Use of non-invasive cardiac monitoring to guide discontinuation of postpartum magnesium sulfate in individuals with preeclampsia with severe features.

OBJECTIVES: To determine the utility of using total peripheral systemic vascular resistance assessed using non-invasive cardiac monitor for individualizing the duration of postpartum magnesium sulfate in individuals with preeclampsia with severe features. STUDY DESIGN: Single center pilot randomized controlled trial in which singleton pregnant individuals with preeclampsia with severe features were randomized to 24 h of postpartum magnesium sulfate per standard of care (control group) or individualized duration of postpartum magnesium sulfate based on reduction in post-delivery systemic vascular resistance (intervention group). Systemic vascular resistance was assessed with non-invasive cardiac monitoring using the Cheetah® system. A 30 % reduction (maintained for 1 h) from baseline post-delivery systemic vascular resistance was used as a cutoff for discontinuation of postpartum magnesium sulfate. Our primary outcome was duration of postpartum magnesium sulfate use in hours. Secondary outcomes included a composite of maternal morbidities associated with preeclampsia. RESULTS: Of 53 individuals enrolled, we excluded 6 from this analysis due to insufficient data to assess primary outcome. Baseline characteristics of the control (n = 26) and intervention (n = 21) groups were similar. Six (28.6 %) individuals in intervention group met the systemic vascular resistance criteria and had their postpartum magnesium sulfate discontinued before 24 h. The duration of postpartum magnesium sulfate infusion was shorter in the intervention group (21.6 ± 4.7 h; range: 7-24 h) compared with control group (24 h, p = 0.02). There was no difference in secondary outcomes between the two groups. There was no difference in adverse outcomes in individuals that had magnesium discontinued earlier than 24 h. CONCLUSION: Non-invasive monitoring of systemic vascular resistance can be a valuable tool to individualize the duration of postpartum magnesium sulfate for preeclampsia with severe features. These findings should be conformed in a larger trial.

Placenta Accreta Spectrum and Postpartum Hemorrhage.

Placenta accreta spectrum is a group of disorders involving abnormal trophoblastic invasion to the deep layers of endometrium and myometrium. Placenta accrete spectrum is one of the major causes of severe maternal morbidity, with increasing incidence in the past decade mainly secondary to an increase in cesarean deliveries. Severity varies depending on the depth of invasion, with the most severe form, known as percreta, invading uterine serosa or surrounding pelvic organs. Diagnosis is usually achieved by ultrasound, and MRI is sometimes used to assess invasion. Management usually involves a hysterectomy at the time of delivery. Other strategies include delayed hysterectomy or expectant management.

Viscoelastic Testing in an Obstetric Population at High Risk of Hemorrhage.

INTRODUCTION: Rotational thromboelastometry (ROTEM) is a point-of-care viscoelastic test used in trauma for goal-directed transfusion. However, there are limited data on baseline ROTEM parameters in the U.S. obstetric population. Obtaining baseline parameters is a first step in implementing a goal-directed massive transfusion protocol in obstetric hemorrhage. OBJECTIVE: Our study aimed to establish pre- and postdelivery baseline parameters in a high-risk obstetric population and determine their association with postpartum hemorrhage (PPH). STUDY DESIGN: Prospective observational study of patients ≥34 weeks' gestation, at high risk of PPH, admitted for delivery. INTEM, EXTEM, FIBTEM, and APTEM assays were performed at the time of admission to labor and delivery and then 2 hours after delivery. Primary outcome was pre- and postdelivery ROTEM parameters among women without PPH. A sample size of 60 women was needed for >90% power to detect at least 50% correlation between pre- and postdelivery assuming a loss of 10% of participants to follow-up. RESULTS: Of 60 women in the study, 10 (17%) had PPH. Baseline characteristics were not different between those with or without PPH. Pre- and postdelivery ROTEM parameters were not significantly different except for APTEM. None of the patients who had PPH, compared with 4 (10%) of those who did not, had shortened clotting time and higher maximum clot firmness in postdelivery APTEM compared with EXTEM, a pattern suggestive of hyperfibrinolysis (p = 0.4). CONCLUSIONS: In this study, we describe baseline ROTEM parameters in women at high risk of PPH. The majority of patients did not have a ROTEM pattern that is suggestive of hyperfibrinolysis, for which tranexamic acid is thought to be beneficial. Based on our findings, previously established obstetric transfusion thresholds for goal-directed massive transfusion protocols are likely valid for the majority of the obstetric population regardless of the presence of comorbidities or pregnancy complications. KEY POINTS: · ROTEM parameters do not vary significantly before and after delivery.. · Most patients did not have a hyperfibrinolysis pattern, for which tranexamic acid is thought to be beneficial.. · Previous goal-directed obstetric transfusion thresholds are likely valid in most populations..

