Preterm birth, neonatal therapies and the risk of childhood cancer.

Our aim was to study the impact of preterm birth and neonatal therapies on the risk of childhood cancer using a nationwide, registry-based, case-control design. Combining population-based data from Finnish Medical Birth Registry (MBR) and Finnish Cancer Registry, we identified a total of 2029 patients diagnosed with cancer under the age of 20 years and 10 103 age- and sex-matched controls over the years 1996 to 2014. Information on the prenatal and perinatal conditions was obtained from the MBR. Gestational age was categorized into early (<32) and late preterm (32-36) and term (≥37 weeks). Cancer risk among the preterm compared to term neonates was evaluated using conditional logistic regression. We identified 141 cancers among the preterm (20.8% of 678) vs 1888 cancers in the term children (16.5% of 11 454). The risk of any cancer was increased for the preterm (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06-1.57), especially for the early preterm (OR 1.84, 95% CI 1.16-2.92). The risk of acute myeloid leukemia (AML; OR 2.33, 95% CI 1.25-4.37), retinoblastoma (OR 3.21, 95% CI 1.22-8.41) and germ cell tumors (OR 5.89, 95% CI 2.29-15.18) was increased among the preterm compared to term. Germ cell tumors were diagnosed at a significantly younger age among the preterm. Neonatal therapies, for example, mechanical ventilation, were associated with an increased risk of childhood cancer independent of gestational age. Preterm, especially early preterm birth, is associated with an increased risk of childhood cancer, especially germ cell tumors and AML. Respiratory distress requiring neonatal intervention also appears to be associated with an increased risk.

Parents tend to underestimate cognitive deficits in 10- to 13-year-olds born with an extremely low birth weight.

AIM: This study determined the cognitive outcomes of Finnish children born with an extremely low birth weight (ELBW) and assessed the agreement between their neuropsychological assessment and how their parents evaluated their cognitive difficulties. METHODS: The study focused on 121 children from an ELBW cohort with a mean age of 11.6 years (range 10.3-13.8) and assessed them using a standardised test of intelligence, a neuropsychological test battery and a parental developmental questionnaire. The results were compared with the test norms. RESULTS: ELBW children exhibited global cognitive impairment compared to the test norms, with no differences between children who were small or appropriate for gestational age. Children with average intelligence displayed specific impairment in executive, sensorimotor and visuospatial functions. Corresponding functions in the parental evaluation and neuropsychological assessment were associated, but 16-26% of children scoring under the clinical cut-off value in the neuropsychological test domains were not detected by the parental evaluations. CONCLUSION: Children born with an ELBW faced a high risk of global cognitive impairment at a mean age of 11.6 years, and those with average intelligence were at risk of specific cognitive sequelae. Compared to the neuropsychological tests, up to one-fourth of the parents underestimated their child's cognitive problems.

[Newborn infants treated with hypothermia therapy]. / Vastasyntyneiden viilennyshoito.

Perinatal asphyxia may lead to neurologic injury and death of the newborn infant. Hypothermia therapy seems to lower this risk. For the present retrospective study, the patient record data of both the mother and the child were collected for the newborn infants treated with hypothermia therapy in 2007-2010 in Helsinki University Central Hospital. Of the 61 children treated with hypothermia therapy, 12 died. Resuscitation response, severity of hypoxic-ischemic encephalopathy, EEG and MRI findings may provide more information than the baseline condition about the prognosis of infants treated with hypothermia therapy.

Latent class growth analysis identified different trajectories in cognitive development of extremely low birthweight children.

BACKGROUND: Recent longitudinal studies suggest stable cognitive development in preterm children, although with great individual variation. This prospective neurocognitive follow-up study of extremely low birthweight (ELBW, <1000 g) children aimed to characterise groups with different developmental trajectories from preschool to preteen age. METHODS: ELBW children (n=115) born in Finland in 1996-1997 participated in cognitive assessments at a median age of 5.0 years and 11.3 years. A standardised test of intelligence (Wechsler Preschool and Primary Scale of Intelligence-Revised or Wechsler Intelligence Scale for Children-third edition) was administered at both ages. RESULTS: Three ELBW groups with different developmental trajectories over time were identified with latent class growth analysis. Children with average (Full-Scale IQ (FSIQ): 85-115) and below average (FSIQ: <85) intelligence at 5 years of age had significant decreases in intelligence scores by 11 years of age (-11.7 points and -14.9 points, respectively, both p<0.001), while those with above average intelligence (FSIQ: >115) showed stable development (-3.2 points, p=0.250). Multiple linear regression showed that neonatal complications (intraventricular haemorrhage grade 3-4 and blood culture positive sepsis) and maternal education significantly predicted lower intelligence at the second assessment (F(3,106)=7.27, p<0.001, adjusted R2=0.147). CONCLUSIONS: ELBW children represent a heterogeneous patient population in which groups with different cognitive trajectories can be detected. Deterioration may occur particularly in children with initial average or below average cognitive performance at 5 years of age, with neonatal complications and lower maternal education presenting as risk factors. Catch-up in cognitive functions seems more uncommon in the ELBW population, which should be noted in clinical work.

