Sonographic markers of fetal adiposity and risk of Cesarean delivery.

OBJECTIVE: Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery. METHODS: This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery. RESULTS: After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2 ; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65-2.94; P < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37). CONCLUSIONS: Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of selective fetal growth restriction and twin-to-twin transfusion syndrome in monochorionic twins.

OBJECTIVE: To study the correlation of discrepancy between crown-rump length (CRL) and nuchal translucency (NT) in monochorionic twins at 11-14 weeks of gestation and subsequent development of twin-to-twin transfusion syndrome (TTTS) and selective fetal growth restriction (sFGR). DESIGN: Retrospective cohort study. SETTING: Tertiary-care Fetal Medicine Unit, London. SAMPLE: Monochorionic twin pregnancies with known outcome. METHODS: Inter-twin discrepancy was calculated as a percentage of the larger CRL and smaller NT and compared among those developing TTTS, those with sFGR and those with normal outcome. Receiver operating characteristic (ROC) curves were constructed to evaluate the performance of inter-twin discrepancy in prediction of sFGR and TTTS. MAIN OUTCOME MEASURES: Development of TTTS and sFGR. RESULTS: A total of 242 monochorionic twin pregnancies were studied (102 TTTS, 36 sFGR and 104 controls). The median CRL discrepancy in the sFGR group (11.9%) was significantly higher (P < 0.001) than in the TTTS group (3.8%) and control group (3.5%). Median inter-twin NT discrepancies were not significantly different (P = 0.869) between sFGR and both TTTS and control groups (15.6%, 16.7% and 14.8%, respectively). Discrepancy in CRL performs well as a screening test for sFGR (area under ROC curve = 0.89), but not for TTTS (area under ROC curve = 0.58). CONCLUSIONS: First-trimester CRL discrepancy in monochorionic twins is a marker for subsequent development of sFGR rather than TTTS. Inter-twin NT discrepancy does not appear to be significantly different in these two groups from those with normal outcome.

Second-trimester assessment of gestational age in twins: validation of singleton biometry charts.

OBJECTIVE: To determine the accuracy of dating twin pregnancies, of between 16 and 26 weeks' gestation, using singleton head circumference (HC) formulae. METHODS: This was a retrospective study of 269 singleton and 119 twin non-anomalous pregnancies conceived by in-vitro fertilization (IVF) with a known embryo transfer date. Fetal ultrasound biometry data for HC, obtained using different formulae, were compared with expected fetal HC size for gestation calculated from the date of conception. Similar comparisons were undertaken for femur length (FL) and for transverse cerebellar diameter. RESULTS: The mean differences in HC between observed ultrasound measurements and those expected from the IVF history were small (1-4 mm) and within the measurement error for both singletons and twins for all formulae. All measurements from the larger and the smaller twins straddled those of singletons, regardless of biometry and formula used. Negative skewing of FL measurements in the smaller twin suggests that fetal growth restriction may occur at this gestation and supports the practice of dating using the HC of the larger twin. CONCLUSIONS: Singleton pregnancy HC charts can be used to date reliably twin pregnancies. The data of the study also suggest that the HC of the larger twin is the most reliable measurement for use in dating.

Systematic labeling of twin pregnancies on ultrasound.

OBJECTIVE: Correct labeling of twin fetuses is needed for consistency in assigning and interpreting longitudinal scan and prenatal screening/diagnostic results. The aim of this study was to describe a standard method of twin labeling in the first trimester of pregnancy and to assess the robustness of such a technique in predicting the presenting twin in subsequent scans and at delivery. METHODS: This was a retrospective first-trimester study of all twin pregnancies assessed by ultrasonography at our center between 2000 and 2010. The fetus contained in the gestational sac closer to the maternal cervix was designated as Twin 1 and the relative orientation of the fetuses to each other was then defined as either lateral (left/right) or vertical (top/bottom). In discordant-sex twins, their sex and presenting order on the final scan prior to delivery were documented and compared with the sex and birth order at delivery. RESULTS: A total of 416 twin pregnancies were seen during the study period. At the 11-14-week scan 90.9% of twins were in lateral orientation while the remainder were oriented vertically. None of the vertically oriented twin pairs but 32 (8.5%) of the laterally oriented twin pairs changed their presenting order between the first and the last ultrasound scan prior to delivery. There were 108 discordant-sex twins scanned in the third trimester, of which the birth order changed in 20.3% that were delivered by Cesarean section and in 5.9% of those delivered vaginally. CONCLUSION: The study demonstrates that antenatal labeling of twins according to laterality or vertical orientation is reliable. The technique ensures continuity of biometric assessment from serial scans at each visit, and as such should be adopted as the preferred method of twin labeling. Furthermore, the use of orientation for antenatal labeling of twins rather than assignment of a number based on proximity to the cervix, precludes any misconception regarding which twin will be born first and ensures that parents and pediatricians are aware of the significant likelihood of a peripartum switch.

