Nandini Raghuraman

Impact of evidence-based interventions on wound complications after cesarean delivery

BACKGROUND: A number of evidence‐based interventions have been proposed to reduce post–cesarean delivery wound complications. Examples of such interventions include appropriate timing of preoperative antibiotics, appropriate choice of skin antisepsis, closure of the subcutaneous layer if subcutaneous depth is ≥2 cm, and subcuticular skin closure with suture rather than staples. However, the collective impact of these measures is unclear. OBJECTIVE: We sought to estimate the impact of a group of evidence‐based surgical measures (prophylactic antibiotics administered before skin incision, chlorhexidine‐alcohol for skin antisepsis, closure of subcutaneous layer, and subcuticular skin closure with suture) on wound complications after cesarean delivery and to estimate residual risk factors for wound complications. STUDY DESIGN: We conducted a secondary analysis of data from a randomized controlled trial of chlorhexidine‐alcohol vs iodine‐alcohol for skin antisepsis at cesarean delivery from 2011–2015. The primary outcome for this analysis was a composite of wound complications that included surgical site infection, cellulitis, seroma, hematoma, and separation within 30 days. Risk of wound complications in women who received all 4 evidence‐based measures (prophylactic antibiotics within 60 minutes of cesarean delivery and before skin incision, chlorhexidine‐alcohol for skin antisepsis with 3 minutes of drying time before incision, closure of subcutaneous layer if ≥2 cm of depth, and subcuticular skin closure with suture) were compared with those women who did not. We performed logistic regression analysis limited to patients who received all the evidence‐based measures to estimate residual risk factors for wound complications and surgical site infection. RESULTS: Of 1082 patients with follow‐up data, 349 (32.3%) received all the evidence‐based measures, and 733 (67.7%) did not. The risk of wound complications was significantly lower in patients who received all the evidence‐based measures compared with those who did not (20.3% vs 28.1%; adjusted relative risk, 0.75; 95% confidence interval, 0.58–0.95). The impact appeared to be driven largely by a reduction in surgical site infections. Among patients who received all the evidence‐based measures, unscheduled cesarean delivery was the only significant risk factor for wound complications (27.5% vs 16.1%; adjusted relative risk, 1.71; 95% confidence interval, 1.12–2.47) and surgical site infection (6.9% vs 1.6%; relative risk, 3.74; 95% confidence interval, 1.18–11.92). Other risk factors, which include obesity, smoking, diabetes mellitus, chorioamnionitis, surgical experience, and skin incision type, were not significant among patients who received all of the 4 evidence‐based measures. CONCLUSION: Implementation of evidence‐based measures significantly reduces wound complications, but the residual risk remains high, which suggests the need for additional interventions, especially in patients who undergo unscheduled cesarean deliveries, who are at risk for wound complications even after receiving current evidence‐based measures.

Effect of Oxygen vs Room Air on Intrauterine Fetal Resuscitation: A Randomized Noninferiority Clinical Trial

Importance Two-thirds of women in labor receive supplemental oxygen to reverse perceived fetal hypoxemia and prevent acidemia. Oxygen is routinely administered for category II fetal heart tracings, a class of fetal tracing used to designate intermediate risk for acidemia. This liberal use of oxygen may not be beneficial, particularly because neonatal hyperoxygenation is harmful. Objective To test the hypothesis that room air is noninferior to oxygen in improving fetal metabolic status among patients with category II fetal heart tracings. Design, Setting, and Participants This was a randomized, unblinded noninferiority clinical trial conducted between June 2016 and July 2017 in the labor and delivery ward of a single tertiary care center. Women with singleton pregnancies at 37 weeks’ gestational age or more who were admitted for delivery were eligible. Of those who met inclusion criteria, the patients who developed category II tracings in labor that necessitated intrauterine resuscitation were randomized in a 1:1 ratio to room air or oxygen. Analyses were intention-to-treat. Interventions The oxygen group received 10 L of oxygen per minute by nonrebreather facemask until delivery. The room air group was exposed to room air only without a facemask. Main Outcomes and Measures The primary outcome was umbilical artery lactate, a marker of metabolic acidosis and neonatal morbidity. Noninferiority was defined as a mean difference between groups of less than 9.0 mg/dL (1.0 mmol/L). Secondary outcomes were other umbilical artery gases, cesarean delivery for nonreassuring fetal status, and operative vaginal delivery. Results Of the 705 patients who met inclusion criteria, 277 (39.3%) were enrolled on admission. During labor, 114 patients (41.2% of the enrolled patients) developed category II tracings and were randomized to room air (57 patients; 50.0% of the randomized patients) or oxygen (57 patients; 50.0% of the randomized patients). A total of 99 patients (86.8% of the randomized patients) with paired cord gases were included in the modified intention-to-treat analysis. The 99 patients included 76 African American women (77%); mean (SD) age was 27.3 (6.3) years in the oxygen group and 27.8 (5.3) years in the room air group. There was no difference in umbilical artery lactate between the group on oxygen and the group on room air (mean, 30.6 mg/dL [95% CI, 27.0 to 34.2 mg/dL] vs 31.5 mg/dL [95% CI, 27.9 to 36.0 mg/dL]); Pu2009=u2009.69). The mean difference in lactate was 0.9 mg/dL (95% CI, −4.5 to 6.3 mg/dL), which was within the noninferiority margin. There was no difference in other umbilical artery gas components or mode of delivery between groups. Conclusions and Relevance Among patients with category II fetal heart tracings, intrauterine resuscitation with room air is noninferior to oxygen in improving umbilical artery lactate. The results of this trial challenge the efficacy of a ubiquitous obstetric practice and suggest that room air may be an acceptable alternative. Trial Registration ClinicalTrials.gov Identifier: NCT02741284

