No impact of parental singing during the neonatal period on cognition in preterm-born children at 2-3 years.

AIM: Studies examining the long-term effects of neonatal music interventions on the cognition of children born preterm are scarce. We investigated whether a parental singing intervention before term age improves cognitive and language skills in preterm-born children. METHODS: In this longitudinal, two-country Singing Kangaroo, randomised controlled trial, 74 preterm infants were allocated to a singing intervention or control group. A certified music therapist supported parents of 48 infants in the intervention group to sing or hum during daily skin-to-skin care (Kangaroo care) from neonatal care until term age. Parents of 26 infants in the control group conducted standard Kangaroo care. At 2-3 years of corrected age, the cognitive and language skills were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: There were no significant differences in cognitive and language skills between the intervention and control groups at the follow-up. No associations between the amount of singing and the cognitive and language scores were found. CONCLUSION: Parental singing intervention during the neonatal period, previously shown to have some beneficial short-term effects on auditory cortical response in preterm infants at term age, showed no significant long-term effects on cognition or language at 2-3 years of corrected age.

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.

Repeated Parental Singing During Kangaroo Care Improved Neural Processing of Speech Sound Changes in Preterm Infants at Term Age.

Preterm birth carries a risk for adverse neurodevelopment. Cognitive dysfunctions, such as language disorders may manifest as atypical sound discrimination already in early infancy. As infant-directed singing has been shown to enhance language acquisition in infants, we examined whether parental singing during skin-to-skin care (kangaroo care) improves speech sound discrimination in preterm infants. Forty-five preterm infants born between 26 and 33 gestational weeks (GW) and their parents participated in this cluster-randomized controlled trial (ClinicalTrials ID IRB00003181SK). In both groups, parents conducted kangaroo care during 33-40 GW. In the singing intervention group (n = 24), a certified music therapist guided parents to sing or hum during daily kangaroo care. In the control group (n = 21), parents conducted standard kangaroo care and were not instructed to use their voices. Parents in both groups reported the duration of daily intervention. Auditory event-related potentials were recorded with electroencephalogram at term age using a multi-feature paradigm consisting of phonetic and emotional speech sound changes and a one-deviant oddball paradigm with pure tones. In the multi-feature paradigm, prominent mismatch responses (MMR) were elicited to the emotional sounds and many of the phonetic deviants in the singing intervention group and in the control group to some of the emotional and phonetic deviants. A group difference was found as the MMRs were larger in the singing intervention group, mainly due to larger MMRs being elicited to the emotional sounds, especially in females. The overall duration of the singing intervention (range 15-63 days) was positively associated with the MMR amplitudes for both phonetic and emotional stimuli in both sexes, unlike the daily singing time (range 8-120 min/day). In the oddball paradigm, MMRs for the non-speech sounds were elicited in both groups and no group differences nor connections between the singing time and the response amplitudes were found. These results imply that repeated parental singing during kangaroo care improved auditory discrimination of phonetic and emotional speech sounds in preterm infants at term age. Regular singing routines can be recommended for parents to promote the development of the auditory system and auditory processing of speech sounds in preterm infants.

Neural processing of changes in phonetic and emotional speech sounds and tones in preterm infants at term age.

OBJECTIVE: Auditory change-detection responses provide information on sound discrimination and memory skills in infants. We examined both the automatic change-detection process and the processing of emotional information content in speech in preterm infants in comparison to full-term infants at term age. METHODS: Preterm (n = 21) and full-term infants' (n = 20) event-related potentials (ERP) were recorded at term age. A challenging multi-feature mismatch negativity (MMN) paradigm with phonetic deviants and rare emotional speech sounds (happy, sad, angry), and a simple one-deviant oddball paradigm with pure tones were used. RESULTS: Positive mismatch responses (MMR) were found to the emotional sounds and some of the phonetic deviants in preterm and full-term infants in the multi-feature MMN paradigm. Additionally, late positive MMRs to the phonetic deviants were elicited in the preterm group. However, no group differences to speech-sound changes were discovered. In the oddball paradigm, preterm infants had positive MMRs to the deviant change in all latency windows. Responses to non-speech sounds were larger in preterm infants in the second latency window, as well as in the first latency window at the left hemisphere electrodes (F3, C3). CONCLUSIONS: No significant group-level differences were discovered in the neural processing of speech sounds between preterm and full-term infants at term age. Change-detection of non-speech sounds, however, may be enhanced in preterm infants at term age. SIGNIFICANCE: Auditory processing of speech sounds in healthy preterm infants showed similarities to full-term infants at term age. Large individual variations within the groups may reflect some underlying differences that call for further studies.

