Maternal ethnicity and socioeconomic deprivation: influence on adverse pregnancy outcomes.

OBJECTIVES: To evaluate the relative importance of ethnicity and socioeconomic deprivation in determining the likelihood and the percentage of composite adverse pregnancy outcomes (CAPO) and composite of severe adverse pregnancy outcomes (CAPO-S) METHODS: This is a single centre retrospective cohort study conducted in a tertiary maternity unit. Data regarding the ethnicity and socioeconomic deprivation were collected for 13,165 singleton pregnant women routinely screened in the first trimester for preeclampsia using the Fetal Medicine Foundation combined algorithm. RESULTS: The prevalence or risk of CAPO was 16.3% for White women, 29.3% for Black women and 29.3% for South Asian women. However, half of all CAPO cases (51.7%) occurred in White women. There is a strong interaction between ethnicity and socioeconomic deprivation (as measured with indices of multiple deprivation). Both influence the prevalence of CAPO and CAPO-S, with the contribution of ethnicity being strongest. CONCLUSIONS: Black and Asian ethnicity as well as socioeconomic deprivation influence the prevalence of placentally-mediated adverse pregnancy outcomes. Despite this, most adverse pregnancy outcomes occur in White women, who represent the majority of the population and are also affected by socioeconomic deprivation. For these reasons, inclusion of socioeconomic deprivation should be considered in early pregnancy risk assessment for placentally-mediated CAPO. This article is protected by copyright. All rights reserved.

Angiogenic markers and maternal echocardiographic indices in women with hypertensive disorders of pregnancy.

OBJECTIVE: The maternal cardiovascular system of women with hypertensive disorders of pregnancy (HDP) can be impaired, with higher rates of left ventricular (LV) remodeling and diastolic dysfunction compared to those with normotensive pregnancy. The primary objective of this prospective study was to correlate cardiac indices obtained by transthoracic echocardiography (TTE) and circulating angiogenic markers, such as soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). METHODS: In this study, 95 women with a pregnancy complicated by HDP and a group of 25 with an uncomplicated pregnancy at term underwent TTE and blood tests to measure sFlt-1 and PlGF during the peripartum period (before delivery or within a week of giving birth). Spearman's rank correlation was used to derive correlation coefficients between biomarkers and cardiac indices in the HDP and control populations. RESULTS: The HDP group included 61 (64.2%) pre-eclamptic patients and, among them, 42 (68.9%) delivered before 37 weeks' gestation. Twelve women with HDP (12.6%) underwent blood sampling and TTE after delivery, and, as they showed significantly lower levels of angiogenic markers, they were excluded from the analysis. There was a correlation between sFlt-1 and LV mass index (LVMI) (r = 0.246; P = 0.026) and early diastolic mitral inflow velocity (E) and early diastolic mitral annular velocity (e') ratio (r = 0.272; P = 0.014) in the HDP group (n = 83), while in the controls, sFlt-1 showed a correlation with relative wall thickness (r = 0.409; P = 0.043), lateral e' (r = -0.562; P = 0.004) and E/e' ratio (r = 0.417; P = 0.042). PlGF correlated with LVMI (r = -0.238; P = 0.031) in HDP patients and with lateral e' (r = 0.466; P = 0.022) in controls. sFlt-1/PlGF ratio correlated with lateral e' (r = -0.568; P = 0.004) and E/e' ratio (r = 0.428; P = 0.037) in controls and with LVMI (r = 0.252; P = 0.022) and E/e' ratio (r = 0.269; P = 0.014) in HDP. CONCLUSIONS: Although the current data are not able to infer causality, they confirm the intimate relationship between the maternal cardiovascular system and angiogenic markers that are used both to diagnose and indicate the severity of HDP. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Routine first-trimester pre-eclampsia screening and maternal left ventricular geometry.

