CDH2 mutation affecting N-cadherin function causes attention-deficit hyperactivity disorder in humans and mice.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder characterized by inattention, impulsivity and hyperactivity. ADHD exhibits substantial heritability, with rare monogenic variants contributing to its pathogenesis. Here we demonstrate familial ADHD caused by a missense mutation in CDH2, which encodes the adhesion protein N-cadherin, known to play a significant role in synaptogenesis; the mutation affects maturation of the protein. In line with the human phenotype, CRISPR/Cas9-mutated knock-in mice harboring the human mutation in the mouse ortholog recapitulated core behavioral features of hyperactivity. Symptoms were modified by methylphenidate, the most commonly prescribed therapeutic for ADHD. The mutated mice exhibited impaired presynaptic vesicle clustering, attenuated evoked transmitter release and decreased spontaneous release. Specific downstream molecular pathways were affected in both the ventral midbrain and prefrontal cortex, with reduced tyrosine hydroxylase expression and dopamine levels. We thus delineate roles for CDH2-related pathways in the pathophysiology of ADHD.

Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaginal swabs of women with acute SARS-CoV-2 infection: a prospective study.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vaginal secretions of both reproductive-aged and postmenopausal women during acute SARS-CoV-2 infection. DESIGN: Prospective study. SETTING: A single tertiary, university-affiliated medical centre in Israel. Time period, 1 June 2020 through to 31 July 2020. POPULATION: Women who were hospitalised in a single tertiary medical centre, who were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. METHODS: Women were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. Vaginal RT-PCR swabs were obtained from all study participants after a proper cleansing of the perineum. MAIN OUTCOME MEASURES: Detection of SARS-CoV-2 in vaginal RT-PCR swabs. RESULTS: Vaginal and nasopharyngeal swabs were obtained from 35 women, aged 21-93 years. Twenty-one women (60%) were in their reproductive years, of whom, five were in their third trimester of pregnancy. Most of the participants (57%) were healthy without any underlying medical conditions. Of the 35 patients sampled, 2 (5.7%) had a positive vaginal RT-PCR for SARS-CoV-2, one was premenopausal and the other was a postmenopausal woman. Both women had mild disease. CONCLUSION: Our findings contradict most previous reports, which did not detect the presence of viral colonisation in the vagina. Although passage through the birth canal exposes neonates to the vaginal polymicrobial flora, an acquisition of pathogens does not necessarily mandate neonatal infection or clinical disease. Nevertheless, when delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation, even if it is uncommon. TWEETABLE ABSTRACT: When delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation.

Uterine electrical activity, oxytocin and labor: translating electrical into mechanical.

PURPOSE: Uterine activity plays a crucial role in labor, especially when utero-tonic materials are administered. We aimed to determine the electrical responsiveness of the uterine musculature to labor augmentation with oxytocin using electrical uterine myography (EUM) technology, and to assess whether the kinetics of the EUM device may serve as a predictor for successful vaginal delivery. METHODS: EUM prospectively measured electrical uterine activity in women with singleton gestations at term (≥ 37 + 0 weeks) undergoing labor augmentation by oxytocin administration. The results were reported as the EUM index, which represented the mean electrical activity in 10-min intervals and measured in units of microwatt per second (mW/s). Measurements were performed at least 30 min before oxytocin initiation and until at least four contractions per 10 min were recorded by standard tocodynamometry. The delta EUM index was defined as the difference between the mean EUM index before and after the initiation of oxytocin. RESULTS: The mean EUM index increased significantly during oxytocin augmentation in all the parturients (P < 0.001). Mean and minimum (but not maximum) uterine electrical activity during oxytocin infusion correlated with the baseline uterine activity. The delta EUM index was not significantly affected by demographic or obstetric parameters. There was no correlation between the delta EUM index and time to delivery or the mean EUM index during oxytocin administration and time to delivery. CONCLUSIONS: Uterine electrical activity as evaluated by EUM is significantly intensified following oxytocin administration, regardless of obstetrical characteristics, and is correlated with the baseline uterine electrical activity prior to oxytocin infusion.

