A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes1. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells2-5. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples. Replicates of the same cell type are more than 99.5% identical, demonstrating the robustness of cell identity programmes to environmental perturbation. Unsupervised clustering of the atlas recapitulates key elements of tissue ontogeny and identifies methylation patterns retained since embryonic development. Loci uniquely unmethylated in an individual cell type often reside in transcriptional enhancers and contain DNA binding sites for tissue-specific transcriptional regulators. Uniquely hypermethylated loci are rare and are enriched for CpG islands, Polycomb targets and CTCF binding sites, suggesting a new role in shaping cell-type-specific chromatin looping. The atlas provides an essential resource for study of gene regulation and disease-associated genetic variants, and a wealth of potential tissue-specific biomarkers for use in liquid biopsies.

Reference Ranges for Left Modified Myocardial Performance Index: Systematic Review and Meta-Analysis.

INTRODUCTION: The modified myocardial performance index (mod-MPI) is a noninvasive Doppler-derived metric used to evaluate fetal cardiac function. However, the reference ranges for mod-MPI in normal fetuses are not clearly defined, which limits the use of this technology in fetuses with potential cardiac compromise. Thus, we aimed to perform a systematic review and meta-analysis of published mod-MPI reference ranges across gestation. METHODS: The published literature was systematically searched, and all published articles in any language that provided values for the left ventricular mod-MPI obtained in low-risk, singleton fetuses were considered eligible for further review. All retrieved titles and abstracts were independently reviewed by two researchers. Mean and standard deviation by gestational week was extracted or calculated from published data. DerSimonian-Laird random-effects models were used to estimate pooled means and 95% confidence intervals (CIs). RESULTS: The search resulted in 618 unique citations, of which 583 did not meet inclusion criteria, leaving 35 abstracts selected for full-text review. Review of the references of these 35 articles identified another 5 studies of interest. Of the 40 articles reviewed, six met inclusion criteria. There was significant heterogeneity seen in the mod-MPI results reported. Mod-MPI increased as pregnancy progressed in all studies. The pooled mean mod-MPI at 11 weeks' gestation was 0.400 (95% CI 0.374-0.426) and increased to 0.585 (95% CI 0.533-0.637) at 41 weeks' gestation. The increase was linear in 5 of 6 studies, while in 1 study, the mod-MPI was stable until 27 weeks' gestation, and then increased throughout the third trimester. Despite all having trends increasing over pregnancy, there was no study in which all the weekly means fell within the pooled 95% CI. CONCLUSION: While mod-MPI does increase over gestation, the true "reference ranges" for fetuses remain elusive. Future efforts to further optimize calculation of time intervals possibly via automation are desperately needed to allow for reproducibility of this potentially very useful tool to assess fetal cardiac function.

Kinetics of Maternally Derived Anti-Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies in Infants in Relation to the Timing of Antenatal Vaccination.

BACKGROUND: SARS-CoV-2 infection during early infancy can result in severe disease. We evaluated the durability of maternally-derived anti-SARS-CoV-2 antibodies in infants and its relation to antenatal vaccination timing. METHODS: Sera were prospectively collected at birth and 3 months after delivery from mother-infant pairs following antenatal BNT162b2 vaccination. SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels and neutralizing activity were evaluated. RESULTS: 56 mother-infant pairs were included: 15 (26.8%) were vaccinated in the first trimester, 16 (28.6%) in the second trimester, and 25 (44.6%) in the third trimester.At the time of delivery, all neonates were positive for anti-RBD-specific IgG with a median concentration of 4046 [IQR 2446-7896] AU/mL, with the highest concentration found after third trimester vaccination (median 6763 [IQR 3857-12561] AU/mL). At 3 months after delivery, anti RBD-specific IgG levels in infants significantly waned with a median concentration of 545 [IQR 344-810] AU/mL (P < .001). The half-life of anti-RBD-specific IgG was 66 days among mothers and 30 days among infants. While at the time of delivery, all neonates had detectable neutralizing activity regardless of gestational age at vaccination, at 3-months of age, a higher proportion of infants born to mothers vaccinated in third trimester had persistent neutralizing activity as compared to those born to mothers vaccinated in second trimester. CONCLUSIONS: Maternal vaccination leads to efficient transplacental antibody transfer, with persistent anti-SARS-CoV-2 antibodies detected at 3 months of age in all infants. The observed effect of antenatal immunization timing on the kinetics of maternally-derived antibodies may have implications for SARS-CoV-2 vaccination strategies.

