The MISOPRED score: Development and validation of a clinical scoring system to predict the effectiveness of Misoprostol treatment for early pregnancy loss.

BACKGROUND: Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. OBJECTIVE: To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. STUDY DESIGN: Retrospective cohort and validation study. METHODS: Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. RESULTS: The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. CONCLUSIONS: MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.

The Accuracy of Sonographically Estimated Fetal Weight and Prediction of Small for Gestational Age in Twin Pregnancy-Comparison of the First and Second Twins.

Accurate sonographic estimation of fetal weight is essential for every pregnancy, especially in twin gestation. We conducted a retrospective analysis of the sonographically estimated fetal weight (sEFW) of all twin gestations performed within 14 days of delivery in a single center that aimed to evaluate the accuracy of sEFW in predicting neonatal weight and small for gestational age (SGA) by comparing the first fetus to the second. A total of 190 twin gestations were evaluated for the study. There was no statistically significant difference in the sEFW between the first and the second twins, but the second twin had a statistically significant lower birth weight (2434 vs. 2351 g, p = 0.028). No difference was found in median absolute systematic error (p = 0.450), random error, or sEFW evaluations that were within 10% of the birth weight between the fetuses (65.3% vs. 67.9%, p = 0.587). Reliability analysis demonstrated an excellent correlation between the sEFW and the birth weight for both twins; however, the Euclidean distance was slightly higher for the first twin (12.21%). For SGA prediction, overall, there was a low sensitivity and a high specificity for all fetuses, with almost no difference between the first and second twins. We found that sEFW overestimated the birth weight for the second twin, with almost no other difference in accuracy measures or SGA prediction.

Abdominal circumference discordance for prediction of small for gestational age at birth in twin pregnancies.

OBJECTIVE: To evaluate whether single sonographic abdominal circumference (AC) discordancy estimation can predict small for gestational age (SGA) at birth in twin gestations. METHODS: A retrospective analysis of prospectively collected data. Cohort included all twin gestations delivered at one university-affiliated medical center between 2010 and 2018, with available sonographic evaluation from 22 gestational weeks to term. Pregnancies complicated by fetal chromosomal abnormalities, major anomalies or twin to twin transfusion syndrome were excluded. One sonographic evaluation per pregnancy was selected randomly. AC discordance was calculated as (large twin AC - small twin AC)/large twin AC*100. Prediction of SGA at birth for at least one newborn (<10% percentile for gestational age by gender-specific local curves for multiples) was evaluated using ROC statistics with calculation of Youden index to establish best AC discordance cutoff. AC discordance prediction performance was compared to estimated fetal weight discordance performance. Results were adjusted for confounders using logistic regression analysis. RESULTS: After exclusion, 236 twin gestations entered analysis. Of them, 200/236 (84.7%) were dichorionic-diamniotic twins. Mean gestational age at ultrasound evaluation and at delivery were 30.9 ± 4.4 and 35.9 ± 2.4 weeks, respectively. In 28/236 (11.8%) pregnancies, at least one neonate was born SGA. AC discordance predicted SGA at birth as good as sonographic estimated fetal weight (sEFW) discordance: ROC-AUC 0.76, 95% CI 0.67-0.85 vs. 0.77 95% CI 0.66-0.87, p < .001 for all. Best AC discordance cutoff for prediction of SGA at birth was 7.1% (57% sensitivity, 87% specificity), ROC-AUC 0.72 (95% CI 0.61-0.84, p < .001). Results remained significant after adjustment for maternal age, nulliparity, chorionicity and ultrasound to delivery interval (aOR 1.21 95% CI 1.1-1.32, p < .001). CONCLUSION: According to our results, AC discordance at single sonographic evaluation can predict SGA at birth in twin gestations as good as sEFW discordance. Best cutoff for SGA prediction was 7.1%.

Determination of reference values for third trimester amniotic fluid index: a retrospective analysis of a large cohort of pregnancies with comparison to previous nomograms.

PURPOSE: To establish a new set of reference values for third-trimester amniotic fluid index (AFI) and compare them to other previously published normograms. METHODS: A retrospective cross-sectional cohort analysis of all singleton sonographic evaluations >22 gestational weeks in one university affiliated medical center between 2013 and 2017. Pregnancies complicated by rupture of membranes, major anomalies/chromosomal abnormalities were excluded. One evaluation per patient per pregnancy was randomly selected. Reference values were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age after normalization of variables and compared with previously published norms. RESULTS: A total of 7037 ultrasound evaluations entered the analysis. Correlation between AFI and gestational age was best represented by a first-degree polynomial equation. AFI decreased gradually from 16.4 at 22 weeks to 13.3 at 40 weeks (cm, median). The standard deviation increased with gestational age with AFI ranging from 12.9-20.2 at 22 weeks and 4.7-26.2 at 40 weeks (cm, 2.5-97.5 percentile). Compared to other curves, our reference values demonstrated a higher median AFI throughout all gestation. CONCLUSIONS: Reference values for the third trimester AFI were established. Curves should be correlated with perinatal outcome prior to wide clinical implementation.

