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Browsing by Author "Tuuli, Methodius G."

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    786 Neonatal outcomes in pregnant women with diagnosis of COVID-19
    (Elsevier, 2021) Izewski, Joanna; Boudova, Sarah; Rouse, Caroline E.; Ibrahim, Sherrine A.; Shanks, Anthony L.; Reinhardt, Jeff C.; Scifres, Christina; Haas, David M.; Peipert, Jeffrey F.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Objective It is unclear whether infection with COVID-19 during pregnancy increases the risk of adverse neonatal outcomes. We tested the hypothesis that a diagnosis of COVID-19 during pregnancy increases the risk of neonatal respiratory morbidity and other adverse neonatal outcomes. Study Design: Retrospective analysis of prospectively collected data from two labor and delivery units with universal COVID-19 testing policy between March 1 and May 31, 2020. Pregnant women with singleton pregnancies who delivered during the study period and underwent testing for COVID-19 at any point in their pregnancy were eligible. The primary outcome was a composite of neonatal respiratory morbidity defined as the occurrence of any one of the following: respiratory distress syndrome, transient tachypnea of the newborn, and need for respiratory support. The risk of neonatal morbidity with and without a COVID-19 diagnosis were compared using univariable and multivariable analyses. Stratified analysis compared the risks of adverse neonatal outcomes in symptomatic and asymptomatic patients with COVID-19 to those without COVID-19. Results: Of 515 subjects meeting inclusion criteria, 55 (10.7%) tested positive for COVID-19; 19 (34.6%) were asymptomatic and 36 (65.4%) were symptomatic. No neonate tested positive for COVID-19. Rates of the primary outcome, composite neonatal respiratory morbidity, were not significantly different in patients with and without COVID-19 (21.8% vs 19.6%, P=0.692). There was no significant difference in the risk of neonatal respiratory morbidity in a Cox regression model accounting for time from diagnosis to delivery, and adjusting for gestational age at delivery, mode of delivery, and maternal diabetes (adjusted hazard ratio: 0.62; 95% CI 0.35, 1.09). There were no significant differences in any of the secondary outcomes in patients with COVID-19 who were asymptomatic or symptomatic (Table). Conclusion: A diagnosis of COVID-19 during pregnancy does not appear to increase the risk of neonatal morbidity. These data may be useful in counseling women diagnosed with COVID-19 during pregnancy.
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    975 ABO blood group, rhesus type and risk of COVID-19 in pregnant women
    (Elsevier, 2021) Ibrahim, Sherrine A.; Boudova, Sarah; Rouse, Caroline E.; Shanks, Anthony L.; Reinhardt, Jeffrey; Scifres, Christina; Haas, David M.; Peipert, Jeffrey F.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Objective: There is controversy regarding the association of ABO blood group, Rhesus (Rh) type and risk of COVID-19. We tested the hypothesis that ABO blood group and Rh type are associated with COVID-19 diagnosis and symptoms during pregnancy. Study Design: Retrospective analysis of prospectively collected data from two labor and delivery units with universal SARS-CoV-2 testing policy between March 1 and May 31, 2020. All pregnant women tested during the study period were eligible. The primary outcome was COVID-19 diagnosis. Secondary outcomes were measures of COVID-19 severity, including symptoms, ICU admission, respiratory support and treatment for COVID-19. Outcomes were compared across ABO blood groups. Women with blood group O or Rh positive blood type were compared with non-O groups and Rh negative, respectively, using univariable and multivariable analyses. Results: Of 586 pregnant women tested, 66 (11.3%) were positive. The most common ABO blood group in the cohort was O (52.2%) and 87.4% were Rh positive. Rates of the primary outcome, COVID-19 diagnosis, were not significantly different across ABO blood groups (P=0.47). There were also no significant differences in measures of COVID-19 severity among blood groups (Table). Compared to other blood groups, the risk of COVID-19 diagnosis was not significantly different in women with group O (13.1% vs 9.3%, adjusted OR 1.43; 95% CI 0.84, 2.4). Rh positive women were at a significantly higher risk of COVID-19 diagnosis (12.3% vs 4.1%, adjusted OR 3.38; 95% CI 1.03, 11.07) and a non-significant increased risk of symptoms (6.8% vs 2.7%, adjusted OR 2.67; 95% CI 0.63, 11.32), after adjusting for ABO blood group (Figure). Conclusion: We found no association between ABO blood group and diagnosis or severity of COVID-19 in pregnant women. However, Rhesus positive women may be at a higher risk of COVID-19.