OBJECTIVE: Pre-eclampsia (PE) is a pregnancy complication associated with premature cardiovascular disease morbidity and mortality (i.e. before 60 years of age or in the first year postpartum). PE is associated with adverse left ventricular (LV) remodeling in the peri- and postpartum periods, an independent risk factor for cardiovascular disease. This study aimed to compare LV geometry by LV mass (LVM) and LVM index (LVMI) between participants with a high vs low screening risk for preterm PE in the first trimester. METHODS: This was a prospective cohort study of singleton pregnancies between 11 + 0 and 13 + 6 weeks' gestation that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, from February 2019 until March 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm. Participants with a screening risk of ≥ 1 in 50 for preterm PE were classified as high risk and those with a screening risk of ≤ 1 in 500 were classified as low risk. All participants underwent two-dimensional and M-mode transthoracic echocardiography. RESULTS: A total of 128 participants in the first trimester of pregnancy were included in the analysis, with 57 (44.5%) participants screened as low risk and 71 (55.5%) participants as high risk for PE. The risk groups did not vary in maternal age and gestational age at assessment. Maternal body surface area and body mass index were significantly higher in the high-risk group (all P < 0.05). The high-risk participants were significantly more likely to be Afro-Caribbean, nulliparous and have a family history of hypertensive disease in pregnancy as well as other cardiovascular disease (all P < 0.05). In addition, mean arterial blood pressure (P < 0.001), mean heart rate (P < 0.001), median LVM (130.06 (interquartile range, 113.62-150.50) g vs 97.44 (81.68-114.16) g; P < 0.001) and mean LVMI (72.87 ± 12.2 g/m2 vs 57.54 ± 12.72 g/m2 ; P < 0.001) were significantly higher in the high-risk group. Consequently, those in the high-risk group were more likely to have abnormal LV geometry (37.1% vs 7.0%; P < 0.001). CONCLUSIONS: Early echocardiographic assessment in participants at high risk of preterm PE may unmask clinically healthy individuals who are at increased risk for future cardiovascular disease. Adverse cardiac remodeling in the first trimester of pregnancy may be an indicator of decreased cardiovascular reserve and subsequent dysfunctional cardiovascular adaptation in pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal prediction of adverse outcome using different charts and definitions of fetal growth restriction.

OBJECTIVE: Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. METHODS: This was a retrospective cohort study of 17 261 singleton non-anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH-21st (IG-21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal-Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5-min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. RESULTS: IG-21, Hadlock and FMF fetal size references classified as growth-restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG-21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA-PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA-PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. CONCLUSIONS: The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA-PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of intrapartum epidural analgesia on rate of emergency delivery for presumed fetal compromise: nationwide registry-based cohort study.

OBJECTIVES: To determine the rate of emergency delivery for presumed fetal compromise after epidural analgesia (EDA) compared with that after alternative analgesia or no analgesia, and to assess whether this rate is increased in pregnancies with reduced placental reserve. METHODS: This was a nationwide registry-based cohort study of 629 951 singleton pregnancies delivered at 36 + 0 to 42 + 0 weeks of gestation that were recorded in the Dutch national birth registry between 2014 and 2018, including 120 426 cases that received EDA, 86 957 that received alternative analgesia and 422 568 that received no analgesia during labor. Pregnancies with congenital anomaly, chromosomal abnormality, fetal demise, planned Cesarean delivery, non-cephalic presentation at delivery and use of multiple forms of analgesia were excluded. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included delivery characteristics and neonatal outcome. Negative binomial regression analysis was stratified by parity and results are presented according to birth-weight centile, after adjusting for confounding. RESULTS: Among women who received EDA, 13.2% underwent emergency delivery for presumed fetal compromise, compared with 4.1% of women who had no analgesia (relative risk (RR), 3.23 (95% CI, 3.16-3.31)) and 7.0% of women who received alternative analgesia (RR, 1.72 (95% CI, 1.67-1.77)). Independent of birth weight, the RR of presumed fetal compromise after EDA vs no analgesia was higher in parous women (adjusted RR (aRR), 2.15 (95% CI, 2.04-2.27)) compared with nulliparous women (RR, 1.88 (95% CI, 1.84-1.94)). Stratified for parity, the effect of EDA was modified significantly by birth-weight centile (interaction P-value, < 0.001 for nulliparous and 0.004 for parous women). The emergency delivery rate following EDA was highest in those with a birth weight < 5th centile (25.2% of nulliparous and 16.6% of parous women), falling with each increasing birth-weight centile category up to the 91st -95th centile (11.8% of nulliparous and 7.2% of parous women). CONCLUSIONS: Intrapartum EDA is associated with a higher risk of emergency delivery for presumed fetal compromise compared with no analgesia and alternative analgesia, after adjusting for relevant confounding. The highest rate of emergency delivery for presumed fetal compromise was observed at the lowest birth-weight centiles. RRs of emergency delivery for presumed fetal compromise after EDA were modestly but consistently modified by birth-weight centile, supporting the hypothesis that the adverse effects of EDA are exacerbated by reduced placental function. While EDA provides effective pain relief during labor, alternative strategies for pain management may be preferable in pregnancies with a high background risk of fetal compromise. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Phase-rectified signal averaging: correlation between two monitors and relationship with short-term variation of fetal heart rate.

