Corrected Age Research Articles

Diseases of bile duct in children.

Several diseases originate from bile duct pathology. Despite studies on these diseases, certain etiologies of some of them still cannot be concluded. The most common disease of the bile duct in newborns is biliary atresia, whose prognosis varies according to the age of surgical correction. Other diseases such as Alagille syndrome, inspissated bile duct syndrome, and choledochal cysts are also time-sensitive because they can cause severe liver damage due to obstruction. The majority of these diseases present with cholestatic jaundice in the newborn or infant period, which is quite difficult to differentiate regarding clinical acumen and initial investigations. Intraoperative cholangiography is potentially necessary to make an accurate diagnosis, and further treatment will be performed synchronously or planned as findings suggest. This article provides a concise review of bile duct diseases, with interesting cases.

Oral feeding trajectories and neurodevelopmental outcomes at 12 and 24 month follow-up for preterm infants.

Few studies characterize feeding performance in the NICU when predicting neurodevelopmental outcomes. Our objective was to investigate the relationship between time to full oral feeds (FULL-PO) and neurodevelopmental and feeding outcomes in the first 2 years in preterm infants admitted to the NICU. This retrospective study included infants born between 01/01/2014-07/31/2017, gestational age < 32 weeks and/or birth weight < 1500 g. We examined feeding difficulties, cerebral palsy, and Bayley scores for those reaching FULL-PO at a post menstrual age (PMA)≤38.0 weeks (EARLY) vs.>38.0 weeks (LATE). Additionally, the oral feeding achieved at various timepoints between 36- and 42-weeks postmenstrual age (PMA) was measured to construct a timeline of oral feeding acquisition. Of 192 infants, 147(77%) achieved FULL-PO EARLY and 45(23%) LATE. Comorbidities and length of stay were higher and unadjusted Bayley scores were lower at 12 months corrected age (CA) and 24 months chronological age (CH) in the LATE group. Feeding difficulties were higher in the LATE group at 24 months CH. Infants born < 27-28 weeks GA were more likely to achieve oral feeding at a later PMA. Infants with bronchopulmonary dysplasia (BPD) had significant feeding and developmental delays. Establishing full oral feeds by 38.0 weeks PMA may be used as a predictor for feeding difficulties at 24 months CH. Infants born < 27-28 weeks GA and those with BPD are more likely to take extended amounts of time to achieve full oral feeding and need additional feeding support. Infants with BPD are high risk for neurodevelopmental delays.

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial—statistical analysis plan for a multicenter randomized controlled trial

BackgroundMortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC.MethodsThe ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent.The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years.To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data.DiscussionThe findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth.Trial registrationClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Effects of an Educational Intervention Program on Positional Cranial Deformity in Premature Infants.

Positional cranial deformities are associated with prematurity evolving during the first 2 years of life due to the malleable characteristics of the skull, the first year being the main/primary therapeutic window for intervention. The objectives were (a) to describe health characteristics, peri- and postnatal pathologies, and positional cranial deformities in infants enrolled in an early intervention program and (b) to analyze the effects of a parent education-based intervention program on positional cranial deformity in premature infants. A quantitative, analytical, longitudinal study was conducted. It included 103 premature infants enrolled in an early intervention program (EIP) during the year 2017, all under 4 months of corrected age, to whom a parent education-based intervention program was applied. Cranial circumference, cranial width, diagonals, and anteroposterior diameter were measured, and the cranial asymmetry index (CAI) and cephalic index (CI) were calculated at baseline and during two subsequent evaluations separated by a 3-month period. The main results showed that 75.7% of the infants belonged to a very premature gestational age category, and 57.3% had an adequate weight for gestational age. The most frequent pathologies were premature jaundice, premature anemia, and hyaline membrane disease. The most frequent positional cranial deformity was plagiocephaly. The parent education-based intervention program resulted in (1) a significant decrease in the CAI and a significant increase in the IC, (2) plagiocephalies: an increase in the mild category and a decrease in the moderate + severe categories, (3) brachycephalies: a decrease in the absence category and an increase in the moderate + severe category, and (4) dolichocephalies: an increase in the absence category and a decrease in the mild category. In conclusion, the recommended first line of intervention was not enough for this population, and future studies should support the development of national clinical guidelines, where education is complemented with other therapeutic measures.

Two-year neurodevelopmental outcome in extremely preterm-born children: The Austrian Preterm Outcome Study Group.

The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.

