Theriogenology 140 (2019) 52e57

Contents lists available at ScienceDirect

Theriogenology
journal homepage: www.theriojournal.com

Incidence of congenital malformations and impact on the mortality of

neonatal canines
Keylla Helena Nobre Pacifico Pereira a, Luiz Eduardo Cruz dos Santos Correia b,
Elton Luís Ritir Oliveira c, Ramona Bastos Bernardo d, Mariana Lemos Nagib Jorge d,
Mariana Luiza Mezzena Gobato d, Fabiana Ferreira de Souza d, Noeme Sousa Rocha a,
Simone Biagio Chiacchio a, Maria Lucia Gomes Lourenço a, *
a ~o Paulo State University (UNESP), Botucatu, SP, Brazil
Department of Veterinary Clinics, School of Veterinary Medicine and Animal Sciences, Sa
b ~o Paulo State University (UNESP), Botucatu, SP, Brazil
Department of Animal Breeding and Nutrition, School of Veterinary Medicine and Animal Sciences, Sa
c
Department of Veterinary Anesthesiology and Surgery, School of Veterinary Medicine and Animal Sciences, Sa~o Paulo State University (UNESP), Botucatu,
SP, Brazil
d
Department of Animal Reproduction and Veterinary Radiology, School of Veterinary Medicine and Animal Sciences, Sa ~o Paulo State University (UNESP),
Botucatu, SP, Brazil

a r t i c l e i n f o a b s t r a c t

Article history: Canine congenital malformations are structural or functional abnormalities of organs present at birth
Received 1 December 2018 that possibly interfere with the viability of newborns, thus contributing to neonatal mortality. This study
Received in revised form evaluated and described the incidence of congenital malformations in neonatal dogs and determined the
23 July 2019
mortality rates among those affected. Of the 178 litters and 803 newborns included in the study, 24.7%
Accepted 27 July 2019
(44/178) of the litters presented neonates with congenital malformations. The total rate of neonates that
Available online 27 July 2019
presented malformations was 6.7% (64/803). The total mortality rate in newborns with congenital defects
was 5.4% (44/803), representing 68.7% (44/64) of the deaths observed among those affected. The early (0
Keywords:
Congenital defects
e2 days old) and late (3e30 days old) mortality rates among the affected neonates were 61.4% (27/44)
Teratogenesis and 38.6% (17/44), respectively. In total, 27 malformations were recorded, and the most common
Canine neonatology congenital defects were cleft palate 2.8% (23/803) and hydrocephaly 1.5% (12/803), either alone or
Newborn dog associated with other malformations. The malformations were recorded in 15 breeds: Pug, Miniature
Puppy Pinscher, Rottweiler, Pitbull, French Bulldog, English Bulldog, Dachshund, Labrador Retriever, Lhasa Apso,
Poodle, German Spitz, Yorkshire Terrier, Shih-tzu, Brazilian Terrier and mixed breed. One case of expo-
sure to a teratogenic agent was reported, but no maternal exposure to teratogens during gestation was
reported with the other litters. The occurrence of congenital defects may be related to genetic factors
since the highest incidence of malformations (84.4%) was observed in purebred dogs.
© 2019 Elsevier Inc. All rights reserved.

1. Introduction resulting in death or euthanasia [2,4]. The incidence rates of such

The neonatal period in the canine species encompasses the first
four weeks of life [1]. Mortality rates are high within this period due
to a wide range of causes, including congenital defects or malfor-
mations [1e3].
Congenital defects may cause structural or functional alterations
in several organs and may interfere with neonate viability, often
* Corresponding author. S~ ao Paulo State University (UNESP), Rubi~
ao Júnior s/n,
CEP 18618970, Botucatu, SP, Brazil.
E-mail address: maria-lucia.lourenco@unesp.br (M.L. Gomes Lourenço).
malformations range between 1% and 3% in newborn dogs [5,6], but
they often go unnoticed or unstudied, suggesting that the actual
numbers may be considerably higher due to the small number of
studies in the field [1].
Congenital malformations may be caused by genetic factors or
by the actions of teratogenic agents during pregnancy [4].
Congenital defects may be inherited from one or both parents, as
they are more common in purebred dogs; they also may be caused
by consanguinity [4,7]. Teratogenic agents including certain medi-
cations administered to the mother, nutritional factors (excessive
intake of proteins and vitamins A and D), irradiations, toxins,
chemical agents and infectious diseases may affect the litter during

