Fetal magnetic resonance imaging in the confirmation of congenital anomalies found on routine mid-trimester ultrasound.

OBJECTIVE: To determine the added value of fetal magnetic resonance imaging (MRI) when clarifying a suspected anomaly detected by mid-trimester scan. METHODS: Women attending two centers of fetal medicine between January 2017 and December 2021 were identified. The centers carried out routine mid-trimester ultrasound scans to detect fetal anomalies. Those with a suspected anomaly which required further clarification were referred for fetal magnetic resonance imaging (MRI). The medical records of all referred women were examined to determine the anomalies found at scan, MRI and termination of pregnancy or delivery. A total of 9571 women had a routine mid-trimester scan and an anomaly was either diagnosed or suspected in 449 (4.7%); an MRI examination was made in 76 cases (0.79%). RESULTS: MRI confirmed the presence of an abnormality in 61 referrals (80%) and failed to yield a result in one case. Outcome information was available for 69 cases: the MRI confirmation rate was 89% (48/54) in those with abnormal outcome and 40% (6/15) if the outcome was normal, P<0.0001. Among defects in the most common anatomical systems identified at ultrasound, the highest confirmation rates were for urinary tract abnormalities (94%, 15/16) and facial abnormalities (100%, 8/8). Results in other systems varied according to the specific defect but the confirmation rate was high for ventriculomegaly (86%, 6/7) and neural tube defects (83%, 5/6). CONCLUSIONS: We have shown that in women with suspected anomaly scan results, requiring further clarification, MRI confirmed ultrasound at a high rate, particularly for urinary tract and facial anomalies.

Antenatal screening for thyroid dysfunction: pre-term birth, low birth-weight, and growth restriction.

OBJECTIVE: To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment. METHODS: This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile). RESULTS: Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, p < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, p < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, p = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, p = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight. CONCLUSIONS: Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.

The prevalence of maternal hypothyroidism in first trimester screening from 11 to 14 weeks of gestation.

AIM: The aim of this study was to determine the prevalence of maternal hypothyroidism in the first trimester from 11 to 14 weeks of gestation according to the American Thyroid Association (ATA) guidelines from 2017 and to compare the rates for singleton and twin pregnancies. METHODS: A total of 4965 consecutive Caucasian singleton pregnancies and 109 Caucasian twin pregnancies were included in the investigation. Patients with a history of thyroid gland disorder were excluded. Subclinical maternal hypothyroidism was defined as a thyroid stimulating hormone (TSH) concentration above the 97.5th percentile and free thyroxine (fT4) within the range of a reference population of women at 11-14 weeks of gestation. Overt maternal hypothyroidism was defined as a TSH concentration above the 97.5th percentile and an fT4 below the 2.5th percentile of the reference population.TSH, fT4, and anti thyroid peroxidase antibody (TPOAb) were measured by immunochemiluminescent assays on an 16200 Abbott Architect analyzer. RESULTS: The prevalence of hypothyroidism for twin pregnancies was no higher than that for singleton pregnancies; 6.42% (7/109) vs. 5.32% (264/4965), respectively; P=0.61. All twin pregnancies were subclinical. Singleton hypothyroid pregnancies included 4.91% (244 cases) of subclinical and 0.41% (20 cases) of overt hypothyroidism. The prevalence of TPOAb positive hypothyroid women for twin pregnancies and singleton pregnancies was 71% (5/7) vs. 52% (137/264 cases), respectively but the differences were not statistically significant; P=0.31. CONCLUSION: Each first trimester screening center should establish its TSH and fT4 reference ranges. Our center had higher upper reference limits of TSH than that of the universally fixed limit of 2.5 mU/L, which led to a lower measured prevalence of maternal hypothyroidism. A large number of hypothyroid women were TPOAb positive.

Maternal thyroid-stimulating hormone reference ranges for first trimester screening from 11 to 14 weeks of gestation.

