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The new Joint Commission requirements on perinatal safety present a unique opportunity for the simulation community to actively engage with labor and delivery units nationwide. Considerations for implementation using "real-life" experience with the programmatic development of an in situ team-based simulation training program in obstetric emergencies are discussed. We urge simulationists to explore opportunities to promote culture change on a large scale to move the needle of maternal morbidity and mortality.

Noninvasive prenatal screening (NIPS) for fetal aneuploidy via cell-free DNA has been commercially available in the United States since 2011. In 2016, the American College of Medical Genetics and Genomics (ACMG) issued a position statement with specific recommendations for testing laboratories. We sought to evaluate adherence to these recommendations. We focused on commercial laboratories performing NIPS testing in the United States as of 1 January 2018. Sample laboratory reports and other materials were scored for compliance with ACMG recommendations. Variables scored for common and sex chromosome aneuploidy detection included detection rate, specificity, positive and negative predictive value, and fetal fraction. Labs that performed analysis of copy-number variants and results for aneuploidies other than those commonly reported were identified. Available patient education materials were similarly evaluated. Nine of 10 companies reported fetal fraction in their reports, and 8 of 10 did not offer screening for autosomal aneuploidies beyond trisomy 13, 18, and 21. There was inconsistency in the application and reporting of other measures recommended by ACMG. Laboratories varied in the degree to which they met ACMG position statement recommendations. No company adhered to all laboratory guidance.

In 2013, twenty-two states enacted seventy provisions restricting access to abortion. The legislation restricted access to abortions by instituting more regulations on providers and facilities, by prohibiting abortion prior to viability, by restricting funding available to patients and by requiring patients to wait a mandatory time period before having a procedure. Genetic counselors are trained to provide unbiased, comprehensive information in a non-directive style in order to allow patients to exercise their reproductive freedom. We developed a survey of 37 questions for genetic counselors to gauge the potential impact these provisions will have on their ability to be a patient advocate. A total of 286 individuals completed the survey; however, not all respondents answered all questions. Qualitative questions complemented quantitative survey entries, allowing respondents to input thoughts and examples. Results indicate genetic counselors in all regions share similar professional opinions about the provisions. More genetic counselors in the South and Midwest noticed changes impacting patients since the provisions have been enacted. These regional differences correlate with the location of states that have seem the greatest increase in antiabortion provisions.

Objectives No previous studies have reported the frequencies of individual chromosomal anomalies in normal-appearing fetuses stratified by maternal age (MA) and gestational age (GA). We therefore sought to (1) characterize the frequency of all fetal karyotype anomalies in sonographically normal appearing fetuses without pretest risk factors, and (2) assess MA and GA impact on the proportion of anomalies targeted by screening and consequent impact on residual risk following a negative result. Methods Fetal karyotypes from samples without prior risk assessment or ultrasound anomalies were analyzed. We calculated, per single-year MA and in two GA intervals, the predicted frequency of each cytogenetic defect. Results 129,263 karyotypes were analyzed. The risk for significant, cytogenetically visible chromosomal anomalies, at 15 to 20 weeks GA, varies between 1/301 at MA of 18 years, and 1/9 at MA of 48 years. The proportion of clinically significant anomalies not addressed by current screening methods is 47% at MA of 18 years and 5% at MA of 48 years. Conclusions By determining frequencies for individual karyotype anomalies stratified by MA and GA, in the setting of normal-appearing fetuses, a more personalized risk assessment, including the residual risk after a normal fetal aneuploidy screening result, can be provided. This article is protected by copyright. All rights reserved.