Start, duration of kangaroo position in preterm newborns and neuropsychomotor development at six and twelve months of corrected age

ObjectiveThe aim of this study was to evaluate the effect of the start and duration time of kangaroo position on motor and cognitive development at 6 and 12 months of gestationally corrected age in preterm infants born younger than 32 weeks of gestational age. MethodThis is an observational and longitudinal study carried out with 130 children at six months and 106 at twelve months of gestationally corrected age, born at a gestational age less than and equal to 32 weeks. ResultsThe early start of kangaroo position (p = 0.039) was associated with better cognitive development at 6 months (p = 0.046) and 12 months of corrected gestational age (p = 0.004) and the children who remained in kangaroo position for longer periods of time per day (p = 0.036) showed better motor development at 12 months of gestational age. ConclusionStarting the kangaroo position early and performing it for longer periods of time per day are practices that favor the neurodevelopment of preterm children.

Socio-familial environment influence on cognitive and language development in very preterm children.

Preterm children are at increased risk of cognitive and language delay compared with term-born children. While many perinatal factors associated with prematurity are well established, there is limited research concerning the influence of the socio-familial environment on the development of preterm children. This study aims to assess the relative impact of perinatal and socio-familial risk factors on cognitive and language development at 2years corrected age (CA). This retrospective cross-sectional study included preterm infants with a gestational age <32 weeks and/or a birth weight <1500 g, who underwent neurodevelopmental assessment at 2years CA. Cognitive and language scores were assessed using the Bayley Scales of Infant-Toddler Development, third edition. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated using a multivariable model to examine the relationship between developmental delays and perinatal and socio-familial factors. The prevalence of language delay was negatively associated with daycare attendance (aOR: 0.25, 95% CI: 0.07-0.85, p < 0.05) and high maternal educational levels (aOR: 0.24, 95% CI: 0.05-0.93, p < 0.05) and positively associated with bilingual environments (aOR: 5.62, 95% CI: 1.46-24.3, p < 0.05). Perinatal and postnatal risk factors did not show a significant impact on cognitive or language development. The development of language appears to be more influenced by the socio-familial environment than by early perinatal and postnatal factors associated with prematurity. These findings highlight the importance of considering socio-familial factors in the early identification and intervention of language delay among preterm children.

Factors Associated with Delayed Palatoplasty Before, During, and After the COVID-19 Pandemic.

Cleft palatoplasty is typically performed around 10 to 12 months of age in the US, and delays can negatively affect speech development. Early during COVID-19, elective surgeries were canceled. The aims of this study were to (1) identify overall risk factors for greater age at palatoplasty and (2) analyze delays in palatoplasty during COVID-19. This study was part of a larger prospective, multicenter comparative study of speech outcomes in palatoplasty. Participants underwent palatoplasty between March 2019 and September 2022 at 18 pediatric hospitals in the United States. Ages were corrected for prematurity. Dates of palatoplasty were divided into 4 periods corresponding to different phases of the pandemic. Factors analyzed included region, language, adoption status, sex, ethnicity, race, rurality, health insurance type, and cleft type. Analyses were performed using ANOVA, Student's test, and multivariable linear regression, with a P value of ≤0.05 being significant. Nine hundred twenty-eight participants were included. Average corrected age at palatoplasty was 374 days. In univariable analysis, palatoplasty was performed later in children who were Hispanic (P=0.003), of a race other than White, Black, or Asian (P<0.001), and without private insurance (P<0.001). On multivariable regression, predictors of delayed palatoplasty were Hispanic ethnicity (P=0.015), from other race (P<0.001), and without private insurance (P<0.001). During COVID-19, disproportionate delays occurred in patients who were female, of other races, from nonrural areas, and on Medicaid. Palatoplasty was performed later in vulnerable populations. Some of these populations were also disproportionately affected by COVID-19 delays. Providers should be aware of these differences as they pertain to equitable access to craniofacial care. III.

Pituitary gland height evaluated with magnetic resonance imaging in premature twins: the impact of growth and sex.

