Tag: premature infants

Preterm Babies Receive Insufficient Pain Management

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A large proportion of babies born very early need intensive care, which can be painful. But the healthcare system fails to provide pain relief to the full extent. This is shown by the largest survey to date of pain in neonatal care, now published in the journal Pain.

Every day for 4.5 years, neonatal care staff have recorded the occurrence of pain, the causes of pain, and how pain is assessed and treated in premature babies in Sweden. The study covers 3686 babies born between 22 and 31 weeks of gestation from 2020 to 2024. The total observation time was just over 185 000 days of care. Data were collected in the Swedish Neonatal Quality register.

In the evaluation of the register data, the researchers found that babies born extremely early, in weeks 22 to 23, had the highest proportion of painful medical conditions and almost daily painful intensive care procedures throughout the first month after birth. However, this is not surprising.

“There is a strong correlation between acute morbidity and being born very early. The earlier a baby is born, the more intensive care it needs. Intensive care involves procedures that can be painful, such as ventilator treatment, tube feeding, insertion of catheters into blood vessels and surgical procedures. It also requires various tests and investigations that may involve pain,” says Mikael Norman, professor of paediatrics at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and lead researcher of the study.

90 percent of the most extremely preterm infants had to undergo painful procedures. Despite this, healthcare professionals reported that only 45 percent of babies experienced pain – which may be because pain was largely prevented or treated. However, a check of the  drugs administered suggests other explanations may exist.

“Somewhat surprisingly, the smallest babies who were most exposed to pain had the lowest proportion of treatment with morphine. This may be a case of undertreatment,” says Mikael Norman.

Could not determine duration of pain

One limitation is that the study could not determine the duration or severity of pain for each day reported.

“The caregivers only answered yes or no to the question of whether the infant had experienced any pain in the last 24 hours. This could range from short-term, so-called procedural pain from for example a needle prick during a test to more continuous pain due to various medical conditions.

“Much is done to alleviate pain in babies. No child in neonatal care is left with severe pain untreated,” he continues.

However, it is a problem and a challenge that healthcare professionals are not always able to determine whether children are in pain.

“This involves developing better rating scales or physiological techniques to measure pain. Better pain treatments are also needed, perhaps with combinations of drugs with less risk of side effects,” says Dr Norman.

It is very important to improve pain management for premature babies, as we now know that their development is negatively affected by the strong signals in the brain that pain causes.

“The vision for all neonatal care is to be pain-free. The results of this survey will be of great importance for improving neonatal care and for future research in the field,” concludes Mikael Norman.

Source: Karolinska Institutet

Does More Postnatal Oxygen for Very Premature Babies Improve Survival?

New evidence shows higher oxygen concentrations may help prevent deaths of preterm babies

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Giving very premature babies high concentrations of oxygen soon after birth may reduce the risk of death by 50%, compared to lower levels of oxygen says new research led by University of Sydney researchers.

Premature babies sometimes need assisted breathing because their lungs haven’t finished developing, so doctors may give them supplemental oxygen via a breathing mask or breathing tube.

The study, published in JAMA Pediatrics, examined clinical trial data and outcomes of over one thousand premature babies who were given different oxygen concentrations. This included low concentrations of oxygen (~30%), intermediate (~50–65%) or high (~90%).

The study found for babies born prematurely, at less than 32 weeks starting resuscitation with high concentrations of oxygen (90% or greater), could increase chances of survival compared to low levels (21–30%).

When a doctor provides oxygen to babies that need help breathing, there is a device that regulates how oxygen is mixed together to reach the desired concentration. The researchers believe higher initial levels of oxygen may jump-start independent breathing, but more research is required to explore the underlying cause for this effect.

The researchers emphasise that additional large studies will be important to confirm this finding, and that even when starting with high oxygen, it needs to be adjusted to lower levels quickly to avoid hyperoxia (oxygen poisoning).

How the oxygen is delivered during the first 10 minutes of the infant’s life is critical. Doctors may give the baby high levels of oxygen at the start but then monitor vital signs and continually adjust the oxygen to avoid over or under exposure.

If confirmed in future studies, the findings challenge current international recommendations that suggest giving preterm babies the same amount of oxygen as babies born at term, 21%–30% oxygen (room air), rather than extra oxygen.

This study also demonstrates that there may not be a one-size-fits-all approach, and babies born prematurely may have different needs than babies born at term.

Worldwide, over 13 million babies are born prematurely each year, and close to 1 million die shortly after birth.