OBJECTIVES: To establish the correlation between phase-rectified signal averaging (PRSA) outputs obtained from a novel self-applicable non-invasive fetal electrocardiography (NIFECG) monitor with those from computerized cardiotocography (cCTG). A secondary objective was to evaluate the potential for remote assessment of fetal wellbeing by determining the relationship between PRSA and short-term variation (STV). METHODS: This was a prospective observational study of women with a singleton pregnancy over 28 + 0 weeks' gestation attending a London teaching hospital for cCTG assessment. Participants underwent concurrent cCTG and NIFECG monitoring for up to 60 min. Averaged accelerative (AAC) and decelerative (ADC) capacities and STV were derived by postprocessing and filtration of signals, generating fully (F) and partially (P) filtered results. Linear correlation and accuracy and precision analysis were performed to assess the relationship between PRSA outputs from cCTG and NIFECG, using varying anchor thresholds, and their association with STV. RESULTS: A total of 306 concurrent cCTG and NIFECG traces were collected from 285 women. F-filtered NIFECG PRSA (eAAC/eADC) results were generated from 65% of traces, whereas cCTG PRSA (cAAC/cADC) outputs were generated from all. Strong correlations were observed between cAAC and F-filtered eAAC (r = 0.879, P < 0.001) and between cADC and F-filtered eADC (r = 0.895, P < 0.001). NIFECG anchor detection decreased significantly with increasing signal loss, and NIFECG PRSA indices showed considerable deviation from those of cCTG when derived from traces in which fewer than 100 anchors were detected. Removing anchor filters from NIFECG traces to generate P-filtered PRSA outputs weakened the correlation (AAC: r = 0.505, P < 0.001; ADC: r = 0.560, P < 0.001). Lowering the anchor threshold to 100 increased the yield of eAAC and eADC outputs to approximately 74%, whilst maintaining strong correlation with cAAC (r = 0.839, P < 0.001) and cADC (r = 0.815, P < 0.001), respectively. Both cAAC and cADC showed a very strong linear relationship with cCTG STV (r = 0.928, P < 0.001 and r = 0.911, P < 0.001, respectively). Similar findings were observed with eAAC (r = 0.825, P < 0.001) and eADC (r = 0.827, P < 0.001). CONCLUSIONS: PRSA appears to be a method of fetal assessment equivalent to STV, but, due to its innate ability to eliminate artifacts, it generates interpretable NIFECG traces with high accuracy at a higher rate. These findings raise the possibility of self-applied at-home or remote fetal heart-rate monitoring with automated reporting, thus enabling increased surveillance in high-risk women without impacting on service demand. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Correlation of short-term variation derived from novel ambulatory fetal electrocardiography monitor with computerized cardiotocography.

