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Fetal growth requires remodelling of maternal spiral arteries to provide an adequate maternal blood supply to the placenta. This arterial transformation is achieved by placental trophoblast cells, which invade into the uterine wall. Under-invasion is associated with fetal growth restriction; but if invasion is excessive large babies can result. A growing body of evidence suggests that this process is controlled by interactions between killer-cell immunoglobulin-like receptors (KIRs) expressed on maternal uterine natural killer cells (uNK) and their corresponding human leukocyte antigen-C (HLA-C) ligands on invading trophoblast. Mothers with the\n                    <jats:italic>KIR AA<\/jats:italic>\n                    genotype and a fetus with a paternal\n                    <jats:italic>HLA-C2<\/jats:italic>\n                    allele tend to have small babies, because this combination inhibits cytokine secretion by uNK. Mothers with the activating\n                    <jats:italic>KIR2DS1<\/jats:italic>\n                    gene and an\n                    <jats:italic>HLA-C2<\/jats:italic>\n                    fetus are more likely to have large babies. When KIR2DS1 binds to HLA-C2 this increases secretion of cytokines that enhance trophoblast invasion. We conclude that specific combinations of the highly polymorphic gene systems,\n                    <jats:italic>KIR<\/jats:italic>\n                    and\n                    <jats:italic>HLA-C<\/jats:italic>\n                    , contribute to successful reproduction by maintaining birthweight between two extremes.\n                  <\/jats:p>","DOI":"10.1098\/rstb.2014.0071","type":"journal-article","created":{"date-parts":[[2015,1,19]],"date-time":"2015-01-19T22:59:03Z","timestamp":1421708343000},"page":"20140071","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":82,"title":["The role of the maternal immune system in the regulation of human birthweight"],"prefix":"10.1098","volume":"370","author":[{"given":"Ashley","family":"Moffett","sequence":"first","affiliation":[{"name":"Department of Pathology and Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, 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