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The objective of the present study was to evaluate the effect of 2 dosages of prepartum cholecalciferol injection on blood minerals, vitamin D metabolites, and milk production. Cows entering their second or greater lactation (n = 158) were randomly assigned to a control group (CON) or one of 2 treatment groups receiving either 6 × 10 6 IU (6VitD) or 12 × 10 6 IU (12VitD) cholecalciferol intramuscularly on d 275 ± 1.2 (SD) of gestation. Concentrations of serum total Ca (tCa), phosphate, and Mg were determined on 1, 2, 3, 5, 7, and 10 d in milk (DIM). For a subsample of 30 cows entering the third lactation (n = 10/group), these samples were analyzed for cholecalciferol, 25-hydroxycholecalciferol (25-OHD 3 ), and 24,25-dihydroxycholecalciferol (24,25-[OH] 2 D 3 ). In these cows, we also determined 1,25-dihydroxycholecalciferol (1,25-[OH] 2 D 3 ), the biologically most active metabolite, on 1, 2, 3, and 5 DIM. Repeated measures ANOVA was performed to evaluate the effect of different dosages of cholecalciferol on blood minerals, vitamin D metabolites, and milk yield over the first 5 test days after calving. Binary outcomes such as retained placenta and metritis were analyzed using a chi-squared test. Although the 12VitD treatment increased tCa concentrations on 1, 2, and 3 DIM compared with CON, administration of 6VitD increased tCa concentrations only on 1 DIM. Compared with CON cows and 6VitD cows, 12VitD cows had greater serum phosphate concentration during the first 10 DIM. Furthermore, 6VitD cows had greater serum phosphate concentrations compared with CON cows. On the contrary, 12VitD cows had lower serum Mg concentrations during the first 10 DIM compared with CON and 6VitD cows. Cholecalciferol was increased by the treatment and decreased quickly until 10 DIM. In respect to 25-OHD 3 , the 6VitD treatment resulted in a 4.1-fold increase in comparison to the CON group, while a 6.5-fold increase was observed in 12VitD animals. The vitamin D metabolite 24,25-(OH) 2 D 3 increased linearly with 25-OHD 3 serum levels, resulting in the highest concentrations in the 12VitD group. An increase of 1,25-(OH) 2 D 3 until 3 DIM was observed in all cows. However, this rise was most pronounced in the CON group. The incidence of retained placenta was 1.9%, 11.5%, and 29.6%, and that of metritis was 11.5%, 15.4%, and 31.5% for CON, 6VitD, and 12VitD cows, respectively. Although none of the treated cows exerted clinical signs of hypocalcemia, one cow in CON incurred clinical hypocalcemia. Cows of the 12VitD group had a lower milk yield over the first 5 monthly test days compared with the control and 6VitD group (42.2 ± 0.5, 42.0, ± 0.5 and 40.7 ± 0.5 kg for control cows, 6VitD cows and 12VitD cows, respectively). Although no negative side effects were observed in 6VitD cows, we do not recommend the general application of 6 × 10 6 IU cholecalciferol before calving as positive effects on calcium homeostasis were marginal and restricted to the first DIM. The present findings confirm that the application of 12 × 10 6 IU cholecalciferol negatively affected milk production on this farm., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The objective of experiment I was to evaluate the association between days in the close-up group (DINCU) and milk production, early lactation diseases, reproductive performance, and culling. In experiment II behavioral changes associated with DINCU were evaluated using a neck-mounted sensor (Smarttag neck, Nedap Livestock Management, Groenlo, the Netherlands). Cow-lactations of 28,813 animals from 14,155 individual cows of 2 farms in northern Germany and western Slovakia, calving between January 2015 and December 2020, were included in the study. After exclusion of cows with a gestation length <262 and >292 d and cows with >42 DINCU data from 8,794 and 19,598 nulliparous and parous cows, respectively, were available for final statistical analyses. To analyze the association between DINCU and second test-d 305-d mature-equivalent milk projection, linear mixed models were calculated. Binary data (i.e., clinical hypocalcemia, hyperketonemia, retained placenta [RP], acute puerperal metritis [APM], mastitis, left displaced abomasum [LDA], first service pregnancy risk) were analyzed using logistic regression models. To analyze the association between DINCU and culling or death during the first 300 DIM Cox proportional hazards were used. To analyze the association between DINCU and behavior 7 d before to 7 d after calving (i.e., activity, inactivity, eating, ruminating time), linear mixed models were calculated. Nulliparous cows with a short (<10 DINCU) and a long stay (>30 DINCU) in the close-up group had a lower milk production an increased risk for hyperketonemia, RP, and APM compared with nulliparous cows with DINCU between 21 to 28 d. Parous cows with a short (<10 DINCU) and a long stay (>30 DINCU) in the close-up group had a lower milk production, an increased risk for RP and mastitis, a reduced first service pregnancy risk, and an increased culling risk, compared with parous cows with DINCU between 21 to 28 