Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.

BACKGROUND: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment. OBJECTIVE: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries. STUDY DESIGN: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated. RESULTS: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively. CONCLUSION: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.

A Program Aimed at Reducing Anxiety in Pregnant Women Diagnosed With a Small-for-Gestational-Age Fetus: Evaluative Findings From a Spanish Study.

The objective of this study was to evaluate the effect of anxiety-reducing techniques including music therapy, sophrology, and creative visualization in pregnant women with a fetus diagnosed as small for gestational age and improved fetal and neonatal weight. This was a quasi-experimental study with a nonrandomized clinical trial design. We compared 2 groups of pregnant women with a fetus diagnosed as small for gestational age with no abnormalities on Doppler studies. The control group (n = 93) received standard care, and the intervention group (n = 65), in addition to standard care, underwent a program of 6 sessions led by a midwife or nurse who taught anxiety-reduction techniques. The State-Trait Anxiety Inventory (STAI) including trait and state subscales were completed by both groups at the start of the study, and only the STAI-State subscale was completed again at the end of the study. Comparisons between the 2 groups regarding fetal weight and centile and maternal STAI scores were performed using the t test and the χ test. There were no significant differences in the STAI-Trait scores between the 2 groups. There were statistically significant differences in the intervention group's STAI-State score percentiles between the start and the end of the study, being lower at the end of the study (P < .001). There were significant differences between the 2 groups in fetal weight trajectory on the basis of fetal weight: the intervention group had a larger weight gain (P < .005). The program designed to reduce anxiety in pregnant women was effective at reducing anxiety in the women in the intervention group, leading to a favorable fetal weight trajectory in this group.

Vertically transmitted cytomegalovirus infection in newborn preterm infants.

OBJECTIVE: To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV. STUDY DESIGN: During 2013 and 2014, preterm newborns who weighed ≤1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols. RESULTS: Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05-0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk. CONCLUSIONS: The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration.

Evaluation of an optimal gestational age cut-off for the definition of early- and late-onset fetal growth restriction.

OBJECTIVE: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms. PATIENTS AND METHODS: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7). RESULTS: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome. CONCLUSIONS: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

Increased fetal brain perfusion and neonatal neurobehavioral performance in normally grown fetuses.

OBJECTIVE: To explore the association between fetal cerebroplacental ratio (CPR) and frontal brain perfusion at third trimester with neonatal neurobehavioral performance in normally grown fetuses. METHODS: CPR and frontal brain perfusion measured by fractional moving blood volume (FMBV) were assessed in 258 consecutive healthy fetuses at routine third trimester scan (32-35.6 weeks). Neonates were evaluated with the Neonatal Behavioral Assessment Scale. The association between Doppler parameters and neurobehavior was analyzed by MANCOVA (multiple analysis of covariance) and logistic regression, with adjustment for smoking, socioeconomic class, mode of delivery, gestational age at birth, postnatal days at examination and gender. RESULTS: Fetuses with increased FMBV (in the upper quartile) had lower neurobehavioral scores in all areas, reaching significance in motor (5.6 vs. 5.8; p = 0.049), social (6 vs. 6.4; p = 0.006) and attention (5.3 vs. 5.9; p = 0.032). Fetuses with increased FMBV had higher risk of abnormal (<10th centile) motor (OR 3.3; 95% CI 1.36-8.1), social (OR 2.9; 95 CI% 1.33-6.5) and attention (OR 2.5; 95% CI 1.1-5.8) scores. Fetuses with lower CPR (in the lower quartile) did not differ in their neurobehavioral scores from those with normal values. CONCLUSIONS: Normally grown fetuses with increased frontal brain perfusion have poorer neurobehavioral competences, suggesting a disrupted neurological maturation. The results support the existence of forms of placental insufficiency not detected by current definitions of growth restriction.

Trends in survival among extremely-low-birth-weight infants (less than 1000 g) without significant bronchopulmonary dysplasia.