First-trimester ultrasound determination of chorionicity in twin pregnancy.

OBJECTIVE: To determine the accuracy of ultrasound at 11-14 weeks' gestation in the diagnosis of chorionicity in twin pregnancy. METHODS: This was a retrospective observational study of data obtained between 1999 and 2010. At the first-trimester routine ultrasound scan, chorionicity was assigned according to the number of placental masses and T or λ-signs for a single placental mass. Chorionicity was confirmed by histology or discordant sex at birth. RESULTS: A total of 648 pregnancies were assigned chorionicity by first-trimester ultrasound during the study period. Chorionicity was ascertained in 613 cases, either by histology (n = 340) or discordant sex (n = 273). Chorionicity was correctly assigned by ultrasound at 11-14 weeks in 612 of 613 pregnancies (accuracy 99.8%). Sensitivity and specificity for determining monochorionicity were 100% and 99.8%, respectively. CONCLUSIONS: First-trimester ultrasound can be used to determine chorionicity reliably by noting the number of placental masses and T or λ-signs. Determination of twin chorionicity is important and should be completed in the first trimester.

First-trimester ultrasound dating of twin pregnancy: are singleton charts reliable?

OBJECTIVE: The aim of this study was to assess the performance of validated singleton crown-rump length (CRL) formulae in dating twin pregnancies at 11-14 weeks of gestation. DESIGN: Retrospective cohort study. SETTING: Fetal medicine unit of a London teaching hospital. SAMPLE: Three hundred and eighty-four pregnancies with known dates of conception. METHODS: Retrospective analysis of 266 singletons and 118 twin pregnancies conceived by in vitro fertilisation (IVF), with a known date of conception. The gestation calculated from the date of conception was compared with the expected gestation from fetal size using a number of different CRL formulae. MAIN OUTCOME MEASURES: Difference in gestational age computed from fetal size (CRL) of the bigger and smaller fetus in twin pregnancies and singleton pregnancies using three formulae. RESULTS: Two of the three studied CRL formulae systematically underestimated the mean gestational age and size of singleton IVF pregnancies (Robinson formula: gestation = 1.4 days, size = 2.7 mm). Twin CRL measurements straddled those of singletons, regardless of the CRL formula used (Robinson formula: larger twin gestation = 2.4 days, size = 4.7 mm; smaller twin gestation = 0.8 days, size = 1.7 mm). These underestimates in gestation and size for IVF singleton and twin pregnancies are well within the known limits of accuracy of first = trimester ultrasound measurements, and are of limited clinical significance. CONCLUSIONS: Currently available CRL charts underestimate both the age and size of IVF singleton pregnancies by a clinically insignificant amount. This difference is similar for twin pregnancies, suggesting that singleton CRL charts can be used to date twin pregnancies accurately.

Cord entanglement and perinatal outcome in monoamniotic twin pregnancies.

