Plugging membranes after fetoscopy in congenital diaphragmatic hernia: early cost-effectiveness analysis.

OBJECTIVES: Fetal endoscopic tracheal occlusion (FETO) improves neonatal survival of fetuses with congenital diaphragmatic hernia (CDH). However, FETO also increases the risk of preterm prelabor rupture of membranes (PPROM) and preterm delivery (PTD), as fetal membrane defects after fetoscopy do not heal. To solve this issue, an advanced sealing plug for closing the membrane defect is being developed. Using early-stage health economic modeling, we aimed to estimate the potential value of this innovative plug in terms of costs and effects, and to determine the properties required for it to become cost-effective. METHODS: Early-stage health economic modeling was applied to the case of performing FETO in women with a singleton pregnancy whose fetus is diagnosed prenatally with CDH. We simulated a cohort of patients using a state-transition model over a 45-year time horizon. In our best-case-scenario analysis, we compared the current-care strategy with the perfect-plug strategy, which reduces the risk of PPROM and PTD by 100%, to determine the maximum quality-adjusted life years (QALYs) gained and costs saved. Using threshold analysis, we determined the minimum percentage reduction in the risk of PPROM and PTD required for the plug to be considered cost-effective. The impact of model parameters on outcome was investigated using a sensitivity analysis. RESULTS: Our model indicated that a perfect-plug strategy would yield on average an additional 1.94 QALYs at a cost decrease of €2554 per patient. These values were influenced strongly by the percentage of cases with early PTD (27-34 weeks). Threshold analysis showed that, for €500 per plug, the plug strategy needs a minimum percentage reduction of 1.83% in the risk of PPROM and PTD (i.e. reduction in the risk from 47.50% to 46.63% for PPROM and from 71.50% to 70.19% for PTD) to be cost-effective. CONCLUSIONS: Our model-based approach showed clear potential of the plug strategy when applied in the context of FETO for CDH fetuses, as only a minor reduction in the risk of PPROM and PTD is needed for the plug to be cost-effective. Its value is expected to be even higher when used in conditions associated with a higher rate of early PTD. Continued investment in research and development of the plug strategy appears to provide value for money. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Hemodynamic assessment in patients with preterm premature rupture of the membranes (pPROM).

OBJECTIVE: The aim of this study was to assess the hemodynamic differences in women with pPROM versus physiological pregnancies. STUDY DESIGN: This was a prospective case control study of 15 patients with pPROM and 45 controls. Patients and controls were submitted at enrollment to a non-invasive hemodynamic evaluation with UltraSonic Cardiac Output Monitor (USCOM), and to blood tests to check white blood cells count and C-reactive protein (CRP) levels. We followed pPROM patients until delivery noting fetal/neonatal and maternal unfavorable outcomes (maternal fever, APGAR 1' and 5'< 7, stillbirth). RESULTS: Patients with pPROM showed higher values of cardiac output (9.1 ± 2.3 vs 7.1 ± 0.85, p < 0.01), lower systemic vascular resistances (792.1 ± 162 vs 1006.2 ± 110.7, p < 0.01), higher minute distance (32.3 ± 7.8 vs 25 ± 2.8, p < 0.01), lower Potential to Kinetic Energy Ratio (16.5 ± 5.3 vs 22.4 ± 6.8, p < 0.01), higher heart rate (97.5 ± 15.4 vs 82.4 ± 12, p < 0.01) and higher oxygen delivery (1313.2 ± 325.8 vs 1080.7 ± 151.8, p < 0.01) vs. controls. Six out of 15 pPROM patients had an unfavorable outcome. There were no significant differences in CRP levels and WBC count at admission in the two pPROM subgroups, whereas maternal hemodynamics was characterized by lower SVR (718 ± 72 vs 863 ± 123, p = 0.02) in subsequently complicated patients. CONCLUSIONS: Maternal hemodynamics is altered in pPROM patients, with a lower Systemic Vascular Resistance and higher Cardiac Output vs. controls. This hyperdynamic circulation appears to anticipates the changes of serum markers of inflammation (CRP, WBC count) and seems to be more pronounced at admission in pPROM patients developing unfavorable outcomes.

Immediate birth for women between 34 and 37 weeks of gestation with prolonged preterm prelabour rupture of membranes and detection of vaginal or urine group B streptococcus: an economic evaluation.

