Veterinary anesthetists and anesthesiologists are uniquely positioned to contribute meaningfully to matters pertaining to the humane taking of animal life. Determining the humaneness of euthanasia, slaughter, or depopulation methods can be difficult because humans can never fully know or understand the subjective experiences of animals during loss of consciousness. Euthanasia, humane slaughter, and depopulation methods initially produce unconsciousness through three basic mechanisms: direct depression of neurons necessary for life functions; hypoxia; and physical disruption of brain activity. Measurements of brain electrical function, such as electroencephalogram (EEG), bispectral analysis (BIS), and visual and auditory evoked potentials (VEP, AEP), have been used to quantify the unconscious state. Fetal sentience during euthanasia of pregnant animals and ovariohysterectomy of pregnant dogs and cats has been extensively reviewed. Foam depopulation uses medium- or high-expansion foam-generating equipment to create a blanket of water-based foam to cover the animals.

Injectable anesthetics are commonly used in laboratory animal medicine. This chapter outlines the majority of injectable anesthetics and injectable combinations used in laboratory animals today. Pharmacokinetics, preparation and route of administration, and side effects seen with these anesthetics are covered in detail. While not always as commonly used, injectable anesthetic delivery systems are also covered in this chapter.

An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and elimination half-life were 134 ± 67.4 ml/kg/min and 44.3 ± 26.3 min, respectively, in the CRI group, and apparent clearance and half-life were 412 ± 306 ml/kg/min (Cl/F) and 38.9 ± 18.6 min, respectively, in the IM group. Analgesia was evaluated using mechanical pressure threshold. Intravenous dexmedetomidine produced faster onset of sedation and increased pressure threshold compared with IM administration. Individual horses had a large variability in dexmedetomidine plasma concentrations between CRI and IM administration. The odds of a decreased GI motility following IV administration was 12.34 times greater compared with IM administration.

Background Little is known about the contemporary mortality experience among adults with congenital heart disease (CHD). The objectives of this study were to assess the age at death, presence of cardiovascular comorbidities, and most common causes of death among adults with CHD in a contemporary cohort within the United States. Methods and Results Patients with CHD who had a healthcare encounter between 2008 and 2013 at 1 of 5 comprehensive CHD centers in North Carolina were identified by International Classification of Diseases, Ninth Revision ( ICD‐9 ), code. Only patients who could be linked to a North Carolina death certificate between 2008 and 2016 and with age at death ≥20 years were included. Median age at death and underlying cause of death based on death certificate data were analyzed. The prevalence of acquired cardiovascular risk factors was determined from electronic medical record data. Among the 629 included patients, the median age at death was 64.2 years. Those with severe CHD (n=157, 25%), shunts (n=202, 32%), and valvular lesions (n=174, 28%) had a median age at death of 46.0, 65.0, and 73.3 years, respectively. Cardiovascular death was most common in adults with severe CHD (60%), with 40% of those deaths caused by CHD. Malignancy and ischemic heart disease were the most common causes of death in adults with nonsevere CHD. Hypertension and hyperlipidemia were common comorbidities among all CHD severity groups. Conclusions The most common underlying causes of death differed by lesion severity. Those with severe lesions most commonly died from underlying CHD, whereas those with nonsevere disease more commonly died from non‐CHD causes.

