Foetal and neonatal exposure prediction and dosing evaluation for ampicillin using a physiologically-based pharmacokinetic modelling approach.

AIMS: Ampicillin is frequently used in neonates for the treatment of sepsis and as an intrapartum prophylaxis option for Group B Streptococcus. Pharmacokinetic data to guide ampicillin dosing in neonates and during the intrapartum period are limited. The objective of this study was to build a physiologically-based pharmacokinetic (PBPK) model to characterize the disposition of ampicillin in neonates and foetuses and to inform corresponding optimal dosing regimens. METHODS: An adult ampicillin PBPK model was first developed using the Simcyp® simulator. The adult model was then scaled to neonates by accounting for maturational changes in physiological parameters and age-dependent drug disposition or extended to a pregnancy model for mothers and foetuses. Models were verified using collected mean or individual-level concentration data from the literature. RESULTS: The developed adult PBPK model included elimination via glomerular filtration, OAT3-mediated tubular secretion and biliary excretion as well as hepatic metabolism, and 89.8% of the observed mean concentrations in adults were within a 2-fold range of model mean predictions. Most of the observed individual-level observations in neonates (78.4%) and foetuses (about 65% in two studies) were within the 90% prediction intervals. The recommended 50 mg/kg every 8 h (q8h) ampicillin regimen achieved the 75% fraction time of total drug concentration above minimum inhibitory concentration (T > MIC) target for an MIC ≤8 mg/L in >90% virtual neonates, and 1 g ampicillin for pregnant women provided adequate foetal exposure (>0.25 mg/L) for 4 h prior to delivery. CONCLUSIONS: A PBPK model was developed to characterize ampicillin's disposition in neonates, pregnant women, and foetuses, and the model supported optimal dosing evaluation in these vulnerable populations.

A flexible approach to modelling stillbirths using the foetuses at risk approach.

BACKGROUND: Survival analysis methods are increasingly used to model the gestational age-specific risk of perinatal phenomena such as stillbirth. OBJECTIVES: To compare two types of survival analysis models, and highlight differences by estimating the relationships between pre-pregnancy BMI and gestational age-specific rates of stillbirth. METHODS: The study was based on singleton live births and stillbirths in the United States in 2016-2017, with data obtained from the natality and fetal death files of the National Center for Health Statistics. We compared Cox regression versus piecewise exponential additive mixed models (PAMMs) for modelling the relationship between BMI and stillbirth across gestational age. In a second analysis, we illustrated the performance of both models for assessing the relationship between the trimester-specific number of cigarettes smoked, a time-dependent covariate, and stillbirth. RESULTS: The study population included 7,567,316 births, of which 42,739 were stillbirths (5.6 per 1000 total births). Stillbirth rates increased with increasing pre-pregnancy BMI and increasing gestational age. In analyses with BMI as a categorical variable, the Cox model and PAMM models yielded similar results. Analyses of BMI as a continuous variable also showed similar results when BMI associations were assumed to be linear, and the changes in gestational age-specific rates were modelled parametrically. However, results differed slightly when PAMMs, modelled with data-driven approaches, were used to estimate changes in BMI effects across gestational age; PAMMs provided a more nuanced modelling of time-varying effects. PAMM models showed an approximately linear increase in the effect of smoking on stillbirth with increasing gestational age. CONCLUSIONS: For survival analyses using the foetuses-at-risk approach, PAMMs provide a valuable alternative to the traditional Cox model, with increased modelling flexibility when proportional hazards assumptions are violated.

A review of the characteristics, mechanisms and clinical significance of habituation in foetuses and newborn infants.

Habituation has been a topic of interest since the early 20th century. We summarise the characteristics of habituation, the proposed habituation mechanisms, the associated cortical responses and the link between habituation and cognitive development. Behavioural and neuroimaging studies have highlighted the early sensory abilities of foetuses and newborn infants, with preterm newborn infants exhibiting decreased habituation and dishabituation capabilities that increase their environmental vulnerability. Habituation provides a foundation for the learning and cognition on which higher functions are constructed. It has been suggested that it is efficient for predicting cognitive developmental outcomes in term and preterm newborn infants.

