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ABSTRACT: The impact of the insecticide chlorpyrifos (CPF) on the mammalian digestive system has been poorly described. The present study aimed at evaluating the effect of chronic, low-dose exposure to CPF on the composition of the gut microbiota in a Simulator of the Human Intestinal Microbial Ecosystem: the SHIME® and in rats. The SHIME® comprises six reactor vessels (stomach to colon). The colonic segments were inoculated with feces from healthy humans. Then, the simulator was exposed to a daily dose of 1 mg of CPF for 30 days. The changes over time in the populations of bacteria were examined at different time points: prior to pesticide exposure (as a control) and after exposure. In parallel, pregnant rats were gavaged daily with 1 mg/kg of CPF (or vehicle) until the pups were weaned. Next, the rats were gavaged with same dose of CPF until 60 days of age (adulthood). Then, samples of different parts of the digestive tract were collected under sterile conditions for microbiological assessment. Chronic, low-dose exposure to CPF in the SHIME® and in the rat was found to induce dysbiosis in the microbial community with, in particular, proliferation of subpopulations of some strains and a decrease in the numbers of others bacteria. In compliance with European guidelines, the use of the SHIME® in vitro tool would help to (1) elucidate the final health effect of toxic agents and (2) minimize (though not fully replace) animal testing. Indeed, certain parameters would still have to be studied further in vivo.
Environmental Science and Pollution Research 11/2012; · 2.65 Impact Factor
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ABSTRACT: Maternal smoking during pregnancy is associated with adverse perinatal outcomes. In view of concerns about underreporting, benzo[a]pyrene (B[a]P)-DNA adducts could be used to provide information about long-term in utero exposure to smoking but have not previously been used with samples from neonates. This study aimed to verify whether B[a]P-DNA adducts could accurately assess tobacco smoke exposure during fetal life. The objectives were to correlate B[a]P-DNA adduct levels with active maternal and passive smoking and to determine the sensitivity and specificity of smoking and nonsmoking status by comparing neonatal B[a]P-DNA adduct levels with those of maternal self-reports.
B[a]P-DNA adducts in neonatal buccal cell samples were determined by a competitive immunoassay. Three groups of neonates were constituted according to maternal self-reported smoking status during pregnancy: nonsmokers (n=25; control group), <10 cigarettes per day (n=18; S- group), or >10 cigarettes per day (n=21; S+ group).
The mean B[a]P-DNA adduct level rose significantly when comparing the controls with the S- and S+ groups. Maternal active smoking had the strongest effect on B[a]P-DNA adduct levels in neonates. A cross analysis between B[a]P-DNA adduct levels and maternal self-reported levels revealed high sensitivity and specificity.
This preliminary study suggests that B[a]P-DNA adducts are reliable biomarkers for the screening of long-term in utero exposure to smoking and are accurate when compared with maternal self-reported levels of active smoking. Detection of B[a]P-DNA adducts in neonates could provide a useful, noninvasive tool in clinical risk assessment studies but would benefit from further confirmation with another validated biomarker.
Therapeutic drug monitoring 06/2011; 33(3):329-35. · 2.43 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the impact of gastro-oesophageal acid reflux on sleep in neonates and, reciprocally, the influence of wakefulness (W) and sleep stages on the characteristics of the reflux (including the retrograde bolus migration of oesophageal acid contents). The pH and multichannel intraluminal impedance were measured during nocturnal polysomnography in 25 infants hospitalised for suspicion of gastro-oesophageal reflux. Two groups were constituted according to whether or not the infants displayed gastro-oesophageal reflux (i.e. a reflux group and a control group). There were no differences between the reflux and control groups in terms of sleep duration, sleep structure and sleep state change frequency. Vigilance states significantly influenced the gastro-oesophageal reflux pattern: the occurrence of gastro-oesophageal reflux episodes was greater during W (59 ± 32%) and active sleep (AS; 35 ± 30%) than during quiet sleep (QS; 6 ± 11%), whereas the mean duration of gastro-oesophageal reflux episodes was higher in QS than in W and AS. The percentage of retrograde bolus migrations of distal oesophageal acid content was significantly higher in AS (62 ± 26%) than in W (42 ± 26%) and QS (4.5 ± 9%). In neonates, gastro-oesophageal reflux occurred more frequently during W, whereas the physiological changes associated with sleep state increase the physiopathological impact of the gastro-oesophageal reflux. The duration of oesophagus-acid contact was greater during sleep; AS facilitated the retrograde migration of oesophageal acid content, and QS was characterised by the risk of prolonged acid mucosal contact.
