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Background: Brain growth in moderate preterm (MP; gestational age (GA) 32(+0)-33(+6) weeks) and late preterm infants (LP; GA 34(+0)-36+6 weeks) may be impaired, even in the absence of brain injury.Aims: The aims of this study were to assess brain measurements of MP and LP infants, and to compare these with full-term infants (GA > 37 weeks) using linear cranial ultrasound (cUS) at term equivalent age (TEA).Study design: cUS data from two prospective cohorts were combined. Two investigators performed offline measurements on standard cUS planes. Eleven brain structures were compared between MP, LP and full-term infants using uni-and multivariable linear regression.Results were adjusted for postmenstrual age at cUS and corrected for multiple testing. Results: Brain measurements of 44 MP, 54 LP and 52 full-term infants were determined on cUS scans at TEA. Biparietal diameter and basal ganglia-insula width were smaller in MP (-9.1 mm and -1.7 mm, p < 0.001) and LP infants (-7.0 mm and -1.7 mm, p < 0.001) compared to full-term infants. Corpus callosum - fastigium length was larger in MP (+2.2 mm, p < 0.001) than in full-term infants. No significant differences were found between MP and LP infants.Conclusions: These findings suggest that brain growth in MP and LP infants differs from full-term infants. Whether these differences have clinical implications remains to be investigated.

BACKGROUND: Accurate prediction of persistent and emerging developmental problems in preterm-born children may lead to targeted interventions.AIMS: To determine whether specific perinatal and social factors were associated with persistent, emerging, and resolving developmental problems of early-preterm (EPs) and moderately-and-late-preterm children (MLPs) from before to after school entry.STUDY DESIGN: Observational longitudinal cohort study, part of the LOLLIPOP cohort-study.SUBJECTS: 341 EPs and 565 MLPs.OUTCOME MEASURES: Developmental problems using the Ages and Stages Questionnaire at ages 4 and 5. We collected data on perinatal and social factors from medical records. Using logistic regression analyses we assessed associations between 48 factors and persistent, emerging, and resolving problems.RESULTS: Of EPs, 8.7% had persistent and 5.1% emerging problems; this was 4.3% and 1.9% for MLPs, respectively. Predictors for persistent problems included chronic mental illness of the mother, odds ratio (95% confidence interval) 8.01 (1.85-34.60), male sex 4.96 (2.28-10.82), being born small-for-gestational age (SGA) 2.39 (1.15-4.99), and multiparity 3.56 (1.87-6.76). Predictors for emerging problems included MLP birth with prolonged premature rupture of membranes (PPROM) 5.01 (1.38-18.14). Including all predictors in a single prediction model, the explained variance (Nagelkerke R2) was 21.9%, whereas this was 3.0% with only EP/MLP birth as predictor.CONCLUSIONS: Only few perinatal and social factors had associations with persistent and emerging developmental problems for both EPs and MLPs. For children with specific neonatal conditions such as SGA, and PPROM in MLPs, problems may persist. Insight in risk factors largely improved the prediction of developmental problems among preterm children.

Objectives To provide a systematic review of brain injury and altered brain development in moderate-late preterm (MLPT) infants as compared to very preterm and term infants. Study design A systematic search in five databases was performed in January 2020. Original research papers on incidence of brain injury and papers using quantitative data on brain development in MLPT infants were selected. The Johanna Briggs Institute ‘Critical Appraisal Checklist for Studies Reporting Prevalence Data’ was used for quality appraisal. Data extraction included: imaging modality, incidences of brain injury, brain volumes, 2D-measurements and diffusivity values. Results In total, 24 studies were eligible. Most studies had a moderate quality. Twenty studies reported on the incidence of brain injury in MLPT infants. The incidence of intraventricular hemorrhage (IVH) ranged from 0.0% to 23.5% and of white matter injury (WMI) from 0.5% to 10.8%. One study reported the incidence of arterial infarction (0.3%) and none of cerebellar hemorrhage. Eleven studies compared incidences of brain injury between MLPT infants and very preterm or term infants. Five studies reported signs of altered brain development in MLPT infants. Conclusions The incidences of IVH and WMI in MLPT infants varied widely between studies. Other abnormalities were sparsely reported. Evidence regarding a higher or lower incidence of brain injury in MLPT infants compared to very preterm or term infants is weak due to moderate methodological quality of reported studies. There is limited evidence suggesting a difference in brain development between MLPT and term infants.

