Effects of strict public health measures on seroprevalence of anti-SARS-CoV-2 antibodies during pregnancy.

INTRODUCTION: A substantial number of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic throughout the course of infection. Nearly half of pregnant women with coronavirus disease 2019 (COVID-19) are asymptomatic upon diagnosis; these cases are not without risk of maternal morbidity. Here, we investigated the seroprevalence of anti-SARS-CoV-2 antibodies in an unselected sample of pregnant women in Hong Kong. METHODS: This prospective cohort study included pregnant women who presented for routine Down syndrome screening (DSS) between November 2019 and October 2020; all women subsequently delivered at the booking hospitals. Serum antibodies against SARS-CoV-2 were analysed using a qualitative serological assay in paired serum samples taken at DSS and delivery for all participants. RESULTS: In total, 1830 women were recruited. Six women (0.33%) were seropositive at the DSS visit; this seropositivity persisted until delivery. Of the six women, none reported relevant symptoms during pregnancy; one reported a travel history before DSS and one reported relevant contact history. The interval between sample collections was 177 days (range, 161-195). Among women with epidemiological risk factors, 1.79% with travel history, 50% with relevant contact history, and 0.77% with community SARS-CoV-2 testing history, were seropositive. CONCLUSION: The low seroprevalence in this study suggests that strict public health measures are effective for preventing SARS-CoV-2 transmission. However, these measures cannot be maintained indefinitely. Until a highly effective therapeutic drug targeting SARS-CoV-2 becomes available, vaccination remains the best method to control the COVID-19 pandemic.

Outcome of radiofrequency ablation for selective fetal reduction before vs at or after 16 gestational weeks in complicated monochorionic pregnancy.

OBJECTIVE: To investigate whether gestational age at intervention (< or ≥ 16 weeks) and other factors affect the risk of loss of the cotwin after selective fetal reduction using radiofrequency ablation (RFA) in monochorionic (MC) pregnancy. METHODS: This was a single-center retrospective analysis of 63 consecutive RFA procedures performed at our institution from January 2011 to October 2019 for selective fetal reduction in complicated MC pregnancies. Indications for RFA were twin reversed arterial perfusion sequence (13 cases), twin-to-twin transfusion syndrome (12 cases), twin anemia-polycythemia sequence (two cases), selective fetal growth restriction (10 cases), discordant anomalies (17 cases) and multifetal pregnancy reduction in triplets or quadruplets with a MC pair (nine cases). Twenty-six (41.3%) of these procedures were performed before and 37 (58.7%) after 16 weeks. Potential factors that could affect the risk of loss of the cotwin, including gestational age at RFA, order of multiple pregnancy, amnionicity, indication for RFA and number of ablation cycles, were assessed first by univariate analysis and then by multivariate analysis. RESULTS: There were 17 (27.0%) cotwin losses. Ablation cycles numbering four or more was the only factor among those investigated to be associated with loss of the cotwin after RFA (P = 0.035; odds ratio, 5.21), while the indication for RFA, order of multiple pregnancy, amnionicity and gestational age at RFA had no effect. Comparing RFA performed at < 16 vs ≥ 16 weeks, there was no difference in the rate of cotwin loss (23.1% vs 29.7%; P = 0.558) or preterm prelabor rupture of the membranes before 34 weeks (7.7% vs 5.4%; P = 0.853), or in the median gestational age at delivery (36.2 vs 37.3 weeks; P = 0.706). CONCLUSIONS: RFA is a promising tool for early selective fetal reduction in MC pregnancy before 16 weeks. Four or more ablation cycles is a major risk factor for cotwin loss. Careful assessment pre- and post-RFA, together with proficient operative skills to minimize the number of ablation cycles, are the mainstay to ensure that this procedure is effective and safe. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE).

Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to be superior to the current method recommended by NICE that is based on maternal demographics and history alone. Enrollment for the study commenced in April 2016. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

ASPRE trial: performance of screening for preterm pre-eclampsia.

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.

Cervical cerclage for preterm birth prevention in twin gestation with short cervix: a retrospective cohort study.

