Obese mice have decreased uterine contractility and altered energy metabolism in the uterus at term gestation.

Over 35% of reproductive-age women in the US are obese, putting them at increased risk for numerous obstetric complications due to abnormal labor. While the association between maternal obesity and abnormal labor has been well documented, the mechanisms responsible for this remain understudied. The uterine smooth muscle, myometrium, has high energy needs in order to fuel regular uterine contractions during parturition. However, the precise mechanisms by which the myometrium meets its energy demands has not been defined. Here, our objective was to define the effects of obesity on energy utilization in the myometrium during labor. We generated a mouse model of maternal diet-induced obesity (DIO) and found that these mice had a higher rate of dystocia than control chow-fed (CON) mice. Moreover, compared to CON mice, DIO mice at term, both before and during labor had lower in vivo spontaneous uterine contractility. Untargeted transcriptomic and metabolomic analyses suggest that DIO is associated with elevated long-chain fatty acid uptake and utilization in the uterus, but also an accumulation of medium-chain fatty acids. DIO uteri also had an increase in the abundance of long chain-specific ß-oxidation enzymes, which may be responsible for the observed increase in long-chain fatty acid utilization. This altered energy substrate utilization may be a contributor to the observed contractile dysfunction.

Pharmacological chaperones for the oxytocin receptor increase oxytocin responsiveness in myometrial cells.

Oxytocin is a potent uterotonic agent administered to nearly all patients during childbirth in the United States. Inadequate oxytocin response can necessitate Cesarean delivery or lead to uterine atony and postpartum hemorrhage. Thus, it may be clinically useful to identify patients at risk for poor oxytocin response and develop strategies to sensitize the uterus to oxytocin. Previously, we showed that the V281M variant in the oxytocin receptor (OXTR) gene impairs OXTR trafficking to the cell surface, leading to a decreased oxytocin response in cells. Here, we sought to identify pharmacological chaperones that increased oxytocin response in cells expressing WT or V281M OXTR. We screened nine small-molecule agonists and antagonists of the oxytocin/vasopressin receptor family and identified two, SR49059 and L371,257, that restored both OXTR trafficking and oxytocin response in HEK293T cells transfected with V281M OXTR. In hTERT-immortalized human myometrial cells, which endogenously express WT OXTR, treatment with SR49059 and L371,257 increased the amount of OXTR on the cell surface by two- to fourfold. Furthermore, SR49059 and L371,257 increased the endogenous oxytocin response in hTERT-immortalized human myometrial cells by 35% and induced robust oxytocin responses in primary myometrial cells obtained from patients at the time of Cesarean section. If future studies demonstrate that these pharmacological chaperones or related compounds function similarly in vivo, we propose that they could potentially be used to enhance clinical response to oxytocin.

Vaginal cleansing before unscheduled cesarean delivery to reduce infection: a randomized clinical trial.

BACKGROUND: Cesarean delivery is the most performed major surgery among women, and surgical-site infections following a cesarean delivery are a significant source of postoperative morbidity. It is unclear if vaginal cleansing before a cesarean delivery decreases post-cesarean delivery infectious morbidity. OBJECTIVE: This study aimed to evaluate if preoperative vaginal cleansing with povidone-iodine among women undergoing a cesarean delivery after labor decreases postoperative infectious morbidity. STUDY DESIGN: This randomized clinical trial was conducted from August 3, 2015 to January 28, 2021, with 30 days of follow-up and the final follow-up completed on February 27, 2021. Patients met the inclusion criteria if they underwent a cesarean delivery after regular contractions with cervical dilation, rupture of membranes, or any cesarean delivery performed at >4 cm dilation. Participants were randomly assigned in a 1:1 ratio to either abdominal cleansing plus vaginal cleansing with 1% povidone-iodine or abdominal cleansing alone. The primary outcome was composite infectious morbidity including surgical-site infection, fever, endometritis, and wound complications within 30 days after the cesarean delivery. Secondary outcomes included individual components of the composite, length of hospital stay, postoperative hospitalization or outpatient treatment related to infectious morbidity, and empirical treatment for neonatal sepsis. RESULTS: A total of 608 subjects (304 vaginal cleansing group, 304 control group) were included in the intention-to-treat analysis. Patient characteristics were similar between groups. There was no significant difference in the primary composite outcome between the 2 groups (11.8% vs 11.5%; P=.90; relative risk, 1.0; 95% confidence interval, 0.7-1.6). Individual components of the composite and secondary outcomes were also not significantly different between the groups. Similar findings were observed in the as-treated analysis (11.3% vs 11.8%; P=.9; relative risk, 1.0; 95% confidence interval, 0.7-1.6). CONCLUSION: Vaginal cleansing with povidone-iodine before an unscheduled cesarean delivery occurring after labor did not reduce the postoperative infectious morbidity. These findings do not support the routine use of vaginal cleansing for women undergoing a cesarean delivery after labor.

