Background/Objectives: Metabolomics has emerged as a tool to gain insight into the body’s biological responses to therapeutic interventions. Bariatric surgery remains the most effective treatment for severe obesity and associated comorbidities, leading to significant weight and metabolic improvements. Using a multi-platform, multi-compartment metabolomics approach, this study systematically characterizes longitudinal changes in fecal and serum metabolomes of 45 patients following sleeve gastrectomy (SG). Participants were stratified by weight loss outcomes to identify metabolic signatures associated with differential responses, which may serve as predictors of weight loss and provide mechanistic insights in developing targeted therapeutic strategies. Methods: Metabolomic and lipidomic responses to SG were analyzed using multivariable linear mixed-effects models based on data collected pre-operatively and at 3 and 12 months post-operatively. Results: The percentage total weight loss for the highest versus lowest weight loss tertiles (T3 vs. T1) at twelve months was 35.81 + 5.4% and 19.49 + 2.62%, p < 0.001, respectively. Substantial alterations in fecal metabolites and lipid species were observed among T3 after twelve months, including aspartate, tyrosine, carnitine, glycine, PC.ae.C36.4, PC.aa.C38.0, PC.ae.C44.4, PC.ae.C40.2, and PC.aa.C40:5. Specifically, changes in serum lipid species including SM.OH.C22:1, PC.ae.C32:1, PC.aa.C34:4, PC.aa.C36:6, PC.ae.C34:3, PC.ae.C34:1, and PC.ae.C32:2, support serum lipidomics as a minimally invasive marker of gut remodeling and adaptation following SG. Sex-stratified analysis revealed unique fecal and serum metabolic changes, highlighting the significance of personalized metabolic monitoring and obesity treatment. Conclusions: Our findings identify metabolic alterations associated with response variability following SG and highlight the potential utility of machine learning to predict weight-loss trajectories and inform personalized interventions.

OBJECTIVE:The aim of this study was to evaluate the incidence of congenital anomalies in dichorionic-diamniotic twins conceived with in vitro fertilization (IVF) vs. unassisted conception pregnancies in a large geographically diverse population. DESIGN:This is a secondary analysis of data from a retrospective cohort study of twin pregnancies seen at 17 centers between December, 2011-February, 2020. SUBJECTS:This study included dichorionic-diamniotic twins conceived unassisted, or by in vitro fertilization. EXPOSURE:The exposure group is dichorionic-diamniotic twins conceived with IVF. MAIN OUTCOME MEASURE:The primary outcome was presence of a congenital anomaly. Neonates with an abnormal newborn examination were evaluated for having a major or minor congenital anomaly and the major anomalies were further classified by organ system (cardiac, renal/genitourinary, gastrointestinal, and musculoskeletal). RESULTS:Of the 968 dichorionic-diamniotic twin pregnancies included, 521 (53.8%) were conceived with IVF and 447 (46.2%) were conceived unassisted. Congenital anomalies were found in 70 pregnancies (7.23%). Of those, 37 were found in pregnancies conceived by IVF (52.9%) vs. 33 unassisted conception pregnancies (47.1). There were no significant differences between IVF and unassisted conception pregnancies for major anomalies or minor anomalies. CONCLUSION:In this large cohort of twin pregnancies, there is no significant difference in the incidence of anomalies for dichorionic-diamniotic twin pregnancies conceived by IVF vs. unassisted conception pregnancies.

Background: Crown-rump length discordance, defined as >= 10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance.Objective: This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance.Study Design; This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders.Results; Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance.Conclusion: Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.

Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management. Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the pathogenesis of such complications. Serum samples from 76 cases of PreE (36 early-onset and 40 late-onset), and 40 unaffected controls were collected. Direct Injection Liquid Chromatography–Mass Spectrometry combined with Nuclear Magnetic Resonance (NMR) spectroscopy was performed. Logistic regression analysis was used to generate models for prediction of adverse maternal and neonatal outcomes in patients with PreE. Metabolite set enrichment analysis (MSEA) was used to identify the most dysregulated metabolites and pathways in PreE. Forty-three metabolites were significantly altered (p < 0.05) in PreE cases with maternal complications and 162 metabolites were altered in PreE cases with newborn adverse outcomes. The top metabolite prediction model achieved an area under the receiver operating characteristic curve (AUC) = 0.806 (0.660–0.952) for predicting adverse maternal outcomes in early-onset PreE, while the AUC for late-onset PreE was 0.843 (0.712–0.974). For the prediction of adverse newborn outcomes, regression models achieved an AUC = 0.828 (0.674–0.982) in early-onset PreE and 0.911 (0.828–0.994) in late-onset PreE. Profound alterations of lipid metabolism were associated with adverse outcomes. Prenatal metabolomic markers achieved robust prediction, superior to conventional markers for the prediction of adverse maternal and newborn outcomes in patients with PreE. We report for the first-time the prediction and metabolomic basis of adverse maternal and newborn outcomes in patients with PreE.

The relationship between fetal fraction and birth weight in twin gestations is poorly understood. This study aimed to investigate the relationship between first-trimester cell-free DNA (cfDNA) fetal fraction and birth weight <10th percentile in twin gestations.This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from December 2011 to February 2022, excluding those with positive screen results for chromosomal aneuploidy. cfDNA testing was performed by a single laboratory using massively parallel sequencing. Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared with those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression.A total of 1,041 twin pregnancies were included. Chronic hypertension, elevated body mass index, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [interquartile range (IQR)] fetal fraction: 12.2% [9.8, 14.8] vs. those with normal birth weight (≥10th percentile) in both twins (median [IQR] fetal fraction: 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p = 0.45) or both (p = 0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p = 0.44) or both (p = 0.74) twins. The results were unchanged after adjustment for potential confounders.In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birth weight <10th percentile, suggesting that first-trimester fetal fraction may not predict impaired fetal growth in twin gestations. · No association between fetal fraction and small for gestational age birth weight in twins.. · Results suggest that fetal fraction does not predict birth weight in twin gestations.. · These results differ from the relationship between fetal fraction and birth weight in singletons..

Postpartum group A streptococcal (GAS) sepsis is a rare obstetric complication with severe clinical implications and high morbidity and mortality, presenting diagnostic and management challenges. This report analyzes a complex case of postpartum GAS sepsis, highlighting the importance of understanding the pathophysiology and clinical trajectories of this often fatal pathogen. A comprehensive analysis was conducted on a patient with postpartum GAS sepsis. Literature review and case comparisons informed the study's context. Medical history, clinical presentation, diagnostic procedures, interventions, and outcomes were reviewed and documented. The patient presented on postpartum day 5 with abdominal pain and vaginal bleeding. Her condition rapidly deteriorated, requiring aggressive interventions and systemic support. Blood cultures confirmed GAS bacteremia. She developed toxic shock syndrome, cardiomyopathy with acute cardiac failure, and seizures secondary to subdural empyema. Multidisciplinary care facilitated eventual clinical recovery. Obstacles in achieving treatment balance were evident, underscoring the systemic nature of GAS infection and the significance of interdisciplinary collaboration. This case underscores the complex pathophysiology of postpartum GAS sepsis and the importance of prompt treatment initiation, aggressive intervention, and a multidisciplinary approach to management. The study contributes to the understanding of disease progression and clinical management in severe peripartum infections, reaffirming the need for further research to improve outcomes.

