Improved contingent screening strategy increased trisomy 21 detection rate in the second trimester.

PURPOSE: This study aimed to establish suitable threshold values for biochemical indicators in low-risk pregnant women who underwent second trimester screening and design strategies for consecutive prenatal testing to increase trisomy 21 detection. METHODS: This study examined singleton pregnant women who underwent double, triple, or quadruple screening in the second trimester over six years. To obtain adequate detection efficiency for low-risk pregnancies, threshold values for serum biochemical indicators were established, and a cost-effectiveness assessment of the improved contingent screening strategy was conducted. RESULTS: Participants were included in serum double- (n = 88,550), triple- (n = 29,991), and quadruple-screening (n = 15,004) groups. Threshold values were defined as having a free beta subunit of human chorionic gonadotropin (free ß-hCG) multiple of the median (MoM) ≥ 2.50, alpha-fetoprotein (AFP) MoM ≤ 0.50, or unconjugated estriol (uE3) MoM ≤ 0.70 for low risk. Low-risk pregnancies, comprising 1.35% (988/73,183), 4.45% (1,171/26,286), and 11.91% (1,559/13,085) of the double-, triple-, and quadruple-screening groups, respectively, underwent further non-invasive prenatal screening. In the double-, triple-, and quadruple-screening groups, we detected 11.76% (2/17), 40.00% (2/5), and 66.67% (2/3) of trisomy 21 cases with false negative results, respectively, with the overall detection rates of 85.00% (85/100), 90.63% (29/32), and 95.24% (20/21), respectively, and decreased ratio of overall costs of 5.26%, 16.63%, and 24.36%, respectively. CONCLUSION: Utilizing threshold values of AFP, free ß-hCG, and uE3 to trigger further non-invasive prenatal screening may increase trisomy 21 detection in pregnancies deemed low risk in the second trimester while reducing the overall costs of screening strategies.

Antenatal reproductive screening for pregnant people including preconception: Provides the best reproductive opportunity for informed consent, quality, and safety.

INTRODUCTION: This antenatal screening review will include reproductive screening evidence and approaches for pre-conception and post-conception, using first to third trimester screening opportunities. METHODS: Focused antenatal screening peer-reviewed publications were evaluated and summarized. RESULTS: Evidenced-based reproductive antenatal screening elements should be offered and discussed, with the pregnancy planning or pregnant person, during Preconception (genetic carrier screening for reproductive partners, personal and family (including reproductive partner) history review for increased genetic and pregnancy morbidity risks); First Trimester (fetal dating with ultrasound; fetal aneuploidy screening plus consideration for expanded fetal morbidity criteria, if appropriate; pregnant person preeclampsia screening; early fetal anatomy screening; early fetal cardiac screening); Second Trimester for standard fetal anatomy screening (18-22 weeks) including cardiac; pregnant person placental and cord pathology screening; pregnant person preterm birth screening with cervical length measurement); Third Trimester (fetal growth surveillance; continued preterm birth risk surveillance). CONCLUSION: Antenatal reproductive screening has multiple elements, is complex, is time-consuming, and requires the use of pre- and post-testing counselling for most screening elements. The use of preconception and trimesters 'one to three' requires clear patient understanding and buy-in. Informed consent and knowledge transfer is a main goal for antenatal reproductive screening approaches.

Emphasis on Early Prenatal Diagnosis and Perinatal Outcomes Analysis of Apert Syndrome.

Apert syndrome is an inherited condition with autosomal dominant transmission. It is also known as acrocephalosyndactyly type I, being characterized by a syndrome of craniosynostosis with abnormal head shape, facial anomalies (median hypoplasia), and limb deformities (syndactyly, rhizomelic shortening). The association can suspect the prenatal diagnosis of these types of anomalies. The methodology consisted of revising the literature, by searching the PubMed/Medline database in which 27 articles were selected and analyzed, comprising 32 cases regarding the prenatal diagnosis of Apert syndrome. A series of ultrasound parameters, the anatomopathological abnormalities found, the obstetric results, and the genetic tests were followed. The distribution of imaging results (US, MRI) identified in the analyzed cases was as follows: skull-shaped abnormalities were evident in 96.8% of cases, facial abnormalities (hypertelorism 43.7%, midface hypoplasia 25%, proptosis 21.8%), syndactyly in 87.5%, and cardiovascular abnormalities in 9.3%. The anomalies detected by the ultrasound examination of the fetus were confirmed postnatally by clinical or gross evaluation or imaging. The management of these cases requires an early diagnosis, an evaluation of the severity of the cases, and appropriate parental counseling.