The relationship between maternal anemia and electronic fetal monitoring patterns.

BACKGROUND: Anemia is a commonly diagnosed comorbidity in pregnancy that is associated with increased risk of maternal and neonatal complications. Recent data demonstrate that maternal anemia is associated with higher umbilical artery and umbilical vein O2 content at the time of delivery. OBJECTIVE: This study aimed to examine the relationship between maternal anemia and electronic fetal monitoring patterns associated with fetal hypoxia. STUDY DESIGN: This is a secondary analysis of a prospective cohort study of singleton term deliveries with cord gases and universal complete blood count collected on admission between 2010 and 2014. Maternal anemia was defined as hemoglobin ≤11.0 g/dL on admission. The primary outcome was a composite of high-risk category 2 electronic fetal monitoring features in the last 60 minutes before delivery (recurrent late and/or variable decelerations, minimal variability, tachycardia, or >1 prolonged deceleration); secondary outcomes were total deceleration area and total deceleration area >90th percentile. Of the 8580 patients in the original study, 8196 were included in the analysis. Outcomes were compared between patients with and without anemia. Multivariable logistic regression was used to adjust for potentially confounding factors, including hypertensive disorders of pregnancy and induction of labor. RESULTS: Of the 8196 patients with complete blood count on admission and fetal monitoring data, 2672 (32.6%; 2672/8196) were anemic and 5524 (67.4%; 5524/8196) were not. Patients with anemia were significantly less likely to have composite high-risk category 2 features on electronic fetal monitoring (34.2% vs 32.0%; adjusted risk ratio, 0.93; 95% confidence interval, 0.86-0.99). Women with anemia also had decreased total deceleration area and were less likely to have total deceleration area >90th percentile (18.7% vs 16.2%; adjusted risk ratio, 0.85; 95% confidence interval, 0.77-0.94). CONCLUSION: Patients with anemia are less likely to have high-risk category 2 electronic fetal monitoring features associated with fetal hypoxia. This finding is consistent with the association between maternal anemia and increased umbilical cord O2 content, and suggests that maternal anemia may be protective against intrapartum fetal hypoxia.

Video Instruction for Pushing in the Second Stage: a randomized controlled trial.

BACKGROUND: The second stage of labor requires active patient engagement. Previous studies suggest that coaching can influence the second stage of labor duration. However, a standardized education tool has not been established, and patients face many barriers to accessing childbirth education before delivery. OBJECTIVE: This study aimed to investigate the effect of an intrapartum video pushing education tool on the second stage of labor duration. STUDY DESIGN: This was a randomized controlled trial of nulliparous patients with singleton pregnancies ≥37 weeks of gestation admitted for induction of labor or spontaneous labor with neuraxial anesthesia. Patients were consented on admission and block randomized in active labor to 1 of 2 arms in a 1:1 ratio. The study arm viewed a 4-minute video before the second stage of labor on what to anticipate in the second stage of labor and pushing techniques. The control arm received the standard of care: bedside coaching at 10 cm dilation from a nurse or physician. The primary outcome was second stage of labor duration. The secondary outcomes were birth satisfaction (using the Modified Mackey Childbirth Satisfaction Rating Scale), mode of delivery, postpartum hemorrhage, clinical chorioamnionitis, neonatal intensive care unit admission, and umbilical artery gases. Of note, 156 patients were needed to detect a 20% decrease in the second stage of labor duration with 80% power, 2-sided alpha level of .05, and 10% loss after randomization. Funding was provided by the Lucy Anarcha Betsy award from the division of clinical research at Washington University. RESULTS: Of 161 patients, 81 were randomized to standard of care, and 80 were randomized to intrapartum video education. Among these patients, 149 progressed to the second stage of labor and were included in the intention-to-treat analysis: 69 in the video group and 78 in the control group. Maternal demographics and labor characteristics were similar between groups. The second stage of labor duration was statistically similar between the video arm (61 minutes [interquartile range, 20-140]) and the control arm (49 minutes [interquartile range, 27-131]) (P=.77). There was no difference in mode of delivery, postpartum hemorrhage, clinical chorioamnionitis, neonatal intensive care unit admission, or umbilical artery gases between groups. Although the overall birth satisfaction score on the Modified Mackey Childbirth Satisfaction Rating Scale was similar between groups, patients in the video group rated their "level of comfort during birth" and "attitude of the doctors in birth" significantly higher or more positively than patients in the control group (P<.05 for both). CONCLUSION: Intrapartum video education was not associated with a shorter second stage of labor duration. However, patients who received video education reported a higher level of comfort and a more favorable perception of their physician, suggesting that video education may be a helpful tool to improve the birth experience.

Association between Elevated Intrauterine Resting Tone during Labor and Neonatal Morbidity.

