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Background and Objectives Thalassemia is the most common monogenic disease worldwide inherited in autosomal recessive manner. Beta-thalassemia is caused by mutations in beta-globin gene. It is characterized by reduction in red blood cell indices including low MCV, low MCH, high RBC count, low HbA1 and high HbA2. Considering these symptoms, finding a relation between erythrocyte indices and kind of mutations can be used as a rapid method in mutation diagnosis and initial screening of carriers. Materials and Methods In this descriptive-analytical study after DNA extraction from 200 beta- thalassemia minors in Khuzestan province by salting out method, we amplified and sequenced beta-globin gene by Sanger sequencing. Finally, we analyzed statistically the beta-globin gene mutations and erythrocyte indices association by SPSS. Results Our results showed that IVSII-1(G > A) is the most common mutation with 22.5% frequency in this population of beta-thalassemia carriers. We found that MCV index variations have a meaningful association with beta-globin gene mutations and the highest mean of MCV (65.4 ± 3.7) was observed in IVSI-110(G > A) mutation. Conclusions The results comply with many other studies performed in this field and can be used for rapid detection of mutation in carrier parents and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Small-for-gestational-age (SGA) is one of the most important conditions, which is associated with the risk of perinatal mortality and morbidity. The levels of pregnancy-associated plasma protein A (PAPP-A) and β-human-derived chorionic gonadotrophic (β-hCG) in the first trimester can predict this adverse outcome, considering the controversial nature of studies in this area, this cohort study was conducted to investigate the role of PAPP-A and freeβ-hCG levels for predicting SGA. Materials and Methods: In this cohort study, from 16 randomly selected health centers in Isfahan, Iran, 4605 volunteer pregnant women who had performed first-trimester fetal anomalies screening tests were chosen based on the census, from July 2016 to June 2018. The multiples of the median (MoM) PAPP-A <0.4 and MoM β-hCG >3 were considered as abnormal; the samples were followed up after childbirth. The biomarkers' serum levels, relative risk, and odds ratio (OR) of SGA were compared in both SGA and appropriate for gestational age (AGA) groups. Results: In the SGA group, the mean of MOM PAPP-A was significantly lower (0.96 vs. 1.1 with P = 0.001) and MoM βhCG was significantly higher (1.24 vs. 1.15 with P = 0.01) than the AGA group. Odds for SGA in subjects with MoM PAPP-A <0.4 were 3.213; P = 0.001 and for subjects with MoM βhCG >3 reported as 0.683; P = 0.111. Conclusion: The results of the study showed that the low levels of PAPP-A would cause 3.213 times increase in the chance of developing SGA and no association between high level of βhCG >3 with SGA. Therefore, low level of the PAPP-A is a warning indicator for SGA. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypoplasia is a significant decrease in lung volume by any cause in comparison to the normal volume for gestational age. Objectives: To evaluate the application of prenatal magnetic resonance imaging in order to predict pulmonary hypoplasia, measurement of fetal lung volume (FLV) was aimed to establish a reference data in normal fetuses. Patients and Methods: Three hundred forty two fetuses with abnormal ultrasound findings underwent fast spin-echo T2-weighted MR imaging at a single tertiary care hospital (Shahid Faghihi Hospital, Shiraz, Iran). Data of 241 fetuses at 18 - 36 weeks' gestation without thoracic malformations were obtained for a FLV normative curve. To acquire a best-fit formula for the mean total fetal lung volume based on each gestational week with 95% confidence interval (CI), we used the regression model applied by Rypens et al. This resulted in a formula calculating the expected fetal lung volume based on gestational age. A one-sample t-test was also carried out to compare the mean total fetal lung volume at each gestational week with the expected mean total fetal lung volume predicted by the formula by Rypens et al., Meyers et al., and Osada et al. Results: Normal FLV increased with gestational age as the spread of values. The expected fetal lung volume was derived from the following formula: Fetal lung volume (mL) = 0.002 x (gestational age [GA]2.913), in which GA is gestational weeks. FLV in our population had a more consistent correlation with Japanese fetuses than European or American fetuses. Conclusion: In fetuses with normal lungs, FLV distribution against gestational age is simply measured prenatally with MR imaging. A single universal formula might not be suitable for fetuses worldwide. In our region, acquired data were more consistent with Asian normal values. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study was to evaluate the use of contingent prenatal screening for the detection of Down's syndrome and neural tube defects (NTDs) in west of Iran. Methods: A prospective study was conducted on 653 pregnant women referred to a medical diagnostic laboratory (Imam Reza Clinic, Kermanshah, Iran) for contingent prenatal screening tests between October 2016 to September 2017. Results: Among 651 women screened in the first trimester, 8 (1.22%) pregnancies were screen-positive for Down's syndrome. In the second trimester, among 605 women, 25 (4.13%) had a positive result and all of these women voluntarily underwent amniocentesis. Overall, five pregnancies were complicated with chromosomal abnormalities, including five cases of Down's syndrome. Conclusion: In a nutshell, the contingent prenatal screening tests were found to be useful for estimation of Down's syndrome as well as NTDs in both young and older mothers in west of Iran. These tests should be performed for pregnant women before an invasive test for Down's syndrome. [ABSTRACT FROM AUTHOR]

