Oxytocin receptor single nucleotide polymorphism predicts atony-related postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage remains a key contributor to overall maternal morbidity in the United States. Current clinical assessment methods used to predict postpartum hemorrhage are unable to prospectively identify about 40% of hemorrhage cases. Oxytocin is a first-line pharmaceutical for preventing and treating postpartum hemorrhage, which acts through oxytocin receptors on uterine myocytes. Existing research indicates that oxytocin function is subject to variation, influenced in part by differences in the DNA sequence within the oxytocin receptor gene. One variant, rs53576, has been shown to be associated with variable responses to exogenous oxytocin when administered during psychological research studies. How this variant may influence myometrial oxytocin response in the setting of third stage labor has not been studied. We tested for differences in the frequency of the oxytocin receptor genotype at rs53576 in relationship to the severity of blood loss among a sample of individuals who experienced vaginal birth. METHODS: A case-control prospective design was used to enroll 119 postpartum participants who underwent vaginal birth who were at least 37 weeks of gestation. Cases were defined by either a 1000 mL or greater blood loss or instances of heavier bleeding where parturients were given additional uterotonic treatment due to uterine atony. Controls were matched to cases on primiparity and labor induction status. Genotype was measured from a maternal blood sample obtained during the 2nd postpartum month from 95 participants. Statistical analysis included bivariate tests and generalized linear and Poisson regression modeling. RESULTS: The distribution of the genotype across the sample of 95 participants was 40% GG (n = 38), 50.5% AG (n = 48) and 9.5% AA (n = 9). Blood loss of 1000 mL or greater occurred at a rate of 7.9% for GG, 12.5% for AG and 55.6% for AA participants (p = 0.005). Multivariable models demonstrated A-carriers (versus GG) had 275.2 mL higher blood loss (95% CI 96.9-453.4, p < 0.01) controlling for parity, intrapartum oxytocin, self-reported ancestry, active management of third stage or genital tract lacerations. Furthermore, A-carrier individuals had a 79% higher risk for needing at least one second-line treatment (RR = 1.79, 95% CI = 1.08-2.95) controlling for covariates. Interaction models revealed that A-carriers who required no oxytocin for labor stimulation experienced 371.4 mL greater blood loss (95% CI 196.6-546.2 mL). CONCLUSIONS: We provide evidence of a risk allele in the oxytocin receptor gene that may be involved in the development of postpartum hemorrhage among participants undergoing vaginal birth, particularly among those with fewer risk factors. The findings, if reproducible, could be useful in studying pharmacogenomic strategies for predicting, preventing or treating postpartum hemorrhage.

Predicting Postpartum Hemorrhage After Low-Risk Vaginal Birth by Labor Characteristics and Oxytocin Administration.

OBJECTIVE: To determine the odds of postpartum hemorrhage (PPH) in low-risk women who gave birth vaginally and were exposed to different durations and dosages of oxytocin across a range of labor durations during spontaneous or induced labor. DESIGN: A retrospective cross-sectional analysis of data from the Consortium for Safe Labor. SETTING: Data were gathered from 12 clinical institutions across the United States from 2002 to 2008. PARTICIPANTS: After exclusion of high-risk conditions associated with PPH, we examined data from 27,072 women who gave birth vaginally. METHODS: PPH was defined as estimated blood loss of greater than 500 ml at the time of birth and/or a diagnostic code for PPH before hospital discharge. We included covariates were if they were associated with oxytocin use and PPH and did not mediate oxytocin use. We used regression models to determine the likelihood of PPH overall and within the induced and spontaneous labor groups separately. We used subgroup analyses within specific durations of labor to clarify the findings. RESULTS: The overall rate of PPH was 3.9%. Women with induced labor experienced PPH more frequently than women who labored spontaneously. Labor augmentation was associated with greater adjusted odds for PPH when oxytocin was infused for more than 4 hours. Longer duration of spontaneous labor and the second stage of labor did not change this association. Oxytocin use during labor induction increased the odds for PPH when administered for more than 7 hours. The odds further increased when induction lasted longer than 12 hours and/or the second stage of labor was longer than 3 hours. CONCLUSION: Strategies for judicious oxytocin administration may help mitigate PPH in low-risk women having vaginal birth.

Factors affecting third-stage management and postpartum hemorrhage in planned midwife-led home and birth center births in the United States.

BACKGROUND: Postpartum hemorrhage (PPH) is a potential childbirth complication. Little is known about how third-stage labor is managed by midwives in the United States, including use of uterotonic medication during community birth. Access to uterotonic medication may vary based on credentials of the midwife or state regulations governing midwifery. METHODS: Using data from the Midwives of North America 2.0 database (2004-2009), we describe the PPH incidence for women giving birth in the community, their demographic and clinical characteristics, and methods used by midwives to address PPH. We also examined PPH rates by midwifery credentials and by the presence of regulations for legal midwifery practice. RESULTS: Of the 17 836 vaginal births, 15.9% had blood loss of over 500 mL and 3.3% had 1000 mL or greater blood loss. Midwives used pharmaceuticals to prevent or treat postpartum bleeding in 6.3% and 13.9% of births, respectively, and the rate of hospital transfer after birth was 1.4% (n = 247). In adjusted analyses, PPH was less likely when births occurred at home vs a birth center, if the midwife had a CNM/CM credential vs a CPM/LM/LDM credential, or if the woman was multiparous without a history of PPH or prior cesarean birth. PPH was more likely in states with barriers to midwifery practice compared with regulated states (OR: 1.26; 95% CI, 1.16-1.38). CONCLUSIONS: Women giving birth in the community experienced low overall incidence of PPH-related hospital transfer. However, the occurrence of PPH itself would likely be reduced with improved legal access to uterotonic medication.