Could audiovisual training be used to improve cognition in extremely low birth weight children?

AIM: To study whether a dyslexia remediation programme, Audilex, improves cognition in extremely low birth (ELBW) children. METHODS: Six-year-old ELBW children were allocated to a 5-week training with Audilex or playing control computer games. Before and after intervention, auditory event-related brain potentials (ERP) to sound changes were recorded and reading related skills assessed. Primary outcome was the mismatch negativity (MMN) component of ERP. Secondary outcomes were Audilex Test (ability to perform the Audilex games), the reading skills after the intervention and 2 years later. Of eligible children, 39 (54%) consented and 22 (30%) completed the protocol. RESULTS: The MMN responses to the frequency (p = 0.02) and duration deviants (p < 0.01) increased after Audilex training (n = 11), but not after control game playing (n = 11). Audilex Test performance was similar in both groups. The reading skills were similar after intervention and 2 years later; word reading score 59.7, 66.8 and 74.9 and comprehensive reading score 8.1, 8.8 and 9.4 in Audilex, Control and healthy class-mate children, respectively. CONCLUSIONS: Although all children did not complete the protocol, the results suggest that training with Audilex dyslexia programme might be beneficial for enhancing neural-level sound discrimation and possibly reading skills in ELBW children. A larger trial is warranted.

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.

[From preterm birth to adulthood]. / Keskosesta aikuiseksi.

Mortality among low birthweight infants has decreased and their neurological prognosis has improved over the recent decades. A major neurological impairment is, however, still found at preschool age in almost one fifth of those born with a birthweight of less than 1000 g. They often have difficulties in scholastic skills and become independent more slowly than their age-mates, but most of them will lead a normal adult life. They do, however, possess more risk factors of cardiovascular disease as compared with those born after a full-term pregnancy. In adult life these premature infants instead exhibit less high-risk behavior.

Economic costs of care in extremely low birthweight infants during the first 2 years of life.

OBJECTIVE: To assess the 2-yr costs of extremely low birthweight infants' (ELBWIs; birthweight, < 1000 g) care in relation to birthweight, outcome, and the costs of normal birthweight infants. DESIGN: Cost data were obtained from care-giving hospitals and by a parental questionnaire. Outcome data from the perinatal and neonatal periods and from the first 2 yrs for both ELBWIs and control infants had been prospectively collected to a national ELBWI register. PATIENTS: We studied 71 ELBWIs and 60 normal birthweight controls born in Helsinki University Hospital in 1996-1997. MEASUREMENTS: Collected data comprised costs resulting from care of ELBWIs and normal birthweight control infants and included hospital, outpatient care, medication, rehabilitation, auxiliary means, and travel costs; ancillary costs from daily care; parent's accommodation during hospitalization periods; and loss of earnings during the infant's first 2 yrs. MAIN RESULTS: The average total 2-yr healthcare cost was 104,635 Euros for surviving ELBWIs and 3,135 Euros for control infants. In ELBWIs, initial hospital costs alone accounted for 64% of total costs; the costs during the first and second postdischarge years accounted for 20% and 13%, respectively. The mean hospital cost of nonsurviving ELBWIs was 19,950 Euros. A normally developed ELBWI had costs 25-fold, a mildly disabled ELBWI had costs 33-fold, and a severely disabled ELBWI had costs 68-fold those of control infants. Birthweight correlated negatively with intensive care costs but did not correlate with costs after initial discharge. CONCLUSION: Total costs of ELBWIs decreased over time up to the age of 2 yrs, but even in normally developed ELBWIs, costs remained higher than those of normal birthweight infants. Low birthweight seemed to be related to increased initial hospital costs but not to annual costs after the first discharge.

Neurocognitive test profiles of extremely low birth weight five-year-old children differ according to neuromotor status.

