Birth defects among offspring of California firefighters, 2007-2019.

PURPOSE: Limited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects. METHODS: Data from California birth certificates (2007-2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories. RESULTS: Offspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings. CONCLUSIONS: Offspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure.

Interoception Primes Emotional Processing: Multimodal Evidence from Neurodegeneration.

Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson's disease (PD), and Alzheimer's disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson's disease), whereas persons with Alzheimer's disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.

Neonatal experiences with ethanol intoxication modify respiratory and thermoregulatory plasticity and affect subsequent ethanol intake in rats.

Different studies have focused on the deleterious consequences of binge-like or chronic exposure to ethanol during the brain growth spurt period (third human gestational trimester) that in the rat corresponds to postnatal days (PDs) 3-10. The present study analyzed behavioral and physiological disruptions caused by relatively brief binge-like exposures (PDs 3, 5, and 7) with an ethanol dose lower (3.0 g/kg) than those frequently employed to examine teratological effects during this stage in development. At PD 9, pups were exposed to ethanol doses ranging between .0-3.0 g/kg and tested in terms of breathing patterns and thermoregulation. At PDs 11 and 12, ethanol intake was examined. The main findings were as follows: i) pre-exposure to the drug resulted in brief depressions in breathing frequencies and an exacerbated predisposition toward apneic episodes; ii) these effects were not dependent upon thermoregulatory alterations; iii) early ethanol treatment increased initial consumption of the drug which also caused a marked hypothermia that appeared to regulate a subsequent decrement in ethanol consumption; and iv) ethanol exposure retarded overall body growth and even one exposure to the drug (PD 9) was sufficient to reduce brain weights although there were no indications of microcephaly. In conjunction with studies performed during the late gestational period in the rat, the results indicate that relatively brief binge-like episodes during a critical window of brain vulnerability disrupts the respiratory network and exacerbates initial acceptance of the drug. In addition, ethanol treatments were not found to induce tolerance relative to respiratory and thermal disruptions.

Assessment of substance exposures in nail clipping samples: A systematic review.

BACKGROUND: Studies of prenatal substance exposure often rely on self-report, urine drug screens, and/or analyses of blood or meconium biomarkers. Accuracy of these measures is limited when assessing exposure over many weeks or months of gestation. Nails are increasingly being considered as a matrix from which to assess substance exposure. This systematic review synthesizes data on the validity of detecting alcohol, nicotine, cannabis, and opioid from nail clippings, with an emphasis on prenatal exposure assessment. METHODS: The systematic review was conducted using PRISMA 2020 guidelines. Seven databases were searched with keywords relevant to the four substances of interest. Results were summarized grouping manuscripts by the exposure of interest with focus on accuracy and feasibility. RESULTS: Of 2384 papers initially identified, 35 manuscripts were included in our qualitative synthesis. Only a few studies specifically looked at pregnant individuals or mother-child dyads. Across the four substances, many studies demonstrated a dose-response relationship between exposure and concentration of analytes in nails. Nail assays appear to detect lower level of exposure compared to hair; however, sample insufficiency, especially for multi-substance assays, remains a limitation. CONCLUSIONS: Based on the reviewed studies, nail clippings are an acceptable and potentially preferable matrix for the evaluation of these four prenatal substances when sampling frequency and/or study design necessitates assessment of past exposures over an extended period. Nails have the advantage of infrequent sampling and minimal invasiveness to assess a broad exposure period. Future studies should examine validity of analytes in toenail versus fingernail clippings.

The HEALthy Brain and Child Development Study (HBCD) experience: Recruiting and retaining diverse families in a longitudinal, multi-method early childhood study.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. Given its aim to examine the impact of adversity and protective factors on children's outcomes, the recruitment and retention of families who have a wide diversity in experiences are essential. However, the unfortunate history of inequitable treatment of underrepresented families in research and the risks with which some participants will contend (e.g., substance use) makes their recruitment and retention in social science and neuroscience research particularly challenging. This article explores strategies that the HBCD Study has developed to recruit and retain participants, including marginalized, underserved, and hard-to-reach populations, capitalizing on the extant literature and the researchers' own experiences. In this paper, we address strategies to recruit and retain families within HBCD, including: 1) creating experiences that engender trust and promote relationships; 2) maintaining connections with participants over time; 3) ensuring appropriate compensation and supports; 4) considerations for study materials and procedures; and 5) community engagement. The implementation of these strategies may increase representation and inclusiveness, as well as improve the quality of the resulting data.

Birth Defects Associated with Prenatal Alcohol Exposure-A Review.

Since the recognition of fetal alcohol syndrome, alcohol has been accepted as a human teratogen. However, little is known about the relation between prenatal alcohol exposure and the spectrum of associated major birth defects. The objective of this review was to summarize data on the association of major congenital abnormalities and prenatal alcohol exposure. We included all major birth defects according to ICD-10 classification. We found that the strongest evidence to date lies in the research examining herniation (gastroschisis and omphalocele), oral clefts (cleft lip with or without palate and cleft palate) and cardiac defects. There is less consistent evidence supporting the association between prenatal alcohol exposure and anomalies of gastrointestinal system, diaphragmatic hernia, genitourinary system and neural tube defects. We found no material support for PAE and choanal atresia, biliary atresia or clubfoot.

Ethanol's disruptive effects upon early breathing plasticity and blood parameters associated with hypoxia and hypercapnia.