Update on Fetal Monitoring: Overview of Approaches and Management of Category II Tracings

Electronic fetal monitoring (EFM) is widely used to assess fetal status in labor. Use of intrapartum continuous EFM is associated with a lower risk of neonatal seizures but a higher risk of cesarean or operative delivery. Category II fetal heart tracings (FHTs) are indeterminate in their ability to predict fetal acidemia. Certain patterns of decelerations and variability within this category may be predictive of neonatal morbidity. Adjunct tests of fetal well-being can be used during labor to further triage patients. Intrauterine resuscitation techniques should target the suspected etiology of intrapartum fetal hypoxia. Clinical factors play a role in the interpretation of EFM.

Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin

BACKGROUND: Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. OBJECTIVES: To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. STUDY DESIGN: Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low‐dose‐requiring, n = 83) or ≥20 mU/min (high‐dose‐requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted‐amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low‐dose‐requiring and high‐dose‐requiring women. The Scale‐Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ2 tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value < .05 was considered statistically significant. RESULTS: The high‐dose‐requiring women had greater rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. High‐dose‐requiring women were more likely to undergo cesarean delivery for first‐stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low‐ and high‐dose‐requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low‐dose‐requiring women. Nine nonsynonymous variants were unique to the high‐dose‐requiring group. These included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V, R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173R were predicted by Scale‐Invariant Feature Transform algorithm to damage oxytocin receptor function. There was no statistically significant association between the numbers of synonymous and nonsynonymous substitutions in the patient groups. CONCLUSION: Obesity, diabetes, and labor induction were associated with the requirement for high doses of oxytocin. We did not identify significant differences in the prevalence of oxytocin receptor variants between low‐dose‐requiring and high‐dose‐requiring women, but novel oxytocin receptor variants were enriched in the high‐dose‐requiring women. We also found 3 oxytocin receptor variants (2 novel, 1 known) that were predicted to damage oxytocin receptor function and would likely increase an individuals risk for requiring a high oxytocin dose. Further investigation of oxytocin receptor variants and their effects on protein function will inform precision medicine in pregnant women.

Clinical implications of umbilical artery Doppler changes after betamethasone administration