OBJECTIVE: The aim of this study was to analyze the evolution from 1997 to 2009 of survival without significant (moderate and severe) bronchopulmonary dysplasia (SWsBPD) in extremely-low-birth-weight (ELBW) infants and to determine the influence of changes in resuscitation, nutrition and mechanical ventilation on the survival rate. STUDY DESIGN: In this study, 415 premature infants with birth weights below 1000 g (ELBW) were divided into three chronological subgroups: 1997 to 2000 (n = 65), 2001 to 2005 (n = 178) and 2006 to 2009 (n = 172).Between 1997 and 2000, respiratory resuscitation in the delivery room was performed via a bag and mask (Ambu®, Ballerup, Sweden) with 40-50% oxygen. If this procedure was not effective, oral endotracheal intubation was always performed. Pulse oximetry was never used. Starting on January 1, 2001, a change in the delivery room respiratory policy was established for ELBW infants. Oxygenation and heart rate were monitored using a pulse oximeter (Nellcor®) attached to the newborn's right hand. If resuscitation was required, ventilation was performed using a face mask, and intermittent positive pressure was controlled via a ventilator (Babylog2, Drägger). In 2001, a policy of aggressive nutrition was also initiated with the early provision of parenteral amino acids. We used standardized parenteral nutrition to feed ELBW infants during the first 12-24 hours of life. Lipids were given on the first day. The glucose concentration administered was increased by 1 mg/kg/minute each day until levels reached 8 mg/kg/minute. Enteral nutrition was started with trophic feeding of milk. In 2006, volume guarantee treatment was instituted and administered together with synchronized intermittent mandatory ventilation (SIMV + VG). The complications of prematurity were treated similarly throughout the study period. Patent ductus arteriosus was only treated when hemodynamically significant. Surgical closure of the patent ductus arteriosus was performed when two courses of indomethacin or ibuprofen were not sufficient to close it.Mild BPD were defined by a supplemental oxygen requirement at 28 days of life and moderate BPD if breathing room air or a need for <30% oxygen at 36 weeks postmenstrual age or discharge from the NICU, whichever came first. Severe BPD was defined by a supplemental oxygen requirement at 28 days of life and a need for greater than or equal to 30% oxygen use and/or positive pressure support (IPPV or nCPAP) at 36 weeks postmenstrual age or discharge, whichever came first. Moderate and severe BPD have been considered together as "significant BPD". The goal of pulse oximetry was to maintain a hemoglobin saturation of between 88% and 93%. Patients were considered to not need oxygen supplementation when it could be permanently withdrawn. The distribution of the variables was not normal based on a Kolmogorov-Smirnov test (p < 0.05 in all cases). Therefore, quantitative variables were expressed as the median and interquartile range (IQR; 25th-75th percentile). Statistical analysis of the data was performed using nonparametric techniques (Kruskal-Wallis test and Mann-Whitney U test). A chi-square analysis was used to analyze qualitative variables. Potential confounding variables were those possibly related to BPD in survivors (p between 0.05 and 0.3 in univariate analysis). Logistic regression analysis was performed with variables related to BPD in survivors (p < 0.05) and potential confounding variables. The forward stepwise method adjusted for confounding factors was used to select the variables, and the enter method using selected variables was used to obtain the odds ratios. RESULTS AND CONCLUSION: There was an increase in the rate of SWsBPD (1997 to 2000: 58.5%; 2001 to 2005: 74.2%; and 2006 to 2009: 75.0%; p = 0.032). In survivors, the occurrence of significant BPD decreased after 2001 (9.5% vs. 2.3%; p = 0.013). The factors associated with improved SWsBPD were delivery by caesarean section, a reduced endotracheal intubation rate and a reduced duration of mechanical ventilation.While the mortality of ELBW infants has not changed since 2001, the frequency of SWsBPD has significantly increased (75.0%) in association with increased caesarean sections and reductions in the endotracheal intubation rate, as well as the duration of mechanical ventilation.