https://doi.org/10.1016/j.theriogenology.2019.07.027
0093-691X/© 2019 Elsevier Inc. All rights reserved.
 K.H. Nobre Pacifico Pereira et al. / Theriogenology 140 (2019) 52e57 53

pregnancy [7,8]. macroscopic analysis, and complementary exams, such as ultraso-

Congenital malformations are being diagnosed more frequently
in canine neonates [2]. Therefore, detailed information regarding
the incidence, causes and mortality is crucial for clinical in-
terventions and the prevention of these anomalies, which will help
minimize neonatal deaths in dog litters. As such, this study aimed
to investigate the incidence of congenital malformations in neonate
dogs, along with potential causes and the overall impact on mor-
tality rates.
2. Materials and methods
This study was approved by the Ethics Committee of the College
of Veterinary Medicine and Animal Sciences (FMVZ, Faculdade de
Medicina Veterinaria e Zootecnia), UNESP, Botucatu, Brazil. It was
conducted at the Service of Small Animal Reproduction at FMVZ e
UNESP and included 803 neonates from 178 litters from 174 bitches.
Cases of neonates presenting congenital malformations from
January 2017 to April 2019 were evaluated and described. The lit-
ters included in the study were of several breeds, including Pug,
Miniature Pinscher, Rottweiler, Pitbull, French Bulldog, English
Bulldog, Dachshund, Labrador Retriever, Lhasa Apso, Poodle,
German Spitz, Yorkshire Terrier, Shih-tzu, Brazilian Terrier,
Australian Cattle Dog, Boxer, Campeiro Bulldog, Bull Terrier, Chow
Chow, English Cocker Spaniel, Golden Retriever, Maltese, Australian
Shepherd and mixed breed, born from bitches between one and
seven years old.
The neonates underwent a careful physical examination, and
those with malformations were included in the study. Stillborn
puppies and neonates that died were examined postmortem via
necropsy to diagnose possible malformations. The malformations
were initially diagnosed through physical examination and
nography and echocardiography, were performed when needed to
confirm the diagnosis. Complementary histological tests were also
performed when necessary, and tissue samples were collected and
kept in 10% formaldehyde for 14 days and then in 70% alcohol.
All newborns that presented malformations and were alive at
the time of the evaluation received follow-up during the neonatal
period in case of early (0e2 days old) or late mortality (3e30 days
old). The causes of death of newborns with malformations were
also recorded. The mortality of the affected pups that could not be
confirmed if the cause of the death was the malformation or other
associated causes was recorded as “unknown causes” because
diagnosis of the cause of death was not possible. Euthanasia was
performed in cases of malformations incompatible with life. In-
formation regarding previous births, matings with the same stud
for litters with malformations and exposure to teratogenic agents
during pregnancy (intoxications, traumas, infections, radiation and
use of medicine) were registered through a questionnaire applied
to the owners to identify possible risk factors. Information such as
history of malformations in previous births, history of malforma-
tions in ancestors, breed and sex, history of consanguineal mating
and mortality of neonates affected by malformations were also
registered.
The mothers underwent a clinical examination, a full blood
count and a biochemical assay during the consultation, birth or c-
section to determine possible signs of infection.
The odds ratio was evaluated to relate the probability of the
reference category with the other categories. The odds ratio was
calculated using the LOGISTIC procedure of the SAS program, where
mixed breed was considered a reference category. Values of the
odds ratio >1 in purebreds meant a greater probability of occur-
rence of malformations relative to mixed breeds.

Table 1
Incidence of congenital malformations in comparison with the total number of neonates, as well as early (0e2 days old) and late mortality (3e30 days old) and survival of the
affected neonates.

