Since in individual cases there is considerable benefit and very little harm, the IQWiG advocates in the final report – unlike the previous report – the early detection of an acquired vitamin B12 deficiency in infants.
On behalf of the Federal Joint Committee (G-BA), the Institute for Quality and Efficiency in Health Care (IQWiG) examined whether the early detection of vitamin B12 deficiency and the diseases homocystinuria, propionic acidemia and methylmalonic aciduria should be included in expanded newborn screening (ENS). should. After carefully evaluating the comments on the preliminary report, the institute has now come to the conclusion in the final report that, at least when it comes to screening for vitamin B12 deficiency, the advantages outweigh the advantages. The knowledge from the available studies is not sufficient to answer the question of whether this also applies to the three other target diseases.
Irreversible damage possible
Vitamin B12 and certain enzymes are essential for the breakdown of protein in the human body. If an expectant mother cannot absorb vitamin B12, this is dangerous for the newborn because the human body cannot produce vitamins itself. It also happens that the breakdown of protein in the newborn is blocked due to a lack of special enzymes. This is the case with the very rare inborn metabolic diseases homocystinuria, propionic acidemia and methylmalonic aciduria. All four conditions (vitamin B12 deficiency, homocystinuria, propionic acidemia, and methylmalonic aciduria) can jeopardize children’s physical and mental development and lead to brain damage, seizures, coma, and damage to the eyes, kidneys, and blood vessels. Sometimes children’s lives are threatened.
To diagnose a vitamin B12 deficiency and other diseases, blood dripped onto filter paper can be analyzed. With ENS, which is already carried out in Germany in accordance with the G-BA children’s guidelines, vein or heel blood is collected between the 36th and 72nd hours of life, dripped onto filter paper and examined for certain diseases. The target diseases that are the focus of this report are not yet included.
The aim of newborn screening for vitamin B12 deficiency and the other target diseases is to identify and treat affected children at an early stage – i.e. before the metabolism gets out of balance and causes irreversible damage, especially to the brain.
For classification purposes, it is important that the target diseases are very rare. Homocystinuria, propionic acidemia and methylmalonic aciduria each affect only about 1 in 100,000 to 500,000 newborns. Maternal vitamin B12 deficiency, on the other hand, is more common with an incidence of less than 1 in 5,000 children, although severe cases are also very rare. A vegan or strict vegetarian diet during pregnancy can cause vitamin B12 deficiency in the newborn. And although it is generally recommended to consume sufficient vitamin B12 during pregnancy, it still happens that babies are born with severe vitamin B12 deficiency due to the mother’s vitamin deficiency.
Advantages of vitamin B12 screening outweigh the advantages
To answer the question of whether early detection of vitamin B12 deficiency and other target diseases should be included in the ENS, IQWiG researched three studies that compared screening with no screening, as well as 13 studies that compared early treatment examined for late treatment.
The three studies that examined the effects of screening provided little meaningful data. Although these three studies included several hundred thousand children in total, only around 20 children were affected by one of the target diseases.
The 13 studies that compared early versus late treatment also had significant flaws. The main problem with these observational studies was that the children treated early and late differed in many aspects: age, duration of follow-up, patient selection, disease severity. Therefore, any differences between the treatment groups could not be attributed to the timing of treatment.
Nevertheless, the IQWiG now sees an indication of the benefit of early detection for the acquired vitamin B12 deficiency in the final report. IQWiG also took into account results from a large pilot project in Heidelberg and a Germany-wide survey of rare diseases (“Survey Unit for Rare Pediatric Diseases in Germany”, ES-PED). New evaluations were presented to IQWiG for this purpose. Above all, however, the comment process for the preliminary report confirmed that ultimately, even without study data, it is clear that early and timely administration of vitamin B12 can prevent possible irreversible damage caused by acquired vitamin B12 deficiency in newborns.
Treatment of acquired vitamin B12 deficiency is causal, short-term and carries a very low risk of harm to the newborn. In newborns with vitamin B12 deficiency at birth, the physical and mental development is at great risk without any vitamin B12 intake. Screening is therefore advantageous with regard to the early start of therapy, especially since babies are usually still symptom-free at the time of abnormal screening findings. On the damage side, three aspects are relevant: parents’ concern until the final diagnosis (even in the event of a false alarm) and possible short-term overtreatment through supplementation with vitamin B12. However, there is no evidence of any relevant potential for harm from an overdose of vitamin B12. Thirdly, in very rare cases it can happen that variants of the disease are identified that are so mild that they would never have caused any symptoms even without treatment.
When weighing up, there is essentially a significant benefit in rare individual cases (avoiding the irreversible damage of an acquired vitamin B12 deficiency) and a very minor harm (psychological stress and administration of vitamin B12 in the event of a false-positive result). . According to the final assessment by IQWiG, the advantages of screening for vitamin B12 deficiency in newborns outweigh the disadvantages.
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Jens Flintrop, press and public relations, Institute for Quality and Efficiency in Health Care (IQWiG)
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Sources: idw-online.de, IQWiG