Towards solving the genetic diagnosis odyssey in Iranian patients with congenital anomalies.

Understanding the underlying causes of congenital anomalies (CAs) can be a complex diagnostic journey. We aimed to assess the efficiency of exome sequencing (ES) and chromosomal microarray analysis (CMA) in patients with CAs among a population with a high fraction of consanguineous marriage. Depending on the patient's symptoms and family history, karyotype/Quantitative Fluorescence- Polymerase Chain Reaction (QF-PCR) (n = 84), CMA (n = 81), ES (n = 79) or combined CMA and ES (n = 24) were performed on 168 probands (66 prenatal and 102 postnatal) with CAs. Twelve (14.28%) probands were diagnosed by karyotype/QF-PCR and seven (8.64%) others were diagnosed by CMA. ES findings were conclusive in 39 (49.36%) families, and 61.90% of them were novel variants. Also, 64.28% of these variants were identified in genes that follow recessive inheritance in CAs. The diagnostic rate (DR) of ES was significantly higher than that of CMA in children from consanguineous families (P = 0·0001). The highest DR by CMA was obtained in the non-consanguineous postnatal subgroup and by ES in the consanguineous prenatal subgroup. In a population that is highly consanguineous, our results suggest that ES may have a higher diagnostic yield than CMA and should be considered as the first-tier test in the evaluation of patients with congenital anomalies.

Pregnancy outcomes of normal karyotype fetuses with increased nuchal translucency.

Background: Although the association between first-trimester increased nuchal translucency (NT) and chromosomal defects is well-defined, there is little knowledge about the importance of increased NT in fetuses with normal karyotypes. Hence, this study was designed to evaluate outcomes of normal karyotype fetuses with increased NT. Methods: This observational retrospective study was conducted on 720 pregnancies with increased NT (>3mm) at 11 to 13 weeks of gestational age in Yas Hospital, Tehran, Iran, from 2016 to 2020. Study outcomes were incidence of preeclampsia, intrauterine growth restriction) IUGR (, preterm labor, fetal anomaly, cardiac malformations, hydrops fetalis, abortion, and intrauterine fetal death (IUFD) in pregnancies without evident chromosomal karyotype abnormalities. Results: Out of 720 participants who underwent karyotyping in the study center, 523 fetuses had normal karyotype results. In the pregnancies assessed for outcome, 357 (68.3%) reached live birth, 104 (19.9%) aborted, and 62 (11.9%) resulted in IUFD. Study outcomes including preeclampsia (<0.001), IUGR (<0.001), preterm labor (<0.001), fetal anomaly (<0.001), cardiac malformations (<0.001), hydrops fetalis (0.017), abortion (<0.001), and IUFD (<0.001) resulted in a statistically significant difference in the distribution of cases across NT intervals. Conclusion: This study demonstrated adverse pregnancy outcomes increased with increasing NT despite normal karyotyping. Hence, tight observation of mothers and fetuses should be done in normal karyotype fetuses with increased NT.

Radiofrequency Ablation and Intrauterine Transfusion in a Delayed Diagnosed Acardiac Twin Pregnancy.

Twin reversed arterial perfusion (TRAP) sequence or acardiac twin is a rare and severe complication of monochorionic multiple pregnancies. Acardiac twin accounts for 10% of all TRAP sequences, which is the most morphologically developed acardius. We present an undiagnosed TRAP sequence case up to 24 weeks of gestation who underwent successful amnioreduction, radiofrequency ablation (RFA), and intrauterine transfusion (IUT). During follow-up, hydrops of surviving co-twin disappeared, and fetal heart function improved. Finally, a healthy girl weighing 2400 g was born at 36 weeks of gestation. To our knowledge, this is the first reported acardiac twin pregnancy, which requires IUT, in addition to RFA, due to late diagnosis. Therefore, this case report presents successful management options for TRAP sequence cases diagnosed late in pregnancy.

Pregnancy Outcome After Selective Fetal Reduction in Dichorionic Twin Pregnancies.