OBJECTIVE: What are the costs, benefits and harms of immediate birth compared with expectant management in women with prolonged preterm prelabour rupture of membranes (PPROM) at 34+0 -36+6  weeks of gestation and detection of vaginal or urine group B streptococcus (GBS)? DESIGN: Mathematical decision model comprising three independent decision trees. SETTING: UK National Health Service (NHS) and personal social services perspective. POPULATION: Women testing positive for GBS with PPROM at 34+0 -36+6  weeks of gestation. METHODS: The model estimates lifetime costs and quality-adjusted life years (QALYs) using evidence from randomised trials, UK NHS data sources and further observational studies. Simulated events include neonatal infections, morbidity associated with preterm birth and consequences of caesarean birth. Deterministic and probabilistic sensitivity analyses (PSAs) were performed. MAIN OUTCOME MEASURES: QALYs, costs and incremental cost-effectiveness ratio (ICER). RESULTS: In this population, immediate birth dominates expectant management: it is more effective (average lifetime QALYs, 24.705 versus 24.371) and it is cheaper (average lifetime costs, £14,372 versus £19,311). In one-way sensitivity analysis, results are robust to all but the odds ratio estimating the relative effect on incidence of infections. Threshold analysis shows that the odds of infection only need to be >1.5% with expectant management for the benefit of avoiding infections to outweigh the disadvantages of immediate birth. In PSA, immediate birth is the preferred option in >80% of simulations. CONCLUSIONS: Neonatal GBS infections are expensive to treat and may result in substantial adverse health consequences. Therefore, immediate birth, which is associated with a reduced risk of neonatal infection compared with expectant management, is expected to generate better health outcomes and decreased lifetime costs. TWEETABLE ABSTRACT: For women with preterm prelabour rupture of membranes and group B streptococcus in vaginal or urine samples, immediate birth is associated with improved health in their babies and reduced costs, compared with expectant management.

Antenatal corticosteroids for pregnant women with COVID-19 infection and preterm prelabor rupture of membranes: a decision analysis.

BACKGROUND: While antenatal corticosteroids are routinely used to decrease adverse neonatal outcomes following preterm delivery, corticosteroids are also associated with worse outcomes in patients with viral respiratory infections. Currently in the setting of the COVID-19 pandemic, it is unclear whether antenatal corticosteroids for infant benefit outweigh the potential harm to a pregnant woman with a COVID-19 infection. OBJECTIVE: To determine at which gestational ages administering antenatal corticosteroids is the optimal management strategy for hospitalized women with preterm prelabor rupture of membranes (PPROM) who have a COVID-19 infection. METHODS: We designed a decision-analytic model to assess the maternal and infant outcomes associated with antenatal corticosteroid administration for risk of preterm delivery following rupture of membranes in the setting of a COVID-19 infection. We used a theoretical cohort of 10,000 women at each gestational age between 24 and 32 weeks who were hospitalized with PPROM and found to be COVID-19 positive. Maternal outcomes included intensive care unit admission and death related to COVID-19 infection. The infant outcomes of interest included respiratory distress syndrome, intraventricular hemorrhage, neurodevelopmental delay, and death, and were assessed along with maternal and infant quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were used to evaluate model assumptions. RESULTS: In our theoretical cohort of 10,000 women with COVID-19 infection and preterm prelabor rupture of membrane between 24 and 32 weeks, corticosteroid administration resulted in 2,200 women admitted to the ICU and 110 maternal deaths at each gestational age. No antenatal corticosteroid use resulted in 1,500 ICU admissions and 75 maternal deaths at each gestational age. Antenatal corticosteroid administration also resulted in fewer cases of respiratory distress syndrome, intraventricular hemorrhage, and infant death. Overall, we found that between 24 and 30 weeks of gestation, administering antenatal corticosteroids was the optimal management strategy as it resulted in higher combined QALYs than no corticosteroid use. For 31 and 32 weeks of gestation, antenatal corticosteroid administration resulted in lower combined QALYs. On sensitivity analyses, we found that with increasing gestational age, the probability which antenatal corticosteroids was the optimal management strategy decreased. CONCLUSION: Administration of antenatal corticosteroids was an effective management strategy compared to no corticosteroid administration at gestational ages less than 31 weeks. These results provide data for clinicians to utilize when counseling pregnant patients hospitalized with PPROM and have a COVID-19 infection.

Preterm prelabor rupture of membranes: evaluating latency and neonatal morbidity for pregnancies with expectant management ≥34 weeks.

OBJECTIVE: To evaluate the association between latency and neonatal morbidity for pregnancies with expectant management of PPROM ≥34 w. MATERIALS AND METHODS: A retrospective cohort of singletons with PPROM from 2011 to 2016. Exposure was defined as latency (period from diagnosis of PPROM to delivery) and was analyzed as a count variable (i.e. number of days) and binary variable (≥7 days and <7 days; ≥21 days and <21 days). Primary outcome was composite neonatal morbidity defined as need for respiratory support, culture positive neonatal sepsis, and/or neonatal antibiotics >72 h. Fisher's exact test, chi-square test, Mann-Whitney U and binary logistic regression tests were performed with p<.05 considered significant. RESULTS: Of 813 pregnancies, 104 met inclusion criteria: 73 (70.2%) pregnancies with PPROM diagnosed at <34 weeks and 31 (29.8%) pregnancies with PPROM diagnosed ≥34 weeks. A total of 58 (55.8%) pregnancies had a latency of ≥7 days and 46 (44.2%) had a latency <7 days. There was no difference in composite neonatal morbidity for latency ≥7 d versus <7 d (aOR 0.92; 95% CI 0.30-2.82) or latency as a count variable (aOR 0.70; 95% CI 0.23-2.13). However, a latency ≥21 d was associated with increased composite neonatal morbidity (aOR 10.24, 95% CI 1.42-73.99). CONCLUSION: In pregnancies with PPROM expectantly managed ≥34 w, a latency of ≥7 d is not associated with significant differences in neonatal morbidity. However, different latency thresholds may be more clinically relevant for late preterm pregnancies. The increase in composite neonatal morbidity associated with a latency >21 days should be an area of future investigation and may suggest there is a population of pregnancies with PPROM which may not benefit from expectant management past 34 weeks.

Expectant management of preterm premature rupture of membranes at 34 weeks: a cost effectiveness analysis.

OBJECTIVE: To examine the outcomes and cost effectiveness of expectant management versus immediate delivery of women who experience preterm premature rupture of membranes (PPROM) at 34 weeks. METHODS: A cost-effectiveness model was built using TreeAge software to compare outcomes in a theoretical cohort of 37,455 women with PPROM at 34 weeks undergoing expectant management until 37 weeks versus immediate delivery. Outcomes included fetal death, neonatal sepsis, neonatal death, neonatal neurodevelopmental delay, healthy neonate, maternal sepsis, maternal death, cost, and quality-adjusted life years. Probabilities were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life year. RESULTS: In our theoretical cohort of 37,455 women, expectant management yielded 58 fewer neonatal deaths and 164 fewer cases of neonatal neurodevelopmental delay. However, it resulted in 407 more cases of neonatal sepsis and 2.7 more cases of maternal sepsis. Expectant management resulted in 3,531 more quality-adjusted life years and a cost savings of $71.9 million per year, making it a dominant strategy. Univariate sensitivity analysis demonstrated expectant management was cost effective until the weekly cost of antepartum admission exceeded $17,536 (baseline estimate: $12,520) or the risk of maternal sepsis following intraamniotic infection exceeded 20%. CONCLUSION: Our model demonstrated that expectant management of PPROM at 34 weeks yielded better outcomes on balance at a lower cost than immediate delivery. This analysis is important and timely in light of recent studies suggesting improved neonatal outcomes with expectant management. However, individual risks and preferences must be considered in making this clinical decision as expectant management may increase the risk of adverse perinatal outcomes when the risk of puerperal infection increases.

The use of functional placental magnetic resonance imaging for assessment of the placenta after prolonged preterm rupture of the membranes in vivo: A pilot study.

INTRODUCTION: Preterm prelabor rupture of membranes (PPROM) complicates 3% of pregnancies in the UK. Where delivery does not occur spontaneously, expectant management until 37 weeks of gestation is advocated, unless signs of maternal infection develop. However, clinical presentation of maternal infection can be a late sign and injurious fetal inflammatory responses may already have been activated. There is therefore a need for more sensitive markers to aid optimal timing of interventions. At present there is no non-invasive test in clinical practice to assess for infection in the fetal compartment and definitive diagnosis of chorioamnionitis is by histological assessment of the placenta after delivery. This study presents comprehensive functional placental magnetic resonance imaging (MRI) quantification, already used in other organ systems, to assess for infection/inflammation, in women with and without PPROM aiming to explore its use as a biomarker for inflammation within the feto-placental compartment in vivo. MATERIAL AND METHODS: Placental MRI scans were performed in a cohort of 12 women (with one having two scans) with PPROM before 34 weeks of gestation (selected because of their high risk of infection), and in a control group of 87 women. Functional placental assessment was performed with magnetic resonance techniques sensitive to changes in the microstructure (diffusion) and tissue composition (relaxometry), with quantification performed both over the entire organ and in regions of interest between the basal and chorionic plate. Placental histology was analyzed after delivery where available. RESULTS: Normative evolution of functional magnetic resonance biomarkers over gestation was studied. Cases of inflammation, as assessed by histological presence of chorioamnionitis, and umbilical cord vasculitis with or without funisitis, were associated with lower T2* (mean T2* at 30 weeks 50 ms compared with 58 ms in controls) and higher fractional anisotropy (mean at 30 weeks 0.55 compared with 0.45 in controls). These differences did not reach significance and there was substantial heterogeneity both in T2* and Apparent Diffusivitiy across the cohort. CONCLUSIONS: This first exploration of functional placental assessment in a cohort of women with PPROM demonstrates that functional placental MRI can reveal a range of placental changes associated with inflammatory processes. It is a promising tool to gain information and in the future to identify inflammation in vivo, and could therefore assist in improving optimal timing for interventions designed to prevent fetal injury.

Child outcomes after induction of labour or expectant management in women with preterm prelabour rupture of membranes between 34 and 37 weeks of gestation: study protocol of the PPROMEXIL Follow-up trial. A long-term follow-up study of the randomised controlled trials PPROMEXIL and PPROMEXIL-2.