Background Late preterm infants (LPI) have a higher risk of developmental delay (DD) than term-born infants. The association of perinatal complications with specific morbidity is not clear. Aim (1) To compare the risk of DD at 4 years of age between LPI who have presence or absence of any morbidity associated with the prematurity at birth, called complicated (cLPI) or uncomplicated (uLPI), and term-born infants, (2) to determine maternal and perinatal factors associated with risk of DD, and (3) to analyze, in LPI, the association between perinatal morbidity and risk of DD. Methods A retrospective cohort study including 163 LPI – 47 cLPI and 116 uLPI – and 158 term-born infants (Terms) was conducted. Parents completed the Ages & Stages Questionnaires®3rd Spanish version (ASQ3). Risk of DD was defined as the presence of any ASQ3 domain scoring below the mean minus 2 SD. Association between risk of DD and maternal and perinatal factors was analysed using a multivariate logistic model. Incidence of risk of DD was analysed according to specific morbidity. Results Compared to Terms, cLPI have a higher risk of DD in the communication domain. Respiratory pathology was associated with a higher risk in the communication domain. Caesarean delivery was the only maternal perinatal risk factor for DD, especially in gross motor domain. Conclusions At the age of 4 years cLPI, especially those with respiratory morbidity, had a higher risk of communication delay. Caesarean delivery was the only perinatal risk factor associated with risk of DD.

Objective The aim of this study was to compare temperament and behavior profiles among groups of preterm toddlers differentiated by level of prematurity and the presence of bronchopulmonary dysplasia (BPD) or retinopathy of prematurity (ROP), controlling for neonatal clinical conditions and chronological age. Method The sample comprised 100 preterm toddlers segregated according to level of prematurity (75 very preterm and 25 moderate/late preterm) and presence of BPD (n = 36) and ROP (n = 63). Temperament was assessed by the Early Childhood Behavior Questionnaire and behavior by the Child Behavior Checklist. The MANOVA was performed with a post-hoc univariate test. Results The level of prematurity and the presence of BPD and ROP did not affect temperament and behavioral problems in toddlers born preterm. However, the covariates age and length of stay in NICU (Neonatal Intensive Care Unit) affected temperament and behavioral problems, respectively. The older toddlers showed higher inhibitory control and lower activity levels than younger toddlers (range of 18–36 months-old). Additionally, toddlers who stayed in the NICU longer showed more pervasive development and emotionally reactive problems than toddlers who stayed in NICU for less time. Conclusion The level of prematurity and the presence of bronchopulmonary dysplasia and retinopathy of prematurity did not affect temperament and behavioral problems in toddlers born preterm. However, a longer stay in the NICU increased the risk for behavioral problems, and age enhanced the regulation of temperament at toddlerhood.

Background A growing body of research suggests that moderate to late preterm children (MLP; 32 through 36 weeks of gestation) may have higher rates of behavioral problems than full-term (FT) children. However, few studies have followed MLP children over time using a longitudinal design with repeated measures. Aim The current prospective longitudinal study aims to examine the relation between MLP birth and trajectories of behavioral problems among children from ages 4 to 10 years. Study design and subjects The data comes from a Canadian representative population-based study including 1841 FT children and 89 MLP children. Outcome measures Four categories of behavioral problems were measured repeatedly from 4 to 10 years using parent and teacher reports: hyperactivity-impulsivity, inattention, anxiety-depression, and aggression. Developmental trajectories were modeled using Mplus. Results After accounting for child sex and family income, a significant and persistent association was found between MLP birth and the developmental trajectory of hyperactivity-impulsivity reported by the parent. No relation was found regarding trajectories of inattention, anxiety-depression, and aggression problems. Conclusions According to parent reports, MLP children were more likely to exhibit hyperactive and impulsive behaviors compared to FT peers during early childhood. However, the relation between MLP birth and the trajectory of parent-reported hyperactivity-impulsivity was small and was not confirmed by teacher evaluation. Moreover, MLP children did not differ from FT children regarding the overall trajectory of inattention, anxiety-depression, and aggression problems.

