Re-evaluating the Use of Contraction Stress Test in Term Fetal Growth Restriction: A Retrospective Study

Re-evaluating the Use of Contraction Stress Test in Term Fetal Growth Restriction: A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Re-evaluating the Use of Contraction Stress Test in Term Fetal Growth Restriction: A Retrospective Study Roie Alter, Hagar HERZ, Adiel COHEN, Naama LESSANS, Yossef EZRA, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4735277/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose This study aimed to evaluate the prognostic utility of the contraction stress test (CST) for fetuses diagnosed with Fetal Growth Restriction (FGR) and its impact on perinatal outcomes. Methods A retrospective cohort study analyzed data from term singleton deliveries over two years. FGR was diagnosed with a birthweight below the 3rd percentile or prenatally below the 10th percentile with abnormal Doppler findings. The comparison included SGA fetuses, defined by birthweight between the 3rd and 10th percentiles. The cohort was categorized into three groups: 1) FGR with negative CST, 2) FGR without CST, and 3) SGA fetuses. Primary outcomes were emergency cesarean delivery rates, and secondary outcomes included composite neonatal adverse events and a combined metric of neonatal and maternal adverse events. Results The analysis included 1,688 records: 33 FGR with negative CST, 275 FGR without CST, and 1,123 SGA. Emergency cesarean delivery rates were similar between FGR with negative CST (15.2%) and without CST (14.9%), but higher compared to SGA (9.7%, p = .025). Composite neonatal adverse events did not differ significantly between FGR groups (21.2% vs 24.7%) but were higher than SGA (8.1%, p < .001). Combined neonatal and maternal adverse events also did not differ between FGR groups (30.3% vs 33.5%) but were higher than SGA (15.1%, p < .001). Conclusion The contraction stress test did not reduce the risk of adverse maternal or neonatal outcomes in fetuses diagnosed with fetal growth restriction. fetal growth restriction neonatal outcomes emergency cesarean delivery contraction stress test induction of labor mode of delivery Figures Figure 1 Figure 2 Introduction Fetal growth restriction (FGR) is a condition in which a fetus fails to achieve its genetically predetermined growth potential. The most common cause of FGR in an otherwise healthy pregnancy, is impaired, placental function, though if variety of factors may contribute[ 1 ]. Consequently, fetuses with FGR are at an elevated risk of perinatal morbidity and mortality, particularly those with birth weights below the 3rd percentile or those presenting with abnormal umbilical artery Doppler velocimetry. Several diagnostic criteria for FGR exist, some based solely on fetal biometric measurements (abdominal circumference [AC] or estimated fetal weight [EFW] below the 3rd percentile)[ 1 ], while others include abnormal Doppler findings. It is critical to distinguish that not all small-sized fetuses (small-for-gestational-age (SGA) – birth weight below the 10th percentile for gestational age) are FGR[ 2 ]. The optimal delivery mode for pregnancies complicated by FGR remains controversial. While vaginal delivery offers potential benefits, FGR fetuses are more susceptible to intrapartum fetal heart rate decelerations, which have been linked to significantly higher lactate levels in FGR fetuses compared to those who are appropriate-for-gestational-age (AGA) fetuses[ 3 ]. This finding suggests that FGR fetuses may have a reduced tolerance to labor stress, potentially increasing the risk of metabolic acidosis at birth. Studies report a substantial increase in cesarean delivery rates (75–95%) for FGR pregnancies with abnormal umbilical artery Doppler velocimetry[ 4 ]. This is likely due to heightened concerns about fetal well-being during labor. However, these high cesarean rates limit our ability to definitively assess the potential risks and benefits associated with vaginal delivery in this specific population. The rate of emergency C-sections (cesarean deliveries) for small-for-gestational-age (SGA) babies is around 15%. However, some prospective studies have found a higher C-section rate (17–32%) in SGA babies with abnormal umbilical blood flow, compared to 6–9% for those with normal umbilical artery Doppler results[ 5 ]. To date, no randomized controlled trials have been conducted to definitively determine the optimal mode of delivery for SGA fetuses. It is established that FGR by itself is not an indication for cesarean delivery[ 6 ]. Traditionally, fetal well-being has been assessed in utero using three modalities: non-stress test (NST), biophysical profile (BPP), and contraction stress test (CST). The CST operates on the principle that uterine contractions may transiently diminish placental blood flow, potentially inducing temporary fetal hypoxia, which can manifest as fetal heart rate decelerations. An antepartum CST with no late or significant variable decelerations is associated with a very low rate of antepartum stillbirth (0.04%), indicating a low risk of perinatal mortality and morbidity[ 7 ]. This study investigates the usefulness of a negative Contraction Stress Test (CST) performed before delivery induction in pregnancies complicated by Fetal Growth Restriction (FGR). We hypothesize that a negative CST result may predict a lower risk of adverse outcomes for both mothers and newborns. Materials and Methods Study Design and Population This retrospective cohort study analyzed data collected from electronic medical records of all live, singleton, SGA deliveries at two campuses of a tertiary referral hospital between 2019 and 2020. Birth weight was recorded immediately after delivery and verified upon the newborn’s admission to the neonatal unit. SGA deliveries were defined as neonates with birth weight below the 10th percentile for gestational age. FGR neonates were defined according to Delphi consensus criteria (e.g., birthweight below the 3rd percentile or the 10th percentile with abnormal Doppler findings) or those who were clinically diagnosed as FGR after abnormal CST. Elective cesarean deliveries, preterm births (< 37 weeks of gestation), major birth defects, and out-of-hospital births were excluded from this study. Contraction Stress Test Protocol This study employed a CST protocol involving continuous electronic fetal heart rate (FHR) monitoring. Intravenous oxytocin was infused to stimulate uterine contractions, aiming for three contractions within a 10-minute window during the 30-minute test duration. CST Interpretation The attending physician in the delivery room interpreted the CST results. A negative test outcome was assigned if no late or significant variable decelerations were observed in the FHR tracing. Conversely, a positive test result was designated if late decelerations occurred in more than 50% of the contractions. Cohort Grouping The cohort was stratified into three comparison groups: 1) FGR with negative CST : Fetuses diagnosed with FGR who had a negative CST result. 