Neonatal Follow-up Research Articles

59 Important Pulmonary Outcomes in Extremely Preterm Infants: Parental Perspectives

Abstract Background Lung Injury is frequent in extremely preterm infants. The definition of bronchopulmonary dysplasia (BPD) has changed since it was first described in 1967. Oxygen need at 36 weeks, the current definition, is not closely associated with long-term pulmonary outcomes. This outcome, used in neonatal research, has been chosen by clinicians and researchers, not by parents. Other outcomes related to chronic respiratory disease (such as hospital readmissions, work of breathing, and/or exercise limitation) are rarely measured or reported in outcome research. What pulmonary outcomes are of importance to parents is unknown. Objectives The primary objective of this part of the “parent voices project” was to create a list of respiratory outcomes that are important to parents, both during the NICU hospitalization and after discharge, to be considered in future respiratory outcome studies. Design/Methods Over one year (2020-2021), parents of infants born <29 weeks’ gestational age (GA) who came for follow-up visits when their children were between 18 months and 7 years old, in a large academic centre, were invited to participate. They were asked both closed and open-ended questions about the following topics: • The child’s health and what they would want to improve. • The impacts (negative and positive) of prematurity on the life of their family. • Their decisional regrets. • What they wish they had known both before birth and in the NICU, and their recommendations for clinicians. We examined all the parental answers with a view to discovering how many invoked pulmonary outcomes and which themes parents described when speaking about respiratory health. The goal was to make a list of all the respiratory outcomes that were important to families, both during the NICU hospitalization and longer term. Results were analyzed using mixed methods. Results Among parents (n=285, 98% participation rate), 44% spoke about important pulmonary outcomes. Parents invoked 25 themes when they described respiratory health, some pertaining to NICU hospitalization and others to long-term outcomes (see Table below). Some themes impacted the child (child-centred), such as exercise limitation. Many other pulmonary outcomes having an impact on parents or the whole family were described by parents (parent or family-centred themes). For example, a child who had difficulty breathing would struggle and could have disturbed sleep, but parents often described their own fear, lack of sleep (or disturbed sleep in other children). When children were hospitalized because of a respiratory illness, many of the outcomes described would be both child- and parent-centred: e.g., parental loss of work or income, and loss of equilibrium for the whole family. None of the 285 parents spoke about oxygen at 36 weeks or BPD. The prevalence of parents who describe pulmonary outcomes as impacting the child and/or family was statistically similar in parents of children with and without BPD, born before or after 25 weeks, with a BW of less or more than 750 g. Parents of male infants and those who were readmitted for respiratory issues were more likely to report important pulmonary outcomes. Conclusion Many parents of children born extremely preterm describe important pulmonary outcomes, independent of BPD. None of the parents mentioned oxygen at 36 weeks or BPD. More parents report such outcomes when their child has been readmitted for pulmonary reasons. These adverse outcomes often impact the whole family. Future research will indicate which outcomes need to be included in neonatal trials (or neonatal follow-up).

54 Preterm Parents Identified Meaningful Outcomes: Involving Parents in Implementing Change

Abstract Background The Canadian Neonatal Follow-Up Network (CNFUN) reports on neurodevelopmental impairments (NDI) in the very preterm population but has never asked parents which outcomes and definitions are meaningful to them. The Parent Voices group conducted four studies which showed differences between parents and CNFUN perspectives on definitions, severity, composite outcomes, which outcomes, and the need to report positive as well as adverse outcomes. Disseminating and implementing change based on these results is the next essential step. Objectives To create consensus statements to guide evidence-based change. Design/Methods Using a modified Delphi method, Parent Voices results were reviewed and discussed with parents, clinicians and researchers in a virtual workshop in Oct 2021. The discussion was analyzed qualitatively to create statements, circulated for feedback, and 80% consensus statements identified by electronic polling. Priority items requiring further work were identified, working groups created, and results presented at a Sept 2022 workshop. Results In the 2021 workshop, 17 consensus statements were identified (7 from the Parent Voices results, 5 from the discussion, and 5 were out of scope). Actionable statements (n=11, Table 1) and items needing further work (n=6, Table 2) were identified and progress was made (Tables 1 and 2). To identify how to measure 7 outcomes which parents and stakeholders identified as important (child well-being, quality of life, socioemotional and behavioural, respiratory, feeding, sleeping, and caregiver well-being), working groups reviewed literature and made recommendations for minimal dataset and funded research at a virtual presentation with parent, clinicians, and researchers in Sept 2022. In the summer of 2022, the Canadian Premature Babies Foundation (CPBF), Parent-EPIQ team members and summer students disseminated the Parent Voices results to lay stakeholder groups via CPBF blogs and webinars. They also pursued a project identified in the 2021 workshop to educate parents about the role of Neonatal Follow-Up Programs using infographics and information sheets. Conclusion We have successfully collaborated with parent partners to implement the actionable results from our Parent Voices Project, and have a process to implement change when further work is required. Involving parents in research, knowledge dissemination and implementation can lead to changes that accurately represent the priorities of families.