OBJECTIVE: Internal contraction monitoring provides a quantitative assessment of intrauterine resting tone. During the course of labor, elevated intrauterine resting tone may be identified. We hypothesized that elevated intrauterine resting tone could lead to compression of the spiral arteries, thus limiting uterine blood flow and resulting in neonatal compromise. Therefore, our objective was to assess the association between elevated resting tone during labor and neonatal morbidity. STUDY DESIGN: This was a secondary analysis of a prospective cohort study of singleton deliveries at ≥37 weeks of gestation. Patients with ruptured membranes and an intrauterine pressure catheter in place for at least 30 minutes prior to delivery were included. Intrauterine resting tone was calculated as the average baseline pressure between contractions during the 30 minutes prior to delivery. The study group had elevated intrauterine resting tone, defined as intrauterine resting tone ≥75th percentile (≥12.3 mm Hg). Primary outcome was composite neonatal morbidity: hypoxic-ischemic encephalopathy, hypothermia treatment, intubation, seizures, umbilical arterial pH ≤7.1, oxygen requirement, or death. Secondary outcomes included umbilical artery pH <7.2, lactate ≥4 mmol/L, and rates of neonatal intensive care unit admission. RESULTS: Of the 8,580 patients in the cohort, 2,210 (25.8%) met the inclusion criteria. The median intrauterine resting tone was 9.7 mm Hg (interquartile range: 7.3-12.3 mm Hg). Elevated resting tone was associated with a shorter median duration of the first stage of labor (10.0 vs. 11.0 hours, p < 0.01) and lower rates of labor induction and oxytocin augmentation (p < 0.01). Neonatal composite morbidity was higher among patients with elevated intrauterine resting tone (5.1 vs. 2.9%, p = 0.01). After adjusting for chorioamnionitis and amnioinfusion, elevated intrauterine resting tone was associated with increased risk of neonatal morbidity (adjusted odds ratio: 1.70, 95% confidence interval: 1.06-2.74). CONCLUSION: Our findings suggest that elevated intrauterine resting tone is associated with increased risk of neonatal composite morbidity. KEY POINTS: · Higher intrauterine resting tone is associated with increased risk of neonatal morbidity.. · Elevated intrauterine tone can negatively impact umbilical artery pH and lactate levels.. · If elevated intrauterine pressure is noted, we recommend close monitoring of fetal status..

The Impact of Cervical Effacement at Time of Amniotomy in Patients Undergoing Induction of Labor.

OBJECTIVE: There is evidence to suggest that early amniotomy during induction of labor is advantageous. However, following cervical ripening balloon removal, the cervix remains less effaced and the utility of amniotomy in this setting is less clear. We investigated whether cervical effacement at the time of amniotomy impacts outcomes among nulliparas undergoing induction of labor. STUDY DESIGN: This was a secondary analysis of a prospective cohort of singleton, term, nulliparous patients at a tertiary care center undergoing induction of labor and amniotomy. The primary outcome was completion of the first stage of labor. Secondary outcomes were vaginal delivery and postpartum hemorrhage. Outcomes were compared between patients with cervical effacement ≤50% (low effacement) and >50% (high effacement) at time of amniotomy. Multivariable logistic regression was used calculate risk ratios (RR) to adjust for confounders including cervical dilation. Stratified analysis was performed in patients with cervical ripening balloon use. A post hoc sensitivity analysis was performed to further control for cervical dilation. RESULTS: Of 1,256 patients, 365 (29%) underwent amniotomy at low effacement. Amniotomy at low effacement was associated with reduced likelihood of completing the first stage (aRR: 0.87 [95% confidence interval, CI: 0.78-0.95]) and vaginal delivery (aRR: 0.87 [95% CI: 0.77-0.96]). Although amniotomy at low effacement was associated with lower likelihood of completing the first stage in all-comers, those who had amniotomy performed at low effacement following cervical ripening balloon expulsion were at the highest risk (aRR: 0.84 [95% CI: 0.69-0.98], p for interaction = 0.04) In the post hoc sensitivity analysis, including patients who underwent amniotomy at 3- or 4-cm dilation, low cervical effacement remained associated with a lower likelihood of completing the first stage of labor. CONCLUSION: Low cervical effacement at time of amniotomy, particularly following cervical ripening balloon expulsion, is associated with a lower likelihood of successful induction. KEY POINTS: · Low cervical effacement at amniotomy was associated with lower rates of complete dilation.. · Effacement at amniotomy is especially important for patients who had a cervical ripening balloon.. · Providers should consider cervical effacement when timing amniotomy for nulliparous term patients..

Clinical significance of umbilical artery intermittent vs persistent absent end-diastolic velocity in growth-restricted fetuses.

