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.

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.

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.

Therapeutic role of enoxaparin in intra-uterine growth restriction: A randomized clinical trial.

OBJECTIVE: Intrauterine growth restriction is a leading cause of perinatal mortality and morbidity. Using enoxaparin may enhance the placental circulation and improve the intrauterine growth. This study was conducted to assess the efficacy and safety of enoxaparin in treatment of intra-uterine growth restriction. STUDY DESIGN: 125 women with intrauterine growth restriction were randomized to control group and intervention group (receiving routine high risk pregnancy prenatal care plus daily subcutaneous injection of 40 mg enoxaparin). Prolongation of pregnancy, fetal birth weight, fetal outcome and enoxaparin side effects were compared in 2 groups. RESULTS: Baseline characteristics were similar in 2 groups. Mean gestational age at delivery was 36.73(±2.71) in enoxaparin group and 36.85(±2.17) in control group which showed no statistically significant difference. Mean fetal birth weight had also no statistically significant difference in enoxaparin and control group (2370.16 ± 580.72 g versus 2456.07 ± 543.06 g). Rate of betamethasone administration, intubation, NICU admission, sepsis, necrotizing enterocolitis, intra-ventricular hemorrhage, hypoglycemia and low apgar score were similar in two groups. No major adverse effect was seen. CONCLUSION: Enoxaparin did not prolong the pregnancy and fetal birth weight and did not improve the fetal outcome even in patients with impaired baseline Doppler findings.

Maternal mortality following thromboembolism; incidences and prophylaxis strategies.

BACKGROUND: Thromboembolism is one of the main causes of maternal mortality, which can be prevented in many cases. The present study was designed to investigate the incidence and prophylaxis strategies for maternal mortality following thromboembolism in postnatal. METHODS: In this case series study, the data of the mortality cases were extracted according to the ethical and security standards of the Ministry of Health of the country and compared with a healthy control group. The thromboembolism risk factors measured and scored using a questionnaire entitled "the evaluation of risk factors for maternal mortality following thromboembolism during pregnancy, labor, or post-partum". RESULTS: The maternal mortality rate was 16 per 100,000 live births. Among 297 mortality cases, 27 (9%) death were due to thromboembolism. The mean gestational age was 32.5 weeks. Dyspnea (88.8%) and tachycardia (18.5%) were found as common clinical manifestations in these patients. Sixteen cases (59.3%) did not get heparin, 6 (22.2%) received single dose and 5 (18.5%) received two doses and more. In these 11 cases, 5 (45%) patients received heparin before surgery, 1 after surgery, and 5 before and after surgery. Twenty cases deceased in the first hours after delivery and the rest after 2 to 12 days. The average score of risk for thromboembolism based on Royal College of Obstetricians & Gynecologist (RCOG) guideline was 4.6. CONCLUSION: It seems that one of the most important cause of maternal mortality in this study was the lack of recognition of high-risk patients and the lack of prescription for prophylaxis with heparin and this clearly explains the need for accurate screening of high-risk mothers, designing a standard form and the care and treatment of these patients.

Correlation of Maternal Stress Because of Positive Aneuploidy Screening Serum Analytes and Uterine Arteries' Doppler Ultrasound Index: A Prospective Cohort Study.

BACKGROUND: Antenatal anxiety or maternal stress is a prevalent chronic mental disorder in pregnant women. We have assessed the effect of maternal stress from positive aneuploidy screening results on the changes in uterine artery blood flow. MATERIALS AND METHODS: We performed a prospective cohort (one sample) pilot study at a hospital in Tehran, Iran. A total of 60 pregnant women who were candidates for amniocentesis due to abnormal sequential screening test results entered the study. We conducted 2 standard psychological tests, the Spielberger's State-Trait Anxiety Inventory and the Beck Anxiety Inventory, to determine anxiety levels in the participants before amniocentesis and two weeks after amniocentesis. The uterine artery resistance index was also measured before and two weeks after amniocentesis. The level of maternal stress was compared with the uterine artery resistance index. RESULTS: Patients had a mean State Trait Anxiety Inventory score before amniocentesis of greater than 40, which meant that the mothers experienced high anxiety. There were no correlations between both inventories' anxiety scores and uterine artery blood flow before amniocentesis. However, two weeks after amniocentesis, we observed significant negative correlations between the State Anxiety (P=0.0041) and Trait Anxiety (P=0.010) Inventory scores and the uterine artery resistance indexes. Also, there was an association between the decreased right uterine artery resistance index and State Anxiety scores (P=0.036). There were significant correlations between State and Trait Anxiety scores and second trimester analytes of ß-human chorionic gonadotropin (ß-hCG, P<0.001), α-fetoprotein (P<0.001), and unconjugated estriol (P=0.048). CONCLUSION: Maternal anxiety because of positive aneuploidy screening serum analytes and amniocentesis can affect perinatal outcomes via mood-based alterations in blood flow of the uterine arteries and the screening markers ß-hCG,unconjugated estriol, and α-fetoprotein.

