Enhanced recovery after cesarean from the patient perspective: a prospective study of the ERAC Questionnaire (ERAC-Q).

OBJECTIVES: To evaluate the impact of an Enhanced Recovery After Cesarean (ERAC) protocol on the post-cesarean recovery experience using a validated ten-item questionnaire (ERAC-Q). METHODS: This is a prospective cohort study of patients completing ERAC quality-of-life questionnaires (ERAC-Q) during inpatient recovery after cesarean delivery (CD) between October 2019 and September 2020, before and after the implementation of our ERAC protocol. Patients with non-Pfannenstiel incision, ICU admission, massive transfusion, bowel injury, existing chronic pain disorders, acute postpartum depression, or neonatal demise were excluded. The ERAC-Q was administered on postoperative day one and day of discharge to the pre- and post-ERAC implementation cohorts, rating aspects of their recovery experience on a scale of 0 (best) to 10 (worst). The primary outcome was ERAC-Q scores. Statistical analysis was performed with SAS software. RESULTS: There were 196 and 112 patients in the pre- and post-ERAC cohorts, respectively. The post-ERAC group reported significantly lower total ERAC-Q scores compared to the pre-ERAC group, reflecting fewer adverse symptoms and greater perceived recovery on postoperative day one (1.6 [0.7, 2.8] vs. 2.7 [1.6, 4.3]) and day of discharge (0.8 [0.3, 1.5] vs. 1.4 [0.7, 2.2]) (p<0.001). ERAC-Q responses did not predict the time to achieve objective postoperative milestones. However, worse ERAC-Q pain and total scores were associated with higher inpatient opiate use. CONCLUSIONS: ERAC implementation positively impacts patient recovery experience. The administration of ERAC-Q can provide real-time feedback on patient-perceived recovery quality and how healthcare protocol changes may impact their experience.

A Prospective Longitudinal Quality Initiative toward Improved Enhanced Recovery after Cesarean Pathways.

OBJECTIVE: This study aimed to evaluate whether enhanced recovery after cesarean (ERAC) pathways reduces inpatient and outpatient opioid use, pain scores and improves the indicators of postoperative recovery. STUDY DESIGN: This is a prospective, longitudinal, quality improvement study of all patients older than 18 undergoing an uncomplicated cesarean delivery (CD) at an academic medical center. We excluded complicated CD, patients with chronic pain disorders, chronic opioid use, acute postpartum depression, or mothers whose neonate demised before their discharge. Lastly, we excluded non-English- and non-Spanish-speaking patients. Our study compared patient outcomes before (pre-ERAC) and after (post-ERAC) implementation of ERAC pathways. Primary outcomes were inpatient morphine milligram equivalent (MME) use and the patient's delta pain scores. Secondary outcomes were outpatient MME prescriptions and indicators of postoperative recovery (time to feeding, ambulation, and hospital discharge). RESULTS: Of 308 patients undergoing CD from October 2019 to September 2020, 196 were enrolled in the pre-ERAC cohort and 112 in the post-ERAC cohort. Patients in the pre-ERAC cohort were more likely to require opioids in the postoperative period compared with the post-ERAC cohort (81.6 vs. 64.3%, p < 0.001). Likewise, there was a higher use of MME per stay in the pre-ERAC cohort (30 [20-49] vs. 16.8 MME [11.2-33.9], p < 0.001). There was also a higher number of patients who required prescribed opioids at the time of discharge (98 vs. 86.6%, p < 0.001) as well as in the amount of MMEs prescribed (150 [150-225] vs. 150 MME [112-150], p < 0.001; different shape of distribution). Furthermore, the patients in the pre-ERAC cohort had higher delta pain scores (3.3 [2.3-4.7] vs. 2.2 [1.3-3.7], p < 0.001). CONCLUSION: Our study has illustrated that our ERAC pathways were associated with reduced inpatient opioid use, outpatient opioid use, patient-reported pain scores, and improved indicators of postoperative recovery. KEY POINTS: · Implementation of ERAC pathways is associated with a higher percentage of no postpartum opioid use.. · Implementation of ERAC pathways is associated with lower delta (reported - expected) pain scores.. · The results of ERAC pathways implementation are increased by adopting a patient-centered approach..

The value of detailed first-trimester ultrasound in the era of noninvasive prenatal testing.

