Sex-specific reference ranges of cerebroplacental and umbilicocerebral ratios: longitudinal study.

OBJECTIVES: Observational studies have shown that low cerebroplacental ratio (CPR) values predict an increased risk of adverse perinatal outcome. The inverse ratio, i.e. the umbilicocerebral ratio (UCR), has been suggested to be a better predictor as it rises with increasing degree of fetal compromise. However, longitudinal reference ranges for UCR have not been established, and whether gestational-age-dependent changes in CPR or UCR differ between male and female fetuses has not been studied. Thus, the aims of this study were to investigate sex-specific, gestational-age-associated serial changes in CPR and UCR during the second half of pregnancy and to establish longitudinal reference ranges. METHODS: This was a secondary analysis of prospectively collected data from a dual-center longitudinal observational cohort study of low-risk singleton pregnancies. Doppler blood-flow velocity waveforms were obtained serially from the umbilical artery (UA) and fetal middle cerebral artery (MCA) from 19-41 weeks' gestation, and pulsatility indices (PIs) were determined. CPR and UCR were calculated as the ratios MCA-PI/UA-PI and UA-PI/MCA-PI, respectively. The course and outcome of pregnancies were recorded, and the sex of the fetus was determined after delivery. Reference intervals for CPR and UCR were constructed using multilevel modeling, and gestational-age-specific Z-scores in male and female fetuses were compared. RESULTS: Of a total of 299 pregnancies enrolled, 284 (148 male and 136 female fetuses) were included in the final analysis, and 979 paired measurements of UA-PI and MCA-PI were used to construct sex-specific longitudinal reference intervals. The relationship of both CPR and UCR with gestational age was U-shaped, but in opposite directions. There was a small but significant difference in Z-scores of CPR and UCR between male and female fetuses throughout the second half of pregnancy (P = 0.007). CONCLUSIONS: We have established longitudinal reference ranges for CPR and UCR suitable for serial monitoring, with the possibility of refining assessment by using fetal sex-specific ranges and conditioning by a previous measurement. The clinical significance of such refinements needs further evaluation. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Maternal exercise, season and sex modify the daily fetal heart rate rhythm.

AIM: The knowledge on biological rhythms is rapidly expanding. We aimed to define the longitudinal development of the daily (24-hour) fetal heart rate rhythm in an unrestricted, out-of-hospital setting and to examine the effects of maternal physical activity, season and fetal sex. METHODS: We recruited 48 women with low-risk singleton pregnancies. Using a portable monitor for continuous fetal electrocardiography, fetal heart rate recordings were obtained around gestational weeks 24, 28, 32 and 36. Daily rhythms in fetal heart rate and fetal heart rate variation were detected by cosinor analysis; developmental trends were calculated by population-mean cosinor and multilevel analysis. RESULTS: For the fetal heart rate and fetal heart rate variation, a significant daily rhythm was present in 122/123 (99.2%) and 116/121 (95.9%) of the individual recordings respectively. The rhythms were best described by combining cosine waves with periods of 24 and 8 hours. With increasing gestational age, the magnitude of the fetal heart rate rhythm increased, and the peak of the fetal heart rate variation rhythm shifted from a mean of 14:25 (24 weeks) to 20:52 (36 weeks). With advancing gestation, the rhythm-adjusted mean value of the fetal heart rate decreased linearly in females (P < .001) and nonlinearly in males (quadratic function, P = .001). At 32 and 36 weeks, interindividual rhythm diversity was found in male fetuses during higher maternal physical activity and during the summer season. CONCLUSION: The dynamic development of the daily fetal heart rate rhythm during the second half of pregnancy is modified by fetal sex, maternal physical activity and season.

