Optimal First Trimester Preeclampsia Prediction: a Comparison of Multimarker Algorithm, Risk Profiles and Their Sequential Application

OBJECTIVE: To compare performance of multimarker algorithm, risk profiles and their sequential application in prediction of preeclampsia and determining potential intervention targets. STUDY DESIGN: Maternal characteristics, ultrasound variables and serum biomarkers were collected prospectively at first trimester. Univariate analysis identified preeclampsia associated variables followed by logistic regression analysis to determine the prediction rule. Combined characteristics of the cardiovascular, metabolic and the personal risk factors were compared to the multimarker algorithm and the sequential application of both methods. RESULTS: Out of 2433 women, 108 developed preeclampsia (4.4%). Probability scores considering nulliparity, prior preeclampsia, body mass index, diastolic blood pressure and placental growth factor had an area under the receiver operating characteristic curve 0.784 (95% CI = 0.721-0.847). While the multimarker algorithm had the lowest false negative rate, sequential application of cardiovascular and metabolic risk profiles in screen positives reduced false positives by 26% and identified blood pressure and metabolic risk in 49/54 (91%) women with subsequent preeclampsia as treatable risk factors. CONCLUSION: Sequential application of a multimarker algorithm followed by determination of treatable risk factors in screen positive women is the optimal approach for first trimester preeclampsia prediction and identification of women that may benefit from targeted metabolic or cardiovascular treatmentinfo:eu-repo/semantics/publishedVersio

Reduced fetal movements and cerebroplacental ratio: evidence for worsening fetal hypoxemia

Objective To investigate the fetal cerebroplacental ratio (CPR) in women presenting with reduced fetal movements (RFM). Methods This was a retrospective cohort study of data collected over an 8‐year period at a fetal medicine unit at a tertiary referral center. The cohort comprised 4500 singleton pregnancies presenting with RFM at or after 36 weeks' gestation and 1527 control pregnancies at a similar gestational age without RFM. Fetal biometry and Doppler parameters were recorded and converted into centiles and multiples of the median (MoM). CPR was defined as the ratio between the fetal middle cerebral artery (MCA) pulsatility index (PI) and the umbilical artery (UA) PI. Subgroup analysis for fetal size and for single vs multiple episodes of RFM was performed. Results Compared with controls, pregnancies with RFM had lower MCA‐PI MoM (median, 0.95 vs 0.97; P < 0.001) and CPR MoM (median, 0.97 vs 0.99; P = 0.018). Compared with women presenting with single episodes of RFM, pregnancies with multiple episodes (≥ 2 episodes) had lower CPR MoM (median, 0.94 vs 0.98; P = 0.003). On subgroup analysis for fetal size, compared with controls, appropriate‐for‐gestational‐age fetuses in the RFM group had lower MCA‐PI MoM (median, 0.96 vs 0.97; P = 0.003) and higher rate of CPR below the 5th centile (5.3% vs 3.6%; P = 0.015). Logistic regression analysis demonstrated an association of risk of recurrent RFM with maternal age (OR, 0.96; 95% CI, 0.93–0.99), non‐Caucasian ethnicity (OR, 0.72; 95% CI, 0.53–0.97), estimated fetal weight centile (OR, 1.01; 95% CI, 1.00–1.02) and CPR MoM (OR, 0.24; 95% CI, 0.12–0.47). Conclusion Pregnancies complicated by multiple episodes of RFM show significantly lower CPR MoM and MCA‐PI MoM compared with those with single episodes and controls. This is likely to be due to worsening fetal hypoxemia in women presenting with recurrent RFM

Birth‐weight differences at term are explained by placental dysfunction and not by maternal ethnicity

Objective To investigate the influence of ethnicity, fetal gender and placental dysfunction on birth weight (BW) in term fetuses of South Asian and Caucasian origin. Methods This was a retrospective study of 627 term pregnancies assessed at two public tertiary hospitals in Spain and Sri Lanka. All fetuses underwent biometry and Doppler examinations within 2 weeks of delivery. The influences of fetal gender and ethnicity, gestational age (GA) at delivery, cerebroplacental ratio (CPR) and maternal age, height, weight and parity on BW were evaluated by multivariable regression analysis. Results Fetuses born in Sri Lanka were smaller than those born in Spain (mean BW = 3026 ± 449 g vs 3295 ± 444 g; P < 0.001). Multivariable regression analysis demonstrated that GA at delivery, maternal weight, CPR, maternal height and fetal gender (estimates = 0.168, P < 0.001; 0.006, P < 0.001; 0.092, P = 0.003; 0.009, P = 0.002; 0.081, P = 0.01, respectively) were associated significantly with BW. Conversely, no significant association was noted for maternal ethnicity, age or parity (estimates = −0.010, P = 0.831; 0.005, P = 0.127; 0.035, P = 0.086, respectively). The findings were unchanged when the analysis was repeated using INTERGROWTH‐21st fetal weight centiles instead of BW (log odds, −0.175, P = 0.170 and 0.321, P < 0.001, respectively for ethnicity and CPR). Conclusion Fetal BW variation at term is less dependent on ethnic origin and better explained by placental dysfunction. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd

Outcome of prenatally diagnosed fetal heterotaxy: A systematic review and meta-analysis.

