Tag: paediatrics

Study Confirms Analgesics during Pregnancy Carries Risks for Newborns

Pregnant with ultrasound image
Source: Pixabay

Researchers have called for a reassessment of medical advice on analgesic use during pregnancy after a new study published in BMJ Open found that pregnant women using over-the-counter analgesics are about 1.5 times more likely to have a baby with health issues.

The study found elevated risks for preterm delivery, stillbirth or neonatal death, physical defects and other problems compared with the offspring of mothers who did not take such medications.

Between 30% and 80% of women globally use non-prescription analgesics in pregnancy for pain relief. However, there is presently great variation in evidence for safety of use during pregnancy, with some drugs considered safe and others not.

“We would encourage a strong reinforcement of the official advice for pregnant women.”

Aikaterini Zafeiri, first author of the study

The study analysed data from more than 151 000 pregnancies over 30 years (1985–2015) which contained medical notes for non-prescribed maternal consumption of five common analgesic. These were paracetamol, aspirin, and non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac, naproxen and ibuprofen – either as single compounds or in combinations.

Overall, 29% of women have taken over-the-counter analgesics during pregnancy, a figure which more than doubled to 60% during the last seven years of the 30-year study period.

When asked specifically at their first antenatal clinic visit, as opposed to later in pregnancy or after labour, 84% of women using painkillers reported use during the first 12 weeks after conception. However, the duration and dose of use and medical reason for use were not recorded.

Nevertheless, given that up to 60% of women reported using over the counter analgesics, they could not all have underlying medical conditions that would cause the increased risks seen in this study.

The study found increases in the following:

  • Neural tube defects: 64% more likely.
  • Admission to a neonatal unit: 57% more likely.
  • Neonatal death: 56% more likely.
  • Premature delivery before 37 weeks: 50% more likely.
  • Baby’s condition at birth based on APGAR score of less than 7 at five minutes: 48% more likely.
  • Stillbirth: 33% more likely.
  • Birthweight under 2.5 kg: 28% more likely.
  • Hypospadias, a birth defect affecting the penis: 27% more likely.

First author of the paper, Aikaterini Zafeiri of the University of Aberdeen said: “In light of the study findings, the ease of access to non-prescription painkillers, in combination with availability of mis-information as well as correct information through the internet, raises safety concerns.

“This is especially when mis-informed or partially-informed self-medication decisions are taken during pregnancy without medical advice.

“It should be reinforced that paracetamol in combination with NSAIDs is associated with a higher risk and pregnant women should always consult their doctor or midwife before taking any over-the-counter drugs. We would encourage a strong reinforcement of the official advice for pregnant women.”

Source: University of Aberdeen

No Added Seizure Risk from Antidepressant Use in Pregnancy

Pregnant with ultrasound image
Source: Pixabay

A large Swedish study in the journal Neurology found that pregnant women taking selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) during the first trimester of was not linked to an increased risk for neonatal seizures and epilepsy in childhood.

Any increase in seizures or epilepsy is likely due to other factors, the researchers said.

“It’s not likely the medications themselves that are causing the seizures and epilepsy in children, but rather the reasons why these women are taking the medication,” according to Kelsey Kathleen Wiggs, a PhD candidate at Indiana University in Bloomington. There are also the other background factors that differ between women who do and do not use SSRI/SNRIs.

“When it rains, it pours,” Wiggs said. “Women who are taking antidepressants in pregnancy are doing that for lots of different reasons, and they might be at risk for different things than women who aren’t taking those medications in pregnancy.”

An elevated risk for neonatal seizures (risk ratio [RR] 1.41) and epilepsy in early childhood (HR 1.21) among offspring of mothers who used antidepressants in pregnancy.

Adjustment for maternal indications for SSRI/SNRI use and background factors like smoking during pregnancy revealed that they were drivers for both associations: neonatal seizures (RR 1.10); epilepsy diagnosis at 5 years (HR 0.96). Parental history of epilepsy was not found to affect the association.