BACKGROUND: To establish maternal thyroid-stimulating hormone (TSH) reference ranges for first trimester screening from 11 + 0 to 13 + 6 weeks of gestation. METHODS: A total of 10 592 singleton and 201 twin consecutive Caucasian pregnant women who underwent simultaneously prenatal first trimester Down's syndrome screening and thyroid function screening from January 2010 to November 2017 were included in the study. Women with positive antithyroid peroxidase antibody (TPOAb) and positive personal history of thyroid disease were previously excluded. TSH was measured by immunochemiluminescent assay on ci 16200 Abbott Architect analyzer. Nonparametric percentile method (also known as CLSI C28.A3) was used for the determination of reference ranges. RESULTS: We established reference ranges of TSH for the period of gestation from 11 + 0 to 13 + 6 weeks of pregnancy as 0.16-3.43 mU/L for singleton Caucasian pregnancies and 0.02-2.95 mU/L for twin Caucasian pregnancies. The median (IQR) of TSH for singleton pregnancies was higher than that for twin pregnancies (1.25 mU/L (0.83-1.81) vs 0.84 (0.37-1.47), respectively; P < .0001). CONCLUSIONS: Each first trimester screening center should be aware of which type of immunoassay their laboratory uses. TSH reference ranges in women during the first trimester of pregnancy are lower than those for general population. Twin pregnancies have lower TSH than singleton pregnancies.

Incorporating thyroid markers in Down syndrome screening protocols.

OBJECTIVE: The article aimed to assess the benefit of incorporating maternal serum thyroid disease marker levels (thyroid-stimulating hormone and free thyroxine) into first trimester Down syndrome screening protocols. METHODS: Statistical modelling was used to predict performance with and without the thyroid markers. Two protocols were considered: the combined test and the contingent cell-free DNA (cfDNA) test, where 15-40% women are selected for cfDNA because of increased risk based on combined test results. Published parameters were used for the combined test, cfDNA and the Down syndrome means for thyroid-stimulating hormone and free thyroxine; other parameters were derived from a series of 5230 women screened for both thyroid disease and Down syndrome. RESULTS: Combined test: For a fixed 85% detection rate, the predicted false positive rate was reduced from 5.3% to 3.6% with the addition of the thyroid markers. Contingent cfDNA test: For a fixed 95% detection rate, the proportion of women selected for cfDNA was reduced from 25.6% to 20.2%. CONCLUSIONS: When screening simultaneously for maternal thyroid disease and Down syndrome, thyroid marker levels should be used in the calculation of Down syndrome risk. The benefit is modest but can be achieved with no additional cost. © 2017 John Wiley & Sons, Ltd.

Clinical Potential of Effective Noninvasive Exclusion of KEL1-Positive Fetuses in KEL1-Negative Pregnant Women.

BACKGROUND: The clinical importance of assessing the fetal KEL genotype is to exclude 'K'-positive fetuses (genotype KEL1/KEL2) in 'K'-alloimmunized pregnant women (genotype KEL2/KEL2). Noninvasive assessment of the fetal KEL genotype is not yet available in the Czech Republic. OBJECTIVE: The aim of this study was to assess the fetal KEL1/KEL2 genotype from cell-free fetal DNA in the plasma of KEL2/KEL2 pregnant women. METHODS: The fetal genotype was assessed by minisequencing (a dilution series including control samples). A total of 138 pregnant women (between the 8th and 23rd gestational week) were tested by minisequencing. The fetal genotype was further verified by analysis of a buccal swab from the newborn. RESULTS: Minisequencing proved to be a reliable method. In 2.2% (3/138) of the examined women, plasma sample testing failed; 94.8% (128/135) had the KEL2/KEL2 genotype, and a total of 3.1% of fetuses (4/128) had the KEL1/KEL2 genotype. Sensitivity and specificity reached 100% (p < 0.0001). CONCLUSION: Minisequencing is a reliable method for the assessment of the fetal KEL1 allele from the plasma of KEL2/KEL2 pregnant women.

Azurocidin levels in maternal serum in the first trimester can predict preterm prelabor rupture of membranes.

OBJECTIVE: To determine the possible association between azurocidin in maternal serum in the first trimester of pregnancy and subsequent spontaneous preterm labor, preterm prelabor rupture of membranes, and iatrogenic preterm delivery. METHODS: Women who underwent first trimester screening for chromosomal abnormalities between January and November 2011 were included in the study, and a sample of maternal serum was obtained. In total, 1905 women were followed-up through the local record system, and 13 women with spontaneous preterm labor, 17 women with preterm prelabor rupture of membranes (PPROM), and 16 women with iatrogenic preterm delivery were identified. Twenty-two women with uncomplicated pregnancies who delivered at term were selected as controls. Maternal serum azurocidin levels in women were determined using ELISA. RESULT: Women with PPROM had lower azurocidin levels (median 0.91 ng/mL, range 0.2-2.07) than women who delivered at term (median 1.63 ng/mL, range 0.4-10.98; p = 0.02). No differences in azurocidin levels between women with labor at term and those with either spontaneous preterm labor (median 1.46 ng/mL, range 0.19-2.59; p = 0.42) or iatrogenic preterm delivery (median 1.60 ng/mL, range 0.66-7.96; p = 0.27) were found. CONCLUSIONS: Low levels of azurocidin in maternal serum in the first trimester were associated with subsequent PPROM.

