PBPK modeling to support risk assessment of pyrethroid exposure in French pregnant women.

BACKGROUND: Pyrethroids are widely used pesticides and are suspected to affect children's neurodevelopment. The characterization of pyrethroid exposure during critical windows of development, such as fetal development and prenatal life, is essential to ensure a better understanding of pyrethroids potential effects within the concept of Developmental Origins of Health and Disease. OBJECTIVE: The aim of this study was to estimate maternal exposure of French pregnant women from biomonitoring data and simulate maternal and fetal internal concentrations of 3 pyrethroids (permethrin, cypermethrin and deltamethrin) using a multi-substance pregnancy-PBPK (physiologically based pharmacokinetics) model. The estimated maternal exposures were compared to newly proposed toxicological reference values (TRV) children specific also called draft child-specific reference value to assess pyrethroid exposure risk during pregnancy i.e. during the in utero exposure period. METHODS: A pregnancy-PBPK model was developed based on an existing adult pyrethroids model. The maternal exposure to each parent compound of pregnant women of the Elfe (French Longitudinal Study since Childhood) cohort was estimated by reverse dosimetry based on urinary biomonitoring data. To identify permethrin and cypermethrin contribution to their common urinary biomarkers of exposure, an exposure ratio based on biomarkers in hair was tested. Finally, exposure estimates were compared to current and draft child-specific reference values derived from rodent prenatal and postnatal exposure studies. RESULTS: The main contributor to maternal pyrethroid diet intake is cis-permethrin. In blood, total internal concentrations main contributor is deltamethrin. In brain, the major contributors to internal pyrethroid exposure are deltamethrin for fetuses and cis-permethrin for mothers. Risk is identified only for permethrin when referring to the draft child-specific reference value. 2.5% of the population exceeded permethrin draft child-specific reference value. CONCLUSIONS: A new reverse dosimetry approach using PBPK model combined with human biomonitoring data in urine and hair was proposed to estimate Elfe pregnant population exposure to a pyrethroids mixture with common metabolites.

Characterizing environmental geographic inequalities using an integrated exposure assessment.

BACKGROUND: At a regional or continental scale, the characterization of environmental health inequities (EHI) expresses the idea that populations are not equal in the face of pollution. It implies an analysis be conducted in order to identify and manage the areas at risk of overexposure where an increasing risk to human health is suspected. The development of methods is a prerequisite for implementing public health activities aimed at protecting populations. METHODS: This paper presents the methodological framework developed by INERIS (French National Institute for Industrial Environment and Risks) to identify a common framework for a structured and operationalized assessment of human exposure. An integrated exposure assessment approach has been developed to integrate the multiplicity of exposure pathways from various sources, through a series of models enabling the final exposure of a population to be defined. RESULTS: Measured data from environmental networks reflecting the actual contamination of the environment are used to gauge the population's exposure. Sophisticated methods of spatial analysis are applied to include additional information and take benefit of spatial and inter-variable correlation to improve data representativeness and characterize the associated uncertainty. Integrated approaches bring together all the information available for assessing the source-to-human-dose continuum using a Geographic Information System, multimedia exposure and toxicokinetic model. DISCUSSION: One of the objectives of the integrated approach was to demonstrate the feasibility of building complex realistic exposure scenarios satisfying the needs of stakeholders and the accuracy of the modelling predictions at a fine spatial-temporal resolution. A case study is presented to provide a specific application of the proposed framework and how the results could be used to identify an overexposed population. CONCLUSION: This framework could be used for many purposes, such as mapping EHI, identifying vulnerable populations and providing determinants of exposure to manage and plan remedial actions and to assess the spatial relationships between health and the environment to identify factors that influence the variability of disease patterns.

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 neonate's 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.

Influence of radiofrequency electromagnetic fields exposure on sleep patterns in preterm neonates.