The findings provide a “conclusive answer” to these concerns with using SSRI/SNRIs during pregnancy, according to Anne Berg, PhD, and Torin Glass, BM, Bch, BAO.

“[SSRI/SNRIs] have been demonstrated to have serotonergic central nervous system effects and are associated with an observable withdrawal syndrome which may be seen in the neonate following in utero exposure,” noted Drs Berg and Glass, in an accompanying editorial.

“The authors understood that with a population-based data registry and huge sample size, they had more than sufficient statistical power to detect even a modest increase in risk,” the editorialists wrote. “They tested this hypothesis and were able to reject it, definitively!”

In order to determine whether antidepressants had a causal association with infant seizures and childhood epilepsy, the researchers analysed data from national Swedish healthcare registries on a total of 1 721 274 children in Sweden born between 1996 and 2011.

Participants were divided into two groups: one group of mothers who reported use of an SSRI (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram) or SNRI (venlafaxine, duloxetine) during the first trimester of pregnancy (n = 24 308), and another group with no reported antidepressant use (n = 1 696 966).

Source: MedPage Today

BCG Vaccine Activates Immune System in Newborns

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In the century since it was first used in humans, the Bacille Calmette-Guérin (BCG) vaccine against tuberculosis has become one of the world’s most widely used vaccines. Administered in countries with endemic TB, it has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. Some evidence even suggests that it can reduce severity of COVID. Now, a new study in Cell Reports sheds light on the mechanisms behind its extra protective effects.

Surprisingly little is known about how BCG exerts its many side benefits. To better understand its mechanism of action, researchers collected and comprehensively profile blood samples from newborns vaccinated with BCG, using a powerful ‘big data’ approach analysing lipid and metabolite biomarkers.

Their study found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns.

First author Dr Joann Diray Arce and her colleagues started off with blood samples from low-birthweight newborns in Guinea Bissau who were enrolled in a randomised clinical trial to receive BCG either at birth or after a delay of six weeks. Blood samples were taken at four weeks for both groups (after BCG was given to the first group, and before it was given to the second group).

The researchers comprehensively profiled the impact of BCG immunisation on the newborns’ blood plasma. They found that BCG vaccines given at birth changed metabolite and lipid profiles in newborns’ blood plasma in a pattern distinct from those in the delayed-vaccine group. The changes were associated with changes in cytokine production, a key feature of innate immunity.

The researchers had parallel findings when they tested BCG in cord blood samples from a cohort of Boston newborns and samples from a separate study of newborns in The Gambia and Papua New Guinea.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Dr Arce. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”

“A growing number of studies show that BCG vaccine protects against unrelated infections,” said Ofer Levy, MD, PhD, the study’s senior investigator. “It’s critical that we learn from BCG to better understand how to protect newborns. BCG is an ‘old school’ vaccine – it’s made from a live, weakened germ – but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”

Source: Boston Children’s Hospital via News-Medical.Net

GI Issues and Anxiety Linked in Children with Autism

Male doctor with young girl patient
Photo by National Cancer Institute on Unsplash

A new study has found a bi-directional relationship between gastrointestinal (GI) issues and internalised symptoms such as anxiety in children and adolescents with autism, which means the symptoms seem to be affecting each other. The findings could inform future precision medicine research aimed at developing personalised treatments for people with autism experiencing gastrointestinal issues. The study appears in the Journal of Autism and Developmental Disorders.

Autism is known to be often associated with GI issues, and is often overlooked in children despite being a source of pain and anxiety. Food preferences are often for carbohydrates and processed foods. The most common cause of GI issues in children with autism are abdominal pain, constipation, chronic diarrhea and gastroesophageal reflux disease (GERD).

“Research has shown gastrointestinal issues are associated with an increased stress response as well as aggression and irritability in some children with autism,” said Brad Ferguson, an assistant research professor. “This likely happens because some kids with autism are unable to verbally communicate their gastrointestinal discomfort as well as how they feel in general, which can be extremely frustrating. The goal of our research is to find out what factors are associated with gastrointestinal problems in individuals with autism so we can design treatments to help these individuals feel better.”

