Proangiogenic Macrophage Development in Human Prenatal Stage:A Key Element in Maternal-Fetal Medicine Puzzle

Introduction Macrophages,a major immune cell type constituting the human innate immune system,are involved in various physiological processes,such as tissue development,remodeling,homeostasis,and repair,crucial for maintaining normal growth and development of embryos/fetuses.1-3 Influenced by their cellular origin and specific tissue environments,macrophages exhibit a diverse range of phenotypes.

Interaction between ozone and paternal smoking on fetal congenital heart defects among pregnant women at high risk a multicenter maternal-fetal medicine study

Background Evidence remains limited on the association between maternal ozone(O,)exposure and congenital heart defects(CHDs)in offspring,and few studies have investigated the interaction and modification of paternal smoking on this association.Methods Using a sample including pregnant women at high risk of fetal CHD(with metabolic disease,first-trimester viral infection,family history of CHD,etc.)from a maternal-fetal medicine study covering 1313 referral hospitals in China during 2013-2021,we examined the associations between maternal O_(3)exposure during 3-8 weeks of gestational age and fetal CHD in offspring and investigated the interaction and modification of paternal smoking on this association.CHD was diagnosed by fetal echocardiograms,maximum daily 8-hour average O,exposure data at a 10 km×10 km spatial resolution came from the Tracking Air Pollution in China dataset,and paternal smoking was collected using questionnaires.Logistic regression models were used to estimate adjusted odds ratios(ORs)and 95%confidence intervals(CIs).Results Among 27,834 pregnant women at high risk of fetal CHD,17.4%of fetuses were diagnosed with CHD.Each 10μg/m^(3)increase in maternal O_(3)exposure was associated with a 17%increased risk of CHD in offspring(OR=1.17,95%CI=1.14-1.20).Compared with paternal nonsmoking and maternal low O_(3)exposure,the ORs(95%CI)of CHD for smoking and low O_(3)exposure,nonsmoking and high O_(3)exposure,and smoking and high O_(3)exposure were 1.25(1.08-1.45),1.81(1.56-2.08),and 2.23(1.84-2.71),respectively.Paternal smoking cessation seemingly mitigated the increased risk of CHD.Conclusions Maternal O_(3)exposure and paternal smoking were interactively associated with an increased risk of fetal CHD in offspring,which calls for effective measures to decrease maternal exposure to O_(3)pollution and secondhand smoke for CHDprevention.

Maternal-Fetal Medicine:The Journey Thus Far and Way Forward

As we shortly welcome the New Year,we are very pleased to share with you that Maternal-Fetal Medicine(MFM)has had another productive year and has reached another milestone with over 70,000 readings and downloads since its inauguration in July 2019.In addition to its inclusion into the DOAJ in 2020,MFM has also been accepted by three other major medical databases,including EMBASE,SCOPUS,and ESCI.

Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant women.However,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood.Here,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy.Compared to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection.However,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface.Notably,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester.Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

Evaluating the Efficacy of Cervical Tactile Ultrasound Technique as a Predictive Tool for Spontaneous Preterm Birth

Background: Premature cervical softening and shortening may be considered an early mechanical failure that predispose to preterm birth. Purpose: This study aims to explore the applicability of an innovative cervical tactile ultrasound approach for predicting spontaneous preterm birth (sPTB). Materials and Methods: Eligible participants were women with low-risk singleton pregnancies in their second trimester, enrolled in this prospective observational study. A Cervix Monitor (CM) device was designed with a vaginal probe comprising four tactile sensors and a single ultrasound transducer operating at 5 MHz. The probe enabled the application of controllable pressure to the external cervical surface, facilitating the acquisition of stress-strain data from both anterior and posterior cervical sectors. Gestational age at delivery was recorded and compared against cervical elasticity. Results: CM examination data were analyzed for 127 women at 240/7 - 286/7 gestational weeks. sPTB was observed in 6.3% of the cases. The preterm group exhibited a lower average cervical stress-to-strain ratio (elasticity) of 0.70 ± 0.26 kPa/mm compared to the term group’s 1.63 ± 0.65 kPa/mm with a p-value of 1.1 × 10−4. Diagnostic accuracy for predicting spontaneous preterm birth based solely on cervical elasticity data was found to be 95.0% (95% CI, 88.5 - 100.0). Conclusion: These findings suggest that measuring cervical elasticity with the designed tactile ultrasound probe has the potential to predict spontaneous preterm birth in a cost-effective manner.