Malformations Frequency % Breeds Mortality Survival

Early Late

Agenesis of abdominal muscles 0.12% (1/803) Miniature Pinschera 1 e e

Anal atresia 0.4% (3/803) French Bulldogm, Poodleg 2 1 e
Anasarca 0.7% (6/803) English Bulldog 1 e 5
Cleft lip 0.6% (5/803) French Bulldogb Yorkshirec, Lhasa Apso, Mixed breedf 2 2 1
Cleft palate 2.8% (23/803) Pugd,e, Pitbull, Yorkshirec, French Bulldogb, English Bulldog, 10 12 1
Labrador Retriever, Miniature Pinschera,k,l, Mixed breedf,i
Duplicated right ribcage 0.12% (1/803) Brazilian Terrier 1 e e
Equinovarus 0.12% (1/803) Miniature Pinschera 1 e e
Exencephaly 0.24% (2/803) Miniature Pinscherk,l 2 e e
Gastroschisis 0.6% (5/803) Mixed breedh 4 1 e
Hydrocephaly 1.5% (12/803) Pugd,e, Miniature Pinscher, German Spitzj, Shih-tzu, Mixed breedh 3 2 7
Lissencephaly 0.24% (2/803) Miniature Pinschera 2 e e
Macroglossia 0.12% (1/803) Mixed breed 1 e e
Microphthalmia 0.12% (1/803) Yorkshire e e 1
Mitral valve dysplasia 0.12% (1/803) French Bulldog e 1 e
Omphalocele 0.24% (2/803) Mixed breedi 2 e e
Palpebral agenesis 0.24% (2/803) Miniature Pinscherk,l 2 e e
Persistent urachus 0.24% (2/803) Shih-tzu, Poodle 2 e e
Polydactyly (preaxial in forelimbs and hindlimbs) 0.5% (4/803) Rottweiler e e 4
Polydactyly (preaxial in hindlimbs) 0.24% (2/803) Dachshund e e 2
Pulmonary hypoplasia 0.12% (1/803) Miniature Pinschera 1 e e
Pulmonary valve stenosis 0.12% (1/803) French Bulldog e 1 e
Rectovaginal fistula 0.12% (1/803) French Bulldogm e 1 e
Rib hypoplasia 0.12% (1/803) Mixed breedf 1 e e
Scoliosis 0.12% (1/803) Miniature Pinschera 1 e e
Segmental aplasia of the intestine 0.4% (3/803) Miniature Pinschera, German Spitzj, Mixed breedh 3 e e
Tricuspid valve dysplasia 0.12% (1/803) French Bulldog e 1
Unilateral renal agenesis 0.12% (1/803) Mixed breedf 1 e e
Vaginal atresia 0.12% (1/803) Poodleg 1 e e

Puppies represented with the same superscript letter denote the associated malformations.
54 K.H. Nobre Pacifico Pereira et al. / Theriogenology 140 (2019) 52e57

