Thermoregulation

Neonatal animals are poor regulators of their body temperature. Newborns can lose body heat because of evaporation, radiation, convection, and cooling. If newborns are wet or placed next to cold objects (cage or kennel floors), in drafts, or in outdoor enclosures, they can lose considerable amounts of heat. Orphaned newborn puppies during their first week of life require environmental temperatures of 85° to 90° F (30° to 32° C).

For puppies, newborns have lower body temperatures than adult dogs. In the first week of life rectal temperatures range from 95° to 97° F (35° to 36° C), and for the second and third weeks temperatures range from 97° to 100° F (36° to 38° C). By the time of weaning, average rectal temperatures are nearly the same as those of adults.

Reflexes, such as shivering, and vasoconstrictive mechanisms to maintain heat are not developed in the neonate. Brown adipose tissue found in newborns is the site of nonshivering thermogenesis. Wet puppies, inappetent puppies, and orphaned newborns are thus unable to successfully maintain their body temperature in cool or drafty environments. Although shivering is absent in newborn puppies, panting is present in overheated neonates.

Maintenance of normal physiologic functions is related to temperature in puppies and kittens. In puppies that become chilled, the heart rate may drop precipitously. A newborn with a rectal temperature of 96° F has a heart rate somewhere between 200 and 250 beats per minute (bpm). Once the rectal temperature reaches 70° F, the heart rate quickly drops to only 40 bpm. A decreased heart rate may result in inappetence, dehydration, and loss of suckling reflexes. In addition, nursing bitches may refuse to nurse and care for cold puppies and even push them away. When body temperature falls below 94° F, a gastrointestinal (GI) ileus develops and a chilled puppy will stop trying to nurse. If chilled puppies are not rewarmed before force feeding, regurgitation and subsequent aspiration pneumonia can result (Box 6-2).

Hypothermia in newborns can, however, have a sparing effect. The hypothermia that results in decreased cardiovascular function may conversely protect puppies from the ischemic brain injury that accompanies cardiovascular collapse. In one investigation, induction of hypothermia resulting in circulatory onset of up to 1 hour was not responsible for subsequent brain injury. If hypothermia-related circulatory arrests lasting more than an hour were induced, neuronal injury resulted. In puppies with sustained hypothermia, tissue hypoxia, metabolic acidosis, and cell death all subsequently ensue.

The ability for lymphocytes to transform and combat infection is significantly decreased when pups are chilled. The cardiovascular and GI systems depend on body temperature, and the immune system is also closely influenced by a change of only a few degrees.

Warming chilled neonates back to normal temperatures can be potentially very dangerous. Newborns must be warmed safely after cooler body temperatures are discovered. Heat sources must be safe, effective, and easily monitored. Warm water bottles wrapped in towels or cloth, boiled rice heated in a sock, or warmed towels can provide adequate heat but must be judiciously scrutinized. Water should be changed and reheated as it cools, since there is the risk of chilling newborns with cold bottles and containers full of cold water. Similarly, newborns are neurologically immature and lack the ability to move away from excessive heat. Cloth coverings or pillow cases can decrease direct contact of the delicate newborn skin with hot water bottles and heat sources, but these types of heat supplements can overheat, dehydrate, and even severely burn ill, comatose, or orphaned newborns. For these reasons, heating pads, heat lamps, and electric blankets are not recommended because they are so difficult to regulate and safely manage.

Pediatric incubators are easily available and are ideal in managing sick, debilitated, or orphaned puppies and kittens. Nevertheless, these devices can also lead to problems if not rigorously attended. Environmental control for newborns must also consider humidity. Use of incubators can lead to mucous membranes that are quickly dried out. A relative humidity of 55% to 65% is considered adequate for the prevention of skin drying. In neonatal, low birth weight puppies, relative humidity of 85% to 90% is most effective in maintenance of hydration and body temperature. If high humidity is provided, care must be taken not to reach environmental temperatures greater than 90° F (32° C). Temperatures of 95° F (35° C) and greater coupled with relative humidities of over 95% lead to respiratory distress in neonatal puppies and kittens. Oxygen cages are also an excellent way to warm newborns.