Early Administration of Remdesivir and Intensive Care Unit Admission in Hospitalized Pregnant Individuals With Coronavirus Disease 2019 (COVID-19).

Remdesivir has been shown to shorten the time to recovery in hospitalized patients with coronavirus disease 2019 (COVID-19). Data on its use in pregnancy are limited. In this single-center retrospective cohort study, our objective was to determine whether early remdesivir use in pregnant individuals is associated with decreased risk of admission to the intensive care unit (ICU). Forty-one pregnant patients were included in this study, and outcomes were compared between those who received remdesivir less than 7 days (early group) and 7 or more days (late group) from onset of patient-reported symptoms. Early remdesivir administration was associated with improved clinical outcomes, including lower rates of ICU admission, decreased length of hospitalization, and decreased progression to critical disease in pregnant individuals hospitalized with COVID-19.

Maternal and fetal outcomes in pregnant women with pulmonary hypertension: The impact of left heart disease.

Background: Pulmonary hypertension (PH) due to left heart disease (World Health Organization (WHO) Group 2 PH) is the largest PH subgroup, however most reports of PH in pregnancy focus on patients with pulmonary arterial hypertension (WHO Group 1 PH). We evaluated pregnancy outcomes across WHO PH subgroups. Methods: We performed a retrospective single center cohort study of maternal and fetal outcomes in pregnant women with PH (2004-2018). Results: We analyzed outcomes of 70 pregnancies in 70 women with PH (30 ± 6 years-old), classified as WHO Group 1 PH (12 (17%)), Group 2 PH (45 (64%)), Group 3 PH (4 (6%)) and Group 5 PH (9 (13%)). Although no peripartum death occurred, 3 (4.3%) women with WHO Group 2 PH had late mortality (7 ± 4 months post- partum). Additionally, 33 major adverse cardiac events occurred in 26 (37%) women, preterm birth occurred in 32 (49%), and post-partum hemorrhage in 10 (14%), such that only 24 (37%) women completed a viable pregnancy free of an adverse cardiac, obstetric or fetal/neonatal event. Major adverse cardiac events were predominantly due to heart failure (24 (73%)), occurring only in WHO Groups 1 and 2 PH (3 (25%) women vs. 17 (38%), p = 0.07), and significantly associated with pre-eclampsia, left ventricular ejection fraction ≤45%, maternal diabetes, and systemic hypertension. Conclusions: WHO Group 2 PH carries similar risk for maternal cardiovascular events when compared to women with WHO Group 1 PH. Further studies evaluating maternal risk in this cohort are needed.

Imaging-Based Risk Stratification for Recurrence Risk in Women with a History of Peripartum Cardiomyopathy.

OBJECTIVE: Peripartum cardiomyopathy (PPCM) affects 1:1,000 U.S. pregnancies, and while many recover from the disease, the risk of recurrence in subsequent pregnancy (SSP) is high. This study aims to evaluate the utility of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) to predict the risk of recurrence of PPCM in SSP. STUDY DESIGN: We retrospectively evaluated outcomes in women with a history of PPCM and SSP at a large-volume cardioobstetrics program (2008-2019). RESULTS: There were 18 women who had incident PPCM and pursued SSP. Of 24 pregnancies in these women, 8 (33%) were complicated by the development of recurrent PPCM. LVEF ≥ 52% or GLS ≤ -16 was associated with a low risk of recurrent PPCM. CONCLUSION: Approximately one-third of women with PPCM developed recurrent PPCM in SSP. LVEF and GLS on prepregnancy echocardiography may predict the risk of recurrence. Additional studies evaluating risk for recurrence are required to better understand which women are the safest to consider SSP. KEY POINTS: · Peripartum cardiomyopathy affects 1:1000 US pregnancies.. · Approximately one third of women with a history of peripartum cardiomyopathy developed recurrent disease in a subsequent pregnancy.. · A left ventricular ejection fraction ≥52% or global longitudinal strain ≤-16 on echocardiogram is associated with a low risk of recurrence..

