Multiples Of The Median Values Research Articles

Increased Nuchal Translucency and Pregnancy Outcomes: A Tertiary Center Data

Aim: This study aimed to evaluate the pregnancy outcomes of patients who applied to our clinic between the 11th and 14th weeks of pregnancy and whose nuchal translucency (NT) measurement was ≥1.5 multiples of the median (MoM). Material and Methods: The study included 85 patients whose NT measurement was determined ≥1.5 MoM and pregnancy results were available. Demographic characteristics of the patients, prenatal invasive diagnostic test results, fetal anomaly screening, fetal echocardiography (ECHO) results, and neonatal and obstetric results were evaluated. Results: Abnormal karyotype was detected in 10.6% (n=9) of the patients. Trisomy 21 was the most common chromosomal anomaly. Fetal structural anomaly was detected in 29.4% (n=25) of the patients. A structural fetal anomaly was detected in 21% (n=13) of fetuses with normal karyotypes and 66.7% (n=6) of fetuses with abnormal karyotypes. Cardiac anomalies were found to be the most common anomalies with 9.7% (n=6) in patients with normal karyotype. NT and NT MoM values in patients with fetal structural (both p=0.001) or chromosomal anomalies (p=0.011, and p=0.019, respectively) were found significantly higher than those without. NT and NT MoM values in patients whose pregnancies resulted in fetal loss were found significantly higher than in patients who had a live birth (both p=0.001). Conclusion: Increasing NT or NT MoM values indicate an increase in the risk of chromosomal anomalies, structural anomalies, and poor pregnancy outcomes in the fetus. Fetal anomaly screening and fetal ECHO should be recommended in patients with increased NT, even if a normal karyotype is detected.

The impact of fresh versus frozen-thawed embryos on maternal serum analyte levels in IVF singleton and twin pregnancies.

To determine whether embryo cryopreservation is associated with a difference in maternal serum analyte levels in singleton and twin pregnancies conceived via in vitro fertilization (IVF). This was a retrospective cohort study of singleton and twin pregnancies conceived via IVF from a university health system from 01/2014 to 09/2019. Patients with available first and second trimester serum analyte data were included and analyzed separately. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A, alpha-fetoprotein (AFP), Inhibin A, and unconjugated estriol (uE3) were compared between two groups: pregnancies conceived after the transfer of fresh embryos versus pregnancies conceived after the transfer of frozen-thawed embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. For singletons, fresh embryos were associated with a lower median first trimester free β-hCG (1.00 MoM vs. 1.14 MoM; parameter estimate [PE] 0.90, 95% CI 0.82-0.99, p = .03) compared to frozen-thawed embryos. Fresh embryos were also associated with a lower median second trimester uE3 (0.93 MoM vs. 1.05 MoM; PE 0.88, CI 0.83-0.95, p = .0004) and AFP (1.02 MoM vs. 1.19 MoM; PE 0.91, CI 0.84-0.99, p = .02) compared to frozen-thawed embryos in singletons. There were no significant differences between median first and second trimester serum analytes in twin pregnancies compared between the two groups. Singleton pregnancies derived from fresh embryos had lower first (free β-hCG) and second (uE3 and AFP) trimester analytes compared to frozen-thawed embryos. Twin pregnancies demonstrated no difference between the groups.

Aspirin for evidence-based preeclampsia prevention trial: effects of aspirin on maternal serum pregnancy-associated plasma protein A and placental growth factor trajectories in pregnancy

BackgroundThe exact mechanism by which aspirin prevents pre-eclampsia (PE) remains unclear. Its effects on serum placental biomarkers throughout pregnancy are also unknown. ObjectiveTo investigate the effects of aspirin on serum pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF) trajectories using repeated measures from women at increased risk of preterm PE. Study DesignThis was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-based Preeclampsia Prevention (ASPRE) trial using repeated measures of PAPP-A and PlGF. In the trial, 1,620 women at increased risk of preterm PE were identified using the Fetal Medicine Foundation algorithm at 11-13+6 weeks, of whom 798 were randomly assigned to receive aspirin 150 mg and 822 to receive placebo daily from before 14 weeks to 36 weeks of gestation. Serum biomarkers were measured at baseline and follow-up visits at 19 to 24, 32 to 34, and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effect of aspirin on biomarker trajectories over time. ResultsOverall, there were 5,507 PAPP-A and 5,523 PlGF measurements. Raw PAPP-A values increased over time, and raw PlGF increased until 32 weeks of gestation followed by a decline. The multiple of the median (MoM) mean values of the same biomarkers were consistently below 1.0 MoM, reflecting the high-risk profile of the study population. Trajectories of mean PAPP-A and PlGF MoM values did not differ significantly between the aspirin and placebo groups (aspirin treatment by gestational age interaction p-values: 0.259 and 0.335, respectively). ConclusionsIn women at increased risk of preterm PE, aspirin 150 mg daily had no significant effects on PAPP-A or PlGF trajectories when compared to placebo.

A Retrospective Cohort Study to Determine Whether the Previous Route of Delivery Affects the Uterine Artery Blood Flow.

In our study, we aimed to investigate the effect of the previous delivery route on uterine artery pulsatility index (PI) and obstetric outcome.We aim to assess the effects of previous cesarean delivery (CD) and placental location on first- and second-trimester uterine artery Doppler indices as well as first-trimester pregnancy-associated plasma protein-A (PAPP-A)multiples of the median (MoM) levels in the subsequent pregnancy. We designed a retrospective cohort study to collect the participants' clinical and uterine artery Doppler.Data regarding pregnant women's first- and second-trimester exams, who were referred to our maternal-fetal medicine unit, were collected from hospital records between June 2015 and December 2019. Uterine artery PI MoM values were not different between the cases with the anterior and non-anterior placental locations. No significant difference was found in the first- and second-trimester uterine artery PI MoMvalues by delivery route (p = 0.57). However, the intrauterine growth restriction rate was higher in the CD group (p < 0.001). In this study, we compared the uterine blood flow indices between the previous cesarean and vaginal delivery groups. We observed no significant difference between the patients with different delivery routes.

Familial Hypercholesterolemia Biomarker Distribution in Dried Blood Spots

To evaluate distribution profiles of total cholesterol (TC), lipoprotein cholesterol (LDL-C), and apolipoprotein B (apoB) as candidate markers of familial hypercholesterolemia (FH) in newborns, taking into consideration potential confounding factors, such as gestational age, birthweight, sex, and race. TC, LDL-C, and apoB were measured from 10,000 residual deidentified newborn dried blood spot cards. Concentrations for each biomarker were reported as multiples of the median (MoM), with emphasis on describing the 99th percentile values based on birth weight, gestational age, sex, and race. Seasonal variation of biomarkers was also explored. LDL-C and apoB had distribution curves with tails showing extreme elevation while the distribution of TC was less elevated and had the smallest range. Neonates born at early gestational age and low birth weight had significantly higher 99th percentile of MoM values for apoB but not TC or LDL-C. Differences in biomarker concentration based on sex and race were minimal. All biomarkers showed highest concentrations in the winter as compared with summer months. LDL-C and apoB had distribution curves supporting candidacy for neonatal FH screening. Future studies are needed to correlate newborn screening results with molecular testing to validate these two biomarkers, along with measured cholesterol levels later in childhood.

Validation of a monoclonal unconjugated estriol antibody for use in prenatal maternal serum screening.

Unconjugated estriol (uE3) is used as a marker for fetal aneuploidy in maternal serum screening tests. The goal of this study was to examine the validity of a new immunoassay for uE3 that uses a monoclonal antibody (m-uE3) rather than the more commonly used polyclonal antibody (p-uE3). Assays were performed in the Special Chemistry laboratory at Women and Infants Hospital of Rhode Island. Residual fresh (n = 100) and frozen (n = 533) second trimester serum samples from routine clinical care were tested using p-uE3 and/or m-uE3 assays. Assay results were compared between methods using Bland-Altman plots. A median equation was developed for m-uE3 results. Down syndrome risks were compared between the two assays in a case-control sample set (21 cases each matched with five controls for the completed week of gestation, duration of freezer storage and race). Log-transformed serum uE3 levels were highly correlated between the assays (r = 0.93, p < 0.001), with the m-uE3 assay levels yielding, on average, 23% higher (standard deviation of differences in log uE3 concentrations = 0.07) results. Assay and gestation-based median equations were calculated and used to convert m-uE3 concentrations to multiples of the median (MoM). The m-uE3 MoM values fit a log Gaussian distribution well with a log standard deviation of 0.11. Down syndrome risk results were not significantly different between assays. The m-uE3 assay, with results expressed in MoMs, is suitable for screening and as a monoclonal-based assay offers the advantage of a predictable and indefinite supply of antibody to perform the assay.