OBJECTIVES: To assess the prevalence of cord entanglement and perinatal outcome in a large series of monoamniotic twin pregnancies and to review the recent literature on similar published large series. METHODS: Prospective observational study of all prenatally detected cases of monoamniotic twin pregnancies during an 8-year period in a tertiary fetal medicine unit. A Medline database review for publications since 2000 containing five or more cases of monoamniotic pregnancies that showed data on cord entanglement and perinatal outcome was also undertaken. RESULTS: A total of 32 monoamniotic pregnancies were diagnosed during the study period, including three conjoined twins, seven pregnancies with twin reversed arterial perfusion (TRAP) syndrome, three surgical pregnancy interruptions for discordant fetal abnormality and one miscarriage before 16 weeks' gestation. The remaining 18 monoamniotic pregnancies were included in the study analysis. All monoamniotic pregnancies were complicated with antenatal cord entanglement diagnosed by B-mode and color Doppler ultrasound. There were 34 live births and a double intrauterine death diagnosed at 19 + 2 weeks' gestation. There were two late neonatal deaths, one from congenital complete heart block and the other after surgery for transposition of the great arteries. The overall perinatal loss rate was 11.1% after 16 weeks and 5.9% after 20 weeks' gestation. The cumulative rates of cord entanglement and perinatal mortality in the reviewed literature were 74% and 21%, respectively. CONCLUSIONS: Umbilical cord entanglement is present in all monoamniotic twins when it is systematically evaluated by ultrasound and color Doppler. Perinatal mortality in monoamniotic twins is mainly a consequence of conjoined twins, TRAP, discordant anomaly and spontaneous miscarriage before 20 weeks' gestation. Expectantly managed monoamniotic twins after 20 weeks have a very good prognosis despite the finding of cord entanglement. The practice of elective very preterm delivery or other interventions to prevent cord accidents in monoamniotic twins should be re-evaluated.

Alpha-adaptin, a marker for endocytosis, is expressed in complex patterns during Drosophila development.

A Drosophila cDNA encoding a structural homologue of the mammalian coated vesicle component alpha-adaptin (AP2 adaptor complex) has been cloned and sequenced. The mammalian and invertebrate sequences are highly conserved, especially within the amino terminal region, a domain that mediates interactions with other components within the AP2 complex and with specific receptors tails. Mammalian alpha-adaptins are encoded by two genes; however, Drosophila alpha-adaptin has a single gene locus, within polytene bands 21C2-C3 on the left arm of the chromosome 2, closely adjacent to the paired homeobox gene aristaless. There seem to be at least two Drosophila alpha-adaptin transcripts expressed, plausibly by alternative splicing. One of the transcripts is more abundant during early embryogenesis and may be of maternal origin. We have studied the distribution of the alpha-adaptin protein throughout embryogenesis and at the neuromuscular junction of the third instar larva. During cellularization of the blastoderm embryo, the protein is seen between and ahead of the elongating nuclei, and then redistributes to the cell surface during gastrulation. These observations suggest a role for endocytosis in cellularization and are consistent with the finding that dynamin (the shibire gene product), another component of the endocytic mechanism, is required for cellularization. At later stages of embryogenesis, alpha-adaptin is expressed in complex and dynamic patterns. It is strongly induced in elements of the central and peripheral nervous system (e.g., in neuroblasts, the presumptive stomatogastric nervous system, and the lateral chordotonal sense organs), in the Garland cells, the adult midgut precursors, the antenno-maxillary complex, the endoderm, the fat bodies, and the visceral mesoderm. In the larva, alpha-adaptin is localized at the plasma membrane in the synaptic boutons of the neuromuscular junctions. The cells expressing high levels of alpha-adaptin are known or expected to support high levels of endocytosis; thus, this coated vesicle protein seems to be an excellent marker for endocytic activity. The expression patterns of dynamin, detected in the embryo by in situ hybridization methods, are very similar to those reported here for alpha-adaptin reflecting the likely coordinated expression of endocytic components. Taken together with previous evidence, our results suggest that endosomal vesicle trafficking, membrane recycling, and the regulation of endocytosis play critical roles in the wide range of developmental processes.

Quality pork genes and meat production.

Functional genomics, including analysis of the transcriptome and proteome, provides new opportunities for understanding the molecular processes in muscle and how these influence its conversion to meat. The Quality Pork Genes project was established to identify genes associated with variation in different aspects of raw material (muscle) quality and to then develop genetic tools that could be utilized to improve this quality. DNA polymorphisms identified in the porcine PRKAG3 and CAST genes illustrate the impact that such tools can have in improving meat quality. The resources developed in Quality Pork Genes provide the basis for identifying more of these tools.

Promoter sequence and expression of the leucine-rich repeat gene LRR47: evidence for cytoplasmic and nuclear localization in Drosophila embryos and cells.