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    Antenatal Corticosteroids in Preterm Small-for-Gestational Age Infants: A Systematic Review and Meta-Analysis
    (Elsevier, 2020) Blankenship, Stephanie A.; Brown, Kristine E.; Simon, Laura E.; Stout, Molly J.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Objective This study aimed to estimate the effect of antenatal corticosteroid administration on neonatal mortality and morbidity in preterm small-for-gestational age infants through a systematic review and meta-analysis. Data Sources A predefined, systematic search was conducted through Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trial Registry Platform, and ClinicalTrials.gov yielding 5324 articles from 1970 to 2019. Study Eligibility Criteria Eligible studies compared neonatal morbidity and mortality among small-for-gestational age infants delivered preterm who received antenatal corticosteroids with those who did not. Methods The primary outcome was neonatal mortality. Secondary outcomes were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and periventricular leukomalacia, bronchopulmonary dysplasia or chronic lung disease of prematurity, or neonatal sepsis. We assessed heterogeneity by means of Higgins I2 statistic and Cochran’s Q test and calculated pooled odds ratios with 95% confidence intervals using random effects models. Results A total of 16 observational cohort and case-control studies published from 1995 to 2018 met the selection criteria for the systematic review and included 8989 preterm small-for-gestational age infants. Antenatal corticosteroid administration was explicitly reported among 8376 small-for-gestational age infants; 4631 (55.3%) received antenatal corticosteroids and 3741 (44.7%) did not. Of note, 13 studies including 6387 preterm small-for-gestational age infants were then included in the meta-analysis. Neonatal mortality was significantly lower among infants who received antenatal corticosteroids than those who did not (12 studies: 12.8% vs 15.1%; pooled odds ratio, 0.63; 95% confidence interval, 0.46–0.86), with significant heterogeneity between studies (I2=55.1%; P=.011). There was no significant difference in respiratory distress syndrome (12 studies: odds ratio, 0.89; 95% confidence interval, 0.69–1.15), necrotizing enterocolitis (7 studies: odds ratio, 0.93; 95% confidence interval, 0.70–1.22), intraventricular hemorrhage and periventricular leukomalacia (10 studies: odds ratio, 0.82; 95% confidence interval, 0.56–1.20), bronchopulmonary dysplasia or chronic lung disease of prematurity (8 studies: odds ratio, 1.11; 95% confidence interval, 0.88–1.41), or neonatal sepsis (6 studies: odds ratio, 1.13; 95% confidence interval, 0.86–1.49). Conclusion These data indicate that antenatal corticosteroid administration reduces neonatal mortality in small-for-gestational age infants delivered preterm, with no apparent effect on neonatal morbidity. This supports the use of antenatal corticosteroids to reduce neonatal mortality in pregnancies with small-for-gestational age infants at risk of preterm birth.
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    Clinical Diagnosis of Placenta Accreta and Clinicopathological Outcomes
    (Thieme, 2019) Rosenbloom, Joshua I.; Hirshberg, Jonathan S.; Stout, Molly J.; Cahill, Alison G.; Macones, George A.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Objective To investigate the association between the intraoperative diagnosis of placenta accreta at the time of cesarean hysterectomy and pathological diagnosis. Study Design This is a retrospective cohort study of all patients undergoing cesarean hysterectomy for suspected placenta accreta from 2000 to 2016 at Barnes-Jewish Hospital. The primary outcome was the presence of invasive placentation on the pathology report. We estimated predictive characteristics of clinical diagnosis of placenta accreta using pathological diagnosis as the correct diagnosis. Results There were 50 cesarean hysterectomies performed for suspected abnormal placentation from 2000 to 2016. Of these, 34 (68%) had a diagnosis of accreta preoperatively and 16 (32%) were diagnosed intraoperatively at the time of cesarean delivery. Two patients had no pathological evidence of invasion, corresponding to a false-positive rate of 4% (95% confidence interval [CI]: 0.5%, 13.8%) and a positive predictive value of 96% (95% CI: 86.3%, 99.5%). There were no differences in complications among patients diagnosed intraoperatively compared with those diagnosed preoperatively. Conclusion Most patients undergoing cesarean hysterectomy for placenta accreta do have this diagnosis confirmed on pathology. However, since the diagnosis of placenta accreta was made intraoperatively in nearly a third of cesarean hysterectomies, intraoperative vigilance is required as the need for cesarean hysterectomy may not be anticipated preoperatively.