Abstract Background: Betamethasone (BMZ) is commonly administered to patients with fetal growth restriction (FGR) and abnormal umbilical artery Doppler (UAD) velocimetry due to the increased risk of preterm delivery; however, the clinical impact of UAD changes after BMZ exposure is unknown. Objective: To test the hypothesis that lack of UAD improvement after BMZ administration is associated with shorter latency and greater neonatal morbidity in patients with FGR. Study design: This was a retrospective cohort study of pregnancies complicated by FGR and abnormal UAD between 240 and 336 weeks gestation. Abnormal UAD included the following categories of increasing severity: elevated (pulsatility index >95%), absent end diastolic flow (EDF), or reversed EDF improvement was defined as any improvement in category of UAD within two weeks of BMZ. Sustained improvement was defined as improvement until the last ultrasound before delivery, whereas transient improvement was considered as unsustained. The primary outcome was latency, defined as interval from betamethasone administration to delivery. Secondary outcomes were gestational age at delivery, umbilical artery pH, and a composite of neonatal morbidity (intubation, necrotizing enterocolitis, ionotropic support, intraventricular hemorrhage, total parenteral nutrition, neonatal death). Outcomes were compared between (a) patients with and without UAD improvement and (b) patients with sustained and unsustained improvement, using univariable, multivariable and time-to-event analyses. Results: Of the 222 FGR pregnancies with abnormal UAD, 94 received BMZ and had follow-up ultrasounds. UAD improved in 48 (51.1%), with 27 (56.3%) having sustained improvement. Patients with hypertension and drug use were less likely to have UAD improvement. Patients without UAD improvement had shorter latency (21.5 days [interquartile range (IQR) 8,45] versus 35 [IQR 22,61], pu2009=u2009.02) and delivered at an earlier gestational age (34 weeks [IQR 31,36] versus 37 [IQR 33,37], pu2009<u2009.01) than those with improvement. There were no differences in umbilical artery pH between groups. Composite neonatal morbidity was higher in patients without UAD improvement, but this was not statistically significant after adjusting for confounders (aOR 2.0; 95% CI 0.08–5.1). There were no differences in outcomes between patients with sustained versus unsustained improvement. Conclusions: UAD improved in half of patients following BMZ. Lack of UAD improvement was associated with shorter latency and earlier gestational age at delivery, but no difference in composite neonatal morbidity. UAD response to BMZ may be useful to further risk stratify FGR pregnancies.

Umbilical Cord Oxygen Content and Neonatal Morbidity at Term

Objective The objective of this study was to investigate the relationship between umbilical cord partial pressure of oxygen (pO2) at delivery and neonatal morbidity. Study Design This is a secondary analysis of a prospective cohort study of term deliveries with universal cord gas collection between 2010 and 2014. The primary composite outcome of neonatal morbidity included neonatal death, meconium aspiration syndrome, intubation, mechanical ventilation, hypoxic‐ischemic encephalopathy, and hypothermia treatment. Umbilical artery (UA), vein (UV), UV minus UA (&Dgr;) pO2, and hypoxemia (pO2 ≤ fifth percentile) were compared between patients with and without neonatal morbidity. Areas under the receiver‐operating characteristic curves were used to assess the predictive ability of pO2. Results Of 7,789 patients with paired umbilical cord pO2, 106 (1.4%) had the composite neonatal morbidity. UA pO2was significantly lower in patients with neonatal morbidity compared with those without (median [interquartile range]: 16 (12, 21) vs. 19 (15, 24) mm Hg, p < 0.001). There was no difference in median UV pO2or &Dgr;pO2between the groups. UA and UV hypoxemia were significantly more common in patients with neonatal morbidity. UA pO2had limited predictive ability for neonatal morbidity (area under the curve: 0.61, 95% confidence interval: 0.6‐0.7). Conclusion Although UA pO2is significantly lower in patients with neonatal morbidity, it is a poor predictor of neonatal morbidity at term.

Utility of the Simplified Bishop Score in Spontaneous Labor

Objectiveu2003The objective of this study was to evaluate the relationship between the simplified Bishop score (SBS) on admission for labor and subsequent labor outcomes to identify women at higher risk for cesareans. Study Designu2003This was a secondary analysis of a prospective cohort study of 4,733 singleton pregnancies. Adjusted odds ratios (aOR) were calculated comparing outcomes in women with an unfavorable SBS ≤ 5 to women with a favorable SBSu2009>u20095. A favorable SBS was compared with the individual parameters of dilation, effacement, and station. The primary outcome was vaginal delivery. Secondary outcomes were prolonged first stage, completion of first stage, oxytocin augmentation, and prolonged second stage. Resultsu200347.8% of the patients admitted in labor had an unfavorable SBS. Nulliparous and multiparous patients with a favorable SBS were more likely to have a vaginal delivery (aOR 1.96, 95% confidence intervals [CI] 1.49-2.57; aOR 1.91, 95% CI 1.44-2.53) and less likely to require oxytocin augmentation (aOR 0.34, 95% CI 0.28-0.42; aOR 0.26, 95% CI 0.22-0.30. Compared with dilation alone, the SBS in its entirety was associated with a higher likelihood of vaginal delivery in nulliparous. Conclusionu2003An unfavorable SBS on admission for labor is associated with a decreased likelihood of having a vaginal delivery.