Multiples Of The Median Research Articles

First-Trimester Reference Intervals for Thyroid Function Testing among Women Screened at a Tertiary Care Hospital in India.

Objectives Due to differences in the method of assay and population-specific factors, each laboratory needs to establish its own gestation-specific reference intervals (GRIs) for thyroid hormones. Materials and Methods Three-hundred forty-one women with less than 14 weeks gestation were screened at a tertiary care hospital in Chhattisgarh, India. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and thyroid peroxidase antibody (anti-TPO) were measured using an ADVIA Centaur XP immunoassay. GRIs (2.5th and 97.5th percentiles) were determined for TSH and fT4. TSH and fT4 concentrations were converted to multiples of the median (MoM) values. Effect of maternal age, gestational age, and maternal weight was analyzed.Statistical Analysis Quantitative variables were expressed as means and standard deviations (SD), and qualitative variables were expressed as frequencies and percentages. Normality of the data was checked using the Kolmogorov–Smirnov test. Values that were normally distributed were expressed only as means and SD. Those that were not normally distributed were expressed as medians and interquartile range. For all statistical analysis, p < 0.05 was considered as statistically significant. Results First-trimester GRI was 0.245 to 4.971 mIU/L for TSH, 10.2 to 18.9 pmol/L for fT4, and 27.0 to 56.89 kIU/L for anti-TPO. There was no significant difference in the mean serum TSH ( p = 0.920), fT4 ( p = 0.714), or anti-TPO ( p = 0.754) values among women in 4 to 7th week and 7 to 14th week of gestation. The 1st and 99th centile MoMs were 0.03 and 4.09 for TSH and 0.66 and 1.39 for fT4. There was a significant positive correlation between the maternal weight and TSH MoM values ( p = 0.027, r = 0.120). Conclusion These laboratory- and first-trimester-specific GRI for TSH and fT4 shall help in proper diagnosis and treatment of subclinical thyroid dysfunctions. TSH and fT4 MoM values can be used to indicate high or low values in a quantitative manner independent of the reference ranges and may be used by other laboratories.

Prenatal cardiac biometry and flow assessment in fetuses with bicuspid aortic valve at 20 weeks' gestation: multicenter cohort study.

To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03-0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95% CI, 0.03-0.28 mm))). Following conversion of the diameter measurements of the aorta and pulmonary artery to Z-scores and Bonferroni correction, the differences between the two groups were no longer statistically significant. Pregnancy-associated plasma protein-A (PAPP-A) multiples of the median (MoM) was significantly lower in the BAV group than in the control group (0.85 vs 1.03; P = 0.04). Our findings suggest that fetuses with BAV may have a larger aortic diameter at the level of the aortic valve, measured in the left-ventricular-outflow-tract view, and a larger pulmonary artery diameter at the level of the pulmonary valve, measured in the three-vessel view, at 20 weeks' gestation. Moreover, we found an association of maternal smoking and low PAPP-A MoM with BAV. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal cerebral blood-flow redistribution: analysis of Doppler reference charts and association of different thresholds with adverse perinatal outcome.

