More Than a Blood Test: What New Research Tells Families About Infection in Newborn Babies

Three 2026 studies by Hanenberg et al., Liu et al. and Andersen et al. on infections that blood tests miss, why infected babies can be so differently ill, and the link with cerebral palsy

Doctors usually decide whether a newborn has a serious infection by growing germs from a blood sample, but this test can miss infections and says little about how sick a baby is. Three new studies from Germany, the United States and Denmark suggest that testing the umbilical cord can reveal hidden infections, that babies with the same germ can be very differently ill, and that early infection in babies born at or near full term is linked to a small but real rise in the chance of cerebral palsy.

Why infection in newborn babies is so hard to pin down

A serious bloodstream infection in a newborn is called sepsis. Babies cannot tell us how they feel, and the early signs, such as breathing difficulties, a change in colour or temperature, or poor feeding, look like many other newborn problems. Specialists agree that there is still no single, universally accepted definition of newborn sepsis and that the main test, the blood culture, has real limitations [1]. A blood culture means putting a few drops of the baby's blood into a bottle and waiting a day or two to see whether bacteria grow.

Families and doctors have faced this uncertainty for decades. In a large American study of very small premature babies born in the early 1990s, fewer than 2 in 100 had an infection proven by blood culture in the first days of life. Yet almost half of all the babies received five days or more of antibiotics, because doctors could not be sure the negative tests were right [2]. Those researchers asked for better ways to diagnose infection. Since then, infections have remained a major danger: in a more recent American study, 29 in 100 premature babies with early infection died [3]. Experts estimate that for every baby with a positive culture, between 6 and 16 babies are treated for a suspected infection that the culture never confirms. One reason is that a newborn has very little blood; experts recommend a sample of around half a millilitre to one millilitre, at most about a fifth of a teaspoon [4]. In one hospital, about a third of culture bottles held less blood than recommended [5]. Meanwhile, doctors caring for adults have moved toward defining sepsis by how much an infection affects the body's organs, such as the lungs, heart and circulation, not only by whether germs grow [6]. A newborn version of such an organ score, called the neonatal Sequential Organ Failure Assessment (nSOFA), was tested in several hospitals and helped show which infected premature babies were most at risk [7]. Earlier research had also hinted that newborn infection is linked to cerebral palsy, but most of that evidence came from premature babies, with less known about babies born at full term [8].

Three separate studies looking at three different groups of babies

The three studies were done by different teams who did not work together. We have put them side by side because each looks at a different part of the same question: finding infection, understanding how sick it makes a baby, and what it may mean years later. The babies in each study were different, so the numbers should not be mixed.

Finding hidden infection (Germany). In the German Neonatal Network (GNN), a research group of 67 newborn intensive care units in Germany, doctors froze a small piece of umbilical cord from very small premature babies (under 1500 g, about 3.3 pounds) born between 2009 and 2021 [9]. Years later, scientists tested 15 290 of these cord samples for the genetic material (DNA) of the two types of bacteria that most often cause infection right after birth, using a technique called quantitative polymerase chain reaction (qPCR), which can find tiny amounts of DNA. They compared this with the babies' blood cultures from the first 3 days.

How sick infection makes a baby (United States). At four university hospital newborn units, one at the University of Florida and three at Johns Hopkins, researchers looked back at the records of 221 premature babies, born at 33 weeks of pregnancy or earlier, who developed a bloodstream infection after their first 3 days of life [10]. Using the nSOFA score, which adds up how much breathing support, blood-pressure medicine and platelet (clotting cell) problems a baby has, they followed each baby hour by hour.

What happens later (Denmark). Using Denmark's national health records, researchers followed 1 034 416 children born at 35 weeks of pregnancy or later between 2004 and 2022 to see whether infection in the first week of life was linked to cerebral palsy, a lifelong condition that affects movement and posture [11].

What the researchers found

In Germany, the cord test was positive in 546 babies, compared with 90 positive blood cultures [9]. Sadly, 34 babies died of infection in their first week. The cord test had picked up 14 of them, while the blood culture had picked up 8. Of the 548 babies who had the most serious kind of bleeding in the brain (called grade IV intraventricular haemorrhage), the cord test had flagged 45 and the blood culture only 9. Babies whose cord test was positive but whose blood culture was negative also had more of these serious problems than babies with two negative tests. However, it is important to know that most babies with a positive cord test did well: only about 3 in 100 of them died of infection in the first week.

In the United States, 20 of the 221 babies (about 9 in 100) died [10]. What stood out was how different the babies were. Some barely changed: about 3 in 10 of the infections in babies who survived never registered any organ problems on the score during the first week. Others became critically ill, some within the first day. This happened even with the same type of germ.