BACKGROUND: In 2020, the American College of Obstetricians and Gynecologists recommended noninvasive prenatal testing be offered to all patients. However, current societal guidelines in the United States do not universally recommend a detailed first-trimester ultrasound. OBJECTIVE: This study aimed to determine the additional findings identified through first-trimester ultrasound that would have otherwise been missed if noninvasive prenatal testing was used alone as a first-trimester screening method. STUDY DESIGN: This was a retrospective cohort study involving 2158 pregnant patients and 2216 fetuses that were seen at a single medical center between January 1, 2020, and December 31, 2022. All those included underwent both noninvasive prenatal testing and detailed first-trimester ultrasound between 11.0 and 13.6 weeks of gestation. Noninvasive prenatal testing results were categorized as low risk or high risk, and first-trimester ultrasound results were categorized as normal or abnormal. Abnormal first-trimester ultrasounds were further classified as first-trimester screening markers (increased nuchal translucency, absent nasal bone, tricuspid regurgitation, and ductus venosus reverse a-wave) or structural defects (the cranium, neck, heart, thorax, abdominal wall, stomach, kidneys, bladder, spine, and extremities). Descriptive statistics were used to report our findings. RESULTS: Of 2216 fetuses, 65 (3.0%) had a high-risk noninvasive prenatal testing result, whereas 2151 (97.0%) had a low-risk noninvasive prenatal testing result. Of those with a low-risk noninvasive prenatal testing result, 2035 (94.6%) had a normal first-trimester ultrasound, whereas 116 (5.4%) had at least 1 abnormal finding on first-trimester ultrasound. The most common screening marker detected within the low-risk noninvasive prenatal testing group was absent nasal bone (52/2151 [2.4%]), followed by reversed a-wave of the ductus venosus (30/2151 [1.4%]). The most common structural defect in this group was cardiac abnormality (15/2151 [0.7%]). Overall, 181 fetuses were identified as having "abnormal screening" through either a high-risk noninvasive prenatal testing result (n=65) or through a low-risk noninvasive prenatal testing result but abnormal first-trimester ultrasound (n=116). In summary, the incorporation of first-trimester ultrasound screening identified 116 additional fetuses (5.4%) that required further follow-up and surveillance than noninvasive prenatal testing alone would have identified. CONCLUSION: Detailed first-trimester ultrasound identified more fetuses with a potential abnormality than noninvasive prenatal testing alone. Therefore, first-trimester ultrasound remains a valuable screening method that should be used in combination with noninvasive prenatal testing.

Obesity impacts placental function through activation of p-IRE1a-XBP1s signaling.

Maternal obesity is associated with a variety of obstetrical outcomes including stillbirth, preeclampsia, and gestational diabetes, and increases the risk of fetuses for congenital heart defects. Obesity during pregnancy represents a major contribution to metabolic dysregulation, which not only plays a key role in the pathogenesis of adverse outcome but also can potently induce endoplasmic reticulum (ER) stress. However, the mechanism associating such an obesogenic metabolic environment and adverse pregnancy outcomes has remained poorly understood. In this study, we aimed to determine whether the ER stress pathways (also named unfolded protein response (UPR)) were activated in the placenta by obesity. We collected placenta from the obese pregnancy (n = 12) and non-obese pregnancy (n = 12) following delivery by Caesarean-section at term. The specimens were assessed with immunocytochemistry staining and RT-QPCR. Our results revealed that in the obese placenta, p-IRE1α and XBP1s were significantly increased, CHOP and nine UPR chaperone genes were upregulated, including GRP95, PDIA6, Calnexin, p58IPK, SIL-1, EDEM, Herp, GRP58 and Calreticulin. However, Perk and BiP are not activated in the obese placenta. Our data suggest that upregulated p-IRE1α and XBP1s signaling, and UPR chaperone genes may play an important role in maternal obesity-induced placental pathology. In conclusion, this is the first report on ER stress and UPR activation in the placenta of maternal obesity. Our findings represent the first step in the understanding of one of the key ER signaling pathways, also referred to IRE1α-XBP1, in placental pathophysiology affected by obesity, which may be an important mechanism accounting for the observed higher maternal and perinatal risks.

The Optimal Cesarean Skin Incision in Patients with Super Obesity.