Different formulas, different thresholds and different performance-the prediction of macrosomia by ultrasound.

OBJECTIVE: The sonographic prediction of fetal macrosomia affects obstetrical decision regarding the timing and mode of delivery. We aimed to compare the accuracy of various formulas for prediction of macrosomia at different thresholds. STUDY DESIGN: This was a retrospective cohort study of singleton gestations at term, with fetal biometrical measurements taken up to 7 days prior to delivery (2007 to 2014). Sonographic estimated fetal weight was calculated using 20 previously published formulas. Macrosomia prediction was evaluated for every formula utilizing: (1) measures of accuracy (sensitivity, specificity and so on); (2) comparison of the systematic and random errors (SE and RE), and the proportion of estimates within 10% of actual birth weight for macrosomic and non-macrosomic neonates. Performance measurements were evaluated for different macrosomia thresholds: 4000, 4250 and 4500 g. Best performing formula for every threshold was defined as the one with the lowest Euclidean distance (=SQRT(SE2+RE2)). RESULTS: Out of 7977 women who met the inclusion criteria, 754 (9.4%) delivered a neonate weighing ⩾4000 g, 266 (3.3%) delivered a neonate weighing⩾4250 g and 75 (0.9%) delivered a neonate weighing⩾4500 g. Considerable variability was noted between the accuracy parameters of the different formulas, with Woo's formula integrating Abdominal circumference (AC) and femur length (FL) as the most sensitive formula with the highest negative predictive value for all thresholds and Woo's formula using AC, FL and biparietal diameter (BPD) as the most specific for all thresholds. The same formula also demonstrated the best overall accuracy. Regardless of threshold chosen, 80% or more of formulas demonstrated negative systematic error, meaning lower EFW than actual birthweight. As for the Euclidean distance, Hadlock's formula (AC, FL and BPD) ranked the highest for the 4000 and 4250 g thresholds, whereas Shepard's formula (AC and BPD) ranked the highest for the 4500 g threshold. CONCLUSION: Considerable variability exist between formulas for prediction of neonatal macrosomia. Formulas by Hadlock's and Shepard's utilizing AC, BPD±FL were most accurate for macrosomia prediction at 4000, 4250 and 4500 g thresholds, respectively.

Prediction of large for gestational age by various sonographic fetal weight estimation formulas-which should we use?

OBJECTIVE: As sonographic estimation of fetal weight (EFW) carries substantial impact, especially in large-for-gestational-age (LGA) neonates, we aimed to compare the accuracy of various formulas for prediction of LGA neonates. STUDY DESIGN: Retrospective cohort study of singleton gestations at term, with EFW up to 7 days before delivery (2007 to 2014). Small-for-gestational-age neonates were excluded. LGA prediction for various formulas was evaluated by: (i) measures of performance (sensitivity, specificity, etc.); (ii) systematic and random errors (SE and RE) and the proportion of estimates (POEs) exceeding 10% of actual birth weight. Best performing formula was defined as the one with the lowest Euclidean distance [=square root of (SE2+RE2)]. RESULTS: Out of 62 102 deliveries, 7996 met inclusion criteria, of which 1618 neonates were LGA (22%). There was a considerable variation in sensitivity (74.6±16.3%, 23.5% to 99%), specificity (86.3±10.6%, 51.7% to 99.6%), positive predictive value (64.9±12.4%, 35.6% to 93.8%), positive likelihood ratio (LR; 9.3±10.9, 2.1 to 54.2) and negative LR (0.3±0.16, 0.02 to 0.8), a mild variation in the negative predictive value (92.9±3.7%, 82.3% to 99.5%) and a minimal variation in the area under the curve (94.3%, 93.0 to 95.1; mean±s.d., range for all). Absolute SE was higher for the LGA group in 11/20 formulas (55%). The RE and POE were lower in 19/20 (95%) and 14/20 (70%) for the LGA neonates, respectively. CONCLUSION: There is a wide variation in EFW formulas performance for detecting LGA. Hadlock's formula (1985) combining abdominal circumference, femur length and biparietal diameter ranked highest.

