Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) can result in cognitive dysfunction. Cognitive functions affected are subserved by few functional brain networks. Functional connectivity (FC) in these networks can be assessed with resting-state functional MRI (rs-fMRI). Alterations of FC have been reported in children and adolescents prenatally exposed to alcohol. Previous reports varied substantially regarding the exact nature of findings. The purpose of this study was to assess FC of cognition-related networks in young adults with FAS. METHODS: Cross-sectional rs-fMRI study in participants with FAS (n = 39, age: 20.9 ± 3.4 years) and healthy participants without prenatal alcohol exposure (n = 44, age: 22.2 ± 3.4 years). FC was calculated as correlation between cortical regions in ten cognition-related sub-networks. Subsequent modelling of overall FC was based on linear models comparing FC between FAS and controls. Results were subjected to a hierarchical statistical testing approach, first determining whether there is any alteration of FC in FAS in the full cognitive connectome, subsequently resolving these findings to the level of either FC within each network or between networks based on the Higher Criticism (HC) approach for detecting rare and weak effects in high-dimensional data. Finally, group differences in single connections were assessed using conventional multiple-comparison correction. In an additional exploratory analysis, dynamic FC states were assessed. RESULTS: Comparing FAS participants with controls, we observed altered FC of cognition-related brain regions globally, within 7 out of 10 networks, and between networks employing the HC statistic. This was most obvious in attention-related network components. Findings also spanned across subcomponents of the fronto-parietal control and default mode networks. None of the single FC alterations within these networks yielded statistical significance in the conventional high-resolution analysis. The exploratory time-resolved FC analysis did not show significant group differences of dynamic FC states. CONCLUSIONS: FC in cognition-related networks was altered in adults with FAS. Effects were widely distributed across networks, potentially reflecting the diversity of cognitive deficits in FAS. However, no altered single connections could be determined in the most detailed analysis level. Findings were pronounced in networks in line with attentional deficits previously reported.

Metabolic control during the neonatal period in phenylketonuria: associations with childhood IQ.

BACKGROUND: In phenylketonuria, treatment and subsequent lowering of phenylalanine levels usually occur within the first month of life. This study investigated whether different indicators of metabolic control during the neonatal period were associated with IQ during late childhood/early adolescence. METHODS: Overall phenylalanine concentration during the first month of life (total "area under the curve"), proportion of phenylalanine concentrations above upper target level (360 µmol/L) and proportion below lower target level (120 µmol/L) during this period, diagnostic phenylalanine levels, number of days until phenylalanine levels were <360 µmol/L, and lifetime and concurrent phenylalanine levels were correlated with IQ scores of 64 PKU patients (mean age 10.8 years, SD 2.9). RESULTS: Overall phenylalanine concentration and proportion of phenylalanine concentrations >360 µmol/L during the first month of life negatively correlated with IQ in late childhood/early adolescence. Separately, phenylalanine concentrations during different periods within the first month of life (0-10 days, 11-20 days, 21-30 days) were negatively correlated with later IQ as well, but correlation strengths did not differ significantly. No further significant associations were found. CONCLUSIONS: In phenylketonuria, achievement of target-range phenylalanine levels during the neonatal period is important for cognition later in life, also when compared to other indicators of metabolic control. IMPACT: In phenylketonuria, it remains unclear during which age periods or developmental stages metabolic control is most important for later cognitive outcomes. Phenylalanine levels during the neonatal period were clearly and negatively related to later IQ, whereas no significant associations were observed for other indices of metabolic control. This emphasizes the relative importance of this period for cognitive development in phenylketonuria. No further distinctions were observed in strength of associations with later IQ between different indicators of metabolic control during the neonatal period. Thus, achievement of good metabolic control within 1 month after birth appears "safe" with respect to later cognitive outcomes.

Approaching altered inhibitory control in phenylketonuria: A functional MRI study with a Go-NoGo task in young female adults.