BACKGROUND:There is a persistent, unexplained disparity in sex ratio among childhood cancer cases, whereby males are more likely to develop most cancers. This male predominance is also seen for most birth defects, which are strongly associated with risk of childhood cancer. We conducted mediation analysis to estimate whether the increased risk of cancer among males is partially explained by birth defect status. METHODS:We used a population-based birth cohort with linked data from birth certificates, birth defects registries, and cancer registries from Arkansas, Michigan, North Carolina, and Texas. We conducted counterfactual mediation analysis to estimate the natural direct and indirect effects of sex on cancer risk, modeling birth defect status as mediator. State; birth year; plurality; and maternal race and ethnicity, age, and education were considered confounders. We conducted separate analyses limited to cancers diagnosed younger than 1 year of age. RESULTS:Our dataset included 10 181 074 children: 15 110 diagnosed with cancer, 539 567 diagnosed with birth defects, and 2124 co-occurring cases. Birth defect status mediated 38% of the association between sex and cancer overall. The proportion mediated varied by cancer type, including acute myeloid leukemia (93%), neuroblastoma (35%), and non-Hodgkin lymphoma (6%). Among children younger than 1 year of age at cancer diagnosis, the proportion mediated was substantially higher (82%). CONCLUSIONS:Our results suggest that birth defects mediate a statistically significant proportion of the relationship between sex and childhood cancer. The proportion mediated varied by cancer type and diagnosis age. These findings improve our understanding of the causal pathway underlying male sex as a risk factor for childhood cancer.

The science of transitional states of consciousness is reviewed. Despite intensive study, determining the subjective experience of animals during transitional states of consciousness remains inherently limited. Until better assessment tools become available, behavior-based observations, such as loss of righting reflex/loss of posture, remain among our most useful guides to the onset of unconsciousness in animals. To minimize potential animal suffering and to ensure a truly unconscious state is unambiguously achieved, a state of general anesthesia relying on gamma amino butyric acid type A agonists or N-methyl-d-aspartate antagonist agents continues to be a necessary component of the companion animal euthanasia process.

BACKGROUND:Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. METHODS:Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. RESULTS:The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. CONCLUSION:National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.

Primary congenital glaucoma (PCG) and anterior segment defects (ASDs) are rare ocular malformations diagnosed early in life which can cause blindness. Pathogenic variants in several genes have been linked to these conditions, but little is known about nongenetic risk factors. We investigated the association between maternal nutrition and PCG and ASDs in the National Birth Defects Prevention Study, a large population-based, multicenter case-control study of major birth defects in the United States. Mothers of cases (n = 152) and control infants without a birth defect (n = 9,178) completed an interview which included a food frequency questionnaire capturing usual dietary intake in the year before pregnancy. Maternal nutrition was assessed through individual nutrient intake, calculating a Diet Quality Index for Pregnancy (DQI-P) score for each mother, and using latent class analysis to empirically derive four dietary patterns. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using logistic regression. The results for individual nutrients varied, with some having an inverse or U-shaped pattern of association with increasing intake. The DQI-P was not associated with risk of PCG and ASDs (aOR 0.91; CI 0.49-1.66, highest vs. lowest quartile). The dietary pattern analysis suggested lower odds among women with a Prudent and Mexican dietary pattern (aOR 0.82, 95% CI 0.52-1.29; aOR 0.80, 95% CI 0.36-1.78, respectively) compared to those with a Western dietary pattern. We found that higher intake of some nutrients and certain dietary patterns may be inversely associated with PCG and ASDs, though caution is urged due to imprecision of estimates.

BACKGROUND:North Carolina's Infant-Toddler Program (NC ITP) provides Early Intervention (EI) services from birth to age three for children at risk for developmental delays. This study examined referral patterns by clinical and sociodemographic characteristics among infants with birth defects and infants born extremely preterm (gestational age < 27 weeks) or extremely low birthweight (<1,000 g).METHODS:A retrospective cohort of North Carolina resident births from 2012 to 2014 was matched to data from the North Carolina Birth Defects Monitoring Program and NC ITP records. A total of 2,463 infants with eligible birth defects and 2,118 extremely preterm or low birthweight infants were identified. Adjusted odds ratios and 95% confidence intervals from multivariable logistic regression models were used to analyze differences in referral by sociodemographic and clinical factors. Referrals resulting in enrollment were also examined.RESULTS:About 70% of infants with eligible birth defects and 85% of extremely premature infants were referred to the NC ITP. Geographic region, maternal race/ethnicity, maternal and infant enrollment in Medicaid, and hospital level of care at delivery were associated with referral among both at-risk groups. Among infants with birth defects, maternal age, education, and marital status were also associated with referral, as well as gestational age, birthweight, and the presence of multiple anomalies. Of the infants with referrals, over 80% in each group were subsequently enrolled.CONCLUSIONS:Many of the sociodemographic and clinical factors examined were associated with EI referral. These findings can be used to address coverage gaps and improve referral and enrollment rates for at-risk infants.