Immediate delivery or expectant management in gestational diabetes at term: the GINEXMAL randomised controlled trial.

OBJECTIVE: To evaluate maternal and perinatal outcomes after induction of labour versus expectant management in pregnant women with gestational diabetes at term. DESIGN: Multicentre open-label randomised controlled trial. SETTING: Eight teaching hospitals in Italy, Slovenia, and Israel. SAMPLE: Singleton pregnancy, diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria (IADPSGC), between 38+0 and 39+0 weeks of gestation, without other maternal or fetal conditions. METHODS: Patients were randomly assigned to induction of labour or expectant management and intensive follow-up. Data were analysed by 'intention to treat'. MAIN OUTCOME MEASURES: The primary outcome was incidence of caesarean section. Secondary outcomes were maternal and perinatal mortality and morbidity. RESULTS: A total of 425 women were randomised to the study groups. The incidence of caesarean section was 12.6% in the induction group versus 11.7% in the expectant group. No difference was found between the two groups (relative risk, RR 1.06; 95% confidence interval, 95% CI 0.64-1.77; P = 0.81). The incidence of non-spontaneous delivery, either by caesarean section or by operative vaginal delivery, was 21.0 and 22.3%, respectively (RR 0.94; 95% CI 0.66-1.36; P = 0.76). Neither maternal nor fetal deaths occurred. The few cases of shoulder dystocia were solved without any significant birth trauma. CONCLUSIONS: In women with gestational diabetes, without other maternal or fetal conditions, no difference was detected in birth outcomes regardless of the approach used (i.e. active versus expectant management). Although the study was underpowered, the magnitude of the between-group difference was very small and without clinical relevance. TWEETABLE ABSTRACT: Immediate delivery or expectant management in gestational diabetes at term?

Association of fetal biparietal diameter with mode of delivery and perinatal outcome.

OBJECTIVE: To determine the association between sonographic assessment of fetal biparietal diameter (BPD) and pregnancy outcome. METHODS: This was a retrospective cohort study of pregnancies at 37-42 weeks of gestation which had antepartum sonographic measurement of BPD within 7 days before delivery. Eligibility was limited to singleton pregnancies with neither known structural or chromosomal abnormalities nor prelabor Cesarean delivery (CD). The association of BPD with outcome was analyzed using multivariate logistic regression, receiver-operating characteristics curves and stratification according to BPD quartiles. RESULTS: In total, 3229 women were eligible for analysis, of whom 2483 (76.9%) had a spontaneous vaginal delivery (SVD), 418 (12.9%) underwent operative vaginal delivery (OVD) and 328 (10.2%) underwent CD. The mean BPD in the obstetric intervention groups (OVD and CD) was significantly higher than that in the SVD group (P < 0.001). After adjusting for confounders, increased BPD was an independent risk factor such that higher values of BPD were associated with progressively higher risk of obstetric intervention (adjusted odds ratio, 1.05 for each 1-mm increase in BPD (95% CI, 1.02-1.09)), but no clear cut-off value for obstetric intervention was found. The fourth quartile group (BPD ≥ 97 mm) was associated with a significantly lower SVD rate (P < 0.001) and higher OVD rate (P = 0.04), relative to the first (BPD 88-90 mm) and second (BPD 91-93 mm) quartile groups, with no apparent adverse impact on immediate neonatal outcome. CONCLUSIONS: Increased BPD within the week prior to delivery is an independent risk factor such that higher values of BPD are associated with progressively higher risk of obstetric intervention; however, in our experience, no adverse neonatal outcome resulted from such intervention. Thus, increased BPD should not discourage a trial of vaginal delivery.

Predictive value of cervical length in women with twin pregnancy presenting with threatened preterm labor.

