# Comparison of oxytocin use between singleton and twin pregnancies during induction of labor: A multicenter case-control study

Ormancey Camille, Martins Laura, Massoud Mona, Huissoud Cyril, de La Fournière Benoit, Atallah Anthony, Rault Emmanuel

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Ormancey Camille, Martins Laura, Massoud Mona, Huissoud Cyril, de La Fournière Benoit, et al. Comparison of oxytocin use between singleton and twin pregnancies during induction of labor: A multicenter case-control study. European Journal of Obstetrics & Gynecology and Reproductive Biology, 2025, 306, pp.25-28. 10.1016/j.ejogrb.2024.12.045. inserm-05344940

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Full length article

# Comparison of oxytocin use between singleton and twin pregnancies during induction of labor: A multicenter case-control study

Ordancey Camille<sup>a</sup>, Martins Laura<sup>a</sup>, Massoud Mona<sup>c</sup>, Huissoud Cyril<sup>a</sup>,
De La Fournière Benoit<sup>d</sup>, Atallah Anthony<sup>a</sup>, Rault Emmanuel<sup>a,b,*</sup>

<figure><img src="image_3.png" /></figure>

## ARTICLE INFO

### Keywords:

Oxytocin

Twin pregnancies

Induction of labor

## ABSTRACT

**Objective:** To compare the oxytocin doses used during induction, relative to the number of labor hours, between singleton and twin pregnancies.

**Materials and methods:** We conducted a retrospective case-control study in two tertiary referral centers in France. Women with twin pregnancies who underwent labor induction with oxytocin in each center were eligible. Matching between cases (twin pregnancies) and controls (singleton pregnancies) was based on age, parity, gestational age, body mass index, and Bishop's score. We performed both univariate and multivariate analyses. The primary outcome was the total dose of oxytocin per hour (mIU/h). Secondary outcome included the maximum oxytocin infusion rate (mIU/min).

**Results:** A total of 400 women were included in the study: 200 women with twin pregnancies were matched with 200 women with singleton pregnancies. In univariate analysis, the total oxytocin dose per hour was significantly higher in the twin pregnancy group compared to the singleton group (360 mIU/h vs. 305 mIU/h, p = 0.01). Significant differences were also found for the secondary outcome: 10 mUI/min in the cases group and 8 mUI/min in the control group (p = 0.03). After adjustment, multivariate analysis showed that twin pregnancies were significantly associated with a higher total oxytocin dose per hour during induction (aOR: 1.95, 95 % CI [2.08, 5.32], p = 0.03).

**Conclusion:** In our study, women with twin pregnancies received significantly higher oxytocin doses during labor induction compared to women with singleton pregnancies. These findings suggest that oxytocin protocols for twin pregnancies may require specific adaptation.

## Introduction

Labor induction is a very common procedure in obstetrics, particularly in the population of pregnant women with twins, where the induction rate in France reaches 34 % [1]. This population is particularly exposed to the risk of induction failure, which is the leading cause of cesarean delivery after induction, affecting 13 % of twin pregnancies in the study by Loscul et al., compared to 4.9 % in the induced singleton population [2]. Despite this, the induction of labor in twin pregnancies has been understudied in the literature, in contrast to populations such as obese women, who are also at a heightened risk of induction failure. In a meta-analysis, Ellis et al. demonstrated a longer duration of labor

and higher doses of oxytocin compared to non-obese women [3]. In a randomized clinical trial, Ruth M. Wei et al. tested the hypothesis that increased doses of oxytocin could reduce labor duration in obese women undergoing induction [4]. However, no studies have specifically evaluated oxytocin use in women with twin pregnancies, despite their elevated rate of cesarean section for induction failure.

Our hypothesis was that oxytocin doses were higher in twin pregnancies compared to singleton pregnancies, and a specific protocol should be used for twin pregnancies. Due to the different length of labor between twins and singleton gestations [5], the objective of this study was to compare the doses of oxytocin used during induction, relative to the number of hours of labor, between singleton and twin pregnancies.