It is about time. The advantage of transabdominal cervical length screening.

PURPOSE: Sonographic cervical length (CL) measurement has become a standard practice for identifying women at increased risk for preterm birth. We aimed to assess the time needed for CL measurement during fetal anatomy scan using either transabdominal or transvaginal ultrasound, and to provide a predictive value of the transabdominal CL measurements for reassuring transvaginal CL measurements of more than 25 mm. METHODS: In a prospective study we measured CL transabdominally, and transvaginally in all the anatomy scans performed at 18-25 weeks' gestation, from January 2017 until January 2018. CL and the duration of the examination were compared between the two approaches. Adjustments were made for, body mass index, previous cesarean sections and parity. RESULTS: Four hundred sixty-eight patients participated in the study. The time needed for the transabdominal CL measurement was significantly lower compare with the transvaginal CL measurement (0.46 ± 0.3 min versus 6.9 ± 1.38 min, p < 0.001). The CL measured transabdominally was significantly shorter than the CL measured transvaginally (36.7 ± 6.7 mm versus 41.9 ± 7.3 mm, respectively p < 0.001). All women with transabdominal CL measurements above 36 mm (64.2% of patients) had a transvaginal CL of more than 25 mm. CONCLUSION: Transvaginal measurement of CL is a time-consuming procedure that prolong fetal anomaly scan by 25%. Transabdominal CL measurement of 36 mm is reassuring CL above 25 mm. Transabdominal ultrasound should be used as an initial tool for CL screening. Transvaginal measurements of CL should be reserved for high-risk women, for women with difficulties in demonstrating the cervix abdominally, and for women with transabdominal measurements of less than 36 mm.

The Accuracy of Sonographic Fetal Head Circumference in Twin Pregnancies.

OBJECTIVE: To assess the accuracy of sonographic estimation of fetal head circumference in twin gestations. METHODS: A retrospective analysis of sonographic evaluations of twin gestations >34 weeks, performed within 7 days of delivery, in a single university-affiliated medical centre. Sonographic head circumference was compared with neonatal head circumference. Measures of accuracy included systematic error, random error, proportion of estimates within 5% of neonatal head circumference, and reliability analysis. Accuracy of sonographic head circumference was compared between the first and second twin. RESULTS: Overall, 103 twin gestations were evaluated at a median of 4 days before delivery. The majority of twins were dichorionic-diamniotic (83%). Median gestational age at delivery was 37 weeks, with a median birth weight of 2645 grams for the first twin and 2625 grams for the second twin. For all fetuses, median sonographic head circumference was lower than the neonatal head circumference (first twin: 317.5 vs. 330 mm; second twin: 318.4 vs. 330 mm, P > 0.05 for both). Measures of accuracy showed no significant difference between first and second twin. There was no difference in the number of sonographic head circumference evaluations that were within 5% of the neonatal head circumference between fetuses (64% for both twins). Cronbach α value was higher for the second twin (0.746 vs. 0.613), suggesting higher accuracy for head circumference measurement for the second twin. CONCLUSION: In our cohort, sonographic head circumference underestimated postnatal head circumference. Accuracy measurements were not significantly different between the first and second twin.

The effect of endometrial thickness and pattern on the success of frozen embryo transfer cycles and gestational age accuracy.

OBJECTIVE: To evaluate the relationship between endometrial thickness measured before embryo transfer, and pregnancy outcomes in frozen-thawed embryo transfer (FET). METHODS: We retrospectively analyzed outcomes of all consecutive FET cycles, from January 2012 to August 2018. Based on ROC analysis for endometrial thickness, we found 8 mm was a reliable cutoff point to predict pregnancy prior to embryo transfer. Accordingly, the cycles were divided into Group A: cycles with endometrial thickness ≤ 8 mm and Group B: > 8 mm. RESULTS: Group A included 485 FET cycles and group B included 626 cycles. Compared with group A, Group B had significantly higher chemical and clinical pregnancy rates (30.3 vs. 24.6%; p = .046, and 24.0 vs. 18.6%; p = .036), respectively. In multivariate analysis, endometrial thickness and the protocols used were the only parameters influencing the chance to achieve pregnancy, with odds ratio 1.54 (95%CI 1.07-2.22, p = .019) for the endometrium and odds ratio 1.95 (95%CI 1.31-2.9; p = .001) to the protocol used. Endometrial thickness might predict crown-rump length (CRL) discordancy with odds ratio 4.61 (p = .001; 95% CI 1.42-14.92). Compared with group B, Group A had more cases of overt discordancy (13.3 vs. 4%; p = .016). CONCLUSIONS: For patients undergoing FET cycles, endometrial thickness and treatment protocol may predict the chemical and clinical pregnancy rates, as well as CRL discordancy. SUMMARY: Endometrial thickness and preparation improved pregnancy rate in FET cycles and significantly greater crown-rump length discordancy was observed with thinner endometria.

