Objectives: To estimate procedure‐related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta‐analysis.Methods: A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000–2014) was performed to review relevant citations reporting procedure‐related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I² statistic and Egger bias. Meta‐analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence–rate difference meta‐analysis was used to estimate pooled procedure‐related risks.Results: The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58–1.08%) and 2.18% (95% CI, 1.61–2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46–0.91%) for amniocentesis and 1.79% (95% CI, 0.61–3.58%) for CVS. The weighted pooled procedure‐related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, –0.04 to 0.26%) and 0.22% (95% CI, –0.71 to 1.16%), respectively.Conclusion: The procedure‐related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Objective: To examine the performance of screening for preterm and term pre‐eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence‐Based Preeclampsia Prevention) trial.Methods: This was a prospective first‐trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy‐associated plasma protein‐A and placental growth factor at 11–13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double‐blind trial of aspirin (150 mg per day) vs placebo from 11–14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false‐positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow‐up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185).Results: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first‐trimester screening for preterm PE with a risk cut‐off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen‐positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797).Conclusion: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Objective: To test the hypothesis that the performance of first‐trimester screening for pre‐eclampsia (PE) by a method that uses Bayes' theorem to combine maternal factors with biomarkers is superior to that defined by current National Institute for Health and Care Excellence (NICE) guidelines.Methods: This was a prospective multicenter study (screening program for pre‐eclampsia (SPREE)) in seven National Health Service maternity hospitals in England, of women recruited between April and December 2016. Singleton pregnancies at 11–13 weeks' gestation had recording of maternal characteristics and medical history and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), serum placental growth factor (PlGF) and serum pregnancy‐associated plasma protein‐A (PAPP‐A). The performance of screening for PE by the Bayes' theorem‐based method was compared with that of the NICE method. Primary comparison was detection rate (DR) using NICE method vs mini‐combined test (maternal factors, MAP and PAPP‐A) in the prediction of PE at any gestational age (all‐PE) for the same screen‐positive rate determined by the NICE method. Key secondary comparisons were DR of screening recommended by the NICE guidelines vs three Bayes' theorem‐based methods (maternal factors, MAP and PAPP‐A; maternal factors, MAP and PlGF; and maternal factors, MAP, UtA‐PI and PlGF) in the prediction of preterm PE, defined as that requiring delivery < 37 weeks.Results: All‐PE developed in 473 (2.8%) of the 16 747 pregnancies and preterm PE developed in 142 (0.8%). The screen‐positive rate by the NICE method was 10.3% and the DR for all‐PE was 30.4% and for preterm PE it was 40.8%. Compliance with the NICE recommendation that women at high risk for PE should be treated with aspirin from the first trimester to the end of pregnancy was only 23%. The DR of the mini‐combined test for all‐PE was 42.5%, which was superior to that of the NICE method by 12.1% (95% CI, 7.9–16.2%). In screening for preterm PE by a combination of maternal factors, MAP and PlGF, the DR was 69.0%, which was superior to that of the NICE method by 28.2% (95% CI, 19.4–37.0%) and with the addition of UtA‐PI the DR was 82.4%, which was higher than that of the NICE method by 41.6% (95% CI, 33.2–49.9%).Conclusions: The performance of screening for PE as currently recommended by NICE guidelines is poor and compliance with these guidelines is low. The performance of screening is substantially improved by a method combining maternal factors with biomarkers. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

