PEDIATRICS recent issues

Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment

OBJECTIVE:

Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood.

METHODS:

This study was a retrospective analysis of prospectively collected data on preterm (22–26 + 6/7 weeks’ gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months’ corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment).

RESULTS:

The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9–25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541–709] vs 660 [572.5–750] g; P = .02) and longer durations of conventional ventilation (35 [21–58] vs 33 [18–49] days; P = .04) and supplemental oxygen (112 [94–120] vs 105 [84.5–120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy.

CONCLUSIONS:

In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.

Neonatal Abstinence Syndrome and Associated Neonatal and Maternal Mortality and Morbidity

OBJECTIVES:

We examined demographic characteristics and birth outcomes of infants with neonatal abstinence syndrome (NAS) and their mothers in Canada.

METHODS:

This retrospective, population-based, descriptive cross-sectional study of mother-infant dyads included all singleton live births in Canada (excluding Quebec), from 2005–2006 to 2015–2016 (N = 2 881 789). Demographic characteristics, NAS, and neonatal and maternal morbidities were identified from delivery hospitalization data (including diagnostic codes). The main composite outcomes were maternal and neonatal mortality and/or severe morbidity, including death and potentially life-threatening conditions in the mother and the infant, respectively. Logistic regression yielded adjusted odds ratios (aORs) and 95% confidence intervals (CIs).

RESULTS:

The study included 10 027 mother-infant dyads with NAS. The incidence of NAS increased from 0.20% to 0.51%. Maternal mortality was 1.99 vs 0.31 per 10 000 women in the NAS group versus the comparison group (aOR = 6.53; 95% CI: 1.59 to 26.74), and maternal mortality and/or severe morbidity rates were 3.10% vs 1.35% (aOR = 2.21; 95% CI: 1.97 to 2.49). Neonatal mortality was 0.12% vs 0.19% (aOR = 0.28; 95% CI: 0.15 to 0.53), and neonatal mortality and/or severe morbidity rates were 6.36% vs 1.73% (aOR = 2.27; 95% CI: 2.06 to 2.50) among infants with NAS versus without NAS.

CONCLUSIONS:

NAS incidence increased notably in Canada between 2005–2006 and 2015–2016. Infants with NAS had elevated severe morbidity, and their mothers had elevated mortality and severe morbidity. These results highlight the importance of implementing integrated care services to support the mother-infant dyad during childbirth and in the postpartum period.

Extended Maternity Leave and Breastfeeding in Active Duty Mothers

BACKGROUND AND OBJECTIVES:

In 2016, the Department of Defense extended maternity leave from 6 to 12 weeks for active duty mothers to support breastfeeding initiation and duration. Limited data exist regarding the impact of prolonged maternity leave. Our objective was to evaluate the prolongation of maternity leave on the initiation and duration of breastfeeding in active duty mothers.

METHODS:

In this single-center retrospective cohort study, we used data collected from Department of Defense electronic health care records of infants born to active duty mothers who were delivered during calendar years 2014 and 2016. The primary outcomes were initiation and duration of breastfeeding and breastfeeding exclusivity evaluated throughout the first year of life. Secondary outcomes were differences in breastfeeding rates between military-branch affiliation and military rank.

RESULTS:

No changes in breastfeeding initiation occurred between the 2 cohorts (n = 423 and 434). However, an increase in breastfeeding establishment was identified at the 2- (81.5% vs 72.4%; P = .002), 4- (70.5% vs 56.7%; P < .001), 6- (60.3% vs 46.5%; P < .001), and 9-month (45.4% vs 34.9%; P = .003) visits in the 12-week leave cohort. Exclusive breastfeeding increased at 2 (56.4% vs 47.2%; P = .007), 4 (47.5% vs 36.4%; P = .001), and 6 (37.3% vs 29.3%; P = .016) months.

CONCLUSIONS:

Increases in maternity leave correlated with increased breastfeeding duration and exclusivity through 9 months for active duty mothers. These data support the benefit of extended maternity leave in the military and the need for future studies to validate findings at other military treatment facilities.

Local Anesthesia With General Anesthesia for Pediatric Bone Marrow Procedures

BACKGROUND:

Pediatric patients with cancer undergo repeated painful procedures, including bone marrow aspirations and biopsies (BMABs). Optimal management of procedure-related pain can reduce discomfort, anxiety, and distress.