Objective: This study was conducted for determining pregnancy outcome after selective fetal reduction in twin pregnancies based on the gestational age at the time of the procedure in a referral academic center between 2017 and 2021. Materials and methods: This retrospective cohort study included all women with twin pregnancies who were diagnosed with a genetic or structural anomaly of one fetus or a desire to reduce the number of fetuses in order to reduce pregnancy complications visited in the period of 2017-2021. Reduction was performed due to an abdominal approach at 11 to 23 weeks of pregnancy. Maternal and pregnancy information were recorded. Results: A total of 159 cases of twin dichorionic pregnancies were included. The highest frequency of reduction was performed at the gestational age of 18-20 weeks, and the most common cause of reduction was major structural anomalies in the fetus. The results showed the average gestational age (GA) at the time of delivery to be 37.6 weeks, the average birth weight of 2,999 grams, the incidence of miscarriage (loss before 22 weeks) to be 9.4% and a rate of preterm birth (delivery before 37weeks) of 33.3%. There is not a statistically significant relationship between the gestational age at the time of reduction and preterm birth, the birth weight, the incidence of RDS and the incidence of SGA. Conclusion: Fetal reduction of twins to singleton pregnancy is associated with lower risk of preterm birth (delivery before37 weeks reduction of twins to singleton pregnancy is associated with lower risk of preterm birth (delivery before37 weeks). It causes an increase in birth weight and perinatal outcome in remaining co-twin so we recommend fetal reduction after counselling with patients for their unique situation to improve pregnancy outcome.

Fetal Outcomes and Prognostic Factors After Radiofrequency Ablation for the Selective Reduction in Complicated Monochorionic Multiple Pregnancies.

RATIONALE AND OBJECTIVES: Monochorionic pregnancies are responsible for some severe complications, and selective reduction of a single fetus can improve pregnancy outcomes. This study evaluated the fetal outcomes and procedure-related prognostic factors after radiofrequency ablation (RFA) in complicated monochorionic multiple pregnancies. MATERIALS AND METHODS: This prospective cross-sectional study was conducted in an academic center from June 2020 to January 2022. The participants were 70 women with monochorionic multiple pregnancies who were candidates for selective fetal reduction by RFA. All participants' demographic data, RFA-related information, and pregnancy outcomes were evaluated and reported. RESULTS: The RFA procedure was successful in all participants. The most frequent RFA indications were twin-to-twin transfusion syndrome following selective intrauterine growth restriction. The mean gestational age at birth was 33.60 ± 5.62 weeks. Also, 11 (15.7%) of the cases had preterm delivery up to 30 days after RFA. The total pregnancy loss rate was 12 (17.14%), and the total fetal survival rate after RFA was 82.85%. The mean time of the RFA procedure was 130.8 ± 83.3 seconds. The procedure was conducted easily in 31 (44.2%) cases. Although the meantime of RFA procedure was longer in the not-easy group, the difference in surgery time was not significant (P = .296). There was no significant relationship (P = .623) between RFA indications and the gestational age of the remained fetus at delivery. The RFA needle was passed through the placenta in 18 (25.7%) cases. The mean gestational age at the delivery time was significantly lower in this group compared to their counterparts' gestational ages without needle placental passage (P = .030). Also, there was no significant correlation between gestational age at pregnancy termination and RFA cycles (P = .219). CONCLUSION: RFA is a relatively safe and minimally invasive procedure for the selective reduction of complicated monochorionic fetuses. Although mortality, premature membrane rupture, and preterm delivery are the potential risk factors for the remaining co-twin. According to this study, gestational age at the time of the procedure and passing the needle through the placenta can affect the outcome. Other procedure-related factors like easy- or hard-access procedures, and the number of RFA cycles are not significantly associated with gestational age at birth.

Severity of SARS-CoV-2 reinfection in vaccinated healthcare workers.

Background and Objectives: The most appropriate approach to control the SARS-CoV-2 epidemic is the widespread adoption of vaccination. Several vaccines against SARS-CoV-2 have been developed and authorized for use in various geographical regions. The aim of this study is to evaluate the efficacy of the vaccination agents presently utilized by healthcare workers (HCWs), and to investigate whether different COVID-19 vaccines would result in the alleviation of symptoms and the severity of clinical presentation. Materials and Methods: This multi-center survey was conducted on 329 vaccinated HCWs who were reinfected with COVID-19 between January 8, 2021 and April 8, 2021, in Tehran, Iran. Results: Overall, 92.1% and 70.8% of the participants had received 2 and 3 cumulative doses of COVID-19 vaccines, respectively. There were no differences between first/second and third-dose vaccines with the severity of SARS-CoV-2 infection. Expectedly, vaccination resulted in a less severe clinical presentation of SARS-CoV-2 infection, as reported by the participants. Conclusion: The results suggest that the efficacy of the vaccination agents presently utilized by HCWs was acceptable with no significant difference in vaccine type. Participants receiving at least two doses of vaccines in this survey exceeded 90%, which is comparably higher than studies conducted in other countries.

