Change in prevalence of preterm birth in Israel following publication of national guidelines recommending routine sonographic cervical-length measurement at 19-25 weeks' gestation.

OBJECTIVE: To compare the prevalence of preterm birth (PTB) (delivery before 37 weeks) in Israel before and after publication of national guidelines recommending second-trimester sonographic cervical-length (CL) measurement. METHODS: The Israeli Society of Obstetrics and Gynecology (ISOG) guidelines, issued on 1 January 2012, specified that CL should be measured transabdominally or, if this is not possible, transvaginally, at the 19-25-week ultrasound anomaly scan and that CL < 25 mm should indicate further work-up and treatment, although the type of treatment was unspecified. In 2000, the Israel Ministry of Health issued a legal requirement for the submission of delivery records to a national registry. These data were used to compare PTB prevalence in the period before (2000-2011) and that after (2012-2020) publication of the guidelines, as well as trends within each time period. Information was available on singleton and multiple pregnancy and maternal age and parity, as well as low birth weight (< 2500 g). RESULTS: During the period 2000-2020, there were 3 403 976 infants liveborn in Israel: 1 797 657 before and 1 606 319 after publication of the ISOG guidelines. There were 247 187 PTBs overall, with a prevalence of 7.64% (95% CI, 7.52-7.77%) before publication of the guidelines and 6.84% (95% CI, 6.43-7.24%) afterwards (P < 0.0002, two-tailed). The annual PTB prevalence was static in the first time period but declined by 0.18% per annum during the second period, after publication of the guidelines. The proportionate reduction in PTB prevalence after compared with before publication of the guidelines was 10% overall, 9% for PTB at 33-36 weeks, 18% for PTB at 28-32 weeks and 24% for PTB at < 28 weeks. After publication of the guidelines, reduced prevalence of PTB was observed among singletons (5.49% before vs 4.83% after, P < 0.0001), but not among infants in twin or higher-order multiple pregnancy. There was a statistically significant reduction in the rate of PTB following publication of the guidelines in both nulliparous and parous women and in the 19-39-year-old maternal-age group. Although reductions in PTB prevalence were also noted in high-risk age groups (maternal age < 19 years and ≥ 40 years), these did not reach statistical significance. Following publication of the guidelines, there was a statistically significant reduction in the prevalence of birth weight under 2500 g, of a magnitude similar to that for PTB prevalence. CONCLUSIONS: The publication of national guidelines recommending routine CL measurement at the time of the second-trimester anomaly scan was associated with a fall in PTB prevalence in singleton pregnancies. Whilst direct evidence linking screening with this fall in prevalence is lacking, it is likely that implementation of routine CL screening played an important role in the reduction of PTB rate. Our experience indicates that screening can be incorporated into the second-trimester anomaly scan. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Quality assessment of first-trimester screening for preterm pre-eclampsia.

OBJECTIVE: To assess the performance and impact of first-trimester preterm pre-eclampsia screening in a single center. METHODS: This was a single-center study of women with a singleton pregnancy who were screened prospectively for preterm pre-eclampsia (i.e. delivery before 37 weeks' gestation) using maternal characteristics, mean arterial pressure (MAP), uterine artery Doppler pulsatility index, maternal serum pregnancy-associated plasma protein-A and placental growth factor. The individual risk for preterm pre-eclampsia was estimated from a published model, and those with a risk above 1 in 200 were recommended to take 150 mg soluble aspirin per day until 34 weeks. Information on the incidence of pre-eclampsia was obtained from the hospital register of adverse pregnancy outcomes. Screening performance indicators, including detection and false-positive rates, were estimated from the distribution of risks. Screening impact was estimated by dividing the observed prevalence by the expected prevalence, which was derived from the distribution of risks. RESULTS: The distributions of MAP, uterine artery Doppler pulsatility index and serum markers were consistent with the risk model parameters. The estimated detection and false-positive rates were 79.7% and 16.2%, respectively. There were six cases of preterm pre-eclampsia, four of which occurred in women with a positive screening result. The prevalence was 62% of that expected, but the 95% CI of 23-140% indicated that the study was underpowered to assess the impact. CONCLUSIONS: This study demonstrates that the performance of preterm pre-eclampsia screening can be estimated in a single center with fewer than 2000 women screened. However, in order to assess the impact of screening on the prevalence of the condition, a much larger cohort is needed. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Early pregnancy prediction of spontaneous preterm birth before 32 completed weeks of pregnancy using plasma RNA: transcriptome discovery and initial validation of an RNA panel of markers.

