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

Abstract

Background: The 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 presentation: Twenty-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.

Conclusion: This 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.

Keywords: Congenital heart defect; Gastroschisis; PPDH; Peritoneopericardial diaphragmatic hernia; Teratogen.

Fig. 1

Echocardiographic image from the right parasternal long-axis view of Dog 1. There is a hyperechoic subaortic ridge present (denoted by arrow) as well as poststenotic dilation of the aorta consistent with subaortic stenosis (SAS). The left ventricular walls appear thickened consistent with concentric hypertrophy secondary to the pressure overload from SAS

Fig. 2

Right parasternal echocardiographic image of Dog 3. There is a small volume of hypoechoic pericardial effusion (denoted by asterisk) and soft tissue structure most consistent with liver (labeled as L) within the pericardial space, adjacent to the heart (left ventricle labeled as LV)

Fig. 3

Image from the laparotomy performed on Dog 3. There is a 4x6cm defect through the central tendon of the diaphragm that communicates with the pericardial sac, consistent with a peritoneopericardial diaphragmatic hernia. A portion of the right medial liver lobe can be seen herniated into the pericardial sac

Fig. 4

Right lateral (a) and dorsoventral (b) thoracic radiographs from Dog 4. The cardiac silhouette is markedly enlarged and rounded and there are visible intestinal loops containing granular and soft tissue opaque material superimposed on the ventral cardiac silhouette. There is border effacement of the ventral margin of the diaphragm, and the intestinal loops superimposed on the cardiac silhouette are confluent with the abdomen. These findings are consistent with a peritoneopericardial diaphragmatic hernia with suspect herniation of intestinal loops and potentially liver