Relationship between fetal middle cerebral artery pulsatility index and cerebroplacental ratio with adverse neonatal outcomes in low-risk pregnancy candidates for elective cesarean section: A cross-sectional study.

Background: The cerebroplacental ratio (CPR) is an important factor for predicting adverse neonatal outcomes in appropriate-for-gestational-age fetuses. Objective: To evaluate whether there is an association between the CPR level and adverse neonatal outcomes in appropriate-for-gestational-age fetuses. Materials and Methods: This cross-sectional study included 150 low-risk pregnant women candidates for elective cesarean sections at the gestational age of 39 wk. CPR and middle cerebral artery pulsatility index (MCA PI) were calculated in participants just before cesarian section. Postnatal complications were defined as an adverse neonatal outcome such as an Apgar score of the neonate ≤ 7 at 5 min, neonatal intensive care unit (NICU) admission, cord arterial pH ≤ 7/14, and meconium stained liquor. Results: The mean age of participants was 31.53 ± 4.91 yr old. The mean CPR was reported as 1.83 ± 0.64. The Chi-square test analysis revealed that a low MCA PI and a low CPR were significantly associated with decreased cord arterial pH, decreased Apgar score at 5 min, and NICU admission (p < 0.001). There was no significant association between umbilical artery PI with arterial cord pH, Apgar score at 5 min, NICU admission, or meconium stained liquor. The Mann-Whitney test showed that a lower fetal weight appropriate for the women's gestational age was significantly associated with a decreased CPR and MCA PI (p < 0.005). There was no significant association between amniotic fluid index and CPR, umbilical artery PI, or MCA PI. Conclusion: The CPR is a significant factor in predicting adverse neonatal outcomes and ultimately neonatal mortality and morbidity of low risk, appropriate-for-gestational-age fetuses.

Comparison of Prenatal and Neonatal Outcomes of Selective Fetal Growth Restriction in Monochorionic Twin Pregnancies with or Without Twin-to-Twin Transfusion Syndrome After Radiofrequency Ablation.

Background: This study aimed to investigate and compare the prenatal and neonatal outcomes of monochorionic twin pregnancies complicated with fetal growth restriction (sFGR) with or without twin-to-twin transfusion syndrome (TTTS) after cord occlusion by radiofrequency ablation (RFA). Methods: This prospective cross-sectional study was conducted in women with monochorionic twin pregnancies of 16 to 26 weeks of gestational age (GA) in an academic hospital from 2016 to 2020. Demographic and obstetrical characteristics such as cervical length, GA of RFA and delivery, amnioreduction, cesarean section (C/S) rate, and maximum vertical pocket as well as prenatal, neonatal, and maternal outcomes were evaluated and compared between groups using Statistical Package for the Social Sciences (SPSS). Mann-Whitney U test or independent t test was used for quantitative data and Chi square test was applied for comparing qualitative variables. The significance level of tests was 0.05. Results: Totally 213 (106 sFGR and 107 TTTS+sFGR) cases were enrolled. The mean of maternal age (P=0.787), body mass index (P=0.932), gestational age at RFA (P=0.265), as well as gestational age of delivery (P=0.482), and C/S rate (P=0.124) were not significant between the two groups, but a significant difference (P<0.001) in cervical length was observed between the two groups. No significant differences were found in newborn and fetal outcomes such as fetal demise (P=0.827), PPROM (P=0.233), abortion (P=0.088), and admission to intensive care unit (P=0.822) between the groups. Conclusion: Although worse fetal and neonatal outcomes were expected in the TTTS+sFGR group after RFA, no significant difference was observed between groups.

Predictive role of Doppler indices of cerebral-placental-uterine ratio and umbilico-cerebral ratio for late-onset fetal growth restriction: a prospective cohort study.