OBJECTIVE: To compare the second-trimester plasma cell-free (PCF) transcriptome of women who delivered at term with that of women with spontaneous preterm birth (sPTB) at or before 32 weeks of gestation and identify/validate PCF RNA markers present by 16 weeks of gestation. DESIGN: Prospective case-control study. SETTING: Academic tertiary care centre. POPULATION: Pregnant women with known outcomes prospectively sampled. METHODS: PCF RNAs extracted from women at 22-24 weeks of gestation (five sPTB up to 32 weeks and five at term) were hybridised to gene expression arrays. Differentially regulated RNAs for sPTB up to 32 weeks were initially selected based on P value compared with control (P < 0.01) and fold change (≥1.5×). Potential markers were then reordered by narrowness of distribution. Final marker selection was made by searching the Metacore™ database to determine whether the PCF RNAs interacted with a reported set of myometrial Preterm Initiator genes. RNAs were confirmed by quantitative reverse transcription polymerase chain reaction and tested in a second group of 40 women: 20 with sPTB up to 32 weeks (mean gestation 26.5 weeks, standard deviation ±2.6 weeks), 20 with spontaneous term delivery (40.1 ± 0.9 weeks) sampled at 16-19+5  weeks of gestation. MAIN OUTCOME MEASURE: Identification of PCF RNAs predictive of sPTB up to 32 weeks. RESULTS: Two hundred and ninety-seven PCR RNAs were differentially expressed in sPTB up to 32 weeks of gestation. Further selection retained 99 RNAs (86 mRNAs and 13 microRNAs) and five of these interacted in silica with seven Preterm Initiator genes. Four of five RNAs were confirmed and tested on the validation group. The expression of each confirmed PCF RNA was significantly higher in sPTB up to 32 weeks of gestation. In vitro study of the four mRNAs revealed higher expression in placentas of women with sPTB up to 32 weeks and the potential to interfere with myometrial quiescence. CONCLUSIONS: The PCF RNA markers are highly associated with sPTB up to 32 weeks by 16 weeks of gestation. TWEETABLE ABSTRACT: Women destined for spontaneous preterm birth can be identified by 16 weeks of gestation with a panel of maternal plasma RNAs.

United States' experience in nuchal translucency measurement: variation according to provider characteristics in over five million ultrasound examinations.

OBJECTIVE: The Nuchal Translucency Quality Review (NTQR) program has provided standardized education, credentialing and epidemiological monitoring of nuchal translucency (NT) measurements since 2005. Our aim was to review the effect on NT measurement of provider characteristics since the program's inception. METHODS: We evaluated the distribution of NT measurements performed between January 2005 and December 2019, for each of the three primary performance indicators of NT measurement (NT median multiples of the median (MoM), SD of log10 NT MoM and slope of NT with respect to crown-rump length (CRL)) for all providers within the NTQR program with more than 30 paired NT/CRL results. Provider characteristics explored as potential sources of variability included: number of NT ultrasound examinations performed annually (annual scan volume of the provider), duration of participation in the NTQR program, initial credentialing by an alternative pathway, provider type (physician vs sonographer) and number of NT-credentialed providers within the practice (size of practice). Each of these provider characteristics was evaluated for its effect on NT median MoM and geometric mean of the NT median MoM weighted for the number of ultrasound scans, and multiple regression was performed across all variables to control for potential confounders. RESULTS: Of 5 216 663 NT measurements from 9340 providers at 3319 sites, the majority (75%) of providers had an NT median MoM within the acceptable range of 0.9-1.1 and 85.5% had NT median MoM not statistically significantly outside this range. Provider characteristics associated with measurement within the expected range of performance included higher volume of NT scans performed annually, practice at a site with larger numbers of other NT-credentialed providers, longer duration of participation in the NTQR program and alternative initial credentialing pathway. CONCLUSIONS: Annual scan volume, duration of participation in the NTQR program, alternative initial credentialing pathway and number of other NT-credentialed providers within the practice are all associated with outcome metrics indicating quality of performance. It is critical that providers participate in ongoing quality assessment of NT measurement to maintain consistency and precision. Ongoing assessment programs with continuous feedback and education are necessary to maintain quality care. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Bedside risk estimation of morbidly adherent placenta using simple calculator.

