Very Preterm/very Low Birth Weight Research Articles

Development of a risk calculator to predict attention-deficit/hyperactivity disorder in very preterm/very low birth weight newborns.

Very preterm/very low birth weight (VP/VLBW) newborns can have lifelong morbidities, as attention-deficit/hyperactivity disorder (ADHD). Clinicians have no markers to discriminate which among those individuals will develop later ADHD, based only on the clinical presentation at birth. Our aim was to develop an individualized risk calculator for ADHD in VP/VLBW newborns. This retrospective prognostic study included a consecutive sample of all VP/VLBW children (gestational age <32 weeks and/or birth weight <1.5 kg) born between 2010 and 2012 from a clinical cohort in a Brazilian tertiary care hospital. Children were clinically assessed at 6 years of age for ADHD using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). The least absolute shrinkage and selection operator (LASSO) method was used for model-building. Ninety-six VP/VLBW children were assessed at 6 years of age (92% follow-up), of whom 32 (33%) were diagnosed with ADHD. The area under the ROC curve (AUC) for ADHD prediction based on seven parameters (late-onset sepsis confirmed by blood culture, necrotizing enterocolitis, neonatal seizures, periventricular leukomalacia, respiratory distress syndrome, length of hospital stay, and number of maternal ADHD symptoms) was .875 (CI, 0.800-0.942, p < .001; AUC corrected for optimism with bootstrapping: .806), a performance that is comparable to other medical risk calculators. Compared to approaches that would offer early intervention to all, or intervention to none, the risk calculator will be more useful in selecting VP/VLBW newborns, with statistically significant net benefits at cost:benefits of around 1:2 to around 10:6 (range of ADHD risk thresholds of 32%-62%, respectively). It also showed specificity for ADHD compared to other prevalent child psychopathologies. The risk calculator showed good performance for early identification of VP/VLBW newborns at high risk of future ADHD diagnosis. External validity in population-based samples is needed to extend clinical usefulness.

Impact of very preterm birth and post-discharge growth on cardiometabolic outcomes at school age: a retrospective cohort study

BackgroundAdverse metabolic outcomes later in life have been reported among children or young adults who were born as preterm infants. This study was conducted to examine the impact of very preterm/very low birth weight (VP/VLBW) birth and subsequent growth after hospital discharge on cardiometabolic outcomes such as insulin resistance, fasting glucose, and systolic and diastolic blood pressure (BP) among children at 6–8 years of age.MethodsThis retrospective cohort study included children aged 6–8 years and compared those who were born at < 32 weeks of gestation or weighing < 1,500 g at birth (n = 60) with those born at term (n = 110). Body size, fat mass, BP, glucose, insulin, leptin, adiponectin, and lipid profiles were measured. Weight-for-age z-score changes between discharge and early school-age period were also calculated, and factors associated with BP, fasting glucose, and insulin resistance were analyzed.ResultsChildren who were born VP/VLBW had significantly lower fat masses, higher systolic BP and diastolic BP, and significantly higher values of fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR), compared to children born at term. VP/VLBW was correlated with HOMA-IR and BPs after adjusting for various factors, including fat mass index and weight-for-age z-score changes. Weight-for-age z-score changes were associated with HOMA-IR, but not with BPs.ConclusionsAlthough children aged 6–8 years who were born VP/VLBW showed significantly lower weight and fat mass, they had significantly higher BPs, fasting glucose, HOMA-IR, and leptin levels. The associations of VP/VLBW with cardiometabolic factors were independent of fat mass and weight gain velocity.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Improving Understanding of Participation and Attrition Phenomena in European Cohort Studies: Protocol for a Multi-Situated Qualitative Study