2) FGR without CST : Fetuses diagnosed with FGR who did not undergo a CST. 3) SGA (not FGR) : Fetuses with birth weight between the 3rd and 10th percentile for gestational age, without a history of abnormal antepartum Doppler velocimetry. Outcome Measures The primary outcomes were composite neonatal adverse eventswhich included any of the following: Apgar score < 7 at 5 minutes, umbilical cord blood pH < 7.1, neonatal intensive care unit (NICU) admission, neonatal admission lasting longer than 4 days, neonatal intubation, or neonatal intraventricular hemorrhage (IVH). Composite neonatal and maternal adverse events included either one of the composite neonatal adverse events fulfilled or an emergent cesarean delivery. Statistical Analysis To test the association between two categorical variables, the Chi-Square (χ 2 ) test and the Fisher's exact test were used. The comparison of a quantitative variable between two independent groups was conducted using the two-sample t-test, while comparison among three independent groups utilized One-way ANOVA. Post-Hoc tests were applied using the Dunnett T3 approach, for the correction of the significance level. All tests applied were two-tailed, and a p -value of less than .05 was considered statistically significant. Data were analyzed using Software Package for Statistics and Simulation (SPSS 25 for Windows, IBM Corp, Armonk, NY, USA). Ethical Consideration The study was approved by the local Institutional Review Board (IRB), with the assigned reference number: 0440-22-HMO. Results During the study period, a total of 1,688 singleton deliveries met the inclusion criteria. Of these, 257 cases were excluded, leaving a final cohort of 1,431 participants dividing into three groups: 1) FGR with negative CST (N = 33), 2) FGR without CST (N = 275) and 3) SGA (N = 1,123). (Fig. 1) Demographic characteristics and outcomes of the study groups are shown in Table 1 . No significant differences were observed in neonatal or composite outcomes between the first two FGR groups. However, significant differences were found between the FGR groups and the SGA group (Fig. 2): both FGR groups had earlier gestational ages (38.78 vs 39.38 weeks of gestation, mean difference [95% Confidence interval] 0.603 [0.455–0.750], p < .01); a higher induction rate was observed in both FGR groups compared to the SGA group (43.7 vs 24.9%, OR 2.34 [1.77–3.1], p < .01; the incidence of cesarean delivery was higher in the FGR group as compared to the SGA group (14.9 vs 9.7%, OR 1.65 [1.14–2.4], p < .01); neonates in the FGR groups required a longer length of stay in the hospital (4.52 vs 2.80 days, mean difference 1.72 [1.42–2.02], p < .01)), and more NICU admissions (7.8 vs 1.3%, OR 6.2 [3.2–12.1], p < .01) compared to the SGA group. Table 1 – Comparison of maternal delivery and neonatal characteristics between study groups. FGR with negative CST n = 33 (2.3%) FGR without CST n = 275 (19.2%) SGA not FGR n = 1123 (78.5%) p -value Maternal Age, years 28.55 ± 5.21 [21–40] 29.55 ± 5.81 [18–44] - .342 BMI, kg/m 2 27.47 ± 5.63 24.95 ± 4.63 - .004 Parity 2.27 ± 2.02 2.51 ± 1.96 - .521 Age, years 28.55 ± 5.21 [21–40] 29.55 ± 5.81 [18–44] 28.09 ± 5.36 [18–46] .998 BMI, kg/m 2 27.47 ± 5.63 24.95 ± 4.63 25.29 ± 4.62 .023 Parity 2.27 ± 2.02 2.51 ± 1.96 2.31 ± 1.74 .249 Labor and delivery Gestational age, weeks 37.85 ± 0.83 [37–40] 38.89 ± 1.24 [37–42] - < .001 Induction of labor 25 (89.3) 90 (38.3) - < .001 Vaginal Delivery 22 (66.7) 200 (72.7) - .464 Cesarean Delivery 5 (15.2) 41 (14.9) - .971 Gestational age, weeks 37.85 ± 0.83 [37–40] 38.89 ± 1.24 [37–42] 39.38 ± 1.15 [37–42] < .001 Induction of labor 25 (89.3) 90 (38.3) 255 (24.9) < .001 Vaginal Delivery 22 (66.7) 200 (72.7) 846 (75.4) .085 Cesarean Delivery 5 (15.2) 41 (14.9) 109 (9.7) .025 Neonatal Male 14 (42.4) 115 (41.8) - .947 Birthweight, gram 2294 ± 190 [1834–2570] 2301 ± 197 [1638–2700] - .848 5-minutes Apgar < 7 0 3 (1.1) - 1 Umbilical Artery pH 7.27 ± 0.10 [6.97–7.38] 7.27 ± 0.09 [7.00-7.48] - .957 pH < 7.2 1 (7.1) 31 (18.9) - .470 pH 4 days 6 (18.2) 64 (23.3) - .510 > 7 days 2 (6.1) 25 (9.1) - .752 NICU admissions 2 (6.1) 22 (8.0) - 1 IVH 0 1 (0.4) - 1 Mechanical ventilation .634 NIPPV 3 (9.1) 18 (6.5) - Intubation 0 3 (1.1) - Male 14 (42.4) 115 (41.8) 562 (50) .040 Birthweight, gram 2294 ± 190 [1834–2570] 2301 ± 197 [1638–2700] 2651 ± 170 [2180–3300] < .001 5-minutes Apgar < 7 0 3 (1.1) 5 (0.4) .333 Umbilical Artery pH 7.27 ± 0.10 [6.97–7.38] 7.27 ± 0.09 [7.00-7.48] 7.28 ± 0.08 [7.02–7.46] .383 pH < 7.2 1 (7.1) 31 (18.9) 115 (17.7) .634 pH < 7.1 1 (7.1) 9 (5.5) 16 (2.5) .054 Admission length, days 4.48 ± 3.193 [2–18] 4.53 ± 4.318 [1–42] 2.80 ± 1.543 [0–26] 4 days 6 (18.2) 64 (23.3) 71 (6.3) 7 days 2 (6.1) 25 (9.1) 15 (1.3) < .001 NICU admissions 2 (6.1) 22 (8.0) 15 (1.3) < .001 IVH 0 1 (0.4) 1 (0.1) .384 Mechanical ventilation .089 NIPPV 3 (9.1) 18 (6.5) 47 (4.2) Intubation 0 3 (1.1) 4 (0.4) Composite Outcome Composite neonatal adverse events 7 (21.2%) 68 (24.7%) - .657 Composite neonatal and maternal adverse events 10 (30.3%) 92 (33.5%) - .717 Composite neonatal adverse events 7 (21.2%) 68 (24.7%) 91 (8.1%) < .001 Composite neonatal and maternal adverse events 10 (30.3%) 92 (33.5%) 170 (15.1%) < .001 Shaded cells compere only FGR groups (1 vs 2). Continuous variables are presented as Mean ± Standard deviation [range], and numerical values are presented as N (%). NICU: Neonatal Intensive Care Unit; IVH: Intraventricular Hemorrhage; NIPPV: Non-invasive Positive Pressure Ventilation. Discussion Principal Findings This study investigated the efficacy of performing a CST before labor induction in pregnancies diagnosed with FGR. The findings revealed no