Olfactory function after mild traumatic brain injury in children-a longitudinal case control study.

The prevalence of posttraumatic olfactory dysfunction in children after mild traumatic brain injury ranges from 3 to 58%, with potential factors influencing this variation, including traumatic brain injury severity and assessment methods. This prospective longitudinal study examines the association between mild traumatic brain injury and olfactory dysfunction in children. Seventy-five pediatric patients with mild traumatic brain injury and an age-matched healthy control group were enrolled. Olfactory function was assessed using the Sniffin' Sticks battery, which focuses on olfactory threshold and odor identification. The study found that children with mild traumatic brain injury had impaired olfactory function compared with healthy controls, particularly in olfactory threshold scores. The prevalence of olfactory dysfunction in the patient group was 33% and persisted for 1 yr. No significant association was found between traumatic brain injury symptoms (e.g. amnesia, loss of consciousness) and olfactory dysfunction. The study highlights the importance of assessing olfactory function in children after mild traumatic brain injury, given its potential impact on daily life. Although most olfactory dysfunction appears transient, long-term follow-up is essential to fully understand the recovery process. The findings add valuable insights to the limited literature on this topic and urge the inclusion of olfactory assessments in the management of pediatric mild traumatic brain injury.

Smelling of the mothers' diet in amniotic fluid by adult noses.

In this study, the transfer of odorants, namely vanilla, and garlic, into the amniotic fluid (AF) during the second trimester was investigated by examination of collected AF samples through healthy adults. Eleven AF samples were collected from pregnant women (aged 32.9 ±â€…4.9 yr, 16-25 wk of gestation) undergoing diagnostic amniocentesis after eating garlic oil or vanilla powder in high-fat yogurt. The control group did not receive food before amniocentesis. Two vanilla, 3 garlic, and 6 control samples were collected through amniocentesis 60-120 min after ingestion. Samples were collected at -80 °C and carefully defrosted over 12 h at the same time point. Sixteen healthy volunteers (8 males, aged 26.5 ±â€…5.0 yr) were asked to judge AF samples with potential garlic or vanilla odors from controls in a 2-alternative forced choice (2AFC) paradigm. Judges were able to identify vanilla in the AF samples with an estimated probability of 50%, resulting in a significant P-value of < 0.001. In contrast, the identification of garlic was unsuccessful with a P-value of 0.86, and only 2 judges were able to identify both vanilla and garlic. According to the results of this study, the vanilla odor probably passes into the amniotic fluid.

Vanilla odor promotes oral feeding in premature infants-A randomized controlled trial.

PROPOSE: Introducing early oral feeding in premature infants is important because it supports intestinal maturation and helps prevent infections. In addition, early oral feeding is likely to contribute to improved neurocognitive outcomes in preterm infants. Several holistic therapeutic strategies have been developed to improve feeding skills, food tolerance, and the ability to drink independently, including practices such as early breastfeeding, oral stimulation, and subsequent olfactory stimulation. Based on several studies using olfactory stimulation with food odors (vanilla, breast milk) to promote oral feeding in preterm infants this study was conducted to test the following hypothesis: Does olfactory stimulation with vanilla or milk odor (breast milk or formula) lead to a reduction in the time required for nasogastric tube weaning in premature infants older than 26 + 6 weeks of gestational age? In addition, does it influence secondary outcomes such as length of hospital stay, weight development, and attainment of greater amounts of independently consumed food? METHODS: Premature with complete or partial feeding by gastric tube and without ventilation were included. For this study, 207 infants over 26 + 6 gestational weeks were randomized into three different study groups. Before each feeding, an olfactory presentation was made with milk odor, a vanilla Sniffin' Stick, or a control stick. In the final analysis, 165 infants were included (87 males, 78 females). At the time of randomization, infants were on average 12 ± 9.5 days old. RESULTS: While the influence of vanilla and milk odor did not provide a significant difference from the control for the primary outcome, a secondary analysis showed a significant group difference in the cumulative amount of independently drunk food consumed in the first ten days was the highest amount in the vanilla group. This time period was chosen due to the high dropout rate after the first ten days. In addition, there was a promising significance for earlier hospital discharge for prematurely below 32 weeks of gestation receiving vanilla odor stimulation in comparison to milk odor stimulation. CONCLUSION: Although the primary outcome of this study (gastric tube removal) did not provide significant results, a significant benefit of vanilla olfactory stimulation for preterm infants was demonstrated in subgroup analysis above milk odor stimulation. Younger preterm infants seem to benefit from the stimulation.