Background: Considering that ethnicity and gestational age (GA) could affect the value of nuchal fold thickness (NFT) in mid-trimester, we aimed to determine the reference intervals of NFT values for each gestational week from 16 to 24 weeks of pregnancy among a group of Iranian pregnant women. Materials and Methods: In this cross-sectional study, medical files of pregnant women who underwent fetal anomaly scanning at 16-24 weeks of gestation were reviewed and the following data were extracted: GA, value of NFT, value of nuchal translucency (NT) in their previous ultrasound study, if available, and head circumference (HC). The 5th, 25th, 50th, 75th, and 95th percentiles of NFT for each gestational week were determined. The association between NFT and HC, GA, and NT were also determined. Results: Medical files of 882 pregnant women were studied. The expected 95th percentile value of NFT between 16th and 24th weeks of gestation ranged from 4 mm to 5.9 mm. The mean (standard deviation) of NFT increased with GA from 2.67 (0.90) mm at 16th weeks to 4.69 (0.71) mm at 24th weeks. There was a significant positive association between NFT and GA (β = 1.11, P < 0.001), HC (β = 0.21, P < 0.001), and NT (β = 0.351, P < 0.001). Conclusion: The findings of this study revealed that before the 20th week of gestation, the appropriate cutoff value of NFT is 5 mm, and for 21st to 24th weeks, the proper cutoff is 6 mm. However, for providing more conclusive results, further studies with larger sample size and considering the impact of other influencing variables are recommended. [ABSTRACT FROM AUTHOR]

Objective To evaluate the repercussions of recent changes to the cut-offs used in the first screening step of the pre-marital screening programme for thalassaemia prevention in Iran. Methods The profiles of 984 subjects referred to a genetic laboratory, and the tests of 242 parents of children with thalassaemia major were assessed for red blood cell (RBC) indices, haemoglobin (Hb) A2 levels and results of Hb electrophoresis. Results Of 407 suspected thalassaemia minor (STM) cases, 18 proved positive for thalassaemia minor on molecular analysis (18/407, confidence interval 2.6–6.9%). If the revised screening cut-offs had been used to determine who would undergo molecular analysis, two of these cases would not have been identified. Only 4.4% of suspected cases with lower than normal RBC indices (mean corpuscular volume <80 fl and mean corpuscular Hb <27 pg) and HbA2 (<3.5%) were diagnosed with thalassaemia minor. Conclusion The thalassaemia major prevention programme is performed in two separate steps. One step involves the screening of subjects and identification of β-thalassaemia minor, suspected cases for thalassaemia minor (STM), and normal subject groups. The other step concerns the identification of thalassaemia minor in the STM group. Changing the cut-offs at the first screening step does not result in significant improvement from an economic view, and is associated with significant risk at the second screening step. [ABSTRACT FROM AUTHOR]