3. Results

A total of 178 litters and 803 neonates were attended at the

veterinary hospital during the study period because of disease and
malformation or because of cesarean section and vaginal parturi-
tion. Of these litters, 24.7% (44/178) presented congenital malfor-
mations. The total rate of neonates presenting malformations was
6.7% (64/803).
The mortality rate of puppies with congenital defects was 5.4%
(44/803), accounting for 68.7% (44/64) of the deaths among the
affected neonates. Of the 44 neonates that died, seven (16%) were
euthanized due to malformations incompatible with life, seven
(16%) were stillborn, and 30 (68%) died during the first four weeks
of life. The incidence of congenital malformations in comparison to
the total number of neonates, as well as the early mortality (0e2
days old), late mortality (3e30 days old), and survival rates of the
affected neonates, are shown in Table 1.
The early mortality rate (0e2 days old) of puppies with mal-
formations was 3.3% (27/803), representing 61.4% (27/44) of the
deaths among neonates with malformations. The late mortality rate
(3e30 days old) was 2.1% (17/803), representing 38.6% (17/44) of
the deaths among neonates that died within four weeks after birth.
The causes of death registered for the neonates with malformations
were unknown causes 54.5% (24/44), euthanasia 16% (7/44), aspi-
ration pneumonia 13.6% (6/44), cardiorespiratory insufficiency 6.8%
(3/44), intestinal obstruction 6.8% (3/44), and intestinal and ure-
thral obstruction 2.3% (1/44).
Among the affected neonates, 81.2% (52/64) presented a single
malformation, and 18.8% (12/64) presented two or more associated
malformations. The multiple malformations afflicting the neonates
are shown in Table 2. Overall, 27 malformations were observed, the
most common of which were cleft palate (Fig. 1) 2.8% (23/803) and
hydrocephaly (Fig. 2) 1.5% (12/803), either alone or associated with
other malformations. Of the affected neonates, 56.2% (36/64) were
females, and 43.8% (28/64) were males.
The malformations affected pups of various breeds: mixed breed
(10), Miniature Pinscher (9), French Bulldog (8), English Bulldog (7),
Pug (6), Shih-tzu (4), Rottweiler (4), Pitbull (3), Yorkshire (3),
Poodle (2), Lhasa Apso (2), Dachshund (2), German Spitz (2), Lab-
rador Retriever (1) and Brazilian Terrier (1).
The numbers of puppies attended by breed, frequency of mal-
formations, and odds ratio of the purebred breeds manifesting
malformations relative to the mixed breeds are shown in Table 3. Fig. 1. Cleft palate in a neonatal puppy.
Among the purebreds of the study, those with a greater chance to
manifest malformations (odds ratio >1) than mixed breeds were
malformations.
French Bulldog, English Bulldog, German Spitz, Miniature Pinscher,
When assessing the litter history, a French Bulldog bitch pre-
Pitbull, Pug, Rottweiler, Shih-tzu and Yorkshire. Among these
sented a pup with pulmonary valve stenosis, and a history of heart
breeds, English Bulldog and Pug presented significant values
disease (a puppy with tricuspid valve dysplasia) existed in a pre-
(P < 0.05). Of the litters studied, the Australian Cattle Dog, Boxer,
vious litter with the same stud. In the other litters of the study, no
Campeiro Bulldog, Bull Terrier, Chow Chow, English Cocker Spaniel,
malformation was reported by the owners in previous litters or in
Golden Retriever, Maltese and Australian Shepherd did not report

Table 2
Multiple congenital malformations in canine neonates.

Associated Malformations N

Anal atresia þ rectovaginal fistula 1

Anal atresia þ vaginal atresia 1
Cleft palate þ cleft lip 2
Cleft palate þ cleft lip þ rib hypoplasia þ unilateral renal agenesis 1
Cleft palate þ exencephaly þ palpebral agenesis 2
Cleft palate þ hydrocephaly 2
Cleft palate þ lissencephaly þ pulmonary hypoplasia þ scoliosis þ equinovarus þ segmental aplasia of the intestine þ agenesis of abdominal muscles 1
Cleft palate þ omphalocele 1
Hydrocephaly þ gastroschisis þ segmental aplasia of the intestine 1
Hydrocephaly þ segmental aplasia of the intestine 1
 K.H. Nobre Pacifico Pereira et al. / Theriogenology 140 (2019) 52e57 55

Fig. 2. Hydrocephaly in a neonatal puppy.

the parents. However, uncommon and undiagnosed deaths were infection or radiation during pregnancy were reported by the
reported in previous litters, and some of those deaths may be owners. The clinical examination, full blood count and biochemical
associated with congenital defects. Among the bitches with mal- assay of the mothers did not reveal relevant alterations consistent
formed puppies, 38.6% (17/44) were primiparous. Two cases of with infections.
consanguineal mating between siblings 4.5% (2/44) were reported
by the owner, in addition to one case of exposure to doxycycline
4. Discussion
2.2% (1/44) at a dosage of 10 mg/kg every 12 h during the first part
of the pregnancy for treatment of pneumonia. This litter had two
Several studies have been published investigating neonatal
neonates, and both presented malformations (cleft palate).
mortality rates, and the mortality rates in newborns with congen-
For most affected litters, no information existed regarding the
ital malformations have varied significantly, with studies observing
causes of the congenital defects. No cases of intoxication, trauma,
rates of 2.2% in 1157 animals [9], 1% in 2872 animals [10] and 1.4% in
56 K.H. Nobre Pacifico Pereira et al. / Theriogenology 140 (2019) 52e57

