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Background/purpose: Influenza vaccine has been recommended in Finland since 2007 for all children of 6–35 months of age and in 2009 for those ≥6 months against pandemic influenza. We investigated the incidence of influenza and vaccine effectiveness in a birth cohort of children in 2008–2011. Methods: We followed 923 children from birth to 2 years of age for respiratory tract infections. A nasal swab sample for PCR for influenza A and B viruses was taken at the onset of acute respiratory infections. Samples were collected either at the study clinic or at home by parents. Vaccination data was retrieved from the health registries. Results: Vaccination coverage of children aged 6–23 months was 22–47% against seasonal influenza and 80% against the A(H1N1)pdm09 virus in the pandemic season 2009–2010. During 3 influenza seasons, 1607 nasal swab samples were collected. Influenza was confirmed in 56 (6.1%) of 923 children (16 A(H1N1), 14 A(H3N2), and 26 B viruses). The incidence of influenza was 5.1% in 2008–2009, 2.7% in 2009–2010, and 5.0% in 2010–2011. Effectiveness of the adjuvanted vaccine against the pandemic influenza A(H1N1)pdm09 was 97% (95% confidence interval, 76–100%). Three children with influenza were hospitalized. Conclusion: The yearly incidence of seasonal influenza was 5% in this cohort of very young children with variable influenza vaccine coverage. Adjuvanted vaccine against the pandemic influenza was highly effective. Both seasonal and pandemic influenza cases were mostly non-severe. Keywords: Children, Infant, Influenza, Pandemic influenza, Vaccination, Vaccine-preventable diseases

Objectives Patient injuries in children can have lifelong effects on the patient and a marked impact on the whole family. The aim of this study was to identify the errors and incidents leading to patient injuries in pediatric otorhinolaryngology (ORL) by evaluating accepted patient injury claims. Methods The records of all accepted patient injury claims in ORL between 2001 and 2011 were searched from the nationwide Patient Insurance Centre registry. Pediatric injuries were reviewed and evaluated in detail, and factors contributing to injury were identified. Results In the 10-year study period, 17 (7.6%) of the 223 patient injuries occurred in children, and of these, 15 (88%) were considered operative care. The median age of the patients was 8 years (range 3–16 years). All operations were performed as daytime elective surgery and by a fully trained specialist in 93% of the cases. One-half of the cases were routine surgeries for common ORL diseases. The most common incidences were incomplete surgery, retained gauze or foreign body, injury to adjacent anatomic structure, and insufficient charts or instructions (each occurred in 3 cases). The most frequent consequence was burn (n = 4). One child died because of post-tonsillectomy hemorrhage. Conclusions Patient injuries in pediatric ORL are strongly related to surgery. Most injuries occurred after routine operations by a fully trained specialist. Clinicians should be aware of the most likely scenarios resulting in claims.

We hypothesized that women undergoing scoliosis surgery who became pregnant would go to full term, have uncomplicated pregnancies, and similar patient-reported outcome measures than non-pregnant patients and healthy controls.Two hundred five women with adolescent idiopathic scoliosis (AIS) undergoing scoliosis surgery between 1998 and 2015 at several institutions in 1 country and 173 healthy women, without AIS, parous and nulliparous, were selected at random.One hundred eight women with scoliosis surgery and no pregnancy (SNP), 97 women with scoliosis surgery and pregnancy (SP), 91 healthy controls and no pregnancy, and 82 healthy controls and pregnancy (HP) were reviewed. Mean follow-up was 5 years in the SNP, 6 years in the SP, 5 years in the healthy controls and no pregnancy, and 5 years in the HP. The average time from surgery to childbirth was 5 years. Back pain (BP) during pregnancy was observed in 48% of the SP and 34% of the HP. BP after childbirth was present in 43% of the SP and 42% of the HP. Patients fused to L3 or L4 experienced more frequent low BP during pregnancy (40%) than those fused above L3 (P0.05). Cesarean section (CS) was performed for 64% and 33% in SP and HP, respectively (P0.05). As the lowest instrumented vertebra moved caudal to L4, the frequency of CS increased (P0.05; R = 0.8). The majority of CS in SP were performed in patients fused to L4 (55%) versus patients fused above and to L3 (45%) (P0.05). The most common analgesia for CS was spinal block (75% in SP and 86% in HP). Patients fused to L4 required general anesthesia significantly more often (7%) versus those fused above L4 (4%, P0.05). The health-related quality of life after spinal fusion showed general satisfaction and were similar for SNP and SP (mean 3.84 and 3.91, respectively). No sexual dysfunction was reported.Women with a history of spinal fusion for AIS fused to L3 or L4 reported a higher incidence of low BP, and CSs are more frequently required. This risk increased to 55% when spinal fusion to L4 was performed. The quality of life and sexual function were at the same level in women after scoliosis surgery than in healthy controls.

