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

A mother’s health during the end of pregnancy and the first weeks following delivery can have an impact on not only her health outcomes, but her offspring’s as well. A 

 looked at the effect that maternal perinatal depression and anxiety had on the offspring’s development in the first 18 years of life.

The investigators used 6 databases: CINAHL Complete, Cochrane Library, Embase, Informit, MEDLINE Complete, and PsycInfo, to search for studies that reported information on the link between perinatal maternal mental health problems and offspring development. They included studies that were published in English, had a human sample, collected quantitative data, utilized a longitudinal design, examined measures of perinatal depression as well as development in the offspring, and investigated whether there was a link between perinatal depression or anxiety and childhood development.

The researchers found 191 unique studies that met their criteria, which created a combined sample of 195,751 unique mother-child pairs. They found that maternal perinatal depression and anxiety were linked with poorer development in the following areas:

cognitive (antenatal period, r = −0.12 [95% CI, –0.19 to –0.05]; postnatal period, r = −0.25 [95% CI, –0.39 to –0.09])

language (antenatal period, r = −0.11 [95% CI, −0.20 to 0.02]; postnatal period, r = −0.22 [95% CI, −0.40 to 0.03])

adaptive behavior (antenatal period, r = −0.26 [95% CI, −0.39 to −0.12])

offspring social-emotional (antenatal period, r = 0.21 [95% CI, 0.16-0.27]; postnatal period, r = 0.24 [95% CI, 0.19-0.28])

motor (antenatal period, r = −0.07 [95% CI, −0.18 to 0.03]; postnatal period, r = −0.07 [95% CI, −0.16 to 0.03])

The investigators found that this went beyond only the infant years and lasted into both childhood and adolescence. The robust nature of the results was confirmed through meta-regression.

They concluded that maternal anxiety and depression in the perinatal period did have a negative association with the child’s development. The results indicated that preventing depression and anxiety in this period as well as utilizing early interventions could have positive impact on the development of many children.

For more on maternal depression's impact on a child's development, click 

1. Rogers A, Obst S, Teague S et al. Association between maternal perinatal depression and anxiety and child and adolescent development. 

. September 14, 2020. Epub ahead of print. doi:10.1001/jamapediatrics.2020.2910

Articles

A mother’s health during pregnancy and in the first weeks following delivery can have an impact on her future health. A new report looks at how her mental health could also impact her child’s development through not only infancy, but childhood and adolescence.

Impact of a mother’s perinatal depression on a child’s development

There is no level of lead exposure that is without risk. Exposure to lead in childhood leads to irreversible neurodevelopmental deficits, which sets children up for a lifetime of suboptimal outcomes. Unfortunately, lead exposure prevention is only secondary in nature. An investigation in 

 assesses whether a machine learning model was better than regression in predicting childhood lead poisoning.

Researchers ran a prognostic study that used data from the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) program linked to the Chicago Department of Public Health. The participants came from a development cohort of children and a validation WIC cohort. Blood lead levels were assessed until December 2018.

There were 6812 children in the WIC validation cohort, which was comprised of mostly Hispanic and non-Hispanic Black children. The median year for house construction in the cohort was 1919. The machine learning prediction model’s area under the curve was 0.69, whereas the logistic regression’s area under the curve was 0.64 (difference, 0.05; 95% CI, 0.02-0.08). When the models were used to predict the 5% of children who were at the highest risk of having elevated blood lead levels, the machine learning model had a positive predictive value of 15.5% and the regression had a predictive value of 7.8% (difference, 7.7%; 95% CI, 3.7%-11.3%). In this same group, the sensitivity was 16.2% for machine learning and 8.1% for the regression (difference, 8.1%; 95% CI, 3.9%-11.7%) and the specificity was 95.5% and 95.1%, respectively (difference, 0.4%; 95% CI, 0.0%-0.7%)

The investigators concluded that the machine learning model was better at predicting childhood lead poisoning than regression. The machine learning was particularly good at identifying children who were at the highest risk of being exposed to lead. The findings are particularly important because many agencies have limited resources to proactively prevent lead exposure. The study’s results indicate that predicting lead exposure is difficult, but utilizing the machine learning model could help agencies use proactive measures to prevent exposure among children who are at the greatest risk.