BACKGROUND: Umbilical artery absent end-diastolic velocity indicates increased placental resistance and is associated with increased risk of perinatal demise and neonatal morbidity in fetal growth restriction. However, the clinical implications of intermittent vs persistent absent end-diastolic velocity are unclear. OBJECTIVE: We compared umbilical artery Doppler velocimetry changes during pregnancy and neonatal outcomes between pregnancies with fetal growth restriction and intermittent absent end-diastolic velocity and those with persistent absent end-diastolic velocity. STUDY DESIGN: In this retrospective study of singletons with fetal growth restriction and absent end-diastolic velocity, umbilical artery Doppler abnormalities were classified as follows: intermittent absent end-diastolic velocity (<50% of cardiac cycles with absent end-diastolic velocity) and persistent absent end-diastolic velocity (≥50% of cardiac cycles with absent end-diastolic velocity). The primary outcome was umbilical artery Doppler progression to reversed end-diastolic velocity. Secondary outcomes included sustained umbilical artery Doppler improvement, latency to delivery, gestational age at delivery, neonatal morbidity composite, rates of neonatal intensive care unit admission, and length of neonatal intensive care unit stay. Outcomes were compared between intermittent absent end-diastolic velocity and persistent absent end-diastolic velocity. Multivariate logistic regression was used to adjust for confounders. A receiver operating characteristic curve was generated to assess the sensitivity and specificity of the percentage of waveforms with absent end-diastolic velocity in predicting the neonatal composite. The Youden index was used to calculate the optimal absent end-diastolic velocity percentage cut-point for predicting the neonatal composite. RESULTS: Of the 77 patients included, 38 had intermittent absent end-diastolic velocity and 39 had persistent absent end-diastolic velocity. Maternal characteristics, including age, parity, and preexisting conditions did not differ significantly between the 2 groups. Progression to reversed end-diastolic velocity was less common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (7.9% vs 25.6%; odds ratio, 0.25; 95% confidence interval, 0.06-0.99). Sustained umbilical artery Doppler improvement was more common in intermittent absent end-diastolic velocity than in persistent absent end-diastolic velocity (50.0% vs 10.3%; odds ratio, 8.75; 95% confidence interval, 2.60-29.5). Pregnancies with intermittent absent end-diastolic velocity had longer latency to delivery than those with persistent absent end-diastolic velocity (11 vs 3 days; P<.01), and later gestational age at delivery (33.9 vs 28.7 weeks; P<.01). Composite neonatal morbidity was less common in the intermittent absent end-diastolic velocity group (55.3% vs 92.3%; P<.01). Neonatal death occurred in 7.9% of intermittent absent end-diastolic velocity cases and 33.3% of persistent absent end-diastolic velocity cases (P<.01). The differences in neonatal outcomes were no longer significant when controlling for gestational age at delivery. The percentage of cardiac cycles with absent end-diastolic velocity was a modest predictor of neonatal morbidity, with an area under the receiver operating characteristic curve of 0.71 (95% confidence interval, 0.58-0.84). The optimal percentage cut-point for fetal cardiac cycles with absent end-diastolic velocity observed at the sentinel ultrasound for predicting neonatal morbidity was calculated to be 47.7%, with a sensitivity of 65% and specificity of 85%. CONCLUSIONS: Compared with persistent absent end-diastolic velocity, diagnosis of intermittent absent end-diastolic velocity in the setting of fetal growth restriction is associated with lower rates of progression to reversed end-diastolic velocity, higher likelihood of umbilical artery Doppler improvement, longer latency to delivery, and higher gestational age at delivery, leading to lower rates of neonatal morbidity and death. Our data support using an absent end-diastolic velocity percentage cut-point in 50% of cardiac cycles to differentiate intermittent absent end-diastolic velocity from persistent absent end-diastolic velocity. This differentiation in growth-restricted fetuses with absent end-diastolic velocity may allow further risk stratification.

Severity of intrapartum fever and neonatal outcomes.

