Synthetic Oxytocin Administration During Labor and Its Impact on Exclusive Breastfeeding in the Immediate Postpartum Period

Synthetic Oxytocin Administration During Labor and Its Impact on Exclusive Breastfeeding in the Immediate Postpartum Period | 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 Synthetic Oxytocin Administration During Labor and Its Impact on Exclusive Breastfeeding in the Immediate Postpartum Period Roza Berkovitz-Shperling, Shai Ram, Reut Stark, Omri Dominsky, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6693597/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 Background Synthetic oxytocin is widely used in obstetric practice, but its potential effects on breastfeeding outcomes remain controversial. Understanding these effects is crucial for optimizing maternal-infant health outcomes. Methods This prospective cohort study was conducted at a university-affiliated tertiary medical center in Israel from September 2021 to June 2022. Participants included 358 women with term singleton spontaneous vaginal deliveries who intended to breastfeed exclusively. Women who received synthetic oxytocin during labor for induction or augmentation (n = 181) were compared with those who did not (n = 177). All participants received standard prophylactic oxytocin (10 IU) during the third stage of labor. The primary outcome was exclusive breastfeeding rate at 24–72 hours postpartum. Secondary outcomes included breastfeeding initiation in the delivery room and factors associated with exclusive breastfeeding success. Results While exclusive breastfeeding rates were lower in the synthetic oxytocin group in univariate analysis (35.4% vs 48.6%, P = .014), multivariate analysis revealed no independent association between synthetic oxytocin and exclusive breastfeeding (adjusted RR 0.67; 95% CI, 0.38–1.20; P = .178). Women in the synthetic oxytocin group had higher rates of epidural analgesia (93.9% vs 52.0%, P < .001), nulliparity (60.2% vs 22.6%, P < .001), and lower rates of delivery room breastfeeding initiation (54.7% vs 78.0%, P < .001). Pre-labor breastfeeding counseling (adjusted RR 2.28; 95% CI, 1.24–4.17; P = .008) and delivery room breastfeeding initiation (adjusted RR 1.87; 95% CI, 1.08–3.25; P = .027) were identified as significant independent predictors of exclusive breastfeeding success. Conclusions Synthetic oxytocin administration during labor was not independently associated with reduced exclusive breastfeeding rates after adjusting for confounding variables. Clinical efforts should focus on promoting prenatal breastfeeding education and facilitating early breastfeeding initiation, which strongly predicted successful exclusive breastfeeding regardless of synthetic oxytocin exposure. Breastfeeding Synthetic oxytocin Labor augmentation Labor induction Lactation Maternal-infant bonding Postpartum care Perinatal interventions Figures Figure 1 Background Breastfeeding provides essential nutritional and immunological benefits for infants and mothers, leading the World Health Organization and other global health authorities to recommend exclusive breastfeeding for the first six months of life [ 1 , 2 ]. Despite these recommendations, breastfeeding rates worldwide remain suboptimal. According to the Centers for Disease Control and Prevention, while 81.1% of women in the United States initiate breastfeeding after delivery, only 44.4% maintain exclusive breastfeeding by three months postpartum [ 3 ]. The establishment of successful lactation relies on complex physiological processes involving hormonal regulation, maternal-infant interaction, and environmental support [ 4 , 5 ]. Multiple factors during the perinatal period can influence these processes, including maternal characteristics, intrapartum interventions, and early postpartum practices. Medical interventions during labor have increasingly gained attention for their potential impact on breastfeeding outcomes. Synthetic oxytocin is among the most frequently used medications in obstetric practice, employed for labor induction, augmentation, and prevention of postpartum hemorrhage. This synthetic hormone mimics the effects of endogenous oxytocin on uterine contractions and milk ejection [ 6 , 7 ]. However, physiological release of endogenous oxytocin occurs in coordinated neuronal bursts [ 8 , 9 ] with its receptors upregulated in both myometrial and mammary tissues during the perinatal period [ 10 , 11 ]. These receptors are integral to maternal-infant bonding and lactation physiology. The natural pulsatile release pattern of endogenous oxytocin differs significantly from the continuous administration of synthetic oxytocin during labor, potentially affecting receptor dynamics and subsequent lactation processes [ 12 , 13 ]. The current literature on synthetic oxytocin's impact on breastfeeding presents conflicting findings. Several systematic reviews and meta-analyses have suggested potential adverse effects on Lactogenesis II timing and early breastfeeding behaviors [ 14 – 16 ]. Proposed mechanisms include oxytocin receptor desensitization, disruption of natural hormonal cascades, and interference with neonatal innate breastfeeding behaviors. Conversely, multiple large cohort studies have found no significant association between synthetic oxytocin exposure and breastfeeding outcomes [ 17 , 18 ]. These contradictory findings likely stem from methodological limitations in previous research, including inadequate dosage assessment, insufficient control for confounding variables (particularly labor interventions and maternal characteristics), and inconsistent definitions of breastfeeding outcomes across studies [ 19 , 20 ]. Our study aimed to investigate whether exposure to synthetic oxytocin during labor influences breastfeeding success in the immediate postpartum period while rigorously controlling for potential confounding factors. Methods Study Design and Setting This prospective cohort study was conducted at a university-affiliated tertiary medical center in Israel from September 2021 to June 2022. The center serves a large and diverse population, with approximately 12,500 deliveries annually and a cesarean delivery rate of around 20%. The institutional review board approved the study protocol (approval number: 0015-21-TLV), and all participants provided written informed consent before enrollment. Participants Women with term singleton spontaneous vaginal deliveries (≥ 37 + 0 weeks of gestation) who were admitted to the low-risk postpartum department and had expressed a pre-delivery desire for exclusive breastfeeding were eligible for inclusion. Exclusive breastfeeding was defined as providing only mother's milk—whether through direct breastfeeding or expressed milk—without any formula supplementation. Exclusion criteria included: maternal age under 18 years, pre-delivery preference for formula feeding (either exclusively or in combination with breastfeeding), preterm delivery (gestational age ≤ 36 + 6 weeks), intrapartum fever (≥ 38.0°C), preeclampsia, small for gestational age infants (≤ 2500 g), fetal malformations, admission of mother or newborn to intensive care, and any medical condition that contraindicated breastfeeding. The study population was divided into two cohorts: women who received synthetic oxytocin during labor (for either induction or augmentation) and those who did not. According to department protocol, all women received 10 IU of synthetic oxytocin during the third stage of labor to prevent postpartum hemorrhage. Data Collection Participant Interviews A physician or trained medical student conducted structured interviews with participants between 24 and 72 hours postpartum. These interviews gathered information on pre-delivery breastfeeding intentions, immediate postpartum breastfeeding initiation (including timing and duration of the first breastfeeding session), skin-to-skin contact practices, and postpartum symptoms that might hinder breastfeeding (including pain, excessive bleeding, or fever). Participants were also asked about prior breastfeeding experiences (for multiparous women) and whether they had received any breastfeeding counseling or education before labor. Medical Records Review Additional data were extracted from medical records, including demographic characteristics (maternal age, pre-pregnancy BMI, education level, smoking status, and parity), pregnancy details (gestational age at delivery, complications during pregnancy), labor characteristics (spontaneous or induced labor onset, active labor status at admission defined as ≥ 4 cm cervical dilation, duration of first and second stages of labor, use of epidural analgesia, oxytocin administration timing and indication, assisted vaginal delivery, and perineal trauma), and neonatal outcomes (birth weight, sex, Apgar scores, and any immediate postpartum complications). Breastfeeding Assessment Breastfeeding status was classified as exclusive (breast milk only) or non-exclusive (any formula supplementation) based on patient reports, which were cross-verified with the neonate's medical records documenting feeding type during the hospital stay. Outcomes The primary outcome was the rate of exclusive breastfeeding in the immediate postpartum period (24–72 hours after delivery). Secondary outcomes included breastfeeding initiation in the delivery room and factors associated with successful exclusive breastfeeding. Statistical Analysis Sample size calculation was performed based on an anticipated effect size derived from previous literature and preliminary analysis. Assuming a 5% baseline rate of postpartum breastfeeding failure based on prior studies [ 3 , 4 ], and after enrolling 180 participants, preliminary analysis indicated exclusive breastfeeding rates of 37% in the no-synthetic oxytocin group