Isolation and characterisation of Brucella melitensis by bacteriological and molecular methods from livestock in North Cyprus.

In this study, the isolation, biotyping and molecular characterisation of Brucella melitensis from cattle, sheep and goats in North Cyprus are reported on. A total of 319 raw milk samples obtained from seropositive dairy livestock (190 cattle, 74 sheep and 55 goats) and tissue samples including the liver, spleen and abomasal contents obtained from 32 aborted foetal samples (5 cattle, 18 sheep and 9 goats) were analysed for the presence and characterisation of the agent. B. melitensis was isolated and identified from 90 out of 319 (28.2%) milk and 19 out of 32 (59.4%) foetal samples by conventional bacteriological methods. Identification of all 109 isolates was confirmed by using real-time PCR with genus and species-specific primers. Following the preliminary identification, 27 selected isolates representing various counties and herds were further analysed by conventional methods. Twenty (74.1%) isolates were identified as B. melitensis biovar 1 and seven (25.9%) were identified as B. melitensis biovar 3. The Bruce-ladder multiplex PCR assay revealed that all the isolates were field strains. The results of the present study confirmed the presence of B. melitensis in livestock including the cattle population in North Cyprus. Even though the majority of the samples came from seropositive cattle, Brucella abortus was not isolated in the study. The results also revealed the potential public health risk of brucellosis in livestock emphasising the need of implementing strict control and eradication strategies against the disease in animal populations in order to protect human health.

Micro-CT yields high image quality in human fetal post-mortem imaging despite maceration.

BACKGROUND: Current clinical post-mortem imaging techniques do not provide sufficiently high-resolution imaging for smaller fetuses after pregnancy loss. Post-mortem micro-CT is a non-invasive technique that can deliver high diagnostic accuracy for these smaller fetuses. The purpose of the study is to identify the main predictors of image quality for human fetal post-mortem micro-CT imaging. METHODS: Human fetuses were imaged using micro-CT following potassium tri-iodide tissue preparation, and axial head and chest views were assessed for image quality on a Likert scale by two blinded radiologists. Simple and multivariable linear regression models were performed with demographic details, iodination, tissue maceration score and imaging parameters as predictor variables. RESULTS: 258 fetuses were assessed, with median weight 41.7 g (2.6-350 g) and mean gestational age 16 weeks (11-24 weeks). A high image quality score (> 6.5) was achieved in 95% of micro-CT studies, higher for the head (median = 9) than chest (median = 8.5) imaging. The strongest negative predictors of image quality were increasing maceration and body weight (p < 0.001), with number of projections being the best positive imaging predictor. CONCLUSIONS: High micro-CT image quality score is achievable following early pregnancy loss despite fetal maceration, particularly in smaller fetuses where conventional autopsy may be particularly challenging. These findings will help establish clinical micro-CT imaging services, addressing the need for less invasive fetal autopsy methods.

ART manipulation after controlled ovarian stimulation may not increase the risk of abnormal expression and DNA methylation at some CpG sites of H19,IGF2 and SNRPN in foetuses: a pilot study.

