PER Survey

Clinical ShowCase™: Developing a Personalized Treatment Plan for a Patient with Sickle Cell Disease

Clinical Showcase Sickle Cell 

The American Academy of Pediatrics (AAP) recently provided updated guidance on physician wellness, in which they discussed burnout among pediatricians.

 Pediatricians are not immune to burnout, according to the AAP. The COVID-19 pandemic has only added stressors, which make burnout more likely. To combat these stressors, the AAP outlined efforts in an updated report titled “Physician Health and Wellness.”

The report stated that all pediatric disciplines saw an increase in rates of burnout from 2011 to 2014, as burnout rates increased from 35.3% to 46.3%. There is no consensus on the definition of burnout, with 142 different definitions among 182 studies.

 However, physicians with burnout are described as “angry, irritable, impatient, [and they have] increased absenteeism, decreased productivity, and decreased quality of care.”

Burnout is notably different from stress and depression. Although depression is a general disease, burnout is a syndrome that is often job related and specific to 1 situation. Stress is also often challenging for physicians but presents with different symptoms from burnout.

“Burnout feels like stress, as we have to push ourselves to function, but [it] has an added element of demoralization, frustration, and a lack of motivation,” said Michael Jellinek, MD, professor of psychiatry and of pediatrics at Harvard Medical School in Boston, Massachusetts. “There is a lack of energy and interest, [and] sometimes this translates into not feeling well or fatigue that becomes a sick day.”

Approximately half of physicians in practice experience burnout, which can lead to medical errors, higher cost, lower quality of care, and worse patient outcomes overall.

 Suicidal thoughts were also frequent, reported by 14% of physicians. Only one-third of these physicians sought treatment.

Burnout was found to be most common in physicians aged 45 to 54 years. Factors that increased the risk of burnout included longer work hours, dissatisfying balance between work and home lives, increased reliance on technology while working, dissatisfying compensation, and lack of respect from colleagues.

“The weight of caring for children who are chronically ill, disabled, maltreated, neglected, or otherwise medically vulnerable can take a toll over time,” said Hilary H. McClafferty, MD, FAAP, lead author of the AAP report.

 “This can lead to overlapping symptoms of compassion fatigue, secondary traumatic stress, vicarious traumatization, moral distress, countertransference, and ultimately burnout.”

McClafferty also noted that most pediatricians are women, and that female physicians have been reported to experience burnout more often than male physicians. Research on the impact of race, gender, ethnicity, and other factors on burnout is still ongoing. Gaps in the response from health care systems have been noted following the COVID-19 pandemic.

Shifts in technology are also a notable factor in increasing physician burnout.

 Many physicians struggle to understand electronic medical records because of confusing user interfaces. “The health care system has moved to higher workloads, less autonomy, and more standardization as groups and delivery systems get larger and more automated,” Jellinek said. “Efficiency and productivity standards, electronic record keeping, [and] intensive measurement may have all added some benefits but have come with almost constant, increased work pressure.”

Jellinek also stated that with influenza, COVID-19, and respiratory syncytial virus circulating, contact with colleagues has become less face-to-face and more virtual. This has increased feelings of isolation in many physicians.

Physician burnout is also tied to symptoms of posttraumatic stress disorder (PTSD), according to a recent study.

 Investigators conducted a multicenter survey among health care professionals from January 2022 to March 2022 and found an association between burnout and PTSD symptoms.

A recent meta-analysis found that burnout in physicians more than doubled the risk of an adverse event related to patient safety, along with leading to worse care and decreased patient satisfaction.

 When experiencing burnout, physicians are more likely to work fewer hours and to leave clinical medicine.

“A physician suffering burnout will dread working, and a physician’s work is important, detailed, and demanding,” Jellinek said. “Quality can suffer, possibly by overlooking lab results or follow-ups.”

Physician health may also be at risk, as an imbalance between work and reward has been associated with negative health outcomes.

For instance, 1 study found that the COVID-19 pandemic exasperated the frequency of burnout in physicians.

 Investigators conducted a cross-sectional study of health care workers (HCWs) registered with the Ministry of Health from January 2022 to June 2022. The study evaluated how the condition, defined as burnout syndrome (BOS), presented in HCWs during the COVID-19 pandemic, which brought about a wave of illness tackled by HCWs worldwide. HCWs were included in the study if they were on duty and consented.

Electronic surveys were sent to HCWs, with questions on sociodemographic- and profession-related data, work environment–related variables, COVID-19–related variables, consequences of BOS, and Maslach Burnout Inventory, which is used to diagnose burnout. Physicians responded using a scale from 0 to 6, with a higher scale indicating a higher level of burnout.

