Systematic analysis of adverse incident reports revealed the need for improvements in the neonatal unit.

AIM: The aims were to characterise adverse incident reports and recommendations to avoid the reoccurrence of adverse incidents and detect a possible increase in incidents outside of office hours and on vacation season. METHODS: Analysis of adverse incidents reported at the neonatal intensive care unit of Tampere University Hospital in Finland between 2013 and 2020. RESULTS: Analysis of 925 fully processed adverse incident reports revealed that 36.3% of the reports were related to medication, fluid management and blood products, and 34.8% of these were administering errors. Nurses reported 828 (89.5%) adverse incidents and physicians reported 37 (4.0%). Near misses constituted 35.3% of nurses' and 21.6% of physicians' reports. There were significantly more adverse incident reports on day shifts, on Thursdays and, Saturdays and in June, November and December than at other times. The interventions recommended were to inform the staff or other parties after 673 (72.7%) reports and to recommend improvements after 56 (6.0%) reports. CONCLUSION: Analysis of adverse incident reports can reveal the need for improvements in existing protocols in the neonatal intensive care unit.

Association of early discharge with increased likelihood of hospital readmission in first four weeks for vaginally delivered neonates.

AIM: The main aim was to determine whether hospital readmission rates by 28 days of age are elevated with early discharge (ED) in Finland. We sought to identify the causes and predictors of ED, readmission rates, admissions to the intensive care unit (ICU) and death. METHODS: The data of 333,321 infants were retrieved from nationwide registers. Vaginally delivered single infants at gestational ages (GAs) of ≥37+0 , born in 2008-2015 and treated in any maternity ward in Finland, were included. ED was defined as discharge on the day of birth or after one night stay on the maternity ward. RESULTS: During the study period, the ED and hospital readmission rates increased. Low-risk infants and those born in high population-density areas were more likely to be discharged early. ED predicted hospital readmission but not ICU admission or death. The most common reason for readmission was jaundice, followed by infection. ED seemed not to predict severe cardiologic problems. Rather than ED, being born at 38+0 -38+6  weeks' GA significantly predicted ICU admission or death. CONCLUSION: Early discharge seems to be associated with increased hospital readmission. Birth at 38+0 -38+6  weeks' GA was a significant predictor of ICU admission or death, as opposed to early discharged infants.

Calcium supplementation during pregnancy and long-term offspring outcome: a systematic literature review and meta-analysis.

The World Health Organization currently recommends calcium supplementation for pregnant women, especially those with low calcium intakes, to reduce the risk of hypertension and preeclampsia. We aimed to evaluate the effect of this intervention on selected offspring outcomes. A systematic search was conducted in 11 databases for published randomized controlled trials (RCTs) on the effect of maternal calcium supplementation with or without vitamin D during pregnancy on selected offspring cardiovascular, growth, and metabolic and neurodevelopmental outcomes. Screening of titles and abstracts of 3555 records and full texts of 31 records yielded six RCTs (nine reports, n = 1616). Forest plot analyses were performed if at least two studies presented comparable data on the same outcome. In one study (n = 591), high-dose calcium supplementation during pregnancy was associated with a decreased risk of offspring high systolic blood pressure at 5-7 years of age (risk ratio = 0.59; 95% confidence interval: 0.39-0.90). The effects of the intervention on offspring growth, metabolic, and neurodevelopmental outcomes remain unknown because of conflicting or insufficient data. High risk of attrition bias decreased the quality of the evidence. Limited available data from RCTs do not provide sufficient evidence to conclude that prenatal calcium supplementation influences offspring health outcomes beyond the newborn period.

Calcium supplementation during pregnancy and maternal and offspring bone health: a systematic review and meta-analysis.

Insufficient calcium intake during pregnancy may lead to maternal bone resorption and lower bone density of offspring. We evaluated the impact of supplementary calcium with or without vitamin D during pregnancy on maternal and offspring bone mineral density (BMD) and teeth firmness of the offspring. Randomized controlled trials (RCTs) were searched systematically in 11 databases. Two researchers independently screened the titles and abstracts of 3555 records and the full texts of 31 records to examine eligibility. The search yielded seven RCTs (11 reports, n = 1566).  No advantage of calcium supplementation was found on maternal BMD after delivery or during breastfeeding, or on offspring BMD, even when dietary calcium intake was low. The results were neither modified by the dose of calcium nor concomitant vitamin D administration. A suspicion of some long-term harm of the intervention on maternal BMD and growth of female offspring was raised based on the data. One study suggested some benefit of high-dose calcium supplementation on offspring teeth firmness at 12 years old. A low number of the studies and abundant missing data reduced the quality of the findings. The impact of calcium supplementation on maternal and offspring bone health was deemed unknown because of inconclusive research results.

