A recurrent de novo missense mutation in COL1A1 causes osteogenesis imperfecta type II and preterm delivery in Normande cattle.

BACKGROUND: Nine male and eight female calves born to a Normande artificial insemination bull named "Ly" were referred to the French National Observatory of Bovine Abnormalities for multiple fractures, shortened gestation, and stillbirth or perinatal mortality. RESULTS: Using Illumina BovineSNP50 array genotypes from affected calves and 84 half-sib controls, the associated locus was mapped to a 6.5-Mb interval on chromosome 19, assuming autosomal inheritance with germline mosaicism. Subsequent comparison of the whole-genome sequences of one case and 5116 control genomes, followed by genotyping in the affected pedigree, identified a de novo missense substitution within the NC1 domain of the COL1A1 gene (Chr19 g.36,473,965G > A; p.D1412N) as unique candidate variant. Interestingly, the affected residue was completely conserved among 243 vertebrate orthologs, and the same substitution in humans has been reported to cause type II osteogenesis imperfecta (OI), a connective tissue disorder that is characterized primarily by bone deformity and fragility. Moreover, three COL1A1 mutations have been described to cause the same syndrome in cattle. Necropsy, computed tomography, radiology, and histology confirmed the diagnosis of type II OI, further supporting the causality of this variant. In addition, a detailed analysis of gestation length and perinatal mortality in 1387 offspring of Ly and more than 160,000 progeny of 63 control bulls allowed us to statistically confirm in a large pedigree the association between type II OI and preterm delivery, which is probably due to premature rupture of fetal membranes and has been reported in several isolated cases of type II OI in humans and cattle. Finally, analysis of perinatal mortality rates and segregation distortion supported a low level of germ cell mosaicism in Ly, with an estimate of 4.5% to 7.7% of mutant sperm and thus 63 to 107 affected calves born. These numbers contrast with the 17 cases reported and raise concerns about the underreporting of congenital defects to heredo-surveillance platforms, even for textbook genetic syndromes. CONCLUSIONS: In conclusion, we describe a large animal model for a recurrent substitution in COL1A1 that is responsible for type II OI in humans. More generally, this study highlights the utility of such datasets and large half-sib families available in livestock species to characterize sporadic genetic defects.

Fetoplacental pathology of equine abortion, premature birth, and neonatal loss due to Chlamydia psittaci.

This report describes the fetoplacental pathology of Chlamydia psittaci-associated abortion, premature birth, and neonatal loss in 46 of 442 equine abortion investigations between 2015 and 2019. Seven abortions, 26 premature births, and 13 neonatal deaths with positive C. psittaci polymerase chain reaction (PCR) were evaluated. In 83% of cases (38/46), C. psittaci infection was considered as the primary cause of loss based on quantitative PCR (qPCR) confirmation, pathological findings, and exclusion of other causes, and was supported by Chlamydia spp immunolabeling in fetoplacental lesions. Lymphohistiocytic placentitis with vasculitis (36/38) affected the amnion, umbilical cord, and chorioallantois at the umbilical vessel insertion and/or cervical pole. Lymphohistiocytic chorionitis in the subvillous stroma extended to the allantois mostly without villous destruction. Lymphohistiocytic amnionitis and funisitis occurred at the amniotic cord attachment. Lymphohistiocytic hepatitis was observed in 19/38 cases and pneumonia was identified in 26 cases. Chlamydia spp immunolabeled in placenta, lung, liver, or splenic tissue in the cases that were tested (14/38). C. psittaci infection was not the cause of loss in 2 cases with other diseases and of uncertain significance in 6 cases with no conclusive cause of loss. immunohistochemistry (IHC) was negative for 6 of these cases (6/8). The highest Chlamydia load was detected in pooled placental tissues by qPCR. qPCR and IHC had 83% congruence at a qPCR cut-off of 1 gene copy. IHC limits of detection corresponded to infections with 2 × 102 gene copies identified by qPCR. This study confirms the etiological role of C. psittaci as a cause of naturally occurring equine reproductive loss.