First-Trimester Biochemical Serum Markers in Female Kidney Transplant Recipients-The Impact of Graft Function.

Data on serum biochemistry markers as a component of the first-trimester screening test in pregnant kidney graft recipients are limited. In the absence of a separate validated algorithm, biochemical testing is commonly used in the first-trimester screening in kidney transplant recipients. Therefore, the study aimed to analyze first-trimester serum biochemical markers and the first trimester combined screening results in pregnant kidney graft recipients. A retrospective study was carried out in pregnant women who underwent the first-trimester combined screening test performed per the Fetal Medicine Foundation (FMF) protocol in 2009−2020. The study group included 27 pregnancies in kidney graft transplant recipients, and the control group was 110 patients with normal kidney function, matched according to age, body mass index (BMI), and gestational age. The biochemical serum markers (free beta-human chorionic gonadotropin [beta-hCG] and pregnancy-associated plasma protein A [PAPP-A]) were evaluated using the FMF-approved Roche Elecsys® assay and exhibited as multiples of the median (MoM) values. Data on first-trimester screening test results, perinatal outcomes, and graft function (assessed using serum creatinine concentrations) were analyzed. The analysis of first-trimester screening parameters revealed no difference in nuchal translucency (NT) measurements and uterine artery flow. However, free beta-hCG MoM and PAPP-A values were higher in posttransplant pregnancies than in controls: 3.47 ± 2.08 vs. 1.38 ± 0.85 (p = 0.035) and 1.46 ± 0.81 vs. 0.98 ± 0.57 (p = 0.007), respectively. The false positive rate of trisomy 21 (T21) screening in graft recipients was 25.9% vs. 3% in the controls. The free β-hCG MoM values positively correlated with serum creatinine levels before (r = 0.653; p < 0.001), during (r = 0.619; p = 0.001), and after pregnancy (r = 0.697; p < 0.001). There was a statistically significant negative correlation for PAPP-A MoM values for postpartum serum creatinine concentration (r = −0.424, p = 0.035). Our results show significantly higher serum concentrations of free beta-hCG and PAPP-A in posttransplant pregnancies than in healthy controls, confirmed when exhibited as MoM values and their association with graft function was assessed by serum creatinine concentration. Taking those changes into account would reduce the high number of false positive test results in this group. The validated first-trimester screening algorithm that considers altered kidney function in pregnant kidney graft recipients remains to be developed.

Increased risk of low infant birth weight in pregnant women with low PAPP-A values measured in the first trimester

Objectives: Testing pregnant women as early as in the first trimester has multiple advantages. Firstly, the first trimester screening combining ultrasound and serum marker testing (PAPP-A and free β-hCG) offers the highest currently possible — except for expensive tests using cell-free DNA biomarkers from the mother’s blood (ccf DNA) — detectability of aneuploid fetuses. Secondly, nuchal translucency (NT) measurement helps determine the risk of numerous abnormalities other than aneuoploidies. Lastly, nearly complete ultrasound assessment of fetal anatomy can be performed as early as in the first trimester of pregnancy. Material and methods: This study is based on prospective analysis. Study subjects were 236 pregnant women. One hundred thirty-one patients with a single pregnancy were qualified into the study group and had a combined ultrasound and biochemical screening for Down’s syndrome performed between 11 + 0 and 13 + 6 weeks of gestation, with the measured PAPP-A value at ≤ 0.50 MoM (multiples of the median). The control group comprised 105 pregnant women with PAPP-A value at a similar stage of pregnancy at &gt; 0.5 MoM. Results: The average observed value of the PAPP-A in the study group was 0.35 MoM while in the control group 1.29 MoM. Moreover, combined observation of infant birth weights in both groups compared to the PAPP-A MoM values has shown a significant relationship between those characteristics (r = 0.15, p = 0.0184). Conclusions: The results showed that pregnant women with low PAPP-A MoM value measured during the first trimester have a higher risk of giving birth to a low-birth-weight infant (which is the value below 2500 g), than the pregnant women whose PAPP-A MoM value in the first trimester did not meet this criterion.