Correlation between a semiautomated method based on ultrasound texture analysis and standard ultrasound diagnosis using white matter damage in preterm neonates as a model.

OBJECTIVES: Diagnosis of white matter damage by cranial ultrasound imaging is still subject to interobserver variability and has limited sensitivity for predicting abnormal neurodevelopment later in life. In this study, we evaluated the ability of a semiautomated method based on ultrasound texture analysis to identify patterns that correlate with the ultrasound diagnosis of white matter damage. METHODS: The study included 44 very preterm neonates born at a median gestational age of 29 weeks 3 days (range, 26 weeks-31 weeks 6 days). Patients underwent cranial ultrasound scans within 1 week of birth and between 14 and 31 days of life. Periventricular leukomalacia was diagnosed by experienced clinicians on the 14- to 31-day scan according to standard criteria. To perform the texture analysis, 4 regions of interest were delineated in stored images: left and right periventricular areas and choroid plexuses. A classification algorithm was developed on the basis of the best combination of texture coefficients to correlate with the clinical diagnosis, and the ability of this algorithm to predict a later diagnosis of periventricular leukomalacia on the first scan was evaluated using a leave-one-out cross-validation. RESULTS: Periventricular leukomalacia was diagnosed by the standard procedure in 14 of 44 neonates. The texture classification algorithm performed on the first scan could identify cases with a later diagnosis of periventricular leukomalacia with sensitivity of 100% and accuracy of 97.7%. CONCLUSIONS: These data support the notion that semiautomated quantitative ultrasound analysis achieves early identification of changes in subclinical stages and warrant further investigation of the role of ultrasound texture analysis methods to improve early detection of neonatal brain damage.

The impact of clinical maternal chorioamnionitis on neurological and psychological sequelae in very-low-birth weight infants: a case-control study.

AIMS: To assess the relationship between clinically maternal chorioamnionitis and outcome in preterm very-low-birth weight (VLBW) infants. METHODS: An observational case-control study was conducted in the neonatology departments of 12 acute care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (≤1500 g) infants who were born to a mother with clinical chorioamnionitis were enrolled. The controls included infants who were born to mothers without chorioamnionitis, matched by gestational age, and immediately born after each index case. At a corrected age of 24 months, a neurological examination and a psychological assessment of the surviving children were performed. RESULTS: Sixty-six of the newborn infants died; therefore, 262 infants from the original sample were available for the study. Follow-up data were obtained at a corrected age of 24 months from a total of 209 children (106 cases and 103 controls, 80% of the original sample size). Seventy children (33.5%) were diagnosed with some type of sequelae. The following conditions were all more prevalent in infants born to mothers with chorioamnionitis in comparison to controls: low development quotient (98.3±12.15 vs. 95.9±15.64; P=0.497), cerebral palsy (4.9% vs. 10.4%; P=0.138), seizures (1.0% vs. 3.8%; P=0.369), and other neurological or sensorial sequelae (32.0% vs. 34.9%; P=0.611). CONCLUSIONS: After controlling for gestational age, the study population demonstrated that the neurological outcomes in infants at a corrected age of 24 months was not worsened by chorioamnionitis.

Twelve-month neurodevelopmental outcome in preterm infants with and without intrauterine growth restriction.

AIM: To evaluate the neurodevelopmental outcome at 12 months' corrected age in preterm infants with and without severe intrauterine growth restriction. METHODS: This prospective follow-up study included 37 infants with severe intrauterine growth restriction and 36 appropriate-for-gestational-age infants born between 26 and 34 weeks. Neonatal and infant data were prospectively recorded. Infants were assessed at 12 ± 2 months' corrected age with the Hammersmith Infant Neurological Examination and the Bayley Scale for Infant Development version-II. RESULTS: Both groups were similar in demographic characteristics and perinatal status. No significant differences in neurodevelopmental performance were found. The mental development index was 98.8 (SD 9.0) vs 98.4 (SD 13.1) (p = 0.9) and the psychomotor development index was 91.7 (SD 9.9) vs 95.5 (SD 13.4) (p = 0.2) for the study and reference groups respectively. Neurological assessment showed no significant differences between the two groups. CONCLUSION: Although the study group showed a non-significant trend towards a lower score in the psychomotor development index than the reference group, significant differences at 12 months could not be demonstrated. IUGR infants continued to have significantly lower weight, length and head circumference at 1 year.