New reference values for biometrical measurements and sonographic estimated fetal weight in twin gestations and comparison to previous normograms.

Objective To construct new reference values for biometrical measurements and sonographic estimated fetal weight (sEFW) in twin gestations and compare them to previously published normograms. Methods A retrospective analysis of sEFW evaluations of twin gestations was performed between 2011 and 2016 in a single university-affiliated medical center. sEFW was calculated using the Hadlock 1985 formula. To avoid selection bias, one evaluation per pregnancy was randomly selected. Following mathematical transformation to obtain normality of values, normograms were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age (GA). Normograms were validated by applying all observations to ensure equal distribution at parallel percentiles. Our normograms were then compared to previously published sEFW normograms for twin gestations. Results A total of 864 sEFW evaluations were performed on 195 twin pregnancies at 22-39 gestational weeks. Of them, 390 entered the primary analysis. The rest were left for validation. Seventy percent of the cohort were dichorionic-diamniotic twins (136/195), 16% (32/195) were monochorionic-diamniotic twins and three (1.5%) were monochorionic-monoamniotic twins. Twenty-four fetuses lacked data on chorionicity. The rest were monochorionic twins or were of unknown chorionicity. Values corresponding to the 2.5th, 10th, 50th, 90th and 97.5th percentiles for sEFW are presented for every GA. Validation by applying all 864 evaluations on constructed normograms was achieved. Comparison to previously published twins' sEFW normograms demonstrated wide variation between curves. Conclusion New reference values for biometrical measurements and sEFW in twin gestations are presented for clinical and research use. Comparison to other curves demonstrates the wide variability and need for further investigation on twin's normal growth.

Cesarean scar pregnancy managed with local and systemic methotrexate: A single center case series.

OBJECTIVE: To report the efficacy of combined systemic and local methotrexate treatment for cesarean scar pregnancy and review data from selected, similar case series. STUDY DESIGN: A retrospective case series of 12 patients with cesarean scar pregnancy treated in a university hospital between 2014 and 2018. The intervention was combined treatment of systemic and local methotrexate. RESULTS: Twelve patients were treated with combined systemic and local methotrexate. Clinical characteristics, clinical course and treatment efficacy were evaluated. Mean gestational age at diagnosis was 7.5 weeks (range 5.9-9.1). ßhCG levels at diagnosis ranged from 1581 to 345,427 U/L with a mean of 77,795 U/L. All 12 patients were successfully treated without surgical intervention and with no significant side-effects. Mean hospitalization duration was 9 days (5.8-12.6) and mean time to normalization of ßhCG levels was 98 days (63-132). CONCLUSIONS: Treatment of cesarean scar pregnancy with a combination of systemic and local methotrexate was effective and safe. Although the treatment course tends to be longer than with other modalities, this protocol offers excellent success rates, with fertility preservation and few complications.

No. 274-Management of Varicella Infection (Chickenpox) in Pregnancy.

OBJECTIVE: To review the existing data regarding varicella zoster virus infection (chickenpox) in pregnancy, interventions to reduce maternal complications and fetal infection, and antepartum and peripartum management . METHODS: The maternal and fetal outcomes in varicella zoster infection were reviewed, as well as the benefit of the different treatment modalities in altering maternal and fetal sequelae. EVIDENCE: Medline was searched for articles and clinical guidelines published in English between January 1970 and November 2010. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table).

Trends in Continuity of Pregnancy in Women with Positive Cytomegalovirus IgM during the First Trimester, 2008-2009.

BACKGROUND: Cytomegalovirus (CMV) infection during pregnancy is the most common cause of intrauterine infection, and is a common cause of sensorineural hearing loss and mental retardation. OBJECTIVES: To evaluate trends in amniocentesis and pregnancy outcome in women with suspected cytomegalovirus (CMV) infection during the first trimester. METHODS: All blood tests for CMV immunoglobulin M (IgM) done between 2008 and 2009 on pregnant women who were enrolled in the Maccabi Healthcare Services were retrieved from laboratory database. Immunoglobulin G (IgG) avidity was measured and women were classified according to the risk of acquiring CMV infection. For each patient, performance of amniocentesis and whether pregnancy came to term were recorded. RESULTS: Of 109,439 pregnant women evaluated during the study period, 76,712 (70.1%) were tested for CMV IgM, and 792 (1.03%) were found to be positive. Among women with positive IgM, only 205 (25.9%) underwent amniocentesis. When compared with women with negative CMV IgM, the rate of pregnancy cessation was doubled in women with positive CMV IgM (28.3% vs. 14.3%, P < 0.05) and mostly elevated in women with a high risk of acquiring CMV (42.3% pregnancy cessation). Among women with positive CMV IgM, those who did not undergo amniocentesis were more likely to abort than those who performed amniocentesis (35.6% vs. 7.3%, P < 0.05). CONCLUSIONS: More women with suspected CMV infection during the first trimester of pregnancy aborted before all means of detection were utilized to rule out or confirm fetal infection with CMV.