qU-Sniff - the development of a short version of the Universal "Sniffin' Sticks" test.

OBJECTIVES: Extensive olfactory testing is sparsely applied in pediatric patients in clinical routine especially because of its time taking nature. Therefore a 5-item odor identification test (quick "U-Sniff", "qU-Sniff") from the 12-item "U-Sniff" test was developed. METHODS: A total of 724 normosmic children between 6 and 17 years of age, divided in four age groups, were included in this retrospective study. Additionally, 17 children with congenital anosmia in the same age range were included. To calculate test-retest reliability 90 participants from the healthy group were tested twice. RESULTS: The five most correctly identified odors from the 12-item "U-Sniff" test were: coffee (98 %), peach (95 %), flower (90 %), fish (88 %) and onion (84 %). Normosmic participants scored 4.71 ± 0.62 points on the "qU-Sniff" test. A significant correlation between results of the 12-item and 5-item test (n = 724; rs = 0.580; p < 0.001) and a significant test-retest reliability (rs = 0.626, p < 0.001) were shown. For "qU-Sniff" validation a ROC analysis to distinguish between anosmic patients and healthy controls was conducted for each age group separately. AUCs were as followed: i) 0.963 ± 0.018, p < 0,001; ii) 0.978 ± 0.013, p < 0.001; iii) 0.992 ± 0.006, p < 0.001; iv) 0.994 ± 0.005, p < 0.001. The cut-off value to determine anosmic and normosmic participants was <4 points. CONCLUSION: With the "qU-Sniff" test, we present a short screening tool for clinical routine with <4 points as cut-off to initiate more detailed olfactory testing.

Olfactory training effects in children after mild traumatic brain injury.

OBJECTIVE: Mild traumatic brain injury (mTBI) might impair the sense of smell and cognitive functioning. Repeated, systematic exposure to odors, i.e., olfactory training (OT) has been proposed for treatment of olfactory dysfunctions, including post-traumatic smell loss. Additionally, OT has been shown to mitigate cognitive deterioration in older population and enhance selected cognitive functions in adults. We aimed to investigate olfactory and cognitive effects of OT in the pediatric population after mTBI, likely to exhibit cognitive and olfactory deficits. METHODS: Our study comprised 159 children after mTBI and healthy controls aged 6-16 years (M = 9.68 ± 2.78 years, 107 males), who performed 6-months-long OT with a set of 4 either high- or low-concentrated odors. Before and after OT we assessed olfactory functions, fluid intelligence, and executive functions. RESULTS: OT with low-concentrated odors increased olfactory sensitivity in children after mTBI. Regardless of health status, children who underwent OT with low-concentrated odors had higher fluid intelligence scores at post-training measurement, whereas scores of children performing OT with high-concentrated odors did not change. CONCLUSION: Our study suggests that OT with low-concentrated odors might accelerate rehabilitation of olfactory sensitivity in children after mTBI and support cognitive functions in the area of fluid intelligence regardless of head trauma.

Genetics of congenital olfactory dysfunction: a systematic review of the literature.

