Véronique Bach

Échanges thermiques et thermorégulation chez le nouveau-né

The newborns energy expenditure is used in order of priority for: (i) basic metabolism; (ii) body temperature regulation and (iii) body growth. Thermal regulation is an important part of energy expenditure, especially for low birth-weight infants or preterm newborns. The heat exchanges with the environment are greater in the infant than in the adult, explaining the increased risk of body hypo- or hyperthermia. The newborn infant is a homeotherm, but over a long period of time, he cannot maintain the thermal processes. Further developments are expected to improve the infants thermal environment, with assessment of the various heat exchange mechanisms by conduction, convection, radiation and evaporation. The quantification of the respective parts of these exchanges would improve nursing care through clinical procedures or equipment used to ensure the control of the optimal thermohygrometric conditions in incubators, especially when the likelihood of excessive body cooling is high. The present review focuses on the various body heat exchange mechanisms, the thermoregulation processes of the newborn, and their implications in clinical usage and limitations in the neonatal intensive care unit.

Ventilatory response to a hyperoxic test is related to the frequency of short apneic episodes in late preterm neonates.

Chemoreception is frequently involved in the processes underlying apnea in premature infants. Apnea could result from a decrease in carotid body effectiveness. However, increased carotid body activity could also initiate apnea through hypocapnia following hyperventilation when the receptors are stimulated. The aim of this study was to analyze the relationship between carotid body effectiveness and short apneic episodes in older preterm neonates. Carotid body effectiveness was assessed at thermoneutrality in 36 premature neonates (2.07 ± 0.26 kg) by performing a 30-s hyperoxic test during sleep, the oxygen inhalation involving a ventilation decrease. Blood O2 saturation (Spo2) and ventilatory parameters were monitored before and during the hyperoxic test. Short episodes of apnea (frequency and mean duration) were recorded during the mornings 3-h interfeeding interval. Pretest Spo2 was not related to any of the measured respiratory parameters. A higher frequency of short apneic episodes was linked to a greater ventilation decrease in response to the hyperoxic test (ρ = −0.32; p = 0.01). Increased carotid body response is correlated with greater apneic episodes frequency, even in the absence of concomitant oxygen desaturation. Fetal or early postnatal hypoxemia could have increased peripheral chemoreceptor activity, which could initiate a “overshoot/undershoot” situation, which in turn could induce a critical Po2/Pco2 combination and apnea.

Chlorpyrifos Exposure During Perinatal Period Affects Intestinal Microbiota Associated With Delay of Maturation of Digestive Tract in Rats.

Objectives: Pesticide exposure via residues in food may be especially harmful when it takes place in the developing child. The present study was designed to assess the impact of perinatal exposure to chlorpyrifos (CPF, an insecticide known to cross the placental barrier). Methods: Female rats were exposed to oral CPF (1 or 5 mg kg−1 day−1 vs vehicle controls) from gestation onset up to weaning of the pups that were individually gavaged (CPF or vehicle) thereafter. Two developmental time points were studied: weaning (day 21) and adulthood (day 60). After sacrifice, samples from the intestinal tract and other organs underwent microbiological and histological analyses. Results: Rat pups exposed to 5 mg kg−1 day−1 CPF were both significantly smaller (body length) and lighter than controls. Exposure to CPF was associated with changes in the histological structures (shorter and thinner intestinal villosities), an intestinal microbial dysbiosis, and increased bacterial translocation in the spleen and liver. These significant microbial changes in the gut were associated with impaired epithelium protection (mucin-2) and microbial pattern recognition receptor (Toll-like 2 and 4) gene expression. Conclusions: Exposure to CPF during gestation and development affected the pups’ intestinal development, with morphological alteration of the structures involved in nutrient absorption, intestinal microbial dysbiosis, alteration of mucosal barrier (mucin-2), stimulation of the innate immune system, and increased bacterial translocation. Perinatal exposure to CPF may therefore have short- and long-term impacts on the digestive tract.

Brain blood flow and extracerebral carotid circulation during sleep in rat.

Cerebral blood flow (CBF) and blood flow (BF) in extracerebral head structures were measured during the sleep-wake cycle in rats using radioactive microspheres. While no statistically significant changes occurred in the transition from Waking to quiet sleep (also referred to as synchronized or non-REM Sleep), CBF increased significantly in active sleep (AS, also referred to as desynchronized or REM Sleep) in all structures considered, with the sole exception of the cerebellum. In extracerebral head structures, no significant state-dependent BF changes were found. Factor Analysis however extracted a common factor accounting for BF variability in the external carotid circulation. This factor was uncorrelated with CBF changes in AS, suggesting independent regulation of the two vascular beds in this sleep state.