BACKGROUND: The few studies that have addressed the relationship between severity of intrapartum fever and neonatal and maternal morbidity have had mixed results. The impact of the duration between reaching maximum intrapartum temperature and delivery on neonatal outcomes remains unknown. OBJECTIVE: To test the association of severity of intrapartum fever and duration from reaching maximum temperature to delivery with neonatal and maternal morbidity. STUDY DESIGN: This was a secondary analysis of a prospective cohort of term, singleton patients admitted for induction of labor or spontaneous labor who had intrapartum fever (≥38°C). Patients were divided into 3 groups according to maximum temperature during labor: afebrile (<38°C), mild fever (38°C-39°C), and severe fever (>39°C). The primary outcome was composite neonatal morbidity (umbilical artery pH <7.1, mechanical ventilation, respiratory distress, meconium aspiration with pulmonary hypertension, hypoglycemia, neonatal intensive care unit admission, and Apgar <7 at 5 minutes). Secondary outcomes were composite neonatal neurologic morbidity (hypoxic-ischemic encephalopathy, hypothermia treatment, and seizures) and composite maternal morbidity (postpartum hemorrhage, endometritis, and maternal packed red blood cell transfusion). Outcomes were compared between the maximum temperature groups using multivariable logistic regression. Cox proportional-hazards regression modeling accounted for the duration between reaching maximum intrapartum temperature and delivery. RESULTS: Of the 8132 patients included, 278 (3.4%) had a mild fever and 74 (0.9%) had a severe fever. The incidence of composite neonatal morbidity increased with intrapartum fever severity (afebrile 5.4% vs mild 18.0% vs severe 29.7%; P<.01). After adjusting for confounders, there were increased odds of composite neonatal morbidity with severe fever compared with mild fever (adjusted odds ratio, 1.93 [95% confidence interval, 1.07-3.48]). Severe fevers remained associated with composite neonatal morbidity compared with mild fevers after accounting for the duration between reaching maximum intrapartum temperature and delivery (adjusted hazard ratio, 2.05 [95% confidence interval, 1.23-3.43]). Composite neonatal neurologic morbidity and composite maternal morbidity were not different between patients with mild and patients with severe fevers. CONCLUSION: Composite neonatal morbidity correlated with intrapartum fever severity in a potentially dose-dependent fashion. This correlation was independent of the duration from reaching maximum intrapartum temperature to delivery, suggesting that clinical management of intrapartum fever, in terms of timing or mode of delivery, should not be affected by this duration.

Association between Maternal Serum Lipids and Intrapartum Oxytocin Requirements during Labor Induction and Augmentation.

OBJECTIVE: This study aimed to investigate the relationship between maternal serum lipid parameters and oxytocin requirements among women with term vaginal deliveries. STUDY DESIGN: In this secondary analysis of a prospective cohort study, women who presented for delivery at ≥37 weeks' gestation and received oxytocin during their labor were included. Maternal serum was collected intrapartum. The cohort was stratified into two groups based on maximum oxytocin infusion dose during labor. Primary outcomes were maternal total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. Generalized linear regression models were used to assess the association between lipid parameters and maximum oxytocin dose requirements while controlling for potential confounders. For secondary analyses, the cohort was stratified by HDL-C into two groups. Multivariable logistic regression was used to evaluate the relationship between low maternal HDL-C and additional intrapartum oxytocin parameters. RESULTS: There were no differences in maternal total cholesterol, LDL-C, or triglyceride values between high and low maximum oxytocin groups. Median serum HDL-C was significantly lower among women in the high oxytocin group compared with those in the low oxytocin group (56 vs. 62 mg/dL, p < 0.01). For every 0.26 mg/dL lower HDL-C, women had 1 mU/min higher maximum oxytocin infusion dose during labor. Women with low serum HDL-C were also more likely to require maximum oxytocin doses above the 75th percentile (adjusted odds ratio [aOR]: 1.99, 95% confidence interval [CI]: 1.06-3.75) and above the 90th percentile (aOR: 2.47, 95% CI: 1.10-5.54). Among women undergoing induction of labor, low serum HDL-C was also associated with longer duration of oxytocin infusion (aOR: 2.07, 95% CI: 1.02-4.20). CONCLUSION: Low maternal HDL-C levels at term are associated with higher maximum oxytocin infusion doses among women undergoing labor induction or augmentation. Given the growing prevalence of metabolic syndrome in the United States and persistently high rates of cesarean delivery, HDL-C or its components may present a new target for predicting and improving labor outcomes. KEY POINTS: · Serum HDL-C at term is inversely correlated with oxytocin infusion doses at term.. · Low maternal serum HDL-C is associated with higher oxytocin requirements during labor induction or augmentation.. · No association between maternal serum total cholesterol, LDL-C, or triglyceride levels and oxytocin requirements in labor..

The impact of physical activity during pregnancy on labor and delivery.