d. Furthermore, the risk for clinical hypocalcemia and LDA was increased in parous cows with >30 DINCU compared with parous cows with <30 DINCU. The risk for APM was increased in parous cows with <10 DINCU compared with parous cows with >10 DINCU. In nulliparous cows no association was found between DINCU and the risk for left displaced abomasum and mastitis. In experiment II, cows with 7 and 35 DINCU had an impaired behavior around calving compared with cows with 14, 21, and 28 DINCU. During the last 7 d before parturition, these cows were more inactive and had a reduced eating and ruminating time. After calving, cows with 7 DINCU spent less time eating. In conclusion, cows with <10 DINCU and cows with >30 DINCU had a lower milk production, a higher risk to incur diseases and an impaired behavior, especially before calving., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Periparturient hypocalcemia is a frequently observed metabolic disorder in fresh cows. While the clinical form affects approximately 7 % of German dairy cows, nearly half of the multiparous cows exhibit subclinical hypocalcemia. Although both diagnosis and therapy have not changed over the last three decades, some farmers and practitioners are still unaware about the prevalence of and risk period for subclinical hypocalcemia. Moreover, various recommendations exist concerning the amount of calcium that is to be administered intravenously to a cow experiencing clinical signs of hypocalcemia. This article reviews the causes and prevalence of periparturient hypocalcemia. The aim is further to summarize the results of studies investigating therapy of clinical hypocalcemia in order to provide an evidence-based recommendation on the treatment of recumbent cows. Despite the high prevalence of hypocalcemia, it has been shown that the majority of German farmers do not implement preventive strategies against hypocalcemia. Therefore, we furthermore describe preventive strategies that may be useful in reducing the risk of hypocalcemia, based on what is known from the current literature., Competing Interests: Die Autoren bestätigen, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The objectives of this study were to evaluate postpartum serum calcium dynamics for different parity groups of dairy cows and to assess whether serum calcium concentration on d 0, 1, and 3 postpartum was associated with the risk of developing acute puerperal metritis (APM). The study took place on a commercial dairy farm in northern Germany and included 4,043 Holstein dairy cows. Calving difficulties, such as dystocia, twins, or stillbirth, were recorded. Blood samples were obtained on d 0, 1, and 3 after calving for analysis of serum calcium concentration. Animals were examined daily for clinical symptoms of retained placenta, APM, mastitis, and displaced abomasum until 10 d in milk. To determine serum calcium dynamics postpartum, we performed repeated-measures ANOVA with first-order autoregressive covariance. A logistic regression model was used to evaluate the association of serum calcium concentration with the risk of developing metritis. Serum calcium concentration was affected by time relative to calving, parity, and APM. Increasing parity negatively affected serum calcium concentration on d 0 and 1. Serum calcium concentration reached its lowest level on d 1 and 3 in multiparous and primiparous cows, respectively. The concentration increased from d 1 to 3 in multiparous cows and decreased from d 0 to 3 in primiparous cows. The association of APM and serum calcium dynamics varied by parity. On d 3, serum calcium concentration was significantly lower in animals with subsequent APM than in those without APM. The overall incidence of APM was 12.0% (primiparous cows, 20.4%; multiparous cows, 8.6%). An association existed between serum calcium concentration on d 3 after calving and APM. Primiparous cows had an odds ratio of 0.12 for serum calcium concentration on d 3, indicating that a primiparous cow with serum calcium concentration of 2.5 mmol/L had a 88% lower chance of developing APM compared with a cow with a concentration of 1.5 mmol/L. Multiparous cows had an odds ratio of 0.34 for serum calcium concentration on d 3, indicating that a multiparous cow with serum calcium concentration of 2.5 mmol/L had a 66% lower chance of developing APM compared with a cow with a concentration of 1.5 mmol/L. Primiparous cows with low serum calcium concentration had the highest predicted probability of developing APM. Our results reveal a dynamic in serum calcium concentration in the first 3 d in milk. Consequently, the day of sampling and the observed risk period for hypocalcemia are important when conducting epidemiological studies to evaluate associations between hypocalcemia and clinical diseases., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Periparturient hypocalcemia is frequently observed and considered as a gateway disease that is associated with various health issues. The objective of this study was to evaluate the association of hypocalcemia with early-lactation milk yield, reproductive performance, and culling across a large