Subtle executive function deficits, particularly regarding inhibitory control, have been reported in patients with phenylketonuria (PKU) despite early dietary treatment. Purpose of this study was to assess whether young female adults with PKU exhibit altered neural activity underlying such deficits, particularly in a fronto-parietal cognitive control network (CCN). Behavioural data and functional magnetic resonance imaging (fMRI) data were acquired during a Go-NoGo task in 16 young adult patients with PKU and 17 control subjects. Hypothesis-driven analyses of behavioural and fMRI data in the CCN were supplemented by exploratory whole brain activation analyses. PKU patients exhibited a trend towards higher errors of commission. Patients exhibited marginally increased activation associated with inhibitory control in only one CCN core region (right middle frontal gyrus, p = .043). Whole brain analyses revealed widespread relatively increased activation in adults with PKU in the main task contrast (NoGo > Go). This increased activation was mainly observed outside the CCN and largely overlapped with the default mode network (DMN). In conclusion, only subtle inhibitory control deficits and associated brain activity differences were observed in young adults with PKU. Thus, this work adds to the notion that this particular population seems to be only slightly affected by such cognitive deficits. While there were also only minimal increases when compared to healthy subjects in brain activity in a cognitive control network, we observed more widespread activation increases outside this network. These results support the assumption of DMN dysfunction in PKU.

Asymmetry-index and orthodontic facial analysis of children with foetal alcohol syndrome using 3D-facial scans.

BACKGROUND: The foetal alcohol spectrum disorder (FASD) is a complex and heterogenic disorder, caused by gestational exposure to alcohol. Patients with foetal alcohol syndrome (FAS-most severe form) show abnormal facial features. Our study aims at finding additional reliable and objective parameters for FAS diagnosis. METHODS: Facial three-dimensional scans of 30 children with FAS and 30 controls were analysed. Orthodontic profile analysis (concerning position of upper and lower jaw) was performed. Vertical facial proportions were taken and facial asymmetry index (right to left side) was calculated. RESULTS: Profile type was significantly different for children with FAS (p = 0.001) with lower jaws more frequently in a retral position. Profile angle was significantly larger in the group with FAS (p = 0.009). Children with FAS had shorter middle thirds and longer lower thirds of the face (p < 0.001). Stomion (point between upper and lower lip) was located significantly more caudally in the FAS group (p < 0.001). Facial asymmetry index was not significantly different. CONCLUSIONS: Children with FAS differ significantly from controls in vertical and sagittal facial measurements. Profile analysis and measurement of vertical proportions are easy to apply standard procedures in everyday orthodontic practice and could be time-saving and objective means for additional verification of FAS.

Malocclusion Can Give Additional Hints for Diagnosis of Fetal Alcohol Spectrum Disorder.

AIMS: Fetal alcohol spectrum disorder (FASD) is a developmental disorder caused by maternal alcohol intake (prevalence: 0.77%). Malocclusion has been described in case reports of patients with FASD, but reliable evidence for associations between FASD and malocclusion is not documented. Malocclusion is defined as tooth irregularity (prevalence: 14.6%) or incorrect relationship between the jaws such as lateral crossbites (prevalence: 3.1%). The purpose of this study was to investigate possible associations between malocclusion and FASD. SHORT SUMMARY: FASD prevalence is high and diagnosis is very difficult; Malocclusions can give additional hints for FASD diagnosis; Patients with FASD show growth deficits concerning the maxilla; Early and consistent orthodontic supervision and therapy can prevent facial asymmetries in FASD patients. METHODS: Thirty patients with FASD and 30 patients of a healthy control group were examined. Inclusion criteria were mixed dentition, verified FASD/absence of FASD (control group), exclusion criteria were orthodontic treatment and disorders other than FASD. The extent and type of malocclusion were quantified with the peer assessment rating (PAR) index based on an analysis of orthodontic plaster models. In addition, anthropometric data such as gestational age, body weight and height at birth as well as present body weight, height and head circumference at examination date were assessed. RESULTS: The PAR index showed a significant increase in malocclusions in FASD patients compared to the group that were not diagnosed with FASD (P = 0.002). FASD patients showed particular differences in the upper transversal dimension with a higher prevalence of crossbites (P = 0.018) and a lower head circumference (P < 0.001). Body weight (P < 0.001) and height (P < 0.001) were significantly lower for FASD patients at time of birth, but not at the present examination date (weight: P = 0.329; height: P = 0.496). When relating weight and height measures to age using percentile curves of physiological growth, clinically relevant discrepancies could be found for FASD patients. CONCLUSIONS: Our results show that malocclusion can provide additional evidence for FASD diagnosis. When FASD is diagnosed in a child, early referral to an orthodontist is advisable to stimulate maxillary growth and consequently prevent further malocclusions.