BACKGROUND: Physical activity in pregnancy is associated with decreased risks of adverse pregnancy outcomes such as gestational diabetes and preeclampsia. However, the relationship between the amount and type of physical activity during pregnancy and subsequent labor outcomes remains unclear. OBJECTIVE: This study aimed to test the hypothesis that higher levels of physical activity across different lifestyle domains in pregnancy are associated with a shorter duration of labor. STUDY DESIGN: This study is a secondary analysis of a prospective cohort study in which patients with singleton pregnancies without a major fetal anomaly were administered the Kaiser Physical Activity Survey in each trimester. The Kaiser Physical Activity Survey was designed specifically to quantify various types of physical activities in women and includes 4 summative indices-housework/caregiving, active living habits, sports, and occupation. The study included women at full-term gestations admitted for induction of labor or spontaneous labor. The primary outcome of this analysis was duration of the second stage of labor. Secondary outcomes were duration of the active stage, prolonged first and second stage, mode of delivery, rates of second-stage cesarean delivery, operative vaginal delivery, severe perineal lacerations, and postpartum hemorrhage. These outcomes were compared between patients with and without high physical activity levels, defined as overall Kaiser Physical Activity Survey score ≥75th percentile in the third trimester. Multivariable logistic regression was used to adjust for obesity and epidural use. In addition, a subgroup analysis of nulliparous patients was performed. RESULTS: A total of 811 patients with complete Kaiser Physical Activity Survey data in the third trimester were included in this analysis. The median Kaiser Physical Activity Survey score was 9.5 (8.2-10.8). Of the 811 patients, 203 (25%) had higher levels of physical activity in pregnancy. There was no difference in the duration of the second stage of labor between patients with and without higher physical activity levels (1.29±2.94 vs 0.97±2.08 hours; P=.15). The duration of active labor was significantly shorter in patients with higher levels of physical activity (5.77±4.97 vs 7.43±6.29 hours; P=.01). Patients with higher physical activity levels were significantly less likely to have a prolonged first stage (9.8% vs 19.4%; P<.01; adjusted relative risk, 0.55; 95% confidence interval, 0.34-0.83). However, rates of prolonged second-stage cesarean delivery, operative vaginal deliveries, and perineal lacerations were similar between the 2 groups. CONCLUSION: Patients who are more physically active during pregnancy have a shorter duration of active labor.

Obesity, Second Stage Duration, and Labor Outcomes in Nulliparous Women.

OBJECTIVE: This study aimed to estimate second stage duration and its effects on labor outcomes in obese versus nonobese nulliparous women. STUDY DESIGN: This was a secondary analysis of a cohort of nulliparous women who presented for labor at term and reached complete cervical dilation. Adjusted relative risks (aRR) were used to estimate the association between obesity and second stage characteristics, composite neonatal morbidity, and composite maternal morbidity. Effect modification of prolonged second stage on the association between obesity and morbidity was assessed by including an interaction term in the regression model. RESULTS: Compared with nonobese, obese women were more likely to have a prolonged second stage (aRR: 1.48, 95% CI: 1.18-1.85 for ≥3 hours; aRR: 1.65, 95% CI: 1.18-2.30 for ≥4 hours). Obesity was associated with a higher rate of second stage cesarean (aRR: 1.78, 95% CI: 1.34-2.34) and cesarean delivery for fetal distress (aRR: 2.67, 95% CI: 1.18-3.58). Obesity was also associated with increased rates of neonatal (aRR: 1.38, 95% CI: 1.05-1.80), but not maternal morbidity (aRR: 1.06, 95% CI: 0.90-1.25). Neonatal morbidity risk was not modified by prolonged second stage. CONCLUSION: Obesity is associated with increased risk of neonatal morbidity, which is not modified by prolonged second stage of labor.

Mild Neonatal Acidemia is Associated with Neonatal Morbidity at Term.

OBJECTIVE: The aim of this study is to determine the association between mild acidemia (umbilical artery [UA] pH: 7.11-7.19) and neonatal morbidity in neonates at term. STUDY DESIGN: This is a secondary analysis of a prospective cohort of women admitted for labor at ≥37 weeks of gestation within a single institution from 2010 to 2015. Universal umbilical cord blood gas assessment was performed and validated. A composite neonatal morbidity index was created including respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected or confirmed sepsis, hypoxic-ischemic encephalopathy, need for therapeutic hypothermia, seizures and death. The cohort was stratified by UA pH into normal (≥7.20), mild acidemia (7.11-7.19), acidemia (7.00-7.10), and severe acidemia (≤7.00). A subanalysis was also performed where neonates with UA pH between 7.11 and 7.19 were further stratified into two groups (7.11-7.14 and 7.15-7.19) to determine if mildly acidotic infants at the lower end of the pH range were at increased risk of morbidity. Multivariable logistic regression was used to estimate the association between UA pH and neonatal morbidity. RESULTS: Among 6,341 participants, 614 (9.7%) had mild acidemia. These infants were more likely to experience morbidity compared with those with normal UA pH (adjusted odds ratio [aOR]: 2.14; [1.68-2.73]). Among neonates with mild acidemia, UA pH 7.11 to 7.14 was associated with increased risk of composite neonatal morbidity (aOR: 3.02; [1.89-4.82]), as well as respiratory distress and suspected or confirmed sepsis when compared with UA pH 7.15 to 7.19. CONCLUSION: These data demonstrate that term neonates with mild acidemia at birth are at higher odds for short-term morbidity compared with neonates with normal UA pH. Furthermore, among neonates with mild acidemia, those with lower UA pH had worse neonatal outcomes than those with higher UA pH. This suggests that closer evaluation of neonates with UA pH higher than traditionally used could allow for earlier detection of morbidity and possible intervention. KEY POINTS: · Neonates with mild acidemia (umbilical artery [UA] pH: 7.11-7.19) demonstrated an increased risk of composite morbidity compared with those with normal UA pH (≥7.20).. · Among neonates with mild acidemia, those with lower UA pH (7.11-7.14) had a greater risk of morbidity compared with those with higher UA pH (7.15-7.19), suggesting a progression of risk of morbidity as UA pH decreases.. · The majority of prior research has focused on severe acidemia (UA pH ≤ 7.00) using outcomes of severe neurologic morbidity and mortality. These data suggest that an increased risk of morbidity exists at higher pH values when more proximal and less severe outcomes are included, such as respiratory distress and neonatal sepsis..