58 Predicting and Preparing for the Future: Parents of Extremely Preterm Infants Give Recommendations to Clinicians

Abstract Background Parents of extremely preterm children face many challenges and uncertainties. The information and support provided by clinicians—both before and after birth—is invaluable to help them prepare for the future. Objectives To explore the information needs of parents of extremely preterm infants, before birth, in the NICU, and at discharge. Design/Methods In 2021, all parents of infants born <29 weeks’ gestational age and seen for neonatal follow-up between the ages of 18 months and 7 years were consecutively recruited over a one-year period in a large academic centre. Parents were asked: “Knowing what you know now, what do you wish doctors would have told you about prematurity before and/or after your child's birth?” Answers were analyzed using mixed methods. Results Nearly half (45%) of the 249 parents (98% participation rate) were satisfied with the medical information and support they received, either before or after birth. Prenatally, 16% felt that more practical information was needed in terms of the function of babies born preterm (not only diagnoses), and some parents would have liked prematurity to be mentioned in their normal pregnancy follow-up. 19% of parents wanted to know more about the life trajectory of babies in the NICU, along with knowing what was “the next step”, and how they could be part of the team to help their baby (“What are the different steps during the stay?” and ”How we can help as parents”. 22% wished discharge to be improved, to be better prepared for the future: e.g., “BPD does not help. We would have liked to know what leaving on oxygen meant, that she should not go to daycare, the risk with infections, RSV shots, sleeping problems many preemies have. This could have been done weeks before we left the hospital”. 14% wished they had known more about resources for psychosocial support. Parents (14%) wished clinicians to be more optimistic and provide them with hope: e.g., “Before birth, I would have liked to know that most micro preemies do well”. Conclusion Although half the parents were satisfied with the information and support they received, the other half recommended improvements, mainly to make our communication positive and practical. Diagnoses did not help parents prepare for the future prenatally, in the NICU, or at discharge, but information on function and what parents could do to assist (in a practical fashion) did.

62 Neurodevelopmental Outcomes Following Preterm Prelabour Rupture of Membranes Versus Spontaneous Preterm Birth among Infants Born at <29 Weeks of Gestation

Abstract Background Few studies examine differences in neurodevelopmental outcomes between spontaneous preterm birth (sPTB) and those additionally complicated by preterm prelabour rupture of membranes (PPROM). Objectives This prospective cohort study from the Canadian Neonatal Follow-Up Network compared mortality and neurodevelopmental outcomes (Bayley-III scores <70 and <85, hearing/vision loss and cerebral palsy) at 18-24 months corrected age following PPROM versus sPTB among infants <29 weeks of gestation born between 2010-2018. Secondarily, this study compared neurodevelopmental outcomes between those with PPROM lasting 1-7 days, >7days, and sPTB. Design/Methods Differences in maternal-infant characteristics and neonatal morbidities were assessed by Chi-square and Student t-tests. Raw and adjusted odds ratios (OR) with 95% CIs were calculated to compare outcomes. Results Study population included 4271 children, 1503 (35%) PPROM, 2768 (65%) sPTB. The sPTB group had younger mothers, and a higher proportion of maternal nulliparity, maternal hypertension, and outborn infants. In the neonatal period, PPROM neonates had lower rates of ROP and severe neurologic injury. Raw OR comparing PPROM vs. sPTB showed decreased mortality (OR: 0.75[0.65, 0.87]), and decreased total cerebral palsy rates (OR: 0.57 [0.41, 0.80]) (Table 1). Conclusion Among Canadian infants born at <29 weeks of gestation, PPROM lasting 1-7 days associated with decreased mortality and decreased rates of non-ambulatory cerebral palsy at 18-24 months corrected age when compared to sPTB. Such findings may be explained by heightened maternal/fetal care in PPROM cases. RESULTS Table1 Comparisons of the neurodevelopmental outcomes between exposure groups.