Airway smooth muscle thickness and contraction are enhanced by intra-amniotic lipopolysaccharide in an ovine model of premature birth.

Abnormalities of the airway smooth muscle (ASM) layer in asthma may develop before birth. We hypothesize that antenatal inflammation causes physiological abnormalities of the ASM that predisposes asthma. This study determined the short-term effects of antenatal inflammation on the developing ASM. Fourteen pregnant ewes were randomly assigned to one of three groups. Fetal lambs were exposed to intra-amniotic injections of lipopolysaccharide (LPS, n = 4) or saline (controls; n = 5) at 127 days' gestational age (GA). Preterm lambs were surgically delivered at 129 days' GA and received intensive care for 7 days before euthanasia. Naïve fetal controls (n = 5) were delivered and euthanized at 136 days' GA. ASM force to acetylcholine was measured in bronchial rings and normalized to ring length (tension) and ASM cross-sectional area (stress). Airway narrowing (% volume) to acetylcholine was assessed in bronchial segments. Fetal controls were structurally and functionally similar to saline-exposed lambs. Compared with saline, LPS-exposed lambs had increased macrophages in lung tissue (P = 0.0002) and interleukin-8 in alveolar wash (P = 0.003). LPS exposure increased ASM thickness (P = 0.005), airway narrowing (P = 0.003), ASM tension (P = 0.0002), and contractile stress (P < 0.0001). Notably, LPS-exposed lambs were more dependent on mechanical ventilation, and both LPS (P < 0.001) and ventilation (P = 0.012) were independent factors in increasing ASM stress. Only LPS independently increased ASM thickness (P = 0.045). Results indicate that antenatal exposure to LPS and subsequent mechanical ventilation promotes intrinsic changes to the ASM that enhances bronchoconstriction. If persistent into postnatal life, these developmental abnormalities may contribute to the known association between chorioamnionitis and asthma.NEW & NOTEWORTHY Abnormalities of the airway smooth muscle (ASM) layer in asthma may develop before birth. Using an ovine model of antenatal inflammation, we demonstrate thickening and increased contraction of the premature ASM layer. If such physiological abnormalities persist throughout postnatal life, this represents a predisposition to an asthma diagnosis.

Prematurity and Dysmaturity Are Associated With Reduced Height and Shorter Distal Limb Length in Horses.

The long-term effects of gestational immaturity in the premature (defined as < 320 days gestation) and dysmature (normal term but showing some signs of prematurity) foal have not been thoroughly investigated. Studies have reported that a high percentage of gestationally immature foals with related orthopedic issues such as incomplete ossification may fail to fulfill their intended athletic purpose, particularly in Thoroughbred racing. In humans, premature birth is associated with shorter stature at maturity and variations in anatomical ratios, linked to alterations in metabolism and timing of physeal closure in the long bones. We hypothesized that gestational immaturity in horses might similarly be associated with reduced height and different anatomical ratios at maturity. In this preliminary study, the skeletal ratios of horses with a history of gestational immaturity, identified through veterinary and breeder records, were compared with those of unaffected, closely related horses (i.e., sire, dam, sibling). External measurements were taken from conformation photographs of cases (n = 19) and related horses (n = 28), and these were then combined into indices to evaluate and compare metric properties of conformation. A principal component analysis showed that the first two principal components account for 43.8% of the total conformational variation of the horses' external features, separating horses with a rectangular conformation (body length > height at the withers), from those that are more square (body length = height at the withers). Varimax rotation of PC1 and analysis of different gestational groups showed a significant effect of gestational immaturity (P = .001), with the premature group being more affected than the dysmature group (P = .009, P = .012). Mean values for the four dominant indices showed that these groups have significantly lower distal limb to body length relationships than controls. The observed differences suggest that gestational immaturity may affect anatomical ratios at maturity, which, in combination with orthopedic issues arising from incomplete ossification, may have a further impact on long-term athletic potential.

Effects of biological traits on capture-induced parturition in a freshwater stingray and perspectives for species management.