OBJECTIVES: To compare short-term variation (STV) outputs from a novel self-applied non-invasive fetal electrocardiography (NIFECG) device with those obtained on computerized cardiotocography (cCTG). Technological and algorithmic limitations and mitigation strategies were also evaluated. METHODS: This was a prospective cohort study of women with a singleton pregnancy over 28 + 0 weeks' gestation attending a tertiary London hospital for cCTG assessment between June 2021 and June 2022. Women underwent concurrent monitoring with both NIFECG and cCTG for up to 1 h. Postprocessing of NIFECG data using various filtering methods produced NIFECG-STV (eSTV) values, which were compared with cCTG-STV (cSTV) outputs. Linear correlation, mean bias, precision and limits of agreement were assessed for STV derived by the different methods of computation and mathematical correction. RESULTS: Overall, 306 concurrent NIFECG and cCTG traces were collected from 285 women. Fully filtered eSTV was correlated very strongly with cSTV (r = 0.911, P < 0.001), but generated results only in 142/306 (46.4%) 1-h traces owing to the removal of traces with lower-quality signals. Partial filtering generated more eSTV data (98.4%), but with a weak correlation with cSTV (r = 0.337, P < 0.001). The difference in STV between the monitors (eSTV - cSTV) increased with signal loss; in traces with > 60% signal loss, the values became highly discrepant. Removal of traces with > 60% signal loss resulted in a stronger correlation with cSTV, while still generating eSTV results for 65% of traces. Correcting these remaining eSTV values for signal loss using linear regression analysis further improved correlation with cSTV (r = 0.839, P < 0.001). CONCLUSIONS: The discrepancy between STV computed by NIFECG and cCTG necessitates signal filtering, exclusion of poor-quality traces and eSTV correction. This study demonstrates that, with such correction, NIFECG is able to produce STV values that are strongly correlated with those of cCTG. This evidence base for NIFECG monitoring and interpretation is a promising step forward in the development of safe and effective at-home fetal heart-rate monitoring. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Improving antenatal detection of small-for-gestational-age fetus: economic evaluation of Growth Assessment Protocol.

OBJECTIVE: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care. METHODS: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained. RESULTS: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA. CONCLUSION: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Routine first-trimester pre-eclampsia screening and risk of preterm birth.

OBJECTIVES: Preterm birth (PTB) is a major public health problem worldwide. It can occur spontaneously or be medically indicated for obstetric complications, such as pre-eclampsia (PE) or fetal growth restriction. The main objective of this study was to investigate whether there is a shared uteroplacental etiology in the first trimester of pregnancy across PTB subtypes. METHODS: This was a retrospective cohort study of singleton pregnancies that underwent screening for preterm PE as part of their routine first-trimester ultrasound assessment at a tertiary center in London, UK, between March 2018 and December 2020. Screening for preterm PE was performed using the Fetal Medicine Foundation algorithm, which includes maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and pregnancy-associated plasma protein-A (PAPP-A). Women with a risk of ≥ 1 in 50 for preterm PE were classified as high risk and offered prophylactic aspirin (150 mg once a day) and serial ultrasound assessments. The following delivery outcomes were evaluated: PTB < 37 weeks, iatrogenic PTB (iPTB) and spontaneous PTB (sPTB). Logistic regression analyses were performed to assess the association of PTB, iPTB and sPTB with an increased risk of preterm PE. A model for prediction of PTB < 37 weeks and < 33 weeks was developed and its performance was compared with that of an existing model in the literature. RESULTS: A total of 11 437 women were included in the study, of whom 475 (4.2%) had PTB. Of these, 308 (64.8%) were sPTB and 167 (35.2%) were iPTB. Patients with PTB had a higher body mass index, were more likely to be of black or Asian ethnicity, be smokers, have pregestational hypertension or diabetes, or have a history of previous PTB. They also had higher MAP (87.7 vs 86.0 mmHg, P < 0.0001), higher UtA-PI multiples of the median (MoM) (0.99 vs 0.92, P < 0.0001) and lower PAPP-A MoM (0.89 vs 1.08, P < 0.0001) compared to women with a term birth. In women at high risk of PE, the odds ratio for iPTB was 6.0 (95% CI, 4.29-8.43; P < 0.0001) and that for sPTB was 2.0 (95% CI, 1.46-2.86; P < 0.0001). A prediction model for PTB < 37 weeks and < 33 weeks, developed based on this cohort, included previous PTB, black ethnicity, chronic hypertension, diabetes mellitus, PAPP-A MoM and UtA-PI MoM. The performance of the model was similar to that of an existing first-trimester prediction model for PTB < 33 weeks (area under the curve, 0.704 (95% CI, 0.653-0.754) vs 0.694 (95% CI, 0.643-0.746)). CONCLUSIONS: Increased first-trimester risk for uteroplacental dysfunction was associated with both iPTB and sPTB, implying a shared etiological pathway. The same factors used to predict PE risk show acceptable discrimination to predict PTB at < 33 weeks. Women at high risk of uteroplacental dysfunction may warrant additional monitoring and management for an increased risk of sPTB. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Maternal echocardiographic changes in twin pregnancies with and without pre-eclampsia.