Journal of Sleep Research 03/2011; 21(1):80-6. · 3.16 Impact Factor
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ABSTRACT: We aimed to assess the involvement of peripheral chemoreceptor tonic activity in the ventilatory pattern during sleep in preterm neonates exposed in utero to maternal smoking.
Peripheral chemoreceptor activity was measured at thermoneutrality in neonates (postmenstrual age: 36.1 +/- 1.2 weeks) born to nonsmoking (n = 21) or smoking (n = 16) mothers by performing a 30-second hyperoxic test during active and quiet sleep. Blood oxygen saturation, baseline ventilatory parameters, and central apnea were monitored.
Prenatal smoking exposure did not modify baseline ventilation. It was interesting to note that prenatal smoking exposure decreased the peripheral chemoreceptor tonic activity during active sleep and increased the response time during quiet sleep. These changes could explain the increase in the time spent in apnea (both with and without blood oxygen desaturation) and in the mean duration of apneic episodes with desaturation found in neonates exposed to smoking in utero. The involvement of a change in the chemoreceptor function is supported by the fact that the peripheral chemoreceptor tonic activity was negatively correlated with the mean duration of apneic episodes with desaturation in the control group only.
To our knowledge, this is the first study to reveal that prenatal smoking exposure does not directly modify baseline ventilatory parameters in the neonate but has a negative impact on peripheral chemoreceptor tonic activity. These alterations may increase the risk of sleep respiratory disorders, especially via apnea with desaturation.
PEDIATRICS 02/2010; 125(3):e592-9. · 4.47 Impact Factor
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ABSTRACT: The authors report the case of a baby boy born at a gestational age of 32 weeks who experienced a life-threatening event triggered by vagal overactivity, associated with a transient phase of inverse coupling with a 1:1 phase ratio between ECG and respiration, resulting in respiratory arrest. This case report highlights the vital importance of coupling between cardiac and respiratory oscillators, especially in premature infants or neonates.
Autonomic neuroscience: basic & clinical 10/2008; 143(1-2):79-82. · 1.82 Impact Factor
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ABSTRACT: To determine whether oral domperidone is associated with QT interval prolongation and ventricular arrhythmia and to identify factors that can influence these effects.
An electrocardiogram was performed before and after oral administration of domperidone in 31 neonates or infants classified into 3 groups according to gestational age.
Oral domperidone is associated with QTc prolongation except in infants with a gestational age less than 32 weeks of amenorrhea (P < .005). Mean QTc prolongation was 14 msec. On univariate analysis, oral domperidone-induced QTc prolongation was correlated with gestational age, birth weight, and elevated serum potassium. On multivariate analysis, after adjustment for gestational age, serum potassium was the only factor independently associated with interval QT prolongation during treatment. No ventricular arrhythmias were observed.
This study shows a significant association between oral domperidone therapy and QTc prolongation. Two risk factors were identified: advanced gestational age and serum potassium at the upper limit of normal. It is recommended that measurement of the QT interval be done before and after oral domperidone therapy.
The Journal of pediatrics 06/2008; 153(5):663-6. · 4.02 Impact Factor
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ABSTRACT: Apneic episodes are frequent in the preterm neonate and particularly in active sleep (AS), when functional residual capacity (FRC) can be decreased. Furthermore, FRC may be inversely correlated with the speed of blood-O(2)-desaturation. We evaluated the potential involvement of FRC in the mechanisms responsible for blood-O(2)-desaturation during short central apneic events (>3 s) in "late-preterm" infants and analyzed the specific influence of sleep state. Apneic events were scored in 29 neonates (postmenstrual age: 36.1 +/- 1.2 wk) during AS and quiet sleep (QS). FRC was measured during well-established periods of regular breathing. Apneas with blood-O(2)-desaturation (drop in SpO(2) >5% from the baseline, lowest SpO(2) during apnea: 91.4 +/- 1.8%) were more frequent in AS than in QS, whereas no difference was seen for apneas without desaturation. The magnitude of the FRC did not depend on the sleep state. In AS only, there was a negative relationship between FRC and the proportion of apneas with desaturation. Even in late preterm infants who do not experience long-lasting apnea, blood-O(2)-desaturation during short apneic events is related (in AS but not QS) to a low baseline FRC. Sleep stage differences argue for a major role of AS-related mechanisms in the occurrence of these apneas.