Effect of maternal clinical chorioamnionitis on neonatal morbidity in very-low birthweight infants: a case-control study.

AIMS: To assess the relationship between maternal clinical chorioamnionitis and neonatal outcome in preterm very-low birthweight (VLBW) infants. METHODS: An observational case-control study was conducted in the Neonatology Services of 12 acute-care teaching hospitals in Spain. Between January 2004 and December 2006, all consecutive VLBW (< or =1500 g) infants born to a mother with clinical chorioamnionitis were enrolled. Controls were infants without chorioamnionitis matched by gestational age who were born immediately after each index case. RESULTS: There were 165 cases and 163 controls. A significantly higher percentage of cases than controls required intubation (53% vs. 35.8%), had normal intrauterine growth (98.1% vs. 84.7%), were born in a tertiary center (inborn) (95.1% vs. 89.1%), from single gestations (76.4% vs. 65.6%) and vaginal delivery (47.3% vs. 33.3%), showed a lower Apgar score at 5 min, and presented a higher rate of early-onset sepsis (10.4% vs. 1.2%). Older maternal age (32.5 vs. 30.8 years), premature labor (67.3% vs. 25.8%), premature rupture of membranes (61.3% vs. 25.8%), and antibiotic treatment (88.5% vs. 52.3%) were significantly more frequent among cases than controls. CONCLUSIONS: After controlling by gestational age, maternal chorioamnionitis was associated with neonatal depression and early sepsis but not with other prematurity-related complications.

Safety and tolerability of ertapenem versus ceftriaxone in a double-blind study performed in children with complicated urinary tract infection, community-acquired pneumonia or skin and soft-tissue infection.

The carbapenem antibiotic ertapenem has been shown to be safe, well tolerated and effective in treating adults with complicated urinary tract infection, skin and soft-tissue infection and community-acquired pneumonia. In this study, we evaluated ertapenem for treating these infections in children in a randomised, double-blind, active-controlled clinical trial. The primary outcome was the incidence of clinical and laboratory drug-related serious adverse events (AEs). Children were randomised in a 3:1 ratio (ertapenem:ceftriaxone) stratified by index infection and age to receive ertapenem or ceftriaxone; 303 children received ertapenem and 100 children received ceftriaxone. The median duration of parenteral therapy was 4 days for both treatments. The most commonly reported drug-related clinical AEs during parenteral therapy were diarrhoea (5.9% ertapenem, 10% ceftriaxone), infusion site erythema (3% ertapenem, 2% ceftriaxone) and infusion site pain (5% ertapenem, 1% ceftriaxone). One child in each group reported a serious drug-related clinical AE. No serious drug-related laboratory AEs were reported. In children aged 3 months to 17 years, ertapenem was well tolerated and had a comparable safety profile to that of ceftriaxone.

Guidelines on CMV congenital infection.

Congenital cytomegalovirus (CMV) infection occurs in 0.6-0.7% of all newborns and is the most prevalent infection-related cause of congenital neurological handicap. Vertical transmission occurs in around 30% of cases, but the fetus is not always affected. Symptomatic newborns at birth have a much higher risk of suffering severe neurological sequelae. Detection of specific IgG and IgM and IgG avidity seem to be the most reliable tests to identify a primary infection but interpretation in a clinical context may be difficult. If a seroconversion is documented or a fetal infection is suspected by ultrasound markers, an amniocentesis should be performed to confirm a vertical transmission. In the absence of a confirmed fetal infection with fetal structural anomalies, a pregnancy termination should be discouraged. Fetal prognosis is mainly correlated to the presence of brain damage. Despite promising results with the use of antiviral drugs and CMV hyperimmune globulin (HIG), results have to be interpreted with caution. Pregnant women should not be systematically tested for CMV during pregnancy. Managing CMV screening should be restricted to pregnancies where a primary infection is suspected or among women at high risk. The magnitude of congenital CMV disease and the value of interventions to prevent its transmission or to decrease the sequelae need to be established before implementing public health interventions. In this paper, aspects of CMV infection in the pregnant woman and her infant are reviewed.