INTRODUCTION: Late preterm prelabour rupture of membranes (PROM between 34+0 and 36+6 weeks gestational age) is an important clinical dilemma. Previously, two large Dutch randomised controlled trials (RCTs) compared induction of labour (IoL) to expectant management (EM). Both trials showed that early delivery does not reduce the risk of neonatal sepsis as compared with EM, although prematurity-related risks might increase. An extensive, structured long-term follow-up of these children has never been performed. METHODS AND ANALYSIS: The PPROMEXIL Follow-up trial (NL6623 (NTR6953)) aims to assess long-term childhood outcomes of the PPROMEXIL (ISRCTN29313500) and PPROMEXIL-2 trial (ISRCTN05689407), two multicentre RCTs using the same protocol, conducted between 2007 and 2010 evaluating IoL versus EM in women with late preterm PROM. The PPROMEXIL Follow-up will analyse children of mothers with a singleton pregnancy (PPROMEXIL trial n=520, PPROMEXIL-2 trial n=191, total IoL n=359; total EM n=352). At 10-12 years of age all surviving children will be invited for a neurodevelopmental assessment using the Wechsler Intelligence Scale for Children-V, Color-Word Interference Test and the Movement Assessment Battery for Children-2. Parents will be asked to fill out questionnaires assessing behaviour, motor function, sensory processing, respiratory problems, general health and need for healthcare services. Teachers will fill out the Teacher Report Form and answer questions regarding school attainment. For all tests means with SDs will be compared, as well as predefined cut-off scores for abnormal outcome. Sensitivity analyses consisting of different imputation techniques will be used to deal with lost to follow-up. ETHICS AND DISSEMINATION: The study has been granted approval by the Medical Centre Amsterdam (MEC) of the AmsterdamUMC (MEC2016_217). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders. This protocol is published before analysis of the results. TRIAL REGISTRATION NUMBER: NL6623 (NTR6953).

Comparison of Childbirth Delivery Outcomes and Costs of Care Between Women Experiencing vs Not Experiencing Homelessness.

Importance: Women and families constitute the fastest-growing segments of the homeless population. However, there is limited evidence on whether women experiencing homelessness have poorer childbirth delivery outcomes and higher costs of care compared with women not experiencing homelessness. Objective: To compare childbirth delivery outcomes and costs of care between pregnant women experiencing homelessness vs those not experiencing homelessness. Design, Setting, and Participants: This cross-sectional study included 15 029 pregnant women experiencing homelessness and 308 242 pregnant women not experiencing homelessness who had a delivery hospitalization in 2014. The study used statewide databases that included all hospital admissions in 3 states (ie, Florida, Massachusetts, and New York). Delivery outcomes and delivery-associated costs were compared between pregnant women experiencing homelessness and those not experiencing homelessness cared for at the same hospital (analyzed using the overlap propensity-score weighting method and multivariable regression models with hospital fixed effects). The Benjamini-Hochberg false discovery rate procedure was used to account for multiple comparisons. Data were analyzed from January 2020 through May 2020. Exposure: Housing status at delivery hospitalization. Main Outcomes and Measures: Outcome variables included obstetric complications (ie, antepartum hemorrhage, placental abnormalities, premature rupture of the membranes, preterm labor, and postpartum hemorrhage), neonatal complications (ie, fetal distress, fetal growth restriction, and stillbirth), delivery method (ie, cesarean delivery), and delivery-associated costs. Results: Among 15 029 pregnant women experiencing homelessness (mean [SD] age, 28.5 [5.9] years) compared with 308 242 pregnant women not experiencing homelessness (mean [SD] age, 29.4 [5.8] years) within the same hospital, those experiencing homelessness were more likely to experience preterm labor (adjusted probability, 10.5% vs 6.7%; adjusted risk difference [aRD], 3.8%; 95% CI, 1.2%-6.5%; adjusted P = .03) and had higher delivery-associated costs (adjusted costs, $6306 vs $5888; aRD, $417; 95% CI, $156-$680; adjusted P = .02) compared with women not experiencing homelessness. Those experiencing homelessness also had a higher probability of placental abnormalities (adjusted probability, 4.0% vs 2.0%; aRD, 1.9%; 95% CI, 0.4%-3.5%; adjusted P = .053), although this difference was not statistically significant. Conclusions and Relevance: This study found that women experiencing homelessness, compared with those not experiencing homelessness, who had a delivery and were admitted to the same hospital were more likely to experience preterm labor and incurred higher delivery-associated costs. These findings suggest wide disparities in delivery-associated outcomes between women experiencing homelessness and those not experiencing homelessness in the US. The findings highlight the importance for health care professionals to actively screen pregnant women for homelessness during prenatal care visits and coordinate their care with community health programs and social housing programs to make sure their health care needs are met.

Prophylactic anticoagulation for preterm premature rupture of membranes: a decision analysis.