<footnote><sup>a</sup> Hôpital Femme Mère Enfant (Hospices Civils de Lyon), Bron, France</footnote>

<footnote><sup>b</sup> INSERM UMR1153, Epope, France</footnote>

<footnote><sup>c</sup> Hôpital Lyon Sud (Hospices Civils de Lyon), Pierre-Bénite, France</footnote>

<footnote><sup>d</sup> Hôpital de la Croix Rousse (Hospices Civils de Lyon), Lyon, France</footnote>

<footnote>* Corresponding author at: Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Obstétrique, 59 Bld Pinel 69500 BRON, France.</footnote>

<footnote>E-mail address: Emmanuel.rault@chu-lyon.fr (R. Emmanuel).</footnote>
## Materials and methods

We conducted a retrospective case-control study in two tertiary referral centers in France. Women with twin pregnancies who delivered between April 2017 and September 2021 were eligible for inclusion. Twin pregnancies that underwent labor induction with oxytocin after 34 weeks of gestation, regardless of the Bishop score, during the study period were included. Exclusion criteria included cases involving cervical ripening, breech presentation, severe fetal malformations, unreduced triplets, intrauterine fetal death, and monochorionic monoamniotic pregnancies. Singleton pregnancies that met the same criteria were eligible. Matching between twin pregnancies (cases) and singleton pregnancies (controls) was performed based on maternal age, parity, gestational age, body mass index (BMI), and Bishop score. Parity was exactly matched, while age and BMI were matched to the closest possible value. Gestational age was rounded to the nearest week and matched within one week. Bishop scores were matched within two units. In cases where multiple singleton pregnancies shared similar characteristics, random selection was used to include the control.

Due to the differences in labor duration between twin and singleton pregnancies, we compared oxytocin doses administered per hour. The primary outcome was the total dose of oxytocin per hour (mUI/hour). Secondary outcomes included the oxytocin dose per hour during the latent phase, active phase, first stage, and second stage of labor, as well as the maximum oxytocin flow rate during labor (mUI/min).

Data were extracted from our computerized medical records (Easily™, Hospices Civils de Lyon) by two investigators and recorded in a dedicated database. General and obstetric characteristics were collected, and the Bishop score was calculated according to the definition provided in Supplementary Data (Table S1). Labor durations were calculated from the initiation of oxytocin infusion. The stages of labor were defined based on the French national guidelines. Specifically, the active phase of labor was defined as beginning at the first examination with a cervical dilation of 5 cm or more and continuing until full cervical dilation. Examinations were routinely performed every one to two hours during labor. Oxytocin doses were documented from the medical records, and total doses were calculated, taking into account all dose changes. Oxytocin was administered by midwives according to local protocols. Maternity Unit A followed national guidelines for oxytocin administration, starting at 2 mUI/min and increasing by 2 mUI/min every 30 min up to a maximum of 20 mUI/min. Maternity Unit B followed regional guidelines, starting at 2.5 mUI/min and increasing by 2.5 mUI/min, with a maximum of 20 mUI/min.

All statistical analyses were performed using R software (R Core Team (2021). R Foundation for Statistical Computing, Vienna, Austria. URL https://www.R-project.org/). Continuous variables were expressed as means with standard deviations, or medians with interquartile ranges, depending on the distribution, which was assessed using the Kolmogorov-Smirnov test. Differences between groups were evaluated using the appropriate statistical tests: Student's t-test, Mann-Whitney U test, Fisher's exact test, and the chi-square test. A p-value of < 0.05 was considered statistically significant, and all p-values were two-sided.

Initially, we conducted a univariate analysis to compare oxytocin doses (mUI), dose per hour (mUI/hour), and maximum flow rates (mUI/min) between twin and singleton pregnancies. Subsequently, we constructed two multivariate logistic regression models to adjust for potential confounders and assess the independent association between pregnancy type and the primary outcome (total oxytocin dose per hour), as well as one secondary outcome (maximum oxytocin flow rate). For each outcome, the median value for the entire population was calculated, and pregnancies above the median were categorized for each group. Variables identified as significant in the univariate analysis and associated with oxytocin doses above the median were included in the regression model. A p-value of < 0.10 was used to identify variables for inclusion in the multivariate models. The multivariate model for total oxytocin dose per hour was adjusted for maternity unit, membrane

status prior to induction, in vitro fertilization (IVF), indication for induction, macrosomia, and Bishop score. The model for maximum oxytocin flow rate was adjusted for maternity unit, fetal malformation, IVF, epidural analgesia, macrosomia, Bishop score, and parity. Adjusted odds ratios (aOR) and 95 % confidence intervals (CI) were calculated.

Ethical approval for this study was obtained from the Scientific and Ethical Committee of our institution (Institutional Review Board number 00013204).

