Genetic Contribution to the Pain and Progress of Labor
Abstract Number: 92
Abstract Type: Original Research
Background: Patient characteristics may contribute to the progress and pain of labor. However, demographic variables only contribute a small amount to observed variability. Genotype at two common SNPs on the B2AR gene appears to influence the incidence of preterm labor and a SNP in the opioid receptor affects pain sensitivity and opioid requirement after surgery. Mixed-effects modeling permits robust separation of individual variability from randomly distributed measurement noise. We developed a population model for labor pain and progress to evaluate the effect of these genetic variables in 150 patients.
Methods: We prospectively enrolled a cohort of 150 nulliparous parturients from a single private practice. Heat, cold and pressure threshold were tested in the third trimester. All relevant labor and delivery information was extracted from the electronic medical record. Cervical dilation, pain scores, labor management data (oxytocin use, induction, analgesia, membrane rupture) were associated with the time of occurrence. Genomic DNA was prepared with standard measures. Polymerase chain reaction was used to amplify the genes for sequencing. Labor progress was modeled with a biexponential function and labor pain, a sigmoidal function. The covariates were tested with NONMEM.
Results: The best multivariate model for labor progress suggested that B2AR genotype CC at the 27 position was associated with later transition to active labor (P<0.04), heavier maternal weight was associated with faster active labor but slower latent labor (P<0.04), Black patients had slower latent labor and Asian patients had a later transition to active labor (P<0.0004) and the presence of an epidural was associated with 73% slower progress (P<0.0001).
Twelve percent of our cohort was homozygous mutant (GG) at the 118 position of the OPRM1 gene; they were all Asian or White. Therefore, we optimized our model for either ethnicity or OPRM1 genotype. When optimized for genotype, OPRM1 (GG) homozygotes had faster development of pain (P<0.01), taller patients had slower development of pain (P<0.04) and patients who had instrumental vaginal deliveries had more pain in early labor (P<0.01). When optimized for ethnicity, Black patients had faster development of pain, (P<0.02), taller patients developed pain more slowly (P<0.04), instrumental vaginal delivery and increased sensitivity to a cold stimulus was associated with more pain in early labor (P<0.01, 0.02).
Conclusions: B2AR genotype at the 27 position was associated with later transition to active labor. The demographic associations with labor progress were similar to those found by Debiec et al (2009) except both Black and Asian patients had later transitions to active labor and heavier mothers had both slower latent labor but faster active labor. Homozygous (GG) genotype at OPRM1 118 position was predictive of more rapid development of painful labor. Cold threshold may be a proxy for OPRM1 genotype.