Complement C6 Null Mutations in Extreme Prematurity

RATIONALE: Since the prevalence of Complement C6 null alleles is increased among African-Americans and the incidence of premature birth is likewise higher among African-American mothers, we conducted a study to assess a possible association of complement C6 null alleles in African-American mothers of extremely low birth weight infants (ELBW) and ELBW African-American infants. METHODS: We screened 78 ELBW infants and 55 mothers of ELBW infants for three loss-of-function C6 mutations using PCR and heteroduplex analysis. RESULTS: Three infants (3.9%) were found to be heterozygous for a C6 null mutation, a prevalence similar to that in our historical control group (4.9%). Five mothers were heterozygous for a C6 null allele, and one was a compound heterozygote indicating complete deficiency; this prevalence was significantly higher than in our historical control group (p = 0.029). Interestingly, six sets of twins and one set of triplets were born to cohort mothers, and three of the mothers who had given birth to twins were heterozygous for C6 null alleles (p = 0.022). Five of the six mothers bearing C6 null alleles compared with 11 of the other 29 evaluable mothers had histological chorioamnionitis (p = 0.073). CONCLUSIONS: These data suggest that partial C6 deficiency and, by implication, partial deficiency of other terminal complement components represent a risk factor for extreme prematurity, and part of this risk may be related to an increased prevalence in multiple births in mothers bearing C6 null alleles.