July 21, 2021 | Volume 12 | Issue 29
Preliminary evidence on Long-COVID in children
"There is increasing evidence that adult patients diagnosed with COVID-19 suffer from Long-COVID (the name given to ongoing symptoms after COVID-19) initially described in Italy.” To date information of Long-COVID in children is scarce.

A cross-sectional study of 129 children diagnosed with confirmed COVID-19 (Mean age 11 years; 48.1% female) had caregiver interviews by questionnaire regarding signs/symptoms. They were then categorized into symptom states during the acute phase (25.6% asymptomatic and 74.4% symptomatic), hospitalization, and time from COVID-19 diagnosis to follow-up evaluation (<60, 60-120, >120 days). Overall, 4.7% of children were hospitalized and 2.3% needed pediatric intensive care.

41.8% of children recover completely after COVID-19, 35.7% have 1 or 2 symptoms and 22.5% have >3 symptoms assessed at 162.5 days (average) after microbiological diagnosis. Symptoms include: Insomnia (18.6%), respiratory symptoms (14.7% including chest pain/tightness), nasal congestion (12.4%), fatigue 10.8%), muscle (10.1%) and joint pain (6.9%) and concentration difficulties (10.1%). These symptoms occur in children following both asymptomatic and symptomatic COVID-19 and are particularly seen after 60 days following initial diagnosis.
The number of words spoken at 2.5 years and intellectual functioning at 7 years of age
A study of 549 children examined the association between the number of words infants use at age 2.5 years (as reported by parents) and deficits in intellectual functioning at age 7 years.

The use of 50 words or less at age 2.5 years is associated with lower Full-Scale IQ, verbal comprehension, working memory and perceptual reasoning at age 7 years (adjusted for sex, maternal education level, parental IQ and smoking during pregnancy).

The number of words used by an infant at 2.5 years appears to be a valuable marker for intellectual functioning later in childhood.


See related video HERE and below:
In this public service video for parents, Lisa Shulman, MD, uses video of babies and toddlers to show the communication milestones expected in typically developing children. Also discussed is what parents should do if they suspect their child is developmentally delayed. Dr. Shulman is associate professor of clinical pediatrics at Albert Einstein College of Medicine of Yeshiva University and an attending physician in pediatrics at The Children's Hospital at Montefiore.
Here are 5 things to look for in a child to know if they need an evaluation.
Comparative efficacy of levetiracetam (Keppra®) to phenobarbital in the treatment of neonatal seizures
“Neonatal seizures are often difficult to diagnose and a therapeutic challenge in neonatal care. Prolonged seizures are associated with development and cognitive impairment.” While phenobarbital is the most commonly used anticonvulsant it has been associated with increased respiratory depression, hypotension and sedation with poor neurocognition and motor development in neonates. Levetiracetam appears to be a safe anticonvulsant with neuroprotective effects on the developing brain.

An interesting and critical comment examined the efficacy and safety of administering levetiracetam vs. phenobarbital as a first-line drug to neonates seizing concludes that while the study showing levetiracetam beneficial effect is important its “generalizability into all clinical contexts is inconclusive…”
Maternal psychological factors and onset of Functional Gastrointestinal Disorders (FGID) in offspring
FGID are a heterogeneous group of aged-dependent, chronic, recurrent gastrointestinal symptoms in the absence of organic pathology (includes infant regurgitation, infantile colic and functional constipation) of unclear origin. They are common in young children (approximately 30%) and are thought to be due to subtle alteration of the normal development or a maladaptive behavioral response to a variety of internal (genetic predisposition) or external risk factors. The relationship between the psychological disposition of the mother and FGID occurrence is poorly understood.

A prospective cohort study of 113 parent-infant dyads who completed a battery of self-reported psychological questions assessed the presence of offspring FGID (using a validated Rome 3 questionnaire) and post-partum depression (PPD) symptoms, “maternal blues presence/severity,” maternal attachment style and the presence of relevant maternal psychiatric symptoms.