Risk of fetal death in growth-restricted fetuses with umbilical and/or ductus venosus absent or reversed end-diastolic velocities before 34 weeks of gestation: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to establish the risk of fetal death in early-onset growth-restricted fetuses with absent or reversed end-diastolic velocities in the umbilical artery or ductus venosus. DATA SOURCES: A systematic search was performed to identify relevant studies published in English, Spanish, French, Italian, or German using the databases PubMed, ISI Web of Science, and SCOPUS, without publication time restrictions. STUDY ELIGIBILITY CRITERIA: The study criteria included observational cohort studies and randomized controlled trials of early-onset growth-restricted fetuses (diagnosed before 34 weeks of gestation), with information on the rate of fetal death occurring before 34 weeks of gestation and absent or reversed end-diastolic velocities in the umbilical artery and/or ductus venosus. STUDY APPRAISAL AND SYNTHESIS METHODS: For quality assessment, 2 reviewers independently assessed the risk of bias using the Newcastle-Ottawa Scale for observational studies and the Cochrane Collaboration's tool for randomized trials. For the meta-analysis, odds ratio for both fixed and random-effects models (weighting by inverse of variance) were used. Heterogeneity between studies was assessed using tau2, χ2 (Cochrane Q), and I2 statistics. Publication bias was assessed by a funnel plot for meta-analyses and quantified by the Egger method. RESULTS: A total of 31 studies were included in this meta-analysis. The odds ratios for fetal death (random-effects models) were 3.59 (95% confidence interval, 2.3-5.6), 7.27 (95% confidence interval, 4.6-11.4), and 11.6 (95% confidence interval, 6.3-19.7) for growth-restricted fetuses with umbilical artery absent end-diastolic velocities, umbilical artery reversed end-diastolic velocities, and ductus venosus absent or reversed end-diastolic velocities, respectively. There was no substantial heterogeneity among studies for any of the analyses. CONCLUSION: Early-onset growth-restricted fetuses with either umbilical artery or ductus venosus absent or reserved end-diastolic velocities are at a substantially increased risk for fetal death.

Measured acoustic intensities for clinical diagnostic ultrasound transducers and correlation with thermal index.

OBJECTIVES: To investigate if the thermal index for bone (TIB) displayed on screen is an adequate predictor for the derated spatial-peak temporal-average (ISPTA.3 ) and spatial-peak pulse-average (ISPPA.3 ) acoustic intensities in a selection of clinical diagnostic ultrasound machines and transducers. METHODS: We calibrated five clinical diagnostic ultrasound scanners and 10 transducers, using two-dimensional grayscale, color Doppler and pulsed-wave Doppler, both close to and far from the transducer, with a TIB between 0.1 and 4.0, recording 103 unique measurements. Acoustic measurements were performed in a bespoke three-axis computer-controlled scanning tank, using a 200-µm-diameter calibrated needle hydrophone. RESULTS: There was significant but poor correlation between the acoustic intensities and the on-screen TIB. At a TIB of 0.1, the ISPTA.3 range was 0.51-50.49 mW/cm2 and the ISPPA.3 range was 0.01-207.29 W/cm2 . At a TIB of 1.1, the ISPTA.3 range was 19.02-309.44 mW/cm2 and the ISPPA.3 range was 3.87-51.89 W/cm2 . CONCLUSIONS: TIB is a poor predictor for ISPTA.3 and ISPPA.3 and for the potential bioeffects of clinical diagnostic ultrasound scanners. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of adverse perinatal outcome of small-for-gestational-age pregnancy using size centiles and conditional growth centiles.

OBJECTIVE: To test whether adding conditional growth centiles to size centiles of estimated fetal weight (EFW) improves prediction of adverse perinatal outcome in pregnancies with or at risk of having a small-for-gestational-age (SGA) fetus. METHODS: This prospective longitudinal study included pregnant women at risk of or diagnosed with an SGA (≤ 5(th) centile) fetus. They underwent serial ultrasound measurements and the final two were included in the analyses for this study. The EFW was categorized into normal (> 5(th) or 10(th) centile) and abnormal (≤ 5(th) or 10(th) centile) for size and conditional growth before entering the variables into log-binomial regression analyses. Adverse outcomes were delivery < 37 weeks, operative delivery due to fetal distress, 5-min Apgar score < 7, newborn hypoglycemia (glucose < 2.0 mmol/L), admission to the neonatal intensive care unit and perinatal mortality. A combined outcome variable ('any adverse outcome') included one or more adverse outcomes. RESULTS: Complete biometric data were obtained for 211 women. Conditional growth and size centiles contributed independently to the prediction of adverse outcome. Combining conditional growth and size centiles significantly improved the prediction of outcomes compared with size centiles alone (e.g. for 5(th) centile cut-off for any adverse outcome, P = 0.023, log-likelihood test). Using a 5(th) centile threshold, for any adverse outcome, the specificity of 78% (95% CI, 70-84%) using size centile as a predictor was improved to 94% (95% CI, 89-97%) when conditional growth centile was added to the model, whereas the sensitivity was not significantly changed (60% (95% CI, 49-69%) vs 39% (95% CI, 30-50%)). CONCLUSIONS: Size centiles and conditional growth centiles contribute independently to the prediction of adverse perinatal outcome, and their combination further improves the prediction model. The results support an increased use of conditional growth centiles in the monitoring of fetuses at risk. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Foetal Doppler abnormality is associated with increased risk of sepsis and necrotising enterocolitis in preterm infants.

