Christina Herrera

Cell-free DNA, inflammation, and the initiation of spontaneous term labor

BACKGROUND: Hypomethylated cell‐free DNA from senescent placental trophoblasts may be involved in the activation of the inflammatory cascade to initiate labor. OBJECTIVE: To determine the changes in cell‐free DNA concentrations, the methylation ratio, and inflammatory markers between women in labor at term vs women without labor. STUDY DESIGN: In this prospective cohort study, eligible participants carried a nonanomalous singleton fetus. Women with major medical comorbidity, preterm labor, progesterone use, aneuploidy, infectious disease, vaginal bleeding, abdominal trauma, or invasive procedures during the pregnancy were excluded. Maternal blood samples were collected at 28 weeks, 36 weeks, and at admission for delivery. Total cell‐free DNA concentration, methylation ratio, and interleukin‐6 were analyzed. The primary outcome was the difference in methylation ratio in women with labor vs without labor. Secondary outcomes included the longitudinal changes in these biomarkers corresponding to labor status. RESULTS: A total of 55 women were included; 20 presented in labor on admission and 35 presented without labor. Women in labor had significantly greater methylation ratio (P = .001) and interleukin‐6 (P < .001) on admission for delivery than women without labor. After we controlled for body mass index and maternal age, methylation ratio (adjusted relative risk, 1.38; 95% confidence interval, 1.13 to 1.68) and interleukin‐6 (adjusted relative risk, 1.12, 95% confidence interval, 1.07 to 1.17) remained greater in women presenting in labor. Total cell‐free DNA was not significantly different in women with labor compared with women without. Longitudinally, total cell‐free DNA (P < .001 in labor, P = .002 without labor) and interleukin‐6 (P < .001 in labor, P = .01 without labor) increased significantly across gestation in both groups. The methylation ratio increased significantly in women with labor from 36 weeks to delivery (P = .02). CONCLUSION: Spontaneous labor at term is associated with a greater cell‐free DNA methylation ratio and interleukin‐6 compared with nonlabored controls. As gestation advances, total cell‐free DNA concentrations and interleukin‐6 levels increase. A greater methylation ratio reflects a greater maternal contribution (vs placental) in women with labor, likely resulting from greater levels of neutrophils, lymphocytes, and uterine activation proteins at the time of labor. Although not significant, women in labor had a greater total cell‐free DNA concentration and thus could theoretically have more hypomethylated DNA available for interaction with the inflammatory cascade. Larger studies are needed to investigate this theory.

Perinatal Asphyxia from the Obstetric Standpoint: Diagnosis and Interventions.

Perinatal asphyxia is a general term referring to neonatal encephalopathy related to events during birth. Asphyxia refers to a deprivation of oxygen for a duration sufficient to cause neurologic injury. Most cases of perinatal asphyxia are not necessarily caused by intrapartum events but rather associated with underlying chronic maternal or fetal conditions. Of intrapartum causes, obstetric emergencies are the most common and are not always preventable. Screening high-risk pregnancies with ultrasound, Doppler velocimetry, and antenatal testing can aid in identifying fetuses at risk. Interventions such as intrauterine resuscitation or operative delivery may decrease the risk of severe hypoxia from intrauterine insults and improve long-term neurologic outcomes.

Tocolysis for Women With Early Spontaneous Preterm Labor and Advanced Cervical Dilation

OBJECTIVE: To characterize tocolytic use and examine perinatal outcomes among women presenting very preterm with spontaneous labor and cervical dilation 4 cm or greater. METHODS: This was a retrospective cohort study. Data from January 2000 to June 2011 in a single health care system were reviewed. Women with singleton, nonanomalous fetuses and preterm labor with intact membranes between 23 and 32 weeks of gestation who had cervical dilation 4 cm or greater and less than 8 cm at admission were included. Women receiving one or more tocolytics (magnesium sulfate, indomethacin, or nifedipine) were compared with those who did not receive tocolysis. The primary outcome was composite major neonatal morbidity. RESULTS: Two hundred ninety-seven women were included; 233 (78.5%) received at least one tocolytic. Women receiving tocolysis were slightly less dilated (median 5 compared with 6 cm, P<.001) at presentation and were more likely to receive at least a partial course of corticosteroids (88.4% compared with 56.3%, P<.001). Initial composite severe neonatal morbidity rates were similar (41.6% compared with 43.8%, P=.761) regardless of tocolytic administration. Those receiving tocolysis were significantly more likely to be pregnant at least 48 hours after admission (23.6% compared with 7.8%, P=.005), but a similar proportion delivered within 7 days of admission (94.8% compared with 95.3%, P>.99), and delivery gestational ages were similar (28.9 compared with 29.2 weeks, P=.408). The incidence of chorioamnionitis and postpartum endometritis was similar between groups. CONCLUSION: The majority of women presenting very preterm with advanced cervical dilation received tocolysis. Although tocolysis administration increased the likelihood of achieving at least 48 hours of latency, initial neonatal outcomes were similar. LEVEL OF EVIDENCE: II

Perinatal outcomes associated with intrahepatic cholestasis of pregnancy

Abstract Objective: The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice. Study design: Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 μmol/L), mild (10–39 μmol/L), moderate (40–99 μmol/L), and severe (≥100 μmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death). Results: 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3–23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6–14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise. Conclusion: Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict.