Routine Doppler ultrasound in twin pregnancy.

Doppler ultrasound when used appropriately is an invaluable tool in monitoring high risk twin pregnancy. There are no recent multicentre randomised controlled trials examining the value of routine umbilical artery doppler (UA), middle cerebral artery doppler (MCA), cerebroplacental ratio (CPR), uterine artery doppler (UtA) and ductus venosus doppler in uncomplicated twins. Thus, there is lack of international consensus in relation to incorporation of doppler ultrasound in the routine surveillance of uncomplicated multiples. In this chapter we will discuss how twins differ from singletons in their growth trajectories and progression of doppler abnormalities. International clinical guidelines are reviewed. Recommendations for doppler surveillance (routine or selective) with reference to recent studies are made.

Fetoscopic Laser Ablation for Twin-to-Twin Transfusion Syndrome: A 15-year Review of Perinatal Survival.

Objective Twin to twin transfusion syndrome (TTTS) complicates 5-15% of monochorionic twin pregnancies and untreated is associated with a 90% mortality rate. The aim was to present the perinatal survival of patients with TTTS treated with laser ablation, by a national fetal medicine team. Methods This was a review of all cases of TTTS treated with fetoscopic laser ablation performed from March 2006 through to December 2020. All patients treated with fetoscopic laser were identified from the hospital database. The perinatal outcomes for the overall cohort and the individual Quintero stages were determined. Results A total of 155 cases of TTTS underwent fetoscopic laser ablation during the study period. The median gestational age at diagnosis was 19+1 weeks, with a mean growth discordance of 23.6%. The Quintero stage at diagnosis was: Stage 1 6.5% (10/155), Stage 2 49% (76/155), Stage 3 38.7% (60/155), Stage 4 5.8% (9/155). There was at least one survivor in 83.2% (129/155) of pregnancies, with dual survival in 52.9% (82/155). An increase in the rate of any survivor was observed from 75% (2006-2014) to 94% (2014-2020) (p<0.05). Dual survival decreased with increasing Quintero Stage (p<0.05). 80.6% (125/155) of pregnancies delivered prior to 34+6 weeks gestation. Conclusion Fetoscopic laser ablation is the recommended first line treatment for severe TTTS. We observed a survival rate of at least one twin in 83.2% pregnancies which is comparable to internationally published data on single-centre outcomes.

Antenatal prediction of fetal macrosomia in pregnancies affected by maternal pre-gestational diabetes.

AIMS: Higher rates of fetal macrosomia may occur in infants of women with pre-gestational diabetes compared with non-diabetic controls. Antenatal predication of fetal macrosomia remains challenging. Ultrasound over-estimated fetal weight could result in over-classification of fetuses as macrosomic with corresponding inappropriate clinical interventions. Previously we had studied a measurement - the anterior abdominal wall measurement (AAW) - to predict fetal macrosomia in fetal estimation of weight. The purpose of the study was to study whether specific third trimester ultrasound measurements with measures of glycaemic control (HbA1c) predicted macrosomia in babies born to women with pre-gestational diabetes. In particular, a new variant of this measurement (fetal anterior abdominal wall thickness (AAW), abdominal circumference (AC) ratio: AAW:AC) was investigated. METHODS: This was a prospective cohort study in a tertiary referral maternity hospital. Serial growth scans including measurement of AAW and AC: AAW ratio was performed at 30, 33- and 36-weeks' gestation. Birth-weight data was collected, and macrosomia was defined as >90th centile based on gestational age and gender of the baby. Serial HbA1c as measured at the first antenatal visit, 14, 20- and 36-weeks' gestation were reported for this study. RESULTS: Of the 416 pregnancies analyzed, mean maternal age was 33.3 years. One in five women were primigravida's. The mean birthweight was 3548 g (+/- 581 g), of which 142 (34%) babies were classified as macrosomic. The median gestational age at delivery was 383 weeks (314 - 402 weeks). There were 37 (9%) babies born preterm at <37 weeks' gestation. Mean AC measurements in fetuses that would be born with macrosomia compared with those with a non-macrosomic birth weight were 282 mm vs. 266 mm at 30 weeks, 318.3 mm vs. 297 mm at 33 weeks and 350 mm vs. 325 mm at 36 weeks' gestation (all p < .001). Mean AAW measurements in macrosomic fetuses compared with normal size fetuses were 3.7 mm vs. 3.3 mm at 30 weeks, 4.9 mm vs 4.3 mm at 33 weeks and 5.9 mm vs. 5.3 mm at 36 weeks' gestation (all p < .001). The mean AC: AAW was 0.01 for both normal and macrosomic fetuses at 30 weeks. There was no clinical or statistical difference in AC:AAW ratios between non-macrosomic and macrosomic infants. Binary logistic regression showed that AC at 36 weeks was most predictive of macrosomia (76.5%), followed by AAW at 30 weeks (68.5%). Using a combination of HbA1c booking, 14, 20, 36 weeks and AAW 30, 33, 36 weeks and AC 30, 33, 36 weeks predicted macrosomia in 80.9%. The ratio of AC: AAW did not act as a useful antenatal clinical predictor of macrosomia at birth. CONCLUSIONS: Abdominal circumference at 36 weeks was the single best predictor of fetal macrosomia. A combined model of HbA1c, AC and AAW was the best antenatal predictor of macrosomia, with intriguing clinical possibilities in the possible prevention of maternal and fetal complications of macrosomia.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine.

Novel placental ultrasound assessment: potential role in pre-gestational diabetic pregnancy.