BACKGROUND: The current standard of care in the setting of preterm premature rupture of membranes involves antenatal hospitalization until delivery. The reduced physical activity during this time compounds the heightened risk for venous thromboembolism in pregnancy. Prophylactic anticoagulation can decrease this risk of venous thromboembolism; however, this benefit must be balanced against the risks of precluding neuraxial analgesia or increasing the risk of postpartum hemorrhage. OBJECTIVE: The objective of this study was to determine the optimal modality for venous thromboembolism prophylaxis during hospitalization for preterm premature rupture of membranes using a decision analysis model. STUDY DESIGN: A decision-analytical Markov model was constructed using the TreeAge software comparing the use of unfractionated heparin, low-molecular-weight heparin or no anticoagulation in women with a singleton pregnancy who were hospitalized for preterm premature rupture of membranes after 24 weeks and remained hospitalized until delivery. Maternal outcomes examined included attainment of neuraxial analgesia (vs no analgesia for vaginal delivery or general anesthesia for cesarean delivery), venous thromboembolism, postpartum hemorrhage, and maternal death. Probabilities and utilities were derived from existing literature. Sensitivity analyses were performed to interrogate model assumptions, and a Monte Carlo probabilistic sensitivity analysis was performed to examine the robustness of the model. RESULTS: In this decision-analytical model, no prophylactic anticoagulation maximized maternal utilities. Clinical outcomes among a theoretical cohort of 100,000 women are shown in the Table. The 1- and 2-way sensitivity analyses supported this conclusion. Monte Carlo probabilistic sensitivity analysis indicated that no prophylaxis was the preferred choice in 56% of simulations, unfractionated heparin in 34% of simulations, and low-molecular-weight heparin in 10% of simulations. CONCLUSION: Our results do not support the routine use of prophylactic anticoagulation in women admitted to the hospital for preterm premature rupture of membranes. These findings can be used to inform clinical decisions when admitting low-risk singleton pregnancies to the hospital in the setting of preterm premature rupture of membranes.

Diagnosis of rupture of membranes: AmniSure, clinical assessment, and the Food and Drug Administration warning.

BACKGROUND: An accurate diagnosis of rupture of membranes is critical to the rendering of appropriate maternity care in both preterm and term patients. Immunoassays, such as the one detecting placental alpha microglobulin-1 (AmniSure) in cervicovaginal secretions, have replaced the traditional speculum-based assessment in some clinical settings; however, the Food and Drug Administration recently issued a warning regarding the potential risks of using the test in isolation. OBJECTIVE: The study aimed to report the performance of AmniSure as a first-line nurse-administered screening test for rupture of membranes in our teaching county hospital obstetrical triage unit and as part of a clinical protocol to diagnose rupture of membranes. STUDY DESIGN: We conducted a retrospective secondary analysis of 310 randomly selected term and preterm patients with concern for rupture of membranes screened with the AmniSure test. We systematically reviewed medical records to determine membrane status at the time of the AmniSure test. We calculated test characteristics of the AmniSure test used independently and in conjunction with speculum-based assessment. RESULTS: Of 302 women evaluated for retrospective determination of membrane status at 17 to 41 weeks' gestation (median, 36.6 weeks' gestation), 208 (68.9%) were intact and 94 (31.1%) were ruptured at the time of the AmniSure test using a gold standard of retrospective membrane status determined by medical record review. A total of 4 false-negative AmniSure results and 16 false-positive AmniSure results were identified. The AmniSure test used independently had a sensitivity of 95.7%, specificity of 92.3%, positive predictive value of 84.9%, and negative predictive value of 98.0%. A rupture of membranes protocol combining AmniSure and clinical assessment had a sensitivity of 98.2%, specificity of 99.5%, positive predictive value of 100.0%, and negative predictive value of 100.0%. CONCLUSION: The AmniSure has a high sensitivity as a first-line nurse-administered screening test for membrane rupture. Consistent with the Food and Drug Administration warning, the sensitivity, specificity, positive predictive value, and negative predictive value are improved when it is used as part of a clinical protocol and not in isolation. Determination of membrane status remains challenging in a small subset of patients, especially those with an equivocal speculum-based assessment; therefore, engaging women in their care and careful follow-up for identifying persistent or recurrent symptoms are required.

Assessment of Fetal Lung Maturity Using Quantitative Ultrasound Analysis in Patients with Prelabor Rupture of Membranes.

