fetal genetic backgrounds also affect nutrient adsorption and functioning at the cellular level. This review discusses the most recent evidence on maternal nutrition and breastfeeding in the development of NCD, the potentiality of the omics technologies in uncovering the molecular mechanisms underlying it, with the future prospective of applying a personalized nutrition approach to prevent and treat NCD from the beginning of fetal life.

Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.