Low-dose aspirin increases 15-epi-lipoxins A4 in pregnancies at high-risk for developing preeclampsia.

BACKGROUND: LDA triggers biosynthesis of endogenous anti-inflammatory molecules, aspirin-triggered 15-epi-lipoxin A4 (15-epi-LXA4), which may counteract inflammatory process of preeclampsia (PE), and play role in LDA's mechanism of action in PE prevention in high-risk patients. OBJECTIVE: Investigate the effects of daily LDA on levels of 15-epi-LXA4 in pregnancies at high-risk for developing PE. MATERIALS AND METHODS: Secondary analysis of multi-centered randomized controlled trial investigating effects of daily LDA (60 mg) in high-risk pregnancies. Maternal samples were drawn at three points: before LDA initiation (13-26 weeks' gestation), 24-28 weeks' gestation (at least two weeks after LDA) and 34-36 weeks' gestation. 15-epi-LXA4 levels were measured by ELISA. RESULTS: Analysis included 82 patients: 63 receiving daily LDA and 29 receiving daily placebo starting between 13 and 25 weeks gestation. Prior to randomization, baseline 15-epi-LXA4 levels were similar between both groups (75.9 pg/mL [IQR; 63.8-114.0] vs 136.2 pg/mL [52.4-476.2]; p = 0.10). Patients receiving daily LDA were noted to have significantly increased levels of 15-epi-LXA4 after LDA administration (136.2 pg/mL [IQR; 52.4-476.2] vs 1758.2 pg/mL [905.4-6638.5]; p < 0.001). They also had higher 15-epi-LXA4 levels compared to those receiving placebo at 24-28 weeks' (50.3 [38.1-94.2] vs 1758.2 [905.4-6638.5]; p < 0.001 and 34-38 weeks' gestation (57.9 [41.9-76.7] vs 2310.3 pg/mL [656.9-10609.4]; p < 0.001). After LDA administration in the second trimester, patients who developed PE had decrease in 15-epi-LXA4 levels compared to those without PE (942 pg/mL [348.3-1810.3] vs 1758.2 pg/mL [905.4-6638.5]; p = 0.129). CONCLUSION: Daily LDA administration increases 15-epi-LXA4 levels in high-risk pregnancies for PE. In LDA group, pregnancies complicated by PE have lower levels of 15-epi-LXA4 compared to pregnancies without PE.

Decline in Sars-CoV-2 antibodies over 6-month follow-up in obstetrical healthcare workers.

PROBLEM: Limited data exists on the temporal trend of the Sars-CoV-2 immunologic response and duration of protection following natural infection. We sought to investigate the presence and duration of Sars-CoV-2 serum antibodies in obstetrical healthcare workers (HCW) on serial assessments over a 6-month period, and to assess rates of vaccine acceptance and reported vaccine side effects among this cohort. METHOD OF STUDY: A prospective cohort study of a convenience sample of obstetrical HCWs at a tertiary hospital. Serum Sars-CoV-2 antibodies for Immunoglobulin G (IgG) and Immunoglobulin M (IgM) were measured longitudinally at four intervals: baseline, 4 weeks, 12 weeks, and 6 months. Participants completed voluntary surveys on COVID19 testing, high-risk exposures, vaccine acceptance, and vaccine side effects. RESULTS: One hundred twenty-six of 150 (84%) HCWs who volunteered for participation completed all four blood draws. Prevalence of seropositive HCWs based on positive Sars-CoV-2 IgG antibodies increased from 2% at baseline to 31% at 12 weeks but declined to 21% by 6 months. Forty-two percent (19/43) of the participants considered seropositive for Sars-CoV-2 IgG antibodies at any of the initial three blood draws converted to seronegative status at the 6-month follow-up. Eighty-seven percent (72/83) of participants who responded to a follow-up survey were willing to accept the COVID19 vaccine. Rates of acceptance did not differ by participant antibody status. Those that experienced symptoms with the first injection were more likely to have positive Sars-CoV-2 IgG antibodies (36.8% vs. 9.6%, p = .01). CONCLUSION: Sars-CoV-2 IgG antibodies wane over time and may not provide prolonged and robust immune protection. This underscores the importance of vaccination and continued research in this area while the COVID19 pandemic continues.

Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial.

BACKGROUND: Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB, < 34 weeks), however, the amount of DHA required is unclear. We hypothesized that 1000 mg DHA per day would be superior to 200 mg, the amount in most prenatal supplements. METHODS: This randomised, multicentre, double-blind, adaptive-design, superiority trial was conducted in three USA medical centres. Women with singleton pregnancies and 12 to 20 weeks gestation were eligible. randomization was generated in SAS® by site in blocks of 4. The planned adaptive design periodically generated allocation ratios favoring the better performing dose. Managing study personnel were blind to treatment until 30 days after the last birth. The primary outcome was EPB by dose and by enrolment DHA status (low/high). Bayesian posterior probabilities (pp) were determined for planned efficacy and safety outcomes using intention-to-treat. The study is registered with ClinicalTrials.gov (NCT02626299) and closed to enrolment. FINDINGS: Eleven hundred participants (1000 mg, n = 576; 200 mg, n = 524) were enrolled between June 8, 2016 and March 13, 2020 with the last birth September 5, 2020. 1032 (n = 540 and n = 492) were included in the primary analyses. The higher dose had a lower EPB rate [1.7% (9/540) vs 2.4% (12/492), pp=0.81] especially if participants had low DHA status at enrolment [2.0% (5/249) vs 4.1%, (9/219), pp=0.93]. Participants with high enrolment DHA status did not realize a dose effect [1000 mg: 1.4% (4/289); 200 mg: 1.1% (3/271), pp = 0.57]. The higher dose was associated with fewer serious adverse events (maternal: chorioamnionitis, premature rupture of membranes and pyelonephritis; neonatal: feeding, genitourinary and neurologic problems, all pp>0.90). INTERPRETATION: Clinicians could consider prescribing 1000 mg DHA daily during pregnancy to reduce EPB in women with low DHA status if they are able to screen for DHA. FUNDING: The National Institutes of Health Child Health and Human Development (NICHD) funded the study. Life's DHA™-S oil, DSM Nutritional Products LLC, Switzerland provided all capsules.

Optimal antenatal corticosteroid exposure in women with history of preterm birth and asymptomatic short cervical length.

BACKGROUND: A proposed benefit of cervical length assessment after 24 weeks' gestation in women with a history of preterm birth is to aid in the timing of antenatal corticosteroids in otherwise asymptomatic women. OBJECTIVE: We sought to investigate whether the use of an ultrasonographic short cervical length as an indication for antenatal corticosteroids in asymptomatic women results in optimal exposure compared with women receiving antenatal corticosteroids for preterm labor symptoms. STUDY DESIGN: Retrospective cohort study of all women with a previous spontaneous preterm birth and a singleton gestation who underwent serial cervical length assessment at a large academic tertiary medical center from 2011 to 2016. Patients were included in the analysis if they received antenatal corticosteroids for either an asymptomatic short cervical length or symptoms of preterm labor. The primary outcome was optimal antenatal corticosteroids exposure (latency to delivery of ≤7 days). PROPOSED CHANGE IN RESULTS: Poisson regression with robust error variance was used to calculate incidence rate ratios (IRR) and confidence intervals (CI) for primary and secondary outcomes adjusting for primary and secondary outcomes adjusting for race, earliest previous preterm birth, and current cerclage. RESULTS: There were 287 women meeting inclusion criteria, among whom 166 (57.8%) received antenatal corticosteroids for a short cervical length and 121 (42.2%) for preterm labor symptoms. Women who received antenatal corticosteroids for a short cervical length were less likely to have optimal exposure (1.2% vs 19.0%; incidence rate ratios, 0.06; confidence interval, 0.02-0.27) compared with women with preterm labor symptoms. They were also more likely to have exposure with eventual term delivery (43.2% vs 33.4%; incidence rate ratios, 1.6; confidence interval, 1.2-2.0). Importantly, women who received antenatal corticosteroids for a short cervical length were significantly less likely to receive either an initial or rescue antenatal corticosteroids course within 7 days of a preterm delivery of less than 34 weeks' gestation (42.9% vs 76.9%; incidence rate ratios, 0.52; confidence interval, 0.35-0.75). CONCLUSION: Women with a previous preterm birth who receive antenatal corticosteroids for an asymptomatic short cervical length are less likely to have optimal exposure than women with symptoms of preterm labor. These data challenge the practice of cervical length surveillance for the sole indication of timing antenatal corticosteroids administration.