Comparison of competing-risks model with angiogenic factors in midgestation screening for preterm growth-related neonatal morbidity.

OBJECTIVES: First, to evaluate the predictive performance for preterm growth-related neonatal morbidity of high soluble fms-like tyrosine kinase-1 (sFLT-1) / placental growth factor (PlGF) ratio or low PlGF at mid-gestation, and second, to compare the performance of the high sFLT-1/PlGF ratio or low PlGF with that of the competing risks model for small for gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI). METHODS: This was a prospective observational study in women attending for a routine hospital visit at 19 to 24 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFLT-1. The primary outcome was delivery <32 and <37 weeks' gestation of SGA neonate with birth weight <10th or <3rd percentile for gestational age, combined with neonatal unit (NNU) admission for ≥48 hours or a composite of major neonatal morbidity. The detection rates in screening by either PlGF <10th percentile, sFLT-1/PlGF ratio >90th percentile and the competing risks model for SGA were estimated and they were compared using McNemar's test. RESULTS: In the study population of 40241 women prediction of preterm growth-related neonatal morbidity provided by the competing risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio. For example, at screen positive rate (SPR) of 10.0%, as defined by the sFLT-1/ PlGF ratio >90th percentile, the competing risks model predicted 70.1% (95% CI 61.0 - 79.2) of SGA <10th percentile and 76.9% (67.6-86.3) of SGA <3rd percentile with NNU admission for ≥48 hours delivered <32 weeks gestation and these were significantly higher than the respective values of 35.0% (25.6-44.6) and 35.9% (25.3 - 46.5), achieved by the application of the sFLT-1/ PlGF ratio >90th percentile (p<0.0001 for both). The respective values for SGA with major neonatal morbidity were 73.8% (64.4-83.2), 77.9% (68.0-87.8), 38.1% (27.7-48.5) and 39.7% (28.1-51.3) (Both p<0.0001). CONCLUSION: At mid-gestation, the prediction of growth-related neonatal morbidity by the competing risks model for SGA is superior to that of high sFlt-1/PlGF ratio or low PlGF. This article is protected by copyright. All rights reserved.

Effect of maternal polycystic ovary syndrome (PCOS) on screening of aneuploidy in the first and second trimesters.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by insulin resistance and hormonal disorder in women. This study aimed to assess the effect of maternal PCOS on screening of aneuploidy in the first and second-trimesters. METHODS: This case-control study was conducted in Arash Hospital and Nilou Laboratory in 2017-2018. The screening test was conducted on 90 PCOS and 90 healthy mothers. Finally, the first and second-trimester screening was compared between the two groups using Chi-square, Mann-Whitney's U and students T tests and regression model by SPSS 21. P < 0.05 was considered as statistically significant. RESULTS: Free Beta-Human Chorionic Gonadotropin (Free-ß-HCG) (P = 0.04), inhibin-A (P = 0.001) and Alpha Fetoprotein (AFP) (P = 0.02) levels were higher in the PCOS women comparing to the healthy women but there was no significant difference between the mean of HCG, Plasma Protein A (PAPP-A), and Unconjugated Estriol (UE3) between the two groups. Pre-eclampsia (P < 0.001) and trisomy 18 risks in quad screening were higher in the PCOS women (P = 0.002) than the control group; however, trisomy 13, trisomy 18 and trisomy 21 risks, Smith-Lemli-Opitz Syndrome (SLOS) and Neural Tube Defect (NTD) risks were not different between the two groups. The logistic regression model showed that the first- and second-trimester screening of aneuploidywas related to PCOS. CONCLUSIONS: There was a significant difference in the mean of free-ß-HCG, inhibin-A, AFP level, and the risks of pre-eclampsia, SLOS and trisomy 18 between the two groups but no significant association was found in the mean of HCG, PAPP-A, UE3, NTD and other aneuploidies between the two groups. PCOS may affect the first- and second-trimester screening tests and pregnancy health. It may also require correction in the calculation of risks related to the first- and second-trimester screening for aneuploidy.

Impact of COVID-19 and vaccination on first and second trimester screening results.