METHODS:

Children with neuroblastoma were randomly assigned to 1 of 2 arms on a prospective, single-blind, crossover trial conducted at Memorial Sloan Kettering Cancer Center from October 2016 to January 2018 (www.clinicaltrials.gov, identifier NCT02924324). Participants underwent 2 sequential BMABs: one with general anesthesia (GA) alone, the other with GA plus local anesthesia (LA) (GA + LA). The objective was to assess procedure-related pain and its interference with quality of life (QoL) with GA versus GA + LA. Primary outcome was percentage of participants requiring postprocedural opioids. Secondary outcomes were total opioid and nonopioid analgesics, pain scores, time to first analgesic, QoL, and toxicity. Management of postprocedural pain was standardized.

RESULTS:

Of 56 participants randomly assigned (3–16.5 years old), 46 completed both procedures. There was no significant difference in percentage of participants requiring opioids with GA versus GA + LA (24% vs 20%, P = .5). Pain scores in the recovery room were significantly lower for GA + LA versus GA (median [IQR]: 0 [0–2] vs 2 [0–4], P = .002). There were no statistically significant differences in total opioid or nonopioid analgesic, 6- and 24-hour pain scores, median time to first analgesic, or pain interference. No adverse events occurred.

CONCLUSIONS:

LA was associated with significant improvement in pain scores in the immediate recovery period. LA did not reduce postprocedural opioid use, nor did it improve QoL for patients undergoing BMAB with GA.

Serious Bacterial Infections in Neonates Presenting Afebrile With History of Fever

BACKGROUND:

Infants ≤28 days of age with fever are frequently hospitalized while undergoing infectious evaluation. We assessed differences in rates of serious bacterial infection (SBI; bacteremia, bacterial meningitis, urinary tract infection) and invasive bacterial infection (IBI; bacteremia, bacterial meningitis) among the following neonates: (1) febrile at presentation (FP), (2) afebrile with history of fever without subsequent fever during hospitalization, and (3) afebrile with history of fever with subsequent fever during hospitalization.

METHODS:

We performed a single-center retrospective study of neonates evaluated for SBI during emergency department evaluation between January 1, 2006, and December 31, 2017. Patients were categorized into FP, afebrile with no subsequent fever (ANF), and afebrile with subsequent fever (ASF) groups. We compared rates of SBI and IBI between groups using logistic regression and assessed time to fever development using time-to-event analysis.

RESULTS:

Of 931 neonates, 278 (29.9%) were in the ANF group, 93 (10.0%) were in the ASF group, and 560 (60.2%) were in the FP group. Odds of SBI in neonates ANF were 0.42 (95% confidence interval [CI] 0.23–0.79) compared with infants FP, although differences in IBI were not statistically significant (0.52, 95% CI 0.19–1.51). In infants ASF, median time to fever was 5.6 hours (interquartile range, 3.1–11.4). Infants ASF had higher odds of SBI compared to infants FP (odds ratio 1.93, 95% CI 1.07–3.50).

CONCLUSIONS:

Neonates with history of fever who remain afebrile during hospitalization may have lower odds for SBI and be candidates for early discharge after an observation period.

Parent Attitudes and Preferences for Discussing Health Care Costs in the Inpatient Setting

OBJECTIVES

To explore parent attitudes toward discussing their child’s health care costs in the inpatient setting and to identify strategies for health care providers to engage in cost discussions with parents.

METHODS:

Using purposeful sampling, we conducted semistructured interviews between October 2017 and February 2018 with parents of children with and without chronic disease who received care at a tertiary academic children’s hospital. Researchers coded the data using applied thematic analysis to identify salient themes and organized them into a conceptual model.

RESULTS:

We interviewed 42 parents and identified 2 major domains. Categories in the first domain related to factors that influence the parent’s desire to discuss health care costs in the inpatient setting, including responsibility for out-of-pocket expenses, understanding their child’s insurance coverage, parent responses to financial stress, and their child’s severity of illness on hospital presentation. Categories in the second domain related to parent preference regarding the execution of cost discussions. Parents felt these discussions should be optional and individualized to meet the unique values and preferences of families. They highlighted concerns regarding physician involvement in these discussions; their preference instead was to explore financial issues with a financial counselor or social worker.

CONCLUSIONS:

Parents recommended that cost discussions in the inpatient setting should be optional and based on the needs of the family. Families expressed a desire for physicians to introduce rather than conduct cost discussions. Specific recommendations from parents for these discussions may be used to inform the initiation and improvement of cost discussions with families during inpatient encounters.