Use and experiences with external fetal monitoring devices among obstetrical providers.

Introduction: Fetal heart rate monitoring presents one of the few available methods for evaluating the fetus prior to birth. However, current devices on the market have significant shortcomings. We sought to describe the use and experiences with external fetal monitoring (EFM) devices among obstetrical providers.Materials and methods: We performed a cross-sectional survey in an academic medical center between April and July 2017 including nurse, midwife, and physician obstetrical providers (n = 217) who were invited to participate in this study regarding their experiences with the external fetal monitoring (EFM) device utilized by their hospital system in the outpatient, inpatient, and labor and delivery (L&D) settings. Associations between provider characteristics, device use, perception of challenging patients, and potential usefulness of an improved system were assessed by Fisher's exact test.Results: The 137 respondents (63.1%) reported difficulties monitoring obese women (98.5%), multiple gestation pregnancies (90.5%), and early gestational ages (71.5%). Over half (59.5%) of L&D nurses reported interacting with EFM devices for greater than 1-hour during a typical 12-hour shift and fewer than half (42.3%) reported being satisfied with current EFM devices. There were no statistically significant associations between provider age, experience, or time spent utilizing the devices with perception of challenging patient types.Conclusions: In conclusion, obstetrical providers perceive shortcomings of current EFM devices across all levels of provider experience and time utilizing these devices. Nurses reported significant time operating the devices, representing an opportunity to reduce time and costs with an improved device.

Compartmentalization of acute phase reactants Interleukin-6, C-Reactive Protein and Procalcitonin as biomarkers of intra-amniotic infection and chorioamnionitis.

BACKGROUND: The arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-Reactive Protein (CRP) and Procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known. METHODS: We used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionitis. RESULTS: PCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers. CONCLUSIONS: In women with subclinical IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.

The probability of neonatal respiratory distress syndrome as a function of gestational age and lecithin/sphingomyelin ratio.

We sought to define the risk of neonatal respiratory distress syndrome (RDS) as a function of both lecithin/sphingomyelin (L/S) ratio and gestational age. Amniotic fluid L/S ratio data were collected from consecutive women undergoing amniocentesis for fetal lung maturity at Yale-New Haven Hospital from January 1998 to December 2004. Women were included in the study if they delivered a live-born, singleton, nonanomalous infant within 72 hours of amniocentesis. The probability of RDS was modeled using multivariate logistic regression with L/S ratio and gestational age as predictors. A total of 210 mother-neonate pairs (8 RDS, 202 non-RDS) met criteria for analysis. Both gestational age and L/S ratio were independent predictors of RDS. A probability of RDS of 3% or less was noted at an L/S ratio cutoff of > or = 3.4 at 34 weeks, > or = 2.6 at 36 weeks, > or = 1.6 at 38 weeks, and > or = 1.2 at term. Under 34 weeks of gestation, the prevalence of RDS was so high that a probability of 3% or less was not observed by this model. These data describe a means of stratifying the probability of neonatal RDS using both gestational age and the L/S ratio and may aid in clinical decision making concerning the timing of delivery.

Hypoxic hepatitis in a pregnant patient: a complication of gastric bypass surgery.