This statement is designed primarily as an educational resource for clinicians to help them provide quality medical services. Adherence to this statement is completely voluntary and does not necessarily assure a successful medical outcome. This statement should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed toward obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this statement. Clinicians also are advised to take notice of the date this statement was adopted and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Noninvasive prenatal screening using cell-free DNA (NIPS) has been rapidly integrated into prenatal care since the initial American College of Medical Genetics and Genomics (ACMG) statement in 2013. New evidence strongly suggests that NIPS can replace conventional screening for Patau, Edwards, and Down syndromes across the maternal age spectrum, for a continuum of gestational age beginning at 9-10 weeks, and for patients who are not significantly obese. This statement sets forth a new framework for NIPS that is supported by information from validation and clinical utility studies. Pretest counseling for NIPS remains crucial; however, it needs to go beyond discussions of Patau, Edwards, and Down syndromes. The use of NIPS to include sex chromosome aneuploidy screening and screening for selected copy-number variants (CNVs) is becoming commonplace because there are no other screening options to identify these conditions. Providers should have a more thorough understanding of patient preferences and be able to educate about the current drawbacks of NIPS across the prenatal screening spectrum. Laboratories are encouraged to meet the needs of providers and their patients by delivering meaningful screening reports and to engage in education. With health-care-provider guidance, the patient should be able to make an educated decision about the current use of NIPS and the ramifications of a positive, negative, or no-call result.Genet Med 18 10, 1056-1065.

Objectives Cell-free DNA (cfDNA) screening can provide false positive/negative results because the fetal fraction originates primarily from trophoblast. Consequently, invasive diagnostic testing is recommended to confirm a high-risk result. Currently, there is debate about the most appropriate invasive method. We sought to estimate the frequency in which a chorionic villus sampling (CVS) performed after a high-risk cfDNA result would require a follow-up amniocentesis due to placental mosaicism. Methods Analyses of the frequencies of the different types of mosaicism involving cytotrophoblasts, for trisomies 21 (T21), 18 (T18), 13 (T13) and monosomy X (MX) among 52 673 CVS karyotypes obtained from cytotrophoblast, mesenchyme and confirmatory amniocentesis. Results After a high-risk cfDNA result for T21, 18, 13 and MX, the likelihood of finding CVS mosaicism and need for amniocentesis is, respectively, 2%, 4%, 22% and 59%. When mosaicism is detected by CVS, the likelihood of fetal confirmation by amniocentesis is, respectively, 44%, 14%, 4% and 26%. Conclusions In cases of high-risk cfDNA results for T21/T18, CVS (combining cytotrophoblast and mesenchyme analysis) can be considered, but with the caveat of 2–4% risk of an inconclusive result requiring further testing. In high-risk results for MX/T13, amniocentesis would appear to be the most appropriate follow-up diagnostic test, especially in the absence of sonographic findings. © 2015 John Wiley & Sons, Ltd.

Advancements in molecular technology coupled with a greater awareness of the human genome and epigenome have broadened our understanding of the genetic contributions to the diabetic pregnancy. There are multiple genes and pathways that can result in a hyperglycemic environment for the fetus. Exposure to this environment in utero has an impact on the risk of adult-onset chronic diseases. How identification of an individual's genetic variants will impact clinical care and outcomes will continue to evolve as our understanding grows.

The unique biological behavior of sex chromosomes has implications for cell-free DNA (cfDNA) testing. Our purpose is to predict the (1) false positive/negative rates of cfDNA testing consequent to fetoplacental mosaicism for any sex chromosome aneuploidies (SCA) and (2) positive predictive value (PPV) and negative predictive values of a high-risk and low-risk cfDNA result for any SCA.This is a retrospective analysis of 67 030 chorionic villus sampling karyotypes, including fetoplacental mosaicism cases.Non-mosaic 45, X is associated with cystic hygroma/increased nuchal translucency and fetal anomalies. The false positive rate consequent to confined placental mosaicism is predicted to be 0.05%. The estimated false negative rate is in the range of 0% to 5.7% for all non-mosaic SCAs; it is 70% for mosaic 45, X with normal ultrasound. The predicted PPV on amniocytes is very high for most SCAs (94.4-99.4%). However, the stratified analysis shows that the PPV is much lower for 45, X without ultrasound anomalies compared with 45, X with abnormal scan (51% or 71%, vs 99%, respectively).Mosaicism is a major issue for SCA cfDNA testing, and prenatal confirmation, preferentially with amniocentesis if there are no ultrasound anomalies, remains important in counseling. As PPV varies on the basis of the presence of an ultrasound anomaly, skilled evaluation is critical. © 2017 John WileySons, Ltd.