Olfaction, as one of our 5 senses, plays an important role in our daily lives. It is connected to proper nutrition, social interaction, and protection mechanisms. Disorders affecting this sense consequently also affect the patients' general quality of life. Because the underlying genetics of congenital olfactory disorders (COD) have not been thoroughly investigated yet, this systematic review aimed at providing information on genes that have previously been reported to be mutated in patients suffering from COD. This was achieved by systematically reviewing existing literature on 3 databases, namely PubMed, Ovid Medline, and ISI Web of Science. Genes and the type of disorder, that is, isolated and/or syndromic COD were included in this study, as were the patients' associated abnormal features, which were categorized according to the affected organ(-system). Our research yielded 82 candidate genes/chromosome loci for isolated and/or syndromic COD. Our results revealed that the majority of these are implicated in syndromic COD, a few accounted for syndromic and isolated COD, and the least underly isolated COD. Most commonly, structures of the central nervous system displayed abnormalities. This study is meant to assist clinicians in determining the type of COD and detecting potentially abnormal features in patients with confirmed genetic variations. Future research will hopefully expand this list and thereby further improve our understanding of COD.

Assessment of Olfactory Function in Children and Adolescents: An Overview.

Valid and reliable tools for assessing olfactory function are necessary for the diagnosis of olfactory dysfunction. Olfactory testing can be challenging in a pediatric population due to shorter attention span, linguistic development, and lower olfactory experience in this age group. The aim of this article is to present an overview about olfactory tests that are suitable for a pediatric population. Publications were included when reporting new developed methods of psychophysical olfactory testing in children or adaptation and applications of existing olfactory tests for a pediatric population. Olfactory tests for all 3 major aspects of olfactory function-olfactory threshold, odor discrimination, and odor identification-were included. Olfactory tests were evaluated regarding test validity, test reliability, normative data, and test availability. The current literature shows that several tests are available to assess olfactory function in children. Especially odor identification abilities in a pediatric population are well examined and understood. Tests for olfactory threshold and odor discrimination are less frequently used. In terms of the abovementioned evaluation criteria, only a few tests met all or 3 of these 4 criteria. Based on the current literature the following tests can be recommended for valid and reliable olfactory testing in children: "U-Sniff" odor identification test, the "Sniffin' Sticks" olfactory threshold test, pBOT-6 olfactory threshold and odor identification test, NIH-Toolbox, and Smell Wheel. Age has to be considered when evaluating olfactory function in children.

Central Nervous System Processing of Floral Odor and Mother's Milk Odor in Infants.

Newborns have a functioning sense of smell at birth, which appears to be highly significant for feeding and bonding. Still, little is known about the cerebral odor processing in this age group. Studies of olfactory function relied mostly on behavioral, autonomic, and facial responses of infants. The aim of the present study was to investigate central odor processing in infants focusing on electroencephalography (EEG)-derived responses to biologically significant odors, namely a food and a non-food odor. A total of 21 term-born, healthy infants participated (11 boys and 10 girls; age range 2-9 months, mean 5.3 ± 2.2 months). Odor stimuli were presented using a computer-controlled olfactometer. Breast milk was used as food odor. Farnesol was presented as a non-food odor. In addition, odorless air was used as a control stimulus. Each stimulus was presented 30 times for 1 s with an interstimulus interval of 20 s. EEG was recorded from 9 electrodes and analyzed in the frequency domain. EEG amplitudes in the delta frequency band differed significantly after presentation of food (breast milk) odor in comparison to the control condition and the non-food odor (farnesol). These changes were observed at the frontal recording positions. The present study indicates that central odor processing differs between a food and a non-food odor in infants. Results are interpreted in terms of focused attention towards a physiologically relevant odor (breast milk), suggesting that olfactory stimuli are of specific significance in this age group.

Odor identification performance in children using the "U-Sniff" test - Administered by an untrained person.