Elevated serum transaminase levels can have many different etiologies, especially in the pregnant patient. Hypoxic hepatitis is a distinct syndrome caused by decreased hepatic blood flow that presents with a marked, but transient, increase in liver enzymes. A 28-year-old woman, gravida 3, para 2 with history of gastric bypass, presented in the second trimester with bright red blood per rectum, syncope, and epigastric pain. Laboratory studies were significant for anemia, elevated liver enzymes, and low platelets, raising concern for hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) and the need for emergent delivery. Complete evaluation included an upper endoscopy, which revealed a bleeding jejunal ulcer that was subsequently cauterized. Shortly after cauterization, the patient's laboratory values normalized and her pain resolved. Diagnosis of hypoxic hepatitis was made after exclusion of other liver-toxic entities, thus preventing delivery of a preterm infant. Hypoxic hepatitis may masquerade as other clinical syndromes, especially in the pregnant patient. Meticulous physical examination and assessment of laboratory values is essential for making a proper diagnosis and guiding management.

Fractional excretion of tumor necrosis factor-alpha in women with severe preeclampsia.

OBJECTIVE: Proinflammatory cytokines of placental or systemic origin are thought to play a central role in the pathophysiology of preeclampsia. We sought to estimate the fractional excretion of tumor necrosis factor (TNF)-alpha in relationship to proteinuria in women with severe preeclampsia. METHODS: In a cross-sectional study, we evaluated the serum and urine levels of TNF-alpha in 45 women diagnosed with severe preeclampsia (mean+/-standard error of the mean, gestational age 29.1+/-0.5 weeks). Forty-five healthy pregnant women matched for parity, maternal age, and gestational age at recruitment (30.1+/-0.4 weeks) made up the control group. Urinary concentrations were normalized to creatinine. The fractional excretion of TNF-alpha was interpreted in relationship to that of total proteins and soluble fms-like tyrosine kinase-1 (sFlt-1). RESULTS: We found that the women with preeclampsia had significantly higher serum TNF-alpha concentrations compared with the women in the control group (mean+/-standard error of the mean, preeclampsia: 1.39+/-0.09 versus control: 0.93+/-0.07 pg/mL, P<.001). In contrast, urinary levels of TNF-alpha were significantly decreased in the women with preeclampsia compared with the healthy women (median [interquartile range], preeclampsia: 0.26 [0.10-0.91] versus control: 0.58 [0.21-1.29] pg/mg creatinine, P=.003), even though the hypertensive women had higher levels of proteinuria. In contrast to sFlt-1, urinary TNF-alpha did not correlate with the degree of proteinuria. Additionally, in preeclampsia, the fractional excretion of TNF-alpha was significantly lower (preeclampsia: 1.92% [0.46-4.20] versus control: 7.2% [2.44-12.07], P<.001). CONCLUSION: The fractional excretion of TNF-alpha is significantly reduced in women with severe preeclampsia despite proteinuria. The decreased clearance and altered renal excretion of this cytokine may contribute to the exaggerated inflammatory response observed in preeclampsia. LEVEL OF EVIDENCE: II.

Fetal heart rate monitoring patterns in women with amniotic fluid proteomic profiles indicative of inflammation.