Effects of mild intrauterine hypoperfusion in the second trimester on memory and learning function in rat offspring

Mild intrauterine hypoperfusion(MIUH)is a serious pathological event that affects the growth and development of fetuses and offspring.MIUH can lead to growth restriction,low birth weight,neurodevelopmental disorders,and other adverse clinical outcomes.To study the effects of MIUH on learning and memory function in offspring,a model of MIUH was established by placing a coil(length 2.5 mm,diameter 0.24 mm)on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy(day 17).Next,120 mg/kg lithium chloride(the MIUH+Li group)or normal saline(the MIUH group)was injected intraperitoneally into these rats.In addition,120 mg/kg lithium chloride(the Li group)or normal saline(the SHAM group)was injected intraperitoneally into pregnant rats without coil placement.The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth.In the MIUH group,the escape latency and journey length before reaching the platform were both increased,and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group.Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67(both cell-proliferation-related proteins)expression was significantly downregulated in the MIUH group compared with the SHAM group.Furthermore,western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats,and revealed that glycogen synthase kinase 3β(GSK3β)expression was upregulated andβ-catenin expression was downregulated in the MIUH group compared with the SHAM group.In addition,compared with the MIUH group,the expression levels of p-GSK3βandβ-catenin were upregulated in the MIUH+Li group.These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3βsignaling pathway.The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No.2018 PS07 K)in June 2018.

妊娠期及产后静脉血栓栓塞的发生率、危险因素及死亡率

Objective: The purpose of this study was to estimate the incidence,risk factors, and mortality from pregnancy-related venous thromboembolism. Study design: The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality for the years 2000 to 2001 was queried for all pregnancy-related discharges with a diagnosis of venous thromboembolism. Results: The rate of venous thromboembolism was 1.72 per 1000 deliveries with 1.1 deaths per 100,000. The risk of venous thromboembolism was 38% higher for women ages 35 and older and 64% higher for black women. Other significant risk factors included thrombophilia, lupus, heart disease, sickle cell disease,obesity, fluid and electrolyte imbalance, postpartum infection,and transfusion. The risk factor with the highest odds ratio, 51.8(38.7- 69.2) was thrombophilia. Conclusion: The incidence of pregnancy-related venous thromboembolism was higher than generally quoted. Women ages 35 and older, black women, and women with certain medical conditions and obstetric complications appear to be at increased risk.

Noninherited Factors in Fetal Congenital Heart Diseases Based on Bayesian Network:A Large Multicenter Study

Background:Current studies have confirmed that fetal congenital heart diseases(CHDs)are caused by various factors.However,the quantitative risk of CHD is not clear given the combined effects of multiple factors.Objective:This cross-sectional study aimed to detect associated factors of fetal CHD using a Bayesian network in a large sample and quantitatively analyze relative risk ratios(RRs).Methods:Pregnant women who underwent fetal echocardiography(N=16,086 including 3,312 with CHD fetuses)were analyzed.Twenty-six maternal and fetal factors were obtained.A Bayesian network is constructed based on all variables through structural learning and parameter learning methods to find the environmental factors that directly and indirectly associated with outcome,and the probability of fetal CHD in the two groups is predicted through a junction tree reasoning algorithm,so as to obtain RR for fetal CHD under different exposure factor combinations.Taking into account the effect of gestational week on the accuracy of model prediction,we conducted sensitivity analysis on gestational week groups.Results:The single-factor analysis showed that the RRs for the numbers of births,spontaneous abortions,and parental smoking were 1.50,1.38,and 1.11(P<0.001),respectively.The risk gradually increased with the synergistic effect of ranging from one to more environmental factors above.The risk was higher among subjects with five synergistic factors,including the number of births,upper respiratory tract infection during early pregnancy,anemia,and mental stress as well as a history of spontaneous abortions or parental smoking,than in those with less than 5 factors(RR=2.62 or 2.28,P<0.001).This result was consistent across the participants grouped by GWs.Conclusion:We identified six factors that were directly associated with fetal CHD.A higher number of these factors led to a higher risk of CHD.These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.