OBJECTIVE: To determine if cervical cerclage reduces the rate of spontaneous early preterm birth in cases of dichorionic-diamniotic (DCDA) twin gestation with an ultrasound-detected short cervix. METHODS: This was a retrospective cohort study of 40 consecutive DCDA twin gestations at Saint Peter's University Hospital from November 2006 to November 2014 in which cervical cerclage was performed for an ultrasound-determined cervical length of 1-24 mm at 16-24 weeks' gestation. The cases were matched with 40 controls without cerclage for cervical length and gestational age at cervical assessment. The primary outcome measure was spontaneous birth < 32 weeks. RESULTS: There was no difference between the two groups in maternal age, body mass index (BMI), cigarette smoking, use of in-vitro fertilization (IVF), parity and prior spontaneous preterm birth. There were more Caucasian women among the controls compared with cases. In the cases, compared with controls, spontaneous delivery < 32 weeks was significantly less frequent (20.0% vs 50.0%; relative risk, 0.40 (95% CI, 0.20-0.80)). In the prediction of spontaneous delivery < 32 weeks, logistic regression analysis demonstrated that the risk was reduced with the insertion of cervical cerclage (odds ratio, 0.22 (95% CI, 0.058-0.835); P = 0.026), corrected for maternal age, BMI, racial origin, cigarette smoking, IVF, parity and previous preterm birth. CONCLUSION: In DCDA twin gestation with a short cervix, treatment with cervical cerclage may reduce the rate of early preterm birth. The findings suggest the need for adequate randomized controlled trials on cerclage in twin gestations with a short cervix. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Birth weight in live births and stillbirths.

OBJECTIVE: To establish a normal range of birth weights for gestational age at delivery and to compare the proportion of live births and stillbirths that are classified as small-for-gestational age (SGA) according to our normal range vs that of the INTERGROWTH-21st standard. METHODS: The study population comprised 113 019 live births and 437 (0.4%) stillbirths. The inclusion criterion for establishing a normal range of birth weights for gestational age was the live birth of a phenotypically normal neonate ≥ 24 weeks' gestation and the exclusion criteria were smoking and prepregnancy hypertension, diabetes mellitus, systemic lupus erythematosus or antiphospholipid syndrome, pre-eclampsia, gestational hypertension, gestational diabetes mellitus or iatrogenic preterm birth for fetal growth restriction in the current pregnancy. Inclusion criteria were met by 92 018 live births. The proportions of live births and stillbirths with birth weights < 5th and < 10th percentiles of our normal range and those according to the INTERGROWTH-21st standard were determined and compared by the chi-square test and McNemar test. RESULTS: The proportions of live births and stillbirths with a birth weight < 5th percentile according to our standard were significantly higher than and discordant with the proportion according to the INTERGROWTH-21st standard (live birth: 5.6% vs 3.4%; stillbirth: 37.2% vs 22.7%). Similarly, the proportion of live births and stillbirths with a birth weight < 10th percentile according to our standard were significantly higher than and discordant with those according to the INTERGROWTH-21st standard (live birth: 11.2% vs 6.9%; stillbirth: 44.3% vs 32.6%). CONCLUSION: The INTERGROWTH-21st standard underestimates the proportion of SGA live births and stillbirths in our population. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

How feasible is expectant management of interstitial ectopic pregnancy?

OBJECTIVE: To review the success rate of expectant management in a series of interstitial pregnancies. METHODS: We identified all women with an ultrasound diagnosis of interstitial pregnancy seen within a 9-year period (January 2004 to April 2013). The clinical history, ultrasound findings and biochemical results were reviewed. The outcome of all interstitial pregnancies managed conservatively was recorded. Treatment was considered as successful when the serum ß-human chorionic gonadotropin (ß-hCG) level declined below 20 IU/L without the need for further intervention. RESULTS: A total of 48 interstitial pregnancies were diagnosed during the study period. Surgery was the first-line treatment in nine (18.8%) cases. Thirty-eight (79.2%) women were offered non-surgical management: 19 (39.6%) had methotrexate (MTX) and 19 (39.6%) were managed expectantly. One (2.1%) woman returned to her local hospital following diagnosis and we were unable to obtain any follow-up information regarding her care. The median initial serum ß-hCG level and ectopic size were not significantly different between any of the groups according to initial treatment. The overall success rate of expectant management was 89.5%. There were no cases of ectopic rupture in this group. Length of follow-up ranged from 7 to 141 days with a median duration of follow-up of 50.6 days. CONCLUSION: Our data show that expectant management is an option for selected women with non-viable interstitial pregnancies and declining serum ß-hCG levels, irrespective of ectopic mass size and initial serum ß-hCG levels.