The impact of preimplantation genetic testing on first- and second-trimester maternal serum analyte levels

Objective To determine whether preimplantation genetic testing (PGT) is associated with a change in maternal serum analyte levels in pregnancies conceived via in vitro fertilization (IVF). Methods Retrospective cohort of singleton and twin IVF pregnancies with available first- or second-trimester serum analyte data from 01/2014 to 09/2019. Multiple of the median (MoM) values for free β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein (AFP), inhibin A, and unconjugated estriol, were compared between two groups: pregnancies conceived after transfer of PGT screened euploid embryos vs. those conceived after transfer of untested embryos. Multiple linear regression of log MoM values with F test was performed to adjust for potential confounders. Results Nine hundred and sixty-two singleton and 165 twin IVF pregnancies with serum analyte data available for analysis were included. PGT was associated with a higher median first- and second-trimester AFP compared to no PGT in singletons (1.23 MoM vs. 1.13 MoM; parameter estimate [PE] 1.08, 95% CI 1.00–1.17, p= .04, and 1.21 MoM vs. 1.07 MoM; PE 1.07, 95% CI 1.01–1.13, p= .01, respectively). PGT was also associated with a lower median PAPP-A compared to no PGT in twins (0.75 MoM vs. 1.18 MoM, PE 0.74, 95% CI 0.60–0.92, p= .006). Conclusions Our data suggest that PGT is associated with higher maternal serum levels of second-trimester AFP in singleton and lower levels of first-trimester PAPP-A in twin pregnancies conceived via IVF.

Midgestation cardiovascular phenotype in women who develop gestational diabetes and hypertensive disorders of pregnancy: comparative study.

Women with gestational diabetes mellitus (GDM) and/or hypertensive disorders of pregnancy (HDP) are at increased long-term cardiovascular risk. Mild cardiac functional alterations have been detected in women with GDM or HDP in midgestation, prior to clinical onset of the disease, but these functional alterations have not been found to be useful as screening tools. In contrast, increased impedance to peripheral blood flow, measured by echocardiography or ophthalmic artery Doppler, has been shown to provide incremental value to maternal characteristics for the prediction of pre-eclampsia. However, it is unknown whether similar changes can be detected in women at risk of GDM. In this study, we performed detailed cardiovascular phenotyping in a large, unselected population of women in midgestation to identify similarities and differences in cardiovascular adaptation in women who are at risk of GDM and/or HDP. 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, echocardiography for assessment of maternal cardiovascular function and measurement of uterine artery pulsatility index and serum placental growth factor (PlGF) for assessment of placental perfusion and function. The measured indices were converted to either multiples of the median (MoM) values or deviation from the median (delta) after adjusting for maternal characteristics and elements of medical history. Biomarker delta or MoM values in the GDM and HDP groups were compared with those in the unaffected group using 95% CI and t-tests. The study population of 5214 pregnancies contained 4429 (84.9%) that were unaffected by GDM or HDP, 509 (9.8%) complicated by GDM without HDP, 41 (0.8%) with GDM and HDP, and 235 (4.5%) with HDP without GDM. In HDP cases, with or without GDM, there was evidence of impaired placentation, with a decrease in PlGF, and increased impedance to flow in the peripheral circulation, suggested by an increase in ophthalmic artery peak systolic velocity (PSV) ratio, peripheral vascular resistance assessed on echocardiography and mean arterial pressure. In the GDM group without HDP, there was no evidence of altered placental perfusion or function and ophthalmic artery PSV ratio was not significantly different from that in the unaffected group; peripheral vascular resistance and mean arterial pressure were increased but to a lesser degree than in the HDP group. In the HDP group, there was an increase in global longitudinal systolic strain and slight increase in isovolumic relaxation time, while in the GDM group, there was an increase in mitral valve E/e', myocardial performance index and global longitudinal systolic strain. In midgestation, women who subsequently develop HDP or GDM have a mild subclinical reduction in left ventricular function. In HDP cases, with or without GDM, there is evidence of impaired placentation and all biomarkers of impedance to peripheral blood flow are consistently increased. In contrast, in the GDM group without HDP, biomarkers of placental function are normal and those of impedance to peripheral blood flow are either marginally increased or not significantly different from those in normal pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal cardiac function in twin pregnancy at 19-23 weeks' gestation.