Amniocentesis: A contemporary review

Amniocentesis is an essential tool in obstetrics. Invasive testing remains the only modality for diagnostic genetic testing and the only way to provide comprehensive test-ing for chromosomal abnormalities. Despite increasing use of cell free fetal deoxyribonucleic acid （DNA） testing, amniocentesis should still be offered to all women who desire more complete and accurate genetic testing. Counseling patients on the limitations of screening tests is of the upmost importance and amniocentesis should continue to be recommended to confrm positive results from cell free fetal DNA testing or in the case of failed cell free fetal DNA test. As cell free fetal DNA screening has not adequately been studied in multiple gestations, its use is not recommended in this population and invasive testing should be offered. Amniocentesis is also very useful in providing additional information in settings other than genetic testing the second and third trimester. If intraamniotic infection is suspected, but the clinical fndings are not enough to guide manage-ment, amniocentesis can provide testing that can both immediately clarify the picture （interleukin-6, gram stain, glucose levels） and finally confirm the presence of infection （culture）. It can also be used to detect the presence of intrauterine viral infections. Additionally, amniocentesis may be used to test for markers of fetal lung maturity. The American Congress of Obstetricians and Gynecologists recommends that amniocentesis for this indication not be used in cases where late preterm delivery is indicated. It may be useful in guiding decision-making, however , when late preterm delivery is indicated, but when exact timing is unclear. Regardless of the indication, amniocentesis appears to be a relatively low risk procedure with minimal risk to the patient. Additional randomized controlled trials are not likely, as they are not feasible to due extremely high number of participants that would be needed to detect a difference in loss rates. Based on current literature, however, the risk of pregnancy loss from second trime-ster amniocentesis is low in both singleton and twin gestations. We counsel patients that technique has changed since the original studies in the 1970s and feel comfortable quoting a loss rate of 1/500-1/1000 based on contemporary data.

Relationship between spiritual well-being and Health-Related Quality of Life and some related factors in patients with AIDS/HIV

Objective:The study of effective factors on the quality of life(QoL),as an important criterion,in the outcome of new therapeutic and preventive strategies in human immunodeficiency virus(HIV)has been considered by researchers.To study the relationship between spiritual well-being and Health-Related Quality of Life(HRQoL)and some related factors in patients with Acquired Immunodeficiency Syndrome([AIDS]/HIV).Methods:In this cross-sectional study,224 people were selected as the study population(112 were male and 112 were female)from patients with AIDS/HIV at the Behavioral Counseling Center of Shiraz with available sampling method.The research tool was Palutzian&Ellison well-being scale and QoL Questionnaire(SF-36).Data were analyzed using Pearson correlation test.Results:There was a significant direct relationship between physical function dimensions(P=0.003).There was a significant relationship between general well-being,mental well-being,and total spiritual well-being(P<0.001).There was a statistically significant relationship between the dimensions of QoL and spiritual well-being with some age section of the patients,and their occupation and education(P<0.001).Conclusions:Spirituality has an impact on the QoL dimensions.Therefore,HIV positive people’s quality of life could be improved by the possibility of the spiritual well-being promotion as a method of adaptation with the disease.

妊娠早期患牙周病与小于胎龄儿的发生风险

Objective: The objective of the study was to determine whether periodontal disease is associated with delivery of a small-for-gestational-age infant. Study design: In a prospective study of oral health, periodontal disease was categorized as health, mild, or moderate/severe on the basis of clinical criteria.Small for gestational age was defined as birth weight less than the 10th percentile for gestational age. A risk ratio(95th percentile confidence interval) for a small-for-gestational-age-infant among women with moderate or severe periodontal disease was calculated. Results: Sixty-seven of 1017 women (6.6% ) delivered a small-for-gestational-age infant, and 143 (14.3% ) had moderate or severe periodontal disease. The small-for-gesta-tional-age rate was higher among women with moderate or severe periodontal disease, compared with those with health or mild disease (13.8% versus 3.2% versus 6.5% ,P < .001). Moderate or severe periodontal disease was associated with a small-for-gestational-age infant, a risk ratio of 2.3 (1.1 to 4.7), adjusted for age, smoking, drugs, marital and insurance status, and preeclampsia. Conclusion: Moderate or severe periodontal disease early in pregnancy is associated with delivery of a small-for-gestational-age infant. Understanding the mechanism of periodontal disease-associated adverse pregnancy out comes could lead to interventions to improve fetal growth.