BACKGROUND: To examine the effects of IVF, ICSI and FET, as well as in vitro culture, on the safety of offspring, this study was conducted from the perspective of genetic imprinting to investigate whether assisted reproductive technology would influence the parental and maternal imprinting genes. METHODS: Eighteen foetuses were collected from multifoetal reduction and divided into 6 groups: multifoetal reduction after IVF fresh transferred D3 embryos (n = 3), multifoetal reduction after IVF frozen transferred D3 embryos (n = 3), multifoetal reduction after IVF frozen transferred D5 embryos (n = 3), multifoetal reduction after ICSI fresh transferred D3 embryos (n = 3), multifoetal reduction after ICSI frozen transferred D3 embryos (n = 3), and multifoetal reduction after controlled ovarian hyperstimulation (COH) (n = 3). The imprinted genes H19, IGF2 and SNRPN were selected for analysis. The expression and DNA methylation at some CpG sites of H19, IGF2, and SNRPN were examined using real-time quantitative polymerase chain reaction (PCR) and pyrosequencing. RESULTS: There were no significant differences in the mRNA expression levels among the groups. The mean percentage of H19 methylation (eight CpG sites), IGF2 methylation (five CpG sites) and SNRPN methylation (nine CpG sites) did not differ significantly. CONCLUSIONS: The results suggest that ARTs after controlled ovarian stimulation (IVF, ICSI, cryopreservation and duration of in vitro culture) may not increase the risk of abnormal expression and DNA methylation at some CpG sites of H19, IGF2 and SNRPN in foetuses. Further study with strict design, expanded sample size and CpG sites is essential.

Detection of APAF1 mutation in Holstein cows and mummified foetuses in Japanese dairy herds.

Some of the highest genetic merit sires have been shown to harbour recessive mutations affecting fertility, which may spread rapidly in the population through AI. These disorders may result in abortion and decline in pregnancy per insemination in cows. This study was carried out on 240 Holstein-Friesian cows and 15 mummified foetuses. Blood and tissue samples were collected from the cows and mummified foetuses, respectively, for DNA extraction. Allele-specific PCR was designed for the detection of the cows and foetuses carrying the nonsense mutation (C/T) in apoptosis peptide activating factor 1 gene (APAF1). The mutant allele frequency of the APAF1 in carrier cows and mummified foetuses was calculated. Milk samples were taken from the carrier and non-carrier cows for progesterone assay. The allele-specific PCR reaction efficiently distinguished the C/T mutation in APAF1. Of 240 cows, seven cows (2.9%) were diagnosed to carry one copy of the mutant allele of APAF1. However, the carrier frequency was 33.3% in mummified foetuses (five of 15). The mutant allele frequency was 0.02 and 0.17 in the cows and mummified foetuses, respectively. Concentrations of progesterone did not differ between cows with APAF1 mutation and non-carrier cows during 45 days post-insemination. This study provided allele-specific PCR for the detection of APAF1 mutation in cows. Moreover, it reports the carrier and mutant allele frequencies of APAF1 in dairy cows and mummified foetuses in Japan.

Quantitative anatomy of the growing quadratus lumborum in the human foetus.

PURPOSES: The purpose of the study was to quantitatively evaluate the size of the quadratus lumborum and to precisely display its growth dynamics in the human foetus. MATERIALS AND METHODS: Using anatomical dissection, digital-image analysis (NIS Elements AR 3.0) and statistical analysis (Student's t test, regression analysis), the length, width, surface area, and cross-sectional area of the quadratus lumborum were measured, and the width-to-length ratio was calculated in 58 human foetuses of both sexes (26♂, 32♀) aged 16-27 weeks. RESULTS: Neither sex nor right-left significant differences were found in relation with the numerical data of the growing quadratus lumborum. The length, width, and cross-sectional area of the quadratus lumborum muscle increased logarithmically, while its surface area increased proportionately to fetal age. The following growth models were computed for the quadratus lumborum: y = -70.397 + 68.501 × ln(age) ± 1.170 for length, y = -20.435 + 8.815 × ln(age) ± 0.703 for width, y = -196.035 + 14.838 × age ± 13.745 for surface area, and y = -48.958 + 20.909 × ln(age) ± 1.100 for cross-sectional area. CONCLUSIONS: The fetal quadratus lumborum reveals neither sex nor bilateral differences. An increase in length and width of the growing quadratus lumborum follows in a commensurate fashion. The quadratus lumborum grows logarithmically with respect to its length, width, and cross-sectional area, and proportionately to age with respect to its surface area.

What can we do to reduce the associated costs in induction of labour of intrauterine growth restriction foetuses at term? A cost-analysis study.