OBJECTIVE: To assess the accuracy and determine the optimal threshold of sonographic cervical length (CL) for the prediction of preterm delivery (PTD) in women with twin pregnancies presenting with threatened preterm labor (PTL). METHODS: This was a retrospective study of women with twin pregnancies who presented with threatened PTL and underwent sonographic measurement of CL in a tertiary center. The accuracy of CL in predicting PTD in women with twin pregnancies was compared with that in a control group of women with singleton pregnancies. RESULTS: Overall, 218 women with a twin pregnancy and 1077 women with a singleton pregnancy, who presented with PTL, were included in the study. The performance of CL as a predictive test for PTD was similar in twins and singletons, as reflected by the similar correlation between CL and the examination-to-delivery interval (r, 0.30 vs 0.29; P = 0.9), the similar association of CL with risk of PTD, and the similar areas under the receiver-operating characteristics curves for differing delivery outcomes (range, 0.653-0.724 vs 0.620-0.682, respectively; P = 0.3). The optimal threshold of CL for any given target sensitivity or specificity was lower in twin than in singleton pregnancies. However, in order to achieve a negative predictive value of 95%, a higher threshold (28-30 mm) should be used in twin pregnancies. Using this twin-specific CL threshold, women with twins who present with PTL are more likely to have a positive CL test, and therefore to require subsequent interventions, than are women with singleton pregnancies with PTL (55% vs 4.2%, respectively). CONCLUSION: In women with PTL, the performance of CL as a test for the prediction of PTD is similar in twin and singleton pregnancies. However, the optimal threshold of CL for the prediction of PTD appears to be higher in twin pregnancies, mainly owing to the higher baseline risk for PTD in these pregnancies.

Macrosomic newborns of non-diabetic mothers: anthropometric measurements and neonatal complications.

OBJECTIVE: To assess the association of anthropometric measurements with neonatal complications in macrosomic newborns of non-diabetic mothers. DESIGN: Retrospective cohort study. PATIENTS: All liveborn, singleton, full term newborns with birth weight ≥4000 g born to non-diabetic mothers at a tertiary medical centre in 1995-2005 (n=2766, study group) were matched to the next born, healthy, full term infant with a birth weight of 3000-4000 g (control group). Exclusion criteria were multiple birth, congenital infection, major malformations and pregnancy complications. INTERVENTION: Data collection by file review. OUTCOME MEASURES: Complication rates were compared between study and control groups and between symmetric and asymmetric macrosomic newborns, defined by weight/length ratio (WLR), Body Mass Index and Ponderal Index. RESULTS: The 2766 non-diabetic macrosomic infants identified were matched to 2766 control infants. The macrosomic group had higher rates of hypoglycaemia (1.2% vs 0.5%, p=0.008), transient tachypnoea of the newborn (1.5% vs 0.5%, p<0.001), hyperthermia (0.6% vs 0.1%, p=0.012), and birth trauma (2% vs 0.7%, p<0.001), with no cases of symptomatic polycythaemia, and only one case of hypoglycaemia. Hypoglycaemia was positively associated with birth weight. It was significantly higher in the asymmetric than the symmetric macrosomic newborns, defined by WLR (1.7% vs 0.3%, p<0.001). CONCLUSIONS: Macrosomic infants of non-diabetic mothers are at increased risk of neonatal complications. However, routine measurements of haematocrit and calcium may not be necessary. Symmetric macrosomic infants (by WLR) have a similar rate of hypoglycaemia as normal-weight infants. Thus, repeat glucose measurements in symmetric macrosomic infants are not justified.

Is measurement of cervical length an accurate predictive tool in women with a history of preterm delivery who present with threatened preterm labor?

