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

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

A comprehensive overview of SMN and NAIP copy numbers in Iranian SMA patients.

Spinal muscular atrophy (SMA) is among the most common autosomal recessive disorders with different incidence rates in different ethnic groups. In the current study, we have determined SMN1, SMN2 and NAIP copy numbers in an Iranian population using MLPA assay. Cases were recruited from Genome-Nilou Laboratory, Tehran, Iran and Pars-Genome Laboratory, Karaj, Iran during 2012-2022. All enrolled cases had a homozygous deletion of exon 7 of SMN1. Moreover, except for 11 cases, all other cases had a homozygous deletion of exon 8 of SMN1. Out of 186 patients, 177 (95.16%) patients showed the same copy numbers of exons 7 and 8 of SMN2 gene. In addition, 53 patients (28.49%) showed 2 copies, 71 (38.17%) showed 3 copies and 53 patients (28.49%) showed 4 copies of SMN2 gene exons 7 and 8. The remaining 9 patients showed different copy numbers of exons 7 and 8 of SMN2 gene. The proportions of SMA patients with different numbers of normal NAIP were 0 copy in 73 patients (39.24%), 1 copy in 59 patients (31.72%), 2 copies in 53 patients (28.49%) and 4 copies in one patient (0.5%). These values are different from values reported in other populations. Integration of the data of the SMN1/2 and NAIP genes showed 17 genotypes. Patients with genotype 0-0-3-3-1 (0 copies of SMN1 (E7,8), 3 copies of SMN2 (E7,8) and 1 copy of NAIP (E5)) were the most common genotype in this study. Patients with 0-0-2-2-0 genotype were more likely to have type I SMA. The results of the current study have practical significance, particularly in the genetic counseling of at-risk families.

Extreme ßHCG levels in first trimester screening are risk factors for adverse maternal and fetal outcomes.

Multiples of the normal median (MoM) of free ßHCG is a valuable parameter in evaluation of risk of adverse pregnancy outcomes. In the current retrospective study, we assessed the maternal and fetal outcomes in pregnant women having free ßHCG MoM levels < 0.2 or > 5 in their first trimester screening (FTS). Relative risk of trisomy 21 was significantly higher in patients having free ßHCG MoM > 5. On the other hand, relative risk of trisomies 13 and 18 and Turner syndrome were higher in those having free ßHCG MoM < 0.2. Other chromosomal abnormalities were nearly equally detected between those having free ßHCG MoM < 0.2 or > 5. Relative risk of hydrocephaly and hydrops fetalis was higher when free ßHCG MoM was below 0.2. On the other hand, relative risk of low birth weight was higher when free ßHCG MoM was above 5. Moreover, frequency of gestational diabetes mellitus, preeclampsia, preterm delivery and vaginal bleeding increased with levels of free ßHCG MoM. However, polyhydramnios had the opposite trend. Frequencies of premature rupture of membranes and pregnancy induced hypertension were highest among pregnant women having levels of free ßHCG MoM < 0.2. The current study indicates importance of free ßHCG MoM in identification of at-risk pregnancies in terms of both fetal and maternal outcomes. In fact, ßHCG MoM < 0.2 or > 5 can be regarded as risk factors for adverse maternal or fetal outcomes irrespective of the presence of other abnormalities in the FTS results.

Incorporation of second-tier tests and secondary biomarkers to improve positive predictive value (PPV) rate in newborn metabolic screening program.

BACKGROUND: Nowadays, neonatal screening has become an essential part of routine newborn care in the world. This is a non-invasive evaluation that evaluated inborn errors of metabolisms (IEMs) using tandem mass spectrometry (LC-MS/MS) for the evaluation of the baby's risk of certain metabolic disorders. METHODS: This retrospective study was conducted on 39987 Iranian newborns who were referred to Nilou Medical Laboratory, Tehran, Iran, for newborn screening programs of IEMs. We incorporated second-tier tests and secondary biomarkers to improve positive predictive value (PPV). RESULTS: Statistical data were recorded via call interviewing in 6-8 months after their screening tests. The overall prevalence of IEM was 1:975. The mean age of all participants was 3.9 ± 1.1 days; 5.1% of participants were over 13 days and 7.7% were preterm or underweight. A total of 11384 (29.4%) of the cases were born in a consanguineous family. The type of delivery was the cesarean section in 8332 (51.3%) valid cases. The neonatal screening results had an overall negative predictive value (NPV) of 100% and the overall PPV of 40.2%. The false-positive rate was 0.15%. CONCLUSION: This study showed a high incidence of metabolic disease due to a high rate of consanguineous marriages in Iran and indicated that incorporation of second-tier tests and secondary biomarkers improves PPV of neonatal screening programs.