Importance: Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population.Objective: This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient.Evidence Acquisition: A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms "pregnancy," "Sturge -Weber," "Neurofibromatosis Type 1," "neurofibromatosis type 2," "von Hippel Lindau," "Tuberous Sclerosis," "neurocutaneous disorder," "treatment," "congenital malformations," "neurodevelopmental defects," "miscarriage," "breastfeeding," "autoimmune," "pathophysiology," and "management." References of included articles were searched to identify any articles that may have been missed after the above method was used.Results: Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder.Conclusion and Relevance: Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients.Target Audience: Obstetricians and gynecologists, family physician.Learning objectives: After completing this activity, the learner will be better able to identify the most common neurocutaneous disorders seen in reproductive women and their implications in pregnancy; propose recommendations for genetic evaluation, diagnosis, management, and a differential diagnosis; describe treatment options including labor and delivery management, emphasizing multidisciplinary approach; and discuss potential maternal and fetal adverse outcomes related to neurocutaneous disorders.

This prospective observational study aimed to evaluate the association of metabolomic alterations with weight loss outcomes following sleeve gastrectomy (SG). We evaluated the metabolomic profile of serum and feces prior to SG and three months post-SG, along with weight loss outcomes in 45 adults with obesity. The percent total weight loss for the highest versus the lowest weight loss tertiles (T3 vs. T1) was 17.0 ± 1.3% and 11.1 ± 0.8%, p < 0.001. Serum metabolite alterations specific to T3 at three months included a decrease in methionine sulfoxide concentration as well as alterations to tryptophan and methionine metabolism (p < 0.03). Fecal metabolite changes specific to T3 included a decrease in taurine concentration and perturbations to arachidonic acid metabolism, and taurine and hypotaurine metabolism (p < 0.002). Preoperative metabolites were found to be highly predictive of weight loss outcomes in machine learning algorithms, with an average area under the curve of 94.6% for serum and 93.4% for feces. This comprehensive metabolomics analysis of weight loss outcome differences post-SG highlights specific metabolic alterations as well as machine learning algorithms predictive of weight loss. These findings could contribute to the development of novel therapeutic targets to enhance weight loss outcomes after SG.

The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure. Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95

Fetal monitoring in the intrapartum and peripartum periods is important for the well-being of both baby and mother. Electronic fetal monitoring was first designed over 50 years ago in an attempt to improve perinatal outcomes. Its purpose is to assess fetal oxygenation and acid-base status during the antepartum course when indicated and during labor. Maternal assessment begins early in gestation with blood pressure monitoring and urine protein excretion to diagnose potential complications, such as severe hypertension and preeclampsia/eclampsia.

Preeclampsia (PreE) is a complex and heterogenous disorder. We combined metabolomics and lipidomics analyses to investigate PreE pathogenesis and thus identify potential therapeutic targets. This is a prospective study in which serum was collected in 76 cases of PreE diagnosed based on ACOG criteria and 39 controls. Direct Injection Liquid Chromatography-Mass Spectrometry and Nuclear Magnetic Resonance spectroscopy were used to perform metabolomic and lipidomic analysis. Metabolite set enrichment analysis was used to identify which pathways were directly related to the pathogenesis of PreE. Variable Importance in Projection (VIP) analysis was used to determine which metabolites were most significantly dysregulated in PreE as compared to controls, with the metabolite VIP rank directly correlated with PreE. The mean (SD) gestational age (weeks) in PreE vs. controls at birth was 33.257 (4.255) vs. 36.025 (3.296), gestational age (weeks) at sample collection was 33.25 (4.22) vs. 36.20 (3.27), and birthweight (grams) was 2378.2 (975.432) vs. 3364.9 (320.845). All comparisons were significant with p< 0.0001 for all. A total of 521 lipids and 93 endogenous metabolites were evaluated. The most significantly altered metabolites include: Isobutyric acid (a short chain fatty acid associated with gut microbiome dysbiosis and linked to hypertension), Probetaine (which reduces homocysteine levels and endothelial dysfunction), and Taurochenodeoxycholic acid (a bile acid involved in lipid metabolism). The significant metabolites and VIP scores are shown (Figure 1). Metabolite set enrichment analysis (Figure 2) revealed significant perturbation in lipid metabolism. Catecholamine metabolism, critical to neurohormonal regulation of blood pressure was also dysregulated. The major dysregulated metabolic pathway in PreE appears to be that of lipid metabolism. This is consistent with increased risk of PreE in obese and diabetic populations. Further, more detailed, and global analysis of lipid dysfunction in PreE is clearly warranted.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