WOS: 000460493000010, PubMed: 30660088, …, Turkish Neonatology Society, This research was supported by Turkish Neonatology Society (grant).

Background There is no standardized method for total serum bilirubin (TSB) monitoring during phototherapy for neonatal hyperbilirubinemia and national guidelines give heterogeneous indications. Aim To assess the hypothesis that TSB values do not exceed exsanguino-transfusion (EXT) threshold during phototherapy and that it is possible to decrease its monitoring frequency in jaundiced infants. Study design We carried out a prospective observational study in which changes in TSB during phototherapy for non-haemolytic hyperbilirubinemia were recorded in a cohort of late preterm and term infants. TSB values after 6, 12, 18, and 24 h of phototherapy were compared to the EXT threshold matched to infants' gestational and postnatal age according to the specific nomogram of the Italian Society of Neonatology guidelines. Results We studied 105 infants who started phototherapy at a mean age of 89 ± 37 h when mean TSB was 17.1 ± 2.5 mg/dL. We found that TSB decreased during phototherapy and the difference between mean TSB and EXT threshold progressively increased during phototherapy; TSB exceeded EXT threshold in none of our patients (0%). Conclusions Our study demonstrates that differences between mean TSB and EXT threshold increased during phototherapy in late preterm and term infants with non-haemolytic hyperbilirubinemia; in none of our patients TSB exceeded EXT threshold. Our findings support the possibility of safely decreasing TSB monitoring during phototherapy, thus limiting noxious painful stimuli in neonates.

Moderate preterm infants (MPI) and late preterm infants (LPI) account for the majority of children born preterm. Up to 5% of MPI and LPI are estimated to manifest neurodevelopmental impairments. However, information about normal early motor development in these patients is lacking.To find characteristic patterns for motor development in the first four months of life among MPI and LPI without risk factors for developmental impairment by using accelerometry of spontaneous movements.Prospective and observational study.Twenty-three MPI and LPI (9 female, 14 male) without known risk factors for neurodevelopmental impairment were included in this study. Spontaneous movements were measured by accelerometry at the time of hospital discharge (mean: 36.6wks postmenstrual age (PMA)) and at the corrected age of three months (mean: 53.0wks PMA).Motor development was described by analyzing 36 parameters calculated from the acceleration signal. Normal neurodevelopmental outcome was confirmed by Bayley Scales of Infant Development at the corrected age of two years.Statistically significant differences (p 0.05) between the two measurements could be shown in 26 out of the 36 parameters. Striking changes in motor development were an increase in acceleration and variability of the spontaneous movements, the main criterion for analyzing spontaneous movements. Furthermore, the regularity of spontaneous movements increased significantly.Characteristic patterns of normal motor development in MPI and LPI can be identified and provide a basis for future investigations aiming at the early detection of abnormal motor development for this specific patient group.