“Ensuring very premature infants get the right treatment from the beginning sets them up to lead healthy lives. There is no better time to intervene than immediately after birth,” said lead author Dr James Sotiropoulos from the University of Sydney’s NHMRC Clinical Trials Centre.

“The goal is to find the right balance – how do we give enough oxygen to prevent death and disability, but not damage vital organs.”

“Whilst promising and potentially practice-changing, these findings will need to be confirmed in future larger studies.”

Historically, oxygen with a 100% concentration was used to resuscitate all newborn infants. But due to studies that found high concentrations of oxygen over time can lead to hyperoxia and subsequent organ damage, in 2010 it prompted changes in international treatment recommendations for the use of blended oxygen (starting with low oxygen) for preterm infants.

Hyperoxia still a danger

However, researchers say the change was mainly based on evidence for full-term infants, who have fully developed lungs and who are often not as sick as premature infants. To date, there is little conclusive evidence to guide best practice for premature infants. The researchers emphasise the findings should not minimise the dangers of hyperoxia.

“The debate around exactly how much oxygen is best for extremely premature babies is still ongoing but, ultimately, everyone has the same shared goal of determining the best treatment for newborns,” said Dr Anna Lene Seidler from the NHMRC Clinical Trials Centre.

“Our findings, together with all the other research that is currently happening, may help the most vulnerable preterm infants have the best chance of survival.”

“We are very lucky to work with a highly collaborative international group on this question, some of whom have been studying it for decades. The group’s diverse expertise and experience is a major strength of this work,” said Dr Sotiropoulos.

Source: University of Sydney

For Extremely Prem Babies’ Milk, Which Enrichment is Best?

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Infants born extremely prematurely need enrichment in addition to breast milk, but it wasn’t clear as to whether enrichments were made from breast milk or cow’s milk had an effect on the risk of severe complications. This has been investigated by a large clinical study led by Linköping University, Sweden, published in eClinicalMedicine.

Infants born extremely prematurely, between weeks 22 and 27 of pregnancy, are among the most vulnerable patients in healthcare, at high risk of serious complications and mortality.

There is strong research support for giving breast milk to these children rather than formula made from cow’s milk. Formula based on cow’s milk is known to increase severe the risks for intestinal inflammation and sepsis.

“In Sweden, all extremely preterm infants receive breast milk from their mother or donated breast milk. Despite this, almost one in ten children get a severe inflammation of the intestine called necrotising enterocolitis. It’s one of the worst diseases you can have. At least three out of ten children die and those who survive often have neurological problems afterwards,” says Thomas Abrahamsson, professor at Linköping University and senior physician at the neonatal department at the University Hospital in Linköping, who led the current study.

Historically, there have been very few studies on extremely preterm infants where treatments have been compared against each other.

Therefore, there is a great need for clinical studies that can provide scientific support for how these children should be treated to have better chances of survival and a good life.

In some countries, such as Sweden, infants are fed exclusively with either their mother’s breast milk or donated breast milk.

However, in order for extremely preterm infants to grow as well as possible, they need more nutrition than breast milk contains. This is why breast milk is supplemented with extra protein, so-called enrichment.

The enrichment has previously been made from cow’s milk. But there have been suspicions that cow’s milk-based enrichment increases the risk of severe complications. Today, there is enrichment that is based on donated breast milk, and which has begun to be used in healthcare in some places.

The big question is whether it can reduce the risk of diseases in extremely preterm infants.

The current study, called N-Forte (the Nordic study on human milk fortification in extremely preterm infants), is the largest that has been carried out to seek answers to this question.

The results have been eagerly awaited by paediatricians and others caring for these fragile infants.

“We concluded that it doesn’t matter whether extremely preterm infants get enrichment made from cow’s milk or made from donated breast milk,” says Thomas Abrahamsson.

Although the study indicates that there was no difference between the two options, its results can be useful – the breast milk enrichment is fairly expensive.

“On the one hand, we’re disappointed that we didn’t find a positive effect of enrichment based on breast milk. On the other hand, it’s a large and well-done study and we can now say with great certainty that it doesn’t have an effect in this patient group. This is also important knowledge, so that we don’t invest in expensive products that don’t have the desired effect,” says Thomas Abrahamsson.

The N-Forte study included 228 extremely preterm infants, randomised 1:1 to receive enrichment made from breast milk and cow’s milk respectively.

The researchers examined whether the two groups differed in the incidence of necrotising enterocolitis, sepsis and death.