The effect of SARS-CoV-2 BNT162b2 vaccine on the symptoms of women with endometriosis.

PURPOSE: As the use of the messenger RNA (mRNA) BNT162b2 (Pfizer-BioNTech) Coronavirus disease 2019 vaccine has grown, reports on menstrual changes have arisen. We aimed to examine menstrual bleeding patterns and endometriosis-associated symptoms after receiving the mRNA BNT162b2 SARS-CoV-2 vaccine in women with endometriosis, as compared to the control group. METHODS: This is a questionnaire-based cross-sectional study including a total of 174 women. The study group included 86 women with a confirmed diagnosis of endometriosis and the control group included 88 women with no diagnosis or suspected diagnosis of endometriosis. Each woman completed a questionnaire on menstrual bleeding patterns and endometriosis-associated symptoms before and after receiving two doses of the BNT162b2 vaccine. Primary outcomes were changes in amount or length of menstrual bleeding, rates of intermenstrual bleeding and worsening in dysmenorrhea in the endometriosis patient group, as compared to the control group. Secondary outcomes included changes in all endometriosis-associated symptoms. RESULTS: In our cohort, women with endometriosis were more likely to experience changes in bleeding patterns (women with endometriosis: 39.5%, control group: 31.0%, p = 0.02), and a significant worsening in endometriosis-associated symptoms with an almost 4.3-fold worsening in dysmenorrhea [95% CI 1.9-9.9, p < 0.01] and 5.5-fold odds for any worsening in symptoms in endometriosis patients, as compared to the control group [95% CI 2.7-11.1, p < 0.01]. CONCLUSION: In our cohort, endometriosis was shown to be a significant risk factor for worsening of menstrual symptoms, after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine. Further research is needed to confirm these findings.

Reference Ranges for Vermis Biometry on Prenatal Ultrasound: Systematic Review and Meta-Analysis.

PURPOSE: To conduct a systematic review and meta-analysis of published nomograms for fetal vermis biometry. MATERIALS AND METHODS: A structured literature search was conducted to identify studies that reported normal measurements of the fetal vermis. A customized quality assessment tool was used to review the selected articles. Random effects meta-analysis was used to calculate normal ranges for vermian craniocaudal diameter, anteroposterior diameter, and surface area. RESULTS: A total of 21 studies were included for qualitative review and 3 studies were included for quantitative synthesis. The 3 included articles comprised a total of 10 910 measurements from gestational ages 17-35 weeks. The quality assessment demonstrated that there was generally poor reporting regarding maternal characteristics and neonatal outcomes. Except for one article with a large sample size, the mean number of fetuses per week of gestational age was 15.9, with the lowest number being 5. There was significant statistical heterogeneity. Non-visualization rates ranged from 0-35.4 %. The craniocaudal diameter (reported in 3 articles) increased from a mean of 7.90 mm (95 % confidence interval [CI] 7.42, 8.38) at 17 weeks to 21.90 mm (95 % CI 20.63, 23.16) at 35 weeks gestation. The anteroposterior diameter (reported in 2 articles) increased from 6.30 mm (95 % CI 5.42, 7.18) at 17 weeks to 15.85 (95 %CI 15.49, 16.21) at 32 weeks. CONCLUSION: Reference ranges for vermis biometry across gestation based on meta-analysis of existing references are provided. However, because many of the underlying studies suffered from significant methodological issues, the ranges should be used with caution.

Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Neutralization After Antenatal Messenger RNA Vaccination.

We evaluated the neutralization efficiency against SARS-CoV-2 Omicron variant in maternal and cord blood sera after antenatal BNT162b2 vaccination. Neutralizing antibodies against Omicron were lacking at the time of delivery after 2-dose vaccination. A third booster dose was essential in building neutralizing antibody capacity against Omicron among mothers and neonates.

The Effect of Gestational Age at BNT162b2 mRNA Vaccination on Maternal and Neonatal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibody Levels.

