George Bugg

Maternal Smoking during Pregnancy and Fetal Organ Growth: A Magnetic Resonance Imaging Study

Objective To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta. Design A case-control study, with operators performing the image analysis blinded. Setting Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom. Participants A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy. Methods Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA). Main outcome measures Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes. Results Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume. Conclusion Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.

Methodological considerations for the correct application of quantitative three‐dimensional power Doppler angiography

We were interested to read the paper by Guiot et al. entitled ‘Is three-dimensional power Doppler ultrasound useful in the assessment of placental perfusion in normal and growth-restricted pregnancies?’ in the February edition of the White Journal1. The authors used ‘3D power Doppler ultrasound indices [for] the assessment of placental perfusion’ and studied the relationship of these indices to ‘gestational age (GA), placental position, and umbilical artery Doppler FVW [flow velocity waveform] patterns in normal and IUGR [intrauterine growthrestricted] pregnancies’. We have some methodological queries and would also like to comment on several statements made about the three-dimensional (3D) vascular indices and their purported relationship to true blood flow characteristics. The authors make many assumptions and several factually incorrect statements about quantitative threedimensional power Doppler angiography. They state that ‘even very small blood movements within the investigated volume can be detected by a combination of power and color Doppler sonography, and their impact in the given volume, representing the overall perfusion, is evaluated by indices computed by built-in algorithms’. Movement of blood, or any fluid for that matter, does not result in a Doppler signal. It is the erythocytes within the blood or scatterers within a fluid medium that are responsible for the Doppler shift that is represented by a color map or waveform. Blood flow and perfusion are distinct entities with differing definitions. Flow is the amount of blood passing per unit time (usually per minute) while perfusion is defined as the amount of flow in a volume of tissue per unit time and is usually measured as milliliters per minute per gram of tissue, although, since the density of most tissues is near to 1 g/mL, units of milliliters per minute per milliliter are often substituted2. The threedimensional vascular indices reported in the study are not a function of time and their quantification cannot, therefore, equate to perfusion or flow. Whilst analysis of Doppler waveforms takes into consideration the cardiac cycle it does not account for volume flow as it is a twodimensional assessment and is not a measure of perfusion either. The authors’ descriptions of the 3D vascular indices are also incorrect and therefore misleading, as they refer to the vascularization index (VI) as being representative of ‘overall perfusion’ and say that the flow index (FI) ‘evaluates the overall blood flow in the sample volume’, but both perfusion and blood flow are time-dependent parameters. The FI represents the average color value of all color voxels, so does not even remotely consider the overall blood flow. The vascularization flow index (VFI) is described as being a measure of ‘blood velocity in the same sample volume’, but power Doppler provides no velocity information and so this statement is illogical. Current opinions are that these indices are representative of the percentage of power Doppler data within the defined volume of interest (VI), the mean signal intensity of the power Doppler information (FI), and a combination of both factors, derived through their multiplication (VFI), and it has been suggested that they are representative of vascularity and flow intensity3,4. One of the aims of the study was to investigate the effect of attenuation on the 3D vascular indices, as the authors quite rightly state that ‘different placental positions require different insonation depths (and) measurements could also be dependent on this parameter’. This is not a matter for debate; power Doppler is depth-dependent and subject to attenuation. This does not require assessment as it has been shown in both in-vitro5 and in-vivo6 studies, but further research is required to develop methodologies to account for this confounding factor, which currently limits all studies other than certain gynecological ones in which the organ of interest is in close proximity to the transducer. The only way to assess vascularity and flow within different subjects is to standardize measurements by calculating an index known as the ‘fractional moving blood volume’ (FMBV), which has been shown to correlate well with true tissue perfusion7,8. Of the 3D vascular indices, the VFI is most similar to the FMBV because it shows the moving blood volume. However, it is not truly fractional as it is not standardized. The concept of comparing different sites within the same placenta is good and, to some degree, addresses the problem of attenuation, as the patient self-standardizes. However, the data presented are the overall median values for the placentae from 30 growth-restricted fetuses and 15 controls. These absolute values are meaningless without information on placental position, as the authors maintained their Doppler settings in all cases. The more posterior placentae will have had lower vascular indices as a function of increasing depth and if these were not evenly distributed amongst the two groups they should not have been compared as separate entities9. Indeed, after accounting for the distribution of the data, the mean sampling depth should have been stated and this should have been equal between the groups before any further comparisons were made. Insufficient details were provided about the Doppler settings, which should have included the power, gain, rise and persistence and reject values. One reason why the ‘intervillous flow velocity [was] below the Doppler