There were 284 completed surveys from HCWs, nearly two-thirds of which were men and approximately 68% had over 10 years of experience. Participants were more often aged under 40 years and married.

Burnout was reported in approximately 48% of HCWs. Roughly 71% of HCWs were on the frontline of combating COVID-19, with almost half having comorbid diseases. Approximately 83% of HCWs reported increased work hours following the start of the pandemic, and approximately three-fourths reported conflicts with patients or family.

Sleep deprivation was seen in approximately 76% of HCWs, dissatisfaction with resources in approximately 20%, an inability to choose days off in approximately 88%, and feeling unappreciated in approximately 71%. Approximately 64% of HCWs were infected with COVID-19, approximately 92% had a colleague or family member get infected, and approximately 22% lost a colleague or family member to COVID-19.

There were 3 domains of burnout: emotional exhaustion (EE), depersonalization (DP), and loss of professional accomplishment (PA). High rates of EE were seen in approximately 53% of participants, high DP rates were seen in approximately 43%, and highly reduced PA was seen in approximately 31% of participants. Over one-third of the study population presented with severe burnout predictors.

These results showed an overall negative impact on the health care system from the COVID-19 pandemic, which has caused high rates of severe burnout. To reduce the frequency of burnout, investigators believe it is necessary to focus on physician wellness.

Emily Aron, MD, a child, adolescent, and adult psychiatrist, discussed some signs of burnout in physicians. These included not showing up to work, frequently talking about feeling tired, not feeling connected, and negative behavior. Aron also noted how unhealthy behaviors could be linked to burnout, such as substance use and suicidal behavior.

In combating burnout, the AAP recommended social support, creating individual awareness and resilience measures, and treating mental and physical conditions that may be unaddressed.

 Structured debriefing between the medical team following challenging experiences was stressed in the report. The AAP also suggested creating a more healthy lifestyle, using vacation time, developing a hobby, practicing gratitude, finding a supportive social network, creating a personal mission statement, and exploring mind-body practices.

“There is often a stigma with seeking help, even among those we typically consider as the helpers,” McClafferty said. “We must work together to make sure physicians are given the respect, privacy, and opportunity to be heard without stigma or professional penalty and continue to advocate for the well-being of physicians at every stage of training and practice.”

Investigators from Pennsylvania State University recommended following a hierarchy of needs, starting with prioritizing the basic physical and mental health needs of physicians.

 Higher-order needs include connection, respect, appreciation, and changes in interactions with electronic systems. Others have recommended system changes to improve burnout. “Burnout is a real problem with real consequences, and every level of the system needs to support practice,” Jellinek said.

On a management level, Jellinek suggested seeking input, sharing decision-making, recognizing good work, supporting workers’ autonomy, providing good communication, giving reasonable responses to physicians’ requests, providing attention to physicians’ workload, and creating a culture of values that can prevent burnout. On a clinical level, Jellinek suggested the same attitudes as on a management level, along with supporting a collegial environment, welcoming input at every level, and supporting autonomy and career growth. On an individual level, Jellinek urged physicians to make time for self-care, create reasonable expectations for work-life balance, take general time off and time for vacations, create opportunities for peer support, and self-monitor their emotional state. This can all lead to early recognition and prevention of burnout.

“We do have an ethical imperative to address burnout in physicians, because [patients’] lives are on the line,” Aron said. She also recommended that systems take the time to understand the needs of medical employees, as not every individual will have the same needs and each will need to be separately addressed.

American Academy of Pediatrics releases updated guidance on physician wellness. American Academy of Pediatrics. October 24, 2022. Accessed October 24, 2022. 

https://www.aap.org/en/news-room/news-releases/aap/2022/american-academy-of-pediatrics-releases-updated-guidance-on-physician-wellness/

. 2020;133(2):160-164. doi:10.1016/j.amjmed.2019.08.034

Liu Y, Zou L, Yan S, et al. Burnout and post-traumatic stress disorder symptoms among medical staff two years after the COVID-19 pandemic in Wuhan, China: social support and resilience as mediators. 

. 2023;321:126-133. doi:10.1016/j.jad.2022.10.027

Al-Otaibi T, Abbas A, Ashry Gheith O, et al. Determinants, predictors and negative impacts of burnout among health care workers during COVID-19 pandemic. 