OBJECTIVE: This study aimed to evaluate if supraumbilical midline vertical incision performed in patients with a hanging pannus (umbilicus at the level of the pubic bone) is a reasonable alternative to the Pfannenstiel in patients with body mass index (BMI) ≥ 50 kg/m2 undergoing cesarean delivery. STUDY DESIGN: Retrospective cohort study in patients with BMI ≥ 50 kg/m2 undergoing cesarean delivery at a single center from 2016 to 2020. Study groups were Pfannenstiel's versus supraumbilical vertical skin incision. If patients had a hanging pannus (umbilicus at the level of the pubic bone), vertical incisions were performed. Otherwise, Pfannenstiel's incision was performed. Decision for the incision was made prospectively. Primary outcome was a composite of need for blood transfusion, presence of immediate surgical complications, and presence of delayed surgical complications. Secondary outcomes included the individual components of the primary outcome, the median surgical blood loss, total operative time, time from skin incision to delivery of neonate, hysterotomy type, and neonatal outcomes. MedCalc 19.5.1 was used for analysis. RESULTS: A total of 103 patients with BMI ≥50 kg/m2 were included. Of those, 68 (66%) had Pfannenstiel's and 35 (34%) had supraumbilical vertical incisions. There was no statistically significant difference in the incidence of the primary outcome (12 vs. 11%, p = 0.96). There was neither significant difference in immediate or delayed postoperative complications nor in neonatal outcomes. However, patients in the vertical midline incision group were more likely to have a classical hysterotomy (52%) compared with the Pfannenstiel group (6%; p < 0.05), increased overall median surgical blood loss (1,000 vs. 835 mL, p < 0.05), and increased total surgical time by a median of 30 minutes (p < 0.05). CONCLUSION: In patients with super obesity and hanging pannus, performing a supraumbilical vertical midline incision offers a reasonable alternative to Pfannenstiel's incision, but patients should be counseled about the increased risk for classical hysterotomy and implications in future pregnancies. KEY POINTS: · Patients with BMI >50 kg/m2 were allocated to different incision types based on subcutaneous fat distribution pattern. If umbilicus was at level of pubic bone, supraumbilical vertical skin incision was made. · There were no significant differences between Pfannenstiel's and supraumbilical vertical incisions in terms of the composite outcome and immediate or delayed postoperative complications and neonatal outcomes.. · In patients with a hanging pannus, performing a supraumbilical vertical midline incision offers a reasonable alternative to Pfannenstiel's incision, but patients should be counseled about the increased risk for classical hysterotomy and subsequent implications in future pregnancies..

Class III obesity is an independent risk factor for unsuccessful induction of labor.

BACKGROUND: Although obesity is a known risk factor for cesarean delivery, there is a paucity of data on the course of induction of labor in these patients. OBJECTIVE: With emerging data on the safety of 39-week inductions, we aimed to: (1) determine if Class III obesity, including morbid obesity, is an independent risk factor for nonachievement of complete dilation and vaginal delivery after induction of labor, (2) evaluate the characteristics of the induction of labor course and immediate complications, and (3) evaluate the number of induction agents necessary to be associated with vaginal deliveries. We hypothesized that as body mass index increased, it would take longer to achieve complete cervical dilation, more induction agents would be required, and there would be a higher rate of cesarean delivery. STUDY DESIGN: This was a retrospective cohort study of singleton gestations undergoing induction of labor from 2013 to 2020 at a single center. Study groups were defined as nonobese (body mass index <30 kg/m2), non-Class III obesity (body mass index of 30-39.9 kg/m2), and Class III obesity (body mass index ≥40 kg/m2). The primary outcome was achievement of complete cervical dilation. Secondary outcomes included time from start of induction to complete dilation, cesarean delivery rates, doses of misoprostol used, combination of induction agents used, and incidence of chorioamnionitis and postpartum hemorrhage. Univariate and multivariate logistic regression analyses were used to estimate risks. A secondary analysis was performed on nulliparous patients. RESULTS: A total of 3046 individuals met the inclusion criteria. As body mass index increased, the indications for induction were more likely to be maternal. Rate of achievement of complete dilation decreased with increasing body mass index (973 [88.5%] in the body mass index <30 group vs 455 [70.8%] in the body mass index ≥40 group; adjusted odds ratio, 0.3; 95% confidence interval, 0.2-0.4). The rate of cesarean delivery also increased (149 [13.5%] in the body mass index <30 group vs 207 [30.9%] in the body mass index ≥40 group; adjusted odds ratio, 3.2; 95% confidence interval, 2.5-4.2), as did the time to complete dilation (15.3 hours in the body mass index <30 group vs 18.8 hours in the body mass index ≥40 group; P<.001). Morbidly obese patients required higher doses and more types of induction agents. Misoprostol was used as the sole induction agent in 362 (35.1%) of patients in the body mass index <30 group vs 160 (25.4%) of patients in the body mass index ≥40 group (adjusted odds ratio, 0.6; 95% confidence interval, 0.5-0.8). In the body mass index ≥40 group, a greater number required a combination of misoprostol, mechanical ripening, and oxytocin for induction (147 [14.3%] in the body mass index <30 group vs 158 [25.0%] in the body mass index ≥40 group; adjusted odds ratio, 1.7; 95% confidence interval, 1.3-2.3). For nulliparous patients, the rate of cesarean delivery was significantly higher with increasing body mass index (118 [18.3%] in the body mass index <30 group and 157 [48.2%] in the body mass index ≥40 group; P<.001), with 5 more hours spent in labor (18.3 hours in the body mass index <30 group vs 23.3 hours in the body mass index ≥40 group; P<.001). Nulliparous patients were also more likely to require multiple induction agents (122 [20.3%] for body mass index <30 vs 108 [33.6%] for body mass index ≥40; P<.001). CONCLUSION: Class III obesity is an independent risk factor for nonachievement of complete dilation and vaginal delivery following induction of labor. Furthermore, inductions in these patients require more time and are more likely to require multiple agents.