An extensive pattern of atypical neural speech-sound discrimination in newborns at risk of dyslexia.

OBJECTIVE: Identifying early signs of developmental dyslexia, associated with deficient speech-sound processing, is paramount to establish early interventions. We aimed to find early speech-sound processing deficiencies in dyslexia, expecting diminished and atypically lateralized event-related potentials (ERP) and mismatch responses (MMR) in newborns at dyslexia risk. METHODS: ERPs were recorded to a pseudoword and its variants (vowel-duration, vowel-identity, and syllable-frequency changes) from 88 newborns at high or no familial risk. The response significance was tested, and group, laterality, and frontality effects were assessed with repeated-measures ANOVA. RESULTS: An early positive and right-lateralized ERP component was elicited by standard pseudowords in both groups, the response amplitude not differing between groups. Early negative MMRs were absent in the at-risk group, and MMRs to duration changes diminished compared to controls. MMRs to vowel changes had significant laterality × group interactions resulting from right-lateralized MMRs in controls. CONCLUSIONS: The MMRs of high-risk infants were absent or diminished, and morphologically atypical, suggesting atypical neural speech-sound discrimination. SIGNIFICANCE: This atypical neural basis for speech discrimination may contribute to impaired language development, potentially leading to future reading problems.

Caffeine and supplemental oxygen effectively suppress periodic breathing with only minor effects during long episodes of apnoea in preterm infants.

AIM: We investigated the characteristics and effects of sleep stage, supplemental oxygen and caffeine on periodic breathing (PB) and apnoea of prematurity (AOP) in preterm infants. METHODS: This 2013-2015 study recruited 21 preterm infants on neonatal wards in the Helsinki and Uusimaa Hospital District, Finland, at a median corrected gestational age of 35.7 weeks and performed polysomnography at baseline, during supplemental oxygen and during caffeine treatment. RESULTS: All infants demonstrated PB, during a median of 11% of sleep time and 85% of PB occurred during non-rapid eye movement sleep (NREM). Apnoea episodes were brief during PB, but 66% were associated with oxygen desaturation. Supplemental oxygen substantially reduced PB time by 99% and caffeine by 91%. Oxygen desaturation decreased from 38 per hour at baseline to 8.5 with oxygen and 24 with caffeine (all p < 0.001). AOPs decreased from 1.4 per hour at baseline to 0.4 with oxygen (p = 0.03) and 0.3 with caffeine (p = 0.07). Most (84%) apnoea episodes over 15 seconds were mixed episodes during REM sleep. CONCLUSION: PB occurred predominantly during NREM sleep, caused intermittent hypoxia, and was suppressed by supplemental oxygen and caffeine. In contrast, long apnoea episodes representing AOP were only modestly decreased.

Behavioral and evoked potential measures of distraction in 5-year-old children born preterm.

Executive and attention dysfunctions are common in very preterm children. We studied their involuntary attention process by using behavioral measurements and auditory event-related potentials (AERP) with a distraction paradigm at age five years. The active task was to distinguish between two animal sounds. As an irrelevant feature the sounds were presented from frequent (standard) or infrequent (deviant, 11%) direction from two loudspeakers. Of the 28 preterm children, only 75% could accomplish the task, whereas all full-term children (n=15) could. When distinguishing the animal sounds, the reaction times were longer to the sounds from the deviant than from the standard direction in both groups, indicating involuntary distraction. The hit rates for the sounds from standard and deviant directions were similar in both groups. AERP amplitudes in the P1 interval and in the P3a interval elicited by standard and deviant stimuli were smaller in the preterm than in the control children. Deviants elicited P3a (indicating attentional orienting) and reorienting negativity (indicating attentional reorienting after distraction) in both groups. Comparable involuntary attentional orienting, distraction, and reorienting suggest similar maturation processes in 5-year-old preterm and full-term children. However, smaller AERP amplitudes in P1 and P3a interval suggest altered processing of auditory stimuli in those born preterm. As one-fourth of the preterm children could not accomplish the paradigm, less demanding paradigms should be used in studying children with increased distractibility.