Is birth out-of-hospital associated with mortality and morbidity by seven years of age?

BACKGROUND AND AIMS: Compared to in-hospital births, the long-term outcome of children born out-of-hospital, planned or unplanned, is poorly studied. This study aimed to examine mortality and morbidity by seven years of age in children born out-of-hospital compared to those born in-hospital. METHODS: This study was registered retrospectively and included 790 136 children born in Finland between 1996 and 2013. The study population was divided into three groups according to birth site: in-hospital (n = 788 622), planned out-of-hospital (n = 176), and unplanned out-of-hospital (n = 1338). Data regarding deaths, hospital visits, reimbursement of medical expenses, and disability allowances was collected up to seven years of age or by the year-end of 2018. The association between birth site and childhood morbidity was determined using multivariable-adjusted Cox hazard regression analysis. RESULTS: No deaths were reported during the first seven years after birth in the children born out-of-hospital. The percentage of children with hospital visits due to infection by seven years of age was lower in those born planned out-of-hospital and in the combined planned out-of-hospital and unplanned out-of-hospital group compared to those born in-hospital. Furthermore, the percentage of children with hospital visits and who received disability allowances due to neurological or mental disorders was higher among those born unplanned out-of-hospital and out-of-hospital in total when compared to those born in-hospital. In the multivariable-adjusted Cox proportional hazard regression analysis, the hazard ratio for hospital visits due to asthma and/or allergic diseases (HR 0.84; 95% CI 0.72-0.98) was lower in children born out-of-hospital when compared to those born in-hospital. A similar decreased risk was found due to infections (HR 0.76; 95% CI 0.68-0.84). However, the risk for neurological or mental health disorders was similar between the children born in-hospital and out-of-hospital. CONCLUSIONS: Morbidity related to asthma or allergic diseases and infections by seven years of age appeared to be lower in children born out-of-hospital. Birth out-of-hospital seemed to not be associated with increased risk for neurological morbidity nor early childhood mortality. Our study groups were small and heterogeneous and because of this the results need to be interpreted with caution.

Real-time detection of cerebrospinal fluid with bioimpedance needle in paediatric lumbar puncture.

BACKGROUND: Lumbar puncture is a common clinical procedure that can occasionally be difficult. Various needle guidance methods can facilitate performing this procedure, but at the expense of special expertise, equipment and facility. In the present study, we evaluated the clinical feasibility of a novel bioimpedance needle system regarding its ability to detect cerebrospinal fluid (CSF) in paediatric lumbar punctures. METHODS: We performed 40 lumbar puncture procedures using the bioimpedance needle system in 37 paediatric patients, aged from 0 days to 17 months, as a part of their prescribed examinations in two university hospitals. The bioimpedance needle is similar to a conventional 22G cutting-edge spinal needle with a stylet, except the needle and stylet are configured as a bipolar electrode with high spatial resolution. The system measures in real-time when the needle tip reaches the subarachnoid space containing CSF. The procedure was considered successful when the erythrocyte count was determined from the obtained CSF sample. RESULTS: Subarachnoid space was verifiably reached in 28 out of 40 procedures (70%). Bioimpedance needle system detected CSF in 23 out of these 28 successful procedures (82%) while failed in 3 out of 28 procedures (11%). No adverse events were reported. CONCLUSION: Bioimpedance spinal needle system was found clinically feasible in paediatric lumbar punctures, and it may offer an objective and simple means to detect the time point when the needle tip is in contact with the cerebrospinal fluid.

Associations Between Neonatal Cry Acoustics and Visual Attention During the First Year.