OBJECTIVE: To evaluate the costs associated with induction of labour in intrauterine growth restriction fetuses comparing different procedures. STUDY DESIGN: 150 pregnancies at term diagnosed with intrauterine growth restriction and indication for induction of labour were included. 24 were ripened with misoprostol 25 µg tablets, 24 with dinoprostone 10 mg vaginal insert, and 77 with Cook® cervical ripening balloon. To determine the costs of induction of labour, method of induction, intrapartum medication, epidural analgesia, type of delivery, and maternal and neonatal admissions were considered. Statistical analysis was performed using the G-Stat 2.0 free statistical software. ANOVA test was used for comparisons between quantitative parametric variables. Chi-squared test or Fisher test was used for qualitative variables. A value of p < 0.05 was considered statistically significant. RESULTS: Up to 70.83% women in dinoprostone group gave birth within the first 24 h compared to 42.66% in misoprostol group and 36.36% in CG (p < 0.01). Misoprostol tablets were cheaper (9.45 ± 1.52 US dollars) than dinoprostone or Cook® balloon (41.67 ± 0 and 59.85 ± 0 54.45 ± 0 US dollars, respectively) (p < 0.01). Costs related to maternal admissions were higher in CG (475.13 ± 146.95$) than dinoprostone group (475.13 ± 146.95$) or MG (427.97 ± 112.65$) (p = 0.03). Total costs in misoprostol group (2765.18 ± 495.38$) were lower than in the dinoprostone group (3075.774 ± 896.14$) or Cook® balloon group (3228.02 ± 902.06$) groups. CONCLUSIONS: Misoprostol for induction of labour had lower related costs than dinoprostone or Cook® balloon, with similar obstetrical and perinatal outcomes.

Positional changes in tendon insertions from bone to fascia: development of the pes anserinus and semimembranosus muscle insertion in human foetuses.

Development of a long muscle belly in foetal extremities generally requires a definite bony insertion of the long tendon. However, in adults, the pes anserinus and the semimembranosus tendon (SMT) are inserted into fasciae. Development of fascial insertions in foetuses was investigated by examining serial histological sections obtained from 7 foetuses at 8-9 weeks and 8 foetuses at 14-16 weeks. The presence of matrix substances and macrophages was also examined by immunohistochemistry. At 8 weeks, the tendons of the semitendinosus, gracilis, sartorius and semimembranosus muscles were straight and inserted into the initial shaft-like proximal end of the tibia on the proximal side of the popliteus muscle. At 9 weeks, however, the medially extending popliteus muscle appeared to push the pes anserinus tendons superficially, with a loss of cartilage insertions. The SMT obtained an attachment to the popliteus muscle. At 14-16 weeks, the SMT divided into thick and thin bundles: the former contained abundant macrophages and inserted into the tenascin-positive perichondrium of the enlarged proximal tibia, while the later without macrophages ended at the joint capsule. The pes anserinus tendons, negative for both versican and tenascin-c, took highly tortuous courses toward the fascia cruris. Because the medial extension of the popliteus muscle was associated with the enlargement of the proximal tibia, the topographical relationship of the popliteus muscle with these 4 tendons changed drastically, resulting in a loss of cartilage insertion of the pes anserinus tendons as well as the division and reconstruction of the SMT.

Oblique cord (chorda obliqua) of the forearm and muscle-associated fibrous tissues at and around the elbow joint: a study of human foetal specimens.