Background: Failed visualization of the fetal nasal bone (NB) by ultrasound at 11 -14 weeks of gestation is strongly associated with chromosomal abnormalities. Meanwhile, the incidence of the absent fetal NB in normal fetuses in the first trimester in mothers of different ethnic origins differs significantly. It is, therefore, important to assess ethnic variations in the first-trimester visualization of the fetal NB before introducing this marker into routine screening programs for aneuploidy. Objectives: The objectives of this study were to determine the NB length and the prevalence of the NB absence as well as calculating the likelihood ratio (LR) for the absence of the NB in normal fetuses of Iranian women undergoing first-trimester screening for trisomy 21. Patients and Methods: In 767 normal fetuses, the fetal profile was examined by ultrasound for the absence/presence of the NB. The NB length was also measured, and the LR for the NB absence was also determined. Results: The NB was absent in 2/767 (0.26%) of the fetuses. The mean length of the NB was 3.6 ± 0.69 mm for the fetuses of 11 -14 weeks gestational age. The LR value of the absent NB was equal to 250 in the normal fetuses of the Iranian population living in the North-West provinces. Conclusion: The low prevalence of the NB absence in normal fetuses in the present study is compatible with the larger size of the NB in Iranian people compared to other communities. Meanwhile, the reference range of the NB length in normal Iranian fetuses was established so that basic data could be recorded for further studies regarding the absence or presence of the NB in screening for chromosomal abnormalities (Down syndrome) within the Iranian population. [ABSTRACT FROM AUTHOR]

BACKGROUND: We have investigated the efficacy of QF-PCR for the prenatal recognition of common aneuploidy and compared our findings with cytogenetic results in our laboratories. METHODS: A total of 4058 prenatal samples (4031 amniotic fluid and 27 chorionic villous samples) were analyzed by QF-PCR using several selected STR markers together with amelogenin. Results were compared to those obtained by conventional cytogenetic analysis. RESULTS: We detected 139 (3.42%) numerical abnormalities in our subjects by QF-PCR. Concordant QF-PCR and karyotype results were obtained in 4001 (98.59%) of the samples. An abnormal karyotype associated with adverse clinical outcome undetected by QF-PCR was found in 16.66% (n = 28) of samples. Using QF-PCR alone, we were able to detect abnormalities in 98.59% of all referred families; however the karyotyping results improved the detection rate to 99.85% of the referred cases. Individuals with neonatal screening result with 1:10 risk ratio showed 11.29% abnormal karyotype while this number was 2.16% in mothers with risk ratio of 1:250 or less. CONCLUSION: In countries where large scale conventional cytogenetic is hampered by its high cost and lack of technical expertise, QF-PCR may be used as the first line of screening for detection of chromosomal abnormalities. We also recommend QF-PCR for all the families that are seeking prenatal diagnosis of single gene disorders aneuploidies screening to be added to their work up. [ABSTRACT FROM AUTHOR]

Objective: Prenatal diagnosis of β-thalassemia carrier couples has helped to prevent bearing affected children. Among 177 couples referred to our laboratory for prenatal diagnosis, 14 mothers had twin pregnancies. Methods: By using direct and indirect methods, we determined their mutations and linkage analysis using polymorphic markers (restriction fragment length polymorphism [RFLP]). Results: It was shown that in five families both fetuses were heterozygote carriers. In another five families, one fetus was normal and the other one was carrier. In two families, one fetus was affected and the other one was heterozygous carrier; in one case one fetus was affected and the other one was homozygote normal. In the last family both fetuses were homozygote normal. If all fetuses were fraternal then one would expect to see seven homozygote normal and the same number affected, and 14 carriers. Conclusion: Our results indicated that at least in cases where both fetuses had identical genotypes, then they may be identical twins. Molecular testing indeed showed that in three cases the twins were identical. Another point is that in three cases, one of the twin fetuses was affected and the other one was either normal or heterozygote in which only the affected fetuses were aborted by the specialist. [ABSTRACT FROM AUTHOR]