Maternal obesity-associated disruption of polarized lactate transporter MCT4 expression in human placenta.

Maternal obesity is associated with an increased risk of adverse pregnancy outcomes including stillbirth, and their etiology is thought to be related to placental and fetal hypoxia. In this study, we sought to investigate the levels of lactate in maternal and umbilical cord blood, a well characterized biomarker for hypoxia, and expression of plasma membrane lactate transporter MCT1 and MCT4 in the placental syncytiotrophoblast (STB), which are responsible for lactate uptake and extrusion, respectively, from pregnant women with a diagnosis of obesity following a Cesarean delivery at term. With use of approaches including immunofluorescence staining, Western blot, RT-qPCR and ELISA, our results revealed that in controls the expression of MCT1 was equally observed between basal (fetal-facing, BM) and microvillous (maternal-facing, MVM) membrane of the STB, whereas MCT4 was predominantly expressed in the MVM but barely detected in the BM. However, obese patients demonstrated significant decreased MCT4 abundance in the MVM coupled with concurrent elevated expression in the BM. We also found a linear trend toward decreasing MCT4 expression ratio of MVM to BM with increasing maternal pre-pregnancy BMI. Furthermore, our data showed that the lactate ratios of fetal cord arterial to maternal blood were remarkably reduced in obese samples compared to their normal counterparts. Collectively, these results suggest that the loss of polarization of lactate transporter MCT4 expression in placental STB leading to disruption of unidirectional lactate transport from the fetal to the maternal compartment may constitute part of mechanisms linking maternal obesity and pathogenesis of stillbirth.

Real-world implementation of a vaginal preparation policy prior to cesarean delivery.

OBJECTIVE: Surgical site infections (SSIs) are a major source of morbidity and mortality for women who undergo cesarean section (c-section). SSIs following c-section include wound infection, infection of the endometrium (endometritis) and intra-abdominal infections. Perioperative interventions to prevent these infections continue to be studied, including the use of vaginal preparation prior to c-section. Although literature has shown that the use of vaginal preparation prior to c-section decreases the rate of SSI, real-world clinical data regarding effective implementation of these policies are lacking. The objectives of this study were to determine (1) if a vaginal preparation policy could be implemented in a real-world setting with a high compliance rate and (2) to identify factors led to differences in compliance with policy. STUDY DESIGN: This was a secondary analysis of a retrospective cohort study designed to examine the incidence of SSI after c-section before and after the implementation of vaginal preparation policy. The primary outcomes included implementation rates of the vaginal preparation for the post policy cohort. Secondary outcomes included subgroup analysis of policy adherence based on time of day, urgency of delivery, membrane status, labor status, and maternal factors. RESULTS: Overall adherence to the vaginal preparation policy was 87.2% of patients. Maternal factors did not impact the rate of policy adherence. 81.4% of patients undergoing c-section at night had vaginal prep completed compared to 89.9% of patients undergoing c-section during the day (p = .016). 63.8% of patients undergoing emergent c-section had vaginal prep completed, compared to 90.1% of patients undergoing non-emergent c-section (p < .001). Laboring patients were more likely to have vaginal preparation completed (143 (95.3%) vs. 225 (82.7%), p = .009). CONCLUSIONS: Compliance with vaginal preparation policy was high. Patients who are undergoing evening deliveries and emergent deliveries are less likely to have vaginal preparation completed. Some of these differences are likely attributable to perceived urgency of the c-section. It is important that interventions are identified such as staff education and standardization of documentation to improve rates of policy adherence.

Marginal placental cord insertion: the need for follow up?

