Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial.

OBJECTIVE: To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. METHODS: This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. RESULTS: Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48-1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2-8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76-6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02-1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. CONCLUSIONS: Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of sonographic fetal weight estimation: influence of the scan-to-delivery interval in combination with the applied weight estimation formula.

INTRODUCTION: To evaluate the influence of the time interval between examination and delivery on the accuracy of sonographic fetal weight estimation (WE). MATERIALS AND METHODS: 8723 singleton pregnancies were included in this retrospective cohort study. Fetuses were divided into eight groups with regard to the time interval between estimation and delivery (group 1: 0 days; group 2: 1-3 days; group 3: 4-7 days; group 4: 8-14 days; group 5: 15-21 days; group 6: 22-28 days; group 7: 29-35 days; group 8: 36-42 days). The accuracy of WE was compared between the different time interval groups and five commonly used formulas using means of percentage errors (MPE), medians of absolute percentage errors, and proportions of estimates within 10 % of actual birth weight. RESULTS: In group one, the Hadlock I and Warsof formula showed a systematic underestimation of fetal weight (negative MPEs). No systematic error was found with the Hadlock II formula and the equations of Merz and Shepard showed a systematic overestimation (positive MPEs). MPE values of the Hadlock I, II and Warsof formulas were closest to zero in WEs of group two. From group three to six, MPE values decreased continuously. With the Merz and Shepard equations MPEs were closest to zero in group four. DISCUSSION: The best accuracy of sonographic WE with most of the commonly used equations is achieved within a scan-to-delivery interval of 1 week.

Sonographic weight estimation in fetal macrosomia: influence of the time interval between estimation and delivery.

PURPOSE: To evaluate the influence of the time interval between examination and delivery on the accuracy of sonographic weight estimation (WE) in fetal macrosomia. MATERIALS AND METHODS: 896 singleton pregnancies (birth weight > 4,000 g) with a total of 1,281 sonographic weight estimations were included in this retrospective cohort study. Fetuses were divided into six groups with regard to the time interval between estimation and delivery: group 1: scan-to-delivery interval: 0 days; group 2: scan-to-delivery interval: 1-3 days; group 3: scan-to-delivery interval: 4-7 days; group 4: scan-to-delivery interval: 8-14 days; group 5: scan-to-delivery interval: 15-21 days; group 6: scan-to-delivery interval: 22-42 days. The accuracy of WE was compared between five commonly used formulas using means of percentage errors (MPE), random error, medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS: Significant differences were found between the time interval groups with regard to MAPE and MPE values (p < 0.001). All formulas showed a systematic underestimation of fetal weight (negative MPEs) (p < 0.05). MPE values were closest to zero in time interval group 1 and 2. From group 3 to 6, a continuous decrease was observed. The lowest MAPE was found with the Merz formula in group 1 and 2. Values increased continuously from group 3 to 6. Differences between time interval group one and three did not reach statistical significance. CONCLUSIONS: WE in fetal macrosomia shows the best results when examinations are performed within 7 days before delivery, using the formula of Merz et al. Accuracy significantly decreases after this time period.

Intrapartum sonographic weight estimation.

PURPOSE: To evaluate the accuracy of intrapartum sonographic weight estimation (WE). MATERIALS AND METHODS: This retrospective, cross-sectional study included 1958 singleton pregnancies. Inclusion criteria were singleton pregnancy with cephalic presentation, vaginal delivery and ultrasound examination with complete biometric parameters performed on the day of delivery during the latent or active phase of labor, and absence of chromosomal or structural anomalies. The accuracy of intrapartum WE was compared to a control group of fetuses delivered by primary cesarean section at our perinatal center and an ultrasound examination with complete biometric parameters performed within 3 days before delivery (n = 392). Otherwise, the same inclusion criteria as in the study group were applied. The accuracy of WE was compared between five commonly applied formulas using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS: In the whole study group, all equations showed a systematic underestimation of fetal weight (negative MPEs). Overall, best MAPE and MPE values were found with the Hadlock II formula, using BPD, AC and FL as biometric parameters (Hadlock II, MPE: -1.28; MAPE: 6.52). MPEs differed significantly between WE in the study and control group for all evaluated formulas: in the control group, either no systematic error (Hadlock III, IV and V) or a significant overestimation (Hadlock I, II) was found. Regarding MAPEs, application of the Hadlock III (HC, AC, FL) and V (AC) formula resulted in significant lower values in the control group (Hadlock III, MAPE: 7.48 vs. 5.95, p = 0.0008 and Hadlock V, MAPE: 8.79 vs. 7.52, p = 0.0085). No significant differences were found for the other equations. CONCLUSIONS: A systematic underestimation of fetal weight has to be taken into account in sonographic WE performed intrapartum. Overall, the best results can be achieved with WE formulas using the BPD as the only head measurement.