COVID-19 has been shown to affect pregnant women. Since pregnant women are at risk of this infection, vaccination against COVID-19 has been suggested as an imperative way to diminish rate of COVID-19 in this population. In the current observational study, we have collected data of first and second trimester screening (FTS and STS) from pregnant women who were infected with SARS-CoV-2 and/or vaccinated against COVID-19 during their pregnancy, and compared this data with a group of control pregnant women. The cohort included 4612 and 2426 women referred for FTS and STS, respectively. There was no significant difference in median values of Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin-beta subunit (ßHCG) between infected women and controls. Moreover, these levels were not different between "Infected + vaccinated" and "Only vaccinated" groups. However, median values of PAPP-A and ßHCG were higher in "Infected + vaccinated" and "Only vaccinated" groups compared with "Infected" and "Control" groups (P < 0.001). Median values of unconjugated Estriol (uE3) and ßHCG markers were not different between "Only vaccinated" and "Control" groups, yet both markers were elevated in "Infected" and "Infected + vaccinated" groups compared with other groups. AFP values were higher in "Infected" group (P = 0.012). However, multiple of the median (MoM) and risk of open spina bifida (OSB) were not affected. Finally, median of calculated risk of trisomy 18 was lower in "Infected" and "Vaccinated" groups compared with controls (P = 0.007). Moreover, AstraZeneca and Sinopharm vaccines were associated with elevation of the calculated risk values of trisomy 21 and trisomy 18 (P < 0.001). While Sinopharm did not affect nuchal translucency (NT) and NT MoM (P = 0.13), AstraZeneca and Barakat increased and decreased these values, respectively (P values = 0.0027 and 0.015, respectively). Taken together, COVID-19 during pregnancy might be associated with some adverse obstetric outcomes. Besides, vaccination against this infection might affect the results of STS or FTS.

Personalized stratification of pregnancy care for small for gestational age neonates from biophysical markers at midgestation.

BACKGROUND: Antenatal identification of pregnancies at high risk of delivering small for gestational age neonates may improve the management of the condition and reduce the associated adverse perinatal outcomes. In a series of publications, we have developed a new competing-risks model for small for gestational age prediction, and we demonstrated that the new approach has a superior performance to that of the traditional methods. The next step in shaping the appropriate management of small for gestational age is the timely assessment of these high-risk pregnancies according to an antenatal stratification plan. OBJECTIVE: This study aimed to demonstrate the stratification of pregnancy care based on individual patient risk derived from the application of the competing-risks model for small for gestational age that combines maternal factors with sonographic estimated fetal weight and uterine artery pulsatility index at midgestation. STUDY DESIGN: This was a prospective observational study of 96,678 singleton pregnancies undergoing routine ultrasound examination at 19 to 24 weeks of gestation, which included recording of estimated fetal weight and measurement of uterine artery pulsatility index. The competing-risks model for small for gestational age was used to create a patient-specific stratification curve capable to define a specific timing for a repeated ultrasound examination after 24 weeks. We examined different stratification plans with the intention of detecting approximately 80%, 85%, 90%, and 95% of small for gestational age neonates with birthweight <3rd and <10th percentiles at any gestational age at delivery until 36 weeks; all pregnancies would be offered a routine ultrasound examination at 36 weeks. RESULTS: The stratification of pregnancy care for small for gestational age can be based on a patient-specific stratification curve. Factors from maternal history, low estimated fetal weight, and increased uterine artery pulsatility index shift the personalized risk curve toward higher risks. The degree of shifting defines the timing for assessment for each pregnancy. If the objective of our antenatal plan was to detect 80%, 85%, 90%, and 95% of small for gestational age neonates at any gestational age at delivery until 36 weeks, the median (range) proportions (percentages) of population examined per week would be 3.15 (1.9-3.7), 3.85 (2.7-4.5), 4.75 (4.0-5.4), and 6.45 (3.7-8.0) for small for gestational age <3rd percentile and 3.8 (2.5-4.6), 4.6 (3.6-5.4), 5.7 (3.8-6.4), and 7.35 (3.3-9.8) for small for gestational age <10th percentile, respectively. CONCLUSION: The competing-risks model provides an effective personalized continuous stratification of pregnancy care for small for gestational age which is based on individual characteristics and biophysical marker levels recorded at the midgestation scan.

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study.

PURPOSE: We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. MATERIALS AND METHODS: This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. RESULTS: Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36-5.13] and major CHDs (aOR 7.30; 95% CI 3.18-15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42-12.46) was associated with non-chromosomal major CHDs. CONCLUSION: Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Effect of antiepileptic drugs on serum biochemical marker levels of first and second trimester screening tests.