PPD symptom prevalence is 20.4% (3 days - 3 months); 40.4% of mothers suffer “severe blues”, 48.7% show a secure attachment pattern with 7.8%-10.9% (at 1 week and 3 months after delivery respectively) have relevant psychiatric symptoms. At 1 month follow-up 23% of infants have regurgitation, 27.4% infantile colic, 15% dyschezia (“voluntary” constipation) and 8% functional constipation.

There is a positive association between maternal PPD symptoms starting 3 days after delivery and subsequent presence of infantile colic and infantile regurgitation with maternal insecurity also playing a role (there appears to be no association between “maternal blues”/psychiatric symptoms and FGIDs).

“Early screening of post-partum depression symptoms and early implementation of psychological interventions within the post-partum period might promote the health of the mother-infant dyad.”


See related video HERE and HERE.
Maternal autoimmune disease and the risk of cancer in offspring
“Autoimmune disease and its medications are associated with increased cancer risk in adults. It is unknown whether maternal autoimmune disease and/or medication use in pregnancy is associated with increased risk of cancer in offspring.”

From a case-control study of all patients <20 years of age with a first cancer diagnosis (172) and a population-base control group, it appears that there is no increased risk of cancer in offspring of mothers with autoimmune exposures and/or medication intake during pregnancy.

Mode of delivery and transient changes in the metabolomic profile of neonates
We know that the early-life gut microbiome appears to be affected by mode of delivery (independent of intra-partum antibiotic exposure); babies born by caesarian section (C/S) have greater quantities of Enterococci and Klebsiella species (vs. bifidobacteria) and this appears to be associated with the subsequent development of various immune disorders (e.g. allergies and inflammatory bowel disease) and obesity.

Fetal cellular metabolism may also be changed by intra-partum factors, and later growth patterns (to adolescence) might be predicted by cord blood metabolites.

A study of 83 normal vaginal births and 32 infants born by C/S examined blood samples for amino acids and acylcarnitines (function in the synthesis of brain lipids, regulate membrane composition and modify the activity of genes) from mothers before birth and from the umbilical cord of infants at birth.

Numerous blood amino acids and some acylcarnitines are transiently but significantly higher in infants born vaginally (vs. C/S) (this has implications for mass spectrometry screening of the newborn for amino acid inborn errors of metabolism at birth. Other implications are unknown at present).


See related video HERE and HERE.
Duration of invasive mechanical ventilation and prediction of bronchopulmonary dysplasia (BPD)/home oxygen in extremely preterm infants (EPI)
From a retrospective study of 11,804 EPIs (median gestational age: 26.0 weeks; median birth weight 0.81kg) of whom 79.7% were alive on discharge from a neonatal intensive care unit (NICU), it appears that BPD occurs in 57.5% and home oxygen is required in 29.4%.

Mechanical ventilation for >8 days predicts BPD development in EPIs; ventilation for >10 days predicts discharge on home oxygen (moderate sensitivity and specificity).
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From the Editor

It appears to me that we in the USA have entered a new phase in the ongoing Covid-19 pandemic. While some states appear to have the case/hospitalization and death rates under control, a number continue to report spread with children & young adults being the predominant groups requiring hospitalization (fortunately deaths remain relatively few).       

While vaccination against SARS-Cov-2 certainly appears to be of great value in preventing spread and protecting the population, recent data from Israel suggests that it’s efficacy is significantly less than previously thought (~ 64% vs 95%). In addition, and equally concerning, the Delta (and Delta Plus) mutation, now the predominant variant in the USA, and a new spike protein mutation labeled Lambda by the WHO, presently circulating in South America, are all believed to be not only significantly more infectious but also more successful in evading vaccine immunity. A booster vaccine dose requirement now seems quite likely.

A recent interesting modeling article looks at what has been a very successful system in minimizing the pandemic. In Taiwan the focus on containing the pandemic has been primarily on public health measures (vs. vaccination) e.g. face masks, social distancing and hand sanitation, with great benefit to all. (The CDC still recommends the wearing of face masks!)

It appears that success against SARS-Cov-2 infection is possible and we’ve known how to achieve it for some time! It’s a combination of vaccination, with distances between us, in our hands (pardon the pun!) and on our faces!

Vaccinate and take care.

Jack Wolfsdorf, MD
Editor in Chief
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