Introduction: In fetal surgery, successful pain management is crucial for postoperative mobilization, prophylaxis of contractions, and fast recovery. This study analyzed patient’s pain experience after open fetal spina bifida (fSB) repair in comparison to pain scores after the subsequent Caesarean section (C-section). Materials and Methods: Data were collected with a questionnaire given to 91 women, who had fSB repair and then C-section at our center between 2019 and 2022. It comprised 12 questions covering different aspects of pain experience and satisfaction with pain therapy and was answered by 67 women after fSB repair and 53 after C-section. Postoperative pain was rated on a Likert scale from 0 (slight/rarely) to 100 (strongest/always). Outcomes after fSB repair were compared to those after C-section. Additionally, subgroup analysis compared outcomes of women with different pain levels (group 1–5) after fSB repair. Results: Compared to women after C-section women after fSB repair reported significantly higher maximum pain scores (MPS) (p = 0.03), higher sleep disturbance due to pain (p = 0.03), and sedation rates (p = 0.001) as side effect from pain therapy. No differences were found regarding feelings of insecurity (p = 0.20) or helplessness (p = 0.40), as well as involvement in (p = 0.3) and satisfaction with pain therapy (p = 0.5). Subgroup analysis revealed that women with higher MPS after fSB repair were significantly more often non-Caucasians (p = 0.003) and more often affected by pain while lying in bed (p = 0.007) and during mobilization (p = 0.005). Additionally, they reported higher rates of dizziness (p = 0.02) and lower satisfaction rates with pain therapy (p = 0.03). Postoperative complication rate did not differ among groups. Conclusion: Although women after fSB repair reported higher MPS compared to after C-section, the current pain management was generally perceived as satisfactory.

In utero fetal spina bifida (fSB) repair has become a compelling treatment option since the Management of Myelomeningocele Study (MOMS) showed better outcomes after prenatal compared to postnatal repair [1]. Our own studies corroborated favorable outcome results after fSB repair [2, 3]. Of note, performing in utero fSB repair entails maternal-fetal surgery since the surgeon needs to enter the mother’s womb to reach the fetus. It is well known that inadequate pain management after surgery causes a stress response of the body with increased production of cortisol [4, 5]. Cortisol promotes uterine activity and therefore increases the risk for preterm labor [5]. Furthermore, inadequate pain control prolongs or complicates postoperative mobilization, which is paramount to achieve early gut function and generally helps maintaining the body’s functional capacities [4]. Additionally, immobilization increases the already elevated risk for thromboembolic events, a complication that still represents one of the leading causes for maternal morbidity and mortality worldwide, as well as the risk for pulmonary complications [4, 6, 7]. Furthermore, severe acute postpartum pain has been shown to increase the risk for persistent pain as well as for postpartum depression [8].

Given that effective postsurgical pain management is of utmost importance and influences outcomes, the aim of this study was to understand pain and emotional experiences of women undergoing fSB repair better, especially in the unique setting of a postoperatively scarred uterus that is constantly exposed to mechanical stress due to fetal movements and growth. Hence, we analyzed and compared the experience of pain and emotions after fSB repair with the ones after the subsequent Caesarean section (C-section) in the same patient cohort.