.2023;35(1):102441. doi:10.1016/j.jksus.2022.102441

Articles

Defining burnout and why it has increased among health care providers

Beating burnout

A new analysis shows offspring of mothers with primary immunodeficiencies are at an increased risk of several 

 disorders, including anxiety and depression, as well as suicidal behavior.

A team, led by Josef Isung, MD, PhD, Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, assessed the association of maternal and paternal primary immunodeficiencies with psychiatric disorders and suicidal behavior in offspring.

“Maternal immune activation (MIA) leading to altered neurodevelopment in utero is a hypothesized risk factor for psychiatric outcomes in offspring,” the authors wrote. “Primary antibody immunodeficiencies constitute a unique natural experiment to test the MIA hypothesis of mental disorders.”

In the study, the investigators examined the data of 4.3 million offspring of parents with and without primary immunodeficiencies in Sweden between 1973-2013 from the Swedish nationwide health and administrative registers. The team exclude parent-offspring pairs where both parents had a history of primary immunodeficiencies, as well as offspring with their own immunodeficiencies and autoimmune diseases.

The investigators identified lifetime records of 10 psychiatric disorders and suicidal behave or, including suicide attempts and death by suicide, among offspring. The covariates included sex, birth year, parent psychopathology, suicide attempts, and autoimmune diseases.

The team fitted Poisson regression models separately for mothers and fathers to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CI) for the risk of psychiatric disorders and suicidal behavior outcomes in offspring with primary immunodeficiencies parents (n = 7270; 0.17%) compared to unexposed mothers or fathers (n = 4.2 million).

Using the fully adjusted models, the investigators found offspring of mothers with primary immunodeficiencies had an increased risk of any psychiatric disorders. On the other hand, offspring of fathers with primary immunodeficiencies had no risk (IRR, 1.17; 95% CI, 1.10-1.25 compared to IRR, 1.10; 95% CI, 0.94-1.14; 

The results also show an increased risk of suicidal behavior among offspring of mothers with primary immunodeficiencies, but similarly did not find the same risk in the offspring of fathers with primary immunodeficiencies (IRR, 1.20; 95% CI, 1.06-1.36 vs IRR, 1.10; 95% CI, 0.91-1.34; 

Specifically in the cohort of offspring of mothers with primary immunodeficiencies, the risk of developing any psychiatric disorder was significantly higher if the mothers had 6 of the 10 individual disorders. The IRR ranged from 1.15 (95% CI, 1.04-1.26) for anxiety and stress-related disorders and 1.15 (95% CI, 1.03-1.30) for substance use disorders to 1.71 (95% CI, 1.37-2.14) for bipolar disorders.

Moreover, the offspring of mothers with both primary immunodeficiencies and autoimmune diseases were at the highest risk of any psychiatric disorder (IRR, 1.24; 95% CI, 1.11-1.38) and suicidal behavior (IRR, 1.44; 95% CI, 1.17-1.78).

“Findings of this cohort study suggest that maternal, but not paternal, PIDs were associated with a statistically significant increased risk of psychiatric disorders and suicidal behavior in the offspring, particularly when PIDs co-occur with autoimmune diseases,” the authors wrote. “These findings align with the MIA hypothesis of mental disorders, but the precise mechanisms remain to be elucidated.”

This article was published by our sister publication HCP Live.

Isung J, Isomura K, Williams K, et al. Association of primary immunodeficiencies in parents with psychiatric disorders and suicidal behavior in their offspring. 

 2023. doi:10.1001/jamapsychiatry.2022.4786

The same risk was not found for offspring of fathers with primary immunodeficiencies.

Offspring of mothers with primary immunodeficiencies at an increased risk of psychiatric disorders

Infant screen use may cause poorer executive function measured through altered cortical electroencephalography (EEG) activity in children aged under 2 years, according to a recent study published in 

Infants aged from 6 to 18 months are on average exposed to 2 to 3 hours per screen time per day, greatly passing recommendations from the American Academy of Pediatrics to avoid screen media use outside of video chatting for children aged under 18 months. This risks impairments to attention and executive functions, based on findings from prior studies.

Associations have been found between screen use in preschool aged children and changes to white matter tracts vital for executive functioning. However, while infants are the most vulnerable to executive functioning deficits, there is little data on possible neural correlates in this age group, or whether deficits last through school age. 

The neural correlates of many cognitive functions can be determined through EGG. Associations have also been recorded between screen exposure and greater functional connectivity in EGG theta waves.

Investigators conducted a study to determine the association between screen use when aged 12 months and neural signals indicating deficit attentional control when aged 18 months, along with analyzing whether any changes lead to different attentional and executive functioning when aged 9 years.

Data was gathered through a population-based cohort known as Growing Up in Singapore Toward Healthy Outcomes. There were 506 mother-child pairs who completed study measures when the child was aged 12 months and 9 years. Exclusion criteria included being born small for gestational age, part of a twin pregnancy, or having major neurological conditions.

Behavioral data of children aged 9 years was analyzed, and EGG data was collected in a subset of 157 children. Parents reported the screen time of their children aged 12 months in the prior month. Screen use time data for children on weekdays, Saturdays, and Sundays were reported.

At 5 other time points when the children were aged 12 months to 54 months, their parents answered the same question on their child’s screen time. Total hours of screen time per week were divided by 7 days to get an estimated hours of screen time per day.

To record resting EGG, investigators had children seated on the lap of a caregiver and watching bubbles being blown into the room. The Harvard Automated Processing Pipeline for EEG (HAPPE) was used to process data. According to authors of the study, “data were segmented into contiguous 2-second segments, and segment rejection was carried out via HAPPE criteria.”

Executive functions were measured as the main outcome. The 3 main executive function components were naming inhibition, shifting, and working memory. The Developmental Neuropsychological Assessment, second edition, was used to measure these categories, with higher scores indicating improved competency.

At 12 months of age, children had a mean recorded screen time of about 2 hours. When applied to regression models, each additional hour of screen time was associated with a decrease of 0.30 to 0.56 points in each task.

A linear correlation was observed between screen time at 12 months and neural correlates, with greater screen time leading to greater neural correlates, including theta ratios. Higher theta ratios were associated with poorer performance in executive function measured by EGG. This indicated longer screen time leads to poorer executive function in young children.

Law EC, Han MX, Lai Z, Lim S, Yan Ong Z, Ng V, et al. Associations between infant screen use, electroencephalography markers, and cognitive outcomes. 

 2023. doi:10.1001/jamapediatrics.2022.5674

In a recent study, infants aged under 2 years had poorer performance in executive function when spending more hours per day using screens. 

Screen use during infancy may poorly impact executive function

Multisystem inflammatory syndrome in children (MIS-C) incidence decreased throughout the COVID-19 pandemic, according to a recent study.

MIS-C is an often serious condition that could require treatment in a pediatric intensive care unit. Challenges remain in diagnostic approach and treatment strategies despite growing awareness, and there is little information on the factors which lead to MIS-C pathogenesis.

As there is a lack of studies on how variants of COVID-19 trigger MIS-C, investigators conducted a study comparing the effects different variants had on MIS-C incidence, along with epidemiologic and clinical characteristics present in children hospitalized with MIS-C.

Children and young people aged under 18 years were evaluated for MIS-C incidence, clinical characteristics, and outcomes throughout 3 waves of the COVID-19 pandemic. Data was provided by the National Public Health Organization.

The predominant variant was recorded for each wave, making up 80% or more of the strains sequenced. The first wave was recorded from August 1, 2020, to January 31, 2021, the second from February 1, 2021, to July 31, 2021, and the third from August 1, 2021, to December 31, 2021.

Patient, demographic, clinical, and laboratory data was collected from 10 participating reference tertiary care centers. Reverse transcription polymerase chain reaction and serology of participants were also available. The rate of MIS-C incidence was calculated as the denominator of total pediatric COVID-19 cases.

There were 119 patients included in the study, 109 of which met criteria from the World Health Organization for MIS-C diagnosis. During the first wave, 26.9% of children diagnosed with MIS-C were hospitalized, 39.5% during the second, and 33.6% during the third.

In a 4-to-6-week period after the peak of COVID-19 infections, a peak of MIS-C cases was observed. Similar peak MIS-C cases followed peak COVID-19 cases by 4 to 6 weeks. 

The first wave of COVID-19 had an MIS-C incidence of 3.4 per 1000, the second 1.1 per 1000, and the third 0.25 per 1000. This showed a decrease throughout the 3 waves. While admissions to intensive care units were highest during the second wave, no significant differences in clinical findings or outcomes were found across the 3 waves.

Eleftheriou I, Maritsi D, Lampidi S, Charisi K, Vantsi P, Skourti K, et al. Decreasing incidence of the multisystem inflammatory syndrome in children over 3 pandemic waves.

 The Pediatric Infectious Disease Journal. 