OBJECTIVE: The objectives of this study were (1) to estimate the association between marginal placental cord insertion (PCI) and small for gestational age (SGA) and other adverse perinatal outcomes and (2) to determine if pregnancy-associated plasma protein A (PAPP-A) levels was altered in these patients. METHODS: It was a retrospective cohort study of singleton pregnancies undergoing ultrasound between 2016 and 2018. Marginal PCI was defined as a distance of ≤2 cm from placental edge to PCI site, visualized in both sagittal and transverse planes, and diagnosed between 16 and 32 weeks. Velamentous PCI were excluded. The primary outcome was SGA, defined as birthweight below 10th percentile for gestational age. Pregnancies with marginal PCI were compared to those with normal PCI with respect to maternal characteristics, PAPP-A levels and adverse perinatal and delivery outcomes. RESULTS: The incidence of marginal PCI was 4.2% (76/1819). Compared to those with a normal PCI, patients with a marginal PCI were more likely to be nulliparous and less likely to be African American or morbidly obese (p < .05). SGA rate was similar between the groups (17.6% vs. 18.1%). There was a trend toward an increased incidence of oligohydramnios, polyhydramnios and breech presentation in patients with marginal PCI; however, these did not reach statistical significance. The incidence of low PAPP-A level was comparable between the groups (18.4% vs. 14.3%, p > .05). CONCLUSION: Our study did not demonstrate any increase in adverse pregnancy outcomes in the presence of marginal PCI. These findings may provide reassurance for counseling patients with this sonographic finding.

Maternal obesity increases DNA methylation and decreases RNA methylation in the human placenta.

Maternal obesity is associated with increased risk of adverse pregnancy and birth outcomes. While increasing body of evidence supports that the etiology is related to fetal and placental hypoxia, molecular signaling changes in response to this pathophysiological condition in human placenta have remained elusive. Here by using varied approaches including immunocytochemistry staining, Western blot, RT-qPCR, and ELISA, we aimed to investigate the changes in epigenetic markers in placentas from obese pregnant women following delivery by Caesarean-section at term. Our results revealed that the levels of 5-methylcytosine (5mC), a methylated form commonly occurring in CpG dinucleotides and an important repressor of gene transcription in the genome, were significantly increased coupled with decreased activity of Ten-Eleven Translocation (TETs) enzymes that principally function by oxidizing 5mC in the obese placenta, consistent with hypoxia-induced genome-wide DNA hypermethylation observed in varied types of cells and tissues. N6-methyladenosine (m6A) represents the most abundant and conserved modification of gene transcripts, especially within mRNAs, which is stalled by m6A methyltransferases or "writers" including METTL-3/-14, WTAP, RBM15B, and KIAA1429. We further showed that obese placentas demonstrated significantly down-regulated levels of m6A along with reduced gene expression of WTAP, RBM15B, and KIAA1429. Our data support that maternal obesity-induced hypoxia may play an important role in triggering genome-wide DNA hypermethylation in the human placenta, and in turn leading to transcriptome-wide inhibition of RNA modifications. Our results further suggest that selectively modulating these pathways may facilitate development of novel therapeutic approaches for controlling and managing maternal obesity-associated adverse clinical outcomes.

Renal artery Doppler compared with the cerebral placental ratio to identify fetuses at risk for adverse neonatal outcome.

Background: Current clinical practice incorporates an umbilical artery resistance index or a ratio of the middle cerebral artery (MCA PI) to the umbilical artery pulsatility index (UA PI) known as the cerebral placental ratio (CPR) to assess wellbeing in the small for gestational age fetus. Previous reports using the renal artery Doppler indices have not been consistent in regards to their design and clinical use. Our objective is to develop reference values for renal artery Doppler indices and validate their use compared with the UA PI or CPR to identify fetuses that will develop a composite neonatal outcome.Methods: We performed 9700 ultrasounds among 2852 women at 20-40 weeks of gestation at the University of Maryland between 1 June 2016 and 1 December 2016. Nomograms were first developed using one randomly selected scan from each of a subgroup of 860 women without any comorbidities. The nomograms were validated among a cohort of 550 women who subsequently delivered at the University of Maryland Medical Center. We compared the area under the receiver operating characteristic curve (AUROC) between the CPR and UA PI, and the renal artery Doppler parameters (renal artery pulsatility index (RA PI), systolic diastolic ratio (RA SDR), and peak systolic velocity (RA PSV)). The primary outcome was the development any one of the composite neonatal outcome components (death, intensive care unit admission, ventilator for more than 6 h, hypoxic ischemic encephalopathy or necrotizing enterocolitis) or admission to the neonatal intensive care unit (NICU) for any indication.Results: The renal artery Doppler indices did not improve identification of fetuses that would subsequently develop one of the components of the composite neonatal outcome (AUROC for CPR 0.54, 95% CI (0.49-0.59), versus the UA PI: 0.59 (0.54-0.64) p = .07, the RA PI: 0.51 (0.48-0.55) p = .41, RA SDR 0.54 (0.49-0.58) p = .99, or RA PSV 0.51 (0.47-0.55) p = .37). There was no difference when comparing AUROC to detect NICU admission (AUROC for CPR 0.53, 95% CI (0.49-0.58), versus the UA PI: 0.57 (0.52-0.62) p = .14, the RA PI: 0.50 (0.47-0.54) p = .44, RA SDR: 0.54 (0.50-0.59) p = .62 or RAPSV: 0.51 (0.47-0.55) p = .54).Conclusion: The renal artery indices do not improve detection of fetuses at risk for adverse neonatal outcomes compared with the CPR or the UA PI.