Sonographic Weight Estimation in Small-for-Gestational-Age Fetuses.

PURPOSE: To determine the accuracy of sonographic weight estimation (WE) for small-for-gestational-age (SGA) fetuses, and to further differentiate the evaluation between symmetric and asymmetric SGA fetuses. MATERIALS AND METHODS: The accuracy of WE in SGA fetuses (n = 898) was evaluated using 14 sonographic models and was further differentiated between symmetric (n = 750) and asymmetric (n = 148) SGA fetuses. SGA fetuses were considered to be asymmetric with a head circumference to abdominal circumference ratio above the 95th percentile. The accuracy of the different formulas was compared using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS: RESULTS for the subgroup of asymmetric SGA fetuses differed significantly from the subgroup of symmetric SGA fetuses. MPE values were closer to zero with most of the formulas in the asymmetric SGA group. Apart from the Siemer, Shepard, Merz and Warsof equations, all formulas showed an underestimation of fetal weight in asymmetric SGA fetuses. In contrast, in the symmetric SGA group, all of the formulas commonly used for fetuses in a normal weight range showed a systematic overestimation of fetal weight. Overall the best accuracy was achieved by using the Sabbagha equation (MPE 1.7 %; SD 9.0 %; MAPE: 6.0). CONCLUSION: An accurate WE in SGA fetuses is feasible using the Sabbagha formula. However, one has to be aware of the significant differences in WE between symmetric and asymmetric SGA fetuses.

A New Sonographic Weight Estimation Formula for Fetuses with Congenital Diaphragmatic Hernia.

PURPOSE: The accuracy of the sonographic weight estimation (WE) of fetuses with congenital diaphragmatic hernia (CDH) is significantly lower than that of fetuses without any malformations. The objective of this study was to develop and evaluate the first specific sonographic weight formula for fetuses with CDH. MATERIALS AND METHODS: In a retrospective, multicenter, cohort study, a statistical estimation technique known as "multivariable fractional polynomial regression" was applied to a group of 146 fetuses with CDH. Each fetus underwent an ultrasound examination with complete biometric parameters within 7 days of delivery. A new formula was derived using the obtained data and was then compared with other commonly used equations. The accuracy of the different formulas was compared using means of signed percentage errors (SPE), medians of absolute percentage errors (MAPE), and fractions of estimates within prespecified error bounds. RESULTS: The new derived formula is: EFW = 10^(4.6729 107 371 + 0.2365 011 768 * HC + 0.2228 897 682 * FL^2 - 0.0129 895 773 * FL^3 - 1.0470 039 072 * (FL * HC)^0.5 + 0.0004 314 661 * (AC * HC) - [in case of liver herniation] 0.0062 112 122), where EFW is the estimated fetal weight, HC is the head circumference, AC is the abdominal circumference, and FL is the femur length. The new formula proved to be superior to other established equations, showing both the lowest median absolute percentage error (MAE: 6.97) and mean signed percentage error (SPE: 0.40), and the best distribution of absolute percentage errors within prespecified error bounds. CONCLUSION: This new formula significantly improves weight estimation in fetuses with CDH.

Proliferation-associated SNF2-like gene (PASG): a SNF2 family member altered in leukemia.

To identify genes involved in cell growth and/or apoptosis in leukemia, differential display was used to identify mRNAs that showed altered expression levels after cytokine withdrawal from the cytokine-dependent MO7e cell line. Sequence analysis of one transcript that showed a profound decrease in expression after cytokine withdrawal revealed it to be a member of the SNF2 family of chromatin remodeling ATPases. This cDNA had a 2514-nucleotide (838-amino acid) open reading frame and encoded an additional 230 amino acids at the NH2 terminus compared with the murine homologue, lsh, and the human counterpart, Hells. This gene locus has been designated SMARCA6 (SWI/SNF2-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 6). The highest levels of mRNA expression in humans are observed in proliferative tissues such as the thymus, testis, and bone marrow. Whereas cytokine withdrawal in MO7e cells leads to apoptosis and decreased mRNA expression, growth arrest without the induction of apoptosis of MO7e cells also leads to down-regulation of mRNA expression, suggesting an association with cell proliferation and not suppression of apoptosis. Nuclear localization of this SNF2-like putative helicase is dependent on a nuclear localization sequence located in the NH2-terminal region. Based on sequence homology to other SNF2-like helicases, the pattern of tissue expression, and the association of expression with cell proliferation, we refer to the protein product as proliferation-associated SNF2-like gene product [PASG (D. W. Lee et al., Blood, 94: 594a, 1999)]. Examination of acute myelogenous leukemia and acute lymphoblastic leukemia samples revealed a high frequency of a PASG transcript containing an in-frame 75-nucleotide deletion, which codes for a conserved motif known to be critical for the transactivation activity of a related yeast SWI/SNF polypeptide. These results extend our knowledge of this SNF2-like family member and suggest a role for PASG in leukemogenesis.