In the study, Ferguson and his team analysed health data from more than 620 under-18 patients with autism who experience gastrointestinal issues. Then, the researchers examined the relationship between the GI issues and internalised symptoms. Ferguson explained the findings provide more evidence on the importance of the ‘gut–brain axis’ in GI disorders in individuals with autism.

“Stress signals from the brain can alter the release of neurotransmitters like serotonin and norepinephrine in the gut which control gastrointestinal motility, or the movement of stool through the intestines. Stress also impacts the balance of bacteria living in the gut, called the microbiota, which can alter gastrointestinal functioning,” Ferguson said. “The gut then sends signals back to the brain, and that can, in turn, lead to feelings of anxiety, depression and social withdrawal. The cycle then repeats, so novel treatments addressing signals from both the brain and the gut may provide the most benefit for some kids with gastrointestinal disorders and autism.”

Ferguson is collaborating with David Beversdorf, a neurologist who also studies gastrointestinal problems in individuals with autism. Beversdorf had recently helped identify specific RNA biomarkers linked with gastrointestinal issues in children with autism.

“Interestingly, the study from Beversdorf and colleagues found relationships between microRNA that are related to anxiety behaviour following prolonged stress as well as depression and gastrointestinal disturbance, providing some converging evidence with our behavioural findings,” Ferguson said.

Ferguson and Beversdorf are now together investigating the effects of a stress-reducing medication on GI issues in a clinical trial. Ferguson cautioned that treatment could be effective for certain people with autism but not others.

“Our team uses a biomarker-based approach to find what markers in the body are common in those who respond favourably to certain treatments,” Ferguson said. “Our goal is to eventually develop a quick test that tells us which treatment is likely to work for which subgroups of patients based on their unique biomarker signature, including markers of stress, composition of gut bacteria, genetics, co-occurring psychological disorders, or a combination thereof. This way, we can provide the right treatments to the right patients at the right time.”

Source: University of Missouri-Columbia

US, Europe Report Severe Hepatitis of Unknown Aetiology in Children

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Public health officials are puzzling over cases of severe hepatitis in children reported in Europe and the US. A number of the cases have tested positive for adenovirus and/or SARS-CoV-2, though what role these viruses play is not yet clear.

On 5 April 2022, UK authorities notified the World Health Organization was of 10 cases of severe acute hepatitis of unknown aetiology in previously healthy young children ranging in from 11 months to five years old across central Scotland. Nine had onset of symptoms in March 2022, and all cases were detected on hospitalisation. Symptoms included jaundice, diarrhoea, vomiting and abdominal pain. An article published in Eurosurveillance detailed the cases.

Further investigations across the UK identified a total of 74 cases as of 8 April (including the 10 cases) that fulfilled the case definition. The clinical syndrome in identified cases is of acute hepatitis with markedly elevated liver enzymes, often with jaundice, sometimes preceded by gastrointestinal symptoms, in children principally up to 10 years old. Some cases have required transfer to specialist children’s liver units and six children have undergone liver transplantation. As of 11 April, no death has been reported among these cases and one epidemiologically linked case has been detected.

Laboratory testing has excluded hepatitis type A, B, C, and E viruses (and D where applicable) in these cases while SARS-CoV-2 and/or adenovirus have been detected in several cases. The United Kingdom has recently observed an increase in adenovirus activity, which is co-circulating with SARS-CoV-2, though the role of these viruses in the pathogenesis is not yet clear. They have however been linked to bladder inflammation and infection, and on occasion to hepatitis, but it is rare in children who are not immunocompromised.

To date, no other epidemiological risk factors have been identified, including recent international travel. Overall, the aetiology of the current hepatitis cases is still considered unknown and remains under active investigation. Laboratory testing for additional infections, chemicals and toxins is underway for the identified cases.