[The royal philanthropic expedition of the vaccine (Xavier de Balmis/Josep Salvany). 1803-1806]. / La real expedición filantrópica de la vacuna (Xavier de Balmis/Josep Salvany): 1803-1806.

Six years after Jenner discovered the anti-smallpox vaccine, King Charles IV mandated the initiation of vaccination campaigns throughout his kingdom. The overseas campaign was coordinated by the Valencian military doctor Xavier de Balmis with the aid of the Catalan Josep Salvany. The vaccine was transported to America "in vivo" in 22 children. The expedition departed from La Coruña on November 1806 and arrived to the Venezuelan port of La Guayra where it was split in two: One sub expedition under the order of Josep Salvany, continued by land to Colombia, Ecuador, Peru and Bolivia. Salvany died in the Bolivian city of Cochabamba. The other sub expedition, leaded by Balmis himself, continued by sea to Cuba and Mexico. From Acapulco it arrived to Manila and from there to Macau followed by inland penetration into China.

Morbidity and mortality of very low birth weight multiples compared with singletons.

BACKGROUND: Previous studies comparing the neonatal outcome of very low birth weight (VLBW) multiples and singletons have suggested a worse outcome for multiples at gestational ages on the limits of viability. OBJECTIVES: The objective of this study is to determine the neonatal mortality and morbidity of VLBW multiples compared to singletons. METHODS: This is a retrospective study including all infants registered in the Spanish network for infants under 1500 g (SEN1500), over a 12-year period (from 2002 to 2013). Mortality and major morbidities were compared between singletons and multiples. RESULTS: About 32,770 infants were included: 21,123 singletons (64.5%) and 11,647 multiples (35.5%), with a mean gestational age of 29.5 weeks (22-38), and mean birth weight of 1115 g (340-1500). When adjusted by other perinatal factors, multiple pregnancy has a significantly higher risk of mortality than singleton pregnancy (odds ratio (OR) 1.15; IC 95% 1.05-1.26, p = .002), but not a higher risk of major morbidity or composite adverse outcome. In the subgroup of infants born before 26 weeks, multiples showed a higher risk of mortality (63.9% versus 51%, OR 1.7; 95% CI 1.47-1.96) and a higher risk of composite adverse outcome (88.9% versus 81.5%, OR 1.82, 95% CI 1.28-2.24). CONCLUSIONS: In preterm infants born with less than 1500 g, multiple pregnancy is a prognostic factor that can slightly increase mortality. Extremely preterm infants born before 26 weeks have a greater risk of mortality and major morbidity if they come from a multiple pregnancy.

Breastfeeding Disparities between Multiples and Singletons by NICU Discharge.

