What methods minimize taking blood samples from babies born too soon?

Key messages

• Taking blood from the umbilical cord or placenta instead of directly from babies born too soon (preterm) likely reduces retinopathy of prematurity, an eye disease that can affect vision, and may reduce complications such as brain bleeding (intraventricular hemorrhage) and bronchopulmonary dysplasia, a type of lung disease.

• We do not know if returning blood after testing or using strict rules to limit blood tests help to minimize blood sampling and the complications associated with it.

• We need large, high-quality studies that follow babies until they are at least three years old to better understand what methods work best and how they affect longer-term development. Future studies should investigate newer approaches, such as taking tiny amounts of blood for testing or using non-blood body fluids, such as saliva and urine, as well as the methods described here.

Why is minimizing blood sampling from babies born too early important?

Babies born before 37 weeks of pregnancy (known as 'preterm') often need many blood tests while they are in hospital. Because these babies are very small, repeated blood sampling can remove a large amount of their total blood volume. This can lead to the need for blood transfusions.

Several methods have been studied to reduce blood loss, such as using blood from the umbilical cord or placenta at birth, using very small blood samples, returning blood to the baby after testing, or following strict rules to limit how often blood is taken. It remains unclear which of these methods is effective and safe.

What did we want to find out?

We wanted to find out whether different strategies to reduce blood sampling in preterm babies:

• improves their survival;

• reduces physical or mental developmental issues, including blindness, deafness, and cerebral palsy (a lifelong condition that affects movement, posture, and muscle control), at 18 months of age and older;

• reduces serious complications, including retinopathy of prematurity (an eye disease that can affect vision), brain bleeding (intraventricular hemorrhage), and bronchopulmonary dysplasia, a type of lung disease.

What did we do?

We searched for studies that compared different blood-saving strategies with the usual care given to preterm babies. We compared and summarized the results of the studies and rated our confidence in the evidence, based on how the studies were designed and how many babies were involved.

What did we find?

We found five studies involving 365 very preterm babies (born more than three months before the due date). Two studies were conducted in India, two in the USA, and one in Israel. The smallest study included 20 babies, and the largest, 102.

One study received funding from the government, a charity telethon, and a technology company. The author of another study was also an owner of the company that made and supplied the blood-returning device used in the study. The three remaining studies either did not provide funding details or stated that there were no conflicts of interest.

Main results

None of the studies reported results for physical or mental developmental issues (including blindness, deafness, and cerebral palsy) when the babies were 18 months of age or older.

Using blood from the umbilical cord or placenta at birth, instead of taking blood directly from the baby:

• may reduce brain bleeding during the first week of life: about 12 fewer babies in every 100 may have severe brain bleeding (from 2 to 16 fewer babies; 2 studies, 160 babies);

• may reduce bronchopulmonary dysplasia: about 13 fewer babies in every 100 may develop this lung condition (from 25 fewer to 4 more babies; 2 studies, 152 babies);

• probably reduces retinopathy of prematurity requiring treatment before hospital discharge: about 19 fewer babies in every 100 are likely to develop retinopathy of prematurity (from 6 to 27 fewer babies; 2 studies, 152 babies).

We do not know if using blood from the umbilical cord or placenta improves babies' survival rates.

We also do not know if (1) devices that return blood into the baby's bloodstream after testing, or (2) following strict rules to limit blood sampling make any difference to:

• survival rates;

• serious complications (including retinopathy of prematurity, brain bleeding, and bronchopulmonary dysplasia).

Only one small study looked at each of these approaches.

What are the limitations of the evidence?

We are moderately confident that using umbilical cord or placenta blood significantly reduces the number of babies who develop retinopathy of prematurity – our confidence was reduced because relatively few babies were studied. We have little to no confidence in the evidence on survival and other serious complications (brain bleeding and bronchopulmonary dysplasia) because the studies were very small, and in some cases, the results varied.

We are not confident in the evidence for (1) devices that return blood into the baby's bloodstream and (2) following strict rules to limit blood sampling because:

• too few studies investigated these methods;

• the number of babies included was small;

• we had concerns about these studies' methods, reporting of results, or both.

How up to date is this evidence?

The evidence is current to September 2025.