AIM: Fetoplacental Doppler abnormalities have been associated with increased neonatal mortality and morbidity. This study evaluated the associations between prenatal Doppler assessments and neonatal mortality and morbidity in premature infants born small for gestational age or after pre-eclampsia. METHODS: This was a population-based study of infants born alive at 22(0) -33(6) weeks of gestation, a birthweight <10th percentile for gestational age and/or maternal pre-eclampsia. Doppler assessments of the umbilical artery, middle cerebral artery and ductus venosus were evaluated in 127, 125 and 95 cases, respectively. Circulatory compromise was defined as absent or reversed end-diastolic velocity in the umbilical artery (AREDF), middle cerebral artery pulsatility index <2.5 percentile for gestational age and ductus venosus pulsatility index for veins >97.5 percentile. RESULTS: AREDF was present in 28% of the infants. This was associated with increased frequencies of neonatal sepsis and necrotising enterocolitis after adjusting for gestational age. Abnormal ductus venosus pulsatility index for veins was associated with increased risk of neonatal sepsis, but only in combination with AREDF. These associations were only present when gestational age was <28 weeks. CONCLUSION: AREDF was associated with increased neonatal morbidity in premature infants born small for gestational age or after pre-eclampsia.

Development of the maternal anal canal during pregnancy and the postpartum period: a longitudinal and functional ultrasound study.

OBJECTIVES: Normal anatomical and physiological development of the maternal anal canal during and after pregnancy has been documented scarcely. We aimed to study the position and volume of the anal canal, during and after pregnancy, in women without previous delivery. METHODS: This was a longitudinal study in which transvaginal three-dimensional ultrasound was used to measure anatomical structures in the anal canal during rest and squeeze in 23 nulliparous women. The total anal canal volume (ACV), anorectal curvature (ARC), anovaginal angle (AVA) and anal canal length were determined at 18, 28 and 36 weeks of pregnancy and at 3 months postpartum. RESULTS: Total ACV at rest increased from a mean of 10.17 cm(3) at 18 weeks to 12.37 cm(3) and 12.21 cm(3) at 28 and 36 weeks, respectively (P = 0.001 and P = 0.010 vs. first measurement). For anal canal length, the corresponding mean measurements were 3.91 cm, 4.07 cm (P = 0.13) and 4.21 cm (P = 0.017). Postpartum, the mean total ACV was 10.86 cm(3) and length was 3.90 cm (P = 0.10 and P = 0.70 vs. first measurement). No significant changes were observed in ARC and AVA during or after pregnancy. Compared to at-rest status, the anal length significantly increased on voluntary squeeze (P = 0.007, 0.007, 0.022 and 0.004 at the four time points), while no differences in total ACV were observed. In mid-pregnancy AVA significantly increased during squeeze (P = 0.006 and 0.002 at weeks 18 and 28, respectively). CONCLUSION: Anal canal length and total ACV increase during pregnancy in women without previous delivery. Voluntary squeezing elongates the anal canal and increases the angle formed with respect to the direction of the vagina. During postpartum involution, the characteristics of the anal canal revert to those observed at 18 weeks of pregnancy.

Ultrasound safety in early pregnancy: reduced energy setting does not compromise obstetric Doppler measurements.

OBJECTIVES: We hypothesized that first-trimester Doppler ultrasonography can be carried out at lower output energies than the currently advocated limits without compromising clinically important information. METHODS: We recruited 42 pregnant women for an ultrasound examination at 12 weeks' gestation. Twenty-one women were examined with a transvaginal transducer, the rest with a transabdominal transducer. We used pulsed Doppler to measure pulsatility index (PI) and peak systolic velocity (PSV) in five clinically relevant fetal and maternal blood vessels. The energy indicator thermal index for bone (TIb) was set at 1.0, 0.5 and 0.1. Each measurement was repeated three times. A mixed linear regression model accounting for correlation between measurements was used to assess the effect of different TIb levels and transducers. RESULTS: We were able to visualize the vessels by color Doppler and measure PI and PSV in all vessels at all energy levels in all the participants with the exception of the ductus venosus in two participants, yielding 1872 recordings for statistical analysis. A reduction in TIb from 1.0 to 0.5 and 0.1 had no effect on the PI or PSV values, nor was there any trend towards higher parameter variance with decreasing TIb. There was no difference between measured values of PI and PSV between the transducers, but the transabdominal technique was associated with a greater parameter variance. CONCLUSION: Reliable first-trimester Doppler data can be obtained with output energy reduced to a TIb of 0.5 or 0.1.