We studied the clinical utility of chromosomal microarray analysis (CMA) in prenatal diagnosis in a clinical setting in New York City.Our center began offering CMA to pregnant women undergoing invasive diagnostic procedures for an abnormal structural finding on ultrasound, maternal age of 35 years or older, or elevated risk on aneuploidy screening, beginning March 2012. Our first six months experience is reported.Benign familial variants were the most common finding (16/22 fetuses). Variants of uncertain significance were frequent, especially when fathers were not available for testing (4/22 fetuses). Most patients undertook CMA as part of evaluation of an ultrasound anomaly (52%). One patient terminated a pregnancy based on an ultrasound finding in the setting of a benign familial variant on CMA, and a second terminated a pregnancy based on a copy number variant identified on CMA.For CMA to be maximally useful in prenatal diagnosis, parental DNA samples as well as robust datasets to provide predictive phenotypic information are required. The most common reason for undertaking CMA was to evaluate an ultrasound anomaly, and benign familial variants were a common finding. Genetic services are required to provide pre- and post-test genetic counseling and help families interpret results.

Noninvasive assessment of the fetal genome is now possible using next-generation sequencing technologies. The isolation of fetal DNA fragments from maternal circulation in sufficient quantity and sizes, together with proprietary bioinformatics tools, now allows patients the option of noninvasive fetal aneuploidy screening. However, obstetric care providers must become familiar with the advantages and disadvantages of the utilization of this approach as analysis of cell-free fetal DNA moves into clinical practice. Once informed, clinicians can provide efficient pretest and posttest counseling with the goal of avoiding patient harm. It is in the public’s best interest that test results contain key elements and that laboratories adhere to established quality control and proficiency testing standards. The analysis of cell-free fetal DNA in maternal circulation for fetal aneuploidy screening is likely the first of major steps toward the eventual application of whole fetal genome/whole fetal exome sequencing. Genet Med advance online publication 00 Month 2013

Background The World Health Organization's Surgical Safety Checklist has demonstrated significant reduction in surgical morbidity. The American Congress of Obstetricians and Gynecologists District II Safe Motherhood Initiative (SMI) safety bundles include eclampsia and postpartum hemorrhage (PPH) checklists. Objective To determine whether use of the SMI checklists during simulated obstetric emergencies improved completion of critical actions and to elicit feedback to facilitate checklist revision. Study Design During this randomized controlled trial, teams were assigned to use a checklist during one of two emergencies: eclampsia and PPH. Raters scored teams on critical step completion. Feedback was elicited through structured debriefing. Results In total, 30 teams completed 60 scenarios. For eclampsia, trends toward higher completion were noted for blood pressure and airway management. For PPH, trends toward higher completion rates were noted for PPH stage assessment and fundal massage. Feedback resulted in substantial checklist revision. Participants were enthusiastic about using checklists in a clinical emergency. Conclusion Despite trends toward higher rates of completion of critical tasks, teams using checklists did not approach 100% task completion. Teams were interested in the application of checklists and provided feedback necessary to substantially revise the checklists. Intensive implementation planning and training in use of the revised checklists will result in improved patient outcomes.

