Frequency and impact of obstetric complications prior and subsequent to unexplained secondary recurrent miscarriage

BACKGROUND The chance of a live birth after a diagnosis of secondary recurrent miscarriage (SRM) is reduced in patients who, prior to the miscarriages, gave birth to a boy and carry HLA class II alleles that efficiently present male-specific (H-Y) antigens to the immune system. Information about obstetric complications in births prior and subsequent to the SRM diagnosis is limited. The relations between maternal carriage of H-Y-restricting HLA, fetal sex, obstetric complications and prognosis are unknown. METHODS Women with unexplained SRM referred to the Danish Recurrent Miscarriage Clinic between 1986 and 2006 (n = 358) were included; 213 gave birth after the diagnosis. Controls, retrieved from the Danish National Birth Registry, were all women with singleton birth of parity 0, 1982–2005 (n = 608 068) and parity 1, 1986–2008 (n = 510 264). Cross-linkage to the National Discharge Registry identified birth complication diagnoses related to the relevant births among patients and controls. RESULTS The sex ratio was 1.49 in births prior to SRM and 0.76 in birth after SRM (P < 0.0001). For SRM patients with only late miscarriages (>10 weeks gestation), the corresponding sex ratios were 2.31 and 0.21. Compared with the control groups, obstetric complications were more frequent both before (39% versus 24% P ≤ 0.01) and after (19% versus 14%, P = 0.01) SRM diagnosis. Births were more frequently complicated when the child was a boy (44% versus 31%, P = 0.02) before and a girl (24% versus 13%, P = 0.04) after SRM diagnosis. SRM patients with H-Y-restricting HLA class II alleles and a firstborn boy gave birth to children who weighed on average 381 g less (P = 0.006) and were born 0.9 weeks earlier (P = 0.06) and their births had more obstetric complications (P = 0.05) than patients with the same HLA alleles but a firstborn girl. CONCLUSIONS Obstetric complications, sex ratios in births prior and subsequent to SRM and maternal carriage of H-Y-restricting HLA class II alleles are associated parameters. Immune responses against fetal H-Y antigens initiated in the pregnancy prior to the SRM may play a causal role in SRM.