Aim To evaluate the reliability of the Ages and Stages Questionnaires (ASQ-3) 24 and 48 month intervals translated to Spanish by Brookes Publishing, and the agreement between both questionnaires, comparing late preterm (LPI) and term-born infants (terms). Methods Two cohort samples of healthy LPI and terms that were born in a private hospital in Barcelona, Spain. Internal consistency was analyzed by Cronbach's alpha scores and Pearson product- moment correlation between the domain scores and the overall score. The agreement was analyzed using Pearson's correlations between the two questionnaires, and the odds ratio (OR) for positive screening at 48 months, given a positive screen in 24 month assessment. Results A total of 473 evaluations were analyzed, representing 331 children. Cronbach's alpha scores for the motor domains on both intervals were low, but acceptable compared with the overall score; a strong positive correlation between the domain and overall score were obtained in the majority of the domains. The correlation between the 24 and 48 month total scores were positive, especially for LPI. Having at least 2 domains in the referral zone at 24 months was associated with an OR of 140 [95% CI 14.85; 3575.65] for positive screen at 48 months. Conclusion The Spanish ASQ-3 24 and 48 month intervals appear to be a reliable for developmental screening and for the follow-up of children, especially for LPI. Having two or more domains in the referral zone at 24 months screening is a significant predictor of developmental delay risk at 48-month questionnaire.

To detect any functional abnormality in the brainstem auditory pathway in late preterm babies born of small-for-gestational age (SGA) using maximum length sequence brainstem evoked response.The response was recorded and analyzed at term in 38 SGA (birthweight3rd centile) babies born at 33-36 week gestation. The results were compared with 40 age-matched babies born of appropriate-for-gestational age (AGA) (birthweight10th centile). None of the subjects had major perinatal problems.All wave latencies and interpeak intervals in the SGA group were slightly longer than those in the AGA group at most click rates. Wave III latency was significantly longer than that in the AGA group at 227/s (P0.05), and wave V latency was at 227 and 910/s (P0.05 and 0.05). Of the interpeak intervals, only the I-V interval in the SGA group was significantly longer than that in the AGA group at the highest rate 910/s (P0.05). The amplitudes of waves I, III and V in the SGA group all tended to be smaller than those in the AGA group at all click rates 91-910/s. The wave V amplitude was significantly smaller at most click rates (227-910/s, all P0.05). The slopes of all wave latency-, interval-, and amplitude-rate functions were similar in SGA and AGA groups.There were marginal abnormalities in MLS BAER of low-risk late preterm SGA babies, suggesting a mild degree of maturational delay in the brainstem. Intrauterine growth retardation occurring in late preterm babies has a minor effect on neural maturation of the immature brainstem.

article i nfo Backgrounds: Healthy late-preterm (LP) infants examined at term equivalent age showed wider median and range of neurological scores than full-term infants; differences between infants born at 34 and those born at 35-36 weeks were also observed. Aims: The aim of this study is to establish the range and frequency distribution of neonatal neurological scores in a cohort of low risk LP infants assessed during the first 3 days from birth. Study design and subjects: 118 low-risk infants born between 34 and 36 weeks of gestational age (GA) were assessed between 48 and 72 h from birth. Outcome measures: The full version of the Hammersmith Neonatal Neurologic Assessment and the screening proforma were used to assess all the infants. The raw scores obtained were compared to those of full-term infants using the same examination. Results: The distribution of neurological scores was similar among the 3 GAs for 26 items, with different median scores among LP infants born at 36 weeks and those born at 34 and 35 in only 2 items. LP infants showed a wider range of findings for each item than that of full term infants assessed soon after birth. Using the screening proforma, in our cohort, for each item the findings falling outside the 90% level were identical to those found in term-born and very preterm infants assessed at term age. Conclusions: The neurological scores obtained in our cohort could help as reference data when examining LP infants at birth compared to age matched low risk infants.

Individuals who are born very preterm (< 32 weeks gestation) show differential development of prefrontal cortex structure, function, and dependent behaviors, including executive function (EF) skills, beginning during late infancy and extending into adulthood. Preschool-aged children born moderate-to-late preterm (PT; 32–36 weeks gestation) show smaller discrepancies in EF development, but it is unclear whether these differences first emerge during the early childhood years, when EF is rapidly developing, or if they arise from alterations in complex cognitive skills measurable in late infancy. In the current study, we examined whether differences in complex attention, memory, and inhibition skills (precursor skills to EF) are altered in healthy infants born moderate-to-late PT at 9-months corrected age. Infants born PT demonstrated poorer memory at test following habituation than their full-term peers. Furthermore, lower gestational age at birth was associated with poorer performance on five of the six early EF tasks. Results indicate that even in the context of low medical and environmental risk, performance on the Bayley within the normal range, and no group-level differences in processing speed, infants born moderate-to-late PT show subtle alterations in cognitive skills presumed to be dependent on prefrontal cortex by 9-months of age, likely setting the stage for long-term differences in EF development.

Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (32weeks gestation) who subsequently develop brain injury. Antenatal steroid exposure can alter neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population.To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure.Retrospective analysis.Late preterm infants (33-36weeks; n=119) and term infants (37-41weeks; n=129) born at the Women's and Children's Hospital, Adelaide.Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA.Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p0.001), while BDNF and NT-3 were not different. In the late preterm period, cord blood NT-3 was reduced when antenatal steroids were administered24h prior to delivery (p0.01).This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period.

Background Neonatal Intensive Care Units (NICUs) protect preterm infants; otherwise, this is a stressful environment including painful stimuli. Aims To compare early neurobehavioral development prior to term-age in preterm infants at 34–36 weeks of post-conceptional age in different gestational ages, and to examine the effects of prematurity level and acute stressful events during NICU hospitalization on neurobehavioral development. Study design Cross-sectional design. Subjects Forth-five preterm infants, 34–36 weeks of post-conceptional age, were distributed into groups: extreme preterm (EPT; 23–28 weeks of gestational age; n = 10), moderate preterm (MPT; 29–32 weeks of gestational age; n = 10), late preterm (LPT; 34–36 weeks of gestational age; n = 25). Outcome measures All of the neonates were evaluated using the Neurobehavioral Assessment of Preterm Infant (NAPI) prior to 37 weeks of post-conceptional age. The Neonatal Infant Stressor Scale (NISS) was applied for EPT and MPT infants during NICU hospitalization, and medical charts were analyzed. Results The EPT group experienced significantly more acute stressful events during NICU hospitalization than the MPT group. The MPT group had lower scores in motor development and vigor than the EPT and LPT group, and they exhibited poorer quality crying than the LPT group. Motor development and vigor and alertness and orientation in preterm infants were predicted by prematurity level and acute stressful events. Conclusion The extreme preterm was exposed to higher stressful experiences than moderate and late preterm infants. However, the moderate preterm infants presented more vulnerable than the other counterparts in motor and vigor outcomes.

Respiratory syncytial virus (RSV) is one of the leading causes of severe respiratory illness in infants and young children. Prematurity, the presence of congenital heart diseases (CHD) especially if haemodynamically unstable, chronic lung disease, neuromuscular disorders, immunodeficiency, and Down syndrome are all well accepted as placing patients at high risk. Late preterm, is an important risk group for RSV infections to lead to severe bronchiolitis with resource utilization. The findings add support to the theory that RSV infection is an important cause of recurrent wheezing in premature babies.

Summary More than 1 in 10 babies are born prematurely and most of them are born after gestational age 32 weeks. Mortality and morbidity are more common in these moderate-to-late preterm infants than in full-term children. In this review, mechanisms and epidemiology of long-term airway morbidity in moderate-to-late preterm infants will be discussed. We discuss the potential of viral respiratory infections to further aggravate abnormal lung function associated with preterm birth.

Late preterm infants are a vulnerable population susceptible to early breastfeeding failure and lactation-associated morbidities. We have found that late preterm gestation has a negative effect on mothers' psychological profiles in the puerperium, with the resulting levels of anxiety, depression, and psychological distress correlating negatively with their early lactation performance.