It has been suggested that early cry parameters are connected to later cognitive abilities. The present study is the first to investigate whether the acoustic features of infant cry are associated with cognitive development already during the first year, as measured by oculomotor orienting and attention disengagement. Cry sounds for acoustic analyses (fundamental frequency; F0) were recorded in two neonatal cohorts at the age of 0-8 days (Tampere, Finland) or at 6 weeks (Cape Town, South Africa). Eye tracking was used to measure oculomotor orienting to peripheral visual stimuli and attention disengagement from central stimuli at 8 months (Tampere) or at 6 months (Cape Town) of age. Only a marginal positive correlation between fundamental frequency of cry (F0) and visual attention disengagement was observed in the Tampere cohort, but not in the Cape Town cohort. This correlation indicated that infants from the Tampere cohort with a higher neonatal F0 were marginally slower to shift their gaze away from the central stimulus to the peripheral stimulus. No associations between F0 and oculomotor orienting were observed in either cohort. We discuss possible factors influencing the current pattern of results suggesting a lack of replicable associations between neonatal cry and visual attention and suggest directions for future research investigating the potential of early cry analysis in predicting later cognitive development.

Analysis of neurodevelopmental outcomes of preadolescents born with extremely low weight revealed impairments in multiple developmental domains despite absence of cognitive impairment.

BACKGROUND AND AIMS: Children with extremely low-birth weight (ELBW) have a high risk for cognitive, motor, and attention impairments and learning disabilities. Longitudinal follow-up studies to a later age are needed in order to increase understanding of the changes in neurodevelopmental trajectories in targeting timely intervention. The aims of this study were to investigate cognitive and motor outcomes, attention-deficit hyperactivity (ADHD) behaviour, school performance, and overall outcomes in a national cohort of ELBW children at preadolescence, and minor neuromotor impairments in a subpopulation of these children and to compare the results with those of full-term controls. The additional aim was to report the overall outcome in all ELBW infants born at 22 to 26 gestational weeks. METHODS: This longitudinal prospective national cohort study included all surviving ELBW (birth weight <1000 g) children born in Finland in 1996 to 1997. No children were excluded from the study. Perinatal, neonatal, and follow-up data up to the age of 5 years of these children were registered in the national birth register. According to birth register, the study population included all infants born at the age under 27 gestational weeks. At 11 years of age general cognitive ability was tested with the Wechsler Intelligence Scale for Children, ADHD behavior evaluated with a report from each child's own teacher (ADHD Rating Scale IV), and school performance with a parental questionnaire. An ELBW subpopulation consisting of a cohort representative children from the two university hospitals from two regions (n = 63) and the age-matched full-term born controls born in Helsinki university hospital (n = 30) underwent Movement Assessment Battery for Children and Touwen neurological examination comprising developmental coordination disorder (DCD) and minor neurological dysfunction (MND), respectively. RESULTS: Of 206 ELBW survivors 122 (73% of eligible) children and 30 (100%) full-term control children participated in assessments. ELBW children had lower full-scale intellectual quotient than controls (t-test, 90 vs 112, P < .001), elevated teacher- reported inattention scores (median = 4.0 vs 1.0, P = .021, r = .20) and needed more educational support (47% vs 17%, OR 4.5, 95% CI 1.6-12.4, P = .02). In the subpopulation, the incidences of DCD were 30% in ELBW and 7% in control children (P = .012, OR 6.0 CI 1.3-27.9), and complex MND 12.5% and 0%, (P = .052; RR 1.1 95% CI 1.04-1.25), respectively. Of survivors born in 24 to 26 gestational weeks, 29% had normal outcome. CONCLUSION: As the majority of the extremely preterm born children had some problems, long-term follow-up is warranted to identify those with special needs and to design individual multidisciplinary support programs.

Unplanned out-of-hospital deliveries in Finland: A national register study on incidence, characteristics and maternal and infant outcomes.

INTRODUCTION: Unplanned out-of-hospital deliveries (UOHDs) have earlier been related to higher perinatal mortality and morbidity, but recent research has not paid much attention to them. Our aim was to evaluate the incidence, characteristics, risk factors, and maternal and perinatal mortality and morbidity in UOHDs in Finland. MATERIAL AND METHODS: We conducted a national register study on births, causes of death and congenital anomalies for all live and stillbirths during 1996-2013. The study group included 1420 infants delivered by mothers with UOHDs. The 1 051 139 infants born in hospitals during the study period were the reference group. Data on maternal and delivery characteristics, obstetric procedures, infants' characteristics, neonatal care unit admissions, diagnoses, congenital anomalies and causes of death were collected. RESULTS: The annual rate of UOHDs increased in 1996-2013 from 46 to 260 per 100 000 deliveries, whereas the number of delivery units decreased from 44 to 29. UOHD infants had five times higher perinatal mortality rates than those delivered in hospitals. The perinatal mortality rate did not change by time in the UOHDs, whereas it diminished among in-hospital deliveries. Maternal morbidity in UOHDs was low. The predictors for UOHDs were delivery after the year 2001, delivery in sparsely populated areas, alcohol, drug abuse and/or smoking during pregnancy, being single, fewer prenatal visits, having delivered earlier and birthweight <2500 g. UOHD was one of the predictors of perinatal morbidity and mortality. Among the UOHD cases, the predictors of perinatal morbidity or mortality included low birthweight and preterm delivery. Time period seemed not to predict morbidity or mortality. CONCLUSIONS: The UOHD rate increased, probably due to multifactorial causes, including living in area with low population density and short duration of labor. UOHD was a significant predictor of perinatal morbidity or mortality, but the numbers were very small. Neonatal morbidity and mortality in UOHDs did not seem to be related to the area or time period of birth.