一项3h葡萄糖耐量试验值升高的妇女其不良围生期结局风险是否升高

Objective: The purpose of this study was to examine whetherw omen with one elevated value of the 3- hour glucose tolerance test are at increased risk for adverse perinatal outcomes.Study design: This was a retrospective cohort study of singleton pregnancies that were screened for gestational diabetes mellitus with the use of the glucose loading test and with a glucose tolerance test for follow up, if screened values were positive. Perinatal outcomes in women with one elevated glucose tolerance test value were compared with the outcomes in women who screened negative by glucose loading test. The chi-square test was used to compare categorical outcomes, and multivariate logistic regression analysis was used to control for potential confounding factors; a P value of < .05 indicated statistical significance. Results:Of 14,036 women who met the study criteria, women with one elevated glucose tolerance test value exhibited higher rates of cesarean delivery (in nulliparous women only)- , preeclampsia, chorioamnionitis, birth weight > 4000 g and > 4500 g, and neonatal admission to the intensive care nursery as compared with women who screened negative (P < .05 for all). Conclusion: Although women with one elevated glucose tolerance test value are not diagnosed with gestational diabetes mellitus, they are still at risk for adverse perinatal outcomes.

早产预测研究:孕妇体重指数与自发性早产及干预性早产的关系

Objective: The purpose of this study was to evaluate the relationship between prepregnancy maternal body mass index and spontaneous preterm birth and indicated preterm birth. Study design: This was a secondary analysis of the Maternal- Fetal Medicine Units Network, Preterm Prediction study. Patients were classified into categories that were based on their body mass index. Rates of indicated and spontaneous preterm birth were compared. Results: Five hundred ninety- seven (20.5% ) of 2910 women were obese. Obese women had fewer spontaneous preterm births at < 37 weeks of gestation (6.2% vs 11.2% ; P <. 001) and at < 34 weeks of gestation (1.5% vs 3.5% ; P =. 012). Women with a body mass index of < 19 kg/m2 had 16.6% spontaneous preterm birth, with a body mass index of 19 to 24.9 kg/m2 had 11.3% spontaneous preterm birth, with a body mass index of 25 to 29.9 kg/m2 had 8.1% spontaneous preterm birth, with a body mass index of 30 to 34.9 kg/m2 had 7.1% spontaneous preterm birth, and with a body mass index of ≥ 35 kg/m2 had 5.2% spontaneous eterm birth (P <. 0001). Indicated delivery was responsible for an increasing proportion of preterm births with increasing body mass index (P =. 001). Obese women had lower rates of cervical length < 25 mm (5% vs 8% pr.; P =. 012). Multivariable regression analysis confirmed a lower rate of spontaneous preterm birth in obese gravid women (odds ratio, 0.57; 95% CI, 0.39- 0.83; P =. 003). Conclusion: Obesity before pregnancy is associated with a lower rate of spontaneous preterm birth.

Adverse Maternal Consequences Associated with Prolonged Acute-Onset Severe Systolic Hypertension during Pregnancy &Early Postpartum: Pitfalls in Practice &Lessons Learned

OBJECTIVE: To determine the types of major maternal-perinatal morbidity associated with prolonged, acute-onset severe systolic hypertension during pregnancy and postpartum. METHODS: A medicolegal database retaining only medical record data was created from all cases involving women with medical/hypertensive disorders of pregnancy evaluated by the first author between 1986-2015. Case files of women that experienced severe systolic hypertension (SSH) sustained for many hours to days were identified for study. RESULTS: Sixty six pregnant/postpartum women met study criteria. Stroke secondary to intracranial hemorrhage or thrombosis (65.2) and acute pulmonary edema (33%) were the leading causes of maternal morbidity and mortality, most often antepartum as a component of early-onset preeclampsia (≤34 weeks). Eclampsia, abruptio placenta and injury to heart, liver and/or kidneys were other frequent co-morbidities. Seven postpartum women developed sudden new-onset postpartum SSH and suffered a stroke 4 - 13 days after delivery. Maternal mortality (54.6%) and morbidity as persistent disability (24.2%) were high in this cohort. CONCLUSION: Failure to rapidly respond, reduce and sustain at a safe level acute-onset SSH poses a significant threat to the wellbeing of mothers and babies, before and in the weeks following delivery. Systems to implement safe practices to identify and emergently treat severe maternal hypertension are needed.