PURPOSE: To construct a calculator for 'bedside' estimation of morbidly adherent placenta (MAP) risk based on ultrasound (US) findings. MATERIALS AND METHODS: This retrospective study included all pregnant women with at least one previous cesarean delivery attending in our US unit between December 2013 and January 2017. The examination was based on a scoring system which determines the probability for MAP. RESULTS: The study population included 471 pregnant women, and 41 of whom (8.7%) were diagnosed with MAP. Based on ROC curve, the most effective US criteria for detection of MAP were the presence of the placental lacunae, obliteration of the utero-placental demarcation, and placenta previa. On the multivariate logistic regression analysis, US findings of placental lacunae (OR = 3.5; 95% CI, 1.2-9.5; P = 0.01), obliteration of the utero-placental demarcation (OR = 12.4; 95% CI, 3.7-41.6; P < 0.0001), and placenta previa (OR = 10.5; 95% CI, 3.5-31.3; P < 0.0001) were associated with MAP. By combining these three parameters, the receiver operating characteristic curve was calculated, yielding an area under the curve of 0.93 (95% CI, 0.87-0.97). Accordingly, we have constructed a simple calculator for 'bedside' estimation of MAP risk. The calculator is mounted on the hospital's internet website ( http://www.assafh.org/Pages/PPCalc/index.html ). The risk estimation of MAP varies between 1.5 and 87%. CONCLUSIONS: The present calculator enables a simple 'bedside' MAP estimation, facilitating accurate and adequate antenatal risk assessment.

First- and second-trimester maternal serum markers of pre-eclampsia in twin pregnancy.

OBJECTIVE: To evaluate the distribution of first- and second-trimester maternal serum markers in twin pregnancy with and without pre-eclampsia. METHODS: One-hundred and forty-four twin and 109 unaffected singleton pregnancies were recruited from the same institution. First- and second-trimester maternal blood samples were stored and measured retrospectively for serum placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotropin (ß-hCG) and α-fetoprotein (AFP). All had measurement of first-trimester serum markers, and 167 (66%) had second-trimester tests. Values were expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight, as appropriate. RESULTS: Pre-eclampsia was diagnosed in 12 (9.0%) twin pregnancies of 133 continuing beyond 22 weeks. In unaffected twin pregnancies, all serum markers were statistically significantly increased (P < 0.0001), consistent with a doubling of concentration. Among twin pregnancies, those with pre-eclampsia had a significantly reduced median PlGF compared with surviving unaffected twin pregnancies (0.96 MoM vs 1.46 MoM; P < 0.0002, two-tailed), whilst median PAPP-A, which is known to be reduced in affected singleton pregnancies, was increased (3.91 MoM vs 2.43 MoM; P < 0.0005, two-tailed). The levels of free ß-hCG (P < 0.02) and AFP (P < 0.05) were also significantly raised, but to a lesser extent than was the level of PAPP-A. Using a logistic regression algorithm based on first- and second-trimester PlGF and PAPP-A, together with previously published uterine artery Doppler and mean arterial pressure measurements in the same series, the predicted pre-eclampsia detection rate was 65% for a 10% false-positive rate. CONCLUSIONS: In twin pregnancy, the predicted detection rate of pre-eclampsia using first- and second-trimester maternal serum and biophysical markers is good. In contrast to singleton pregnancy, PAPP-A levels are raised in the first trimester of twin pregnancies destined to develop pre-eclampsia and therefore a different prediction algorithm is needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Nuchal Translucency Quality Review (NTQR) program: first one and half million results.

OBJECTIVE: To evaluate the performance of first-trimester nuchal translucency (NT) measurement by providers (physician-sonologists and sonographers) within the Nuchal Translucency Quality Review (NTQR) program. METHODS: After training and credentialing providers, the NTQR monitored performance of NT measurement by the extent to which an individual's median multiple of the normal median (MoM) for crown-rump length (CRL) was within the range 0.9-1.1 MoM of a published normal median curve. The SD of log10 MoM and regression slope of NT on CRL were also evaluated. We report the distribution between providers of these performance indicators and evaluate potential sources of variation. RESULTS: Among the first 1.5 million scans in the NTQR program, performed between 2005 and 2011, there were 1 485 944 with CRL in the range 41-84 mm, from 4710 providers at 2150 ultrasound units. Among the 3463 providers with at least 30 scans in total, the median of the providers' median NT-MoMs was 0.913. Only 1901 (55%) had a median NT-MoM within the expected range; there were 89 above 1.1 MoM, 1046 at 0.8-0.9 MoM, 344 at 0.7-0.8 MoM and 83 below 0.7 MoM. There was a small increase in the median NT-MoM according to providers' length of time in the NTQR program and number of scans entered annually. On average, physician-sonologists had a higher median NT-MoM than did sonographers, as did those already credentialed before joining the program. The median provider SD was 0.093 and the median slope was 13.5%. SD correlated negatively with the median NT-MoM (r = -0.34) and positively with the slope (r = 0.22). CONCLUSION: Even with extensive training, credentialing and monitoring, there remains considerable variability between NT providers. There was a general tendency towards under-measurement of NT compared with expected values, although more experienced providers had performance closer to that expected.