The neurocognitive outcome of children born with extremely low birth weight (ELBW) is highly variable due to the complexity of morbidity. So far, no study has compared comprehensive neuropsychological test profiles in groups with different neuromotor status. In a national cohort of ELBW children neuropsychological test profiles were assessed in 4 groups defined according to a neurological examination at 5 years of age: normal neuromotor status (N = 56), motor coordination problems (N = 32), multiple subtle neuromotor signs including both motor coordination problems and deviant reflexes (N = 20), and spastic diplegia (N = 12). The neurocognitive assessment included a test of intelligence, the Wechsler Primary and Preschool Scale of Intelligence-Revised (WPPSI-R) and 14 subtests of attention and executive functions, verbal functions, manual motor functions, visuoconstructional functions and verbal learning (NEPSY). The children with normal neuromotor status performed within the average range; children with motor coordination problems had widespread impairment; and children with spastic diplegia and children with multiple minor neuromotor signs had uneven test profiles with stronger verbal results but weaknesses in attention and executive functions, and in manual motor and visuoconstructional tasks. In conclusion, very preterm children with neuromotor signs, including motor coordination problems, are at risk for neurocognitive impairment, in spite of average intelligence. More impaired children have more irregular test profiles. Follow-up and neuropsychological assessment of very preterm children with minor neuromotor signs are therefore indicated.

No improvement in outcome of nationwide extremely low birth weight infant populations between 1996-1997 and 1999-2000.

OBJECTIVE: Our goal was to investigate whether outcome in extremely low birth weight infants changes over time in Finland. PATIENTS AND METHODS: All infants with a birth weight <1000 g born in Finland in 1996-1997 and 1999-2000 were included in the study. Perinatal and follow-up data were collected in a national extremely low birth weight infant research register. Data concerning cerebral palsy and visual impairment were obtained from hospitals, the national discharge, and visual impairment registers. RESULTS: A total of 529 and 511 extremely low birth weight infants were born during 1996-1997 and 1999-2000. No changes were detected in prenatal, perinatal, neonatal, and postneonatal mortality rates between the periods. The survival rates including stillborn infants were 40% and 44%. The incidence of respiratory distress syndrome and septicemia increased from 1996-1997 to 1999-2000 (75% vs 83% and 23% vs 31%). The overall incidence of intraventricular hemorrhage increased (29% vs 37%), but the incidence of intraventricular hemorrhage grades 3 through 4 did not (16% vs 17%). The rates of oxygen dependency at the age corresponding with 36 gestational weeks, retinopathy of prematurity stages 3 to 5, cerebral palsy, and severe visual impairment did not change. Mortality remained higher in 1 university hospital area during both periods compared with the other 4 areas, but no regional differences in morbidity were detected during the later period. CONCLUSIONS: No significant changes were detected in birth or mortality rate in extremely low birth weight infants born in Finland during the late 1990s, but some neonatal morbidities seemed to increase. Regional differences in mortality were detected in both cohorts. Repeated long-term follow-up studies on geographically defined very preterm infant cohorts are needed for establishing reliable outcome data of current perinatal care. Regional differences warrant thorough audits to assess causalities.

Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996-1997.

OBJECTIVE: Increasing survival of extremely low birth weight (ELBW; birth weight < 1000 g) infants raises a concern regarding the risks of adverse long-term outcome such as cognitive dysfunction. Few studies have reported long-term follow-up of representative regional cohorts. The objective of this study was to assess the 5-year outcome of a prospectively followed national ELBW infant cohort. METHODS: Of all live-born ELBW infants (n = 351) who were delivered in the 2-year period 1996-1997 in Finland, 206 (59%) survived until the age of 5 years. Of these, 103 were born at < 27 gestational weeks (GW). A total of 172 children were assessed with neurocognitive tests (Wechsler Preschool and Primary Scale of Intelligence-Revised and a Developmental Neuropsychological Assessment [NEPSY]). Nine children with cognitive impairment and inability to cooperate in testing were not assessed. Motor development was assessed with a modified Touwen test. RESULTS: The rate of cognitive impairment in the ELBW survivors was 9%. The rate of cerebral palsy was 14% (19% of ELBW infants who were born at < 27 GW). The mean full-scale IQ of the assessed children was 96 +/- 19 and in children of GW < 27 was 94 +/- 19. Attention, language, sensorimotor, visuospatial, and verbal memory values of NEPSY assessment were significantly poorer compared with normal population means. Four percent needed a hearing aid, and 30% had ophthalmic findings. Of 21 children who had been treated with laser/cryo for retinopathy of prematurity, 17 (81%) had abnormal ophthalmic findings. Of the whole cohort, 41 (20%) exhibited major disabilities, 38 (19%) exhibited minor disabilities, and 124 (61%) showed development with no functional abnormalities but subtle departures from the norm. Only 53 (26%) of the total ELBW infant cohort were classified to have normal outcome excluding any abnormal ophthalmic, auditory, neurologic, or developmental findings. Being small for gestational age at birth was associated with suboptimal growth at least until age 5. CONCLUSIONS: Only one fourth of the ELBW infants were classified as normally developed at age 5. The high rate of cognitive dysfunction suggests an increased risk for learning difficulties that needs to be evaluated at a later age. Extended follow-up should be the rule in outcome studies of ELBW infant cohorts to elucidate the impact of immaturity on school achievement and social behavior later in life.