Association between Uterine Tachysystole during the Last Hour of Labor and Cord Blood Lactate in Parturients at Term Gestation.

OBJECTIVE: To assess whether uterine tachysystole (UT) in labor causes an increase in cord blood lactate. STUDY DESIGN: Secondary analysis of a prospective cohort study of all consecutive singleton gestations ≥ 37 weeks admitted for labor to a single tertiary care institution with universal cord gas policy. Patients with UT in the last hour ("always") were compared with those without UT ("never"). Primary outcome of interest was cord blood lactate ≥ 4 mmol/L. Secondary outcomes included pH ≤ 7.10, base deficit ≥ 8 mmol/L, and admission to the neonatal intensive care unit (NICU). Multivariable logistic regression was used to estimate the risk for elevated cord blood lactate after adjusting for maternal age and body mass index. RESULTS: Of the 8,580 patients included in the analysis, 513 experienced UT 1 hour before delivery (5.9%). UT was significantly associated with elevated cord blood lactate in the "always" (33.5%) compared with the "never" group (26%) (adjusted odds ratio 1.47 [1.17, 1.86]; p < 0.01). However, there were no differences in either umbilical arterial pH, base deficit, or NICU admission rates. CONCLUSION: UT in the last hour preceding delivery increases arterial cord blood lactate suggesting that UT proximate to delivery should be considered as a variable when interpreting cord blood gas values.

Spontaneous Labor Onset and Outcomes in Obese Women at Term.

OBJECTIVE: The objective of this study was to compare the rates of spontaneous labor onset and its progression in obese and nonobese women after 37 weeks. STUDY DESIGN: We performed a secondary analysis of a retrospective cohort of all women who were admitted for delivery at ≥ 37 weeks of gestation at a university-based tertiary care center between 2004 and 2010. The cohort was stratified by weeks of gestation at which the patient presented for delivery. The rates of spontaneous labor, vaginal delivery, and augmentation with oxytocin were compared between obese (body mass index [BMI] ≥ 30) and nonobese (BMI < 30) women. RESULTS: Obese women had lower rates of spontaneous labor than nonobese women at every gestational week (37 weeks, 6.1 vs. 9.3%, p < 0.001; 38 weeks, 12.8 vs. 19.2%, p < 0.001; 39 weeks 26.0 vs. 37.0%, p < 0.001; 40 weeks, 39.6 vs. 50.2%, p < 0.001; 41 weeks, 30.8 vs. 38.0%, p < 0.012). Among women who presented in spontaneous labor, obesity was associated with higher rates of augmentation with oxytocin and lower rates of vaginal delivery. CONCLUSION: Obese women at or beyond 37 weeks are less likely to experience spontaneous labor compared with nonobese women. In addition, obese women presenting in spontaneous labor are less likely that nonobese women to have a vaginal delivery at 37 to 40 weeks, even after oxytocin augmentation.

Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

OBJECTIVES: The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer. MATERIALS AND METHODS: We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer. RESULTS: Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83). CONCLUSIONS: Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

Impact of an immunohistochemistry-based universal screening protocol for Lynch syndrome in endometrial cancer on genetic counseling and testing.

OBJECTIVE: Evaluate effects of a Lynch syndrome universal screening protocol in newly diagnosed endometrial cancers on subsequent genetic counseling (GC) and germline testing (GT) referral and acceptance rates. METHODS: We performed a retrospective cohort study of women who underwent a hysterectomy for endometrial cancer at Barnes Jewish Hospital in St. Louis, MO between 1/1/2011 and 12/31/2013 (n=637). An immunohistochemistry-based (IHC) universal screening protocol for Lynch syndrome was initiated on 12/17/2012. The cohorts consisted of women presenting prior to (Pre-Em-USP; n=395) and those presenting following (Em-USP; n=242) initiation of the universal screening protocol. GC and GT referrals were based on risk factors and/or IHC results. Comparisons were made using the Fisher's exact test and the Kruskal-Wallis test. RESULTS: A greater proportion of individuals in the Em-USP cohort underwent GT than in Pre-Em-USP (9.1% vs 4.8%, p<0.05). Of individuals with an IHC screening result suggestive of LS, those within the Em-USP cohort were significantly more likely to accept GC compared to those in the Pre-Em-USP cohort (95% vs 64%, p=0.02). Specifically within the Em-USP cohort, patients referred to GC due to a concerning IHC screening result, versus those who were referred based on other risk factors, had a higher counseling acceptance rate (95% vs 61%, p=0.03) and underwent genetic testing more readily (76% vs 30%, p<0.001). CONCLUSIONS: Implementation of an IHC-based universal screening protocol for LS in endometrial cancer leads to higher acceptance of genetic counseling and higher rates of genetic testing compared to referral based on risk factors alone.