Increased gut permeability and bacterial translocation after chronic chlorpyrifos exposure in rats.

The epitheliums barrier function is crucial for maintaining homeostasis and preventing the passage of food antigens and luminal bacteria. This function is essentially subserved by tight junctions (TJs), multiprotein complexes located in the most apical part of the lateral membrane. Some gastrointestinal disease states are associated with elevated intestinal permeability to macromolecules. In a study on rats, we determined the influence of chronic, daily ingestion of chlorpyrifos (CPF, a pesticide that crosses the placental barrier) during pre- and postnatal periods on intestinal permeability and TJ characteristics in the pups. Fluorescein isothiocyanate (FITC)-dextran was used as a marker of paracellular transport and mucosal barrier dysfunction. Pups were gavaged with FITC-dextran solution and blood samples were collected every 30 min for 400 min and analyzed spectrofluorimetrically. At sacrifice, different intestinal segments were resected and prepared for analysis of the transcripts (qPCR) and localization (using immunofluorescence) of ZO-1, occludin and claudins (scaffolding proteins that have a role in the constitution of TJs). In rats that had been exposed to CPF in utero and after birth, we observed a progressive increase in FITC-dextran passage across the epithelial barrier from 210 to 325 min at day 21 after birth (weaning) but not at day 60 (adulthood). At both ages, there were significant changes in intestinal TJ gene expression, with downregulation of ZO-1 and occludin and upregulation of claudins 1 and 4. In some intestinal segments, there were changes in the cellular localization of ZO-1 and claudin 4 immunostaining. Lastly, bacterial translocation to the spleen was also observed. The presence of CPF residues in food may disturb epithelial homeostasis in rats. Changes in TJ protein expression and localization may be involved in gut barrier dysfunction in this model. Uncontrolled passage of macromolecules and bacteria across the intestinal epithelium may be a risk factor for digestive inflammatory diseases.

Development of an analytical strategy based on LC-MS/MS for the measurement of different classes of pesticides and theirs metabolites in meconium: Application and characterisation of foetal exposure in France

It is important to evaluate the impact of pesticides on human health because exposure to these compounds has been linked to harmful effects in many research studies. This exposure may be particularly harmful during the early stages of development (e.g. the prenatal period). The aim of the present study was to develop an analytical strategy for quantifying a number of pesticides and their metabolites in meconium (the neonates first faeces), in order to characterize the extent of foetal exposure. The meconium sample was dried and grinded in order to homogenize the sample, prior to solid-liquid extraction and a purification by solid-phase extraction using a weak anion mixed-mode polymeric sorbent. Analyte separation and quantification was performed by liquid chromatography coupled to electrospray-triple quadrupole mass spectrometry. Five pesticide families (carbamates, organophosphates, pyrethroids, phenylureas and phenoxy herbicides) and their metabolites could be quantified in meconium with limits of quantification ranging between 0.2 ng/g and 200 ng/g. This method was applied to a set of 171 meconium samples collected in the Picardie region of northern France. The highest prevalence was observed for metabolites of organophosphates and carbamates (57.9% and 22.8%, respectively). The parent pesticides were rarely present and were only found at very low concentrations, except for the pyrethroids cyfluthrin and cypermethrin, which were found in 7.6% of meconium samples at concentrations of between 43.8 and 480 ng/g. The most frequently detected contaminant was the organophosphate metabolite dimethyl thiophosphate detected in 49.1% of the samples and quantified with a median concentration of 344 ng/g. These data evidence significant foetal exposure to organophosphate pesticides, pyrethroids and carbamates.