OBJECTIVE: To determine whether sonographically measured cervical length is an effective predictive tool in women with threatened preterm labor and a history of past spontaneous preterm delivery. METHODS: This was a retrospective cohort study of all women with singleton pregnancies who presented with preterm labor at less than 34 + 0 weeks' gestation and underwent sonographic measurement of cervical length in a tertiary medical center between 2007 and 2012. The accuracy of cervical length in predicting preterm delivery was compared between women with and those without a history of spontaneous preterm delivery. Women with risk factors for preterm delivery other than a history of preterm delivery were excluded from both groups. RESULTS: Overall, 1023 women who presented with preterm labor met the study criteria, of whom 136 (13.3%) had a history of preterm delivery (past-PTD group) and 887 (86.7%) had no risk factors for preterm delivery (low-risk group). The rate of preterm delivery was significantly higher for women with a history of preterm delivery (36.8% vs 22.5%; P < 0.001). Cervical length was significantly correlated with the examination-to-delivery interval in low-risk women (r = 0.32, P < 0.001) but not in women who had had a previous preterm delivery (r = 0.07, P = 0.4). On multivariable analysis, cervical length was independently associated with the risk of preterm delivery for women in the low-risk group but not for women with a history of previous preterm delivery. For women with previous preterm delivery who presented with threatened preterm labor, cervical length failed to distinguish between those who did and those who did not deliver prematurely (area under the receiver-operating characteristics curve range, 0.475-0.506). When using standardized thresholds, the sensitivity and specificity of cervical length for the prediction of preterm delivery were significantly lower in women with previous preterm delivery than in women with no risk factors for preterm delivery. CONCLUSION: Cervical length appears to be of limited value in the prediction of preterm delivery among women with threatened preterm labor who are at high risk for preterm delivery owing to a history of spontaneous preterm delivery in a previous pregnancy.

Does use of a sex-specific model improve the accuracy of sonographic weight estimation?

OBJECTIVE: To determine whether the use of a sex-specific sonographic model improves the accuracy of fetal weight estimation. METHODS: New regression models (sex-independent and sex-specific) were developed, based on 1708 sonographic weight estimations performed within 3 days prior to delivery. The accuracy of these models was compared to that of several published models including two of the original Hadlock models (which incorporate the biometric indices abdominal circumference (AC), biparietal diameter (BPD), femur diaphysis length (FL) and head circumference (HC) as follows: AC-FL-BPD and AC-FL-HC, designated here as Hadlock I and Hadlock II, respectively), modified versions of the Hadlock I and II models for which coefficients were adjusted to our local cohort, sex-specific versions of the Hadlock I and II models and Schild's model (a previously published sex-specific model). RESULTS: The unadjusted models of Hadlock and Schild were associated with the highest systematic error (1.6-4.9%; P < 0.001) which was significantly higher for females (2.3-4.9%) compared to males (1.6-2.0%; P < 0.001). Adjustment of model coefficients to the local population decreased the systematic error (-1.4% to 1.5%) and resulted in a systematic error that was of similar magnitude (P = 0.3) but opposite in direction for male and female fetuses. The sex-specific models (adjusted or newly developed) were associated with the lowest systematic error (-0.4 to 0.5%) and were the only models for which the systematic error was similar for male and female fetuses. There were no differences in the systematic error between adjusted sex-specific versions of the Hadlock I and II models and the newly developed sex-specific models (0.0% to 0.4% vs. - 0.4% to 0.5%; P = 0.4). The random error was similar for all models and, for most of the models, was unrelated to fetal sex. CONCLUSIONS: The use of sex-specific models appears to improve the accuracy of fetal weight estimation, principally because the optimal set of model coefficients differs for male and female fetuses. The improved accuracy is mainly the result of a decrease in systematic error, as the random error was not affected by the use of such sex-specific models.

Accuracy of sonographic fetal weight estimation: a matter of presentation.

