2009: Neonatology Neonatology 1 2 A. P. Davidson 3 School of Veterinary Medicine, University of California, Davis, CA, USA 4 5 Neonatal survival 6 Average reported neonatal puppy and kitten mortality rates (greatest during the first week of life) 7 vary, ranging from 9-26%.1 Prudent veterinary intervention in the prenatal, parturient and postpartum 8 periods can increase neonatal survival by controlling or eliminating factors contributing to puppy and 9 kitten morbidity and mortality. Poor prepartum condition of the dam, dystocia, congenital malformations, 10 genetic defects, injury, environmental exposure, malnutrition, parasitism and infectious disease all 11 contribute to neonatal morbidity and mortality. 12 Neonates that fail to survive to weaning are most commonly stillborn or die within the first three 13 days of life. Factors implicated in perinatal deaths include prematurity, in utero infection with viruses such 14 as canine distemper, canine parvovirus, feline herpes, feline infectious peritonitis, panleukopenia, and 15 feline leukemia virus, as well as anatomic birth defects, birth trauma/dystocia, low birth weight, 16 inadequate nutrition, maternal neglect, and environmental stresses. Optimal husbandry impacts neonatal 17 survival favorably by managing labor and delivery to reduce stillbirths, controlling parasitism and reducing 18 infectious disease, preventing injury and environmental exposure, and optimizing nutrition of the dam and 19 neonates. Proper genetic screening for selection of sires and dams minimizes inherited defects.1-4 The 20 neonatal period here is defined as the first 4-6 weeks of life. 21 Keywords: Neonatal, pediatric, physiology, disease 22 Neonatal physiology 23 Cardiovascular system 24 1. The neonate has a low pressure, low volume, low peripheral resistance circulatory system. 25 2. Higher heart rate, cardiac output, plasma volume and central venous pressure result. 26 3. Sympathetic innervation of the heart is incompletely developed, response to anticholinergics 27 minimal. 28 127 4. Baroreceptor reflexes are present after 4 days of age, prior to that hypotension results from 29 anoxia.5 30 Clinical implications: One of the most important considerations of cardiovascular physiology in the 31 neonate is that in the fetus and during the first 4 days of life bradycardia is not vagally mediated and 32 is indicative of hypoxemia. Although during this time the neonate appears able to resist circulatory 33 failure to a greater extent than the adult animal, it is far more appropriate to supplement oxygen than 34 to administer parasympatholytic agents such as atropine; administration of which will only exacerbate 35 cardiac hypoxemia via increasing oxygen demand in the face of hypoxemia. Additionally, due to 36 incomplete maturity of the autonomic nervous system, the neonate is less able to respond to 37 physiological stresses. Care should be given to maintain the neonate environment such that demands 38 on the cardiovascular system are minimal. 39 Respiratory system 40 1. Stimulation of the genital or umbilical region of the neonate induces reflex respiration in the first 41 three days after birth and may be clinically used to stimulate respiration in the immediate post 42 partum period. 43 2. Normal respiratory rate in the neonate is low, ranging from 10 – 18 breaths per minute during the 44 first week, despite a high metabolic oxygen demand. 45 3. The mechanisms that control respiratory function (carotid body chemoreceptors) in the newborn 46 develop well before birth but require maturation in the post natal period. 47 4. The amount of work and pressure that is required by a neonate to maintain tidal breathing is 48 increased as compared to that of the adult due to the high compliance of the chest wall.5 49 Clinical implications. The neonate is very susceptible to the development of hypoxemia and/or 50 jeopardized ventilation and gas exchange due to the immaturity of chemoreceptor responses to 51 hypoxia and chest wall construction. Although there are adaptations present to help compensate for 52 this physiological state, such as an extremely low circulatory failure pressure until four days of age, it 53 is important to recognize that hypoxemia in the neonate may result in life threatening sequelae such 54 as septic shock due to bacterial translocation despite a lack of mucosal lesions. It is vital that the 55 environment be kept free of airway irritants and oxygenation is adequate. 56 128 Hematopoietic system 57 1. At birth the neonate red blood cell exhibits macrocytosis with corpuscle volume decreasing to that 58 of the adult by four weeks of age as fetal red blood cells are replaced by adult red blood cells. 