Population reduction or eradication of domestic or non-domestic species may be required to address their impacts on the environment, other species, or human interests. Firearms are often used to accomplish these practical management objectives, and there is increased concern that the methods used may compromise animal welfare. We document the accuracy and humaneness of gunshot placement to the brain and cervical vertebrae of Philippine deer (Rusa marianna) on Guam during depopulation activities as a model for meeting AVMA standards of euthanasia under field conditions (e.g., animal is not in hand). Deer were shot with a .223 caliber rifle from 10-125 m and approached immediately (<20 s) for assessment. A subset of adult deer was further evaluated for physiological responses including cessation of heart rate, respiration, ocular reflexes, and post-mortem spasms. All deer shot in the brain (n = 132) and upper cervical spine (C1-C3; n = 18) died immediately due to the destruction of the brain or spinal tissue. Shot placements were all within 1.9 cm of the point of aim (i.e., the center of the target region). The accuracy and immediate insensibility resulting from targeting of C1-C3 demonstrates that this is an alternative target site when animal positioning is not optimal for targeting the brain, or there is a need to preserve brain tissue (e.g., Chronic Wasting Disease testing). While targeting of C4 -C7 vertebrae (n = 6) was accurate and resulted in immediate incapacitation, the failure to produce immediate insensibility does not support the use of this shot placement when upper cervical or brain shot placement is an option. It is reasonable to achieve sufficient accuracy to target the brain or upper cervical vertebrae of deer under field conditions and meet standards of euthanasia while accomplishing management objectives.

OBJECTIVE To investigate first-year survival of infants born with spina bifida, and examine the association of maternal prepregnancy body mass index (BMI) with infant mortality. METHODS This is a retrospective cohort study of 1,533 liveborn infants with nonsyndromic spina bifida with estimated dates of delivery from 1998 to 2011 whose mothers were eligible for the National Birth Defects Prevention Study (NBDPS). NBDPS data were linked to death records to conduct survival analyses. Kaplan-Meier survival functions estimated mortality risk over the first year of life. Cox proportional hazards models estimated hazard ratios (HRs) for maternal prepregnancy BMI categorized as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), and obese (≥30). RESULTS Infant mortality risk among infants with spina bifida was (4.4% [3.52, 5.60%]). Infants with multiple co-occurring defects, very preterm delivery, multiple gestation, high-level spina bifida lesions, or non-Hispanic Black mothers had an elevated risk of infant mortality. Maternal prepregnancy underweight and obesity were associated with higher infant mortality (15.7% [7.20, 32.30%] and 5.82% [3.60, 9.35%], respectively). Adjusted HR estimates showed underweight and obese mothers had greater hazard of infant mortality compared to normal weight mothers (HR: 4.5 [1.08, 16.72] and 2.6 [1.36, 8.02], respectively). CONCLUSION The overall risk of infant mortality for infants born with spina bifida was lower than most previously reported estimates. Infants born with spina bifida to mothers who were underweight or obese prepregnancy were at higher risk of infant mortality. This study provides additional evidence of the importance of healthy maternal weight prior to pregnancy.

ImportanceBirth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. ObjectivesTo identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. Design, Setting, and ParticipantsThis multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10181074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. ExposuresBirth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. Main Outcomes and MeasuresCancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. ResultsCompared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P<.05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. Conclusions and RelevanceSeveral significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

: The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found that provide a safe and reliable way to induce unconsciousness in groups of animals, and also cause less distress than CO2. Here, we revisit the current and historical literature to identify key research questions that may lead to the identification and implementation of more humane alternatives to induce unconsciousness in mice, rats, poultry, and pigs. In addition to the evaluation of novel methods and agents, we identify the need to standardise the terminology and behavioural assays within the field. We further reason that more accurate measurements of consciousness state are needed and serve as a central component in the assessment of suffering. Therefore, we propose a roadmap toward improving animal welfare during end-of-life procedures.

