Fetal MBL2 haplotypes combined with viral exposure are associated with adverse pregnancy outcomes

Abstract

Objective. To investigate the roles of inherited polymorphisms in the MBL2 gene and exposure to viral infection in the development of a range of adverse pregnancy outcomes, including birthweight <10th percentile (small-for-gestational age, SGA), antepartum hemorrhage (APH), pregnancy-induced hypertensive disorders (PIHD), and preterm birth (PTB).

Methods. This was a case–control study using DNA from newborn screening cards of 717 cases (babies with at least one of the adverse pregnancy outcomes listed above) and 609 controls, to screen for six polymorphisms within the MBL2 gene. These combine to create haplotypes with high (HYPA), intermediate (LYQA, LYPA), low (LXPA), and defective (HYPD, LYQC, LYPB) circulating MBL2 levels.

Results. Significant associations were found between variant MBL2 haplotypes and SGA (LYPA <32 weeks OR 5.37, 95% CI 1.50–17.27), antepartum hemorrhage (LYPA <37 weeks OR 2.29, 95% CI 1.25–4.18), and PIHD (LYQC <32 weeks (OR 17.89, 95% CI 2.20–139.57). Evidence of exposure to infection increased the effect of these associations, (SGA OR 17.00, 95% CI 1.03–252.48; APH OR 5.67, 95% CI 1.73–18.84; PIHD OR 23.80, 95% CI 1.08–1414.76), while no evidence of exposure to infection demonstrated no associations. PTB was significantly associated with the defective HYPD haplotype with evidence of exposure to infection (OR 6.14, 95% CI 1.21–29.89).

Conclusions. This research suggests that the combination of fetal MBL2 haplotypes and exposure to in utero viral infection increases the risk of adverse pregnancy outcomes, including PTB, antepartum hemorrhage, small-for-gestational age and PIHD.

Keywords:

• Fetal MBL2 haplotype
• preterm birth
• small-for-gestational age
• pregnancy-induced hypertension
• antepartum hemorrhage

Acknowledgments

We thank Professor Malcolm Turner (Immunobiology Unit, Institute of Child Health, University College London, UK), for providing us with control material and Universal Heteroduplex Generator sequences for the MBL heteroduplexing. We also thank the staff of the Neonatal Screening Laboratory (Women's and Children's Hospital) for their technical assistance, and Barry Slobedman (Westmead Millenium Institute, NSW, Australia) for providing us with positive control viral material. This research was supported by the National Health and Medical Research Council, The Cerebral Palsy Foundation, The Channel 7 Children's Research Foundation, The University of Adelaide, and The South Australian Government Captive Insurance Corporation. The supporting sources had no influence on the analysis, writing or submission of the manuscript. Professor Gustaaf Dekker is currently an Associate Editor for the Journal of Maternal–Fetal and Neonatal Medicine.