An Evaluation of Mid-upper Arm Circumference Measurement in a Neonatal Intensive Care Unit Follow-up Population

An Evaluation of Mid-upper Arm Circumference Measurement in a Neonatal Intensive Care Unit Follow-up Population

Neurodevelopmental Outcomes of Preterm Infants Born

This study aimed to determine neurodevelopmental outcomes of preterm infants born at <29 weeks' gestational age (GA) with bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) at 18 to 24 months' corrected age (CA). In this retrospective cohort study, preterm infants born at <29 weeks' GA between January 2016 and December 2019, admitted to level 3 neonatal intensive care units, who developed BPD and were evaluated at 18 to 24 months' CA in the neonatal follow-up clinics were included. We compared demographic characteristics and neurodevelopmental outcomes between the two groups: Group I: BPD with PH and Group II: BPD with no PH, using univariate and multivariate regression models. The primary outcome was a composite of death or neurodevelopmental impairment (NDI). NDI was defined as any Bayley-III score < 85 on one or more of the cognitive, motor, or language composite scores. Of 366 eligible infants, 116 (Group I [BPD-PH] =7, Group II [BPD with no PH] = 109) were lost to follow-up. Of the remaining 250 infants, 51 in Group I and 199 in Group II were followed at 18 to 24 months' CA. Group I and Group II had median (interquartile range [IQR]) birthweights of 705 (325) and 815 g (317; p = 0.003) and median GAs (IQR) were 25 (2) and 26 weeks (2; p = 0.015) respectively. Infants in the BPD-PH group (Group I) were more likely to have mortality or NDI (adjusted odds ratio: 3.82; bootstrap 95% confidence interval; 1.44-40.87). BPD-PH in infants born at <29 weeks' GA is associated with increased odds of the composite outcome of death or NDI at 18 to 24 months' CA. · Long-term neurodevelopmental follow-up of preterm infants born <29 weeks' GA.. · Association of neurodevelopmental outcomes with BPD-associated PH.. · Need for longitudinal follow-up of children with BPD-associated PH..

Neurodevelopmental outcomes of very preterm infants born following early foetal growth restriction with absent end-diastolic umbilical flow

This study aims to assess the impact of time of onset and features of early foetal growth restriction (FGR) with absent end-diastolic flow (AEDF) on pregnancy outcomes and on preterm infants’ clinical and neurodevelopmental outcomes up to 2 years corrected age. This is a retrospective, cohort study led at a level IV Obstetric and Neonatal Unit in Bologna, Italy. Pregnant women were eligible if having singleton pregnancies, with no major foetal anomaly detected, and diagnosed with early FGR + AEDF (defined as FGR + AEDF detected before 32 weeks gestation). Early FGR + AEDF was further classified according to time of onset and specific features into very early and persistent (VEP, FGR + AEDF first detected at 20–24 weeks gestation and persistent at the following scans), very early but transient (VET, FGR + AEDF detected at 20–24 weeks gestation and progressively improving at the following scans) and later (LA, FGR + AEDF detected between 25 and 32 weeks gestation). Pregnancy and neonatal outcomes and infant follow-up data were collected and compared among groups. Neurodevelopment was assessed using the revised Griffiths Mental Developmental Scales (GMDS-R) 0–2 years. A regression analysis was performed to identify early predictors of preterm infants’ neurodevelopmental impairment. Fifty-two pregnant women with an antenatal diagnosis of early FGR + AEDF were included in the study (16 VEP, 14 VET, 22 LA). Four intrauterine foetal deaths occurred, all in the VEP group (p = 0.010). Compared to LA infants, VEP infants were born with lower gestational age and lower birth weight, had lower arterial cord blood pH and were at higher risk for intraventricular haemorrhage and periventricular leukomalacia (p < 0.05 for all comparisons). At 12 months, VEP infants had worse GMDS-R scores, both in the general quotient (mean [SD] 91.8 [12.4] vs 104.6 [8.7] in LA) and in the performance domain (mean [SD] 93.3 [15.4] vs 108.8 [8.8] in LA). This latter difference persisted at 24 months (mean [SD] 68.3 [17.0] vs 92.9 [17.7] in LA). In multivariate analysis, at 12 months corrected age, PVL was found to be an independent predictor of impaired general quotient, while the features and timing of antenatal Doppler alterations predicted worse scores in the performance domain. Conclusion: Timing of onset and features of early FGR + AEDF might impact differently on neonatal clinical and neurodevelopmental outcomes. Shared awareness of the importance of FGR + AEDF features between obstetricians and neonatologists may offer valuable tools for antenatal counselling and for tailoring pregnancy management and neonatal follow-up in light of specific antenatal and neonatal risk factors.What is Known:• Foetal growth restriction (FGR), together with antenatal umbilical Doppler abnormalities, is known to affect maternal and neonatal outcomes.• Infants born preterm and growth-restricted face the highest risk for neurodevelopmental impairment, especially when FGR occurs early during pregnancy (early FGR, before 32 weeks gestation).What is New:• The timing of onset and features of FGR and antenatal umbilical Doppler abnormalities impact differently on maternal and neonatal outcomes; when FGR and Doppler abnormalities occur very early, at the limit of neonatal viability, and persist until delivery, infants face the highest risk for neurodevelopmental impairment.• Shared knowledge between obstetricians and neonatologists about timing of onset and features of FGR would provide a valuable tool for informed antenatal counselling in high-risk pregnancies.