This retrospective single-center longitudinal cohort study was performed between 2019 and 2022 at the Zurich Center for Fetal Diagnosis and Therapy. After having performed 105 open fSB repairs, a questionnaire regarding postoperative pain was created and handed out to all subsequent women undergoing fSB repair. Women received the same questionnaire once after fSB repair and after the subsequent C-section. For this study, a total of 91 consecutively operated women were included (shown in Fig. 1), independent of the exact pain management they received. Postoperative pain was assessed using a standardized pain questionnaire that already showed good applicability in a previous study, when we analyzed postoperative pain after C-section without prior fSB repair [9]. For this current study, the original questionnaire was shortened to enable faster completion and therefore increase participation and can be found in the supplementary materials (for all online suppl. material, see https://doi.org/10.1159/000538588). The questionnaire was initially handed out on postoperative day 4, in paper form in German, in the first 57 women, whereas all remaining women received an online link, on postoperative day 4, to fill out the questionnaire in German or English. Women filled out all questionnaires by themselves. The questionnaire contained 12 questions regarding the topics of pain intensity, degree of pain relief, emotional impact of pain, patient’s involvement in and satisfaction with pain therapy, as well as pain history within the last 3 months. Quantitative parameters were rated on a Likert scale, which is a numeric rating scale ranging from: 0–9 (none/never), 10–39 (slight/rarely), 40–69 (moderate/sometimes), 70–99 (strong/often), and 100 (strongest/always). Data were collected in our registry using REDCap® (Research Electronic Data Capture) [10]. In case of not answering any questionnaire, women were excluded from the study, leaving a cohort of 78 women. Inclusion criteria for fSB repair, surgical technique, as well as peri- and postoperative management at our center have been published previously [11‒14]. Additionally, the following demographic, obstetric, and fetal parameters were analyzed: maternal age at fetal surgery, maternal body mass index at fetal surgery, maternal ethnicity and education, parity, previous open uterine surgeries (open fetal surgery, hysterotomy, myomectomy, classical C-section, low transverse C-section), total operative duration of fSB repair, length and location of hysterotomy, hysterotomy status at delivery, fetal gender, gestational age at surgery and delivery, fetal birth weight, as well as use, type, and duration of postoperative tocolytics. Furthermore, the occurrence of postoperative maternal complications after fSB repair was analyzed with the help of the Zurich classification system, as previously described [15].

Fig. 1.

Flow diagram of women answering the questionnaire after fSB repair and C-section.

Fig. 1.

Flow diagram of women answering the questionnaire after fSB repair and C-section.

Close modal

Outcomes after fSB repair were compared to the ones after C-section. In order to better understand the characteristics and effects of postoperative pain after fSB repair, women were furthermore divided into 5 groups, according to their maximum pain scores (MPS) after fSB repair, and compared among groups: group 1 (pain score 1–9), group 2 (pain score 10–39), group 3 (pain score 40–69), group 4 (pain scores 70–99), group 5 (pain score 100) (shown in Fig. 2).

Fig. 2.

Women divided into groups 1–5 according to their maximal postoperative pain score.

Fig. 2.

Women divided into groups 1–5 according to their maximal postoperative pain score.

Close modal

Pain management after fSB repair consisted of a thoracic epidural analgesia (EDA), as the main component of postoperative analgesia. We opted for the thoracic instead of the lumbar puncture side to achieve better mobilization postoperatively. The EDA was placed prior to fSB repair, but only started prior to skin closure in order to avoid vasoplegia. It was then generally maintained until postoperative day 3. In cases with insufficient EDA, we established an opioid based analgesia without any delay, in most cases a patient controlled analgesia. Additionally, women received Targin®, an opioid consisting of a combination of oxycodone and naloxone, as well as paracetamol as regular, basic pain therapy. In case of further need for pain relief, morphine, tramadol, or oxycodone were given. On the other hand, regular pain therapy after C-section consisted of a combination of non-steroidal anti-inflammatory drug (NSAID) and paracetamol with tramadol or morphine as rescue medication.

SPSS (version 29, IBM, USA) was used for statistical analysis. Shapiro-Wilk test was performed to evaluate normal distribution. Baseline characteristics were analyzed with descriptive statistics. Mann-Whitney U test, T test for independent parameters, χ2 test or Fisher’s exact test were used as appropriate to compare outcomes after fSB repair with the ones after C-section. Subgroup analysis was conducted with Kruskal-Wallis and χ2 tests. In case of multiple comparison, Bonferroni correction was used where needed to protect from type 1 error. Categorical variables are given as percentages. Quantitative data are presented as mean ± standard deviation in case of normal distribution and as median with interquartile range if normal distribution was not given. A p value <0.05 was considered statistically significant.

All women included in this study signed written informed consent. The study was approved by the Local Ethics Commission Zurich (KEK-ZH, No. 2021-01101) and was conducted in compliance with the Declaration of Helsinki.