Background: Understanding early-life relationships between the Ideal Cardiovascular Health (ICVH) score and vascular phenotypes could inform likely effectiveness and timing of cardiovascular disease prevention strategies. We aimed to describe associations between ICVH scores and vascular phenotypes in 11- to 12-year-old children and their parents. Methods and results: Cross-sectional ICVH scores (range 0–7, higher indicating better health), derived by summing dichotomized metrics for cholesterol, glucose, blood pressure (BP), body mass index (BMI), diet, physical activity and smoking, were constructed for 1235 adults (89% female, mean age 43 years) and 1028 children (48% female, 12 years). The median scores were 4 and 5 for adults and children respectively. Child ICVH scores were associated with parent scores (0.18 higher child score per additional point in parent's score, 95% CI 0.12 to 0.22, P Conclusion: Few Australian children and even fewer parents have ideal cardiovascular health. Lower ICVH scores were associated with adverse adult vascular phenotypes and adverse child vascular function. Family-based interventions optimizing ICVH metrics may delay onset and progression of subclinical atherosclerosis and later cardiovascular disease.

Aim We evaluated whether nasal high-flow therapy was better than no respiratory support during the weaning phase in preterm infants. Methods The study was conducted in the neonatal intensive care unit of the Turku University Hospital between September 2014 and August 2015. Preterm infants who were alternating between nasal high-flow therapy and unassisted breathing were enrolled. Electrical activity of the diaphragm (EAdi) was recorded and compared during three-hour time periods for each option. Results We studied eight infants at a median gestational age of 31 weeks. The EAdi peak was lower during nasal high-flow therapy when compared to no respiratory support (6.1 μV vs 7.1 μV, p = 0.02), but the EAdi minimum was similar with and without respiratory support. Neural respiratory rate (62 vs 68 per minute, p = 0.02) and the frequency of sighs (27.8 vs 37.9 per hour, p = 0.03) were lower during nasal high-flow therapy than no respiratory support. Conclusion Nasal high-flow therapy reduced diaphragm activation in our cohort when compared to no respiratory support, as indicated by the lower Edi peak. An increase in the respiratory rate and the sigh frequency without respiratory support also suggests that nasal high-flow therapy provided support during the weaning phase.

Neurocognition in Childhood Epilepsy: Impact on Mortality and Complete Seizure Remission 50 Years Later Sillanpää M, Saarinen MM, Karrasch M, Schmidt D, Hermann BP. Epilepsia. 2019;60(1):131-138. doi:10.1111/epi.14606. Epub 2018 Nov 22.Objective:To study associations of the severity of impairment in childhood neurocognition (NC) with long-term mortality and complete seizure remission.Methods:A population-based cohort of 245 subjects with childhood-onset epilepsy was followed up for 50 years (median = 45, range = 2-50). Childhood NC before age 18 years was assessed as a combination of formal intelligence quotient scores and functional criteria (school achievement, working history, and psychoneurological development). Impaired NC was categorized with respect to definitions of intellectual functioning in International Classification of Diseases, Tenth Revision (R41.83, F70-F73). The outcome variables, defined as all-cause mortality and 10-year terminal remission with the 5 past years off medication (10YTR), were analyzed with Cox regression models.Results:Of the 245 subjects, 119 (49%) had normal childhood NC, whereas 126 (51%) had various degrees of neurocognitive impairment. During the 50-year observation period, 71 (29%) of the subjects died, 13% of those with normal and 44% of those with impaired NC. The hazard of death increased gradually in line with more impaired cognition, reaching significance in moderate, severe, and profound impairment versus normal NC (hazard ratio [Bonferroni corrected 95% confidence interval] = 3.3 [1.2-9.2], 4.2 [1.2-14.2], and 5.5 [2.4-12.3], respectively). The chance for 10YTR was highest among subjects with normal NC (61%), whereas none of those with profound impairment reached 10YTR. In the intermediate categories, the chance was, however, not directly related to the increasing severity of impairment.Significance:The severity of neurocognitive impairment during childhood shows a parallel increase in the risk of death. In comparison with normal NC, subjects with lower childhood NC are less likely to enter seizure remission. However, normal NC does not guarantee complete remission or prevent premature death in some individuals with childhood-onset epilepsy.

Aims/Hypothesis: Evidence of the role of cytomegalovirus (CMV) infection in the pathogenesis of type 1 diabetes (T1D) has remained inconclusive. Our aim was to elucidate the possible role of CMV infection in the initiation of islet autoimmunity and in the progression to clinical T1D among children with human leukocyte antigen (HLA)‐conferred T1D risk. Methods: A total of 1402 children from the prospective Type 1 Diabetes Prediction and Prevention (DIPP) study were analyzed for CMV‐specific IgG antibodies during early childhood. All the children carried HLA‐DQ genotypes associated with increased risk for T1D. The effect of CMV infection on the appearance of T1D‐associated autoantibodies (insulin autoantibodies [IAA], glutamic acid decarboxylase [GADA], and insulinoma antigen‐2 [IA‐2A], n = 356) and on the progression rate to clinical T1D (n = 233) were analyzed with Kaplan‐Meier survival analysis and Log‐rank test. Results: Early childhood CMV infection was inversely associated with the development of T1D during childhood. Cumulative progression to T1D was decreased in subjects with an early CMV infection (P = 0.035). In further analyses, the effect of early CMV infection on the initiation of islet autoimmunity and progression to clinical T1D were examined separately. Interestingly, early CMV infection did not affect the appearance of T1D‐associated autoantibodies but a decelerating effect was observed on the progression rate from islet autoimmunity to clinical T1D (P = 0.015). Conclusion: Our results suggest that an early childhood CMV infection may decelerate the progression from islet autoimmunity to clinical T1D among at‐risk children and may thus protect these children from progressing to T1D during childhood.