OBJECTIVE: Twin pregnancies are at increased risk of developing hypertensive disorders of pregnancy (HDP) compared with singleton pregnancies, resulting in a substantially higher rate of maternal and perinatal complications. The strain caused by twin pregnancy on the maternal cardiovascular system has not been studied extensively. The objective of this study was to evaluate the changes in maternal cardiac morphology and diastolic function in a cohort of women with normotensive and those with hypertensive twin pregnancies. METHODS: This was a cross-sectional study conducted at a tertiary referral university center. Women with singleton or twin pregnancy were enrolled prospectively to undergo maternal transthoracic echocardiography throughout pregnancy. Multiples of the median (MoM) were calculated for each index using a reference group of uncomplicated singleton pregnancies (n = 411) in order to adjust for changes associated with gestational age. Cardiac findings were indexed for body surface area and compared among normotensive twin pregnancies, singleton pregnancies complicated by HDP and twin pregnancies complicated by HDP. RESULTS: The total cohort included 119 HDP singleton pregnancies, 52 normotensive twin pregnancies and 24 HDP twin pregnancies. Left ventricular mass index (LVMi) MoM (median (interquartile range)) did not differ between singleton pregnancies complicated by HDP and normotensive twin pregnancies, but was significantly higher in HDP twin compared with HDP singleton pregnancies (1.31 (1.08-1.53) vs 1.17 (0.98-1.35), P = 0.032). Two diastolic indices, left atrial volume index MoM (1.12 (0.66-1.38) vs 0.65 (0.55-0.84), P = 0.003) and E/e' MoM (1.29 (1.09-1.54) vs 0.99 (0.99-1.02), P = 0.036), were significantly higher in HDP twin compared with normotensive twin pregnancies. In normotensive twin compared with HDP singleton pregnancies, stroke volume index (SVi) MoM was higher (1.20 (1.03-1.36) vs 1.00 (0.81-1.15), P = 0.004) and total vascular resistance index (TVRi) was lower (0.73 (0.70-0.86) vs 1.29 (1.04-1.56), P < 0.0001). In contrast, SVi MoM was lower (1.10 (1.02-1.35) vs 1.20 (1.03-1.36), P = 0.018) and TVRi was higher (1.00 (0.88-1.31) vs 0.73 (0.70-0.86), P = 0.029) in HDP twin compared with normotensive twin pregnancies. CONCLUSION: The maternal cardiovascular system is altered severely in twin pregnancy with or without HDP. Despite the low total vascular resistance, cardiac changes in normotensive twin pregnancies are comparable to those seen in singleton pregnancies complicated by HDP, reflecting the high cardiovascular demand imposed by twin pregnancy. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal cardiovascular potential and kinetic energy indices in pre-eclamptic and small-for-gestational-age pregnancies.

OBJECTIVE: Non-invasive assessment of maternal cardiovascular potential and kinetic energy can be used to derive potential-to-kinetic-energy ratio (PKR) and Smith-Madigan inotropic index (SMII), which reflect the balance between blood pressure and blood flow. The aim of this study was to evaluate PKR and SMII in pregnancies complicated by hypertensive disorders of pregnancy (HDP) and/or small-for-gestational-age (SGA) birth. METHODS: This was a prospective study that enrolled women with a singleton pregnancy between 5 and 41 weeks' gestation. Women who developed HDP and/or SGA underwent cardiovascular profiling from 20 weeks. To establish reference ranges for PKR and SMII, women without any pre-existing medical problems at the time of booking who did not develop HDP, SGA or other complications during pregnancy were also recruited for cardiovascular profiling. Measurements of cardiovascular parameters were obtained using a non-imaging ultrasound cardiac output monitor. RESULTS: A total of 688 women completed the study, including 626 controls, 21 cases with HDP, 19 cases with SGA and 22 cases with HDP and SGA. PKR was significantly elevated in pregnancies with placental dysfunction compared with controls (HDP only, 29.81 ± 9.5; HDP and SGA, 44.33 ± 24.27; SGA only, 31.05 ± 13.14; vs controls, 22.30 ± 7.93; all P < 0.05). SMII values were significantly lower only in cases affected by SGA alone when compared with controls (1.47 ± 0.23 W/m2 vs 1.75 ± 0.40 W/m2 ; P < 0.005). These differences remained statistically significant when the analysis was undertaken using multiples of the median values corrected for gestational age. CONCLUSIONS: The findings of this study suggest that point-of-care non-invasive cardiovascular profiling using PKR and SMII may help distinguish between pregnancies affected by specific placental disorders and those exhibiting healthy cardiovascular adaptation to pregnancy. Women with HDP and/or SGA appear to have distinctive PKR and SMII profiles that reflect low kinetic energy in pregnancies with SGA and high potential energy in pregnancies affected by HDP. Finally, non-invasive assessment of potential and kinetic cardiovascular energy demonstrates physiological high-flow and low-resistance adaptation in uncomplicated pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