Out of 91 women, 78 (86%) answered at least one and 42 (46%) answered both questionnaires. Of the 182 questionnaires handed out, 120 were answered, 67 (74%) after fSB repair, and 53 (58%) after C-section. Baseline characteristics of the cohort are shown in Table 1. Results from the questionnaires are shown in Table 2. Questionnaires were filled out significantly earlier after fSB repair compared to C-section (after 4 [4–4] days vs. 4 [4–7] days, p = 0.04). Maximal postoperative pain was significantly higher after fSB repair compared to C-section (68 [50–80] vs. 56 ± 21, p = 0.03) (shown in Fig. 2-4), whereas no differences were identified regarding minimal postoperative pain (0 [0–10] vs. 2 [0–20], p = 0.31), or pain occurrence (30 [11–49] vs. 30 [20–39], p = 1.0). When analyzing the impact of pain on different activities, results showed that sleep was significantly more often disturbed by pain after fSB repair compared to C-section (40 [20–66] vs. 30 [10–50], p = 0.03). Rates of postoperative mobilization after fSB repair and C-section did not significantly differ (100 vs. 98%, p = 0.44). Regarding side effects from pain therapy, women after fSB repair significantly more often reported sedation (15 [0–45] vs. 0 [0–24], p = 0.001), but no significant differences were found regarding nausea, itching, or dizziness. There was also no significant difference regarding feelings of insecurity (30 [10–60] vs. 20 [10–50], p = 0.18) and helplessness (30 [10–66] vs. 29 [1–61], p = 0.38). Both groups reported pain relief consequent to pain therapy of around 80% of the pain intensity; however, the wish for additional pain therapy was not significantly higher after fSB repair compared to after C-section (12 vs. 6%, p = 0.34). Satisfaction with pain therapy did not significantly differ between the two groups (95 [78–100] after fSB repair vs. 100 [80–100] after C-section, p = 0.46).

Table 1.

Baseline characteristics

ParametersN = 78
Maternal age at fSB repair, years 32.6±4.7 
Maternal BMI at fSB repair, kg/m2 27.0 (24.1–30.8) 
Ethnicity, N (%) 
 Caucasian 75 (96.2) 
 Mediterranean 2 (2.6) 
 Afro-American 1 (1.3) 
Maternal education, N (%) N = 751 
 Elementary school 4 (5.3) 
 Vocation school 40 (53.3) 
 Collage 14 (18.7) 
 University, bachelor degree 10 (13.3) 
 University, master degree 5 (6.7) 
 University, doctor degree 2 (2.7) 
Primiparous, N (%) 41 (52.6) 
Previous open uterine surgery, N (%) 3 (3.4) 
 Hysterotomy 0 (0.0) 
 Myomectomy 0 (0.0) 
 Classical C-section 1 (1.1) 
 Low-transverse C-section 2 (2.2) 
Total operative time of fSB repair, min 134 (120–152) 
Length of hysterotomy, cm 6.5 (6.0–7.0) 
Location of hysterotomy, N (%) 
 Anterior 37 (40.7) 
 Posterior 54 (59.3) 
Postoperative tocolysis, N (%) 77 (100)1 
Type of postoperative tocolysis, N (%) 
 Atosiban 76 (98.7) 
 Gynipral 55 (71.4) 
 Nifedipin 75 (97.4) 
Duration of tocolysis, days 
 Atosiban 5 (4–8) 
 Gynipral 9 (7–14) 
 Nifedipin 67 (55–76) 
Hysterotomy status at delivery, N (%) 
 Intact 21 (31.8) 
 Thin 40 (60.6) 
 Focal dehiscence 4 (6.1) 
 Complete dehiscence 1 (1.5) 
Fetal gender, N (%) 
 Male 43 (47.3) 
 Female 48 (52.7) 
GA at fSB repair, weeks 25.2±0.7 
GA at delivery, weeks 37.0 (34.9–37.0) 
Fetal weight at delivery, g 2,695 (2,283–2,948) 
ParametersN = 78
Maternal age at fSB repair, years 32.6±4.7 
Maternal BMI at fSB repair, kg/m2 27.0 (24.1–30.8) 
Ethnicity, N (%) 
 Caucasian 75 (96.2) 
 Mediterranean 2 (2.6) 
 Afro-American 1 (1.3) 
Maternal education, N (%) N = 751 
 Elementary school 4 (5.3) 
 Vocation school 40 (53.3) 
 Collage 14 (18.7) 
 University, bachelor degree 10 (13.3) 
 University, master degree 5 (6.7) 
 University, doctor degree 2 (2.7) 
Primiparous, N (%) 41 (52.6) 
Previous open uterine surgery, N (%) 3 (3.4) 
 Hysterotomy 0 (0.0) 
 Myomectomy 0 (0.0) 
 Classical C-section 1 (1.1) 
 Low-transverse C-section 2 (2.2) 
Total operative time of fSB repair, min 134 (120–152) 
Length of hysterotomy, cm 6.5 (6.0–7.0) 
Location of hysterotomy, N (%) 
 Anterior 37 (40.7) 
 Posterior 54 (59.3) 
Postoperative tocolysis, N (%) 77 (100)1 
Type of postoperative tocolysis, N (%) 
 Atosiban 76 (98.7) 
 Gynipral 55 (71.4) 
 Nifedipin 75 (97.4) 
Duration of tocolysis, days 
 Atosiban 5 (4–8) 
 Gynipral 9 (7–14) 
 Nifedipin 67 (55–76) 
Hysterotomy status at delivery, N (%) 
 Intact 21 (31.8) 
 Thin 40 (60.6) 
 Focal dehiscence 4 (6.1) 
 Complete dehiscence 1 (1.5) 
Fetal gender, N (%) 
 Male 43 (47.3) 
 Female 48 (52.7) 
GA at fSB repair, weeks 25.2±0.7 
GA at delivery, weeks 37.0 (34.9–37.0) 
Fetal weight at delivery, g 2,695 (2,283–2,948) 