2022;42(2):122-124. doi:10.1097/INF.0000000000003766

In a recent study, it was found that while clinical findings and outcomes of multisystem inflammatory syndrome in children (MIS-C) were consistent across the COVID-19 pandemic, incidence decreased over time.

MIS-C incidence decreased throughout COVID-19 pandemic

Tezepelumab (TEZSPIRE; Amgen and AstraZeneca) pre-filled pen has been approved by the US Food and Drug Administration (FDA) for treatment of severe asthma in pediatric patients aged 12 years and older.

After the original FDA approval for tezepelumab in 2021, the recent approval allows the use of a pre-filled pen for asthma treatment.

About 2.5 million individuals worldwide experience severe asthma, 1.3 million of which are in the United States. Maintaining asthma control is difficult in many of these patients because of an inadequate response to biologics and oral corticosteroids which are currently available.

Tezepelumab is a self-administered, single use pen and currently the only biological approved for severe asthma with no phenotype. It was approved after the PATHFINDER clinical trial program, which included the PATH-BRIDGE phase 1 trial and the PATH-HOME phase 3 trial.

Administration of tezepelumab was successful from 92% of providers, patients, and caregivers, both at home and in the clinic. Safety and efficacy outcomes were consistent with those observed in prior clinical trials.

"Severe asthma continues to be a very complex condition to manage," said Kenneth Mendez, president and CEO of the Asthma and Allergy Foundation of America. Mendez stated self-administration could be a key factor in addressing unmet needs for individuals with severe asthma.

Thymic stromal lymphopoietin (TSLP) is anepithelial cytokine present at the top of multiple inflammatory cascades. In severe asthma, it causes the immune system to overreact to types of airway inflammation. Tezepelumab blocks TSLP, reducing this reaction.

Pharyngitis, arthralgia, and back pain were the most common adverse reactions from tezepelumab, with an incidence of 3% or more. Other observed adverse reactions include hyposensitivity reactions such as rash and allergic conjunctivitis, along with postmarketing cases of anaphylaxis.

The FDA granted an Orphan Drug designation to tezepelumab for treating eosinophilic esophagitisin October 2021. Amgen plans to develop the drug for other indications such as chronic obstructive pulmonary disease, chronic spontaneous urticaria, and chronic rhinosinusitis with nasal polyps.

TEZSPIRE approvedforself-administrationinthe U.S. witha newpre-filledpen. Amgen. February 2, 2023. Accessed February 2, 2023. 

https://www.amgen.com/newsroom/press-releases/2023/02/tezspire-approved-for-self-administration-in-the-u-s--with-a-new-pre-filled-pen

The US Food and Drug Administration has approved the use of a pre-filled tezepelumab (TEZSPIRE; Amgen and AstraZeneca) pen in patients aged 12 years and older with severe asthma.

FDA approves pre-filled tezepelumab pen for severe asthma in adolescents

COVID-19 was a leading cause of death for children and young people (CYP) in the United States from August 1, 2021, to July 31, 2022, according to a recent study published in 

Over 360,000 deaths occurred in the United States from COVID-19 between August 1, 2021, and July 31, 2022. Of these, 821 were reported in CYP aged 0 to 19 years, with the risk of death from COVID-19 significantly lower in children than in other age groups.

As death from all causes is rare in pediatric patients, the mortality burden of COVID-19 can be measured through comparison to other significant causes of death in CYP. Mortality statistics can be obtained from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database.

Investigators determined the 10 leading causes of death among CYP in 2019, then determined whether COVID-19 was within the 10 leading causes of death in this age group during the study period. The 10 leading causes of death were determined by the US National Center for Health Statistics.

According to authors of the study, “an underlying cause of death is defined as a disease or injury that initiates a series of events leading directly to death.” Investigators reported crude death rates per 100,000 individuals.

The crude death rate from COVID-19 among CYP was 1 per 100,000. This rate was 4.3 per 100,000 in infants aged under 1 year, 0.6 per 100,000 in children aged 1 to 4 years, 0.4 per 100,000 in children aged 5 to 9 years, 0.5 per 100,000 in children aged 10 to 14 years, and 1.8 per 100,000 in adolescents aged 15 to 19 years.

Leading causes of death among CYP in 2019 were perinatal conditions at 12.7 per 100,000, unintentional injuries at 9.1 per 100,000, congenital malformations or deformations at 6.5 per 100,000, assault at 3.4 per 100,000, suicide at 3.4 per 100,000, malignant neoplasms at 2.1 per 100,000, heart diseases at 1.1 per 100,000, and influenza and pneumonia at 0.6 per 100,000. In this ranking, COVID-19 is ranked as the eighth leading cause of death.