OBJECTIVES: Our aim in this study was to evaluate the effect of antiepileptic drugs on biochemical components of screening tests. MATERIALS AND METHODS: This longitudinal case-control study was performed at Ankara City Hospital, Ankara, Turkey, from June 2020 to January 2021. The case group included epileptic singleton pregnant women which were using antiepileptic drugs, between 18 and 44 years of age. The control group included healthy pregnant women between 18 and 44 years old who did not use any drugs. Maternal medical, obstetric, and gynecological history were recorded. The antiepileptic agents that are used in our study were; lamotrigine, levetiracetam, carbamazepine, oxcarbazepine, valproic acid, and clonazepam. For the aneuploidy screening program conducted in our laboratory, the biochemical markers that are analyzed include; free b-hCG and PAPP-A in the first trimester, as well as AFP, HCG, and unconjugated estriol (uE3) in the second trimester. MoM values of these markers were compared between the case and control groups. RESULTS: Fifty-three pregnant women with epilepsy using antiepileptic drugs were compared with 106 healthy pregnant women. The levels of serum-free b-hCG, and PAPP-A were similar between the case and control groups (p = 0.653, p = 0.351). For the second-trimester screening biochemical markers, the maternal serum uE3 and AFP levels expressed as MoM were significantly higher in the epileptic group than in the control patients (p = 0.015 and p = 0.001). CONCLUSION: Serum marker levels of second-trimester screening tests may be affected by antiepileptic drugs, which may lead to misinterpretation of the risk level. Antiepileptic drug usage should be considered when evaluating screening test results.

Clinically Relevant Prenatal Ultrasound Diagnosis of Umbilical Cord Pathology.

Umbilical cord abnormalities are not rare, and are often associated with structural or chromosomal abnormalities, fetal intrauterine growth restriction, and poor pregnancy outcomes; the latter can be a result of prematurity, placentation deficiency or, implicitly, an increased index of cesarean delivery due to the presence of fetal distress, higher admission to neonatal intensive care, and increased prenatal mortality rates. Even if the incidence of velamentous insertion, vasa praevia and umbilical knots is low, these pathologies increase the fetal morbidity and mortality prenatally and intrapartum. There is a vast heterogeneity among societies' guidelines regarding the umbilical cord examination. We consider the mandatory introduction of placental cord insertion examination in the first and second trimester to practice guidelines for fetal ultrasound scans. Moreover, during the mid-trimester scan, we recommend a transvaginal ultrasound and color Doppler assessment of the internal cervical os for low-lying placentas, marginal or velamentous cord insertion, and the evaluation of umbilical cord entanglement between the insertion sites whenever it is incidentally found. Based on the pathological description and the neonatal outcome reported for each entity, we conclude our descriptive review by establishing a new, clinically relevant classification of these umbilical cord anomalies.

Prediction of late-onset fetal growth restriction using a combined first- and second-trimester screening model.

BACKGROUND: Prediction models for early fetal growth restriction (FGR) have been exhibited in many researches. However, prediction models for late FGR are limited. Late-onset FGR is easy to miss clinically because of its insidious onset. This study aimed to develop a simple combined first- and second-trimester prediction model for screening late-onset FGR in fetuses. METHODS: This retrospective study included 2746 women who had singleton pregnancies and received routine ultrasound scans as training dataset. Late FGR is that diagnosed >32 weeks. Multivariate logistic regression was used to develop a prediction model. RESULTS: One hundred and twenty-nine fetuses were identified as late-onset FGR. The significant predictors for late-onset FGR were maternal height, weight, and medical history; the first-trimester mean arterial pressure, the second-trimester head circumference/ abdominal circumference ratio; and the second-trimester estimated fetal weight. This model achieved a detection rate (DR........) of 51.6% for late-onset FGR at a 10% false positive rate (FPR) (area under the curve (AUC): 0.80, 95%CI 0.76-0.84). CONCLUSIONS: A multivariate model combining first- and second-trimester default tests can detect 51.6% of cases of late-onset FGR at a 10% FPR. Further studies with more screening markers are needed to improve the detection rate.

Predictive performance for placental dysfunction related stillbirth of the competing risks model for small-for-gestational-age fetuses.

