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.

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..

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.

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.

The impact of chorionicity on maternal pregnancy outcomes.

OBJECTIVE: Women carrying twin pregnancies often receive similar counseling, regardless of chorionicity, with the notable exception of twin-twin transfusion syndrome (TTTS); however, little is known about whether the presence of 1 vs 2 placentas confers dissimilar maternal risks. We sought to determine differences in maternal and neonatal outcomes based on chorionicity. STUDY DESIGN: This was a retrospective cohort study of all twin pregnancies at our institution undergoing routine second-trimester ultrasound for anatomic survey from 1990 through 2010. Secondary outcomes included other adverse maternal and neonatal outcomes. Relative risks and adjusted odds ratios (aORs) were calculated. Cluster analysis was used to account for nonindependence of twin pairs. RESULTS: Of 2301 pregnancies, 1747 (75.9%) were dichorionic and 554 (24.1%) were monochorionic. Rates of preeclampsia, gestational diabetes, placental abruption, placenta previa, preterm labor, and preterm premature rupture of membranes (PPROM) were not significantly different in dichorionic vs monochorionic pregnancies. Early preterm delivery less than 34 weeks (aOR, 1.47; 95% confidence interval [CI], 1.17-1.86) and less than 28 weeks (aOR, 2.58; 95% CI, 1.58-4.20) were more likely in monochorionic twins, as was neonatal intensive care unit admission (aOR, 1.41; 95% CI, 1.12-1.78). Monochorionic twins delivered earlier at a mean gestational age of 34.2 weeks vs 35.0 weeks for dichorionic twins (P < .001). Hospital length of stay was significantly longer for monochorionic twins with a mean of 13.7 days vs 10.8 days for dichorionic twins (P = .01). CONCLUSION: There are no significant differences in maternal outcomes by chorionicity; however, monochorionicity is associated with increased fetal risks. This information may be helpful in guiding more targeted counseling to expectant parents of twins that, although the presence of an additional placenta does not confer additional maternal risks, monochorionic infants tend to deliver earlier and require longer hospital stays.

First-trimester 3-dimensional power Doppler placental vascularization indices from the whole placenta versus the placental bed to predict preeclampsia: does pregnancy-associated plasma protein a or uterine artery Doppler sonography help?

OBJECTIVES: The purpose of this study was to compare the use of vascular indices derived from the whole placenta to those from the placental bed only for predicting preeclampsia and to determine whether the addition of pregnancy-associated plasma protein A (PAPP-A) and mean uterine artery Doppler values improves prediction. METHODS: We conducted a secondary analysis of a prospective cohort of women with singletons between 11 and 14 weeks' gestation undergoing sonography for aneuploidy screening. Placental vascularization indices from the whole placenta versus the placental bed were combined with first-trimester maternal serum PAPP-A levels, mean uterine artery Doppler values, or the combination of both to predict the development of preeclampsia or early preeclampsia (delivery <34 weeks). The predictive ability of each vascular index was calculated by using areas under receiver operating characteristic curves. The sensitivity of the model for predicting preeclampsia and early preeclampsia at fixed false-positive rates of 10% and 20% was calculated. RESULTS: Of 570 women, 48 (8.4%) had preeclampsia, and 10 (1.7%) had early preeclampsia. The area under the curve and sensitivity values for the prediction of preeclampsia or early preeclampsia were not different when evaluating the whole placenta versus the placental bed. Additionally, there was no significant improvement when adding PAPP-A, uterine artery Doppler values, or both. The variables in the model were more sensitive for the prediction of early preeclampsia than preeclampsia. CONCLUSIONS: Although placental bed vascular indices are modestly predictive of preeclampsia, the addition of PAPP-A and uterine artery Doppler values to vascularization indices in the whole placenta or the placental bed did not significantly improve their predictive ability.

Screening for abnormal placentation and adverse pregnancy outcomes with maternal serum biomarkers in the second trimester.

Second trimester biomarkers were initially introduced with the intent of screening for neural tube defects and then subsequently for Down syndrome. It was soon realized that these markers can be indirect evidence of abnormal placentation and, therefore, can be used for screening for adverse pregnancy outcomes. Several new biomarkers have subsequently been described with conflicting findings regarding their efficiency for screening for adverse pregnancy outcomes. Although a biologically feasible mechanism has been proposed for the role of these biomarkers, they still fall short of an ideal screening test to be clinically useful.

Combined sonographic testing index and prediction of adverse outcome in preterm fetal growth restriction.