BackgroundCohort studies represent a strong methodology for increasing one’s understanding of human life-course development and etiological mechanisms. Retention of participants, especially during long follow-up periods, is, however, a major challenge. A better understanding of the motives for participation and attrition in cohort studies in diverse sociogeographic and cultural settings is needed, as this information is most useful in developing effective retention strategies.ObjectiveThis study aims to improve our understanding of participation and attrition phenomena in a European cohort study of very preterm/very-low-birth-weight (VPT/VLBW) infants from various sociogeographic and cultural settings to better understand variability and ultimately contribute to developing novel and more “in-context” strategies to improve retention.MethodsThis study uses a triangulation of multisituated methods to collect data on various cohorts in the Research on European Children and Adults Born Preterm (RECAP) network, which include focus group discussions, individual semidriven interviews, and a collaborative, reflexive visual methodology (participant-generated VideoStories) with relevant key actors involved with these cohort studies such as adult participants, parents (caregivers), cohort staff, health care professionals, and academic researchers. The methodological strategy aims to provide a shared flexible framework of various qualitatively driven methods to collect data on VPT/VLBW adult and child cohorts, from which research partners may choose and combine those most pertinent to apply in their own specific contexts. Data from all sources and sites will be submitted to a triangulation of phenomenological thematic analysis with discourse analysis.ResultsAs of January 2020, in this study, we enrolled 92 participants variously involved with child and adult RECAP partnering cohorts from six countries. Multisite enrollment and data collection are expected to be completed in all seven study settings by June 2020. Findings will be reported in future publications.ConclusionsQualitative research methods are a useful complement for enriching and illuminating quantitative results. We expect that opting for a multisituated study approach addressing the interplay of the lived experience of individuals in both researcher and researched stances of particular cohort study settings will contribute to filling some gaps in the understanding of participation variability and effectiveness of different implemented strategies in context. Moreover, health research subjects have traditionally been positioned as passive objects of study rather than active participants, even though they have the greatest stake in improving health care policies and practices. Including collaborative methods allows us to counteract the “top-down” model by handing over some research control to the very people who are providing the data on which research findings will be based while also acknowledging the value of their involvement.International Registered Report Identifier (IRRID)DERR1-10.2196/14997

Small for gestational age-cognitive performance from infancy to adulthood: an observational study.

To determine whether cognitive performance from infancy to adulthood is affected by being born small for gestational age (SGA), and if this depends on the SGA reference used. Furthermore, to determine SGA's effect while considering the effects of very preterm/very low birthweight (VP/VLBW), socio-economic status (SES) and parent-infant relationship. A total of 414 participants (197 term-born, 217 VP/VLBW) of the Bavarian Longitudinal Study. Small for gestational age was classified using neonatal or fetal growth references. SES and the parent-infant relationship were assessed before the infant was 5months old. Developmental (DQ) and intelligence (IQ) tests assessed cognitive performance on six occasions, from 5months to 26years of age. The fetal reference classified more infants as SGA (<10th centile) than the neonatal reference (n=138, 33% versus n=75, 18%). Using linear mixed models, SGA was associated with IQ -8 points lower than appropriate for gestational age, regardless of reference used (95% CI -13.66 to -0.64 and 95% CI -13.75 to -1.98). This difference narrowed minimally into adulthood. Being VP/VLBW was associated with IQ -16 (95% CI -21.01 to -10.04) points lower than term-born participants. Low SES was associated with IQ -14 (95% CI -18.55 to -9.06) points lower than high SES. A poor parent-infant relationship was associated with IQ -10 points lower than those with a good relationship (95% CI -13.91 to -6.47). Small for gestational age is associated with lower IQ throughout development, independent of VP/VLBW birth, low SES or poor parent-child relationship. Social factors effects on IQ comparable to those of SGA and should be considered for interventions. Small for gestational age is associated with lower cognitive performance from infancy to adulthood.

Decreased BOLD fluctuations in lateral temporal cortices of premature born adults.

Lasting volume reductions in subcortical and temporal-insular cortices after premature birth suggest altered ongoing activity in these areas. We hypothesized altered fluctuations in ongoing neural excitability and activity, as measured by slowly fluctuating blood oxygenation of resting-state functional MRI (rs-fMRI), in premature born adults, with altered fluctuations being linked with underlying brain volume reductions. To investigate this hypothesis, 94 very preterm/very low birth weight (VP/VLBW) and 92 full-term born young adults underwent structural and rs-fMRI data acquisition with voxel-based morphometry and amplitude of low-frequency fluctuations (ALFF) as main outcome measure. In VP/VLBW adults, ALFF was reduced in lateral temporal cortices, and this reduction was positively associated with lower birth weight. Regions of reduced ALFF overlapped with reduced brain volume. On the one hand, ALFF reduction remained after controlling for volume loss, supporting the functional nature of ALFF reductions. On the other hand, ALFF decreases were positively associated with underlying brain volume loss, indicating a relation between structural and functional changes. Furthermore, within the VP/VLBW group, reduced ALFF was associated with reduced IQ, indicating the behavioral relevance of ALFF decreases in temporal cortices. These results demonstrate long-term impact of premature birth on ongoing BOLD fluctuations in lateral temporal cortices, which are linked with brain volume reductions. Data suggest permanently reduced fluctuations in ongoing neural excitability and activity in structurally altered lateral temporal cortices after premature birth.