significant difference for either mothers or newborns in terms of adverse outcomes when comparing those who underwent a CST prior to induction versus those who did not. Notably, both FGR groups exhibited a higher risk of adverse outcomes compared to pregnancies affected by SGA but without FGR. These findings raise questions about the role of CST in FGR management prior to labor induction. Results The role of CST in managing FGR deliveries remains controversial considering these findings. However, some studies continue to support its use. Freeman et al. (1982) reported that CST was superior to the non-stress test (NST) for primary fetal surveillance in high-risk pregnancies with suspected uteroplacental insufficiency, associated with reduction in neonatal complications, including respiratory distress syndrome (RDS), low 5-minute Apgar scores, antepartum death, and perinatal mortality. Tanaka et al. (2019) conducted a retrospective case-control study of 73 neonates, comparing outcomes in FGR pregnancies managed with and without CST, finding a higher umbilical artery pO 2 levels in the CST group, though no significant differences in umbilical artery blood pH or delivery mode[ 8 ]. Similarly, a recent retrospective study by Różańska-Walędziak et al. (2023) suggested a potential role for CST in modern obstetrics, noting that a positive CST results could be a predictor of cesarean delivery[ 9 ]. Our study is the first, to our knowledge, to investigate the negative predictive value of CST performed before labor induction in pregnancies with FGR. Clinical Implications While some historical studies suggest benefits, the current study does not demonstrate a reduction in maternal and neonatal complications associated with a negative CST result prior to induction of labor in term singleton pregnancies affected by FGR. This aligns with several models that have tried to predict urgent cesarean sections, taking into account the severity of the FGR (EFW < 3rd percentile), cerebral Doppler velocimetry, and bishop score[ 10 ]. Another cohort study confirms similar results, with nearly 90% of successful inductions of FGR-affected pregnancies ending in vaginal delivery[ 11 ]. Research Implications The inconclusive role of CST in FGR management highlights the persistent unanswered question regarding the optimal management of FGR-affected fetus. However, it is possible that using a combined model that takes into account the severity of the growth restriction (i.e., EFW < 3rd percentile), placental function represented by Doppler flows (Cerebroplacental ratio and uterine artery velocimetry), and maternal cervical conditions represented by the Bishop score, instead of a single predictor, will provide better prediction of the mode of delivery. Strengths and Limitations The study design, comparing two FGR groups – one exposed to CST and the other not – compared with an SGA group, emphasize that the FGR group, even when selected by negative CST, remain susceptible to adverse perinatal and maternal effects. The use of composite neonatal and maternal adverse event outcomes provides a broader perspective on potential benefits or risks associated with CST. However, the retrospective nature of the study subject it to potential selection bias and confounding variables that may influence the results. Additionally, the lack of information on long-term neonatal outcomes limits our ability to assess the full impact of CST. Conclusions This study suggests that the routine use of CST in managing FGR may need to be reevaluated. However, well-designed, prospective studies are needed to confirm these findings and definitively determine the role of CST in this setting, considering the limitations of this current study. Overall, the current evidence is insufficient to recommend the routine use of CST in FGR management conclusively, considering the alternatives. Further research is necessary to elucidate the optimal role of CST in this clinical setting. Declarations Author Contributions RA: Conceptualization, Methodology, Visualization, Writing - Original Draft, Review & Editing. HH : Investigation, Formal analysis, Data Curation, Writing - Original Draft, Review & Editing. AC, NL : Validation, Investigation, Writing - Review & Editing. YE : Validation, Supervision, Writing - Review & Editing. DK : Conceptualization, Methodology, Supervision, Writing - Review & Editing Disclosure The authors report no conflict of interest. No funds, grants, or other support was received. References Lees CC, Stampalija T, Baschat A et al (2020) ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol 56(2):298–312 Fetal Growth Restriction (2021) ACOG Practice Bulletin, Number 227. Obstet Gynecol 137(2):E16–E28 Lin CC, Moawad AH, Rosenow PJ, River P (1980) Acid-base characteristics of fetuses with intrauterine growth retardation during labor and delivery. Am J Obstet Gynecol 137(5):553–559 Martins JG, Biggio JR, Abuhamad A (2020) Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012). Am J Obstet Gynecol 223(4):B2–B17 Royal College of Obstetricians and Gynaecologists (2014) Green-Top Guideline 31: The Investigation and Manangement of the Small-for-Gestational-Age Fetus. RCOG Green-top Guidel 31. ;(31):1–34 Melamed N, Baschat A, Yinon Y et al (2021) FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynecol Obstet 152(S1):3–57 Signore C, Freeman RK, Spong CY (2009) Antenatal testing-a reevaluation: Executive summary of a Eunice Kennedy Shriver National Institute of Child Health and Human Development wrkshop. Obstet Gynecol 113(3):687–701 Tanaka H, Furuhashi FH, Toriyabe K et al (2019) Management of fetal growth restriction using the contraction stress test: a case-control study. J Matern Neonatal Med 32(19):3221–3225 Różańska-Walędziak A, Czajkowski K, Walędziak M, Teliga-Czajkowska J (2020) The Present Utility of the Oxytocin Challenge Test—A Single-Center Study. J Clin Med 9(1):131 Garcia-Simon R, Figueras F, Savchev S, Fabre E, Gratacos E, Oros D (2015) Cervical condition and fetal cerebral Doppler as determinants of adverse perinatal outcome after labor induction for late-onset small-for-gestational-age fetuses. Ultrasound Obstet Gynecol 46(6):713–717 Figueras F, Savchev S, Triunfo S, Crovetto F, Gratacos E (2015) An integrated model with classification criteria to predict small-for-gestational-age fetuses at risk of adverse perinatal outcome. Ultrasound Obs Gynecol . ;45:279–285. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4735277","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":330649852,"identity":"bd74cb1f-ab72-43db-bcb9-ae03d43c7408","order_by":0,"name":"Roie Alter","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYDACdjApwcAPohIKiNHCzAzRItkA0mJAvBYGBoMDYJIIHfzN/AcfV1RYyBmfX5344YEBgzy/2AH8WiQOMzMbnjkjYWx24+1mCaDDDGfOTiBgzWFmNsnGNonEbTfObgBpSTC4TUCL/GFm9p9ALfWbZ5zd/IMoLQZAWxiBWhIM+Hu3EWeL4WFmY8mGMxKGM27wbrNIMJAg7Be5440PPzZU1Mnz95/dfPNHhY08vzQBLQggAVYpQaxyEOA/QIrqUTAKRsEoGEkAACP3PzaQGH3aAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5502-0135","institution":"Hadassah Hospital Ein Kerem: Hadassah University Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Roie","middleName":"","lastName":"Alter","suffix":""},{"id":330649853,"identity":"d3d83a6f-8899-43ae-9c6f-c20aef604233","order_by":1,"name":"Hagar HERZ","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hagar","middleName":"","lastName":"HERZ","suffix":""},{"id":330649854,"identity":"0f24845f-8787-482a-a684-04038d2a03a0","order_by":2,"name":"Adiel COHEN","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Adiel","middleName":"","lastName":"COHEN","suffix":""},{"id":330649855,"identity":"f370446e-4d52-4bd4-be4d-cee4e575cd89","order_by":3,"name":"Naama LESSANS","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Naama","middleName":"","lastName":"LESSANS","suffix":""},{"id":330649856,"identity":"5821ed1b-9ef0-4c08-ab81-0285c5e7ddff","order_by":4,"name":"Yossef EZRA","email":"","orcid":"","institution":"Hadassah Medical Organization: Hadassah University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yossef","middleName":"","lastName":"EZRA","suffix":""},{"id":330649857,"identity":"653683ab-9802-48bf-84ee-77699627e85a","order_by":5,"name":"Doron KABIRI","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Doron","middleName":"","lastName":"KABIRI","suffix":""}],"badges":[],"createdAt":"2024-07-13 13:13:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4735277/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4735277/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63280719,"identity":"0a5c175a-4650-4e7b-92c2-081f867ef369","added_by":"auto","created_at":"2024-08-26 12:51:57","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":104841,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4735277/v1/2ee706513216f451fae132f8.jpeg"},{"id":63280718,"identity":"7ccdbf96-9de6-4026-a29e-e0782c24651b","added_by":"auto","created_at":"2024-08-26 12:51:57","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":82581,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4735277/v1/808d79f9782b0e0980aad46e.jpeg"},{"id":64971885,"identity":"9003b271-820c-4121-bca6-641e33335da4","added_by":"auto","created_at":"2024-09-21 06:47:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":702100,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4735277/v1/a96276b2-bdd6-4e1b-b418-8bcda5e599ad.pdf"}],"financialInterests":"","formattedTitle":"Re-evaluating the Use of Contraction Stress Test in Term Fetal Growth Restriction: A Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFetal growth restriction (FGR) is a condition in which a fetus fails to achieve its genetically predetermined growth potential. The most common cause of FGR in an otherwise healthy pregnancy, is impaired, placental function, though if variety of factors may contribute[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Consequently, fetuses with FGR are at an elevated risk of perinatal morbidity and mortality, particularly those with birth weights below the 3rd percentile or those presenting with abnormal umbilical artery Doppler velocimetry. Several diagnostic criteria for FGR exist, some based solely on fetal biometric measurements (abdominal circumference [AC] or estimated fetal weight [EFW] below the 3rd percentile)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], while others include abnormal Doppler findings. It is critical to distinguish that not all small-sized fetuses (small-for-gestational-age (SGA) \u0026ndash; birth weight below the 10th percentile for gestational age) are FGR[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe optimal delivery mode for pregnancies complicated by FGR remains controversial. While vaginal delivery offers potential benefits, FGR fetuses are more susceptible to intrapartum fetal heart rate decelerations, which have been linked to significantly higher lactate levels in FGR fetuses compared to those who are appropriate-for-gestational-age (AGA) fetuses[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This finding suggests that FGR fetuses may have a reduced tolerance to labor stress, potentially increasing the risk of metabolic acidosis at birth. Studies report a substantial increase in cesarean delivery rates (75\u0026ndash;95%) for FGR pregnancies with abnormal umbilical artery Doppler velocimetry[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This is likely due to heightened concerns about fetal well-being during labor. However, these high cesarean rates limit our ability to definitively assess the potential risks and benefits associated with vaginal delivery in this specific population. The rate of emergency C-sections (cesarean deliveries) for small-for-gestational-age (SGA) babies is around 15%. However, some prospective studies have found a higher C-section rate (17\u0026ndash;32%) in SGA babies with abnormal umbilical blood flow, compared to 6\u0026ndash;9% for those with normal umbilical artery Doppler results[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo date, no randomized controlled trials have been conducted to definitively determine the optimal mode of delivery for SGA fetuses. It is established that FGR by itself is not an indication for cesarean delivery[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Traditionally, fetal well-being has been assessed in utero using three modalities: non-stress test (NST), biophysical profile (BPP), and contraction stress test (CST). The CST operates on the principle that uterine contractions may transiently diminish placental blood flow, potentially inducing temporary fetal hypoxia, which can manifest as fetal heart rate decelerations. An antepartum CST with no late or significant variable decelerations is associated with a very low rate of antepartum stillbirth (0.04%), indicating a low risk of perinatal mortality and morbidity[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study investigates the usefulness of a negative Contraction Stress Test (CST) performed before delivery induction in pregnancies complicated by Fetal Growth Restriction (FGR). We hypothesize that a negative CST result may predict a lower risk of adverse outcomes for both mothers and newborns.