Blood flow in the foetal superior vena cava and the effect of foetal breathing movements.

OBJECTIVES: The superior vena cava (SVC) drains venous blood from the upper foetal body, mainly the head. Data on the human foetus is scarce. Here we present reference values for the blood flow during the second half of pregnancy, and test the hypothesis that foetal breathing movements (FBM) enhance this flow. METHODS: Based on a power calculation, 110 women with low-risk singleton pregnancies were recruited to a longitudinal study that included three sets of observations during the second half of pregnancy. Ultrasound was used to determine inner diameter, peak systolic blood velocity and time-average maximum velocities in the SVC during rest and respiratory activity. RESULTS: During the second half of pregnancy, SVC blood flow increased from 57.8 mL/min (95% CI 51.7-64.3) to 221.5 (204.5-239.3). Based on 558 sets of observations obtained during foetal rest and FBM, we found an overall increase in diameter from 0.41 cm (0.40-0.42) to 0.46 (0.44-0.48), peak systolic velocity from 35.9 cm/s (34.9-37.0) to 62.2 (59.1-65.5), and time-averaged maximum velocity from 20.3 cm/s (19.7-20.8) to 27.3 (26.1-28.6). This resulted in an overall 90% increase in mean SVC blood flow, from 108.1 mL/min (98.8-117.9) at rest to 205.9 (183.2-230.5) during FBM. CONCLUSION: The blood flow in the SVC increases during the second half of pregnancy and is substantially augmented during FBM. Since high-amplitude FBM additionally reduces flow in the inferior vena cava, the net effect is a prioritised venous drainage from the foetal head enhancing the washout of CO(2) in that area, which also contains the chemoreceptors.

IFPA Meeting 2011 workshop report II: Angiogenic signaling and regulation of fetal endothelial function; placental and fetal circulation and growth; spiral artery remodeling.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, three of which are summarized in this report. These workshops related to vascular systems and circulation in the mother, placenta and fetus, and were divided in to 1) angiogenic signaling and regulation of fetal endothelial function; 2) placental and fetal circulation and growth; 3) spiral artery remodeling.

Fetal hemodynamic development in macrosomic growth.

OBJECTIVE: To determine the venous and arterial hemodynamics underlying macrosomic fetal growth. METHODS: Fifty-eight healthy women who previously had given birth to a large neonate were included in a prospective longitudinal study. Of these, 29 gave birth to neonates with birth weight ≥ 90th percentile and were included in the statistical analysis. Umbilical vein blood flow and Doppler measurements of the ductus venosus, left portal vein and the hepatic, splenic, superior mesenteric, cerebral and umbilical arteries were repeated at 3-5 examinations during the second half of pregnancy and compared with the corresponding reference values. Ultrasound biometry was used to estimate fetal weight. RESULTS: Umbilical blood flow increased faster in macrosomic fetuses, showed less blunting near term and was also significantly higher when normalized for estimated fetal weight (P < 0.0001). The portocaval perfusion pressure of the liver (expressed by the ductus venosus systolic blood velocity) and the left portal vein blood velocity (expressing umbilical venous distribution to the right liver lobe) were significantly higher. Systolic velocity was higher in the splenic, superior mesenteric, cerebral and umbilical arteries, while the pulsatility index was unaltered in the cerebral, hepatic, splenic and mesenteric arteries, but lower in the umbilical artery. CONCLUSIONS: There is an augmented umbilical flow in macrosomic fetuses particularly near term, also when normalized for estimated fetal weight, providing increased liver perfusion, including the right liver lobe. Signs of increased vascular cross section and flow are also seen on the arterial side but not expressed in the pulsatility index of organs with prominent auto-regulation (i.e., brain, liver, spleen and gut).

Hemodynamics of fetal breathing movements: the inferior vena cava.