ABSTRACTObjectivesFirst, to compare published Doppler reference charts of the ratios of flow in the fetal middle cerebral and umbilical arteries (i.e. the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR)). Second, to assess the association of thresholds of CPR and UCR based on these charts with short‐term composite adverse perinatal outcome in a cohort of pregnancies considered to be at risk of late preterm fetal growth restriction.MethodsStudies presenting reference charts for CPR or UCR were searched for in PubMed. Formulae for plotting the median and the 10th percentile (for CPR) or the 90th percentile (for UCR) against gestational age were extracted from the publication or calculated from the published tables. Data from a prospective European multicenter observational cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks' gestation, in which fetal arterial Doppler measurements were collected longitudinally, were used to compare the different charts. Specifically, the association of UCR and CPR thresholds (CPR < 10th percentile or UCR ≥ 90th percentile and multiples of the median (MoM) values) with composite adverse perinatal outcome was analyzed. The association was also compared between chart‐based thresholds and absolute thresholds. Composite adverse perinatal outcome comprised both abnormal condition at birth and major neonatal morbidity.ResultsTen studies presenting reference charts for CPR or UCR were retrieved. There were large differences between the charts in the 10th and 90th percentile values of CPR and UCR, respectively, while median values were more similar. In the gestational‐age range of 28–36 weeks, there was no relationship between UCR or CPR and gestational age. From the prospective observational study, 856 pregnancies at risk of late‐onset preterm fetal growth restriction were included in the analysis. The association of abnormal UCR or CPR with composite adverse perinatal outcome was similar for percentile thresholds or MoM values, as calculated from the charts, and for absolute thresholds, both on univariable analysis and after adjustment for gestational age at measurement, estimated fetal weight MoM and pre‐eclampsia. The adjusted odds ratio for composite adverse perinatal outcome was 3.3 (95% CI, 1.7–6.4) for an absolute UCR threshold of ≥ 0.9 or an absolute CPR threshold of < 1.11 (corresponding to ≥ 1.75 MoM), and 1.6 (95% CI, 0.9–2.9) for an absolute UCR threshold of ≥ 0.7 to < 0.9 or an absolute CPR threshold of ≥ 1.11 to < 1.43 (corresponding to ≥ 1.25 to < 1.75 MoM).ConclusionsIn the gestational‐age range of 32 to 36 weeks, adjustment of CPR or UCR for gestational age is not necessary when assessing the risk of adverse outcome in pregnancies at risk of fetal growth restriction. The adoption of absolute CPR or UCR thresholds, independent of reference charts, is feasible and makes clinical assessment simpler than if using percentiles or other gestational‐age normalized units. The high variability in percentile threshold values among the commonly used UCR and CPR reference charts hinders reliable diagnosis and clinical management of late preterm fetal growth restriction. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A prospective cohort study on association of first-trimester serum biomarkers and risk of isolated foetal congenital heart defects

Background This study aims to assess the association between first-trimester biomarkers in foetuses with a non-chromosomal congenital heart defect (CHD) and compares it to the matched healthy foetuses. Method Nuchal Translucency (NT), Pregnancy-Associated Plasma Protein-A (PAPP-A) and free beta-human Chorionic Gonadotropin (β-hCG) were evaluated in 56 isolated foetal heart defects and 224 controls. The CHDs were further divided into Critical CHD (C-CHD) and Non-critical CHD (N-CHD) groups. Results The multiple of the median (MoM) values for PAPP-A were significantly lower (0.87 MoM vs. 0.92 MoM; p = 0.008) in the total CHD group than in controls. The median of foetal NT values was significantly higher in the total CHDs than in controls (1.16 MoM vs. 1.03 MoM; p < 0.001), especially for C-CHDs (1.28 MoM; P < 0.001). There were no significant differences in terms of PAPP-A (p = 0.779) and foetal NT values (p = 0.760) between the N-CHDs and control groups. There were no significant differences within the groups based on free β-hCG, except for a lower β-hCG in C-CHD group than in the control group (0.95 MoM vs. 1.11 MoM; p = 0.022). Conclusion Lower PAPP-A levels and increased NT thickness were associated with an increased risk of CHDs, especially the critical type of CHDs. Clinical significance Maternal serum PAPP-A, measured in the first trimester, is significantly lower in CHD. Foetal NT is significantly thicker in foetuses with CHD, especially those with critical CHD. Maternal serum β-hCG was only decreased among critical CHD group.

Which is the best ultrasound parameter for the prediction of adverse perinatal outcome within 1 day of delivery?

Objective To compare the accuracies of several sonographic parameters for the prediction of adverse perinatal outcome (APO) prior to delivery. Methods This was a prospective study of fetuses attending the day hospital unit of a tertiary referral hospital that were scanned at 34-41 weeks and gave birth within 24 h of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring urgent cesarean section, neonatal umbilical cord pH < 7.10, 5’ Apgar score <7 and postpartum admission to neonatal or pediatric intensive care units. The accuracies of the middle cerebral, vertebral and umbilical arteries pulsatility index multiples of the median (MoM), the cerebroplacental and vertebroplacental ratios MoM and the EFW in centiles for the prediction of APO was evaluated by means of ROC curves and logistic regression analysis. Results A total of 2140 fetuses were prospectively scanned, however only 182 entered into spontaneous or induced labor and were delivered within 24 h of examination. In this group, MCA PI MoM was the best predictor of APO (AUC = 0.76, 95% CI 0.66–0.85, p < .0001) followed by the CPR MoM (AUC = 0.73, 95% CI 0.63–0.84, p < .0001) and the VPR MoM (AUC = 0.71, 95% CI 0.61–0.81, p < .001). Logistic regression analysis indicated that MCA PI MoM was the only independent determinant for the prediction of APO. Conclusion In a high-risk population of third-trimester fetuses delivering within 24 h of examination, the outcome may be moderately anticipated just with the information provided by the cerebral flow.