Objective: To estimate the procedure‐related risk of miscarriage after amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta‐analysis.Methods: A search of MEDLINE, EMBASE and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. Eligible for inclusion were large controlled studies reporting data for pregnancy loss prior to 24 weeks' gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had an invasive procedure and controls were inputted into contingency tables and the risk of miscarriage was estimated for each study. Summary statistics based on a random‐effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure‐related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. Subgroup analyses were performed according to the similarity in risk levels for chromosomal abnormality between the invasive‐testing and control groups. Heterogeneity was assessed using the I² statistic. Egger's bias was estimated to assess reporting bias in published studies.Results: The electronic search yielded 2943 potential citations, from which 12 controlled studies for amniocentesis and seven for CVS were selected for inclusion in the systematic review. A total of 580 miscarriages occurred following 63 723 amniocentesis procedures, resulting in a weighted risk of pregnancy loss of 0.91% (95% CI, 0.73–1.09%). In the control group, there were 1726 miscarriages in 330 469 pregnancies with a loss rate of 0.58% (95% CI, 0.47–0.70%). The weighted procedure‐related risk of miscarriage following amniocentesis was 0.30% (95% CI, 0.11–0.49%; I² = 70.1%). A total of 163 miscarriages occurred following 13 011 CVS procedures, resulting in a risk of pregnancy loss of 1.39% (95% CI, 0.76–2.02%). In the control group, there were 1946 miscarriages in 232 680 pregnancies with a loss rate of 1.23% (95% CI, 0.86–1.59%). The weighted procedure‐related risk of miscarriage following CVS was 0.20% (95% CI, −0.13 to 0.52%; I² = 52.7%). However, when studies including only women with similar risk profiles for chromosomal abnormality in the intervention and control groups were considered, the procedure‐related risk for amniocentesis was 0.12% (95% CI, −0.05 to 0.30%; I² = 44.1%) and for CVS it was −0.11% (95% CI, −0.29 to 0.08%; I² = 0%).Conclusions: The procedure‐related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions were compared to control groups of the same risk profile. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Objective: To develop fetal and neonatal population weight charts. The rationale was that, while reference ranges of estimated fetal weight (EFW) are representative of the whole population, the traditional approach of deriving birth‐weight (BW) charts is misleading, because a large proportion of babies born preterm arise from pathological pregnancy. We propose that the reference population for BW charts, as in the case of EFW charts, should comprise all babies at a given gestational age, including those still in utero.Methods: Two sources of data were used for this study. For both, the inclusion criteria were singleton pregnancy, dating by fetal crown–rump length at 11 + 0 to 13 + 6 weeks' gestation, availability of ultrasonographic measurements of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) and live birth of phenotypically normal neonate. Dataset 1 comprised a sample of 5163 paired measurements of EFW and BW; ultrasound examinations were carried out at 22–43 weeks' gestation and birth occurred within 2 days of the ultrasound examination. EFW was derived from the HC, AC and FL measurements using the formula reported by Hadlock et al. in 1985. Dataset 2 comprised a sample of 95 579 pregnancies with EFW obtained by routine ultrasonographic fetal biometry at 20 + 0 to 23 + 6 weeks' gestation (n = 45 034), 31 + 0 to 33 + 6 weeks (n = 19 224) or 35 + 0 to 36 + 6 weeks (n = 31 321); for the purpose of this study we included data for only one of the three visits per pregnancy. In the development of reference ranges of EFW and BW according to gestational age, the following assumptions were made: first, that EFW and BW have a common median, dependent on gestational age; and second, that deviations from the median occur in both EFW and BW and these deviations are correlated with different levels of spread for EFW and BW, dependent on gestational age. We adopted a Bayesian approach to inference, combining information from the two datasets using Markov Chain Monte‐Carlo sampling. The fitted model assumed that the mean log transformed measurements of EFW and BW are related to gestational age according to a cubic equation and that deviations about the mean follow a bivariate Gaussian distribution.Results: In the case of EFW in Dataset 2, there was a good distribution of values < 3^rd, < 5^th, < 10^th, > 90^th, > 95^th and > 97^th percentiles of the reference range of EFW according to gestational age throughout the gestational age range of 20 + 0 to 36 + 6 weeks. In the case of BW, there was a good distribution of values only for the cases delivered > 39 weeks' gestation. For preterm births, particularly at 27–36 weeks, BW was below the 3^rd, 5^th and 10^th percentiles in a very high proportion of cases, particularly in cases of iatrogenic birth. The incidence of small‐for‐gestational‐age fetuses and neonates in the respective EFW and BW charts was higher in women of black than those of white racial origin.Conclusion: We established a BW chart for all babies at a given gestational age, including those still in utero, thereby overcoming the problem of underestimation of growth restriction in preterm birth. BW and EFW charts have a common median but differ in the levels of spread from the median. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.