BACKGROUND: Coronavirus disease 2019 (COVID-19) during pregnancy and early infancy can result in severe disease. Evaluating the effect of gestational age at the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on maternal antibody levels and transplacental antibody transfer has important implications for maternal care and vaccination strategies. METHODS: Maternal and cord blood sera were collected from mother-newborn dyads (n = 402), following term delivery after antenatal 2-dose SARS-CoV-2 BNT162b2 mRNA vaccination. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)-specific IgG levels were evaluated in the samples collected. RESULTS: Median anti-S and anti-RBD-specific IgG levels in maternal sera at the time of delivery were lowest following first-trimester vaccination (n = 90; anti-S IgG: 76 AU/mL; anti-RBD-specific IgG: 478 AU/mL), intermediate in those vaccinated in the second trimester (n = 124; anti-S IgG: 126 AU/mL; anti-RBD-specific IgG: 1263 AU/mL), and highest after third-trimester vaccination (n = 188; anti-S IgG: 240 AU/mL; anti-RBD-specific IgG: 5855 AU/mL). Antibody levels in neonatal sera followed a similar pattern and were lowest following antenatal vaccination in the first trimester (anti-S IgG: 126 AU/mL; anti-RBD-specific IgG: 1140 AU/mL). In a subgroup of parturients vaccinated in the first trimester (n = 30), a third booster dose was associated with significantly higher maternal and neonatal antibody levels. CONCLUSIONS: These results suggest a considerable antibody waning throughout pregnancy in those vaccinated at early gestation. The observed boosting effect of a third vaccine dose hints at its potential benefit in those who completed the 2-dose vaccine series at early pregnancy or before conception. The impact of antenatal immunization timing on SARS-CoV-2 transplacental antibody transfer may influence neonatal seroprotection.

Duration of the second stage of labour and risk of subsequent spontaneous preterm birth.

OBJECTIVES: To determine the risk of spontaneous preterm birth (sPTB) associated with the length of second stage of labour in the first term delivery. DESIGN: Retrospective cohort study. SETTING: University hospital. POPULATION: Women with first two consecutive singleton births and the first birth at term. Those who did not reach the second stage of labour in the first delivery were excluded. METHODS: Charts from 2007 to 2019 were reviewed. MAIN OUTCOME MEASURES: Rate of sPTB (<37 weeks of gestation) in the second delivery. RESULTS: Of 13 958 women who met study inclusion criteria, 1464 (10.5%) parturients had a prolonged second stage (≥180 min) in their first term delivery. The rate of sPTB in the second delivery was similar in those with and without a prolonged second stage in first delivery (2.8% versus 2.8%; adjusted odds ratio [aOR] 1.35, 95% CI 0.96-1.90). After adjustment for mode of delivery, prolonged second stage was also not associated with subsequent sPTB in those who delivered by spontaneous and operative vaginal delivery. Those delivered by second-stage caesarean section in the first delivery had a higher risk of sPTB in the second delivery (25/526, 4.8%; aOR 2.66, 95% CI 1.71-4.12; p < 0.001), with a more pronounced risk in those with second-stage caesarean following a prolonged second stage of labour (15/259, 5.8%; aOR 3.40, 95% CI 1.94-5.94; p < 0.001). CONCLUSION: Second-stage duration in a first term vaginal delivery is not associated with subsequent sPTB. The risk of sPTB is increased following second-stage caesarean section, particularly if performed after a prolonged second stage. TWEETABLE ABSTRACT: Second-stage caesarean delivery, particularly after prolonged second stage, increases the risk of preterm birth.

The many etiologies of nonimmune hydrops fetalis diagnosed by exome sequencing.

OBJECTIVE: To explain the importance of identifying an etiology for the pathological finding of nonimmune hydrops fetalis (NIHF) and to explore the impact of exome sequencing in recurrent NIHF. In addition, we present two cases of pregnancies affected with recurrent NIHF, in which genetic investigation was advantageous. METHODS: Our study aimed to investigate the genetic background, if available, of all fetuses with NIHF referred to our tertiary medical center from January 2013 to August 2020. We summarized the etiology of NIHF if known, sonographic findings, genetic investigation and the pregnancies' outcomes. RESULTS: We encountered 144 families with NIHF. Genetic investigation was performed by chromosomal microarray analysis (CMA) in 63 (63/144. 44%) fetuses. Seventeen of 63 (27%) had a positive CMA result. In the negative CMA group, 15 (15/46, 33%) opted for exome sequencing, of which seven exomes were positive (47%). Among these, there were four couples with recurrent pregnancies affected by hydrops. Among the remaining 11 exome investigations for non-recurrent hydrops, another three were diagnostic. CONCLUSION: As identifying the etiology of the NIHF is an invaluable tool for the prognosis of the pregnancy, exome sequencing can provide further elucidation of the underlying pathogenesis of NIHF. Thus, genetic investigation should be recommended for cases of NIHF.

Artificial rupture of membranes as a mode for induction of labor in women with a previous cesarean section- a retrospective cohort study.

BACKGROUND: Induction of labor in women with a previous cesarean section (CS) is associated with increased rates of uterine rupture and failed attempt for vaginal delivery. Prostaglandins use is contraindicated in this population, limiting available options for cervical ripening. OBJECTIVE: To evaluate the efficacy and safety of artificial rupture of membranes (AROM) as a mode of Induction of labor (IOL) in women with a previous cesarean section. METHODS: A retrospective cohort study conducted in a single tertiary care center between January 2015 and October 2020. Women with one previous cesarean section and a current singleton term pregnancy requiring IOL, with an unfavorable cervix, were included. The primary outcome was a successful vaginal delivery (VBAC); secondary outcomes were rates of chorioamnionitis, uterine rupture and low Apgar score (< 7). RESULTS: Of the 665 women who met the inclusion criteria, 492 (74%) did not receive subsequent oxytocin and 173 (26%) did. There were significant differences in the baseline characteristics between these two groups, including maternal age, cervical dilation at presentation, parity, and a history of a previous VBAC. Among women who were induced solely by AROM the rate of a successful TOLAC was higher (81.3% vs 73.9%), total time of IOL was shorter (mean 8.7 h vs.16.1 h) and the risk of chorioamnionitis was lower (7.3% vs 18.4%). When subdividing the women who received oxytocin into early (< 12 h after AROM) vs late (> 12 h after AROM) administration, there were no significant changes in the rates of successful VBAC or of chorioamnionitis. CONCLUSION: AROM as a single mode of IOL in women with a previous CS is a safe and efficient practice with high rates of successful VBAC. When spontaneous labor does not develop, there is no advantage to delay the administration of oxytocin.

Reference Ranges for Corpus Callosum and Cavum Septi Pellucidi Biometry on Prenatal Ultrasound: Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis of published nomograms for fetal corpus callosum and cavum septi pellucid biometry. A structured literature search was conducted to identify studies that reported normal measurements of the fetal corpus callosum and cavum septi pellucidi. Random effects metaanalysis was used to calculate normal ranges, and reference curves are provided. The quality assessment demonstrated that there was generally poor reporting regarding maternal characteristics and neonatal outcomes. Our findings emphasize that standardization of research protocols and publishing criteria for normal biometric ranges is needed.

Hyponatremia among preeclampsia patients - a potential sign of severity.

OBJECTIVES: Although hyponatremia in preeclamptic patients was previously described, its significance remains unknown. We aimed to describe the prevalence and clinical significance of hyponatremia among a cohort of preeclamptic patients. METHODS: An electronic medical record based retrospective cohort study included all singleton deliveries at Hadassah University Medical Center between 2003 and 2015. Preeclampsia, with and without severe features, was defined using the American College of Obstetrics and Gynecology (ACOG) Hypertension in Pregnancy Guidelines. Hyponatremia was defined as a sodium (Na) level ≤130 mEq/L, and severe hyponatremia as <125 mEq/L. A group of normotensive pregnant women, matched for gestational age, gravdity and parity, served as control. RESULTS: A total of 700 preeclamptic patients were identified during the study period. Hyponatremia was noted in 14.6% compared to 0 of 79 patients in the control group. Hyponatremia was strongly correlated with severe features of preeclampsia, adverse neonatal and obstetrical outcome. Severe hyponatremia was strongly correlated with preeclampsia with severe features. Furthermore, even among subgroup of preeclamptic patients without severe features, hyponatremia correlated with less favorable pregnancy outcomes. CONCLUSIONS: Among relatively large cohort of preeclamptic patients, hyponatremia was not a rare finding. We found it more common in patients with preeclampsia and severe features. As women with preeclampsia are at risk for hyponatremia, serum sodium levels should be monitored, especially in those with severe features. In preeclamptic patients without severe features, hyponatremia may indicate a need for closer surveillance. However, larger studies are needed to establish hyponatremia as a marker of severity.

