Fetal growth influences lymphocyte subset counts at birth: the Generation R Study
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Updated: Jul 1, 2026
Mapping Infant Immunity with Minimal Input: Integrative Single-Cell and Multiomic Profiling
Published on: April 3, 2026
Liesbeth Duijts1, Liesbeth E Bakker-Jonges, Joost A M Labout
1The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.
Insights
Immune system development continues during pregnancy. Longer gestation increases T, B, and NK lymphocyte counts, while birth weight and fetal growth primarily impact B lymphocyte levels in newborns.
Area of Science:
- Neonatal immunology
- Perinatal health
- Immune system development
Background:
- Infants born preterm or with low birth weight face increased infection risk.
- Immature immune systems are suspected in these vulnerable infants.
Purpose of the Study:
- To investigate the relationship between gestational age, birth weight, and fetal growth with lymphocyte subset counts at birth.
- To understand how factors in late pregnancy influence neonatal immune cell populations.
Main Methods:
- Analysis of cord blood lymphocyte subsets (T, B, NK, T subsets) in 571 infants from the population-based Generation R Study.
- Utilized 6-color flow cytometry for cell counting.
- Employed multivariate linear regression, adjusting for covariates like gender, maternal factors, and delivery mode.
Main Results:
- Each additional week of gestation correlated with a 3-6% increase in T, B, and NK lymphocyte counts (p < 0.05).
- Helper, cytotoxic, and naive T lymphocyte counts increased with gestation (3-5%, p < 0.05), but memory T cells did not.
- Higher birth weight and fetal growth were linked to increased B lymphocyte counts, independent of gestational age.
Conclusions:
- Prolonged gestation is associated with increased lymphocyte subset counts, indicating ongoing immune system maturation.
- Birth weight and fetal growth appear to selectively influence B lymphocyte numbers at birth.
Background:
Preterm born and low-birth-weight infants are at risk for severe infections in infancy. It has been suggested that these infants have an immature immune system.
Objective:
To assess the associations of gestational age, birth weight and fetal growth with absolute lymphocyte subset counts at birth.
Methods:
This study was conducted in 571 infants participating in the Generation R Study, a population-based prospective cohort study from fetal life onwards. Gestational age and birth weight were obtained from midwives and hospital registries. Fetal growth was defined as increase in weight between late pregnancy and birth. Lymphocytes and T lymphocyte subset counts in cord blood were determined by 6-color flow cytometry. Multivariate linear regression models with adjustment for gender, maternal education, smoking, alcohol use, fever and mode of delivery were applied.
Results:
Per week increase of gestational age, T, B and NK lymphocyte counts increased with 3, 5 and 6%, respectively (p < 0.05). Helper, cytotoxic and naive T lymphocyte counts increased with 3, 4 and 5%, respectively (p < 0.05), but memory T lymphocyte counts did not. Increased birth weight and fetal growth were significantly associated with higher B lymphocyte counts, independent of gestational age, but not with the other lymphocyte subset counts.
Conclusions:
Lymphocyte subset counts increase with prolonged gestation, suggesting an ongoing development of the immune system. Birth weight and fetal growth seem to influence only B lymphocyte counts.