Refined fluorescent STR quantification of cell-free fetal DNA during pregnancy in physiological and Down syndrome fetuses.

BACKGROUND: Cell-free fetal (cff) DNA analysis by short tandem repeats (STR) has the advantage of better recognizing the different genotypes. However, quantitative examination by quantitative fluorescent (QF) polymerase chain reaction (PCR) by STRs is limited to only a rough approximation. This project focuses on a more precise calculation of the relative cff DNA amount tested in the STRs' loci. METHODS: The cff DNA was analyzed in 363 samples from 258 pregnant women with physiological fetuses in different stages of pregnancy (from 4-37 gestational weeks) separately in three STRs [D21S1435, D21S1446 and PentaD (pD)] and also by gonosomal sequences amelogenin gene, X/Y-linked/testis specific protein, Y-linked (AMELX/Y/TSPY). Seventeen samples of cff DNA from fetuses with Down syndrome (DS) were compared. We optimized the refined quantitative fluorescent (RQF) PCR for STRs in a particular locus. RESULTS AND CONCLUSIONS: The cff DNA detection rate was 74% in at least one of the STRs. The efficiency decreased from shorter to longer PCR fragments. All three STR and gonosomal loci proved an increase in cff DNA during pregnancy. The stutter variability rate is greatest in short STR fragments and decreases as the STR fragments increase in length. Results showed that DS samples had a significantly higher amount of cff DNA.

Single umbilical artery and its siding in the second trimester of pregnancy: relation to chromosomal defects.

OBJECTIVES: To determine the possible association between single umbilical artery (SUA) in the second trimester of pregnancy and the incidence of chromosomal abnormalities. To determine whether the presence of chromosomal defects in fetuses with SUA is related to the side of the missing artery. METHODS: Color flow imaging of the fetal pelvis was used to determine the number of umbilical arteries in 2147 fetuses immediately before amniocentesis for karyotyping in the second trimester of pregnancy. RESULTS: SUA was diagnosed in 102/2147 (4.8%) cases. The left umbilical artery was absent in 60/102 (58.8%) fetuses, compared with the 42/102 (41.2%) for the right artery. The rate of chromosome abnormalities was significantly higher among fetuses with SUA than among those with 2 umbilical arteries (19/102 or 18.6% versus 109/2045 or 5.3%; OR = 4.1, 95% CI 2.3-7.1, p < 0.0001). Among fetuses with SUA, there was no significant difference in the rate of chromosome abnormalities between those with absence of the left versus the right artery (11/60 or 18.3% versus 8/42 or 19.0%, p = 0.93). There was an SUA in 5/39 (12.8%) cases with trisomy 21, 8/16 (50%) with trisomy 18, 1/4 (25%) with trisomy 13 and 5/69 (7.2%) with other chromosomal defects. There were no chromosome abnormalities in fetuses where a single umbilical artery was an isolated sonographic finding. All fetuses with SUA and chromosomal defects had associated abnormalities detected by ultrasound. CONCLUSION: A single umbilical artery (SUA) in the second trimester of pregnancy has a high association with trisomy 18, 13, 21 and other chromosomal defects, but all chromosomally abnormal fetuses had associated malformations detected by ultrasound. The absence of the left artery is more frequent than the absence of the right artery. The association with chromosomal abnormalities seems to be equal on each side.

Fetal enterolithiasis: prenatal sonographic and MRI diagnosis in two cases of urorectal septum malformation (URSM) sequence.