OBJECTIVES: To assess the perinatal outcomes of fetuses affected by heterotaxy. METHODS: Medline, Embase and Cinhal were searched. Only studies reporting a prenatal diagnosis of isomerism were included. The outcomes observed were: associated cardiac and extra-cardiac anomalies, fetal arrhythmias, abnormal karyotype, type of surgical repair and perinatal mortality. The analysis was stratified according the type of heterotaxy syndrome (left, LAI, and right, RAI, atrial isomerism). Meta-analyses of proportions were used to combine data. RESULTS: 16 studies (647 fetuses) were included. Atrioventricular septal defect (AVSD) was the most common associated major cardiac anomaly found in fetuses with LAI (Pooled Proportion [PP] 59.3%, 95% CI 44.0-73.7), while obstructive lesions of the right outflow tract occurred in 35.5% (95% CI 21.4-51.0). Fetal arrhythmias occurred in 36.7% (95% CI 26.9-47.2) of the cases and were mainly represented by complete atrio-ventricular block (26.5%, 95% CI 15.0-40.0). Abnormal stomach and liver position were found in 59.4% (95% CI 38.1-79.0) and 32.5% (95% 11.9-57.6) of cases, while intestinal malrotation was detected in 14.2% (95% CI 2.5-33.1). Hydrops developed in 11.8% (95% CI 2.9-25.6) of these fetuses. Biventricular repair was accomplished in 78.2% (95% CI 64.3-89.4) of the cases while univentricular repair or palliation was needed for 17.0% (95% CI 9.7-25.9). Death during or after surgery occurred in 26.8% (95% CI 4.6-58.7) of cases. Almost all (99.0% 95% CI 97.5-99.9) cases with RAI had associated cardiac anomalies, with AVSD being the most common heart defect (PP 72.9%, 95% CI 60.4-83.7). Abnormal heart rhythm was not common with an incidence of 1.3% (95% CI 0.2-3.2). Abnormal stomach and liver position were found in 54.5% (95% CI 38.5-70.1) and 45.9% (95% CI 11.3-83.0) of cases, respectively, while intestinal malrotation was detected in 27.1% (95% CI 7.9-5.2). Most children with RAI had univentricular repair and 27.8% (95% CI 15.5-42.1) died during or after surgery. CONCLUSION: Fetal heterotaxy is affected by a high prevalence of cardiac and extra-cardiac anomalies. Approximately one quarter of these fetuses died during or after surgery. Abnormal heart rhythm, especially heart block is common in fetuses with LAI while is uncommon in RAI. Univentricular repair is common in RAI

A Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints: the COSGROVE study.

BACKGROUND: Fetal growth restriction refers to a fetus that does not reach its genetically predetermined growth potential. It is well-recognized that growth-restricted fetuses are at increased risk of both short- and long-term adverse outcomes. Systematic evaluation of the evidence from clinical trials of fetal growth restriction is often difficult because of variation in the outcomes that are measured and reported. The development of core outcome sets for fetal growth restriction studies would enable future trials to measure similar meaningful outcomes. OBJECTIVE: The purpose of this study was to develop core outcome sets for trials of prevention or treatment of fetal growth restriction. STUDY DESIGN: This was a Delphi consensus study. A comprehensive literature review was conducted to identify outcomes that were reported in studies of prevention or treatment of fetal growth restriction. All outcomes were presented for prioritization to key stakeholders (135 healthcare providers, 68 researchers/academics, and 35 members of the public) in 3 rounds of online Delphi surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core outcome set at a face-to-face meeting with 5 healthcare providers, 5 researchers/academics, and 6 maternity service users. RESULTS: In total, 22 outcomes were included in the final core outcome set. These outcomes were grouped under 4 domains: maternal (n=4), fetal (n=1), neonatal (n=12), and childhood (n=5). CONCLUSION: The Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints study identified a large number of potentially relevant outcomes and then reached consensus on those factors that, as a minimum, should be measured and reported in all future trials of prevention or treatment of fetal growth restriction. This will enable future trials to measure similar meaningful outcomes and to ensure that findings from different studies can be compared and combined

Core Outcome Set for GROwth restriction: deVeloping Endpoints (COSGROVE).