The effect of father's participation in newborn care during hospitalization on survival and attendance at follow-up clinics in a tertiary care facility

BackgroundThe traditional role of a man has been to provide protection and economic support to their families. This study examines the role of men on duration of hospitalization, neonatal survival, and follow-up attendance at a tertiary institution, south-west Nigeria. MethodsThe study is a prospective cohort study involving fathers whose babies were admitted to a neonatal unit. We compared the fathers' provision of kangaroo mothers' care, financial support, readiness to stand in for mother and any other support with the outcomes of duration of hospital care, neonatal survival, and follow-up clinic attendance. We report adjusted odds ratio and 95% confidence interval of the outcome's variables. ResultsOne eighty-eight of the 201 selected had complete dataset. The median age of the babies at admission was 1 day (IQR: 1, 5; range 1-28-days). The overall median duration of hospitalization was 6 days (range 0.4–56) days. The median and interquartile range (IQR) of neonates who received father support at admission was shorter 5 days (IQR: 3, 7) compared to 7 days (IQR: 4, 11) for those who did not (p = 0.006). The survival rate and clinic attendance for preterms whose fathers provided KMC did not reach significant level(p = 0.201). The father's financial support significantly affected neonatal survival and follow-up clinic attendance (P = <0.001). The father's willingness to care for infant while the mother rests was associated with survival (p = 0.023). On multivariable logistic regression, infants whose fathers provided financial support had 27.8 (aOR: 27.778, 95% CI: 7.353–100.0) odds of survival and 6.155 (2.205–17.182) odds of clinic follow-up compared to those without. Other support from fathers was 20.8 (95% CI 4.587–100) times more likely to attend clinic follow-up. ConclusionsFather participation in newborn care significantly improves clinic follow-up attendance, shortens hospital stays, and improved newborn survival. Family-centered-father-focused newborn-care, are required in tertiary nurseries.

Parental Experiences of Neonatal Follow-up for Infants With Hypoxic Ischemic Encephalopathy in India: A Qualitative Study

Abstract Date Presented 04/22/2023 Low follow up rate of infants with perinatal asphyxia leads to inefficient early intervention of these children in developing countries. The reasons for this are discovered in this study and can be applied to improve the rate of follow up and therapy Primary Author and Speaker: Suja Angelin Chandrasekaran Contributing Authors: Hima B John, Benjamin Jeyanth Ross, Asha Arumugam, Indira Balan, Reema Samuel

Universal screening programme for cytomegalovirus infection in the first trimester of pregnancy: study protocol for an observational multicentre study in the area of Barcelona (CITEMB study)

IntroductionCongenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no universal screening programme for cCMV has...