A reproducible means of assessing the metabolic heat status of preterm neonates

The aim of the present study was to validate the measurement of metabolic heat production using partitional calorimetry (PC) in preterm neonates exposed to a near-thermoneutral environment in an incubator. In order to reduce experimental uncertainty (due to the different variables involved in the calculation of body heat exchanges between the infant and the environment), the mean radiant temperature and the heat transfer coefficients for convection, radiation and evaporation were measured using a multisegment, anthropometric thermal mannequin which represents a small-for-gestational-age neonate (body surface area: 0.150 m2; simulated birth weight: 1500 g). The metabolic heat production calculated by PC was compared with the results of indirect respiratory calorimetry, which is rarely done in clinical setting since this method interferes with the neonates environment and requires a high degree of technical preparedness. The oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured in 20 preterm neonates exposed to thermoneutral (32.3 degrees C) and to slightly cool environments (30.2 degrees C). The mean skin temperature was measured by infrared thermography. The measurements were made during well-established periods of active and quiet sleep. Metabolic heat production was assessed by weighting each value of VO2 and VCO2 by the duration of the sleep stages. Our results showed that there was no significant difference between the two methods in terms of their estimation of metabolic activity at thermoneutrality (mean overall difference: 0.34 kJ h(-1) kg(-1)) and in the cool environment (0.26 kJ h(-1) kg(-1)). We observed significant interneonate variability. Partitional calorimetry enabled the prediction of body growth with a daily error of less than 5.3 g (2.38 kJ h(-1) kg(-1)) for all the neonates at thermoneutrality and for 85% of the subjects (3.03 kJ h(-1) kg(-1)) in the cool environment. Despite this limitation, we demonstrate here that PC provides reliable information for calculating the energy expenditure of individual preterm neonates on the basis of standard environmental input variables. We suggest that the technique can be advantageously used to assess the energy expenditure and normal growth of these infants.

Effects of warm and cool thermal conditions on ventilatory responses to hyperoxic test in neonates

Body temperature interacts with respiratory control, but it is unclear what sites or mechanisms mediate those interactions. We hypothesized that warm and cool thermal conditions affect the decrease in ventilation (VE) seen during the hyperoxic test (HT), a breathing response believed to reflect the strength of the peripheral chemoreceptor drive. A breath-by-breath analysis during a 30 s HT was performed in eight premature neonates (postconceptional age: 36 +/- 1 weeks) under neutral, warm, and cool thermal conditions. Quiet sleep (QS) and active sleep (AS) were scored by neurophysiological criteria. The VE fall was higher in AS than in QS, and warm and cool conditions significantly enhanced the response only in AS (-24.2 +/- 6.0, -39.1 +/- 9.1, and -37.5 +/- 14.1% in neutral, warm, and cool conditions, respectively). Central control mechanisms of the respiratory chemoreflex may explain the increase in peripheral chemoreceptor drive during AS in response to thermal challenges, which may produce increased breathing instability leading to apnea in early life.

Interindividual differences in the thermoregulatory response to cool exposure in sleeping neonates.

Abstract The responses of the thermoregulatory effectors vary greatly among neonates. Therefore, we assume that a small decrease in air temperature from thermoneutrality induces various thermoregulatory responses within neonates that represent an energy cost due to the cold defence processes. To determine the importance of this variability in nursing, 26 neonates were explored at thermoneutrality and in a cool environment (−1.5 °C from thermoneutrality) similar to that which occurs currently in clinical procedure. Oxygen consumption (V˙O2), oesophageal and skin temperatures, as well as sleep parameters were recorded continuously in both conditions. Analysis of all of the data from all of the neonates revealed that the cool exposure induced thermal and sleep disturbances, but V˙O2 did not increase and was not negatively correlated to body temperature (as might be expected). Analyses of individual data showed large variability in body temperature regulation: the neonates could be assigned to one of three groups according to the direction of the individual slopes of V˙O2 versus oesophageal or skin temperature. The groups also differed according to the sleep changes recorded in the cool condition. The results show that the definition of thermoneutrality should be revised by incorporating non only changes in the body temperature, but also the sleep disturbances (increased wakefulness and active sleep, decreased quiet sleep), which are criteria that are more sensitive to mild cool exposure. Thermoneutrality should be defined for each individual, since the results stress that the variability does not help to predict a general pattern of thermoregulatory responses in cool-exposed neonates.

Body temperature regulation in the newborn infant: interaction with sleep and clinical implications

Thermoregulation in newborn infant differs from that of adult. Comparisons between sleep stages show that, during rapid eye movements (REM) sleep, the impairment of thermoregulatory responses in adult is not observed in newborn. Both behavioral and autonomic temperature regulations are always operative in the range of air temperatures usually imposed. The interaction between sleep and thermoregulation seems to be less important in newborns than in adults, suggesting that sleep processes are well protected, reducing the probability of occurrence of central dysfunction. According to the model describing thermoregulation during sleep on the basis of changes in the hierarchical dominance of brain structures, either the influence of diencephalic structures is never depressed in REM sleep or the functional autonomy of the rhombencephalon is still relevant in the immature encephalon of the newborn. The thermoregulatory model also allows understanding of inter-individual differences in thermoregulation and levels of thermoneutrality. An attempt has also been made to learn the role of heat stroke in the production of sudden infant death syndrome when body heat loss is hampered.