OBJECTIVE: The examination of olfactory function of patients with psychophysical olfactory tests such as the "Sniffin' Stick" test is a central component of any olfactory clinical diagnostics and clinical trials. Because olfactory disorders can also occur in childhood, reliable, valid and time-efficient olfactory tests are important. With the "U-Sniff", a child-friendly odor identification test that has already been sufficiently validated is available The aim of this study was to investigate whether untrained persons (e.g. parents with their children) are able to administer the "U-Sniff" odor identification test with appropriate guidance. METHOD: A total of 80 kindergarten children, aged 6 years, underwent an odor identification test. Half of the children were tested by their parents and the other half by a trained examiner. In addition, the examiner performed a concentration test (Kaseler Konzentrationsaufgaben). The results of the two groups were compared. RESULTS: All children completed the rapid testing protocol. No significant differences between the results of the two testing procedures occurred. On average an odor identification score of 9.68 ± 2.02 points (mean ± SD) was reached in the examiner's group while 9.65 ± 2.38 points were observed in the parents' group. CONCLUSION: It can be concluded that this study presents a new testing procedure using the "U-Sniff" odor identification test for children by untrained persons. Further validation of this test procedure examining olfactory impaired children should follow.

Odor identification performance in children aged 3-6 years.

BACKGROUND: While valid and reliable olfactory tests have been developed for children aged >5 years, olfactory testing has not systematically been evaluated in younger children. The aim of this study was to evaluate the reliability and validity of the "U-Sniff" odor identification test in children aged 3-6 years. METHODS: We included 160 healthy children (age range 3-6 years) and 14 congenitally anosmic children. Participants were investigated in two identical sessions. The "U-Sniff" test was used to evaluate olfactory function. A picture identification test (PIT) and the Kasel-Concentration-Task (KKA) were administered to identify factors influencing odor identification performance. RESULTS: Age significantly influenced odor identification performance, with older children achieving higher scores. PIT and KKA scores correlated positively with odor identification scores. The "U-Sniff" test demonstrated a high test-retest reliability (r160 = 0.75, p < 0.001). It was possible to distinguish between healthy and anosmic children by means of "U-Sniff" scores starting at age 4 years with high sensitivity (79-93%) and specificity (88-95%). CONCLUSIONS: The "U-Sniff" test is feasible for children starting at age 3 years. In children aged ≥4 years, it is a reliable and valid method to distinguish between normal olfactory function and anosmia. IMPACT: Olfactory testing is reliable and valid starting at an age of 4 years. The study adds a systematic evaluation of olfactory testing in young children. Results of this study are especially interesting for clinicians in the diagnosis of olfactory dysfunction.

The Influence of Cognitive Parameters on Olfactory Assessment in Healthy Children and Adolescents.

Olfactory threshold and odor identification tests are frequently used for assessment of olfactory function in children and adolescents. Whether olfactory test results are influenced by cognitive parameters or sex in children and adolescents is largely unknown. The aim of this study was to investigate the influence of cognition, age and sex on "Sniffin' Sticks" olfactory threshold and "U-Sniff" odor identification performance in a pediatric population. A total of 200 participants between age 6 and 17 years were included. Olfactory function (olfactory threshold and odor identification) was assessed using the "Sniffin' Sticks." In addition, age appropriate cognitive testing was applied. The results of this study indicate that odor identification test performance is positively correlated with age (r = 0.31) and verbal abilities of children (r = 0.24). Olfactory threshold results are only marginally influenced by age (r = 0.18) and are not associated with cognitive test performance. Olfactory assessment using olfactory threshold and "U-Sniff" odor identification testing is suitable for children and adolescents when considering age in the interpretation of test results.

Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia.