To compare maternal cardiovascular indices at 19-23 weeks' gestation between twin and singleton pregnancies and assess the impact of chorionicity on these parameters. This was a prospective observational study in women with twin pregnancy attending for a hospital visit at 19 + 1 to 24 + 3 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history and maternal cardiovascular assessment. In a previous study of 4795 women with singleton pregnancies at 19-23 weeks' gestation, multivariable linear regression models were fitted between the various cardiovascular indices and elements of maternal characteristics and medical history. In this study, we calculated multiples of the median (MoM) and delta values according to the singleton models and assessed the distributional properties of these MoM and delta values in twin as compared with singleton pregnancies. The study population of 155 women with twin pregnancy included 86 dichorionic and 69 monochorionic cases. In general, there was a similar distribution of maternal cardiovascular indices in monochorionic and dichorionic twin pregnancies. In both types of twin pregnancy, compared with singleton pregnancy, there was an increase in isovolumetric relaxation time, left atrial area and myocardial performance index, and a decrease in mitral valve E/A. Left ventricular mass indexed for body surface area and relative wall thickness were also increased in twin compared with singleton pregnancy. The magnitude of the increase in left atrial area was greater in dichorionic compared with monochorionic pregnancies. Additionally, mitral valve E was decreased and left atrial volume was increased in dichorionic but not in monochorionic pregnancies, while isovolumetric contraction time was increased in monochorionic but not in dichorionic pregnancies. Left ventricular myocardial deformation was similar between twin and singleton pregnancies. In twin pregnancies at mid-gestation, maternal systolic and diastolic function is reduced when compared with singletons. The patterns of cardiovascular adaptation are similar between monochorionic and dichorionic pregnancies and resemble those reported in uncomplicated singleton pregnancy later in gestation. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Multi-marker risk-based screening for prostate cancer.

ObjectiveTo determine prostate cancer screening performance using prostate specific antigen (PSA) along with other markers, expressing markers in age-specific multiples of the median (MoM), and age.MethodsA prospective nested case-control study used stored serum from 571 men who died of, or with history of, prostate cancer (cases), and 2169 matched controls. Total, free and intact PSA, human kallikrein-related peptidase 2 (hK2), and microseminoprotein were measured and converted into MoM values. Screening marker distribution parameters were estimated in cases and controls. Monte Carlo simulation used these in a risk-based algorithm to estimate screening performance (detection rates [DRs] and false-positive rates [FPRs]).ResultsAlmost all (99%) cases occurred aged ≥55. Marker values were similar in cases who did and did not die of prostate cancer. Combining age, total PSA and hK2 MoM values (other markers added little or no discrimination) yielded a 1.2% FPR (95% CI 0.2–4.8%) for a 90% DR (59–98%) in men who died of or with a prostate cancer diagnosis within 5 years of blood collection (risk cut-off 1 in 20), two-thirds less than the 4.5% FPR using total PSA alone measured in ng/ml for the same 90% DR (cut-off 3.1 ng/ml). Screening performance over 10 years yielded a 33% (22–46%) FPR for a 90% DR.ConclusionScreening performed up to every 5 years from age 55 using the multi-marker risk-based screening algorithm for future prostate cancer achieves a high DR and a much lower FPR than using PSA alone, resulting in reductions in overdiagnosis and overtreatment.

Maternal serum Lamin A is a potential biomarker that can predict adverse pregnancy outcomes.

