pediatrics
Perinatal Physiology
Neonatal Immunologic Function
(See also Cellular Components of the Immune System and Fetal immune function develops throughout gestation, and, thus, immunodeficiency is most severe in preterm infants born at earlier gestational ages. Most immune mechanisms are not fully functional even in full-term infants. Thus, all neonates and young infants are immunodeficient relative to adults and are at increased risk of overwhelming infection. This risk is enhanced by maternal illness, neonatal stress, and medications (eg, immunosuppressants, antiseizure medications). Neonates’ decreased immune response may explain the absence of fever or localized clinical signs (eg, meningismus) with infection. In the fetus, phagocytic cells present at the yolk sac stage of development are critical for the inflammatory response that combats bacterial and fungal infection. Granulocytes can be identified in the second month of gestation, and monocytes can be identified in the fourth month of gestation. Their level of function increases with Gestational Age but is still low at term. At birth, the ultrastructure of neutrophils is normal, but in most neonates, chemotaxis of neutrophils and monocytes is decreased because of an intrinsic abnormality of cellular locomotion and adherence to surfaces. These functional deficits are more pronounced in preterm infants. By about the 14th week of gestation, the thymus is functioning, and hematopoietic stem cell–produced lymphocytes accumulate in the thymus for development. Also by 14 weeks, T cells are present in the fetal liver and spleen, indicating that mature T cells are established in the secondary peripheral lymphoid organs by this age. The thymus is most active during fetal development and in early postnatal life. It grows rapidly in utero and is readily noted on chest x-ray in a healthy neonate, reaching a peak size at age 10 years then involuting gradually over many years. The number of T cells in the fetal circulation gradually increases during the second trimester and reaches nearly normal levels by 30 to 32 weeks gestation. At birth, neonates have a relative T lymphocytosis compared to adults. However, neonatal T cells do not function as effectively as adult T cells. For example, neonatal T cells may not respond adequately to antigens and may not produce cytokines. B cells are present in fetal bone marrow, blood, liver, and spleen by the 12th week of gestation. Trace amounts of IgM and IgG can be detected by the 20th week, and trace amounts of IgA can be detected by the 30th week. Because the fetus is normally in an antigen-free environment, only small amounts of immunoglobulin (predominantly IgM) are produced in utero. Elevated levels of cord serum IgM indicate in utero antigen challenge, usually caused by congenital infection. Almost all IgG is acquired maternally from the placenta. After 22 weeks gestation, placental transfer of IgG increases to reach maternal levels or greater at term. IgG levels at birth in preterm infants are decreased relative to gestational age. The passive transfer of maternal immunity from transplacental IgG and secretory IgA and antimicrobial factors in breast milk (eg, IgG, secretory IgA, white blood cells, complement proteins, lysozyme, lactoferrin) compensate for the neonate’s immature immune system and confer immunity to many bacteria and viruses. Protective immune factors in breast milk coat the gastrointestinal and upper respiratory tracts via mucosa-associated lymphoid tissue and decrease the likelihood of invasion of mucous membranes by respiratory and enteric pathogens. Over time, passive immunity begins to wane, reaching a nadir when the infant is 3 to 6 months old. Preterm infants, in particular, may become profoundly hypogammaglobulinemic during the first 6 months of life. By age 1 year, the IgG level rises to about 60% of average adult levels. IgA, IgM, IgD, and IgE, which do not cross the placenta and therefore are detectable only in trace amounts at birth, increase slowly during childhood. IgG, IgM, and IgA reach adult levels by about age 10 years. Although the antibody response to initial doses of vaccines may be lower in preterm infants than in term infants, preterm infants are still able to mount a protective response to most vaccines and should be Childhood Vaccination Schedules as term infants. However, infants who weigh < 2 kg when they receive their first dose of 1.Gagneur A, Pinquier D, Quach C: Immunization of preterm infants.Hum Vaccin Immunother11(11):2556–2563, 2015. doi: 10.1080/21645515.2015.1074358 