Ms. Hester is Content Specialist with Contemporary OB/GYN and Contemporary Pediatrics.

Childhood asthma is one of the most common respiratory diseases in children. Having a mother who has asthma is a strong risk factor for her offspring also having the condition. Recent research has shown that vitamin D is a modifiable prenatal exposure. A report from the 

Journal of Allergy and Clinical Immunology

 looked at the effect of both early and late prenatal vitamin D status in pregnancy in both women with asthma and without on the development of recurrent wheeze or childhood asthma.

Investigators ran a cohort study that used prospectively collected data from the vitamin D Antenatal Asthma Reduction Trial, which was a randomized, double-blinded, placebo-controlled vitamin D supplementation trial in pregnant women who were at high risk of offspring asthma. The women were either randomized into the control group (a multivitamin containing 400 IU of vitamin D daily) or the intervention group (4400 IU of VD daily). The 25-Hydroxyvitamin-D (25(OH)D) level was measured early and late in the pregnancy. The main exposure for the study was an ordered variable that represented early and late prenatal vitamin D sufficiency (25(OH)D level ≥30 ng/mL) status in pregnant women with or without asthma.

The study included 776 mother-offspring pairs who had vitamin D measurements from both early and late pregnancy. Among the 766 children, 202 children either had physician-diagnosed asthma or recurrent wheeze before their third birthday. Children who had mothers with asthma had nearly 2 times odds of developing asthma or a recurrent wheeze by age 3 years when compared to those children with mothers who did not have asthma, even after adjusting for a number of variables including maternal income, maternal atopy, paternal asthma, preterm birth, child sex, and child race. An examination of early and late prenatal vitamin D status and its impact on offspring asthma or recurrent wheeze, the investigators noted a significant interaction seen between prenatal vitamin D and maternal status, with the highest decrease in risk of offspring asthma or recurrent wheeze seen among mothers with asthma who had prenatal vitamin D sufficiency at both measurements.

The investigators concluded that vitamin D sufficiency throughout pregnancy appears to have a protective role, particularly when mitigating the risk caused by maternal asthma on the development of childhood asthma or recurrent wheeze.

1. Lu M, Litonjua A, O’Connor G, et al. Effect of early and late prenatal vitamin D and maternal asthma status on offspring asthma or recurrent wheeze. 

. 2021;147(4):1234-1241.e3. doi:10.1016/j.jaci.2020.06.041

Articles

Maternal asthma is a major risk factor for a child also developing asthma. A report examines whether vitamin D sufficiency in pregnancy can change that risk.

Using vitamin D to mitigate risk of childhood asthma in offspring of mothers with asthma

During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of children developing Kawasaki disease (KD) was significantly higher than that for other infectious diseases, suggesting that KD arises as a result of airborne infections, investigators concluded in a recent study.

The study, published in JAMA Network Open, provides evidence contradicting the dominant theory for KD development—that KD is associated with contact or droplet transmission of pathogens similar to how respiratory syncytial virus (RSV) causes respiratory tract infections and rotavirus causes gastrointestinal infections.1

KD is an acute, self-limited, febrile disease predominately detected in children aged 6 months to 5 years. According to the American Heart Association, the disease is characterized by inflammation of the blood vessels, particularly the coronary artery, potentially causing permanent arterial damage, aneurysms, and heart attacks.

Past evidence has suggested that KD can occur in patients who are genetically predisposed to the disease after being exposed to certain environmental triggers. However, despite long-term research, investigators are still unsure of what exactly causes KD development.

Since February 2020, when the first outbreak of COVID-19 occurred, Japanese officials heavily encouraged handwashing, mask wearing, and social distancing and issued a state of emergency lasting from April 7 to May 25, 2020. These measures decreased the spread of SARS-CoV-2, the virus that causes COVID-19, and other pathogens transmitted through contact or droplets, giving an opportunity to investigate whether the incidence of KD did as well.

To conduct the multicenter, longitudinal, cross-sectional study, the investigators analyzed the number of admissions for KD and infectious diseases at 6 hospitals in Fukuoka, Japan and 11 nationwide hospitals between 2015 to 2020.

A total of 1649 pediatric patients with KD and 15,586 with infectious diseases were admitted. The median (interquartile range) age for patients with KD was 25 (13-43) months, and 54.6% (n = 901) were boys.

There was no significant change in the number of KD-related admissions between April and May in 2015 to 2019 compared with the same months in 2020 (mean [SD], 24.8 [5.6] vs 18.0 [4.0] monthly admissions; 27.4% decrease; adjusted incidence rate ratio [aIRR], 0.73; 95% CI, 0.48-1.10; P = .12).

