Life-limiting fetal conditions: Are Australian student midwives prepared? A mixed-methods survey

Aim: To document current teaching methods, curriculum, and perceived educational preparation related to the teaching of life-limiting fetal conditions, termination, and perinatal palliative care to Australian student midwives. Background: Australian women receiving a diagnosis of a life-limiting fetal condition are generally offered a choice between termination of pregnancy and perinatal palliative care. Midwives are often involved with caring for these women. What Australian student midwives are being taught about life-limiting fetal conditions, termination of pregnancy, and perinatal palliative care during their entry-to-practice program is unknown. Design: This study utilised a mixed-methods descriptive approach for data collection and analysis. Methods: Academic Leads of all Australian entry-to-practice midwifery programs received a questionnaire exploring topics taught, teaching time, teacher role, and perceived effectiveness of student preparation. Data was analysed statistically and thematically. Results: Twelve of 24 Academic Leads responded (50%); only five stated their programs taught all three areas. More respondents taught about termination of pregnancy (10/12) than perinatal palliative care (7/12). On average 5.8 ( ± 2.8) total hours was spent teaching about life-limiting fetal conditions, termination of pregnancy, and perinatal palliative care during the entire midwifery program, with a range of 1 – 10 h. The free-text data identified three central themes: lack of value within the curriculum; disconnect between the university and the placement hospital; and preparation for practice. Most (10/12) Academic Leads did not believe student midwives are prepared to care for affected families. Conclusions: Entry-to-practice midwifery programs vary considerably in their education surrounding life-limiting fetal conditions, however teaching hours overall were low and most Academic leads did not feel (or know if) their students were adequately prepared. Further research is required to determine if early career midwives find their university education in life-limiting fetal conditions adequate preparation for practice, and to then remediate identified deficiencies

Fetal myocardial performance index in assessment and management of small-for-gestational-age fetus: A cohort and nested case–control study

Objective: To assess the clinical utility of the fetal myocardial performance index (MPI) in assessment and management of the small-for-gestational-age (SGA) fetus/growth-restricted fetus (FGR). Methods: This was a prospective cohort study in metropolitan Australia of patients referred in the period June 2012 to March 2015 to fetal medicine services at 24–38 weeks' gestation for suspected singleton SGA/FGR (estimated fetal weight (EFW) < 10th centile with or without abnormal umbilical artery (UA) Doppler) pregnancy. Patients had MPI assessed in addition to routine measures, and were followed through to birth. We compared MPI values against those of a local reference population and gestational age-matched controls, and assessed the correlation with perinatal outcome and other Doppler measures. Results: Fifty-two cases were included, 38 diagnosed < 32 weeks and 14 diagnosed ≥ 32 weeks. None demonstrated significantly elevated left, right or delta MPI compared with the reference population or with gestational age-matched controls at the time of first MPI evaluation. There were no consistent longitudinal patterns in MPI that would suggest its clinical utility. The mean ± SD gestational age at delivery was 34.6 ± 3.8 weeks and birth weight was 1.7 ± 0.6 kg, and the median neonatal hospital admission time was 27 days, confirming a pathological cohort. There were no significant correlations between left, right or delta-MPI and perinatal outcome, although there were significant correlations between UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler and perinatal outcome (birth weight, gestational age at birth and length of neonatal hospital stay). Exploratory subgroup comparisons (EFW < 3rd vs 3rd–10th centile; early- vs late-onset; abnormal vs normal UA Doppler) found only minor differences in MPI, reaching statistical, but not clinical, significance, only in the EFW < 3rd vs 3rd–10th centile comparison. Conclusions: MPI did not demonstrate clinical utility in either triage or longitudinal follow-up of an SGA/FGR cohort presenting to fetal medicine services. Given that prior research suggesting its utility originates from single-center cohorts, while multicenter, large cohorts have suggested little utility or no additional utility if routine UA/MCA/DV Doppler is performed, publication bias may have affected previous reports. It seems unlikely that MPI has clinical utility in assessment and management of SGA/FGR fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd

The aortic isthmus: A significant yet underexplored watershed of the fetal circulation

