"It's Not SCID — So What Is It?" Understanding Low T-Cell Results From Newborn Screening

What four recent studies from Switzerland, the Netherlands, Spain and England tell families about babies whose immune screening test is abnormal but who do not have SCID

A screening result that can be confusing for families

In many countries, the heel-prick blood test taken in a baby's first days now checks for a rare but serious immune condition called severe combined immunodeficiency, or SCID. Most babies who get an abnormal result turn out not to have SCID. Many of them do, however, have lower-than-usual numbers of an important type of white blood cell, called T cells, for some other reason. Four studies published in 2025 and 2026 followed these babies and their families, and together they suggest that most of these children do well, that many need less medicine than once thought, and that parents need clearer information and more support along the way.

Why doctors started screening every baby for SCID

T cells are the "trained soldiers" of the immune system. They learn to fight infections in a small organ in the chest called the thymus. Babies with SCID are born with almost no working T cells. They look perfectly healthy at birth, but without treatment most become seriously ill with infections and do not survive their first year. The good news is that SCID can be cured, usually with a stem-cell (bone marrow) transplant, and results are better when babies are treated before they catch a serious infection [1].

Before screening, families usually found out only after their baby became very sick, or because an older child in the family had already been affected. That began to change when scientists developed a way to measure tiny pieces of DNA, called TRECs, that are left behind whenever the thymus makes a new T cell [2]. Few TRECs in the heel-prick blood spot means the thymus is making few T cells. The US state of Wisconsin began testing every newborn this way in 2008 [3], and other programmes followed across the United States and Europe [4][5].

Early on, doctors noticed something important. The test is very good at finding SCID, but it also finds babies whose T cells are low for other reasons [6][7]. Some have a genetic condition such as 22q11.2 deletion syndrome (a small missing piece of chromosome 22, sometimes called DiGeorge syndrome). Some have a temporary cause, such as being born very early, fluid around the lungs, or a mother who took certain medicines in pregnancy. And in some, no cause is found. Doctors call this whole group "non-SCID T-cell lymphopenia" — lymphopenia simply means too few lymphocytes, the family of white blood cells that includes T cells. Experts agreed on names for these groups [8], but there was little guidance on how to care for these babies over time.

What the four new studies did

In Switzerland, doctors looked at every baby screened across the whole country from 2019 to 2023 — 435,985 babies in all [9]. They focused on 42 babies with low T cells who did not have SCID and had no obvious temporary cause, and followed how their T cells changed over the first few years.

In the Netherlands, doctors at all seven of the country's university hospitals reviewed six and a half years of screening, including a pilot study and the national programme [10]. They looked at all 130 babies referred after an abnormal result and asked which ones really needed treatment.

In Catalonia, Spain — the first region in Europe to screen for SCID — doctors reviewed seven years of results from one screening laboratory and one specialist clinic in Barcelona, covering 420,263 babies [11].

In England, researchers interviewed 12 parents whose babies had been found through screening to have either SCID or non-SCID T-cell lymphopenia, to understand what the experience was like for families [12].

What the studies found about the babies

The first finding is about numbers. In the Netherlands, only 7 of the 130 babies referred after an abnormal result (about 1 in 19) actually had SCID [10]. In Catalonia, about 1 in every 47,000 babies had SCID or a similar condition, while about 1 in every 8,000 had non-SCID T-cell lymphopenia — roughly six times as many [11]. In other words, if your baby's screening result is abnormal, SCID must be checked for quickly, but it is not the most likely answer.

The second finding is about causes. In all three countries, the most common genetic cause was 22q11.2 deletion syndrome, although temporary causes and cases with no cause found were also common [9][10][11]. Finding it early can help in other ways too: in Switzerland, the check-ups that followed screening led doctors to discover heart problems in four babies and low calcium-regulating hormone levels in two [9].

The third finding is the most reassuring. In the Swiss study, about half of the babies had a clear genetic cause for their low T cells. Babies without a clear genetic cause usually saw their T cells recover much sooner [9]. A simple blood count at the first visit, showing how many "helper" T cells (CD4 cells) a baby has, was more useful for predicting the future than the original screening number. Babies who started with very low helper-cell counts were the ones whose counts stayed low.