## Results

A total of 1,391 women with twin pregnancies were eligible between April 2017 and September 2021. After applying the inclusion and exclusion criteria, 200 women with twin pregnancies were included in the analysis. General and obstetric characteristics are presented in Table 1. When comparing both groups in terms of general characteristics, no statistically significant differences were observed in age, BMI, medical and obstetric history, parity, or nulliparity. However, the twin pregnancy group had a significantly higher proportion of pregnancies conceived via IVF (p < 0.01).

Regarding obstetric characteristics, there were no statistically significant differences between the groups in terms of non-severe fetal malformations, gestational diabetes, preterm rupture of membranes, preeclampsia, fetal growth restriction, or cholestasis. However, the twin pregnancy group had significantly more women receiving corticosteroid treatments (p < 0.01) and a higher incidence of threatened preterm labor (p = 0.03). Conversely, the incidence of macrosomia was significantly higher in the singleton pregnancy group (p = 0.02).

The characteristics of labor induction and delivery are presented in Table 2. Concerning the indications for labor induction, twin pregnancies were more frequently induced due to gestational age, whereas singleton pregnancies were primarily induced for maternal or fetal reasons. Additionally, there was a significantly higher incidence of membrane rupture prior to induction in the singleton group (p < 0.01). No significant difference was found between the two groups in the

<table><caption>**Table 1**

General and obstetrical characteristics.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Twins (n = 200)</th><th colspan="2">Singleton (n = 200)</th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td colspan="5"><strong>General characteristics</strong></td></tr><tr><td>Age (median [IQR])</td><td>32.00</td><td>[29.00, 36.00]</td><td>32.00</td><td>[29.00, 35.00]</td></tr><tr><td>BMI (median [IQR])</td><td>23.00</td><td>[21.00, 26.00]</td><td>23.00</td><td>[21.00, 26.00]</td></tr><tr><td>Parity (mean (SD))</td><td>0.79</td><td>±1.03</td><td>0.79</td><td>(1.03)</td></tr><tr><td>Nullipare</td><td>104</td><td>(52.0)</td><td>104</td><td>(52.0)</td></tr><tr><td>IVF</td><td>62</td><td>(31.0)</td><td>8</td><td>(4.0)</td></tr><tr><td>History of Diabete</td><td>2</td><td>(1.0)</td><td>5</td><td>(2.5)</td></tr><tr><td>History of HBP</td><td>2</td><td>(1.0)</td><td>2</td><td>(1.0)</td></tr><tr><td>History of late miscarriage or FDIU</td><td>2</td><td>(1.0)</td><td>7</td><td>(3.5)</td></tr><tr><td>History of previous preterm birth</td><td>2</td><td>(1.0)</td><td>7</td><td>(3.5)</td></tr><tr><td>History of preeclampsia</td><td>4</td><td>(2.0)</td><td>5</td><td>(2.5)</td></tr><tr><td>History of cesarean section</td><td>6</td><td>(3.0)</td><td>8</td><td>(4.0)</td></tr><tr><td colspan="5"><strong>Obstetrical characteristics</strong></td></tr><tr><td>Chorionicity</td><td></td><td></td><td></td><td></td></tr><tr><td>BCBA</td><td>150</td><td>(75.0)</td><td></td><td></td></tr><tr><td>MCBA</td><td>50</td><td>(25.0)</td><td></td><td></td></tr><tr><td>Non severe fetal malformation</td><td>4</td><td>(2.0)</td><td>5</td><td>(2.5)</td></tr><tr><td>Gestational diabetes</td><td>28</td><td>(14.0)</td><td>44</td><td>(22.0)</td></tr><tr><td>Threatened preterm birth</td><td>37</td><td>(18.5)</td><td>16</td><td>(8.0)</td></tr><tr><td>Preterm rupture of membranes</td><td>16</td><td>(8.0)</td><td>20</td><td>(10.0)</td></tr><tr><td>Preeclampsia</td><td>14</td><td>(7.0)</td><td>6</td><td>(3.0)</td></tr><tr><td>Fetal growth restriction</td><td>17</td><td>(8.5)</td><td>13</td><td>(6.5)</td></tr><tr><td>Macrosomia</td><td>0</td><td>(0.0)</td><td>11</td><td>(5.5)</td></tr></tbody></table>