3D Analysis of Philtrum Depth in Children with Fetal Alcohol Syndrome.

AIMS: Diagnosis of fetal alcohol spectrum disorder (FASD) is complex and difficult. The estimated number of unreported FASD is thus assumed to be substantial. In our cross-sectional study, we aimed to identify possible metric differences in philtrum depth in children with fetal alcohol syndrome (FAS) compared to healthy controls based on non-invasive 3D facial scanning in order to provide an objective, metrical tool improving FASD diagnosis. METHODS: Twenty-five children with confirmed FAS and 30 healthy school children without FAS, both in the mixed dentition, were prospectively recruited and 3D facial scans were performed after recording body length, weight and head circumference. Philtrum surface data were extracted and metric philtrum depth was determined at four geometrically defined measuring points (P1-P4) along the vertical length of the philtrum. RESULTS: Philtrum depths at P1 (P = 0.025), P2 (P = 0.001), P3 (P < 0.001) and P4 (P = 0.001) as well as mean philtrum depth P1-P4 (P < 0.001) differed significantly between patients with and without FAS. Compared to controls, the philtrum was shallower in patients with FAS by on average 0.4 mm at each of the respective points. Whereas no differences could be determined for body height and weight, head circumference was significantly smaller in patients with FAS (P = 0.001), particularly in girls (P = 0.008). CONCLUSIONS: Apart from head circumference, philtrum depth is significantly reduced in children with FAS and can thus be used as diagnostic indicator to aid and confirm FAS diagnosis. In contrast to visual assessments, 3D face scan methods allow a more objective quantification and can thus provide additional evidence in FAS diagnosis.

Sapropterin treatment does not enhance the health-related quality of life of patients with phenylketonuria and their parents.

AIM: Sapropterin causes reductions in blood phenylalanine concentrations in sensitive patients with phenylketonuria (PKU). We examined whether the subsequent relaxation of dietary restrictions influenced the quality of life (QoL) of patients and parents. METHODS: The study cohort comprised 112 patients with PKU followed at the metabolic centre at Münster University Children's Hospital, Germany, from 2012 to 2015. A sapropterin response was defined as a ≥30% reduction in blood phenylalanine levels. The QoL of 38 children and adolescents from the study cohort, with a mean age of 12.4 (range 6.6-18.7) years, was assessed in an outpatient setting and 49 parents of children with PKU also commented on their child's QoL and their own. The participants' QoL was assessed before the start of therapy, and again after six months, using self-report questionnaires. RESULTS: After six months of continuous therapy or diet, QoL was largely unchanged in the patients, according to their self-reports and the parental reports. QoL also remained unchanged in the parents. CONCLUSION: Sapropterin did not seem to improve QoL in PKU patients and their parents. Patients with PKU had already reached high levels of QoL following classic diets, and these levels were not easily improved by sapropterin.

Adolescents' use of alcohol, tobacco and illicit drugs in relation to prenatal alcohol exposure: modifications by gender and ethnicity.