Conversely, there was a significant decrease in admissions linked to contact- or droplet-transmitted respiratory (mean [SD], 157.6 [14.4] vs 39.0 [15.0] admissions per month; 75.3% decrease; aIRR, 0.25; 95% CI, 0.17-0.35; P < .001) and gastrointestinal (mean [SD], 43.8 [12.9] vs 6.0 [2.0] admissions per month; 86.3% decrease; aIRR, 0.14; 95% CI, 0.04-0.43; P < .001) infections from April to May in 2015 through 2019 compared with the same time frame in 2020.

After the Japanese COVID-19 state of emergency was lifted in June to December 2020, the number of patients with KD significantly decreased by 45% in the 6 Fukuoka hospitals and 47% in the 11 nationwide hospitals compared with the same months in 2015 to 2019. However, the decrease was not comparable to the 68.9% decrease observed for respiratory infections. A smaller 18.2% decrease was observed for gastrointestinal infections.

“These persistently low RSV and rotavirus incidence rates suggest that people continued engaging in infection-preventive behaviors (eg, physical distancing, hand washing, and wearing masks) even after the COVID-19 state of emergency was lifted,” wrote the investigators.

The investigators suggested that the persistence of KD decrease may be linked to airborne transmission partially being blocked by COVID-19 preventive measures or potential KD-causing environmental triggers were reduced as a consequence of restricted socioeconomic activity, leading to reduced motor vehicle emissions and shutdowns of power plants and factories.

The limitations associated with the study included the limited potential for generalizability and the inability to definitively determine PD pathogenesis.

“Despite these limitations, we believe that the results of this work provide intriguing clues toward clarification of the pathogenesis of KD and the establishment of preventive methods for KD,” wrote the investigators.

This article was originally published on 

1. Hara T, Furuno K, Yamamura K, et al. Assessment of pediatric admissions for Kawasaki disease or infectious disease during the COVID-19 state of emergency in Japan. JAMA Netw Open. 2021;4(4):e214475. doi:10.1001/jamanetworkopen.2021.4475

Given the high prevalence of Kawasaki disease during the pandemic, Japanese investigators determined that droplet or contact transmission of pathogens is likely not a major route causing the development of the disease.

Pandemic offers insight into potential cause of Kawasaki disease

For young athletes, the female athlete triad and male athlete triad can be a potential issue. An article will cover the ways to recognize both of them and how to treat them.

Addressing coronavirus disease 2019 vaccine hesitancy head on will be an important component of getting the pediatric population vaccinate. We have an article this week that discusses the efficacy and safety profile, as well as provides talking points to address.

Plus, Dr. Tan welcomes a new editorial board member and addresses the mental toll of the pandemic.

A look at what to expect from Contemporary Pediatrics this week

 What's new on Contemporary Pediatrics: April 12 to April 16

Wanting clarification on a possible higher risk of adult-onset heart failure from a preterm live birth, or gestation of less than 37 weeks, investigators from Sweden conducted a national cohort study of all live singleton births in the country between 1973 and 2014.

Their data show a 42% greater risk of new adult-onset heart failure between the ages of 18 and 43 years if the individual was born before 37 weeks gestation, according to the study published in 

 There also was an overall 0.1% incidence of heart failure, with a median age of 15.4 years at diagnosis.

“Preterm birth has been associated with increased risk of heart failure early in life, but its association with new-onset heart failure in adulthood appears to be unknown,” the authors noted when explaining why they looked into this outcome.

With a primary outcome of heart failure, the authors also stratified their data by several measures of gestational age: extremely preterm births (22-27 weeks), moderately preterm births (28-33 weeks), late preterm births (34-36 weeks), and early term births (37-38 weeks).

The median age of the 4 million-plus individuals included in the study was 22.5 years, and there were 85 million person-years of follow-up. Among this entire cohort, preterm birth age was associated with elevated risk of heart failure at any age vs full-term birth (39-41 weeks):

Younger than 1 year (adjusted HR [aHR], 4.49; 95% CI, 3.86-5.22)

Aged 1 to 17 years (aHR, 3.42; 95% CI, 2.75-4.27)

Aged 18 to 43 years (aHR, 1.42; 95% CI, 1.19-1.71)

When stratifying by each measure of gestational age among the adult cohort, the risks remained elevated, as did the incidence of heart failure (per 100,000 person years), but both measures dropped with the longer gestational periods:

Extremely preterm births (HR, 4.72; 95%CI, 2.11-10.52); 31.7 cases

Moderately preterm births (HR, 1.93; 95% CI, 1.37-2.71); 13.8 cases

Late preterm births (HR, 1.24; 95% CI, 1.00-1.54); 8.7 cases

Early term births (HR, 1.09; 95% CI, 0.97-1.24); 7.3 cases

The incidence of heart failure among full-term single births was 6.6 cases per 100,000 person-years in comparison. This association was seen even after “excluding persons with structural congenital cardiac anomalies,” the authors noted.

