Parturient paresis (milk fever, hypocalcemia, paresis puerperalis, parturient apoplexy) is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid paralysis of that occurs most commonly at or soon after parturition. Clinical signs also include changes in mentation and circulatory collapse.
Etiology of Parturient Paresis in Cows
Dairy cows are at considerable risk for hypocalcemia at the onset of lactation, when daily calcium excretion suddenly increases from about 10 g to 30 g per day. This stresses calcium homeostasis and may cause blood calcium concentrations to fall well below the normal lower reference range of approximately 8.5 mg/dL. Blood calcium concentrations typically decrease around the onset of parturition (see Plasma total calcium concentration, parturient paresis, dairy cows) but recover quickly. Cows with parturient paresis have a more profound decrease in blood calcium concentration—typically below 5.5 mg/dL.
Courtesy of Dr. Garrett Oetzel. Data extrapolated from Kimura et al., Journal of Dairy Science, 89:2588, 2006 and Goff, Veterinary Clinics of North America: Food Animal Practice, 15:619, 1999.
Hypocalcemia initially causes hyperexcitability of the nervous system, which typically progresses to decreased strength of muscle contractions and paresis. Parturient paresis may occur in cows of any age; however, it is most common in high-producing dairy cows entering their third or later lactations. Incidence is higher in Jersey and Guernsey breeds.
Clinical Findings and Diagnosis of Parturient Paresis in Cows
Recumbency around the time of parturition
Hyperexcitability that progresses to flaccid paralysis
Most cases of parturient paresis occur between the onset of parturition and ~3 days after parturition. Besides causing parturient paresis, hypocalcemia may contribute to dystocia, uterine prolapse, retained fetal membranes, metritis, abomasal displacement, and mastitis.
Parturient paresis has three discernible stages. In stage 1, cows are standing and ambulatory; however, they show clinical signs of hypersensitivity and excitability. They may be mildly ataxic, have fine tremors over the flanks and triceps, and display ear twitching and head bobbing. Cows may appear restless, shuffle their rear feet, and bellow. If calcium treatment is not instituted during stage 1, cows will likely progress to stage 2, which is more severe.
Cows with stage 2 parturient paresis are paretic to the point that they cannot stand. They do have enough muscle control to maintain sternal recumbency. They are typically obtunded, anorectic, and have a dry muzzle, subnormal body temperature, and cold extremities. Auscultation reveals tachycardia and decreased intensity of heart sounds due to impaired cardiac contractility. Peripheral pulses are weak. Smooth muscle paralysis leads to gastrointestinal stasis, which can manifest as bloat, failure to defecate, and loss of anal sphincter tone. An inability to urinate may manifest as a distended bladder on rectal examination. Cows often tuck their heads into their flanks. If the cow is able to extend its head, an S-shaped curve to the neck may be present due to asymmetry of the cervical musculature.
Cows in stage 3 parturient paresis lose consciousness progressively to the point of coma. They are unable to maintain sternal recumbency and lie flat on their sides. They have extreme muscle flaccidity, may be unresponsive to stimuli, and can have severe bloat. As cardiac output worsens, heart rate can approach 120 bpm, and peripheral pulses may be undetectable. If untreated, cows in stage 3 may survive only a few hours.
Differential diagnoses for parturient paresis include toxic mastitis, toxic metritis, other systemic toxic conditions, traumatic injury (eg, stifle injury, coxofemoral luxation, fractured pelvis, spinal compression), calving paralysis syndrome (damage to the L6 lumbar roots of sciatic and obturator nerves), and compartment syndrome. Some of these diseases, in addition to aspiration pneumonia, may also occur concurrently with parturient paresis or as complications of it.
(Also see Bovine Secondary Recumbency.)
Treatment of Parturient Paresis in Cows
Oral calcium supplementation for standing cows
Intravenous calcium infusion for recumbent cows
Prevention of hypocalcemic relapses in all affected cows
Recumbent cows are at extremely high risk for muscle and nerve damage; therefore, treatment of parturient paresis must be prompt. Excessive exogenous calcium administration increases the risk for hypocalcemic relapse. The lowest dose of calcium needed to restore normal blood calcium concentration should be used.
Cows with stage 1 parturient paresis (ie, cows that are still standing) should be treated with an oral calcium supplement. Oral calcium is rapidly absorbed into the bloodstream and poses little risk for subsequent hypercalcemia followed by a rebound hypocalcemia.
The preferred approach to oral calcium supplementation is an acidogenic source of calcium (usually calcium chloride or calcium sulfate) in a bolus formulation. Acidogenic sources of calcium are highly available and promote the cow’s own calcium homeostasis by enhancing parathyroid hormone (PTH) receptor responsiveness.
A standard oral dose provides 40–55 g of elemental calcium. Blood calcium increases to peak concentrations within 30 minutes of oral administration and equals about 4 g of IV calcium. Oral calcium administration of a standard dose does not cause hypercalcemia, does not contribute to hypocalcemic relapses, and does not increase blood glucose. Higher doses could cause uncompensated metabolic acidosis, decreased feed intake, and increased risk for hypocalcemic relapses.