and 18.5% in the synthetic oxytocin group. Based on this observed effect size of 18.5%, it was calculated using Fleiss and Klessy with continuity correction that a total of 103 participants per group would be required to achieve 80% statistical power at 5% Type I error rate. Statistical analyses were performed using IBM SPSS Statistics software (version 29; IBM Corporation, New York, NY). Categorical variables were compared using Chi-square tests. Continuous variables were assessed for normal distribution and compared using two-sided t-tests for normally distributed data or Mann-Whitney U tests for non-normally distributed parameters. A probability value of < .05 was considered statistically significant. To evaluate the independent association between synthetic oxytocin administration and exclusive breastfeeding, multivariate logistic regression analysis was performed with adjustment for potential confounding variables. These included maternal characteristics (age, parity, BMI, previous breastfeeding experience), labor interventions (epidural use, labor duration, mode of delivery), and postpartum factors (breastfeeding counseling, delivery room breastfeeding initiation). Results are presented as adjusted relative risks (RR) with 95% confidence intervals. Patient and Public Involvement Patients were not directly involved in the study's design, recruitment, or conduct. However, the research questions and outcome measures were developed based on clinical experience, patient feedback regarding labor interventions, and concerns about breastfeeding success. Results Study Population Of the 400 women initially recruited for participation, 358 had complete evaluable data (Fig. 1 ) and were divided into two groups: those exposed to synthetic oxytocin during labor (n = 181) and those without exposure (n = 177). The 42 women excluded from the final analysis included cases where mothers did not exclusively breastfeed despite initial intentions (n = 20), those who declined participation after initial recruitment (n = 6), women who delivered before 37 weeks' gestation (n = 1), and those who declined to receive routine oxytocin during the third stage of labor according to our department's standard protocol (n = 15). Maternal Characteristics Baseline demographic and pregnancy characteristics were comparable, with several notable differences (Table 1 ). Women in the synthetic oxytocin group had a slightly lower mean age (31.6 ± 4.6 vs 32.8 ± 4.3 years, P = .014) and higher pregnancy BMI (23.2 ± 4.3 vs 22.7 ± 4.4 kg/m², P = .277). Pre-pregnancy smoking rates were significantly higher in the oxytocin group (19.9% vs 9.0%, P = .030), and nulliparity was more common (60.2% vs 22.6%, P < .001). Among multiparous women, past breastfeeding experience was less common in the synthetic oxytocin group (81.4% vs 92.9%, P = .015). Table 1 Baseline and current pregnancy characteristics for the study and the control group Synthetic oxytocin (n = 181) No- synthetic oxytocin (n = 177) p -Value Maternal Age (years) (mean±SD) 31.6 ± 4.6 32.77 ± 4.3 .014 Pre-pregnancy-BMI (Kg/m 2 ) (mean±SD) 23.15 ± 4.3 22.7 ± 4.4 .277 BMI at delivery (Kg/m 2 ) (mean±SD) 28.3 ± 4.6 27.1 ± 4.4 .028 Education > 12 years (n (%)) 154 (85.1%) 156 (88.1%) .396 Pre-pregnancy smoking (n (%)) 36 (19.9%) 16 (9.0%) .030 Pregnancy smoking (n (%)) 3 (1.7%) 9 (5.0%) .140 Previous Cesarean section (median [IQR]) 0 [0–1] 0 [0–0] NS Nulliparity (n (%)) 109 (60.2%) 40 (22.6%) < 0.001 Previous breast surgery (n (%)) 5 (2.7%) 5 (2.8%) .971 Spontaneous conception (n (%)) 158 (87.8%) 156 (88.6%) .802 Gestational diabetes mellitus ^a^ (n (%)) 22 (12.2%) 16 (8.9%) 0.581 Gestational hypertension (n (%)) 5 (2.8%) 1 (0.6%) .215 Multipara (n = 210) Past Breastfeeding 57 (81.4%) 130 (92.9%) 0.015 Data are presented as mean ± standard deviation, n (%), or median [interquartile range]. Bold indicates statistical significance (P < .05). ^a^ including the diagnosis of GDMA119 (10.5%) vs. 14 (7.9%) – gestational diabetes class A1; GDMA2 3 (1.7%) vs. 2 (1.1%)– gestational diabetes class A2, in the Synthetic oxytocin vs. no- Synthetic oxytocin group; HTN-hypertension. Education levels and pre-pregnancy BMI were similar between groups. All participants in both groups had expressed a clear intention to breastfeed exclusively before delivery, which was confirmed during the postpartum interview. Labor and Delivery Characteristics Labor and delivery characteristics demonstrated significant variations between groups (Table 2 ). Active labor at admission was considerably less frequent in the synthetic oxytocin group (15.5% vs 71.8%, P < .001), with 50.3% requiring augmentation and 37.1% undergoing induction. Women receiving synthetic oxytocin experienced a significantly longer second stage of labor (83.2 ± 69.4 vs 34.2 ± 60.1 minutes, P < .001). Table 2 Labor and Delivery characteristics for the study and the control group Synthetic Oxytocin (n = 181) No- synthetic Oxytocin (n = 177) p-Value Gestational age at delivery (weeks) (mean±SD) 39.7 ± 1.1 39.5 ± 0.9 .098 Active labor at admission (n (%)) 28 (15.5%) 127 (71.8%) < .001 Spontaneous onset of labor (n (%)) Augmentation of labor Induction of Labor 23 (12.7%) 91 (50.3%) 67 (37.1%) 162 (91.5%) 1 (0.6%) 14 (7.9%) < .001 Second stage duration (min) (mean±SD) 83.2 ± 69.4 34.2 ± 60.1 < .001 Third stage duration (min) (mean±SD) 14.8 ± 11.4 15.1 ± 8.2 .964 Mode of delivery < .001 Spontaneous vaginal (n (%)) 150 (82.9%) 169 (95.5%) Assisted vaginal (n (%)) 31 (17.1%) 8 (4.5%) Perineal tears ^a^ (n (%)) 133 (73.5%) 95(53.7%) < .001 Epidural analgesia (n (%)) 170 (93.9%) 92 (52.0%) 7 (%) 100% 100% NS Male fetus (n (%)) 116 (64.1%) 84 (47.5%) < .001 Data are presented as mean ± standard deviation or n (%). Bold indicates statistical significance (P < .05). ^a^ Including first- and second-degree tears. The synthetic oxytocin group had substantially higher rates of assisted vaginal delivery (17.1% vs 4.5%, P < .001), epidural analgesia (93.9% vs 52.0%, P < .001), and perineal tears (73.5% vs 53.7%, P < .001). Neonatal Outcomes Neonatal outcomes were comparable between groups, although newborns in the synthetic oxytocin group had slightly higher birth weights (3320 ± 413 vs 3232 ± 392 g, P = .039), and male neonates were more frequent (64.1% vs 47.5%, P < .001). Apgar scores at 1 and 5 minutes were similar in both groups, with over 99% of all neonates having 5-minute Apgar scores ≥ 8. No significant differences were observed in immediate neonatal complications. Breastfeeding Outcomes Postpartum breastfeeding characteristics revealed several significant differences between groups (Table 3 ). Exclusive breastfeeding rates were notably lower in the synthetic oxytocin group (35.4% vs 48.6%, P = .014), and breastfeeding initiation in the delivery room occurred less frequently (54.7% vs 78.0%, P < .001). While women who received synthetic oxytocin reported more breastfeeding counseling before labor (21.5% vs 12.4%, P = .022), pain-related breastfeeding avoidance did not differ significantly between groups (34.2% vs 35.0%, P = .302). Table 3 Postpartum Characteristics and Breastfeeding Outcomes for the study and the control group Synthetic oxytocin (n = 181) No- synthetic oxytocin (n = 177) p -Value Exclusive Breastfeeding (n (%)) 64 (35.4%) 86 (48.6%) .014 Time to interview (hours) (mean±SD) 48.1 ± 14.6 45.4 ± 14.6 .139 Delivery room breastfeeding (n (%)) 99 (54.7%) 136 (78.0%) < 001 Skin-to-skin contact (n (%)) 141 (77.9%) 151 (85.3%) .070 Pacifier use (n (%)) 71 (39.2%) 75 (42.4%) .545 Breastfeeding counseling Pre-labor (n (%)) 39 (21.5%) 22 (12.4%) .022 Post-labor (n (%)) 114 (63%) 106 (59.9%) .547 Pain-related Breastfeeding avoidance ^a^ (n (%)) 62 )34.2%) 62 (35.0%) .302 Data are presented as mean ± standard deviation or n (%). Bold indicates statistical significance (P < .05). ^a^ Including discomfort associated with uterine contractions and breast pain Both groups reported similar rates of skin-to-skin contact in the first hour after birth (77.9% vs 85.3%, P = .070) and comparable duration of the first breastfeeding session (22.4 ± 18.7 vs 24.6 ± 20.3 minutes, P = .145). Multivariate Analysis In the multivariate logistic regression analysis adjusting for potential confounding factors (Table 4 ), pre-labor breastfeeding counseling emerged as the strongest independent predictor of exclusive breastfeeding (adjusted RR 2.28; 95% CI, 1.24–4.17; P = .008), followed by delivery room breastfeeding initiation (adjusted RR 1.87; 95% CI, 1.08–3.25; P = .027). Notably, synthetic oxytocin use during labor did not independently predict exclusive breastfeeding rates (adjusted RR 0.67; 95% CI, 0.38–1.20; P = .178) after controlling for maternal characteristics, labor interventions, and postpartum factors. Table 4 Multivariate Analysis of Factors Associated with Exclusive Breastfeeding Adjusted RR 95% C.I. for Adjusted RR P-value Synthetic oxytocin administration 0.674 0.379–1.198 .178 Delivery room breastfeeding 1.868 1.075–3.246 .027 Breastfeeding counseling - Post-labor - Pre-labor .872 2.277 0.379–1.522 1.242–4.173 .747 .008 Maternal age (Years) 0.955 0.901–1.012 .119 Pre-pregnancy BMI 1.035 0.978–1.096 .230 Education ≥ 12 years 0.563 0.254–1.248 .157 Multiparity 1.170 0.601–2.257 .644 Active labor at admission 0.806 0.422–1.536 .512 Second stage length (min) .998 0.994–1.002 .340 Perineal tears .776 0.448–1.344 .366 Epidural Analgesia .909 0.489–1.691 .763 Male newborn 1.063 0.657–1.720 .803 CI, confidence interval; RR, relative risk. Bold indicates statistical significance (P < .05) Other variables showing associations with exclusive breastfeeding in the multivariate model included previous breastfeeding experience (adjusted RR 1.89; 95% CI, 1.03–3.49; P = .041) and nulliparity (adjusted RR 0.67; 95% CI, 0.45-1.00; P = .048). Epidural use, labor duration, maternal age, and BMI did not demonstrate significant independent associations with breastfeeding success in the adjusted analysis. Discussion Main Findings In this prospective study of women who intended to breastfeed exclusively, synthetic oxytocin administration during labor was not independently associated with reduced exclusive breastfeeding rates in the immediate postpartum period. Our findings indicate that while exclusive breastfeeding rates were lower in the synthetic oxytocin group in univariate analysis, this association disappeared after controlling for confounding variables—parity, previous breastfeeding experience, epidural use, and early breastfeeding initiation. Pre-labor breastfeeding counseling (adjusted RR 2.28; 95% CI, 1.24–4.17; P = .008) and delivery room breastfeeding initiation (adjusted RR 1.87; 95% CI, 1.08–3.25; P = .027) emerged as the strongest independent predictors of exclusive breastfeeding success. These findings highlight the critical importance of education and immediate postpartum breastfeeding support, regardless of labor interventions. Strengths and Limitations This study has several strengths that enhance our findings' validity and clinical applicability. First, the prospective design allowed for assessing temporal relationships between exposures and outcomes, reducing recall bias. Second, we collected detailed information on labor interventions and potentially confounding variables, enabling comprehensive multivariate analysis. Third, we verified breastfeeding status through participant reports and medical records, enhancing outcome accuracy. Fourth, our analysis incorporated pre-labor factors (breastfeeding counseling, previous experience) and intrapartum interventions, providing a holistic assessment of influences on breastfeeding success. However, several limitations should be considered when interpreting our results. As a single-center study conducted in a specific healthcare setting, generalizability to other populations or healthcare systems may be limited. While we cross-verified breastfeeding status with medical records, self-reported data regarding pre-labor intentions and postpartum experiences may still introduce some recall bias. Our focus on the immediate postpartum period (24–72 hours) precludes conclusions about long-term breastfeeding success or duration, which peripartum interventions may influence differently. Additionally, we could not account for all possible confounding variables in the complex labor and delivery environment, particularly psychosocial factors and variations in postpartum support. A standardized assessment of oxytocin exposure duration and cumulative dosing was also lacking, which might have revealed dose-dependent effects not captured in our binary exposure classification. Interpretation Our findings should be interpreted in the context of previous research on synthetic oxytocin and breastfeeding outcomes, which has shown conflicting results. Several studies have hypothesized that synthetic oxytocin might interfere with lactation through receptor desensitization or disruption of the natural hormonal cascade [ 11 , 13 ]. The physiological basis for this potential interference centers on oxytocin receptor dynamics, where continuous synthetic administration might differ from the natural pulsatile release pattern that characterizes endogenous oxytocin secretion [ 8 , 9 ]. However, many previous studies failed to adequately account for critical confounding variables such as parity, previous breastfeeding experience, labor duration, and epidural use—factors that differed significantly between our study groups. The notable differences we observed in previous breastfeeding experience (81.4% vs 92.9%, P = .015) and nulliparity (60.2% vs 22.6%, P < .001) likely contributed to the unadjusted difference in breastfeeding rates, which disappeared after multivariate adjustment. The high rate of epidural analgesia in our synthetic oxytocin group (93.9%) and significant differences in labor onset patterns (50.3% augmentation, 37.1% induction) align with previous studies showing increased intervention requirements during induced or augmented labor [ 21 , 22 ]. This interconnection between interventions highlights the complexity of studying isolated effects in modern obstetric practice, where interventions often cluster together. Our observation that pre-labor counseling and early breastfeeding initiation strongly predict success supports growing evidence about the critical importance of education and the immediate postpartum period for establishing successful lactation [ 19 , 20 ]. The relatively low rates of exclusive breastfeeding in both groups (35.4% and 48.6%), despite stated intentions, suggest that additional factors beyond those measured in our study may influence early breastfeeding success, warranting further investigation. The relationship between synthetic oxytocin and breastfeeding is complex and likely influenced by the interplay of physiological, psychological, and institutional factors. While our findings do not support an independent effect of synthetic oxytocin on breastfeeding outcomes, they emphasize the importance of modifiable factors such as education and early breastfeeding support, which showed strong associations with successful exclusive breastfeeding regardless of labor interventions. Conclusions Synthetic oxytocin administration during labor was not independently associated with reduced exclusive breastfeeding rates after adjusting for confounding variables. Pre-labor breastfeeding counseling and early breastfeeding initiation in the delivery room were the primary determinants of successful exclusive breastfeeding, regardless of synthetic oxytocin exposure. Our findings have important clinical implications. First, concerns about oxytocin's impact on breastfeeding should not influence clinical decision-making when synthetic oxytocin is otherwise indicated for maternal or fetal benefit. Second, healthcare providers should prioritize interventions promoting successful breastfeeding, particularly prenatal breastfeeding education and facilitating early breastfeeding initiation, even in cases requiring synthetic oxytocin and other labor interventions. Future research should include longitudinal studies examining long-term effects of labor interventions on breastfeeding duration, dose-response relationships between synthetic oxytocin and breastfeeding outcomes, optimization of prenatal education programs, and investigation of the complex interplay between multiple peripartum interventions on lactation physiology and behavior. Abbreviations BMI: Body Mass Index CI: Confidence Interval RR: Relative Risk IU: International Units Declarations Ethics approval and consent to participate This study was approved by the institutional review board of Tel Aviv Sourasky Medical Center (approval number: 0015-21-TLV). All participants provided written informed consent before enrollment. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution R.B.S. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. R.B.S. and Y.Y. conceptualized and designed the study. S.R., R.S., O.D., and M.R.W. acquired the data. R.B.S. performed the statistical analysis. R.B.S., S.R., and R.S. interpreted the data. R.B.S. drafted the original manuscript. S.R. and R.S. prepared tables 1-4. O.D., M.R.W., and Y.Y. critically revised the manuscript for important intellectual content. All authors reviewed and approved the final manuscript. Acknowledgements The authors thank the nursing staff of the maternity department at Tel Aviv Sourasky Medical Center for their assistance with participant recruitment and the medical students who assisted with data collection. We also thank all the women who participated in this study. None of these individuals received compensation for their contributions. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request, subject to approval from the institutional ethics committee. References Mosca F, Giannì ML. Human milk: composition and health benefits. Pediatr Med Chir. 2017;39(2):155. World Health Organization. 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Segura-Pérez S, Hromi-Fiedler A, Adnew M, Nyhan K, Pérez-Escamilla R. Risk factors for self-reported insufficient milk during the first 6 months of life: A systematic review. Matern Child Nutr. 2022;18(Suppl 3):e13353. Dewey KG, Nommsen-Rivers LA, Heinig MJ, Cohen RJ. Risk factors for suboptimal infant breastfeeding behavior, delayed onset of lactation, and excess neonatal weight loss. Pediatrics. 2003;112(3):607–19. Mauri PA, Contini NN, Giliberti S, Barretta F, Consonni D, Negri M, Di Benedetto I. Intrapartum epidural analgesia and onset of lactation: a prospective study in an Italian birth centre. Matern Child Health J. 2015;19(3):511–8. Wiklund I, Norman M, Uvnäs-Moberg K, Ransjö-Arvidson AB, Andolf E. Epidural analgesia: breast-feeding success and related factors. Midwifery. 2009;25(2):e31–8. Additional Declarations No competing interests reported. 