The aortic isthmus (AoI) is a unique fetal watershed with a waveform reflecting its complex haemodynamic physiology. The systolic component represents left and right ventricular systolic ejection, and the diastolic component represents comparative downstream vascular impedance between the brachiocephalic and subdiaphragmatic fetal circulations. Several indices have been devised to quantify different components of the waveform, including the pulsatility index, resistance index, isthmic flow index, and recently the isthmic systolic index. There have been promising preliminary studies applying these indices to both cardiac (congenital) and extracardiac pathologies, including intrauterine growth restriction and twin-twin transfusion syndrome. However, the waveform's multifactorial origin has proven to be challenging, and the difficulty in separating various components of the waveform could explain that AoI evaluation does not have a clear clinical utility. Further research is underway to realise the full potential of this vessel in fetal cardiac and haemodynamically compromised pathological conditions. In this review article we outline the physiological origin of this Doppler waveform, describe in detail the various published indices, summarise the published literature to date, and finally outline potential future research and hopefully clinical applications. © 2016 S. Karger AG, Basel. Copyright: All rights reserved

Is there a measurable difference between the left and right modified myocardial performance indices, and does this change to reflect unilateral myocardial dysfunction in pathology?

Introduction: Fetal cardiac dysfunction may manifest itself unilaterally as right and left ventricles differing in design, function and load, measurable as differing in myocardial performance indices (MPIs). We wished to define this difference ('delta-MPI' or DMPI), present its normal range and pilot its use in pathological pregnancy. Material and Methods: Prospective cross-sectional study of 324 normal singleton fetuses (16-38 weeks of gestation). Left and right modified MPI (LMPI and RMPI) were performed during a single examination using the 'peak' valve click technique. Thirty-seven pathological singleton and monochorionic diamniotic twin pregnancies were compared as pilot data. Results: Modified MPIs (mean ± SD) were 0.45 ± 0.06 (LMPI) and 0.47 ± 0.09 (RMPI), being similar at 18 weeks' gestation with DMPI increasing slightly throughout pregnancy (0.02 ± 0.08). Both singleton intrauterine growth restriction (IUGR) and recipient twin-twin transfusion syndrome (TTTS) showed significantly elevated RMPI, LMPI and DMPI, most pronounced for DMPI (450 and 500% increase, respectively; p < 0.01). DMPI acquisition rates were 83.3% normal and 87.0% pathological. Discussion: We demonstrate for the first time differing intrafetal LMPI and RMPI in a large gestational cohort, with this difference increasing with gestational age. Pilot data confirm the potential for DMPI as a tool to assess unilateral myocardial function in singleton IUGR and recipient twins in TTTS, and further studies are under way to evaluate its clinical utility. © 2015 S. Karger AG, Basel

Use of the foetal myocardial performance index in monochorionic, diamniotic twin pregnancy: A prospective cohort and nested case-control study

Aims: Assess clinical utility of the foetal Myocardial Performance Index (MPI) in evaluation and management of monochorionic, diamniotic twin (MCDA) pregnancies. Methods: Prospective cohort of (a) initially uncomplicated MCDA (b) Complicated MCDA, including twin–twin transfusion syndrome (TTTS), selective intrauterine growth restriction (sIUGR), and liquor and/or growth discordance (L/GD) not meeting TTTS or sIUGR criteria. TTTS and sIUGR were case-control matched. Routine Dopplers and MPI were taken and correlated to diagnosis and final outcome. Results: Twenty-six always uncomplicated pairs, 51 always complicated pairs, and seven uncomplicated to pathological pairs were included. TTTS recipient (n = 25) left and right MPI and intertwin difference (ITD) were significantly elevated, however, were already elevated in Stage I (n = 10), and did not predict progression or pregnancy outcome. sIUGR MPI (n = 11) did not differ significantly from control. Of 15-L/GD pairs, two that progressed to TTTS had significantly higher left and right MPI values in the future recipient (0.61 and 0.72) versus future sIUGR larger twins (0.48 and 0.51) or stable L/GD (0.47 and 0.52): p <.01 for all comparisons. Conclusions: In this cohort, MPI did not add substantial diagnostic/prognostic information to current routine evaluation in established TTTS or sIUGR though potentially differentiated L/GD cases progressing to TTTS. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

Use of the myocardial performance index in decreased fetal movement assessment: A case-control study