AIMS: The study aimed to investigate (a) the association between low to moderate prenatal alcohol exposure (PAE) and the use of alcohol, tobacco and illicit drugs in adolescence and (b) whether the associations are modified by gender and ethnicity. METHODS: The subjects of the study were 5922 children and adolescents, aged from 11 to 17 years, enrolled in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents (the KiGGS study). Information on PAE is based on parental self-report questionnaires. Use of alcohol, tobacco and illicit drugs was assessed through self-report questionnaires for adolescents. RESULTS: Low to moderate PAE was associated with an increased risk of drinking alcohol (adjusted odds ratio (OR) 1.73, 95% confidence interval (CI) 1.34, 2.18) and also of illicit drug use (adjusted OR 1.62, 95% CI 1.23, 2.14). The associations between PAE and the use of alcohol, tobacco and illicit drugs differed according to gender and ethnicity. Gender-stratified analyses resulted in adverse effects of PAE on drinking alcohol, smoking and illicit drug use in females; however, in German males, the associations disappeared. Stronger associations between PAE and the outcome measures were found in non-Germans. CONCLUSIONS: Our findings indicate that low to moderate levels of maternal alcohol intake during pregnancy are a risk factor for use of alcohol, tobacco and illicit drugs by the offspring, with stronger associations in females and non-Germans.

Children and Adolescents with Early Treated Phenylketonuria: Cognitive Development and Fluctuations of Blood Phenylalanine Levels.

BACKGROUND: We assessed the relationship between the cognitive development of children and adolescents with phenylketonuria (PKU) and fluctuations in peripheral phenylalanine (Phe) levels. METHODS: We examined the neurocognitive performance of 33 children and adolescents with early treated PKU, of whom 18 were treated with sapropterin dihydrochloride, and 15 were on a classic diet. For 26 weeks, patients were assessed weekly for their blood phenylalanine (Phe) levels. Phe levels were analyzed for fluctuations indicated by the individual standard deviation. Fluctuations were compared to the standard deviation of 26 Phe level measurements before the study interval. We also assessed the concurrent IQ of the patients. This was repeated at one-, two-, and seven-year intervals. RESULTS: Full-scale IQ in patients treated with a classic diet did not change within the follow-up. In patients treated with Sapropterin dihydrochloride, however, there was a considerable gain in full-scale IQ. This was particularly true if blood Phe fluctuations increased in patients of this treatment group. CONCLUSIONS: Sapropterin dihydrochloride enhances Phe tolerance in patients with PKU. Increasing blood Phe fluctuations following enhanced Phe tolerance may indicate that the treatment not only allows patients to relax their Phe-restricted diet but also may support cognitive development in patients.

Preterm birth and small for gestational age in relation to alcohol consumption during pregnancy: stronger associations among vulnerable women? Results from two large Western-European studies.

BACKGROUND: Inconsistent data on the association between prenatal alcohol exposure and a range of pregnancy outcomes, such as preterm birth (PTB) and small for gestational age (SGA) raise new questions. This study aimed to assess whether the association between low-moderate prenatal alcohol exposure and PTB and SGA differs according to maternal education, maternal mental distress or maternal smoking. METHODS: The Amsterdam Born Children and their Development (ABCD) Study (N = 5,238) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (N = 16,301) are both large studies. Women provide information on alcohol intake in early pregnancy, 3 months postpartum and up to 17 years retrospectively. Multivariate logistic regression analyses and stratified regression analyses were performed to examine the association between prenatal alcohol exposure and PTB and SGA, respectively. RESULTS: No association was found between any level of prenatal alcohol exposure (non-daily, daily, non-abstaining) and SGA. The offspring of daily drinkers and non-abstainers had a lower risk of PTB [ABCD: odds ratio (OR) 0.31, 95% confidence interval (CI) 0.13, 0.77; KiGGS: OR 0.75, 95% CI 0.57, 0.99]. Interactions with maternal education, maternal distress or maternal smoking were not significant. CONCLUSIONS: Although these results should be interpreted with caution, both studies showed no adverse effects of low-moderate prenatal alcohol exposure on PTB and SGA, not even in the offspring of women who were disadvantaged in terms of low education, high levels of distress, or smoking during pregnancy.

A systematic review: facial, dental and orthodontic findings and orofacial diagnostics in patients with FASD.