Evaluating the Intra- and Interobserver Reliability of Three-Dimensional Ultrasound and Power Doppler Angiography (3D-PDA) for Assessment of Placental Volume and Vascularity in the Second Trimester of Pregnancy

Three-dimensional (3-D) power Doppler angiography (3-D-PDA) allows visualisation of Doppler signals within the placenta and their quantification is possible by the generation of vascular indices by the 4-D View software programme. This study aimed to investigate intra- and interobserver reproducibility of 3-D-PDA analysis of stored datasets at varying gestations with the ultimate goal being to develop a tool for predicting placental dysfunction. Women with an uncomplicated, viable singleton pregnancy were scanned at 12, 16 or 20 weeks gestational age groups. 3-D-PDA datasets acquired of the whole placenta were analysed using the VOCAL software processing tool. Each volume was analysed by three observers twice in the A plane. Intra- and interobserver reliability was assessed by intraclass correlation coefficients (ICCs) and Bland Altman plots. At each gestational age group, 20 low risk women were scanned resulting in 60 datasets in total. The ICC demonstrated a high level of measurement reliability at each gestation with intraobserver values >0.90 and interobserver values of >0.6 for the vascular indices. Bland Altman plots also showed high levels of agreement. Systematic bias was seen at 20 weeks in the vascular indices obtained by different observers. This study demonstrates that 3-D-PDA data can be measured reliably by different observers from stored datasets up to 18 weeks gestation. Measurements become less reliable as gestation advances with bias between observers evident at 20 weeks.

Measurement of fetal fat in utero in normal and diabetic pregnancies using magnetic resonance imaging

To assess the reliability of magnetic resonance imaging (MRI) to measure fetal fat volume in utero, and to study fetal growth in women with and without diabetes in view of the increased prevalence of macrosomia in the former.

Induction of labour versus expectant management for nulliparous women over 35 years of age: a multi-centre prospective, randomised controlled trial

BackgroundBritish women are increasingly delaying childbirth. The proportion giving birth over the age of 35 rose from 12% in 1996 to 20% in 2006. Women over this age are at a higher risk of perinatal death, and antepartum stillbirth accounts for 61% of all such deaths. Women over 40 years old have a similar stillbirth risk at 39 weeks as women who are between 25 and 29 years old have at 41 weeks.Many obstetricians respond to this by suggesting labour induction at term to forestall some of the risk. In a national survey of obstetricians 37% already induce women aged 40–44 years. A substantial minority of parents support such a policy, but others do not on the grounds that it might increase the risk of Caesarean section. However trials of induction in other high-risk scenarios have not shown any increase in Caesarean sections, rather the reverse. If induction for women over 35 did not increase Caesareans, or even reduced them, it would plausibly improve perinatal outcome and be an acceptable intervention. We therefore plan to perform a trial to test the effect of such an induction policy on Caesarean section rates.This trial is funded by the NHS Research for Patient Benefit (RfPB) Programme.DesignThe 35/39 trial is a multi-centre, prospective, randomised controlled trial. It is being run in twenty UK centres and we aim to recruit 630 nulliparous women (315 per group) aged over 35 years of age, over two years. Women will be randomly allocated to one of two groups:Induction of labour between 390/7 and 396/7weeks gestation.Expectant management i.e. awaiting spontaneous onset of labour unless a situation develops necessitating either induction of labour or Caesarean Section.The primary purpose of this trial is to establish what effect a policy of induction of labour at 39 weeks for nulliparous women of advanced maternal age has on the rate of Caesarean section deliveries. The secondary aim is to act as a pilot study for a trial to answer the question, does induction of labour in this group of women improve perinatal outcomes? Randomisation will occur at 360/7 – 396/7 weeks gestation via a computerised randomisation programme at the Clinical Trials Unit, University of Nottingham. There will be no blinding to treatment allocation.DiscussionThe 35/39 trial is powered to detect an effect of induction of labour on the risk of caesarean section, it is underpowered to determine whether it improves perinatal outcome. The current study will also act as a pilot for a larger study to address this question.Trial registrationISRCTN11517275

