Very early introduction of semisolid foods in preterm infants does not increase food allergies or atopic dermatitis.

BACKGROUND: The optimal age for the introduction of solid foods for infants has long been a controversial issue. OBJECTIVE: To determine whether the early introduction of semisolid foods influences the incidence of food allergy or atopic dermatitis among preterm infants. METHODS: Retrospective data from 464 preterm infants born in Oulu University Hospital between 2008 and 2012 were analyzed. Age- and sex-matched full-term control children from the general population were identified. The primary outcome of the study was the difference in timing of the introduction of complementary feeding between preterm and full-term infants. The secondary outcomes were the incidences of food allergies and atopic dermatitis by the ages of 1 and 2 years. RESULTS: Semisolid food was introduced at the median corrected age of 1.4 months for all preterm infants, at 1.9 months for late preterm, at 0.9 months for very preterm, and at 0.1 months for extremely preterm infants. The cumulative incidence, either of food allergies or of atopic dermatitis, did not differ significantly between preterm infants and controls by the ages of 1 and 2 years. CONCLUSION: The very early introduction of complementary foods into the diet of preterm babies did not increase the incidence of food allergies or atopic dermatitis even among the most preterm infants. This finding supports the hypothesis that the gut-associated lymphoid tissue of preterm infants is ready to encounter food proteins and to begin the maturation process within 3 to 6 months of birth, regardless of gestational age.

Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial.

OBJECTIVE: To study the biologic effect of paracetamol, an inhibitor of prostaglandin synthase, on early closure of ductus arteriosus, and to evaluate possible adverse effects associated with the drug. STUDY DESIGN: In a controlled, double-blind, phase I-II trial, very low gestational age (<32 weeks) infants requiring intensive care were randomly assigned to intravenous paracetamol or placebo (0.45% NaCl). A loading dose of 20 mg/kg was given within 24 hours of birth, followed by 7.5 mg/kg every 6 hours for 4 days. Daily cardiac ultrasound examinations of ductal calibers were performed before the first dose, and until 1 day after the last dose. The main outcome was a decrease in the ductal caliber without side effects. RESULTS: Of 63 screened infants, 48 were randomized: 23 were assigned to paracetamol and 25 to placebo. Before the intervention, their ductal calibers were similar. During the intervention, the ductus closed faster in the paracetamol group (hazard ratio 0.49, 95% CI 0.25-0.97, P = .016). The mean (95% CI) postnatal ages for ductal closure were 177 hours (31.1-324) for the paracetamol-treated vs 338 hours (118-557) for controls (P = .045). Paracetamol serum levels were within the therapeutic range, and no adverse effects were evident. CONCLUSIONS: Prophylactic paracetamol induced early closure of the ductus arteriosus without detectable side effects. Further trials are required to determine whether intravenous paracetamol may safely prevent symptomatic patent ductus arteriosus. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01938261; European Clinical Trials Database: EudraCT 2013-008142-33.

Event-Related Potentials Reflect Deficits in Lexical Access: The N200 in Prematurely Born School-Aged Children.

OBJECTIVES: Children born preterm have a high prevalence of neurocognitive deficits early in life. We examined whether the neural correlates of lexical access are atypical in 9-year-old children born preterm, and whether the findings of acoustic mapping correlate with language- and attention-related skills. PATIENTS AND METHODS: The subjects were fourteen 9-year-old children born preterm and 14 full-term, typically developing controls. Two auditory event-related potential (ERP) components, the N200 and the N400, were used to assess discrimination response and word recognition. A set of behavioral tests (naming ability, auditory attention, phonological processing, pseudoword repetition, and comprehension of instructions) was performed, and the results were compared with the amplitudes, latencies, and scalp distribution of the ERP results. RESULTS: In prematurely born children, neurophysiological deficits were associated with difficulties in auditory discrimination. The N200 amplitude correlated significantly with auditory attention and pseudoword repetition. The scalp distribution of both the N200 and the N400 was broader in children born preterm than in the controls. Low scores in the neuropsychological tasks referred to difficulties in auditory processing and memory. CONCLUSIONS: Children born preterm have difficulties in lexical access together with memory- and attention-related processes, which may have a longstanding impact on their school outcomes and academic skills.

Preterm-Born Young Women Have Weaker Hand Grip Strength Compared to Their Full-Term-Born Peers.