Background: The fetal alcohol spectrum disorder is a group of developmental disorders caused by maternal alcohol consumption. Patients with fetal alcohol syndrome show abnormal orofacial features. This review presents an overview over the facial, oral, dental or orthodontic findings and diagnostic tools concerning these features. Methods: For this systematic review Cochrane, Medline and Embase databases were considered and the review was performed according to the PRISMA checklist. Two independent reviewers evaluated all studies and recorded results in a summary of findings table. Risk of bias was analyzed via Quadas-2 checklist. Results: 61 studies were eligible for inclusion. All included studies were clinical studies. Methods and results of the studies were not comparable, guidelines or methods for the detection of FASD varied across studies. Facial features most often measured or found as distinguishing parameter were: palpebral fissure length, interpupillary or innercanthal distance, philtrum, upper lip, midfacial hypoplasia or head circumference. Conclusions: This review shows that to date a multitude of heterogeneous guidelines exists for the diagnosis of FASD. Uniform, objective diagnostic criteria and parameters for the orofacial region in FASD diagnosis are needed. A bio database with values and parameters for different ethnicities and age groups should be made available for diagnosis.

Beta-Hydroxybutyrate (BHB), Glucose, Insulin, Octanoate (C8), and Decanoate (C10) Responses to a Medium-Chain Triglyceride (MCT) Oil with and without Glucose: A Single-Center Study in Healthy Adults.

MCTs are increasingly being used to promote ketogenesis by patients on ketogenic diet therapy, but also by people with other conditions and by the general public for the perceived potential benefits. However, consumption of carbohydrates with MCTs and untoward gastrointestinal side effects, especially at higher doses, could decrease the sustainability of the ketogenic response. This single-center study investigated the impact of consuming carbohydrate as glucose with MCT oil compared to MCT alone on the BHB response. The effects of MCT oil versus MCT oil plus glucose on blood glucose, insulin response, levels of C8, C10, BHB, and cognitive function were determined, and side effects were monitored. A significant plasma BHB increase with a peak at 60 min was observed in 19 healthy participants (24.4 ± 3.9 years) after consuming MCT oil alone, and a more delayed but slightly higher peak was observed after consuming MCT oil plus glucose. A significant increase in blood glucose and insulin levels occurred only after MCT oil plus glucose intake. The overall mean plasma levels of C8 and C10 were higher with the intake of MCT oil alone. MCT oil plus glucose consumption showed improved scores for the arithmetic and vocabulary subtests.

Inhibitory control in young adult women with fetal alcohol syndrome: Findings from a pilot functional magnetic resonance imaging study.

BACKGROUND: Executive dysfunction, especially impaired inhibitory control, is a common finding in individuals with fetal alcohol syndrome (FAS). Previous research has mostly focused on neural correlates of inhibitory deficits in children and adolescents. We investigated inhibitory functions and underlying cerebral activation patterns in young adult women with FAS. METHODS: Task performance and functional magnetic resonance imaging (fMRI) data were acquired during a Go/NoGo (GNG) inhibition task in 19 young adult women with FAS and 19 healthy female control subjects. Whole-brain activation and task performance analyses were supplemented by region of interest (ROI) analyses of fMRI data within a predefined cognitive control network (CCN). RESULTS: Task performance did not differ significantly between groups on errors of commission, associated with inhibitory control. Similarly, overall activation within the preselected ROIs did not differ significantly between groups for the main inhibitory contrast NoGo > Go. However, whole-brain analyses revealed activation differences in the FAS group when compared to controls under inhibitory conditions. This included hyperactivations in the left inferior frontal, superior temporal, and supramarginal gyri in the FAS group. Likewise, lateralization tendencies toward right-hemispheric ROIs were weaker in FAS subjects. In contrast to comparable inhibitory performance, attention-related errors of omission were significantly higher in the FAS group. Correspondingly, FAS subjects had lower activity in attention-related temporal and parietal areas. CONCLUSIONS: The known alterations of inhibitory functions associated with prenatal alcohol exposure in children and adolescents were not seen in this adult sample. However, differential brain activity was observed, reflecting potential compensatory mechanisms. Secondary results suggest that there is impaired attentional control in young adult women with FAS.

Tackling frontal lobe-related functions in PKU through functional brain imaging: a Stroop task in adult patients.