Table 3 muscular dystrophy of the X chromosome in Golden Retrievers

Number of puppies attended (N), frequency of puppies with malformations by breed [15]. This neonate died during the first week, presumably from
and odds ratio of purebred relative to mixed breed.
starvation.
a
N Frequency (%) Odds ratio CI (95%) Hydrocephaly was the second most prevalent congenital defect
Purebred 663 8.1 1.15 0.57e2.3 at 1.5%, but in contrast to the cases of cleft palate, the associated
Australian Cattle Dog 18 0.0 e e mortality rates were low. Only five of the 12 afflicted neonates died,
Australian Shepherd 14 0.0 e e representing 11.3% (5/44) of all deaths within the first four weeks of
Boxer 11 0.0 e e
life. This result is due to the highly variable clinical manifestations
Brazilian Terrier 17 5.9 0.81 0.1e6.8
Bull Terrier 1 0.0 e e of the defect; in some cases, the patient is asymptomatic, whereas
Campeiro Bulldog 3 0.0 e e in others, marked signs of progressive neurological dysfunction are
Chow Chow 6 0.0 e e present [16]. Hydrocephaly is described as an autosomal recessive
Dachshund 28 7.1 1.0 0.2e4.8
defect that occurs more frequently in small and brachycephalic
English Bulldog 30 23.3 3.96* 1.4e11.5
English Cocker Spaniel 12 0.0 e e
breeds [17]. In this study, it was observed in a Pug, Pinscher,
French Bulldog 67 11.9 1.76 0.7e4.7 German Spitz, Shih-tzu and a mixed breed dog.
German Spitz 24 8.3 1.18 0.2e5.8 To the best of our knowledge, this is the first report of congenital
Golden Retriever 28 0.0 e e rib hypoplasia, lung hypoplasia, and duplicated right ribcage in
Labrador Retriever 46 2.2 0.29 0.04e2.3
dogs. In addition, this is the first report of lissencephaly in
Lhasa Apso 31 6.5 0.90 0.19e4.3
Maltese 28 0.0 e e Pinschers. Mitral valve dysplasia, tricuspid valve dysplasia, and
Miniature Pinscher 69 13.0 1.95 0.75e5.1 pulmonary valve stenosis were described in this study in the French
Pitbull 38 7.9 1.11 0.3e4.3 Bulldog breed. These congenital heart diseases are commonly
Poodle 33 6.1 0.84 0.18e4.0 found in Bulldogs, with a genetic factor involved; however, reports
Pug 35 17.1 2.69* 1.02e8.0
Rottweiler 45 8.9 1.27 0.38e4.3
in the literature of mitral valve dysplasia in the French Bulldog are
Shih-tzu 43 9.3 1.33 0.4e4.5 uncommon [18e20]. No information exists regarding the causes of
Yorkshire 36 8.3 1.18 0.3e4.5 the congenital defects in the remaining litters included in the study,
Mixed Breed 140 7.1 1.0 e but they were possibly genetic due to the lack of exposure to
*P < 0.05 by the maximum likelihood method. teratogenic agents such as toxins, drugs, chemical agents, radiation,
a
CI: confidence interval. infectious diseases or trauma during the pregnancy, which would
suggest a teratogenic factor in the malformations.
We observed a high incidence of malformations and high mor-
518 animals [11]. This study observed mortality rates in newborns
tality rates among the affected. However, the mortality rate for
with congenital malformations of 5.4% in 803 animals, compared to
puppies with congenital malformations could be higher because
thesis work reporting 15% mortality rates due to congenital
these puppies were followed for only the first four weeks of life.
anomalies from 2574 animals [2]. Not all newborns that died in the
Additionally, not all newborns that died in the 178 litters treated in
178 litters treated in the veterinary hospital were available for
the veterinary hospital were available for postmortem examina-
postmortem examinations. Therefore, the actual incidence of
tions. Therefore, the actual incidence of congenital defects is