INTRODUCTION: Prelabor rupture of membranes (PROM) is a frequent clinical situation, and the decision about the best time for delivery remains controversial, mainly due to the risk of neonatal respiratory morbidity (NRM). Assessment of fetal lung maturity using ultrasound, a safe method and widely used in current obstetrical practice, could change this scenario. This study was designed to evaluate the ability of quantitative ultrasound method QuantusFLM® to predict NRM in patients with PROM and whether maternal BMI, gestational age, occurrence of the disease, and presence of oligohydramnios influenced the performance. METHODS: Patients with singleton gestations, diagnosis of PROM, and gestational age between 24 and 38 weeks and 6 days were included. Fetal lung image was acquired by ultrasound within 48 h prior to delivery and analyzed by QuantusFLM®. The results were then paired with neonatal outcomes to assess the program's ability to predict the NRM in this specific group. A logistic regression model was created to analyze factors that could affect the test results. RESULTS: Fifty-four patients were included. Mean maternal BMI was 28.99 kg/m2, and in 25 patients (46.2%), oligohydramnios was observed at the time of examination. Mean gestational age at delivery was 35 weeks and 4 days, and the NRM prevalence was of 18.5%. QuantusFLM® predicted NRM with a 60% sensitivity, 79.5% specificity, 40% positive predictive value, 89.7% negative predictive value, and 75.6% accuracy. Maternal BMI, disease occurrence, presence of oligohydramnios, and gestational age did not interfere with the evaluation. CONCLUSION: This study demonstrates a good accuracy of QuantusFLM® as a NRM predictor in patients with PROM, with particular reliability in identifying that pulmonary maturity has already occurred.

Utility of ultrasound assessment in management of pregnancies with preterm prelabor rupture of membranes.

OBJECTIVES: To evaluate the utility of ultrasound markers in the management of pregnancies complicated by preterm prelabor rupture of membranes (PPROM) between 23 + 0 and 33 + 6 weeks' gestation, and to assess the ability of ultrasound markers to predict adverse neonatal outcomes. METHODS: This was a retrospective cohort study of all patients with PPROM between 23 + 0 and 33 + 6 weeks' gestation and latency period (PPROM to delivery) > 48 h, who delivered before 34 weeks' gestation at a tertiary referral center between 2005 and 2017. All patients underwent a non-stress test daily and an ultrasound scan twice a week for assessment of amniotic fluid volume, biophysical profile (BPP) and umbilical artery (UA) pulsatility index (PI). In patients with suspected fetal growth restriction, fetal middle cerebral artery (MCA)-PI was also assessed and the cerebroplacental ratio (CPR) calculated. The last ultrasound examination performed prior to delivery was analyzed. We compared the characteristics and outcomes between women who were delivered owing to clinical suspicion of chorioamnionitis and those who were not delivered for this indication. The primary objective was to evaluate the utility of ultrasound in the management of patients with PPROM. The secondary objective was to assess the diagnostic performance of ultrasound markers (BPP score < 6, oligohydramnios, UA-PI > 95th percentile, MCA-PI < 5th percentile, CPR < 5th percentile) for the prediction of composite adverse neonatal outcome, which was defined as the presence of one or more of: perinatal death, respiratory distress syndrome, periventricular leukomalacia, intraventricular hemorrhage Grade 3 or 4, necrotizing enterocolitis, hypoxic ischemic encephalopathy, neonatal sepsis or neonatal seizures. RESULTS: A total of 504 women were included in the study, comprising 120 with suspected chorioamnionitis and 384 without. Women with suspected chorioamnionitis, compared with those without, were less likely to be nulliparous (34.2% vs 45.3%; P = 0.03) and more likely to have fever (50.8% vs 2.6%; P < 0.001) and be delivered by Cesarean section (69.2% vs 42.4%; P < 0.001), mainly owing to a history of previous Cesarean section (18.3% vs 9.1%; P = 0.005) and to having non-reassuring fetal heart rate tracings (32.5% vs 14.6%; P < 0.001). No significant differences were found between the two groups with regard to the median amniotic fluid volume, overall BPP score, BPP score < 6, MCA-PI or CPR. Median UA-PI was slightly higher in the suspected-chorioamnionitis group, yet the incidence of UA-PI > 95th percentile was similar between the two groups. There was a higher incidence of composite adverse neonatal outcome in the group with suspected chorioamnionitis than in the group without (78.3% vs 64.3%, respectively; P = 0.004). However, on logistic regression analysis, none of the ultrasound markers evaluated was found to be associated with chorioamnionitis or composite adverse neonatal outcome, and they all had a poor diagnostic performance for the prediction of chorioamnionitis and composite adverse neonatal outcome. CONCLUSIONS: Commonly used ultrasound markers in pregnancies complicated by PPROM were similar between women delivered for suspected chorioamnionitis and those delivered for other indications, and performed poorly in predicting composite adverse neonatal outcome. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

A retrospective cohort study of fetal assessment following preterm premature rupture of membranes.

OBJECTIVE: To evaluate maternal and neonatal outcomes following management of preterm premature rupture of membranes (PPROM) by two fetal assessment strategies. METHODS: In a retrospective cohort study performed at two hospitals in Philadelphia, Pennsylvania between July 2010 and June 2015, data were reviewed from 180 singleton pregnancies with PPROM at 230 -336  weeks of gestation that underwent expectant management. Outcomes were compared between continuous electronic fetal heart monitoring (EFM) with daily biophysical profile (BPP) ("continuous monitoring") and non-stress test (NST) three times per day ("periodic monitoring") using Mann-Whitney U and Fisher exact tests. RESULTS: Overall, 119 (66.1%) pregnancies were assessed by continuous monitoring and 61 (33.9%) by periodic monitoring. There was no difference in frequency of intrauterine death between the continuous monitoring (1, 0.8%) and periodic monitoring (3, 4.9%) groups (OR, 0.16; 95% CI, 0.02-1.61). The continuous monitoring group was more likely to have an interventional (OR, 2.17; 95% CI, 1.06-4.44) or cesarean (OR 3.30, 95% CI 1.70-6.38) delivery. CONCLUSION: Continuous EFM with daily BPP was associated with higher rates of intervention and cesarean delivery compared with periodic NST, but there was no difference in intrauterine or perinatal mortality.