SummaryBackgroundMaternal serum Lamin A (LMNA) was reported to have potential diagnostic value in the prenatal diagnosis of congenital heart disease (CHD). In this study, we aimed to further assess the prognostic value of maternal serum LMNA in predicting adverse pregnancy outcomes.MethodsA prospective screening study was performed on singleton pregnancies at 15–18 weeks of gestation. After a routine test for alpha fetoprotein (AFP), chorionic gonadotropin (hCG), and unconjugated estriol (uE3), serum LMNA levels were measured. Serum LMNA levels were then converted into multiples of the median (MoM). The median MoM values for adverse pregnancy outcomes were compared with those in normal pregnancies. For diseases with differential LMNA expression in the prospective study, another case-control cohort was recruited. The diagnostic value of LMNA in these diseases was further evaluated.FindingsBetween January 1, 2017 and June 30, 2018, a total of 2906 singleton pregnancies were recruited. Of the 2,906 cases, 2711 had data available for analysis. Congenital structural abnormalities, chromosomal abnormalities, and obstetric complications were observed in 152 (5·6%), 15 (0·6%), and 278 (10·3%) patients, respectively. LMNA was downregulated in pregnancies with fetal CHD, fetal neural tube defects (NTD), and preeclampsia (PE). The case-control study cohort included 256 CHD, 60 NTD, 67 PE, and 400 normal pregnancies. The areas under the curve for the prenatal diagnoses of CHD, NTD, and PE were 0·875, 0·871, and 0·816, respectively.InterpretationMaternal serum LMNA was found to be a potential biomarker for the prenatal diagnosis of fetal CHD, NTD, and PE.FundingNational Key Research and Development Program, National Natural Science Foundation of China, LiaoNing Revitalization Talents Program, National Natural Science Foundation of Liaoning, and 345 Talent Project of Shengjing Hospital.

External Quality Assessment of Maternal Serum Levels of Alpha-Fetoprotein, Free Beta-Human Chorionic Gonadotropin, and Unconjugated Estriol in Detecting Down Syndrome and Neural Tube Defects in the Second Trimester of 87 Maternal Serum Samples, Based on 105-139 Days.

BackgroundWe aimed to insure the accuracy and reproducibility of alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin (free β-hCG), and unconjugated estriol (uE3) concentrations for the screening for trisomy 21 (T21) and neural tube defects (NTD) in the second trimester. We conducted an external quality assessment of 6 laboratories, using maternal serum specimens.Material/MethodsSerum specimens collected from 87 women of singleton pregnancies (4 with T21, 5 with NTD, and 78 with normal fetuses) were divided into 6 equivalent-volume fractions and transported to 6 laboratories (A, B, C, D, E, and F). All laboratories used the time-resolved fluorescence analyzer and supporting reagents to measure concentrations of AFP, free β-hCG, and uE3. The screening efficacies of T21 and NTD were compared with the certified or accredited status of the participants’ quality systems.ResultsConcentrations of AFP measured by laboratory F were low compared with those determined by the other 5 laboratories, and the differences were significant (P<0.01). There was no statistically significant difference in the free β-hCG and uE3 concentrations measured by the 6 laboratories (P>0.05). The correlation coefficients for the 3 multiples of the median values were all >0.900. The McNemar paired chi-squared test showed the differences in the positivity and detection rates were not statistically significant (P=1.000).ConclusionsAFP, freeβ-hCG, and uE3 values measured by the other 5 laboratories were comparable with those of laboratory A, with good linear correlation. When used in the maternal prenatal screening of T21 and NTD, the test results met the clinical requirements.

Serial Inhibin B Measurements in Boys with Congenital Monorchism Indicate Compensatory Testicular Hypertrophy in Early Infancy.

Congenital monorchism is considered a condition in which an initially normal testis has existed but subsequently atrophied and disappeared due to a third trimester catastrophe (presumably torsion). Since inhibin B concentrations appear related to Sertoli and germ cells number, we evaluated pre- and postoperative inhibin B of boys with congenital monorchism to determine whether the well-known hypertrophy of the contralateral testis was reflected in inhibin B concentrations. Twenty-seven boys consecutively diagnosed with congenital monorchism (median age 12 months) underwent follow-up with reproductive hormones 1 year postoperatively (median age 25 months). The results were compared with inhibin B of 225 boys with congenital nonsyndromic unilateral cryptorchidism, by converting values to multiple of the median (MoM) for age in normal boys. Ten boys (37%) had blind-ending vessels and ductus deferens (vanished testis) and the remaining (63%) had testicular remnants. At the time of diagnostic procedure, monorchid boys did not have significantly lower inhibin B (median 114, range 20-208) than unilateral cryptorchid boys (136, 47-393) (p = 0.27). During follow-up, MoM values of inhibin B increased in monorchid boys (median 0.59 to 0.98) and in unilateral cryptorchid boys (0.69 to 0.89) (both p < 0.0001). Compared with the concentration at surgery, an additional 44% monorchid boys had inhibin B MoM values higher than 1.0, whereas only additional 23% of unilateral cryptorchid boys exhibited such values (p = 0.04). Generally, inhibin B MoM values were normalized during follow-up in boys with congenital monorchism, reflecting compensatory hypertrophy within the first 2.5 years of life. The compensatory capacity to increase was better in monorchism than in unilateral cryptorchidism.