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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-6693597","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":476300952,"identity":"c35281ad-53c1-4272-863a-dc2c82f57c28","order_by":0,"name":"Roza Berkovitz-Shperling","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYJACZhBhwMB8AEhJyJCihS0BpIWHFC08BiCasBbz9uMPmAsq7tmbS/d8fnWjxoKHgf3w0Q34tMicSUhgnnGmOHHnnLPbrHOOAR3Gk5Z2A58WCYaEA8y8bQkJBjdytxnnsAG1SPCY4dfC/7CBmfdfgr3BjZxnxjn/iNEikczAzNuQwLjhRg7z49w2orQ8Yzg841hC4oY7x8yYc/skeNgI+oU//eHjghqgw243P/6c861Ojp/98DG8WkDgAEQzA5sEiGYjpBzJPgbmD8SrHgWjYBSMgpEEAA2tRFDRSXCOAAAAAElFTkSuQmCC","orcid":"","institution":"Lis Hospital for Women’s Health Tel Aviv Sourasky Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Roza","middleName":"","lastName":"Berkovitz-Shperling","suffix":""},{"id":476300953,"identity":"1ab9ee08-4a48-40e3-9986-b8981f0763b4","order_by":1,"name":"Shai Ram","email":"","orcid":"","institution":"Lis Hospital for Women’s Health Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Shai","middleName":"","lastName":"Ram","suffix":""},{"id":476300954,"identity":"77c015a1-df94-4d83-9399-beb964b5bbc5","order_by":2,"name":"Reut Stark","email":"","orcid":"","institution":"Lis Hospital for Women’s Health Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Reut","middleName":"","lastName":"Stark","suffix":""},{"id":476300955,"identity":"c2ec9d9b-a849-4ac4-bf63-ab2c35e7dd8d","order_by":3,"name":"Omri Dominsky","email":"","orcid":"","institution":"Lis Hospital for Women’s Health Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Omri","middleName":"","lastName":"Dominsky","suffix":""},{"id":476300956,"identity":"7ffb7fc2-e3ec-418d-a254-028a47f3c0f5","order_by":4,"name":"Maya Ram-weiner","email":"","orcid":"","institution":"Lis Hospital for Women’s Health Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Maya","middleName":"","lastName":"Ram-weiner","suffix":""},{"id":476300957,"identity":"9b376ca6-7904-4617-8512-a6adf58dca16","order_by":5,"name":"Yariv Yogev","email":"","orcid":"","institution":"Lis Hospital for Women’s Health Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yariv","middleName":"","lastName":"Yogev","suffix":""}],"badges":[],"createdAt":"2025-05-18 20:38:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6693597/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6693597/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85735334,"identity":"a67ac080-ed67-4fa0-a644-0f7eafac3d94","added_by":"auto","created_at":"2025-07-01 07:58:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16880,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow Diagram of Study Participants.\u003c/strong\u003e This diagram illustrates the enrollment and allocation of study participants. Of the 400 women initially screened for eligibility, 42 were excluded for reasons including: declining participation after initial recruitment (n=6), not exclusively breastfeeding despite initial intentions (n=20), delivery before 37 weeks' gestation (n=1), and declining routine oxytocin during the third stage of labor (n=15). The 358 women who met all inclusion criteria were allocated to either the synthetic oxytocin group (n=181) or the control group with no synthetic oxytocin during labor (n=177).\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6693597/v1/78f43882919b95c042c18cd8.png"},{"id":102296354,"identity":"210a133b-5dad-49f2-ab5d-78b2e06581b2","added_by":"auto","created_at":"2026-02-10 10:18:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":909895,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6693597/v1/9c774216-7d08-4f46-9b22-407805fd6208.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synthetic Oxytocin Administration During Labor and Its Impact on Exclusive Breastfeeding in the Immediate Postpartum Period","fulltext":[{"header":"Background","content":"\u003cp\u003eBreastfeeding provides essential nutritional and immunological benefits for infants and mothers, leading the World Health Organization and other global health authorities to recommend exclusive breastfeeding for the first six months of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite these recommendations, breastfeeding rates worldwide remain suboptimal. According to the Centers for Disease Control and Prevention, while 81.1% of women in the United States initiate breastfeeding after delivery, only 44.4% maintain exclusive breastfeeding by three months postpartum [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe establishment of successful lactation relies on complex physiological processes involving hormonal regulation, maternal-infant interaction, and environmental support [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Multiple factors during the perinatal period can influence these processes, including maternal characteristics, intrapartum interventions, and early postpartum practices. Medical interventions during labor have increasingly gained attention for their potential impact on breastfeeding outcomes.\u003c/p\u003e \u003cp\u003eSynthetic oxytocin is among the most frequently used medications in obstetric practice, employed for labor induction, augmentation, and prevention of postpartum hemorrhage. This synthetic hormone mimics the effects of endogenous oxytocin on uterine contractions and milk ejection [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, physiological release of endogenous oxytocin occurs in coordinated neuronal bursts [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] with its receptors upregulated in both myometrial and mammary tissues during the perinatal period [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. These receptors are integral to maternal-infant bonding and lactation physiology. The natural pulsatile release pattern of endogenous oxytocin differs significantly from the continuous administration of synthetic oxytocin during labor, potentially affecting receptor dynamics and subsequent lactation processes [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe current literature on synthetic oxytocin's impact on breastfeeding presents conflicting findings. Several systematic reviews and meta-analyses have suggested potential adverse effects on Lactogenesis II timing and early breastfeeding behaviors [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Proposed mechanisms include oxytocin receptor desensitization, disruption of natural hormonal cascades, and interference with neonatal innate breastfeeding behaviors. Conversely, multiple large cohort studies have found no significant association between synthetic oxytocin exposure and breastfeeding outcomes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These contradictory findings likely stem from methodological limitations in previous research, including inadequate dosage assessment, insufficient control for confounding variables (particularly labor interventions and maternal characteristics), and inconsistent definitions of breastfeeding outcomes across studies [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study aimed to investigate whether exposure to synthetic oxytocin during labor influences breastfeeding success in the immediate postpartum period while rigorously controlling for potential confounding factors.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis prospective cohort study was conducted at a university-affiliated tertiary medical center in Israel from September 2021 to June 2022. The center serves a large and diverse population, with approximately 12,500 deliveries annually and a cesarean delivery rate of around 20%. The institutional review board approved the study protocol (approval number: 0015-21-TLV), and all participants provided written informed consent before enrollment.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eWomen with term singleton spontaneous vaginal deliveries (\u0026ge;\u0026thinsp;37\u0026thinsp;+\u0026thinsp;0 weeks of gestation) who were admitted to the low-risk postpartum department and had expressed a pre-delivery desire for exclusive breastfeeding were eligible for inclusion. Exclusive breastfeeding was defined as providing only mother's milk\u0026mdash;whether through direct breastfeeding or expressed milk\u0026mdash;without any formula supplementation.\u003c/p\u003e \u003cp\u003eExclusion criteria included: maternal age under 18 years, pre-delivery preference for formula feeding (either exclusively or in combination with breastfeeding), preterm delivery (gestational age\u0026thinsp;\u0026le;\u0026thinsp;36\u0026thinsp;+\u0026thinsp;6 weeks), intrapartum fever (\u0026ge;\u0026thinsp;38.0\u0026deg;C), preeclampsia, small for gestational age infants (\u0026le;\u0026thinsp;2500 g), fetal malformations, admission of mother or newborn to intensive care, and any medical condition that contraindicated breastfeeding.\u003c/p\u003e \u003cp\u003eThe study population was divided into two cohorts: women who received synthetic oxytocin during labor (for either induction or augmentation) and those who did not. According to department protocol, all women received 10 IU of synthetic oxytocin during the third stage of labor to prevent postpartum hemorrhage.\u003c/p\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eParticipant Interviews\u003c/h2\u003e \u003cp\u003eA physician or trained medical student conducted structured interviews with participants between 24 and 72 hours postpartum. These interviews gathered information on pre-delivery breastfeeding intentions, immediate postpartum breastfeeding initiation (including timing and duration of the first breastfeeding session), skin-to-skin contact practices, and postpartum symptoms that might hinder breastfeeding (including pain, excessive bleeding, or fever). Participants were also asked about prior breastfeeding experiences (for multiparous women) and whether they had received any breastfeeding counseling or education before labor.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eMedical Records Review\u003c/h3\u003e\n\u003cp\u003eAdditional data were extracted from medical records, including demographic characteristics (maternal age, pre-pregnancy BMI, education level, smoking status, and parity), pregnancy details (gestational age at delivery, complications during pregnancy), labor characteristics (spontaneous or induced labor onset, active labor status at admission defined as \u0026ge;\u0026thinsp;4 cm cervical dilation, duration of first and second stages of labor, use of epidural analgesia, oxytocin administration timing and indication, assisted vaginal delivery, and perineal trauma), and neonatal outcomes (birth weight, sex, Apgar scores, and any immediate postpartum complications).