OBJECTIVES: To assess the accuracy of sonographic weight estimation for fetuses in breech presentation, and to determine whether certain sonographic models perform better than others in cases of breech presentation. METHODS: This was a retrospective cohort study of all sonographic weight estimations of fetuses in breech presentation performed within 3 days prior to delivery (n = 165). The accuracy of weight estimation was evaluated using eight sonographic models and was compared with a control group of fetuses in vertex presentation matched to the study group by birth weight and fetal gender (n = 165). RESULTS: After exclusion of a model based on femur diaphysis length alone, which was found to be highly inaccurate, the systematic error for fetuses in breech presentation was smaller than that observed for fetuses in vertex presentation (mean of all models - 0.14% vs. 2.0%, P = 0.01). The random error was higher in cases of breech presentation (9.4-13.2% vs. 7.5-8.9%, P < 0.05), and was lower for models that are based on three to four biometric indices (9.4-9.5%) compared with models that incorporate one to two biometric indices (10.8-13.6%, P < 0.05). Overall, the higher random error outweighed the decrease in the systematic error, as reflected by the lower fraction of weight estimations within 10% of birth weight among fetuses in breech presentation. Models based on three to four biometric indices were more accurate in detecting the weight thresholds beyond which a trial of vaginal delivery is usually not recommended. CONCLUSION: Sonographic weight estimation appears to be less accurate for fetuses in breech presentation, principally because of a larger random error. The use of sonographic models that are based on three to four biometric indices, training aimed at improving measurement in breech fetuses and the development of sonographic models derived from fetuses in breech presentation, may improve the accuracy of weight estimation in these cases.

Prediction of fetal macrosomia: effect of sonographic fetal weight-estimation model and threshold used.

OBJECTIVE: To compare the accuracy of 21 sonographic fetal weight-estimation models and abdominal circumference (AC) as a single measure for the prediction of fetal macrosomia (> 4000 g) using either fixed or optimal model-specific thresholds. METHODS: A total of 4765 sonographic weight estimations performed within 3 days prior to delivery were analyzed. The predictive accuracy of 21 published sonographic fetal weight-estimation models was calculated using three different thresholds: a fixed threshold of 4000 g; a model-specific threshold obtained from the inflexion point of the receiver-operating characteristics (ROC) curve; and a model-specific threshold associated with the highest overall accuracy. Cluster analysis was used to determine whether a certain combination of fetal biometric indices is associated with a higher predictive accuracy than others. RESULTS: For a fixed threshold of > 4000 g, there was considerable variation among the models in sensitivity (range, 13.6-98.5%) and specificity (range, 63.6-99.8%) for fetal macrosomia. Use of the threshold derived from the inflexion point of the ROC curve decreased the intermodel variation to a minimum (sensitivity, 84.4-91.4%; and specificity, 79.5-86.3%). Even when this optimal model-specific threshold was applied, models based on three to four biometric indices were more accurate than were models based on only two biometric indices or on AC as a single measure (P=0.03). CONCLUSIONS: Sonographic fetal weight-estimation models based on three to four biometric indices appear to be more accurate than are models based on two indices or on AC as a single measure, for the diagnosis of macrosomia. In these cases, the use of an optimal, model-specific threshold is associated with a higher degree of accuracy than is the uniform use of a fixed threshold of an estimated weight of > 4000 g.

Accuracy of sonographic weight estimation as a function of fetal sex.

OBJECTIVES: To determine whether the accuracy of sonographic fetal weight estimation is related to fetal sex. METHODS: The accuracy of sonographic fetal weight estimation was compared between male and female fetuses using 3672 sonographic weight estimations performed within 3 days prior to delivery. Fetal weight was estimated using eight regression models that are based on different combinations of the following biometric parameters: abdominal circumference (AC), femur diaphysis length (FL), biparietal diameter (BPD) and head circumference (HC). RESULTS: In seven out of the eight models tested, the presence of a male fetus was associated with a significantly lower systematic error compared with a female fetus (-0.2 to 2.1% vs. 1.3 to 6%, P<0.001). On multivariate analysis, fetal sex was independently associated with sonographic accuracy so that the likelihood of a weight estimation within 10% of birth weight was 30% higher for male fetuses compared with female fetuses. The biometric parameters that contributed most to these sex-related differences were FL and AC, while models that included HC were associated with the lowest differences in the systematic error between male fetuses and female fetuses. For most models, the random error and correlation between estimated weight and birth weight were not affected by fetal sex (8.1-12.8% vs. 8.2-13.6%, and 0.856-0.944 vs. 0.842-0.944, respectively). CONCLUSION: Sonographic estimation of fetal weight is more accurate for male fetuses than for female fetuses. The use of sex-specific models may improve the accuracy of fetal weight estimation for female fetuses.