59 2. The hematocrit of the neonate may be as high as 60 per cent accounting for the red mucous 60 membrane color often noted at birth. By three days of age red blood cell counts have decreased 61 dramatically and continue to decrease for approximately three weeks. Adult levels for red blood 62 cell count, hemoglobin, and hematocrit are generally not detected in most dogs until six months of 63 age. 64 3. Neonatal isoerythrolysis is uncommon in the cat and rare in the dog. In the feline, the 65 phenomenon occurs in association with a type A kitten born to a type B queen that has anti-A 66 alloantibodies (agglutinating and hemolytic). White blood cell parameters in the canine and feline 67 neonate are typically consistent with those of their adult counterparts. Lymphocytosis may also be 68 noted in the normal neonate.5 69 Clinical implications. During the neonatal period, as fetal red blood cells are replaced 70 polychromasia and elevated reticulocyte counts may be noted. Care must be taken to ensure 71 adequate ectoparasite control as iron demands are high; the presence of microcytosis is suggestive 72 of iron deficiency anemia. Extramedullary hematopoeisis is commonly noted in the neonate liver. 73 Urinary system 74 1. In the canine, the neonatal kidney is morphologically and functionally immature; nephrogenesis 75 continues for at least two weeks after birth. 76 2. The canine neonatal kidney is functionally characterized by a low glomerular filtration rate (GFR.), 77 low renal plasma flow (RPF), low filtration fraction (FF), depressed reabsorption of amino acids 78 and phosphate, exaggerated proximal tubule natriuresis and low concentrating ability. 79 3. Serum creatinine levels and blood urea nitrogen (BUN) concentrations are lower than in the adult 80 animal; typically 0.4 mg/dl and 8 – 10 mg/dl respectively. Serum phosphorous concentrations are 81 elevated; typically 9 mg/dl, due to skeletal growth. 82 4. At birth arterial pressure is low (50 – 60 mmHg). During renal maturation increased blood 83 pressure and decreased vascular resistance result in an increase in GFR and RPF. In the 84 129 neonate, renal blood flow is directly correlated with arterial pressure and does not appear to be 85 altered by inhibition of angiotensin until approximately 6 weeks of age.5 86 Clinical implications. A urine sample is easy to obtain from the neonate with gentle stimulation. 87 The immature nature of the kidney alters interpretation of urinalysis. Low urine specific gravity (1.006 88 – 1.0017) is normal as is detection of protein, glucose and various amino acids due to the immaturity 89 of the proximal tubule. By three weeks of age urine protein and glucose concentrations approach that 90 of the adult dog and urine concentration is expected to compare to that of the adult dog by six to eight 91 weeks of age. 92 As the neonatal kidney is less able to concentrate or dilute urine, renal blood flow parallels blood 93 pressure, and there is altered sodium excretion by the proximal tubule. Fluid therapy should be 94 administered with care to ensure adequate volume maintenance without over hydration or oncotic 95 loading. Recommended daily fluid rates for the canine neonate range from 60–180 ml/kg/day. 96 Caution must be exercised when administering renally excreted or metabolized antimicrobials 97 (penicillin, ampicillin, cephalosporins, fluroquinolones, and aminoglycosides) to neonates. Generally, 98 ß-Lactam antibiotics (penicillins, cephalosporins) are the antimicrobial drugs of choice, as although 99 the half-life may be prolonged there is a large therapeutic margin. Ceftiofur, for example, 100 administered at 2.5mg/kg SQ q 12hrs, maximum five days is an acceptable antimicrobial choice. Due 101 to altered metabolism of nonsteroidal antiinflammatories the potential for renal toxicity from their use 102 in the neonate is far greater than in the adult animal.5 103 Hepatobiliary system 104 1. During pregnancy, the maternal placenta supports many functions performed by the liver and 105 biliary system in the adult animal. Prior to birth, the ductus venosis shunts blood through the 106 liver, effectively bypassing the neonatal sinusoid. The canine neonatal liver and biliary system is 107 functionally immature at birth. 108 2. There is a significant reduction in bile flow in the newborn puppy as compared to the adult dog, 109 and a complete failure of secretin and glucagon to stimulate bile flow at 3-28 days of age. Despite 110 a relative functional cholestasis in the neonate, serum bile acids may be used to detect 111 hepatocirculatory abnormalities in puppies and kittens as young as four weeks. Alkaline 112 130 phosphatase (ALP) and gamma-glutamyltransferase (GGT) liver enzyme activities are markedly 113 elevated in neonates less than two weeks old and moderately elevated after two weeks of age. 114 Elevations in ALP and GGT enzyme activity have been attributed to placental, colostral, and 115 intestinal activity. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are 116 typically comparable to that of the adult. Alkaline phosphatase can be physiologically elevated 117 during skeletal growth. 118 3. Postnatal hepatic microsomal enzyme activities at four weeks of age are 85% of that seen in an 119 adult dog. Adult dog levels of microsomal enzyme activity are achieved by four and one-half 120 months of age.5 121 Clinical implications. At birth, the neonate experiences functional cholestasis with altered liver 122 enzyme serum biochemical profiles. Due to the absence of fully developed microsomal and P450 123 enzyme activity in the neonate until four to five months of age, caution must be exercised when 124 prescribing medication that requires hepatic metabolism or excretion. The detection of serum 125 increases in GGT and ALP in the newborn may be indicative of colostrum intake and potentially 126 passive transfer. 127 Gastrointestinal system 128 1. Dentition eruption in the neonate first occurs at two to three weeks of age. All deciduous teeth 129 should be present by 12-16 weeks of age. 130 2. At birth, the gastrointestinal tract is sterile and has a neutral gastric pH. It is characterized by a 131 time-dependent increased permeability of the intestinal mucosa which decreases dramatically 132 after ten hours. Normal nursing pup feces are semiformed and tan in color (acholic). GI motility 133 prior to 30-40 days of life is dependent upon pressure gradients rather than electrical intestinal 134 motility. 135 3. Body temperature is known to have a dramatic effect on gastrointestinal movement in the 136 neonate. At rectal temperatures below 94 °F, ileus develops. As ileus progresses, the willingness 137 to nurse decreases and the necessity for tube feeding puppies increases. Inherent to the tube 138 feeding process is the risk for aspiration and subsequent development of pneumonia.5 139 131 Clinical implications. Care should be taken to ensure adequate environmental conditions to 140 maintain normal body temperature in neonates to minimize gastrointestinal ileus. Due to altered 141 absorption from increased gastrointestinal permeability and neutral gastric pH in the immediate post 142 natal period, care must be taken if administering oral drug therapy. Diarrhea can result from 143 overeating, and is then complicated by subsequent bacterial overgrowth. 144 Immune system 145 1. Five to ten percent of canine neonatal serum antibodies are derived from trans-placental 146 transfer. At birth, the canine neonate is antibody deficient and immunologically incompetent. The 147 acquisition of passive immunity requires adequate ingestion and absorption of colostrum during 148 the first 24 hours of life. Gastrointestinal absorption of colostral antibodies decreases markedly 149 after 12 hours. 150 2. Providing adequate ingestion of quality colostrum, the puppy is protected by maternally derived 151 immunoglobulins during the neonatal period. Puppies are capable of producing challenge 152 specific antibodies within two weeks and with repeated challenge can produce a secondary 153 immune response at 40 days. However, even by 40 days of age, T cell mitogenesis and 154 differentiation, and phagocytic cell function systems may not be fully mature.5 155 Clinical implications. Incompletely developed immune systems and inadequate thermoregulation 156 during the first days of life make neonates vulnerable to systemic infection (bacterial and viral). Adequate 157 ingestion of colostrum must occur promptly post partum for puppies to acquire passive immunity. The 158 transmission of protective immunity (placental or colostral antibodies) between a bitch and her puppies 159 depends upon the prior existence of adequate serum maternal antibodies. When colostral intake is not 160 possible or is of questionable quality, pooled adult dog serum (20-150 ml/kg SC divided) may be 161 administered to elevate serum immunoglobulin concentrations in the puppy.5-7 162 Neurologic system 163 1. The neonatal puppy’s main activities during the first two weeks of life are sleeping and nursing. 164 The rooting reflex orients the neonate to its source of food, the dam. Vestibular function is present 165 at birth and is important for positioning during nursing. Muscular coordination however is absent. 166 Initial movements are characterized by swimming-like movements of the limbs, while sliding along 167 132 on the ventral abdomen and thorax. The ability to raise the head is present at birth in puppies and 168 the head may be used initially for righting reflex. An upright posture in puppies cannot be 169 maintained until ten to 14 days. 170 2. The EEG of the neonatal puppy initially is similar during periods of sleep and waking. 171 3. At birth the body posture is primarily one of flexion. If suspended by the head, flexor hypertonicity 172 is present. At four to five days in puppies, the flexor hypertonicity is replaced by extension until 173 three to four weeks of age when the puppies will begin to struggle to escape when held in 174 suspension. 