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.

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.

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.

Fetal fraction of cell free DNA in screening for hypertensive disorders at 11–13 weeks

Objective To investigate whether first-trimester maternal plasma fetal fraction is altered in women that subsequently develop preeclampsia (PE) or gestational hypertension (GH) and to examine its potential value in improving the performance of screening for PE and GH by maternal factors and maternal serum pregnancy associated plasma protein-A (PAPP-A), mean arterial pressure (MAP) and uterine artery pulsatility index (UtA-PI). Methods The study population of 10,131 pregnancies undergoing cell free fetal DNA testing at 11–13 weeks’ gestation included 91 (0.9%) cases with preterm-PE, 222 (2.2%) cases with term-PE, 360 (3.6%) with GH and 9,458 (93.4%) cases unaffected by hypertensive disorders. Maternal plasma fetal fraction levels were expressed as multiples of the median (MoM) after adjustment for maternal factors and crown-rump length. The performance of screening for preterm-PE, term PE and GH by maternal factors and MoM values of fetal fraction, PAPP-A, UtA-PI and MAP was evaluated by receiver operating characteristic (ROC) curves. Results The median fetal fraction MoM was significantly lower in the preterm-PE (0.825; IQR 0.689–1.115 MoM, p < .001), term-PE (0.946; IQR 0.728–1.211 MoM, p = .028) and GH (0.928; IQR 0.711–1.182 MoM, p < .001) groups than in the unaffected group (1.002; IQR 0.785–1.251 MoM). However, the performance of screening for PE or GH by maternal factors alone or by maternal factors and PAPP-A, UtA-PI and MAP was not significantly improved by the addition of fetal fraction. Conclusions First trimester maternal plasma fetal fraction is not useful in screening for hypertensive disorders of pregnancy.

Can the Severity of Intrahepatic Cholestasis of Pregnancy be Predicted by Second Trimester Screening Test Parameters?

Abstract Objective The second trimester triple test although declared inadequate for the screening of aneuploidies by the International Society for Prenatal Diagnosis remains a widely employed test. We aim to investigate the associations between the biochemical parameters of the triple test and the severity of intrahepatic cholestasis of pregnancy (ICP). Material and Methods The triple test parameters of 102 healthy pregnant women and 100 pregnant women with ICP were evaluated retrospectively. Serum bile acid level of ≥ 40 μmol/L was categorized as severe ICP. Serum α-fetoprotein (AFP), β-human chorionic gonadotropin (β-hCG), and unconjugated estriol (uE3) multiple of the median (MoM) values and the perinatal outcomes were recorded. The Student’s t-test, Mann–Whitney U test, Kruskal–Wallis test, and receiver operating characteristic curve analysis were used to compare the data. Results The AFP, β-hCG, and uE3 MoM values were higher in the severe ICP group when compared to those with mild ICP and those without ICP (p &lt; 0.01). The sensitivity and specificity values for ICP were 80.95% and 73.42%, respectively, with AFP values ≥ 1.26 MoM, 76.19% and 88.61%, respectively, with β-hCG values ≥ 1.78 MoM, and 61.90% and 94.94%, respectively, with uE3 values ≥ 1.58 MoM [95% confidence interval; area under the curve (AUC) ± standard error (SE) = 0.810 ± 0.049, AUC ± SE: 0.790 ± 0.065, and AUC ± SE: 0.797 ± 0.065, respectively]. Conclusion An increase in the AFP, β-hCG, and uE3 MoM values in the triple test can predict the risk of developing severe ICP.