Elasmobranchs are particularly vulnerable to overexploitation and population depletion, especially due to their life-history traits, such as low reproductive output and slow growth. Given that capture-induced parturition (abortion or premature birth) is a common consequence of fisheries in elasmobranchs, but still little studied, we investigated how the abortion/premature birth process varies in response to reproductive traits in a freshwater stingray, Potamotrygon amandae. Our results revealed that capture-induced parturition was affected by reproductive traits, such as litter size (one to seven) and gestation stage. The event occurred faster in pregnant females with high litter size during late pregnancy. Also, as found in other elasmobranchs, litter size was positively correlated with maternal size. These findings indicate that larger pregnant females in late pregnancy are more vulnerable to capture-induced parturition. This study improves our understanding of the capture-induced parturition process in stingrays, and provides useful information for management strategies and future recommendations for elasmobranch conservation.

Chronic Intra-Uterine Ureaplasma parvum Infection Induces Injury of the Enteric Nervous System in Ovine Fetuses.

Background: Chorioamnionitis, inflammation of the fetal membranes during pregnancy, is often caused by intra-amniotic (IA) infection with single or multiple microbes. Chorioamnionitis can be either acute or chronic and is associated with adverse postnatal outcomes of the intestine, including necrotizing enterocolitis (NEC). Neonates with NEC have structural and functional damage to the intestinal mucosa and the enteric nervous system (ENS), with loss of enteric neurons and glial cells. Yet, the impact of acute, chronic, or repetitive antenatal inflammatory stimuli on the development of the intestinal mucosa and ENS has not been studied. The aim of this study was therefore to investigate the effect of acute, chronic, and repetitive microbial exposure on the intestinal mucosa, submucosa and ENS in premature lambs. Materials and Methods: A sheep model of pregnancy was used in which the ileal mucosa, submucosa, and ENS were assessed following IA exposure to lipopolysaccharide (LPS) for 2 or 7 days (acute), Ureaplasma parvum (UP) for 42 days (chronic), or repetitive microbial exposure (42 days UP with 2 or 7 days LPS). Results: IA LPS exposure for 7 days or IA UP exposure for 42 days caused intestinal injury and inflammation in the mucosal and submucosal layers of the gut. Repetitive microbial exposure did not further aggravate injury of the terminal ileum. Chronic IA UP exposure caused significant structural ENS alterations characterized by loss of PGP9.5 and S100ß immunoreactivity, whereas these changes were not found after re-exposure of chronic UP-exposed fetuses to LPS for 2 or 7 days. Conclusion: The in utero loss of PGP9.5 and S100ß immunoreactivity following chronic UP exposure corresponds with intestinal changes in neonates with NEC and may therefore form a novel mechanistic explanation for the association of chorioamnionitis and NEC.

Staphylococcus epidermidis sepsis induces hypercoagulability in preterm pigs.

Gram positive bacteria are a cause of sepsis in human preterm infants, and associates with high mortality and hemostatic dysfunction. It is unknown whether bovine colostrum may protect against sepsis and prevent hemostatic dysfunction. The current study was part of an overall sepsis study investigating Staphylococcus epidermidis (SE) induced sepsis in premature pigs including investigation of the effect of feeding bovine colostrum. The specific hypothesis of this study was that the hemostatic response would be hypercoagulable in septic pigs compared to non-infected controls, and that feeding bovine colostrum would increase the hypercoagulant response. Thromboelastography, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were characterized in SE infected pigs, SE infected pigs fed bovine colostrum, and uninfected controls. All pigs were followed for 24 h. In addition, the same parameters were evaluated in a group of premature pigs and a group of full born pigs all followed for 11 days. SE septic premature pigs were characterized by increased clot strength and decreased fibrinolysis, significantly low platelet count and high fibrinogen concentration. Feeding bovine colostrum did not affect the hemostatic response. Compared to full born pigs, preterm newborn pigs demonstrated reduced clot strength, prolonged prothrombin time and low fibrinogen concentration. In all pigs, the fibrinogen concentration increased 11 days post-partum. To conclude, SE induced sepsis in premature pigs resulted in hypercoagulability. Bovine colostrum did not mitigate the hemostatic response. A hypocoagulable hemostatic response was present in healthy preterm pigs compared to full born pigs, similar to previous reports in infants.