Prematurity has been linked to lower muscular fitness and increased morbidity across the human lifespan. Hand grip strength is widely used as a measure of muscle strength. Previous studies have shown inconsistent results regarding the role of vitamin D in hand grip strength. Here, we investigated hand grip strength and the effects of a yearlong vitamin D supplementation in healthy preterm-born young adults. We recruited 38 young adults born preterm at either ≤32 weeks' gestation or <34 weeks' gestation and weighing <1500 g, as well as 39 gender- and age-matched controls, for this study. Anthropometric measurements, hand grip strengths, and vitamin D concentrations were recorded. These investigations were repeated after a yearlong vitamin D supplementation intervention. There was a significant difference in the age- and gender-specific hand grip strength ranks between the preterm- and full-term-born young adults: 57.9% and 30.7%, respectively, were below average (p = 0.009). In the preterm-born group, the females had significantly lower hand grip strengths compared to their full-term-born peers, with a mean difference of -3.46 kg (95% CI: -6.68 to -0.247; p = 0.035). In a linear regression analysis, the preterm-born female adult height was negatively associated with hand grip strength (R2 = 0.24, F (1.43) = 13.61, p < 0.001). The vitamin D concentrations were increased after the supplementation period, with no association with hand grip strength. According to our results, preterm-born young females are at risk for lower muscle strength, independent of their current vitamin D status.

Heart Rate and Heart Rate Variability in Healthy Preterm-Born Young Adults and Association with Vitamin D: A Wearable Device Assessment.

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring autonomic cardiac regulation and Vitamin D concentrations in 30 PT and 16 full-term (FT) young adults in a free-living context. The PT subjects were born between 1994 and 1997 at Oulu University Hospital. The inclusion criteria were (1) being born ≤ 32 gestation weeks or (2) being born < 34 gestation weeks with a birth weight under 1500 g. Participants wore an Oura ring sleep tracer, a smart ring device, for 2 weeks to monitor cardiac autonomic function. Parameters related to autonomic cardiac regulation, lowest nighttime resting HR, and the root mean square of successive differences (RMSSD) to describe HRV were collected. PT males exhibited a tendency toward lower RMSSD (71.8 ± 22.6) compared to FT males (95.63 ± 29.0; p = 0.10). Female participants had a similar mean RMSSD in the FT and PT groups at 72.04 ± 33.2 and 74.0 ± 35.0, respectively. Serum 25-hydroxyvitamin D concentration did not correlate with cardiac autonomic function parameters. When assessing the lowest resting nighttime HRs and HRVs in a long-term, real-world context, healthy female PT young adults performed similarly to their FT peers. In contrast, the present study's results suggest that male PT young adults exhibit impaired autonomic cardiac function, potentially putting them at risk for cardiovascular disease later in adulthood.

Occlusal asymmetries in children with congenital hip dislocation.

Developmental dysplasia of the hip (DDH) has been associated with other congenital postural deformities and associated with asymmetric features in the body. The aim of this study was to examine the associations between developmental DDH and malocclusions in preschool and school children. The subjects were 60 children (40 girls and 20 boys) born during 1997-2001 in Northern Ostrobothnia Hospital District and having developmental DDH and treated by Von Rosen method. The control group consisted of 71 Finnish children (46 girls and 25 boys) matched by age and gender. Children participated the cross-sectional study at the age of 5-10 years; the mean age of the DDH children was 8.0 (SD 1.4) and controls 7.9 (SD 1.4) years. Dental examinations, intra-oral photographs, and clinical examination including growth measurements were carried out. The DDH children had significantly more lateral crossbites than controls (30/9.9 per cent; P < 0.003). Overall, 77.8 per cent of cases were unilateral crossbites and found more on the right side (50 per cent) compared to the left side (22.2 per cent). Girls had more crossbite compared to boys (77.8/22.2 per cent; odds ratio 2.53). Children with congenital hip dislocation are more predisposed to the asymmetric growth of occlusion and the development of crossbite. The genetic and environmental factors including intrauterine conditions in addition to the splint therapy may be possible influencing factors. This study will give additional information of the development of occlusal asymmetries and the multifactorial nature of the aetiology of lateral malocclusions.

Inflammatory biomarkers in very preterm infants during early intravenous paracetamol administration.