A novel approach to reduce blood loss in patients with placenta accreta spectrum disorder.

OBJECTIVE: Cesarean hysterectomy for the treatment of placenta accreta spectrum (PAS) disorders has the potential to be associated with significant blood loss, massive transfusion, and operative morbidity. Two major contributors to blood loss are the hysterotomy and the bladder dissection. We introduce a new surgical technique and hypothesize that developing the hysterotomy with a linear cutter and mobilization of the bladder using a vessel sealing system (VSS) before clamping uterine arteries will lead to a total reduction in blood loss and transfusion rates. MATERIALS AND METHODS: This was a case series, which presents clinical outcomes according to our described surgical technique. The following surgical outcomes were collected: operation time (minutes), estimated blood loss (EBL), intraoperative complications, need for reoperation before discharge, and transfusion rates. Our surgical technique utilizes a linear cutter to create a bloodless hysterotomy and a VSS to dissect the vesicouterine tissue. The VSS cauterizes and transects the small vesicouterine and placental-vesical vascular anastomoses that are prone to bleeding. Once the bladder is mobilized below the level of the cervix, the uterine arteries are ligated to complete the key components of the hysterectomy. RESULTS: Of the 23 cases, the median EBL was 1500 cubic centimeters and patients received a median of 1 unit of packed red blood cells. Eleven of the 23 cases did not require any blood transfusion and no patients required massive transfusion. The EBL did not differ between procedures that were performed emergently versus scheduled and it also did not differ between patients that had placenta increta versus placenta percreta, as diagnosed by histopathology. CONCLUSION: Use of a linear cutter and closure of the lower anastomosis with VSS prior to clamping uterine artery during cesarean hysterectomy can significantly reduce blood loss and transfusion rates. This technique is applicable in emergent and nonemergent settings as well as for the most challenging procedures complicated by placenta percreta.

The joint effects of obesity and pregestational diabetes on the risk of stillbirth.

Objective: Obesity and pregestational diabetes (PGDM) may interact to further increase the risk of stillbirth than either risk factors independently. The objective of this study was to determine the risk of stillbirth in pregnancies complicated by both conditions.Method: This was a retrospective cohort analysis of singleton nonanomalous births using the updated Texas vital records database between 2006 and 2014. Gestational diabetes and hypertensive diseases were additionally excluded from analysis. Analysis was stratified into 10 strata based on BMI class: underweight, normal weight, overweight, obese and morbidly obese, and PGDM. Furthermore, gestational age was stratified into the four periods for analysis: 24-33, 34-36, 37-39, and 40-42 weeks. The rate of stillbirth per 10,000 pregnancies were calculated for each stratum. The risks of stillbirth associated with each BMI class and PGDM were compared to normal weight nondiabetic pregnancies for each gestational period using proportional hazard regression models.Result: After all exclusions, 3,097,123 births remained for analysis, including 5997 stillbirths. The overall rate of stillbirth increased from 15.0 per 10,000 pregnancies in normal weight pregnancies to 26.7 per 10,000 pregnancies in the morbidly obese group. The rate of stillbirth further increased with coexistence of PGDM to 119.9 per 10,000 pregnancies in the normal weight group and 209.8 per 10,000 pregnancies in the morbidly obese group. Compared to normal weight nondiabetic pregnancies the overall adjusted hazard ratio (aHR) of stillbirth associated with morbid obesity without PGDM was 1.57 [1.38, 1.79]. However, when further complicated by PGDM, the aHR was 6.67 [5.05, 8.81] in normal weight pregnancies and 12.86 [9.36, 17.67] in morbidly obese pregnancies. The highest risk of stillbirth was seen between 37 and 39 weeks, when the aHR in the diabetic normal weight group was 9.63 [5.65, 16.40] and the aHR in the diabetic morbidly obese group was 25.34 [15.58, 41.22].Conclusion: PGDM and obesity both independently increased the risk of stillbirth. The joint effect of obesity and PGDM is stronger than the summation or multiplication of the individual effects of each risk factor.