Hospital admissions for lower respiratory tract infections after early-, late-, and post-term birth.

BACKGROUND: Recent data suggest that early-term births are associated with later respiratory morbidity (LRTI), and post-term births may decrease this risk. OBJECTIVES: The objective was to determine the impact of early-term, late-term, and post-term birth on hospital admission for LRTI up to the age of seven years. Additionally, we explored maternal and perinatal factors associated with the risk of admission for LRTIs. METHODS: The association of early-term (37+0 -38+6  weeks), late-term (41+0 -41+6  weeks), and post-term (≥42 weeks) birth with hospital admissions for lower respiratory tract infections (LRTI) in comparison with infants born full-term (39+0 -40+6  weeks) was assessed and early predictors of LRTI were established. The register study included 948 695 infants born in Finland in 1991-2008. Data were analysed in four-term subgroups. Hospital admissions for bronchiolitis/bronchitis and pneumonia were collected up to 7 years of age. Adjusted Cox proportional hazards models were used to assess risk factors of LRTI admissions. RESULTS: The rates of hospital admission in the early-, full-, late-, and post-term groups were 6.7%, 5.5%, 5.1%, and 4.8% for bronchiolitis/bronchitis, and 2.8%, 2.4%, 2.3%, and 2.3% for pneumonia. Early-term birth was associated with an increased risk of admission for bronchiolitis/bronchitis (hazard ratio HR 1.21, 95% confidence interval CI 1.18, 1.23) and pneumonia (HR 1.16, 95% CI 1.12, 1.20), while late-term (HR 0.93, 95% CI 0.91, 0.95) and post-term births (HR 0.89, 95% CI 0.85, 0.93) were associated with a decreased risk of bronchiolitis/bronchitis admission compared with the full-term group. Maternal age ≤ 20 years, smoking during pregnancy, male sex, caesarean delivery, small for gestational age, 1-minute Apgar score < 4, ventilator support, and neonatal antibiotic therapy were associated with an increased risk of LRTI admission, while being firstborn, born in a level-II hospital and in the Northern region was associated with decreased risk. CONCLUSION: Early-term birth was associated with a higher risk of all LRTI admissions while late-term and post-term births were associated with lower risk of bronchiolitis/bronchitis admission. Modifiable risk factors of LRTIs were smoking during pregnancy, birth by elective caesarean delivery, neonatal ventilator support, and antibiotic therapy.

Planned home deliveries in Finland, 1996-2013.

OBJECTIVE: To evaluate trends and perinatal outcomes of planned home deliveries in Finland. STUDY DESIGN: All infants born in 1996-2013, excluding those born preterm, by operative delivery, and without information on birth mode or gestational age, were studied. The study group included 170 infants born at home as planned, 720,047 infants born at hospital were controls. RESULT: The rate of planned home deliveries increased from 8.3 to 39.4 per 100,000. In the study group 63%, containing two perinatal deaths, were not low-risk pregnancies according to national guidelines. The rate of hypothermia, asphyxia, and need of invasive ventilation was increased in low-risk home deliveries. One infant had a major congenital malformation. Maternal outcomes were favorable. CONCLUSION: The rate of planned home deliveries increased. Guidelines for low-risk deliveries were not followed in a majority of cases, including two perinatal deaths. Even in low-risk home deliveries, the neonatal morbidity appeared to be increased.

Visual and Hearing Impairments After Preterm Birth.