BACKGROUND: Paracetamol promotes early closure of patent ductus arteriosus (PDA), and it may affect inflammation after preterm birth. OBJECTIVE: The aim of this study was to evaluate the association between paracetamol treatment and serum inflammatory biomarkers in very preterm infants with respiratory distress. STUDY DESIGN: The infants were randomly assigned to intravenous paracetamol or placebo during the first 4 days of life, and others received a lower dose of paracetamol unblinded. Serum samples were used for the analysis of 10 cytokines, C-reactive protein (CRP) and malondialdehyde (MDA). The impact of paracetamol on the biomarkers was evaluated, based on the levels during the early (<60 h) and the later (60-120 h) postnatal age. RESULTS: Altogether, 296 serum samples from 31 paracetamol and 25 placebo group infants were analysed. Paracetamol had no effect on cytokine levels during the first 60 h when most induced PDA contractions took place. Later paracetamol treatment was associated with lower serum levels of several cytokines, including interleukin (IL-) 10, interferon gamma-induced protein (IP-) 10, and monocyte chemoattractant protein-1. CRP levels were lower in the paracetamol group during the early treatment. Amongst the infants who had severe morbidities, MDA was higher (p = .045), regardless of paracetamol treatment. CONCLUSION: No significant differences in the cytokine levels were evident between the treatment and placebo groups. However, during early treatment, CRP levels were lower in the paracetamol group. To clarify whether this was due to a decrease in cardiopulmonary distress, or a distinct anti-inflammatory effect, requires further studies.

Treatment outcome of neonatal hip instability.

AIMS: We aimed to determine hip-related quality of life and clinical findings following treatment for neonatal hip instability (NHI) compared with age- and sex-matched controls. We hypothesized that NHI would predispose to hip discomfort in long-term follow-up. METHODS: We invited those born between 1995 and 2001 who were treated for NHI at our hospital to participate in this population-based study. We included those that had Von Rosen-like splinting treatment started before one month of age. A total of 96 patients treated for NHI (75.6 %) were enrolled. A further 94 age- and sex-matched controls were also recruited. The Copenhagen Hip and Groin Outcome Score (HAGOS) questionnaire was completed separately for both hips, and a physical examination was performed. RESULTS: The mean follow-up was 18.2 years (14.6 to 22.0). The HAGOS scores between groups were similar and met statistical and clinical significance only in the Symptoms subscale (mean difference 3.80, 95% confidence interval (CI) 0.31 to 7.29; p = 0.033). Those patients who had undergone treatment for NHI had a higher frequency of positive flexion-adduction-internal rotation test (odds ratio (OR) 2.6, 95% CI 1.2 to 5.6; p = 0.014), resisted straight leg rise test (OR 4.5, 95% CI 1.4 to 14.9; p = 0.014), and also experienced more pain in the groin during passive end range hip flexion (OR 2.5, 95% CI 1.2 to 5.3; p = 0.015) than controls. CONCLUSION: NHI predisposes to hip discomfort in clinical tests, but no clinically relevant differences in experience of pain, physical function, and hip-related quality of life could be observed between the treated group and matched controls in 18 years of follow-up. Cite this article: Bone Joint J 2020;102-B(12):1767-1773.

Subgroup analysis of the early paracetamol trial to preterm infants found haemodynamic changes and improved oxygenation.

BACKGROUND: We previously reported in a randomised trial that early intravenous paracetamol accelerated contraction of ductus arteriosus in very preterm infants (<32 gestation weeks). AIMS: To monitor sequentially paracetamol effects on the blood pressure and brain tissue oxygenation in the infants participating the trial. METHODS: In a double-blind trial, intravenous paracetamol or placebo was infused to 48 very premature infants starting within 24 h of birth for four days. Besides the ductus arteriosus, we systematically measured blood pressure, peripheral (spO2) and regional cerebral oxygen saturation (rcSO2), and cerebral fractional tissue oxygen extraction (cFTOE) during the study period. RESULTS: Compared to the placebo, the paracetamol loading dose transiently decreased the arterial blood pressure. During treatment, the paracetamol-treated infants had higher spO2 (p = .042) and rcSO2 (p = .036) values than the placebo group infants. Additionally, the cFTOE values were lower in the paracetamol group during the study without statistical significance. All infants with closed ductus had higher tissue oxygenation and a lower cFTOE than infants with open ductus. CONCLUSIONS: Paracetamol caused modest haemodynamic effects and increased cerebral oxygenation. They were mostly due to early contraction of ductus. Additional direct drug-effects in brain are not ruled-out.

Neurophysiologic correlates of deficient phonological representations and object naming in prematurely born children.