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBreastfeeding Assessment\u003c/h2\u003e \u003cp\u003eBreastfeeding status was classified as exclusive (breast milk only) or non-exclusive (any formula supplementation) based on patient reports, which were cross-verified with the neonate's medical records documenting feeding type during the hospital stay.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the rate of exclusive breastfeeding in the immediate postpartum period (24\u0026ndash;72 hours after delivery). Secondary outcomes included breastfeeding initiation in the delivery room and factors associated with successful exclusive breastfeeding.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eSample size calculation was performed based on an anticipated effect size derived from previous literature and preliminary analysis. Assuming a 5% baseline rate of postpartum breastfeeding failure based on prior studies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and after enrolling 180 participants, preliminary analysis indicated exclusive breastfeeding rates of 37% in the no-synthetic oxytocin group and 18.5% in the synthetic oxytocin group. Based on this observed effect size of 18.5%, it was calculated using Fleiss and Klessy with continuity correction that a total of 103 participants per group would be required to achieve 80% statistical power at 5% Type I error rate.\u003c/p\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics software (version 29; IBM Corporation, New York, NY). Categorical variables were compared using Chi-square tests. Continuous variables were assessed for normal distribution and compared using two-sided t-tests for normally distributed data or Mann-Whitney U tests for non-normally distributed parameters. A probability value of \u0026lt;\u0026thinsp;.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eTo evaluate the independent association between synthetic oxytocin administration and exclusive breastfeeding, multivariate logistic regression analysis was performed with adjustment for potential confounding variables. These included maternal characteristics (age, parity, BMI, previous breastfeeding experience), labor interventions (epidural use, labor duration, mode of delivery), and postpartum factors (breastfeeding counseling, delivery room breastfeeding initiation). Results are presented as adjusted relative risks (RR) with 95% confidence intervals.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePatient and Public Involvement\u003c/h2\u003e \u003cp\u003ePatients were not directly involved in the study's design, recruitment, or conduct. However, the research questions and outcome measures were developed based on clinical experience, patient feedback regarding labor interventions, and concerns about breastfeeding success.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eOf the 400 women initially recruited for participation, 358 had complete evaluable data (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and were divided into two groups: those exposed to synthetic oxytocin during labor (n\u0026thinsp;=\u0026thinsp;181) and those without exposure (n\u0026thinsp;=\u0026thinsp;177). The 42 women excluded from the final analysis included cases where mothers did not exclusively breastfeed despite initial intentions (n\u0026thinsp;=\u0026thinsp;20), those who declined participation after initial recruitment (n\u0026thinsp;=\u0026thinsp;6), women who delivered before 37 weeks' gestation (n\u0026thinsp;=\u0026thinsp;1), and those who declined to receive routine oxytocin during the third stage of labor according to our department's standard protocol (n\u0026thinsp;=\u0026thinsp;15).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eMaternal Characteristics\u003c/h2\u003e \u003cp\u003eBaseline demographic and pregnancy characteristics were comparable, with several notable differences (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Women in the synthetic oxytocin group had a slightly lower mean age (31.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6 vs 32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 years, P\u0026thinsp;=\u0026thinsp;.014) and higher pregnancy BMI (23.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 vs 22.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4 kg/m\u0026sup2;, P\u0026thinsp;=\u0026thinsp;.277). Pre-pregnancy smoking rates were significantly higher in the oxytocin group (19.9% vs 9.0%, P\u0026thinsp;=\u0026thinsp;.030), and nulliparity was more common (60.2% vs 22.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001). Among multiparous women, past breastfeeding experience was less common in the synthetic oxytocin group (81.4% vs 92.9%, P\u0026thinsp;=\u0026thinsp;.015).\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\u003eBaseline and current pregnancy characteristics for the study and the control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSynthetic\u003c/p\u003e \u003cp\u003eoxytocin (n\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo- synthetic oxytocin (n\u0026thinsp;=\u0026thinsp;177)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\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\" colname=\"c1\"\u003e \u003cp\u003eMaternal Age (years)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.6 \u0026plusmn; 4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.77 \u0026plusmn; 4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy-BMI (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.15 \u0026plusmn; 4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.7 \u0026plusmn; 4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI at delivery (Kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28.3 \u0026plusmn; 4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.1 \u0026plusmn; 4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation\u0026thinsp;\u0026gt;\u0026thinsp;12 years\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154 (85.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156 (88.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.396\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy smoking\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (19.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (9.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy smoking\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious Cesarean section\u003c/p\u003e \u003cp\u003e(median [IQR])\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 [0\u0026ndash;1]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 [0\u0026ndash;0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNulliparity\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109 (60.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious breast surgery\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpontaneous conception\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e158 (87.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e156 (88.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.802\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational diabetes mellitus ^a^\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (12.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (8.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.581\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational hypertension\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.215\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultipara (n\u0026thinsp;=\u0026thinsp;210)\u003c/p\u003e \u003cp\u003ePast Breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (81.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e130 (92.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eData are presented as\u003c/em\u003e mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, n (%), or median [interquartile range]. Bold indicates statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;.05). ^a^ \u003cem\u003eincluding the diagnosis of GDMA119 (10.5%) vs. 14 (7.9%) \u0026ndash; gestational diabetes class A1; GDMA2 3 (1.7%) vs. 2 (1.1%)\u0026ndash; gestational diabetes class A2, in the\u003c/em\u003e Synthetic oxytocin vs. no- Synthetic oxytocin group; \u003cem\u003eHTN-hypertension.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eEducation levels and pre-pregnancy BMI were similar between groups. All participants in both groups had expressed a clear intention to breastfeed exclusively before delivery, which was confirmed during the postpartum interview.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLabor and Delivery Characteristics\u003c/h2\u003e \u003cp\u003eLabor and delivery characteristics demonstrated significant variations between groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Active labor at admission was considerably less frequent in the synthetic oxytocin group (15.5% vs 71.8%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001), with 50.3% requiring augmentation and 37.1% undergoing induction. Women receiving synthetic oxytocin experienced a significantly longer second stage of labor (83.2\u0026thinsp;\u0026plusmn;\u0026thinsp;69.4 vs 34.2\u0026thinsp;\u0026plusmn;\u0026thinsp;60.1 minutes, P\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLabor and Delivery characteristics for the study and the control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSynthetic Oxytocin (n\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo- synthetic Oxytocin (n\u0026thinsp;=\u0026thinsp;177)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery (weeks)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39.7 \u0026plusmn; 1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.5 \u0026plusmn; 0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive labor at admission\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (15.