Following the notification from the UK, less than five cases (confirmed or possible) have been reported in Ireland, further investigations into these are ongoing. Additionally, three confirmed cases of acute hepatitis of unknown aetiology have been reported in children (ranging in age from 22 months-old to 13 years old) in Spain. A further 9 have been reported in the US state of Alabama, with five testing positive for adenovirus.

Karen Landers, district medical officer for the Alabama Department of Public Health, said that the cases were spread across the state, and no links were found among the children.

“It is not common to see children with severe hepatitis,” Landers told STAT in an interview. “Seeing children with severe [hepatitis] in the absence of severe underlying health problems is very rare. That’s what really stood out to us in the state of Alabama.”

Source: WHO

Report Finds One in Four Preschool Children in SA Malnourished

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One in four preschool children (aged four to five years) shows signs of long-term malnutrition, according to a new survey.

The Thrive by Five Index, released on 8 April, was produced by First National Bank and Innovation Edge in collaboration with the Department of Basic Education (DBE). The study surveyed more than 5000 children enrolled in early learning programmes across the country.

The study found about 25% of children were physically stunted, as a result of malnutrition in pregnancy and the early years of life. About 65% of children are either cognitively delayed, physically stunted, or both. This means they are not meeting the learning or growth standards expected of a child their age, and will start school at a disadvantage.

“Children from poorer households tended to perform worse,” said Sonja Giese, the lead researcher in the study. Giese is the founder of Innovation Edge, which was set up to support innovation in early childhood development. The rates of stunting were highest among the poorest children.

She said each child was assessed for about an hour. Children were assessed for things such as early mathematical skills, literacy and communication, motor development and coordination, among other things.

But Giese also drew attention to the positive outcomes of the study, saying that even within the poorest group of children there were some children who performed very well, causing a kind of “positive deviance”.

“I think there are some really interesting lessons we can learn from these outliers …Some children just thrive in difficult circumstances,” said Giese. She said more research could help to figure out how and why these children are thriving.

Giese said as the DBE had just taken over responsibility for early childhood education from the Department of Social Development, the study could show where attention should be focused.

In a statement about the survey, the DBE said that the first five years of the child’s life are the most important and stressed the importance of physical development during this stage.

Data for the survey was collected in late 2021 from a nationally representative sample of children aged 50-59 months enrolled in early learning programmes. The final weighted sample used for analysis included 5,139 children from 1,247 programmes across the country. The school quintile system was used to measure the probable socio-economic background of the children who were assessed. School quintiles are based on the income, education and unemployment levels of households in the school catchment area and for the purposes of the Thrive by Five study, the researchers assumed that the income level of children attending early learning programmes within each school cluster matched the income level of children attending the nearest school.

The researchers included more children from quintile 1 – the poorest – in order for the study to be representative of the country and each province. “That’s how we tried to make sure that it really provides a window into the world of children today in South Africa, exactly where they are and how they’re living,” said Giese.

Giese said that some of the data had not yet been analysed and further findings would be released over the next year.

This story was written by Liezl Human for GroundUp and is reproduced under a Creative Commons 4.0 Licence.

Source: GroundUp

Kids are a Significant Source of COVID Spread in Households

COVID spreads extensively in households, with children being a significant source of that spread. These are the findings from an antibody surveillance study published in CMAJ Open, which also shows that about 50% of household members were infected from the first-infected individual during the study period.

Although kids were less likely to spread the virus compared to adults, children and adults were equally likely to become infected from the first-infected individual.

The antibody surveillance study included 695 participants from 180 households in the Canadian city of Ottawa in Ontario, between September 2020 and March 2021. Included households had at least one member having had a confirmed COVID infection and at least one child within their household.

“Our study was conducted when we were dealing with a less transmissible virus and pandemic restrictions were strongly in place, and we still had a 50% transmission rate within households. Flash forward to where we are today with an extremely transmissible variant of COVID and the majority of pandemic restrictions lifted; it’s safe to say transmission rates will be higher even though we have a high vaccination rate amongst those who are eligible,” said Dr Maala Bhatt, the study’s lead author. 

