Effects of Gestational Age on Physical Findings of Immaturity, Body Weight, and Survival in Neonatal Alpacas (2002–2010)
- The work for this article was performed at the University of Wisconsin-Madison. Results from this retrospective were presented in abstract form at the Perinatal Society of Australia and New Zealand Foetal and Neonatal Workshop in Hobart on April 8, 2011
Corresponding author:Dr Simon Peek, 2015 Linden Drive West, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706; e-mail: firstname.lastname@example.org.
Gestational duration is highly variable in camelids (reference range 330–360 days), and a definition for prematurity has not been established. Anecdotally, it is suggested that crias born outside of this have increased incidence of physical findings of immaturity (tendon laxity, floppy ears, and unerupted teeth) and need increased intensive support in the neonatal period.
Low gestational age (<330 days) is associated with physical findings of immaturity, low birth weight, more intensive and expensive care, but not decreased short-term survival.
A total of 130 alpacas presented to the University of Wisconsin.
Retrospective study of all neonatal crias <1 month of age.
Of 130 neonatal alpacas presented, 86 (66%) had gestational age recorded (range 312–393 days). There were 16 (18.6%) crias with gestational age below 330 days. Crias born before 330 days were lighter at birth (mean 6.4 kg, SD 1.3 kg) than those born after 330 days (mean 7.4 kg, SD 1.7 kg, P = .002). Clinically immature crias had lower birth weights (mean 6.5 kg, SD 1.5 kg) than physically mature crias (mean 8.8 kg, SD 3.2 kg, P = .05). Survival rates were similar in all groups (premature 77%, mature 88%, P = .12). However, treatment costs were higher in crias born prior to 330 days with physical findings at birth consistent with immaturity compared with gestationally mature crias and those born prior to 330 days but with a physically mature appearance.
Crias born before 330 days and those with physical findings of immaturity have a good prognosis, but require more intensive care, resulting in higher treatment costs.
Gestational duration is highly variable in alpacas (reference range 325–360 days[1, 2]), and definitions for the terms prematurity, immaturity, and dysmaturity have not been fully established. Anecdotally, it has been noted that crias born outside of this window have an increased incidence of physical findings that are consistent with fetal immaturity (tendon laxity, floppy ears, teeth not erupted) and an increased need for support in the immediate neonatal period. Many, but not all, of these crias might be born before the lower end of the species gestational range (330 days). Prematurity in foals and human neonates, as defined as delivery before normal, species expected, gestational duration is associated with poorer survival outcomes.[3, 4] Similar physical characteristics of fetal immaturity such as small body size, droopy ears, periarticular laxity, and poor muscle development and strength have been documented in both premature neonatal horses as well as neonatal crias born before 330 days of gestation. However, clinical experience suggests that some of these immature appearing crias can be born after normal gestational lengths or occasionally even after 360 days in utero. Based on our clinical experience, we hypothesized that low gestational age (prematurity) would be associated with an increased incidence of clinical findings of immaturity and lower birth weights, but that it would not be associated with a decrease in short-term survival.
Materials and Methods
Records from neonatal (<4 weeks at presentation) crias presenting to the University of Wisconsin between 2000 and 2010 were examined. Duration of gestation, physical examination findings, birth weight, results of blood analysis, clinical diagnosis, and cost of treatment were examined. Prematurity was defined as having a gestational duration less than 330 days. Crias were considered immature if any of the following were found on physical examination at admission or at birth in the hospital: tendon laxity, poor cartilage formation of the pinnae, failure of eruption of the incisors before birth, or low birth weight. Short-term survival was defined as discharge from hospital and was compared between the group of crias that were born before 330 days of gestation (premature) and those born after 330 days of gestation, as well as between the group of crias that had signs of immaturity and those that did not. Similarly, statistical comparisons were made between these groups for birth weight, clinicopathologic variables, physical examination findings, and costs of treatment. Statistical comparisons were also made between the proportion of crias with phenotypic signs of immaturity on physical examination in the population of crias born before 330 days of gestation and those that were born after 330 days in gestation and an odds ratio calculated describing the likelihood of physical signs of immaturity being found in premature versus gestationally mature crias. Statistical significance was determined by one-way analysis of variance or Fisher's exact test.1 Average costs of treatment and duration of hospitalization were compared between the surviving members of the following groups: gestationally premature and gestationally mature crias (1), phenotypically immature and phenotypically mature crias (2), gestationally premature/phenotypically immature and gestationally mature/phenotypically immature crias (3), Average costs of treatment and days of hospitalization and normally distributed clinicopathologic data were compared using the Student's t-test and significance was set for all statistical analyses at P < .05.