Performance of middle cerebral artery doppler for prediction of recurrent fetal anemia

Objective To assess the predictive value of middle cerebral artery Doppler peak systolic velocity (MCA-PSV) for moderate-severe fetal anemia following one intrauterine transfusion (IUT) and test the performance of alternate cutoffs to the recommended threshold ≥1.69 multiples of the median (MoM). Methods This was a retrospective cohort study of patients with pregnancies affected by alloimmunization who underwent percutaneous umbilical blood sampling (PUBS) procedures from 2000 to 2020. An MCA-PSV ≥1.69 MoM was the indication for the second IUT. The primary outcome was recurrent moderate-severe fetal anemia. Receiver-operating characteristic (ROC) curves assessed the predictive ability of MCA-PSV for the primary outcome and the Youden index identified the “optimal” cutoff value. Predictive characteristics of MCA-PSV ≥1.69 MoM and the “optimal” cutoff were compared. Results Of the 58 patients who underwent IUT during the study period, 36 (62%) did not meet inclusion criteria. Of the remaining 22 patients who underwent a second PUBS, 12 (54.6%) fetuses had moderate or severe anemia. Following one IUT, the AUC for MCA-PSV was 0.86 (95% CI 0.70–1.00) for the primary outcome. The “optimal” cutoff MCA-PSV value was 1.74 MoM, which had a greater specificity than ≥1.69 MoM (90 vs. 50%, p = .05), but was not statistically significant. The sensitivity was similar between the two cutoff values of ≥1.69 and ≥1.74 MoM (83.3 vs. 75.0%, p = .65) (Table 2). Conclusion Raising the recommended MCA-PSV cutoff to ≥1.74 MoM for recurrent moderate-severe fetal anemia after one IUT would decrease the number of unnecessary procedures without significantly changing the sensitivity of this screening test.

Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women.

Maternal serum inhibin-A, pregnancy associated plasma protein-A (PAPP-A) and PAPP-A2 together with placental growth factor (PlGF), maternal risk factors and uterine artery pulsatility index (UtA PI) were analysed to study their ability to predict pre-eclampsia (PE). Serial serum samples for the nested case-control study were collected prospectively at 12-14, 18-20 and 26-28weeks of gestation from 11 women who later developed early-onset PE (EO PE, diagnosis<34+0weeks of gestation), 34 women who developed late-onset PE (LO PE, diagnosis≥34+0weeks) and 89 controls. Gestational age -adjusted multiples of the median (MoM) values were calculated for biomarker concentrations. Multivariate regression analyses were performed to combine first trimester biomarkers, previously reported results on PlGF, maternal risk factors and UtA PI. Area under curve (AUC) values and 95% confidence intervals (CIs) for the prediction of PE and its subtypes were calculated. A high first trimester inhibin-A predicted PE (AUC 0.618, 95%CI, 0.513-0.724), whereas PAPP-A and PlGF predicted only EO PE (0.701, 0.562-0.840 and 0.798, 0.686-0.909, respectively). At 26-28weeks PAPP-A2 and inhibin-A predicted all PE subtypes. In the multivariate setting inhibin-A combined with maternal pre-pregnancy body mass index, prior PE and mean UtA PI predicted PE (0.811,0.726-0.896) and LO PE (0.824, 0.733-0.914). At first trimester inhibin-A show potential ability to predict not only EO PE but also LO PE whereas PlGF and PAPP-A predict only EO PE. At late second trimester inhibin-A and PAPP-A2 might be useful for short-term prediction of PE.

Perinatal outcomes in women affected by different types of headache disorders: A prospective cohort study.