Trial of labor after cesarean in primiparous women with fetal macrosomia.

KEY MESSAGE: Spontaneous labor onset, epidural anesthesia and prior cesarean for non-arrest disorders are strong predictors of successful vaginal birth after cesarean in women delivering a macrosomic fetus. PURPOSE: Lower rates of successful vaginal birth after cesarean in association with increasing birthweight were previously reported. We aimed to determine the factors associated with successful trial of labor after cesarean (TOLAC) among primiparous women with fetal macrosomia. METHODS: A retrospective cohort study conducted during 2005-2019 at two university hospitals, including all primiparous women delivering a singleton fetus weighing ≥ 4000 g, after cesarean delivery at their first delivery. A multivariate analysis was performed to evaluate the characteristics associated with TOLAC success (primary outcome). RESULTS: Of 551 primiparous women who met the inclusion criteria, 50.1% (n = 276) attempted a TOLAC and 174 (63.0%) successfully delivered vaginally. In a multivariate analysis, spontaneous onset of labor (aOR [95% CI] 3.68 (2.05, 6.61), P < 0.001), epidural anesthesia (aOR [95% CI] 2.38 (1.35, 4.20), P = 0.003) and history of cesarean delivery due to non-arrest disorder (aOR [95% CI] 2.25 (1.32, 3.85), P = 0.003) were the only independent factors associated with TOLAC success. Successful TOLAC was achieved in 82.0% (82/100) in the presence of all three favorable factors, 61.3% (65/106) in the presence of two factors and 38.6% (27/70) in the presence of one or less of these three factors (P < 0.001). CONCLUSION: Spontaneous onset of labor, epidural anesthesia and prior cesarean delivery due to non-arrest disorders were independently associated with higher vaginal birth after cesarean rate among women with fetal macrosomia, with an overall favorable success rate in the presence of these factors. These findings should be implemented in patient counseling in those contemplating a vaginal birth in this setting.

Efficient Maternofetal Transplacental Transfer of Anti- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Antibodies After Antenatal SARS-CoV-2 BNT162b2 Messenger RNA Vaccination.

Maternal and cord blood sera were collected from 20 parturients who received the BNT162b2 vaccine. All women and infants were positive for anti S- and anti-receptor binding domain antibody-specific immunoglobulin G. Cord blood antibody concentrations were correlated to maternal levels and to time since vaccination. Antenatal severe acute respiratory syndrome coronavirus 2 vaccination may provide maternal and neonatal protection.

Vaginal delivery in SARS-CoV-2-infected pregnant women in Israel: a multicenter prospective analysis.

KEY MESSAGE: Among SARS-CoV-2-infected mothers, vaginal delivery rates were high and associated with favorable outcomes with no cases of neonatal COVID-19. PURPOSE: To investigate the mode of delivery and its impact on immediate neonatal outcome in SARS-CoV-2-infected women. METHODS: A prospective study following pregnant women diagnosed with COVID-19 who delivered between March 15th and July 4th in seven university affiliated hospitals in Israel. RESULTS: A total of 52 women with a confirmed diagnosis of COVID-19 delivered in the participating centers during the study period. The median gestational age at the time of delivery was 38 weeks, with 16 (30.8%) cases complicated by spontaneous preterm birth. Forty-three women (82.7%) underwent a trial of labor. The remaining 9 women underwent pre-labor cesarean delivery mostly due to obstetric indications, whereas one woman with a critical COVID-19 course underwent urgent cesarean delivery due to maternal deterioration. Among those who underwent a trial of labor (n = 43), 39 (90.7%) delivered vaginally, whereas 4 (9.3%) cases resulted in cesarean delivery. Neonatal RT-PCR nasopharyngeal swabs tested negative in all cases, and none of the infants developed pneumonia. No maternal and neonatal deaths were encountered. CONCLUSIONS: In this prospective study among SARS-CoV-2-infected mothers, vaginal delivery rates were high and associated with favorable outcomes with no cases of neonatal COVID-19. Our findings underscore that delivery management among SARS-CoV-2-infected mothers should be based on obstetric indications and may potentially reduce the high rates of cesarean delivery previously reported in this setting.

Is There a Familial Tendency for Same Sex Offspring? A Lesson Learned from a Large Non-Selected Israeli Population.