1. Potash E, Ghani R, Walsh J, et al. Validation of a machine learning model to predict childhood lead poisoning. 

. 2020;3(9):e2012734. doi:10.1001/jamanetworkopen.2020.12734

No level of exposure to lead is safe and predicting exposure can be difficult. An investigation assesses the effectiveness of a machine learning model in predicting lead exposure.

Predicting lead exposure with a machine learning model

The 2020-2021 school year is going to be an unusual one. Some children are still solely learning virtual and some have returned to in-class learning. Then there are the children who are getting a hybrid education, with some virtual and some on-site teaching . Regardless of where and how a child is learning, there are many hurdles for families to get over to get the most out of school. The American Academy of Pediatrics has come up with 

 to help every child have the best year possible.

Create and maintain a built-in routine for each weekday. Maintain this routine both when the child has virtual learning and when the child has in-person education.

For the child who is learning virtually, make sure he/she/they has a quiet place to attend school and that they have the supplies and login information needed for necessary accounts.

For the child who is learning in-school, make sure the child has multiple face masks that are labelled with the child’s name. Rehearse proper mask technique with child.

Ensure the child is up-to-date on all vaccinations. If vaccinations are needed or there is uncertainty about whether a child has all needed vaccinations, the parent should contact the child’s pediatrician.

Encourage the child to take ownership of his or her learning. Parents should provide help only when absolutely necessary.

Discuss mental health with the child and watch out for signs that more mental health help may be needed. If the child is having trouble with school, contact the school and the child’s pediatrician.

Talk to the child’s teacher about how the child is handling the situation. Be sure to bring up any specific concerns.

Watch out for signs of struggle with school work. If a child is struggling, contact the child’s pediatrician to schedule an appointment for a learning disability evaluation or to see if the struggles are linked to something else.

Do not send the child to school if he or she is showing any sign of illness. Contact the pediatrician to talk about the next steps.

For children with disabilities, discuss an individualized plan with both the pediatrician and educators.

Ensure that parents have some time to themselves, when they don’t have to worry about caring for their child.

1. American Academy of Pediatrics. AAP offers back-to-school tips amid COVID-19. 

. Published September 1, 2020. Accessed September 16, 2020. 

https://services.aap.org/en/news-room/news-releases/aap/2020/aap-offers-back-to-school-tips-amid-covid-19/

The current school year will be an unusual one and will present many hurdles for families to cross. The American Academy of Pediatrics (AAP) has some tips to ensure each child has the best school year.

AAP offers 11 tips for the 2020-2021 school year

Sepsis can be a serious problem with over 70,000 children hospitalized with severe sepsis every year in the United States, which results in more than $7.3 billion in health care costs. A research letter in 

 looked at how outpatient health visits changed among children who had survived sepsis.

Researchers ran a cohort study, which followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. They looked at pediatric severe sepsis hospitalizations that were in Optum’s deidentified Clinformatics Data Mart database. Sepsis cases were found either through an explicit diagnosis cord or concurrent codes. The comparison of the number of the outpatient visits before and the year after a severe sepsis hospitalization used a 

 test and the type of visit was compared using a χ2 test. The children included in the analysis had to be consecutively enrolled in insurance for at least 3 months before their hospitalization for sepsis.

From the 167,497 hospitalizations found, 952 were for severe sepsis. Among those 952 children hospitalized for sepsis, 855 survived to discharge. The cohort of sepsis survivors had a median age of 12 years who had a median length of stay in the hospital of 9 days. The researchers found that the outpatient visits increased from a median of 5 visits in the year before hospitalization to 8 visits in the year after hospitalization as well as from 2 visits in the 90 days before the hospitalization to 3 visits in the 90 days following hospitalization. Among the 855 patients, 478 had more visits in the 90 days following hospitalization versus before hospitalization and overall 514 had more visits after hospitalization than before sepsis.

The investigators concluded that the median number of outpatients visit increased by 60% in the year following hospitalization when compared with each patient’s baseline. However, the increase in outpatient visits did not occur in every patient, which they said highlights how different the postsepsis life can be.