175 4. The nociceptive threshold is much lower than in adults. This may be due to a lack of some of the 176 descending inhibitory mechanisms found in older animals. The coordination of motor responses 177 to noxious stimuli is not well-developed and the animal may have much wider receptive fields to 178 noxious events. Neurotransmitters may not have reached full function.8 179 Clinical implications. Although the nervous system of the neonate is immature there is no doubt 180 that nociceptive pathways are present and that pain is perceived by the neonate subjected to noxious 181 stimuli. Drugs which might be effective in adults may not be as effective in neonates. Procedures 182 carried out on neonates with insufficient pain control produce greater stress responses than those 183 where analgesia has been provided. A local anesthetic (lidocaine, dose extrapolated from humans) 184 can be used and is very effective; The dose requirement is lower because of the immaturity of the 185 nerves but the neonate does not appear to be at any greater risk of toxic side effects with a single 186 dose of lidocaine. Bupivicaine is not advised in the neonate due to the risk of cardiotoxicity with 187 overdosage. 188 The pharmacokinetics of the opioid analgesics are different in the neonate versus the adult. 189 Lower doses of these drugs are required for analgesia at one day of age compared with 34 days 190 (three to four-fold differences). 191 Metabolism 192 1. The normal birth weight of the puppy is breed dependent; generally, 500 gm ± 150 gm for a 193 medium breed dog. Birth weights lower than 300 gm in the medium size dog are associated with 194 an increased risk of neonatal mortality. Increased mortality in low birth weight puppies is most 195 133 likely associated with negative effects of chilling (higher body surface area: mass) and the ability 196 to nurse and maintain glucose concentrations. Generally, there is a similar pattern of growth 197 amongst different breeds of dogs; the most rapid weight gain occurring during the first 12 weeks. 198 Puppies should gain on average 10% of their body weight each day for the first few weeks of life. 199 2. Unlike their homeothermic adult counterparts, neonates are poikilothermic. However, they have 200 well-developed behavioral heat-seeking responses which enable them to maintain a stable rectal 201 temperature providing sources of heat are available. Shivering and vasoconstrictive reflexes are 202 not functional in the newborn. Physiological responses noted during hypothermia include 203 bradycardia, cardiovascular failure, neuronal injury, and ileus. Normal rectal temperatures in the 204 puppy are 95 – 99 °F (week one), 97 – 100 °F (weeks two and three) and by weaning rectal 205 temperatures approach that of the adult. 206 3. At birth the neonate must transition from placental support to endogenous food stores for glucose 207 production. During the first three to 24 hours after birth, hepatic glycogen stores decline by more 208 than 50% and there is a shift from glycogenolysis to a mixture of glycogenolysis and 209 gluconeogenesis. For maintenance of blood glucose concentrations, regular feeding is required. 210 In addition to regular nursing, the dam’s nutritional state must be adequate to provide for the 211 needs of her puppies.5 212 Clinical implications. The neonate is susceptible to a wide variety of toxic, environmental, 213 infectious and congenital insults; however, the ability for them to respond is limited. One of the first 214 signs of illness in both the kitten and puppy is a failure to gain weight. This finding is often noted well 215 before any other clinical signs of disease are present. Twice daily weighing of neonates during the 216 first week(s) of life dramatically facilitates early detection of illness, ensures adequate intervention in a 217 timely manner to prevent poor weight gain and positively impacts neonatal survival.1 218 Neonatal/pediatric conundrums 219 Fading Puppies 220 A fading puppy commonly dies following the onset of rapidly progressive, vague signs of illness. 221 Premortem diagnosis is challenging. Immediate necropsy of a neonate dying without obvious cause is 222 134 warranted to provide proper veterinary care of the littermates. Clients should be advised to refrigerate (not 223 freeze) deceased neonates and present them promptly for evaluation. 