OBJECTIVE: We sought to test the hypothesis that a combined sonographic scoring system (CSTI) that incorporates features of the biophysical profile (BPP) and multivessel Doppler evaluation improves prediction of adverse outcomes in preterm intrauterine growth restriction. METHODS: This was a prospective cohort study of growth-restricted fetuses with abnormal umbilical artery (UA) Doppler studies, defined as pulsatility index (PI) > 95 th percentile for gestational age or absent/reversed end diastolic flow. Fetuses were followed with weekly BPP and Doppler evaluation of the UA, middle cerebral artery (MCA), and ductus venosus (DV) until the time of delivery. The cerebroplacental Doppler ratio (CPR) was then calculated (MCA PI/UA PI). MCA PI < 5 th percentile, MCA peak systolic velocity (PSV) > 1.5 multiples of the median, DV PI > 95 th percentile with or without absent/reversed flow, and CPR < 1.08 were considered abnormal. Using logistic regression modeling, a weighted scoring index for the prediction of a composite fetal vulnerability index (FVI), which included 5-minute Apgar score < 3, cord pH < 7.2, seizures, necrotizing enterocolitis, grade 4 intraventricular hemorrhage, periventricular leukomalacia, and neonatal death, was developed. A receiver operating characteristic (ROC) curve was used to identify the best score associated with the FVI. RESULTS: Of 66 patients meeting inclusion criteria over a 5-year period, 17 (25.8%) had a positive FVI. Abnormal BPP (< 8), MCA PI, MCA PSV, DV PI, and CPR were observed in 6, 27.3, 13.6, 56.1, and 33.3% of patients, respectively. From the logistic regression model, a CSTI was developed including a score of 1 for abnormal BPP, 3 for MCA PSV, 1 for DV, 6 for CPR, and 3 for oligohydramnios. The ROC curve identified a score of ≥ 7 to be the best predictor of FVI with sensitivity of 35.1% and specificity of 91.8% and a positive likelihood ratio of 4.3 (area under ROC curve 0.73). These test characteristics were better than those for any of the individual component antenatal tests. CONCLUSION: Although this novel scoring system performs modestly in predicting adverse outcomes in FGR, it appears to perform better than any individual antenatal test currently available.

Development and validation of a risk factor scoring system for first-trimester prediction of preeclampsia.

OBJECTIVE: The aim of this study was to develop a multiparameter risk-based scoring system for first-trimester prediction of preeclampsia and to validate this scoring system in our patient population. STUDY DESIGN: Secondary analysis of a prospective cohort of 1,200 patients presenting for first-trimester aneuploidy screening. Maternal serum pregnancy-associated plasma protein A (PAPP-A) levels were measured and bilateral uterine artery (UA) Doppler studies performed. Using the first half of the study population, a prediction model for preeclampsia was created. Test performance characteristics were used to determine the optimal score for predicting preeclampsia. This model was then validated in the second half of the population. RESULTS: Significant risk factors and their weighted scores derived from the prediction model were chronic hypertension (4), history of preeclampsia (3), pregestational diabetes (2), body mass index ≥ 30 kg/m(2) (2), bilateral UA notching (1), and PAPP-A MoM < 10 th percentile (1). The area under the curve (AUC) for the risk scoring system was 0.76 (95% confidence interval [CI], 0.69-0.83), and the optimal threshold for predicting preeclampsia was a total score of ≥ 6. This AUC did not differ significantly from the AUC observed in our validation cohort (AUC, 0.78 [95% CI, 0.69-0.86]; p = 0.75]. CONCLUSION: Our proposed risk factor scoring system demonstrates modest accuracy but excellent reproducibility for first-trimester prediction of preeclampsia.

Efficiency of first-trimester uterine artery Doppler, a-disintegrin and metalloprotease 12, pregnancy-associated plasma protein a, and maternal characteristics in the prediction of preeclampsia.

OBJECTIVES: The purpose of this study was to estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), and maternal characteristics in the prediction of preeclampsia. METHODS: We conducted a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11 and 14 weeks' gestation. Maternal serum ADAM12 and PAPP-A levels were measured by an immunoassay, and mean uterine artery Doppler pulsatility indices were calculated. Outcomes of interest included preeclampsia, early preeclampsia (defined as requiring delivery at <34 weeks' gestation), and gestational hypertension. Logistic regression analysis was used to model the prediction of preeclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler pulsatility index MoM, either individually or in combination. The sensitivity, specificity, and area under the receiver operating characteristic curves were used to compare the screening efficiency of the models using nonparametric U statistics. RESULTS: Among 578 patients with complete outcome data, there were 54 cases of preeclampsia (9.3%) and 13 cases of early preeclampsia (2.2%). Median ADAM12 levels were significantly lower in patients who developed preeclampsia compared to those who did not (0.81 versus 1.01 MoM; P = .04). For a fixed false-positive rate of 10%, ADAM12, PAPP-A, and uterine artery Doppler parameters in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed preeclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. CONCLUSIONS: First-trimester ADAM12, PAPP-A, and uterine artery Doppler characteristics are not sufficiently predictive of preeclampsia. Combinations of these parameters do not further improve their screening efficiency.