This study aims to investigate pregnancy and perinatal outcomes in women with tension-type headache, migraine without aura and migraine with aura by comparing them to women without any headache disorders. Prospective cohort study including singleton pregnancies attending the first trimester aneuploidy screening at the University Hospital of Modena, in Northern Italy, between June 2018 and December 2019. A total of 515 consecutive women were included and headache disorders were reported in 43.5% of them (224/515). Tension-type headache was diagnosed in 24.3% of the cases, while 14% suffered from migraine without aura and 5.2% from migraine with aura. Birthweight was significantly lower in women affected by migraine with aura respective to other groups, and a significantly higher rate of small for gestational age infants was found in tension-type headache (10.4%) and in migraine with aura (24.9%) groups respective to the others (p < 0.001). Moreover, the admission to the neonatal intensive care unit was significantly higher in all the headache groups (p = 0.012). Multivariate analysis showed that women presenting tension-type headache (OR 4.19, p = 0.004), migraine with aura (OR 5.37, p = 0.02), a uterine artery pulsatility index >90th centile (OR 3.66, p = 0.01), low multiple of the median (MoM) of Pregnancy-associated plasma protein-A (PAPP-A) (OR 0.48, p = 0.05) and high MoM of Inhibin-A (OR 3.24, p = 0.03) at first trimester, are independently associated with the delivery of small for gestational age infants when compared to women without headache disorders. Migraine with aura and tension type headache expose women to an increased risk of delivering small for gestational age infants, in association with some utero-placenta markers evaluated at first trimester. These women with headache disorders have an additional indication to undergo first trimester aneuploidy screening and would possibly benefit from specific interventions.

The Diagnostic Ability of the Cerebroplacental Ratio for the Prediction of Adverse Perinatal Outcome and Intrapartum Fetal Compromise within One Day of Delivery

Objectives: The objectives of this study were to evaluate the diagnostic abilities of the cerebroplacental ratio (CPR) for the prediction of adverse perinatal outcome (APO) and cesarean section for intrapartum fetal compromise (CS-IFC) within 1 day of delivery. Design: Retrospective observational case-control study. Methods: This was a study of 254 high-risk fetuses attending the day hospital unit of a tertiary referral hospital that underwent an ultrasound examination at 32–41 weeks and gave birth within 1 day of examination. APO was defined as a composite of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section, neonatal umbilical cord pH <7.10, 5-min Apgar score <7, and postpartum admission to neonatal or pediatric intensive care units. CS-IFC was defined in case of abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20 requiring urgent cesarean section. The diagnostic ability of CPR for the prediction of APO and CS-IFC was calculated alone and in combination with estimated fetal weight and gestational clinical parameters, including the type of labor onset, using ROC curves and logistic regression analysis. Results: CPR in multiples of the median (MoM) was a moderate predictor of APO (area under the curve [AUC] = 0.77, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001). The predictive abilities of the multivariable model for APO (AUC = 0.81, p < 0.0001) and CS-IFC (AUC = 0.82, p < 0.0001) did not differ from those of CPR alone . Limitations: The small number of cases and the scarcity of information concerning labor induction. Conclusion: In high-risk pregnancies, CPR MoM is a moderate predictor of APO and CS-IFC when performed within 24 h of delivery.

Newborn Screening for Severe Combined Immunodeficiency Using the Multiple of the Median Values of T-Cell Receptor Excision Circles.

All newborn screening programs screen for severe combined immunodeficiency by measurement of T-cell receptor excision circles (TRECs). Herein, we report our experience of reporting TREC assay results as multiple of the median (MoM) rather than using conventional copy numbers. This modification simplifies the assay by eliminating the need for standards with known TREC copy numbers. Furthermore, since MoM is a measure of how far an individual test result deviates from the median, it allows normalization of TREC assay data from different laboratories, so that individual test results can be compared regardless of the particular method, assay, or reagents used.

Predictive Performance of Serum β-hCG MoM Levels for Preeclampsia Screening: A Meta-Analysis.

ObjectiveThe aim of the present study was to investigate the predictive value of using the multiple of the median (MoM) of β-human chorionic gonadotropin (β-hCG) levels in patients with preeclampsia (PE) and healthy pregnant women.MethodsElectronic databases including PubMed, EBSCO, Ovid, Web of Science, China National Knowledge Infrastructure (CNKI), SinoMed, Wangfang and the Weipu Journal were searched up to May 31, 2020. Two reviewers independently selected the articles and extracted data on study characteristics, quality and results. A random-effects model was employed, and standardized mean difference and 95% confidence intervals were calculated. Twenty-one case-control studies were analyzed in the present meta-analysis, including a total of 2,266 cases and 25,872 healthy controls.ResultsWomen who were diagnosed with PE were found to have higher early second-trimester levels of serum β-hCG MoM compared with healthy controls, although the levels in the first trimester were not significantly different. Ethnicity subgroup analysis demonstrated that the MoM of β-hCG serum levels was significantly higher in PE patients in both Asian and Caucasian populations during the early second trimester.ConclusionThe MoM of β-hCG serum levels was found to be a valuable clinical indicator for predicting PE in the early second trimester, but had little predictive value in the first trimester. However, further assessment of the predictive capacity of β-hCG within larger, diverse populations is required.