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    Effect of Prophylactic Negative Pressure Wound Therapy vs Standard Wound Dressing on Surgical-Site Infection in Obese Women After Cesarean Delivery
    (JAMA, 2020-09-22) Tuuli, Methodius G.; Liu, Jingxia; Tita, Alan T.N.; Longo, Sherri; Trudell, Amanda; Carter, Ebony B.; Shanks, Anthony L.; Woolfolk, Candice; Caughey, Aaron B.; Warren, David K.; Odibo, Anthony O.; Colditz, Graham; Macones, George A.; Harper, Lorie; Obstetrics and Gynecology, School of Medicine
    Importance: Obesity increases the risk of both cesarean delivery and surgical-site infection. Despite widespread use, it is unclear whether prophylactic negative pressure wound therapy reduces surgical-site infection after cesarean delivery in obese women. Objective: To evaluate whether prophylactic negative pressure wound therapy, initiated immediately after cesarean delivery, lowers the risk of surgical-site infections compared with standard wound dressing in obese women. Design, setting, and participants: Multicenter randomized trial conducted from February 8, 2017, through November 13, 2019, at 4 academic and 2 community hospitals across the United States. Obese women undergoing planned or unplanned cesarean delivery were eligible. The study was terminated after 1624 of 2850 participants were recruited when a planned interim analysis showed increased adverse events in the negative pressure group and futility for the primary outcome. Final follow-up was December 18, 2019. Interventions: Participants were randomly assigned to either undergo prophylactic negative pressure wound therapy, with application of the negative pressure device immediately after repair of the surgical incision (n = 816), or receive standard wound dressing (n = 808). Main outcomes and measures: The primary outcome was superficial or deep surgical-site infection according to the Centers for Disease Control and Prevention definitions. Secondary outcomes included other wound complications, composite of surgical-site infections and other wound complications, and adverse skin reactions. Results: Of the 1624 women randomized (mean age, 30.4 years, mean body mass index, 39.5), 1608 (99%) completed the study: 806 in the negative pressure group (median duration of negative pressure, 4 days) and 802 in the standard dressing group. Superficial or deep surgical-site infection was diagnosed in 29 participants (3.6%) in the negative pressure group and 27 (3.4%) in the standard dressing group (difference, 0.36%; 95% CI, -1.46% to 2.19%, P = .70). Of 30 prespecified secondary end points, 25 showed no significant differences, including other wound complications (2.6% vs 3.1%; difference, -0.53%; 95% CI, -1.93% to 0.88%; P = .46) and composite of surgical-site infections and other wound complications (6.5% vs 6.7%; difference, -0.27%; 95% CI, -2.71% to 2.25%; P = .83). Adverse skin reactions were significantly more frequent in the negative pressure group (7.0% vs 0.6%; difference, 6.95%; 95% CI, 1.86% to 12.03%; P < .001). Conclusions and relevance: Among obese women undergoing cesarean delivery, prophylactic negative pressure wound therapy, compared with standard wound dressing, did not significantly reduce the risk of surgical-site infection. These findings do not support routine use of prophylactic negative pressure wound therapy in obese women after cesarean delivery.