1. Carlton E, Kohne J, Hensley M, Prescott H. Comparison of outpatient health care use before and after pediatric severe sepsis. 

. 2020;3(9):e2015214. doi:10.1001/jamanetworkopen.2020.15214

Sepsis is an unexpected event that can have aftereffects. A research letter looks at how sepsis can impact outpatient visits for the effected child.

How sepsis impacts outpatient visits

Congenital cytomegalovirus is a common source of birth defects. Microcephaly has been a birth defect that received a lot of media attention in 2016 because of the Zika virus epidemic. A new 

 looks at how many cases of microcephaly occur as a result of congenital microcephaly and how that number of cases could be more than were found to be linked to the 2016 Zika epidemic.

Investigators ran a population-based cohort study that included pregnant women and their offspring who had been identified in 2 insurance claims databases in the United States: IBM Researcher MarketScan, which included data for employer-sponsored private health insurance, and Medicaid Analytic eXtract. Every pregnancy that ended with a live delivery to a woman with full health birth was included.

There were a total of 2,338,580 pregnancies included in the cohort. Among these pregnancies, there were 336 infants who had a congenital cytomegalovirus diagnosis. The prevalence of microcephaly among infants with a congenital cytomegalovirus diagnosis was 655 per 10,000 live birth and it was 2.8 per 10,000 among newborns without a congenital cytomegalovirus diagnosis (prevalence ratio [PR], 232; 95% CI, 154-350). Following restricting to cytomegalovirus-test newborns, 572 individuals, to correct for preferential testing, the PR was 15 (95% CI, 5.2-41). This PR is biased if other congenital cytomegalovirus-related outcomes trigger testing as congenital cytomegalovirus prevalence in tested infants would overestimate it in the source population. This meant that the researchers compared the prevalence of congenital cytomegalovirus in overall infants with microcephaly to an external unbiased sample of US infants who were screened at birth to get an estimated PR of 7.4 (95% CI, 4.8-11.5) to serve as a conservative lower bound.

The researchers concluded that a congenital cytomegalovirus infection increases the prevalence of microcephaly at delivery by at least 7-fold. The researchers believe that preventing cytomegalovirus in pregnancy could be a substantial way to shrink the number of newborns who are born with microcephaly as well as other outcomes linked to congenital cytomegalovirus, such as hearing loss, in the United States.

1. Messinger C, Lipsitch M, Bateman B, et al. Association between congenital cytomegalovirus and the prevalence at birth of microcephaly in the United States. 

r. September 14, 2020. Epub ahead of print. doi:10.1001/jamapediatrics.2020.3009

The 2016 Zika epidemic made microcephaly a common term, but a new investigation indicates that congenital cytomegalovirus, which is much less studied, could be an even bigger cause of the birth defect.

Is congenital cytomegalovirus a leading cause of microcephaly?

Trying substances in adolescence is common, as teenagers push back on parental and societal expectations, to say nothing of believing that nothing can hurt them. However, problematic substance use can have far-reaching negative outcome. A 

 looking at the impact of brief behavioral interventions on problematic substance use was published in 

The investigators searched Embase, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials, PsycInfo, and Medline. They selected 22 randomized controlled trials, which examined brief intervention, that met the eligibility criteria. They separated the brief interventions into groups including motivational interviewing, psychoeducation, and treatment as usual. The outcomes included substance use for alcohol as well as cannabis and substance-related problem scales.

The researchers conducted pairwise and network meta-analysies with random effects models. When compared to treatment as usual, motivational interviewing was found to reduce heavy alcohol use days by 0.7 days per month (95% credible interval [CrI]: −1.6 to 0.02), alcohol use days by 1.1 days per month (95% CrI −2.2 to −0.3), and overall substance-related problem reduced by a standardized net mean difference of 0.5 (95% CrI –1.0 to 0). Motivational interviewing was not found to reduce cannabis use days, with a net mean difference of −0.05 days per month (95% CrI: −0.26 to 0.14). The researchers did note that the meta-analysis had a lack of consistent reported outcomes as well as limited available comparisons.