HBP: High Blood Pressure; BMI: Body Mass Index; BCBA: bichorionic diamniotic; MCBA: monochorionic diamniotic; IVF: In Vitro Fecundation; FDIU: Fetal Death In Utero.
<table><caption>**Table 2**
Characteristics of induction of labor and delivery.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Twins (n = 200)</th><th colspan="2">Singletons (n = 200)</th><th rowspan="2">P value</th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td><strong>Indications of IOL</strong></td><td></td><td></td><td></td><td></td><td>&lt;0.01</td></tr><tr><td>Maternal reasons</td><td>38</td><td>(19.0)</td><td>52</td><td>(26.0)</td><td></td></tr><tr><td>Fetal reasons</td><td>53</td><td>(26.5)</td><td>148</td><td>(74.0)</td><td></td></tr><tr><td>Term</td><td>109</td><td>(54.5)</td><td>0</td><td>(0.0)</td><td></td></tr><tr><td><strong>Ruptured membranes before induction</strong></td><td>21</td><td>(10,5)</td><td>114</td><td>(57.0)</td><td>&lt;0.01</td></tr><tr><td><strong>Bishop Score</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-3</td><td>47</td><td>(23.5)</td><td>46</td><td>(23.0)</td><td>1.00</td></tr><tr><td>4-6</td><td>80</td><td>(40.0)</td><td>98</td><td>(49.0)</td><td>0.09</td></tr><tr><td>7 and more</td><td>73</td><td>(36.5)</td><td>56</td><td>(28.0)</td><td>0.09</td></tr><tr><td><strong>Delivery</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Vaginal delivery</td><td>163</td><td>(81.5)</td><td>183</td><td>(91.5)</td><td>0.01</td></tr><tr><td><strong>Indication of cesarean section</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Induction failure</td><td>11</td><td>(5.5)</td><td>6</td><td>(3.0)</td><td>0.32</td></tr><tr><td>Failure to progress in active phase</td><td>15</td><td>(7.5)</td><td>2</td><td>(1.0)</td><td>0.01</td></tr><tr><td>Non reassuring fetal status</td><td>8</td><td>(4.0)</td><td>9</td><td>(4.5)</td><td>1.00</td></tr><tr><td>Extraction failure</td><td>3</td><td>(1.5)</td><td>0</td><td>(0.0)</td><td>0.25</td></tr></tbody></table>

occurrence of uterine tachysystole (21.5 % vs 17.0 %; p = 0.31).

As expected, due to matching, the Bishop scores were comparable between the groups, with a median score of 6.00 for both (p = 0.22). The median gestational age at delivery, rounded to the nearest week, was significantly higher in the singleton group than in the twin group (38.0 vs 37.6 weeks, p = 0.03). Vaginal delivery was more frequent in the singleton group (p = 0.05). Among cesarean section indications, there was a significant difference, with more cesarean sections performed for failure to progress during the active phase in the twin group (p = 0.03).

Regarding complications, twin pregnancies were associated with significantly higher rates of postpartum hemorrhage (PPH) and severe PPH (p < 0.01), more transfusions (p < 0.01), and a greater volume of blood loss (p < 0.01). Maternal and neonatal outcomes are detailed in Table 3.

The results of the univariate analysis are presented in Table 4. The primary outcome was significant, with higher total oxytocin doses per hour in the twin pregnancy group (360 mUI/h [255,496]) compared to the singleton pregnancy group (305 mUI/h [174,417]; p < 0.01). Fig. 1 illustrates the hourly doses of oxytocin for each outcome.

For the secondary outcomes, significant differences were also observed. Oxytocin doses per hour were significantly higher in the twin