Cost Analysis of Azithromycin versus Erythromycin in Pregnancies Complicated by Preterm Premature Rupture of Membranes.

OBJECTIVE: To quantify the potential cost savings if azithromycin is substituted for erythromycin in women with preterm premature rupture of membranes (PPROM). STUDY DESIGN: Secondary analysis of a multicentered study investigating magnesium sulfate for the prevention of cerebral palsy in premature infants. All patients with PPROM who received antibiotics for prophylaxis were included in the analysis. The number of expected doses each patient would have received was calculated for erythromycin, multidose azithromycin, and single-dose azithromycin regimens accounting for latency from PPROM to delivery. The wholesale acquisition cost was used to calculate the expected cost of each regimen. RESULTS: There were 981 PPROM patients who received a penicillin class antibiotic and erythromycin. Patients would have received 7,528 intravenous doses and 10,194 oral doses of erythromycin at a combined cost of $357,169. In comparison, patients would have received 6,422 and 3,942 doses at a cost of $15,669 and $9,574 for the multidose and single-dose azithromycin regimens respectively, which represents a more than 95% cost reduction for either regimen compared with erythromycin. CONCLUSION: The use of azithromycin substituted for erythromycin in the standard antibiotic regimen of women with PPROM represents a potential for substantial cost reduction.

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis.

BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

Assessment of oxidative damage and enzymatic antioxidant system activity on the umbilical cord blood and saliva from preterm newborns with risk factors for early-onset neonatal sepsis

SUMMARY BACKGROUND: To determine the concentration of the Lipid Peroxidation Marker: Malondialdehyde (MDA), and Antioxidant Markers: Superoxide Dismutase (SOD), Glutathione Peroxidase (GPX), Catalase (CAL) in umbilical cord blood and in unstimulated saliva in the first 24 and 48 hours of life in the PTNB of mothers with and without risk factors for early-onset neonatal sepsis. METHODS: Cross-sectional study with the signing of informed consent by the pregnant women and application of a standard questionnaire classifying the PTNB in Group 1 or 2. RESULTS: Twenty-one PTNB were studied. Regarding gender, birth weight, need for oxygen, use of phototherapy, diagnosis of assumed sepsis, presence of fetal distress, number of pregnancies, type of delivery, use of corticosteroids, premature rupture of membranes, maternal fever, chorioamnionitis, APGAR at the 5th and 10th minute of life. Statistical analysis was performed with the Mann-Whitney test (p = 0.019) on the GPX variable of umbilical cord blood in the group of mothers with risk factors for early-onset neonatal sepsis. There was no statistical difference in the MDA, SOD, and CAT variables of the group with risk factors and in any variable of the group without risk factors. CONCLUSION: There was an increase of the GPX concentration in the blood from the umbilical vein in the group with risk factors for early-onset neonatal sepsis. There was no statistical significance in the comparison of saliva and umbilical cord blood. There was no statistically significant difference in MDA, SOD, CAT.

RESUMO OBJETIVOS: Determinar a concentração do marcador de peroxidação lipídica: Malondialdeído (MDA) e dos marcadores antioxidantes: Superóxido Dismutase (SOD), Glutationa Peroxidase (GPX), Catalase (CAL) no sangue do cordão umbilical e na saliva não estimulada nas primeiras 24 e 48 horas de vida nos RNPT de mães com e sem fatores de risco para sepse neonatal precoce. METODOLOGIA: Estudo transversal com a assinatura do termo de consentimento livre esclarecido pela gestante e aplicação de um questionário padrão classificando o RNPT no Grupo 1 ou 2. RESULTADOS: Foram estudados 21 RNPT. Quanto ao gênero, peso ao nascimento, necessidade de oxigênio, uso de fototerapia, diagnóstico de sepse presumida, presença de sofrimento fetal, número de gestações, tipo de parto, uso de corticoide, rotura prematura de membranas, a presença de febre materna, a presença de corioamnionite, Apgar no 50 e 100 minuto de vida, a análise estatística foi feita com o teste de Mann-Whitney (p=0,019) na váriável GPX do sangue do cordão umbilical no grupo das mães com fatores de risco para sepse neonatal precoce. Não houve diferença estatística nas outras variáveis MDA, SOD, CAT do grupo com fatores de risco e em nenhuma variável do grupo sem fatores de risco. CONCLUSÃO: O aumento de duas vezes a concentração da GPX no sangue da veia umbilical dos RNPT do grupo das mães com fatores de risco para sepse neonatal precoce. Sem significância estatística na comparação entre a saliva e o sangue do cordão umbilical. Não houve diferença estatisticamente significante nas variáveis MDA, SOD e CAT.