Previous missed visits and independent risk of loss to follow-up in the high-risk neonatal follow-up clinic

BackgroundNeonatal intensive care unit (NICU) patients are at high risk for developmental delays. As a result, many are seen in neonatal follow-up (NFU) clinics. Disparities in NFU follow-up rates by social determinants of health exist. AimsDetermine how the number of missed visits (composed of patient-canceled visits and no-show visits) relates to risk of loss to follow-up in the NFU clinic. Study designRetrospective cohort study at a regional specialty center in the United States. Subjects262 patients born between January 1, 2014, and December 31, 2017, who were referred to the NFU clinic. Outcome measuresLogistic binomial regression was used to model risk ratio of loss to follow-up over two years, defined as not attending a recommended follow-up visit and not informing the clinic of a reason for discontinued care. ResultsOf 262 infants, 220 patients (84 %) were seen for at least one visit and 143 (65 %) completed follow-up. Younger maternal age, maternal smoking during pregnancy, maternal drug use during pregnancy, and public insurance were all associated with missing more visits. For each additional missed visit, the risk of loss to follow-up was 1.73 times higher unadjusted (95 % CI: 1.33, 2.26) and 1.81 times higher (95 % CI: 1.36, 2.40) after adjusting for confounders. The risk ratio of loss to follow-up for no-show visits was three times higher than that for patient-canceled visits. ConclusionsEach missed visit was independently associated with higher risk of loss to follow-up from NFU clinic, even after adjusting for other risk factors.

High-risk children and social isolation: the importance of family functioning.

High-risk newborns are exposed to neonatal conditions such as prematurity, very low birth weight, and congenital malformations that can affect development and behavior. Coronavirus disease 2019 (COVID-19) restraint and control measures have been identified as important stressor events and cumulative risk factors for behavioral changes in these children. This study examined social isolation-related factors that contribute to internalizing and externalizing behavior problems in children already at risk for neurodevelopmental disorders. This cross-sectional, multicenter study included 113 children (18 months to 9 years) who were followed in reference services for neonatal follow-up in tertiary units of the public health system in the city of Rio de Janeiro, Brazil. Behavior was assessed using the child behavior checklist, and a structured questionnaire was used to assess sociodemographic aspects. In the bivariate analysis, prematurity was associated with externalizing problems and change in eating habits with internalizing problems. The logistic model indicated that both parents having completed high school and both sharing care of the child were protective factors for behavioral problems; however, reports of sleep problems and living with another child were risk factors. In conclusion, the study identified internalizing and externalizing behavior problems related to prematurity and aspects of family structure and routine in children at risk. The findings confirm the importance of family functioning for child health and family-centered interventions.

0791 The Association of Sleep with Developmental and Behavioral Factors in Premature Infants

Abstract Introduction Children with neurodevelopmental conditions often experience sleep problems. Whereas sleep is a predictor of behavioral outcomes in children, there is limited evidence regarding sleep as an indicator of neurodevelopmental concerns. This study examined the prevalence of sleep issues and neurodevelopmental conditions in children with a history of prematurity, as well as the role of sleep as a potential indicator for future developmental and behavioral concerns. Methods Electronic health records of 57 young children (M = 31.9 gestational weeks, range = 23 to 40 weeks; 35.1% girls) presenting to a neonatal follow-up clinic were reviewed. Caregivers completed the Brief Infant Sleep Questionnaire (BISQ-R) between 6-16 corrected months (Mage = 11.6 mos) and then completed the Modified Checklist for Autism in Toddlers (M-CHAT) between 16-26 corrected months (Mage = 20.9 mos). Caregivers also completed the Survey of Wellbeing of Young Children (SWYC; n = 56; Mage = 20.9 mos) and the Brief Infant-Toddler Social and Emotional Assessment (BITSEA; n = 32; Mage = 17.4 mos). Results Approximately one-quarter (26.3%) of subjects had a caregiver-perceived child sleep problem at ages 6-16 corrected months. A total of 40.4% of children had clinically significant autism concerns on the M-CHAT and 67.9% had clinically significant concerns on the SWYC. Subsequent caregiver ratings showed that 25.0% of children exhibited challenging behaviors and 34.4% lower social-emotional competency on the BITSEA. Children who demonstrated clinically significant autism risk on the M-CHAT were more likely to have a prior caregiver-identified child sleep problem. Those who later failed the M-CHAT also had increased night waking frequency (2.43 vs 1.82 wakings) earlier in development. Logistic regression indicated that caregiver-identified sleep problems significantly predicted subsequent challenging behaviors on the BITSEA but not later neurodevelopmental concerns on the SWYC or social-emotional competencies on the BITSEA. Conclusion These pilot data suggest that a caregiver-identified child sleep problem at age 6-16 months corrected is linked to more frequent challenging child behaviors in toddlerhood (16-26 corrected months). Caregiver-identified child sleep problems and more night wakings also predicted later neurodevelopmental concerns. Sleep problems in premature infants may thus be an early indication of later behavioral and neurodevelopmental issues. Support (if any)