Male and female participants also had similar case totals of heart failure stemming from a preterm birth, preterm infants were more likely to be born to mothers either younger than 20 years or 40 years and older, and most preterm births in the study were first in birth order.

An important distinction the authors add is that the greater risk of heart failure among those aged 18 to 43 years may be linked to family histories of heart failure and preterm birth, whereas this is not the case for individuals with young-onset heart failure.

All diagnoses of heart failure were identified by 

 codes, and the entire study cohort was followed up with from their earliest heart failure diagnosis after birth through the end of the study period. Variables adjusted for included birth year, sex, birth order, family history of ischemic heart disease, and maternal factors such as age, education level, smoking status, and diabetes history before delivery.

“To our knowledge, this is the largest population-based study of preterm birth in association with heart failure risks and the first to examine such risks into mid-adulthood or include co-sibling analyses,” the authors concluded, with study strengths that included the large national cohort design, highly complete nationwide birth and medical registry data, and the large sample size.

Their findings indicate a possible long-term need for clinical follow-up among adult survivors of preterm births, with monitoring for heart failure one of the focus areas, especially with the median age of heart failure onset dropping, they added.

1. Crump C, Groves A, Sundquist J, Sundquist K. Association of preterm birth with long-term risk of heart failure into adulthood. JAMA Pediatr. April 5, 2021. Epub ahead of print. doi:10.1001/jamapediatrics.2021.0131

A higher risk of adult-onset heart failure was found in this Swedish study that investigated its association with singleton live births before 37 weeks gestation.

Is there a link between adult-onset heart failure and preterm birth?

In 2015, the annual estimated cost of atopic dermatitis in the United States was 5 billion dollars.

 The onset of atopic dermatitis usually occurs in childhood. The majority of patients present with this disease prior to 12 months of age and 85% of patients develop this disease before age 5 years.

 Typically, atopic dermatitis has a chronic, relapsing course that may persist from childhood well into adulthood. In this article, we address frequently asked questions from patients.

1. If eczema is adequately controlled, is the risk of developing other disorders in the atopic march reduced?

The atopic march refers to the progression of diseases in certain patients. These patients usually start with atopic dermatitis and subsequently develop asthma, allergic rhinitis, food allergies, or other atopic diseases throughout their life.

 For example, approximately 30% to 50% of patients with atopic dermatitis also have allergic rhinitis and the prevalence of asthma among patients with atopic dermatitis is about 26%.

 A dysfunctional skin barrier can cause sensitization to antigens leading to other atopic diseases and a number of studies show that early treatment of eczema can reduce the risk of developing other atopic disorders.

2. What factors cause exacerbation of atopic dermatitis?

Some of the most common triggers include anxiety, dry skin, high temperatures, ichthyosis, irritants, itching, stress, and sweat.

Maintaining skin hydration is crucial in atopic dermatitis and emollients are one of the mainstay treatments for this condition. Regular emollient use can decrease the need for topical corticosteroids. Most providers recommend a water-based, fragrance-free moisturizer. Patients should apply emollients at least daily, particularly after swimming and bathing, and avoid taking long, hot showers. They should also avoid or limit their use of nonsoap cleansers. Irritants include detergents, perspiration, solvents, wool, and other rough materials.

Scratching can exacerbate and maintain the inflammation and drive the itch-scratch cycle, so any measures that decrease inflammation and scratching may decrease symptoms and skin findings. Patients should also avoid high humidity, temperature extremes, and attempt to decrease their stress as much as possible.

3. How does atopic dermatitis affect quality of life (QOL)?

It significantly decreases [a patient’s] QOL. In one study, among all chronic conditions in children, atopic dermatitis had the second highest impact on QOL.

 In adults, QOL is also severely impacted by the symptoms and emotional impact of this disease.

 In some cases, patients with atopic dermatitis may even change their occupation because of the skin condition.

 Atopic dermatitis can cause constant itching or scratching, difficulty sleeping, and embarrassment.

This skin condition is also associated with cardiovascular, inflammatory, and psychiatric conditions.

 Many of the symptoms of atopic dermatitis, such as sleep disturbance and decreased self-esteem, are risk factors for the development of psychiatric disorders. Atopic dermatitis is also associated with increased risk of anxiety and depression.