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Population\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study analyzed data collected from electronic medical records of all live, singleton, SGA deliveries at two campuses of a tertiary referral hospital between 2019 and 2020. Birth weight was recorded immediately after delivery and verified upon the newborn\u0026rsquo;s admission to the neonatal unit. SGA deliveries were defined as neonates with birth weight below the 10th percentile for gestational age. FGR neonates were defined according to Delphi consensus criteria (e.g., birthweight below the 3rd percentile or the 10th percentile with abnormal Doppler findings) or those who were clinically diagnosed as FGR after abnormal CST. Elective cesarean deliveries, preterm births (\u0026lt;\u0026thinsp;37 weeks of gestation), major birth defects, and out-of-hospital births were excluded from this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eContraction Stress Test Protocol\u003c/h2\u003e \u003cp\u003eThis study employed a CST protocol involving continuous electronic fetal heart rate (FHR) monitoring. Intravenous oxytocin was infused to stimulate uterine contractions, aiming for three contractions within a 10-minute window during the 30-minute test duration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eCST Interpretation\u003c/h2\u003e \u003cp\u003eThe attending physician in the delivery room interpreted the CST results. A negative test outcome was assigned if no late or significant variable decelerations were observed in the FHR tracing. Conversely, a positive test result was designated if late decelerations occurred in more than 50% of the contractions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eCohort Grouping\u003c/h2\u003e \u003cp\u003eThe cohort was stratified into three comparison groups: 1) \u003cb\u003eFGR with negative CST\u003c/b\u003e: Fetuses diagnosed with FGR who had a negative CST result. 2) \u003cb\u003eFGR without CST\u003c/b\u003e: Fetuses diagnosed with FGR who did not undergo a CST. 3) \u003cb\u003eSGA (not FGR)\u003c/b\u003e: Fetuses with birth weight between the 3rd and 10th percentile for gestational age, without a history of abnormal antepartum Doppler velocimetry.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eOutcome Measures\u003c/h2\u003e \u003cp\u003eThe primary outcomes were composite neonatal adverse eventswhich included any of the following: Apgar score\u0026thinsp;\u0026lt;\u0026thinsp;7 at 5 minutes, umbilical cord blood pH\u0026thinsp;\u0026lt;\u0026thinsp;7.1, neonatal intensive care unit (NICU) admission, neonatal admission lasting longer than 4 days, neonatal intubation, or neonatal intraventricular hemorrhage (IVH). Composite neonatal and maternal adverse events included either one of the composite neonatal adverse events fulfilled or an emergent cesarean delivery.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eTo test the association between two categorical variables, the Chi-Square (χ\u003csup\u003e2\u003c/sup\u003e) test and the Fisher's exact test were used. The comparison of a quantitative variable between two independent groups was conducted using the two-sample t-test, while comparison among three independent groups utilized One-way ANOVA. Post-Hoc tests were applied using the Dunnett T3 approach, for the correction of the significance level. All tests applied were two-tailed, and a \u003cem\u003ep\u003c/em\u003e-value of less than .05 was considered statistically significant. Data were analyzed using Software Package for Statistics and Simulation (SPSS 25 for Windows, IBM Corp, Armonk, NY, USA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eEthical Consideration\u003c/h2\u003e \u003cp\u003e The study was approved by the local Institutional Review Board (IRB), with the assigned reference number: 0440-22-HMO.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, a total of 1,688 singleton deliveries met the inclusion criteria. Of these, 257 cases were excluded, leaving a final cohort of 1,431 participants dividing into three groups: 1) FGR with negative CST (N\u0026thinsp;=\u0026thinsp;33), 2) FGR without CST (N\u0026thinsp;=\u0026thinsp;275) and 3) SGA (N\u0026thinsp;=\u0026thinsp;1,123). (Fig.\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eDemographic characteristics and outcomes of the study groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No significant differences were observed in neonatal or composite outcomes between the first two FGR groups. However, significant differences were found between the FGR groups and the SGA group (Fig.\u0026nbsp;2): both FGR groups had earlier gestational ages (38.78 vs 39.38 weeks of gestation, mean difference [95% Confidence interval] 0.603 [0.455\u0026ndash;0.750], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01); a higher induction rate was observed in both FGR groups compared to the SGA group (43.7 vs 24.9%, OR 2.34 [1.77\u0026ndash;3.1], \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;.01; the incidence of cesarean delivery was higher in the FGR group as compared to the SGA group (14.9 vs 9.7%, OR 1.65 [1.14\u0026ndash;2.4], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01); neonates in the FGR groups required a longer length of stay in the hospital (4.52 vs 2.80 days, mean difference 1.72 [1.42\u0026ndash;2.02], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01)), and more NICU admissions (7.8 vs 1.3%, OR 6.2 [3.2\u0026ndash;12.1], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.01) compared to the SGA group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Comparison of maternal delivery and neonatal characteristics between study groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFGR with negative CST\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;33 (2.3%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFGR without CST\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;275 (19.2%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSGA not FGR\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;1123 (78.5%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eMaternal\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.55\u0026thinsp;\u0026plusmn;\u0026thinsp;5.21 [21\u0026ndash;40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.55\u0026thinsp;\u0026plusmn;\u0026thinsp;5.81 [18\u0026ndash;44]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.342\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.47\u0026thinsp;\u0026plusmn;\u0026thinsp;5.