Fetal Death Associated With Premature Mammary Gland Development and Lactation in a Mare Treated With Weekly Injections of Long-Acting Progesterone.

A 14-year-old, 530-kg, multiparous, pregnant Quarter Horse mare was referred for evaluation of premature mammary gland development and lactation. The mare was in the seventh month of gestation. The mare had a history of subfertility and was receiving weekly injections of long-acting progesterone, prescribed by the referring veterinarian. The last dose had been administered four days before presentation. Upon presentation, the mare had vital signs within normal limits, a moderately developed, nonpainful udder with galactorrhea, and no vulvar discharge. Transrectal palpation revealed a well-toned uterus and cervix and discreetly palpable fetal parts, however, ballottement of the fetus did not result in appreciable fetal movement. Transrectal ultrasound was unremarkable, but transabdominal ultrasound revealed one underdeveloped, immotile fetus in the left uterine horn with no heartbeat. Abortion was induced with repeated doses of cloprostenol. Fifty-four hours after the first cloprostenol injection, the mare displayed signs of labor, the cervix was manually dilated, and the fetus and fetal membranes were expelled with gentle manual manipulation. Standard postabortion care included uterine lavage and oxytocin for 48 hours before being discharged to the care of her owners. Fetal crown-rump length (53 cm) was consistent with a 6-month fetus rather than its gestational age of 7 months. The umbilical cord was edematous, and a distended, fluid-filled structure surrounded the cord at the intersection of the allantoic and amniotic segments of the umbilical cord. This structure was determined to be the severely dilated urachus. Microscopic findings included placental stromal mineralization, distended umbilicus adventitia, and dilated umbilical lymphatics with no other significant findings. Remaining abortion diagnostic tests were unremarkable. The mare recovered well and was discharged to the care of her owner two days after abortion. The following breeding season the mare carried a healthy foal to term.

Splenic development and injury in premature lambs supported by the artificial placenta.

INTRODUCTION: The purpose of this study is to evaluate splenic effects during artificial placenta (AP) support. METHODS: AP lambs (118-121 d, n = 14) were delivered and placed on the AP support for a goal of 10-14 days. Cannulation used right jugular drainage and umbilical vein reinfusion. Early (ETC; 115-120 d; n = 7) and late (LTC; 125-131 d; n = 7) tissue controls were delivered and immediately sacrificed. Spleens were formalin fixed, H&E stained, and graded for injury, response to inflammation, and extramedullary hematopoiesis (EMH). CD68 and CD163 stains were used to assess for macrophage activation and density. Clinical variables were correlated with splenic scores. Groups were compared using Fisher's Exact Test and descriptive statistics. p < 0.05 indicated significance. RESULTS: Mean survival for AP lambs was 12 ±â€¯5 d. There was no necrosis found in any of the groups. Vascular congestion and sinusoidal histiocytosis did not significantly differ between AP and control groups (p = 0.72; p = 0.311). There were significantly more pigmented macrophages (p = 0.008), CD163 (p = <0.001), and CD68 (p = <0.001) stained cells in the AP group. ETC and LTC demonstrated more EMH than AP spleens (p = <0.001). CONCLUSIONS: During AP support, spleens appear to develop normally and exhibit an appropriate inflammatory response. After initiation of AP support, EMH transitions away from the spleen. STUDY TYPE: Research Paper/Therapeutic Potential. LEVEL OF EVIDENCE: N/A.

Early neuropathological and neurobehavioral consequences of preterm birth in a rabbit model.