Sonographic estimation of fetal head circumference: how accurate are we?

OBJECTIVES: To assess the accuracy of sonographic estimation of fetal head circumference (HC). METHODS: We compared sonographic estimations of fetal HC with actual measurements performed immediately after delivery using 3008 sonographic examinations performed within 3 days prior to delivery. The following measures of accuracy were calculated: correlation with actual HC, systematic error, random error, simple error, mean absolute percentage error and fraction of estimates within 5% of actual HC. Multivariate logistic regression analysis was used to identify factors affecting the accuracy of sonographic HC estimation. RESULTS: There was a high correlation between sonographic and postnatal measurements of HC (r = 0.845, P < 0.001). Overall, sonographic HC measurements consistently underestimated actual HC measured postnatally (mean simple error, - 13.6 mm; 95% CI, - 13.2 to - 13.9), and the difference increased with gestational age. A high cephalic index (> 0.81) (odds ratio (OR), 0.3; 95% CI, 0.2-0.4), HC > 90(th) centile (OR, 0.5; 95% CI, 0.3-0.6), delivery by vacuum extraction (OR, 0.6; 95% CI, 0.4-0.8), gestational week (OR, 0.7; 95% CI, 0.6-0.9) and male fetal gender (OR, 0.8; 95% CI, 0.6-0.9) were associated with decreased sonographic accuracy. At term, breech presentation at the time of sonographic examination was associated with a higher sonographic accuracy compared with vertex presentation (-12.0; 95% CI, - 10.5 to - 13.5 vs. - 13.9 mm; 95% CI, - 13.6 to - 14.3; P = 0.02). The random error was relatively constant, and was unaffected by any of the obstetric factors studied. CONCLUSION: Sonographic estimation of HC is associated with significant underestimation compared with the actual postnatal HC. This measurement error may have important clinical implications and should be taken into account in the interpretation of sonographically measured HC.

Prostaglandin E2 induction of labor for isolated oligohydramnios in women with unfavorable cervix at term.

OBJECTIVE: To evaluate the maternal and neonatal outcomes of pregnancies complicated with isolated oligohydramnios at term, managed by induction of labor. METHODS: We conducted a retrospective case-control study. 138 women with uncomplicated oligohydramnios at term [amniotic fluid index (AFI) < or =5 cm] and a low Bishop score (< or =6) underwent induction of labor with prostaglandin E2. These women were compared to 67 women who underwent induction of labor at 42 weeks' gestation and 276 women at low-risk pregnancy and spontaneous onset of labor, matched for parity and race. RESULTS: Cesarean section (CS) rate was similar in the study and the post-date group (17.4 and 17.9%, respectively), but significantly higher than the spontaneous labor group (5.8%, OR 3.42, 95% CI 1.75-6.68). No differences were found with other outcomes. CONCLUSION: Pregnancies with isolated oligohydramnios at term apparently are not at higher risk of perinatal complications, but induction of labor is associated with increased rate of CS.

Attitudes of Israeli gynecologists towards the levonorgestrel-releasing intrauterine system: a questionnaire survey.

