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Long-term effects of a modified, low-protein infant formula on growth and body composition: Follow-up of a randomized, double-blind, equivalence trial.
Kouwenhoven, SMP, Antl, N, Finken, MJJ, Twisk, JWR, van der Beek, EM, Abrahamse-Berkeveld, M, van de Heijning, BJM, van Goudoever, JB, Koletzko, BV
Clinical nutrition (Edinburgh, Scotland). 2021;(6):3914-3921
Abstract
BACKGROUND & AIM: High protein intake in early life is associated with an increased risk of childhood obesity. Feeding a modified lower-protein (mLP) infant formula (1.7 g protein/100 kcal) until the age of 6 months is safe and supports adequate growth. The aim of the present study is to assess longer-term anthropometry with BMI at 1 and 2 years as primary outcome parameter and body composition in children fed mLP formula. METHODS Healthy term-born infants received mLP or control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double-blinded RCT. A breast-fed (BF) group served as a reference. Anthropometry data were obtained at 1 and 2 years of age. At the age of 2 years, body composition was measured with air-displacement plethysmography. Groups were compared using linear mixed model analysis. RESULTS At 1 and 2 years of age, anthropometry, including BMI, and body composition did not differ between the formula groups (n = 74 mLP; n = 69 CTRL). Compared to the BF group (n = 51), both formula-fed groups had higher z scores for weight for age, length for age, waist circumference for age, and mid-upper arm circumference for age at 1 year of age, but not at 2 years of age (except for z score of weight for age in the mLP group). In comparison to the BF group, only the mLP group had higher fat mass, fat-free mass, and fat mass index. However, % body fat did not differ between feeding groups. CONCLUSIONS In this follow-up study, no significant differences in anthropometry or body composition were observed until 2 years of age between infants fed mLP and CTRL formula, despite the significantly lower protein intake in the mLP group during the intervention period. The observed differences in growth and body composition between the mLP group and the BF reference group makes it necessary to execute new trials evaluating infant formulas with improved protein quality together with further reductions in protein content. CLINICAL TRIAL REGISTRY This trial was registered in the Dutch Trial Register (Study ID number NTR4829, trial number NL4677). https://www.trialregister.nl/trial/4677.
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Maternal metabolic health drives mesenchymal stem cell metabolism and infant fat mass at birth.
Erickson, ML, Patinkin, ZW, Duensing, AM, Dabelea, D, Redman, LM, Boyle, KE
JCI insight. 2021;(13)
Abstract
Exposure to maternal obesity may promote metabolic dysfunction in offspring. We used infant mesenchymal stem cells (MSCs) to experimentally examine cellular mechanisms of intergenerational health transmission. Our earlier reports show MSCs collected from infants of mothers with obesity had a dichotomous distribution in metabolic efficiency; they were either efficient (Ef-Ob) or inefficient (In-Ob) with respect to fatty acid oxidation (FAO). Here, we sought to determine if this was due to a primary defect in FAO. Accordingly, we measured FAO in myogenic differentiating MSCs under 3 conditions: (a) myogenesis alone, (b) excess fatty acid exposure, and (c) excess fatty acid exposure plus a chemical uncoupler to increase metabolic rate. Compared with normal weight and Ef-Ob MSCs, In-Ob displayed lower FAO in myogenesis alone and after fatty acid plus uncoupler, indicating In-Ob were less metabolically flexible after increasing lipid availability and metabolic rate, demonstrating a primary deficit in FAO. MSC FAO was negatively associated with fasting maternal glucose and insulin and positively associated with fasting HDL-cholesterol. MSC FAO was negatively associated with infant fat mass. These data indicate a less favorable maternal metabolic milieu, independent of maternal BMI, reduces intrinsic MSC FAO and is linked to higher infant adiposity as early as birth.
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Maternal Urinary Organophosphate Esters and Alterations in Maternal and Neonatal Thyroid Hormones.
Percy, Z, Vuong, AM, Xu, Y, Xie, C, Ospina, M, Calafat, AM, Hoofnagle, A, Lanphear, BP, Braun, JM, Cecil, KM, et al
American journal of epidemiology. 2021;(9):1793-1802
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Abstract
Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003-2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed.