Background Very early life pain exposure and stress induces alterations in the developing brain and leads to altered pain sensitivity. In premature infants with a history of numerous early postnatal adverse events, behavioral responsiveness and hypothalamic–pituitary–adrenal (HPA) axis reactivity may show alterations as well. Aims We compared a multidimensional response to a painful situation (vaccination) in three month old infants. The study involved very preterm, moderate to late preterm infants and full-term infants with varying exposure to pain and stress within the first weeks of life. Study design At the age of three months, we evaluated the infants' reactivity to intramuscular injections for immunization. Subjects The study included 61 very preterm infants, 30 moderate to late preterm infants and 30 full-term infants. Outcome measures We assessed heart rate recovery, Bernese pain Score and increase of salivary cortisol following vaccination. We also evaluated the flexor withdrawal reflex threshold as well as Prechtl's General Movements. Secondly, we assessed factors potentially influencing pain reactivity such as exposure to pain/stress, gender, use of steroids or opioids and mechanical ventilation. Results Very preterm, moderate to late preterm and full-term infants showed different reactivity to pain in all analyzed aspects. Very preterm infants showed a lower level of behavioral and physiologic reactivity and exposure to pain/stress predicted lower cortisol increase. Conclusion At three months of age, very preterm infants show an altered level of HPA axis reactivity. Efforts aiming at minimizing pain and stress in premature infants should be taken.

Background Late preterm infants (LPIs), born at 34 + 0 to 36 + 6 weeks of gestation contribute a significant proportion of all neonatal intensive care (NIC) admissions and are regarded as being at risk of adverse outcomes compared to term-born infants. Aim To explore the health outcomes and family functioning of LPIs who required neonatal intensive care, at three years of age. Study design and subjects This cohort study included 225 children born late preterm, between 1 January and 31 December 2006 in Northern Ireland. Children admitted for NIC (study group, n = 103) were compared with children who did not require NIC or who required special care only for up to three days (comparison group, n = 122). Outcome measures Health outcomes were measured using the Health Status Questionnaire, health service usage by parent report and family functioning using the PedsQL™ Family Impact Module. Results LPIs who required NIC revealed similar health outcomes at three years in comparison to those who did not. Despite this, more parents of LPIs who required NIC reported visiting their GP and medical specialists during their child's third year of life. Differences in family functioning were also observed with mothers of LPIs who required NIC reporting, significantly lower levels of social and physical functioning, increased difficulties with communication and increased levels of worry. Conclusions LPIs were observed to have similar health outcomes at three years of age regardless of NIC requirement. The increase in GP and medical specialist visits and family functioning difficulties observed among those infants who required NIC merits further investigation.

During the period studied, late preterm infants accounted for approximately 77% of all preterm births and 50.5% were male. Of the mothers, 15.4% had a morbidity. Caesarean-section delivery rate was 42.2%. Need for oxygen and respiratory distress rates were significantly higher (p

During the period studied, late preterm infants accounted for approximately 77% of all preterm births and 50.5% were male. Of the mothers, 15.4% had a morbidity. Caesarean-section delivery rate was 42.2%. Need for oxygen and respiratory distress rates were significantly higher (p

From a total of 94 children (52-GA; 42-GB), 26/52(50%) and 30/42 (71%) infants of group A and B, respectively, had indication for PVZ prophylaxis. In GB, 14/30(47%) were immunized. The estimated cost of prophylaxis (5 doses) was 26,000€-GA and 30,000€-GB. Ten infants (17.8%) were admitted with RSV bronchiolitis: 8(31%)-GA and 2(6.6%)-GB, median age 4 months (range 1–22) and 80% male. In GA, 4(50%) children were admitted to paediatric intensive care unit (PICU), 3 needing mechanical ventilation. One infant was readmitted. In GB, one infant, admitted for 11 days in the PICU without mechanical ventilation, was infected 13 days after 2 doses of PVZ. The other, was admitted in the nursery 40 days after the fifth dose of PVZ. The total cost of admission was 36,129€-GA and 27,318€-GB. Comparing both groups, mechanical ventilation was only needed for GA (1.62 vs. 0; p=0.003). No differences occurred between total and PICU length of stay (8.8 vs. 10.5; p=0.07) (3.5 vs. 5.5; p=0.12).