Nausea and vomiting of pregnancy (NVP) is frequent, affecting up to 70-85% of pregnant women. However, severity of NVP especially in clinical practice is often uncertainly assessed and thus both under- and overdiagnosing is probable. Furthermore, risk factors for NVP, although recognized, are not well established. The aim of our study was to evaluate the severity of NVP with a structured questionnaire and evaluate associative risk factors.Sample of 2411 women were recruited from maternity health care clinics. Severity of NVP was assessed with pregnancy-unique quantification of emesis (PUQE) questionnaire. Age, previous pregnancies, previous deliveries, previous miscarriages including ectopic pregnancies, previous pregnancy terminations, nationality, pre-pregnancy body mass index, smoking, marital status and employment were used as explanatory factors.Altogether 88.0% of the women reported some level of NVP, of which 6.4% was severe, 52.2% moderate and 29.4% mild. Daily duration of NVP was ≥ four hours in 12 h in 45.0%. Further, 18.8% of the women had vomiting episodes ≥ three times and 37.4% retching episodes ≥ three times in 12 h. Women with ≥ two previous pregnancies had increased risk for more severe NVP (OR 2.17, 95%CI; 1.34-3.51, p 0.0001). Older women had increased daily duration of nausea (OR 1.03, 95%CI; 1.00-1.06, p = 0.004) but lower number of vomits (OR 0.93, 95%CI; 0.93-0.97, p 0.0001) and lower number of retching (OR 0.93, 95%CI; 0.90-0.96, p 0.0001). Smokers had shorter daily duration of nausea (OR 0.49, 95%CI; 0.33-0.73, p 0.0001), but higher number of vomiting episodes compared to non-smokers (OR 1.83, 95%CI; 1.26-2.66, p = 0.021).Women suffered from NVP very frequently. The daily duration of NVP was moderately long, in nearly half of the women four hours or more. In addition, retching was more frequent than vomiting. From studied risk factors, few associations with different aspects of NVP emerged, but only multiparity was associated with the severity of NVP. As NVP affects several women during pregnancy, in future, the impact of NVP on quality of life, future family planning and health costs should be evaluated.

Objective Maternal thrombophilia is a risk factor for adverse pregnancy outcomes. The aim of this study was to elucidate the controversial role of fetal and paternal thrombophilia in the development of severe placenta-mediated pregnancy complications. Study Design The study group comprised 126 mothers, 72 fetuses and 58 fathers. 111 mothers, 50 fetuses and 91 fathers acted as controls. 106 couples were selected to study the thrombophilias of paternal inheritance, 58 from the study group and 48 from the control group. The prevalence of factor V Leiden mutation, prothrombin G20210 A mutation and homozygous 10-methylenetetrahydrofolate reductase C677 T mutations were compared between the study and control groups to study whether maternal, fetal or paternal thrombophilias increase the risk of severe preeclampsia, intrauterine growth restriction, placental abruption and stillbirth. Results The total prevalence of fetal thrombophilic mutations was 8.3% in the study group and 14.0% in the control group. Paternal prevalence of thrombophilic mutations was 6.8% and 4.3%, respectively. There were no statistical differences between fetal or paternal thrombophilic mutations between the study and control groups. Conclusion Fetal or paternal factor V Leiden mutation is not associated with severe placenta-mediated pregnancy complications.

INTRODUCTION Recently, it has been suggested that the occurrence of posthysterectomy vaginal cuff dehiscence has increased. Consequently, we evaluated the incidence of vaginal cuff dehiscence after different types of hysterectomies. Our hypothesis is that vaginal cuff dehiscence is more often associated with total laparoscopic hysterectomy (TLH) than other types of uterine removal. MATERIAL AND METHODS A total of 13 645 hysterectomies from 1992 to 2015 were evaluated in the Turku University Hospital district, Finland. The primary outcome was occurrence of vaginal dehiscence after different types of hysterectomy. The hysterectomy and postoperative vaginal dehiscence trends were analyzed as the secondary outcome. In a subanalysis of dehiscence cases, women's characteristics and perioperative vaginal cuff opening and closure techniques were compared between conventional hysterectomies (vaginal, abdominal, and laparoscopic with vaginal closure) and TLH. RESULTS Altogether, 22 cases of vaginal cuff dehiscence were included. Most cases (n = 15) occurred after TLH (n = 1104), resulting in an incidence of 1.27%. After conventional laparoscopic hysterectomy with vaginal closure (n = 2853), vaginal (n = 4150), and abdominal (n = 5538) hysterectomies, the incidence rates were 0.11%, 0.05%, and 0.02%, respectively. Compared to abdominal hysterectomy, which was associated with the lowest incidence rate, vaginal dehiscence after TLH had an odds ratio (OR) 71.1 (9.34-541.38, P

