The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response.

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.

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Over the last decades, several genetic disorders have been discovered in cattle. However, the genetic background of disorders in calves is less reported. Recently, German cattle farmers reported on calves from specific matings with chronic diarrhea and retarded growth of unknown etiology. Affected calves did not respond to any medical treatment and died within the first months of life. These calves were underdeveloped in weight and showed progressive and severe emaciation despite of normal feed intake. Hallmark findings of the blood biochemical analysis were pronounced hypocholesterolemia and deficiency of fat-soluble vitamins. Results of the clinical and blood biochemical examination had striking similarities with findings reported in human hypobetalipoproteinemia. Postmortem examination revealed near-complete atrophy of the body fat reserves including the spinal canal and bone marrow. To identify the causal region, we performed a genome-wide association study with 9 affected and 21,077 control animals genotyped with the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA), revealing a strong association signal on BTA 11. Subsequent autozygosity mapping identified a disease-associated haplotype encompassing 1.01 Mb. The segment of extended homozygosity contains 6 transcripts, among them the gene APOB, which is causal for cholesterol disorders in humans. However, results from multi-sample variant calling of 1 affected and 47 unaffected animals did not detect any putative causal mutation. The disease-associated haplotype has an important adverse effect on calf mortality in the homozygous state when comparing survival rates of risk matings vs. non-risk matings. Blood cholesterol values of animals are significantly associated with the carrier status indicating a codominant inheritance. The frequency of the haplotype in the current Holstein population was estimated to be 4.2%. This study describes the identification and phenotypic manifestation of a new Holstein haplotype characterized by pronounced hypocholesterolemia, chronic emaciation, growth retardation, and increased mortality in young cattle, denominated as cholesterol deficiency haplotype. Our genomic investigations and phenotypic examinations provide additional evidence for a mutation within the APOB gene causing cholesterol deficiency in Holstein cattle.

Feeding dairy calves at high intensity has been demonstrated to increase milk yield in later life. We investigated the effect of 3 different feeding regimens in the preweaning period on the metabolic and endocrine status during calfhood and in heifers at the onset of the first lactation. In trial 1, 57 German Holstein calves were allocated to 3 different feeding groups: milk replacer restricted to 6.78 kg/calf per day, 11.5% solids (MR-res, n = 20), milk replacer 13.8% solids, ad libitum (MR-ad lib, n = 17), and whole milk ad libitum (WM-ad lib, n = 20). All calves received ad libitum colostrum for 3 d postnatal (p.n.). From d 4 to 27, all calves were fed according to their respective feeding regimen, resulting in average intakes of 6.38, 9.25, and 9.47 kg/d in MR-res, MR-ad lib, and WM-ad lib, respectively. Thereafter, all calves were fed according to the MR-res regimen until weaning at d 55 (gradually until d 69 p.n.). Blood samples were collected on d 0 before colostrum intake and on d 1, 3, 11, 22, 34, 43, 52, 70, 90, and 108 p.n. Liver biopsies were taken on d 19 and 100, and on d 22, 52, and 108 p.n. intravenous glucose tolerance tests were performed. The male calves (n = 8 to 10 per group) underwent also an insulin tolerance test on d 24, 54, and 110 p.n. The females (n = 28) from trial 1 were further reared and bred as common practice, and were enrolled in trial 2 when beginning the last trimester of pregnancy. Blood samples were collected monthly antepartum starting 91 d before calving and weekly (0-70 d) postpartum. Trial 1 was subdivided into 4 phases (P): P0 (d 0-1), P1 (d 2-27), P2 (d 28-69), and P3 (d 70-110 p.n.). In trial 1, the leptin and adiponectin concentrations increased with colostrum intake. Differences in fatty acids, insulin, adiponectin, revised quantitative insulin sensitivity check index (RQUICKI), and variables from the glucose tolerance tests were largely limited to P1. The MR-res group had greater RQUICKI and fatty acid values, and lower insulin and, as a trend, adiponectin concentrations than in 1 or both ad lib groups. These differences were partly sustained in P2 (fatty acids, adiponectin, and RQUICKI) and in P3 (adiponectin). The hepatic mRNA abundance of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and pyruvatcarboxylase increased from d 19 to 100. None of the blood variables were different between the groups when tested in pregnancy and lactation. Our results do not support a sustained deflection of metabolic regulation by rearing at different feeding intensities; nevertheless, the differences observed during rearing might influence nutrient utilization in later life or the cellular development of organs, such as the mammary gland, and thereby affect milk yield. Further studies involving greater animal numbers and, thus, improved power will help to sort out the mechanisms of programming body function in later life via nutrition in early life.