External validation of prognostic models to predict stillbirth using International Prediction of Pregnancy Complications (IPPIC) Network database: individual participant data meta-analysis.

OBJECTIVE: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance. METHODS: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit. RESULTS: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes. CONCLUSIONS: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Peripartum echocardiographic changes in women with hypertensive disorders of pregnancy.

OBJECTIVE: Hypertensive disorders of pregnancy (HDP) are associated with significant myocardial dysfunction on echocardiography. The impact of hemodynamic changes related to volume redistribution following delivery on myocardial function in women with HDP has not been evaluated systematically. The aim of this study was to compare echocardiographic findings immediately before and after delivery in women with HDP. METHODS: This was a prospective longitudinal study including 30 women with a diagnosis of HDP who underwent two consecutive transthoracic echocardiographic (TTE) examinations, before delivery and in the early postpartum period. Paired comparisons of the findings from the two assessments were performed. RESULTS: Left-ventricular (LV) concentric remodeling or hypertrophy was detected in 21 (70%) patients. There was no significant difference in cardiac morphology indices such as LV mass index (78.9 ± 16.3 g/m2 vs 77.9 ± 15.4 g/m2 ; P = 0.611) or relative wall thickness (0.45 ± 0.1 vs 0.44 ± 0.1; P = 0.453) before vs after delivery. LV diastolic function did not demonstrate any peripartum variation, with similar left-atrial volume (52.4 ± 15.3 mL vs 51.0 ± 15.6 mL; P = 0.433), lateral E' (0.12 ± 0.03 m/s vs 0.12 ± 0.03 m/s; P = 0.307) and E/E' ratio (7.9 ± 2.2 vs 7.9 ± 1.7; P = 0.934) before vs after delivery. Systolic function indices, such as LV ejection fraction (57.5 ± 3.4% vs 56.4 ± 2.1%; P = 0.295) and global longitudinal strain (-15.3 ± 2.6% vs -15.1 ± 3.1%; P = 0.582), also remained unchanged between before vs after delivery. CONCLUSIONS: Maternal hemodynamic changes associated with delivery did not influence significantly peripartum TTE indices in women with HDP. Suboptimal maternal echocardiographic findings in HDP are likely to be the consequence of chronic pregnancy cardiovascular load changes or pre-existing maternal cardiovascular impairment. Severity and persistence of myocardial dysfunction in the postpartum period may be related to the long-term maternal cardiovascular disease legacy of HDP. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of routine first-trimester combined screening for pre-eclampsia on small-for-gestational-age birth: secondary interrupted time series analysis.

OBJECTIVE: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome. METHODS: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA). RESULTS: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile. CONCLUSIONS: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Routine first-trimester combined screening for pre-eclampsia: pregnancy-associated plasma protein-A or placental growth factor?