Prematurity and low birth weight associated with increased risk of ADHD diagnosis and symptoms: Meta‐analysis

Preterm and low‐birth‐weight (LBW) newborns have an increased risk of being diagnosed with attention‐deficit/hyperactivity disorder (ADHD) compared with controls, researchers have found in a literature review. These risks are even greater as preterm and low birth weight are more extreme. The researchers, whose study is published in the January issue of Pediatrics, found that very preterm/very low‐birth‐weight (VP/VLBW) subjects have an increased risk of ADHD diagnosis and symptomatology, and the findings are even stronger in the extremely preterm/extremely low‐birth‐weight (EP/ELBW) group. They recommend that future research look at which risk factors related to prematurity or low birth weight lead to ADHD.

Associations Between Feeding Problems and Maternal Sensitivity Across Infancy: Differences in Very Preterm and Full-Term Infants

To determine the influence of maternal sensitivity on infant feeding problems in very preterm/very low birth weight (VP/VLBW) and full-term (FT) infants. Longitudinal study of 178 infants (73 VP/VLBW and 105 FT). Feeding problems and maternal sensitivity were assessed at term, 3 and 18 months. A cross-lagged path model was tested to assess the longitudinal associations. The direction of the association between maternal sensitivity and feeding problems differed among VP/VLBW and FT infants. In VP/VLBW infants, higher feeding problems at term and 3 months were associated with less maternal sensitivity at 3 months (β = -.27, p < .05) and at 18 months (β = -.36, p < .05), respectively. In FT infants, a reciprocal relationship of feeding problems and maternal sensitivity over time was found. Feeding problems at 3 months were associated with decreased maternal sensitivity at 18 months (β = -.32, p < .05), whereas decreased maternal sensitivity at 3 months was related to increased feeding problems at 18 months (β = -.25, p < .05). Feeding problems are frequent in VP/VLBW infants and subsequently are associated with poorer maternal sensitivity. In FT infants, poorer levels of maternal sensitivity were both predicted by feeding problems but also were associated with more feeding problems over time.

Neonatal predictors of cognitive ability in adults born very preterm: a prospective cohort study.

To identify neonatal predictors to allow a developmental prognosis of the cognitive abilities of survivors born very preterm/very low birthweight (VLBW) into adult life. The Bavarian Longitudinal Study is a prospective whole-population study that followed 260 infants born very preterm/VLBW from birth to adulthood. Regression analyses examined which neonatal factors predicted adult IQ. Neonatal morbidity, neonatal treatment, and early social environment of infants born very preterm/VLBW explained 37.6% of the variance in adult IQ. Seven unique early-life predictors of lower adulthood IQ were found: respiratory distress syndrome, intraventricular haemorrhage, problems with mobility, mechanical ventilation, less parenteral nutrition, low/middle socioeconomic status, and poor early parent-infant relationships. Specifically, modifiable factors such as mechanical ventilation predicted a drop of 0.43 IQ points for each day of treatment, adjusted for initial respiratory problems. Good early parent-infant relationships predicted an approximately 5-point increase in adult IQ, adjusted for other significant predictors such as socioeconomic status. Mechanical ventilation, parenteral feeding, and early parenting were identified as significant modifiable factors that were strongly related to adult IQ. Mechanical ventilation policies have changed but there is scope for early interventions that focus on positive parenting, which may reduce the adverse effects of very preterm/VLBW birth on cognitive abilities.

Population-based trends in mortality and neonatal morbidities among singleton, very preterm, very low birth weight infants over 16 years

BackgroundImproved survival of singleton very preterm, very low birth weight (VPTVLBW) infants has been associated with increasing rates of severe neonatal morbidities. AimTo assess changes in mortality and neonatal morbidities among singleton VPT-VLBW infants. Study designPopulation-based observational study of data collected by the Israel Neonatal Network. Subjects10,705 singleton VPT-VLBW infants born at 24–32 gestational weeks in 1995–2010. Outcome measuresMortality and major neonatal morbidities over 3 time periods: 1995–2000, 2001–2005, and 2006–2010. Major neurological morbidities comprised intraventricular hemorrhage grades 3–4, periventricular leukomalacia and retinopathy of prematurity grades 3–4. ResultsThe mortality rate decreased over time from 20.2% to 13.8% for all birth weight and gestational age groups. Compared to the 1995–2000 period, the adjusted odds ratios (aORs) (95% confidence intervals,) for mortality in 2001–2005 and 2006–2010 were 0.78 (0.67–0.90) and 0.72 (0.62–0.84), respectively. The combined outcomes of death or major neurological morbidities, aOR 0.74 (0.65–0.84) and death or major neurological morbidities and/or bronchopulmonary dysplasia aOR 0.85 (0.75–0.96) decreased significantly between the first and last periods. A significant improvement in mortality rates and survival without one or more major neonatal morbidity was observed for all birth weight and gestational age groups.Among 8,886 surviving infants the rates of major neurological morbidities decreased from 16.4% to 12.8%, aOR 0.80 (0.68–0.95). ConclusionThe improving survival of singleton VTP-VLBW infants was not associated with a concomitant increase in the risk for major neonatal neurological morbidities among surviving infants. Bronchopulmonary dysplasia, however, remained a significant burden. This analysis emphasizes the need to direct efforts towards the prevention and treatment of adverse respiratory sequelae.