The role of fetal growth restriction in the association between Down syndrome and perinatal mortality.

Objective: Down syndrome (DS) is associated with significant risk of perinatal mortality. We hypothesize that this association is primarily mediated through the effects of fetal growth restriction (FGR).Methods: This was a retrospective cohort analysis using the US Natality Database from 2011 to 2013. Analysis was limited to singleton nonanomalous pregnancies or confirmed DS pregnancies without severe structural anomalies between 24 and 42 w in gestation. The risk of stillbirth (SB) associated with DS was estimated using both Cox proportional Hazard (HR) regression and accelerated failure time (AFT) methods. The risk of neonatal mortality was estimated using logistic regression analyses. Mediation analysis was then performed to estimate the effect of small for gestational age (SGA), defined as birthweight ≤10th percentile for gestational age, on perinatal mortality associated with DS. All regression models were selected using backward stepwise elimination method. The final regression models included adjustment for maternal age, hypertension, and diabetes.Results: The final cohort included 2446 DS cases among 9,804,718 births. The overall SB rate was 223.6/1000 births in DS group and 4.7/1000 births without DS (p < .001, adjusted hazard ratio (aHR): 58.25; 95% CI [53.44,63.49]). Based on the AFT model, DS survival-to-delivery rate is 4.3 times lower (TR: 0.23; 95% CI [0.22,0.24]). Thirty-five percentage of the effect of DS on stillbirth was mediated through SGA (% mediation:35.1%; 95% CI [33.7,36.4]). The rate of neonatal mortality among DS was 69.0/1000 births compared with 2.8/1000 births without DS (p < .001, adjusted odds ratio (aOR): 27.16; 95% CI: [22.63,32.60]). Only 11.6% of the effect of DS on neonatal deaths was mediated through SGA (%mediation:11.6%; 95% CI [8.4,10.6]).Conclusion: Over one-third of overall stillbirths were mediated through SGA. Routine surveillance of fetal growth and standard SGA surveillance protocols may reduce the risk of perinatal mortality in DS pregnancies. Conversely, it is important to point out that these surveillance strategies may not be effective two-third of the cases not affected by growth restriction.

Adverse perinatal outcomes associated with trial of labor after cesarean section at term in pregnancies complicated by maternal obesity.

INTRODUCTION: Obesity is associated with higher risks for intrapartum complications. Therefore, we sought to determine if trial of labor after cesarean section (TOLAC) will lead to higher maternal and neonatal complications compared to repeat cesarean section (RCD). METHODS: This was a retrospective cohort analysis of singleton nonanomalous births between 37 and 42 weeks GA complicated by maternal obesity (body mass index (BMI) ≥ 30 kg/m2) and history of one or two previous cesarean deliveries. Outcomes were compared between TOLAC and RCD. The maternal outcomes of interest included blood transfusion, uterine rupture, hysterectomy, and intensive care unit admission. Neonatal outcomes of interest included 5-minute Apgar score <7, prolonged assisted ventilation, neonatal intensive care unit admission, neonatal seizures, and neonatal death. RESULTS: There were 538,264 pregnancies included. Compared with RCD, TOLAC was associated with an absolute increase in the following neonatal outcomes: low 5-min Apgar score (0.6%, p < .001), neonatal intensive care unit (NICU) admission (0.8%, p < .001), neonatal seizure (0.1 per 1000 births, p = .037), and neonatal death (0.2 per 1000 births, p = .028). Additionally, TOLAC was associated with an absolute increase in following maternal outcomes: blood transfusion (0.1%, p < .001), uterine rupture (0.18%, p < .001) and ICU admission (0.1%, p = .011). CONCLUSIONS: TOLAC among obesity pregnancies at term increases the risk of maternal and neonatal complications compared with RCD.

Three-Dimensional Power Doppler Evaluation of Cerebral Vascular Blood Flow: A Novel Tool in the Assessment of Fetal Growth Restriction.