224 Neonatal bacterial peritonitis with septicemia can cause rapid deterioration of the puppy resulting 225 in death if not recognized and treated promptly. Factors shown to predispose a puppy to septicemia 226 include endometritis in the bitch, a prolonged (often not recognized or reported) delivery/dystocia, feeding 227 of replacement formulas, the use of ampicillin, stress, low birth weight (< 350 gms), and chilling with body 228 temperature <35.5 °C. The umbilicus of neonates should be treated with tincture of iodine immediately 229 after birth to reduce contamination and prevent ascent of environmental bacteria into the peritoneal cavity 230 (omphalitis-peritonitis). 231 The bacterial organisms most frequently associated with septicemia are E. coli, Streptococci, 232 Staphylococci, and Klebsiella spp. Commonly, a decrease in weight gain, failure to suckle, hematuria, 233 persistent diarrhea, unusual vocalization, abdominal distention and pain, and sloughing of the extremities 234 indicate septicemia may be present. 235 Prompt therapy with broad spectrum, bactericidal antibiotics, optimal nutrition via 236 supported nursing, tube feeding or bottle-feeding, maintenance of body temperature, and 237 appropriate fluid replacement are indicated. The third generation antibiotic, ceftiofur 238 sodium, is an appropriate choice for neonatal septicemia as it alters normal intestinal flora 239 minimally and is usually effective against the causative organisms. The prognosis for septicemic 240 neonates is poor. Failure to respond to antibiotic therapy should prompt consideration of canine herpes 241 virus infection. 242 Canine herpesvirus (CHV) is a widely recognized and commonly blamed cause of fading puppy 243 syndrome. Premortem and postmortem diagnosis of CHV infection in neonates can be challenging. 244 Typical necropsy findings include multifocal petechial renal hemorrhages. Confoundingly, these can be 245 also be present with bacterial septicemia. Intranuclear inclusion bodies can be difficult to find. Diagnosis 246 by virus isolation or CHV-specific PCR is confirmatory. Treatment has been reported to be unrewarding 247 and recovery is rare. Recovery has been reported to result in residual cardiac and neurologic damage. 248 Treatment with immune serum from affected dams is reported to be ineffective in infected puppies. One 249 case report of successful treatment with the antiviral drug, acyclovir exists. Successful vaccine 250 135 development has been hampered by the poor immunogenicity of other herpesviral vaccines developed for 251 other species, as with feline and bovine rhinotracheitis. Neonates of a naïve bitch exposed to CHV during 252 the last two to three weeks of gestation or the first three weeks postpartum are at risk.9,10 253 Acyclovir is an antiviral agent with activity against a variety of viruses including herpes 254 simplex. Acylcovir is preferentially taken up by susceptible viruses and converted into 255 the active triphosphate form, which inhibits viral DNA replication. Acyclovir is poorly 256 absorbed after oral administration and is primarily metabolized by the liver. Acyclovir 257 can increase the toxicity of nephrotoxic drugs. The half-life in humans is approximately 258 three hours. Its use in veterinary medicine is not well established and it should be used 259 with caution and only in situations where indicated. The safety and effectiveness in 260 humans less than two weeks of age is not established. The dose is extrapolated from 261 that for humans.10 262 Juvenile cellulitis 263 Juvenile cellulitis (puppy strangles) is a progressive, granulomatous, pustular disorder of puppies, 264 most commonly occurring in dogs younger than four months of age, but it is occasionally reported in dogs 265 up to four years of age. The eyelids, pinnae, lips, chin, muzzle, paws, abdomen, thorax, vulva, prepuce 266 and anus can be affected with lesions that fistulate, drain and crust. Lymphadenomegaly, most commonly 267 mandibular and superficial cervical, can be distant from the affected skin sites and is often painful. 268 Pustules and lymph nodes are usually sterile when cultured. Superficial cutaneous flora can be cultured 269 from open, draining lesions. Pyrexia, anorexia, sterile suppurative painful arthritis and an inflammatory 270 hemogram can occur. The diagnosis is confirmed by histopathologic evaluation but is commonly made on 271 the basis of clinical appearance. The predominant inflammatory cell in juvenile cellulitis, characterized by 272 light and electron microscopy and immunohistochemical staining, is an epithelioid macrophage Juvenile 273 cellulitis requires aggressive immunosuppressive therapy early in the course of the disease for resolution 274 and to avoid the sequellae of cicatricial lesions. Traditionally, puppies have been placed on 275 immunosuppressive doses of prednisone (2.2 mg/kg/day), causing concerns with immunization efforts. 