Pregnane concentrations of ill, neonatal foals remain increased following birth, reflecting a delayed, or interrupted, transition from intra- to extra-uterine life. Serial progesterone and pregnenolone measurement may be useful in aiding diagnosis of NMS.

Summary Use of antimicrobial drugs is central to the treatment of primary and secondary bacterial infection in horses. When selecting an antimicrobial to treat confirmed or suspected bacterial infection multiple factors should be considered, including: the likely infectious agent; distribution and dosage of selected drugs; mechanisms of action; and potential side effects. Many of these issues will be covered in subsequent articles in this series. The aim of this paper is to aid the clinician in the rational selection of antimicrobials by reviewing the mode of action, spectrum of activity, pharmacokinetics, pharmacodynamics, indications and potential side effects of the main classes of antimicrobial drugs. Extralabel use of drugs is common in veterinary medicine due to a lack of licensed products. This increases the importance of a thorough understanding of antimicrobials and their possible adverse effects.

SummaryReasons for performing the study: Increased plasma progestagen concentrations have been reported in foals with neonatal maladjustment syndrome (NMS). These steroids may cross the blood-brain barrier and have dampening effects in the central nervous system. Objectives: To evaluate if the infusion of a progesterone derivative (allopregnanolone) in a healthy neonatal foal would induce clinical signs compatible with NMS. Methods: A healthy neonatal foal from a healthy mare with a normal gestation (length, no complications), birth and placenta was infused with allopregnanolone to observe its neurobehavioural effects. Heparinised blood samples were collected pre-and post infusion to determine various progestagen concentrations using liquid chromatography mass spectrometry. A second healthy neonatal foal was infused with ethanol and saline for comparison of clinical observations. Results: Infusion of allopregnanolone resulted in obtundation, lack of affinity for the mare and decreased response to external stimuli. These effects were short-lasting and associated with measurable concentrations of progestagens. Conclusions and potential relevance: Infusion of a steroid metabolite to a healthy neonatal foal resulted in neurobehavioural alterations compatible with those observed in foals with NMS. These findings suggest that increased progestagen concentrations may be responsible for some of the behavioural changes observed in foals with NMS.

Aims To determine the pregnane profile of foals with neonatal maladjustment syndrome (NMS) and compare it with that of healthy controls and sick, non‐NMS foals. Methods Thirty‐two foals with a clinical diagnosis of NMS, 12 foals with other neonatal disorders and 10 healthy control foals were selected for the study. Heparinised blood samples were collected from each group of foals and pregnane and androgen concentrations were determined using liquid chromatography mass spectrometry at 0, 24 and 48 h of age. Results Healthy foals showed a significant decrease in pregnane concentrations over the first 48 h of life (P<0.01). Foals with NMS and sick, non‐NMS foals had significantly increased progesterone, pregnenolone, androstenedione dehydroepiandrosterone and epitestosterone concentrations compared with healthy foals (P<0.05). Progesterone and pregnenolone concentrations of sick, non‐NMS foals decreased significantly over 48 h (P<0.05), whereas concentrations in NMS foals remained elevated. Conclusions and practical relevance Pregnane concentrations of ill, neonatal foals remain elevated following birth, reflective of a delayed, or interrupted, transition from intra‐ to extra‐uterine life. These pregnanes are potent allosteric modulators of the GABAA receptor and are important in providing tonic inhibition of fetal central nervous system activity and damping movement to prevent maternal damage. Infusion of the pregnane allopregnanolone into neonatal foals leads to somnolence and loss of affinity for the dam (Madigan et al. ). Together, these findings suggest that the pathogenesis of NMS may be associated with the persistence of high concentrations of pregnanes. Serial progesterone and pregnenolone measurement may be useful in aiding diagnosis of NMS. Ethical animal research The UC Davis IACUC approved the project. Sources of funding: Private donation. Competing interests: None.