Birth Order and Cord Immunoglobulin E: Results Using a High-Sensitivity Immunoglobulin E Protocol

Abstract

Background: Studies have shown an inverse association between birth order and allergic disease risk; some but not all have shown an inverse association between cord blood immunoglobulin E (IgE) and birth order. We further examined the relationship between birth order and cord blood IgE in a racially diverse birth cohort. Methods: Women were interviewed about their pregnancy history, and their babies’ cord blood was collected to measure total IgE using a high-sensitivity protocol (lower detection limit 0.01 IU/ml). We analyzed cord IgE as both a continuous and categorical measure. Results: Of the 733 children, 171 (23%) were first born, 92 (13%) were first born with the mother having prior pregnancies but no live births, and 470 (64%) were born second or later. By birth order, the geometric means ± standard deviations were: first born 0.26 ± 4.2 IU/ml, first born after prior pregnancies 0.35 ± 3.9 IU/ml, second born 0.30 ± 4.8 IU/ml, third born 0.28 ± 5.1 IU/ml, and fourth born or greater 0.28 ± 4.5 IU/ml (trend p = 0.51). Other factors considered (maternal allergic disease history, age, race, exposure to smoking and cats/dogs during pregnancy, fetal gender, season of delivery) neither modified nor confounded these relationships. Conclusions: Unlike some previous reports, there was no association between total cord IgE level and birth order. Mechanisms other than cord IgE should be studied in the quest to understand the role of birth order in allergic disease risk. Categorization of a continuous measure of IgE may incorrectly create statistically significant results.

Relationship of Cord Blood Immunoglobulin E and Maternal Immunoglobulin E with Birth Order and Maternal History of Allergy in Albanian Mother/Neonate Pairs

“…In contrast to reports from some other regions in the world, we did not find a statistically significant birth order effect in cIgE. Our results are in line with the results reported by Bergmanini [ 20 ] and several other authors [ 7 , 22 , 23 ] who found a nonsignificant relationship between these parameters. Significant differences in cIgE levels by birth order were found only in neonates born by mothers with mIgE < 100 and, non-significant difference in neonates born by mothers with mIgE > 100.…”

“…In this study, we found that cIgE levels were not normally distributed and that most cIgE levels were below 0.5 kIU/L, as stated in previous reports [ 20 , 21 ]. The frequency of newborns with detectable levels of cIgE was 26.12% which is higher than frequencies reported in several studies which used the same cut-off values of 0.5 kIU/L [ 21 , 22 ], but lower than in some other [ 7 , 23 , 24 ] and similar to results of Edenharter et al [ 25 ]. Whereas, the mean cIgE level among detectable samples was 1.59 IU/l, with a range of 0.51 to 8.24 kIU/l, similar to findings from Nabavi et al [ 10 ] but lower than the one reported by Goldstein which resulted from a sample taken from a community cohort with high prevalence of asthma [ 23 ].…”

“…Several studies have been conducted to investigate the effect of parity on cIgE levels and to determine whether the sibling effect might be mediated in part by in utero programming rather than postnatal exposure [ 26 ]. Data from several investigations show that birth order is associated with lower IgE levels in cord blood [ 14 , 20 , 26 - 28 ] but also, there are other studies which found no association between birth order and cIgE levels [ 7 , 22 , 23 ]. We came across only one study which found that birth order is associated with higher cIgE levels [ 10 ].…”

Toll-like receptors and microbial exposure: gene–gene and gene–environment interaction in the development of atopy

“…For total IgE levels at birth, one study showed an association between larger sibship size and decreased cord blood total IgE levels [23]. However, other studies, including one in one of our own birth cohorts, did not replicate this protective effect on cord blood IgE levels [26,27]. Furthermore, no evidence for association of larger sibship size on decreased total IgE levels at older ages has been reported [22,28].…”

Sibling number and prevalence of allergic disorders in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study

“…According to this theory, maternal immunomodulation acquired through multiple pregnancies might be transmitted to the developing fetus [5-7]. Although a cohort study in the USA found no association between birth order and total cord blood IgE level [8], another recent study reported a significant interaction between birth order and IL13 polymorphisms affecting allergic sensitization: the effect of IL13 was restricted only to firstborn children, suggesting adverse prenatal programming in firstborn offspring [9]. …”