When disaggregating rankings by age group, COVID-19 remained in the top 10 leading causes of death in CYP, being seventh for those aged under 1 year, seventh for those aged 1 to 4 years, sixth for those aged 5 to 9 years, sixth for those aged 10 to 14 years, and fifth for those aged 15 to 19 years.

The 10 leading causes of death remained mostly unchanged from 2015 to 2019, and from 2019 to 2020 and 2021. The exception to this was COVID-19 being among the 10 leading causes of death in 2021. This showed COVID-19 to be a leading cause of death among CYP.

Flaxman S, Whittaker C, Semenova E, Rashid T, Park RM, Blenkinsop A, et al. Assessment of COVID-19 as the underlying cause of death among children and young people aged 0 to 19 years in the US. 

2023;6(1):e2253590. doi:10.1001/jamanetworkopen.2022.53590

When analyzing morbidity data from 2021, investigators found that COVID-19 was among the 10 leading causes of death among children and young people.

COVID-19 leading cause of death among youths

Maternal depression during pregnancy may be associated with offspring brain age through young adulthood, according to a recent study.

Maternal stress, anxiety, and depression have been associated with offspring development, increasing the risk of behavioral and emotional problems in children, and anxiety and depression in adulthood. Brain structure changes throughout different stages of life, making it possible to use age-dependent changes in brain structure to estimate brain age in an individual.

The difference between structural and chronological brain age is the brain age gap estimate (BrainAGE), with a more significant positive BrainAGE indicating neurodevelopmental or aging trajectories. This has been associated with age-related health problems, neuropsychiatric disease, dementia risk, and cognitive impairment risk.

Evidence has indicated a strong impact on brain age from early life events. Therefore, early adversity may put children at a greater risk of accelerated brain aging. This logic is used in the diathesis-stress model, which states that early-life predisposition can lead to psychological disorders. However, this model has not been applied to brain age.

To analyze how prenatal exposure to maternal depression and more recent stress affects brain age, investigators conducted a second neuroimaging follow-up of the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort.

Data was available for a subset of patients, indicating maternal depression during pregnancy. Neuroimaging data was also gathered during the first neuroimaging follow-up.

An Edinburgh Postnatal Depression Scale questionnaire was filled out by mothers of participants in the early 1990s, answering questions related to mental health and emotional well-being. Mothers answered these questionnaires during the twentieth week of pregnancy, 2 weeks after birth, 6 months after birth, and 18 months after birth.

A subset of young adult offspring underwent structural magnetic resonance imaging (MRI) in 2015, with another, overlapping sample of young adults undergoing MRI from 2020 to 2022. The first neuroimaging follow-up was completed by 131 participants aged 23 and 24 years, and the second neuroimaging follow-up was completed by 260 participants aged 28 to 30 years.

The 260 participants also completed a Social Readjustment Rating Scale, which included 43 questions on stressful life events in the previous year. MRI data between ages 28 and 30 years and data on maternal depression were available for 199 participants, 51% of which were males.

Investigators also measured brain age in participants. The difference between brain age based on cortical thickness and the chronological age of participants was used to calculate BrainAGE.

The mean age of participants was 29.5 years. The brain age of participants participating in the second neuroimaging follow-up ranged from 18.5 to 43.3 years. As their chronologic age was 28 to 30 years the BrainAGE of participants ranged from about 11 to 14 years. 

A high correlation was found between the BrainAGE of participants in their early 20s and late 20s. Some participants experienced accelerated brain age pacing, while others experienced decelerated pacing. Participants with a greater positive BrainAGE in their early 20s more often had a slower aging pace in the following 5 years.

While women in their late 20s had a more positive average BrainAGE than their male counterparts, no other significant sex differences were found. There was also no association found between recent stress and BrainAGE for participants in their late 20s, but greater age pacing was associated with greater recent stress in young adulthood.

Antenatal depression based on the Edinburgh Postnatal Depression Scale was found in 33% of mothers. A correlation was found between maternal depression during pregnancy and BrainAGE, with greater maternal depression associated with greater positive BrainAGE in participants in their late 20s. This association was independent of sex and recent stress.

Maternal depression was associated with brain age, while recent stress was associated with the pace of aging. This indicates that preventing and treating depression in pregnant mothers may impact long-term brain development in offspring.

Mareckova K, Mareček R, Jani M, Zackova L, Andryskova L, Brazdil M, et al. Association of maternal depression during pregnancy and recent stress with brain age among adult offspring. 