OBJECTIVE: The aim of this follow-up study was to evaluate the development of object naming ability and auditory processing in prematurely born children. Furthermore, we investigated whether the mismatch negativity (MMN) parameters at the age of 4 years correlate with the MMN parameters and naming ability at the age of 6 years. METHODS: Twelve very low birth weight (VLBW) preterm children (mean age 5 years 7 months) and matched controls were studied. Object naming was measured by the Boston naming test. Auditory event-related potentials (ERPs), especially the MMN, were recorded for Finnish syllables (standard /taa/; deviants /ta/ and /kaa/) in an oddball paradigm. RESULTS: VLBW preterm children scored significantly lower in the object naming test than their controls. The MMN amplitude for consonant change was significantly smaller in the preterm group compared to the controls. The MMN amplitude at the age of 4 years correlated with the MMN amplitude at the age of 6 years. Furthermore, absence of the MMN at the age of 4 years predicted naming difficulties at the age of 6 years. CONCLUSIONS: VLBW preterm children with a difficulty to preattentively discriminate changes in syllables, as indexed by the diminished change detection response, MMN, seem to have sustained naming difficulty. Therefore, it is reasonable to record the MMN along with the language development from infancy, in order to identify the children at risk for language deficiencies and to provide appropriate rehabilitation.

Deficient speech-sound processing, as shown by the electrophysiologic brain mismatch negativity response, and naming ability in prematurely born children.

Very low birth weight (VLBW, <1500 g) preterm birth has been associated with anatomic abnormalities in brain development and cognitive and language disorders. We examined object naming ability, and an electrophysiologic index of auditory sensory discrimination of speech sounds (the mismatch negativity, MMN) in 4-year-old VLBW prematurely born children. We found that half of the VLBW children were inferior to their controls in the object naming ability. Also the MMN amplitudes were smaller in the preterm group as compared with the controls. Further, the MMN amplitude varied as a function of children's performance on object naming, such that the weaker object-naming performance of the preterm group was paralleled by the diminished MMN amplitudes. Therefore, difficulties in auditory discrimination seem to be implicated in language difficulties encountered in VLBW prematurely born children.

Is prematurity associated with adult cognitive outcome and brain structure?

Previous studies have indicated that preterm birth and low birth weight are associated with structural brain abnormalities and neurocognitive deficits in childhood and adolescence, although very few studies have included follow-up in adulthood. Here we assessed the effect of preterm delivery (524 subjects; mean 34.6 weeks, S.D. = 1.7) or low birth weight (366 subjects; mean 2159 g, S.D. = 303) on educational and occupational outcomes at age 31 years in the Northern Finland 1966 Birth Cohort, along with 10,132 term, normal birth weight control subjects. Cognitive tests and brain morphology using magnetic resonance imaging were assessed at age 33-35 years in a subset of the cohort (9 subjects; 95 controls). The preterm or low birth weight subjects had slightly lower school ratings and lower educational levels in adulthood, and they performed worse in verbal learning. The low birth weight subjects were less likely to be employed. There were no mean differences in the magnetic resonance imaging tissue segmentation analysis of the brain. In conclusion, although there were no overall changes in brain morphology in the preterm or low birth weight group, there was evidence for slightly poorer educational and occupational careers and cognitive capacity, which may reflect functional disruption not evident in structure.

3-D analysis of facial asymmetry in children with hip dysplasia.

OBJECTIVE: To determine whether facial asymmetry existed in patients with developmental dysplasia of the hip (DDH). MATERIALS AND METHODS: Subjects consisted of children between ages 5 and 10 years having DDH, and treated by the Von Rosen splint method. Three-dimensional (3-D) facial photographs were taken on all subjects using the 3dMDface system. Using RF6 PP2 software, anthropometric landmarks were plotted and used to calculate asymmetry based on 3-D coordinates in a reference framework. RESULTS: Of a total of 60 subjects with a mean age of 8 years (SD, 1.4 years), 30 had dysplasia of the left hip; 13, of the right; and 17 were bilateral. Twenty-seven subjects had upper face (UF) dominance values of 2 mm or more; of those, 26 were right-side dominant. Twenty-four subjects (40%) had a chin-point (CP) deviation of 2 mm or more; of those, 21 had right-side deviations. Statistically, UF and CP deviations were not significantly independent of each other (P > .05). Thirty percent of subjects had a posterior dental crossbite. CONCLUSIONS: The results indicate that facial asymmetry exists in patients with DDH.