4. How does atopic dermatitis evolve over time?

In infants, atopic dermatitis primarily affects the face, scalp, and extensor surfaces of the extremities. In children, atopic dermatitis primarily affects the flexural folds of the extremities and neck. In adults, atopic dermatitis primarily affects the hands and inner creases of the elbows and knees. Older kids and adults with severe itching and behavioral issues may be at risk for prurigo nodularis, which presents as dramatically thickened plaques and nodules in these areas or at times disseminated.

Standard of care can vary depending on the severity of the disease. In general, topical emollients and corticosteroids are the mainstay therapies.

Topical corticosteroids decrease inflammation, colonization of 

, and pruritus. The potency should be based on the severity and location of the atopic dermatitis. For patients with atopic dermatitis in regions where corticosteroid use is not recommended, such as the face or skin folds, topical calcineurin inhibitors can be used. These include the tacrolimus ointment and pimecrolimus cream, which were approved nearly a decade ago, and these medications should be considered as an alternative treatment for atopic dermatitis.

 Although a black box warning was implemented in 2005 for the topical calcineurin inhibitors because of limited safety data and concern of risk of malignancies (despite protests by the American Academy of Dermatology and American Academy of Allergy, Asthma, and Immunology), long-term studies showed no evidence for these claims.

Emollients are also crucial in atopic dermatitis because they improve the barrier function and prevent dryness.

 Along with medications, skin protective measures should be emphasized to avoid exacerbations of the disease. In addition, many patients have trouble sleeping and melatonin can be helpful.

For many of the topical medications and emollients, providers often underestimate the quantity needed. The quantity should depend on the severity and surface area of the skin that is involved. For reference, approximately 2 g are required for a single application to the face, 3 g are required for a single application to 1 arm, and 4 g are required for a single application to 1 leg. Approximately 30 to 60 g are needed to cover the entire body for a single application. For 3 daily applications to the entire body for 2 weeks, approximately 42 to 84 oz are needed.

6. Is topical steroid use safe and effective for treating atopic dermatitis?

Studies have consistently demonstrated that topical steroids are effective in treating atopic dermatitis and topical steroids are currently one of the mainstay therapies for the treatment of this disease.

 They are safe in adults and children when used appropriately with careful discussion of frequency and length of application with guidelines for specific body sites. All patients should be counseled on the possible adverse effects of corticosteroids, including atrophy and striae.

7. How can bleach baths help patients with atopic dermatitis? How does the formation of biofilms complicate treatment?

Patients with atopic dermatitis have more flares and greater eczema severity with higher levels of 

 Liquid chlorine beach, which is sodium hypochlorite 6% solution, is active against 

 and therefore diluted bleach baths with mildly warm water may improve symptoms in many patients.

 species can form biofilms in these patients, which makes the bacteria resistant to many antibiotics and the immune response.

8. What are some of the new and evolving therapies for atopic dermatitis?

Crisaborole is a topical phosphodiesterase inhibitor that was approved by the US Food and Drug Administration (FDA) in 2016 for adults and children aged as young as 2 years and in 2020, it was approved for infants as young as 3 months.

 Studies have shown that crisaborole is safe for long-term use.

Dupilumab, an interleukin (IL)-4 and IL-13 receptor-alpha antagonist, was also recently approved by the FDA for children aged 6 years or older with severe atopic dermatitis.

9. Are low vitamin D levels an issue and does supplementation help?

Vitamin D plays a role in the barrier function of the skin and immune regulation. Serum vitamin D levels are lower in patients that have atopic dermatitis and vitamin D supplementation may be beneficial for some patients.

10. If topical medications do not adequately treat the atopic dermatitis, what are the next steps?

Patients with moderate to severe disease despite adequate topical treatments may be treated with phototherapy. Patients with severe unresponsive disease may also respond to off-label systemic agents including methotrexate, cyclosporine, mycophenolate, and azathioprine. The newer systemic agents include dupilumab, as mentioned above, and other biologics. Dupilumab requires no routine laboratory monitoring and is much safer for long-term use compared with off-label systemic agents.

11. What to expect in the next few years?

There are many medications that may be used for atopic dermatitis in the future. As discussed above, crisaborole and dupilumab were recently approved by the FDA.

Future medications that show promise include the JAK-STAT inhibitors, baricitinib, upadacitinib, PF-04965842, ASN002, tofacitinib, ruxolit inib, and delgocit inib.22 Other medications that show promise include tapinarof (aryl hydrocarbon receptor modulating agent), lebrikizumab and tralokinumab (IL-4/IL-13 antagonists), and nemolizumab (IL-31Rα antagonist).

Because of the high prevalence among children, it is crucial for pediatricians to be familiar with atopic dermatitis. As summer approaches, it is important to recognize that heat can lead to dryness of the skin and histamine release in the skin. Furthermore, the warm weather leads to sweat production, which irritates the skin. Thus, summertime is associated with increased atopic dermatitis flare-ups.