The investigators concluded that in comparison to treatment as usual, motivational interview did help reduce both days of alcohol use as well as heavy alcohol use. They believe that these results should to lead to further utilization of motivational interviewing in the primary care setting with teenagers who have problematic alcohol use. However, there was no evidence that the use of motivational interviewing was linked with reduced cannabis use. Due to the large number of teenagers who do use cannabis, the results highlight the need to find effective interventions that target problematic cannabis use.

1. Steele D, Becker S, Danko K et al. Brief behavioral interventions for substance use in adolescents: a meta-analysis. 

. September 15, 2020. Epub ahead of print. doi:10.1542/peds.2020-0351

Problematic substance use during adolescence can have long-term health consequences. Could brief interventions help turn things around?

Using brief interventions to target substance use

Routine immunization has been a topic of much discussion over at least the past decade. Many of those vaccinations still occur in enough high enough numbers to do good. However, the human papillomavirus (HPV) vaccine has fought an uphill battle to be accepted in the United States. Other countries are well on their way to meeting their HPV vaccination goals, but the United States has frequently lagged behind. A 

 looks at whether the country will meet the Healthy People 2020 goal of 80% vaccine coverage.

Investigators used the MarketScan health care database to find participants. The children included in the study were followed from when they reached their 9th birthday until they received the HPV vaccination, were disenrolled from insurance, or had reached their 17th birthday, whichever came first.

The investigators included 7,837,480 children who represented a total of 19.8 million person-years. They found that proportion of girls and boys aged 15 years who had been administered at least 1 dose of the HPV vaccination increased from 38% and 5% in 2011 to 57% to 51% in 2017. Similarly, the proportion of 15-year-old girls and boys who had been given 2 doses of the HPV vaccine increased from 30% and 2% in 2011 to 46% and 39% in 2017. The investigators also found variation in vaccination according to geography. In 2017, the 2-dose HPV vaccine coverage ranged from 80% in the District of Columbia among girls to 15% in Mississippi among boys. The geographic range has a positive correlation with legislation for HPV vaccine education as well as pediatrician availability.

The investigators concluded that the current HPV coverage in children who are commercially insured was behind the set target of 80% total coverage. There were also frustrating disparities across states. A number of interventions have been tried to increase the vaccination’s coverage, but this investigation indicates that the most likely path to better coverage includes education legislation as well as better access to care.

1. Chen S, Huybrechts K, Bateman B, Hernández-Díaz S. Trends in human papillomavirus vaccination in commercially insured children in the United States. 

. September 14, 2020. Epub ahead of print. doi:10.1542/peds.2019-3557


Human papillomavirus (HPV) vaccination coverage has lagged in the United States. A report looks at whether the coverage will meet the Healthy People 2020 goal.

 Will HPV vaccination coverage hit the mark?

The past decades have brought greater insight into how mental health issues can lead to suboptimal physical health outcomes. The research has also provided some information on how the mental health of family members can impact the rest of the family. A 

 offered a look at how exposure to a mother’s depression before reaching the age of 5 years could influence developmental vulnerability.

Investigators ran a cohort study that included every child born in Manitoba, Canada who had completed the Early Development Instrument between 2005 and 2016. Physician visits, pharmaceutical data, and hospitalizations were used to define maternal depression. The Early Development Instrument was used to define the developmental vulnerability.

The study’s sample included 52,103 children. Investigators found that the children who had been exposed to maternal depression when they were aged younger than 5 years had a 17% higher risk of showing at least 1 developmental vulnerability at the time of school entry, when compared to the children who did not have an exposure to maternal depression before age 5 years. Exposure to maternal depression was found to be most strongly linked with physical health and well-being (adjusted relative risk [aRR] = 1.28; 95% CI: 1.20–1.36), emotional maturity (aRR = 1.27; 95% CI: 1.18–1.37), and difficulties in social competence (aRR = 1.28; 95% CI: 1.20–1.38). Exposure to maternal depression before age 1 year and between ages 4 to 5 years was found to have the strongest tie with developmental vulnerability for most of the developmental domains.

The researchers concluded that children who had exposure to maternal depression were at greater risk for showing developmental vulnerability when they entered school. The finding was consistent with previous research on the topic. The researchers said that further research on the topic should focus on what has made children resilient when exposed to maternal depression, in an effort to identify factors that could help prevent other children from dealing with developmental vulnerabilities.