Induction of Labour: Change of Method and its Effects.

Aim: The combination of mechanical and drug procedures for the induction of labour seems to be beneficial. Accordingly, the normal procedure in clinical routine has been changed and induction of labour by means of a balloon catheter has been implemented. The aim of this study was to find out if this procedural change has resulted in a more effective induction of labour. Materials and Method: In this historical cohort study 230 inductions of labour at term in the year 2012 were compared with 291 inductions of labour in the year 2013, all at the University of Erlangen Perinatal Centre. Exclusion criteria were, among others, a multiple pregnancy, a premature rupture of membranes and a prior Caesarean section. In 2012 births were induced solely by use of the drugs dinoprostone and misoprostol, in 2013 not only with misoprostol but also mainly by use of a balloon catheter. The primary target parameter was the rate of failed labour inductions, defined as "no birth within 72 hours". Results: Altogether 521 inductions of labour were analysed. The rate of failed inductions of labour could be reduced by the changes in induction method (first-time mothers: 23 vs. 9 %, p = 0.0059; multiparous women: 10 vs. 1 %, p = 0.0204). Furthermore, the rate of primary Caesarean sections due to failed induction of labour (5.7 vs. 1.4 %, p = 0.0064), that of the observation of green amniotic fluid (first-time mothers: 23 vs. 9 %, p = 0.0059; multiparous women: 10 vs. 1 %, p = 0.0204) and of infantile infections (first-time mothers: 23 vs. 9 %, p = 0.0059; multiparous women: 10 vs. 1 %, p = 0.0204) were all reduced as well. Conclusion: The routine use of a balloon catheter for induction of labour has markedly improved the procedure. There were fewer failed labour inductions and fewer Caesarean sections due to failed induction of labour.

Differential laminin isoform expression in the developing rat olfactory system.

Members of the laminin family influence mammalian cells in a variety of ways, mediating adhesion, proliferation, migration, and growth of neuronal processes. Specific laminin domains act through a number of cellular interaction sites to mediate these activities. In the developing olfactory system, axons grow from the olfactory epithelium to synaptic sites in the olfactory bulb a matrix rich in laminins and known mediators of laminin-axon interactions include integrins and a galectin-1/glycoconjugate adhesion system. Using biochemistry, immunocytochemistry, and in situ hybridization, we identified alpha 2, alpha 3, beta 1, beta 2 and gamma 1 laminin isoforms in the late embryonic and neonatal rat olfactory system. However, alpha 1-containing laminin could not be detected in association with olfactory neurons. Immunocytochemistry revealed that beta 2 laminin is preferentially expressed in the ventral and lateral nerve layer of the olfactory bulb and in the main olfactory axon tracks, but is undetectable in the accessory system during embryonic and early postnatal development. In contrast, beta 1 and gamma 1 laminins are evenly distributed throughout the olfactory bulb and in both the main and accessory olfactory axon tracks. The differential localization of laminin chains in vivo is likely to have functional significance for the development and maintenance of the olfactory system.

Glucoseoxidase from Aspergillus niger in reverse micelles: pH and wo dependence.

The well known enzymatic method for the determination of glucose in aqueous solution with the system glucose oxidase/peroxidase/o-dianisidine was modified in a way that enables the quantitative determination of glucose in various reverse micellar systems. For instance in the 0.1 M sodium-bis-(2-ethylhexyl)-sulfosuccinate/n-octane system the useable glucose measuring range is between 10 and 70 micrograms glucose per 3 ml micellar solution. Investigations concerning the influence of the pH-value and the wo-value on the enzyme activity of glucose oxidase in the system 0.1 M sodium-bis-(2-ethylhexyl) sulfosuccinate/n-octane led to a shift of the pH-optimum from pH 5.5-6.0 in aqueous solution, to pH 4.0, in reverse micellar solution. The bell-shaped wo-dependence of the enzyme activity, typical for many other enzymes, was not found for glucose oxidase at pH 4.0, and was less clearly visible at the other investigated pH-values with an optimum at wo = 5.6.