Background Higher prevalence of selected birth defects has been reported among American Indian/Alaska Native (AI/AN) newborns. We examine whether known risk factors for birth defects explain the higher prevalence observed for selected birth defects among this population. Methods Data from 12 population‐based birth defects surveillance systems, covering a birth population of 11 million from 1999 to 2007, were used to examine prevalence of birth defects that have previously been reported to have elevated prevalence among AI/ANs. Prevalence ratios (PRs) were calculated for non‐Hispanic AI/ANs and any AI/ANs (regardless of Hispanic ethnicity), adjusting for maternal age, education, diabetes, and smoking, as well as type of case‐finding ascertainment surveillance system. Results After adjustment, the birth prevalence of two of seven birth defects remained significantly elevated among AI/ANs compared to non‐Hispanic whites (NHWs): anotia/microtia was almost threefold higher, and cleft lip +/− cleft palate was almost 70% higher compared to NHWs. Excluding AI/AN subjects who were also Hispanic had only a negligible impact on adjusted PRs. Conclusions Additional covariates accounted for some of the elevated birth defect prevalences among AI/ANs compared to NHWs. Exclusion of Hispanic ethnicity from the AI/AN category had little impact on birth defects prevalences in AI/ANs. NHWs serve as a viable comparison group for analysis. Birth defects among AI/ANs require additional scrutiny to identify modifiable risk and protective factors.

To evaluate birth defect risk in children conceived with IVF and non-IVF ART (subfertile), IVF siblings, and fertile controls. Cohort study, with exposure groups defined as IVF-exposed, siblings of IVF-exposed, subfertile, and fertile. IVF cycles in SART CORS resulting in live births in 2004-13 were linked to birth certificates and birth defects registries in four States (NY, TX, MA, and NC). Other births to each IVF-treated woman were also identified (IVF siblings). A 10:1 sample of non-IVF births in the same month as the IVF births were selected as controls; those with infertility treatment indicated on the birth certificate (but not in SART CORS) were categorized as subfertile, all others were categorized as fertile. Risks were modeled separately by plurality using logistic regression (AOR, 95% CI), adjusted for maternal age, race, ethnicity, education, parity, pre-gestational and gestational diabetes and hypertension, State and year of birth; children of fertile women were the reference group. The study population included 942,920 children (see table). Analyses limiting the IVF group to cycles with autologous oocytes and sperm, and fresh embryos are shown by (*). Birth defect risk was increased for IVF, siblings, and subfertile children by 32%, 22%, and 16%, respectively, for singletons, and 11%, 37%, and 14% for multiples (see table). The estimated risks for these 3 groups did not differ significantly (their 95% CIs overlap). The risk of birth defects was increased for IVF children and IVF siblings, and non-significantly increased for children of subfertile women; some estimates were limited by small sample size.Tabled 1FertileIVFIVF SiblingsSubfertileN, children811,989106,72118,6515,559Singletons789,30657,57117,4433,815% with birth defects3.8%4.9%4.3%4.7%All defects, AOR, 95% CI1.00 (Reference)1.29 (1.23, 1.35)1.23 (1.13, 1.33)1.17 (1.00, 1.36)All defects*, AOR, 95% CI1.32 (1.24, 1.39)1.22 (1.13, 1.32)1.16 (1.00, 1.35)Multiples22,68349,1501,2081,744% with birth defects6.2%7.1%8.6%7.6%All defects, AOR, 95% CI1.00 (Reference)1.11 (1.02, 1.21)1.38 (1.11, 1.72)1.14 (0.94, 1.37)All defects*, AOR, 95% CI1.11 (1.01, 1.21)1.37 (1.10, 1.71)1.14 (0.94, 1.38) Open table in a new tab