Medical records of 130 crias presented to the hospital were examined. Twelve crias were born in hospital. Crias ranged from 0 – 21 days of age on presentation and were presented for a range of clinical problems as established by the referring veterinarian, the most frequent of which were weakness (13), failure of passive transfer (11), failure to nurse (9), or prematurity (7). Five crias were presented for signs relating to the respiratory system. Of these 5 crias, 2 were diagnosed with sepsis, 2 with congenital abnormalities, and 1 with pneumonia. None of these 5 crias had radiographic evidence of atelectasis suggestive of surfactant deficiency. Gestational age was recorded in 86 of these animals (range 312–393 days, mean 340 days). There were 16 (18.6%) crias with gestational age below 330 days, 11 (69%) of which had physical findings of immaturity. There were 63 (73.3%) crias born within the normal gestational period (330–360 days), 15 (24%) of which had physical findings of immaturity. There were 7 (8.1%) crias born after day 360 of gestation, 1 (14%) of which had clinical findings of immaturity. The mean gestational duration of phenotypically immature crias (347.9 days) was less than the mature appearing crias (360.1 days, P = .001). Odds ratio calculation revealed that crias with physical examination findings of immaturity were 3 times more likely to have been born prematurely before 330 days of gestation, than at term. The most common signs of immaturity were failure of incisors to erupt (13/16), periarticular laxity (9/16), and soft cartilage of the pinnae (8/16).
Physically immature crias had lower birth weights (mean 6.5 kg, SD 1.5 kg) than physically mature crias (mean 8.8 kg, SD 3.2 kg, P = .05). Similarly, crias born before 330 days were lighter at birth (mean 6.4 kg, SD 1.3 kg) than those born after 330 days (mean 7.4 kg, SD 1.7 kg, P = .002).
Overall survival in the entire study was 83.1%. There was no significant difference in survival between those crias born prematurely (77%) and those born with normal gestational duration (88%), with a P value of >.1. There was also no difference in survival between those crias with physical findings of immaturity (82%) and those that were physically mature (71%) at presentation.
Costs of treatment were higher in immature crias that survived (mean $1748.90, SD $866.2) compared to mature appearing crias that survived (mean $1064.30, SD $1122.84, P = .0049). The cost of treatment in surviving crias that were both premature and immature (mean $1831, SD $1395) did not differ from the cost of treatment in surviving gestationally mature but physically immature crias (mean $1661, SD $1095). However, in both cases (P < .001) these groups had higher treatment costs than the surviving premature but physically mature population (mean $950, SD $173). There was no difference in treatment cost in the overall population of crias born before 330 days compared with those born after 330 days of gestation if one included both nonsurviving crias and surviving crias in the analysis. Duration of hospitalization did not differ between surviving crias in any of the groups examined (surviving crias that were both immature and premature; mean 6.1 days SD 15.1, those that were immature but not premature; mean 7.5 days SD 1.8, and those that were premature but not immature; mean 4.9 days SD 11).