Of the children treated with breast milk-based enrichment, 35.7% had these complications, while the corresponding proportion was 34.5% in the group receiving cow’s milk-based enrichment, which means that there was no difference between the groups.

The results of the study are in line with a smaller study from Canada published in 2018, where researchers also saw no difference between the two types of enrichment on necrotising enterocolitis and severe sepsis.

Source: Linköping University

Magnesium Sulfate Reduces Cerebral Palsy Risk by a Third

Preterm baby
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Premature birth is the main cause of brain injury and cerebral palsy in babies. Evidence shows that babies can be protected from brain injury by giving magnesium sulfate to women who are at risk of premature birth, reducing the risk of cerebral palsy by a third. From a societal and lifetime perspective, the health gains and cost savings associated with the preventative treatment generated a net monetary benefit of £866 per preterm baby, according to an evaluation published in Archives of Disease in Childhood.

The prevention of cerebral palsy in pre-term labour (PReCePT) programme was developed in 2014 and aimed to support all maternity units in England to increase the use of magnesium sulfate in premature births. It was then piloted in five NHS trusts in the West of England, and this pilot was evaluated by the NIHR Applied Research Collaboration West (NIHR ARC West). It has since been rolled out across England via the AHSN Network as a national programme.

The evaluation of the national programme, also led by NIHR ARC West, found that PReCePT was both effective and cost-effective. The researchers looked at data from the UK National Neonatal Research Database for the year before and year after PReCePT was implemented in maternity units in England.

While use of magnesium sulfate had been increasing before, the study showed that PReCePT was able to accelerate uptake. It increased by 6.3 percentage points on average across all maternity units in England during the first year, over and above the increase that would be expected over time as the practice spread organically. After also adjusting for variations in when maternity units started the programme, the increase in use of magnesium sulfate was 9.5 percentage points. By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate.

The researchers also estimated that the programme’s first year could be associated with a lifetime saving to society of £3 million. This accounts for the costs of the programme, administering the treatment and of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. This is across all the extra babies the programme helped get access to the treatment during the first year.

In the five pilot sites, the improved use of magnesium sulfate has been sustained over the years since PReCePT was implemented. As the programme costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is even more cost-effective over a longer period.

John Macleod, NIHR ARC West Director, Professor in Clinical Epidemiology and Primary Care at the University of Bristol and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT programme is both effective and cost-effective. The programme has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.

Professor Lucy Chappell, Chief Executive Officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service. We look forward to seeing ongoing use of magnesium sulfate across our maternity units so that these benefits continue.”

Source: University of Bristol

Female Blood Donors Better for Very-low-birthweight Transfusions

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The sex of adult blood donors may affect the risk of common complications in transfusions of red blood cells (RBCs) to premature or very-low-birthweight infants while in the neonatal intensive care unit (NICU), according to new research.

Anaemia is common in premature or very-low-birthweight infants, often requiring an RBC transfusion. Common negative outcomes that can occur with very low birth weight infants include necrotising enterocolitis, lung damage or retinopathy of prematurity. Studies provided conflicting evidence of transfusions being a risk factor.

The study was led by Dr Ravi Patel is director of neonatal research in the Department of Pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta. Dr Patel and colleagues followed 181 very-low-birth-weight infants at three hospitals from 2010 to 2014. The infants were selected who received RBC transfusions from only male donors or only female donors.\

The study, published in JAMA Network Open, found that a typical very-low-birth-weight infant who received red blood cell transfusion from only female donors had a three times lower risk of negative outcomes than one who received red blood cells from only male donors.

Increasing donor age increased the protective effect of female donors. Some potential explanations for the protective effect could be reduced breakdown during storage of RBCs from female donors, along with less inflammation and more antioxidant capacity, the authors wrote.

RBC transfusion is common, according to Dr Patel, with about half of very low birth infants receiving at least one RBC transfusion while in the NICU. RBC transfusion is necessary to treat anaemia related to prematurity. In rare circumstances, this can lead to an infection or transfusion reaction. It is uncertain whether RBC transfusion increases the risks of some adverse clinical outcomes.
  Is it correct to say that the suspected mechanism for the difference in risk has to do with the characteristics of the RBCs, rather than immune differences, the suspected reason for the reverse effect in adults?

Future research should investigate inflammation or antioxidant capacity of red blood cells since these mechanisms may differ from adults, Dr Patel suggested.
Should their findings that age and sex have an effect on transfusion outcomes be confirmed, the next step would be transfusing blood from only males or only females, which could inform changes in practice.
Source: Emory University