Brothers and reduction of the birth weight of later-born siblings

It has been speculated whether maternal immune responses against male-specific minor histocompatibility (H-Y) antigens affect pregnancies negatively. This study explores, on a population level, whether previous births of boys compared with girls are associated with a decrease in birth weight of later-born siblings. The population was identified in the Danish Birth Registry and consisted of all Danish women who gave birth to their first-born singleton from 1980 to 1998. The women were followed until 2004, and their subsequent births were recorded. A total of 545,839 second- to fourth-born children were identified. The authors used linear regression to analyze the association between sex of preceding children and birth weight of subsequent siblings. Brothers compared with sisters reduced the birth weight of later-born siblings. One or two brothers, respectively, reduced the mean birth weight of later-born boys by 29 g (p = 0.0001) and 38 g (p = 0.0001) and later-born girls by 17 g (p = 0.0001) and 21 g (p = 0.0001) compared with later-born siblings with no brothers. Part of this association was due to a shorter gestation among later-born siblings with brothers. An explanation for these results could be maternal immune reactions directed against the H-Y antigens initiated during pregnancies with boys. The findings might add to the understanding of both normal and pathologic pregnancies.