Blood cultures were performed in 52% (14/27) of immature crias and grew pathogens in 36% (5/14) cases. Bacteria isolated were Escherichia coli (n = 5), Enterobacter sp. (n = 5), Klebsiella spp. (n = 3), Staphlococcus aureus (n = 1), Pasteurella spp. (n = 1), and Corynebacterium spp. (n = 1). White blood cell count was performed in 25 cases and was abnormal in 56% (14/25) cases with 13/14 crias having leukopenia and only 1/14 having leucocytosis. Toxic changes were reported within neutrophils in 36% of cases (9/25 crias; 1 with leucocytosis, 1 with normal white blood cell count, and 7 with leukopenia). Animals that were blood culture positive were leukopenic in 4/5 cases. Radial immunodiffusion2 was used to measure immunoglobulin G levels in 8 animals, and was low in 7; however, plasma transfusions were administered to 82% of animals with signs of immaturity (22/27). No differences were noted in any of the admission of clinicopathologic variables measured between the groups.
The results of this study show that crias born before day 330 of gestation, and those with physical examination findings of immaturity, have a prognosis similar to other crias presenting to a tertiary referral hospital. Survival was similar, in this population, to that reported in an abstract by Gerspach and Anderson. Mature crias in this study were born at the outer limit (mean 360 days) of the “normal” gestational range (325–360 days[1, 2]) for the species.
It is challenging to explain this finding although worthwhile remembering that published normal gestational duration for the species is all based on population studies performed in the southern hemisphere. It is possible that by retrospectively examining a referred population of sick animals, we had already selected out a good proportion of more typical, healthy, mature crias, and that longer gestational crias, although apparently phenotypically mature, are more likely to require veterinary attention and therefore be referred.
Prematurity in equine, bovine, and human neonates is commonly associated with immaturity of the pulmonary system and lack of surfactant at birth. Interestingly, none of the crias that had thoracic radiographs performed had evidence of an interstitial pattern that would have been suggestive of atelectasis because of surfactant deficiency. The low incidence of respiratory signs in this population of crias might reflect an earlier maturation of the pulmonary tree, which could be a contributing factor to the positive outcome of the majority of cases. Although the timing of surfactant production in fetal alpaca crias is not documented, by analogy with other species it is possible that our study did not include sufficiently premature neonates for failure of primary surfactant production to have been an issue. Based on maturation statistics from other species, and utilizing a midgestational estimated duration of 345 days for the alapca, crias would possibly need to be born less than 275–295 days of gestation to expect to see respiratory failure because of surfactant deficiency. The shortest gestational duration recorded for any of our crias was only 312 days such that is was unlikely that even the most premature neonates in our study would have experienced surfactant related issues unless it related to postparturition consumption.
Dysmaturity has been a quite commonly used term in equine medicine, typically being coined to describe equine neonates for whom placental insufficiency or chronic severe maternal disease during pregnancy have led to varying degrees of in utero growth retardation.[7, 11] Pregnancy duration for affected foals might be short, of expected duration, or even protracted. There is 1 case report in the literature of an alpaca with urogenital leiomyosarcoma that gave birth to a dysmature cria; however, neither the incidence of this phenomenon nor an adequate definition for the term has been established in camelids. To avoid confusion, we have referred to crias throughout this manuscript as being physically immature if certain physical examination findings were present at presentation, reserving use of the term premature for those whose gestational duration was known to have been <330 days.
Body weight was significantly less in immature and premature crias at birth compared to other crias presenting to the hospital. This is consistent with findings in other species where birth weight is associated with gestational age. However, body weight at birth did not differ significantly within the group of physically immature crias between those born before 330 days of gestation and those that were born either between 330 and 360 days or after 360 days of gestation. The absolute accuracy of this observation might be negatively influenced by the relatively small numbers of immature crias in the normal and long gestational duration groups. In equine neonates, birth weight is associated with cuboidal bone ossification. Crias in this study did not have radiographic investigation for joint maturation, although angular limb deformity has been reported in an alpaca cria. Long-term follow-up has not been performed to assess the incidence of angular limb deformities in crias from this study.