OBJECTIVES: The aim of the study was to examine the current attitudes and practices of gynecologists regarding the use of the levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena, Schering AG, Germany) as a contraceptive device and for the treatment of menorrhagia in the premenopausal period. In addition, physician knowledge of patient satisfaction with the device was evaluated. METHODS: A written, self-administered questionnaire was given to 300 gynecologists actively employed in gynecological departments and outpatient clinics in urban centers in Israel. The items covered the indications for which the LNG-IUS was prescribed, the estimated rate of use of the LNG-IUS compared to copper intrauterine devices (IUDs), patient satisfaction with the LNG-IUS and previous knowledge about it, and demographic characteristics of the population using IUDs. All forms were completed on an anonymous basis. RESULTS: The questionnaire was returned, properly completed, by 298 physicians, yielding a response rate of 99.3%. Almost one-half of the physicians (n = 147, 49.3%) used the LNG-IUS only as a contraceptive device, 17.4% only as treatment for menorrhagia, and 33.2% for both indications. The vast majority of gynecologists (82.2%) reported a patient satisfaction rate of 70% or more. Among the gynecologists using the LNG-IUS as treatment for menorrhagia, the estimated overall patient satisfaction rate was more than 50%. Although most physicians expressed greater patient satisfaction with the LNG-IUS than with copper-releasing IUDs (p < 0.004), the majority of gynecologists still used the copper-releasing IUDs more frequently. Most considered the LNG-IUS as an appropriate method for endometrial protection in postmenopausal women using estrogen replacement therapy. CONCLUSIONS: Physicians should be made aware of the beneficial health effects of the LNG-IUS, particularly in premenopausal women with menorrhagia and for endometrial protection during hormone replacement.

The importance of diagnostic work-up in the management of candidal vulvovaginitis. A prospective study.

OBJECTIVE: To assess the accuracy of the diagnostic work-up in identifying vaginal candidal infection, and to determine the safety, efficacy and speed of action of clotrimazole vaginal tablets. PARTICIPANTS: Two hundred and twenty-three patients with symptoms and signs of candidal infection, a presence of vaginal pH < or = 4.5 and positive 10% KOH examination. METHODS: After vaginal culture was taken, the eligible patients were treated with clotrimazole 200 mg vaginal tabs (manufactured by Teva or Agis). RESULTS: Cultures grew Candida albicans in 189 cases (85%), and Candida non-albicans in five (2.2%); 29 patients (13%) did not have any candidal infection. Of the 189 C. albicans-positive patients, 174 were reassessed for effects of clotrimazole treatment by self-reports and objective measures. Ninety-four percent of the patients reported improvement after treatment, rated moderate to high by 87%. The physician evaluation was similar: some improvement in 96%, and moderate or high improvement in 91%. At the second examination, 7.5% of the treated patients still had a positive culture for Candida albicans, and they remained positive on KOH microscopic examination, although vaginal pH was significantly higher. Maximal improvement was recorded three to four days after starting treatment. CONCLUSION: It is important that the diagnostic work-up for suspected candidal infections consist of at least vaginal pH measurement and microscopy study with KOH. We encourage the use of vaginal cultures, especially in recurrent cases. Clotrimazole is a safe and effective treatment.

Efficacy and safety of standard versus low-dose Femarelle (DT56a) for the treatment of menopausal symptoms.

OBJECTIVE: In a previous study treatment with a daily standard dose of Femarelle (644 mg/day) resulted in a significant elevation in bone mineral density (BMD) while a reduced dose resulted in a decrease in BMD. The aim of the current study was to examine the efficacy and safety of the two doses of Femarelle in the treatment of menopausal symptoms. MATERIALS AND METHODS: Eighty healthy postmenopausal women were randomly allocated to receive either the standard dose (SD) or low dose (LD) of Femarelle (644 mg/day vs 344 mg/day). A detailed medical history was taken on enrollment, followed by a physical examination, pelvic ultrasound, and sex hormone and lipid profiles. A detailed Kupperman index for each patient was completed. These measures were repeated every three months for 12 months. RESULTS: In both groups there was a significant reduction in the Kupperman index following 12 weeks of treatment, which was sustained throughout the 12 months of treatment (p < 0.01). Seventy-six percent of the patients in the SD group reported a decrease in vasomotor symptoms and seventy eight % in the LD group (NS). This decrease was sustained following 12 months of treatment. There was no change in TSH and sex hormone levels or endometrial thickness during the study period. CONCLUSIONS: In the current study we found that menopausal symptoms were reduced similarly by LD and SD, however for the combined treatment of menopausal symptoms and osteoporosis the standard dosage of 644 mg/day of Femarelle is needed.