To evaluate the risk of blastogenesis birth defects (those occurring within the first four weeks after conception) in children conceived with IVF and non-IVF ART (subfertile), IVF siblings, and fertile controls. Cohort study, with exposure groups defined as IVF-exposed, siblings of IVF-exposed, subfertile, and fertile. IVF cycles in SART CORS resulting in live births in 2004-13 were linked to birth certificates and birth defects registries in four States (NY, TX, MA, and NC). All other births to each IVF-treated woman were also identified (IVF siblings). A 10:1 sample of non-IVF births in the same month as the IVF births were selected as controls; those with infertility treatment indicated on the birth certificate (but not in SART CORS) were categorized as subfertile, all others were categorized as fertile. Risks were modeled separately by plurality using logistic regression (AOR, 95% CI), adjusted for maternal age, race and ethnicity, education, parity, pre-gestational and gestational diabetes and hypertension, State and year of birth; children of fertile women were the reference group. The study population included 942,920 children (see table). Analyses limiting the IVF group to cycles with autologous oocytes, partner sperm, and fresh embryos are shown by (*). There was an increased risk of blastogenesis birth defects for singleton IVF births, but not for multiples born with IVF. There also appeared to be an increased risk in subfertile children, especially in multiple births.Tabled 1FertileIVFIVF*IVF SiblingsSubfertileAllN, Children811,989106,72172,51518,6515,559SingletonsN, Children789,30657,57138,59117,4433,815Rate/10,000All birth defects377.7485.7482.5431.7474.4Rate/10,000Blastogenesis defects21.927.326.918.328.8AOR, 95% CIBlastogenesis defects1.00 (Reference)1.43 (1.18, 1.74)1.53 (1.22, 1.90)1.06 (0.74, 1.52)1.57 (0.86, 2.85)MultiplesN, Children22,68349,15033,9241,2081,744Rate/10,000All defects619.8708.0708.9860.9756.9Rate/10,000Blastogenesis defects37.035.635.449.768.8AOR, 95% CIBlastogenesis defects1.00 (Reference)1.00 (0.72, 1.39)0.93 (0.65, 1.32)1.25 (0.52, 2.97)2.36 (1.25, 4.47) Open table in a new tab

Background Children with nonsyndromic orofacial clefts (NS OFCs) may require exceptional children's (EC) services for academic delays. We examined EC service use of children with and without NS OFCs in NC in elementary school. Methods We included 559 children with NS OFCs and 6,822 children without birth defects who had NC educational records. We estimated prevalence ratios, trends in enrollment, and characteristics of eligibility classification using descriptive statistics and logistic regression by cleft subtype and race/ethnicity. We estimated the odds of third grade retention by EC enrollment using logistic regression with inverse probability of treatment weights. Results Children with NS OFCs were 3.02 (95% CI: 2.50, 3.64) times as likely to receive third grade special education (SE) services compared to unaffected peers. The prevalence odds was highest among children with CL+P (OR: 4.61, 95% CI: 3.49, 6.09) declining by 54% by fifth grade. The prevalence odds of SE for white children was approximately 1.50 times that for African American children in fourth and fifth grades. Approximately 33% of children with NS OFCs within each racial/ethnic group received SE in third grade. African American children were twice as likely to receive services under specific learning disability. Children with NS OFCs receiving EC services were 44% (OR: 0.56; 95% CI: 0.13, 2.38) less likely to be retained in third grade compared to children with NS OFCs who were not receiving services. Conclusions Children with NS OFCs are more likely to receive SE services in elementary school compared to their unaffected peers. The eligibility category differed by racial/ethnic group.

Background: Improved pediatric congenital heart disease (CHD) outcomes have led to rapid growth of the adult CHD population. There are few contemporary studies examining causes of death (COD) in ad...