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.

First-trimester prediction of preterm birth using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics.

OBJECTIVE: The objective of this study was to estimate the efficiency of first-trimester a disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A), uterine artery Doppler, and maternal characteristics in the prediction of preterm birth (PTB). METHODS: This was a prospective cohort study of patients presenting for first-trimester aneuploidy screening. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices were calculated. The primary outcome was PTB <34 weeks' gestation, and the secondary outcome was PTB <37 weeks' gestation. Logistic regression was used to model the prediction of PTB using ADAM12, PAPP-A, uterine artery Doppler, and maternal characteristics, individually and in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves were compared between models. RESULTS: Of 578 patients, 36 (6.2%) delivered <34 weeks, and 78 (13.5%) delivered <37 weeks. For a 20% fixed false positive rate, ADAM12, PAPP-A, and uterine artery Doppler identified 58%, 52%, and 62% of patients with PTB <34 weeks and 42%, 48%, and 50% of patients with PTB <37 weeks, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. CONCLUSION: First-trimester ADAM12, PAPP-A, and uterine artery Doppler are each modestly predictive of PTB; however, combinations of these parameters do not further improve their screening efficiency.

Isolated short femur length on second-trimester sonography: a marker for fetal growth restriction and other adverse perinatal outcomes.

OBJECTIVES: To estimate the association between isolated second-trimester short femur length and fetal growth restriction as well as other adverse perinatal outcomes. METHODS: We conducted a retrospective cohort study of patients with singleton gestations presenting for sonography between 16 and 24 weeks' gestation from 1990 to 2009. Cases of aneuploidy, skeletal dysplasia, and major anomalies were excluded. Short femur length was defined as length below the 10th percentile for gestational age and was considered isolated when both the estimated fetal weight and abdominal circumference were above the 10th percentile for gestational age. Isolated short femur length below the 5th percentile was also evaluated. The primary outcome was fetal growth restriction, defined as birth weight below the 10th percentile. Secondary outcomes included preeclampsia and preterm birth before 37 and 34 weeks. Univariable and multivariable logistic regression analyses were used to estimate the risk of these outcomes in fetuses with isolated short femur length. RESULTS: Of 73,884 patients, 569 (0.8%) had a fetus with a femur length below the 10th percentile, of which 268 (47.1%) were isolated; 210 patients (0.3%) had a fetus with a femur length below the 5th percentile, of which 34 (16.2%) were isolated. Isolated short femur lengths below the 10th and 5th percentiles were associated with an increased risk of fetal growth restriction (<10th: adjusted odds ratio [aOR], 3.4; 95% confidence interval [CI], 2.4-4.6; <5th: aOR, 4.6; 95% CI, 2.0-10.7) and also with an increased risk of preterm birth before 37 and 34 weeks. There was no significant association between isolated short femur length and preeclampsia. CONCLUSIONS: Isolated short femur length on second-trimester sonography is associated with a greater than 3-fold increased risk of fetal growth restriction and an increased risk of preterm birth. Serial growth assessment may be warranted in these cases.

The relationship between maternal body mass index and tobacco use on small-for-gestational-age infants.

We sought to estimate the association between prepregnancy body mass index (BMI) and small-for-gestational-age (SGA) neonates and to determine if there is a synergistic effect of tobacco use on SGA across all BMI strata. We performed a retrospective cohort study of 65,104 patients seen for second-trimester ultrasound. BMI was categorized into underweight, normal weight, overweight, and obese. SGA was defined as birth weight <10th percentile and <5th percentile. Univariable and multivariable logistic regression analyses were used to evaluate the association between BMI and SGA. Stratified analyses and tests for effect modification were performed to evaluate for a potential synergistic effect between tobacco use and abnormal prepregnancy BMI on SGA. After controlling for potential confounders, underweight BMI was associated with an increased risk for SGA <10th percentile (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.5 to 2.1), while overweight (aOR 0.7, 95% CI 0.7 to 0.8) and obese BMIs (aOR 0.6, 95% CI 0.5 to 0.7) were associated with a decreased risk of SGA. There was no effect modification of tobacco use on the risk of SGA across all BMI categories. Although both tobacco and underweight BMI are independently associated with SGA, there was no evidence of synergism. Continued emphasis on both smoking cessation and maintenance of normal prepregnancy BMI remains paramount to decreasing the incidence of SGA.

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-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.

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.