Predictors of Cranial Ultrasound Abnormalities in Intrauterine Growth-Restricted Fetuses Born between 28 and 34 Weeks of Gestation: A Prospective Cohort Study.

BACKGROUND: Doppler parameters have been commonly used for the prediction of neonatal outcomes. However, controversies exist with regard to the value of Doppler parameters in predicting the risk of neurological outcomes among neonates. OBJECTIVE: This prospective cohort study attempted to assess the value of Doppler parameters in predict ing cranial ultrasound abnormalities (CUAs) in intrauterine growth restriction (IUGR) among fetuses at 28-34 weeks of gestation. METHODS: This was a prospective cohort study of 83 delivered IUGR fetuses and 75 control fetuses matched for gestational age (GA). The value of mentioned Doppler parameters and GA in predicting the risk of CUAs, including periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and basal ganglia lesions (BGLs), was analyzed. RESULTS: The incidence of CUAs among IUGR fetuses (66.3%) was significantly higher (p < 0.001) than in the control group (40%). The incidence of neonatal mortality among IUGR fetuses was significantly higher (p < 0.001) than in the control group. Absent or reversed end-diastolic velocity (AREDV) in the umbilical artery (UA) and the ductus venosus (DV) after adjustment for GA was associated with increased odds of IVH, PVL, BGLs, and any CUA. CONCLUSIONS: GA at birth and AREDV in the UA and the DV within 1 week before childbirth were reliable predictors of CUAs during the neonatal period.

Ectopic decidual reaction mimicking irritable bowel syndrome: a case report.

Ectopic decidualization with gross involvement of the peritoneum is one of the rare findings in pregnant women particularly when ectopic decidualization disseminated as an asymptomatic intra-abdominal nodule. We present here a case of an ectopic decidualization in a 33-year-old pregnant woman with symptoms of irritable bowel syndrome during pregnancy.

Risk factors and clinical aspects of recurrent invasive cervical carcinoma.

OBJECTIVES: Recurrence of cervical cancer is one of the important and plausible discussions in oncology especially in patients with advanced stages. The purpose of this study was to introduce probability invasive cervical carcinoma recurrence as well as determining characteristics and the prognostic factors of this entity. METHODS: A retrospective study was designed to identify risk factors and pattern of uterine cervical carcinoma recurrence evaluating the outcome of 36 registered patients. Recurrence was defined based on clinical or para-clinical documentation over at least 6 months after complete remission following surgery or radiotherapy. Treatment consisted of a radiosurgical combination and exclusive radiotherapy. RESULTS: Mean age in selected patients is 54.8 ± 12.0 years. The pathological reports of primary diagnosis are squamous cell carcinoma in 94.44 % and adenocarcinoma in remaining patients. Mean duration of recurrence among patients is 2.75 ± 1.5 years after the initial treatment. Metrorrhagia is mostly revealing symptom which patients present in recurrent episode. Usually, the recurrence of cervical cancer is presented in pelvic cavity locally. Marginal involvement is documented in 50 % of cases and lymph node in 33.3 % of patients with recurrent episode being involved. Most important prognostic factors are improper treatment (16.66 % of cases) after initial diagnosis. CONCLUSIONS: Prognostic factors such as selection of appropriate method for treatment are an important point for reducing the rate of recurrence. Moreover, warning patients about symptoms and frequent episodes of follow up is necessary for early diagnosis of recurrence.