Antenatal magnetic resonance imaging versus ultrasound for predicting neonatal macrosomia: a systematic review and meta‐analysis

Fetal macrosomia is associated with an increased risk of adverse maternal and neonatal outcomes.

Evaluation of offline analysis of archived three-dimensional volume datasets in the diagnosis of fetal brain abnormalities.

To retrospectively evaluate the reliability of offline manipulation of archived three‐dimensional (3D) ultrasound volumes in the assessment of the normal fetal brain and the diagnosis of fetal brain abnormalities.

Evaluation of the Intraobserver and Interobserver Reliability of Data Acquisition for Three-Dimensional Power Doppler Angiography of the Whole Placenta at 12 Weeks Gestation

The aim of this study was to investigate the intra- and interobserver reproducibility of three-dimensional (3-D) power Doppler (3-DPD) data acquisition from women at 12 weeks gestation, which were then subsequently measured by a single observer. Women with an uncomplicated, viable singleton pregnancy were scanned between 12 + 0 and 13 + 6 weeks gestations with a Voluson 730 Expert. 3-DPD data were acquired of the whole placenta by two observers: the first observer captured two datasets and the second a single dataset. Each dataset was analysed using VOCAL in the A plane with 9 degree rotation steps. Eighteen low risk women were recruited with a total of 54 datasets analysed. The intraclass correlation coefficient (ICC) was highest for the vascular indices vascularisation index (VI) and vascularisation-flow index (VFI), greater than 0.75. ICC for flow index (FI) showed moderate correlation at 0.47 to 0.65. Bland Altman plots showed the most precise vascular index to be the FI (-15% to 10% for interobserver agreement). There was no bias between datasets. Prospective studies are now required to identify if this analysis tool and method is sensitive enough to recognise patients with early-onset placental dysfunction.

Induction of labour at term for women over 35 years old: a survey of the views of women and obstetricians

OBJECTIVES To determine the views of UK women and obstetricians relating to induction of labour at term for women over 35 years of age. STUDY DESIGN Cross-sectional web-based survey sent to members of the British Maternal and Fetal Medicine Society (BMFMS) and pregnant or recently delivered members of a large social network site for parents (www.mumsnet.com). One hundred and twenty-eight consultant obstetrician members of BMFMS and 663 pregnant or recently delivered women responded. RESULTS Two hundred and eighty-eight women (43%) would consider induction of labour for maternal age alone, and 192 women (29%) would consider participating in a randomised trial of induction of labour at term versus expectant management in a future pregnancy. Three percent (n=4) of consultant obstetricians offer induction of labour at term to women at 35-39 years of age, 37% (n=47) to women at 40-44 years of age and 55% (n=70) to those over 45 years. Sixty-one consultants (48%) would participate in a trial to test the effect of a policy of induction for nulliparous women over 35 years old. CONCLUSIONS The policy of offering induction of labour at term for advanced maternal age is widespread and a significant percentage of women consider it to be a valid indication.

Changes in myometrial ‘perfusion’ during normal labor as visualized by three‐dimensional power Doppler angiography

Myometrial contractions are one of the most important aspects of effective labor. For cells within the myometrium to work efficiently they need to be well oxygenated and this requires an adequate blood supply. This study used quantitative three‐dimensional (3D) power Doppler angiography to calculate the percentage change in myometrial blood flow during a relaxation–contraction–relaxation cycle of active labor.