BACKGROUND: Profound mental retardation in phenylketonuria (PKU) can be prevented by a low phenylalanine (Phe) diet. However, even patients treated early have inconsistently shown deficits in several frontal lobe-related neuropsychological tasks such as the widely accepted Stroop task. The goal of this study was to investigate whether adult patients exhibit altered brain activation in Stroop-related locations in comparison to healthy controls and if an acute increase in blood Phe levels in patients has an effect on activation patterns. METHODS: Seventeen male, early-treated patients with classic PKU (mean ± SD age: 31.0 ± 5.2 years) and 15 male healthy controls (32.1 ± 6.4 years) were compared using a color-word matching Stroop task in a functional magnetic resonance imaging (fMRI) study at 3T. Participants were scanned twice, and an oral Phe load (100 mg/kg body weight) was administered to patients prior to one of the fMRI sessions (placebo-controlled). Activity in brain regions that are known to be involved in Stroop tasks was assessed. RESULTS: PKU patients exhibited poorer accuracy in incongruent trials. Reaction times were not significantly different. There were no consistent differences in BOLD activations in Stroop-associated brain regions. The oral Phe administration had no significant effect on brain activity. CONCLUSIONS: Neither a generally slower task performance nor distinctively altered functioning of brain networks involved in a task representing a subset of dopamine-dependent executive functions could be proven. Decreased accuracy and inconsistent findings in posterior areas necessitate further study of frontal-lobe functioning in PKU patients in larger study samples.

Simplifying Diagnosis of Fetal Alcohol Syndrome Using Machine Learning Methods.

INTRODUCTION: The fetal alcohol spectrum disorder (FASD) is a complex and heterogeneous disorder, caused by gestational exposure to alcohol. Patients with fetal alcohol syndrome (FAS-most severe form of FASD) show abnormal facial features. The aim of our study was to use 3D- metric facial data of patients with FAS and identify machine learning methods, which could improve and objectify the diagnostic process. MATERIAL AND METHODS: Facial 3D scans of 30 children with FAS and 30 controls were analyzed. Skeletal, facial, dental and orthodontic parameters as collected in previous studies were used to evaluate their value for machine learning based diagnosis. Three machine learning methods, decision trees, support vector machine and k-nearest neighbors were tested with respect to their accuracy and clinical practicability. RESULTS: All three of the above machine learning methods showed a high accuracy of 89.5%. The three predictors with the highest scores were: Midfacial length, palpebral fissure length of the right eye and nose breadth at sulcus nasi. CONCLUSIONS: With the parameters right palpebral fissure length, midfacial length and nose breadth at sulcus nasi, machine learning was an efficient method for the objective and reliable detection of patients with FAS within our patient group. Of the three tested methods, decision trees would be the most helpful and easiest to apply method for everyday clinical and private practice.

Development of MRI T2 hyperintensities and cognitive functioning in patients with neurofibromatosis type 1.

BACKGROUND: In patients with neurofibromatosis type 1 (NF1), cognitive deficits are frequent manifestations. They are associated with focal areas of high signal intensity (T2H) on T2-weighted MRI of the brain. Changes in T2H may affect cognitive development. Our study was to analyse the relations between the long-term development of T2H development and the cognitive abilities in patients with NF1. METHOD: In a controlled prospective study, we investigated 67 patients with NF1 for their IQ with the patients having T2H (MRI) examination. Assessments and MRI were repeated at a 3- year follow-up. RESULTS: Patients without T2H performed at the average IQ level. Patients with stable T2H performed below average level but within normal limits of IQ. Patients with T2H that decreased over study period performed well below normal limits at first examination but within limits at follow-up. Stable T2H were found primarily in the cerebellum and the capsula interna. T2H that decreased were found primarily in the thalamus and the basal ganglia. CONCLUSIONS: T2H in the cerebellum and the capsula interna are more permanent but exert a minor left shift in IQ. T2H in the thalamus or the basal ganglia are related to severely reduced performance. Decreasing they give way for performance improvement. There may be a different pathology in T2H related to the intracranial regions the T2H affect in patients with NF1.

Children with Fetal Alcohol Syndrome (FAS): 3D-Analysis of Palatal Depth and 3D-Metric Facial Length.