Parental mental disorders have been shown to predict offspring's mental health problems. We examined whether pathways from parental mental disorders to offspring's psychiatric work disability in early adulthood are mediated through offspring's mental disorders and social disadvantage in adolescence.Study population consisted of the 1987 Finnish Birth Cohort. Data on parents' psychiatric care or work disability due to mental diagnosis between 1987 and 2000 and the cohort participants' health and social factors between 2001 and 2005 were derived from administrative national registers. From 2006 through 2015, 52,182 cohort participants were followed for admittance of psychiatric work disability due to depressive or anxiety disorders. First, we applied a pathway analysis to examine the occurrence of each path. We then used mediation analysis to assess the proportion of association between parental mental disorders and work disability mediated by offspring's health and social disadvantage.The pathway model indicated that the association from parental mental disorders to offspring's work disability due to depressive or anxiety disorder is through mental disorders and social disadvantage in adolescence. Odds Ratio for the total effect of parental mental disorders on offspring's psychiatric work disability was 1.85 (95% confidence interval [CI] 1.46-2.34) in the model including offspring's mental disorders that mediated this association by 35%. Corresponding results were 1.86 (95% CI 1.47-2.35) and 28% for social disadvantage in adolescence.These findings suggest that intergenerational determination of work disability due to mental disorders could be addressed by actions supporting mental health and social circumstances in adolescence.

Background Wheezing illnesses among young children are common and are a risk factor for asthma. However, determinants of childhood bronchial reactivity, a key feature of asthma, are largely unknown. The aim of this study was to determine how patient characteristics during the first severe virus-induced wheezing episode are associated with pulmonary function at preschool age. Methods Study consisted of 76 children presenting with their first wheezing episode at the ages of 3 to 23 months. At study entry, viral etiology, rhinovirus genome load, atopic and clinical characteristics, and standardized questionnaire were analyzed. At 4-year follow-up visit, impulse oscillometry with exercise challenge was performed. Results At study entry, the mean age of the children was 12 months (SD 6.0), 57 (75%) were rhinovirus positive, and 22 (30%) were sensitized. At follow-up visit four years later, the mean age of the children was 60 months (SD 7.9) and 37 (49%) were using asthma medication regularly (discontinued before testing in 25 [68%] children). Bronchial reactivity (≥35% change in mean crude values of resistance) after exercise challenge or bronchodilation was present in nine (12%) children. Children with atopic sensitization at the time of the first wheezing episode were more often likely to develop bronchial reactivity (odds ratio 8.8, P = 0.03) than the children without sensitization. No other significant associations were found. Conclusions Atopic sensitization at the time of the first severe wheezing episode is an important early risk factor for increased bronchial reactivity at preschool age.

Pikkukeskosena syntyneiden (syntynyt < 32 raskausviikkoa ja/tai syntymäpaino ≤ 1500 grammaa) lasten varhaista eleiden ja esinetoimintojen kehitystä on tutkittu vähän ja sen yhteyttä myöhempään kognitiiviseen kehitykseen ei ole tutkittu lainkaan, vaikka mahdollinen yhteys antaisi tärkeää erotusdiagnostistatietoa kliiniseen työhön. Tämän tutkimuksen tavoitteena oli saada lisää tietoa pikkukeskosena syntyneiden lasten eleiden kehityksestä sekä tarkastella ele-esinetoimintojen kehityksen ja kognitiivisen kehityksen välistä yhteyttä. Pikkukeskosten (N = 57) eleiden ja esinetoimintojen kehitystä arvioitiin Varhaisen kommunikaation ja kielen kehityksen arviointimenetelmällä (CDI) vuoden korjatussa iässä ja kognitiivista kehitystä Bayley Scales of Infant and Toddler Development -testin (Bayley-III) avulla kahden vuoden korjatussa iässä. Keskosten eleiden ja esinetoimintojen kehitys oli kokonaisuutena heikompaa kuin käytetyn menetelmän normiaineistossa. Kognitiivinen kehitys oli ryhmätasolla tarkastellen ikätasoista. Ele-esinetoimintojen ja kognitiivisen kehityksen välillä todettiin merkitsevä, positiivinen yhteys. Pikkukeskosena syntyneiden lasten varhaista kielellistä ja kommunikatiivista kehitystä tulisi seurata kliinisessä työssä, sillä se auttaa tunnistamaan varhain ne lapset, jotka tulevat mahdollisesti tarvitsemaan tukea kehitykseensä.