Preterm birth is the most significant problem in contemporary obstetrics accounting for 5-18% of worldwide deliveries. Encephalopathy of prematurity encompasses the multifaceted diffuse brain injury resulting from preterm birth. Current animal models exploring the underlying pathophysiology of encephalopathy of prematurity employ significant insults to generate gross central nervous system abnormalities. To date the exclusive effect of prematurity was only studied in a non-human primate model. Therefore, we aimed to develop a representative encephalopathy of prematurity small animal model only dependent on preterm birth. Time mated New-Zealand white rabbit does were either delivered on 28 (pre-term) or 31 (term) postconceptional days by caesarean section. Neonatal rabbits underwent neurobehavioral evaluation on 32 days post conception and then were transcardially perfuse fixed. Neuropathological assessments for neuron and oligodendrocyte quantification, astrogliosis, apoptosis and cellular proliferation were performed. Lastly, ex-vivo high-resolution Magnetic Resonance Imaging was used to calculate T1 volumetric and Diffusion Tensor Imaging derived fractional anisotropy and mean diffusivity. Preterm birth was associated with a motoric (posture instability, abnormal gait and decreased locomotion) and partial sensory (less pain responsiveness and failing righting reflex) deficits that coincided with global lower neuron densities, less oligodendrocyte precursors, increased apoptosis and less proliferation. These region-specific histological changes corresponded with Magnetic Resonance Diffusion Tensor Imaging differences. The most significant differences were seen in the hippocampus, caudate nucleus and thalamus of the preterm rabbits. In conclusion this model of preterm birth, in the absence of any other contributory events, resulted in measurable neurobehavioral deficits with associated brain structural and Magnetic Resonance Diffusion Tensor Imaging findings.

Stable Control of Physiological Parameters, But Not Infection, in Preterm Lambs Maintained on Ex Vivo Uterine Environment Therapy.

Ex vivo uterine environment (EVE) therapy is an experimental neonatal intensive care strategy wherein gas exchange is performed by membranous oxygenators attached to the umbilical vessels. Our aim was to assess the ability of a newly refined EVE system to maintain key physiological parameters in preterm lambs within optimal ranges for 48 h. EVE group; n = 6: Preterm lambs were delivered under general anesthesia at 115 ± 2 days of gestational age. Animals were submerged in a bath of artificial amniotic fluid on EVE therapy for 48 h. Physiological parameters were monitored in real-time over the length of the experiment. Control group; n = 11: Ewes carrying a single fetus (115 ± 2 days of gestational age) underwent recovery surgery to allow placement of a fetal carotid artery catheter. Fetuses received an infusion of sterile saline only. After euthanasia, EVE and Control group fetuses underwent necroscopy to perform static pressure-volume curves and for sampling of lung and cord blood plasma for molecular analyses. Five out of six fetuses in the EVE group completed the study period with key physiological variables remaining within their respective reference ranges for the duration of the 48 h study. Bacteremia was identified in four out of five EVE fetuses, and was associated with a systemic inflammatory response. Using our refined EVE therapy platform, preterm lambs were maintained in a stable physiological condition for 48 h. These findings represent a significant advance over earlier work with this system; however, the identification of bacteremia and a fetal inflammatory response suggests that further refinement to the EVE therapy platform is required.

Reproductive losses caused by the ingestion of Poincianella pyramidalis in sheep.

Malformations have been observed in sheep and goats in the Brazilian semiarid region in areas where Poincianella pyramidalis is dominant. The objective of this trial was to determine whether Poincianella pyramidalis causes reproductive changes in pregnant sheep. Sixteen non-pregnant sheep were mated with two rams. After confirmation of the pregnancy by ultrasonography on the 18th day after mating, pregnant sheep were randomly divided into four groups (#1, 2, 3, and 4), with four animals each. Sheep received roughage in an amount equivalent to 2% of their body weight, mixed with 0%, 10%, 20% and 40% of dried leaves of P. pyramidalis for groups 1, 2, 3 and 4, respectively. In Groups 1 and 2, all animals lambed normally. In Group 3 (20% P. pyramidalis in the roughage), one lamb was born with arthrogryposis and three sheep gave birth to premature weak lambs within 128, 132, and 133 days of gestation. In Group 4 (40% P. pyramidalis in the roughage), one sheep lambed a normal lamb; another ewe had embryonic mortality after seven days of plant consumption, and two aborted on days 103 and 144 of pregnancy. One of the aborted fetuses was normal and the other showed arthrogryposis and prognathism. These results suggest that P. pyramidalis causes embryonic deaths, abortions, and malformations in sheep. Grazing pregnant sheep in areas where this plant is dominant should be avoided, and roughage for confined pregnant females should not contain more than 10% P. pyramidalis.

