Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment

BACKGROUND: Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. STUDY DESIGN: We investigated the impact of imple- menting a protocol aiming at reducing the number of dia- gnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. RESULTS: Among the 11,503 infants born at 35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving an- tibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of dia- gnostic tests was associated with earlier antibiotic treat- ment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. CONCLUSION: Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treat- ment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.

Evolution of T1 Relaxation, ADC, and Fractional Anisotropy during Early Brain Maturation: A Serial Imaging Study on Preterm Infants.

BACKGROUND AND PURPOSE: The alteration of brain maturation in preterm infants contributes to neurodevelopmental disabilities during childhood. Serial imaging allows understanding of the mechanisms leading to dysmaturation in the preterm brain. The purpose of the present study was to provide reference quantitative MR imaging measures across time in preterm infants, by using ADC, fractional anisotropy, and T1 maps obtained by using the magnetization-prepared dual rapid acquisition of gradient echo technique. MATERIALS AND METHODS: We included preterm neonates born at <30 weeks of gestational age without major brain lesions on early cranial sonography and performed 3 MRIs (3T) from birth to term-equivalent age. Multiple measurements (ADC, fractional anisotropy, and T1 relaxation) were performed on each examination in 12 defined white and gray matter ROIs. RESULTS: We acquired 107 MRIs (35 early, 33 intermediary, and 39 at term-equivalent age) in 39 cerebral low-risk preterm infants. Measures of T1 relaxation time showed a gradual and significant decrease with time in a region- and hemispheric-specific manner. ADC values showed a similar decline with time, but with more variability than T1 relaxation. An increase of fractional anisotropy values was observed in WM regions and inversely a decrease in the cortex. CONCLUSIONS: The gradual change with time reflects the progressive maturation of the cerebral microstructure in white and gray matter. Our study provides reference trajectories from 25 to 40 weeks of gestation of T1 relaxation, ADC, and fractional anisotropy values in low-risk preterm infants. We speculate that deviation thereof might reflect disturbed cerebral maturation; the correlation of this disturbed maturation with neurodevelopmental outcome remains to be addressed.

Imaging findings of bronchial atresia in fetuses, neonates and infants.

Congenital lung malformations are increasingly detected before birth. However, bronchial atresia is rarely identified in utero and not always recognized in neonates. There are two types of atresia: 1) proximal, located at the level of the mainstem or the proximal lobar bronchi, which is extremely rare and usually lethal during pregnancy, causing a tremendous volume increase of the distal involved lung with secondary hypoplasia of the normal lung, and 2) peripheral, located at the segmental/subsegmental bronchial level, which may present as an isolated lesion or as part of a complex congenital malformation. Prenatal findings are mostly nonspecific. Postnatal exams show overinflated lung areas and focal bronchial dilations. The typical fluid-filled bronchoceles are not always observed in neonates but develop progressively in the first months of life. This pictorial essay describes the spectrum of imaging findings of bronchial atresia in fetuses, neonates and infants.

IV paracetamol versus IV ibuprofen for the treatment of PDA in LBW infants: a randomized controlled trial

Patent ductus arteriosus is a prevalent problem in low birth weight infants and it has an important morbidity and mortality in this group of patients. Classical treatment options include drugs (intravenous cyclooxygenase inhibitors: indomethacin and ibuprofen) and surgical ligation, but these treatments are associated with significant adverse effects. An alternative treatment with fewer side effects is needed. The role of oral paracetamol has gained importance in recent years, this new therapeutic option is being widely studied, and there are already many studies which support oral paracetamol as first line treatment for PDA, due to its better safety profile than classical drugs. In LBW infants is difficult to administer enteral treatment, since they are often multi pathological patients with several complications that preclude oral administration and they usually receive intravenous treatments. This multicenter, prospective, single blinded, randomized, controlled, parallel-group and noninferiority trial is designed to evaluate the efficacy and safety of intravenous paracetamol versus intravenous ibuprofen in the treatment of PDA in LBW infants. Sixty eight infants with echocardiography confirmed PDA will be randomly assigned to receive either intravenous paracetamol or intravenous ibuprofen. The main endpoints will be the rate of ductal closure of each drug and adverse events in each group of treatment