Background: Drinking alcohol during pregnancy can result in severe developmental disorders in the child. Symptoms of the fetal alcohol spectrum disorder (FASD) comprise growth deficiencies, abnormal facial phenotype and damage or dysfunction of the central nervous system. Numerous diagnostic methods for facial phenotyping in FASD exist, but diagnoses are still difficult. Our aim was to find additional and objective methods for the verification of FAS(D). Methods: Three-dimensional dental models of 60 children (30 FAS and 30 controls) were used to metrically determine maximum palatal depths at the median palatine raphe. Three-dimensional facial scans were taken, and vertical distances of the face were measured at five defined facial landmarks (FP1-FP5) for each child. Results: Mean palatal height, total facial length (FP1-FP5) as well as FP4-FP5 did not significantly differ between the FAS group and the control group. Comparing vertical facial subdivisions, however, resulted in significant differences for distances FP1 to FP2 (p = 0.042, FAS > controls), FP2 to FP3 (p < 0.001, FAS < controls), FP3 to FP4 (p < 0.001, FAS > controls) and FP3 to FP5 (p = 0.007, FAS > controls). Conclusions: Metric vertical measurements of the face can be used as additional objective criteria for FAS diagnoses. However, no significant differences were reported for palatal depth evaluation in the specific age range tested in the present study.

Tooth Malformations, DMFT Index, Speech Impairment and Oral Habits in Patients with Fetal Alcohol Syndrome.

Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder with severe negative lifetime consequences. Although knowledge about the harmfulness of alcohol consumption during pregnancy has spread, the prevalence of fetal alcohol spectrum disorder is very high. Our study aims at identifying fetal alcohol syndrome (FAS)-associated dental anomalies or habits, which need early attention. Methods: Sixty children (30 FAS; 30 controls) were examined prospectively. Swallowing pattern, oral habits, breastfeeding, speech therapy, ergotherapy, physiotherapy, exfoliation of teeth, DMFT (decayed, missing, filled teeth) index, modified DDE (developmental defects of enamel) index and otitis media were recorded. Results: Swallowing pattern, exfoliation of teeth, and otitis media were not significantly different. Significant differences could be found concerning mouthbreathing (p = 0.007), oral habits (p = 0.047), age at termination of habits (p = 0.009), speech treatment (p = 0.002), ergotherapy, physiotherapy, and breastfeeding (p ≤ 0.001). DMFT (p ≤ 0.001) and modified DDE (p = 0.001) index showed significantly higher values for children with fetal alcohol syndrome. Conclusions: Children with fetal alcohol syndrome have a higher need for early developmental promotion such as speech treatment, ergotherapy, and physiotherapy. Mouthbreathing, habits, and lack of breastfeeding may result in orthodontic treatment needs. High DMFT and modified DDE indexes hint at a higher treatment and prevention need in dentistry.

3D-Analysis of Mouth, Nose and Eye Parameters in Children with Fetal Alcohol Syndrome (FAS).

Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder with severe negative lifetime consequences for the affected person. Numerous diagnostic methods for facial assessment in FAS exist, but most of them are based on subjective evaluations. Our aim was therefore to find objective methods for the verification of FAS(D). Methods: 58 children (28 FAS; 30 controls) were examined prospectively. 3D facial scans were performed for each child and facial parameters at the mouth, nose and eye regions were measured and compared between the groups. Results: Significant differences could be found for the distance between right and left sulcus nasi at the transition point to the philtrum (p < 0.001), for the inner canthal distance (p = 0.001) as well as for the right and left palpebral fissure length (p < 0.001). No significant difference between the FAS and control children could be found for the measurements of mouth breadth (p = 0.267) and breadth between the left and right alares nasi (p = 0.260). Conclusions: Measurements of mouth breadth and nose breadth for the alares nasi are not suitable for FAS diagnosis. In contrast, digital contactless measurements of the distance between the right and left sulcus nasi at the transition point to the philtrum, as well as the inner canthal distance and palpebral fissure length of the left and right eyes, showed significant differences when comparing children with FAS to healthy controls. These measurements could thus be additional objective means for the verification of FAS.