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e.004\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.521\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.55\u0026thinsp;\u0026plusmn;\u0026thinsp;5.21 [21\u0026ndash;40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.55\u0026thinsp;\u0026plusmn;\u0026thinsp;5.81 [18\u0026ndash;44]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.09\u0026thinsp;\u0026plusmn;\u0026thinsp;5.36 [18\u0026ndash;46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27.47\u0026thinsp;\u0026plusmn;\u0026thinsp;5.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.29\u0026thinsp;\u0026plusmn;\u0026thinsp;4.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eLabor and delivery\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age, weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83 [37\u0026ndash;40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24 [37\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInduction of labor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (89.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200 (72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age, weeks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.85\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83 [37\u0026ndash;40]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.24 [37\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39.38\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15 [37\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInduction of labor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (89.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e255 (24.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVaginal Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e200 (72.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e846 (75.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.085\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCesarean Delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (15.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (14.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e.025\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNeonatal\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight, gram\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2294\u0026thinsp;\u0026plusmn;\u0026thinsp;190 [1834\u0026ndash;2570]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2301\u0026thinsp;\u0026plusmn;\u0026thinsp;197 [1638\u0026ndash;2700]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.848\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5-minutes Apgar\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUmbilical Artery pH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 [6.97\u0026ndash;7.38]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 [7.00-7.48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.957\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u0026thinsp;\u0026lt;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.470\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u0026thinsp;\u0026lt;\u0026thinsp;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.569\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission length, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.48\u0026thinsp;\u0026plusmn;\u0026thinsp;3.193 [2\u0026ndash;18]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;4.318 [1\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.956\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.752\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admissions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.634\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIPPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e115 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e562 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e.040\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight, gram\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2294\u0026thinsp;\u0026plusmn;\u0026thinsp;190 [1834\u0026ndash;2570]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2301\u0026thinsp;\u0026plusmn;\u0026thinsp;197 [1638\u0026ndash;2700]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2651\u0026thinsp;\u0026plusmn;\u0026thinsp;170 [2180\u0026ndash;3300]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5-minutes Apgar\u0026thinsp;\u0026lt;\u0026thinsp;7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.333\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUmbilical Artery pH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 [6.97\u0026ndash;7.38]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 [7.00-7.48]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08 [7.02\u0026ndash;7.46]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.383\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u0026thinsp;\u0026lt;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (18.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.634\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epH\u0026thinsp;\u0026lt;\u0026thinsp;7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.054\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission length, days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.48\u0026thinsp;\u0026plusmn;\u0026thinsp;3.193 [2\u0026ndash;18]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;4.318 [1\u0026ndash;42]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.80\u0026thinsp;\u0026plusmn;\u0026thinsp;1.543 [0\u0026ndash;26]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;4 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (23.