Self-reported perinatal depressive symptoms and postnatal symptom severity after treatment with antidepressants in pregnancy: a cross-sectional study across 12 European countries using the Edinburgh Postnatal Depression Scale Angela Lupattelli,1 Michael J Twigg,2 Ksenia Zagorodnikova,3 Myla E Moretti,4 Mariola Drozd,5 Alice Panchaud,6,7 Andre Rieutord,8 Romana Gjergja Juraski,9 Marina Odalovic,10 Debra Kennedy,11,12 Gorazd Rudolf,13 Herbert Juch,14 Hedvig Nordeng1,15 1PharmacoEpidemiology and Drug Safety Research Group, School of Pharmacy and PharmaTox Strategic Research Initiative, University of Oslo, Oslo, Norway; 2School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, UK; 3Northwest Medical Center for Drug Safety in Pregnancy and Lactation, Northwest State Medical University named after I. I. Mechnikov, St. Petersburg, Russia; 4Clinical Trials Unit, Ontario Child Health Support Unit, The Hospital for Sick Children, Toronto, ON, Canada; 5Department of Applied Pharmacy, Medical University of Lublin, Lublin, Poland; 6School of Pharmaceutical Sciences, University of Geneva and Lausanne, Geneva, Switzerland; 7Division of Clinical Pharmacology and Swiss Teratogen Information Service, Lausanne University Hospital, Lausanne, Switzerland; 8Pharmacy Service, Hospital Antoine-Béclère, GH HUPS, APHP, Clamart France and Européenne de Formation pour les Pharmaciens, Clamart, France; 9Children’s Hospital Srebrnjak, Medical School of Osijek, Josip Juraj Strossmayer University, Osijek, Croatia; 10Faculty of Pharmacy, University of Belgrade, Beograd, Serbia; 11MotherSafe, Royal Hospital for Women, Sydney, NSW, Australia; 12School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW, Australia; 13Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia; 14Cell Biology, Histology and Embryology, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University Graz, Graz, Austria; 15Department of Child Health and Development, Norwegian Institute of Public Health, Oslo, Norway Purpose: This study aimed at exploring the prevalence of self-reported antenatal and postnatal depressive symptoms by severity across multiple countries and the association between antidepressant treatment in pregnancy and postnatal symptom severity. Materials and methods: This was a multinational web-based study conducted across 12 European countries (n=8069). Uniform data collection was ensured via an electronic questionnaire. Pregnant women at any gestational week and mothers of children with <1 year of age could participate. We used the Edinburgh Postnatal Depression Scale (EPDS) to measure the prevalence of antenatal and postnatal depressive symptoms according to severity, which were corrected by survey weight adjustment (descriptive analysis). Within mothers with a psychiatric disorder (n=173), we estimated the association between antidepressant treatment in pregnancy and postnatal depressive symptom severity, as standardized EPDS mean scores, via the inverse probability of treatment weight (association analysis). Results: In the descriptive analysis (n=8069), the period prevalence of moderate-to-very severe depressive symptoms was higher in the western and eastern regions relative to the northern region, both in the antenatal period (6.8%–7.5% vs 4.3%) and in the postnatal period (7.6% vs 4.7%). One in two mothers with psychiatric disorders used an antidepressant in pregnancy (86 of 173). In the association analysis, women medicated at any time during pregnancy (adjusted β=−0.34, 95% confidence interval [CI] =−0.66, −0.02) had a significant postnatal symptom severity reduction compared with the nonmedicated counterpart. This effect was larger (β=−0.74, 95% CI =−1.24, −0.24) when the analysis was restricted to mothers within 6 months after childbirth. Conclusion: The prevalence of self-reported antenatal and postnatal depressive symptoms differs across European countries. Among women with psychiatric disorders, those who had been on treatment with antidepressants during pregnancy were less likely to report postnatal depressive symptoms, particularly within the 6-month period after childbirth, compared with the nonmedicated counterpart. Keywords: antidepressants, pharmacotherapy, pregnancy and postpartum, depression, anxiety, web-based