L'impacte de la separació o divorci parental en els infants i adolescents

Les separacions i divorcis són un fenomen social en el que una gran quantitat de menors i adolescents es veuen implicats. La dissolució matrimonial es conceptualitza com un procés, en el que s’observen diferents etapes familiars potencialment estressants on tots els membres que la constitueixen viuen un període de crisis d’aproximadament 2 anys. Es descriuen diferents efectes negatius com a conseqüència de la separació o divorci parental, totes elles però modulades per un conjunt de variables com el temperament, el desenvolupament evolutiu, el gènere o els canvis en els processos familiars, escolars i socials, doncs per sí mateixes les separacions o divorcis no són les causants dels efectes psicològics negatius que pateixen infants i adolescents implicats en aquest procés. De les diferents variables moduladores el conflicte parental és verifica com el major responsable del malestar psicològic en infants i adolescents amb pares separats o divorciats

Antenatal inflammation and brain pathology in preterm infants

Chorioamnionitis is known to be an important risk factor underlying preterm delivery, and it has also been suggested to associate with brain lesions and deviant neurological development in both preterm and term infants. Cytokines are believed to be the link causing the deleterious effects of inflammation to the nervous system. Their genetic regulation has also been suggested to play a role, as interleukin (IL)-6 -174 and -572 genotypes, which partly regulate IL-6 synthesis responses, have been connected with deviant neurological development in preterm infants. We evaluated the association of histological chorioamnionitis with brain lesions, regional brain volumes, and the functioning of the auditory pathway in very low birth weight/very low gestational age (VLBW/VLGA) infants. In addition, we investigated the association between IL-6 -174 and -572 genotypes and histological chorioamnionitis, neonatal infections, and brain lesions and regional brain volumes in VLBW/VLGA infants. This study is a part of a larger multidisciplinary project PIPARI (Development and Functioning of Very Low Birth Weight Infants from Infancy to School Age), in which the survivors of a 6-year cohort of VLBW/VLGA infants (n=274) are being followed until school age in Turku University Central Hospital, Finland. Placental samples were collected in the delivery room, and were analyzed for histological inflammatory findings. Blood samples from the infants were collected and DNA was genotyped for IL-6-174 and -572 polymorphisms (GG/GC/CC). Brain ultrasound examinations were performed repeatedly in the neonatal intensive care unit and at term age, and were analysed for structural brain lesions. Brain magnetic resonance imaging was performed at term age, and was analysed for regional brain volumes. In addition, diffusion tensor imaging was performed at term, and was used to analyse fractional anisotrophy and the apparent diffusion coefficient of inferior colliculus. The brainstem auditory evoked potential recordings were carried out according to the routine clinical procedure at median age of 30 days after term age. In our study, we found that histological chorioamnionitis was not an independent risk factor for brain lesions, reduced regional brain volumes or abnormal functioning of the auditory pathway in VLBW/VLGA infants. In addition, we found that IL-6 -174 GG and -572 GC genotypes were associated with a higher incidence of histological chorioamnionitis, and that -174 CC genotype associated with higher incidence of septicaemia. The analysed IL-6 genotypes were not associated with other brain lesions, but a reduced volume of basal ganglia and thalami was associated with IL-6 -174 CC and -572 GG genotypes. In conclusion, our findings suggest that histological chorioamnionitis is not an independent risk factor for the brain development of VLBW/VLGA infants, or that the risk caused by inflammation does not exceed the risks attributed to other underlying pathologies behind preterm deliveries. In addition, our findings give reason to propose that IL-6 promoter genotypes have a role in the defence against serious infections and in the brain development of VLBW/VLGA infants.

Epigenètica i futur dels infants

Una de les característiques que defineixen els éssers vius és la seva capacitat per adaptar-se a l'entorn. Evolutivament parlant, les espècies es van adaptant per l'acumulació de mutacions atzaroses que alteren el missatge genètic i per l'acció de la selecció natural. Tanmateix, a curt termini, en el decurs de la vida d'un organisme, aquest també s'ha d'adaptar al seu entorn particular. En el cas dels vertebrats superiors, com les persones, bona part d'aquesta adaptació individual s'aconsegueix amb el comportament, que s'origina al cervell [...].

Estudi comparatiu de la qualitat de vida dels discapacitats intel·lectuals i del desenvolupament en els centres penitenciaris de Catalunya

El present estudi té com a objectiu principal conèixer la qualitat de vida que presenten les persones amb discapacitat intel·lectual i del desenvolupament (DID) que es troben complint condemna en els centres penitenciaris de Catalunya. També pretén explorar i descriure les característiques sociodemogràfiques i criminològiques dels interns amb DID que es troben ubicats als diferents centres penitenciaris, i a diferents unitats o mòduls residencials, així com comparar la qualitat de vida dels interns que estan en el Departament d’Atenció Especialitzada per la DID (DAE-DID) del Centre Penitenciari de Quatre Camins, en funcionament des de juny del 2013, amb la d’altres interns amb DID que es troben complint condemna a d’altres centres penitenciaris de Catalunya, i amb els quals s’intervé de forma menys intensiva. També s’analitzaran les diferències en la qualitat de vida dels DID que estan a presó i els DID amb trastorns de conducta que estan ingressats en centres residencials del medi comunitari. La mostra es va composar de 185 subjectes. Els professionals que tenen contacte amb ells van respondre l’Escala GENCAT (Verdugo, Arias, Gómez, Schalock, 2009). Les diferències trobades en aquest estudi indiquen que els interns amb DID que resideixen al DAE i aquells interns dels quals es té sospita de presència de discapacitat i que no es troben atesos pel programa Accepta presenten un nivells de qualitat de vida similars i significativament superiors als d’aquells interns amb DID atesos pel programa Accepta, apuntant en la línia que els interns ja diagnosticats amb DID estan millor si s’ubiquen en mòduls específics, al marge del funcionament ordinari del centre. Malgrat això, el nivell de qualitat de vida que presenten aquests dos grups no és superior a aquell que presenten els interns sense discapacitat. Tanmateix, el nivell de qualitat de vida dels discapacitats a presons és superior al d’aquelles persones discapacitades que es troben ingressades a centres de la xarxa comunitària. En l’estudi s’apunten alguns possibles factors que poden estar influenciant aquest resultat.

The effect of the birth hospital and the time of birth on the outcome of Finnish very preterm infants

The purpose of this study was to evaluate the effect of the birth hospital and the time of birth on mortality and the long-term outcome of Finnish very low birth weight (VLBW) or very low gestational age (VLGA) infants. This study included all Finnish VLBW/VLGA infants born at <32 gestational weeks or with a birth weight of ≤1500g, and controls born full-term and healthy. In the first part of the study, the mortality of VLBW/VLGA infants born in 2000–2003 was studied. The second part of the study consisted of a five-year follow-up of VLBW/VLGA infants born in 2001–2002. The study was performed using data from parental questionnaires and several registers. The one-year mortality rate was 11% for live-born VLBW/VLGA infants, 22% for live-born and stillborn VLBW/VLGA infants, and 0% for the controls. In live-born and in all (including stillbirths) VLBW/VLGA infants, the adjusted mortality was lower among those born in level III hospitals compared with level II hospitals. Mortality rates of live-born VLBW/VLGA infants differed according to the university hospital district where the birth hospital was located, but there were no differences in mortality between the districts when stillborn infants were included. There was a trend towards lower mortality rates in VLBW/VLGA infants born during office hours compared with those born outside office hours (night time, weekends, and public holidays). When stillborn infants were included, this difference according to the time of birth was significant. Among five-year-old VLBW/VLGA children, morbidity, use of health care resources, and problems in behaviour and development were more common in comparison with the controls. The health-related quality of life of the surviving VLBW/VLGA children was good but, statistically, it was significantly lower than among the controls. The median and the mean number of quality-adjusted life-years were 4.6 and 3.6 out of a maximum five years for all VLBW/VLGA children. For the controls, the median was 4.8 and the mean was 4.9. Morbidity rates, the use of health care resources, and the mean quality-adjusted life-years differed for VLBW/VLGA children according to the university hospital district of birth. However, the time of birth, the birth hospital level or university hospital district were not associated with the health-related quality of life, nor with behavioural and developmental scores of the survivors at the age of five years. In conclusion, the decreased mortality in level III hospitals was not gained at the expense of long-term problems. The results indicate that VLBW/VLGA deliveries should be centralized to level III hospitals and the regional differences in the treatment practices should further be clarified. A long-term follow-up on the outcome of VLBW/VLGA infants is important in order to recognize the critical periods of care and to optimise the care. In the future, quality-adjusted life-years can be used as a uniform measure for comparing the effectiveness of care between VLBW/VLGA infants and different patient groups

Very preterm infants in Finland - Use of health care services and economic consequences during the first five years of life