The best incubators, whelping boxes, or closed environments present the newborn with a gradient of temperatures and allow the puppies and kittens to select the most comfortable zones. Nevertheless, even healthy pups and kittens initially are neurologically immature and unable to move away from excessive heat.

Regulation of Carbohydrates

Newborns differ substantially from adults with regard to their ability to maintain normal blood glucose levels. Ill neonates must always be evaluated for hypoglycemia. Hypoglycemia in the newborn can be due to a variety of causes and can appear in conjunction with hypothermia, sepsis, starvation, toxic milk syndrome, or any combination of these things. The capacity of the newborn for the regulation of blood glucose may be directly related to the nutritional state of the dam during pregnancy. Starvation of the mother can lead to lower birth rates, lower fetal blood glucose concentrations, and increased fetal ketone levels. Starvation of the mother also reduced fetal birth weight by 23% and resulted in significantly lower fasting blood glucose levels in pups at 3 hours of age when compared to controls in one study. Furthermore, bitches fed a low-carbohydrate diet had both a higher incidence of stillbirths and a higher incidence of neonatal losses in the first 3 days after whelping.

Neonates born to healthy, well-fed mothers are better able to maintain blood glucose for even several hours after the fast. However, since the neonatal liver contains minimal glycogen stores, even slight fasts can cause hypoglycemia. The neonate is born with limited capacities for gluconeogenesis and glycogenolysis because of the immaturity of the newborn’s liver. In addition, initial limited hepatic glycogen stores, small muscle mass, lack of adipose tissue, and decreased use of free fatty acids as an alternative energy source place neonates at great risk for developing hypoglycemia in the face of even the briefest fast. Impaired gluconeogenesis caused by the delayed maturation and induction of the rate-limiting gluconeogenic enzymes has been shown to result in hypoglycemia in human infants and is suspected in the same condition in kittens and puppies.

Hypoglycemia of immature (less than 6 months old) toy and miniature dog breeds is frequently reported. Just as in human infants, alanine deficiency has been implicated in this condition in young dogs. The rate of alanine release from muscle determines the rate of gluconeogenesis during starvation. These toy breeds have much smaller muscle mass, immature enzymatic machinery, and smaller muscle stores to begin with, thus hypoglycemia develops more easily.

Hypoglycemic neonates have often been under extreme stresses; they have only recently been purchased or otherwise obtained and have had a huge change in their environment, as well as their diet. GI problems, anorexia, diarrhea, and vomiting are commonly reported. These signs may also be the result of parasites. Neonates lack the feedback mechanism between hepatic gluconeogenesis and blood glucose concentrations, making regulation of blood glucose much more difficult than for adult dogs, and a variety of other factors can lead to this hypoglycemia. In addition, a host of other conditions inherited, contracted, or acquired can cause hypoglycemia in newborns. Endotoxemia, sepsis, portosystemic shunts, and glycogen storage abnormalities have all been recognized as conditions that can cause a profound decline in blood sugar concentrations.

Inherited, inborn errors in amino acid and/or carbohydrate metabolism; inadequate protein, glycogen, or carbohydrate stores; and immature, deficient, or faulty enzyme systems should be considered in neonates with repeated bouts of hypoglycemia in the absence of any identifiable contagious cause (septicemia/endotoxemia). If hypoglycemia recurs in neonates with a good diet and adequate nutrition, glycogen storage disease should be suspected. Glycogen storage disease also might be considered if neonates with recurrent hypoglycemia episodes also display acidosis, ketosis, and hepatomegaly.

Normal concentrations for blood glucose in neonates are considered to be 52 to 127 mg/dl for neonatal pups between the ages of 1 to 3 days and 111 mg/dl at 4 weeks of age. The normal adult range of blood glucose concentrations has been reported at 65 to 110 mg/dl. Blood glucose less than 40 mg/dl in pups 2 to 6 weeks of age should be considered abnormal, particularly if clinical signs are present.