PURPOSE: The study objective was to assess the influence of radiofrequency electromagnetic fields (RF-EMF) exposure on sleep patterns in preterm newborns. We hypothesized that an increase in RF-EMF exposure levels would alter infants' sleep structure parameters. MATERIALS AND METHODS: Individual, continuous measurements of RF-EMF levels were performed in 29 hospitalized preterm newborns throughout the first 21 days after birth. The last day, overnight sleep structure was recorded by polysomnography. Relationships between both chronic (three-week period) and acute (polysomnographic period) RF-EMF levels with sleep parameters were computed. RESULTS: At median levels, the main chronic effect was an increase in indeterminate sleep with RF-EMF exposure. At the highest exposure levels found in our study, an increase in RF-EMF levels increased sleep fragmentation. No significant relationship was found between acute RF-EMF levels and sleep parameters. CONCLUSIONS: Despite no consolidated disruption in sleep structure, this study is the first to show that some sleep parameters seem to have a certain sensitivity to chronic - but not acute - RF-EMF exposure in preterm newborns. Further studies are needed to confirm our results and examine possible mid- to long-term, sleep-related cardiorespiratory and neurodevelopmental outcomes.

Optimizing coronary artery opacification and 3D reconstruction from human cadaver hearts in anatomy research.

OBJECTIVE: This study seeks to identify the ideal dilution rate of a radiopaque product to optimize the visualization of coronary arteries and their branches within human cadaver hearts. The process involves obtaining images in the anatomy laboratory and subsequently constructing a three-dimensional model. MATERIALS AND METHODS: We utilized 30 human hearts fixed in 10 % formalin (9 females and 21 males) with a mean age of 79 ± 5 years. The initial experiment, involving the first four hearts (referred to as "group 1"), encountered difficulties in opacifying coronary arteries. In this phase, a probabilistic injection of 20 % Visipaque and 80 % latex, with coronary sinus ostium closure, was performed. The optimal mixture ratio was then determined as 33 % Visipaque and 66 % latex. Recognizing the need for on-site injection at the CT Scan table, this protocol was applied to the subsequent 11 hearts in "group 2." Closure of the coronary sinus was deemed unnecessary. The final 15 hearts, constituting "group 3," revealed that the injection should be gradual, maintaining controlled pressure between 120 and 150 mm Hg. Post-injection, hearts were scanned with the injected coronary arteries using an Optima 660 CT scanner. Two-dimensional images were acquired with parameters set at 64 × 0.625 mm, 100 kV, 300-400 mA, and a rotation of 0.5 s. Subsequently, 3D reconstruction was conducted using Advantage Workstation 4.7 (GE Healthcare) and volume rendering with Volume Viewer software, version 15. RESULTS: Significant differences in the percentage of opacified coronaries were observed among the three groups (p < 0.005). This variation underscores the learning curve and comprehension required before establishing a reliable method. Group 1 (N = 4) demonstrated minimal opacification, group 2 (N = 11) displayed partial opacification, while group 3 (N = 15) achieved 100 % opacification of coronary arteries. CONCLUSION: The successive experiments culminated in the development of a protocol for CT imaging, enabling accurate three-dimensional reconstruction of the normal anatomy of the main and secondary coronary arteries. Our work is grounded in a series of progressively refined and successful experiments.

How to Control Exposure to Fifth-Generation Radiofrequencies in Preterm Newborns in Incubator.

Infant and family centered development care reduces infant distress and supports the parent and infant's individual abilities. However, a new environmental factor is daily encountered: the radiofrequency electromagnetic fields (RF EMFs) with the most recent fifth-generation (5G) technology. Currently, the effects of RF EMF during development are discussed in animal models. The neonatal intensive care units are not spared from this stressor. The objective of this study was to evaluate the efficacy of a novel, electromagnetically insulating incubator cover to prevent the preterm infant from RF EMF exposure. A personal dosimeter was placed on the mattress of a closed incubator. Periods of exposure to low, medium, and high levels of 5G RF were delivered in the presence or absence of the incubator cover. The use of a silver-copper cover reduced the intensity of 5G radiofrequency levels from 52% to 57% (p < 0.0001), allowing to easily apply the precautionary principle.

Spatio-temporal assessment of pregnant women exposure to chlorpyrifos at a regional scale.