Objectives To study first and second/third trimester levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) and soluble endoglin (sEng) in FINNPEC case-control cohort. The participants were further divided into subgroups based on parity and onset of the disease. Recommended cut-off values in aid of pre-eclampsia (PE) prediction and diagnosis were also tested. Methods First trimester serum samples were available from 221 women who later developed PE and 239 women who did not develop PE. Second/third trimester serum samples were available from 175 PE and 55 non-PE women. sFlt-1 and PlGF were measured electro-chemiluminescence immunoassays and sEng by ELISA. Results In all timepoints PlGF, endoglin and the sFlt-1/PlGF ratio were increased in the PE group compared to the non-PE group. The serum concentrations of sFlt-1 were increased only at second/third trimester in PE women. Higher concentrations of s-Flt1, endoglin and higher sFlt/PlGF ratio were found at the third trimester in primiparous women compared to multiparous women. Primiparous PE women also had lower concentrations of PlGF at the third trimester. The proportion of women exceeding all cut-offs of the sFlt-1/PlGF ratio (≥33, ≥38, ≥85 and ≥110) was greater in the PE group, but there were also pre-eclamptic women who met rule-out cut-off or did not meet rule-in cut-off. Conclusions Primiparous pregnancies have more anti-angiogenic profile during second/third trimester compared with multiparous pregnancies. Our findings also suggest that certain maternal characteristics, e.g. BMI, smoking and pre-existing diseases, should be taken into account when different sFlt-1/PlGF ratio cut-offs are utilized.

More people are living with the long-term effects of cancer owing to improvements in cancer treatments and an aging population. Many people diagnosed with cancer report a negative impact on sexual identity, sexual functioning, and their sexual relationship. Gynecologic cancer survivors are often the most severely affected. These cancers involve cancers of the ovaries, uterus, cervix, vagina, and vulva. The impact of these cancers on sexual health results not only from the disease process itself, but may also be due to the necessary treatments required. These can have a profound impact on psychological, physiological, and social well-being both in the short and long term, which may result in negative impact on the quality of life of the patient as well as her partner. Although most patients express that they would like to be more informed about sexual health and would like to have the opportunity to discuss these issues with their therapeutic team, sexual health is often not discussed with the patient.

BACKGROUND Non-invasive neurally adjusted ventilatory assist (NIV-NAVA), a mode of non-invasive ventilation (NIV) controlled by diaphragmatic electrical activity, may be superior to other NIV as a respiratory support after extubation in preterm infants, but no report has compared NIV-NAVA with other NIV methods. We evaluated the effectiveness and adverse effects of NIV-NAVA after extubation in preterm infants

ObjectivesIn order to evaluate the safety of tonsillectomy among children, we retrospectively studied the incidence of post-operative complications, adverse events and their association with peri-operative medication.MethodsData were collected from the medical records of 691 patients aged 1–16 years, including details of post-operative complications (any unplanned contact with the hospital), analgesics, dexamethasone, 5-HT3 antagonists, local anaesthetic and haemostatic agents.ResultsRecovery was complicated in 13.6 per cent of patients, of whom 8.4 per cent were re-admitted to the ward. The most common complication was post-tonsillectomy haemorrhage, experienced by 7.1 per cent of patients. Re-operation under general anaesthesia (for grade III post-tonsillectomy haemorrhage) was required by 4.2 per cent of patients. Peritonsillar infiltration of lidocaine with adrenaline increased the risk of post-tonsillectomy haemorrhage (odds ratio = 4.1; 95 per cent confidence interval = 2.1 to 8.3).ConclusionEvery seventh paediatric patient experienced a complicated recovery after tonsillectomy, caused by post-tonsillectomy haemorrhage in most cases. Local peritonsillar infiltration of lidocaine with adrenaline was associated with an increased risk of post-tonsillectomy haemorrhage.

Objectives Chronic stress, also associated with climacteric-related symptoms, may influence cortisol secretion. We studied cortisol metabolism in peri- and postmenopausal women with diverse climacteric-related symptoms. Study design and main outcome measures The study population was 35 women, aged 45–70 years. Plasma cortisol levels were measured from blood samples collected every 20 min over 24 h. Urinary cortisol was analysed from 24-hour urine collections. Climacteric-related symptoms (vasomotor, sleep, depressive, anxiety, cognitive, sexual, menstrual, and somatic) were evaluated with the Women’s Health Questionnaire (WHQ). Associations between cortisol variables (24-hour, night, day, maximum, minimum, morning baseline, cortisol awakening response (CAR), area under the curve, slope, and 24-hour urinary cortisol) and the symptoms were first examined with a correlation analysis. Then, the women were divided into two groups according to their climacteric symptomatology, and differences in cortisol variables between the groups were investigated. Diurnal cortisol curves by symptomatology were also analyzed visually. Results In the correlation analysis, more frequent vasomotor symptoms were associated with a higher CAR (rs = 0.37, p = 0.039) and lower 24-hour urinary cortisol excretion (rs= -0.45, p = 0.012), and more frequent depressive symptoms were associated with a higher minimum cortisol level (rs = 0.33, p = 0.0498). When the women were divided into two groups, women with more frequent vasomotor (p = 0.012) or somatic symptoms (p = 0.021) had a lower 24-hour urinary cortisol excretion than less symptomatic women. Conclusions Although previous studies have reported associations between climacteric-related symptoms and cortisol secretion, these two factors were not substantially interrelated in our study.

