Metabolomic prediction of severe maternal and newborn complications in preeclampsia.

INTRODUCTION: Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical implications of crown-rump length discordance at 11 to 14 weeks in dichorionic twins.

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.

First-Trimester Cell-Free DNA Fetal Fraction and Birth Weight in Twin Pregnancies.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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. KEY POINTS: · 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..

Fetal effects of mild maternal COVID-19 infection: metabolomic profiling of cord blood.

INTRODUCTION: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. OBJECTIVES: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. METHODS: 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. RESULTS: 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% CI) = 0.841 (0.725-0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response. CONCLUSION: We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Fetal and Maternal Monitoring.

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.

Does Maternal SARS-CoV-2 Infection or SARS-CoV-2 Vaccination Trigger an Inflammatory Response in the Fetus? A Prospective Cohort Study.

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.

The Value of Rectal Cultures in Treatment of Sepsis Following Post-Transrectal Ultrasound-Guided Prostate Biopsy.

BACKGROUND: Cases with sepsis after transrectal ultrasound-guided prostate biopsy (TRUSPB) were documented, with special focus on cultures and susceptibility of isolates. We also evaluated the contribution of concomitant rectal cultures to the treatment of selective cases. MATERIALS AND METHODS: Patients with sepsis after TRUSPB were followed prospectively. Manifestations and risk factors for antimicrobial resistance were documented. Results of urine and blood cultures and antimicrobial susceptibility were recorded for all participating patients. In 40 patients, rectal swab cultures were obtained concomitantly. RESULTS: Ninety-five patients were consecutively studied. Sepsis symptoms started showing up within 48 h after biopsy in 93% of patients. At least one of the cultures was positive in 72 patients. E. coli grew in 70 cases; isolates were highly resistant: 67% displayed multidrug-resistance. Rectal cultures grew E. coli in 38 cases. In patients with positive E. coli in rectum and in at least one additional culture (blood and/or urine), the antibiogram was identical in all cases but one. Eight cases had negative cultures. CONCLUSION: The prevalence of antimicrobial resistance among E. coli isolates from patients with TRUSPB sepsis was alarming. Susceptibilities of rectal E. coli isolates used for deescalation of initial empiric treatment in culture-negative TRUSPB sepsis can contribute to the reduction of broad-spectrum antibiotics exposure.

Surviving Postpartum Group A Streptococcus Sepsis Complicated by Multiorgan System Failure: A Complex Case Presentation.

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.

Neurocutaneous Disorders in Pregnancy.

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.

Association of Metabolomic Biomarkers with Sleeve Gastrectomy Weight Loss Outcomes.

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.

Acute liver failure in pregnancy due to autoimmune hepatitis.

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.

The association of HBB-related significant hemoglobinopathies and low fetal fraction on noninvasive prenatal screening for fetal aneuploidy.

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 (ß - 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 screeningHigh 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 fractionReduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate.

Medical genetics and genomics training in obstetrics and gynecology residencies: are we ready for the future?

OBJECTIVE: The primary objective of this study is to evaluate the availability and duration of formal medical genetics and genomics (MGG) education during obstetrics and gynecology (OB/GYN) residency training in the United States compared to other noncore OB/GYN rotations. METHODS: We performed a review of rotation schedules published in all American Council for Graduate Medical Education (ACGME)-accredited OB/GYN residency programs' websites during the month of December 2016. Information regarding availability and duration of MGG rotation and other noncore OB/GYN rotations (ultrasound, breast health, and family planning) were collected. RESULTS: Among 256 ACGME-accredited OB/GYN residency programs, rotation schedule was available for 238 (93%). Only 34 programs (14.3%) had some form of MGG rotations. In the GLM, when compared to other noncore OB/GYN rotations, the mean duration of MGG rotation was significantly less than ultrasound (0.07 versus 0.57 months, p < .05) and family planning (0.07 versus 0.42 months, p < .05). The number of residents was the only variable significantly correlated with the availability of an MGG rotation (OR 1.07, 95%CI 1.02-1.13). CONCLUSIONS: Despite the growing importance of MGG in day-to-day OB/GYN practice, only a limited number of ACGME-accredited OB/GYN residency programs offer an MGG rotation. When compared to other noncore OB/GYN rotations, such as, ultrasound and family planning, any MGG rotation was significantly shorter. With clear evidence that MGG will continue to radically change practice of OB/GYN in the future, it is imperative that steps need to be taken to address this deficiency in training.

Intrahepatic Cholestasis of Pregnancy Leading to Severe Vitamin K Deficiency and Coagulopathy.

Intrahepatic cholestasis of pregnancy is seldom associated with significant vitamin K deficiency. We report a case of a 16-year-old primigravid patient at 24 weeks and 3 days of gestation who presented with pruritus, hematuria, and preterm labor. Laboratory work-up showed severe coagulopathy with Prothrombin Time (PT) of 117.8 seconds, International Normalized Ratio (INR) of 10.34, and elevated transaminases suggestive of intrahepatic cholestasis of pregnancy. Her serum vitamin K level was undetectable (<0.1 nMol/L). Initial therapy consisted of intramuscular replacement of vitamin K and administration of fresh frozen plasma. Her hematuria and preterm labor resolved and she was discharged. She presented in active labor and delivered at 27 weeks and 1 day. Her bile acids (93 µ/L) and INR (2.32) had worsened. She delivered a male infant, 1150 grams with Apgar scores 7 and 9. The newborn received 0.5 mg of intramuscular vitamin K shortly after delivery but went on to develop bilateral grade III intraventricular hemorrhages by day 5. Intrahepatic cholestasis in pregnancy and nutrition issues were identified as the main risk factors for the severe coagulopathy of this patient. This case underlines the importance of evaluation of possible severe coagulopathy in patients with intrahepatic cholestasis of pregnancy in order to avoid serious maternal or fetal adverse outcomes.