congenital defects is possibly even higher. This increased incidence
possibly even higher.
could be explained by selective breeding, a practice that has gained
The malformations can be difficult to diagnose, and many may
popularity in recent years and that may lead to decreased genetic
remain unnoticed, mainly due to lack of physical examination,
variance and increased homozygosity, predisposing the animals to
complementary examinations or absence of clinical signs. Many
congenital anomalies [12,13]. In the current study, 84.4% (54/64) of
malformations will be diagnosed by necropsy, but there are still
pups with malformations were purebred.
difficulties due to the smaller sizes of the organs of these patients.
Cleft palate was the most common congenital defect observed in
Therefore, the veterinarian in charge always should conduct an
the current study (23/64). This malformation may have environ-
examination looking for the presence of congenital defects, and the
mental (teratogenic) or genetic causes, the latter of which is more
breeder should be instructed to examine their litters and encour-
common in brachycephalic breeds [4]. One litter of Pugs was
aged to allow necropsies of dead animals to help identify possible
exposed to doxycycline during the first third of gestation, and two
malformations. Details of breeding and the prenatal period are of
of that litter presented cleft palates. Doxycycline is considered a
utmost importance in the prevention of congenital malformations.
teratogenic substance that may potentially induce embryotoxicity
Choosing the progenitors carefully and avoidance of exposure to
or congenital malformations, but a genetic cause could not be ruled
teratogenic agents during pregnancy are essential to preventing
out. However, the three previous litters from the mother with the
malformations and losses within the litter [1,7].
same stud resulted in no malformations. Most (50%, 22/44) neonate
deaths during the first four weeks of life were in neonates that
presented with a cleft palate. The high mortality rate was due to
difficulties in feeding that resulted in starvation and aspiration 5. Conclusion
pneumonia.
A litter resulting from consanguineous breeding between sibling The incidence and associated mortality rates of congenital
Miniature Pinschers produced two pups with multiple associated malformations in canine neonates are high. Investigation of mal-
malformations, including exencephaly, cleft palate and palpebral formations in neonates immediately after birth is essential. The
agenesis. In this case, no maternal exposure to teratogenic agents early diagnosis of these conditions often leads to timely clinical
during gestation was reported. One mixed breed litter with four interventions and helps minimize mortality.
puppies and a history of consanguineal breeding between siblings
had one neonate with macroglossia. The causes of the malforma-
tion are unknown, but they may have been of genetic origin [13].
Conflicts of interest
Macroglossia has been reported with other malformations, such as
anencephaly and cleft lip [14], and may be associated with canine
The authors have no conflicts of interest to declare.
 K.H. Nobre Pacifico Pereira et al. / Theriogenology 140 (2019) 52e57
Acknowledgments
We acknowledge the support of the Brazilian National Council
for Scientific and Technological Development (CNPq, Conselho
gico), Brazil.
Nacional de Desenvolvimento Científico e Tecnolo
We acknowledge the support of the Small Animal Reproduction
Service of the Department for Animal Reproduction and Veterinary