 2023;6(1):e2254581. doi:10.1001/jamanetworkopen.2022.54581

In a recent study, maternal depression during pregnancy was associated with offspring brain age, while recent stress in offspring was associated with a greater aging pace.

Maternal depression associated with offspring brain age

Results of a study conducted by investigators at Texas Tech University underlines the need for reform in health screenings and a more holistic approach to care for people with autism.

Results of the systematic review and meta-analysis, which included nearly 3 dozen published articles reporting cardiometabolic risk factors among people with autism spectrum disorder and matched controls, indicate people with autism had a greater relative risk of developing a slew of cardiometabolic disorders compared to their counterparts without autism, including both type 1 and type 2 diabetes, dyslipidemia, and 

“To our knowledge, this was the first comprehensive systematic review and meta-analysis exploring the autism associated risks of diabetes mellitus, hypertension, dyslipidemia, and macrovascular disease,” wrote investigators. “Based on our results, individuals with autism seem to be at a greater associated risk of developing DM by 57.3%, type 1 diabetes mellitus by 64.1%, type 2 diabetes mellitus by 146.7%, dyslipidemia by 69.4%, and atherosclerotic heart disease by 45.9%.”

Citing previous data outlining the potential for elevated cardiometabolic risk, a team of investigators led by Chanaka Kahathuduwa, MD, MPhil, PhD, of the Department of neurology at Texas Tech University, designed the current study as a systematic review and meta-analysis of observational or baseline data of intervention studies reporting prevalence of cardiometabolic risk factors among children or adults with autism and matched participants without autism. With this in mind, the investigators performed a search of the PubMed, Scopus, Web of Science, ProQuest, Emboss, and Ovid databases from inception through July 21, 2022 without restrictions on date of publication or language.

From their search, investigators identified 34 studies encompassing more than 8 million individuals for inclusion in the systematic review and meta-analysis. The overall study cohort included 276,173 participants with autism and 7,733,306 participants without autism. The cohort of participants without autism had a mean age of 31.2 (range, 3.8-72.8) years and the cohort of participants with autism had a mean age of 22.8 (range, 3.8-72.8) years. The pooled cohort was 47% were female.

The primary outcome of interest for the study was the RR of diabetes, hypertension, dyslipidemia, and atherosclerotic macrovascular disease among people with autism. Secondary outcomes of interest included the RR of type 1 and type 2 diabetes, cardiovascular disease, stroke, and peripheral artery disease. Of the 34 studies identified for inclusion, 22 reported statistics allowing for computation of relative risk (RR) of cardiometabolic risk factors and the other 12 reported laboratory measurements of interest.

Upon analysis, results indicated a diagnosis of autism was associated with greater risks of developing diabetes overall (RR, 1.57 [95% CI, 1.23-2.01]; 20 studies) as well as for type 1 diabetes (RR, 1.64 [95% CI, 1.06-2.54]; 6 studies) and type 2 diabetes (RR, 2.47 [95% CI, 1.30-4.70]; 3 studies) as individual outcomes of interest. Further analysis indicated a diagnosis of autism was associated with a greater risk of dyslipidemia (RR, 1.69. [95% CI, 1.20-2.40]; 7 studies) and cardiovascular disease (RR, 1.46 [95% CI, 1.42-1.50]; 3 studies).

However, investigators pointed out no statistically significant association of increased risk was observed for hypertension (RR, 1.22 [95% CI, 0.98-1.52]; 12 studies) and stroke (RR, 1.19 [95% CI, 0.63-2.24]; 4 studies) among people with autism. In meta-regression analyses, results indicated children with a diagnosis of autism were at a greater is of developing hypertension and diabetes than adults, but investigators called attention to a concerningly high level of between-study heterogeneity for several meta-analyses.

, Elizabeth Weir, PhD, of the Autism Research Centre in the Department of Psychiatry at the University of Cambridge, underlined the importance of the study’s findings on emphasizing the need for reform in management given the rising rates of autism spectrum disorder and the already shortened life expectancy for these patients.

“The results from this systematic review and meta-analysis require clinicians and researchers alike to radically rethink the health care provision that is currently provided to autistic people,” Weir wrote. “More support for both mental and physical health care across the life span should be offered and new research on how to improve outcomes is critical.”

Association Between Autism Spectrum Disorders and Cardiometabolic Diseases

A systematic review and meta-analysis of nearly 3 dozen published articles details the apparent increase in risk of cardiovascular disease and diabetes associated with a diagnosis of autism.