No previous studies have reported the frequencies of individual chromosomal anomalies in normal-appearing fetuses stratified by maternal age (MA) and gestational age (GA). We therefore sought to (1) characterize the frequency of all fetal karyotype anomalies in sonographically normal appearing fetuses without pretest risk factors, and (2) assess MA and GA impact on the proportion of anomalies targeted by screening and consequent impact on residual risk following a negative result.Fetal karyotypes from samples without prior risk assessment or ultrasound anomalies were analyzed. We calculated, per single-year MA and in two GA intervals, the predicted frequency of each cytogenetic defect.A total of 129 263 karyotypes were analyzed. The risk for significant, cytogenetically visible chromosomal anomalies, at 15 to 20 weeks GA, varies between 1/301 at MA of 18 years, and 1/9 at MA of 48 years. The proportion of clinically significant anomalies not addressed by current screening methods is 47% at MA of 18 years and 5% at MA of 48 years.By determining frequencies for individual karyotype anomalies stratified by MA and GA, in the setting of normal-appearing fetuses, a more personalized risk assessment, including the residual risk after a normal fetal aneuploidy screening result, can be provided. © 2016 John WileySons, Ltd.

Background More than a decade ago, researchers described a survey of Maternal Fetal Medicine fellows that showed that chorionic villus sampling training was limited for Maternal Fetal Medicine fellows in the United States. Prenatal screening and diagnosis have rapidly evolved since then and include the introduction of noninvasive aneuploidy screening that uses cell-free fetal DNA. Yet, chorionic villus sampling remains the only method available for first-trimester genetic diagnosis. Objective This study evaluated the chorionic villus sampling training of Maternal Fetal Medicine fellows with respect to availability, competency standards, and education methods. Study Design In November 2015, an electronic survey was sent to Maternal Fetal Medicine fellows and fellowship directors of accredited Maternal Fetal Medicine fellowship programs in the United States. Results Fifty-eight percent of fellows (179/310) and 46% of program directors (35/76) responded. Ninety-five percent of Maternal Fetal Medicine fellows think that invasive diagnostic testing is essential to their training; 100% of fellows have amniocentesis training; and 65% have chorionic villus sampling training. The median number of chorionic villus sampling procedures that are expected during a fellowship in those who trained was 10. Eighty-eight percent of fellows and 89% of program directors state that chorionic villus sampling training could be better; 89% of fellows and 97% of directors would like access to simulated models. Barriers to training included lack of patients (71%) and lack of proficient attending supervisors (43%). Conclusion Since the last survey, >10 years ago, chorionic villus sampling training has declined further. A decrease in the number of procedures that are performed is the leading barrier to this training.

A 26-year-old healthy gravida 3 woman (with history of two spontaneous pregnancy losses) delivers at term a 2,730-g female infant by normal spontaneous vaginal delivery. The second trimester maternal serum alpha-fetoprotein was elevated, and amniocentesis revealed normal female karyotype. The pregnancy was complicated by oligohydramnios (diagnosed at 20 weeks' gestation) that progressed to anhydramnios by 29 weeks' gestation. Fetal ultrasonography showed bilaterally enlarged echogenic kidneys (Fig. 1) and signs suggestive of a Dandy-Walker variant. Figure 1. Fetal ultrasonography at 20 weeks' gestation showing increased renal echogenicity. At delivery, the Apgar scores are 9 and 9 at 1 and 5 minutes, respectively. The baby develops tachypnea and is transferred to the neonatal intensive care unit on nasal continuous positive airway pressure. Initial physical examination reveals asymmetry of the head and face (right ear pinna “crumpled” and left ear pinna flattened), multiple positional contractures that are predominantly in the upper extremities, and clenched fists. Abdominal ultrasonography shows bilateral echogenic kidneys with small cysts predominantly at the periphery (Fig. 2). Figure 2. Renal ultrasonography showing mildly enlarged, echogenic kidneys with multiple small cysts, predominantly at the periphery. Neurosonography shows bilateral subependymal hemorrhages with small intraventricular hemorrhage and signs suggestive of lissencephaly. Magnetic resonance imaging of the brain confirms these findings. A 4-week-old male neonate presents to the clinic with a history of “noisy breathing since birth.” His mother reports that the noise is unaffected by crying, feeding, agitation, or position. She denies any history of fever, cyanosis, vomiting, choking, diaphoresis, murmur, or seizures. The infant was born at term, weighing 3,600 g, to a primigravida mother via normal vaginal delivery, and there were no perinatal complications. There are no findings of note on family history. The child is gaining weight satisfactorily on formula feedings. On physical examination, the well-nourished infant appears in no apparent distress. His …