<table><caption>**Table 3**
Maternal and neonatal outcomes.</caption><thead><tr><th rowspan="2"></th><th rowspan="2"></th><th colspan="2">Twins (n = 200)</th><th colspan="2">Singletons (n = 200)</th><th rowspan="2">P value</th></tr><tr><th>n</th><th>%</th><th>n</th><th>%</th></tr></thead><tbody><tr><td colspan="7"><strong>Maternal outcomes</strong></td></tr><tr><td>3rd and 4th degree tears</td><td></td><td>3</td><td>(1.5)</td><td>5</td><td>(2.5)</td><td>0.72</td></tr><tr><td>PPH</td><td></td><td>57</td><td>(28.5)</td><td>15</td><td>(7.5)</td><td>&lt;0.01</td></tr><tr><td>severe PPH</td><td></td><td>16</td><td>(8.0)</td><td>2</td><td>(1.0)</td><td>&lt;0.01</td></tr><tr><td>transfusion</td><td></td><td>12</td><td>(6.0)</td><td>1</td><td>(0.5)</td><td>&lt;0.01</td></tr><tr><td>Volume of blood loss (ml), median [IQR]</td><td></td><td>300 [150,600]</td><td></td><td>100 [100,250]</td><td></td><td>&lt;0.01</td></tr><tr><td colspan="7"><strong>Neonatal outcomes</strong></td></tr><tr><td>Weight (g), median [IQR]</td><td></td><td>2544 [2324,2750]</td><td></td><td>2930 [2600,3227]</td><td></td><td>&lt;0.01</td></tr><tr><td rowspan="2">Apgar &lt; 7 at 5 min</td><td>First twin</td><td>1 (0.5)</td><td></td><td>4 (2.0)</td><td></td><td>0.37</td></tr><tr><td>Second twin</td><td>3 (1.5)</td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Pha &lt; 7,10</td><td>First twin</td><td>0 (0.0)</td><td></td><td>1 (0.5)</td><td></td><td>1.00</td></tr><tr><td>Second twin</td><td>5 (2.5)</td><td></td><td></td><td></td><td></td></tr><tr><td rowspan="2">Neonatal hospitalization</td><td>First twin</td><td>38 (19.0)</td><td></td><td>22 (11.0)</td><td></td><td>0.04</td></tr><tr><td>Second twin</td><td>41 (20.5)</td><td></td><td></td><td></td><td></td></tr></tbody></table>

PPH: Postpartum hemorrhage; AROM: artificial rupture of the membranes.

<table><caption>**Table 4**
Cumulative doses, maximum flow and hourly doses of oxytocin according to stage of labor.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Twins (n = 200)</th><th colspan="2">Singleton (n = 200)</th><th rowspan="2">p</th></tr><tr><th>median</th><th>IQR</th><th>median</th><th>IQR</th></tr></thead><tbody><tr><td><strong>Cumulative doses (mUI)</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Latent phase</td><td>2067</td><td>[971,3843]</td><td>1228</td><td>[692,2602]</td><td>&lt;0.01</td></tr><tr><td>Active phase</td><td>425</td><td>[1,1117]</td><td>80</td><td>[1,526]</td><td>&lt;0.01</td></tr><tr><td>First stage of labor</td><td>2701</td><td>[1475,5000]</td><td>1686</td><td>[812,3127]</td><td>&lt;0.01</td></tr><tr><td>Second stage of labor</td><td>286</td><td>[34,00, 777.00]</td><td>140</td><td>[14,50, 604]</td><td>0.02</td></tr><tr><td>Total dose</td><td>318</td><td>[1868,5312]</td><td>2075</td><td>[975,3594]</td><td>&lt;0.01</td></tr><tr><td><strong>Maximum flow (mUI/min)</strong></td><td>10</td><td>[6,12]</td><td>8</td><td>[6,10]</td><td>0.03</td></tr><tr><td><strong>Doses per hour (mUI/h)</strong></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Latent phase</td><td>354</td><td>[234,495]</td><td>314</td><td>[186,420]</td><td>0.02</td></tr><tr><td>Active phase</td><td>360</td><td>[240,480]</td><td>300</td><td>[120,465]</td><td>0.06</td></tr><tr><td>First stage of labor</td><td>355</td><td>[233,480]</td><td>312</td><td>[183,416]</td><td>0.04</td></tr><tr><td>Second stage of labor</td><td>371</td><td>[222,575]</td><td>298</td><td>[120,450]</td><td>&lt;0.01</td></tr><tr><td>Total dose</td><td>360</td><td>[255,496]</td><td>305</td><td>[173,417]</td><td>0.01</td></tr></tbody></table>

group during the first phase of labor (35 mUI/h vs 31 mUI/h, p = 0.04), the latent phase (354 mUI/h vs 314 mUI/h, p = 0.02), and the second stage of labor (371 mUI/h vs 298 mUI/h, p < 0.01). During the active phase, the hourly oxytocin dose was higher in the twin group, though not significantly so (360 mUI/h vs 300 mUI/h, p = 0.06). The median maximum oxytocin flow rate was significantly higher in the twin pregnancy group (10 mUI/min) compared to the singleton group (10 mUI/min vs 8 mUI/min, p = 0.03).