Atopic dermatitis has a significant effect on a patient’s QOL. The mainstay therapy for atopic dermatitis includes topical corticosteroids and emollients. Early treatment of atopic dermatitis can prevent the development of subsequent atopic disorders. Alternative treatments include diluted liquid chlorine bleach baths and phototherapy. Several off-label systemic agents, such as methotrexate and cyclosporine, can also be used. However, dupilumab, a new biologic drug that was recently approved for atopic dermatitis, is much safer than systemic agents.

Nutten S. Atopic dermatitis: global epidemiology and risk factors. 

Drucker AM, Wang AR, Li W-Q, Sevetson E, Block JK, Qureshi AA. The burden of atopic dermatitis: summary of a report for the National Eczema Association. 

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Oliveira C, Torres T. More than skin deep: the systemic nature of atopic dermatitis. 

. 2019;29(3):250-258. doi:10.1684/ejd.2019.3557

Weller K, Soost S, Worm M, Maurer M, Zuberbier T. Atopic dermatitis and allergic rhinitis--do co-effects in therapy exist? 

. 2012;10(4):221-239. doi:10.1111/j.1610-0387.2011.07885.x

Ravnborg N, Ambikaibalan D, Agnihotri G, et al. Prevalence of asthma in patients with atopic dermatitis: a systematic review and meta-analysis. 

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Bantz SK, Zhu Z, Zheng T. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. 

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Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. 

 2006;155(1):145-151. doi:10.1111/j.1365-2133.2006.07185.x

Paller A, Jaworski JC, Simpson EL, et al. Major comorbidities of atopic dermatitis: beyond allergic disorders. 

 2018;19(6):821-838. doi:10.1007/s40257-018-0383-4

Silverberg JI. Comorbidities and the impact of atopic dermatitis. 

 2019;123(2):144-151. doi:10.1016/j.anai.2019.04.020

Thyssen JP, Hamann CR, Linneberg A, et al. Atopic dermatitis is associated with anxiety, depression, and suicidal ideation, but not with psychiatric hospitalization or suicide. 

 2018;73(1):214-220. doi:10.1111/all.13231

Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. 

 2014;71(1):116-132. doi:10.1016/j.jaad.2014.03.023

Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC. Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. 

 2005;330(7490):516. doi:10.1136/bmj.38376.439653.D3

Alsterholm M, Strömbeck L, Ljung A, et al. Variation in Staphylococcus aureus colonization in relation to disease severity in adults with atopic dermatitis during a five-month follow-up. 

 2017;97(7):802-807. doi:10.2340/00015555-2667

Tauber M, Balica S, Hsu C-Y, et al. Staphylococcus aureus density on lesional and nonlesional skin is strongly associated with disease severity in atopic dermatitis. 

 2016;137(4):1272-1274.e3. doi:10.1016/j.jaci.2015.07.052

Mohan GC, Lio PA. Comparison of dermatology and allergy guidelines for atopic dermatitis management. 

 2015;151(9):1009-1013. doi:10.1001/jamadermatol.2015.0250

Gonzalez T, Biagini Myers JM, Herr AB, Khurana Hershey GK. Staphylococcal biofilms in atopic dermatitis. 

 2017;17(12):81. doi:10.1007/s11882-017-0750-x

Paller AS, Tom WL, Lebwohl MG, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. 

 2016;75(3):494-503.e6. Published correction appears in 

Simpson EL, Akinlade B, Ardeleanu M. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. 

2017;376(11):1090-1091. doi:10.1056/NEJMc1700366

Kim MJ, Kim S-N, Lee YW, Choe YB, Ahn KJ. Vitamin D status and efficacy of vitamin D supplementation in atopic dermatitis: a systematic review and meta-analysis. 

Deleuran M, Thaçi D, Beck LA, et al. Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study. 

 2020;82(2):377-388. doi:10.1016/j.jaad.2019.07.074

Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. 

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Nguyen HL, Anderson KR, Tollefson MM. New and emerging therapies for pediatric atopic dermatitis. 

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Atopic dermatitis is a chronic, inflammatory skin condition that affects 15% to 20% of children and 1% to 3% of adults in the United States. The prevalence of atopic dermatitis, which is also known as eczema, is increasing in developing and industrialized countries.

What you need to know about atopic dermatitis

Osterholm: B.1.1.7 variant poses challenge to in-school education

Michael Osterholm, PhD, MPH, warns that the B.1.1.7 variant of coronavirus disease 2019 could necessitate a return to at-home school because of the variant’s impact on children.

FDA approves non-stimulant Qelbree to treat ADHD

The US Food and Drug Administration (FDA) approves first novel non-stimulant medication to treat attention-deficit/hyperactivity disorder (ADHD) in children in a decade.