276 Griseofulvin therapy offers an apparently effective treatment without the side effects associated with 277 corticosteroid administration, enabling discontinuation of corticosteroids sooner in the course of the 278 136 disease. It has been reported to be effective as sole immunomodulatory therapy (14.2 to 34 mg/kg PO Q 279 12 h). Griseofulvin is postulated to induce down regulatory signals within the lesions. The use of 280 griseofulvin as sole therapy could be attempted in early cases. Vaccination of puppies undergoing 281 immunosuppressive therapy is not advised and they must be strictly isolated from sources of infectious 282 disease.11,12 283 Bacterial overgrowth syndrome-associated diarrhea 284 Pediatric dogs and cats are often presented to the veterinarian for signs referable to the 285 abdominal cavity. Dietary indiscretions, parasitism and infectious disease (primarily viral, less commonly 286 bacterial) account for most of these presentations. Congenital and developmental disorders should also 287 be considered. 288 Symbiotic colonic bacteria assist digestion. The upper GI tract was once believed to be sterile, 289 but normal colonization of the duodenum, jejunum, and ileum is now appreciated. Bacterial overgrowth 290 syndrome (BOS) occurs when the normally low bacterial colonization in the upper GI tract significantly 291 increases. Neonates are particularly at risk for developing BOS. Mucosal injury resulting from a minor 292 viral or bacterial gastroenteritis can induce BOS in these individuals if a proper post infectious dietary 293 regimen is not followed. 294 A particular bacterial pathogen has never been implicated; instead, abnormally large numbers of 295 normal or pathological flora appear to cause BOS. Under normal conditions, gram-positive bacteria and 296 fungi colonize the duodenum and jejunum in quantities less than 1 X 105 organisms per milliliter of fluid. 297 Aerobic and anaerobic bacteria colonize the ileum in quantities less than 1 X 108 organisms per milliliter 298 of fluid. This is in sharp contrast to the 1 X 1011 organisms per milliliter of fluid that colonize the colon. 299 Studies of duodenal aspirates have not identified any particular bacteria as a cause of BOS; however, 1 X 300 105 organisms per milliliter of aspirate fluid is diagnostic for BOS. Usually, abnormally large numbers of 301 anaerobic bacteria and normal florae grow from cultured fluid of patients with BOS. 302 137 The following are protective factors that stabilize the number and type of bacteria that colonize 303 the upper GI tract. Abnormalities in these mechanisms put a patient at risk for bacterial overgrowth. 304 1. Two coordinated motor phenomena produce the continuous propulsive peristaltic action of the 305 upper GI tract. Both the migrating motor complex and the migrating action potential complex clear 306 the upper intestine of unwanted bacteria and undigested substances. Desynchronization of these 307 complexes results in diarrhea and weight loss in animal models. Neonates lack propulsive 308 peristaltic action. Gut motility in neonates results from aboral pressure. 309 2. Gastric acid normally reduces the proximal small intestine bacteria populations, particularly 310 anaerobic bacteria. The bowel mucosa integrity and mucin layer protect the gut from bacteria. 311 Neonates have reduced gastric acidity. 312 3. Malabsorption of bile acids, fats, carbohydrates, proteins, and vitamins causes many of the 313 symptoms of diarrhea and weight loss associated with BOS. Anaerobes and Bacteroides fragilis 314 actively deconjugate bile acids, thereby preventing proper bile acid function and enterohepatic 315 circulation. Fatty acid absorption is reduced because deconjugated bile acids cannot help micelle 316 formation. Deconjugated bile acids directly inhibit carbohydrate transporters. These unabsorbed 317 sugars ferment into organic acids because of the intestinal flora, which reduces the intraluminal 318 pH and produces osmotic diarrhea. The unconjugated bile acids also damage intestinal 319 enterocytes and induce water secretion by the colonic mucosa. 320 4. Fat, protein, carbohydrate, and vitamin malabsorption result from poor enterocyte function and 321 bacterial transformation of nutrients into nonabsorbable and toxic metabolites. Toxic metabolites 322 damage the intestinal mucosa. Malabsorption and enterocyte dysfunction further degrade the 323 health of the gut by reducing local and systemic nutrition delivery. 