“I know many want to ‘live with COVID’ and abandon the layers of protection that were previously mandated, but it’s important to be aware of the high transmissibility of this virus in closed, indoor settings, such as schools,” she cautioned.  “Our most vulnerable and our youngest children who are not yet able to be vaccinated are still at risk for COVID infection.”

In the Canadian province of Eastern Ontario, where the study was done, COVID is on the rise once again. Three-quarters of all children admitted to CHEO with COVID have come during the Omicron wave. Since the beginning of January this year a third of the roughly 4900 monthly visits to the Emergency Department were for COVID-related symptoms.

The study hypothesised that children would act as “an even greater source of spread within households with the emergence of more infectious variants.” Children also have “considerable potential to spread” in settings such as school and daycare, where they congregate indoors for long periods, especially now when masking is not required in many jurisdictions.

“While we’re lucky hospitals aren’t currently overloaded, emergency departments are and positivity rates are on the rise, even amongst children,” said Dr Bhatt, paediatric emergency physician and Director of Emergency Medicine Research at CHEO and an Investigator at the CHEO Research Institute.

“We continue to learn more about COVID and its potential long-term health impacts, and we still aren’t clear about how long immunity lasts; these are all things researchers continue to study.”

Source: University of Ottawa

Cardiovascular Risk Factors in Childhood Predict Adulthood Risks

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By tracking more than 38 000 participants from childhood for fifty years, researchers have uncovered direct evidence that the five cardiovascular risk factors when present in childhood predicted cardiovascular risk in adulthood. 

Body mass index, blood pressure, cholesterol, triglycerides and youth smoking, particularly in combination in early childhood, were clinically linked with cardiovascular events that predict poor cardiovascular health in adults.

The international study conducted by the International Childhood Cardiovascular Consortium (i3C) and published in the New England Journal of Medicine, found that the increased cardiovascular risk began as early as 40 years of age.

Paper co-author Prof Terence Dwyer at the University of Oxford commented: “Despite the effect medical and surgical care have had on treating heart disease, achieving the greatest possible reduction in the heart disease burden will depend on including preventive strategies that commence in childhood.”

The findings confirm that prevention must start in childhood. “Longitudinal studies like these have been hampered by a lack of inclusion of comprehensive childhood data around body measurements, blood pressure, and blood lipids and a failure to follow-up at ages when cardiovascular disease becomes common.”

The study involved 38 589 participants from Australia, Finland and the US, who were followed from age 3-19 years for a period of 35-50 years. 

The results showed that increased risk for cardiovascular events was seen in over half the children, with those having the highest risk factor levels, at 9 times the risk for an event as for children with below average risk factors.

“While this evidence had not been available previously, the findings were not entirely surprising as it had been known for some time that children as young as five already showed early signs of fatty deposits in arteries. This new evidence justified a greater emphasis on programs to prevent the development of these risk factors in children. Clinicians and public health professionals should now start to focus on how this might best be achieved,” Prof Dwyer concluded.

Source: Murdoch Childrens Research Institute

Fall in Paediatric Post-surgical Opioid Prescriptions

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A large study has shown that opioid prescriptions for children who underwent one of eight common outpatient surgeries declined over a period of five years. These findings, reported in the journal Pediatrics, suggest that clinicians are using more discretion when considering which paediatric patients require an opioid prescription after their procedures.

Opioids are routinely prescribed after a surgery to help paediatric patients manage mild or moderate pain. However, recent studies have suggested that recovery is similar with limited or no opioid use. Additionally, opioids prescribed to children can result in respiratory depression, which causes carbon dioxide to not be expelled from the lungs properly, and the continued use of those opioids, after acute pain has resolved. Despite these findings, no prior studies had looked at recent data on national opioid trends for surgery in children in the context of whether there has been any shift away from prescribing opioids more broadly.

“Children grow throughout their childhood, and because opioids are often prescribed based on weight, we cannot assume that what is appropriate for a 5-year-old could also apply to an adolescent,” said the study’s lead author Tori N. Sutherland, MD, MPH. “In our study, we wanted to be responsible with our data and consider surgical distribution by age group.”