The aim of this thesis was to study the health, the hospitalisations, and the use of communal health care services in very preterm children during the first five years of life. In addition, the effect of very preterm birth and prematurity-related morbidities on the costs of hospitalisations, other health care services and the cost per quality adjusted life years (QALY) were studied. This population-based study included all very preterm children (gestational age (GA) <32 weeks or birth weight<1501g, N=2 064) and full-term controls (GA 37+0−41+6, N=200 609) born in Finland during 2000-2003. The data sources included national register data, costing data from the participating hospitals and parental questionnaires. This study showed that most very preterm infants born in Finland survived without prematurity-related morbidities diagnosed during the first years of life. They required relatively little hospital care after the initial discharge, which accounted for the vast majority of the total four-year hospitalisation costs. However, a minority of children born very preterm later developing morbidities had a long initial length of stay and more re-admissions and outpatient visits during the five-year follow-up period. In particular, the number and costs of non-emergency outpatient visits were considerable in individuals with prematurity-related morbidities. The need and costs of hospitalisations decreased clearly with each follow-up year, even in individuals with morbidities. The health-care related costs during the fifth year of life in children born very preterm without prematurity-related morbidities were close to the costs in infants born healthy at term. The cost per QALY of 19,245 € was at an acceptable level already by four years of age in the very preterm population as a whole. Prematurity-related later morbidities and decreasing GA increased the costs per QALY. As the initial hospital stay accounted for a great majority of the total four-year costs, and the costs of hospitalisation decreased with each follow-up year, the cost per QALY is likely to decrease with age. In conclusion, the majority of costs arising after the initial hospitalisation were associated with morbidities related to prematurity. Therefore offering high-quality neonatal care to prevent later morbidities in very preterm survivors has a long-term impact on the cost per QALY. In addition, this study indicates that when estimating the costs of prematurity after the first year of life, one should calculate not only the hospitalisation costs, but also other costs for social welfare services, primary care, and therapies, as these exceed the hospitalisation costs in very preterm infants during the fifth year of life.

Parents as Pain Killers in the Pain Management of Preterm Infants

Vanhemmat keskoslasten kivun lievittäjinä Tutkimuksen tarkoituksena oli kehittää uusi kivunlievitysmenetelmä, Vanhempien käsikapalo, keskoslasten kivunhoitoon vastasyntyneiden teho-osastolla. Vanhempien käsikapalon tehokkuutta verrattiin kahdessa satunnaistetussa kontrolloidussa crossover-tutkimusasetelmassa ei-lääkkeelliseen näyttöön perustuvaan hoitoon (P.O. glukoosiliuos), lääkkeelliseen menetelmään (I.V. oksikodoni) ja lumeeseen (P.O. vesi) tai kontrolli hoitoon kantapääpiston ja hengitysteiden imemisen aikana. Lisäksi mitattiin kivunhoidon lyhytaikaisia sivuvaikutuksia (hapetuksen- ja pulssinlasku) ja pidempiaikaisia vaikutuksia uneen. Tutkittujen lasten ikä oli 28 raskausviikkoa (n = 20) ja 28 1/7 (n = 20). Toimenpidekipua arvioitiin Premature Infant Pain Profile (PIPP) -kipumittarilla. Interventioiden jälkeen unen rakenne analysoitiin 13 tunnin polysomnografia-rekisteröinneistä. Viimeisessä vaiheessa haastateltiin äitejä (n = 23), jotka olivat käyttäneet vanhempien käsikapaloa 2–4 viikkoa vastasyntyneiden teho-osastolla, strukturoidulla the Clinical Interview for Parents of High-Risk Infants -haastattelulla, johon oli lisätty kysymyksiä lapsen kivunhoidosta. Kantapääpiston aikana PIPP–pisteet olivat merkitsevästi matalampia P.O. glukoosiliuoksella (ka 4,85 ± 1,73, p ≤ 0,001) ja vanhempien käsikapalolla (ka 5,20 ± 1,70, p = 0,004) verrattuna lumeeseen (ka 7,05 ± 2,16). Hengitysteiden imemisen yhteydessä PIPP–pisteet olivat matalampia P.O. glukoosiliuoksella (ka 11,05 ± 2,31, p = 0,014) ja vanhempien käsikapalolla (ka 11,25 ± 2,47, p = 0,034) verrattuna lumeeseen (ka 12,40 ± 2,06). Oksikodonin teho oli verrattavissa lumeeseen kummankin toimenpiteen aikana. P.O. glukoosiliuoksen (21,3 %) ja lumeen (12,5 %) annosteluun liittyi merkittävästi enemmän lyhytaikaisia sivuvaikutuksia verrattuna oksikodoniin (5 %) tai vanhempien käsikapaloon (5 %). Oksikodoni muutti keskoslasten unen rakennetta vähentämällä merkittävästi aktiivisen unen määrää verrattuna muihin hoitoihin. Vanhemmat suhtautuivat positiivisesti käsikapalon käyttöön. Äitien osallistuminen kivunhoitoon voitiin jaotella kolmeen eri tyylin, jotka selittyivät äidin kiintymyksen tunteilla ja lapsen tehohoitoon liittyvällä stressillä. Vanhempien käsikapalo on suositeltavampi lyhyen toimenpidekivun lievittäjä kuin P.O. glukoosiliuos tai I.V. oksikodoni, kun tehokkuus, turvallisuus ja perhe otetaan huomioon.