Bolus formulations of oral calcium are the safest means of providing oral calcium supplementation. Oral paste, gel, or liquid formulations of supplemental calcium are not recommended due to unnecessary risk for aspiration and pharyngeal irritation. Oral calcium boluses should include a coating to protect the cow from mucosal damage should the bolus remain in contact with pharyngeal or esophageal mucosa.
Nonacidogenic calcium sources (usually calcium propionate) can be used for oral calcium supplementation; however, they are not preferred for cows in stage 1 parturient paresis. Oral calcium propionate requires a higher dose of elemental calcium (100 g or more), does not enhance the cow’s own calcium homeostatic mechanisms, and unnecessarily increases blood glucose at a time when many cows are hyperglycemic. Oral calcium propionate is best reserved for cows that are two or more days post-calving.
Cows with stage 2 or 3 hypocalcemia (ie, cows that are recumbent) require immediate correction of their hypocalcemia by intravenous calcium infusion. The standard treatment for an adult dairy cow is 500 mL of a 23% calcium gluconate solution. These solutions must contain boric acid to solubilize the calcium gluconate and stabilize the solution; thus, they may be labeled as calcium borogluconate. This standard treatment provides 10.7 g of elemental calcium, which is more than sufficient to restore normocalcemia for even the largest cows with the most profound hypocalcemia. A lower dose of intravenous calcium is probably ideal for most cows; however, lower doses have not been adequately investigated. Calcium infusion products vary slightly in different parts of the world; most provide between 8 g and 12 g of calcium per dose, which is reasonable.
Many products marketed for treatment of hypocalcemia include phosphorus, magnesium, glucose, or potassium in addition to calcium. No additional electrolytes are needed to treat parturient paresis, and some could be harmful. Calcium gluconate alone is the best choice for intravenous treatment of parturient paresis.
The jugular vein is the preferred site for intravenous calcium infusion. Asepsis at the injection site and accurate placement of the needle within the lumen of the jugular vein is necessary to lower the risk for thrombosis and perivascular leakage.
The cranial superficial epigastric (mammary) vein may be more accessible than the jugular vein in some recumbent cows. However, the mammary vein is prone to thrombosis and phlebitis and should be used only when neither jugular vein is available.
Intraperitoneal injection of calcium can be effective; however, it poses substantial safety concerns for the cow. Placement of the needle is blind, which could lead to retroperitoneal, perirenal, or intraluminal deposition of the calcium solution. An intraperitoneal injection may also damage a viscus and cause peritonitis.
The response to intravenous calcium infusion for cows with parturient paresis is usually immediate and rewarding. Response to intravenous treatment is the main means of confirming the diagnosis. It is an excellent practice to routinely collect a pre-treatment blood sample before starting the intravenous calcium infusion. If the cow does not respond favorably, this sample can be submitted for laboratory confirmation of hypocalcemia. Blood samples collected after intravenous calcium infusion cannot be used for diagnostic purposes, because the calcium concentration has been confounded.
A typical response to intravenous calcium infusion in cases of parturient paresis includes declining heart rate and increasing pulse intensity as cardiac contractility is restored. Muscular paresis is reversed, resulting in muscle tremoring and attempts by the cow to rise. About 75% of recumbent cows are able to rise within 2 hours. Pre-existing musculoskeletal and nerve damage is the main reason that cows remain recumbent after successful correction of hypocalcemia. Intravenous infusion of calcium transiently raises blood calcium concentrations to nearly twice the normal upper limit. This puts the cow at risk for fatal cardiac arrhythmia. Therefore, calcium-containing solutions should be administered slowly (over 10–20 minutes) while cardiac rhythm is monitored by auscultation or carotid pulse. If severe dysrhythmias or bradycardia develop, administration should be stopped until the heart rhythm has returned to normal. Endotoxic animals are especially prone to dysrhythmias due to intravenous calcium treatment.
Transient hypercalcemia due to intravenous calcium infusion places the cow at risk of a hypocalcemic relapse. Hypercalcemia shuts down the cow’s efforts to mobilize its own calcium stores by halting PTH release and triggering calcitonin (CT) secretion instead. About 25% to 40% of recumbent cows that are able to rise after intravenous calcium infusion become recumbent again (usually in 12 to 24 hours) unless measures are taken to decrease the risk for relapse.
The treatment of choice for preventing hypocalcemic relapses is oral calcium administration, as described above for treatment of stage 1 cases of parturient paresis. Cows should be standing, alert, and able to swallow before administering an oral calcium bolus.
Subcutaneous calcium is a second choice for the prevention of hypocalcemic relapses. Subcutaneous calcium alone may not be adequately absorbed because of poor peripheral perfusion during the initial hypocalcemia and should not be the sole route of treatment. Strict asepsis is necessary to prevent infection at the site of the subcutaneous injection. Solutions containing formaldehyde or dextrose should not be administered subcutaneously because they are highly irritating. Calcium gluconate (500 mL, 23% solution [the same as used for IV infusion]) is the best choice for SC calcium administration. This solution is still quite irritating and should be divided into multiple sites with smaller volume.