Quality control of ultrasonography markers for Down's syndrome screening: a retrospective study by the laboratory.

Quality control of ultrasonography markers is necessary to ensure greater efficacy of prenatal aneuploidy screening. The aim of this study was to assess the quality of the crown-rump length (CRL) and nuchal translucence (NT) measurement accuracy by the laboratory according to quality indicators. Retrospective observational study on 4,908 single-foetus pregnant women who underwent prenatal aneuploidy screening in the first trimester of pregnancy. Euploid foetuses with CRL between 45 and 84mm were included, while those with NT≥3.5mm were excluded. CRL measurement was considered to be accurate if the median multiples of the median (MoM) for pregnancy-associated plasma protein A (PAPP-A) was between 0.90 and 1.10. Fifteen sonographers participated in the study, six of whom comprised the control group. Systematic error for a sonographer was considered when CRL measurement was greater than ±2mm with respect to the control group. Quality for NT was assured by means of the WHIRI method and each sonographer cumulative sum control chart (CUSUM). For CRL accuracy, five sonographers underestimated the measurements, while another four overestimated them, with no statistical differences. For smaller sized foetuses, all sonographers met the established specifications. Regarding NT control, three sonographers did not meet the quality criteria for the median MoM. All sonographers met the specifications for the logarithmic standard deviation of the NT MoM levels. Thirteen sonographers met the CUSUM specifications. Evaluation of a quality control of ultrasonography parameters by laboratory professionals is necessary to avoid under- or overestimation tendencies for CRL and NT measurements. CUSUM is a useful tool for the immediate correction of errors in NT measurements.

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to −112.8%] and −23.3% [95%CI −41.9% to −4.7%]. Passing–Bablok indicated significant systematic (−2.78 [95%CI −3.57 to −2.04]) and proportional bias (1.30 [95%CI 1.15 to −1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65–0.78]) between inhibin-A assays. The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and −0.0001 [SD = 0.2078], and −0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81–83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Reexamining the optimal nuchal translucency cutoff for diagnostic testing in the cell-free DNA and microarray era: results from the Victorian Perinatal Record Linkage study