The intestinal-renal axis for arginine synthesis is present and functional in the neonatal pig.

The intestinal-renal axis for endogenous arginine synthesis is an interorgan process in which citrulline produced in the small intestine is utilized by the kidney for arginine synthesis. The function of this axis in neonates has been questioned because during this period the enzymes needed for arginine synthesis argininosuccinate synthase (ASS1) and lyase (ASL) are present in the gut. However, evidence of high plasma citrulline concentrations in neonates suggests otherwise. We quantified in vivo citrulline production in premature (10 days preterm), neonatal (7 days old), and young pigs (35 days old) using citrulline tracers. Neonatal pigs had higher fluxes (69 µmol·kg-1·h-1, P < 0.001) than premature and young pigs (43 and 45 µmol·kg-1·h-1, respectively). Plasma citrulline concentration was also greater in neonatal pigs than in the other age groups. We also determined the site of synthesis and utilization of citrulline in neonatal and young pigs by measuring organ balances across the gut and the kidney. Citrulline was released from the gut and utilized by the kidney in both neonatal and young pigs. The abundance and localization of the enzymes involved in the synthesis and utilization were determined in intestinal and kidney tissue. Despite the presence of ASS1 and ASL in the neonatal small intestine, the lack of colocalization with the enzymes that produce citrulline results in the release of citrulline by the PDV and its utilization by the kidney to produce arginine. In conclusion, the intestinal-renal axis for arginine synthesis is present in the neonatal pig.

Orthopedic Conditions of the Premature and Dysmature Foal.

Incomplete ossification of the cuboidal bones is a common finding in premature and dysmature foals, and possibly in foals with hypothyroidism. Radiographs of the carpus and tarsus should be performed in any high-risk foal to obtain a diagnosis. Goals of treatment include limiting weight bearing and exercise. The prognosis is guarded depending on the degree of incomplete ossification.

Venous lactate, pH and partial pressure of carbon dioxide levels as prognostic indicators in 110 premature calves with respiratory distress syndrome.

Hyperlactatemia, hypercapnia, low pH and low oxygen saturation (SatO2) are commonly observed in premature calves. These clinical indicators are associated with increased mortality in preterm human newborns with respiratory distress syndrome (RDS). The aim of this study was to investigate the prognostic importance of venous pH, partial pressure of carbon dioxide (pCO2) and lactate level and which parameters are related with mortality in premature calves with RDS. All premature calves (52 male/58 female) were admitted to clinic within 12-24 hours after birth and blood samples were also taken into heparinised plastic syringes from the jugular vein within 30 minutes following admission. Diagnosis of RDS was made by both clinical signs and blood gas results. For the evaluation of independent samples, t test was used to compare the venous blood gas indicators of surviving and non-surviving premature calves. Receiver operating characteristics curves were used to determine a cut-off value in terms of lactate and pCO2 measurements among non-surviving and surviving calves. Venous pH, pCO2, SatO2, base deficit, bicarbonate (HCO3) and lactate levels showed a significant variance between surviving and non-surviving calves. Mean venous pH, pCO2, SatO2, lactate levels in non-surviving premature calves was 7.05, 78.9 mm Hg, 16.1 per cent and 9.50 mmol/l, respectively. Mean pH, pCO2, SatO2 and lactate levels in surviving premature calves were 7.29, 56.3 mm Hg, 25.5 per cent and 5.1 mmol/l, respectively. The cut-off values for lactate and pCO2 were 7.5 mmol/l and 63.5 mm Hg, respectively. In conclusion, the results of the study show that venous blood lactate and pCO2 have prognostic importance in premature calves with RDS.

