Simon Nusinovici

Calf-Level Factors Associated with Bovine Neonatal Pancytopenia – A Multi-Country Case-Control Study

Bovine neonatal pancytopenia (BNP), a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves). Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health) vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval – ci 2.4, 134.4; pu200a=u200a0.005), and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; pu200a=u200a0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; pu200a=u200a<0.001). Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; pu200a=u200a0.012), but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; pu200a=u200a0.024). Feeding exclusively dam’s milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; pu200a=u200a0.002). The population attributable fractions were 0.84 (ci 0.68, 0.92) for PregSure vaccination, 0.13 (ci 0.06, 0.19) for feeding other cows’ colostrum, and 0.15 (ci 0.08, 0.22) for feeding dam’s milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in others.

Post-term growth and cognitive development at 5 years of age in preterm children: Evidence from a prospective population-based cohort

While the effects of growth from birth to expected term on the subsequent development of preterm children has attracted plentiful attention, less is known about the effects of post-term growth. We aimed to delineate distinct patterns of post-term growth and to determine their association with the cognitive development of preterm children. Data from a prospective population-based cohort of 3,850 surviving infants born at less than 35 weeks of gestational age were used. Growth was assessed as the Body Mass Index (BMI) Z-scores at 3, 9, 18, 24, 36, 48, and 60 months. Cognitive development at five years of age was evaluated by the Global School Adaptation score (GSA). Latent class analysis was implemented to identify distinct growth patterns and logistic regressions based on propensity matching were used to evaluate the relationship between identified growth trajectories and cognitive development. Four patterns of post-term growth were identified: a normal group with a Z-score consistently around zero during childhood (n = 2,469; 64%); a group with an early rapid rise in the BMI Z-score, but only up to 2 years of age (n = 195; 5%); a group with a slow yet steady rise in the BMI Z-score during childhood (n = 510; 13%); and a group with a negative Z-score growth until 3 years of age (n = 676; 18%). The group with a slow yet steady rise in the BMI Z-score was significantly associated with low GSA scores. Our findings indicate heterogeneous post-term growth of preterm children, with potential for association with their cognitive development.

Using Animal Performance Data to Evidence the Under-Reporting of Case Herds during an Epizootic: Application to an Outbreak of Bluetongue in Cattle

Following the emergence of the Bluetongue virus serotype 8 (BTV-8) in France in 2006, a surveillance system (both passive and active) was implemented to detect and follow precociously the progression of the epizootic wave. This system did not allow a precise estimation of the extent of the epizootic. Infection by BTV-8 is associated with a decrease of fertility. The objective of this study was to evaluate whether a decrease in fertility can be used to evidence the under-reporting of cases during an epizootic and to quantify to what extent non-reported cases contribute to the total burden of the epizootic. The cow fertility in herds in the outbreak area (reported or not) was monitored around the date of clinical signs. A geostatistical interpolation method was used to estimate a date of clinical signs for non-reported herds. This interpolation was based on the spatiotemporal dynamic of confirmed case herds reported in 2007. Decreases in fertility were evidenced for both types of herds around the date of clinical signs. In non-reported herds, the decrease fertility was large (60% of the effect in reported herds), suggesting that some of these herds have been infected by the virus during 2007. Production losses in non-reported infected herds could thus contribute to an important part of the total burden of the epizootic. Overall, results indicate that performance data can be used to evidence the under-reporting during an epizootic. This approach could be generalized to pathogens that affect cattle’s performance, including zoonotic agents such as Coxiella burnetii or Rift Valley fever virus.

Fetal and Postnatal Head Circumference Growth: Synergetic Factors for Neurodevelopmental Outcome at 2 Years of Age for Preterm Infants