Early ethanol exposure affects respiratory neuroplasticity; a risk factor associated with the Sudden Infant Death Syndrome. High and chronic ethanol doses exert long-lasting effects upon respiratory rates, apneic episodes and ventilatory processes triggered by hypoxia. The present study was performed in 3-9-day-old rat pups. Respiratory processes under normoxic and hypoxic conditions were analyzed in pups intoxicated with different ethanol doses which were pre-exposed or not to the drug. A second major goal was to examine if acute and/or chronic early ethanol exposure affects blood parameters related with hypercapnic or hypoxic states. In Experiment 1, at postnatal day 9, animals previously treated with ethanol (2.0 g/kg) or vehicle (0.0 g/kg) were tested sober or intoxicated with 0.75, 1.37 or 2.00 g/kg ethanol. The test involved sequential air conditions defined as initial normoxia, hypoxia and recovery normoxia. Motor activity was also evaluated. In Experiment 2, blood parameters indicative of possible hypoxic and hypercapnic states were assessed as a function of early chronic or acute experiences with the drug. The main results of Experiment 1 were as follows: i) ethanol's depressant effects upon respiratory rates increased as a function of sequential treatment with the drug (sensitization); ii) ethanol inhibited apneic episodes even when employing the lowest dose at test (0.75 g/kg); iii) the hyperventilatory response caused by hypoxia negatively correlated with the ethanol dose administered at test; iv) ventilatory long-term facilitation (LTF) during recovery normoxia was observed in pups pre-exposed to the drug and in pups that received the different ethanol doses at test; v) self-grooming increased in pups treated with either 1.37 or 2.00 g/kg ethanol. The main result of Experiment 2 indicated that acute as well as chronic ethanol exposure results in acidosis-hypercapnia. The results indicate that early and brief experiences with ethanol are sufficient to affect different respiratory plasticity processes as well as blood biomarkers indicative of acidosis-hypercapnia. An association between the LTF process and the acidosis-hypercapnic state caused by ethanol seems to exist. The mentioned experiences with the drug are sufficient to result in an anomalous programming of respiratory patterns and metabolic conditions.

Fetal Alcohol Programming of Subsequent Alcohol Affinity: A Review Based on Preclinical, Clinical and Epidemiological Studies.

The anatomo-physiological disruptions inherent to different categories of the Fetal Alcohol Spectrum Disorder do not encompass all the negative consequences derived from intrauterine ethanol (EtOH) exposure. Preclinical, clinical and epidemiological studies show that prenatal EtOH exposure also results in early programming of alcohol affinity. This affinity has been addressed through the examination of how EtOH prenatally exposed organisms recognize and prefer the drug's chemosensory cues and their predisposition to exhibit heightened voluntary EtOH intake during infancy and adolescence. In altricial species these processes are determined by the interaction of at least three factors during stages equivalent to the 2nd and 3rd human gestational trimester: (i) fetal processing of the drug's olfactory and gustatory attributes present in the prenatal milieu; (ii) EtOH's recruitment of central reinforcing effects that also imply progressive sensitization to the drug's motivational properties; and (iii) an associative learning process involving the prior two factors. This Pavlovian learning phenomenon is dependent upon the recruitment of the opioid system and studies also indicate a significant role of EtOH's principal metabolite (acetaldehyde, ACD) which is rapidly generated in the brain via the catalase system. The central and rapid accumulation of this metabolite represents a major factor involved in the process of fetal alcohol programming. According to recent investigations, it appears that ACD exerts early positive reinforcing consequences and antianxiety effects (negative reinforcement). Finally, this review also acknowledges human clinical and epidemiological studies indicating that moderate and binge-like drinking episodes during gestation result in neonatal recognition of EtOH's chemosensory properties coupled with a preference towards these cues. As a whole, the studies under discussion emphasize the notion that even subteratogenic EtOH exposure during fetal life seizes early functional sensory and learning capabilities that pathologically shape subsequent physiological and behavioral reactivity towards the drug.

Respiratory and emotional reactivity to ethanol odor in human neonates is dependent upon maternal drinking patterns during pregnancy.

BACKGROUND: Beyond the well-known deleterious effects of ethanol defining Fetal Alcohol Spectrum Disorders (FASD), the notion of fetal alcohol programming has gained scientific support. This phenomenon implies early neural plasticity relative to learning mechanisms comprising ethanol´s sensory cues and physiological effects of the drug; among others, its reinforcing properties and its depressant effects upon respiration. In this study, as a function of differential ethanol exposure during gestation, we analyzed neonatal physiological and behavioral responsiveness recruited by the odor of the drug. METHODS: A factorial design defined by maternal ethanol intake during pregnancy (Low, n = 38; Moderate, n = 18 or High, n = 19) and olfactory stimulation (ethanol odor and/or or a novel scent) served as the basis of the study. Neonatal respiratory and cardiac frequencies, oxygen saturation levels and appetitive or aversive facial expressions, served as dependent variables. RESULTS: Newborns of High drinkers exhibited significant physiological and behavioral signs indicative of alcohol odor recognition; specifically, respiratory depressions and exacerbated appetitive facial reactions coupled with diminished aversive expressions. Respiratory depressions were not accompanied by heart rate accelerations (cardiorespiratory dysautonomia). According to ROC curve analyses respiratory and behavioral reactivity were predictive of high maternal intake patterns. CONCLUSIONS: These results validate the notion of human fetal alcohol programming that is detected immediately after birth. The reported early functional signs indicative of relatively high alcohol gestational exposure should broaden our capability of diagnosing FASD and lead to appropriate primary or secondary clinical interventions (Registry of Health Research N.3201- RePIS, Córdoba, Argentina).