Predicting late-onset foetal growth restriction (FGR) has proven to be rather challenging. In this study, we propose a new parameter, cerebral-placental-uterine (CPU) ratio and umbilico-cerebral (UC) ratio for this matter. Results of this study which included a total of 227 nulliparous women showed that an increase in CPU ratio (OR = 0.45; 95% CI: 0.23-0.88; p=.020) was associated with lower odds of foetal weight above the 10th percentile at birth. CPU ratio measured at 35-37 weeks of gestation had an AUC of 0.78 (95% CI: 0.58, 0.98), sensitivity of 0.62 (95% CI: 0.24, 0.91) and specificity of 0.90 (95% CI: 0.79, 0.96) for prediction of late-onset FGR, which showed higher accuracy than UC ratio. As some cases of the late-onset FGR are not diagnosed by foetal biometry, it is important to find Doppler parameters that can help us predict these cases and CPU ratio may help physicians in detection of high-risk foetuses that will benefit from earlier intervention. Impact StatementWhat is already known on this subject? Late-onset foetal growth restriction (FGR) defined by an FGR diagnosis after 32 weeks of gestational age, can lead to short- and long-term morbidities and early diagnosis is the key to prevent these complications.What do the results of this study add? Results showed that each unit increase in numeric variables including CP ratio (OR = 0.29, p=.006), and CPU ratio (OR = 0.40, p=.006) was associated with lower odds of the foetal weight above the 10th percentile in the second ultrasound at 35-37 weeks. In other words, CPU ratio can prove to be useful marker in prediction of late-onset FGR.What are the implications of these findings for clinical practice and/or further research? Our prospective cohort study confirms the added value of low CPU ratio, with higher predictive accuracy than UC ratio, in predicting late-onset FGR. Detection of late FGR remains poor, but it is important to prevent stillbirth so further studies on the role of CPU ratio in predicting FGR and perinatal outcomes are needed.

The role of first-trimester HbA1c in the early detection of gestational diabetes.

BACKGROUND: We aimed to assess the utility of HbA1c in the early detection of gestational diabetes (GDM) in the first trimester. METHODS: This prospective study was performed on 700 pregnant women in the perinatology clinic at a tertiary university hospital from March 2018 to March 2020. For all pregnant women, HbA1c and fasting blood glucose (FBG) levels were examined during the first trimester. Then, a GDM screening test was done within 24-28 weeks of pregnancy using a 100 g oral glucose tolerance test (OGTT) as the gold standard test. The GDM diagnosis was made according to the American Diabetes Association (ADA) criteria. Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of HbA1c and FBG were calculated using the receiver operating characteristic (ROC) curve. RESULTS: Of 700 participants, one hundred and fifteen (16.4%) women had GDM. The GDM patients were significantly older and had a higher pre-gestational body mass index and pregnancy weight gain compared to the non-GDM participants. The sensitivity and specificity for ruling out GDM at an HbA1c cut-off value of 4.85% was 92.2 and 32.8%, respectively, with a 95.5% NPV and a 21.2% PPV. Furthermore, sensitivity and specificity for diagnosing GDM at an HbA1c cut-off value of 5.45% was 54.8 and 96.8%, respectively, with a 91.5% NPV and a 76.8% PPV. Using HbA1c could decline OGTT in 40.4% of the pregnant women (28.7% with HbA1c < 4.85 and 11.7% with HbA1c ≥ 5.45%). CONCLUSION: It seems that the first-trimester HbA1c cannot replace OGTT for the diagnosis of GDM because of its insufficient sensitivity and specificity. However, women with higher first-trimester HbA1c had a high risk for GDM incidence.

Creating a novel strategy to reduce unnecessary laboratory testing based on healthcare cost analysis in high-risk pregnancies and delivery ward.

INTRODUCTION: Inappropriate request for laboratory tests is a challenging problem and an important cause for additional healthcare costs. Indeed, it may have further ambiguity for the clinicians. This study aimed to design an education-based program to reduce unnecessary laboratory testing orders and the associated costs. MATERIALS AND METHODS: In this interventional prospective study that took place in an educational hospital, the type and frequency of selected laboratory testing requested by gynecology, and obstetrics residents in the patients with gestational diabetes mellitus, preeclampsia, preterm labor, and premature preterm rupture of the membrane as well as cesarean section and normal vaginal delivery were analyzed periodically in a 1-year interval. At the same time, continuous educational supports and monitoring were performed. The results were compared before and after interventions. RESULTS: The educational intervention regardless of the etiologies of the admission, decreased the requested laboratory testing significantly (p < 0.001), except for CBC. Indeed, no near misses or delays in treatment were observed. Cost analysis showed a 31.3% reduction of expenses per inpatient day due to the decrease in the number of daily laboratory testing ordered. CONCLUSIONS: Appropriate education and continuous monitoring of the residents could reduce the unrequired laboratory testing as well as healthcare costs.