To determine the prevalence, number, and location of multiple (≥2) T2-hyperintensities on brain magnetic resonance imaging (MRI) in children with neurofibromatosis type 1 (NF1) and their correlation with age, and to establish their sensitivity, specificity, and accuracy for the diagnosis of NF1 in children, especially in the early age (2-7 years). We performed a cross-sectional study of 162 patients with NF1 from Croatian Neurofibromatosis Association Database and 163 control children between the ages of 2 and 18 years who underwent brain MRI between 1989 and 2009. Multiple T2-hyperintensities were present in 74% of NF1 patients and 1.8% of controls. They were mainly located in the basal ganglia, brainstem, and cerebellum and were significantly decreased in prevalence and number in the older age. T2-hyperintensities had excellent diagnostic accuracy with the area under the receiver operating characteristic (ROC) curve of 0.849 and 95% confidence interval (CI) of 0.805-0.886. The diagnostic sensitivity, specificity, and accuracy rate of T2-hyperintensities for NF1 were highest in the youngest age (2-7 years): 81% (95% CI 71%-89.1%), 99% (95% CI 92.3%-100%), and 85.8 (95% CI 83.3-93.8), respectively. This study strongly suggests the inclusion of T2-hyperintensities on brain MRI on the list of diagnostic criteria for NF1, especially in children of early age, when the clinical penetration of the NF1 gene has not yet been completely finished.

Background: Respiratory syncytial virus (RSV) stimulates the production of specific immunoglobulin (Ig) E and IgG4 antibodies as a hallmark of the Th2 immune response. In this paper, we evaluated the occurrence of atopic diseases in 10-year-old children who were positive for RSV-specific IgG antibodies during infancy. Methods: The prospective follow-up of 72 children included a physical examination, an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and the determination of RSV-specific antibodies and total and allergen-specific IgE. Results: Children with asthma had their first wheezing episode at a younger age (χ2 8.097, df = 1, p = 0.004). RSV-specific IgG4 levels at year one were positively correlated with atopic dermatitis (AD) (tau_b = 0.211, p = 0.049) and current AD (tau_b = 0.269, p = 0.012); and RSV-specific IgE levels were positively correlated with allergic rhinitis (AR) (tau_b = 0.290, p = 0.012) and current AR (tau_b = 0.260, p = 0.025). Positive RSV-specific IgE at the age of one increased the chances of asthma occurrence by 5.94 (OR = 5.94, 95% CI = 1.05–33.64; p = 0.044) and the chances of AR by more than 15 times (OR = 15.03, 95% CI = 2.08–108.72; p = 0.007). A positive family history of atopy increased the chances of asthma occurrence by 5.49 times (OR = 5.49, 95% CI = 1.01–30.07; p = 0.049), and a longer duration of exclusive breastfeeding lowered that chance (OR = 0.63, 95% CI = 0.45–0.89; p = 0.008). Prenatal smoking increased the chances of AR occurrence by 7.63 times (OR = 7.63, 95% CI = 1.59–36.53; p = 0.011). Conclusion: RSV-specific IgE and RSV-specific IgG4 antibodies could be risk markers for the development of atopic diseases in children.

There is an indication for EEG entrainment of rhythm, in particular in association with the regulation of frequencies related to epileptic seizures. We present the X-System model, which may predict the neurophysiological effects of music. We suggest that this may "entrain" healthy electrical brain activity more effectively than previously-used, intuitive choices of music. We enrolled 19 subjects (5-17 years old) with epilepsy. All children had overnight video/EEG monitoring and polysomnography before, upon starting and three weeks after starting all-night music treatment. A section of the EEG from the area contralateral to the epileptic region was audified to produce an audio representation of healthy brain activity. Using the X-System model to find the closest musical equivalents, tracks were selected from culturally relevant repertoires and processed into a personalized, all-night playlist for each individual subject. QOLIE-31 and ELDQOL were used to assess their quality of life. The mean age was 10.74 years (range 5-17 years), 63% were male. The mean spike reduction for the whole group, n = 19, was 28.42%. The mean spike reduction in patients with focal epilepsies, n = 6, was 28.46%, and with generalized epilepsies, n = 13, was 28.33%. Polysomnography showed improvement in REM sleep in all patients (p = 0.0006) and an increase in sleep spindles along with reduced awakenings and improved sleep efficiency. During music treatment, melatonin saliva levels increased, on average, by 52.70%, p < 0.0017. QOLIE-31 showed improvements in the Overall Score, Seizure Worry, Energy/Fatigue and Emotional Well-Being domains. In ELDQOL, the Total Average score and the Side-Effect Profile domain significantly improved. Personalized music treatment was associated with changes suggestive of decreased epileptiform activity, improved REM sleep, and improved quality of life in this uncontrolled study. This may expand possibilities for adjunctive epilepsy treatment. Further research is needed in larger, randomized trials to confirm this association and evaluate for potential confounding factors.