The atypical antipsychotic clozapine is one of the most potent drugs of its class, yet its precise mechanisms of action remain insufficiently understood. Recent evidence points toward the involvement of endogenous retinoic acid (RA) signaling in the pathophysiology of schizophrenia. Here we investigated whether clozapine may modulate RA-signaling. Effects of clozapine on the catabolism of all-trans RA (at-RA), the biologically most active metabolite of Vitamin A, were assessed in murine and human brain tissue and peripheral blood-derived mononuclear cells (PBMC). In patients with schizophrenia with and without clozapine treatment and matched healthy controls, at-RA serum levels and blood mRNA expression of retinoid-related genes in PBMCs were quantified. Clozapine and its metabolites potently inhibited RA catabolism at clinically relevant concentrations. In PBMC-derived microsomes, we found a large interindividual variability of the sensitivity toward the effects of clozapine. Furthermore, at-RA and retinol serum levels were significantly lower in patients with schizophrenia compared with matched healthy controls. Patients treated with clozapine exhibited significantly higher at-RA serum levels compared with patients treated with other antipsychotics, while retinol levels did not differ between treatment groups. Similarly, in patients without clozapine treatment, mRNA expression of RA-inducible targets CYP26A and STRA6, as well as at-RA/retinol ratio, were significantly reduced. In contrast, clozapine-treated patients did not differ from healthy controls in this regard. Our findings provide the first evidence for altered peripheral retinoid homeostasis in schizophrenia and suggest modulation of RA catabolism as a novel mechanism of action of clozapine, which may be useful in future antipsychotic drug development.

Influence of chronic diseases on the olfactory function in children.

The association between smell impairment and chronic diseases has been reported in some studies in adults. Such information is not available for chronic diseases in children. The aim of this study was to examine olfactory function of children with chronic diseases such as diabetes mellitus type 1, hypothyroidism, and bronchial asthma in combination with allergic rhinitis in comparison to healthy controls. The data were obtained from n = 205 participants (104 boys, 101 girls) between the age of 6 and 17 years. Seventy-eight of the participants were healthy controls, n = 43 had diabetes mellitus type 1, n = 50 suffer from allergic rhinitis or bronchial asthma, and 34 presented a reduced function of their thyroid in medical history. All participants underwent olfactory testing including olfactory threshold using "Sniffin' Sticks" and odor identification using the "U-Sniff" test. In addition, a depression inventory and cognitive testing using the Ravens Progressive Matrices was performed. No significant difference in olfactory function was observed for any of the chronic diseases in children in comparison to healthy controls. Further analysis showed a trend in significance for a subpopulation of children with bronchial asthma and comorbidities performed worse on the olfactory threshold test compared to patients with bronchial asthma without comorbidities. Pediatric patients suffering from chronic diseases scored higher on the depression inventory compared to healthy controls.Conclusion: In conclusion, this study demonstrates that the influence of chronic diseases (bronchial asthma, diabetes mellitus type 1 and hypothyroidism) on olfactory function in childhood, if any, seems to be insignificant. This is partly in contrast to adult patients. Further research should be conducted in a subgroup of patients with bronchial asthma, allergic rhinitis, and atopic dermatitis or other comorbidities to better understand the association of allergic diathesis and olfactory function and the putative pathogenesis of olfactory dysfunction. What is known: • The association between smell impairment and chronic diseases has been reported in some studies in adults. • Such information is not available for chronic diseases in children. What is new: • The influence of chronic diseases (bronchial asthma, diabetes mellitus type 1, and hypothyroidism) on olfactory function in childhood, if any, seems to be insignificant. • In patients with bronchial asthma and allergic rhinitis, only a subgroup of patients with additional comorbidity (atopic dermatitis) showed a tendency to a reduced sense of smell.

Normative data for olfactory threshold and odor identification in children and adolescents.