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    Intensive glycaemic targets in overweight and obese individuals with gestational diabetes mellitus: clinical trial protocol for the iGDM study
    (BMJ, 2024-02-29) Scifres, Christina M.; Battarbee, Ashley N.; Feghali, Maisa N.; Pierce, Stephanie; Edwards, Rodney K.; Smith, Emily M.; Guise, David; Bhamidipalli, Sruthi; Daggy, Joanne; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Introduction: The prevalence of both obesity and gestational diabetes mellitus (GDM) has increased, and each is associated with adverse perinatal outcomes including fetal overgrowth, neonatal morbidity, hypertensive disorders of pregnancy and caesarean delivery. Women with GDM who are also overweight or obese have higher rates of pregnancy complications when compared with normal-weight women with GDM, which may occur in part due to suboptimal glycaemic control. The current recommendations for glycaemic targets in pregnant women with diabetes are based on limited evidence and exceed the mean fasting (70.9±7.8 mg/dL) and 1-hour postprandial (108.9±12.9 mg/dL) glucose values in pregnant individuals without diabetes. Our prior work demonstrated that the use of intensive (fasting <90 mg/dL and 1-hour postprandial <120 mg/dL) compared with standard (fasting <95 mg/dL and 1-hour postprandial <140 mg/dL) glycaemic targets resulted in improved glycaemic control without increasing the risk for hypoglycaemia in pregnant individuals with GDM, but the impact of intensive glycaemic targets on perinatal outcomes is unknown. Methods and analysis: The Intensive Glycemic Targets in Overweight and Obese Women with Gestational Diabetes Mellitus: A Multicenter Randomized Trial (iGDM Trial) is a large, pragmatic randomised clinical trial designed to investigate the impact of intensive versus standard glycaemic targets on perinatal outcomes in women with GDM who are overweight and obese. During the 5-year project period, a multidisciplinary team of investigators from five medical centres representing regions of the USA with high rates of obesity will randomise 828 overweight and obese women with GDM to either intensive or standard glycaemic targets. We will test the central hypothesis that intensive glycaemic targets will result in lower rates of neonatal composite morbidity including large for gestational age birth weight, neonatal hypoglycaemia, respiratory distress syndrome and need for phototherapy when compared with standard glycaemic targets using the intention-to-treat approach to analysis. Ethics and dissemination: The Institutional Review Board (IRB) at Indiana University School of Medicine approved this study (IRB# 11435; initial approval date 25 August 2021). We will submit the results of the trial for publication in peer-reviewed journals and presentations at international scientific meetings.
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    Iron-deficiency anaemia in pregnancy: the role of hepcidin
    (Elsevier, 2019) Lewkowitz, Adam K.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
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    Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation: A Systematic Review and Meta-analysis
    (American Medical Association, 2021) Raghuraman, Nandini; Temming, Lorene A.; Doering, Michelle M.; Stoll, Carolyn R.; Palanisamy, Arvind; Stout, Molly J.; Colditz, Graham A.; Cahill, Alison G.; Tuuli, Methodius G.; Obstetrics and Gynecology, School of Medicine
    Importance: Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice. Objective: To compare the association of peripartum maternal oxygen administration with room air on umbilical artery (UA) gas measures and neonatal outcomes. Data sources: Ovid MEDLINE, Embase, Scopus, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials were searched from February 18 to April 3, 2020. Search terms included labor or obstetric delivery and oxygen therapy and fetal blood or blood gas or acid-base imbalance. Study selection: Studies were included if they were randomized clinical trials comparing oxygen with room air at the time of scheduled cesarean delivery or labor in patients with singleton, nonanomalous pregnancies. Studies that did not collect paired umbilical cord gas samples or did not report either UA pH or UA Pao2 results were excluded. Data extraction and synthesis: Data were extracted by 2 independent reviewers. The analysis was stratified by the presence or absence of labor at the time of randomization. Data were pooled using random-effects models. Main outcomes and measures: The primary outcome for this review was UA pH. Secondary outcomes included UA pH less than 7.2, UA Pao2, UA base excess, 1- and 5-minute Apgar scores, and neonatal intensive care unit admission. Results: The meta-analysis included 16 randomized clinical trials (n = 1078 oxygen group and n = 974 room air group). There was significant heterogeneity among the studies (I2 = 49.88%; P = .03). Overall, oxygen administration was associated with no significant difference in UA pH (weighted mean difference, 0.00; 95% CI, -0.01 to 0.01). Oxygen use was associated with an increase in UA Pao2 (weighted mean difference, 2.57 mm Hg; 95% CI, 0.80-4.34 mm Hg) but no significant difference in UA base excess, UA pH less than 7.2, Apgar scores, or neonatal intensive care unit admissions. Umbilical artery pH values remained similar between groups after accounting for the risk of bias, type of oxygen delivery device, and fraction of inspired oxygen. After stratifying by the presence or absence of labor, oxygen administration in women undergoing scheduled cesarean delivery was associated with increased UA Pao2 (weighted mean difference, 2.12 mm Hg; 95% CI, 0.09-4.15 mm Hg) and a reduction in the incidence of UA pH less than 7.2 (relative risk, 0.63; 95% CI, 0.43-0.90), but these changes were not noted among those in labor (Pao2: weighted mean difference, 3.60 mm Hg; 95% CI, -0.30 to 7.49 mm Hg; UA pH<7.2: relative risk, 1.34; 95% CI, 0.58-3.11). Conclusions and relevance: This systematic review and meta-analysis suggests that studies to date showed no association between maternal oxygen and a clinically relevant improvement in UA pH or other neonatal outcomes.