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e127 (71.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpontaneous onset of labor (n (%))\u003c/p\u003e \u003cp\u003eAugmentation of labor\u003c/p\u003e \u003cp\u003eInduction of Labor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (12.7%)\u003c/p\u003e \u003cp\u003e91 (50.3%)\u003c/p\u003e \u003cp\u003e67 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e162 (91.5%)\u003c/p\u003e \u003cp\u003e1 (0.6%)\u003c/p\u003e \u003cp\u003e14 (7.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond stage duration (min)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e83.2 \u0026plusmn; 69.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.2 \u0026plusmn; 60.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThird stage duration (min)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.8 \u0026plusmn; 11.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.1 \u0026plusmn; 8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.964\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMode of delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpontaneous vaginal\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e150 (82.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169 (95.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAssisted vaginal\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (17.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerineal tears ^a^\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e133 (73.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95(53.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpidural analgesia\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170 (93.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92 (52.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirthweight (grams)\u003c/p\u003e \u003cp\u003e(mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3320 \u0026plusmn; 413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3232 \u0026plusmn; 392\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5-min Apgar Score\u0026thinsp;\u0026gt;\u0026thinsp;7\u003c/p\u003e \u003cp\u003e(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNS\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale fetus\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116 (64.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or n (%). Bold indicates statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;.05). ^a^ Including first- and second-degree tears.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe synthetic oxytocin group had substantially higher rates of assisted vaginal delivery (17.1% vs 4.5%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001), epidural analgesia (93.9% vs 52.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001), and perineal tears (73.5% vs 53.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eNeonatal Outcomes\u003c/h2\u003e \u003cp\u003eNeonatal outcomes were comparable between groups, although newborns in the synthetic oxytocin group had slightly higher birth weights (3320\u0026thinsp;\u0026plusmn;\u0026thinsp;413 vs 3232\u0026thinsp;\u0026plusmn;\u0026thinsp;392 g, P\u0026thinsp;=\u0026thinsp;.039), and male neonates were more frequent (64.1% vs 47.5%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001). Apgar scores at 1 and 5 minutes were similar in both groups, with over 99% of all neonates having 5-minute Apgar scores\u0026thinsp;\u0026ge;\u0026thinsp;8. No significant differences were observed in immediate neonatal complications.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eBreastfeeding Outcomes\u003c/h2\u003e \u003cp\u003ePostpartum breastfeeding characteristics revealed several significant differences between groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Exclusive breastfeeding rates were notably lower in the synthetic oxytocin group (35.4% vs 48.6%, P\u0026thinsp;=\u0026thinsp;.014), and breastfeeding initiation in the delivery room occurred less frequently (54.7% vs 78.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001). While women who received synthetic oxytocin reported more breastfeeding counseling before labor (21.5% vs 12.4%, P\u0026thinsp;=\u0026thinsp;.022), pain-related breastfeeding avoidance did not differ significantly between groups (34.2% vs 35.0%, P\u0026thinsp;=\u0026thinsp;.302).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostpartum Characteristics and Breastfeeding Outcomes for the study and the control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSynthetic oxytocin (n\u0026thinsp;=\u0026thinsp;181)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo- synthetic oxytocin (n\u0026thinsp;=\u0026thinsp;177)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\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\" colname=\"c1\"\u003e \u003cp\u003eExclusive Breastfeeding (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (35.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to interview (hours) (mean\u0026plusmn;SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.1 \u0026plusmn; 14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.4 \u0026plusmn; 14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.139\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelivery room breastfeeding\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (54.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136 (78.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin-to-skin contact\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141 (77.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151 (85.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.070\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePacifier use\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (39.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (42.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.545\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBreastfeeding counseling\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-labor\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.022\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-labor\u003c/p\u003e \u003cp\u003e(n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e114 (63%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e106 (59.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.547\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain-related Breastfeeding avoidance ^a^ (n (%))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 )34.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62 (35.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.302\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or n (%). Bold indicates statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;.05).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e^a^ Including discomfort associated with uterine contractions and breast pain\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBoth groups reported similar rates of skin-to-skin contact in the first hour after birth (77.9% vs 85.3%, P\u0026thinsp;=\u0026thinsp;.070) and comparable duration of the first breastfeeding session (22.4\u0026thinsp;\u0026plusmn;\u0026thinsp;18.7 vs 24.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.3 minutes, P\u0026thinsp;=\u0026thinsp;.145).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eMultivariate Analysis\u003c/h2\u003e \u003cp\u003eIn the multivariate logistic regression analysis adjusting for potential confounding factors (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), pre-labor breastfeeding counseling emerged as the strongest independent predictor of exclusive breastfeeding (adjusted RR 2.28; 95% CI, 1.24\u0026ndash;4.17; P\u0026thinsp;=\u0026thinsp;.008), followed by delivery room breastfeeding initiation (adjusted RR 1.87; 95% CI, 1.08\u0026ndash;3.25; P\u0026thinsp;=\u0026thinsp;.027). Notably, synthetic oxytocin use during labor did not independently predict exclusive breastfeeding rates (adjusted RR 0.67; 95% CI, 0.38\u0026ndash;1.20; P\u0026thinsp;=\u0026thinsp;.178) after controlling for maternal characteristics, labor interventions, and postpartum factors.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate Analysis of Factors Associated with Exclusive Breastfeeding\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\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\u003eAdjusted RR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% C.I. for Adjusted RR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSynthetic oxytocin administration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.379\u0026ndash;1.198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelivery room breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.075\u0026ndash;3.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreastfeeding counseling\u003c/p\u003e \u003cp\u003e- Post-labor\u003c/p\u003e \u003cp\u003e- Pre-labor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.872\u003c/p\u003e \u003cp\u003e2.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.379\u0026ndash;1.522\u003c/p\u003e \u003cp\u003e1.242\u0026ndash;4.173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.747\u003c/p\u003e \u003cp\u003e.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal age (Years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.955\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.901\u0026ndash;1.