Multiple midline defects identified in a litter of golden retrievers following gestational administration of prednisone and doxycycline: a case series

Abstract

BackgroundThe teratogenic effects of immunomodulatory and certain antimicrobial therapies are described in small rodents and humans. While the described teratogenic effects in small rodents have been extrapolated to make conclusions about its use in the pregnant dam, teratogenic effects of prednisone and doxycycline have not yet been reported in the dog. Here we report and describe midline defects observed in a litter of golden retriever puppies exposed to mid-gestational immunosuppressive and antimicrobial therapy.Case presentationTwenty-one days into gestation, the dam of a litter of eight golden retriever puppies was administered prednisone, doxycycline, and tramadol as treatment for immune-mediated polyarthritis. The individuals in the litter were subsequently diagnosed with a variety of midline defects and congenital cardiac defects. This case series describes the variety of identified defects and presents a descriptive account of complex congenital abnormalities that are likely secondary to teratogenic effects of one or more drugs administered during gestation. The available puppies, dam, and grand dam underwent thorough physical examination, complete echocardiogram, and where indicated, advanced imaging with various surgical corrections when possible.Numerous midline congenital defects and congenital heart disease were identified in the puppies evaluated. Ultimately 5 of 8 puppies born to the dam were presented for thorough evaluation. The midline defects include: gastroschisis (1), peritoneopericardial diaphragmatic hernias (4, PPDH), umbilical hernia (4), unilateral cryptorchidism (1 of 4 males), cleft palate (1), renal agenesis (1), renal abnormalities (1), sternal and vertebral abnormalities (3), remnant liver lobe (1) and malformations consistent with ductal plate malformations with congenital hepatic fibrosis (1). The congenital cardiac defects include: ventricular septal defect (4, VSD) and subaortic stenosis (4, SAS). The presence of greater than one congenital defect was noted in all 5 of the dogs evaluated. Surgical correction was necessary for PPDH in 4 puppies. Medical intervention was recommended for congenital cardiac disease in 1 puppy.ConclusionThis case report is the first to describe midline defects in dogs that have been exposed to immunomodulatory therapy during gestation. A causative relationship between mid-gestational immunomodulatory exposure and midline defects cannot be proven, however, this case supports a clear association and provides case-based evidence to support its avoidance when possible.

Agenesis of hepatic lobes in a dog

“…Recently, in veterinary literature, liver malformation due to diaphragmatic hernia was reported in puppies whose mother was under doxycycline, prednisone and tramadol administration (Kaplan et al, 2018). However, no similar information was observed in this case.…”

Incomplete pentalogy of Cantrell in a Border terrier puppy

“…Cantrell’s syndrome or pentalogy have been well described in humans, with an estimated prevalence between 1:65 000 and 1:200 000,2 whereas, to the authors’ knowledge, an incomplete form of the syndrome has been reported in dogs and cats rarely3–10; a complete pentalogy has only been reported in one litter of puppies 11. Therefore, the true prevalence in animals is unknown due to the rare nature of this syndrome.…”

“…Eiger et al 10 used a titanium contourable mesh plate, as the age of the patient prevented primary closure. Other case reports did not address the sternal cleft 5 8 9…”

Case Report: Unusual Peritoneopericardial Diaphragmatic Hernia in an 8-Month-Old German Shepherd Dog, Associated With a Pericardial Pseudocyst and Coexisting Severe Pericardial Effusion Resulting in Right-Sided Heart Failure

“…Animals with PPDH often have other concurrent congenital abnormalities such as midline defects (e.g., umbilical hernia, cleft palate, sternal abnormalities) and cardiac defects (e.g., ventricular septal defects, subaortic stenosis, pulmonic stenosis, atrial septal defect) (4)(5)(6)(7)(8). Peritoneopericardial diaphragmatic hernia is commonly seen as a congenital abnormality in several animals of the same litter (6)(7)(8)(9). Therefore, breeding of affected animals is not recommended, and screening of littermates for PPDH should be performed.…”