Surviving crias born with physical examination findings of immaturity were discharged from hospital with larger costs of treatment than those that appeared mature on presentation, suggesting that more intensive care was required for a similar outcome. Furthermore, the costs of treatment for surviving crias that were both immature and premature as well as those that were immature but not premature were higher than those for premature crias without phenotypic signs of immaturity. Although there was not a statistically significant difference noted (P > .10) between overall survival rates of immature crias (82%) compared to physically mature crias (71%), nor in the survival rates (P > .1) of premature crias (77%) compared to normal gestational duration crias (87%), the observed differences may still be clinically relevant for veterinarians who work with alpacas. The absence of statistical significance could just be a consequence of sample size although a power analysis suggests that a sample size approximately 4–5 times that of our study would be necessary to demonstrate significance. The trend, alongside the treatment cost finding, suggests that physical signs of immaturity at admission confer a greater therapeutic challenge to the clinician and cost to the client. In comparing costs of surviving crias, we hoped to remove some of the confounding influence caused by financial pragmatism when euthanasia was being discussed with clients. Within the limitations of a retrospective study, it is rarely possible to glean from the medical record to what extent the decision to stop treatment is financial or more based upon prognosis. Our observation that treatment costs for surviving crias were higher in the phenotypically immature population compared to the phenotypically mature group is hard to explain. It was not related to the cost of a single high cost item such as plasma, for example, as the administration of 1 unit of commercial plasma from a single commercial source was consistent between these 2 groups. Similarly because the duration of hospitalization did not vary significantly in surviving crias in any of the groups examined, it appears unlikely that the added costs were related to an extended duration of stay. It might reflect increased cost of care and treatment related to ancillary diagnostics and nonplasma components of treatment but the nature of an almost decade long retrospective study precludes us from being able to analyze this. Immature crias were often reported to have biochemical signs consistent with septicemia such as leukopenia (52%) and toxic changes to white blood cells (36%). Blood culture of these animals was positive in 36% of cases. It is possible, even probable, that physically immature crias have an increased incidence of septicemia because of a concurrent failure of the immune system to fully mature before birth or failure of passive transfer because of musculoskeletal weakness affecting the ability to nurse in the immediate neonatal period. Plasma transfusions were administered to 82% of animals with phenotypic immaturity, with presumed failure of passive transfer the major reason given for transfusion. Unfortunately measurement of immunoglobulin G levels was performed rarely, likely because of the long delay before results are returned with radio-immunodiffusion. Establishing failure of transfer of passive immunity is often challenging in alpaca crias because of the practicality and availability of radial immunodiffusion for clinicians and the poor predictive value of other measurable values such as total protein, particularly in sick crias.14 Undoubtedly, clinicians in our hospital erred on the side of colloidal and passive immunoglobulin therapy in many of the crias of this study by giving plasma to over 80% of phenotypically immature crias, but substantiating passive transfer or true bacteremia in only a much smaller number of neonates. The extent to which this practice conferred a survival benefit is of course impossible to quantify but it is likely that many clinicians would promote this practice in what is considered a higher risk neonatal population. Treatment for presumed failure of passive transfer, and septicemia, likely increased the cost of these cases compared to the general hospital population. These findings are in contrast to a previous study of prematurity and dysmaturity in crias that demonstrated that hyperphosphatemia and acidosis were most commonly associated with death.
There are several limitations to this study. Only crias presenting to this tertiary institution were investigated, so the incidence of immaturity cannot be estimated nor conclusions drawn regarding the prognosis of those animals that are born with signs of immaturity but are not presented to a veterinarian. The number of immature crias seen by the hospital over the study period was quite low, and data were often missing from the medical records making statistical investigation of blood analysis challenging.
Conflict of Interest: Authors disclose no conflict of interest.
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Camelid IgG RID, Triple J Farm, Bellingham, WA