In this study, the researchers used data from a private insurance database to study opioid-naïve patients under the age of 18 who underwent one of eight surgical procedures between 2014 and 2019. The procedures ranged from tonsillectomies to knee surgery. The primary outcome of the study was whether a prescription for opioids was filled within 7 days of surgery, and the secondary outcome was the total amount of opioid dispensed. A total of 124 249 patients were included in the study. Patients were separated by age into adolescents, school-aged children and preschool-aged children.

The researchers found that the percentage of children who had an opioid prescription filled after their surgery fell across all three age categories. For adolescents, prescriptions dropped from 78.2% to 48%; for school-aged children, from 53.9% to 25.5%; and for preschool-aged children, from 30.4% to 11.5%. Additionally, the average morphine milligram equivalent dispensed declined by approximately 50% across all three age groups.

The researchers also found that there was a steeper decline in opioid prescriptions beginning in late 2017, first in the adolescent group and then followed by school- and preschool-aged children. This trend appeared to represent a ‘trickle down’ effect, but more research is needed to explore the difference in trends by age group.

“Our findings demonstrate that pain treatment for children and adolescents undergoing surgery has changed dramatically over the past 5 years,” said Mark Neuman, MD, senior author. “Understanding what these trends mean for patient experiences and health outcomes is a key next step.”

Source: EurekAlert!

Intranasal Flu Vaccine OK for Kids with Asthma

Young girl sneezing
Photo by Andrea Piacquadio on Unsplash

A small clinical trial published in Pediatrics has shown that intranasal flu vaccine is just as safe for children with asthma as the intramuscular vaccine. According to the researchers, within 42 days of vaccination, 10.8% of children who received the intranasal quadrivalent live attenuated influenza vaccine (LAIV4) had an asthma exacerbation compared with 14.7% of those who received the intramuscular quadrivalent inactivated influenza vaccine (IIV4).

According to the researchers, regardless of asthma severity, LAIV4 remained noninferior to IIV4. Among those with mild asthma, one of 25 kids who received the LAIV4 experienced an asthma exacerbation versus three of 16 in the IIV4 group, the researchers reported. In children with moderate to severe asthma, exacerbations occurred in seven of 49 in the LAIV4 group and seven of 52 in the IIV4 group.

“These data add to the compelling safety record of LAIV in children, including those with persistent asthma,” the researchers wrote.

The two groups also did not differ significantly in the frequency of asthma-related symptoms, including nighttime awakening, unscheduled albuterol use, cough, wheezing, or chest tightness, within 14 days of administration. Similarly, no differences were seen in peak expiratory flow rate, or changes in childhood asthma control test or asthma control test scores from baseline through 42 days.

At present, the CDC recommends against the nasal spray vaccine for children and people with asthma, citing an increased risk of exacerbations.

A previous study had suggested that the LAIV was linked increased asthma risk and reactive airway disease in children under 36 months of age, but more recent research has found no difference in risk between the LAIV and IIV, the researchers explained.

“Building off these previous studies, our prospective study suggests that LAIV may be appropriate for some children with asthma,” they noted.

“These data support reexamining precautions to using LAIV4 in children with asthma, which could be particularly important during influenza pandemics, at times when IIV4 supplies are limited, in situations of public/school mass vaccination clinics using LAIV, or for children with significant needle aversions,” they added.

The study was conducted over the 2018 and 2019 flu seasons with children aged five to 11 but expanded to include children ages 5 to 17 in its second year. The primary outcome of asthma exacerbation after 42 days was defined as an episode for which the participant sought medical care or a new prescription for corticosteroids.

The median age of the 151 enrolled participants was 9 years, and 58% were boys.

Systemic reactogenicity events in the 14 days after vaccination were not different between the LAIV4 and IIV4 groups, with the exceptions of myalgia and sore throat, which were more common in the IIV4 group.

Source: MedPage Today