Prevention of Parturient Paresis in Cows
The prevention of parturient paresis has been historically approached by feeding low-calcium diets during the dry period. Negative calcium balance triggers calcium mobilization before calving and better equips the cow to respond to the massive calcium needs at the onset of lactation.
Unfortunately, calcium intake must be limited to <20 g per day for calcium restriction to be effective. This is nearly impossible under normal feeding conditions. Feeding a calcium binder such as sodium aluminosilicate (zeolite A) before calving mimics a calcium deficiency and decreases the risk for parturient paresis. However, this approach is costly and the mineral binding accomplished by aluminosilicates is not specific to calcium alone.
The most practical and proven method for preventing hypocalcemia is by feeding an acidogenic diet for ~3 weeks before calving. This approach creates a compensated metabolic acidosis (as opposed to the cow’s normally alkalotic state), increases gastrointestinal calcium absorption, improves PTH receptor responsiveness, and mobilizes more calcium from bone.
Dietary cation-anion difference (DCAD), calculated as milliequivalents of [(Na + K) – (Cl + S)], quantifies the ability of a diet to evoke an acidic or alkaline response. Feeding a prepartum diet with a DCAD between -50 to -150 meq/kg of diet dry matter is generally optimal for the prevention of parturient paresis. Dairy nutritionists create acidogenic diets for prepartum cows by selecting feed ingredients that have an inherently low DCAD (usually low potassium or high chloride forages) and by adding supplemental anions (pre-blended hydrochloric acid or anionic salts such as calcium chloride, magnesium chloride, calcium sulfate, and magnesium sulfate).
It is challenging to consistently optimize dietary acidification because the mineral content of forages can change rapidly during feedout. Frequent monitoring of urinary pH allows for dietary adjustments to maintain optimal acidification, which is mean urinary pH of about 6.5. Urinary pH below ~5.5 suggests overacidification, uncompensated metabolic acidosis, and impaired dry matter intake. Urinary pH above ~7.5 suggests metabolic alkalosis, impaired PTH responsiveness, and inadequate protection against hypocalcemia.
Urinary pH should be monitored approximately twice weekly in prepartum cows being fed acidogenic diets. Frequent testing allows for prompt adjustment of the dose of supplement anions. Any cow on the acidogenic diet for more than 24 hours is eligible for urinary pH testing, and a minimum of eight cows should be tested.
Acidogenic diets are associated with decreased dry matter intake. Small decreases (<10%) in intake are acceptable. However, large decreases could lead to inadequate energy intake and increased risk for energy-related disorders such as retained placenta, metritis, fatty liver, and ketosis after calving. The most common cause of excessive decrease in dry matter intake is overacidification, which will be revealed by urinary pH monitoring. The dose of anions should be reduced until dry matter intake is restored.
An alternative method to prevent hypocalcemia is to delay milking or to milk cows incompletely after calving. This maintains pressure within the udder, decreases milk production, and decreases calcium outflow. However, this practice is impractical because it increases the risk for mastitis. Inflating the udder with air likewise may decrease calcium outflow; however, it also increases the risk for mastitis.
Courtesy of Dr. Garrett Oetzel. Data extrapolated from Blanc et al., Journal of Dairy Science, 97:6901, 2014.
Prophylactic treatment of susceptible cows with oral calcium around calving decreases the risk for parturient paresis. Oral calcium supplementation is the preferred route of administration. See Serum calcium concentration, multiparous cows, calcium supplementation, which shows the expected kinetics of oral calcium supplementation for cows without clinical signs of parturient paresis.
The prophylactic use of oral calcium is most efficacious when the first dose of oral calcium is administered to cows just before calving. However, this is often difficult to predict. Prepartum dosing should be followed by two more doses administered 12 to 24 hours apart.
Subcutaneous calcium can be used for prophylactic prevention of hypocalcemia. The disadvantages of this approach are tissue irritation and risk for infection at the injection sites, along with the relatively short duration of blood calcium support.
The prophylactic use of intravenous calcium for preventing hypocalcemia is discouraged. Cows supplemented with intravenous calcium at calving experience substantial hypocalcemia by 24 hours postcalving which persists until at least 48 hours postcalving.
Vitamin D3 and its metabolites have been historically attempted as a means of preventing parturient paresis. Although some approaches are clinically effective if the cow calves very near its due date, the risk for toxicity is too great for routine use.
Key Points
Parturient paresis in dairy cattle is generally easy to recognize and treat.
Prompt and effective treatment is necessary to prevent secondary complications.
Treatment should include reducing the risk for a hypocalcemic relapse.
Prevention is always preferable to treatment and is most commonly accomplished by feeding an acidogenic diet before calving.
For More Information
Oetzel GR. Diseases of dairy animals | Non-infectious diseases: milk fever. In: Fuquay, JW, ed. Encyclopedia of Dairy Sciences. 2nd ed. Academic Press; 2011:239-245. https://doi.org/10.1016/B978-0-12-374407-4.00145-X.