(Abstracted from Am J Obstet Gynecol 2023;229:435.e1–435.e7 Cell-free DNA (cfDNA) screening is an effective way to identify trisomy 21 in singleton pregnancies and has been shown to have both a high detection rate and a low false-positive rate. For twin pregnancies, however, there are challenges relating to fetal fraction and the ability to obtain and distinguish fetal DNA.

OBJECTIVES:SARS-CoV-2 infection triggers a significant maternal inflammatory response. There is a dearth of information regarding whether maternal SARS-CoV-2 infection at admission for delivery or SARS-CoV-2 vaccination triggers an inflammatory response in the fetus. This study aims at evaluating fetal inflammatory response to maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination compared to control group. Design, Participants, Setting, and Methods: A prospective cohort study was performed with a total of 61 pregnant women who presented for delivery at a single medical center (William Beaumont Hospital, Royal Oak, MI). All mothers were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) on admission to labor and delivery unit. Three groups were evaluated: 22 pregnant with a positive SARS-CoV-2 test (case group), 23 pregnant women with a negative SARS-CoV-2 test (control group), and 16 pregnant women who had recent SAR-CoV-2 vaccination and a negative SARS-CoV-2 test (vaccine group). At delivery, cord blood was collected to determine the levels of IL-6, C-reactive protein (CRP), and SARS-CoV-2 nucleocapsid IgG and IgM antibodies. In all cases, the newborn had a negative PCR test or showed no clinical findings consistent with SARS-CoV-2 infection.RESULTS:Mean (SD) IL-6 level was not significantly different for the three groups: case group 9.00 ± 3.340 pg/mL, control group 5.19 ± 0.759 pg/mL, and vaccine group 7.11 ± 2.468 pg/mL (p value 0.855). Pairwise comparison also revealed no statistical difference for IL-6 concentrations with p values for case versus control, case versus vaccine, and control versus vaccine = 0.57, 0.91, and 0.74, respectively. Similarly, there was no statistically significant difference in the frequency of elevated IL-6 (>11 pg/mL) between groups (p value 0.89). CRP levels across the three groups were not statistically significant different (p value 0.634). Pairwise comparison of CRP levels among the different groups was also not statistically different. SARS-CoV-2 nucleocapsid IgG was positive in 12 out of 22 cord blood samples in the case group, 2 out of 23 of the control group (indicating old resolved maternal infection), and 0 out of 16 of the vaccine group. SARS-CoV-2 nucleocapsid IgM was negative in all cord blood samples of the case group, control group, and vaccine group.LIMITATIONS:A total number of 61 mothers enrolled in the study which represents a relatively small number of patients. Most patients with positive SARS-CoV-2 PCR were mainly asymptomatic. In addition, our vaccine group received the mRNA-based vaccines (mRNA1273 and BNT162b2). We did not study fetal response to other SARS-CoV-2 vaccines.CONCLUSION:In our prospective cohort, neither IL-6 nor CRP indicated increased inflammation in the cord blood of newborns of SARS-CoV-2-infected or vaccinated mothers.

Autoimmune hepatitis is a diagnosis rarely made in pregnancy, especially in the setting of acute liver failure. If unrecognised and untreated, it can result in significant fetal and maternal morbidity and mortality. We report a case of acute liver failure in a patient presenting at 17 weeks' gestation. She was diagnosed with autoimmune hepatitis via transjugular liver biopsy. Prednisone therapy was initiated, resulting in disease remission for the remainder of her pregnancy. Induction of labour at 37 weeks' gestation resulted in delivery of a healthy small for gestational age neonate. Prompt diagnosis of a non-obstetrical aetiology for acute liver failure in pregnancy is critical to provide the appropriate therapy to achieve an optimal pregnancy outcome.