OBJECTIVE: Based on the hypothesis that fetal breathing movements (FBM) enhance sections of the circulation to meet the needs of gas transport, we studied the effects of FBM on the fetal inferior vena cava (IVC), which transports blood with the lowest oxygen saturation in the fetal body. METHODS: One-hundred and ten women with low-risk singleton pregnancies were included in a longitudinal study during the second half of pregnancy. Inner diameter, peak systolic velocity and time-averaged maximum blood velocity were measured in the IVC below the ductus venosus outlet during rest and FBM. Volume flow and pressure gradient were estimated in 55 observations of forced inspiratory movements at 36 weeks of gestation. The results are presented as mean and 95% CI of the mean. RESULTS: Based on 585 observations obtained during fetal rest and FBM, we found no difference in diameter, 0.42 (95% CI, 0.41-0.43) cm vs. 0.41 (95% CI, 0.39-0.42) cm, respectively, apart from during high-amplitude inspiratory movement, when the diameter was 0.15 (95% CI, 0.13-0.17) cm. The peak systolic velocity was different during rest and FBM, 34.0 (95% CI, 32.7-35.3) cm/s vs. 81.5 (95% CI, 76.2-87.5) cm/s, respectively, and correspondingly for time-averaged maximum velocity, 19.7 (95% CI, 18.9-20.5) cm/s vs. 37.2 (95% CI, 34.9-39.9) cm/s, respectively. Forced inspiratory movements at 36 weeks significantly reduced flow in the IVC compared with rest, 63.6 (95% CI, 44.4-88.1) mL/min vs. 186.0 (95% CI, 142.8-238.1) mL/min, respectively. The pressure gradient increased 14-fold during forced inspiration, from 0.64 to 8.76 mmHg. CONCLUSIONS: High-amplitude fetal inspiration substantially constricts the abdominal IVC and creates a negative pressure in the chest. The IVC constriction withholds abdominal blood, thus temporarily giving way to other flows.

Transvaginal three-dimensional ultrasound: a method of studying anal anatomy and function.

OBJECTIVES: To explore the possibility of using transvaginal 3D ultrasound as a method of assessing the compartments of the anal canal during rest, to determine the effect of squeeze, and to compare these findings with those obtained using the endoanal technique in the same women. METHODS: Transvaginal 3D ultrasound was used in a cross-sectional study measuring the anal mucosa and sphincters during rest and squeeze in 20 nulligravida women, comparing the results with those of endoanal measurements. Measurements were also performed of the anal mucosa, anorectal curvature (ARC), and anovaginal angle (AVA) and distance (AVD). RESULTS: Volume measurements of the anal mucosa were only possible using transvaginal ultrasound. The mean volume of the anal canal using the transvaginal technique was 7.93 (SD 2.26) and 7.34 (1.54) cm(3) during rest and squeeze, respectively (P = 0.082). The ARC became more acute (3.46 vs. 4.12°/mm, P = 0.031) during squeeze and AVA increased (31.7° vs. 35.8°, P = 0.010). The volume of the anal mucosa (3.12 cm(3)) did not change (P = 0.193), but was distorted during squeeze at the level of the puborectalis sling (P < 0.001 for upper cross-section and diameter). The anal canal was 1 cm longer (P < 0.001), the IAS volume larger (2.97 and 2.08 cm(3), P = 0.003), and the EAS volume smaller (1.85 and 3.96 cm(3), P < 0.001) using the 3D transvaginal technique compared with the endoanal measurements at rest, with similar differences observed on squeeze. CONCLUSION: In contrast to the endoanal method, transvaginal 3D ultrasound provides a complete assessment of the anal canal, including the mucosa. This method seems suitable for functional studies such as in the present one, which shows that voluntary squeeze increases the angulation of the anal canal and distorts the bowel cross-section at the level of the puborectal muscle.

Preterm elective caesarean section and early enteral feeding in gastroschisis.

AIMS: To evaluate the effect of elective caesarean section (CS) before term and early enteral nutrition on length of parenteral nutrition and hospital stay in infants with gastroschisis. METHODS: Retrospective review of all infants with gastroschisis treated in a regional level III hospital from 1993 to 2008. During 1993-97, there was no established standard for management of pregnancy or delivery while a protocol on close foetal monitoring and early elective CS was adhered to for 1998-2008. Introduction of human milk on the first day after complete closure of the abdominal wall and rapid increase was the policy during the whole period. RESULTS: With early elective CS, no foetal deaths occurred after 28-week gestational age (GA). Ten infants were born during the first period and 20 during the second period at a median GA (range) of 36.5 (34-40) and 35 (34-37) weeks (p = 0.013). Seven and 20, respectively, were born by CS. Median (range) days before full enteral feeds and hospital stay were 11.5 (7-39) and 13.0 (7-46) (p = 0.85), and 17.5 (12-36) and 22.5 (13-195) (p = 0.67), respectively. One child died of volvulus after discharge. CONCLUSION: Close surveillance of pregnancy, elective preterm caesarean section, early surgery and active approach to primary closure and early enteral feeds appears to be a safe and effective line of management in gastroschisis.