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    Obesity, Second Stage Duration, and Labor Outcomes in Nulliparous Women
    (Thieme, 2021-03) Frolova, Antonina I.; Raghuraman, Nandini; Stout, Molly J.; Tuuli, Methodius G.; Macones, George A.; Cahill, Alison G.; Obstetrics and Gynecology, School of Medicine
    Objective: This study aimed to estimate second stage duration and its effects on labor outcomes in obese versus nonobese nulliparous women. Study design: This was a secondary analysis of a cohort of nulliparous women who presented for labor at term and reached complete cervical dilation. Adjusted relative risks (aRR) were used to estimate the association between obesity and second stage characteristics, composite neonatal morbidity, and composite maternal morbidity. Effect modification of prolonged second stage on the association between obesity and morbidity was assessed by including an interaction term in the regression model. Results: Compared with nonobese, obese women were more likely to have a prolonged second stage (aRR: 1.48, 95% CI: 1.18-1.85 for ≥3 hours; aRR: 1.65, 95% CI: 1.18-2.30 for ≥4 hours). Obesity was associated with a higher rate of second stage cesarean (aRR: 1.78, 95% CI: 1.34-2.34) and cesarean delivery for fetal distress (aRR: 2.67, 95% CI: 1.18-3.58). Obesity was also associated with increased rates of neonatal (aRR: 1.38, 95% CI: 1.05-1.80), but not maternal morbidity (aRR: 1.06, 95% CI: 0.90-1.25). Neonatal morbidity risk was not modified by prolonged second stage. Conclusion: Obesity is associated with increased risk of neonatal morbidity, which is not modified by prolonged second stage of labor.
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    Perinatal outcomes after intrauterine growth restriction and umbilical artery Doppler pulsatility index of less than the fifth percentile
    (Taylor & Francis, 2021-03) Lewkowitz, Adam K.; Tuuli, Methodius G.; Cahill, Alison G.; Macones, George A.; Dicke, Jeffrey M.; Obstetrics and Gynecology, School of Medicine
    Objective: To analyze perinatal morbidity and stillbirth after intrauterine growth restriction (IUGR) with an umbilical artery Doppler pulsatility index (UA PI) less than the fifth centile.Study design: This retrospective cohort study included nonanomalous singleton, IUGR pregnancies receiving UA PI testing at a tertiary-care prenatal diagnostic center. Women with persistently elevated UA PI, absent or reversed end-diastolic flow on UA PI, or who had only one UA PI result were excluded. Low UA PI was defined as having ≥1 UA PI <5%. Women with low UA PI were matched by gestational age at IUGR diagnosis in a random 1 case: 4 control computer-generated algorithm to those with normal UA PI (≤95% and ≥5%). The primary outcome was composite neonatal morbidity and mortality (stillbirth, mechanical ventilation, sepsis, intraventricular hemorrhage, and necrotizing enterocolitis). Secondary outcomes included 5-minute Apgar, umbilical artery pH, delivery type, and interval from IUGR diagnosis to delivery. We compared outcomes after low UA PI to those after normal UA PI with multivariable logistic regression, adjusting for gestational age at delivery, betamethasone use, infant gender, and maternal factors.Results: Of the 1893 IUGR pregnancies, 25 (1.3%) had low UA PI <5% and were randomly matched via computer algorithm to 100 controls. There were no stillbirths in either group; the odds of composite neonatal morbidity was similar among IUGR pregnancies with UA PI <5% versus normal (adjusted odds ratio 0.89 (95% confidence interval 0.27-2.75)). There was no difference in 5-minute Apgars, umbilical artery pH, rate of cesarean delivery for fetal distress, or interval from IUGR diagnosis to delivery between the two groups.Conclusion: Among IUGR pregnancies, UA PI <5% is uncommon and not associated with improved neonatal outcomes compared to normal UA PI. These findings suggest low UA PI can continue to be managed as normal UA PI.
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