Fetal fraction in maternal plasma cell-free DNA at 11-13 weeks' gestation: relation to maternal and fetal characteristics.

OBJECTIVE: To examine the possible effects of maternal and fetal characteristics on the fetal fraction in maternal plasma cell-free (cf) DNA at 11-13 weeks' gestation and estimate the proportion of pregnancies at high risk of non-invasive prenatal testing (NIPT) failure because the fetal fraction is less than 4%. METHODS: In 1949 singleton pregnancies at 11-13 weeks' gestation cf-DNA was extracted from maternal plasma. Chromosome-selective sequencing of non-polymorphic and polymorphic loci, where fetal alleles differ from maternal alleles, was used to determine the proportion of cf-DNA that was of fetal origin. Multivariable regression analysis was used to determine significant predictors of the fetal fraction among maternal and fetal characteristics. RESULTS: The fetal fraction decreased with increased maternal weight, it was lower in women of Afro-Caribbean origin than in Caucasians and increased with fetal crown-rump length, serum pregnancy-associated plasma protein-A, serum free ß-human chorionic gonadotropin, smoking and trisomy 21 karyotype. The median fetal fraction was 10.0% (interquartile range, 7.8-13.0%) and this decreased with maternal weight from 11.7% at 60 kg to 3.9% at 160 kg. The estimated proportion with fetal fraction below 4% increased with maternal weight from 0.7% at 60 kg to 7.1% at 100 kg and 51.1% at 160 kg. CONCLUSIONS: Fetal fraction in maternal plasma cf-DNA is affected by maternal and fetal characteristics.

Meta-analysis of second-trimester markers for trisomy 21.

OBJECTIVE: To summarize by meta-analysis the accumulated data on the screening performance of second-trimester sonographic markers for fetal trisomy 21. METHODS: We conducted a literature search to identify studies between 1995 and September 2012 that provided data on the incidence of sonographic markers in trisomy 21 and euploid fetuses at 14-24 weeks' gestation. Weighted independent estimates of detection rate, false-positive rate and positive and negative likelihood ratios (LR) of markers were calculated. RESULTS: A total of 48 studies was included in the analysis. The pooled estimates of positive and negative LR were, respectively: 5.83 (95% CI, 5.02-6.77) and 0.80 (95% CI, 0.75-0.86) for intracardiac echogenic focus; 27.52 (95% CI, 13.61-55.68) and 0.94 (95% CI, 0.91-0.98) for ventriculomegaly; 23.30 (95% CI, 14.35-37.83) and 0.80 (95% CI, 0.74-0.85) for increased nuchal fold; 11.44 (95% CI, 9.05-14.47) and 0.90 (95% CI, 0.86-0.94) for hyperechogenic bowel; 7.63 (95% CI, 6.11-9.51) and 0.92 (95% CI, 0.89-0.96) for mild hydronephrosis; 3.72 (95% CI, 2.79-4.97) and 0.80 (95% CI, 0.73-0.88) for short femur; 4.81 (95% CI, 3.49-6.62) and 0.74 (95% CI, 0.63-0.88) for short humerus; 21.48 (95% CI, 11.48-40.19) and 0.71 (95% CI, 0.57-0.88) for aberrant right subclavian artery (ARSA); and 23.27 (95% CI, 14.23-38.06) and 0.46 (95% CI, 0.36-0.58) for absent or hypoplastic nasal bone. The combined negative LR, obtained by multiplying the values of individual markers, was 0.13 (95% CI, 0.05-0.29) when short femur but not short humerus was included and 0.12 (95% CI, 0.06-0.29) when short humerus but not short femur was included. CONCLUSION: The presence of sonographic markers increases, and absence of such markers decreases, the risk for trisomy 21. In the case of most isolated markers there is only a small effect on modifying the pre-test odds for trisomy 21, but with ventriculomegaly, nuchal fold thickness and ARSA there is a 3-4-fold increase in risk and with hypoplastic nasal bone a 6-7-fold increase.