羊水粪染与孕周及新生儿酸碱平衡状态

OBJECTIVE: To estimate whether the acid-base status of neonates born to women with meconium-stained amniotic fluid varies across gestation. METHODS: We carried out a retrospective cohort study of all pregnancies that were complicated by meconium-stained amniotic fluid in 2004. Cases were identified from a perinatal pathology database that contained data on all pregnancies complicated by meconium- stained amniotic fluid. Data abstracted from the charts included gestational age at delivery, umbilical arterial pH, birth weight, and the presence or absence of labor. Cases were stratified according to gestational age at delivery. The distribution of meconium-stained amniotic fluid across gestation was computed. The mean umbilical arterial pH values (with 95% confidence intervals) across gestation were assessed by analysis of variance. RESULTS: The mean umbilical arterial pH in women with meconium-stained amniotic fluid did not differ across gestation. The overall incidence of meconium-stained amniotic fluid was 12.0% (766 of 6,403 deliveries). The rates of meconium-stained amniotic fluid increased from 1.2% at 32 weeks to 100% at 42 weeks. CONCLUSION: The rising incidence of meconium-stained amniotic fluid with gestational age is consistent with the hypothesis that fetal maturation is a major etiologic factor in meconium passage. Also, the lack of variation of mean umbilical arterial pH across gestation suggests that fetal acidemia is not increased when meconium passage occurs earlier in pregnancy rather than at later gestational ages.

Compound heterozygous mutation of MUSK causing fetal akinesia deformation sequence syndrome: A case report

BACKGROUND Fetal akinesia deformation sequence(FADS)is a broad spectrum disorder with absent fetal movements as the unifying feature.The etiology of FADS is heterogeneous and mostly still unknown.A prenatal diagnosis of FADS relies on clinical features obtained by ultrasound and fetal muscle pathology.However,the recent advances of next-generation sequencing(NGS)can effectively provide a definitive molecular diagnosis.CASE SUMMARY A fetus presented after 24 wk and 6 d of gestation with absent fetal movements and multiple abnormal ultrasonographic signs.The mother had had a previous abortion due to a similarly affected fetus a year before.A clinical diagnosis of FADS was made.The parents refused cord blood examination and chose abortion.A molecular diagnosis of fetal muscle using NGS of genes found a compound heterozygous mutation in the MUSK gene:c.220C>T(chr9:113449410 p.R74W)and c.421delC(chr9:113457745 p.P141fs).CONCLUSION To our knowledge,this is the first report in China showing that a mutation in MUSK is associated with FADS.This supports previous finding that a lethal mutation of MUSK will cause FADS.A precise molecular diagnosis for genetic counseling and options for a prenatal diagnosis of FADS are very important,especially for recurrent FADS;this may also provide evidence for both prenatal and preimplantation genetic diagnoses.

Gestational Weight Gain in Obese Patients and Adverse Pregnancy Events

Objectives: To examine pre-pregnancy obesity and gestational weight gain as predictors for adverse pregnancy outcomes in a predominantly non-white obstetric resident clinic population. Methods: Prenatal charts for patients with pre-pregnancy obesity cared for at our resident clinic from January 1, 2008 through December 31, 2010 were reviewed. Adverse maternal outcomes were grouped into a “Composite Morbidity Index” (CMI-M) and included gestational diabetes, gestational hypertension, preeclampsia, superimposed preeclampsia, dystocia, operative delivery, Cesarean section for arrest disorders, wound infection and disruption, and thromboembolic events. Fetal events, similarly categorized into a composite adverse fetal index (CMI-F), included macrosomia, Apgar at 5 minutes (≤3), NICU admission, congenital anomalies and intrauterine fetal demise. Results: 627 women with a singleton pregnancy and a pre-pregnancy body mass index (BMI) of 30 and greater were included in the analysis. As measured by the composite morbidity index, women with Class III obesity at their first prenatal visit were more likely to have at least one or more maternal and fetal complications compared to women with Class II or Class I obesity. For adverse maternal outcomes (CMI-M), 40.2%, 33.8%, and 27.4% of women within each respective obesity class experienced an adverse event (p = 0.027). Applying the CMI-F, fetal complications were observed in 28.2%, 18%, and 13.9% of Class III, II, and I obesity (p = 0.003). Total gestational weight gain per week was significantly greater for patients with one or more maternal complications (p = 0.045). Conclusion: Among an obese, resident clinic population comprised primarily of women of ethnic minorities, pre-pregnancy body mass index was the strongest indicator for adverse maternal and fetal outcomes.