In Drosophila, proteins containing leucine-rich repeats (LRR) play diverse roles during embryonic development. In particular, they function in cell adhesion and cellular signalling and have in common the ability to mediate reversible protein-protein interactions. The sequence and chromosomal location of Drosophila LRR47, which encodes a protein with eight LRR repeats, were reported previously. In this paper the 5' flanking region of the LRR47 gene is described and the initiation point for the maternal transcription unit is defined. LRR47 belongs to a subfamily of LRR proteins that have in common the ability to interact with ras GTPase. Whole-mount in situ hybridization studies show that the LRR47 transcript is uniformly distributed in early cleavage embryos but becomes depleted at the termini by the blastoderm stage. There is a specific requirement for ras function in the embryonic termini at this developmental stage. The distribution of LRR47 protein in embryos and tissue culture cells was also studied. The protein is present in both the cytoplasm and nuclei of embryos until gastrulation and is seen to persist in the nuclei of the amnioserosa until later stages of development. The protein is also constitutively present in growing SL2 culture cells and again is present in both cytoplasm and nuclei. These results suggest that LRR47 function may be modulated in the cell or nuclear division cycle.

High efficiency electroporation of Lactococcus lactis subsp. lactis LM0230 with plasmid pGB301.

Electroporation-mediated transformation of Lactococcus lactis with plasmid pGB301, a 9.8 kilobase pair vector (Behnke et al. 1981), has been reported by McIntyre & Harlander (1989a). Improved transformation efficiencies of 10(2)-10(3)/micrograms DNA were achieved by altering the conditions under which the bacteria were grown prior to electroporation (McIntyre & Harlander 1989b). This present investigation sought to improve still further transformation efficiencies in order to provide a reliable high frequency transformation system for Lc. lactis subsp. lactis.

An audit of the accuracy of upper gastrointestinal diagnoses in Scottish Morbidity Record 1 data in Tayside.

INTRODUCTION: Scottish Morbidity Record (SMR1) data are coded by trained clerical staff from case records and discharge summaries. They form the basis of many strategic NHS decisions. Their accuracy for upper gastrointestinal (UGI) diagnosis is unknown and the study was undertaken to assess this accuracy in Tayside. METHOD: Patients who fulfilled the following criteria were identified using a record-linkage pharmacoepidemiological database, and their case records retrieved: over 50 years of age, had encashed at least one prescription for a non-steroidal anti-inflammatory drug at a Tayside pharmacy and who had SMR1 records containing one or more symptom/diagnosis codes between January 1989 and December 1991. Medically qualified staff were trained to examine case records and to code UGI diagnoses. They searched the case records for every UGI SMR1 entry for these patients from 1980-1992 and produced re-coded diagnoses (RCD) for each hospital event (admission and discharge), using all the data available in the case records. They also abstracted data on the clinical presentation, investigations and management of patients. Each event was then examined by a single medically qualified researcher who compared the original SMR1 codes with the RCDs. RESULTS: 2,101 patients had a total of 3,764 events in 1989-1991. 317 events were either day case procedures or elective surgery or the case records were not found. They were therefore excluded. Of the remainder, the SMR1 and RCD codes were judged equivalent in 1,608 events (46.6%). However, 1,005 SMR1 events (29.2%) contained a symptom code but no diagnosis code and the remaining 834 (24.2%) were judged suboptimal for other reasons. Of those with a symptom code only, 406 could not be improved upon and were transformed into RCD symptom codes only, 435 were assigned symptom and diagnostic RCDs and 164 were assigned diagnostic RCDs only. In the other 834 events, 279 had one or more diagnoses missing, 425 had one or more diagnoses inaccurate, 23 had both missing and inaccurate diagnoses and 107 were not UGI. Thus 1,433 (41.6%) of UGI SMR1 events could be more accurately coded. Examination of investigation data revealed that coding inaccuracy was not due to diagnostic procedures being carried out after admission. CONCLUSION: UGI SMR1 data were satisfactory in about half of all events. In about a quarter there were symptom codes but no satisfactory diagnosis codes, whilst in another quarter the data were inaccurate. These findings have implications for health care activities and research that use these data.