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e71 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNICU admissions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIVH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.384\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNIPPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntubation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite Outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite neonatal adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (24.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.657\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite neonatal and maternal adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (33.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e.717\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite neonatal adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (24.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91 (8.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComposite neonatal and maternal adverse events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (33.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e170 (15.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eShaded cells compere only FGR groups (1 vs 2). Continuous variables are presented as Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;Standard deviation [range], and numerical values are presented as N (%). NICU: Neonatal Intensive Care Unit; IVH: Intraventricular Hemorrhage; NIPPV: Non-invasive Positive Pressure Ventilation.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrincipal Findings\u003c/p\u003e \u003cp\u003eThis study investigated the efficacy of performing a CST before labor induction in pregnancies diagnosed with FGR. The findings revealed no significant difference for either mothers or newborns in terms of adverse outcomes when comparing those who underwent a CST prior to induction versus those who did not. Notably, both FGR groups exhibited a higher risk of adverse outcomes compared to pregnancies affected by SGA but without FGR.\u003c/p\u003e \u003cp\u003eThese findings raise questions about the role of CST in FGR management prior to labor induction.\u003c/p\u003e\n\u003ch3\u003eResults\u003c/h3\u003e\n\u003cp\u003eThe role of CST in managing FGR deliveries remains controversial considering these findings. However, some studies continue to support its use. Freeman et al. (1982) reported that CST was superior to the non-stress test (NST) for primary fetal surveillance in high-risk pregnancies with suspected uteroplacental insufficiency, associated with reduction in neonatal complications, including respiratory distress syndrome (RDS), low 5-minute Apgar scores, antepartum death, and perinatal mortality. Tanaka et al. (2019) conducted a retrospective case-control study of 73 neonates, comparing outcomes in FGR pregnancies managed with and without CST, finding a higher umbilical artery pO\u003csub\u003e2\u003c/sub\u003e levels in the CST group, though no significant differences in umbilical artery blood pH or delivery mode[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Similarly, a recent retrospective study by R\u0026oacute;żańska-Walędziak et al. (2023) suggested a potential role for CST in modern obstetrics, noting that a positive CST results could be a predictor of cesarean delivery[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study is the first, to our knowledge, to investigate the negative predictive value of CST performed before labor induction in pregnancies with FGR.\u003c/p\u003e \u003cp\u003eClinical Implications\u003c/p\u003e \u003cp\u003eWhile some historical studies suggest benefits, the current study does not demonstrate a reduction in maternal and neonatal complications associated with a negative CST result prior to induction of labor in term singleton pregnancies affected by FGR. This aligns with several models that have tried to predict urgent cesarean sections, taking into account the severity of the FGR (EFW\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile), cerebral Doppler velocimetry, and bishop score[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Another cohort study confirms similar results, with nearly 90% of successful inductions of FGR-affected pregnancies ending in vaginal delivery[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eResearch Implications\u003c/p\u003e \u003cp\u003eThe inconclusive role of CST in FGR management highlights the persistent unanswered question regarding the optimal management of FGR-affected fetus. However, it is possible that using a combined model that takes into account the severity of the growth restriction (i.e., EFW\u0026thinsp;\u0026lt;\u0026thinsp;3rd percentile), placental function represented by Doppler flows (Cerebroplacental ratio and uterine artery velocimetry), and maternal cervical conditions represented by the Bishop score, instead of a single predictor, will provide better prediction of the mode of delivery.\u003c/p\u003e \u003cp\u003eStrengths and Limitations\u003c/p\u003e \u003cp\u003eThe study design, comparing two FGR groups \u0026ndash; one exposed to CST and the other not \u0026ndash; compared with an SGA group, emphasize that the FGR group, even when selected by negative CST, remain susceptible to adverse perinatal and maternal effects. The use of composite neonatal and maternal adverse event outcomes provides a broader perspective on potential benefits or risks associated with CST. However, the retrospective nature of the study subject it to potential selection bias and confounding variables that may influence the results. Additionally, the lack of information on long-term neonatal outcomes limits our ability to assess the full impact of CST.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study suggests that the routine use of CST in managing FGR may need to be reevaluated. However, well-designed, prospective studies are needed to confirm these findings and definitively determine the role of CST in this setting, considering the limitations of this current study.\u003c/p\u003e \u003cp\u003eOverall, the current evidence is insufficient to recommend the routine use of CST in FGR management conclusively, considering the alternatives. Further research is necessary to elucidate the optimal role of CST in this clinical setting.