In the multivariate analysis, we tested the independent association between pregnancies exceeding the median total dose of oxytocin per hour and baseline obstetric characteristics (Table S2). A similar analysis was performed for the maximum oxytocin flow rate (Table S3). After multivariate adjustment, twin pregnancy was significantly associated with higher total hourly oxytocin doses (aOR: 1.95, 95 % CI [1.20, 3.32], p = 0.03) and higher maximum oxytocin flow rates during labor induction (aOR: 2.14, 95 % CI [1.34, 3.43], p = 0.01) (Table 5).

Discussion

In our study, women with twin pregnancies received higher doses of oxytocin and had higher maximum flow rates compared to those with singleton pregnancies. When adjusted for labor duration, oxytocin doses per hour remained higher in twin pregnancies throughout the course of labor. After controlling for confounding factors, twin pregnancies were still independently associated with increased oxytocin doses per hour and higher maximum oxytocin flow rates.

Few studies have investigated oxytocin dosing in twin gestations. A retrospective case-control study published in 1997 found that oxytocin stimulation in twin pregnancies was comparable to singleton pregnancies in terms of dosage, duration, complications, and the ability to achieve vaginal delivery, without adverse effects [6]. In 2013, Wolfe et al. evaluated the success of labor induction in twin pregnancies using protocols designed for singleton pregnancies in a cohort of 40 women. They found comparable oxytocin doses and concluded that singleton protocols applied to twin pregnancies were safe and generally led to favorable outcomes [7]. However, our study suggests that oxytocin protocols may need to be adapted for twin gestations. As Amikam et al. underlined previously, studies comparing different regimens of oxytocin for IOL in twin pregnancies are lacking [8]. A randomized clinical trial comparing different oxytocin dosing regimens would be essential to optimize the management of labor induction in women with twin pregnancies.
<figure><img src="image_4.png" /><figcaption>Fig. 1. Hourly doses of oxytocin (mUI/h).</figcaption></figure>

**Table 5**

Multivariate logistic regression analysis for the association between baseline characteristics and total doses per hour of oxytocin and maximum flow of oxytocin.

<table><thead><tr><th>Total doses of oxytocin</th><th>p</th><th>aOR</th><th>95 %CI</th></tr></thead><tbody><tr><td>Maternity B</td><td>&lt; 0.01</td><td>3.31</td><td>[2.08-5.32]</td></tr><tr><td>Ruptured membranes before induction</td><td>0.42</td><td>1.29</td><td>[0.69-2.45]</td></tr><tr><td>IVF</td><td>0.95</td><td>1.02</td><td>[0.55-1.89]</td></tr><tr><td>Indication of IOL*</td><td></td><td></td><td></td></tr><tr><td>Term</td><td>0.60</td><td>1.20</td><td>[0.60-2.43]</td></tr><tr><td>Fetal reasons</td><td>0.31</td><td>0.71</td><td>[0.37-1.37]</td></tr><tr><td>Macrosomia</td><td>0.01</td><td>17.55</td><td>[3.04-333.55]</td></tr><tr><td>Bishop's score**</td><td></td><td></td><td></td></tr><tr><td>4-6</td><td>0.90</td><td>0.95</td><td>[0.44-2.02]</td></tr><tr><td>&gt; 6</td><td>0.39</td><td>0.69</td><td>[0.29-1.60]</td></tr><tr><td>Twin pregnancy</td><td>0.03</td><td>1.95</td><td>[2.08, 5.322]</td></tr><tr><td>Maximum flow of oxytocin</td><td></td><td></td><td></td></tr><tr><td>Maternity B</td><td>&lt; 0.01</td><td>3.42</td><td>[2.13-5.56]</td></tr><tr><td>Fetal malformation</td><td>0.98</td><td>1.02</td><td>[0.22-4.39]</td></tr><tr><td>IVF</td><td>0.68</td><td>1.13</td><td>[0.61-2.10]</td></tr><tr><td>Epidural analgesia</td><td>0.30</td><td>1.69</td><td>[0.64-4.85]</td></tr><tr><td>Nulliparity</td><td>0.19</td><td>0.74</td><td>[0.48-1.15]</td></tr><tr><td>Macrosomia</td><td>&lt; 0.01</td><td>18.82</td><td>[3.26-358.1]</td></tr><tr><td>Bishop's score**</td><td></td><td></td><td></td></tr><tr><td>4-6</td><td>0.87</td><td>0.94</td><td>[0.43-1.99]</td></tr><tr><td>&gt; 6</td><td>0.42</td><td>0.70</td><td>[0.30-1.63]</td></tr><tr><td>Twin pregnancy</td><td>&lt; 0.01</td><td>2.14</td><td>[1.34-3.43]</td></tr></tbody></table>