Angular pregnancy is an eccentric intrauterine pregnancy located in the superior-lateral angle of the endometrial cavity. The risk associated with angular pregnancy remains controversial, as some reported cases may have been misdiagnosed interstitial ectopic pregnancies. Our goal was to investigate the pregnancy outcomes for angular pregnancy diagnosed by first trimester ultrasound. This was a retrospective matched case-control study comparing pregnancy outcomes of women with angular pregnancy (n=27) and unaffected controls (n=108), both diagnosed by early first trimester ultrasound (≤10 weeks). Four controls were matched to each case according to the history of miscarriage, maternal age, and the gestational age at ultrasound examination. The sonographic diagnosis of angular pregnancy was made by: 1) eccentric location of the gestational sac in the superior-lateral angle of the endometrial cavity; and 2) surrounding endometrium and myometrium along their superior and lateral borders. Interstitial ectopic pregnancies and congenital uterine anomalies were excluded. All women with angular pregnancy were expectantly managed. Nine of the 27 angular pregnancies (33.3%) were initially thought to be interstitial based on outside ultrasound diagnosis, but our follow-up ultrasounds were found to be angular. There were no differences between cases vs. controls in mean maternal age, mean gestational age at ultrasound, history of miscarriage, and vaginal bleeding. There were no cases of uterine rupture in the angular pregnancy cohort. The number of pregnancies ending in miscarriage in women with and without angular pregnancy was 12 (44.4%) and 18 (16.7%), respectively (P=0.002). The odds ratio (OR) of miscarriage in angular pregnancy was 4.0 (95% confidence interval [CI] 1.6-10.0). The OR adjusted for maternal and medical comorbidities was 4.9 (95% CI 1.8-13.3). In women with angular pregnancy diagnosed by a first trimester ultrasound, there is an increased rate of miscarriage. Otherwise, overall pregnancy outcomes are favorable.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Objectives: HBB-related significant hemoglobinopathies have been anecdotally associated with low fetal fraction on noninvasive prenatal screening (NIPS). We sought to compare the difference in fetal fraction using NIPS in women with HBB-related significant hemoglobinopathies (HSH) and women with normal hemoglobin. Study design: This is a retrospective case-control study. Cases were women with a diagnosis of HSH using NIPS from a commercial laboratory. The comparison group was women with hemoglobin AA from a tertiary care center database. We tested for differences in median fetal fraction using quantile regression analysis, adjusting for maternal body weight and gestational age. Results: This study includes 35 women with clinically significant HSH and a comparison group of 636 women with hemoglobin AA. Adjusting for gestational age and body weight, the median fetal fraction was 4.1 point lower in the HSH than in the comparison group (beta - 4.1; 95% -5.7 to -2.5, p < .05). The rate of no-calls due to low fetal fraction was significantly higher in the clinically significant HSH group than in the comparison group [HSH: n = 9/35, 25.7% versus comparison: n = 32/636, 5.0% (p < .001)]. Conclusion: Women with HSH were more likely to have a lower fetal fraction and ultimately a five-fold higher no-call rate. What's already known about this topic? Low fetal fraction is one of the most common causes of no-call result in noninvasive prenatal screening High maternal weight, early gestational age and fetal aneuploidies are associated with low fetal fraction What does this study add? HBB-related significant hemoglobinopathies are associated with low fetal fraction Reduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate

RESULTS: We identified 17 observational studies (70 women), which evaluated outcomes in pregnancies complicated by aplastic anemia. Overall, in 36 out of 70 (51.4%) cases at least one significant maternal complication was reported (Table 1). The most common maternal complications included antepartum and/or postpartum hemorrhage, which occurred in 11 (15.7%) cases, and postpartum relapse which developed in 13 (18.6%) cases. Three (4.3%) women experienced intracranial hemorrhage or thrombosis, while four (5.7%) women died within 1 year of pregnancy. Across these reported cases, pancytopenia was observed with a mean starting hemoglobin of 6.9g/dL, white blood cell count of 2.7x109/L and platelet count of 31x109/L. In 14 of 31 (45.2%) cases preterm birth ensued, with 20% of the women delivering prior to 34 weeks. Three cases of intrauterine fetal demise were also reported.