Maternal plasma cell-free fetal and maternal DNA at 11-13 weeks' gestation: relation to fetal and maternal characteristics and pregnancy outcomes.

OBJECTIVE: To examine the possible relationship between maternal and fetal characteristics and pregnancy outcomes on fetal and maternal cell-free (cf) DNA in maternal plasma at 11-13 weeks' gestation. METHODS: cfDNA was extracted from maternal plasma of 1,949 singleton pregnancies and chromosome-selective sequencing was used to determine the proportion of cfDNA and total cfDNA counts which was of fetal and maternal origin. Multivariate regression analysis was used to determine whether specific maternal and fetal characteristics and pregnancy complications, such as preeclampsia (PE), early spontaneous preterm birth (SPB) and delivery of small for gestational age (SGA) neonates, were significant predictors of fetal and maternal cfDNA in maternal plasma. RESULTS: The fetal and maternal cfDNA plasma concentration increased with serum pregnancy-associated plasma protein-A and free ß-human chorionic gonadotropin level, was higher in women of Afro-Caribbean and East-Asian racial origin than in Caucasians, and lower in smokers, but it was not significantly altered in pregnancies complicated by PE, SPB or SGA. The fetal cfDNA level was inversely related to maternal weight and uterine artery pulsatility index, and maternal cfDNA increased with maternal weight. CONCLUSIONS: The fetal and maternal cfDNA level in maternal plasma is affected by maternal and fetal characteristics, but it is not altered in pregnancy complications.

Large loop excision of transformation zone and cervical length in the prediction of spontaneous preterm delivery.

OBJECTIVES: To investigate the association between previous large loop excision of transformation zone (LLETZ) and risk for subsequent spontaneous preterm delivery (sPD) and whether this effect is reflected in the measurement of cervical length at mid-gestation. DESIGN AND SETTING: A secondary analysis of data from women recruited for clinical trials of interventions to prevent preterm labour. POPULATION: A total of 26,867 women with singleton pregnancies attending for routine antenatal care. METHODS: Transvaginal sonographic measurement of cervical length was carried out at 20(+0) to 24(+6) weeks. Logistic regression analysis was used to determine the significant predictors of sPD among maternal characteristics, obstetric history, previous history of LLETZ and cervical length. MAIN OUTCOME MEASURES: Spontaneous preterm delivery. RESULTS: In the 473 women who had undergone LLETZ, compared with the 25,772 without a history of LLETZ, the rate of sPD before 34 weeks of gestation was higher (3.4 versus 1.3%, P = 0.0002) and the median cervical length was shorter (32 mm versus 34 mm, P < 0.0001). Regression analysis demonstrated that in the prediction of sPD there were significant contributions from racial origin, cigarette smoking, previous preterm delivery and LLETZ and the detection rate of sPD was 29.8%, at a false-positive rate of 10%. However, after addition of cervical length, LLETZ did not remain a significant predictor in the model, which detected 52.6% of sPD, at a false-positive rate of 10%. CONCLUSIONS: LLETZ increases the risk of sPD, even after adjustment for maternal risk factors. The effect of a previous LLETZ on sPD in a subsequent pregnancy is reflected in the measurement of cervical length at mid-gestation.

Protocol for measurement of mean arterial pressure at 11-13 weeks' gestation.

OBJECTIVES: To identify the best protocol for measurement of mean arterial pressure (MAP) in early pregnancy for the prediction of preeclampsia (PE). METHODS: This was a prospective study in singleton pregnancies attending for a routine hospital visit at 11-13 weeks' gestation when a minimum of four recordings of MAP were taken from each arm. The performance of screening for PE by different combinations of MAP was compared to the protocol of the National Heart Foundation of Australia (NHFA). RESULTS: The MAP was measured in 587 (2.4%) cases that developed PE and in 22,900 that were unaffected by hypertensive disorders in pregnancy. The area under the receiver operating characteristic curve (AUROC) for prediction of PE by MAP as recommended by the NHFA protocol was 0.773 (95% CI 0.768-0.778). This AUROC was not significantly different from the AUROC obtained by the average MAP of the first three measurements from one arm (0.765, 95% CI 0.760-0.771) or the average of the first (0.766, 95% CI 0.760-0.771), the first two (0.771, 95% CI 0.766-0.777), or the first three measurements from the two arms (0.773, 95% CI 0.768-0.778). CONCLUSION: Performance of screening for PE by taking the average of a minimum of two measurements from both arms is comparable to the NHFA protocol.

Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11-13 weeks.

OBJECTIVE: To examine the performance of screening for pre-eclampsia (PE) and gestational hypertension (GH) by a combination of maternal factors and various biophysical and biochemical markers at 11-13 weeks' gestation. METHODS: This was a case-control study of 26 cases of early PE, 90 of late PE, 85 of GH and 201 unaffected controls. Maternal history was recorded, the uterine artery with the lowest pulsatility index (L-PI) and mean arterial pressure (MAP) were measured and stored plasma and serum were analyzed for placental growth factor (PlGF), inhibin-A, activin-A, tumor necrosis factor receptor-1, matrix metalloproteinase-9, pentraxin-3 and P-selectin. RESULTS: Multivariate logistic regression analysis demonstrated that significant prediction for early PE was provided by maternal factors, MAP, uterine artery L-PI and serum PlGF. Significant prediction of late PE was provided by maternal factors, MAP, uterine artery L-PI, PlGF, activin-A and P-selectin. For GH significant prediction was provided by maternal factors, MAP, uterine artery L-PI and activin-A. In screening by a combination of maternal factors, biophysical and biochemical markers the estimated detection rates, at a 5% false-positive rate, were 88.5% (95% CI, 69.8-97.4%) for early PE, 46.7% (95% CI, 36.1-57.5%) for late PE and 35.3% (95% CI, 25.2-46.4%) for GH. CONCLUSION: Combined biophysical and biochemical testing at 11-13 weeks could effectively identify women at high risk for subsequent development of hypertensive disorders in pregnancy.

First-trimester maternal serum pregnancy-associated plasma protein-A and pre-eclampsia.

OBJECTIVES: To examine the relationship between low maternal serum pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks with subsequent development of pre-eclampsia (PE). METHODS: UtA-PI and serum PAPP-A were measured in women attending for routine care at 11+0 to 13+6 weeks of gestation. In the population, 156 (1.9%) women developed PE, including 32 (0.4%) in whom delivery was before 34 weeks (early PE) and 124 (1.5%) with delivery at 34 weeks or more (late PE); 7895 (98.1%) women had no PE. Regression analysis was used to examine which of the factors amongst maternal characteristics, log PAPP-A multiples of the median (MoM) and log UtA-PI MoM contributed to the prediction of PE. RESULTS: The median PAPP-A MoM was 1.002 (interquartile range (IQR), 0.685-1.411) in the unaffected group, 0.555 (IQR, 0.463-0.922) in early PE and 0.911 (IQR, 0.580-1.247) in late PE. Serum PAPP-A was below the 5th centile in 21.9% of early PE and 6.5% of late PE cases. The PAPP-A-related patient-specific risk for PE was strongly influenced by maternal characteristics. There was a significant association between log UtA-PI MoM and log PAPP-A MoM (P=0.001), and the detection rate of screening for PE by maternal variables and UtA-PI was not improved by inclusion of PAPP-A. Regression analysis was used to establish tables that allow modification of the maternal history and PAPP-A-related patient-specific risk for PE by the measurement of UtA-PI. CONCLUSIONS: Low PAPP-A is a marker for subsequent development of PE. The PAPP-A-related patient-specific risk for PE can be modified by the measurement of UtA-PI.

First-trimester maternal serum tumor necrosis factor receptor-1 and pre-eclampsia.