The Vulnerable Brain and Very Preterm Infants - Findings from the PIPARI-Study

Preterm birth is a risk for normal brain development. Brain maturation that normally happens in the uterus is in very preterm infants a developmental challenge during their stay in a neonatal intensive care unit (NICU). Typical brain injuries of preterm infants include ischemic injuries, brain haemorrhages, ventricular dilatation (VD), and reduced brain volumes. Brain injury is a serious complication of prematurity leading to possible long term consequences for the neurodevelopment of the very low birth weight (VLBW) infant, such as cerebral palsy (CP), hearing impairments, vision problems, and delay in cognitive development.There is a need for further studies to ascertain the potential risk factors and their causal relationships to brain vulnerability, growth and development in the increasing number of surviving VLBW infants. This thesis consists of four studies evaluating the definitions, causes and consequences of brain lesions in VLBW(<1500g) or very low gestationalage (VLGA) (gestational age <32 gestational weeks) infants. We showed that the redistribution of fetal blood flow is a risk factor for smaller brain volumes at term. In addition,we showed that brain lesions related to prematurity are not associated with increased spontaneous crying behaviour or circadian rhythm development in infancy. However, the preterm infants began to fuss more often and were held more than term infants at five months of age. Furthermore, we showed that VD is associated with brain lesions and smaller brain volumes. Therefore, brain magneticresonance imaging can be recommended for infants with VD. VD together with other brain pathology is a risk factor for the onset of developmental impairments in VLBW/VLGA infants at two years of age.

Diffusion Tensor Imaging as a Diagnostic and Research Tool: A Study on Preterm Infants

Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) technique. DTI is based on free thermal motion (diffusion) of water molecules. The properties of diffusion can be represented using parameters such as fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, which are calculated from DTI data. These parameters can be used to study the microstructure in fibrous structure such as brain white matter. The aim of this study was to investigate the reproducibility of region-of-interest (ROI) analysis and determine associations between white matter integrity and antenatal and early postnatal growth at term age using DTI. Antenatal growth was studied using both the ROI and tract-based spatial statistics (TBSS) method and postnatal growth using only the TBSS method. The infants included to this study were born below 32 gestational weeks or birth weight less than 1,501 g and imaged with a 1.5 T MRI system at term age. Total number of 132 infants met the inclusion criteria between June 2004 and December 2006. Due to exclusion criteria, a total of 76 preterm infants (ROI) and 36 preterm infants (TBSS) were accepted to this study. The ROI analysis was quite reproducible at term age. Reproducibility varied between white matter structures and diffusion parameters. Normal antenatal growth was positively associated with white matter maturation at term age. The ROI analysis showed associations only in the corpus callosum. Whereas, TBSS revealed associations in several brain white matter areas. Infants with normal antenatal growth showed more mature white matter compared to small for gestational age infants. The gestational age at birth had no significant association with white matter maturation at term age. It was observed that good early postnatal growth associated negatively with white matter maturation at term age. Growth-restricted infants seemed to have delayed brain maturation that was not fully compensated at term, despite catchup growth.

The Association between Growth and Neurodevelopment in Very Preterm Infants – A Follow-up Study in the PIPARI Study

Placental insufficiency is one major cause of intrauterine growth restriction and also relates to neurodevelopment. Preterm infants with very low birth weight are at risk of postnatal growth restriction as well as neurodevelopmental impairments. However, the optimal postnatal growth for long-term neurodevelopment is still unclear. The objective of this study was thus to investigate the association between growth and neurodevelopment in very preterm infants. The study populations consisted of 83 (I), 55 (II), 36 (III) and 181 (IV) infants with very low birth weight (below 1501 grams), and very or extremely low gestational age (below 32 and 26 weeks). Foetal blood circulation in relation to two-year neurodevelopment and the association between early growth and brain maturation at term age were studied. Postnatal growth, and its association with five-year cognitive outcome, was analysed. Changes in foetal blood circulation related to placental insufficiency associated with an adverse two-year cognitive outcome. Early postnatal growth in extremely preterm infants was comparable to a similar Swedish cohort. Preterm infants with slow intrauterine growth had less mature brains at term age; rapid catch-up growth until term age did not eliminate this difference. Weight gain and head circumference growth from birth until two years of age associated positively with five-year cognitive outcome in appropriate for gestational age infants. In small for gestational age infants, head circumference growth from term age to four months (corrected age) associated positively with their five-year cognitive outcome. The association between postnatal growth and neurodevelopment was different for prenatally normally grown versus slow grown preterm infants.