PURPOSE This study examined how motor skills are associated with physical activity (PA), sedentary time, body fat, and day care attendance among young children. Also, the motor skills of healthy weight children were compared to those who were overweight or obese. METHODS The study population consisted of five to six years old children (n = 111; 45 boys) who participated in the longitudinal STEPS Study carried out in Southwest Finland in 2013-2014. Motor skills were measured with the Bruininks-Oseretsky test, second edition (BOT-2) including fine manual control, manual coordination, body coordination, and strength and agility. Moderate-to-vigorous intensity PA (MVPA) and sedentary time were objectively measured with hip-worn accelerometers. Body mass index (BMI) was calculated based on measured weight and height. Body fat percentage (BF%) was measured using segmental multifrequency bio impedance analysis. Day care attendance was measured with parental questionnaires. Linear regression analyses were adjusted by age, sex, and parental education. RESULTS Day care attendance was positively associated with body coordination and strength and agility. Lower BF% in girls was associated with higher strength and agility scores. There were no associations between manual coordination or fine manual control and the explanatory variables. Objectively measured MVPA and sedentary time showed no associations with motor skills. Overweight children had significantly lower scores in all motor skill composites (P

Maternal cytokine profiles during pregnancy are characterized by significant deviations, varying substantially between gestational time points and tissues. Obesity, in turn, is linked with low-grade inflammation in adipose tissue and increased concentrations of systemic inflammatory mediators. However, the balance of pro- and anti-inflammatory cytokines in obese pregnancy has remained elusive. In view of the demonstrations that the obesity is a global epidemic in the population at reproductive age with a strong intergenerational impact, we investigated the relation of gestational immune adaptations and obesity-induced inflammation. We found a significant decrease in systemic IL-1β and MCP-1 concentration from 1st to 3rd trimester of pregnancy while IL-10 concentration increased, respectively. However, in obese pregnancies this reduction of pro-inflammatory mediators was not detected. This may constitute an additional risk factor in obese pregnancies in which the concentration of MCP-1 is already upregulated compared to normal weight mothers.

AIM: The aim was to assess the influence of dietary counselling on the pubertal development and hormonal status in healthy adolescents.METHODS: We used a subcohort of 193 healthy boys (52%) and girls (48%) from the Special Turku Coronary Risk Factor Intervention Project. Participants were recruited by nurses at the well-baby clinics in Turku Finland in 1990-1992 and randomised into intervention and control groups. Intervention children received low-saturated fat and low-cholesterol dietary counselling initiated at seven months of age. Participants were examined once a year with Tanner staging, anthropometric measurements and serial reproductive hormones from 10 to 19 years of age. In girls, postmenarcheal hormones were not analysed.RESULTS: Pubertal hormones in boys or girls did not differ between the intervention and control groups. However, we observed slight differences in pubertal progression by Tanner staging and in anthropometric parameters. The intervention boys progressed faster to G4 (p = 0.008), G5 (p = 0.008) and P5 (p = 0.03). The intervention boys were taller than control boys (p = 0.04), while weight and body mass index did not differ.CONCLUSION: Dietary intervention did not affect pubertal hormonal status. This finding supports the safety of implemented counselling in respect to puberty.

The oxytocin receptor gene (OXTR) may function as a "plasticity gene" that increases or decreases sociability in those individuals susceptible to growing up in a beneficial versus more adverse environment. This study used data from 2289 (55% female) participants from the ongoing prospective Young Finns Study. Maternal emotional warmth was assessed in 1980 when the participants were 3-18 years old. Participants' sociability temperament was measured at five follow-ups, from 1992 to 2012. Emotional warmth in childhood and OXTR genotype were not directly associated with temperamental sociability. We found a nominally significant gene environment interaction (p = .03) suggesting that participants with a genetic profile of rs1042778 T-allele and rs2254298 A-allele are affected high versus low emotional warmth, whereas homozygotes of both G-alleles are unaffected by the same environmental influence. Our findings should be, however, interpreted as a null result as the interaction effect did not survive correction for multiple testing.

Objective. In clinical practise, prognostication of endometrial cancer is based on clinicopathological risk factors. The use of immunohistochemistry-based markers as prognostic tools is generally not recommended and a systematic analysis of their utility as a panel is lacking. We evaluated whether an immunohistochemical marker panel could reliably assess endometrioid endometrial cancer (EEC) outcome independent of clinicopathological information. Methods. A cohort of 306 EEC specimens was profiled using tissue microarray (TMA). Cost- and time-efficient immunohistochemical analysis of well-established tissue biomarkers (ER, PR, HER2, Ki-67, MLH1 and p53) and two new biomarkers (L1CAM and ASRGL1) was carried out. Statistical modelling with embedded variable selection was applied on the staining results to identify minimal prognostic panels with maximal prognostic accuracy without compromising generalizability. Results. A panel including p53 and ASRGL1 immunohistochemistry was identified as the most accurate predictor of relapse-free and disease-specific survival. Within this panel, patients were allocated into high- (5.9%), intermediate- (295%) and low- (64.6%) risk groups where high-risk patients had a 30-fold risk (P

Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype.We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses.No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n = 9) and the control children without disease or associated autoantibodies (n = 18).Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.

AimFor previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). MethodsFrom the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. ResultsAll 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (Europerkg) were 4391Euro (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448Euro (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. ConclusionsEarly high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.

Objectives The aim of the study was to compare long-term mortality and causes of death in children post admission to an ICU with a control population of same age. Design Longitudinal follow-up study. Setting Registry study of a national ICU register and hospital registries. Patients Children admitted to an ICU in the years 2009 and 2010. Interventions None. Measurements and main results The mortality and causes of death following ICU discharge were analyzed retrospectively. The median follow-up period was 4.9 years (25-75th percentiles, 4.4-5.5 yr). The causes of death in survivors 30 days after ICU discharge were compared with a cohort of 1 million children of the general population of same age. In total, 2,792 children were admitted to an ICU during the study period. Of those, 53 (1.9%) died in the ICU and 2,739 were discharged. Thirteen children died within 30 days of discharge, and 68 died between 30 days and the end of follow-up (December 31, 2014). In the control population (n = 1,020,407 children), there were 1,037 deaths (0.10%) from 2009 to 2014. The standardized mortality rate for the children admitted to the ICU during the study period was 53.4 (95% CI, 44.7-63.2). The standardized mortality rate for those children alive 1 year after discharge was 16.7 (12.1-22.6). One-year cumulative mortality was 3.3%. The most common causes of death in subjects alive 30 days post ICU were cancer (35.3%), neurologic (17.6%), and metabolic diseases (11.7%), whereas trauma was the most common cause in the control group (45.3%). Conclusions There was an increased risk of death in a cohort of ICU-admitted children even 3 years after discharge. In those who survived 30 days after discharge, medical causes of death were dominant, whereas deaths due to trauma were most common in the control group.

OBJECTIVE: Cesarean section (C-section) is associated with various immune-mediated diseases in the offspring. We investigated the relationship between mode of delivery and celiac disease (CD) and CD autoimmunity (CDA) in a multinational birth cohort. METHODS: From 2004 to 2010, infants from the general population who tested positive for HLA DR3-DQ2 or DR4-DQ8 were enrolled in The Environmental Determinants for Diabetes in the Young (TEDDY) study. Children were annually screened for transglutaminase autoantibodies, if positive, they are retested after 3 to 6 months and those persistently positive defined as CDA. Associations of C-section with maternal (age, education level, parity, pre-pregnancy weight, diabetes, smoking, weight gain during pregnancy) and child characteristics (gestational age, birth weight) were examined by Fisher exact test or Wilcoxon rank-sum test. Hazard ratios (HRs) for CDA or CD were calculated by Cox proportional hazard regression models. RESULTS: Of 6087 analyzed singletons, 1600 (26%) were born by C-section (Germany 38%, United States 37%, Finland 18%, Sweden 16%), and the remaining were born vaginally without instrumental support; 979 (16%) had developed CDA and 343 (6%) developed CD. C-section was associated with lower risk for CDA (hazard ratio [HR] = 0.85; 95% confidence interval [CI] 0.73, 0.99 P = 0.032) and CD (HR = 0.75; 95% CI 0.58, 0.98; P = 0.034). After adjusting for country, sex, HLA-genotype, CD in family, maternal education, and breast-feeding duration, significance was lost for CDA (HR = 0.91; 95% CI 0.78, 1.06; P = 0.20) and CD (HR = 0.85; 95% CI 0.65, 1.11; P = 0.24). Presurgical ruptured membranes had no influence on CDA or CD development. CONCLUSION: C-section is not associated with increased risk for CDA or CD in the offspring.

We evaluated the feasibility of a multi-feature mismatch negativity (MMN) paradigm in studying auditory processing of healthy newborns. The aim was to examine the automatic change-detection and processing of semantic and emotional information in speech in newborns. Brain responses of 202 healthy newborns were recorded with a multi-feature paradigm including a Finnish bi-syllabic pseudo-word/ta-ta/as a standard stimulus, six linguistically relevant deviant stimuli and three emotionally relevant stimuli (happy, sad, angry). Clear responses to emotional sounds were found already at the early latency window 100-200 ms, whereas responses to linguistically relevant minor changes and emotional stimuli at the later latency window 300-500 ms did not reach significance. Moreover, significant interaction between gender and emotional stimuli was found in the early latency window. Further studies on using multi-feature paradigms with linguistic and emotional stimuli in newborns are needed, especially those containing of follow-ups, enabling the assessment of the predictive value of early variations between subjects.