OBJECTIVES: Our aim was to determine and compare the incidences of sensory impairments among very preterm (VP) (<32 + 0/7 weeks), moderately preterm (MP) (32 + 0/7-33 + 6/7 weeks), late preterm (LP) (34 + 0/7-36 + 6/7 weeks), and term infants (≥37 weeks) and to establish risk factors of neurosensory disabilities. METHODS: This national register study included all live-born infants in Finland between 1991 and 2008. Infants who died before the age of 1 year, who had any major congenital anomaly, or had missing data were excluded (n = 21 007; 2.0%). A total of 1 018 256 infants were analyzed. Incidences of hearing loss, visual disturbances or blindness, other ophthalmologic disorders, and retinopathy of prematurity were determined for gestational age (GA) groups. Risk factors of hearing loss and visual disturbances or blindness were analyzed. RESULTS: The incidences of sensory impairments decreased with advancing GA at birth (P < .001). The most prominent factors associated with increased risks of hearing loss and visual impairment were intracranial hemorrhage and convulsions. VP (odds ratio [OR] 2.34; 95% confidence interval [CI] 1.75-3.14) and LP (OR 1.26; 95% CI 1.04-1.52) births were associated with an increased risk of hearing loss, and VP (OR 1.94; 95% CI 1.55-2.44), MP (OR 1.42; 95% CI 1.11-1.80), and LP (OR 1.31; 95% CI 1.16-1.49) births predicted an increased risk of visual impairment. CONCLUSIONS: Incidences of sensory impairment decreased with increasing GA at birth. The most prominent risk factors predictive of sensory disabilities were intracranial hemorrhage and convulsions. VP and LP births were associated with an increased risk of hearing loss, and VP, MP, and LP births were associated with an increased risk of visual impairment.

Asthma and atopic dermatitis after early-, late-, and post-term birth.

OBJECTIVE: To assess the incidence and risk factors of asthma and atopic dermatitis by seven years of age after early-term (ET) (37+0 -38+6 weeks), full-term (FT) (39+0 -40+6 weeks), late-term (LT) (41+0 -41+6 weeks), and especially post-term (PT) (≥42 weeks) birth. METHODS: Altogether, 965 203 infants born between 1991 and 2008 in Finland were investigated in ET, FT, LT, and PT groups. Data on asthma medication reimbursement and hospital visits for atopic dermatitis were retrieved from national health databases. RESULTS: The frequencies of asthma medication reimbursement in the ET, FT, LT, and PT groups were 4.5%, 3.7%, 3.3%, and 3.2%, respectively. Hospital visits due to atopic dermatitis were most common after PT birth. Compared with FT births, ET births were associated with an increased risk of asthma (adjusted odds ratio (aOR), 95% confidence interval (CI) 1.20, 1.17-1.23), while LT (aOR, 95%CI 0.91, 0.89-0.93) births and PT (aOR, 95%CI 0.87, 0.83-0.92) births decreased this risk. PT birth (aOR, 95%CI 1.06, 1.01-1.10) predicted atopic dermatitis. From a population point of view, the most relevant risk factors for asthma were male sex, ET birth, smoking during pregnancy and birth by elective cesarean section, and for atopic dermatitis male sex, first delivery, birth in a level II hospital and birth by cesarean section. CONCLUSIONS: Early-term birth was a predictor of asthma, and PT birth was associated with atopic dermatitis. Counseling against smoking and following strict indications for planned ET deliveries and cesarean sections may be means to reduce the risk of later asthma.

A Serratia marcescens outbreak in a neonatal intensive care unit was successfully managed by rapid hospital hygiene interventions and screening.

AIM: Serratia marcescens is a rare, but important, pathogen in hospital-acquired infections, especially in neonatal units. Outbreaks may cause significant mortality among neonates. This study describes how an outbreak of S. marcescens was handled in a neonatal intensive care unit in Finland in June 2015. METHODS: Tampere University Hospital is the only hospital that offers intensive care for preterm neonates in the Pirkanmaa health district area in Finland. Between June 9, 2015 and June 29, 2015, seven neonates were screened positive for S. marcescens in the hospital. We examined the management and outcomes, including environmental sampling. RESULTS: Two of the seven neonates developed a bloodstream infection, and one with S. marcescens sepsis died after six days of antibiotic treatment. The outbreak was rapidly managed with active hospital hygiene interventions, including strict hand hygiene, cleaning, patient screening, contact precautions and education. Environmental sampling was limited to one water tap and a ventilator, and the results were negative. The outbreak was contained within three weeks, and no further cases appeared. The screening of healthcare workers was not necessary. CONCLUSION: A S. marcescens outbreak caused significant morbidity in neonates and one death. Rapid hospital hygiene interventions and patient screening effectively contained the outbreak.