Abstract: Preterm infants present higher risk of non-optimal neurodevelopmental outcome. Fetal and postnatal growth, in particular head circumference (HC), is associated with neurodevelopmental outcome. Objectives: We aimed to calculate the relationship between HC at birth, HC delta Z-score (between birth and hospital discharge), and non-optimal neurodevelopmental outcome at 2 years of corrected age in preterm infants. Methods: Surviving infants born ≤34 weeks of gestation were included in the analysis. The relationship between the risk of being non-optimal at 2 years and both HC at birth and HC growth was assessed. The 2 Z-scores were considered first independently and then simultaneously to investigate their effect on the risk of non-optimality using a generalized additive model. Results: A total of 4,046 infants with both HC measures at birth and hospital discharge were included. Infants with small HC at birth (Z-score <-2 SD), or presenting suboptimal HC growth (dZ-score <-2 SD), are at higher risk of non-optimal neurodevelopmental outcome at 2 years (respectively OR 1.7 [95% CI 1.4-2] and OR 1.4 [95% CI 1.2-1.8]). Interestingly, patients cumulating small HC Z-score at birth (-2 SD) and presenting catch-down growth (HC dZ-score [-2 SD]) have a significantly increased risk for neurocognitive impairment (OR >2) while adjusting for gestational age, twin status, sex, and socioeconomic information. Conclusions: HC at birth and HC dZ-score between birth and hospital discharge are synergistically associated to neurodevelopmental outcome at 2 years of corrected age, in a population-based prospective cohort of preterm infants born ≤34 weeks of gestation.

Impact of parental separation or divorce on school performance in preterm children: A population-based study

The objective of this study was to quantify the possible decrease in school performance at five years of age in preterm children associated with parental separation or divorce, and to test whether this effect varies according to the child’s age at the time of the separation. This study included 3,308 infants delivered at < 35 weeks of gestation born between 2003 and 2011 who were enrolled in the population-based LIFT cohort and who had an optimal neurodevelopmental outcome at two years of age. These infants were evaluated by their teachers to assess their abilities and behavior when they had reached five years of age, using the Global School Adaptation (GSA) questionnaire. The mean GSA score was 50.8 points. Parental separations (assessed as parents either living together or living separately) were associated with a decrease in school performance at five years of age, although this was only the case for children who exhibited difficulties at school (3.7 points, p < 0.01). A decrease in school performance only occurred when parental separations took place between 3 and 5 years after the child’s birth. Parental separation was associated with a decrease in these children’s levels of motivation, autonomy, and manual dexterity. This study indicates that preterm infants of parents who had separated are particularly at risk of a lower scholar performance.

Efficacy of Antenatal Corticosteroid Treatment on Neurodevelopmental Outcome according to Head Circumference at Birth

Background: There are concerns about the efficacy of antenatal corticosteroid treatment (ACT) in the growth-restricted fetus. Objective: To evaluate the effect of ACT on neurodevelopmental outcome at 2 years of corrected age according to the z score of birth head circumference (ZS HC) in a large prospective cohort of preterm infants. Methods: This study was conducted as a population-based, prospective, multicenter study, including 4,965 infants born between 24 and 33 weeks gestation and whose status regarding ACT and the measurement of head circumference at birth were available. They were evaluated at 2 years of corrected age to assess neurological outcome. Three approaches were considered to estimate the effect of ACT on neurodevelopment: (i) logistic regression with adjustment on propensity score, (ii) weighted logistic regression using the inverse probability of treatment weighting method, and (iii) 1:1 matching of gestational age, ZS HC, and propensity score between treated and nontreated infants. Results: ACT was documented in 60% of infants. Three groups of infants were considered according to their ZS HC: between -3 and -1 standard deviation (SD), -1 and +1 SD, and +1 and +3 SD, respectively. ACT was associated with a significant improvement of neurodevelopmental outcome only for infants with an ZS HC of between +1 and +3 SD (adjusted OR 1.72; 95% CI 1.06-2.79). Moreover, ORs estimated in the -3 to -1 and +1 to +3 categories were significantly different. Conclusion: We found beneficial effects of ACT on neurodevelopmental outcomes at 2 years of corrected age only in preterm infants with a ZS HC >1 SD.

Herd-level animal management factors associated with the occurrence of bovine neonatal pancytopenia in calves in a multi-country study