Neoadjuvant chemotherapy versus primary cytoreductive surgery for stage IV uterine serous carcinoma.

OBJECTIVE: This study compares surgical and survival outcomes of women with stage IV uterine serous carcinoma (USC) treated with neoadjuvant chemotherapy (NAC) and interval cytoreduction to women treated with primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy. METHODS: This retrospective dual cohort study included women diagnosed with stage IV USC at a single academic institution. Kruskal-Wallis and Fisher exact tests were used to compare demographics and surgical outcomes. Progression-free survival (PFS) and overall survival (OS) were estimated by using Kaplan-Meier methods. Comparison between study groups was tested by log-rank statistics. RESULTS: Ten women with stage IV USC who received NAC and 34 who underwent PCS met inclusion criteria. Neoadjuvant chemotherapy patients had a lower mean body mass index and were more often African American. Compared with PCS, the NAC cohort had shorter mean operative times (137 ± 66 vs 203 ± 80 minutes, P = 0.025) and were discharged from the hospital earlier (median length of stay, 3 vs 5 days; P = 0.002). Rates of debulking to no gross residual disease (70% NAC vs 32.3% PCS) or less than 1 cm of disease (30% NAC vs 50% PCS) did not differ (P = 0.10). Median follow-up time was 17.5 months. There was no difference in median PFS (10.4 vs 12 months, P = 0.29) or OS (17.3 vs 20.7 months, P = 0.23) for NAC and PCS cohorts. CONCLUSIONS: Women receiving NAC for stage IV USC had shorter surgeries and hospital stays than did those receiving PCS. There was no difference in PFS or OS, although our sample size was small. Neoadjuvant chemotherapy may be an appropriate therapy for select patients with advanced-stage USC.

Quantification of surface-localized and total oxytocin receptor in myometrial smooth muscle cells.

Oxytocin acts through the oxytocin receptor (OXTR) to modulate uterine contractility. We previously identified OXTR genetic variants and showed that, in HEK293T cells, two of the OXTR protein variants localized to the cell surface less than wild-type OXTR. Here, we sought to measure OXTR in the more native human myometrial smooth muscle cell (HMSMC) line on both the cell-surface and across the whole cell, and used CRISPR editing to add an HA tag to the endogenous OXTR gene for anti-HA measurement. Quantitative flow cytometry revealed that these cells possessed 55,000 ± 3200 total OXTRs and 4900 ± 390 cell-surface OXTRs per cell. To identify any differential wild-type versus variant localization, we transiently transfected HMSMCs to exogenously express wild-type or variant OXTR with HA and green fluorescent protein tags. Total protein expression of wild-type OXTR and all tested variants were similar. However, the two variants with lower surface localization in HEK293T cells also presented lower surface localization in HMSMCs. Overall, we confirm the differential surface localization of variant OXTR in a more native cell type, and further demonstrate that the quantitative flow cytometry technique is adaptable to whole-cell measurements.

Dietary risk factors for hypertensive disorders of pregnancy.

OBJECTIVE: To assess whether diet quality and specific dietary components are associated with hypertensive disorders of pregnancy (HDP). STUDY DESIGN: Nested case control study in a prospectively collected cohort of 450 participants with singleton pregnancies who completed the National Institutes of Health Diet Health Questionnaire II (DHQ-II) in the third trimester or within 3 months of delivery. Patients with fetal anomalies, conception by in-vitro fertilization, and deliveries at outside hospitals were excluded from the original prospective cohort study. Cases were patients diagnosed with HDP and controls were patients without HDP. Cases and controls were matched by BMI class in a 1:2 ratio. Exposures of interest were HEI-2015 score components and other DHQ-II dietary components including minerals, caffeine, and water. These dietary components were compared between cohorts using univariate analyses. MAIN OUTCOME MEASURES: HEI-2015 total scores representing diet quality, component scores, and objective background data between patients with HDP and patients without HDP. RESULTS: 150 patients with HDP were matched to 300 controls without HDP. Baseline demographics were similar between groups, including BMI. Patients with HDP were less likely to have high quality diets (HEI ≥ 70) than controls (7.3 % v 15.7 %, P = 0.02). HDP were associated with significantly higher dairy, saturated fat, and sodium intake compared to controls. Other components were similar between groups. CONCLUSION: Patients with HDP are more likely to have lower diet quality and higher consumption of sodium, dairy, and saturated fats. These results can be used to study antenatal diet modification in patients at high risk of HDP.