In Denmark, about 8 in 1000 children (8151 children) were diagnosed with sepsis in their first week [11]. Cerebral palsy was later diagnosed in 68 of them, which is just under 1 in 100. Among children without early sepsis, it was about 1 in 1000. After accounting for other factors, children with early sepsis had about 8 times higher odds of cerebral palsy. The link looked stronger when the infection was confirmed by a culture, and stronger still for meningitis (infection of the lining around the brain), but these figures were based on small numbers and were not adjusted for other factors.

What these findings mean for your baby

These studies do not change how your baby is tested or treated today. The cord test was done years after birth on frozen samples, it only looked for two kinds of bacteria, and the researchers could not rule out that some positive results came from bacteria that reached the cord sample after delivery rather than from true infection [9]. It is not yet a hospital test. What the study does show is something many neonatal teams already know: a negative blood culture does not always rule out infection, which is why doctors look at the whole baby and not only at a test result. If you would like to know how teams decide which babies need antibiotics at birth, our article on the early-onset sepsis calculator trial explains one approach.

If your baby has a bloodstream infection, the American study is a reminder that the name of the germ does not tell the whole story [10]. Asking the team how your baby's breathing, circulation and blood counts are doing can give you a clearer picture than the germ's name alone.

If your baby born at or near full term had sepsis in the first week, the Danish study may sound worrying, but the numbers are reassuring in an important way: more than 99 in 100 such children did not develop cerebral palsy [11]. This kind of study shows a link, not proof that infection causes cerebral palsy. Your baby's doctors may suggest checking movement and development at routine visits, and our article on early detection of cerebral palsy explains how early signs can be spotted.

Honest limits of the research

Each study has weaknesses. In Germany, the sickest babies were less likely to be enrolled, probably because parents had to give written consent and some babies died very soon after birth [9]. The American study looked back at existing records and had only a few babies with some germs [10]. In Denmark, many diagnoses of newborn sepsis in health records turned out, when checked, not to be clearly proven infections [12]. That is why the researchers also looked separately at infections confirmed by culture.

What researchers are working on next

The German team suggests that a bedside version of the cord DNA test could one day give answers much sooner after birth than a blood culture, although this has not yet been tried [9]. Experts who reviewed earlier DNA-based blood tests have called for proper trials to show whether such tests actually improve care [13]. Others want future studies of newborn infection to measure how sick organs become, not just which germ grew, and to build a newborn definition of sepsis around this [10]. Longer follow-up of children who had early infection will help show who needs extra developmental support.

The bottom line

Infection in newborn babies is more than a single blood test result. Some infections are hidden from today's tests, infected babies can be very differently ill, and early infection in babies born at or near full term is linked to a small but real increase in the chance of cerebral palsy. For families, the practical message is to trust a team that looks at the whole baby, to ask how your baby's organs are coping, and to take part in routine developmental check-ups.

References

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  2. Stoll BJ, Gordon T, Korones SB, et al. Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr. 1996;129(1):72-80. doi:10.1016/S0022-3476(96)70192-070192-0) ↩
  3. Stoll BJ, Puopolo KM, Hansen NI, et al. Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies. JAMA Pediatr. 2020;174(7):e200593. doi:10.1001/jamapediatrics.2020.0593 ↩
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  6. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. doi:10.1001/jama.2016.0287 ↩
  7. Fleiss N, Coggins SA, Lewis AN, et al. Evaluation of the Neonatal Sequential Organ Failure Assessment and Mortality Risk in Preterm Infants With Late-Onset Infection. JAMA Netw Open. 2021;4(2):e2036518. doi:10.1001/jamanetworkopen.2020.36518 ↩
  8. Ong WJ, Seng JJB, Yap B, et al. Impact of neonatal sepsis on neurocognitive outcomes: a systematic review and meta-analysis. BMC Pediatr. 2024;24(1):505. doi:10.1186/s12887-024-04977-8 ↩
  9. Hanenberg L, Fortmann I, Rupp J, et al. Umbilical Cord Quantitative Polymerase Chain Reaction and Sepsis Complications for Neonates. JAMA Netw Open. 2026;9(10):e2637159. doi:10.1001/jamanetworkopen.2026.37159 ↩
  10. Liu S, Missigman E, Al Gharaibeh FN, et al. Heterogeneity of Critical Organ Dysfunction During Late-Onset Bacteremia in Preterm Infants. JAMA Netw Open. 2026;9(9):e2632792. doi:10.1001/jamanetworkopen.2026.32792 ↩
  11. Andersen M, Matthiesen NB, Murra M, Nielsen SY, Henriksen TB. Early-Onset Neonatal Infection and Cerebral Palsy. JAMA Netw Open. 2026;9(5):e2614775. doi:10.1001/jamanetworkopen.2026.14775 ↩
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  13. Dierikx TH, Visser DH, de Meij T, et al. Molecular assays for the diagnosis of sepsis in neonates: a diagnostic test accuracy review. Cochrane Database Syst Rev. 2025;3(3):CD011926. doi:10.1002/14651858.CD011926.pub3 ↩