IS-034 The Health, Wealth And Social Relationships Of Ex Very Preterm/very Low Birth Weight (vp/vlbw) Children At 26 Years Of Age? The Bavarian Longitudinal Study (best, 1985–86 Cohort)

This presentation will focus on “real” life outcomes including health, wealth, crime and risky behaviour and social adaptation. Previous evidence of studies in childhood that suggest that very preterm/very low birth weight (VP/VLBW) children are at higher risk for autism spectrum symptoms and may have more social problems with peers but may be less risky in their behaviour in adolescence. Social integration is a central feature of overall life satisfaction. The BEST investigated health, wealth, risky and crime behaviour and social relationships from birth to 26 years in VP/VLBW and full term borns. We found that ex-VP/VLBW adults reported significantly lower health, less wealth (e.g. less further education, more often periods of unemployment, less income), and in particular, more social relationship problems with peers (e.g. less friends, less friend support, being bullied more often, less sexual relationships) but equally good relationships and support from their parents compared to full term comparisons. VP/VLBW adults also reported broader spectrum of autism symptoms such as rigidity in daily routines or communication problems more often. However, they were significantly less likely to be involved in risky behaviour or crime. Overall, VP/VLBW adults reported lower quality of life and less life satisfaction and these were related to their poorer social relationships with peers. VP/VLBW children need more support in forming and maintaining social relationships with peers. No or few friends and failing to partner by early adulthood may increase the burden on parents and on health and social services.

Visual sensory and perceptive functioning in 5‐year‐old very preterm/very‐low‐birthweight children

To examine visual sensory and perceptive functions, study their interrelations, and explore associations between visual dysfunctions and intelligence in very preterm/very-low-birthweight (VP/VLBW) children. One-hundred and sixteen VP/VLBW children (57 males, 59 females; mean gestational age 30.1 wks, SD 2.3; mean corrected age 5 y 6 mo, SD 1 mo) and 73 term-born children (40 males, 33 females; mean gestational age 39.9 wks, SD 1.3; mean age 5 y 6 mo, SD 3 mo) completed visual sensory (acuity, visual field, contrast-, color-, and stereovision), perceptive (visual coherence, and Developmental Test of Visual Perception non-motor scale), and intelligence assessments. Compared with term-born children, VP/VLBW children had reduced acuity (d=0.70, p<0.001), inferior visual field (d=0.67, p<0.001), and stereovision (v=0.19, p=0.008). VP/VBLW children showed weaker static coherence (d=0.49, p=0.001) and Position in Space (d=0.41, p=0.006) performance, independent of visual sensory deficits, and showed lower Verbal IQ (VIQ) and Performance IQ (PIQ; p<0.001). Visual perceptive functioning accounted for 13% of variance in VIQ, and for 35% of variance in PIQ. Visual sensory and perceptive dysfunctions are present in VP/VLBW children and occur largely independently of each other. Visual perceptive dysfunctions are moderately associated with PIQ, and weakly with VIQ.

Visual search and attention in five-year-old very preterm/very low birth weight children