In adults, the oblique cord or chorda obliqua separates the origins of the flexor pollicis longus (FPL) and flexor digitorum profundus (FDP) muscles from the supinator muscle and elbow joint. This study examined the topographic anatomy of the oblique cord and related muscles in foetuses. Semiserial sections of five mid-term foetuses of gestational age (GA) 14-16 weeks and 12 late-stage foetuses of GA 28-30 weeks were histologically examined and three forearms at GA 30 weeks were macroscopically evaluated. Late-stage foetuses showed a fascial structure between the supinator and FDP muscles. The latter extended proximally to the elbow joint and the muscle origin thickened the distal, ulnar part of the capsule. The FPL origin also extended proximally but did not reach the joint capsule. These morphologies were consistent with macroscopic examinations. The brachialis muscle was widely inserted into the proximal, anterior part of the capsule. In addition, the medial collateral ligament was not covered by the pronator-flexor muscles but by the triceps brachii muscle. The oblique cord apparently did not form prenatally. After birth, the proximal parts of the FDP and FPL muscles were likely replaced by collagenous tissues, providing a specific type of intermuscular septum i.e., the oblique cord. This type of muscle-ligament transition was observed in the annular ligament of the radius. The foetal elbow joint was characterised by strong support by the FDP, brachialis and triceps brachii muscles. Therefore, the foetal elbow is not a miniature version of the adult elbow.

Primary and secondary olfactory centres in human ontogeny.

The olfactory centres are the evolutionary oldest and most conservative area of the telencephalon. Olfactory deficiencies are involved in a large spectrum of neurologic disorders and neurodegenerative diseases. The growing interest in human olfaction has been also been driven by COVID-19-induced transitional anosmia. Nevertheless, recent data on the human olfactory centres concerning normal histology and morphogenesis are rare. Published data in the field are mainly restricted to classic studies with non-uniform nomenclature and varied definitions of certain olfactory areas. While the olfactory system in model animals (rats, mice, and more rarely non-human primates) has been extensively investigated, the developmental timetable of olfactory centres in both human prenatal and postnatal ontogeny are poorly understood and unsystemised, which complicates the process of analysing human material, including medical researches. The main purpose of this review is to provide and discuss relevant morphological data on the normal ontogeny of the human olfactory centres, with a focus on the timetable of maturation and developmental cytoarchitecture, and with special reference to the definitions and terminology of certain olfactory areas.

Tocolytic Therapy Inhibiting Preterm Birth in High-Risk Populations: A Systematic Review and Meta-Analysis.

This systematic review aimed to identify the benefits and possible harms of tocolytic therapy for preterm labour management in the context of pregnant women with extremely preterm birth, multiple gestations, or growth-restricted foetuses. A comprehensive search using MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, and the WHO Global Index Medicus databases was conducted from 10 to 15 July 2021. We included randomized controlled trials and non-randomized studies that assessed the effects of tocolysis compared with placebo or no treatment. We found 744 reports and, finally, nine studies (three randomized controlled trials and six cohort studies) pertaining to women with <28 weeks of gestation were included. No eligible studies were identified among women with a multiple pregnancy or a growth-restricted foetus. A meta-analysis of the trial data showed that there were no clear differences in perinatal death nor for a delay in birth. Non-randomized evidence showed that tocolysis delayed birth by 7 days, though there was no clear difference for preterm birth. In summary, it remains unclear whether tocolytic therapy for inhibiting preterm labour is beneficial for these subgroups of women and their newborns. Further well-designed randomized controlled trials and observational studies are needed to address the lack of evidence regarding tocolytic agents in these populations.

Variations of the popliteal artery: A review.

The popliteal artery is located in the popliteal fossa. In addition to its other branches, it divides into two terminal branches, the anterior and posterior tibial arteries, which are subject to numerous morphological variations. The purpose of this review is to compile several authors' classifications of the patterns of terminal branching of the popliteal artery among adults and to describe the division among foetuses, as described in the current literature. Pathologies of the popliteal artery such as popliteal artery aneurysm and popliteal artery entrapment syndrome and methods for treating them, like open surgery and endovascular interventions are also discussed. Awareness of the morphological variations of the popliteal artery is important for radiologists and surgeons as it allows the risk of complications during surgery to be reduced.

Topography of the common fibular nerve terminal division in human foetuses.