OBJECTIVE: Although previous studies have demonstrated the feasibility and validity of olfactory testing in children and adolescents using the "Sniffin' Sticks" odor threshold and "U-Sniff" odor identification test, normative data obtained in a large sample for these tests are missing. Aim of this study was therefore to obtain normative data of healthy children and adolescents for olfactory assessment. MATERIAL AND METHODS: Olfactory testing was conducted using the "Sniffin' Sticks" olfactory threshold (THR) and the 12-item "U-Sniff" odor identification (ID) test. The data were collected from 490 children and adolescents (234 girls, 257 boys) between the age of 6 and 17 years (mean age: 11.2 ±â€¯3.4 years). In line with previous studies, participants were divided into subgroups regarding their age: i) 6-8 years, ii) 9-11 years, iii) 12-14 years and iv) 15-17 years. RESULTS: All participants were able to perform the task. Neither sex nor age significantly influenced THR. Girls outperformed boys in ID. In addition, the youngest age group scored lower than the three other age groups on the "U-Sniff" odor identification test. Using the 10th percentile to distinguish normosmia from a reduced sense of smell the following values were obtained for the four age groups: i) THR 4.25 points, ID 7 points, ii) THR 5.0 points, ID 9 points, iii) THR 4.75 points, ID 10 points and iv) THR 5.5 points, ID 10 points. CONCLUSION: The present study provides normative data for olfactory assessment in children and adolescents using both an olfactory threshold and a suprathreshold test to distinguish between normosmia and a reduced sense of smell using the 10th percentile.

Acquired Olfactory Dysfunction in Children and Adolescents: A Systematic Review of the Literature.

Olfactory function can be influenced by many factors and olfactory dysfunction is associated with several diseases. But even considering this, the causes of acquired olfactory dysfunction in children are not well understood. This review was conducted to gain an overview of the etiologies of acquired olfactory dysfunction in a pediatric population. Studies were identified using a predefined literature search, including studies if patients were ≤18 years of age and results of psychophysical olfactory testing were reported. A total of 44 articles met the inclusion criteria for this review and were included in the qualitative analysis. The influence of 6 disease groups on olfactory function in children was observed (otorhinolaryngology, traumatic brain injury, oncology, psychiatric diseases, environmental factors, and other diseases). The current literature is convincing that diseases in the otorhinolaryngology group and traumatic brain injury can lead to acquired olfactory dysfunction, whereas according to the current literature, the role of other influencing factors such as most psychiatric disorders remains uncertain. A number of diseases and circumstances affect olfactory function in children and may cause acquired olfactory dysfunction in this age group. Nevertheless, more research is needed to better understand the causes of acquired olfactory dysfunction in children. Future research should have the goal of early diagnosis and, if possible, early treatment of the condition to prevent a negative impact of olfactory dysfunction on children and adolescents.

Sniffin' Away the Feeding Tube: The Influence of Olfactory Stimulation on Oral Food Intake in Newborns and Premature Infants.

Because of their immaturity, many premature infants are fed via nasogastric tube. One objective of the neonatal care is to feed infants orally early. The olfactory function of premature infants is developed before birth and odorants have a significant impact on nutrition in infants. The aim of the study was to test whether odor stimulation has a positive effect on the transition from gavage to oral feeding in infants. Participants were premature infants with gestational age of more than 27 weeks, with full or partial gavage feeding, stable vital parameters and without invasive ventilation. Before each feeding procedure an odorant was presented in front of the infant's nose. Infants were randomized into 1 of 3 groups and received either rose odor (not food-associated), vanilla odor (food-associated), or placebo (no odor). The primary outcome of the study was defined as the time until complete oral nutrition. About 150 children born at a postnatal age of 9.5 ± 7.8 days were included in this study. The duration until complete oral nutrition was reached after 11.8 ± 7.7 (vanilla), 12.2 ± 7.7 (rose), and 12.9 ± 8.8 (control) days. A nearly linear relation between odor presentation frequency and effect size was detectable. For infants that received the intervention for more than 66.7% of the time the length of gavage feeding (8 ± 5.4) and hospitalization (11 ± 6.5) was significantly lower in the vanilla group when compared with control (15 ± 7.3 and 21 ± 13.7, respectively). Odor stimulation with vanilla has an impact on oral feeding in premature infants, however the odor has to be presented on regular basis.