OBJECTIVES: To determine whether fetuses with fetal growth restriction (FGR) are more likely to have abnormal cerebral vascular flow patterns compared to fetuses who are appropriate for gestational age (AGA) when quantified by using 3-dimensional (3D) power Doppler ultrasound. METHODS: We conducted a prospective cohort study of singleton gestations presenting for growth ultrasound examination between 24 and 36 weeks' gestation. Patients with FGR (estimated fetal weight < 10th percentile) were enrolled and matched 1:1 for gestational age (±7 days) with AGA fetuses. A standardized 3D power Doppler image of the middle cerebral artery territory was obtained from each patient. The vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were calculated by the Virtual Organ computer-aided analysis technique (GE Healthcare, Milwaukee, WI). These indices were compared between FGR and AGA fetuses and correlated with 2-dimensional Doppler parameters. Neonatal outcomes were also compared with respect to the 3D parameters. RESULTS: Of 306 patients, there were 151 cases of FGR. There was no difference in the VI (6.0 versus 5.7; P = .65) or VFI (2.0 versus 1.8; P = .31) between the groups; however, the FI was significantly higher in FGR fetuses compared to AGA controls (33.9 versus 32.3; P = .009). There was a weak, but significant, negative correlation between the FI and both the middle cerebral artery pulsatility index (r = -0.34; P < .001) and cerebroplacental ratio (r = -0.29; P < .001). Within the FGR group, there was no difference in any of the 3D vascular indices with regard to neonatal outcomes. CONCLUSIONS: Three-dimensional power Doppler measurement of cerebral blood flow, but not the vascularization pattern, is significantly altered in FGR. This measurement may play a future role in distinguishing pathologic FGR from constitutionally small growth.

Association of Maternal Obesity With Maternal and Neonatal Outcomes in Cases of Uterine Rupture.

OBJECTIVE: To describe the risk of adverse outcomes associated with uterine rupture in the setting of maternal obesity. METHODS: This was a retrospective cohort analysis of singleton nonanomalous neonates born after uterine rupture between 34 and 42 weeks of gestation. We derived data from the U.S. Natality Database from 2011 to 2014. Maternal prepregnancy body mass index (BMI) was categorized according to the World Health Organization classification. The rates of neonatal and maternal complications were calculated for each BMI class. Multivariable logistic regression analysis was used to estimate the risks of these complications among obese pregnancies compared with normal-weight pregnancies. RESULTS: There were 3,942 cases of uterine rupture identified among 15,860,954 births (0.02%) between 2011 and 2014. Of these, 2,917 (74%) met inclusion criteria for analysis. There was an increased risk of low 5-minute Apgar score (22.9% compared with 15.9%; adjusted odds ratio [OR] 1.49 [1.19-1.87]), neonatal intensive care unit admission (31% compared with 24.6%; adjusted OR 1.51 [1.23-1.85]), and seizure (3.7% compared with 1.9%; adjusted OR 1.80 [1.05-3.10]) in obese compared with normal-weight pregnancies. The rate of prolonged assisted ventilation was 8.5% compared with 6.2% (P=.13), which, after adjustment for confounders, was a statistically significant difference (adjusted OR 1.47 [1.05-2.07]). The rate of neonatal death was similar (12.4 compared with 6.5/1,000 births; adjusted OR 2.03 [0.81-5.05]). The rates of various maternal complications were similar between groups. CONCLUSION: In the setting of uterine rupture, maternal obesity moderately increases the risks of low Apgar score, neonatal intensive care unit admission, prolonged ventilation, and seizure. Risk of maternal complications and the risk of neonatal death, however, are similar to risks in patients of normal BMI.

Advanced Maternal Age and the Risk of Major Congenital Anomalies.

Objective This study aims to determine if advanced maternal age (AMA) is a risk factor for major congenital anomalies, in the absence of aneuploidy. Study Design Retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over a 19-year study period. Aneuploid fetuses were excluded. Study groups were defined by maternal age ≤ 34 and ≥ 35 years. The primary outcome was the presence of one or more major anomalies diagnosed at the second trimester ultrasound. Univariable and multivariable logistic regression analyses were used to estimate the risk of major anomalies in AMA patients. Results Of 76,156 euploid fetuses, 2.4% (n = 1,804) were diagnosed with a major anomaly. There was a significant decrease in the incidence of major fetal anomalies with increasing maternal age until the threshold of age 35 (p < 0.001). Being AMA was significantly associated with an overall decreased risk for major fetal anomalies (adjusted odds ratio: 0.59, 95% confidence interval: 0.52-0.66). The subgroup analysis demonstrated similar results for women ≥ 40 years of age. Conclusion AMA is associated with an overall decreased risk for major anomalies. These findings may suggest that the "all or nothing" phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive.

Genetic Carrier Screening in the Twenty-first Century.

Historically, carrier screening for a small number of autosomal recessive disorders has been offered to targeted populations based on ethnicity and family history. These chosen disorders are associated with severe morbidity or mortality, have a well-established carrier frequency in the targeted population, and have an acceptably high detection rate to make screening efficient. With advancing genetic technology, expanded panels rapidly are being designed and offered to the panethnic general population. This article reviews current recommendations for ethnicity-specific carrier screening for common disorders as well as the limitations and counseling complexities associated with expanded panels.