BACKGROUND: The aim of this study was to use an integrated exposure assessment approach, combining spatiotemporal modeling of environmental exposure and fate of the chemical to assess the exposure of vulnerable populations. In this study, chlorpyrifos exposure of pregnant women in Picardy was evaluated at a regional scale during 1 year. This approach provided a mapping of exposure indicators of pregnant women to chlorpyrifos over fine spatial and temporal resolutions using a GIS environment. METHODS: Fate and transport models (emission, atmospheric dispersion, multimedia exposure, PBPK) were combined with environmental databases in a GIS environment. Quantities spread over agricultural fields were simulated and integrated into a modeling chain coupling models. The fate and transport of chlorpyrifos was characterized by an atmospheric dispersion statistical metamodel and the dynamiCROP model. Then, the multimedia model Modul'ERS was used to predict chlorpyrifos daily exposure doses which were integrated in a PBPK model to compute biomarker of exposure (TCPy urinary concentrations). For the concentration predictions, two scenarios (lower bound and upper bound) were built. RESULTS: At fine spatio-temporal resolutions, the cartography of biomarkers in the lower bound scenario clearly highlights agricultural areas. In these maps, some specific areas and hotspots appear as potentially more exposed specifically during application period. Overall, predictions were close to biomonitoring data and ingestion route was the main contributor to chlorpyrifos exposure. CONCLUSIONS: This study demonstrated the feasibility of an integrated approach for the evaluation of chlorpyrifos exposure which allows the comparison between modeled predictions and biomonitoring data.

Are benzo[a]pyrene-DNA adducts an accurate biomarker of long-term in utero exposure to smoking?

BACKGROUND: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Relationship between vertical jumping performance and anthropometric characteristics during growth in boys and girls.

The aim of the study was to compare vertical jumping performances in boys and girls during growth. The maximum heights attained in a countermovement jump (CMJ) and squat jump (SJ) were measured using an Ergojump Bosco System. Average power output (PO) was recorded, and percentage of fast-twitch (%FT) muscle fiber distribution was estimated during the rebound jump. Differences in the maximum CMJ and SJ (CMJ-SJ) heights were calculated. Regressions between PO and age, lean body mass (LBM), and leg muscle volume (LMV), respectively, were computed for 240 boys and 239 girls (aged 11-16 years). Height, LMV, and body mass values were larger in boys than girls aged 14 years. Both groups had a similar body mass index independently of age. The CMJ, SJ, PO, and %FT were larger in boys than in girls between 12 and 16 years of age. Strong correlations were found between PO and age in the population as a whole, and between PO and LBM, PO and LMV in each group. The CMJ-SJ decreased with increasing age in both groups without significant differences. Conclusion Jumping performance increases during growth, with gender differences manifesting from 14 years onwards due to the much greater increase in leg length and LMV in boys than in girls.

The influence of in utero exposure to smoking on sleep patterns in preterm neonates.

BACKGROUND: In utero exposure to smoking is known to adversely affect brain regions involved in behavioral state organization and could therefore interact with the neurophysiological development of neonates. STUDY OBJECTIVES: The present study investigated the effects of prenatal smoking exposure on sleep patterns in the preterm neonate. DESIGN: Overnight sleep patterns were polysomnographically assessed at thermoneutrality. Sleep continuity and structure were scored for the respective frequencies, durations and percentages of active, quiet, and indeterminate sleep and wakefulness after sleep onset. The number and duration of body movements were also analyzed. SETTING: The neonatal intensive care unit at Amiens University Medical Center (France). PARTICIPANTS: Healthy preterm neonates (postconceptional age: 33.9 +/- 6.0 weeks) were enrolled according to whether their mothers had not smoked at all during pregnancy (control group, n=19), smoked less during pregnancy (low-smoking group, Slow, n=10), or smoked more (heavy-smoking group, Sheavy n=10) than 10 cigarettes per day throughout pregnancy. MEASUREMENTS AND RESULTS: Neonates born to heavy-smoking mothers had a significantly lower mean birth weight than controls (-21%) and displayed disrupted sleep structure and continuity: they slept less overall (with a higher proportion of active sleep and a lower proportion of quiet sleep) and had more wakefulness after sleep onset. Compared with controls, neonates from both smoking groups displayed more body movements and, as a result, more disturbed sleep. CONCLUSIONS: High prenatal smoking exposure modifies sleep patterns in preterm neonates by disrupting sleep organization and increasing nocturnal body movements. These findings raise the question of the repercussions of these sleep disturbances (at what is a critical stage in brain development) on the child's physiological and neurobehavioral outcomes.

