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..

Single fetal demise following fetoscopic ablation for twin-to-twin transfusion syndrome-cohort study, systematic review, and meta-analysis.

BACKGROUND: Several studies have assessed preoperative and operative factors associated with fetal demise after laser for TTTS, yet these findings are not completely conclusive. OBJECTIVE: This study aimed to identify risk factors for single fetal demise (recipient and donor twins) after fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome. STUDY DESIGN: We searched PubMed, Scopus, and Web of Science systematically from the inception of the database to June 2020. We conducted a systemic review on studies investigating risk factors for fetal demise (donor and/or recipient) after fetoscopic laser photocoagulation in monochorionic pregnancies complicated with twin-to-twin transfusion syndrome. Initially, we investigated the cohort of women with twin-to-twin transfusion syndrome that underwent fetoscopic laser photocoagulation at our 2 high-volume fetal centers between 2012 and 2020 to identify risk factors for donor demise and recipient demise. Furthermore, we conducted a systematic review of the literature to better characterize these factors. Among studies that met the entry criteria, multiple preoperative and operative factors were tabulated. The random-effect model was used to pool the standardized mean differences or odds ratios and corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 514 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were included in the final analysis. Following the logistic regression, factors that remained significant for donor demise were selective fetal growth restriction (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P=.001) and umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.06; 95% confidence interval, 1.2-3.4; P=.004). A significant factor associated with recipient demise was absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 1.74; 95% confidence interval, 1.07-3.13; P=.04). Data from 23 studies and our current cohort were included. A total of 4892 pregnancies with twin-to-twin transfusion syndrome managed with fetoscopic laser photocoagulation were analyzed for risk factors for donor demise, and 4594 pregnancies with twin-to-twin transfusion syndrome were analyzed for recipient demise. Among studies, the overall incidence rates ranged from 10.9% to 35.8% for donor demise and 7.3% to 24.5% for recipient demise. Significant risk factors for donor demise were intertwin estimated fetal weight discordance of >25% (odds ratio, 1.86; 95% confidence interval, 1.44-2.4; I2, 0.0%), selective fetal growth restriction (odds ratio, 1.78; 95% confidence interval, 1.4-2.27; I2, 0.0%), twin-to-twin transfusion syndrome stage III (odds ratio, 2.18; 95% confidence interval, 1.53-3.12; I2, 0.0%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the donor (odds ratio, 2.31; 95% confidence interval, 1.9-2.8; I2, 23.7%), absent or reversed a-wave in the ductus venosus of the donor (odds ratio, 1.83; 95% confidence interval, 1.45-2.3; I2, 0.0%), and presence of arterioarterial anastomoses (odds ratio, 2.81; 95% confidence interval, 1.35-5.85; I2, 90.7%). Sequential selective coagulation was protective against donor demise (odds ratio, 0.31; 95% confidence interval, 0.16-0.58; I2, 0.0%). Significant risk factors for recipient demise were twin-to-twin transfusion syndrome stage IV (odds ratio, 2.18; 95% confidence interval, 1.01-4.6; I2, 16.5%), umbilical artery blood flow with absent or reversed end-diastolic velocity of the recipient (odds ratio, 2.68; 95% confidence interval, 1.91-3.74; I2, 0.0%), absent or reversed a-wave in the ductus venosus of the recipient (odds ratio, 2.37; 95% confidence interval, 1.55-3.64; I2, 60.2%), and middle cerebral artery peak systolic velocity of >1.5 multiple of the median (odds ratio, 3.06; 95% confidence interval, 1.36-6.88; I2, 0.0%). CONCLUSION: Abnormal blood flow patterns represented by abnormal Doppler studies and low fetal weight were associated with single fetal demise in women with twin-to-twin transfusion syndrome undergoing laser therapy. Although sequential selective coagulation was protective against donor demise, the presence of arterioarterial anastomoses was considerably associated with donor demise. This meta-analysis extensively investigated the association of a wide range of preoperative and operative factors with fetal demise. These findings may be important inpatient counseling, in further understanding the disease, and perhaps in improving surgical techniques.

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.

Evaluating the Optimal Definition of Abnormal First-Trimester Uterine Artery Doppler Parameters to Predict Adverse Pregnancy Outcomes.

OBJECTIVES: To investigate the optimal definition of abnormal first-trimester uterine artery Doppler parameters associated with adverse pregnancy outcomes. METHODS: A prospective cohort of women with singleton gestations between 11 and 14 weeks consented to uterine artery Doppler measurements. Doppler parameters were measured bilaterally, and mean pulsatility index (PI) and resistive index (RI) values were calculated. The presence of notching was also determined. Each parameter was evaluated for prediction of preeclampsia, early preeclampsia (<34 weeks), preterm birth (<37 weeks), early preterm birth (<34 weeks), and small for gestational age (SGA; birth weight <10th percentile). Descriptive statistics evaluated the association between abnormal Doppler indices and outcomes. A receiver operating characteristic (ROC) analysis was used to define the best cutoff points for mean PI and RI. The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were calculated for bilateral notching and mean PI and RI percentiles. RESULTS: Of 1192 patients with complete outcome data, preeclampsia was seen in 8.4%, early preeclampsia in 1.8%, preterm birth in 12.9%, early preterm birth in 5.6%, and SGA in 8.5%. A mean PI above the 75th percentile (>1.91) was the best index for predicting early preeclampsia (sensitivity, 45.0%; specificity, 75.5%; NPV, 98.7%; ROC area, 0.65). A mean PI above the 75th percentile was also the best index for predictive early preterm birth (sensitivity, 40.0%; specificity, 76.0%; NPV, 95.5%; ROC area, 0.65). None of the parameters were significant for predicting SGA. CONCLUSIONS: A mean uterine PI above the 75th percentile is the most discriminative abnormal uterine artery Doppler parameter for predicting both early preeclampsia and early preterm birth.

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.