Elsevier

Early Human Development

Volume 87, Issue 2, February 2011, Pages 67-72
Early Human Development

Best Practice Guideline article
Transplacental transport of IgG antibodies to preterm infants: A review of the literature

https://doi.org/10.1016/j.earlhumdev.2010.11.003Get rights and content

Abstract

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections. Therefore, the newborn is dependent on transplacental transport of Immunoglobulin G (IgG), an active, FcRn receptor mediated process. Fetal IgG rises from approximately 10% of the maternal concentration at 17–22 weeks of gestation to 50% at 28–32 weeks of gestation. If transplacental acquired IgG is lower in preterm than in term infants, preterm infants are especially at risk for these vaccine-preventable diseases.

The aim of this study was to review the transplacental transfer of IgG against vaccine-preventable diseases (measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, tetanus, pertussis and polio) to (pre)term infants and to identify factors that influence the transplacental transfer of these antigens.

After selection, 18 studies on transplacental transport to preterm infants were included. In general, these studies showed for all antibodies that preterm infants have lower antibody concentrations compared with term infants. Maternal and infants antibody concentrations showed a strong correlation in 7 of the included studies. Infant antibody concentration was not associated with parity, maternal age, height or weight. Infants of vaccinated mothers had lower anti-measles antibody titers than infants of natural immunized mothers. IgG titers of preterm infants decrease earlier in life below protective antibody titers than term infants. Combined with their immature immune system, this puts preterm infants at increased risk for vaccine-preventable diseases.

Introduction

Newborn infants, especially preterm infants, have an immature immune system, which is not capable to actively protect against vaccine-preventable infections like diphtheria, tetanus, pertussis, measles, mumps, rubella, Haemophilus influenzae type B and Neisseria meningitidis C [1], [2], [3]. Maternal Immunoglobulin G (IgG) is transported over the placenta (transplacental transport) by an active, FcRn receptor mediated process during pregnancy and protects (pre)term infants against the different infections during the first months of life [4].

In 1967, Hobbs et al found an exponential relationship between total IgG and gestational age (GA) in preterm infants [5]. In the first trimester, very little IgG is transported to the fetus [6], [7]. In the second trimester, the fetal IgG rises from approximately 10% of the maternal concentration at 17–22 weeks of gestation to 50% at 28–32 weeks of gestation as determined by chordocentesis [4], [8]. In the third trimester, the increase of fetal IgG concentration between 29 and 41 weeks of gestation is two times as high as between 17 and 28 weeks of gestation [7]. The concentrations of the IgG subclasses in the fetus are not equally distributed [9], because IgG1 and IgG4 are transported more efficiently than IgG3, and IgG2 is transported the least efficiently [10]. This is caused by different affinity for FcY receptors [11]. Therefore, transplacental transport of antibodies of vaccine components differs between the elicited types of IgG antibodies, as polysaccharides vaccines (like MenC and Hib) elicit mainly IgG2 antibodies [12], [13], whereas protein vaccines (like diphtheria, tetanus, and pertussis) elicit more IgG1 and IgG3 antibodies [14], [15]. In general, higher IgG levels at birth are thought to be associated with better and longer protection and until the first vaccinations are administered, transplacental transported maternal IgG is the main humoral protectin against vaccine-preventable diseases for infants, adjusted with herd immunity in vaccination areas. We hypothesize that preterm infants have lower amounts of transplacental acquired IgG than term infants, which poses them especially at risk for these vaccine-preventable diseases. Beside GA, other factors, such as birth weight (BW), age of the mother or parity may influence transplacental transport of IgG. Increased insight in the factors involved in transplacental transport of IgG may help to identify infants at risk for vaccine-preventable infections and to develop strategies to decrease these risks in (pre)term infants.

Therefore, the aim of this study was to review the literature on transplacental transfer of IgG, against measles, rubella, varicella-zoster, mumps, Haemophilus influenza type B, diphtheria, pertussis tetanus and polio especially in preterm infants and to identify factors that influence the transplacental transfer of these antigens.

Section snippets

Methods

A literature search was performed in Pubmed including articles published until February 2010.

Key words and limits were: ((“gamma-Globulins”[Mesh] OR “Immunoglobulin G”[Mesh]) AND (“Infant, Premature”[Mesh])) OR ((“Antibody Formation”[Mesh]) AND (“Infant, Premature”[Mesh])) OR (((“Maternal–Fetal Exchange”[Mesh]) OR (“Immunity, Maternally-Acquired”[Mesh])) AND (“Infant, Premature”[Mesh])) OR ((“Antibodies, Viral”[Mesh]) AND (“Infant, Premature”[Mesh])). Related articles in PubMed were also

Measles (n = 8)

Measles antibody titers or percentages of protective measles antibody titers were lower in preterm compared with term infants or compared to their mothers (Table 1). [16], [17], [18], [22], [23], [30], [31], [32] Preterm infants of vaccinated mothers had lower measles antibody concentrations than preterm infants of naturally infected mothers, since mothers who have suffered from measles have higher antibody concentrations [32]. In all studies which analyzed the transplacental transport ratio,

Influencing factors

A strong correlation between maternal and infant IgG concentrations for both preterm and term infants was observed in 8 of the included studies [18], [19], [20], [21], [22], [24], [25], [26], [28], [32], [33], while 3 of the included studies found this correlation only between term infants and their mothers [20], [21], [28].

In 6 of the included studies, none of the measured antibodies was associated with parity [17], [25], [26], [30], [31], maternal age [17], [30], [31], maternal weight [29],

Discussion

Our review shows that the transplacental transfer of maternal antibodies against measles, rubella, varicella-zoster, mumps, Hib, diphtheria, tetanus, bordetella pertussis and polio is lower in preterm infants than in term infants. This difference is more pronounced in very preterm infants (GA < 32 weeks) than in preterm infants with a GA of 32–36 weeks. There is a strong correlation between maternal and infant antibody concentrations and maternal vaccination status influences infant IgG antibody

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