1. Wall-Wieler E, Roos L, Gotlib I. Maternal depression in early childhood and developmental vulnerability at school entry. 

. 2020;146(3):e20200794. doi:10.1542/peds.2020-0794

The mental health of immediate family members can have an impact on the remaining family. A recent report offers insight on how maternal depression impacts a child’s development.

How maternal depression can lead to developmental vulnerability in kids

A 5-year-old female with no significant past medical history presented to the emergency department (ED) in 2016 with altered mental status, decreased activity, fever, and decreased oral intake. Her mother reports that she was in her usual state of health until 1 week prior to presentation when she developed low grade fevers and abdominal pain with associated complaints of headaches, neck pain, and muscle aches. She was able to tolerate water but her overall oral intake was diminished with a marked decrease in urine output, worsening to once daily.

The patient’s mother took her to a local hospital 4 days prior to her ED presentation with complaints of fever (maximum temperature 104°F), headache, and neck pain. She was discharged home when her influenza, streptococcal throat swab, chest x-ray, and urinalysis were all unremarkable. In the days following, she became increasingly too weak to get out of bed, was intermittently confused, refused to answer questions, and was more lethargic. The night before her ED presentation, her mother was extremely concerned when the patient could not remember her name or her parents’ names. Parents denied any rashes, vision changes, vomiting, or diarrhea.

The patient had no previous hospitalizations and was otherwise a healthy child. Her family history was reviewed and was non-contributory. She attended school and lived with her parents, aunt, and grandmother. The patient does not have any siblings. There were no reported sick contacts, allergies, recent travel, or new exposures. The patient’s immunizations were up to date.

On presentation to the ED, her vital signs were as follows: temperature 99.5°F; heart rate 135 beats/min; respiratory rate 24 breaths/min; blood pressure 71/52 mm Hg; oxygen saturation was 99% on room air; weight was 20.4 kg. On physical examination, she was awake, ill-appearing, but not toxic. She was not answering questions but would respond “ow” and “nothing is helping” to painful stimuli. Physical exam was otherwise significant for a normocephalic and atraumatic head, sunken eyes, and dry mucosal membranes. She was tachycardic with 2+ distal pulses bilaterally and a brisk capillary refill. Neurologically, she was altered and had positive Brudzinski and Kernig signs. Her Glasgow Coma Scale (GCS) was 13 (eyes 4, verbal 4, and motor 5).

Preliminary laboratory data in the ED revealed leukocytosis with a white blood cell count of 17,830/mm

, with 86% neutrophils, 6% lymphocytes and 6% monocytes. Her hemoglobin was low at 11.6 g/dL and she was thrombocytopenic with a platelet count of 22,000/mm

. A comprehensive metabolic panel revealed the following data: sodium 123 meq/L, potassium 5.0 meq/L, chloride 80 meq/L, carbon dioxide 13 meq/L, BUN 105 mg/dL, creatinine 2.5 mg/dL, glucose 105 mg/dL, calcium 8.2 mg/dL, total protein was 5.7 g/dL, and albumin were 2.8 g/dL. Her anion gap was elevated at 30 meq/L. All other metabolic panel results were unremarkable. Her C-reactive protein (CRP) was elevated at 20.8 mg/dL (normal range <0.5 mg/dL). Her lactic acid levels, PT and INR, and PTT were unremarkable. Due to her altered mental status, a computed tomography (CT) scan of her head was obtained and did not reveal any acute abnormalities.

The most common cause of altered mental status in children is infection

 which is consistent with this patient’s presentation of altered mental status in the setting of fever and found to have an elevated CRP and neutrophilia (Table 1). Given the patient’s positive Brudzinski and Kernig signs, bacterial, viral, fungal, and tubercular meningitides were possible sources of infection

 that could not be excluded because the patient was not a candidate for LP given her significant thrombocytopenia. Encephalitis commonly presents with decreased consciousness

 and could not be ruled out definitively without further infectious disease workup, including repeat head imaging. Other sources of infection included myocarditis, endocarditis, urinary tract infection, or pneumonia, but were less congruent with the patient’s presenting symptoms. Given the patients’ hypotension in the setting of infection, altered mental status secondary to sepsis should be considered. Sepsis-associated encephalopathy (SAE) is a term that refers to diffuse brain dysfunction resulting from cerebral hypoperfusion and/or alterations of the blood brain barrier due to systemic infection causing cognitive impairment.