We hypothesized that abnormal fetal heart rate monitoring patterns (FHR-MPs) occur more often in pregnancies complicated by intra-amniotic inflammation. Therefore, our objective was to examine the relationships among FHR-MP abnormalities, intra-amniotic inflammation and/or infection, acute histological chorioamnionitis, and early-onset neonatal sepsis (EONS) in pregnancies complicated by preterm birth. Additionally, the ability of various FHR-MPs to predict EONS was investigated. FHR-MPs from 87 singleton premature neonates delivered within 48 hours from amniocentesis (gestational age, mean +/- SD: 28.9 +/- 3.3 weeks) were analyzed blindly using strict National Institute of Child Health and Human Development criteria. Strips were evaluated at three time points: at admission, at amniocentesis, and prior to delivery. Intra-amniotic inflammation was established based on a previously validated proteomic fingerprint (mass-restricted score). Diagnoses of histological chorioamnionitis and EONS were based on well-recognized pathological, clinical, and laboratory criteria. We determined that fetuses of women with severe intra-amniotic inflammation had a higher FHR baseline throughout the entire monitoring period and an increased frequency of a nonreactive FHR-MP at admission. Of all FHR-MPs, a nonreassuring test at admission had 32% sensitivity, 95% specificity, 73% positive predictive value, 77% negative predictive value, and 76% accuracy in predicting EONS. Although a nonreassuring FHR-MP at admission was significantly associated with EONS after correcting for gestational age (odds ratio, 5.6; 95% confidence interval, 1.2 to 26.2; P = 0.030), the majority of the neonates that developed EONS had an overall reassuring FHR-MP. Nonreassuring FHR-MPs at either amniocentesis or delivery had no association with EONS. We conclude that in cases complicated by preterm birth, a nonreassuring FHR-MP at the initial evaluation is a specific but not a sensitive predictor of EONS. An abnormal FHR-MP can thus raise the level of awareness that a fetus with EONS may be born, but it is not a useful clinical indicator of the need for antibiotic treatment of the neonate.

Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis.

OBJECTIVE: The objective of the study was to test the hypothesis that inflammation modulates fetal erythroblastosis and/or the release of nucleated red blood cells (NRBCs) independent of hypoxia or fetal stress. We sought to determine whether fetal inflammation is associated with an elevation in neonatal NRBC count in the setting of inflammation-associated preterm birth. STUDY DESIGN: The relationships between peripheral NRBC count, histological chorioamnionitis, umbilical cord interleukin (IL)-6, erythropoietin (EPO), cortisol, and acid-base status were analyzed in 68 preterm singletons, born to mothers who had an amniocentesis to rule out infection. Proteomic profiling of amniotic fluid identified presence of intraamniotic inflammation according to established parameters. NRBC counts were assessed within 1 hour of birth. Early-onset neonatal sepsis (EONS) was established based on hematological and microbiological indices. IL-6, EPO, and cortisol levels were measured by immunoassays. Fetal acid-base status was determined within 10 minutes of delivery. Parametric or nonparametric statistics were used. RESULTS: Fetuses with EONS (n = 19) were delivered at earlier gestational ages (mean +/- SD: 27.1 +/- 2.8 weeks, P = .001) and more often by mothers with intraamniotic inflammation (P = .022) and histological chorioamnionitis (P < .001). Neonates with EONS had higher absolute NRBC counts (P = .011). NRBC counts were directly correlated with cord blood IL-6 levels (P < .001) but not with EPO, cortisol or parameters of acid-base status levels regardless of EONS status. These relationships remained following correction for gestational age, diabetes, intrauterine growth restriction, and steroid exposure. CONCLUSION: In the setting of inflammation-associated preterm birth and in the absence of hypoxia, elevations in NRBCs in the early neonatal period may be a direct response of exposure to inflammatory mediators in utero.

Effect of 2 stitches vs 1 stitch on the prevention of preterm birth in women with singleton pregnancies who undergo cervical cerclage.

OBJECTIVE: This study investigates whether 2 cerclage stitches are more effective than 1 stitch in the prevention of preterm birth. STUDY DESIGN: This is a retrospective cohort study of 150 singleton pregnancies that underwent cervical cerclage. Gestational age at delivery and clinical characteristics were compared. RESULTS: One hundred twelve patients (74.7%) received 1 stitch, and 38 patients (25.3%) received 2 stitches. There were no baseline differences between the groups. Analysis showed no significant difference in gestational age at delivery between the 1 vs 2 cerclage groups overall (median, 38.0 vs 38.3 weeks of gestation, respectively; P = .356) or for a given gestational age cut-off (<37 weeks of gestation: 37.4% vs 34.2% [P = .727]; <34 weeks of gestation: 16.8% vs 18.4% [P = .823]; <28 weeks of gestation: 9.4% vs 2.6% [P = .179]). CONCLUSION: This study shows no measurable benefit to the placement of 2 stitches over 1 stitch during cervical cerclage in singleton pregnancies; however, further study of preterm birth at <28 weeks of gestation and postcerclage outcomes among a larger cohort is merited.