IVF: in vitro fecundation, IOL: induction of labor, *maternal reasons as reference, **bishop's score 0-3 as reference.

This study is the first to directly compare oxytocin doses administered during labor induction between twin and singleton pregnancies. We included a large cohort of 200 patients per group from two tertiary referral centers, each using different protocols for oxytocin administration. Given the differences in labor duration between singleton and twin gestations, oxytocin doses were normalized per hour to ensure accurate comparisons. Importantly, there were no missing data, as all information was extracted from our comprehensive computerized records. Our findings were consistent across different labor stages and phases. Multivariate analysis allowed us to explore the independent association between oxytocin doses and type of pregnancy, adjusting for potential confounding factors.

However, our study did not address the underlying reasons for the increased oxytocin dosing, as we did not assess uterine dynamics. It is unclear whether the higher oxytocin doses were administered in excess (i.e., according to protocol increments every 20 or 30 min despite adequate uterine dynamics) or out of necessity due to suboptimal uterine activity. Nevertheless, we did record incidences of tachysystole from the clinical reports, and no significant difference was observed

between the twin and singleton groups (21.5 % vs. 17 %, p = 0.31). Given that inappropriate or excessive oxytocin administration can affect fetal heart rate, it would be valuable to evaluate fetal monitoring in relation to varying oxytocin doses.

**Conclusion**

This retrospective multicenter case-control study demonstrates that women with twin pregnancies are more likely to receive higher doses of oxytocin during labor induction compared to those with singleton pregnancies. These findings should be taken into account when developing induction protocols for twin pregnancies. Further studies, particularly randomized controlled trials, are needed to determine whether higher oxytocin doses can optimize labor induction management in twin pregnancies under safe conditions.

**Declaration of competing interest**

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

**Appendix A. Supplementary data**

Supplementary data to this article can be found online at https://doi.org/10.1016/j.ejogrb.2024.12.045.

**References**

[1] Cinelli, H., Lelong, N., et Le Ray, C. Rapport de l'Enquête Nationale Périnatale 2021 En France Métropolitaine: Les Naissances, Le Suivi à 2 Mois et Les Établissements—Situation et Évolution Depuis 2016. Inserm, Octobre, 2022.

[2] Loscul C, Schmitz T, Blanc-Petitjean P, Goffinet F, Le Ray C. JUMODA and MEDIP study groups. Risk of cesarean after induction of labor in twin compared to singleton pregnancies. Eur J Obstet Gynecol Reprod Biol juin 2019;237:68-73.

[3] Ellis JA, Brown CM, Barger B, Carlson NS. Influence of Maternal Obesity on Labor Induction: A Systematic Review and Meta-Analysis. J Midwifery Womens Health janv 2019;64(1):55-67.

[4] Wei RM, Bounthavong M, Hill MG. High- vs low-dose oxytocin in lean and obese women: a double-blinded randomized controlled trial. Am J Obstet Gynecol MFM juill 2022;4(4):100627.

[5] Hochler H, Guedalia J, Lipschuetz M, Walfisch A, Yagel S, Guedalia Friedman E, et al. Normal labor curve in twin gestation. Am J Obstet Gynecol Nov 2021;225(5): 546.e1-546.e11.

[6] Fausett MB, Barth WH, Yoder BA, Satin AJ. Oxytocin labor stimulation of twin gestations: effective and efficient. Obstet Gynecol août 1997;90(2):202-4.

[7] Wolfe MD, de la Torre L, Moore LE, Myers O, Rayburn WF. Is the protocol for induction of labor in singletons applicable to twin gestations? J Reprod Med 2013; 58(3-4):137-42.

[8] Amikam U, Hiersch L, Barrett J, Melamed N. Labour induction in twin pregnancies. Best Pract Res Clin Obstet Gynaecol. 1 mars 2022;79:55-69.