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRA:\u0026nbsp;\u003c/strong\u003eConceptualization, Methodology, Visualization, Writing - Original Draft, Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHH\u003c/strong\u003e: Investigation, Formal analysis, Data Curation, Writing - Original Draft, Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAC, NL\u003c/strong\u003e: Validation, Investigation, Writing - Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYE\u003c/strong\u003e: Validation, Supervision, Writing - Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDK\u003c/strong\u003e: Conceptualization, Methodology, Supervision, Writing - Review \u0026amp; Editing\u003c/p\u003e\n\u003cp\u003eDisclosure\u003c/p\u003e\n\u003cp\u003eThe authors report no conflict of interest. No funds, grants, or other support was received.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLees CC, Stampalija T, Baschat A et al (2020) ISUOG Practice Guidelines: diagnosis and management of small-for-gestational-age fetus and fetal growth restriction. Ultrasound Obstet Gynecol 56(2):298\u0026ndash;312\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFetal Growth Restriction (2021) ACOG Practice Bulletin, Number 227. Obstet Gynecol 137(2):E16\u0026ndash;E28\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin CC, Moawad AH, Rosenow PJ, River P (1980) Acid-base characteristics of fetuses with intrauterine growth retardation during labor and delivery. Am J Obstet Gynecol 137(5):553\u0026ndash;559\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartins JG, Biggio JR, Abuhamad A (2020) Society for Maternal-Fetal Medicine Consult Series #52: Diagnosis and management of fetal growth restriction: (Replaces Clinical Guideline Number 3, April 2012). Am J Obstet Gynecol 223(4):B2\u0026ndash;B17\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoyal College of Obstetricians and Gynaecologists (2014) Green-Top Guideline 31: The Investigation and Manangement of the Small-for-Gestational-Age Fetus. RCOG Green-top Guidel 31. ;(31):1\u0026ndash;34\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMelamed N, Baschat A, Yinon Y et al (2021) FIGO (international Federation of Gynecology and obstetrics) initiative on fetal growth: best practice advice for screening, diagnosis, and management of fetal growth restriction. Int J Gynecol Obstet 152(S1):3\u0026ndash;57\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSignore C, Freeman RK, Spong CY (2009) Antenatal testing-a reevaluation: Executive summary of a Eunice Kennedy Shriver National Institute of Child Health and Human Development wrkshop. Obstet Gynecol 113(3):687\u0026ndash;701\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka H, Furuhashi FH, Toriyabe K et al (2019) Management of fetal growth restriction using the contraction stress test: a case-control study. J Matern Neonatal Med 32(19):3221\u0026ndash;3225\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR\u0026oacute;żańska-Walędziak A, Czajkowski K, Walędziak M, Teliga-Czajkowska J (2020) The Present Utility of the Oxytocin Challenge Test\u0026mdash;A Single-Center Study. J Clin Med 9(1):131\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia-Simon R, Figueras F, Savchev S, Fabre E, Gratacos E, Oros D (2015) Cervical condition and fetal cerebral Doppler as determinants of adverse perinatal outcome after labor induction for late-onset small-for-gestational-age fetuses. Ultrasound Obstet Gynecol 46(6):713\u0026ndash;717\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFigueras F, Savchev S, Triunfo S, Crovetto F, Gratacos E (2015) An integrated model with classification criteria to predict small-for-gestational-age fetuses at risk of adverse perinatal outcome. \u003cem\u003eUltrasound Obs Gynecol\u003c/em\u003e. ;45:279\u0026ndash;285. \u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"fetal growth restriction, neonatal outcomes, emergency cesarean delivery, contraction stress test, induction of labor, mode of delivery","lastPublishedDoi":"10.21203/rs.3.rs-4735277/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4735277/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eThis study aimed to evaluate the prognostic utility of the contraction stress test (CST) for fetuses diagnosed with Fetal Growth Restriction (FGR) and its impact on perinatal outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA retrospective cohort study analyzed data from term singleton deliveries over two years. FGR was diagnosed with a birthweight below the 3rd percentile or prenatally below the 10th percentile with abnormal Doppler findings. The comparison included SGA fetuses, defined by birthweight between the 3rd and 10th percentiles. The cohort was categorized into three groups: 1) FGR with negative CST, 2) FGR without CST, and 3) SGA fetuses. Primary outcomes were emergency cesarean delivery rates, and secondary outcomes included composite neonatal adverse events and a combined metric of neonatal and maternal adverse events.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe analysis included 1,688 records: 33 FGR with negative CST, 275 FGR without CST, and 1,123 SGA. Emergency cesarean delivery rates were similar between FGR with negative CST (15.2%) and without CST (14.9%), but higher compared to SGA (9.7%, p\u0026thinsp;=\u0026thinsp;.025). Composite neonatal adverse events did not differ significantly between FGR groups (21.2% vs 24.7%) but were higher than SGA (8.1%, p\u0026thinsp;\u0026lt;\u0026thinsp;.001). Combined neonatal and maternal adverse events also did not differ between FGR groups (30.3% vs 33.5%) but were higher than SGA (15.1%, p\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe contraction stress test did not reduce the risk of adverse maternal or neonatal outcomes in fetuses diagnosed with fetal growth restriction.\u003c/p\u003e","manuscriptTitle":"Re-evaluating the Use of Contraction Stress Test in Term Fetal Growth Restriction: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 12:51:52","doi":"10.21203/rs.3.rs-4735277/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c6b81ef5-7e66-4f8a-96ae-8491b9f2db77","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-18T07:08:49+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-26 12:51:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4735277","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4735277","identity":"rs-4735277","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}