The fourth finding is about medicines. Some babies are given a daily antibiotic to prevent a particular kind of pneumonia while their T cells are low. In Switzerland, babies without a clear genetic cause who started this antibiotic typically stopped it at around six months of age, and all by about one year, without serious infections [9]. The Dutch doctors, looking at babies with no cause found and babies with a gene change called FOXN1 that can lower T cells [13], found that infections were uncommon and mild, and they recommend "watchful waiting" rather than medicine for babies who are well and whose counts are not very low [10]. In Catalonia, none of the 15 babies with no cause found had serious or repeated infections over about four years, even though their T cells often stayed somewhat low [11]. Live vaccines, such as the measles–mumps–rubella vaccine, were given safely to most babies once their counts allowed, though doctors hold them back while T cells remain very low [9][10].

And for babies who did have SCID, early detection worked: all seven Dutch babies were alive and well after treatment, and eight of nine Catalan babies were alive and well [10][11].

What the studies found about parents

The English study listened to parents' own words [12]. Many described deep shock: their baby looked healthy, and suddenly they were told something might be seriously wrong. Some said that being told on the phone that it was "probably nothing" made the later news harder. When the result turned out to be "not SCID", parents felt huge relief — but then often a long period of uncertainty while tests continued. Some kept their babies away from other people much more than doctors had asked, worried about older brothers and sisters bringing home germs, felt strain in their relationships, or became unsure about having more children. Parents also said that their family doctors often knew little about these results.

Even so, every parent interviewed said screening was worth it and would recommend it. They asked for simple leaflets and trusted websites, clearer explanation before the heel-prick test that screening can find conditions other than SCID, and the chance to hear from other families who had been through the same thing [12].

What these findings mean for your family

If your baby has been told they have low T cells but not SCID, these studies offer some real reassurance. Most babies in this group stayed well. Many recovered normal T-cell numbers over months or years, and many did not need long-term medicine. Your baby's care team will usually look for a cause, which may include a genetic test, and will use your baby's blood counts to decide whether preventive medicine or a delay in certain vaccines is needed.

It is also completely understandable to feel anxious, even when the news is mostly good. It is reasonable to ask your team what your baby's counts mean, what signs of illness to watch for, how long follow-up is likely to last, and whether there is a nurse, psychologist or parent group you can talk to. The Spanish clinic, for example, includes a psychologist at the very first visit [11].

A few important cautions

These studies were fairly small, because these conditions are rare, and each country used a slightly different version of the screening test, so the numbers are not exactly the same everywhere [5]. None of the studies directly tested whether preventive antibiotics help or not. And although screening is excellent, it can occasionally miss rare forms of immune problems, so any baby with repeated or unusual infections should still be checked, whatever the screening result [14]. The parents in the English study were mostly English-speaking and from similar backgrounds, so families facing language barriers may have even greater needs [12].

What researchers are working on next

Doctors in these countries want to pool their results in international registries (shared databases of patients from many countries), so that they can give families clearer answers about which babies will recover and when follow-up can safely stop [10]. Researchers are also testing extra laboratory steps that could reduce the number of babies referred who turn out not to need care [10][11]. If you are interested in how newer, genome-based newborn screening raises similar questions, In[Neo]Sight has covered the GUARDIAN genomic newborn screening study.

The bottom line for families

Screening for SCID saves lives, and it also finds a larger group of babies whose T cells are low for other reasons. For most of those babies, the outlook is good. What these four studies show is that care works best when it is matched to each baby's own blood results and genetics, and when parents receive clear information and support from the very first phone call.

References

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  9. Soomann M, Prader S, Agyeman PKA, Blanchard-Rohner G, Buettcher M, Kahlert CR, et al. Natural History of Swiss Infants with Non-SCID T-cell Lymphopenia Detected by Newborn Screening: A Cohort Study. J Clin Immunol. 2025;45(1):166. doi:10.1007/s10875-025-01945-4 ↩
  10. Duintjer AJ, Bredius RGM, van den Berg JM, van de Corput L, Dik WA, van Gijn ME, et al. Managing non-SCID T cell lymphopenia after TREC-based newborn screening. J Hum Immun. 2026;2(2):e20250205. doi:10.70962/jhi.20250205 ↩
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  13. Bosticardo M, Yamazaki Y, Cowan J, et al. Heterozygous FOXN1 variants cause low TRECs and severe T cell lymphopenia, revealing a crucial role of FOXN1 in supporting early thymopoiesis. Am J Hum Genet. 2019;105(3):549–561. doi:10.1016/j.ajhg.2019.07.014 ↩
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