[An unusual case of a 35 days preterm birth of a German Holstein calf]. / Ein außergewöhnlicher Fall eines 35 Tage zu früh geborenen Deutschen Holstein Kalbes.

A female calf of the breed German Holstein (GH) was spontaneously born on July 28, 2013 which was 35 days before the expected term of birth. The dam was a heifer when she got pregnant from the first insemination on November 23, 2012. Calving was without complications. The calf was fully viable and without visible anomalies. We assume that the calf was fully mature at the termination of the pregnancy. Growth rate after the second month of life was comparable to calves born in the same herd after normal length of gestation. The sire of this preterm calf was a GH-bull used for artificial insemination. This bull had already sired 151 daughters. For this bull, preterm calvings were not yet reported. The dam was a heifer, and neither external influences on this dam or in the herd could be identified that could have induced this premature calving. In the herd, no further premature calvings were observed or reasons associated with a preterm calving were found. In this exceptional case, however, gestation length was 248 days and the prematurely born calf survived without any signs of debility, organ defects and respiratory distress.

Phospholipid Composition in Synthetic Surfactants Is Important for Tidal Volumes and Alveolar Stability in Surfactant-Treated Preterm Newborn Rabbits.

BACKGROUND: The development of synthetic surfactants for the treatment of lung pulmonary diseases has been going on for many years. OBJECTIVES: To investigate the effects of phospholipid mixtures combined with SP-B and SP-C analogues on lung functions in an animal model of respiratory distress syndrome. METHODS: Natural and synthetic phospholipid mixtures with/without SP-B and/or SP-C analogues were instilled in ventilated premature newborn rabbits. Lung functions were evaluated. RESULTS: Treatment with Curosurf or phospholipids from Curosurf combined with SP-B and SP-C analogues gave similar results. Treatment with phospholipids from adult rabbit lungs or liver combined with dipalmitoylphosphatidylcholine (DPPC) and palmitoyloleoylphosphatidylglycerol (POPG) gave tidal volumes (VT) well above physiological levels, but alveolar stability at end-expiration was only achieved when these phospholipids were combined with analogues of SP-B and SP-C. Treatment with egg yolk-PC mixed with DPPC with and without POPG gave small VT, but after addition of both analogues VT was only somewhat lower and lung gas volumes (LGV) similar to those obtained with Curosurf. Substitution of egg yolk-PC (≥99% PC) with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and combining them with DPPC, POPG and 2% each of the SP-B and SP-C analogue gave a completely synthetic surfactant with similar effects on VT and LGV as Curosurf. CONCLUSIONS: Phospholipid composition is important for VT while the SP-B and SP-C analogues increase alveolar stability at end-expiration. Synthetic surfactant consisting of unsaturated and saturated phosphatidylcholines, POPG and the analogues of SP-B and SP-C has similar activity as Curosurf regarding VT and LGV in an animal model using preterm newborn rabbits ventilated without positive end-expiratory pressure.

Quantification of the increase in the frequency of early calving associated with late exposure to bluetongue virus serotype 8 in dairy cows: implications for syndromic surveillance.

A recent study evaluating whether reproductive data could be used for syndromic surveillance found an increased frequency of early calving (calving occurring a few days earlier than expected) in areas exposed to the Bluetongue virus serotype 8 (BTV-8) in northern Europe. A high proportion of herds infected during the 2006-2009 European outbreak were not reported through the surveillance system. The objectives of this study were (1) to quantify the increase in the frequency of early calving associated with the exposure to BTV-8 in late gestation and (2) to determine whether this association could be found in populations exposed to BTV-8 but without reported clinical signs. Increases in frequency of early calving were quantified for cows in herds located in the 2007 outbreak area in France, reported or not as cases. Increases were detected for cows in both categories of herds with a larger effect in herds reported after clinical signs. Moreover, the largest effect was found for exposures occurring during the latest stage of pregnancy, suggesting that BTV infection could trigger calving in cows in late gestation, a few days earlier than expected. This is the first study quantifying the association between a viral infection and a shortened pregnancy length (still within a normal range). The high magnitude of the increase in frequency of early calving, their occurrence in herds from infected areas but not reported, and the short time interval between exposure and the occurrence of the event confirm the interest of using early calving as an indicator for syndromic surveillance.