Introduction of Inhaled Nitrous Oxide and Oxygen for Pain Management during Labour - Evaluation of Patients' and Midwives' Satisfaction.

Aim: Effective pain management during labour is important because pain affects the birth experience. Epidural analgesia is effective but often it may not be possible; however, inhaled analgesia offers another option. Use of inhaled nitrous oxide and oxygen for pain management in labour is well established in obstetrics but is still not used much in Germany. This study aimed to investigate the acceptance of the inhaled analgesia of inhaled nitrous oxide and oxygen by midwives and pregnant women during labour. Material and Methods: In this observational study carried out between April and September 2013, a total of 66 pregnant women received inhaled nitrous oxide and oxygen during labour on request and after prior assessment of suitability. After the birth, all of the women and the responsible midwives were interviewed about their experience and satisfaction with the inhaled analgesia. Results: A statistically significant reduction of pain was achieved with nitrous oxide and oxygen. The inhaled analgesia was mostly used by women who refused epidural analgesia. The likelihood of using inhaled nitrous oxide and oxygen again was reported as higher for patients who tolerated it well (p = 0.0129) and used it in the second stage of labour (p = 0.0003) and when bearing down (p = 0.0008). Conclusion: Inhaled nitrous oxide and oxygen is an effective method for pain management during labour and is accepted well by women in labour and by midwives.

Prevalence and functional consequence of PHOX2B mutations in neuroblastoma.

PHOX2B is a homeodomain-containing protein that is involved in the development of the peripheral nervous system and is the major disease gene for the rare congenital breathing disorder congenital central hypoventilation syndrome (CCHS). Germline PHOX2B alterations were also recently discovered in neuroblastoma cases with CCHS and/or Hirschsprung disease, but a comprehensive survey for mutational frequency and functional consequence has not been performed. We therefore studied a large panel of hereditary neuroblastomas to understand the frequency and functional effects of PHOX2B mutations. Three of 47 individuals with presumed genetic predisposition to neuroblastoma showed a germline PHOX2B mutation (6.4%). Mutations were also discovered in 2 of 30 human neuroblastoma-derived cell lines, but none of 86 primary tumors from patients with sporadically occurring neuroblastoma. The vast majority of primary tumors showed abundant PHOX2B mRNA expression relative to the remainder of the transcriptome. Consistent with its role as an important neurodevelopmental gene, forced overexpression of wild-type PHOX2B in neuroblastoma cell lines suppressed cell proliferation and synergized with all-trans retinoic acid to promote differentiation. Patient-derived mutant PHOX2B constructs retained the ability to suppress cellular proliferation, but were not able to promote differentiation or activate expression of a known PHOX2B target gene in vitro. These findings show that PHOX2B alterations are a rare cause of hereditary neuroblastoma, but disruption of this neurodevelopmental pathway can interfere with transcription-dependent terminal differentiation. These data also suggest that the genetics of neuroblastoma initiation are complex, and highlight genes involved in normal noradrenergic development as candidate predisposition genes.

An SNF2 factor involved in mammalian development and cellular proliferation.

Members of the SNF2 (Sucrose Non-Fermenter) family of chromatin-remodeling proteins function in processes ranging from DNA repair to transcription to methylation. Using differential display, we recently identified a novel member of the SNF2 family that is highly expressed at the mRNA level in proliferating cells and is down-regulated during apoptosis. We have named this gene PASG (Proliferation-Associated SNF2-like Gene). Northern blot analysis of adult mouse tissues shows PASG to be highly expressed in proliferating organs such as thymus, bone marrow, and testis and absent from nonproliferative tissues such as brain and heart. In situ hybridization analysis of mouse embryos shows that PASG is differentially expressed during development, with highest expression in developing face, limbs, skeletal muscle, heart, and tail. In vitro, PASG expression correlates with a shift from a quiescent to a proliferative state. Mice null for PASG (also known as LSH or Hells) are reported to die perinatally, although the mechanism for lethality is unclear (Geiman and Muegge, 2000). To test the hypothesis that PASG functions in cell proliferation, we compared 5-bromodeoxyuridine (BrdU) incorporation in C33A cells transiently transfected with PASG versus empty vector and found that PASG transfected cells showed a significant decrease in the amount of BrdU incorporation. These findings suggest that PASG plays a role in cell proliferation and may function in the development of multiple cell lineages during murine embryogenesis.