 It is characterized by diffuse brain dysfunction elsewhere in the body without overt central nervous system infection.

 The source and etiology of infection are important factors in the development of SAE.

 The greatest risk of SAE is associated with biliary tract or intestinal infections followed by pulmonary infections. The most commonly implicated organisms are 

 More severe brain dysfunction and higher mortality rates were observed in patients with SAE infected with multiple bacteria or 

 Although not as well studied in children, SAE in adults presents with nonfocal neurologic manifestations and can present as a depressed state.

Another potential cause of altered mental status could be toxic exposure. Exploratory ingestions are common in children aged younger than 6 years. (Table 1).

 The clinical presentation of occult ingestion varies depending on the ingested substance and occult toxic exposure should be considered in the differential diagnosis of a child who presents with acute onset multisystem dysfunction, unexplained metabolic acidosis, and altered mental status.

 However, the likelihood of a toxic ingestion underlying this patient’s presentation was low as the patient was not in the “at risk” age group of incidental ingestions (aged 1 to 4 years old), lacked a history of previous ingestions, and did not have exposure to commonly ingested agents such as cleaning products, analgesics, cough medications, topical agents, or pesticides. Additionally, the timeline of the onset of her presentation was inconsistent with an acute toxic ingestion.

The patient’s basic metabolic panel was indicative of an anion gap metabolic acidosis and thus, metabolic disorders should be considered as a cause of her altered mental status (Table 1). Diabetic ketoacidosis could have been underlying her anion gap metabolic acidosis, but was less likely in the absence of polyuria, polydipsia, hyperglycemia, and a negative past medical history. Lactic acidosis in the setting of hypoperfusion due to sepsis could be considered, but her lactate levels were only mildly elevated suggesting that lactic acidosis was unlikely the underlying cause of her altered mental status. Other causes of anion gap metabolic acidosis include ingestion of toxic materials such as methanol, ethylene glycol, and salicylate poisoning. Her lack of exposure to these substances and more insidious onset of illness were inconsistent with toxic ingestion. Her presenting hypotension and elevated creatinine suggest that the most likely etiology of her anion gap metabolic acidosis was acute kidney injury (AKI) precipitated by severe dehydration. This may have contributed to her altered mental status, but would not account for the patient’s initial fever and lethargy that were more consistent with an infectious etiology.

The patient’s hypotension, tachycardia, and leukocytosis raised concern for sepsis. The incidence of sepsis, characterized by immune dysregulation, has been steadily increasing in children since the mid-1990s

 with an estimated global incidence of pediatric and neonatal sepsis of 25.2 million in 2017.

 Sepsis accounts for 4.4% of admissions to children’s hospitals with approximately 75,000 children hospitalized for severe sepsis each year.

 Definitions of sepsis and organ dysfunction developed by the International Consensus Conference on Pediatric Sepsis help physicians identify sepsis, determine its severity, and monitor progression of a child’s illness.

 The consensus criteria also divide sepsis into categories based on the severity of presentation: severe inflammatory response (SIRS), severe sepsis, and septic shock, and multiple organ failure.

 The definition and clinical markers of sepsis differs in children compared to adults. In adults, elevated lactate is an important marker of sepsis and reduction of lactate levels is associated with improved adult survival.

 However, little evidence supports the use of lactate as a marker of clinical significance in children.

 Other inflammatory biomarkers, such as c-reactive protein (CRP) and procalcitonin may be useful in identifying infection, especially in patients with no apparent infection source

 C-reactive protein is also useful as a guide for de-escalation of antibiotics in patients without an identifiable source of infection.

 There has been some literature supporting the use of molecular methods to distinguish between bacterial and viral infections, including polymerase chain reaction (PCR) and detection of bacteria 16S (RNA) genes. Some evidence suggests that these methods have the potential to differentiate bacterial from viral infection in children with high accuracy,

 which has potential benefits regarding antibiotic stewardship.