The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine recently recommended offering genetic counseling and diagnostic testing for enlarged nuchal translucency at ≥3.0 mm, regardless of previous negative screening with noninvasive prenatal testing. This study aimed to perform a population-based, individual record linkage study to determine the optimal definition of an enlarged nuchal translucency for the detection of atypical chromosome abnormalities. This was a retrospective study of women resident in Victoria, Australia, undergoing combined first-trimester screening during the 24-month period from January 2015 to December 2016. Linkages between statewide results for combined first-trimester screening, prenatal diagnostic procedures, and postnatal cytogenetic results from products of conception and infants up to 12 months of age were used to ascertain the frequency and type of chromosome abnormality by gestation and nuchal translucency measurement. An atypical chromosome abnormality was defined as any major chromosome abnormality other than whole chromosome aneuploidy involving chromosomes 21, 18, 13, X, and Y. Of the 81,244 singleton pregnancies undergoing combined first-trimester screening, 491 (0.60%) had a nuchal translucency of ≥3.5 mm, 534 (0.66%) had a nuchal translucency of 3.0 to 3.4 mm, and 80,219 (98.74%) had a nuchal translucency of < 3.0 mm. When grouped by nuchal translucency multiples of the median (MoM), 192 (0.24%) had a nuchal translucency of ≥3.0 MoM, 513 (0.63%) had a nuchal translucency of 1.9 to 2.9 MoM, and 80,539 (99.13%) had a nuchal translucency of <1.9 MoM. A total of 1779 pregnancies underwent prenatal or postnatal diagnostic testing, of which 89.60% were performed by whole-genome single-nucleotide polymorphism chromosomal microarray. The frequency of total major chromosome abnormalities was significantly higher in the group with a nuchal translucency of ≥3.5 mm (147 of 491, 29.94%) than the group with a nuchal translucency of 3.0 to 3.4 mm (21 of 534, 3.93%) or a nuchal translucency of <3.0 mm (71 of 80,219, 0.09%) (P<.001). There were 93 atypical chromosome abnormalities in the total screened cohort. The frequency of an atypical chromosome abnormality was 4.07% (95% confidence interval, 2.51-6.22), 0.37% (95% confidence interval, 0.05-1.35), and 0.09% (95% confidence interval, 0.07-0.11) in the groups with a nuchal translucency of ≥3.5 mm, 3.0 to 3.4 mm, and <3.0 mm, respectively. The frequency of atypical chromosome abnormalities was 4.69% (95% confidence interval, 2.17-8.71), 2.53% (95% confidence interval, 1.36-4.29), and 0.09% (95% confidence interval, 0.07-0.11) in the groups with a nuchal translucency of ≥3.0 MoM, 1.9 to 2.9 MoM, and <1.9 MoM, respectively. When defining thresholds for offering diagnosis with chromosomal microarray at 11 to 13 weeks, both a nuchal translucency threshold of 1.9 MoM and a fixed threshold of 3.0 mm captured 22 of 93 fetuses (23.7%) with an atypical chromosome abnormality. Of these, 50.0% had a coexisting fetal abnormality on ultrasound. However, the gestation-specific threshold of 1.9 MoM had a better specificity than 3.0 mm. The positive predictive value of an enlarged nuchal translucency for any atypical chromosome abnormality was 1 in 47 for nuchal translucency of >3.0 mm and 1 in 32 for nuchal translucency of >1.9 MoM. Our nuchal translucency threshold of 1.9 MoM captured 0.87% of fetuses, thus approximating the 99th centile. A gestational age-adjusted nuchal translucency threshold of 1.9 MoM or 99th centile is superior to the fixed cutoff of 3.0 mm for the identification of atypical chromosome abnormalities. The risk of an atypical chromosome abnormality in a fetus with an enlarged nuchal translucency is more than tripled in the presence of an additional ultrasound abnormality.

Relationship between ophthalmic artery Doppler and maternal cardiovascular function.

In mid-gestation, the finding of an increase in the ophthalmic artery second to first peak of systolic velocity ratio (PSV ratio) provides useful prediction of subsequent development of pre-eclampsia (PE). The objective of this study of an unselected population at 19-23 weeks' gestation was to gain a better understanding of the factors that influence ophthalmic artery Doppler by examining the possible association between the PSV ratio and maternal cardiovascular function. This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included assessment of flow velocity waveforms from the maternal ophthalmic arteries and assessment of maternal cardiovascular function. The following nine cardiovascular indices were examined: E/A ratio; E/e' ratio; myocardial performance index; global longitudinal systolic strain; left ventricular ejection fraction; peripheral vascular resistance; left ventricular cardiac output; left ventricular mass indexed for body surface area; and mean arterial pressure. The ophthalmic artery PSV ratio and the nine cardiovascular indices were converted to either log10 multiples of the median (MoM) values or deviations from the median (deltas) values after adjustment for maternal characteristics and elements of medical history. Regression analysis was then used to examine the significance of the association between PSV ratio delta and MoM or delta values of each cardiovascular index in the total population and in the subgroup that developed PE. The study population of 2853 pregnancies contained 76 (2.7%) that developed PE. In the total population, there were significant but weak associations between the PSV ratio and most of the cardiovascular indices, with r-values of < 0.1, except for mean arterial pressure with r = 0.178. In the subgroup that developed PE, a moderately strong association between the PSV ratio and left ventricular mass indexed for body surface area was noted (r = 0.308). The findings of this study suggest that Doppler assessment of PSV ratio in the ophthalmic artery provides information about peripheral vascular status. The increase in PSV ratio in women who develop PE is associated with increased afterload and an increase in left ventricular thickness. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Placental Growth Factor and Adverse Obstetric Outcomes in a Mixed-Risk Cohort of Women Screened for Preeclampsia in the First Trimester of Pregnancy