An investigation examines whether moving from paper vouchers to electronic benefits transfer (EBT) cards improved participation numbers for Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

How the pandemic has impacted how HCPs view their career path and development

The past year has seen a lot of celebrating of health care professionals (HCPs) for their relentless work during the pandemic, but how are they feeling about their career path and potential for development now? A study offers some answers.

It was a very busy week for the Contemporary Pediatrics team.

In case you missed it: April 5 to April 9

The past year in particular has fostered the importance of patients needing to feel safe in medical surroundings. The presentation, “Patient Safety Program in Pediatric Primary Care: Speak up for Safety,” given by Cheryl Cairns, DNP, CPNP, RN at the 2021 virtual conference for the National Association of Pediatric Nurse Practitioners discussed how to ensure that the medical office is a safe place to receive care and not at high risk of medical error. Cairns noted that health care facilities are highly reliability organizations, which means that they are capable of operating under extremely trying circumstances at all times, but have fewer accidents than would be expected because of increased safeguards.

In order for health care facilities to maintain the standard of being highly reliable sites for safety, there are a number of steps that need to be met including:

Deferring to expertise – Using the expert in the facility, rather than the overall facility authority to make decisions.

Sensitivity to operations – Front line staff can offer the best picture of the current situation. Use them to recognize possible problems and to note opportunities for improvement. Leadership should work to ensure that there is open communication and respectful dialogue.

Preoccupation with failure – Small and inconsequential errors should be looked at as a sign of something that’s wrong. Staff should feel comfortable about reporting concerns.

Reluctance to simplify – Don’t say “but this is how we’ve always done it.” Clinicians and staff should be comfortable in challenging long-held beliefs. Facilities should continually review performance metrics to see if there are areas for improvement. A diversity of experience and opinion should be promoted.

Commit to resilience – Staff should be anticipating trouble spots as well as identifying errors at the same time as creating solutions. Organizations should remove barriers that hinder the collaboration of multidisciplinary teams.

When creating a high reliability organization, the first step is to create a culture of safety, which will set the expectations for behavior that will ensure that safety is a priority. In a culture of safety there should be 3 main behavior expectations: a personal commitment to safety, accountability for clear and complete communication, and supporting a questioning attitude. With the personal commitment to safety, some methods that can help, including asking a team member to review the plan, which promotes working together and checking one’s work or thought process, while another method is taking the time to stop and think about what needs to be done, which should ensure attention to detail. If concerns are discovered, a health care professional should clearly explain it, suggest a review of it, work on developing a consensus of next steps, and escalate the concern to higher-ups when necessary. Discussion of concerns should not occur in front of patients or families.

The second behavioral expectation of clear and complete communication may be the most important one. Cairns noted that previous research conducted over the course of 10 years from 1995 to 2005 showed that ineffective communication in a team was the cause for roughly 66% of all medical errors during that period. Additionally, the Joint Commission’s Sentinel Event database found that communication issues were the leading cause of sentinel events in the United States. Developing strong patient-provider communication is one key to improving overall communication and should include clear setting of expectations, ensuring that the patient plays an active role in the dialogue, and focusing on the exchange of direct information. One technique to ensure good communication is the “repeat and read back” technique. Using this technique, one writes or states the information clearly, repeats back information to ensure accurate understanding of the information; and acknowledge the accuracy of the information. Clinicians should also encourage the asking of clarifying questions.

The final behavioral expectation is to support a questioning attitude. When faced with information, a health care provider should qualify the source of the information, validate whether it made sense to her or him, and check the information against an independent and expert source. If a health care provider is uncertain in a situation, he or she should take the time to stop and review, reassess, and resolve the uncertainty before going forward with care.

Ensuring patient care is safe and free from error is the number 1 priority of health care professionals. A presentation at the 2021 virtual conference for the National Association of Pediatric Nurse Practitioners offered guidance on how to ensure that the medical office is a safe place to receive care.

Speak up for patient safety

A 19-year-old woman presents to a pediatric emergency department (ED), accompanied by her parents, with a chief complaint of weight loss.

The patient reports that she used to be “chubby.” Her highest weight was 75 kg with a height of 4’10” when she was 16 years old (body mass index [BMI] > 95th percentile). Two years ago, she began avoiding junk food because she was worried that she was overweight. She gradually dropped to 54 kg (BMI at 56th percentile) over 18 months. However, 6 months ago, she began restricting more aggressively and lost weight more rapidly. Her current weight is 34 kg (BMI < 0.01 percentile), representing 20 kg of additional weight loss over 6 months. She denies using other methods to lose weight such as excessive exercise, self-induced vomiting, or abuse of diuretics, laxatives, or diet pills. At the time of admission, the patient felt that she was underweight.