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-pregnancy BMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.978\u0026ndash;1.096\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation\u0026thinsp;\u0026ge;\u0026thinsp;12 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.563\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.254\u0026ndash;1.248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiparity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.601\u0026ndash;2.257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.644\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive labor at admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.422\u0026ndash;1.536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.512\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecond stage length (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.998\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.994\u0026ndash;1.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.340\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerineal tears\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.776\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.448\u0026ndash;1.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpidural Analgesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e.909\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.489\u0026ndash;1.691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.763\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale newborn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.657\u0026ndash;1.720\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e.803\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eCI, confidence interval; RR, relative risk. Bold indicates statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;.05)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOther variables showing associations with exclusive breastfeeding in the multivariate model included previous breastfeeding experience (adjusted RR 1.89; 95% CI, 1.03\u0026ndash;3.49; P\u0026thinsp;=\u0026thinsp;.041) and nulliparity (adjusted RR 0.67; 95% CI, 0.45-1.00; P\u0026thinsp;=\u0026thinsp;.048). Epidural use, labor duration, maternal age, and BMI did not demonstrate significant independent associations with breastfeeding success in the adjusted analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003eMain Findings\u003c/h2\u003e \u003cp\u003eIn this prospective study of women who intended to breastfeed exclusively, synthetic oxytocin administration during labor was not independently associated with reduced exclusive breastfeeding rates in the immediate postpartum period. Our findings indicate that while exclusive breastfeeding rates were lower in the synthetic oxytocin group in univariate analysis, this association disappeared after controlling for confounding variables\u0026mdash;parity, previous breastfeeding experience, epidural use, and early breastfeeding initiation.\u003c/p\u003e \u003cp\u003ePre-labor breastfeeding counseling (adjusted RR 2.28; 95% CI, 1.24\u0026ndash;4.17; P\u0026thinsp;=\u0026thinsp;.008) and delivery room breastfeeding initiation (adjusted RR 1.87; 95% CI, 1.08\u0026ndash;3.25; P\u0026thinsp;=\u0026thinsp;.027) emerged as the strongest independent predictors of exclusive breastfeeding success. These findings highlight the critical importance of education and immediate postpartum breastfeeding support, regardless of labor interventions.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eThis study has several strengths that enhance our findings' validity and clinical applicability. First, the prospective design allowed for assessing temporal relationships between exposures and outcomes, reducing recall bias. Second, we collected detailed information on labor interventions and potentially confounding variables, enabling comprehensive multivariate analysis. Third, we verified breastfeeding status through participant reports and medical records, enhancing outcome accuracy. Fourth, our analysis incorporated pre-labor factors (breastfeeding counseling, previous experience) and intrapartum interventions, providing a holistic assessment of influences on breastfeeding success.\u003c/p\u003e \u003cp\u003eHowever, several limitations should be considered when interpreting our results. As a single-center study conducted in a specific healthcare setting, generalizability to other populations or healthcare systems may be limited. While we cross-verified breastfeeding status with medical records, self-reported data regarding pre-labor intentions and postpartum experiences may still introduce some recall bias. Our focus on the immediate postpartum period (24\u0026ndash;72 hours) precludes conclusions about long-term breastfeeding success or duration, which peripartum interventions may influence differently.\u003c/p\u003e \u003cp\u003eAdditionally, we could not account for all possible confounding variables in the complex labor and delivery environment, particularly psychosocial factors and variations in postpartum support. A standardized assessment of oxytocin exposure duration and cumulative dosing was also lacking, which might have revealed dose-dependent effects not captured in our binary exposure classification.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003eInterpretation\u003c/h2\u003e \u003cp\u003eOur findings should be interpreted in the context of previous research on synthetic oxytocin and breastfeeding outcomes, which has shown conflicting results. Several studies have hypothesized that synthetic oxytocin might interfere with lactation through receptor desensitization or disruption of the natural hormonal cascade [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The physiological basis for this potential interference centers on oxytocin receptor dynamics, where continuous synthetic administration might differ from the natural pulsatile release pattern that characterizes endogenous oxytocin secretion [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, many previous studies failed to adequately account for critical confounding variables such as parity, previous breastfeeding experience, labor duration, and epidural use\u0026mdash;factors that differed significantly between our study groups. The notable differences we observed in previous breastfeeding experience (81.4% vs 92.9%, P\u0026thinsp;=\u0026thinsp;.015) and nulliparity (60.2% vs 22.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001) likely contributed to the unadjusted difference in breastfeeding rates, which disappeared after multivariate adjustment.\u003c/p\u003e \u003cp\u003eThe high rate of epidural analgesia in our synthetic oxytocin group (93.9%) and significant differences in labor onset patterns (50.3% augmentation, 37.1% induction) align with previous studies showing increased intervention requirements during induced or augmented labor [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This interconnection between interventions highlights the complexity of studying isolated effects in modern obstetric practice, where interventions often cluster together.\u003c/p\u003e \u003cp\u003eOur observation that pre-labor counseling and early breastfeeding initiation strongly predict success supports growing evidence about the critical importance of education and the immediate postpartum period for establishing successful lactation [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The relatively low rates of exclusive breastfeeding in both groups (35.4% and 48.6%), despite stated intentions, suggest that additional factors beyond those measured in our study may influence early breastfeeding success, warranting further investigation.\u003c/p\u003e \u003cp\u003eThe relationship between synthetic oxytocin and breastfeeding is complex and likely influenced by the interplay of physiological, psychological, and institutional factors. While our findings do not support an independent effect of synthetic oxytocin on breastfeeding outcomes, they emphasize the importance of modifiable factors such as education and early breastfeeding support, which showed strong associations with successful exclusive breastfeeding regardless of labor interventions.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eSynthetic oxytocin administration during labor was not independently associated with reduced exclusive breastfeeding rates after adjusting for confounding variables. Pre-labor breastfeeding counseling and early breastfeeding initiation in the delivery room were the primary determinants of successful exclusive breastfeeding, regardless of synthetic oxytocin exposure.\u003c/p\u003e \u003cp\u003eOur findings have important clinical implications. First, concerns about oxytocin's impact on breastfeeding should not influence clinical decision-making when synthetic oxytocin is otherwise indicated for maternal or fetal benefit. Second, healthcare providers should prioritize interventions promoting successful breastfeeding, particularly prenatal breastfeeding education and facilitating early breastfeeding initiation, even in cases requiring synthetic oxytocin and other labor interventions.\u003c/p\u003e \u003cp\u003eFuture research should include longitudinal studies examining long-term effects of labor interventions on breastfeeding duration, dose-response relationships between synthetic oxytocin and breastfeeding outcomes, optimization of prenatal education programs, and investigation of the complex interplay between multiple peripartum interventions on lactation physiology and behavior.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBMI: Body Mass Index CI: Confidence Interval RR: Relative Risk IU: International Units\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the institutional review board of Tel Aviv Sourasky Medical Center (approval number: 0015-21-TLV). All participants provided written informed consent before enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eR.B.S. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. R.B.S. and Y.Y. conceptualized and designed the study. S.R., R.S., O.D., and M.R.W. acquired the data. R.B.S. performed the statistical analysis. R.B.S., S.R., and R.S. interpreted the data. R.B.S. drafted the original manuscript. S.R. and R.S. prepared tables 1-4. O.D., M.R.W., and Y.Y. critically revised the manuscript for important intellectual content. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eThe authors thank the nursing staff of the maternity department at Tel Aviv Sourasky Medical Center for their assistance with participant recruitment and the medical students who assisted with data collection. We also thank all the women who participated in this study. None of these individuals received compensation for their contributions.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request, subject to approval from the institutional ethics committee.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMosca F, Giann\u0026igrave; ML. Human milk: composition and health benefits. Pediatr Med Chir. 2017;39(2):155.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. Infant and young child feeding: model chapter for textbooks for medical students and allied health professionals. Geneva: World Health Organization; 2009.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCenters for Disease Control and Prevention. Breastfeed Rep Card 2016 CDC. 2016:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWagner EA, Chantry CJ, Dewey KG, Nommsen-Rivers LA. Breastfeeding concerns at 3 and 7 days postpartum and feeding status at 2 months. Pediatrics. 2013;132(4):e865\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnderson AM. Disruption of lactogenesis by retained placental fragments. J Hum Lact. 2001;17(2):142\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArrowsmith S, Wray S. Oxytocin: its mechanism of action and receptor signalling in the myometrium. J Neuroendocrinol. 2014;26(6):356\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvensen A, Anderson JM, Fontaine P. Postpartum hemorrhage: prevention and treatment. Am Fam Physician. 2017;95(7):442\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoos F, Fontanaud P, Mekaouche M, Brown D. Oxytocin neurones are recruited into coordinated fluctuations of firing before bursting in the rat. Neuroscience. 2004;125(2):391\u0026ndash;410.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIsrael JM, Le Masson G, Theodosis DT, Poulain DA. Oxytocin-induced postinhibitory rebound firing facilitates bursting activity in oxytocin neurons. J Neurosci. 2008;28(2):385\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKenkel WM, Yee JR, Carter CS. Is oxytocin a maternal-foetal signalling molecule at birth? Implications for development. J Neuroendocrinol. 2014;26(10):739\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGimpl G, Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol Rev. 2001;81(2):629\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinson C, Schumann R, Zhang P, Young RC. Oxytocin-induced desensitization of the oxytocin receptor. Am J Obstet Gynecol. 2003;188(2):497\u0026ndash;502.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJonas W, Johansson LM, Nissen E, Ejdeb\u0026auml;ck M, Ransj\u0026ouml;-Arvidson AB, Uvn\u0026auml;s-Moberg K. Effects of intrapartum oxytocin administration and epidural analgesia on the concentration of plasma oxytocin and prolactin, in response to suckling during the second day postpartum. Breastfeed Med. 2009;4(2):71\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarc\u0026iacute;a-Fortea P, Gonz\u0026aacute;lez-Mesa E, Blasco M, Cazorla O, Delgado-R\u0026iacute;os M, Gonz\u0026aacute;lez-Valenzuela MJ. Oxytocin administered during labor and breastfeeding: A systematic review. Breastfeed Med. 2022;17(3):189\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBell AF, Erickson EN, Carter CS. Beyond labor: the role of natural and synthetic oxytocin in the transition to motherhood. J Midwifery Womens Health. 2014;59(1):35\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmith A, Zhu Y, Friedman AM, Gregory KD, Varda D, Landy HJ, Srinivas SK. Impact of synthetic oxytocin on breastfeeding outcomes in the first month after birth: a retrospective cohort study. Obstet Gynecol. 2023;141(2):276\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlza Fern\u0026aacute;ndez I, Mar\u0026iacute;n Gabriel M, Malalana Mart\u0026iacute;nez A, Fern\u0026aacute;ndez-Ca\u0026ntilde;adas Morillo A, L\u0026oacute;pez S\u0026aacute;nchez F, Costarelli V. Newborn feeding behaviour depressed by intrapartum oxytocin: a pilot study. Acta Paediatr. 2012;101(7):749\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFern\u0026aacute;ndez-Ca\u0026ntilde;adas Morillo A, Mar\u0026iacute;n Gabriel MA, Olza Fern\u0026aacute;ndez I, et al. The relationship of the administration of intrapartum synthetic oxytocin and breastfeeding initiation and duration rates. Breastfeed Med. 2017;12(2):98\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSegura-P\u0026eacute;rez S, Hromi-Fiedler A, Adnew M, Nyhan K, P\u0026eacute;rez-Escamilla R. Risk factors for self-reported insufficient milk during the first 6 months of life: A systematic review. Matern Child Nutr. 2022;18(Suppl 3):e13353.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDewey KG, Nommsen-Rivers LA, Heinig MJ, Cohen RJ. Risk factors for suboptimal infant breastfeeding behavior, delayed onset of lactation, and excess neonatal weight loss. Pediatrics. 2003;112(3):607\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMauri PA, Contini NN, Giliberti S, Barretta F, Consonni D, Negri M, Di Benedetto I. Intrapartum epidural analgesia and onset of lactation: a prospective study in an Italian birth centre. Matern Child Health J. 2015;19(3):511\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiklund I, Norman M, Uvn\u0026auml;s-Moberg K, Ransj\u0026ouml;-Arvidson AB, Andolf E. Epidural analgesia: breast-feeding success and related factors. Midwifery. 2009;25(2):e31\u0026ndash;8.\u003c/span\u003e\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":"Breastfeeding, Synthetic oxytocin, Labor augmentation, Labor induction, Lactation, Maternal-infant bonding, Postpartum care, Perinatal interventions","lastPublishedDoi":"10.21203/rs.3.rs-6693597/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6693597/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSynthetic oxytocin is widely used in obstetric practice, but its potential effects on breastfeeding outcomes remain controversial. Understanding these effects is crucial for optimizing maternal-infant health outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective cohort study was conducted at a university-affiliated tertiary medical center in Israel from September 2021 to June 2022. Participants included 358 women with term singleton spontaneous vaginal deliveries who intended to breastfeed exclusively. Women who received synthetic oxytocin during labor for induction or augmentation (n\u0026thinsp;=\u0026thinsp;181) were compared with those who did not (n\u0026thinsp;=\u0026thinsp;177). All participants received standard prophylactic oxytocin (10 IU) during the third stage of labor. The primary outcome was exclusive breastfeeding rate at 24\u0026ndash;72 hours postpartum. Secondary outcomes included breastfeeding initiation in the delivery room and factors associated with exclusive breastfeeding success.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWhile exclusive breastfeeding rates were lower in the synthetic oxytocin group in univariate analysis (35.4% vs 48.6%, P\u0026thinsp;=\u0026thinsp;.014), multivariate analysis revealed no independent association between synthetic oxytocin and exclusive breastfeeding (adjusted RR 0.67; 95% CI, 0.38\u0026ndash;1.20; P\u0026thinsp;=\u0026thinsp;.178). Women in the synthetic oxytocin group had higher rates of epidural analgesia (93.9% vs 52.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001), nulliparity (60.2% vs 22.6%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001), and lower rates of delivery room breastfeeding initiation (54.7% vs 78.0%, P\u0026thinsp;\u0026lt;\u0026thinsp;.001). Pre-labor breastfeeding counseling (adjusted RR 2.28; 95% CI, 1.24\u0026ndash;4.17; P\u0026thinsp;=\u0026thinsp;.008) and delivery room breastfeeding initiation (adjusted RR 1.87; 95% CI, 1.08\u0026ndash;3.25; P\u0026thinsp;=\u0026thinsp;.027) were identified as significant independent predictors of exclusive breastfeeding success.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eSynthetic oxytocin administration during labor was not independently associated with reduced exclusive breastfeeding rates after adjusting for confounding variables. Clinical efforts should focus on promoting prenatal breastfeeding education and facilitating early breastfeeding initiation, which strongly predicted successful exclusive breastfeeding regardless of synthetic oxytocin exposure.\u003c/p\u003e","manuscriptTitle":"Synthetic Oxytocin Administration During Labor and Its Impact on Exclusive Breastfeeding in the Immediate Postpartum Period","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-01 07:58:13","doi":"10.21203/rs.3.rs-6693597/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":"41b289b1-7532-477c-9a2b-bf1aff267201","owner":[],"postedDate":"July 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-07T17:40:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-01 07:58:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6693597","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6693597","identity":"rs-6693597","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}