Early identification of sepsis is important to ensure timely administration of broad-spectrum antibiotics and identification of an infection source to enable more targeted treatment. Although mortality in children due to severe sepsis is less than 10%,

 morbidity is significant in pediatric patients with septic shock further emphasizing the importance of early identification and treatment of sepsis to prevent adverse outcomes. Because children can compensate for circulatory dysfunction, hypotension is a late finding and this can make early identification of sepsis difficult.

Non-bacterial infections may cause a systemic inflammatory response that mimics sepsis, which should be taken into account when considering a clinical picture of sepsis. Epstein-Barr Virus-associated hemophagocytic syndrome (HPS) can present with signs of severe sepsis.

 Hemophagocytic syndrome is a condition in which T-cells, natural killer cells, and macrophages are abnormally activated causing hypercytokinemia leading to cell death and eventually multiorgan failure.

 Epstein-Barr Virus is the most common infectious cause of HPS.

 Hemophagocytic symdrome should be considered in the differential in patients presenting with prolonged fever, pancytopenia, and a sepsis-like picture that is unresponsive to antibiotics.

In the ED, the patient was given intravenous (IV) ceftriaxone after blood cultures were drawn due to the high concern for meningitis and IV ketorolac for pain prior to the return of her laboratory results. The patient was not a candidate for LP given her thrombocytopenia. Vancomycin was held when her laboratory results revealed an AKI. She remained hypotensive after 3 normal saline boluses and was started on dopamine at 10 mcg/kg/min, titrated down to 5 mcg/kg/min for normotension. She was admitted to the pediatric intensive care unit for further management of her hypotension, which was thought to be due to septic shock and subsequently intubated due to concern for respiratory failure likely due to aggressive fluid resuscitation and infection (Figures 1a,b,c). Ceftriaxone was continued; vancomycin was started; and steroids were held given low likelihood of 

 as the patient was up to date on her vaccinations. She was also started on acyclovir given concern for viral meningitis. An echocardiogram ruled out myocarditis and endocarditis as an infectious source. Her AKI was thought to be caused by volume depletion secondary to decreased fluid intake prior to admission and exacerbated by home ibuprofen use and ketorolac administration in the ED. Her renal function and hyponatremia noted on her initial labs resolved quickly with fluid resuscitation and without further renal sequelae.

Given her altered mental status, a brain magnetic resonance imaging (MRI/MRA) was ordered and significant for a tiny focus of restricted diffusion in the white matter of the posterior left frontal lobe consistent with early subacute infarct (Figure 2a). On hospital day 5, she was extubated and found to have right-sided motor deficits. Repeat imaging revealed extensive skull base and cervical osteomyelitis and arteritis with complete occlusion of flow in the left carotid artery and limited flow in the right carotid artery with primary circulation through the posterior vessels (Figure 2b,c,d). The MRI also showed an extensive left side frontal lobe infarct (Figure 2b,c). The CT angiogram of her head and neck confirmed occlusion of the left internal carotid artery and marked narrowing of the right internal carotid artery. The CT was also significant for opacification of the sphenoid sinus and left mastoid air cells thought to be consistent with an infectious process. The following day, she had sphenoid abscess drainage via functional endoscopic sinus surgery and tympanostomy tubes placed by otolaryngology due to the extensive middle ear effusion noted on CT. She was treated with vancomycin, ceftriaxone, and clindamycin for 5 days, at which time the clindamycin was discontinued. Aerobic culture of sinuses was positive for coagulase positive 

 and anaerobic culture of sinuses was negative for growth. Cultures including blood cultures drawn in the ED and bacterial and viral CSF cultures were negative. The final diagnosis was skull base and cervical osteomyelitis caused by coagulase positive 

. Origin of her osteomyelitis remained unclear.

She was hospitalized for 6 weeks. Prior to discharge, she regained speech function; hemiparesis improved; renal function normal. She was treated with Lovenox for her infarcts. One month after discharge, she had no neurological deficits and returned to school. She has been seen in the ED for minor infections and injuries and is doing well without any sequelae from hospitalization.