IntroductionThis study aimed to establish visual search performance and attention functioning in very preterm/very low birth weight (VP/VLBW) children using novel and well established measures, and to study their contribution to intellectual functioning. MethodsVisual search and attention network efficiency were assessed in 108 VP/VLBW children and 72 age matched term controls at 5.5years corrected age. Visual search performance was investigated with a newly developed paradigm manipulating stimulus density and stimulus organization. Attention functioning was studied using the Attention Network Test (ANT). Intellectual functioning was measured by a short form of the Wechsler Preschool and Primary Scale of Intelligence. Data were analyzed using ANOVAs and multiple regression analyses. ResultsVisual search was less efficient in VP/VLBW children as compared to term controls, as indicated by increased search time (0.31 SD, p=.04) and increased error rate (0.36 SD, p=.02). In addition, VP/VLBW children demonstrated poorer executive attention as indicated by lower accuracy for the executive attention measure of the ANT (0.61 SD, p<.001). No differences were found for the alerting (0.06 SD, p=.68) and orienting attention measures (0.13 SD, p=.42). Visual search time and error rate, and executive attention, collectively, accounted for 14% explained variance in full scale IQ (R2=.14, p<.001). DiscussionVP/VLBW children were characterized by less efficient visual search ability and reduced executive attention. Visual attention dysfunctions contributed to intelligence, suggesting the opportunity to improve intellectual functioning by using interventions programs that may enhance attention capacities.

Effects of Sensitive Parenting on the Academic Resilience of Very Preterm and Very Low Birth Weight Adolescents

Although sensitive and cognitively stimulating parenting is a powerful predictor of school success, it may not protect against increased neonatal risk resulting from underlying neurological damage. A total of 314 very preterm/very low birth weight (VP/VLBW) and 338 term control children were studied from birth to age 13 years. Socioeconomic status was examined at birth. Neurological and physical impairment was assessed at age 20 months, and sensitive and cognitively stimulating parenting at age 6 years. School success was measured from 6 to 13 years of age. Very preterm/very low birth weight children had lower school success between 6 and 13 years, after statistically controlling for child disability and socioeconomic status. Cognitively stimulating parenting promoted all children's school success whereas highly sensitive parenting at age 6 years partly protected against the adverse effects of VP/VLBW birth on academic outcomes. Very preterm/very low birth weight children's school success to age 13 years may be partly protected with sensitive parenting in middle childhood, despite the neurodevelopmental impairments associated with VP/VLBW birth. This suggests potential avenues for interventions for children born at high neonatal risk.

Increased morbidity and mortality in very preterm/VLBW infants with congenital heart disease

To study the association between congenital heart diseases (CHD) and in-hospital mortality and morbidity of very preterm/very low birth weight (VLBW) infants. The area-based prospective cohort study ACTION included all infants with gestational age (GA) 22-31 weeks or birth weight <1,500 g admitted to neonatal care between July 2003 and June 2005 in six Italian regions (n = 3,684). CHD were coded according to ICD9-CM. Cluster multivariable logistic regression analyses were used to assess the relationship between CHD and mortality and selected morbidities [neonatal infection, ultrasound brain abnormalities, retinopathy of prematurity (ROP), and bronchopulmonary dysplasia (BPD)] adjusting for potential confounders. Seventy-one patients had CHD [19.3 ‰, 95 % confidence interval (CI) 15.1-24.2 ‰]. The most common lesions were isolated atrial and ventricular septal defects (31.1 and 26.8 %, respectively), pulmonary valvar stenosis (12.7 %), and tetralogy of Fallot (5.6 %). Compared with other infants, CHD patients showed significantly higher GA and frequency of small for gestational age (SGA, i.e., birth weight ≤3rd centile). After adjustment for GA, sex, SGA, presence of extracardiac malformations or chromosomal anomalies, and region of birth, CHD patients had a significantly higher likelihood of infection, BPD, ROP, and, after 27 weeks gestation only, hospital mortality. The increased risk of ROP appeared to be partly due to infection. In very preterm/VLBW infants CHD are more prevalent than in the general liveborn population, and confer an increased risk of death and serious morbidities independently of other risk factors. These results may be useful to better tailor prognostic assessment and diagnostic and therapeutic interventions for these children.

Comparison of Active Motor Items in Infants Born Preterm and Infants Born Full Term

The study was designed to compare active motor items at term age of infants born very preterm, very low birth weight (VPT-VLBW) and without impairments with infants born full-term (FT) and healthy and to evaluate a method of assessment using video recordings and computer software. Video recordings of head lag and head righting on pull to sit, head control in sitting, and hip flexion in prone were obtained at term age for 29 infants born VPT-VLBW and 22 infants born FT. Motor items were analyzed using digitizing computer software. Infants born VPT-VLBW had less head lag on pull to sit than infants born FT, p = 0.005. No other differences were found for the remaining motor items. The method of assessment demonstrated high intrarater reliability (intraclass coefficient correlation (3,1) = 0.77-0.997). Infants born VPT-VLBW who are at "low risk" performed at term age similarly to healthy infants born FT on four active motor items. The reliability of the measurement method supports the method's further development.