Factors Associated with Compliance of Folic Acid Consumption among Pregnant Women.

BACKGROUND: The prevalence of major malformations in the general population is estimated at 5% of all live births. Prenatal diagnosis is an important scientific tool that allows reliable consultation and improves pregnancy outcome. In 2008, congenital malformations were the leading cause of death in Muslim infants and the second cause of death in Jewish infants in Israel. It is known that folic acid consumption prior to pregnancy decreases the rate of several fetal malformations. OBJECTIVES: To assess the folic acid consumption rate and to characterize variables associated with its use among pregnant women attending a rural medical center. METHODS: A cross-sectional observational study was conducted at our institution. Pregnant women in the second or third trimester of pregnancy or within 3 days postpartum were interviewed. The main variable measured was the use of folic acid. Demographic variables and the rate of prenatal testing were assessed. A secondary analysis of the population that reported no consumption of folic acid was carried out. RESULTS: Out of 382 women who participated in the study, 270 (71%) reported consumption of folic acid. Using a multivariate analysis model, we found that maternal education, planning of pregnancy, and low parity were independent predictors of folic acid consumption. Women who were not consuming folic acid tended to perform fewer prenatal tests during pregnancy. CONCLUSIONS: High maternal educational level, planning of pregnancy, and low parity are related to high consumption rates of folic acid. Women who were not taking folic acid performed fewer prenatal tests during pregnancy.

Prenatal diagnosis of 17q12 deletion syndrome: from fetal hyperechogenic kidneys to high risk for autism.

OBJECTIVE: The linkage between 17q12 microdeletions, renal anomalies, and higher risk for neurodevelopmental disorders is well described in the literature. The current study presents prenatal diagnosis of normal-sized fetal hyperechogenic kidneys leading to the diagnosis of 17q12 deletion syndrome and autism spectrum disorder. METHODS: Over a period of 9 years in a single referral center, seven fetuses were diagnosed with hyperechogenic renal parenchyma and were followed up prospectively. Amniocentesis for molecular diagnosis was performed in all cases, and subsequently, five fetuses were found to harbor a 17q12 deletion by chromosomal microarray analysis. Postnatal evaluation was carried out by a developmental neurologist. RESULTS: Five of the seven fetuses had molecular diagnosis of 17q12 deletion. One patient elected termination of pregnancy. On long-term follow-up, all of the four children showed symptoms consistent with neurodevelopmental disorders. The two fetuses with no deletion have a normal follow-up with regression of the renal hyperechogenicity. CONCLUSIONS: We report a strikingly high correlation between prenatal hyperechogenic kidneys, 17q12 microdeletion, and autism spectrum disorder with the advantage of optimal prenatal counseling as well as early diagnosis and intervention. © 2016 John Wiley & Sons, Ltd.

Maternal characteristics of pregnancies with intrauterine fetal demise.

OBJECTIVE: To identify maternal characteristics independently associated with pregnancies resulting in intrauterine fetal demise (IUFD). STUDY DESIGN: This was a population-based cohort study of all births taking place at the McGill University Health Centre in Montreal, Canada, between 2001 and 2007, using the McGill University Obstetrics and Neonatal Database. Maternal characteristics were compared between pregnancies that resulted in IUFD and control pregnancies resulting in live newborns. A logistic regression analysis was constructed to identify parameters independently associated with IUFD. RESULTS: We identified 20,744 births during the study period, 87 of which were complicated by IUFD. Mothers with IUFD were more likely to be younger, with less formal education, higher rates of smoking during pregnancy, and more fetal anomalies (42.5% vs. 7.5%, P<0.001). After exclusion of pregnancies with congenital and/or chromosomal abnormalities, less formal education (7 vs. 13.6 school years, P<0.001) and smoking during pregnancy (24% vs. 7.7%, P<0.001) remained significantly more common in pregnancies resulting in IUFD. In the multivariable regression analysis both smoking and number of maternal school years were independently associated with IUFD pregnancies (OR 2.22 for smoking, P=0.007 and OR 0.865 for number of school years, P<0.001). CONCLUSION: Lower levels of education and smoking during pregnancy are independent predictors of IUFD.