A Framework for Evaluation of the Higher-Risk Infant After a Brief Resolved Unexplained Event

In 2016, the American Academy of Pediatrics published a clinical practice guideline that more specifically defined apparent life-threatening events as brief resolved unexplained events (BRUEs) and provided evidence-based recommendations for the evaluation of infants who meet lower-risk criteria for a subsequent event or serious underlying disorder. The clinical practice guideline did not provide recommendations for infants meeting higher-risk criteria, an important and common population of patients. Therefore, we propose a tiered approach for clinical evaluation and management of higher-risk infants who have experienced a BRUE. Because of a vast array of potential causes, the initial evaluation prioritizes the diagnosis of time-sensitive conditions for which delayed diagnosis or treatment could impact outcomes, such as child maltreatment, feeding problems, cardiac arrhythmias, infections, and congenital abnormalities. The secondary evaluation addresses problems that are less sensitive to delayed diagnosis or treatment, such as dysphagia, intermittent partial airway obstruction, and epilepsy. The authors recommend a tailored, family-centered, multidisciplinary approach to evaluation and management of all higher-risk infants with a BRUE, whether accomplished during hospital admission or through coordinated outpatient care. The proposed framework was developed by using available evidence and expert consensus.

School Readiness in Preschoolers With Symptoms of Attention-Deficit/Hyperactivity Disorder

OBJECTIVE:

To compare school readiness in preschoolers with and without attention-deficit/hyperactivity disorder (ADHD) symptoms using a comprehensive framework. We hypothesized that preschoolers with ADHD symptoms have higher odds of school readiness impairment.

METHODS:

Children ages 4 to 5 years (n = 93) were divided into 2 groups on the basis of presence of ADHD symptoms (ADHD group, n = 45; comparison group, n = 48). School readiness was assessed through 10 component measures, including direct assessments and standardized questionnaires, regarding 5 school readiness domains: physical well-being and motor development, social and emotional development, approaches to learning, language, and cognition and general knowledge. Analysis of covariance compared group mean scores on component measures. Domain impairment was defined as score ≥1 SD from the test population mean in the unfavorable direction on ≥1 measure in the domain. School readiness impairment was defined as impairment in ≥2 of 5 domains. Logistic regression predicted impairment within domains and overall readiness.

RESULTS:

The ADHD group demonstrated significantly worse mean scores on 8 of 10 component measures and greater odds of impairment in all domains except for cognition and general knowledge. Overall, 79% of the ADHD group and 13% of the comparison group had school readiness impairment (odds ratio 21, 95% confidence interval 5.67–77.77, P < .001).

CONCLUSIONS:

Preschoolers with ADHD symptoms are likely to have impaired school readiness. We recommend early identification of school readiness impairment by using a comprehensive 5-domain framework in children with ADHD symptoms paired with targeted intervention to improve outcomes.

Cardiometabolic Risk and Body Composition in Youth With Down Syndrome

BACKGROUND AND OBJECTIVES:

Whether BMI captures adiposity and cardiometabolic risk in Down syndrome (DS), a condition associated with obesity, short stature, and altered body proportions, is not known. We compared cardiometabolic risk measures in youth with DS and typically developing matched controls.

METHODS:

Youth with (n = 150) and without (n = 103) DS of comparable age (10–20 years), sex, race, ethnicity, and BMI percentile underwent whole-body dual-energy X-ray absorptiometry, fasting glucose, insulin, lipids, lipoprotein particles, inflammatory factors, and when BMI percentile ≥85, an oral glucose tolerance test.

RESULTS:

Sixty-four percent of youth with DS had BMI percentile ≥85. Among these, no difference in glucose, insulin, or insulin resistance was detected, but prediabetes was more prevalent with DS (26.4% vs 10.3%; P = .025) after adjustment for demographics, pubertal status, and BMI z score (odds ratio = 3.2; P = .026). Among all participants, those with DS had higher low-density lipoprotein cholesterol (median 107 [interquartile range 89–128] vs 88.5 [79–103] mg/dL; P < .00005), triglycerides (89.5 [73–133] vs 71.5 [56–104] mg/dL; P < .00005), non–high-density lipoprotein cholesterol (non-HDL-C; 128 [104–153] vs 107 [92–123] mg/dL; P < .00005), and triglycerides/HDL-C (2.2 [1.6–3.4] vs 1.7 [1.1–2.5] mg/dL; P = .0003) and lower levels of HDL-C (41 [36.5–47] vs 45 [37–53] mg/dL; P = .012). DS youth had higher high-sensitivity C-reactive protein, interleukin-6, small low-density lipoprotein particles (LDL-P), and total LDL-P, but similar LDL-P size. Youth with DS had less visceral fat (VFAT), fat mass, and lean mass for BMI z score, but greater VFAT at higher fat mass. However, VFAT did not fully explain the increased prevalence of dyslipidemia or prediabetes in youth with DS.