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Vitamin D status in women with dichorionic twin pregnancies and their neonates: a pilot study in China.
Li, X, Yu, J, Wen, L, Li, Q, Yan, J, Tian, J, Tong, C, Tong, Q, Qi, H, Saffery, R, et al
BMC pregnancy and childbirth. 2021;(1):279
Abstract
BACKGROUND Vitamin D deficiency is a global public health issue in women and children and is associated with adverse impacts on child growth, such as rickets. However, prior studies have mainly focused on measuring vitamin D levels in singleton pregnant women and their offspring, and very limited studies have revealed the prevalence of vitamin D deficiency in twin pregnant women and their offspring. The aim of this study was to investigate vitamin D levels in twin-pregnant women and their neonates. We also explored the correlation of maternal vitamin D levels with neonatal outcomes and infant growth. METHODS A prospective subcohort investigation was carried out among 72 dichorionic, diamniotic twin-pregnant mothers and their twin offspring from the Longitudinal Twin Study. Peripheral blood was collected from the mothers in the third trimester, and cord blood was collected from neonates at birth to identify 25[OH]D levels. Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. RESULTS The average maternal 25[OH]D level was 31.78 ng/mL, with 19.4% being deficient and 20.8% insufficient, while the average neonatal 25[OH]D level was 15.37 ng/mL, with 99.3% being deficiency or insufficient. A positive correlation was found between maternal and neonatal 25[OH]D levels (beta-value: 0.43, 95% CI: 0.37, 0.49). Interestingly, the higher the maternal 25[OH]D level was, the smaller the cotwin birthweight discordance (beta-value: -2.67, 95% CI: - 5.11, - 0.23). In addition, the infants of mothers with vitamin D deficiency were more likely to be allergic to foods at 6 months than those of mothers with vitamin D sufficiency. CONCLUSIONS Twin neonates were at high risk of vitamin D deficiency, although their mothers' vitamin D deficiency partially improved. Higher maternal vitamin D levels were associated with smaller discordance of cotwin birthweight. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR-OOC-16008203 , 1st April 2016.
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Pharyngoesophageal motility reflex mechanisms in the human neonate: importance of integrative cross-systems physiology.
Sultana, Z, Hasenstab, KA, Jadcherla, SR
American journal of physiology. Gastrointestinal and liver physiology. 2021;(2):G139-G148
Abstract
Swallowing is a critical function for survival and development in human neonates and requires cross-system coordination between neurological, airway, and digestive motility systems. Development of pharyngoesophageal motility is influenced by intra- and extrauterine development, pregnancy complications, and neonatal comorbidities. The primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biological conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiological and pathophysiological neonatal aerodigestive functions.
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Effect of amino acid infusion during cesarean delivery on newborn temperature: a randomized controlled trial.
