Hum. Reprod. Advance Access originally published online on October 16, 2008
Human Reproduction 2009 24(2):291-299; doi:10.1093/humrep/den377
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Mannose-binding lectin-2 genotypes and recurrent late pregnancy losses
1 Fertility Clinic 4071, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark 2 Department of Clinical Immunology, Aalborg Hospital, Aarhus University, Aalborg, Denmark
3 Correspondence address. E-mail: obc{at}pregnancyloss.dk, rh08636{at}rh.dk
BACKGROUND: Low levels of mannose-binding lectin (MBL) predispose to various infectious and inflammatory disorders and have been reported to be associated with recurrent early miscarriages. Recurrent late pregnancy losses (RLPL) in the second trimester is a rare but devastating syndrome where maternal rather than fetal causes are likely to play a stronger role than in early recurrent miscarriage.
METHODS: We identified 75 patients with at least two late losses of pregnancies with apparently normal fetuses between gestational week 14 and 30 among patients with recurrent pregnancy losses referred to our clinic. Polymorphisms in the MBL2 gene associated with plasma MBL levels were investigated in all patients and in 104 women with two or more children and no miscarriages. The patients were divided into three groups: one with clinical signs of cervical insufficiency, one positive for the lupus anticoagulant (LAC) and an idiopathic group.
RESULTS: Among all patients with RLPL, 26.7% had MBL2 genotypes associated with MBL deficiency compared with 12.5% in controls [odds ratio (OR) 2.55; 95% confidence interval (CI) 1.17–5.52; P < 0.02]. Among patients with clinical signs of cervical insufficiency or the LAC, the frequency of genotypes associated with MBL deficiency was not significantly increased. However, among 38 patients with idiopathic RLPL, 36.8% carried low-producing MBL2 genotypes, which was significantly more than in controls (OR 4.08, 95% CI 1.70–9.83, P = 0.001).
CONCLUSIONS: MBL deficiency is strongly associated with idiopathic RLPL. This may point towards a role for excessive inflammatory disturbances as a cause of the syndrome.
Key words: cervical insufficiency/mannose-binding lectin/miscarriage/recurrent miscarriage/stillbirth
Submitted on July 30, 2008; resubmitted on September 17, 2008; accepted on September 22, 2008.