Hospital admissions for lower respiratory tract infections in children born moderately/late preterm.

OBJECTIVE: To evaluate the frequency and predictors of hospital admissions for lower respiratory tract infections (LRTIs) in moderately preterm (MP, 32+0 to 33+6 weeks) and late preterm (LP, 34+0 to 36+6 weeks) infants compared to term (T ≥37 weeks) and very preterm (VP, <32+0 weeks) infants. STUDY DESIGN: This national register-based study covered all infants born in Finland in 1991-2008. Data on 1 018 256 infants were analyzed in four gestational age-based groups: VP (n = 6329), MP (n = 6796), LP (n = 39 928), and T (n = 965 203) groups. Data on hospital admissions due to bronchiolitis/bronchitis and pneumonia were collected up to the age of 7 years. RESULTS: Hospital admissions for LRTIs were more common in the MP and LP groups than in the T group but less frequent than in the VP group: bronchiolitis/bronchitis (VP 24.4%, MP 13.9%, LP 9.5%, and T 5.6%) and pneumonia (VP 8.8%, MP 4.5%, LP 3.3%, and T 2.4%). Compared to the term group, MP and LP birth predicted bronchiolitis/bronchitis (MP OR 1.89; 95%CI 1.75-2.03, LP 1.51; 1.45-1.56) and pneumonia (MP 1.49; 1.32-1.67, LP 1.25; 1.18-1.33) admissions. Statistically significant risk factors for LRTIs included maternal smoking, cesarean section, male sex, admission to a neonatal unit and ventilator therapy. In addition, being first-born, being born SGA and neonatal antibiotic therapy were associated with bronchiolitis/bronchitis. CONCLUSIONS: MP and LP births, in addition to VP birth, have a significant impact on respiratory infectious morbidity and the need of hospital admissions for LRTIs.

The incidence and risk factors of epilepsy in children born preterm: A nationwide register study.

OBJECTIVES: The aim was to compare the incidence of epilepsy between very preterm (VP) (<32+0 weeks), moderately preterm (MP) (32+0-33+6 weeks), late preterm (LP) (34+0-36+6 weeks) and term infants (≥37 weeks) and to establish and compare risk factors of epilepsy in these groups. METHODS: The national register study included all live born infants in Finland in 1991-2008. Excluding infants with missing gestational age, a total of 1,033,349 infants were included in the analysis and they were analyzed in four subgroups (VP, MP, LP and term) and three time periods (1991-1995, 1996-2001 and 2002-2008). RESULTS: 5611 (0.54%) children with epilepsy were diagnosed. The incidence of epilepsy was 2.53% in the VP, 1.08% in the MP, 0.75% in the LP and 0.51% in the term group. Intracranial hemorrhage (OR 3.48; 95% CI 2.47-4.89) and convulsions in the neonatal period (OR 13.4; 95% CI 10.2-17.6) were associated with an increased risk of epilepsy. Compared to the term group, preterm birth (VP OR 4.59; 95% CI 3.79-5.57, MP 1.97; 1.48-2.63, LP 1.44; 1.25-1.68) was associated with an increased risk of epilepsy after adjusting for maternal, pregnancy, delivery and sex variables. CONCLUSIONS: The incidence of epilepsy decreased by advancing gestational age at birth and preterm birth predicted an increased risk of epilepsy in childhood. Intracranial hemorrhage and neonatal convulsions were strongly associated with an increased risk of epilepsy.

Genome-wide association study of bronchopulmonary dysplasia: a potential role for variants near the CRP gene.