BACKGROUND: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring. OBJECTIVES: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB. METHODS: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB. RESULTS: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB. CONCLUSIONS: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.

Preferred way of delivery of the impacted fetal head in cesarean sections during second stage of labor.

AIM: To compare maternal and neonatal outcomes between the 'head first' and 'legs first' delivery methods during a second stage cesarean section. METHODS: We conducted a retrospective study between January 2009 and May 2015 at a large public university tertiary referral center. Included were all women who underwent cesarean delivery with a fully dilated cervix and a fetal head at the level of the ischial spines or below. The study population was divided into two groups according to way of fetal delivery: The 'legs first' (reverse breech) method and the 'head first' method. Demographics and maternal and fetal outcomes were retrieved for both groups. RESULTS: During the study period 447 women underwent a cesarean section while their cervix was fully dilated. Of them, 321 met the inclusion criteria: One hundred and twenty-one (38%) were delivered using the 'legs first' method and 200 (62%) were delivered using the 'head first' method. Indication for surgery and fetal head station was similar for both groups. While no difference in overall intraoperative uterine incision extension rate was observed, a higher rate of uterine incision extension was demonstrated in the 'head first' group in cases in which the second stage was longer than 180 min (33 vs 8 cases, P = 0.02). No differences in maternal postoperative complication rates and neonatal outcomes were observed. CONCLUSION: Fetal extraction via the 'legs first' method during prolonged second stage of labor may lower maternal morbidity. Method of delivery does not seem to have an effect on neonatal outcomes.

The role of repeat misoprostol dose in the management of early pregnancy failure.

PURPOSE: We aimed to assess the role of repeat misoprostol administration in those with thickened endometrium in the management of early pregnancy failure (EPF). METHODS: A retrospective cohort study in two university hospitals among women receiving misoprostol treatment for EPF. Those with thickened endometrium at the first follow-up visit, who received a repeat 800 µg dose of vaginal misoprostol in institution B and no treatment in institution A, constituted the study group. The primary outcome was treatment success, defined as complete uterine evacuation without the need for any operative intervention RESULTS: Overall, 608 women with thickened endometrium as assessed by transvaginal ultrasonography 2 days following initial misoprostol administration for EPF were included. Of them, 427 did not receive repeat misoprostol dose, and 181 received repeat misoprostol dose. The rate of surgical intervention did not differ between those who received a repeat misoprostol dose (6.1%) and those who did not (4.3%) (P = 0.32). The median endometrial thickness was similar in those that did and did not require subsequent surgical intervention (P = 0.65), and was a poor predictor of treatment outcome. CONCLUSIONS: Repeat misoprostol administration among women with thickened endometrium following initial misoprostol administration for EPF was not associated with improved treatment success rates.

The Accuracy of Sonographic Assessment for Fetal Weight: Technicians versus Ultrasound-Certified Physicians.

BACKGROUND: Sonographic estimation of birth weight may differ among evaluators due to its operator-dependent nature. OBJECTIVES: To compare the accuracy of estimation of fetal birth weight by sonography between ultrasound-certified physicians and registered diagnostic medical technicians. METHODS: The authors reviewed ultrasound examinations that had been performed by either technicians or ultrasound-certified obstetricians between 2010 and 2017, and within 2 days of delivery. Inclusion criteria were: singleton viable pregnancy, details of four ultrasound measurements (abdominal circumference, bi-parietal diameter, head circumference, and femur length), and known birth weight. The estimated fetal weight (EFW) was calculated according to the Hadlock formula, incorporating the four ultrasound measurements. The mean percentage error (MPE) was calculated by the formula: (EFW-birth weight) x100 / birth weight. RESULTS: Technicians performed 9741examinations and physicians performed 352 examinations. The proportion of macrosomic neonates was similar in both groups. Technicians were more accurate than physicians in terms of the MPE, absolute MPE, proportion of estimates that fell within ± 10% of birth weight, and Euclidean distance (P < 0.0001 for all comparisons). They were also more accurate in terms of sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating curve. Furthermore, for fetuses weighing more than 4000 grams the technicians had a lower total false prediction rate. CONCLUSIONS: Medical technicians in our institute performed better than physicians in estimating fetal weight. Further studies are warranted to confirm our findings and better delineate the role of repeat physician's examination after an initial estimation by an experienced technician.