Clinical signs of hypoglycemia in neonates include lethargy, failure to suckle, depression, mental dullness, stupor, tremors, and seizures. Accompanying signs may include agitation, vocalization, irritability, intense hunger, and loss of consciousness.

Treatment for hypoglycemia is initiated after a diagnosis has been made. Dextrose 0.2 to 0.5 gm/lb (0.5 to 1.0 gm/kg) can be administered slowly (over several minutes) intravenously through the jugular veins of most pups. Solutions of 5% to 10% dextrose are recommended for intravenous (IV) administration. Higher concentrations of dextrose may be directly applied to mucous membranes but should never be given intravenously because of the risk of phlebitis (Table 6-1). Because of the immature metabolic mechanisms in neonatal animals concerning glucose metabolism and the potential for inherited glycogen storage diseases, blood glucose levels should be determined before more dextrose is administered to a neonate who fails to respond to therapy.

TABLE 6-1 Treatment of hypoglycemia in newborn dogs

Hepatic and Renal Considerations

Veterinarians treating neonates must come to recognize the differences between adult animals and the immature liver and kidneys of newborns. These differences are critical in terms of drug metabolism and excretion. Nephrogenesis is not completed until the third week after birth. As cortical blood flow changes and as maturation of nephrons occurs, various parts of the kidney are vulnerable to drug toxicity at various times. Protein, glucose, and amino acids are higher in the urine of neonatal pups than in adult dogs. Nevertheless, urine specific gravity is usually lower. During the first 8 weeks after whelping, the urine specific gravity ranges from 1.006 to 1.017. At or about 8 weeks, the urine specific gravity of the neonate approaches that of an adult animal. Urination begins soon after birth. The dam stimulates the vulva or prepuce of the neonate in order to get the newborn to urinate. After a few weeks, they are urinating on their own.

A variety of functions of the liver are immature or incompletely developed in the neonate enzyme system such as the P450; reduction, hydroxylation, and demethylation are not fully mature until animals are at least 5 months of age. Drugs that are metabolized and excreted by the liver should be avoided in neonates or a modified dosage scheme should be developed. However, for many drugs, no such schemes or schedules are available.

Cardiopulmonary Competence (see Chapters 32 and 34)

Cutaneous stimulation and manipulation of a newborn puppy initiates a reflex respiration. This reflexive response can be seen when the bitch licks and nips the newborn or when surgery assistants rub puppies after cesarean section. Respiratory rates of adult dogs are 16 to 32 bpm. Respiratory rates of pups are 10 to 18 bpm during the first week of life, 18 to 36 bpm during the second week, and by the third week of life it becomes the same as the rate of adult dogs. Newborn pups respond to hypercapnia by reflexively increasing bronchomotor tone. However, a pulmonary response to hypoxia is either lacking or minimal. In pups, bradycardia can occur as oxygen partial pressure drops, quite unlike the tachycardia shown in response to hypoxemia by adult dogs. Veterinary clinicians must realize that hypoxemic neonatal pups may have heart rates expected for healthy adult dogs (this despite the fact that the heart rate of normal newborn pups is 200 to 250 bpm).

Baroceptors for blood pressure are operational by the fourth day of life. This causes the heart rate of pups to vary in reaction to changes in blood pressure just as occurs in adult dogs. Mean arterial blood pressure is between 30 and 70 mm Hg in 1- to 4-week-old pups, which is much lower than that found in adults. Blood pressure is affected by a multitude of factors, including body temperature and blood glucose concentration. For severely hypoglycemic pups, the mean arterial blood pressure may drop as much as 50%. After the first week, arterial blood pressure increases with age and reaches adult levels somewhere between 6 weeks and a few months of age. The electrocardiogram (ECG) of neonates is much different than that of adults. In one report, the QRS modal axis of the ECG switched from a right cranioventral direction in the first week after birth to a left caudoventral orientation 12 weeks after whelping. This significant cardiac axis change may represent the change in ratio of right ventricular to left ventricular mass. At birth, the mass of right ventricle relative to the left ventricle is 1:1 in neonates and 1:2 or 1:3 in normal, mature adult dogs. This change in mass is intimately reflected in the ECG.