Since its introduction four years ago, noninvasive prenatal screening for fetal aneuploidy (NIPS) has been widely adopted as a screening tool for women at a high risk for fetal aneuploidy. As use expands into the general population, questions arise concerning the integration of NIPS into preexisting screening paradigms. This study aims to examine the use of NIPS in current practice among prenatal counselors, predominantly in the United States, in order to inform strategies for the optimal use of both new and existing screening techniques. We electronically surveyed 208 members of the National Society of Genetic Counselors to ascertain how NIPS is currently being used. Genetic counselors were also queried as to the advantages and disadvantages of offering NIPS to all patients regardless of a priori risk. Results indicate substantial variation in practice regarding which patients are offered NIPS and how counselors have incorporated this technology into existing screening routines. The majority of participants report offering NIPS in conjunction with another method of screening for fetal aneuploidy, indicating that NIPS is being used as an addition rather than as a replacement. These screening methods primarily include nuchal translucency (NT) (45.1 %, n = 78) and first trimester serum screening, with or without an NT (19.7 %, n = 34). Furthermore, the majority report that they would be concerned about losing the clinical value of an NT in a complete transition to NIPS (85.4 %, n = 164). Counselors are evenly split on the merits of expanding the use of NIPS to the general population (con: 55.3 %, n = 105; pro: 44.7 %, n = 85). The lack of consensus suggests that updated practice guidelines might benefit counselors. In addition, respondents emphasized the need to better educate patients and providers about the risks, benefits, and limitations of the test.

Cell-free DNA (cfDNA) screening can provide false positive/negative results because the fetal fraction originates primarily from trophoblast. Consequently, invasive diagnostic testing is recommended to confirm a high-risk result. Currently, there is debate about the most appropriate invasive method. We sought to estimate the frequency in which a chorionic villus sampling (CVS) performed after a high-risk cfDNA result would require a follow-up amniocentesis due to placental mosaicism.Analyses of the frequencies of the different types of mosaicism involving cytotrophoblasts, for trisomies 21 (T21), 18 (T18), 13 (T13) and monosomy X (MX) among 52,673 CVS karyotypes obtained from cytotrophoblast, mesenchyme and confirmatory amniocentesis.After a high-risk cfDNA result for T21, 18, 13 and MX, the likelihood of finding CVS mosaicism and need for amniocentesis is, respectively, 2%, 4%, 22% and 59%. When mosaicism is detected by CVS, the likelihood of fetal confirmation by amniocentesis is, respectively, 44%, 14%, 4% and 26%.In cases of high-risk cfDNA results for T21/T18, CVS (combining cytotrophoblast and mesenchyme analysis) can be considered, but with the caveat of 2-4% risk of an inconclusive result requiring further testing. In high-risk results for MX/T13, amniocentesis would appear to be the most appropriate follow-up diagnostic test, especially in the absence of sonographic findings.

This study was undertaken to determine whether the benefits of a single course of antenatal steroid treatment for neonatal respiratory morbidity diminish beyond 7 days.A retrospective chart review was performed of all deliveries less than 34 weeks' gestation where delivery occurred after completing a single course of antenatal steroids (dexamethasone or betamethasone). Maternal and neonatal charts were reviewed, treatment course was confirmed, and neonatal morbidities were collected.Of 197 neonates whose mothers received a full course of antenatal steroids, 98 delivered within 7 days and 99 delivered more than 7 days after the initial dose. The 2 groups were similar in gestational age at delivery (30 weeks 0 days vs 30 weeks 4 days). The groups were also similar in maternal age, race, payor status, type of steroid given, route of delivery, gender, and birth weight. Overall, infants delivering within 7 days had a lower incidence of receiving respiratory support for more than 24 hours (62% vs 81%, P.01), but there were no significant differences between the groups in surfactant treatment (39% vs 47%), use of mechanical ventilation (49% vs 59%), necrotizing enterocolitis (6% vs 4%), intraventricular hemorrhage (15% vs 20%), oxygen dependence at 28 days (24% vs 23%) or at 36 weeks estimated gestational age (13% vs 12%), length of stay (34 days vs 38 days), or mortality (2 vs 0). These results were no different when evaluating only infants delivered before 30 weeks.Among infants exposed to a single course of antenatal steroids, delivering more than 7 days after initiation of treatment was associated with an increased need for short-term respiratory support, but not other measures of neonatal morbidity. These data challenge the concept of diminishing efficacy of steroids after 7 days, and question the need for considering a rescue course.