First trimester markers of preeclampsia in twins: maternal mean arterial pressure and uterine artery Doppler pulsatility index.

OBJECTIVE: This study aims to evaluate the distribution of mean arterial pressure (MAP) and uterine artery Doppler pulsatility index (PI) in first trimester twins with and without preeclampsia. METHOD: A total of 147 twins were recruited from a specialist clinic and 110 unaffected singleton pregnancies attending the same institution served as controls. MAP and Doppler PI values were expressed in multiples of the gestation-specific median using published equations. RESULTS: Among the twins, 12 had preeclampsia and two had pregnancy-induced hypertension. Among unaffected pregnancies, there was no significant difference in MAP levels between twins and singletons (P = 0.17, Wilcoxon rank sum test, two-tail). However, the Doppler PI levels were highly statistically significantly lower than in singletons (P < 0.0005). MAP was unrelated to chorionicity (P = 0.46), but there was a statistically significant increase in Doppler PI among monochorionic compared with dichorionic twins (P < 0.01). In twins with preeclampsia, MAP was significantly higher than in unaffected twins (P < 0.02, one-tail), whereas Doppler PI levels were significantly reduced (P < 0.01, two-tail). CONCLUSION: If first trimester screening for preeclampsia is extended to twins, a different normal median Doppler PI equation will be needed. Contrary to expectations, Doppler PI levels may not be raised in affected twins, although this needs confirmation in a larger study.

Nuchal translucency in twins according to mode of assisted conception and chorionicity.

OBJECTIVES: The impact of nuchal translucency (NT) screening in twins conceived after use of assisted reproduction technology (ART) has not been addressed properly in the literature. The aim of the current study was to assess, in a large cohort from a single center, NT in twins following various modes of ART as compared with NT in spontaneously-conceived twins and to differentiate results with regard to chorionicity. METHODS: Retrospective data from 825 twin pregnancies were available for this study. All pregnant women underwent NT screening and chorionicity determination between 11 + 0 and 13 + 6 weeks' gestation in our center. Information about mode of conception and pregnancy outcome was obtained from hospital records and by telephone interviews. Twins were classified as having been conceived after in-vitro fertilization (IVF) with the woman's own or a donated embryo, after non-IVF ART or spontaneously. NT distribution in subgroups of fetuses was compared on the basis of the multiple of the normal median (MoM), SD of log10 MoM estimated by the 90(th) -10(th) centile range divided by 2.563 and the proportion of NT values exceeding the normal 95(th) centile which was 1.641 MoM in the singletons. RESULTS: NT values were statistically significantly higher in ART pregnancies as compared with spontaneously-conceived pregnancies (Wilcoxon rank-sum test, P < 0.05) with medians of 1.073 and 1.038 MoM, respectively, but the proportion with values above the normal 95(th) percentile did not differ (chi-square test, P = 0.89). Among the ART twins, NT values were significantly higher for those conceived using IVF methods (P < 0.005), with a median of 1.082 MoM, compared with a median of 1.022 MoM using other methods. However, although a greater proportion exceeded the 95(th) centile (7.3% compared with 4.8%) this difference did not reach statistical significance (P = 0.17). There were no differences in NT values according to chorionicity (Wilcoxon rank-sum test, P = 0.75). The standard deviation of log10 NT was similar for all subgroups of twins. The correlation coefficient between fetuses in ART pregnancies was statistically significantly lower than that in spontaneously-conceived pregnancies (P < 0.05) but no significant differences were found between types of ART or according to chorionicity. CONCLUSIONS: There was a small but significant increase in NT levels among ART pregnancies, which appeared to be confined to those conceived using IVF, and a small reduction in the correlation between fetuses. These effects probably have little impact on the estimated risk based on algorithms in use today.