Parent-Integrated Interventions to Improve Language Development in Children Born Very Preterm

Neurodevelopmental challenges in children born very preterm are common and not improving. This study tested the feasibility of using Evidence-based Practice to Improve Quality (EPIQ), a proven quality improvement technique that incorporates scientific evidence to target improving language abilities in very preterm populations in 10 Canadian neonatal follow-up programs. Feasibility was defined as at least 70% of sites completing four intervention cycles and 75% of cycles meeting targeted aims. Systematic reviews were reviewed and performed, an online quality improvement educational tool was developed, multidisciplinary teams that included parents were created and trained, and sites provided virtual support to implement and audit locally at least four intervention cycles of approximately 6 months in duration. Eight of ten sites implemented at least four intervention cycles. Of the 48 cycles completed, audits showed 41 (85%) met their aim. Though COVID-19 was a barrier, parent involvement, champions, and institutional support facilitated success. EPIQ is a feasible quality improvement methodology to implement family-integrated evidence-informed interventions to support language interventions in neonatal follow-up programs. Further studies are required to identify potential benefits of service outcomes, patients, and families and to evaluate sustainability.

Live birth rates following individualized dosing algorithm of follitropin delta in a long GnRH agonist protocol

PurposeTo explore the efficacy and safety of individualized follitropin delta dosing, based on serum anti-Müllerian hormone (AMH) concentration and bodyweight, in a long gonadotropin-releasing hormone (GnRH) agonist protocol.MethodsClinical outcomes after one treatment cycle are reported in women with AMH: 5–35 pmol/L. Oocytes were inseminated by intracytoplasmic sperm injection, blastocyst transfer was on Day 5 and remaining blastocysts were cryopreserved. Data collection included live births and neonatal health follow-up for all fresh/frozen transfers performed within one year after treatment allocation.ResultsIn total, 104 women started stimulation, of whom 101 had oocyte recovery and 92 had blastocyst transfer. The average daily dose of follitropin delta was 11.0 ± 1.6 µg and the duration of stimulation was 10.3 ± 1.6 days. The mean number of oocytes was 12.5 ± 6.4, the mean number of blastocysts was 5.1 ± 3.4, and 85% had at least one good-quality blastocyst. Following mostly single blastocyst transfer (95%), the ongoing pregnancy rate was 43%, the live-birth rate was 43%, and the cumulative live-birth rate was 58% per started stimulation. There were 6 cases of early OHSS (5.8%) graded as mild (n = 3) and moderate (n = 3) and 6 cases of late OHSS (5.8%) graded as moderate (n = 3) and severe (n = 3).ConclusionIn this first evaluation of the individualized follitropin delta dosing in a long GnRH agonist protocol, the cumulative live-birth rate was high. A randomized trial comparing follitropin delta in a long GnRH agonist protocol versus in a GnRH antagonist protocol should provide further insight into the efficacy and safety of this treatment option.Trial registration numberNCT03564509; June 21, 2018.