Karyotype analysis of amniotic fluid cells and report of chromosomal abnormalities in 15,401 cases of Iranian women.

The aim of present study was to assess the karyotypes of amniotic fluid cells and find the frequency of chromosomal abnormalities and their significance in clinical setting. A total of 15,401 pregnant women were assessed from March 2016 to May 2019, and 14,968 amniotic fluid samples were successfully cultured. These fetuses were grouped according to different indications including advanced maternal age, abnormal nuchal translucency (NT) values, positive first/second trimester screening results, high risk NIPT results, very low PAPP-A and free ß-hCG multiples of the normal median (MoM) results, abnormal ultrasound findings or previous history of chromosomal abnormalities. Results indicated the presence of normal karyotype in 90.2% (13,497/14,968) of fetuses. Totally, 46.4% (6945/14,968) of fetuses were 46,XX and 43.8% (6552/14,968) had 46,XY chromosome pattern. A total of 1077 abnormal karyotypes were found among 14,968 fetuses, thus the rate of abnormal fetuses was calculated to be 7.2% (1072/14,968). Meanwhile, a total of 394 cases (2.8%) had a normal polymorphism in their karyotype. In other words, abnormal karyotypes were detected in one of 13.9 cases of patients underwent amniocentesis. Down syndrome, Edward's syndrome, abnormal mosaicisms and Patau's syndrome were detected in 4.4% (659/14,968), 0.57% (85/14,968), 0.49% (74/14,968) and 0.24% (36/14,968) of cases, respectively. Sex chromosomal abnormalities including Klinefelter syndrome, Turner syndrome and 47,XXX karyotype were detected in 64 cases (0.43%). In this article, the rates of chromosomal abnormalities are compared between different groups of patients based on the advanced maternal age, abnormal NT values, very low PAPP-A and free ß-hCG MoMs results, and positive FTS results. The current investigation provides insight into the most appropriate indications for amniocentesis in Iran.

Fine-tuning of routine combined first- trimester screening: The ratio of serum-free- beta-human chorionic gonadotropin (fß-hCG) to pregnancy-associated plasma protein-A (PAPP-A) could improve performance of Down syndrome screening program, a retrospective cohort study in Iran.

OBJECTIVES: To evaluate the performance of the current national screening policy for Down syndrome (DS) in Iran and suggest a more efficient protocol with a wealth of a large series of first-trimester screening (FTS) data obtained from Nilou medical laboratory. To fulfill this aim, detection rate (DR), positive screening rate (PSR), false negative rate (FNR) and odds of being affected given a positive results (OAPR) were calculated at different cutoff risk. In the latest update of DS screening program in Iran, there is no place for intermediate group to be further investigated. Next, we proposed a novel parameter namely the ratio of fß-hCG multiple of the median (MoM) value to PAPP-A MoM value to delicately categorize FTS results in a way that reduce FNR without imposing unnecessary anxious and extra money on most families. METHODS: The present investigation was conducted retrospectively on 197,210 pregnancies undergoing FTS for aneuploidies in Nilou medical laboratory, Tehran, Iran, from March 2015 to February 2016. RESULTS: Intermediate risk group is important as 23 out of 45 FN fell in the range 1:250 to 1:1100. By applying the proposed index, the ratio of fß-hCG MoM to PAPP-A MoM and subsequent decision about NIPT, 8 out of 23 FN cases in intermediate group could be detected. CONCLUSION: Compared with the current policy, our novel proposed approach had better performance and could be applied by the Iran National Health Service to improve the screening program guideline.