OBJECTIVES: To examine the predictive performance for placental dysfunction related stillbirths of the competing risks model for small-for-gestational-age (SGA) fetuses based on a combination of maternal risk factors, estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI); and second, to compare the performance of this model with that of a stillbirth-specific model using the same biomarkers and with the Royal College of Obstetricians and Gynecologists (RCOG) guideline for the investigation and management of the SGA fetus. DESIGN: Prospective observational study. SETTING: Two UK maternity hospitals. POPULATION: A total of 131 514 women with singleton pregnancies attending for routine ultrasound examination at 19-24 weeks of gestation. METHODS: The predictive performance for stillbirth achieved by three models was compared. MAIN OUTCOME MEASURE: Placental dysfunction related stillbirth. RESULTS: At 10% false-positive rate, the competing risks model predicted 59%, 66% and 71% of placental dysfunction related stillbirths, at any gestation, at <37 weeks and at <32 weeks, respectively, which were similar to the respective figures of 62%, 70% and 73% for the stillbirth-specific model. At a screen positive rate of 21.8%, as defined by the RCOG guideline, the competing risks model predicted 71%, 76% and 79% of placental dysfunction related stillbirths at any gestation, at <37 weeks and at <32 weeks, respectively, and the respective figures for the RCOG guideline were 40%, 44% and 42%. CONCLUSION: The predictive performance for placental dysfunction related stillbirths by the competing risks model for SGA was similar to that of the stillbirth-specific model and superior to that of the RCOG guideline. TWEETABLE ABSTRACT: The competing risks approach for SGA is superior to the RCOG guideline in the prediction of placental dysfunction related stillbirths.

Second-trimester contingent screening for small-for-gestational-age neonate.

OBJECTIVES: First, to investigate the additive value of second-trimester placental growth factor (PlGF) for the prediction of a small-for-gestational-age (SGA) neonate. Second, to examine second-trimester contingent screening strategies. METHODS: This was a prospective observational study in women with singleton pregnancy undergoing routine ultrasound examination at 19-24 weeks' gestation. We used the competing-risks model for prediction of SGA. The parameters for the prior model and the likelihoods for estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI) were those presented in previous studies. A folded-plane regression model was fitted in the dataset of this study to describe the likelihood of PlGF. We compared the prediction of screening by maternal risk factors against the prediction provided by a combination of maternal risk factors, EFW, UtA-PI and PlGF. We also examined the additive value of PlGF in a policy that uses maternal risk factors, EFW and UtA-PI. RESULTS: The study population included 40 241 singleton pregnancies. Overall, the prediction of SGA improved with increasing degree of prematurity, with increasing severity of smallness and in the presence of coexisting pre-eclampsia. The combination of maternal risk factors, EFW, UtA-PI and PlGF improved significantly the prediction provided by maternal risk factors alone for all the examined cut-offs of birth weight and gestational age at delivery. Screening by a combination of maternal risk factors and serum PlGF improved the prediction of SGA when compared to screening by maternal risk factors alone. However, the incremental improvement in prediction was decreased when PlGF was added to screening by a combination of maternal risk factors, EFW and UtA-PI. If first-line screening for a SGA neonate with birth weight < 10th percentile delivered at < 37 weeks' gestation was by maternal risk factors and EFW, the same detection rate of 90%, at an overall false-positive rate (FPR) of 50%, as that achieved by screening with maternal risk factors, EFW, UtA-PI and PlGF in the whole population can be achieved by reserving measurements of UtA-PI and PlGF for only 80% of the population. Similarly, in screening for a SGA neonate with birth weight < 10th percentile delivered at < 30 weeks, the same detection rate of 90%, at an overall FPR of 14%, as that achieved by screening with maternal risk factors, EFW, UtA-PI and PlGF in the whole population can be achieved by reserving measurements of UtA-PI and PlGF for only 70% of the population. The additive value of PlGF in reducing the FPR to about 10% with a simultaneous detection rate of 90% for a SGA neonate with birth weight < 3rd percentile born < 30 weeks, is gained by measuring PlGF in only 50% of the population when first-line screening is by maternal factors, EFW and UtA-PI. CONCLUSIONS: The combination of maternal risk factors, EFW, UtA-PI and PlGF provides effective second-trimester prediction of SGA. Serum PlGF is useful for predicting a SGA neonate with birth weight < 3rd percentile born < 30 weeks after an inclusive assessment by maternal risk factors and biophysical markers. Similar detection rates and FPRs can be achieved by application of contingent screening strategies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Competing Risks Model for Prediction of Small for Gestational Age Neonates and the Role of Second Trimester Soluble Fms-like Tyrosine Kinase-1.