Children, adults with autism face heightened risk of cardiometabolic illnesses

The American Academy of Pediatrics (AAP) has provided a policy statement for ensuring the water children drink from private wells is safe.

Water quality can be affected by factors such as climate change, with children being more susceptible to illness from water quality than adults. There are over 23 million households in the United States relying on water from private wells which risk contamination without proper maintenance and testing.

The AAP’s policy statement, “Drinking Water from Private Wells and Risks to Children,” provided updated recommendations for inspecting, testing, and remediating private wells. This policy statement also noted how many wells are still unregulated by federal or state government.

“It’s important to know, when children drink well water at home, childcare, school, or a travel destination, whether that well water has been regularly tested for coliform bacteria, nitrates, and other chemicals,” said Alan D. Woolf, MD, MPH, FAAP. “Families may not be aware that natural disasters, such as floods, can affect well water, as well as chemical spills or new agricultural, fracking, or industrial operations nearby.”

According to the policy statement, children are more likely than adults to become ill because of contaminated water. Various regions also have different natural chemical compositions of water, which can also be affected by underlying geologic formation and type of aquifer. 

Chemicals such as nitrate and nitrite, heavy metals, organic chemicals, and radionuclides can cause illness, hospitalization, and death.

Recommendations for pediatricians include familiarizing themselves with how issues such as climate change and fracking affect water quality, becoming familiar with well water considerations in the area and advocating for safe water practices, and asking families whether they drink from a private well in any context.

The AAP also recommended testing well water for fluoride levels, along with encouraging health care providers to counsel families on safe drinking and families to stop using water from private wells and consult their local or state health department if they are concerned about contamination.

American Academy of Pediatrics updates policy statement on safety of water from private wells. January 30, 2023. Accessed January 30, 2023. 

https://www.aap.org/en/news-room/news-releases/aap/2022/american-academy-of-pediatrics-updates-policy-statement-on-safety-of-water-from-private-wells/

In an updated policy statement, the American Academy of Pediatrics has provided recommendations for providing children with safe drinking water from private wells. 

AAP: Drinking safe water from private wells

Vaginal metabolites may be early predictors of spontaneous preterm birth (sPTB), according to a recent study.

Despite sPTB being a leading cause of maternal and neonatal morbidity, there are few options for early risk identification and prevention. While the vaginal microbiome has been associated with sPTB, the relationship between these 2 factors remains unclear.

Metabolites have been observed to cause local and systemic effects, having associations with the microbiome, inflammation, and preterm birth. Investigators conducted a study to further understand the role of metabolites on sPTB.

The second-trimester vaginal metabolome was measured in 232 pregnant women. Of these, 80 pregnancies ended preterm. There were 635 metabolites identified, 549 of which were seen in over half of the study population, and 108 of which were seen in the entire population. 

Associations were found between the metabolome and microbiome, but community state types (CSTs) were not well separated. Microbiomes however were well separated. This indicated a strong but imperfect correlation between the vaginal microbiome and metabolome.

Six metabolite clusters (MC) were found, without as significant of separation as that between the vaginal microbiome and CSTs. Polyamine metabolism was the most enriched metabolite sub-pathway within each MC. Also, investigators found various enrichments of CSTs in MCs.

There was a significant difference between the metabolome of Black and White women, but only mild differences when looking at the correlation to MCs. Several MCs were significantly associated with sPTB in Black women but not White women. This indicated prematurity in Black women rather than with the microbiome structure.

Four metabolites were significantly associated with sPTB, 3 of which were of exogenous source. These 3 were ethyl β-glucopyranoside, tartrate, and diethanolamine. Investigators found these metabolites in over 95% of the study population.

Choline, an essential nutrient, was found to have lower levels in women with subsequent sPTB. Low levels of choline have also been linked to low betaine levels. As diethanolamine has been associated with disrupted choline metabolism, investigators hypothesized higher diethanolamine levels in sPTB may lower choline and betaine levels.

There were 13 vaginal metabolites associated with earlier sPTB. This included sugar or sugar alcohol metabolites found to be higher in early preterm birth. Interactions were found with both race and sPTB timing, with an additional sPTB-associated xenobiotic found as well.

These results showed enriched metabolite signatures among Black women with sPTB. Exogenous metabolites were also strongly associated with sPTB, indicating important risk factors.

Kindschuh WF, Baldini F, Liu MC, Liao J, Meydan Y, Lee HH, et al. Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome. 

In a recent study, an association was found between vaginal metabolites and spontaneous preterm birth.