OBJECTIVE: To compare the screening performance of serum pregnancy-associated plasma protein-A (PAPP-A) vs placental growth factor (PlGF) in routine first-trimester combined screening for pre-eclampsia (PE), small-for-gestational age (SGA) at birth and trisomy 21. METHODS: This was a retrospective study nested in pregnancy cohorts undergoing first-trimester combined screening for PE and trisomy 21 using The Fetal Medicine Foundation (FMF) algorithm based on maternal characteristics, nuchal translucency thickness, PAPP-A, free beta-human chorionic gonadotropin, blood pressure and uterine artery Doppler. Women at high risk for preterm PE (≥ 1 in 50) received 150 mg of aspirin per day, underwent serial fetal growth scans at 28 and 36 weeks and were offered elective birth from 40 weeks of gestation. PlGF was quantified retrospectively from stored surplus first-trimester serum samples. The performance of combined first-trimester screening for PE and SGA using maternal history, blood pressure, uterine artery pulsatility index and either PAPP-A or PlGF was calculated. Similarly, the performance of combined first-trimester screening for trisomy 21 was calculated using either PAPP-A or PlGF in addition to maternal age, nuchal translucency thickness and free beta-human chorionic gonadotropin. RESULTS: Maternal serum PAPP-A was assayed in 1094 women, including 82 with PE, 111 with SGA (birth weight < 10th centile), 53 with both PE and SGA and 94 with fetal trisomy 21. PlGF levels were obtained retrospectively from 1066/1094 women. Median serum PlGF multiples of the median was significantly lower in pregnancies with PE (1.0 (interquartile range (IQR), 0.8-1.4); P < 0.01), SGA (1.0 (IQR, 0.8-1.3); P < 0.001) and trisomy 21 (0.6 (IQR, 0.5-0.9); P < 0.0001) compared to in controls (1.2 (IQR, 0.9-1.5)). There was no significant difference in the performance of first-trimester screening using PAPP-A vs PlGF for either preterm PE (area under the receiver-operating-characteristics curve (AUC), 0.78 vs 0.79; P = 0.55) or term PE (AUC, 0.74 vs 0.74; P = 0.60). These findings persisted even after correction for the effect of targeted aspirin use on the prevalence of PE. Similarly, there were no significant differences in sensitivity and specificity of combined screening for SGA or trisomy 21 when using PAPP-A vs PlGF. CONCLUSIONS: Using either PlGF or PAPP-A in routine first-trimester combined screening based on maternal characteristics, blood pressure and uterine artery Doppler does not make a significant clinical difference to the detection of PE or SGA. Depending on the setting, biomarkers should be chosen to achieve a good compromise between performance and measurement requirements. This pragmatic clinical-effectiveness study suggests that combined screening for PE can be implemented successfully in a public healthcare setting without changing current protocols for the assessment of PAPP-A in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of monochorionicity on perinatal outcome and growth discordance in triplet pregnancy: collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To compare perinatal outcome and growth discordance between trichorionic triamniotic (TCTA) and dichorionic triamniotic (DCTA) or monochorionic triamniotic (MCTA) triplet pregnancies. METHODS: This was a multicenter cohort study using population-based data on triplet pregnancies from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort, for 2000-2013. Perinatal outcomes (from ≥ 24 weeks' gestation to 28 days of age), intertriplet fetal growth and birth-weight (BW) discordance and neonatal morbidity were analyzed in TCTA compared with DCTA/MCTA pregnancies. RESULTS: Monochorionic placentation of a pair or trio in triplet pregnancy (n = 72) was associated with a significantly increased risk of perinatal mortality (risk ratio, 2.7 (95% CI, 1.3-5.5)) compared with that in TCTA pregnancies (n = 68), due mainly to a much higher risk of stillbirth (risk ratio, 5.4 (95% CI, 1.6-18.2)), with 57% of all stillbirth cases resulting from fetofetal transfusion syndrome, while there was no significant difference in neonatal mortality (P = 0.60). The associations with perinatal mortality and stillbirth persisted when considering only pregnancies not affected by a major congenital anomaly. DCTA/MCTA triplets had lower BW and demonstrated greater BW discordance than did TCTA triplets (P = 0.049). Severe BW discordance of > 35% was 2.5-fold higher in DCTA/MCTA compared with TCTA pregnancies (26.1% vs 10.4%), but this difference did not reach statistical significance (P = 0.06), presumably due to low numbers. Triplets in both groups were delivered by Cesarean section in over 95% of cases, at a similar gestational age (median, 33 weeks' gestation). The rate of respiratory (P = 0.28) or infectious (P = 0.08) neonatal morbidity was similar between the groups. CONCLUSIONS: Despite close antenatal surveillance, monochorionic placentation of a pair or trio in triamniotic triplet pregnancy was associated with a significantly increased stillbirth risk, mainly due to fetofetal transfusion syndrome, and with greater size discordance. In liveborn triplets, there was no adverse effect of monochorionicity on neonatal outcome. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.