BACKGROUND: The progress of paediatric surgery and increasingly better diagnosis of foetal defects require detailed knowledge of human developmental anatomy. Precise knowledge of the anatomy of innervation of the lower extremities corresponds to this subject and is not only cognitive but also clinically important. The end of the common fibular nerve is superficially located in the area exposed to frequent injuries as well as in the area subject to possible surgical repair procedures. MATERIALS AND METHODS: The analysis was carried out on 200 human foetuses aged from the 113th day to 222nd day of foetal life. The study material is a part of local foetal collection. The study incorporated the following methods: anthropological, preparational and image acquisition which was acquired with the use of high-resolution digital camera. Statistical analysis was carried out with the use of STATISTICA package. RESULTS: Based on the research results the new typology of the examined nerve was determined. The head of the fibula was the criterion: (i) high division - above the head of the fibula (1%); (ii) intermediate division - at the height of the head of the fibula (34%); (iii) low division - below the head of the fibula (65%). The mathematical analysis did not reveal statistically significant bilateral and gender differences. Moreover the additional branch was observed in 30% of foetuses, regardless of age class. This branch occurred in 50% of cases in both sides of the foetus. This nerve was defined as the accessory fibular nerve (nervous fibularis/peroneus accessorius). CONCLUSIONS: The created unique typology of the terminal division of common fibular nerve is an important supplement to the anatomical knowledge and at the same time, due to the peripheral and superficial location of the described structures, it has a relatively high clinical significance.

Morphometric profile in foetuses and evolution of Achilles tendon.

BACKGROUND: The Achilles tendon (AT) develops from the merge of the tendinous part of the gastrocnemius (GM) and soleus (SM) muscles. The AT is the structural base for the biomechanical work of the ankle joint. Understanding morphometry of the AT is crucial due to the tendon vulnerability to rupture and damage which requires further surgical repair and management. Despite its clinical significance, data concerning measurements of the AT in human foetuses are scare. The aim of our study was to assess the AT, GM and SM morphometry in human foetuses. MATERIALS AND METHODS: Thirty-seven spontaneously-aborted human foetuses (17 male, 20 female) aged 18-38 weeks of gestation were examined. The morphometry of the GM, SM and AT were evaluated. RESULTS: No significant correlation between sex or side and size of the AT in human foetuses was observed. The only significant correlation was between sex and the length of the tendon of the SM; in 3rd trimester it was longer in male than in female. In 2nd trimester the SM muscle to tendon ratio was higher in female than in male. CONCLUSIONS: There was no significant correlation between sex or side and size of the AT in human foetuses, probably due to scant muscle load during prenatal period.

Morphological variability of the fibularis tertius tendon in human foetuses.

BACKGROUND: In adults, the fibularis tertius (FT) demonstrates great morphological variation. The present study classifies the types of FT insertion in human foetuses and compares their prevalence to the prevailing classification among adults. MATERIALS AND METHODS: Fifty spontaneously-aborted human foetuses (19 male, 31 female, 100 upper limbs in total) aged 18-38 weeks of gestation at death were examined. The foetuses were obtained from spontaneous abortion after parental consent. The study was performed in accordance with the legal procedures in force in Poland and with the Body Donation Programme for both adults and foetuses. RESULTS: The most common type of FT found was type VI (32%), characterised by a bifurcated distal attachment: a main tendon inserting onto the base of the fourth metatarsal bone, and accessory bands inserting onto the fourth interosseous space. Five other types were observed: type IV (20%), with a single tendon inserting distally to the fascia covering the fourth interosseous space; type I (18%), with a single tendon inserting distally onto the shaft of the fifth metatarsal bone; type V (14%), with a bifurcated arrangement comprising a main tendon characterised by a very wide insertion onto the base of the fifth metatarsal bone and an accessory band inserting onto the base of the fourth metatarsal bone; and type III (12%) with a single tendon inserting distally onto the shaft of the fourth metatarsal bone and fascia covering the fourth interosseous space. Finally, type II (4%) was characterised by a single tendon inserting onto the base of the fifth metatarsal bone via a very wide distal insertion. CONCLUSIONS: The FT demonstrates high morphological variability, with the most common configuration found in adults - a single insertion onto metatarsal 5 - being actually uncommonly found in foetuses.

The morphological variability of fibularis tertius origin in human foetuses.