CONCLUSIONS:

Despite similar insulin resistance, youth with DS had greater prevalence of dyslipidemia and prediabetes than typically developing youth, which was not fully explained by VFAT.

Integration of Pediatric Palliative Care Into Cardiac Intensive Care: A Champion-Based Model

Integration of pediatric palliative care (PPC) into management of children with serious illness and their families is endorsed as the standard of care. Despite this, timely referral to and integration of PPC into the traditionally cure-oriented cardiac ICU (CICU) remains variable. Despite dramatic declines in mortality in pediatric cardiac disease, key challenges confront the CICU community. Given increasing comorbidities, technological dependence, lengthy recurrent hospitalizations, and interventions risking significant morbidity, many patients in the CICU would benefit from PPC involvement across the illness trajectory. Current PPC delivery models have inherent disadvantages, insufficiently address the unique aspects of the CICU setting, place significant burden on subspecialty PPC teams, and fail to use CICU clinician skill sets. We therefore propose a novel conceptual framework for PPC-CICU integration based on literature review and expert interdisciplinary, multi-institutional consensus-building. This model uses interdisciplinary CICU-based champions who receive additional PPC training through courses and subspecialty rotations. PPC champions strengthen CICU PPC provision by (1) leading PPC-specific educational training of CICU staff; (2) liaising between CICU and PPC, improving use of support staff and encouraging earlier subspecialty PPC involvement in complex patients’ management; and (3) developing and implementing quality improvement initiatives and CICU-specific PPC protocols. Our PPC-CICU integration model is designed for adaptability within institutional, cultural, financial, and logistic constraints, with potential applications in other pediatric settings, including ICUs. Although the PPC champion framework offers several unique advantages, barriers to implementation are anticipated and additional research is needed to investigate the model’s feasibility, acceptability, and efficacy.

The Challenge of Treating Pulmonary Vasculitis in Behcet Disease: Two Pediatric Cases

Behcet disease (BD) is a multisystemic autoinflammatory disorder characterized by recurrent mucocutaneous, ocular, musculoskeletal, gastrointestinal, central nervous system, and vascular manifestations. Pulmonary arterial involvement (PAI) of BD is probably the most severe form of vasculitis, at least in children. PAI has a high mortality, morbidity, and recurrence rate. There are limited data regarding treatment and outcomes of pediatric patients with BD with PAI. Herein, we report 2 pediatric patients with BD presented with hemoptysis and support our data with a systematic review. These patients were given immunosuppressive therapy, which covered pulse methylprednisolone followed by oral prednisolone, intravenous cyclophosphamide every 3 weeks for a total of 6 cycles, and interferon-α2a concomitantly. These are the first reported cases in the literature successfully treated with this treatment modality in a complication with 50% mortality. These patients have been followed up for a period of at least 4 years without any vascular recurrence. Pediatricians should be aware that patients with BD may not present with full diagnostic criteria. They should consider BD in a child with PAI to avoid diagnostic delay and start life-saving accurate immunosuppressive treatment.

Pediatric Respiratory Illness Measurement System (PRIMES) Scores and Outcomes

BACKGROUND AND OBJECTIVES:

The Pediatric Respiratory Illness Measurement System (PRIMES) generates condition-specific composite quality scores for asthma, bronchiolitis, croup, and pneumonia in hospital-based settings. We sought to determine if higher PRIMES composite scores are associated with improved health-related quality of life, decreased length of stay (LOS), and decreased reuse.

METHODS:

We conducted a prospective cohort study of 2334 children in 5 children’s hospitals between July 2014 and June 2016. Surveys administered on admission and 2 to 6 weeks postdischarge assessed the Pediatric Quality of Life Inventory (PedsQL). Using medical records data, 3 PRIMES scores were calculated (0–100 scale; higher scores = improved adherence) for each condition: an overall composite (including all quality indicators for the condition), an overuse composite (including only indicators for care that should not be provided [eg, chest radiographs for bronchiolitis]), and an underuse composite (including only indicators for care that should be provided [eg, dexamethasone for croup]). Multivariable models assessed relationships between PRIMES composite scores and (1) PedsQL improvement, (2) LOS, and (3) 30-day reuse.

RESULTS:

For every 10-point increase in PRIMES overuse composite scores, LOS decreased by 8.8 hours (95% confidence interval [CI] –11.6 to –6.1) for bronchiolitis, 3.1 hours (95% CI –5.5 to –1.0) for asthma, and 2.0 hours (95% CI –3.9 to –0.1) for croup. Bronchiolitis overall composite scores were also associated with shorter LOS. PRIMES composites were not associated with PedsQL improvement or reuse.