Small for gestational age (SGA) fetuses/neonates are characterized by the increased risk for adverse outcomes that can be reduced if the condition is identified antenatally. We have recently developed a new approach in SGA prediction that considers SGA a spectrum condition that is reflected in two dimensions: gestational age at delivery and Z score in birth weight for gestational age. The new method has a better predictive ability than the traditionally used risk-scoring systems and logistic regression models. In this prospective study in 40241 singleton pregnancies, at 19-24 weeks' gestation, we examined the potential value of the antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and the ratio of sFlt-1 to the angiogenic placental growth factor (PlGF) in the prediction of SGA. We found that first, sFlt-1 did not improve the performance of screening by maternal risk factors, and second, the ratio of sFlt-1/PlGF had a worse performance than PlGF alone in the prediction of SGA. Consequently, second trimester sFlt-1 and sFlt-1/PlGF are not useful in screening for SGA.

Prenatal detection of congenital heart disease - results of a Swedish screening program 2013-2017.

BACKGROUND: This report evaluates results of a screening program on prenatal detection of congenital heart defects in a geographical cohort of western Sweden between January 1st, 2013 and June 31st, 2017. During the study period 88,230 children were born in VGR. METHODS: Retrospective data on pregnant women from the Västra Götaland region that were referred to fetal cardiologists in Gothenburg were retrieved. To determine prenatal detection rate, all neonates who underwent surgery or catheter intervention for a critical congenital heart defect born between January 1st, 2014 and December 31st, 2016 were included. The four-chamber view was implemented into the routine scan in 2009 and implementation of the ISUOG guidelines, including the outflow tracts, started in the region in 2015. RESULTS: 113 fetuses received a prenatal diagnosis of a major congenital heart defect. 89% of these were referred because of a suspected cardiac malformation and 88% were diagnosed before 22 completed weeks. 59% of the patients diagnosed before 22 completed weeks opted for termination of pregnancy. During 2014-2016, 61 fetuses had a prenatal diagnosis of a critical congenital heart defect and a further 47 were diagnosed after birth, hence 56% were diagnosed prenatally, 82% for those which had a combination with an extracardiac abnormality and/or chromosomal aberration compared to 50% if an isolated critical congenital heart defect was diagnosed. For single ventricle cardiac defects such as hypoplastic left heart syndrome, double inlet left ventricle and tricuspid atresia, the detection rate was 100%. The detection rate for transposition of the great arteries and coarctation of the aorta was 9 and 18% respectively. CONCLUSIONS: 56% of all fetuses with a critical congenital heart defect were diagnosed prenatally during 2014-2016 and approximately 53% of all major congenital heart defects 2013-2017 as compared to 13.8% in 2009 in the same region. An increased focus towards the fetal heart in the routine scan improved the prenatal detection rate of major congenital heart defects. The detection of congenital heart defects affecting the four-chamber view seems sufficient, but more training is needed to improve the quality of the examination of the outflow tracts.

Evaluation of the RCOG guideline for the prediction of neonates that are small for gestational age and comparison with the competing risks model.

OBJECTIVE: To examine the predictive performance of the relevant guideline by the Royal College of Obstetricians and Gynaecologists (RCOG) for neonates that are small for gestational age (SGA), and to compare the performance of the RCOG guideline with that of our competing risks model for SGA. DESIGN: Prospective observational study. SETTING: Obstetric ultrasound departments in two UK maternity hospitals. POPULATION: A total of 96 678 women with singleton pregnancies attending for routine ultrasound examination at 19-24 weeks of gestation. METHODS: Risks for SGA for different thresholds were computed, according to the competing risks model using maternal history, second-trimester estimated fetal weight, uterine artery pulsatility index and mean arterial pressure. The detection rates by the RCOG guideline scoring system and the competing risks model for SGA were compared, at the screen positive rate (SPR) derived from the RCOG guideline. MAIN OUTCOME MEASURES: Small for gestational age (SGA), <10th or <3rd percentile, for different gestational age thresholds. RESULTS: At an SPR of 22.5%, as defined by the RCOG guideline, the competing risks model predicted 56, 72 and 81% of cases of neonates that are SGA, with birthweights of <10th percentile, delivered at ≥37, <37 and <32 weeks of gestation, respectively, which were significantly higher than the respective figures of 36, 44 and 45% achieved by the application of the RCOG guideline. The respective figures for neonates that were SGA with birthweights of <3rd percentile were 66, 79, 85 and 41, 45, 44%. CONCLUSION: The detection rate for neonates that were SGA with the competing risk approach is almost double than that obtained with the RCOG guideline. TWEETABLE ABSTRACT: The competing risks approach for the prediction of SGA performs better than the existing RCOG guideline.