Noninvasive prenatal screening for fetal aneuploidy analyzes cell-free fetal DNA circulating in the maternal plasma. Because cell-free fetal DNA is mainly of placental trophoblast origin, false-positive and false-negative findings may result from placental mosaicism. The aim of this study was to calculate the potential contribution of placental mosaicism in discordant results of noninvasive prenatal screening.We performed a retrospective audit of 52,673 chorionic villus samples in which cytogenetic analysis of the cytotrophoblast (direct) and villus mesenchyme (culture) was performed, which was followed by confirmatory amniocentesis in chorionic villi mosaic cases. Using cases in which cytogenetic discordance between cytotrophoblast and amniotic fluid samples was identified, we calculated the potential contribution of cell line-specific mosaicism to false-positive and false-negative results of noninvasive prenatal screening.The false-positive rate, secondary to the presence of abnormal cell line with common trisomies in cytotrophoblast and normal amniotic fluid, ranged from 1/1,065 to 1/3,931 at 10% and 100% mosaicism, respectively; the false-negative rate was calculated from cases of true fetal mosaicism, in which a mosaic cell line was absent in cytotrophoblast and present in the fetus; this occurred in 1/107 cases.Despite exciting advances, underlying biologic mechanisms will never allow 100% sensitivity or specificity.

To develop a targeted aneuploidy and microdeletion detection platform for use in the prenatal setting, to assess the integrity of the platform with a robust validation system, and to prospectively determine the performance of the platform under routine clinical conditions.To generate proxies for the various disorders assessed by the assay for analytical validation purposes, cells from ten microdeletion syndromes as well as from common aneuploidies were spiked into cleared amniotic fluid. Genomic DNA was isolated, labeled, and hybridized to microbeads that have been coupled to DNA derived from Bacterial Artificial Chromosome (BAC) from the relevant regions targeted by the array. Beads were read using a flow cytometric multiplex bead array detection system. In the prospective part of the study, 104 amniotic fluid samples were collected and analyzed.All microdeletion syndromes and aneuploidies were validated in a blinded fashion. In the prospective study, the total number of readable samples was 101 of 104 (97%). All sample results were confirmed independently.The bead array approach is a rapid and reliable test for detecting aneuploidies and microdeletions. This assay has the potential to provide the benefit of expanded molecular cytogenetic testing to pregnant women undergoing invasive prenatal diagnosis. This approach may be especially useful in parts of the world where cytogenetic personnel and facilities may be limited.