number of different managerial systems. A prospective cohort study was conducted based on a convenience sample of 125 dairy herds from 8 federal states of Germany between February 2015 and August 2016. A blood sample was drawn from 1,709 animals within 48 h after parturition and analyzed for serum calcium concentration. After discarding cows (n = 283) with missing data, a total of 1,426 cows were considered for final analyses. The median time from calving to sampling was 14.0 h (interquartile range = 5.0-24.9 h). For each herd, a record of the herd management software was requested 150 d after the last cow was sampled. Serum calcium concentration of each cow was associated with early-lactation milk yield (Dairy Herd Improvement Association equivalent test 1 to 3), reproductive performance [days in milk (DIM) at first artificial insemination (AI), pregnancy at first AI, time to pregnancy within 150 DIM], and culling (until 60 DIM) data. Generalized linear mixed models were used to analyze continuous or categorical data. Shared frailty models were used for time to event data. Five different thresholds were used to define hypocalcemia. Thresholds ranged from 1.8 to 2.2 mmol/L using 0.1-mmol/L increments. Clinical hypocalcemia was defined as serum calcium concentration <2.0 mmol/L in combination with clinical signs (e.g., recumbency). The effect of hypocalcemia on milk yield was conditional on parity. In primiparous cows a serum calcium concentration <2.0 mmol/L (6.4% of cows were below this threshold) had no effect on milk production, whereas there was a tendency for multiparous cows with a serum calcium concentration <2.1 mmol/L (63.2% of cows were below this threshold) to produce 0.80 kg/d more milk compared with multiparous cows at or above the threshold. Multiparous cows suffering from clinical hypocalcemia produced 2.19 kg/d less milk compared with normocalcemic cows in early lactation. Calcium status was not associated with days to first insemination. Cows with a serum calcium concentration <1.9 mmol/L (34.6% of cows below this threshold) had decreased odds (odds ratio = 0.56) of pregnancy at first AI. A serum calcium concentration <1.8 mmol/L (24.1% of cows below this threshold) had a significant effect on time to pregnancy. Compared with animals with a serum calcium concentration ≥1.8 mmol/L, the hazard of becoming pregnant within 150 DIM was reduced when cows had a serum calcium concentration <1.8 mmol/L (hazard ratio = 0.68). Cows with a serum calcium concentration <2.0 mmol/L (44.3% of cows were below this threshold) had a 1.69 times greater hazard of being culled within the first 60 DIM compared with normocalcemic animals. The present study shows that the association of hypocalcemia with milk yield was conditional on parity and serum calcium concentration measured once within 48 h after calving. Considering reproductive performance and culling in early lactation, a negative effect of postpartum hypocalcemia was demonstrated., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Hypocalcemia around calving is considered a gateway disease that can lead to health disorders and decreased milk production. The objective of this cross-sectional study was to evaluate the prevalence of clinical and subclinical hypocalcemia 0 to 48 h after calving. Blood samples were drawn from 12 animals of each dairy farm (n = 115) and analyzed for serum calcium, magnesium, and phosphorus concentration. Cows not affected clinically but with a serum calcium concentration below 2.0 mmol/L were characterized as subclinical hypocalcemic animals. Recumbent cows with a serum calcium concentration below 2.0 mmol/L were defined as cows suffering from clinical milk fever. Herds were classified into negative (0 to 2/12), borderline (3 to 5/12), and positive (≥6/12) according to the number of animals with hypocalcemia. Strategies to control hypocalcemia were documented. Prevalence of clinical milk fever was 1.4, 5.7, and 16.1% for second, third, and ≥fourth parity cows, respectively. None of the cows in first lactation were suffering from clinical milk fever. Based on the threshold of 2.0 mmol/L, 5.7, 29.0, 49.4, and 60.4% of cows in first, second, third, and ≥fourth lactation were suffering from subclinical hypocalcemia, respectively. Fourteen, 51, and 50 herds were classified as negative, borderline, and positive, respectively. A positive association was observed between serum calcium and serum phosphorus concentration. Serum calcium and magnesium concentration were negatively associated. Only 50 of 115 farms had a control strategy implemented to avoid hypocalcemia. Most common was the use of oral calcium products (40/115 herds), followed by feeding of anionic salts in the close-up diet (10/115 herds). These results indicate that the prevalence of clinical and subclinical hypocalcemia in German dairy herds was high and that an active control strategy was not implemented on all farms. The negative association between calcium and magnesium warrants further research regarding the physiological regulation of these 2 minerals around parturition., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)