Objective: The study aimed to investigate the association between placental growth factor (PlGF) and adverse obstetric outcomes in a mixed-risk cohort of pregnant women screened for preeclampsia (PE) in the first trimester. Methods: We included women with singleton pregnancies screened for PE between April 2014 and September 2016. Outcome data were retrieved from the New South Wales Perinatal Data Collection (NSW PDC) by linkage to the prenatal cohort. Adverse outcomes were defined as spontaneous preterm birth (sPTB) before 37-week gestation, birth weight (BW) below the 3rd centile, PE, gestational hypertension (GH), stillbirth, and neonatal death. Results: The cohort consisted of 11,758 women. PlGF multiple of the median (MoM) was significantly associated with maternal sociodemographic characteristics (particularly smoking status and parity) and all biomarkers used in the PE first trimester screening model (notably pregnancy-associated plasma protein A MoM and uterine artery pulsatility index [PI] MoM). Low levels of PlGF (<0.3 MoM and <0.5 MoM) were independently associated with sPTB, low BW, PE, GH, and a composite adverse pregnancy outcome score, with odds ratios between 1.81 and 4.44 on multivariable logistic regression analyses. Conclusions: Low PlGF MoM levels are independently associated with PE and a range of other adverse pregnancy outcomes. Inclusion of PlGF should be considered in future models screening for adverse pregnancy outcomes in the first trimester.

Maternal cardiac function at 19-23 weeks' gestation in prediction of pre-eclampsia.

First, to examine the factors from maternal characteristics and medical history that affect maternal cardiovascular indices, and, second, to examine the potential value of maternal cardiovascular indices at 19-23 weeks' gestation, on their own and in combination with maternal factors and the established biomarkers of pre-eclampsia (PE), including uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1), in the prediction of subsequent development of PE. This was a prospective observational study in women attending for a routine hospital visit at 19 + 1 to 23 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, assessment of maternal E/A ratio, E/e' ratio, myocardial performance index, global longitudinal systolic strain, left ventricular ejection fraction, peripheral vascular resistance, left ventricular cardiac output and left ventricular mass indexed for body surface area, and measurement of MAP, UtA-PI, serum PlGF and serum sFlt-1. The measurements of the eight maternal cardiac indices were standardized to remove the effects of maternal characteristics and elements from the medical history. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE and determine the detection rate, at a 10% false-positive rate, in screening by a combination of maternal demographic characteristics and medical history with biomarkers. The study population of 2853 pregnancies contained 76 (2.7%) that developed PE. In pregnancies that subsequently developed PE, there was evidence of altered cardiac geometry, impaired myocardial function and increased peripheral vascular resistance. All maternal cardiovascular indices were affected significantly by maternal demographic characteristics and elements of medical history known to be associated with an increased risk for subsequent development of PE. After adjustment for maternal demographic characteristics and medical history, the only cardiovascular index that was affected significantly by subsequent development of PE was peripheral vascular resistance. Peripheral vascular resistance multiples of the median (MoM) was correlated with MAP MoM, which is not surprising because blood pressure is involved in the estimation of both. There were weak correlations between several cardiovascular indices and MAP MoM, but none was correlated with MoM values of UtA-PI, PlGF or sFlt-1. The performance of screening for delivery with PE at < 37 weeks' gestation or delivery with PE at any gestational age in screening by maternal demographic characteristics and medical history or combinations of maternal factors with MAP, UtA-PI, PlGF and sFlt-1 was not improved by the addition of peripheral vascular resistance. Assessment of maternal cardiovascular function provides information on the pathophysiology of PE but is not useful in the prediction of PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum: A prospective cohort study.

IntroductionLittle is known about the pathophysiology of hyperemesis gravidarum (HG). Proposed underlying causes are multifactorial and thyroid function is hypothesized to be causally involved. In this study, we aimed to assess the utility of thyroid‐stimulating hormone (TSH) and free thyroxine (FT4) as a marker and predictor for the severity and clinical course of HG.Material and methodsWe conducted a prospective cohort study including women admitted for HG between 5 and 20 weeks of gestation in 19 hospitals in the Netherlands. Women with a medical history of thyroid disease were excluded. TSH and FT4 were measured at study entry. To adjust for gestational age, we calculated TSH multiples of the median (MoM). We assessed HG severity at study entry as severity of nausea and vomiting (by the Pregnancy Unique Quantification of Emesis and nausea score), weight change compared with prepregnancy weight, and quality of life. We assessed the clinical course of HG as severity of nausea and vomiting and quality of life 1 week after inclusion, duration of hospital admissions, and readmissions. We performed multivariable regression analysis with absolute TSH, TSH MoMs, and FT4.ResultsBetween 2013 and 2016, 215 women participated in the cohort. TSH, TSH MoM, and FT4 were available for, respectively, 150, 126, and 106 of these women. Multivariable linear regression analysis showed that lower TSH MoM was significantly associated with increased weight loss or lower weight gain at study entry (ΔKg; β = 2.00, 95% CI 0.47‐3.53), whereas absolute TSH and FT4 were not. Lower TSH, not lower TSH MoM or FT4, was significantly associated with lower nausea and vomiting scores 1 week after inclusion (β = 1.74, 95% CI 0.36‐3.11). TSH and FT4 showed no association with any of the other markers of the severity or clinical course of HG. Twenty‐one out of 215 (9.8%) women had gestational transient thyrotoxicosis. Women with gestational transient thyrotoxicosis had a lower quality of life 1 week after inclusion than women with no gestational transient thyrotoxicosis (p = 0.03).ConclusionsOur findings show an inconsistent role for TSH, TSH MoM, or FT4 at time of admission and provide little guidance on the severity and clinical course of HG.