324 Treatment of BOS is aimed at reducing the damage caused by malabsorption and restoring 325 nutritional health and normal gut flora. Prompt recognition and treatment can prevent the development of 326 138 severe malnutrition. The antimicrobials of choice for therapy of BOS-associated diarrhea are ampicillin or 327 amoxicillin in the pediatric patient (due to the neurotoxicity associated with metronidazole overdosage).14 328 Anasarca 329 Anasarca, a lethal congenital edema, can occur with or without concurrent cardiovascular 330 abnormalities. Generalized subcutaneous edema, with intrathoracic and intraperitoneal fluid accumulation is 331 present. Congenital hereditary lymphedema causes edema of the extremities and sometimes head, and is 332 associated with morphologic lymphatic abnormalities. Prepartum ultrasonographic evaluation of the fetuses 333 can be used to screen for this disorder. Dystocia can result due to fetal oversize. Anasarca is a problem 334 common in Bulldogs, but recognized in other breeds as well (Labrador retriever). It is suspected to have 335 a heritable component. Its exact pathophysiology in the dog is not understood. The genetics are not 336 known; anasarca is thought to be inherited as an autosomal dominant trait. There are multiple anecdotal 337 remedies, none proven or reported in the scientific literature. It is debated and discussed on 338 theriogenology list serves and on the layman’s internet exhaustively. As well as causing dystocia, 339 anasarca usually results in stillborn puppies or puppies needing to be euthanized. Some veterinarians 340 promote various therapies, usually doomed to failure. Diuretic therapy of affected neonates can sometimes 341 cause slight normalization, but euthanasia is usually indicated if the neonate is not stillborn. Environmental, 342 dietary, and pharmacologic contributory factors are not scientifically defined. Anasarca has been 343 recognized for many years, yet its incidence remains unchanged. An attempt to recognize the presence 344 of anasarca prepartum with ultrasonography should be made in bitches with a history of affected puppies 345 or in breeds with high incidence, due to the higher incidence of dystocia associated with the syndrome. 346 “Swimmer” puppies 347 Swimmer puppies fail to develop normal ambulation at ten to 14 days of life, moving instead by paddling 348 their limbs laterally and caudally. Compression and deformation of the sternum and thorax occur 349 concurrently. Obese puppies from small litters, commonly raised on relatively slippery surfaces are 350 predisposed. Treatment should be instituted immediately upon diagnosis, consisting of caloric restriction, 351 physical therapy, and improved traction in the nest box. If diagnosed early (three to five weeks of age) the 352 condition is reversible and does not require binding of puppies. 353 139 Puppy vaginitis 354 Puppy vaginitis is characterized by an apparently healthy female puppy presented with mucoid 355 vulvar discharge that is usually white to yellow, and sometimes copious. The discharge can be 356 accompanied by mild perivulvar dermatitis. The puppy is not typically attentive to the discharge, and 357 there is not any associated change in urinary behavior (dysuria or polakiura). Clients often have a difficult 358 time deciding if a puppy has normal urinary behavior or not. The age of onset ranges from six weeks to 359 puberty, the duration is from days to months, and the disorder is often intermittent. 360 Cytologic examination of the discharge finds suppurative inflammation. Vaginal cultures (aerobic) 361 generally fail to grow anything but normal flora in small numbers, similar to unaffected littermates. A 362 urinalysis, acquired by cystocentesis, is characteristically normal (a decreased urine specific gravity is 363 typical for young dogs lacking adult concentrating abilities), and the urine culture negative. The clinician 364 needs to perform enough diagnostics to rule out more significant causes of vulvar discharge and feel 365 comfortable with the diagnosis of benign puppy vaginitis. 366 The specific etiology of puppy vaginitis is unknown. An imbalance of juvenile vaginal glandular 367 epithelium is postulated. The condition is reported in the literature to resolve both with puberty and with 368 ovariohysterectomy, two very different events endocrinologically, therefore neither likely to truly cause 369 resolution. Puppy vaginitis diminishes with maturity. The term “puppy vaginitis” is a misnomer, as it is 370 asymptomatic and not indicative of inflammation. Important rule-outs (some of which are associated with 371 inflammation) include urinary tract infection, urinary incontinence with associated mucosal scalding, the 372 onset of the initial estrous cycle, vaginal foreign bodies (i.e. foxtails) and urogenital anatomic anomalies 373 (ectopia, disorders of sexual differentiation, significant strictures). Cleansing the perivulvar area with a 374 gentle solution (non-alcoholic otic preparations or “baby wipes”), benign neglect and tincture of time are 375 advised.14,15 376 References 377 1. Johnston SD, Root Kustritz MV, Olson PNS: The neonate – from birth to weaning. Canine and 378 feline theriogenology. Philadelphia: WB Saunders; 2001. p.146–167. 379 2. Moon PF, Erb HN, Ludders JW, et al: Perioperative risk factors for puppies delivered by 380 cesarean section in the United States and Canada. 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