BACKGROUND: Foetal growth restriction (FGR) refers to a foetus that does not reach its genetically predetermined growth potential. It is well recognised that growth-restricted foetuses are at increased risk of stillbirth, foetal compromise, early neonatal death and neonatal morbidity. Later in life, they are prone to health problems, including increased risk of cardiovascular diseases and neurodevelopmental disorders. Interventions for preventing and treating FGR have been studied in many trials, but evidence is often difficult to synthesise and compare because of differences in the selection and definition of outcomes. To enable future trials to measure similar, meaningful outcomes, we are developing two core outcome sets (COS) - one for prevention and the other for treatment of FGR. METHODS: We will review the literature to identify previously reported outcomes. An international panel of relevant stakeholders who have experience of FGR (parent or carer of a baby that was growth restricted, health professional involved in the care of mothers and babies affected by FGR, a person with expertise in FGR research) will rate the importance of each of those outcomes in a series of three sequential online rounds of a Delphi study. Participants will be able to add items to the proposed list in round 1. A final face-to-face consensus meeting will be held with representatives of each stakeholder group at which a final list of outcomes for inclusion in the COS will be agreed. DISCUSSION: The development of COSs in FGR will ensure the collection and reporting of a minimum dataset agreed by stakeholder consensus and will reduce inconsistencies in the reporting of outcomes across relevant trials. Such standardisation in the reporting of outcomes will improve synthesis of evidence and generalisability of knowledge in the future by reducing heterogeneity in outcomes between trials and thus improve the results of systematic reviews and meta-analyses. Ultimately, we hope that the COSs will lead to an improvement in the quality of evidence-based clinical practice, enhance patient care, and improve the quality and consistency of research. TRIAL REGISTRATION: Not applicable. This study is registered in the Core Outcome Measures for Effectiveness (COMET) database

Association of chronic hypertension with birth of small-for-gestational-age neonate

Objective: To examine the effect of chronic hypertension (CH), with and without superimposed preeclampsia (PE), on the incidence of small for gestational age (SGA) neonates, and explore possible mechanisms for such association. Methods: The data for the study were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancies attending for their first routine hospital visit at 11-13 weeks’ gestation, which included recording of maternal characteristics and medical history and measurement of mean arterial pressure (MAP). Birth weight z-score, adjusted for gestational age and for maternal and pregnancy characteristics, and incidence of SGA were compared between those with and without CH in the total population and in the subgroups with and without PE. Regression analysis was used to examine the relationship between MAP and birth weight z-score and incidence of SGA and PE in those with and without CH. Results: The study population constituted 74,226 pregnancies, including 1,052 (1.4%) with CH and 73,174 without CH. Preeclampsia developed in 233 (22.1%) cases of the group with CH and in 1,662 (2.3%) of those without CH. In the group that developed PE, there was no significant difference between those with CH and those without CH in either the median birth weight z-score or the incidence of SGA. In the group without PE, the incidence of SGA was twice as high in those with than in those without CH. There was a significant association between log10 MAP multiple of the median and incidence of SGA and PE which was more marked in those with CH than in those without CH. Conclusion: CH is associated with increased risk of SGA and PE and this is related to MAP at 11-13 weeks’ gestation

Is Cerebroplacental Ratio A Marker of Impaired Fetal Growth Velocity and Adverse Pregnancy Outcome?

BACKGROUND: The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term. OBJECTIVE: The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between low cerebroplacental ratio at term, reduced fetal growth velocity and adverse pregnancy outcome. DESIGN: retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation, and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within two weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio, low abdominal circumference growth velocity (in the lowest decile), and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small for gestational age neonates. RESULTS: The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted OR 2.10; 95%CI 1.71-2.57, p<0.001) and small for gestational age (adjusted OR 3.60; 95%CI 3.04-4.25, p<0.001). After the exclusion of pregnancies resulting in small for gestational age neonates, low cerebroplacental ratio multiples of median remained significantly associated with both low abdominal circumference growth velocity (adjusted OR 1.76; 95%CI 1.34-2.30, p<0.001) and birthweight centile (adjusted OR 0.99; 95%CI 0.998-0.995, p<0.001). The need for operative delivery for fetal compromise was significantly associated with low cerebroplacental ratio (adjusted OR 1.40; 95%CI 1.10-1.78, p=0.006), even after adjusting for both the umbilical artery pulsatility index multiples of median and middle cerebral artery pulsatility index multiples of median. The results were similar even after the exclusion of pregnancies resulting in small for gestational age neonates (adjusted OR 1.39; 95%CI 1.06-1.84, p=0.018). Low cerebroplacental ratio multiples of median remained significantly associated with the risk of operative delivery for presumed fetal compromise (p<0.001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted even after exclusion of small for gestational age births. In appropriate for gestational age sized fetuses, abdominal circumference growth velocity was significantly lower in those with low cerebroplacental ratio multiples of median than in those with normal cerebroplacental ratio multiples of median (p<0.001). CONCLUSION: Cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry