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Objective: Serum pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) at 11-13 weeks' gestation are reduced in pregnancies with fetal trisomy and in those that subsequently develop pre-eclampsia (PE). In screening for trisomy, the established biochemical marker is PAPP-A, whereas in screening for PE, the preferred marker is PlGF. The objective of this study was to examine the impact of replacing PAPP-A by PlGF in first-trimester screening for trisomies 21, 18 and 13 by maternal age, fetal nuchal translucency thickness (NT) and free β-human chorionic gonadotropin (β-hCG).Methods: This was a prospective screening study in singleton pregnancies for trisomies 21, 18 and 13 by a combination of maternal age, fetal NT and serum PAPP-A and free β-hCG at 11-13 weeks' gestation in which we also measured PlGF. Multiples of the median (MoM) values were calculated for PAPP-A, free β-hCG and PlGF. The dataset was split randomly into training and test datasets of roughly equal size, and the parameters for PlGF obtained from the training dataset were used in risk calculation for the test dataset. Standardized detection rates were computed by obtaining the likelihood ratios for biochemistry and fetal NT for trisomy-21, -18 and -13 pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific detection rates. These were then weighted according to the maternal age distributions of trisomy-21, -18 and -13 pregnancies in England and Wales in 2018. Similarly, standardized false-positive rates (FPR) were computed by obtaining the likelihood ratios for biochemistry and NT, as appropriate, in normal pregnancies in the sample and then applying these to each year of maternal age from 12 to 50 to estimate the age-specific FPRs. A modeling approach was used to assess the performance of screening according to gestational age at biochemical testing.Results: The study population of 71 266 pregnancies included 70 858 (99.4%) with normal fetal karyotype or birth of a phenotypically normal neonate and 263 with trisomy 21, 109 with trisomy 18 and 36 with trisomy 13. There are five main findings of this study. First, the performance of screening for trisomy by the first-trimester combined test or the combined test in which PAPP-A is replaced by PlGF is substantially better at 11 than at 13 weeks' gestation; for example, the detection rates of trisomy 21 by the combined test were 94%, 90% and 84%, at 5% FPR, when testing was carried out at 11, 12 and 13 weeks, respectively, and the corresponding values in screening by a test in which PAPP-A is replaced by PlGF were 90%, 87% and 86%, respectively. Second, in trisomy-21 pregnancies, the deviation of median PAPP-A MoM from normal decreases with increasing gestational age, whereas the deviation in PlGF does not change with gestational age. Third, the performance of screening for trisomy 21 during the 11th and 12th gestational weeks is superior if screening includes PAPP-A rather than PlGF, whereas during the 13th week the performance is slightly higher with the use of PlGF rather than PAPP-A. Fourth, in our population with mean gestational age at testing of 12.7 weeks, screening by maternal age, fetal NT, serum free β-hCG and serum PAPP-A predicted 88%, 96% and 97% of cases of fetal trisomies 21, 18 and 13, respectively, at a FPR of 5%; the respective values in screening by a test in which PAPP-A is replaced by PlGF were 85%, 96% and 96%. Fifth, addition of serum PlGF does not improve the prediction of trisomy provided by maternal age, fetal NT and serum free β-hCG and PAPP-A.Conclusion: In first-trimester screening for trisomy, the preferred biochemical marker is PAPP-A rather than PlGF, especially when biochemical testing is carried out during the 11th week of gestation or earlier. However, if PlGF was to be used rather than PAPP-A, the same detection rate can be achieved but at a higher FPR. This may be an acceptable compromise to minimize cost and achieve effective screening for both trisomy and PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: Fetal hydrops is associated with increased perinatal morbidity and mortality. The etiology and outcome of fetal hydrops may differ according to the gestational age at diagnosis. The aim of this study was to evaluate the cause, evolution and outcome of non-immune fetal hydrops (NIFH), according to the gestational age at diagnosis.Methods: This was a retrospective cohort study of all singleton pregnancies complicated by NIFH, at the Fetal Medicine Unit at St George's University Hospital, London, UK, between 2000 and 2018. All fetuses had detailed anomaly and cardiac ultrasound scans, karyotyping and infection screening. Prenatal diagnostic and therapeutic intervention, gestational age at diagnosis and delivery, as well as pregnancy outcome, were recorded. Regression analysis was used to test for potential association between possible risk factors and perinatal mortality.Results: We included 273 fetuses with NIFH. The etiology of the condition varied significantly in the three trimesters. Excluding 30 women who declined invasive testing, the cause of NIFH was defined as unknown in 62 of the remaining 243 cases (25.5%). Chromosomal aneuploidy was the most common cause of NIFH in the first trimester. It continued to be a significant etiologic factor in the second trimester, along with congenital infection. In the third trimester, the most common etiology was cardiovascular abnormality. Among the 152 (55.7%) women continuing the pregnancy, 48 (31.6%) underwent fetal intervention, including the insertion of pleuroamniotic shunts, fetal blood transfusion and thoracentesis. Fetal intervention was associated significantly with lower perinatal mortality (odds ratio (OR), 0.30 (95% CI, 0.14-0.61); P < 0.001); this association remained significant after excluding cases with a diagnosis of anemia or infection (OR, 0.29 (95% CI, 0.13-0.66); P = 0.003). In 104 fetuses not undergoing active fetal intervention, the gestational age at diagnosis was the only parameter that was significantly associated with the risk of perinatal mortality (OR, 0.92 (95% CI, 0.85-0.99); P = 0.035), while the affected body cavity and polyhydramnios were not (P > 0.05).Conclusions: An earlier gestational age at diagnosis of NIFH was associated with an increased risk of aneuploidy and worse pregnancy outcome, including a higher risk of perinatal loss. Fetal therapy was associated significantly with lower perinatal mortality. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the natural history and outcome of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancy, according to gestational age at onset and various reported diagnostic criteria, and to quantify the risk of superimposed twin-to-twin transfusion syndrome (TTTS).Methods: This was a cohort study of MCDA twin pregnancies that had their routine antenatal care from the first trimester at St George's Hospital, London, UK. Pregnancies had ultrasound examinations every 2 weeks at 16-24 weeks and then every 2-3 weeks until delivery. The diagnostic criteria for sFGR were estimated fetal weight (EFW) of one twin < 10th centile and intertwin EFW discordance ≥ 25%. We also applied other diagnostic criteria reported in a recent Delphi consensus. Pregnancies in which the diagnosis of TTTS was made before that of sFGR were not included in the analysis. Pregnancies that underwent fetal intervention for sFGR were excluded. The incidence of sFGR was compared between the different diagnostic criteria, overall and according to gestational age at onset. In all subsequent analyses, cases of sFGR included those diagnosed according to any of the criteria. The Gratacós classification of sFGR was applied (Type I, II or III). Pregnancy outcomes included miscarriage, intrauterine death, neonatal death and admission to the neonatal unit. Comparisons between groups were carried out using the Mann-Whitney U-test for continuous variables and the chi-square or Fisher's exact test for categorical variables.Results: The analysis included 287 MCDA twin pregnancies. According to the International Society of Ultrasound in Obstetrics and Gynecology diagnostic criteria, the incidence of early (< 24 weeks) sFGR was 4.9%, while that of late sFGR was 3.8%. When applying the various diagnostic criteria, the incidence of early sFGR varied from 1.7% to 9.1% and that of late sFGR varied from 1.1% to 5.9%. In early-onset cases, the incidence of Type I sFGR was 80.8%, that of Type II was 15.4% and that of Type III was 3.8%. The corresponding figures in late-onset cases were 94.4%, 5.6% and 0%. The incidence of superimposed TTTS was 26.9% in cases affected by early-onset sFGR and 5.6% in those affected by late-onset sFGR. The incidence of perinatal death was 8.0% in early-onset sFGR and 5.6% in late-onset sFGR (P = 0.661). Admission to the neonatal unit occurred in 61.0% and 52.9% of cases, respectively (P = 0.484).Conclusions: In MCDA twin pregnancies, early-onset sFGR is slightly more common than is late-onset sFGR, although this difference was not significant, and is associated with worse perinatal outcome. The incidence of Types II and III sFGR is higher in early-onset sFGR. The incidence also varies according to the diagnostic criteria used, which supports the use of standardized international diagnostic criteria. Superimposed TTTS is more common in early- than in late-onset sFGR. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: The M6 risk-prediction model was published as part of a two-step protocol using an initial progesterone level of ≤ 2 nmol/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step 2). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two-step protocol in clinical practice by evaluating the number of protocol-related adverse events and how effectively patients were triaged.Methods: This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP/PPUL as high-risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was ≤ 2 nmol/L, patients were discharged and were asked to have a follow-up urine pregnancy test in 2 weeks to confirm a negative result. If the progesterone level was > 2 nmol/L or a measurement had not been taken, hCG level was measured again at 48 h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as 'low risk, probable FPUL' were advised to perform a urine pregnancy test in 2 weeks and those classified as 'low risk, probable IUP' were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP ≥ 5%) she was reviewed clinically within 48 h. One center used a progesterone cut-off of ≤ 10 nmol/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics.Results: Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow-up, while 330 were evaluated using a progesterone cut-off of ≤ 10 nmol/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone ≤ 2 nmol/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445/2625 PUL (55.0%) were classified as low risk, of which 15 (1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty-two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines.Conclusions: This study has shown that the two-step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To estimate the patient-specific risk of pre-eclampsia (PE) at 35-37 weeks' gestation by a combination of maternal characteristics and medical history with multiples of the median (MoM) values of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), and stratify women into high-, intermediate- and low-risk management groups.Methods: This was a prospective observational study in women attending a third-trimester ultrasound scan at 35-37 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at < 4 weeks from assessment and PE at < 42 weeks' gestation were calculated using the competing-risks model to combine the prior risk from maternal characteristics and medical history with MoM values of MAP, UtA-PI, PlGF and sFlt-1. On the basis of these risks, the population was stratified into high-, intermediate- and low-risk groups. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category and the performance of screening for delivery with PE at < 40 and ≥ 40 weeks' gestation was estimated.Results: The study population of 3703 singleton pregnancies included 38 (1.0%) with PE < 40 weeks' gestation and 22 (0.6%) with PE ≥ 40 weeks. Using a risk cut-off of 1 in 50 for PE delivering at < 4 weeks after assessment to define the high-risk group and a risk cut-off of < 1 in 100 for PE delivering at < 42 weeks' gestation to define the low-risk group, the proportion of the population stratified into high, intermediate and low risk was 12.7%, 28.8% and 58.5%, respectively. The high-risk group contained 92% of pregnancies with PE at < 40 weeks' gestation and 73% of those with PE at ≥ 40 weeks. The intermediate-risk group contained a further 27% of women with PE at ≥ 40 weeks. In the low-risk group, none of the women developed PE at < 40 or ≥ 40 weeks' gestation.Conclusion: The study presents risk stratification of PE by the combined test at 35-37 weeks, aiming to identify a high-risk group in need of intensive monitoring from the time of the initial assessment and up to 40 weeks' gestation, an intermediate-risk group in need of reassessment at 40 weeks' gestation and a low-risk group that can be reassured that they are unlikely to develop PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of chronic hypertension (CH), with and without superimposed pre-eclampsia (PE), on the incidence of a small-for-gestational-age (SGA) neonate and to explore the possible mechanism for such association.Methods: Data for this study were derived from prospective screening for adverse pregnancy outcomes in women with singleton pregnancy attending 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 maternal and pregnancy characteristics, and incidence of SGA were compared between those with and those without CH in the total population and in the subgroups of pregnancies 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 those without CH.Results: The study population constituted 74 226 pregnancies, including 1052 (1.4%) with CH and 73 174 without CH. PE developed in 233 (22.1%) cases of the group with CH and in 1662 (2.3%) of those without CH. In the group that developed PE, there was no significant difference for either median birth-weight Z-score or incidence of SGA between those with CH and those without CH. In the group without PE, the incidence of SGA was twice as high in those with CH than in those without. There was a significant association between log10 MAP multiples of the median and incidence of SGA and PE, which was more marked in those with CH than in those without.Conclusion: CH is associated with an increased risk of SGA and PE and this is related to MAP at 11-13 weeks' gestation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential value of repeat measurements of uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP) and serum placental growth factor (PlGF) at 12, 22 and 32 weeks' gestation in the prediction of pre-eclampsia (PE) developing after 32 weeks.Methods: Data were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 11-13, 19-24 and/or 30-34 weeks' gestation in two maternity hospitals in England. UtA-PI, MAP and PlGF were measured. Bayes' theorem was used to combine the a-priori risk from maternal factors with UtA-PI, MAP and PlGF multiples of the median values. The performance of screening for PE developing after the 30-34-week visit by UtA-PI, MAP and PlGF measured at 11-13, 19-24 and 30-34 weeks and their combinations was examined.Results: Screening at 30-34 weeks by UtA-PI, MAP and PlGF detected, at a 10% false-positive rate, 79%, 86% and 92% of preterm PE and 42%, 50% and 56% of term PE. The addition of biomarker values at 11-13 and/or 19-24 weeks was not associated with any improvement in the detection rate of preterm PE; in the case of term PE, there was a marginal (< 2%) improvement in detection for UtA-PI and MAP and a modest improvement of about 5% for PlGF.Conclusion: Measurements of UtA-PI, MAP and PlGF in the first and/or second trimester have a small or no effect on improving the prediction of PE provided by screening in the early third trimester. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between chronic hypertension (CH) and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics.Methods: This was a prospective screening study for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. Data on maternal characteristics, medical and obstetric history and pregnancy outcome were collected. Regression analysis was performed to examine the association between CH and adverse pregnancy outcomes, including late miscarriage, stillbirth, pre-eclampsia (PE), gestational diabetes mellitus (GDM), spontaneous and iatrogenic preterm birth (PTB), small-for-gestational-age (SGA) neonate, large-for-gestational-age (LGA) neonate and elective and emergency Cesarean section (CS).Results: The study population of 109 932 pregnancies included 1417 (1.3%) women with CH. After adjusting for potential confounding variables from maternal characteristics, medical and obstetric history, CH was associated with increased risk of stillbirth (odds ratio (OR), 2.38 (95% CI, 1.51-3.75)), PE (OR, 5.76 (95% CI, 4.93-6.73)), SGA (OR, 2.06 (95% CI, 1.79-2.39)), GDM (OR, 1.61 (95% CI, 1.27-2.05)), iatrogenic PTB < 37 weeks (OR, 3.73 (95% CI, 3.07-4.53)) and elective CS (OR, 1.79 (95% CI, 1.52-2.11)), decreased risk of LGA (OR, 0.65 (95% CI, 0.53-0.78)) and had no significant effect on late miscarriage, spontaneous PTB or emergency CS.Conclusion: CH should be combined with other maternal characteristics and medical and obstetric history when calculating an individualized adjusted risk for adverse pregnancy complications. CH increases the risk of stillbirth, PE, SGA, GDM, iatrogenic PTB and elective CS and reduces the risk for LGA. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To identify whether preterm surveillance clinics (PSCs) risk-stratify high-risk women accurately by comparing outcomes of those admitted to hospital on the basis of asymptomatic testing with those not admitted.Methods: We performed a subanalysis from a larger prospective cohort study on sonographic cervical length, quantitative fetal fibronectin (qfFN) and risk of spontaneous preterm birth. We identified 1130 asymptomatic singleton pregnancies at high risk of preterm birth, screened between 23 and 28 weeks of gestation at a PSC in a tertiary hospital in London, UK. Gestational age at delivery, the proportion of preterm births that delivered < 30 weeks and neonatal outcomes were compared between women admitted electively when asymptomatic as a consequence of screening-test results and those who were not routinely admitted.Results: In total, 66 (6%) women attending the PSC were admitted to hospital following asymptomatic screening (inpatient group). The mean gestational age at delivery for those not admitted electively (outpatient group) was at term and was significantly higher than that of those admitted from PSC (38.4 vs 31.2 weeks; P < 0.0001). Preterm birth < 30 weeks' gestation was rare in the outpatient group relative to those admitted (1.32% vs 36.4%; P < 0.0001). Neonatal mortality was 0.188% in the outpatient group compared with 4.55% in those admitted electively (P < 0.0001). The incidence of other complications such as neonatal death, 5-min Apgar score < 7, special care baby unit/neonatal intensive care unit admission, respiratory distress syndrome, intraventricular hemorrhage and low birth weight were significantly lower in those managed as outpatients than in those admitted electively.Conclusion: PSCs measuring cervical length and qfFN accurately triage asymptomatic high-risk pregnant women, enabling those at highest risk of adverse outcome to be identified for elective admission to hospital and appropriate management. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to solicit views from those with personal experience with cystic fibrosis (CF) on the aspects of the condition that are most important to include in prenatal screening materials. The researchers detail the study design, participants and setting, data collection procedure and outcomes. The study highlights the challenge of a complex genetic condition in a balanced and accurate screening information.

Background: Pregnant women with hepatitis B virus (HBV) infection can transmit the infection to their infants, screening of patients and appropriate interventions reduce vertical transmission. This audit was conducted to assess adherence to the national guidelines for management of HBV infection in pregnancy.Methods: A retrospective audit was conducted on pregnant women diagnosed with hepatitis B on screening in antenatal clinics, across four hospitals in London over 2 years (2009-2010). Data was collected from antenatal records and discharge summaries using a standard audit form. The outcomes measured included HBV serological markers, HBV DNA, detection of other blood borne viruses and referral to hepatology services, administration of active and passive prophylaxis to infants at birth. Descriptive statistics are presented. Proportions were compared using the χ2 test and 95% confidence intervals (CI) were calculated for prevalence estimates. Analyses were conducted using STATA 12.Results: HBsAg was detected in 1.05% (n = 401, 95% CI 0.95-1.16) of women attending an antenatal appointment, 12% (n = 48) of the women were at a high risk of vertical transmission (HBe Ag positive or antiHBe and HBeAg negative or HBV DNA >106 IU/ml). Only 62% (n = 248) women were referred to hepatology or specialist clinics and 29% (n = 13) of women of high infectivity were on antiviral agents. Testing for hepatitis C and delta virus was suboptimal. 75% (n = 36) of the infants at a high risk of acquisition of HBV received both active and passive prophylaxis.Conclusion: In certain sectors of London, implementation of the pathway for management of women with hepatitis B and their infants is suboptimal. National guidelines should be followed and improved intersectorial sharing of information is needed to reduce the risk of women of high infectivity being lost to follow up. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of the introduction of a Down syndrome screening policy in England, including implementation of the first-trimester combined screening test, on reducing prenatal invasive diagnostic procedure rates. Methods All English cytogenetic laboratories were asked to submit data from the fiscal years 2003/2004 until 2011/2012 on all samples received from prenatal invasive procedures, including those that were undertaken following a higher-risk Down syndrome screening result. Results There was a gradual decline in the number of invasive procedures undertaken subsequent to a positive Down syndrome screening result in England, from 36?968 in 2003/2004 to 11?446 in 2008/2009, with only a relatively small subsequent decrease, to 10?215, in 2011/2012. This corresponds to a 72% reduction in the number of referrals received by the cytogenetic laboratories over a 9-year period and correlates with the national policy of implementing the combined screening test in place of second-trimester screening, which has reduced the overall screen-positive rate to 3.1% from an initial level of 6.0%. Conclusions Implementation of a national Down syndrome screening policy based on the combined screening test has significantly reduced the number of invasive tests performed. However, as the combined screening test has become the replacement for second-trimester testing and has been almost completely implemented it appears that improvements in screening using current approaches may have reached their limits. [ABSTRACT FROM AUTHOR]

Objective To estimate the pre-eclampsia screening performance of placental growth factor (PlGF) and endoglin with second-trimester Quadruple test markers used for antenatal Down's syndrome screening. Methods A nested case-control study of 88 pregnant women with known early second-trimester Down's syndrome Quadruple test marker levels who subsequently developed pre-eclampsia and 275 unaffected controls. Frozen maternal serum samples were thawed and assayed for PlGF and endoglin. Monte Carlo simulation was used to estimate the pre-eclampsia screening performance of a pre-eclampsia detection algorithm using the Quadruple test markers with or without the addition of PlGF and/or endoglin. Results Median PlGF was 33% lower (95% confidence interval 24-41%) and endoglin 31% (20- 43%) higher in pre-eclampsia than in unaffected pregnancies. Adding PlGF to the Quadruple test markers increased the pre-eclampsia detection rate from 34% to 45% at a 5% false-positive rate -- it increased it to 43% with endoglin and to 50% with both. The corresponding estimates for early pre-eclampsia (before 36 weeks' gestation) were a few percentage points higher (48%, 48% and 55% respectively). Including information on parity, pre-eclampsia in a previous pregnancy, family history (woman's mother) and assuming a pre-eclampsia prevalence of 2%, the detection rates for a 5% false-positive rate were 39% with the Quadruple test markers, 48% with addition of endoglin, 49% with addition of PlGF, and 54% with addition of both. Conclusions Adding PlGF to the Quadruple test Down's syndrome screening markers improves preeclampsia screening performance. There is a modest extra benefit in also adding the measurement of endoglin. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the prevalence of vitamin D deficiency in the antenatal patients attending North Middlesex University Hospital between March 2008 and March 2009. Study design: A prospective study of maternal levels of vitamin D at booking. Results: The prevalence of both deficient and insufficient levels of 25[OH]D was 87.6% across all included patients. Conclusion: There is a high prevalence of asymptomatic vitamin D deficiency in the antenatal booking population. [ABSTRACT FROM AUTHOR]

Objective To provide current population-based prevalence and prenatal diagnosis rates (PND) for specified major congenital anomalies in England and Wales to enable monitoring of the Fetal Anomaly Screening Programme (FASP). Design Secondary analysis of prospectively collected registry data. Setting Seven multiple-source, population-based congenital anomaly registers, members of the British Isles Network of Congenital Anomaly Registers (BINOCAR) in 2005 and 2006. Population 2,883 births with congenital anomalies from a total of 601,545 live and stillbirths. Main outcome measures PND and birth prevalence of selected congenital anomaly groups/ subtypes (anencephaly, spina-bifida, serious cardiac, diaphragmatic hernia, gastroschisis, exomphalos, bilateral renal agenesis, lethal/severe skeletal dysplasia, cleft lip with or without cleft palate [CL + /−P]). Results Of the selected anomaly groups, the most frequently reported were serious cardiac (14.1 per 10,000 births [95% CI 13.0−15.2]) and CL + /−P (9.7 per 10,000 births [8.9-10.5]); the least frequent were bilateral renal agenesis and lethal/severe skeletal dysplasia (<1.5 per 10,000 births). The PND varied for different anomalies from 53.1% (95% CI 43.5-65.2) for serious cardiac anomalies to 99.6% (95% CI 97.9-100.0) for anencephaly. Least variation in PND rates was for anencephaly (range 98.9-100%) and gastroschisis (93.5-100%); greatest variation was for serious cardiac (43.5-65.2%) and lethal/severe skeletal dysplasias (50.0-100%). Conclusions BINOCAR registers can, uniquely, provide contemporary data on PND and birth prevalence rates to enable monitoring of the ultrasound component of FASP at a national and regional level, allowing comparisons between populations to be made, planning of resources facilitated and assistance for parents making informed decisions on whether to enter the screening programme. [ABSTRACT FROM AUTHOR]

The role of applied theatre in engaging both lay and professional publics with debate on health policy and practice is an emergent field. This paper discusses the development, production performance and discussion of 'Inside View'. The objectives were to produce applied theatre from research findings of a completed study on genetic prenatal screening, exploring the dilemmas for women and health professionals of prenatal genetic screening, and to engage audiences in debate and reflection on the dilemmas of prenatal genetic screening. 'Inside View' was developed from a multidisciplinary research study through identification of emergent themes from qualitative interviews, and development of these by the writer, theatre producer and media technologist with input from the researchers. Inside View was performed in London and the Midlands to varied audiences with a panel discussion and evaluation post performance. The audiences were engaged in debate that was relevant to them professionally and personally. Knowledge translation through applied theatre is an effective tool for engaging the public but the impact subsequently is unclear. There are ethical issues of unexpected disclosure during discussion post performance and the process of transforming research findings into applied theatre requires time and trust within the multidisciplinary team as well as adequate resourcing. [ABSTRACT FROM AUTHOR]

Objective To illustrate regional changes that occurred in screening for Down's syndrome (trisomy 21) in England and Wales from 1989 to 2008. Methods The National Down Syndrome Cytogenetic Register has collected data on all ante- and postnatal diagnoses of Down's syndrome in England and Wales since 1989 (n = 27,954). The percentages of (i) diagnoses made antenatally, (ii) antenatal diagnoses that had nuchal translucency (NT) measured, and (iii) antenatal diagnoses in mothers aged 37 and over with advanced maternal age as the sole recorded indication for diagnosis are presented according to where the mother lived Government Office Region), year of diagnosis (1989-1994, 1995-2000, 2001-2006, 2007-2008), and maternal age (<37 years, ≥37 years). Results The percentage of cases diagnosed antenatally has increased in younger women but varies between regions. It remained relatively constant at approximately 70% in older women. The use of NT measurement in antenatal screening has expanded rapidly but varies regionally, being most common in London and the South East where, in 2007-2008, over 75% of antenatal diagnoses in older women had NT measured. The sole indication of advanced maternal age has substantially reduced, and was less than 10% in older mothers in all regions in 2007-2008. Conclusions There are regional and maternal age variations in Down's syndrome screening and diagnosis. Some regions used NT measurements, and eliminated advanced maternal age as sole reason for antenatal diagnostic testing more quickly than others. The reasons for variations need to be identified and addressed to ensure that when new screening techniques become available, regional differences are minimized. [ABSTRACT FROM AUTHOR]

The article presents a study on acute infection as a major cause of infant mortality on more than 1,000 children born in Newcastle, England in 1947. The current sample of cohorts are survivors of the original cohorts in the 1947 study. Data were collected using analysis of antenatal charts of mothers, housing surveys and educational and growth data from schools. Findings of the study include data on health and development, mental health and cognition and respiratory health.

We carried out an audit of antenatal screening for Down's syndrome using the Integrated test (which provides a single screening result from information collected in the late first and early second trimesters of pregnancy) which was introduced into routine antenatal care at two London hospitals, University College Hospital (UCH) and St Mary's Hospital, in 2003-4. The audit was based on 15,888 women who accepted screening and booked in the first trimester. The Down's syndrome detection rate was 87% (95% confidence interval [CI], 74-95) consistent with an expected detection rate of 89% based on applying the estimates of screening performance of the Serum, Urine and Ultrasound Screening Study (SURUSS) to the maternal age distribution of women who were screened at UCH and St Mary's. The observed false-positive rate was 2.1% (95% CI, 1.9-2.3), compared with an expected of 2.5% for women of the same age. An audit trail (conducted at UCH) indicated that 98% (10,746/10,961) of women accepted integrated screening (2% having a first trimester test) and of these, 94% (10,116) completed both stages of the test. The audit demonstrated that it is feasible to conduct integrated screening within the NHS with a high acceptance rate and a screening performance consistent with that determined from previous research studies. [ABSTRACT FROM AUTHOR]

Objectives: To determine the prevalence of pregnancies with a neural tube defect (NTD) in England and Wales between 1964 and 2004 and to estimate the relative impact of antenatal screening and a change in the incidence of these defects on the prevalence of births with NTDs. Settings: Use of data published by the Office for National Statistics (ONS) on terminations of pregnancies with an NTD and births with an NTD from 1964 to 2004. Methods: Estimates were made of the total number of terminations of pregnancies and births with an NTD by taking account of the under-reporting of these terminations and births using a previously described method. In 1995 ONS started to report the number of terminations with an NTD rather than the total numbers of terminations with a central nervous system (CNS) malformation that had previously been used to estimate the number of NTD terminations. Adjustment was made for this and new estimates of the total number of NTD pregnancies were produced to 2004. Results: There were an estimated 969 pregnancies with NTDs (168 (17%) births and 801(83%) terminations) in England and Wales in 2004. An estimated 44% of NTD terminations and 32% of births were not reported as such. The birth prevalence per 1000 decreased fallen 93% from 3.6 in 1964 to 0.3 in 2004, 59% due to an underlying decrease in the prevalence of NTDs and 34% due to screening diagnosis and subsequent termination of affected pregnancies. Conclusion: The prevalence of NTD pregnancies decreased by around two per 1000 from 1964 to 1990 and thereafter remained fairly constant. The prevalence of NTD pregnancies is substantially underestimated if it is based only on reported NTD births (by 88%) and also if it is based on reported NTD births and terminations (by 52%), because most NTD pregnancies in England and Wales are terminated following antenatal screening and most of these terminations are not reported. [ABSTRACT FROM AUTHOR]

This qualitative cross-sectional survey, undertaken in the antenatal booking clinics of a hospital in central London, explores pregnant women's responses to routine HIV testing, examines their reasons for declining or accepting the test, and assesses how far their responses fulfil standard criteria for informed consent. Of the 32 women interviewed, only 10 participants were prepared for HIV testing at their booking interview. None of the women viewed themselves as being particularly at risk for HIV infection. The minority (n = 6) of the participants who declined testing differed from those who accepted, by interpreting test acceptance as risky behaviour, privileging the negative outcomes of HIV positivity and expressing an inability to cope with these, should they occur. Troublingly, only a minority of women (n = 9) had a broad understanding of the rationale for the test, and none fulfilled the standard criteria for informed consent. This study suggests that, although routine screening combined with professional recommendation may be successful in increasing uptake, this may be at the cost of eroding informed consent. Protecting third parties (notably fetuses) from a preventable disease may outweigh the moral duty of respecting autonomy, enshrined in Western bioethical tradition. Nevertheless, such a policy should be made transparent, debated in the public domain and negotiated with women seeking antenatal care. [ABSTRACT FROM AUTHOR]

Focuses on the antenatal services provided for pregnant women in England. Causes of delays in obtaining referral to a hospital antenatal clinic; Benefits of contact antenatal care; Information on the prenatal screening program for Down's syndrome patients in the region; Rate of pregnant women contacting the services.