[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.

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.

Fetal growth restriction in preterm infants and cardiovascular function at five years of age.

OBJECTIVES: We have previously reported an increased cardiac workload in newborn preterm small (SGA) infants, but not in infants appropriate for gestational age (AGA). We hypothesized that these cardiovascular changes will persist at follow-up at 5 years of age. STUDY DESIGN: We assessed blood pressure, echocardiography, and skin perfusion with laser Doppler flowmetry in 22 SGA (821 +/- 248 g, 28.5 +/- 2.5 gestational weeks) and in 25 AGA (1065 +/- 241 g, 27.6 +/- 0.8 weeks) preterm children at age 5 years. Laser Doppler flowmetry also was used in 13 control children (3982 +/- 425 g, 40.4 +/- 1.8 weeks). RESULTS: The preterm children in both the SGA and AGA groups had similar higher systolic blood pressures, increased interventricular septum thicknesses, and smaller left ventricular end-diastolic diameters compared with population reference values. Maximal endothelium-independent perfusion to sodium nitroprusside was higher and maximal endothelium-dependent perfusion to acetylcholine reached a plateau earlier in the AGA preterm group than in the control group. CONCLUSIONS: Prematurity may impair cardiovascular function independently of intrauterine growth restriction. Altered cardiac dimensions and differences in perfusion responses may reflect increased cardiac afterload.

Auditory event-related potentials and cognitive function of preterm children at five years of age.

OBJECTIVE: In our previous study, auditory event-related potentials (AERPs) in preterm 1-year-old children had a positive deflection at 150-350 ms that correlated positively with their 2-year neurodevelopmental outcome. In a study of the same subjects at age 5, our aim was to assess AERPs and their relationship to neuropsychological test results. METHODS: Preterm small (SGA, n=13), appropriate for gestational age (AGA, n=15), and control (n=13) children were assessed with an Easy paradigm presenting a large frequency change accompanied with occasional novel sounds, and a Challenging paradigm presenting small frequency and duration changes with a rapid rate. The preterm children underwent neurocognitive tests. RESULTS: Easy paradigm. The P1 response to frequency deviant was smaller and MMN larger in the preterm than in the control children. Challenging paradigm. The P1 response to standard, frequency, and duration deviants was smaller in the preterm than in the control children. The N2 response to frequency deviant was larger in the preterm than in the control children. AGA and SGA children had similar AERPs. The P1, N2, and MMN amplitudes correlated with verbal IQ and NEPSY language subtests. CONCLUSIONS: Small P1 response(s) appears to be typical for preterm children. SIGNIFICANCE: Small P1 response in preterm children may suggest altered primary auditory processing.

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.

Atypical auditory event-related potentials in preterm infants during the first year of life: a possible sign of cognitive dysfunction?

We assessed auditory event-related potentials in small-for-gestational-age (SGA; 850 +/- 258 g, 28.9 +/- 3.3 gestational wk; n = 15) and appropriate for gestational age (AGA; 1014 +/- 231 g, 26.9 +/- 1.9 gestational wk; n = 20) preterm infants and healthy term infants (n = 22). An oddball paradigm was used with a harmonic tone of 500-Hz frequency as the standard and of 750-Hz frequency as the deviant stimulus. The preterm infants were studied at 40 gestational wk and at 6 and 12 mo of corrected age, and the control subjects were studied at 2-4 d and at 3, 6, 9, 12, and 15 mo of age. The peaks of interest were the main positive peak (P350), the negative peaks at 250 ms (N250) and 650 ms (Nc), and the mismatch negativity at 200 ms (MMN). At term, the P350 in the preterm infants was similar to that of the newborn control subjects. In response to the deviant, the Nc was smaller in the SGA than in the AGA (P < 0.02) and control (P < 0.005) infants. The N250 amplitude was also lower in the SGA infants. At 12 mo, the MMN was observed in the control but not in the preterm infants, whose broad difference positivity correlated with the Bayley developmental index. The decreased Nc and N250 peaks in the SGA infants may suggest an increased risk for cognitive dysfunction. The broad difference positivity at 1 y of age may indicate atypical cortical auditory processing. Whether cognitive dysfunction can be predicted by these findings needs to be assessed in a study with extended follow-up.