Pediatric Research 05/2008; 64(2):171-6. · 2.70 Impact Factor
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ABSTRACT: The incidence of apnea in neonates depends on a number of factors, including sleep state and thermoregulation.
To assess the role of thermal drive (body heat loss [BHL]) in the mechanisms underlying short episodes of central apnea during active and quiet sleep in neonates.
Twenty-two neonates (postconceptional age: 36.3 +/- 0.9 weeks) were exposed at thermoneutral (incubator temperature: 32.5 degrees C), warm (34.2 degrees C), and cool (30.4 degrees C) conditions during 3 consecutive morning naps. Oxygen consumption (VO2), skin and rectal temperatures, and central apnea were scored during active sleep and quiet sleep. The thermal drive was expressed as BHL calculated using indirect partitional calorimetry.
As expected, apnea occurred more frequently in active sleep than in quiet sleep (P < 0.001). The frequency of apnea in active sleep was higher in the warm condition (P < 0.05). In contrast, apnea episodes were less frequent (P < 0.05) and shorter (P < 0.05) for cool exposure, during which VO2 and rectal temperature increased. The frequency (P < 0.001, r2 = 0.31), mean (P < 0.05, r2 = 0.06), and maximum (P < 0.001, r2 = 0.19) durations of apnea were correlated with the BHL: the greater the BHL (body cooling), the less frequent and the shorter the apnea episodes. In contrast, no relationship between apnea and mean skin or rectal temperature was observed.
Apneic events were more closely related to BHL than to body temperatures. In cool exposure, the decreases in the duration and frequency of apneic episodes suggest that these events depend on the metabolic drive (which is proportional to energy expenditure).
Sleep 04/2008; 31(4):549-56. · 5.05 Impact Factor
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ABSTRACT: 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 O(2) saturation (Sp(o2)) and ventilatory parameters were monitored before and during the hyperoxic test. Short episodes of apnea (frequency and mean duration) were recorded during the morning's 3-h interfeeding interval. Pretest Sp(o2) 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 (rho = -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 P(o2)/P(co2) combination and apnea.
Pediatric Research 12/2007; 62(5):591-6. · 2.70 Impact Factor
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ABSTRACT: The aim of the present study was to test the thermoregulatory feeding control hypothesis in sleeping, premature infants.
In premature infants, the energy supply from food intake is crucial for (in order of importance): organ operation, body homeothermia, and optimal growth. The Himms-Hagen model of thermoregulatory feeding control involving activation of heat production by brown adipose tissue (BAT) was formulated on the basis of work in (awake) rats. This hypothesis has also been put forward for the human neonate, which can also use BAT to produce metabolic heat. According to the model, feeding episodes occur during a transient increase in body temperature. Feeding is initiated by a dip in blood glucose concentration after sugar uptake by activated BAT.
In 14 neonates (bottle-fed on demand), food intake always took place during an increase in skin temperature (+0.19 +/- 0.21 degrees C). Awakening occurred 18 +/- 17 minutes after the minimum skin temperature level had been reached. When feeding time was imposed, feeding was not necessarily situated during an increase in skin temperature, and the sleep duration after food intake increased significantly (+43%). This could be considered as an adaptive response to the short-term sleep deprivation and/or stress elicited by an imposed feeding rhythm.
The validity of the model supports the use of on-demand feeding in neonatal care units, in accordance with the infant's physiological body temperature oscillations.
Obesity 10/2006; 14(9):1535-42. · 4.28 Impact Factor