An implementation study of barriers to universal cervical length screening for preterm birth prevention at tertiary hospitals in Thailand:Healthcare managers’perspectives

Objective:To identify healthcare managers’perspectives on the barriers to implementing cervical length screening to prevent preterm births.Methods:In PhaseⅠ,10 healthcare managers were interviewed.PhaseⅡcomprised questionnaire development and data validation.In PhaseⅢ,the questionnaire was administered to 40 participants,and responses were analyzed.Results:Their average related work experience was(21.0±7.2)years;39(97.5%)respondents also had healthcare management responsibilities at their respective hospitals.Most hospitals were reported to have enough obstetricians(31 cases,77.5%)and to be able to accurately perform cervical length measurements(22 cases,55.0%).However,no funding was allocated to universal cervical length screening(39 cases,97.5%).Most respondents believed that implementing universal screening,as per Ministry of Public Health policies,would prevent preterm births(28 cases,70.0%).Moreover,they suggested that hospital fees for cervical length measurements should be waived(34 cases,85.0%).Three main perceived barriers to universal screening at tertiary hospitals were identified.They were heavy obstetrician workloads(20 cases,50.0%);inadequate numbers of medical personnel(24 cases,60.0%);not believing that the screening test could prevent preterm birth(8 cases,20%)and lack of free drug support for preterm birth prevention in high-risk cases(29 cases,72.5%).Conclusions:The main obstacles to universal cervical length screening are heavy staff workloads and inadequate government funding for ultrasound scanning and hormone therapy.The healthcare managers do not believe that the universal cervical length screening can help to reduce preterm birth.

Two polymorphisms in methylenetetrahydrofolate reductase gene(C677T and A1298C) frequently associated with recurrentspontaneous abortion show no association in Saudi women

Methylenetetrahydrofolate reductase(MTHFR)deficiency is the most common genetic cause of hyperhomocysteinemia,which has been implicated in the etiology of recurrent spontaneous abortion(RSA).This study was designed to investigate the association between two single nucleotide polymorphisms(SNP)(rs1801133[C677T]and rs1801131[A1298C])in the MTHFR gene and RSA,in Saudis.These two SNPs were selected as these polymorphisms have a different effect on the activity and stability of the enzyme,and significantly diverse effects have been reported in relation to the association with RSA.Ethical approval was acquired from the IRB at King Saud University(KKUH),Saudi Arabia,and written informed consent was obtained from each participant.The study group comprised of 100 Saudi women with unexplained RSA and 100 age-matched controls,both attending KKUH for a routine checkup.Blood was drawn in EDTA tubes,and DNA was extracted.Genotyping was conducted using TaqMan SNP genotyping assay kits.The frequency of the T allele of C677T was 0.165 in patients and 0.17 in controls.Genotype frequencies for CC,CT and TT genotypes were 70%,27%and 3%,respectively in RSA,and 71%,24%and 5%,respectively,in the controls(p>0.05).For the A1298C polymorphism,the C allele frequencies were 0.345 in patients and 0.28 in controls,while genotype frequencies for AA,AC and CC genotypes were 44%,43%,and 13%,respectively,in patients,and 54%,36%,and 10%,respectively,in controls(p>0.05).The frequency of CC genotype and C allele of A1298C were higher in the patients with RSA,but not significantly,while C677T genotypes and allele frequencies did not differ between patients and controls.The results suggested that MTHFR gene polymorphisms are population-specific and may not associate with RSA in Saudi women.

In Utero Bipolar Diathermy to Salvage a Phenotypically Normal Fetus in 45,X/46,XY Heterokaryotypic Monochorionic Twins

Heterokaryotypic monozygotic twins are rare. We report a set of monochorionic diamniotic twins complicated with lethal malformations and hydrops in one fetus at menstrual age of 16 weeks’. Sonographic appearances and genetic am-niocentesis result suggested for 45,X and 46,XY heterokaryotypic twins. Coexisting polyhydramnios found in the sac of severely malformed 45,X fetus threatened miscarriage and premature delivery. To salvage the phenotypically normal male fetus, the hydropic 45,X co-twin was selectively terminated by occlusion of its umbilical cord with bipolar dia-thermy. Complete cessation of funicular flow was achieved, resulting in normalization of total amniotic fluid volume. A healthy 2200-gram baby boy was born at 38 weeks’. His neurodevelopment was intact at 2 years of age. His physical examination was significant for slight growth delay (15 percentiles), with 6% of 45,X mosaicism found in his peripheral blood. Owing to the rarity of the cases, limited data is available regarding an optimal treatment for heterokaryotypic monochorionic twins with discordant lethal malformation. Intrauterine intervention may be offered should demise or permanent disabilities are imminent to the apparently normal fetus.