Total plasma magnesium in healthy and critically ill foals.

Abnormalities in total Mg (tMg) concentration in plasma and/or serum are common in critically ill humans, and the association with increased mortality has been documented in several clinical studies in adults and newborns with hypoxic-ischemic encephalopathy. Abnormalities in tMg were studied in hospitalized dogs, cats, and adult horses. Newborn foals were scarcely studied with regard to Mg concentration. The aims of the present study were: (1) to compare two analytical methods for the determination of tMg in plasma: the automated colorimetric method and the atomic absorption spectrometry; (2) to measure plasma tMg in healthy foals during the first 72 hours after birth and in sick foals during the first 72 hours of hospitalization; (3) to compare total plasma Mg concentration among healthy foals, foals affected by perinatal asphyxia syndrome (PAS), prematurity and/or dismaturity, and sepsis; (4) to evaluate tMg plasma concentration in surviving and non-surviving foals. One hundred seventeen foals were included in the study: 20 healthy and 97 sick foals. The automated method used in clinical practice probably overestimates plasma tMg. Due to its higher sensitivity and specificity, the atomic absorption spectrometry should be considered the method of choice from an analytical point of view, but requires an instrumentation not easily available in any laboratory and specific technical skills and competencies. Plasma tMg in healthy foals were included in the range 0.52 to 1.01 mmol/L and did not show any time-dependent change during the first 72 hours of life. In sick foals, tMg evaluated at T0 was statistically higher than tMg measured at subsequent times. Foals affected by PAS had a tMg at T0 significantly higher (P < 0.01) than healthy, septic, and premature and/or dysmature foals. The t test found significantly higher (P < 0.01) plasma tMg measured at T0 in non-surviving than in surviving foals. Plasma tMg could be a useful parameter for the diagnosis of PAS and the formulation of the prognosis in critically ill foals.

Provision of Amniotic Fluid During Parenteral Nutrition Increases Weight Gain With Limited Effects on Gut Structure, Function, Immunity, and Microbiology in Newborn Preterm Pigs.

BACKGROUND: Small enteral boluses with human milk may reduce the risk of subsequent feeding intolerance and necrotizing enterocolitis in preterm infants receiving parenteral nutrition (PN). We hypothesized that feeding amniotic fluid, the natural enteral diet of the mammalian fetus, will have similar effects and improve growth and gastrointestinal (GI) maturation in preterm neonates receiving PN, prior to the transition to milk feeding. MATERIALS AND METHODS: Twenty-seven pigs, delivered by cesarean section at ~90% of gestation, were provided with PN and also fed boluses with amniotic fluid (AF; n = 13, 24-72 mL/kg/d) or no oral supplements (nil per os [NPO]; n = 14) until day 5 when blood, tissue, and fecal samples were collected for analyses. RESULTS: Body weight gain was 2.7-fold higher in AF vs NPO pigs. AF pigs showed slower gastric emptying, reduced meal-induced release of gastric inhibitory peptide and glucagon-like peptide 2, changed gut microbiota, and reduced intestinal permeability. There were no effects on GI weight, percentage mucosa, villus height, plasma citrulline, hexose absorptive capacity, and digestive enzymes. Intestinal interleukin (IL)-1ß levels and expression of IL1B and IL8 were increased in AF pigs, while blood biochemistry and amino acid levels were minimally affected. CONCLUSION: Enteral boluses of AF were well tolerated in the first 5 days of life in preterm pigs receiving PN. Enteral provision of AF before the initiation of milk feeding may stimulate body growth and improve hydration in preterm infants receiving PN. Furthermore, it may improve GI motility and integrity, although most markers of GI maturation remain unchanged.