A risk model that combines MAP, PlGF, and PAPP-A in the first trimester of pregnancy to predict hypertensive disorders of pregnancy.

Whether the first trimester maternal mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) can predict hypertensive disorders of pregnancy (HDP) is unclear. We conducted a retrospective case-control study with the total population of 539 gravidas, of these 447 had normal pregnancy, 27 had gestational hypertension (GH), 36 had preeclampsia (PE), and 29 had preeclampsia with severe features (SPE). Prediction for HDP was determined by the area under curve (AUC). Compared to the healthy group, the multiple of the median (MoM) for MAP was increased in the study groups, while PlGF and PAPP-A were decreased. When the cutoff values for MAP, PlGF, and PAPP-A were 1.069, 0.769, and 0.673 MoM, respectively, the sensitivities for predicting HDP were 0.517, 0.446, and 0.500 and the specificities were 0.744, 0.826, and 0.769, respectively. To predict GH, the highest AUC was 0.755 (95% CI: 0.655-0.856, p < 0.001) based on MAP, PlGF, and PAPP-A. The combined PlGF and PAPP-A had the highest AUC (0.683 [95% CI: 0.584-0.782, p < 0.001] and 0.755 [95% CI: 0.682-0.829, p < 0.001]) for prediction of PE and SPE. We found that MAP, serum levels of PlGF, and PAPP-A in the first trimester pregnancy are markers that predict HDP in the third trimester. The combination of markers is far superior to single markers alone. To improve the diagnostic value, specific cutoff values should be applied to GH, PE, SPE in each condition.

965 Accuracy of middle cerebral artery doppler ultrasound for fetal anemia prior to 24 weeks gestation

Fetal middle cerebral artery (MCA) peak systolic velocity of Doppler ultrasound varies with gestational age, and it is unclear if established reference ranges are applicable to pregnancies less than 24 weeks. We aimed to estimate the positive predictive value and false positive rate of MCA Doppler ultrasound for assessment of fetal anemia at gestational ages less than 24 weeks. A retrospective cohort study was performed in a single healthcare system over a 10-year period. All fetuses at risk of alloimmunization less than 24 weeks gestation who had MCA Doppler ultrasounds were identified. Non-immune causes of fetal anemia were excluded. Peak MCA systolic velocity > 1.5 multiples of the median (MoM) were considered positive and periumbilical blood sampling was considered. Pregnancy and neonatal outcomes were reviewed for all patients. The positive predictive value of MCA Doppler peak systolic velocity for fetal anemia prior to 24 weeks was estimated with 95% confidence intervals based on the binomial exact method. 126 pregnancies at risk for fetal anemia due to maternal alloimmunization had MCA Doppler ultrasound assessments prior to 24 weeks gestation. Of these, eleven had MCA peak systolic velocity > 1.5 MoM. Seven of the eleven were confirmed to have fetal anemia on percutaneous umbilical sampling while four were false positives, corresponding to a positive predictive value of 7/11 (64%, 95% CI 31%, 89%) and a false positive rate of 4/11 (36%, 95% CI 11%, 69%). MCA Doppler assessment performed at less than 24 weeks gestation had a positive predictive value of 64% for identification of fetal anemia, suggesting that 1 in 3 are false positives. This must be taken into account when considering percutaneous umbilical sampling in patients were positive fetal MCA Dopplers before 24 weeks.