Competing risks model for prediction of small-for-gestational-age neonates from biophysical markers at 19 to 24 weeks' gestation.

BACKGROUND: Antenatal identification of women at high risk to deliver small-for-gestational-age neonates may improve the management of the condition. The traditional but ineffective methods for small-for-gestational-age screening are the use of risk scoring systems based on maternal demographic characteristics and medical history and the measurement of the symphysial-fundal height. Another approach is to use logistic regression models that have higher performance and provide patient-specific risks for different prespecified cutoffs of birthweight percentile and gestational age at delivery. However, such models have led to an arbitrary dichotomization of the condition; different models for different small-for-gestational-age definitions are required and adding new biomarkers or examining other cutoffs requires refitting of the whole model. An alternative approach for the prediction of small-for-gestational-age neonates is to consider small for gestational age as a spectrum disorder whose severity is continuously reflected in both the gestational age at delivery and z score in birthweight for gestational age. OBJECTIVE: This study aimed to develop a new competing risks model for the prediction of small-for-gestational-age neonates based on a combination of maternal demographic characteristics and medical history with sonographic estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure at 19 to 24 weeks' gestation. STUDY DESIGN: This was a prospective observational study of 96,678 women with singleton pregnancies undergoing routine ultrasound examination at 19 to 24 weeks' gestation, which included recording of estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure. The competing risks model for small for gestational age is based on a previous joint distribution of gestational age at delivery and birthweight z score, according to maternal demographic characteristics and medical history. The likelihoods of the estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure were fitted conditionally to both gestational age at delivery and birthweight z score and modified the previous distribution, according to the Bayes theorem, to obtain an individualized posterior distribution for gestational age at delivery and birthweight z score and therefore patient-specific risks for any desired cutoffs for birthweight z score and gestational age at delivery. The model was internally validated by randomly dividing the data into a training data set, to obtain the parameters of the model, and a test data set, to evaluate the model. The discrimination and calibration of the model were also examined. RESULTS: The estimated fetal weight was described using a regression model with an interaction term between gestational age at delivery and birthweight z score. Folded plane regression models were fitted for uterine artery pulsatility index and mean arterial pressure. The prediction of small for gestational age by maternal factors was improved by adding biomarkers for increasing degree of prematurity, higher severity of smallness, and coexistence of preeclampsia. Screening by maternal factors with estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure, predicted 41%, 56%, and 70% of small-for-gestational-age neonates with birthweights of <10th percentile delivered at ≥37, <37, and <32 weeks' gestation, at a 10% false-positive rate. The respective rates for a birthweight of <3rd percentile were 47%, 65%, and 77%. The rates in the presence of preeclampsia were 41%, 72%, and 91% for small-for-gestational-age neonates with birthweights of <10th percentile and 50%, 75%, and 92% for small-for-gestational-age neonates with birthweights of <3rd percentile. Overall, the model was well calibrated. The detection rates and calibration indices were similar in the training and test data sets, demonstrating the internal validity of the model. CONCLUSION: The performance of screening for small-for-gestational-age neonates by a competing risks model that combines maternal factors with estimated fetal weight, uterine artery pulsatility index, and mean arterial pressure was superior to that of screening by maternal characteristics and medical history alone.

Fetal intracranial structures: differences in size according to sex.