Pokharel, K, Subedi, A, Tripathi, M, Biswas, BK
BMC pregnancy and childbirth. 2021;(1):267
Abstract
BACKGROUND The effect of maternal amino acid (AA) infusion before and during cesarean delivery on neonatal temperature remains unknown. We hypothesized that thermogenic effects of AA metabolism would help maintain body temperature of newborn babies and their mothers. METHODS Seventy-six parturients scheduled for elective singleton term cesarean delivery were equally randomized to receive intravenous 200 ml of AA or placebo approximately 1 h before subarachnoid block (infusion rate:100 ml/h). The primary outcome was the newborn rectal temperature at 0, 5 and 10 min after birth. The secondary outcomes included the maternal rectal temperature at six time-points: T0 = before starting study solution infusion, T1 = 30 min after starting infusion, T2 = one hour after starting infusion, T3 = during spinal block, T4 = half an hour after spinal block, T5 = at the time of birth and T6 = at the end of infusion, as well as maternal thermal discomfort and shivering episodes. RESULTS There were no differences in newborn temperature between the two groups at any of the time-points (intervention-time-interaction effect, P = 0.206). The newborn temperature (mean [95%CI] °C) at birth was 37.5 [37.43-37.66] in the AA and 37.4 [37.34-37.55] in the placebo group. It showed a significant (P < 0.001) downward trend at 5 and 10 min after birth (time effect) in both groups. One neonate in the AA and five in the placebo group were hypothermic (temperature < 36.5 °C) (P = 0.20). There was a significant difference in the maternal temperature at all time points between the two groups (Intervention-time interaction effect, P < 0.001). However, after adjustment for multiplicity, the difference was significant only at T6 (P = 0.001). The mean difference [95%CI] in temperature decline from baseline (T0) till the end of infusion (T6) between the two groups was - 0.39 [- 0.55;- 0.22] °C (P < 0.0001). Six mothers receiving placebo and none receiving AA developed hypothermia (temperature < 36 °C) (P = 0.025). Maternal thermal discomfort and shivering episodes were unaffected by AA therapy. CONCLUSIONS Under the conditions of this study, maternal AA infusion before and during spinal anesthesia for cesarean delivery did not influence the neonatal temperature within 10 min after birth. In addition, the maternal temperature was only maintained at two hours of AA infusion. TRIAL REGISTRATION ClinicalTrials.government, Identifier NCT02575170 . Registered on 10th April, 2015 - Retrospectively registered.
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Maternal Dietary Quality and Dietary Inflammation Associations with Offspring Growth, Placental Development, and DNA Methylation.
Lecorguillé, M, Teo, S, Phillips, CM
Nutrients. 2021;(9)
Abstract
The 'Developmental Origins of Health and Diseases' hypothesis posits that prenatal maternal diet influences offspring growth and later life health outcomes. Dietary assessment has focused on selected nutrients. However, this approach does not consider the complex interactions between foods and nutrients. To provide a more comprehensive approach to public health, dietary indices have been developed to assess dietary quality, dietary inflammation and risk factors for non-communicable diseases. Thus far, their use in the context of placental development is limited and associations with offspring outcomes have been inconsistent. Although epidemiological studies have focused on the role of maternal diet on foetal programming, the underlying mechanisms are still poorly understood. Some evidence suggests these associations may be driven by placental and epigenetic changes. In this narrative review, we examine the current literature regarding relationships between key validated diet quality scores (Dietary Inflammatory Index [DII], Mediterranean diet [MD], Healthy Eating Index [HEI], Alternative Healthy Eating Index [AHEI], Dietary Approaches to Stop Hypertension [DASH], Glycaemic Index [GI] and Glycaemic Load [GL]) in pregnancy and birth and long-term offspring outcomes. We summarise findings, discuss potential underlying placental and epigenetic mechanisms, in particular DNA methylation, and highlight the need for further research and public health strategies that incorporate diet quality and epigenetics.
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Branched-chain amino acid supplementation for improving growth and development in term and preterm neonates.
Amari, S, Shahrook, S, Namba, F, Ota, E, Mori, R
The Cochrane database of systematic reviews. 2020;(10):CD012273
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Abstract
BACKGROUND Branched-chain amino acids (BCAAs) play a vital role in neonatal nutrition. Optimal BCAA supplementation might improve neonatal nutrient storage, leading to better physical and neurological development and other outcomes. OBJECTIVES To determine the effect of BCAA supplementation on physical growth and neurological development in term and preterm neonates. We planned to make the following comparisons: parenteral nutrition with and without BCAA supplementation; enteral BCAA supplementation versus no supplementation; and any type of supplementation including enteral, parenteral and both ways versus no supplementation. To investigate the supplementation effectiveness for different dosages assessed in the eligible trials. SEARCH METHODS We conducted comprehensive searches using Cochrane Neonatal's standard search strategies: Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6), MEDLINE, Embase and CINAHL (up to July 2016). We updated the search with CENTRAL (2019, Issue 8), MEDLINE, Embase and CINAHL (up to August 2019). We also searched clinical trials registries and reference lists of retrieved articles. SELECTION CRITERIA We planned to include individual and cluster-randomised and quasi-randomised controlled trials comparing BCAA supplementation versus placebo or no supplementation in term and preterm neonates. We excluded trials presented only as abstracts and cross-over trials. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the eligibility of all potential studies identified from the search strategy. We planned to extract data using a pilot-tested standard data extraction form and assess risk of bias of the included studies following the methods described in the Cochrane Handbook for Systematic Reviews of Interventions. We planned to analyse treatment effects and report their effect estimates as per dichotomous or continuous data with 95% confidence intervals. We planned to conduct subgroup analysis to investigate heterogeneity, and perform sensitivity analysis where possible. We planned to use fixed-effect meta-analysis to combine data wherever appropriate. We planned to assess evidence quality using the GRADE approach. MAIN RESULTS We did not identify any potentially eligible studies that met the inclusion criteria in this review. AUTHORS' CONCLUSIONS We found no trial data to support or refute the idea that BCAA supplementation affects physical and neurological development and other outcomes in term and preterm neonates.