Bronchopulmonary dysplasia (BPD), the main consequence of prematurity, has a significant heritability, but little is known about predisposing genes. The aim of this study was to identify gene loci predisposing infants to BPD. The initial genome-wide association study (GWAS) included 174 Finnish preterm infants of gestational age 24-30 weeks. Thereafter, the most promising single-nucleotide polymorphisms (SNPs) associated with BPD were genotyped in both Finnish (n = 555) and non-Finnish (n = 388) replication cohorts. Finally, plasma CRP levels from the first week of life and the risk of BPD were assessed. SNP rs11265269, flanking the CRP gene, showed the strongest signal in GWAS (odds ratio [OR] 3.2, p = 3.4 × 10-6). This association was nominally replicated in Finnish and French African populations. A number of other SNPs in the CRP region, including rs3093059, had nominal associations with BPD. During the first week of life the elevated plasma levels of CRP predicted the risk of BPD (OR 3.4, p = 2.9 × 10-4) and the SNP rs3093059 associated nominally with plasma CRP levels. Finally, SNP rs11265269 was identified as a risk factor of BPD (OR 1.8, p = 5.3 × 10-5), independently of the robust antenatal risk factors. As such, in BPD, a potential role for variants near CRP gene is proposed.

Velocity vector imaging shows normal cardiac systolic function in survivors of severe bronchopulmonary dysplasia at six to 16 years of age.

AIM: This study evaluated global myocardial function and associations between cardiac function and lung function in very low birth weight (VLBW) children, with and without severe radiographic bronchopulmonary dysplasia (BPD), at six to 14 years of age. METHODS: We studied 34 VLBW and 19 term-born controls, and the VLBW group was further divided into a BPD group with severe radiographic BPD and those without radiographic BPD in infancy. Detailed right and left ventricular myocardial functions were analysed by velocity vector imaging, and the left ventricular mass was calculated. The associations between cardiac function and lung function were assessed by impulse oscillometry. RESULTS: The right and left ventricular myocardial systolic functions and the left ventricular mass were similar in the three groups. Lung function was not associated with cardiac systolic function. Neonatal exposure to dexamethasone treatment was negatively associated with right ventricular function, as measured by the automated fractional area change, with an odds ratio of 7.9 and 95% confidence interval of 1.9-33.5 (p = 0.005). CONCLUSION: Lung function measurements were not associated with cardiac systolic function in preterm infants at six to 14 years of age. Neonatal exposure to dexamethasone, used for weaning from the ventilator, was negatively associated with right ventricular function.

Very low birthweight bronchopulmonary dysplasia survivors had similar cardiac outcomes to controls at six years to 14 years of age.

AIM: This study evaluated cardiac function and its associations with lung function and neonatal pulmonary morbidity in very low birthweight (VLBW) children, with and without severe radiographic bronchopulmonary dysplasia (radBPD), at school age. METHODS: We examined 18 VLBW children with radBPD, 17 VLBW children without radBPD and 18 healthy term-born children using conventional echocardiography, tissue Doppler imaging, speckle tracking echocardiography and real-time three-dimensional echocardiography at six years to 14 years of age. Lung function was studied by impulse oscillometry. Plasma N-terminal-proBNP concentrations were measured. RESULTS: Cardiac function and N-terminal-proBNP concentrations did not differ between the groups. No associations were found between cardiac function and neonatal dexamethasone, oxygen or ventilator therapies. In VLBW children, poorer reactance correlated with larger left ventricle (LV) end-systolic (Spearman's ρ = -0.45) and end-diastolic (ρ = -0.50) volumes and higher resistance correlated with higher LV dyssynchrony indexes, with ρ ranging from 0.37 to 0.48. Greater bronchodilation responses correlated with lower early diastolic myocardial relaxation velocities, with ρ ranging from 0.39 to 0.42. CONCLUSION: BPD survivors had normal cardiac function at the age of six years to 14 years. No associations were found between neonatal pulmonary morbidity and cardiac parameters. Poorer lung function correlated modestly with LV echocardiographic parameters in VLBW children.

Severe Bronchopulmonary Dysplasia, Growth, Nutrition, and Adipokines at School Age.

This study evaluated nutrition and growth in relation to plasma adipokine levels in 21 very-low-birth-weight (VLBW) children with radiographic bronchopulmonary dysplasia (BPD), 19 VLBW controls, and 19 term controls with a median age of 11.3 years. We took anthropometric measurements; assessed plasma levels of adipsin, resistin, adiponectin, and leptin; and analyzed the children's 3-day food records. Children with BPD had a smaller age-adjusted head circumference and more microcephaly but no other significant growth differences. Daily recommended nutritional intake levels were poorly met but did not differ between the groups. Leptin levels correlated positively with the body mass index standard deviation score in VLBW children. No other associations between adipokine concentrations and growth were found. There were negative correlations between leptin concentrations and fat intake, resistin levels and carbohydrate intake, and adiponectin, adipsin, and leptin levels and energy intake.