OBJECTIVES: To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-alpha (TNF-R1) at 11-13 weeks of gestation in pregnancies that subsequently develop pre-eclampsia is different from that in women without this complication. METHODS: The concentration of TNF-R1 at 11 + 0 to 13 + 6 weeks was measured in samples from 128 cases that subsequently developed pre-eclampsia and 569 controls with no pregnancy complications. TNF-R1 and uterine artery pulsatility index (UtA-PI) values were expressed as multiples of the median (MoM) adjusted for maternal factors. The distributions of log TNF-R1 MoM and log UtA-PI MoM in the control and pre-eclampsia groups were compared. Logistic regression analysis was used to determine whether a significant contribution is provided by maternal factors, TNF-R1 and UtA-PI in predicting pre-eclampsia. The performance of screening was determined by analysis of receiver-operating characteristics curves. RESULTS: Median TNF-R1 and UtA-PI were significantly higher in the pre-eclampsia group (TNF-R1, 1.062 MoM; UtA-PI, 1.301 MoM) than in the control group (TNF-R1, 0.996 MoM; UtA-PI, 1.037 MoM). There was no significant association between TNF-R1 and gestational age at delivery, birth weight percentile or UtA-PI. Logistic regression analysis demonstrated significant contributions to the detection of pre-eclampsia from maternal factors and UtA-PI but not from TNF-R1. CONCLUSIONS: In pregnancies developing pre-eclampsia the maternal serum TNF-R1 concentration at 11-13 weeks of gestation is increased, but the level of TNF-R1 is not associated with the degree of impairment in placental perfusion or the severity of pre-eclampsia. Measurement of serum TNF-R1 does not improve the prediction of pre-eclampsia provided by screening based on a combination of maternal factors and UtA-PI.

Maternal serum placental growth factor at 11-13 weeks in chromosomally abnormal pregnancies.

OBJECTIVES: To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for trisomy 21 and other major chromosomal abnormalities. METHODS: The maternal serum concentration of PlGF at 11 + 0 to 13 + 6 weeks was measured in 609 euploid and 175 chromosomally abnormal pregnancies, including 90 with trisomy 21, 28 with trisomy 18, 19 with trisomy 13, 28 with Turner syndrome and 10 with triploidy. The levels of PlGF were compared in cases and controls, and were assessed for association with free beta-human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A). RESULTS: Logistic regression analysis demonstrated in the euploid group that significant independent contributions for log PlGF were provided by fetal crown-rump length, maternal weight, cigarette smoking and ethnic origin; after correction for these variables the median multiple of the median (MoM) PlGF was 0.991. Significantly lower values were observed in pregnancies with trisomy 21 (0.707 MoM), trisomy 18 (0.483 MoM), trisomy 13 (0.404 MoM), triploidy (0.531 MoM) and Turner syndrome (0.534 MoM). Significant contributions in the prediction of trisomy 21 were provided by maternal age, serum PlGF, PAPP-A and free beta-hCG, and the detection rates of screening with the combination of these variables were 70% and 80% at respective false-positive rates of 3% and 5%. CONCLUSIONS: Maternal serum PlGF concentration at 11-13 weeks of gestation is potentially useful in first-trimester screening for trisomy 21 and other major chromosomal abnormalities.

Hypertensive disorders in pregnancy: screening by uterine artery Doppler at 11-13 weeks.

OBJECTIVES: To examine the performance of screening for hypertensive disorders in pregnancy by a combination of the maternal factor-derived a-priori risk with the uterine artery (UtA) pulsatility index (PI) and to determine whether it is best in such screening to use the mean PI of the two arteries, the highest PI or the lowest PI. METHODS: This was a prospective screening study for pre-eclampsia (PE) requiring delivery before 34 weeks (early PE), late PE and gestational hypertension (GH) in women attending their routine first hospital visit in pregnancy at 11 + 0 to 13 + 6 weeks of gestation. Maternal history was recorded and color flow Doppler imaging was used to measure the left and right UtA-PI. The performance of screening for PE and GH by a combination of the maternal factor-derived a-priori risks determined in a previous study and the UtA-PI was assessed. RESULTS: There were 8061 (96.4%) cases unaffected by PE or GH, 37 (0.4%) that developed early PE, 128 (1.5%) with late PE and 140 (1.7%) with GH. The lowest, mean and highest UtA-PI were significantly higher in early PE and late PE than in the controls (P < 0.0001) and in early PE than late PE (P < 0.0001). The lowest UtA-PI was higher in GH than in controls (P = 0.014). The best performance in screening was provided by the lowest PI. The detection rate of early PE at a 10% false-positive rate increased from 47% in screening by maternal factors alone to 81% in screening by maternal factors and the lowest UtA-PI. The respective detection rates for late PE increased from 41% to 45% and those for GH increased from 31% to 35%. CONCLUSIONS: The patient-specific risk for PE and GH can be derived by combining the disease-specific maternal factor-derived a-priori risk with the measurement of the lowest UtA-PI in a multivariate regression model.