Influence of thermal drive on central sleep apnea in the preterm neonate.

BACKGROUND: The incidence of apnea in neonates depends on a number of factors, including sleep state and thermoregulation. OBJECTIVE: 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. MATERIAL AND METHOD: 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. RESULTS: 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. CONCLUSION: 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).

The hypoxic test in preterm neonates reinvestigated.

AIM: We currently lack a suitable gold-standard method for implementation on modern equipment to assess peripheral chemoreceptor sensitivity. The aim of the present study was to develop an accurate and reproducible method for assessing peripheral chemoreceptors sensitivity in sleeping preterm neonates. METHODS: A poïkilocapnic hypoxic test was performed twice during rapid eye movement sleep (REM sleep) and non-rapid eye movement sleep (nonREM sleep). The infant breathed hypoxic gas (15% O2 ) for 60 s. The ventilatory response to hypoxia was assessed by comparing minute ventilation during the control period (21% O2 ) with successive 4-cycles sequences during hypoxia. We detected the first statistically significant increase in minute ventilation and recorded the corresponding response time. RESULTS: During normoxia, minute ventilation was higher during REM sleep than in nonREM sleep (428.1 mL · min-1 · kg-1 [307.7-633.6]; 388.8 mL · min-1 · kg-1 [264.7-608.0], respectively; P = 0.001). After hypoxia, minute ventilation increased in both REM and nonREM sleep. The response was significantly higher in REM than in nonREM (25.3% [10.8-80.0] and 16.8% [7.5-33.2], respectively; P = 0.005). The intraclass correlation coefficients for all respiratory parameters were above 0.90. CONCLUSION: We have developed a highly reliable method for assessing peripheral chemoreceptors sensitivity at the response time to hypoxia. In the future, researchers could use this method to assess the involvement of peripheral chemoreceptors in infants who experience chronic hypoxia (e.g. in bronchopulmonary dysplasia and recurrent apnea).

Isolated hypospadias: The impact of prenatal exposure to pesticides, as determined by meconium analysis.

Although endocrine-disrupting chemicals (EDCs, including pesticides) are thought to increase the risk of hypospadias, no compounds have been formally identified in this context. Human studies may now be possible via the assessment of meconium as a marker of chronic prenatal exposure. The objective of the present study was to determine whether or not prenatal exposure to pesticides (as detected in meconium) constitutes a risk factor for isolated hypospadias. In a case-control study performed between 2011 and 2014 in northern France, male newborns with isolated hypospadias (n = 25) were matched at birth with controls (n = 58). Newborns with obvious genetic or hormonal anomalies, undescended testis, micropenis, a congenital syndrome or a family history of hypospadias were not included. Neonatal and parental data were collected. Foetal exposure was assessed by determining the meconium concentrations of the pesticides or metabolites (organophosphates, carbamates, phenylurea, and phenoxyherbicides) most commonly used in the region. Risk factors were assessed in a multivariate analysis. The pesticides most commonly detected in meconium were organophosphates (in up to 98.6% of samples, depending on the substance) and phenylurea (>85.5%). A multivariate analysis revealed an association between isolated hypospadias and the presence in meconium of the phenylurea herbicide isoproturon and of the phenoxyherbicide 2-methyl-4-chlorophenoxyacetic acid (odds ratio [95% confidence interval]: 5.94 [1.03-34.11] and 4.75 [1.20-18.76]) respectively). We conclude that prenatal exposure to these two herbicides (as assessed by meconium analysis) was correlated with the occurrence of isolated hypospadias. The results of our case-control study (i) suggest that prenatal exposure to pesticides interferes with the development of the male genitalia, and (ii) emphasize the importance of preventing pregnant women from being exposed to EDCs in general and pesticides in particular.

Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates.

BACKGROUND AND OBJECTIVE: Caffeine treatment is widely used in nursing care to reduce the risk of apnoea in premature neonates. To check the therapeutic efficacy of the treatment against apnoea, caffeine concentration in blood is an important indicator. The present study was aimed at building a pharmacokinetic model as a basis for a medical decision support tool. METHODS: In the proposed model, time dependence of physiological parameters is introduced to describe rapid growth of neonates. To take into account the large variability in the population, the pharmacokinetic model is embedded in a population structure. The whole model is inferred within a Bayesian framework. To update caffeine concentration predictions as data of an incoming patient are collected, we propose a fast method that can be used in a medical context. This involves the sequential updating of model parameters (at individual and population levels) via a stochastic particle algorithm. RESULTS: Our model provides better predictions than the ones obtained with models previously published. We show, through an example, that sequential updating improves predictions of caffeine concentration in blood (reduce bias and length of credibility intervals). The update of the pharmacokinetic model using body mass and caffeine concentration data is studied. It shows how informative caffeine concentration data are in contrast to body mass data. CONCLUSION: This study provides the methodological basis to predict caffeine concentration in blood, after a given treatment if data are collected on the treated neonate.

Response to Elwood, M. et al., Comment on: Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. Int. J. Environ. Res. Public Health 2017, 14, 27.

Dear Editor, Thank you for inviting us to reply to a "Comment" paper to our published paper "Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring" (Authors: Elodie Haraux, Karine Braun, Philippe Buisson, Erwan Stéphan-Blanchard, Jannick Ricard, Camille Devauchelle, Bernard Boudailliez, Pierre Tourneux, Richard Gouron, Karen Chardon).[...].

Erratum: Haraux, E., et al. Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring. Int. J. Environ. Res. Public Health 2016, 14, 27.

Due to an error during production, some data presented in Table 1 in the Experimental section of the published paper [1] were incorrect.[...].

Impact of oocytes with CLCG on ICSI outcomes and their potential relation to pesticide exposure.

BACKGROUND: Oocyte quality is a key limiting factor in female fertility which is primarily reflected in morphological features. Centrally located cytoplasm granulation (CLCG) is one type of cytoplasmic dimorphism exhibited by oocytes that could be linked to pesticide exposure with a significant risk of decreased ICSI outcomes. METHODS: This retrospective study included 633 women who were part of an intracytoplasmic spermatozoa injection (ICSI) program between 2009 and 2011. The participants lived in the Picardy region of France and had been exposed to pesticides. The participants were divided in two groups based on prevalence of oocytes with CLCG (LCLCG [n = 83]: low prevalence of oocytes with CLCG under 25%. HCLCG [n = 68]: high prevalence of CLCG over 75%). The embryological and clinical outcomes were analysed for both groups and were calculated using the difference between the two values. RESULTS: Results for couples with HCLCG compared to LCLCG showed a decrease in embryo cleavage, ongoing pregnancy, and live birth rates (82%, 14%, 13% vs 99%, 32%, 30%, respectively).The early miscarriage rate was increased (47% vs 11%), with an OR of 3.1 (95%CI [2.1-4.1]). Due to high pesticide exposure (over 3000 g/ha), there is a higher risk of a resulting disturbed oocyte cohort with a high prevalence of CLCG over 75%. CONCLUSION: The high prevalence of oocytes with CLCG over 75% has a negative effect on embryos and the general ICSI clinical outcomes. Furthermore, a putative association between pesticide exposure and risk of CLCG was identified, justifying the need for further research and a potential need to find alternative assisted reproductive technologies for these couples. TRIAL REGISTRATION: Tabacfertimasc. ID number: ID2011-A00634-37 ; registered 2011/2/8.

The dynamics of cardiac autonomic control in sleeping preterm neonates exposed in utero to smoking.