Objectives: To determine whether there are any fetal cardiac function changes, as measured by the myocardial performance index (MPI), in pregnancies complicated by decreased fetal movement (DFM). Methods: We performed a prospective cross-sectional case-control study of 50 DFM and 50 uncomplicated third-trimester pregnancies matched within 2 gestational weeks. Routine ultrasound growth and well-being parameters as well as MPI were measured. Average MPI measurements and its component values were compared between the DFM and the control group, as were demographics, other ultrasound data, and perinatal outcomes. Results: Average left MPI (LMPI) and right MPI (RMPI) was similar between groups (LMPI: 0.54 ± 0.08 [DFM], 0.53 ± 0.08 [controls], p = 0.76; RMPI: 0.60 ± 0.12 (DFM), 0.59 ± 0.11 [controls], p = 0.79). However, subgroup analysis of DFM fetuses with (n = 20) or without (n = 30) any adverse perinatal outcome demonstrated modestly higher average RMPI and LMPI in the adverse perinatal outcome group (RMPI: 0.64 ± 0.08 vs. 0.57 ± 0.13, p = 0.02; LMPI: 0.56 ± 0.07 vs. 0.52 ± 0.07, p = 0.052). Conclusion: The MPI did not demonstrate clinically usable differences between the overall DFM population and controls. However, higher LMPI and RMPI values in the exploratory subgroup of DFM fetuses with adverse perinatal outcomes may warrant further exploration of the MPI in DFM. © 2017 S. Karger AG, Basel

Applying spatial-temporal image correlation to the fetal kidney: Repeatability of 3D segmentation and volumetric impedance indices

Introduction: Spatiotemporal image correlation (STIC) can evaluate fetal renal impedance using four‐dimensional volumetric indices. We assessed repeatability of three‐dimensional kidney segmentation and the repeatability of the resultant indices. Methods: In each of 57 healthy pregnant women, three renal artery pulsed‐wave Doppler (PWD) traces and three STIC volumes were acquired from the same fetal kidney and segmented by two observers. Vascularisation‐flow index (VFI) and fractional moving blood volume (FMBV) were calculated for every STIC frame and used to determine the volumetric pulsatility index (vPI), volumetric resistance index (vRI) and volumetric systolic/diastolic ratio (vS/D). Segmentation performance was assessed using Dice similarity coefficients (DSCs), Hausdorff distances, coefficient of variation (CoV) and the intraclass correlation coefficient (ICC). Intra/Inter volumetric index repeatability was assessed using ICCs. Results: Forty‐eight cases (84%) provided full data. Mean intra‐ and interobserver DSCs were 0.90 and 0.81. Mean intra‐ and interobserver Hausdorff distances were 3.88 mm and 5.27 mm. Average kidney volumes for observers 1 and 2 were 9.88 mL and 8.54 mL (mean difference 16.1%). Mean intra‐observer volumetric CoVs were 5.3% and 8.1%. Intra‐ and interobserver ICCs for kidney volume (same STIC volume) were 0.97 and 0.85. When assessing volume variation between STIC volumes, intra‐observer ICC was 0.97. ICCs were 0.77–0.81 for VFI‐derived volumetric indices and 0.61–0.62 for FMBV‐derived indices; ICCs for all PWD indices were between 0.58 and 0.59. Conclusions: Periodical variation in vascularity was demonstrated in the fetal kidney, and three‐dimensional segmentation was highly repeatable. Derived volumetric impedance indices show moderate variability but outperform corresponding two‐dimensional PWD indices in terms of reproducibility

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects

Regional association plots of novel loci implicated for pulmonary function.

<p>Three novel loci contained SNPs associated with FEV₁/FVC or FEV₁ at the standard genome-wide significance threshold (<i>P</i>&lt;5×10⁻⁸) in joint meta-analyses of SNP and SNP-by-smoking interaction. SNPs are shown within 500 kb of the most significant SNPs on chromosomes (A) 2q36.3 associated with FEV₁/FVC, (B) 6p21.32 associated with FEV₁/FVC, and (C) 17q24.3 associated with FEV₁. Pairwise r² values were based on the HapMap CEU population, and progressively darker shades of red indicate higher r² values. Estimated recombination rates from HapMap are shown as background lines.</p

Genome-wide significant SNPs from the joint meta-analysis (JMA) of SNP and SNP-by-smoking (ever-smoking or pack-years) interaction in relation to pulmonary function.

<p>After removing SNPs with known associations with FEV₁/FVC or FEV₁, three novel loci with genome-wide significant SNPs (standard threshold of <i>P</i>&lt;5×10⁻⁸) remained from the JMA testing in the current study. The most significant SNP from each locus is shown.</p><p>FEV₁, forced expiratory volume in the first second; FVC, forced vital capacity; JMA, joint meta-analysis; SE, standard error ; SNP, single nucleotide polymorphism.</p>1<p>Weighted average coded allele frequency across the 19 studies. The coded allele refers to the effect allele.</p>2<p>β_SNP, per allele change in the FEV₁/FVC standardized residual due to the SNP main association.</p>3<p>β_INT, per allele change in the FEV₁/FVC standardized residual due to the interaction between SNP and smoking.</p