Background The transition from early childhood wheezing to persistent asthma is linked to lung function impairment over time. Little is known how the methods used to study lung function at different ages correlate longitudinally. Methods Sixty-four children with a history of hospitalization for bronchiolitis before 6 months of age were prospectively studied with impulse oscillometry (IOS) at the mean age of 6.3 years and these preschool IOS results were compared with flow-volume spirometry (FVS) measurements at mean age of 11.4 years. Results The baseline respiratory system resistance at 5 Hz (Rrs5) showed a modest statistically significant correlation with all baseline FVS parameters except FVC. The post-bronchodilator (post-BD) Rrs5 showed a modest statistically significant correlation with post-BD FEV1 and FEV1 /FVC. The bronchodilator-induced decrease in Rrs5 showed a modest statistically significant correlation with the percent increase in FEV1 . Baseline and post-BD respiratory reactance at 5 Hz (Xrs5) showed a modest statistically significant correlation with baseline and post-BD FVS parameters except post-BD FEV1 /FVC, respectively, and post-BD Xrs5 showed a strong correlation with post-BD FVC (ρ = 0.61) and post-BD FEV1 (ρ = 0.59). In adjusted linear regression, preschool Xrs5 remained as a statistically significant independent predictor of FVS parameters in adolescence; the one-unit decrease in the Z-score of preschool post-BD Xrs5 predicted 9.6% lower post-BD FEV1 , 9.3% lower post-BD FVC, and 9.7% lower post-BD MEF50 when expressed as %-predicted parameters. Conclusion Persistent post-BD small airway impairment in children with a history of bronchiolitis detected with IOS at preschool age predicted FVS results measured in early adolescence.

This study explores the moderators affecting the success of an Internet-based and telephone assisted remote parent training intervention and compares them to an educational control group. We prospectively identified 464 parents who reported at a health check that their 4-year-old children showed elevated levels of externalizing behavior. The moderators explored included parental attention deficit and hyperactivity disorder (ADHD) and parental distress. The dependent variables were child externalization scores and self-reported parenting skills. The measures were completed at baseline, six and 12-months follow-up. The 232 families randomized to active treatment received 11 Internet-based training sessions with weekly phone calls from a coach. The other 232 families had access to a website that provided general positive parenting advice and one 45-minute phone-call from a coach. Using hierarchical linear models, we explored if the parental ADHD or parental distress modified the treatment effects on child externalizing behavior or parenting skills. The results showed that none of the independent variables moderated intervention effects on child externalizing behavior or parenting skills. The lack of significant moderator effects could have been due to the treatment's personalization, the format's flexibility and adaptability to when and how the parents wanted to complete the sessions or the relatively low levels of ADHD and parental distress among the participants.

Background Oseltamivir has been used to treat children with influenza for nearly 2 decades, with treatment currently approved for infants aged ≥2 weeks. However, efficacy and safety remain controversial. Newer randomized, placebo-controlled trials (RCTs), not included in previous meta-analyses, can add to the evidence base. Methods We conducted a systematic review to identify RCTs of oseltamivir therapy in children. We obtained individual patient data and examined protocol-defined outcomes. We then conducted a 2-stage, random-effects meta-analysis to determine the efficacy of treatment in reducing the duration of illness, estimated using differences in restricted mean survival time (RMST) by treatment group. We also examined complications and safety. Results We identified 5 trials that included 2561 patients in the intention-to-treat (ITT) and 1598 in the intention-to-treat infected (ITTI) populations. Overall, oseltamivir treatment significantly reduced the duration of illness in the ITTI population (RMST difference, -17.6 hours; 95% confidence interval [CI], -34.7 to -0.62 hours). In trials that enrolled patients without asthma, the difference was larger (-29.9 hours; 95% CI, -53.9 to -5.8 hours). Risk of otitis media was 34% lower in the ITTI population. Vomiting was the only adverse event with a significantly higher risk in the treatment group. Conclusions Despite substantial heterogeneity in pediatric trials, we found that treatment with oseltamivir significantly reduced the duration of illness in those with influenza and lowered the risk of developing otitis media. Alternative endpoints may be required to evaluate the efficacy of oseltamivir in pediatric patients with asthma.

Preeclampsia is a vascular pregnancy disorder that often involves impaired placental development. HO-1 (heme oxygenase 1, encoded by HMOX1 ) is a stress response enzyme crucial for endothelial and placental function. Long version of the guanine–thymine (GT n ) microsatellite in the HMOX1 promoter decreases HO-1 expression, and the long maternal repeat is associated with late-onset preeclampsia. Our aim was to study whether the length of fetal repeat is associated with mother’s preeclampsia, whether the length of fetal and maternal repeats affect HO-1 levels in placenta and maternal serum, and whether HO-1 levels are altered in preeclampsia. We genotyped the repeat in the cord blood of 609 preeclamptic and 745 nonpreeclamptic neonates. HO-1 levels were measured in 36 placental samples, and in the first (222 cases/243 controls) and third (176 cases/53 controls) pregnancy trimester serum samples using enzyme-linked immunosorbent assay. The long fetal GT n repeat was associated with preeclampsia and its severe and early-onset subtypes. Interaction analysis suggested the maternal and fetal effects to be independent. Placental or serum HO-1 levels were not altered in preeclamptics, possibly reflecting heterogeneity of preeclampsia. Carriers of the long fetal and maternal repeats had lower placental and serum HO-1 levels, respectively, providing functional evidence for the association. We conclude that the long fetal GT n repeat may increase mother’s risk for especially severe and early-onset preeclampsia. The fetal and maternal risk alleles likely predispose to different disease subtypes.