Cerclage is associated with the increased risk of preterm birth in women who had cervical conization.

BACKGROUND: The aim of this study was to determine the effect of cerclage in women who underwent cervical conization. METHODS: Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2009-2013. Women who had a conization in 2009 and a subsequent first delivery between 2009 and 2013 in Korea were enrolled. RESULTS: Among the women who had conization in 2009, 1075 women had their first delivery between 2009 and 2013. A cerclage was placed in 161 of the women who were treated by conization. The rate of preterm birth was higher in the women who were treated with cerclage following a conization compared with those without cerclage (10.56 vs 4.27, p < 0.01, respectively). The multivariate regression analysis revealed that the women who were treated cerclage following a conization had an increased risk of preterm delivery compared with women without cerclage (odds ratio (OR), 2.6, 95% confidence interval (CI), 1.4-4.9). CONCLUSION: Our study showed that cerclage associated with an increased risk of preterm birth and preterm premature rupture of membranes in women who underwent conization. Further studies are required to clarify the mechanism by which cerclage affects the risk of preterm birth.

Maternal lead exposure and premature rupture of membranes: a birth cohort study in China.

OBJECTIVES: Maternal exposure to lead (Pb) has been suggested to correlate with adverse birth outcomes, but evidence supporting an association between Pb exposure and premature rupture of membranes (PROM) is limited. The aim of our study was to investigate whether maternal Pb exposure was associated with PROM and preterm PROM. DESIGN: Cross-sectional cohort study. STUDY POPULATION: The present study involved 7290 pregnant women from the Healthy Baby Cohort in Wuhan, China, during 2012-2014. MAIN OUTCOME MEASURES: PROM was defined as spontaneous rupture of amniotic membranes before the onset of labour and was determined with a pH ≥6.5 for vaginal fluid. Maternal urinary Pb level was adjusted by creatinine concentration, and its relationship with PROM was analysed by logistic regression. RESULTS: The IQR of maternal urinary Pb concentrations of the study population was 2.30-5.64 µg/g creatinine with a median of 3.44 µg/g creatinine. Increased risk of PROM was significantly associated with elevated levels of Pb in maternal urine (adjusted OR 1.23, 95% CI 1.0 to 1.47 for the medium tertile; adjusted OR 1.51, 95% CI 1.27 to 1.80 for the highest tertile). The risk of preterm PROM associated with Pb levels was significantly higher when compared with the lowest tertile (adjusted OR 1.24, 95% CI 0.80 to 1.92 for the medium tertile; adjusted OR 1.73, 95% CI 1.15 to 2.60 for the highest tertile). In addition, the relationship between Pb and PROM was more pronounced among primiparous women than multiparous women (p for interaction <0.01). CONCLUSIONS: Our study found that higher levels of maternal Pb exposure was associated with increased risk of PROM, indicating that exposure to Pb during pregnancy may be an important risk factor for PROM.

Interbirth Interval and Pregnancy Complications and Outcomes: Findings from the Pregnancy Risk Assessment Monitoring System.

INTRODUCTION: Although the definition of a short interbirth interval has been inconsistent in the literature, Healthy People 2020 recommends that women wait at least 18 months after a live birth before attempting their next pregnancy. In the United States, approximately 33% of pregnancies are conceived within 18 months of a previous birth. Pregnancies that result from short interbirth intervals can pose serious risks. The objective of this study was to determine the association between interbirth interval and understudied pregnancy complications and outcomes, including small for gestational age (SGA) infants, premature rupture of membranes (PROM), preterm PROM (PPROM), placenta previa, and gestational diabetes, using Pregnancy Risk Assessment and Monitoring System data from Mississippi and Tennessee. METHODS: This study collected self-reported information from 2212 women on interbirth interval (≤18 months, ie, short; 19-35 months, ie, intermediate; and ≥36 months, ie, long; referent), PPROM, placenta previa, and gestational diabetes. SGA and PROM data were obtained from birth certificates. Logistic regression was used to calculate odds ratios (ORs) and 95% CIs. RESULTS: After adjustment, there were no strong associations between interbirth interval and PPROM, gestational diabetes, or SGA infants. However, women with shorter intervals had increased odds of PROM (short: OR, 3.54; 95% CI, 1.22-10.23 and intermediate: OR, 4.09; 95% CI, 1.28-13.03) and placenta previa (short: OR, 2.58; 95% CI, 1.10-6.05 and intermediate: OR, 1.69; 95% CI, 0.94-3.05). DISCUSSION: The study's findings provide further support for encouraging women to space their pregnancies appropriately. Moreover, findings underscore the need to provide women with family planning services so that closely spaced pregnancies and unintended pregnancies can be avoided. Additional studies of the role of interbirth interval on these understudied pregnancy complications and outcomes are warranted.