We report a prenatally diagnosed case of partial trisomy 2p and partial monosomy 3p, resulting from unbalanced translocation (2;3)(p25.1;p25.3) of paternal origin. Parents were non consanguineous Caucasians, with familial history of recurrent miscarriages on the father’s side. Detailed sonographic examination of the fetus showed a septated cystic hygroma measuring 6 mm at 13 weeks’ gestation. Karyotyping and fluorescent in situ hybridization (FISH) analysis of cultured amniotic fluid cells revealed an unbalanced translocation der(3)t(2;3)(p25.1; p25.3) and apparently balanced inv(3)(p13p25.3) in a fetus. Parental cytogenetic evaluation using karyotyping and FISH analysis showed the presence of both a balanced translocation and a paracentric inversion in father t(2;3) (p25.1;p25.3) inv(3)(p13p25.3). Microarray analysis showed a 11.6 Mb deletion at 3p26.3-p25.3 and duplication of 10.5 Mb at the 2p25.3-p25 region. The duplicated region at 2p25.1p25.3 contains 45 different genes, where 12 are reported as OMIM morbid genes with different phenotypical implications. The deleted region at 3p26.3-p25.3 contains 65 genes, out of which 27 are OMIM genes. Three of these ( CNTN4 , SETD5 and VHL ) were curated by Clingene Dosage Gene Map and were given a high haplo-insufficiency score. Genes affected by the unbalanced translocation could have contributed to some specific phenotypic changes of the fetus in late pregnancy. The application of different cytogenetic methods was essential in our case, allowing the detection of different types of structural chromosomal aberrations and more thorough genetic counseling for future pregnancies.

Background/Objectives: Abnormal general movements (GMs) in high-risk infants are among the most sensitive early predictors of cerebral palsy (CP) and other neurodevelopmental disorders. This study described changes in the quality of GMs over time in high-risk infants who received the Early Intensive Stojčević–Polovina Rehabilitation Method (EIR–SPM). The EIR–SPM is a rehabilitation method designed for children with CP, those at risk of developing CP, and children with other developmental disabilities. In high-risk infants, it is initiated within the first three months of corrected age, preferably while writhing movements (WMs) are still present. Methods: This study was conducted in eight high-risk infants with abnormal WMs and structural brain injury. The EIR–SPM was initiated between 41 and 47 weeks postmenstrual age (PMA) and was applied until 60 weeks PMA. Prechtl’s General Movements Assessment (GMA), the Detailed GM score, and the Motor Optimality Score–Revised (MOS–R) were assessed. Results: During the writhing period, two infants showed a poor repertoire (PR) pattern and six showed a cramped–synchronized (CS) pattern of GMs; at follow-up, three showed PR, and five showed CS. During the fidgety period, two infants showed normal fidgety movements (F+), two sporadic fidgety movements (sFM), one infant showed abnormal fidgety movements (aFM), and three showed absent fidgety movements (F−) at the first assessment, while at the second assessment, three infants showed F+, two sFM, one aFM, and two F−. The median Detailed GM score increased from 12 (range 11–17) to 13.5 (range 11–19; p = 0.068). The median MOS–R increased from 17.0 (range 12–24) to 19.5 (range 17–27) between the two fidgety assessments (p = 0.027). Conclusions: Improvements in motor repertoire, reflected by increased MOS–R scores, were observed during the EIR–SPM initiated in the writhing period. Larger controlled studies are needed to confirm these preliminary observations.