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  • Title: Frequency and impact of obstetric complications prior and subsequent to unexplained secondary recurrent miscarriage.
    Author: Nielsen HS, Steffensen R, Lund M, Egestad L, Mortensen LH, Andersen AM, Lidegaard Ø, Christiansen OB.
    Journal: Hum Reprod; 2010 Jun; 25(6):1543-52. PubMed ID: 20395221.
    Abstract:
    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 <or= 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.
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