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Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health.
Lyons, KE, Ryan, CA, Dempsey, EM, Ross, RP, Stanton, C
Nutrients. 2020;(4)
Abstract
Human breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower mortality rates than formula fed infants. As well as providing fundamental nutrients to the growing infant, breast milk is a source of commensal bacteria which further enhance infant health by preventing pathogen adhesion and promoting gut colonisation of beneficial microbes. While breast milk was initially considered a sterile fluid and microbes isolated were considered contaminants, it is now widely accepted that breast milk is home to its own unique microbiome. The origins of bacteria in breast milk have been subject to much debate, however, the possibility of an entero-mammary pathway allowing for transfer of microbes from maternal gut to the mammary gland is one potential pathway. Human milk derived strains can be regarded as potential probiotics; therefore, many studies have focused on isolating strains from milk for subsequent use in infant health and nutrition markets. This review aims to discuss mammary gland development in preparation for lactation as well as explore the microbial composition and origins of the human milk microbiota with a focus on probiotic development.
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Association of objectively measured physical fitness during pregnancy with maternal and neonatal outcomes. The GESTAFIT Project.
Baena-García, L, Coll-Risco, I, Ocón-Hernández, O, Romero-Gallardo, L, Acosta-Manzano, P, May, L, Aparicio, VA
PloS one. 2020;(2):e0229079
Abstract
AIM: To analyse i) the association of physical fitness during early second trimester and late pregnancy with maternal and neonatal outcomes; and ii) to investigate whether physical fitness is associated with the type of birth (vaginal or caesarean section). METHODS Pregnant women from the GESTAFIT Project (n = 159) participated in this longitudinal study. Maternal physical fitness including upper- and lower-body strength, cardiorespiratory fitness (CRF) and flexibility were measured through objective physical fitness tests at the 16th and 34th gestational weeks. Maternal and neonatal outcomes were collected from obstetric medical records. Umbilical arterial and venous blood gas pH and partial pressure of carbon dioxide (PCO2) and oxygen (PO2), were assessed. RESULTS At the 16th week, greater upper-body muscle strength was associated with greater neonatal birth weight (r = 0.191, p<0.05). Maternal flexibility was associated with a more alkaline arterial pH (r = 0.220, p<0.05), higher arterial PO2 (r = 0.237, p<0.05) and lower arterial PCO2 (r = -0.331, p<0.01) in umbilical cord blood. Maternal CRF at the 16th gestational week was related to higher arterial umbilical cord PO2 (r = 0.267, p<0.05). The women who had caesarean sections had lower CRF (p<0.001) at the 16th gestational week and worse clustered overall physical fitness, both at the 16th (-0.227, p = 0.003, confidence interval (CI): -0.376, -0.078) and 34th gestational week (-0.223; p = 0.018; CI: -0.432, -0.015) compared with the women who had vaginal births. CONCLUSION Increasing physical fitness during pregnancy may promote better neonatal outcomes and is associated with a decrease in the risk of caesarean section. This trial was registered at ClinicalTrials.gov (NCT02582567) on October 20, 2015.