The effects of progesterone therapy in pregnancy: vaginal and intramuscular administration.

AIM: This study was performed to evaluate the effects of vaginal versus intramuscular progesterone supplementations on the mood, quality of life, and metabolic changes in pregnant women with the history of previous preterm birth. METHODS: This study was conducted as a prospective, randomized, open label, clinical trial evaluated 100 pregnant women who referred for prenatal visit, with 16-17 weeks of gestation from September 2014 through October 2015. The mothers were then randomly allocated into two groups: the vaginal progesterone group to receive 400 mg cyclogest vaginal suppositories (Actavis, UK limited, England) once daily, and the intramuscular progesterone group to receive weekly intramuscular injections of 250 mg of 17-hydroxyprogesterone caproate (17-HPC) (Bayer Schering Pharma, Germany), starting from the 16th to the 35th weeks of pregnancy. Demographics, medical and obstetrical history, sleeping disturbances, alteration in sexual desire, nausea/vomiting, serum levels of fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were evaluated, first and 8 weeks later. RESULTS: About 11 (11.2%) screened positive for psychosocial disorders; 25 (25.5%) had sleep disturbance, 11 (11.2%) had alteration in sexual desire, and 29 (29.6%) had nausea/vomiting upon enrollment. After 2 months of receiving daily vaginal progesterone, there was a significant increase in the GHQ-28 score (p < .001), and rates of positive screening for psychosocial disorders (p = .001) in this group. No statistically significant differences were observed in the HDL levels (p = .06), LDL levels (p = .15), rates of impaired FBS (p = .08), nausea/vomiting (p = .2), sexual desire alteration (p = .56), and sleep disturbance (p = 1) in the participants who were randomized to this group. CONCLUSION: Our results indicated that psychosocial disorders increased significantly at 24th week gestational age after 2 months of progesterone consumption in both groups which could show psychological impact of progesterone regardless of the route of consumption. This calls for higher psychological attention in these women.

Effect of the Fractional CO2 Laser on the Quality of Life, General Health, and Genitourinary Symptoms in Postmenopausal Women With Vaginal Atrophy: A Prospective Cohort.

Introduction: After menopause women experience vaginal atrophy related to hormonal changes and estrogen deficiency. The purpose of this paper was to evaluate the effect of the fractional CO2 laser on the quality of life, vaginal atrophy symptoms, and urine incontinency in menopause women. Methods: This prospective study was conducted among 140 women from 2017 to 2018 in Yas hospital, Tehran University of Medical Sciences. They encountered the fractional microablative CO2 laser system three times at four-week intervals. The short form of the Health Questionnaire (SF-12) and the Female Sexual Functional Index (FSFI) questionnaire were utilized to assess the participants' quality of life. Also, the standard measuring tools including the vaginal health index (VHI) and International Consultation on Incontinence Questionnaire (ICIQ) Form were used to evaluate the vaginal atrophy symptoms. Results: The quality of life improved significantly in somatic, social function, and mental health. In the sexual context, arousal and satisfaction status improved significantly. Also, the frequency of urinary incontinence, enuresis, urgency, and the leak improved significantly (P<0.05). Among the scale variables for urinary function, it was seen that the urgency impact had no improvement. All vaginal indices improved (P<0.05). Conclusion: The fractional CO2 laser can be effective in treating vaginal atrophy and urinary symptoms. Besides, it improved the quality of life and the sexual function of post-menopausal women.

Ultrasound Assessment of Fetal Biometry in Iranian Normal Pregnancies.

BACKGROUND: The objective of this study was to provide biometric charts for Iranian fetuses. METHODS: One thousand four hundred and twenty-two women enrolled. Four hundred and eighty-four were in the second trimester of pregnancy and 940 were in the third trimester. Data were presented as mean ± standard deviation for continuous variables. Percentiles (5th, 50th, 75th, and 90th) reported. RESULTS: Mean femoral length ranged from 16 to 53 mm in our study in the second trimester and 55-79 mm in the third trimester. Mean biparietal diameter (BPD) for fetuses with in the second trimester was between 14 and 71 and for fetuses in the third trimester was between 74 and 98 mm. Mean abdominal circumference (AC) in our cases with gestational age between 14 and 41 ranged between 86 and 365 mm. CONCLUSIONS: We have provided normal reference ranges and percentiles for BPD, AC, femur length, and weight during the second and third trimester of pregnancy in an Iranian population.