Since 2007, mortality associated with a previously unreported haemorrhagic disease has been observed in young calves in several European countries. The syndrome, which has been named ‘bovine neonatal pancytopenia’ (BNP), is characterised by thrombocytopenia, leukocytopenia and a panmyelophthisis. A herd-level case-control study was conducted in four BNP affected countries (Belgium, France, Germany and the Netherlands) to identify herd management risk factors for BNP occurrence. Data were collected using structured face-to-face and telephone interviews of farm managers and their local veterinarians. In total, 363 case farms and 887 control farms were included in a matched multivariable conditional logistic regression analysis. Case-control status was strongly associated with the odds of herd level use of the vaccine PregSure® BVD (PregSure, Pfizer Animal Health) (matched adjusted odds ratio (OR) 107.2; 95% CI: 41.0–280.1). This was also the case for the practices of feeding calves colostrum from the calf’s own dam (OR 2.0; 95% CI: 1.1–3.4) or feeding pooled colostrum (OR 4.1; 95% CI: 1.9–8.8). Given that the study had relatively high statistical power and represented a variety of cattle production and husbandry systems, it can be concluded with some confidence that no other herd level management factors are competent causes for a sufficient cause of BNP occurrence on herd level. It is suggested that genetic characteristics of the dams and BNP calves should be the focus of further investigations aimed at identifying the currently missing component causes that together with PregSure vaccination and colostrum feeding represent a sufficient cause for occurrence of BNP in calves.

Impact of preterm birth on parental separation: a French population-based longitudinal study.

Objective The objective of this study was to investigate both the effects of low gestational age and infant’s neurodevelopmental outcome at 2u2009years of age on the risk of parental separation within 7u2009years of giving birth. Design Prospective. Setting 24 maternity clinics in the Pays-de-la-Loire region. Participants This study included 5732 infants delivered at <35 weeks of gestation born between 2005 and 2013 who were enrolled in the population-based Loire Infant Follow-up Team cohort and who had a neurodevelopmental evaluation at 2u2009years. This neurodevelopmental evaluation was based on a physical examination, a psychomotor evaluation and a parent-completed questionnaire. Outcome measure Risk of parental separation (parents living together or parents living separately). Results Ten percent (572/5732) of the parents reported having undergone separation during the follow-up period. A mediation analysis showed that low gestational age had no direct effect on the risk of parental separation. Moreover, a non-optimal neurodevelopment at 2 years was associated with an increased risk of parental separation corresponding to a HR=1.49(1.23 to 1.80). Finally, the increased risk of parental separation was aggravated by low socioeconomic conditions. Conclusions The effect of low gestational age on the risk of parental separation was mediated by the infant’s neurodevelopment.

Comparaison de l’efficacité à 2 ans du fingolimod versus natalizumab sur la cohorte nantaise de patients atteints de sclérose en plaques rémittente-récurrente

Introduction Le fingolimod et le natalizumab partagent la meme indication de traitement de seconde intention dans la SEP remittente-recurrente (RR). Pourtant, l’efficacite de ces deux molecules est-elle comparablexa0? Objectifs L’objectif de notre etude etait de comparer l’efficacite du fingolimod versus celle du natalizumab sur des criteres de jugement cliniques et morphologiques, dans la cohorte de patients nantais atteints de SEP-RR a deux ans de suivi. Patients et methodes Deux cent douze patients ont ete inclus entre 2007xa0et janvier 2013, en intention de traiter. Les patients etaient âges de 18xa0a 65xa0ans, avaient eu une IRM cerebrale et un score EDSS inferieur a 5,5xa0dans les six mois precedent le traitement. Les criteres de jugement a deux ans etaient la proportion de patients avec au moins une poussee, une majoration du score EDSS, une nouvelle lesion gadolinium positive ou une nouvelle lesion T2xa0sur l’IRM. Resultats Quarante-neuf patients ont ete inclus dans le groupe fingolimod et 73xa0dans le groupe natalizumab. L’ odd ratio ajuste sur les facteurs confondants, calcule sur la proportion de patients avec une nouvelle lesion gadolinium a deux ans, retrouvait un effet protecteur du natalizumab en comparaison au fingolimod, 0,11 (0,02–0,61) vs 1xa0 p xa0=xa00,011xa0; ainsi que pour ceux avec une nouvelle lesion T2, 0,11 (0,03–0,38) vs 1xa0 p Discussion Notre etude a montre une plus grande efficacite du natalizumab sur le controle des lesions IRM. Elle n’a pas permis de montrer une difference d’efficacite sur les criteres de jugement cliniques probablement a cause des biais lies aux etudes observationnelles et a un groupe de patients plus severe a l’inclusion, dans le groupe natalizumab. Conclusion Dans notre cohorte de patients nantais atteints de SEP-RR a deux ans de suivi, le natalizumab etait significativement plus efficace que le fingolimod sur le controle des lesions IRM.