ALAN PEACEMAN, KOMAL BAJAJ, PRAVEEN KUMAR, WILLIAM GROBMAN, Northwestern University, Obstetrics and Gynecology, Chicago, Illinois, Northwestern University, Neonatology, Chicago, Illinois OBJECTIVE: To determine whether the benefits of a single course of antenatal steroid (AS) treatment for neonatal respiratory morbidity diminish beyond seven days from initiating treatment. STUDY DESIGN: A retrospective chart review was performed of deliveries !34 wks gestation where delivery occurred after completing a single course of AS (dexamethasone or betamethasone). Maternal and neonatal charts were reviewed, treatment course was confirmed, and neonatal morbidities were collected. A review of 190 charts provided more than 80% power for demonstrating a 50% reduction in the need for respiratory support (ventilation, CPAP) if delivery occurred within 7 days of treatment. RESULTS: Of 197 infants whose mothers received a full course of AS, 98 delivered within 7 days, and 99 delivered more than 7 days after the initial dose. The two groups were similar in gestational age at delivery (30 wk 0 d vs 30 w 4 d). The groups were also similar in maternal age, race, payor status, type of steroid given, route of delivery, gender and birth weight. Overall, infants delivering within 7d had a lower incidence of receiving respiratory support for >24 hours (62% vs 81%, P ! .01), but there were no significant differences between the groups in need for surfactant (39% vs 47%), mechanical ventilation (49% vs 59%), NEC (6% vs 4%), IVH (15% vs 20%), oxygen dependence at 28d (24% vs 23%) or at 36 weeks EGA (13% vs 12%), length of stay (34 d vs 38 d) or mortality (2 vs 0). These results were no different when evaluating only infants delivered before 30 weeks. Further, for those infants who delivered greater than 7 days after AS, there was no association between increasing time intervals after AS and neonatal morbidity. The power to observe a 50% reduction in surfactant use and mechanical ventilation was 94% and 99%, respectively. CONCLUSION: Among infants exposed to a single course of AS, delivering more than 7 days after initiation of treatment did not appear to be a disadvantage. These data challenge the concept of diminishing efficacy of steroids after 7 days, and question the need for considering a rescue course. 383 THE ASSOCIATION OF FETAL GENOTYPE FOR THE MTHFR GENE AND PRETERM PREMATURE RUPTURE OF MEMBRANES AMIE HOLLARD, RHONDA FLORA, PAMELA RUMNEY, JUDITH CHUNG, MICHAEL NAGEOTTE, University of California, Irvine, Maternal Fetal Medicine, Lincoln, Nebraska, University of California, Irvine, Maternal Fetal Medicine, Orange, California, Long Beach Memorial Medical Center, Maternal Fetal Medicine, Long Beach, California OBJECTIVE: Methylenetetrahydrofolate reductase (MTHFR) plays a role in folate/homocysteine metabolism. The common polymorphisms in the MTHFR gene are C677T and A1298C, the presence of which has been associated with adverse pregnancy outcome. Given that folate and homocysteine are involved in collagen synthesis, we hypothesize the presence of MTHFR mutations in the fetus may increase the risk for preterm premature rupture of membranes (PPROM). STUDY DESIGN: A nested case control pilot study of 2 groups. Group I (n = 18): patients with PPROM delivering between 24 and 35 weeks. Group II (n = 25): patients without PPROM delivering between 24 and 42 weeks. Patients with diabetes, hypertension, preeclampsia, or multiple gestations were excluded. At delivery, a placental biopsy was obtained. The fetal RNA was extracted and multiplex PCR/ RFLP was performed for the presence of C677T and A1298C alleles. Univariate analysis, Chi-Square, Fisher’s Exact, & unpaired t tests were used as appropriate. Significance was set at P ! .05. RESULTS: The allele frequencies for C677T & A1298C are 28% & 44%, and 48% & 44% for Group I and Group II respectively . In Group II, there was an equal distribution of of the alleles between patients delivering at ! or >34 weeks gestation. In the Caucasion patients, 100% of Group I patients and only 60% of Group II patients had one or more mutations present. However, in the combined population there was no overall increased risk of PPROM if the fetus had one or more C677T P = .31) or A1298C mutations (P = .98). CONCLUSION: In our study, it appears that the presence of fetal C677T and A1298C polymorphisms are not uniquely associated with PPROM, but it may influence PPROM in certain ethnic groups. The effect of maternal genotype was not evaluated in this study, there may be additive effect when both genotypes are considered concurrently. An unexpected finding in this study was the large number of control patients with either mutation. A larger sample size is needed to discern if a true association is found between the presence of MTHFR mutations and PPROM.