Multiple pregnancy increases the risk of a range of adverse perinatal outcomes, including breastfeeding failure. However, studies on predictive factors of breastfeeding duration in preterm twin infants have a conflicting result. The purpose of this observational study was to compare feeding practices, at hospital discharge, of twin and singleton very low birth weight infants. The study is part of a prospective survey of a national Spanish cohort of very low birth weight infants (SEN1500) that includes 62 neonatal units. The study population comprised all infants registered in the network from 2002 to 2013. They were grouped into singletons and multiples. The explanatory variables were first analyzed using univariate models; subsequently, significant variables were analyzed simultaneously in a multiple stepwise backward model. During the twelve-year period, 32,770 very low birth weight infants were included in the database, of which 26.957 were discharged alive and included in this analysis. Nine thousand seven hundred and fifty-eight neonates were multiples, and 17,199 were singletons. At discharge, 31% of singleton infants were being exclusively breastfed, 43% were bottle-fed, and 26% were fed a combination of both. In comparison, at discharge, only 24% of multiple infants were exclusively breastfed, 43% were bottle-fed, and 33% were fed a combination of both (p < 0.001). On multivariable analysis, twin pregnancy had a statistically significant, but small effect, on cessation of breastfeeding before discharge (OR 1.10; 95% CI: 1.02, 1.19). Risks of early in-hospital breastfeeding cessation were also independently associated with multiple mother-infant stress factors, such as sepsis, intraventricular hemorrhage, retinopathy, necrotizing enterocolitis, intubation, and use of inotropes. Instead, antibiotic treatment at delivery, In vitro fertilization and prenatal steroids were associated with a decreased risk for shorter in-hospital breastfeeding duration. Multiple pregnancy, even in the absence of pathological conditions associated to very low birth weight twin infants, may be an impeding factor for in-hospital breastfeeding.

Influence of perinatal inflammation on the neurodevelopmental outcome of premature infants.

OBJECTIVE: To evaluate the influence of perinatal inflammation on neurodevelopmental outcome of premature infants. STUDY DESIGN: From a retrospective cohort study of women with preterm labor with intact membranes or preterm prelabor rupture of membranes (PPROM) with an amniocentesis to rule out intra-amniotic inflammation (IAI) and microbial invasion of the amniotic cavity (MIAC), we evaluated neurodevelopmental outcome of their infants born between 24.0 and 34.0 weeks gestation. Women with clinical chorioamnionitis at admission were excluded. Neurodevelopmental outcome was screened with the Ages & Stages Questionnaire (ASQ)-3. We analyzed the relationship between an altered ASQ-3 and antenatal, intra-partum and post-partum factors related to perinatal inflammation. RESULT: Among 98 infants evaluated, 22% had an abnormal score. Amniotic fluid interleukin-6 levels and early-onset sepsis (EOS) were independent factors of an altered ASQ-3 with delivery <26.0 weeks being the strongest predictor. CONCLUSIONS: In premature infants, the presence of IAI, delivery <26.0 weeks and EOS were found to be independent factors of an altered ASQ-3.

Corpus callosum and prefrontal functions in adolescents with history of very preterm birth.

Very preterm (VPT) birth can account for thinning of the corpus callosum and poorer cognitive performance. Research findings about preterm and VPT adolescents usually describe a small posterior corpus callosum, although our research group has also found reductions of the anterior part, specifically the genu. The aim of the present study was to investigate the functional implications of this concrete reduction. Fifty-two VPT adolescents were compared with 52 adolescents born at term; there were no significant differences in age and gender, and socioeconomic status was similar between the groups. All participants underwent a magnetic resonance imaging (MRI) study and assessment of prefrontal functioning and vocabulary. The VPT group showed significant reductions of the genu, isthmus and splenium, as well as a significantly worse performance on category verbal fluency, executive functions, everyday memory and vocabulary. Although several parts of the corpus callosum correlated with some prefrontal functions, the genu was the part which principally explained these correlations. The subtest Vocabulary only correlated with the splenium. The relationship between genu and prefrontal functions and between splenium and vocabulary may be due to the fact that these parts of the corpus callosum connect prefrontal and posterior parietal cortex, respectively. The work presented here provides evidence of specific associations between reductions in the anterior corpus callosum (genu) and lower prefrontal functioning in VPT adolescents.

Patterns of cerebral white matter damage and cognitive impairment in adolescents born very preterm.