OBJECTIVE: We aimed to determine whether in utero exposure to smoking may influence the activity and dynamics of cardiac autonomic control in preterm infants. We hypothesized that cardiac autonomic control is altered in preterm infants exposed prenatally to smoking and that these effects may vary as a function of the sleep state. METHODS: We studied healthy, preterm neonates born to mothers who had smoked throughout pregnancy but not since birth (n=16). In utero-exposed neonates were matched with control preterm neonates born to non-smoking mothers (n=18). Cardiac autonomic control was monitored as a function of the sleep state by assessing heart rate variability with both linear and non-linear methods. RESULTS: Preterm neonates with in utero exposure to smoking displayed alterations (relative to control neonates) in short-term cardiac autonomic control in all sleep states. These alterations included low vagal activity, elevated sympathetic activity, and low complexity and adaptability in heart rate control dynamics. CONCLUSIONS: Our results constitute direct evidence that cardiac autonomic activity and control are altered in sleeping preterm infants exposed to smoking in utero. SIGNIFICANCE: These alterations may place the affected infants at a higher risk of neurological and cardiovascular complications, which could conceivably persist throughout childhood and adulthood.

Maternal Exposure to Domestic Hair Cosmetics and Occupational Endocrine Disruptors Is Associated with a Higher Risk of Hypospadias in the Offspring.

Pregnant women are exposed to various chemical products at home and at work. Some of these products contain endocrine-disrupting chemicals (EDCs) such as cosmetics, pesticides, industrial chemicals, heavy metals, plastics or medications that could alter sexual differentiation and increase the risk of hypospadias. We evaluated maternal occupational and household exposures that could constitute risk factors for hypospadias. From 2011 to 2014, we enrolled 57 full-term newborns with hypospadias and three randomly selected controls per case (162 control newborns), matched for gestational age, from 11 maternity units in Picardy, France. Neonatal and parental data were collected at birth (personal characteristics, maternal lifestyle, and medical history). Maternal occupational exposure was assessed by a job-exposure matrix for EDCs from a job history questionnaire completed by mothers. Odds ratios (OR) and 95% confidence intervals (CI) were calculated with univariate and multivariable logistic regression, and adjusted for relevant covariates. Multivariate analysis showed a strong association between hypospadias and potential maternal occupational exposure to EDCs and maternal household use of hair cosmetics (OR 6.1, 95% CI: 1.1-34.9; OR: 9.6, 95% CI: 1.4-66.1, respectively). Our results suggest that maternal occupational exposure to EDCs is a risk factor for hypospadias and suggests a possible influence of household use of hair cosmetics during early pregnancy on the incidence of hypospadias in the offspring. A larger study with more accurate exposure assessment should evaluate the impact of EDCs in hair cosmetics on the incidence of hypospadias.

Feeding behavior in neonates whose diet contained medium-chain triacylglycerols: short-term effects on thermoregulation and sleep.

BACKGROUND: Feeding formulas for premature infants often contain medium-chain triacylglycerols (MCTs). However, previous studies in animals and adults showed that MCTs may decrease food intake. OBJECTIVES: The objectives were to determine in hospitalized premature infants whether food intake is modified by dietary MCT supply and to assess the effects on thermoregulation and sleep, which are involved in the regulation of energy metabolism and in the optimal physiologic development of the neonates. DESIGN: Food intake, body mass, and nutritional efficiency during 3 consecutive days were compared in 2 groups of neonates according to the fat composition of their feeding formula [MCT group: 37% MCT, 63% long-chain triacylglycerols (LCTs); LCT group: 100% LCT]. On the third day, sleep and metabolic rate were recorded in the morning during an interval between meals. RESULTS: Regardless of day, energy intake was greater in the MCT group than in the LCT group (x difference: 67.3 kJ x kg(-1) x d(-1); P = 0.007). Metabolic rate (1.8 mL x min(-1) x kg(-1); P < 0.001), cheek skin temperature (0.31 degrees C; P = 0.04), and total sleep time (52 min; P = 0.01) were also higher in the MCT group. CONCLUSION: The ratio of MCTs to LCTs in neonates' feeding formulas can modify physiologic functions involved in energy-balance regulation.