Pituitary gland height reflects secretory activity of the hypothalamo-pituitary axis. To assess the cumulative impact of fetal growth and sex on pituitary gland height in premature twins, dissociated from prematurity. A retrospective study was conducted, assessing the pituitary gland height in 63 pairs of preterm twins, measured from T1-weighted magnetic resonance imaging (MRI). Auxological parameters, including body weight, body length, and head circumference, at birth and at the time of MRI, were used as proxies for fetal and postnatal growth, respectively. The study population was divided into two groups, using corrected age at around term equivalent as the cutoff point. Statistical analysis was performed using mixed-effects linear regression models. When pituitary gland height was evaluated at around term equivalent, a greater pituitary gland height, suggesting a more immature hypothamo-pituitary axis, was associated with the twin exhibiting lower auxological data at birth. The same association was observed when body weight and length at MRI were used as covariants. In the group evaluated after term equivalent, a smaller pituitary gland height, suggesting a more mature hypothamo-pituitary axis, was associated with male sex. This difference was observed in twin pairs with higher average body weight at birth, and in babies exhibiting higher auxological data at MRI. After isolating the effect of prematurity, at around term equivalent, pituitary gland height reflects the cumulative impact of fetal growth on the hypothalamo-pituitary axis. Subsequently, pituitary gland height shows effects of sex and of fetal and postnatal growth.

Preterm infants experience a nadir in cerebral oxygenation during sleep three months after hospital discharge.

Preterm infants are at increased risk of Sudden Infant Death Syndrome (SIDS) and frequently experience short central apnoeas which can occur in isolation or a repetitive pattern (periodic breathing). We investigated the relationship between central apnoeas experienced before and over the 6 months after hospital discharge and cerebral oxygenation. Preterm infants born between 28 and 32 weeks gestational age (GA) were studied during supine daytime sleep at 32-36 weeks post menstrual age (PMA) (n = 40), 36-40 weeks PMA (n = 27), 3-months corrected age (CA) (n = 20) and 6-months CA (n = 26). Cerebral tissue oxygenation (TOI), peripheral oxygenation (SpO2) and heart rate were recorded continuously. The percentage total sleep time (%TST) spent having central apnoeas at each study and cerebral fractional oxygen extraction (SpO2-TOI/SpO2) were calculated. %TST spent with central apnoeas decreased with increasing age in both active sleep (AS) and quiet sleep (QS). TOI tended to be lower and cerebral fractional oxygen extraction higher at 3 months compared to the other studies and this reached statistical significance compared to 32-36 weeks in QS. The nadir in cerebral tissue oxygenation at 3 months of age coincides with the peak risk period for SIDS and this may contribute to increased risk in these infants.

Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study

BackgroundFollow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability.MethodsWe developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine.ResultsOne thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4–10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76–0.81(95% CI, 0.73–0.83) for cognitive regress with 4 variables and 0.79–0.83 (95% CI, 0.76–0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75–0.78 (95% CI, 0.72–0.82) for cognitive delay with 10 variables and 0.73–0.82 (95% CI, 0.72–0.85) for motor delay with 4 variables.ConclusionsOur EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Agreement between Hammersmith Neonatal Neurological Examination (HNNE) and Test of Infant Motor Performance (TIMP) in neurodevelopmental assessment of preterm infants

ObjectivesTo determine the agreement between HNNE and TIMP at TCA for preterm infants born <32+0 weeks' gestation, and to evaluate their correlation to PDMS-2 at 12-month corrected age (CA). MethodsInfants born between November 2013 to June 2022 who had both HNNE and TIMP performed at TCA of 37+0–41+6 weeks gestation, and motor outcome assessed using the PDMS-2 at 12-month old were enrolled. The HNNE and 12-month PDMS-2 findings were categorized as optimal vs sub-optimal. TIMP was categorized as typical vs atypical. Cohen's kappa was used to determine the agreement between HNNE and TIMP. Sensitivity analysis and Receiver Operating Characteristic (ROC) curves were used to evaluate the predictive values of HNNE and TIMP on motor outcome at CA of 12-months. ResultsHNNE and TIMP done on 125 infants at TCA do not show reliable agreement. HNNE demonstrated slight and fair agreement with the 12-month Total Motor Quotient (TMQ) and Fine Motor Quotient (FMQ) of the PDMS-2 respectively. TIMP at TCA demonstrated fair agreement with all sub-domains of motor function on PDMS-2 at 12-months. In comparison with TIMP, HNNE at TCA is more sensitive at predicting suboptimal total, gross and fine motor outcomes at 12-month CA with sensitivity of 68.4 %, 51.9 %, and 83.3 % vs 44.4 %, 31.8 % and 53.3 % respectively. Atypical TIMP at TCA is more specific for suboptimal total, gross and fine motor outcomes at 12-month CA with specificity of 90.3 %, 89 % and 90.5 % respectively.Neurobehavioral assessments at TCA using HNNE and TIMP were predictive of suboptimal fine motor quotient at CA of 12-months with AUC of 0.760 (p = 0.011) and 0.718 (p = 0.032) respectively. The difference in AUC between the 2 instruments of 0.042 was not statistically significant (p = 0.741). ConclusionsWhile the HNNE and TIMP done at TCA did not demonstrate significant agreement, suboptimal HNNE and atypical TIMP at TCA were predictive of suboptimal FMQ on PDMS-2 at 12-month CA.

Screening for functional gastrointestinal disorders in preterm infants up to 12 months of corrected age: a prospective cohort study

Functional gastrointestinal disorders (FGIDs) are characterized by a variety of symptoms that are frequently age-dependent, chronic, or recurrent and are not explained by structural or biochemical abnormalities. There are studies in the literature reporting different results regarding the relationship between prematurity and FGIDs. The main objective of this study was to compare the frequency of FGIDs between preterm and term infants. The secondary objective was to evaluate whether there was any association between neonatal characteristics and development of FGIDs. A multicenter prospective cohort study that included preterm infants born before 37 weeks of gestation and healthy term infants was carried out. At 1, 2, 4, 6, 9, and 12 months of age, infants were assessed for the presence of FGIDs using the Rome IV criteria. In preterm infants, an additional follow-up visit was made at 12 months corrected age. 134 preterm and 104 term infants were enrolled in the study. Infantile colic, rumination syndrome, functional constipation, and infant dyschezia were more common in preterm infants. Incidence of other FGIDs (infant regurgitation, functional diarrhea and cyclic vomiting syndrome) were similar among preterm and term infants. Preterm infants who are exclusively breastfeed in the first 6 months of life have a lower incidence of infantile colic (18.8% vs 52.1%, p = 0.025). In terms of chronological age, FGIDs symptoms started later in preterm infants; this difference was statistically significant for infantile colic and regurgitation (median age 2 months vs 1 month, p < 0.001). Conclusions: Preterm infants have a higher prevalence of FGIDs compared with term controls. Therefore, especially if they have gastrointestinal complaints, they should be screened for FGIDs. Possibly due to maturational differences, the time of occurrence of FGIDs may differ in preterm infants. Infantile colic incidence decreases with exclusive breastfeeding.What is Known:• The functional gastrointestinal disorders are a very common in infancy.• Data on preterm infants with FGIDs are currently very limited.What is New:• Preterm infants have a higher incidence of infantile colic, rumination syndrome, functional constipation and infant dyschezia when compared to term infants.• Preterm infants who are exclusively breastfed during the first 6 months of life experience a lower incidence of infantile colic.

Increasing Prevalence of Cerebral Palsy Among Two-Year-Old Children Born at

ObjectiveTo evaluate changes in prevalence and severity of cerebral palsy (CP) among surviving children born at <27 weeks of gestation over time and to determine associations between CP and other developmental domains, functional impairment, medical morbidities, and resource utilization among two-year old children who were born extremely preterm. Study DesignRetrospective cohort study using prospective registry data, conducted at 25 centers of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Participants were children born at <27 weeks of gestation and followed at 18 through 26 months corrected age (CA) from 2008 through 2019. Outcomes of interest were changes in prevalence of any CP and severity of CP over time, and associations between CP and other neurodevelopmental outcomes, functional impairment, and medical comorbidities. Adjusted logistic, linear, multinomial logistic, and robust Poisson regression evaluated the relationships between child characteristics, CP severity, and outcomes. ResultsAmong 6,927 surviving children with complete follow-up data, 3,717 (53.7%) had normal neurologic examinations, 1,303 (18.8%) had CP, and the remainder had abnormal neurologic examinations not classified as CP. Adjusted rates of any CP increased each year of the study period (aOR 1.11 per year, 95% CI 1.08-1.14). Cognitive development was significantly associated with severity of CP. Children with CP were more likely to have multiple medical comorbidities, neurosensory problems, and poor growth at follow-up. ConclusionsThe rate of CP among surviving children who were born extremely preterm increased from 2008 through 2019. At 18 to 26 months CA, neurodevelopmental and medical comorbidities are strongly associated with all severity levels of CP.

Age Group-Specific Improvement of Vertebral Scoliosis after the Surgical Release of Congenital Muscular Torticollis.

Background Congenital muscular torticollis (CMT) is a common musculoskeletal disorder in children. Secondary scoliosis can occur in patients with CMT; however, the extent of inclination and improvement of scoliosis after surgical correction of CMT have not been adequately studied. In this study, we aimed to evaluate and measure the improvement in vertebral tilting after surgical correction according to age at the time of surgery. Methods Between June 2007 and January 2020, 831 patients with CMT underwent sternocleidomastoid release. Among them, 426 patients were enrolled, and their medical records were retrospectively reviewed. Ultimately, 210 patients available for radiological evaluation and analysis were enrolled in this study. The patients were divided into four groups according to age at the time of surgery to determine the relationship between age and changes in scoliosis. Results Our findings showed an improvement in scoliosis in all age groups after surgery. The results for follow-up after 1 year confirmed long-term improvement in vertebral tilting. The degree of improvement in scoliosis was significantly higher in the younger age group than in patients aged 18 years or older. Conclusion The effect of surgical release on scoliosis was significant in all age groups. The findings of this study suggest that CMT should be corrected before the age of 3 years to ensure an optimal surgical mitigation of scoliosis. Furthermore, in cases of neglected CMT, surgical release should be actively attempted because there is significant improvement.

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2-3-Year Neurodevelopmental Outcome.

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.

Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Complication rates rise with age and Haller index in minimally invasive correction of pectus excavatum: A high-volume, single-center retrospective cohort study

ObjectivesThe study objectives were to describe the compounded complication rate of minimally invasive repair of pectus excavatum, identify predisposing risk factors, and evaluate the optimal timing of correction. Minimally invasive repair of pectus excavatum is the standard treatment for pectus excavatum and consists of 2 invasive procedures, for example, correction with bar insertion followed by bar removal after 2 to 3 years. MethodsA retrospective cohort study identifying children, adolescents, and adults of both genders corrected for pectus excavatum with minimally invasive repair of pectus excavatum between 2001 and 2022. Information on complications related to bar insertion and removal procedures for each individual patient was compiled into a compounded complication rate. Complication severities were categorized according to the Clavien-Dindo classification. ResultsA total of 2013 patients were corrected by minimally invasive repair of pectus excavatum with a median age (interquartile range) for correction of 16.6 (5) years. Overall compounded complication rate occurred at a frequency of 16.4%, of which 9.3% required invasive reinterventions (Clavien-Dindo classification ≥IIIa). The complication rate related to bar insertion was 2.6-fold higher compared with bar removal (11.8% vs 4.5%, respectively). Multivariable analysis revealed age (adjusted odds ratio, 1.05; P < .001), precorrection Haller Index (adjusted odds ratio, 1.10; P < .033), and early-phase institutional experience (adjusted odds ratio, 1.59; P < .002) as independent predisposing risk factors. The optimal age of correction was 12 years, and the compounded complication rate correlated exponentially with age with a doubling time of 7.2 years. Complications increased 2.2-fold when the Haller index increased to 5 or more units. ConclusionsMinimally invasive repair of pectus excavatum is associated with a high compounded complication rate that increases exponentially with age and high Haller Index. Consequently, we recommend repair during late childhood and early adolescence, and emphasize the importance of informing patients and relatives about the significant risks of adult correction as well as the need of 2 consecutive procedures taking the complication profile into account before planning surgery.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula

Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. ClinicalTrials.gov Identifier: NCT01534481.

Non Breast-Milk-Fed Very Preterm Infants Are at Increased Risk of Iron Deficiency at 4-6-Months Corrected Age: A Retrospective Population-Based Cohort Study.

Iron supplementation is routinely recommended for breast-milk-fed preterm infants. However, the Canadian Pediatric Society recommends no additional iron supplementation for preterm infants fed primarily with iron-rich formula. Other pediatric societies don't provide specific guidance on supplemental iron for formula-fed preterm infants. This study investigated how feeding type influences iron status of very preterm infants at 4-6-months corrected age (CA). A retrospective cohort study was conducted using a population-based database on all very preterm infants (<31 weeks gestational age) born in Nova Scotia, Canada from 2005-2018. Information about feeding type, iron intake from formula, supplemental iron therapy and iron status at 4-6-months CA was extracted. Iron deficiency (ID) was defined as serum ferritin <20 and <12 µg/L at 4-and 6-months CA, respectively. Of 392 infants, 107 were "breast-milk-fed" (exclusively or partially) and 285 were "not breast-milk-fed" (exclusively fed with iron-rich formula) at 4-6-months CA. Total daily iron intake was higher in the non-breast-milk-fed group (2.6 mg/kg/day versus 2.0 mg/kg/day). Despite this, 36.8% of non-breast-milk-fed infants developed ID versus 20.6% of breast-milk-fed infants. ID is significantly more prevalent in non-breast-milk-fed infants than breast-milk-fed infants despite higher iron intake. This suggests the need to revisit recommendations for iron supplementation in non-breast-milk-fed preterm infants.