There is increasing evidence about the presence of white matter damage in subjects with a history of premature birth, even in those classified as good outcome because of an apparently normal development. Although intellectual performance is within normal limits in premature children it is significantly decreased compared to paired controls. The purpose of this study was to investigate the relationship between a lower performance intelligence quotient and white matter damage in preterm adolescents. The sample comprised 44 adolescents (mean age+/-S.D.: 14.4+/-1.6 years) born before 32 weeks of gestational age and 43 term-born adolescents (14.5+/-2.1 years). Individual voxel-based morphometry analyses demonstrated that 35/44 (80%) preterm subjects had white matter abnormalities. The centrum semiovale and the posterior periventricular regions were the most frequently affected areas. Correlation analysis showed that in preterms the performance intelligence quotient correlated with the whole-brain white matter volume (r=0.32; P=0.036) but not with grey matter volume. Complementary analysis showed that low scores in the Digit Symbol subtest, a measure of processing speed, in the preterm group correlated with reductions in white matter concentration. These results suggest that white matter damage is highly common and that it persists until adolescence. Hence, diffuse white matter loss may be responsible for performance intelligence quotient and processing speed decrements in subjects with very preterm birth.

Proton magnetic resonance spectroscopy reveals medial temporal metabolic abnormalities in adolescents with history of preterm birth.

Prematurity is associated with volumetric reductions in specific brain areas such as the hippocampus and with metabolic changes that can be detected by spectroscopy. Short echo time (35 ms) Proton magnetic resonance spectroscopy (1H MRS) was performed to assess possible medial temporal lobe metabolic abnormalities in 21 adolescents with preterm birth (mean age: 14.8, SD: 1.3) compared with an age-matched control sample (mean age: 14.8, SD: 1.6). 1H MRS spectra were analyzed with linear combination model fitting, obtaining the absolute metabolite concentrations for Creatine (Cr), and myo-inositol (Ins). In addition, the following metabolite sums were measured: total Cho (glycerophospho-choline + phosphocholine), total N-acetyl-aspartate + N-acetyl-aspartylglutamate (NA), and total Glx (glutamate + glutamine). A stereological analysis was performed to calculate hippocampal volume. Absolute Cr, and total NA values were decreased in the preterm group (p = 0.016; p = 0.002, respectively). The preterm also showed a hippocampal reduction (p < 0.0001). Significant relationships were found between gestational age and different metabolites and the hippocampal volume. Moreover, hippocampal volume correlated with brain metabolites in the whole sample. Results demonstrate that prematurity affects medial temporal lobe metabolites, and that the alteration is related to structural changes, suggesting that the cerebral changes persist until adolescence.

Gestational age at preterm birth in relation to corpus callosum and general cognitive outcome in adolescents.

Prematurity is associated with corpus callosum abnormalities and low general cognitive functioning. The present study explores the specific relationship between gestational age, corpus callosum, and intelligence quotient (IQ) in a sample of preterm-born adolescents. Sixty-four adolescents born at a gestational age of 36 weeks or less were divided into 4 groups attending to their gestational age (GA) (group 1, < or = 27; group 2, 28-30; group 3, 31-33; group 4, 34-36). These individuals were compared with 53 adolescents born at term and of similar age, gender, and sociocultural status. Individuals born at a gestational age of 27 or less (group 1) presented a generalized corpus callosum reduction in the posterior part (posterior midbody, isthmus, and splenium) as well as in the anterior part (anterior midbody and genu), a reduced total white-matter volume, and a low Full-Scale IQ. Group 2 (GA between 28 and 30) also showed a low IQ, but corpus callosum reduction was only found in the splenium, without total white-matter volume reductions. Group 3 (GA between 31 and 33) did not present differences in corpus callosum size or a reduced total white- matter volume, but they showed a low Full-Scale IQ. Group 4 (GA between 34 and 36) did not show a smaller corpus callosum or a lower general cognitive performance. Specific significant correlations were found between corpus callosum subregions and gestational age. These results suggest the importance of gestational age in prematurity in relation to brain structural and functional outcome. Premature babies born at a gestational age of 27 weeks or less are the target group for long-term corpus callosum and white-matter anomalies and for a low IQ.