CONCLUSIONS:

Better performance on some PRIMES condition-specific composite measures is associated with decreased LOS, with scores on overuse quality indicators being a primary driver of this relationship.

Thyroid-Stimulating Hormone Reference Ranges for Preterm Infants

BACKGROUND AND OBJECTIVES:

Many newborn screening (NBS) programs now perform repeat or serial NBS to detect congenital hypothyroidism. There is wide variation in thyroid-stimulating hormone (TSH) cutoffs used by NBS programs. Data on TSH reference ranges in preterm infants at increasing postnatal age are limited. Our study objective was to determine TSH reference ranges for preterm infants born at <32 weeks’ gestation.

METHODS:

We analyzed serial TSH levels on NBS performed on infants born between 22 and 31 weeks’ gestation from 2012 to 2016 in Wisconsin. The study cohort was divided into 2 groups (22–27 and 28–31 weeks), and TSH percentiles were defined from birth to the term equivalent gestational age.

RESULTS:

The study cohort consisted of 1022 and 2115 infants born at 22 to 27 and 28 to 31 weeks’ gestation, respectively. The 95th percentile TSH level for the group born at 22 to 27 weeks’ gestation gradually decreased and reached a nadir at ~10 to 11 weeks. In contrast, for the group born at 28 to 31 weeks’ gestation, the 95th percentile TSH level reached a nadir at ~5 to 6 weeks. At 3 to 4 weeks after birth, the 95th percentile TSH level ranged from 11 to 11.8 μIU/mL for the group born at 22 to 27 weeks’ gestation and ranged from 8.2 to 9 μIU/mL for the group born at 28 to 31 weeks’ gestation.

CONCLUSIONS:

Using a statewide cohort of preterm infants, we constructed TSH reference charts from birth to the term equivalent gestation for preterm infants born at <32 weeks’ gestation. Use of a single cutoff for all preterm infants might lead to misdiagnosis. The differences in TSH levels according to gestational-age categories might explain the increased frequency in congenital hypothyroidism diagnoses among preterm infants. These data are useful for defining age-adjusted NBS TSH cutoffs for preterm infants.

Cognitive and Behavioral Impact on Children Exposed to Opioids During Pregnancy

The developmental impact of opioid use during pregnancy is a subject of ongoing debate. Short-term neonatal outcomes, such as lower birth weight and neonatal abstinence syndrome, are the most well-recognized outcomes. However, knowledge gaps exist regarding longer-term neurocognitive and mental health outcomes. In this article, we summarize an expert panel discussion that was held in April 2018 by the Substance Abuse and Mental Health Services Administration and attended by national experts in the field of perinatal opioid exposure and its impact on child development. Despite the challenges with research in this area, there is emerging literature revealing an association between neonates exposed to opioids in utero and longer-term adverse neurocognitive, behavioral, and developmental outcomes. Although adverse sequalae may not be apparent in the neonatal period, they may become more salient as children develop and reach preschool and school age. Multiple variables (genetic, environmental, and biological) result in a highly complex picture. The next steps and strategies to support families impacted by opioid use disorder are explored. Model programs are also considered, including integrated care for the child and mother, parenting supports, and augmentations to home visiting.

Improving Information Sharing for Youth in Foster Care

There are ~443 000 children in child protective custody (ie, foster care) in the United States. Children in protective custody have more medical, behavioral, and developmental problems that require health care services than the general population. These health problems are compounded by poor information exchange impeding care coordination. Health care providers often do not know which of their patients are in protective custody and are not privy to the critical social history collected by child protective services, including placement history and maltreatment history. Meanwhile, the custodial child protection agency and designated caregivers (ie, foster caregivers and kinship providers) often lack vital elements of the health history of children in their care, which can result in poor health care delivery such as medication lapses, immunization delay, and poor chronic disease management. In this case study, we address this critical component of health care delivery for a vulnerable population by describing a process of developing an information sharing system between health care and child welfare organizations in collaboration with child protection community partners. Lessons learned include recommended steps for improved information sharing: (1) develop shared community vision, (2) determine shareable information components, (3) implement and analyze information sharing approaches, and (4) evaluate information sharing efforts. A successful example of advocating for improvement of information sharing for youth in protective custody is explored to highlight these steps. In collaboration with child protective services, pediatricians can improve information sharing to impact both health care delivery and child protection outcomes.

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