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17. Juutilainen A, Hämäläinen S, Pulkki K, et al. Biomarkers for bacteremia and severe sepsis in hematological patients with neutropenic fever: Multivariate logistic regression analysis and factor analysis. 

18. Downes KJ, Weiss SL, Gerber JS, et al. A pragmatic biomarker-driven algorithm to guide antibiotic use in the pediatric intensive care unit: The optimizing antibiotic strategies in sepsis (OASIS) study. 

19. Herberg JA, Kaforou M, Wright VJ, et al. Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children. 

20. Stoller J, Halpin L, Weis M, et al. Epidemiology of severe sepsis: 2008-2012. 

21. Schwaitzberg SD, Bergman KS, Harris BH. A pediatric trauma model of continuous hemorrhage. 

22. Marik P, Spivack T, Chawla R. Epstein-Barr virus-associated hemophagocytic syndrome mimicking severe sepsis. 

24. Imashuku S. Clinical features and treatment strategies of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. In: 

. 2002. doi:10.1016/S1040-8428(02)00117-8

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. 2007. doi:10.1016/S1473-3099(07)70290-6

A 5-year-old female with no significant past medical history presented to the emergency department in 2016 with altered mental status, decreased activity, fever, and decreased oral intake. What's the diagnosis?

Bad to the bone: A case of altered mental status

Research has shown over the past decades just how much pregnancy can impact the offspring’s life and health outcomes. Exposure to cigarette smoke has been shown to be an avoidable risk factor for birth complications and could even have an impact on the risk of a child being overweight. An 

The investigators ran a data meta-analysis of 28 pregnancy/birth cohorts from both North America and Europe. Every cohort included in the meta-analysis contained information on the mother’s smoking and 16 of the cohorts also had information on the father’s smoking. Additionally, 22 of the cohorts were population-based and the birth years ranged from 1991 to 2015. Across the cohorts, the maternal median age was 30.0 years and overall the mothers were either medium or highly educated.

Researchers found that when compared to nonsmoking mothers, maternal first trimester smoking only had no link to adverse birth outcomes, but was linked with an increased risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02–1.35], 

 value = 0.030). For children who had mothers that continued to smoke throughout pregnancy, there were higher risks of preterm birth (OR 1.08 [95% CI 1.02–1.15], 

 value = 0.012), childhood overweight (OR 1.42 [95% CI 1.35–1.48], 

 value < 0.001), and small size for gestational age (OR 2.15 [95% CI 2.07–2.23], 

 value < 0.001). The mothers who reduced the number of cigarettes smoked between the first and third trimester, but did not quit smoking, were found to still have a higher risk of small for gestation age. The corresponding risk estimates were still smaller than for women who smoked the same number of cigarettes for the duration of the pregnancy (OR 1.89 [95% CI 1.52–2.34] instead of OR 2.20 [95% CI 2.02–2.42] when reducing from 5–9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39–3.25] and OR 1.93 [95% CI 1.46–2.57] instead of OR 2.95 [95% CI 2.75–3.15] when reducing from ≥10 to 5–9 and ≤4 cigarettes/day, respectively [

 values < 0.001]). Among the mothers who didn’t smoke, paternal smoking was not linked to adverse birth outcomes, but it was linked to childhood overweight (OR 1.21 [95% CI 1.16–1.27], 

The researchers concluded that mothers smoking during pregnancy was linked to a higher risk of childhood overweight than among mothers who did not smoke. Paternal smoking was also linked to an increased risk of childhood overweight, independent of maternal smoking. The researchers believe that parental smoking prevention programs should focus on urging parents to quit before or at the start of pregnancy, not during the pregnancy.

1. Philips E, Santos S, Trasande L, et al. Changes in parental smoking during pregnancy and risks of adverse birth outcomes and childhood overweight in Europe and North America: An individual participant data meta-analysis of 229,000 singleton births. 

. 2020;17(8):e1003182. doi:10.1371/journal.pmed.1003182

Smoking has many negative health effects and a new investigation adds an increased risk of childhood weight issues when exposure to smoking in utero.

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Bad to the bone: A case of altered mental status

How parental smoking during pregnancy impacts overweight risk