Radiology at FMVZ e UNESP, Campus Botucatu, Sa ~o Paulo, Brazil.
References
[1] Lourenço MLG. Cuidados com neonatos e filhotes. In: Jerico  MM, Kogika MM,
de Andrade Neto JP, editors. Tratado de medicina interna de c~ aes e gatos. Rio
de Janeiro: Guanabara Koogan; 2015.
[2] Gill MA. Perinatal and late neonatal mortality in the dog. thesis. Sydney
(NSW): University of Sydney; 2001.
[3] Münnich A, Küchenmeister U. Causes, diagnosis and therapy of common
diseases in neonatal puppies in the first days of life: cornerstones of practical
approach. Reprod Domest Anim 2014;49:64e74. https://doi.org/10.1111/rda.
12329.
[4] Peterson ME, Kutzler MA. Small animal pediatrics. Saint Louis: Elsevier; 2011.
[5] Blunden TS. Neonato: defectos conge nitos y mortalidade neonatal. In:
Simpson GM, England GCM, Harvey MJ, editors. Manual de reproduccíon y
neonatologia en pequenos animals. Madrid: Harcourt; 2000.
rez R, Zagorskaia A, Jouanisson E, Diaz-Betrana L, et al.
[6] Vilar JM, Batista M, Pe
Comparison of 3 anesthetic protocols for the elective cesarean-section in the
dog: effects on the bitch and the newborn puppies. Anim Reprod Sci
2018;190:53e62. https://doi.org/10.1016/j.anireprosci.2018.01.007.
[7] Casal ML. Congenital and genetic diseases of puppies before the weaning: can
we prevent them?. In: VIII International Symposium on Canine and Feline
Reproduction, 2016, Paris. Proceedings of the international symposium on
canine and feline reproduction, vol 46; 2016. Paris.
57
[8] Prats A, Dumon C, Garcia F, Martí S, Coll V. Neonatologia y pediatria. Buenos
Aires: Inter-medica; 2004.
[9] Andersen AC. Puppy production to the weaning age. J Am Vet Med Assoc
1957;130:151e8.
[10] Potkay S, Bacher JD. Morbidity and mortality in a closed fox hound breeding
colony. Lab Anim Sci 1977;27:78e84.
[11] Blunden AS. A review of the fading puppy syndrome (also known as fading
puppy complex). Vet Annu 1986;26:264e9.
[12] Akey JM, Ruhe AL, Akey DT, Wong AK, Connelly CF, Madeoy J, et al. Tracking
footprints of artificial selection in the dog genome. Proc Natl Acad Sci
2010;107:1160e5. https://doi.org/10.1073/pnas.0909918107.
[13] Le Vaillant C, Beneteau C, Chan-Leconte N, David A, Riteau AS. Beckwith-
Wiedemann syndrome: what do you search in prenatal diagnosis? About 14
cases. Gynecol Obstet Fertil 2015;43:705e11. https://doi.org/10.1016/j.
gyobfe.2015.10.003.
[14] Wammes JCS, Filadelpho AL, Birck AJ, Peres JA, Pinto e Silva JRC, Filho JG, et al.
Anencefalia, macroglossia e fenda labial em c~ ao: relato de caso. Rev Cient
Eletro^ nica Med Vet 2013;21:1e8.
[15] Thibaud JL, Monnet A, Bertoldi D, Barthelemy I, Blot S, Carlier PG. Charac-
terization of dystrophic muscle in golden retriever muscular dystrophy dogs
by nuclear magnetic resonance imaging. Neuromuscul Disord 2007;17:
575e84. https://doi.org/10.1016/j.nmd.2007.03.013.
[16] Hoskins JD. Veterinary pediatrics: dogs and cats from birth to six months. 3a
ed. Philadelphia: Saunders; 2001.
[17] Sorribas CE. Atlas de neonatologia e pediatria em c~ aes. Sa~o Paulo: MedVet;
2013.
[18] Oliveira P, Domenech O, Silva J, Vannini S, Bussadori R, Bussadori C. Retro-
spective review of congenital heart disease in 976 dogs. J Vet Intern Med
2011;25:477e83. https://doi.org/10.1111/j.1939-1676.2011.0711.x.
[19] Parker HG, Kilroy-Glynn P. Myxomatous mitral valve disease in dogs: does
size matter? J Vet Cardiol 2012;14:19e29. https://doi.org/10.1016/
j.jvc.2012.01.006.
[20] Garncarz M, Parzeniecka-Jaworska M, Szalus-Jordanow O. Congenital heart
defects in dogs: a retrospective study of 301 dogs. Med Weter 2017;73:
651e6. https://doi.org/10.21521/mw.5784.