Hyperbilirubinemia Among Infants Born Preterm: Peak Levels and Association with Neurodevelopmental Outcomes

To describe the distribution of peak bilirubin levels among infants born before 29weeks of gestation in the first 14days of life and to study the association between quartiles of peak bilirubin levels at different gestational ages and neurodevelopmental outcomes. Multicenter, retrospective, nationwide cohort study of neonatal intensive care units in the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network, including neonates born preterm at 220/7 to 286/7weeks of gestation born between 2010 and 2018. Peak bilirubin levels were recorded during the first 14days of age. Main outcome was significant neurodevelopmental impairment, defined as cerebral palsy with Gross Motor Function Classification System ≥3, or Bayley III-IV scores of <70 in any domain, or visual impairment, or bilateral hearing loss requiring hearing aids. Among 12 554 included newborns, median gestational age was 26weeks (IQR 25-28) and birth weight was 920 g (IQR 750-1105 g). The median peak bilirubin values increased as gestational age increased (112mmol/L [6.5mg/dL] at 22weeks and 156mmol/L [9.1mg/dL] at 28weeks). Significant neurodevelopmental impairment was identified in 1116 of 6638 (16.8%) of children. Multivariable analyses identified an association between peak bilirubin in the highest quartile and neurodevelopmental impairment (aOR 1.27, 95% CI 1.01-1.60) and receipt of hearing aid/cochlear implant (aOR 3.97, 95%CI: 2.01-7.82) compared with the lowest quartile. In this multicenter cohort study, peak bilirubin levels in neonates of <29weeks of gestation increased with gestational age. Peak bilirubin values in the highest gestational age-specific quartile were associated with significant neurodevelopmental and hearing impairments.

Ranking Future Outcomes Most Important to Parents of Children with Bronchopulmonary Dysplasia

To assess which potential future outcomes are most important to parents of children with bronchopulmonary dysplasia, a disease that affects future respiratory, medical, and developmental outcomes for children born preterm. We recruited parents from 2 children's hospitals' neonatal follow-up clinics and elicited their importance rating for 20 different potential future outcomes associated with bronchopulmonary dysplasia. These outcomes were identified and selected through a literature review and discussions with panels of parents and clinician stakeholders, via a discrete choice experiment. One hundred and 5 parents participated. Overall, parents ranked "Will my child be more vulnerable to other problems because of having lung disease?" as the most important outcome, with other respiratory health related outcomes also highly ranked. Outcomes related to child development and effects on the family were among the lowest ranked. Individually, parents rated outcomes differently, resulting in a broad distribution of importance scores for many of the outcomes. The overall rankings suggest that parents prioritize future outcomes related to physical health and safety. Notably, for guiding research, some top-rated outcomes are not traditionally measured in outcome studies. For guiding individual counseling, the broad distribution of importance scores for many outcomes highlights the extent to which parents differ in their prioritization of outcomes.

Fungal infection and neurodevelopmental outcomes at 18-30 months in preterm infants.

Invasive fungal infection (IFI) is associated with significant mortality and morbidity among preterm infants but there has been no population-based study of long-term neurodevelopmental outcomes. The objective of this study was to examine population-based incidence trends as well as mortality, short term in-hospital morbidity and long-term neurodevelopmental outcomes among preterm infants with IFI, non-fungal infections (NFI) and no infections in Canada. We conducted a retrospective cohort study of 8,408 infants born at <29 weeks gestational age (GA), admitted to Canadian Neonatal Network neonatal intensive care units (NICU) from April 2009 to December 2017, and followed up at 18-30 months corrected age (CA) in Canadian Neonatal Follow-Up Network clinics. We compared mortality, long term neurodevelopmental outcomes and short term in-hospital morbidity among 3 groups of infants (IFI, NFI, and no infections). The incidence of IFI was 1.3%, non-IFI 26.9% and no infections 71.7%. IFI incidence varied between 0.93% and 1.94% across the study period with no significant trend over time. Infants of higher gestational age were significantly (p < 0.01) less likely to have IFI. Among infants with IFI, NFI and no infections, the incidence of the significant neurodevelopmental impairment (sNDI) was 44.26%, 21.63% and 14.84% respectively, while mortality was 50%, 25.35% and 22.25% respectively. Even after risk adjustment for confounders (GA, Score for Neonatal Acute Physiology Version II, ruptured membranes >24 h, maternal antibiotic treatment, antenatal steroid use, cesarean section), infants with IFI had significantly higher odds of sNDI than NFI (aOR: 2.19; 95% CI: 1.23, 3.91) or no infections (aOR: 2.97; 95% CI: 1.55, 5.71), and higher odds of mortality than NFI (aOR: 1.55; 95% CI: 1.07, 2.26) or no infections (aOR: 1.45; 95% CI: 0.97, 2.17). Preterm infants with invasive fungal infections have significantly higher incidence of mortality and adverse neurodevelopmental outcomes than those with non-invasive fungal infections and no infections.