OBJECTIVES: Management of women with pre-gestational diabetes continues to be challenging for clinicians. This study aims to determine if 3D power Doppler (3DPD) analysis of placental volume and flow, and calculation of placental calcification using a novel software method, differ between pregnancies with type 1 or type 2 diabetes and normal controls, and if there is a relationship between these ultrasound placental parameters and clinical measures in diabetics. METHODS: This was a prospective cohort study of 50 women with diabetes and 250 controls (12-40 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental calcification was calculated by computer analysis. Results in diabetics were compared with control values, and correlated with early pregnancy HbA1c, Doppler results and placental histology. RESULTS: Placental calcification and volume increased with advancing gestation in pre-gestational diabetic placentae. Volume was also found to be significantly higher than in normal placentae. VI and VFI were significantly lower in diabetic pregnancies between 35 and 40 weeks gestation. A strong relationship was seen between a larger placental volume and both increasing umbilical artery pulsatility index and decreasing middle cerebral artery pulsatility index. FI was significantly lower in cases which had a booking HbA1c level ≥6.5%. Ultrasound assessed placental calcification was reduced with a histology finding of delayed villous maturation. No other correlation with placental histology was found. CONCLUSIONS: This study shows a potential role for 3D placental evaluation, and computer analysis of calcification, in monitoring pre-gestational diabetic pregnancies.

Mode of delivery in pregnancies complicated by major fetal congenital heart disease: a retrospective cohort study.

OBJECTIVE: To determine the mode of delivery in pregnancies complicated by complex fetal congenital heart disease (CHD). STUDY DESIGN: Five-year retrospective cohort study at a tertiary fetal medicine center (2007 to 2011). Cases of complex fetal CHD (n=126) were compared with 45 069 non-anomalous singleton infants ⩾500 g to determine rates of emergency intrapartum cesarean section (CS), preterm delivery and induction of labor. RESULT: Intrapartum CS is significantly higher in fetal CHD than non-anomalous controls (21% vs 13.5%, odds ratio (OR) 1.7, 95% confidence interval (CI): 1.0 to 2.7; P=0.035), predominantly related to CS for non-reassuring fetal status (OR 2.2, 95% CI: 1.1 to 4.1; P=0.022). Although fetal CHD did not increase emergency CS rates in nulliparous women, CS was significantly increased in multiparous pregnancies (OR 2.4, 95% CI: 1.8 to 4.6; P=0.014). Rates of preterm delivery (OR 3.4, 95% CI: 2.0 to 5.4; P<0.0001) and induction of labor (OR 1.9, 95% CI: 1.3 to 2.9; P=0.001) were higher in the CHD cases. CONCLUSION: Emergency CS is increased in fetal CHD, attributed to a higher rate of CS for non-reassuring fetal status and seen mostly in multiparous women.

Umbilical and fetal middle cerebral artery Doppler reference ranges in a twin population followed longitudinally from 24 to 38 weeks' gestation.

OBJECTIVE: To construct monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin reference ranges for umbilical artery (UA) pulsatility index (PI), UA resistance index (RI), fetal middle cerebral artery (MCA) PI and peak systolic velocity (PSV) and cerebroplacental ratio (CPR) from 24 weeks' to 38 weeks' gestation and compare these with published normal values for singleton pregnancies. METHODS: This prospective multicenter cohort study included 1028 unselected twin pairs recruited over a 2-year period. Participants with dichorionic twins underwent fortnightly ultrasound surveillance from 24 weeks' gestation, with monochorionic twins being followed every 2 weeks from 16 weeks until delivery. A total of 7536 fetal Doppler examinations in 618 twin pregnancies were included in the analysis, with reference ranges for MCDA and DCDA pregnancies constructed for each of the Doppler indices using multilevel modeling. RESULTS: UA-PI and UA-RI appear to be higher in twins than in singletons, and MCA-PI and MCA-PSV appear to be lower. The CPR also appears to be lower in twins than in singletons. Similar MCA indices were observed in MCDA and DCDA twins. CONCLUSION: We have established longitudinal reference ranges for UA-PI and UA-RI, MCA-PI and MCA-PSV and CPR in twin pregnancies, which appear to differ from those in singleton pregnancies. The derived twin-specific reference ranges may be more appropriate in the surveillance of these high-risk pregnancies. Applying the singleton CPR cut-off of ≤ 1.0 may lead to a large number of false-positive diagnoses of cerebral redistribution in twin fetuses.

Measurement of misfit at the implant-prosthesis interface: an experimental method using a coordinate measuring machine.

Measurement of misfit at the implant-prosthesis interface is a difficult procedure. One factor common to all methods that attempt to measure 3-dimensional distortion to the micron level is the difficulty in providing verifiably consistent reference points between individual measurement sets. Consequently, the majority of studies use a relative distortion model in which the coordinate reference system is integral to the framework, thus limiting the value of the data gathered. In the method described, the datum plane and the coordinate reference system were set up external to the framework and could be re-established between measurement sets in a verifiable manner.

An investigation into the development of early postural control.

Eighteen normal infants were studied longitudinally using video and photographic records of their levels of lying and sitting ability. A developmental sequence of postural control in lying and sitting was confirmed in the normal infants. All infants reached level 4 prone and supine lying ability before achieving level 3 sitting ability (maintaining independent sitting). 34 children with cerebral palsy in a cross-sectional study could be ascribed a level of sitting or lying ability. The relationship found in normal infants between lying and sitting was confirmed in all the children with cerebral palsy.

Clinical aspects of the Chailey Adaptaseat.

A methodological assessment procedure for seating has been established and seven levels of sitting ability defined from which prescription criteria for seating are established. The inappropriateness of intimately moulded seating for individuals with sitting abilities of levels 2-7 is explained and the principle features of the Chailey Adaptaseat described. The sitting ability of six children and adolescents taking part in the clinical trials of the prototype Adaptaseat has improved or been maintained and a brief case history of a 26-year-old man with cerebral palsy is presented.