She experiences lightheadedness daily, but denies syncope. She has cold extremities, constipation, and says that her last menstrual period was 2 years ago. The patient reports no abdominal pain, blood in her stool, diarrhea, difficulty swallowing, fever, headache, jaundice, joint pain or swelling, nausea, night sweats, polyuria or polydipsia, rash, or vomiting.

Over the last 3 months, her mother has observed decreased energy and altered cognition, which are worsening. The patient struggles with word finding, is slow to respond to questions, and is less alert. She rarely sleeps more than 3 hours a night. The patient endorses feeling “slow.”

Her mother reports that she does not eat unless someone supervises her. She eats very slowly and will only take a few bites if not frequently redirected. She does not even want to drink water. When her mother offers her food, the patient cries, shakes, appears anxious, and asks her mother to take it away.

The patient admits that she previously worried about being overweight, but now her weight loss is unintentional because she “keeps a strict schedule” and does not know how to “fit eating into her day.” Specifically, she needs to pray a certain number of times per day, making it hard to find time to eat. Her mother says that her daughter spends the majority of the day in prayer; her praying increased dramatically when her eating got worse 6 months ago.

The patient lives with her parents and older sister, attending community college. Her family is very religious. She reports that her favorite activities are reading the Bible and praying. She reports no use of alcohol, tobacco, or other drugs. She has never had sex and has never been in a romantic relationship, but identifies as heterosexual. She has no history of depressed mood, self-harm, or suicidal ideation.

She has no other significant past medical or psychiatric history, takes no medications, has no allergies, and is fully immunized. There is no pertinent family history, including no known anxiety, eating, or depressive disorders, or substance abuse. She has no known travel history.

Her initial vital signs include blood pressure 102/64; pulse 52 beats/minute; temperature 36.6°C; respiratory rate 14/minute; height 147.4 cm; weight 34.8 kg; and BMI 14.06 kg/m­.

Physical exam is significant for an extremely thin female patient who is alert but slow to respond to questions and pauses to find words, which occasionally causes her frustration. She has staring spells and appears to be responding to internal stimuli. She is calm with restricted affect, occasionally smiling inappropriately. She has cool extremities, dry skin, and lanugo on her trunk and arms. She has a 2- x 3-cm mass on the right side of her neck, mobile and nontender without overlying erythema, which elevates when she swallows. The patient reports that she has had the mass for years, but has been too self-conscious to show it to a doctor. There is no lymphadenopathy. Abdominal, cardiovascular, and respiratory exams are unremarkable. There are no hand callouses, palatal abrasions, or poor dentition to suggest purging.

Initial labs include a complete blood count (CBC) significant for a mildly decreased white blood cell count of 3.4 (reference 4.0-10.5 TH/uL) with an absolute neutrophil count of 1.88 (reference 2.00-6.50 TH/uL) and an absolute lymphocyte count of 1.2 (reference 1.5-3.5 TH/uL). Hemoglobin is slightly decreased at 12.3 (reference 12.5-16 g/dL) but the anemia is normocytic. Sodium, potassium, chloride, bicarbonate, magnesium, phosphorus, renal function tests, liver enzymes, prealbumin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), thyroid stimulating hormone (TSH), free thyroxine (T4), urinalysis, pregnancy test, and urine drug screen are all unremarkable. Estradiol is < 2 pg/mL. Electrocardiogram (EKG) shows a rate of 73 beats/min and normal sinus rhythm, but with right axis deviation, counterclockwise QRS axis, and no Q wave in the left chest.

The patient is admitted to the hospital for severe malnutrition of unknown etiology. She is initially placed on bed rest and 24-hour cardiorespiratory monitoring with vital signs checked every 6 hours, including daily orthostatic vitals. She is started on a 1600 kcal/day refeeding diet with close supervision and daily bloodwork monitoring for refeeding syndrome.

What is the differential diagnosis of an adolescent girl with significant weight loss?

The differential diagnosis of weight loss in an adolescent is broad and includes both organic and inorganic causes (Table 1).

Gastrointestinal (GI) causes include inflammatory bowel disease, celiac disease, malabsorption syndromes, pancreatic insufficiency, and hepatic disease including infectious or autoimmune hepatitis. Suggestive symptoms include abdominal discomfort, diarrhea, fever, hematochezia, jaundice, melena, nausea, and/or vomiting. Given the patient’s lack of these signs/symptoms and a normal ESR/CRP, it is unlikely that her weight loss is because of a GI cause.