Analysis of clinical features, biochemical indices and genetic variants among children with Short/branched-chain acyl-CoA dehydrogenase deficiency detected by neonatal screening

To investigate the clinical manifestations, biochemical abnormalities and pathogenic variants among children with Short/branched-chain acyl-CoA dehydrogenase (SBCAD) deficiency detected by neonatal screening. A total of 2 730 852 newborns were screened from January 2016 to December 2021 with liquid chromatography tandem mass spectrometry. Suspected SBCAD deficiency patients were diagnosed by urine organic acid analysis and high-throughput gene sequencing analysis. The clinical, biochemical and genetic changes of the confirmed cases were analyzed, in addition with guidance for diet and life management, L-carnitine supplement, and survey of growth and intellectual development. Twelve cases of SBCAD deficiency were diagnosed, which yielded a prevalence of 1/227 571. The lsovaleryl carnitine (C5) of primary screening blood samples was between 0.6 and 2.1 µmol/L, all exceeded the normal range. C5/acety1 carnitine (C2) was between 0.02 and 0.12, with 6 cases exceeding the normal range. C5/propionyl carnitine (C3) was between 0.1 and 1.16, with 5 cases exceeding the normal range. Free carnitine (C0) was between 18.89 and 58.12 µmol, with 1 case exceeding the normal range. Three neonates with abnormal screening results were recommended to have appropriate restriction for protein intake and two were given L-carnitine. During follow-up, their C5 has ranged from 0.22 to 2.32 µmol/L, C5/C2 has ranged from 0.01 to 0.31, C5/C3 has ranged from 0.14 to 1.7. C5 or C5/C2 and C5/C3 were transiently normal in all patients except for case 8 during the neonatal screening and follow-up. C0 was 17.42 ∼ 76.83 µmol/L Urine organic acid analysis was carried out in 9 of the 12 cases, and 2-methylbutyroglycine was elevated in 8 cases. Urine organic acid analysis was carried out in 9 cases, and 2-methylbutyrylglycine was increased in 8 cases. Genetic analysis was carried out for 11 children, and in total 6 ACADSB gene variants were identified, which included 4 missense variants (c.655G>A, c.923G>A, c.461G>A, c.1165A>G), 1 frameshift variant (c.746del) and 1 nonsense variant (c.275C>G). Among these, the C.461G>A variant was unreported previously. The most common variants were c.1165A>G (40.9%) and C.275C>G (22.7%). The patients were followed up for 18 days to 55 months. Only one patient had mental retardation, with the remainders having normal physical and mental development. SBCAD deficiency is a rare disease. The detection rate of newborn screening in this study was 1/227 571. Early intervention can be attained in most asymptomatic patients through neonatal screening. In this study, the common gene variants are c.1165A>G and c.275C>G.

Structural Brain Alterations and Their Associations With Function in Children, Adolescents, and Young Adults With Congenital Heart Disease.

Most neonates who receive surgery for complex congenital heart disease (CHD) will survive well into adulthood, however, many of them will face functional challenges at one point during their life as a consequence of their atypical neurodevelopment. Recent advances in neuroscience and the increasing accessibility of magnetic resonance imaging have allowed numerous studies to identify the nature and extent of the brain alterations that are particular to survivors with CHD. Nevertheless, and considering that the range of outcomes is broad in this population, the functional effect of these brain differences is not always evident. In this review we summarize the present state of knowledge regarding the structure-function relationships evaluated in children, adolescents, and young adults with CHD using structural magnetic resonance imaging. Overall smaller total and regional brain volume, as well as lower fractional anisotropy in numerous brain regions, were frequently associated with lower cognitive outcomes including executive functioning and memory in adolescents and young adults with CHD. However, we identify several gaps in knowledge including the limited number of prospective investigations involving neonatal imaging and follow-up during childhood or adolescence, as well as the need for studies that evaluate a broader range of functional outcomes and not only cognitive abilities. Future interdisciplinary investigations using multimodal imaging techniques could help address these gaps.