OBJECTIVES: We aimed to compare gender difference on sizes of some structures in the brain of normal male and female fetuses between 20 and 22 week gestations. METHODS: A total of 300 female and 300 male singleton pregnancies with low risk were included in the study. Biparietal diameter, head circumference, transcerebellar diameter, cisterna magna, nuchal fold thickness, anterior and posterior horn of lateral ventricles, length and width of cavum septum pellucidum were measured transabdominally. Mean±SD values were calculated and comparison of measurements were done between male and female fetuses. Kolmogorov-Smirnov and independent samples t-test were used for statistical analysis. A value of p<0.05 were accepted as statistically significant. RESULTS: We determined statistically significant difference in sizes of some structures of the brain of male and female fetuses. Mean±SD value of cavum septi pellucidi width was 3.38±0.61 and 3.85±0.96 in female and males, respectively (p<0.05). Male fetuses were also found to have larger anterior (1.92±0.30 vs. 1.58±0.26, p<0.0001) and posterior horn of lateral ventricles (6.00±0.87 vs. 5.53±1.17, p<0.05). CONCLUSIONS: Difference in sizes of some structures of the brain starts in fetal life. This finding may be important in evaluating the intracranial structures more precisely. These results may also give a contribution to the understanding physiological and pathologic differences between males and females.

Competing-risks model for prediction of small-for-gestational-age neonate from estimated fetal weight at 19-24 weeks' gestation.

OBJECTIVE: To develop further a new competing-risks model for the prediction of a small-for-gestational-age (SGA) neonate, by including second-trimester ultrasonographic estimated fetal weight (EFW). METHODS: This was a prospective observational study in 96 678 women with singleton pregnancy undergoing routine ultrasound examination at 19-24 weeks' gestation. All pregnancies had ultrasound biometry assessment, and EFW was calculated according to the Hadlock formula. We refitted in this large dataset a previously described competing-risks model for the joint distribution of gestational age (GA) at delivery and birth-weight Z-score, according to maternal demographic characteristics and medical history, to obtain the prior distribution. The continuous likelihood of the EFW was fitted conditionally to GA at delivery and birth-weight Z-score and modified the prior distribution, according to Bayes' theorem, to obtain individualized distributions for GA at delivery and birth-weight Z-score and therefore patient-specific risks for any cut-offs for GA at delivery and birth-weight Z-score. We assessed the discriminative ability of the model for predicting SGA with, without or independently of pre-eclampsia occurrence. A calibration study was carried out. Performance of screening was evaluated for SGA defined according to the Fetal Medicine Foundation birth-weight charts. RESULTS: The distribution of EFW, conditional to both GA at delivery and birth-weight Z-score, was best described by a regression model. For earlier gestations, the association between EFW and birth weight was steeper. The prediction of SGA by maternal factors and EFW improved for increasing degree of prematurity and greater severity of smallness but not for coexistence of pre-eclampsia. Screening by maternal factors predicted 31%, 34% and 39% of SGA neonates with birth weight < 10th percentile delivered at ≥ 37, < 37 and < 30 weeks' gestation, respectively, at a 10% false-positive rate, and, after addition of EFW, these rates increased to 38%, 43% and 59%, respectively; the respective rates for birth weight < 3rd percentile were 43%, 50% and 64%. The addition of EFW improved the calibration of the model. CONCLUSION: In the competing-risks model for prediction of SGA, the performance of screening by maternal characteristics and medical history is improved by the addition of second-trimester EFW. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Performance of second-trimester maternal biochemistry screening (quadruple test vs. triple test) for trisomy 21: An Indian experience.

Background & objectives: Down syndrome (DS) is one of the most common causes of developmental delay. In India, there is no protocol for prenatal screening of DS. Second-trimester biochemical screening is still being done by triple test. Quadruple test is with better sensitivity and specificity but is not advised routinely. So, the objective of this study was to evaluate the sensitivity and accuracy of the second-trimester screening (quadruple test with genetic sonogram) for trisomy 21 as compared to biochemical testing. Methods: This retrospective observational study was carried out in a Fetal Medicine Centre to analyze the odds of being affected with DS, given a positive risk (OAPR) upon screening in the quadruple test; triple test and quadruple test plus a genetic sonogram for high-risk singleton pregnancies (in view of advanced maternal age; an anomaly scan showing some abnormality, etc). Results: 3175 high-risk singleton pregnancies were screened for trisomy 21. 394 women underwent amniocentesis on the basis of triple test, quadruple test or quadruple plus genetic sonogram positive. 17 foetuses were diagnosed to have DS. The quadruple test was found to have a higher OAPR as compared to the triple test (1:30.1 as compared to 1: 40.2). Quadruple test plus the genetic sonogram was found to have the highest OAPR of 1:6. Interpretation & conclusions: Best screening for trisomy 21 is provided with quadruple test with genetic sonogram which can lower the rates of unnecessary amniocentesis in high-risk population.