Endocrine causes include adrenal insufficiency, diabetes mellitus, and hyperthyroidism. The patient has normal electrolytes and blood pressure making adrenal insufficiency unlikely, and has no polyuria, polydipsia, or glucose abnormalities suggestive of diabetes mellitus. Hyperthyroidism could have a variety of causes including autoimmune thyroiditis or a productive thyroid nodule, and may present with psychiatric symptoms. Other symptoms of hyperthyroidism might include diarrhea, heat intolerance, increased appetite, increased perspiration, palpitations, tremor, and/or weakness, which are absent. The patient has a normal TSH and T4, but even in the absence of hyperthyroidism, the presence of thyroid antibodies alone could cause neuropsychiatric changes.

Given the patient’s neck mass, malignancy is a concerning possibility, particularly a thyroid malignancy as it elevates with swallowing. Further questioning about risk factors for malignancy and biopsy of the mass would be important next steps. Malignancy of any kind could cause weight loss and may be associated with fatigue, fevers, and night sweats. The most common malignancies in adolescents are leukemias/lymphomas and central nervous system tumors. The patient has cytopenias on her CBC but this is often seen in malnourished states and reverses with renourishment

; usually more severe cell line suppression is seen with hematologic malignancy. Her neurological examination is unremarkable, but her neuropsychiatric symptoms in association with weight loss warrant intracranial imaging.

Cardiorespiratory failure is frequently associated with weight loss. The patient has an abnormal EKG, which should be followed up with an echocardiogram. Of note, weight loss itself causes cardiac muscle wasting, which could create the EKG abnormalities observed.

Inflammatory disorders such as systemic lupus erythematosus, juvenile idiopathic arthritis, or other vasculitis can cause weight loss and neuropsychiatric symptoms. However, a normal ESR/CRP makes this unlikely in our patient. She also has no hematuria, joint swelling, rash, or other typical associated symptoms.

Infectious etiologies include chronic GI infections such as amoebiasis, giardiasis, or cryptosporidium, which would present with chronic diarrhea and/or vomiting; tuberculosis, which might present with fever, adenopathy and/or hemoptysis; or HIV/AIDS with recurrent infections and other manifestations of immunodeficiency. However, given the patient’s past medical history, lack of known travel history, lack of substance abuse or sexual exposure, and absence of typical presenting symptoms or physical examination findings, an infectious cause is unlikely.

Inorganic causes of weight loss include eating disorders, primary psychiatric disorders, and psychosocial causes. Restrictive eating disorders include anorexia nervosa, avoidant restrictive food intake disorder, and other unspecified eating disorders with features of restriction, overexercise, and/or purging. The patient previously struggled with body image and was intentionally trying to lose weight. Although she states that her current weight loss is unintentional and that she recognizes she is underweight, she still has fear around eating, making a restrictive eating disorder a possibility.

Primary psychiatric disorders such as major depressive disorder (MDD), generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), primary psychotic disorders, and bipolar disorder may all cause weight loss through changes in appetite and/or behavioral changes that interfere with eating. Our patient exhibits decreased concentration and energy, difficulties with sleep, low mood, and weight loss, all of which could suggest MDD. Her rigid daily routines and hyper-religiosity suggest OCD or psychosis. Although she has had decreased need for sleep and appears distractible, she does not meet criteria for mania as her family does not describe grandiosity, pressured speech, racing thoughts, or increased goal-directed behavior. In adolescents, one should always consider Wilson’s disease as a medical cause of psychosis.

Psychosocial contributors to weight loss include abuse, food insecurity, neglect, or substance abuse. History about this should be obtained.

Importantly, malnutrition itself may be causing many of this patient’s physical symptoms including amenorrhea, cold intolerance, constipation, cytopenias, EKG abnormalities, fatigue, impaired cognition, and neuropsychiatric changes, all of which would be reversible with renourishment.

 Deficiency of micronutrients such as vitamin B12, folate, iron, or zinc can contribute to neuropsychiatric changes and fatigue.

The patient is admitted to a pediatric inpatient ward. She begins a standard refeeding diet with gradual increases in caloric intake. A dietitian is consulted to guide safe weight gain. Electrolytes are checked daily to monitor for refeeding syndrome.

Micronutrient labs reveal no deficiencies in B12, folate, iron, vitamin D, or zinc. Ceruloplasmin is normal. An echocardiogram demonstrates there is normal structure and function of the heart.

Further history determines that she has never had radiation exposure to her neck and has no family history of thyroid disorders. Endocrinology is consulted. Antithyroglobulin and antithyroid peroxidase antibodies are undetectable. Ultrasound reveals a 1.8-cm diameter complex mass in the right lobe of the thyroid gland. Fine needle aspiration of the nodule reveals that it is benign. Endocrinology recommends nonurgent removal of the mass after the patient’s nutritional status improves.

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