OBJECTIVES: Enterolithiasis (multiple calcifications of intraluminal meconium) is a rare, prenatal ultrasonographic finding. In this study, our aim was to evaluate the prenatal diagnostic features and discuss the management of the patients. METHODS: The data of two cases of prenatally diagnosed fetal enterolithiasis were collected from ultrasound scan, magnetic resonance imaging (MRI) and neonatal or postnatal autopsy records. The findings were evaluated in both prenatal and postnatal periods. Chromosomal analysis was performed in one case. An evaluation of primary and secondary malformations was done. Coexisting anomalies were searched for via radiology, neonatal surgery and histopathology. RESULTS: Malformations in two cases (both males) with partial and complete urorectal septum malformation (URSM) sequence were described. The absence of an anal opening and presence of a fistula between the urinary and gastrointestinal tract were common findings. These features were considered as primary malformations contributing to the formation of enterolithiasis. Secondary anomalies (urinary and gastrointestinal system malformations, pulmonary hypoplasia, genital and other coexisting anomalies) were evaluated. CONCLUSIONS: The prenatal detection of enterolithiasis carries a poor prognosis. Most of the previously reported cases were invariably associated with major fetal malformations of the urinary and gastrointestinal tract. It is a warning sign for large bowel obstruction with or without enterourinary fistula. Therefore, adequate gastrointestinal and urologic studies must be undertaken after birth for the final diagnosis. There is a high mortality rate in the reported cases, mostly attributed to associated anomalies, and all survivors required neonatal surgery. It is important to differentiate the partial from the full URSM sequence because the prognosis in the partial URSM sequence is generally good, with long-term survival being common.

Screening for chromosomal anomalies in the first trimester: a report on the first year of prospective screening for chromosomal anomalies in the first trimester in the Czech Republic.

BACKGROUND: The increase in maternal age in recent years has intensified the effort to develop early non-invasive methods for screening for trisomy 21 and other chromosomal abnormalities in prenatal diagnosis. In the first trimester of pregnancy, maternal age, fetal nuchal translucency (NT), maternal levels of free beta- human chorionic gonadotropin (beta-hCG) and pregnancy-associated plasma protein-A (PAPP-A) are used as screening markers. We evaluated the introduction of this method of screening for the first time in the Czech Republic. METHODS: it is a prospective study for one-year from the beginning of 2004. The risk of trisomy 21(Down's syndrome) was estimated for 686 singleton pregnancies. The specific risk was calculated using the Fetal Medicine Foundation software (FMF) by accredited sonographers. Karyotyping was offered to women with risk >or= 1 in 250. RESULTS: In the population screened 18 % of women were aged 35 and more. We found 2 cases of trisomy 21 and 1 case of trisomy 18 (Edward syndrome) resulting in a detection rate of 100 % for trisomy 21 for a 5 % false positive rate (33 of 683). The maternal age of the detected cases was 30, 38 and 42 years. CONCLUSION: Introduction of the first trimester screening to our clinic, reduced the number of invasive genetic testing from 18 % to 5 %. First trimester screening for trisomy 21 and other aneuploidies has a high sensitivity with a low false positive rate and can be delivered in an efficient manner in a university hospital.

Uterine rupture during pregnancy and delivery among women attending the Al-Tthawra Hospital in Sana'a City Yemen Republic.

BACKGROUND: About 20 percent of the population in developing countries is composed of women of reproductive age. These women face one of the catastrophic risks of pregnancy "uterine rupture". Studies conducted in the developing world give strong evidence that uterine rupture is a major health problem in these countries with the rate being high in rural areas. AIM: The purpose of the study was to estimate the incidence and determine the risk factors and outcome of uterine rupture among women using the referral hospital Al-thawra in Sana'a City, Yemen republic and to extrapolate the data to the whole of Yemen. METHODS: The data was collected retrospectively; by interviewing, examining and following up all the cases of uterine rupture coming to the hospital during a period of 9 months between September 1996 and May 1997. A descriptive analysis and distribution frequency of the commonest causes of uterine rupture in 37 cases are presented taking into account medical, reproductive, health services provided and sociodemographic factors. RESULTS: Incidence of uterine rupture in Yemen was found to be (0.63), obstructed labor 83 %, contracted pelvis 19 %, previous surgery in 48 %, Oxytocine infusion in 42 %. Grand-multiparty was in 65 % and maternal age over 35 years in 50 %. Antenatal care was only in 34 %. CONCLUSION: The high percentage of malpresentation, cephalopelvic disproportion, previous uterine surgery accompanied by the high percentage of use of Oxytocin in this study highlights very clearly the role of this medication in increasing the risk of uterine rupture in Yemen.

Khat habit and its health effect. A natural amphetamine.

Chewing the leaves of the khat shrub is common in certain countries of East Africa and Arabian Peninsula mainly Yemen. It has been established that a khat plant leaves contain an active psycho-stimulant substance known as cathinone that is similar in structure and pharmacological activity to amphetamine in affecting the CNS. Intoxication with khat is self-limiting but chronic consumption can cause certain health disturbances in the user and also lead to social and economic damage to the individual and the community. In recent years, several cases of intoxication have been observed outside the area of its use. In this view, the khat habit, its health effects and socioeconomic aspects are described with the political issue they imply.