BACKGROUND: The purpose of this study was to characterize the morphology of the fibularis tertius (FT) in human fetuses, and to provide a classification based on its modes of origin in human fetuses. METHODS: The material comprised 100extremities from 50 spontaneously aborted human fetuses (19 male, 31 female, 100 lowerlimbs in total), aged 18-38 weeks of gestation. These were dissected and the presence or absence of the FT muscle as well as the type of its proximal attachment were determined, and the FT was measured morphometrically. RESULTS: The FT was present in 50% of fetuses. Four types of FT muscle origin were identified. The most common was Type 2, characterized by an origin on the middle third of the fibula and the intermuscular septum. Three other types were observed: Type 1 with an origin located on proximal third of the fibula and to the intermuscular septum, Type 3 characterized by an absent muscle belly, and an independent tendon originating from the that of the extensor digitorum longus, and Type 4 with an origin located on the distal third of the fibula and the intermuscular septum. CONCLUSIONS: The fibularis tertius demonstrates high morphological variability, with the most common origin located on third of the fibula and to the intermuscular septum.

Causes of spontaneous sow deaths in the farrowing units of 10 Danish sow herds.

This study established the causes and timing of spontaneous sow deaths in the farrowing units of ten Danish sow herds. Herds participated for seven to 15 months during 2018-19. We received data (production data and detailed information on the sows that died) on a total of 126 sows. Fifty-three sows were necropsied, and tissues were evaluated histopathologically. Twenty-four percent of the sows died 0-5 days postpartum. The main cause of death in the study was liver lobe torsion, which was diagnosed in 22 of 53 necropsied sows (42%). Deaths caused by liver lobe torsions were less often seen during the 0-5 day postpartum period compared to deaths caused by other reasons (P = 0.002). Seven of the necropsied sows (13%) died from endotoxaemic shock from retained foetuses. This cause of death was seen in seven of ten herds. These sows typically died 1-3 days postpartum. Pneumonia accounted for 13% of deaths in the necropsied sows, but the majority of these sows originated from one herd experiencing a respiratory outbreak caused by the introduction of M. hyopneumonia. Less prevalent causes of death in the study were torsion of the intestinal segment (8%), suspected cardiovascular collapse (8%), rupture of blood vessels (uterine and nonuterine) (8%), gastric ulcer (4%), sepsis (2%) and liver abscess (2%). We concluded that liver lobe torsion needs further attention to establish the background of this surprisingly prevalent cause of death. Furthermore, a need for procedures that ensure efficient farrowing was identified.

Relationship between Prenatal Characteristics and Body Condition and Endocrine Profile in Rabbits.

This study evaluated the relationship between prenatal characteristics and body condition and endocrine profile. A total of 25 non-lactating multiparous females were used. Body condition, measured as body weight and perirenal fat thickness, non-esterified fatty acids (NEFA), leptin, progesterone and 17ß-estradiol were recorded at mating and 12 d of gestation. Ovulation rate, number of foetuses, ovary and foetal weight, length and weight of uterine horn, available space per foetus and maternal and foetal placental morphometry were recorded at 12 d of gestation. Ovulation rate showed a positive linear relationship with number of foetuses, ovary weight and NEFA. A negative linear relationship between ovulation rate and perirenal fat thickness and leptin was obtained. Ovulation rate was maximum when body weight and 17ß-estradiol were 4.4 kg and 22.7 pg/mL, respectively. Foetal weight showed a positive relationship with perirenal fat thickness and a negative relationship with leptin. An increase in progesterone and NEFA concentration was related to a positive linear increase in number of foetuses and in uterine horn weight. Space available per foetus was affected both by the number of vessels that reach the implantation site and by position of the foetus in the uterine horn. In conclusion, body condition during mating and early gestation should be maintained within an optimal range to ensure the best prenatal characteristics. While 17ß-estradiol, NEFA and leptin affected the ovulation rate, progesterone and NEFA affected foetal development. The number of vessels that reach the implantation site determines early foetal survival.