Chronic maternal comorbidities including sickle cell disease (SCD), chronic hypertension (CHTN) and pregestational diabetes may cause vasculopathies that lead to tissue hypoxia and subsequently an increase in maternal cell necrosis which create a dilutional effect in fetal fraction on non-invasive prenatal screening (NIPS). We sought to evaluate the impact of chronic maternal comorbidities on the NIPS no-call rate. We hypothesized that chronic maternal comorbidities would increase the no-call rate for NIPS. This was a retrospective nested cohort study. A cohort was assembled of women with singleton pregnancy who obtained NIPS from June 2016 to August 2017 in a tertiary care center and a cohort of women with SCD and NIPS from Natera, Inc. laboratory. The primary outcome was no-call rate due to low fetal fraction. Women were classified based on the trimester. And differences in fetal fraction percent across trimesters were compared using the Kruskal- Wallis test. Fisher's exact test was used to compare no-call rates for SCD, chronic hypertension and pregestational diabetes with Those of women who didn't have these comorbidities. The potential association between no-call rate and maternal comorbidities, gestational age and weight was evaluated using logistic regression. The cohort consisted of 521 women. The median fetal fraction for first, second and third trimester were 6.8%, 8.9% and 9.2% (p<0.05). No-call rates in the first, second and third trimester were 10.6%, 3.9% and 1.8% (p<0.05). Overall no-call rate is significantly higher among women with comorbidities (table 2). In the regression model, SCD and CHTN were significant predictors of a no-call report in the first trimester (p<0.05), while SCD and weight were significant predictors of a no-call report in the second trimester (p<0.05). No predictors were significant in the third trimester. CHTN and SCD appear to be significantly associated with an increase in the no-call rate during the first trimester. Providers need to consider chronic maternal comorbidities during counseling for aneuploidy screening.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

INTRODUCTION: Multifetal pregnancies are associated with poor outcomes. The goal of this study was to compare perinatal outcomes, in twin pregnancies complicated by short cervix managed with cerclage placement, to those managed expectantly. METHODS: We performed a retrospective cohort study of twin pregnancies complicated with short cervix (defined as <2.5cm) diagnosed before 24 weeks of gestation, at our institution between 2010 and 2015. Neonatal and pregnancy outcomes of patients who had cerclage placed were compared to those who did not. Independent t-test and Pearson’s chi-square test was used for the data analysis. RESULTS: 835 twin pregnancies were reviewed. 33 patients (3.9%) had short cervix before 24 weeks of gestation. Fourteen (42.4%) of these patients had a cerclage placed. Of those whose pregnancies reached viability (75%), 15 (62.5%) did not have a cerclage in place, while nine (37.5%) did. Mean gestational age at delivery was significantly earlier in those who had a cerclage placed as compared to those who did not (27 versus 32 weeks; p = 0.03). Admission to the neonatal intensive care unit (NICU) was significantly higher in those who had a cerclage placed (9 vs. 12; p= 0.03). Birth weight was significantly lower, with a mean of 1010 grams in the cerclage group as compared to 1748 grams for those without a cerclage (p = 0.01). CONCLUSION: Consistent with other meta-analyses, our study demonstrates that cerclage placement in twin pregnancies complicated by short cervix is associated with poorer outcomes. Cerclage placement should be used with caution, after performing a detailed risk-benefit analysis.