Objectives: The proportion of Down's syndrome pregnancies detected prenatally in England and Wales is lower in younger mothers than in older mothers. This paper examines the reasons for this apparent age inequality. Methods: We used data from the National Down Syndrome Cytogenetic Register (NDSCR) to examine the time trend of the proportion of Down's syndrome pregnancies diagnosed prenatally according to maternal age over the years 1989–2004 in England and Wales. Results: A lower proportion of younger mothers had their Down's syndrome pregnancy detected prenatally than older mothers; however, this gap has been closing over time. For example, for mothers under 25 years of age only 13% of Down's syndrome pregnancies were detected prenatally from 1989 to 1992, with this figure rising to 34% in 2001–2004, compared with proportions of 74% in both periods for mothers over 44 years of age. A lower uptake of screening among younger women could not explain these differences. The differences in detection rates of the screening methods according to maternal age, particularly of the older screening tests, could account for these differences. Conclusions: The closing gap between the proportions of younger and older women having their affected pregnancy prenatally diagnosed is a confirmation of the improvement of screening methods over time. [ABSTRACT FROM AUTHOR]

This paper describes the successful implementation of universal antenatal screening for HIV and hepatitis B in Southampton and South West Hampshire Health Authority. This was achieved through formation of a multi‐disciplinary planning group of clinicians and managers from local trusts. The approach taken in implementing screening is described, key elements of this being the appointment of screening co‐ordinators and consultation with local midwives to ensure their training needs were addressed. Lessons for future work are discussed. [ABSTRACT FROM PUBLISHER]

Antenatal sickle and thalassaemia screening programmes are now established in most high prevalence areas in England. Although screening reliably detects β-thalassaemia trait, in many cases, results state that α-thalassaemia trait cannot be excluded. The detection of couples at risk of a child with hydrops fetalis is one of the aims of the national programme. We, therefore, performed polymerase chain reaction (PCR) for the common α-thalassaemia gene deletions to assess the usefulness of this technique in routine screening practice. Between August 2001 and August 2002, of the 5092 women booked at the antenatal clinic, 425 were found to have a mean corpuscular haemoglobin (MCH) <27 pg in the absence of β-thalassaemia trait; 189 (44.5%) had an MCH <25 pg. All 425 patients underwent PCR analysis for the common deletions: –SEA (South-East Asian), –MED (Mediterranean), -α20.5, –FIL (Filipino), -α 3.7 and -α 4.2 genotypes. In total, 130 (31%) women were positive for α-thalassaemia deletion; 86 (24.7%) were heterozygous for -α 3.7, 19 (4.4%) were homozygous for -α 3.7, 12 (2.8%) were heterozygous for -α 4.2, 1 (0.2%) was homozygous for -α 4.2, 11 (2.6%) were heterozygous for –SEA and one (0.2%) was heterozygous for the –MED genotype. Although the detection rate for α+-thalassaemia was high, a strategy of selective screening using MCH <25 pg and ethnic group (SEA, Middle East or Eastern MED) would have identified all individuals heterozygous for α0-thalassaemia. Routine molecular screening for all forms of α-thalassaemia trait is unjustified in antenatal screening. [ABSTRACT FROM AUTHOR]

Relates the story of the Michael Drummond, a health services researcher concerned with the management of the National Health Service in England. Personal experiences surrounding the birth of their second child; Detail on the antenatal received by Dummond's wife; Conclusions drawn based on the experience.