N (%), mean ± standard deviation (SD), mean with interquartile range (25%, 75%).

fSB, fetal spina bifida; BMI, body mass index; C-section, cesarean section; GA, gestational age.

1Missing outcome data of other women.

Table 2.

Postoperative pain, feelings, and additional information regarding the pain therapy

After fSB repair (N = 67)After C-section (N = 53)p value
Postoperative day of questionnaire fill out, days 4 (4–4)2 4 (4–7) 0.04 
Maximal pain1 68 (50–80)2 56±21 0.03 
Maximal pain, N (%) N = 66  0.13 
 Group 1: none 0 (0.0) 2 (3.8) 0.20 
 Group 2: slight 7 (10.6) 5 (9.4) 1.00 
 Group 3: moderate 26 (39.4) 29 (54.7) 0.10 
 Group 4: strong 25 (37.9) 15 (28.3) 0.33 
 Group 5: strongest 8 (12.1) 2 (3.8) 0.18 
Minimal pain1 0 (0–10) 2 (0–20) 0.31 
Minimal pain, N (%)  N = 51 0.15 
 Group 1: none 42 (62.7) 28 (54.9) 0.45 
 Group 2: slight 20 (29.9) 19 (37.3) 0.43 
 Group 3: moderate 5 (7.5) 1 (2.0) 0.23 
 Group 4: strong 0 (0.0) 2 (3.9) 0.18 
 Group 5: strongest 0 (0.0) 1 (2.0) 0.43 
Pain occurrence1 30 (11–49)2 30 (20–39)4 1.00 
Influence of pain on the following activities1 
 Lying in bed 51±26 51±25 0.91 
 Breathing, coughing 43±272 45 (20–70)4 0.73 
 Sleeping 40 (20–66) 30 (10–50)4 0.03 
 Mobilization 32 (20–60) 42±245 0.76 
Mobilization, N (%) 67 (100.0) 52 (98.1) 0.44 
Feelings1 
 Insecurity 30 (10–60) 20 (10–50) 0.18 
 Helplessness 30 (10–66) 29 (1–61) 0.38 
Side effects1 
 Nausea 10 (0–36) 0 (0–19) 0.67 
 Sedation 15 (0–45) 0 (0–24) 0.001 
 Itching 2 (0–20)2 0 (0–25) 0.79 
 Dizziness 20 (4–50) 10 (0–33) 0.08 
Pain relief due to pain therapy1 80 (70–90)3 79 (67–90)6 0.95 
Wish for additional pain therapy, N (%) 8 (11.9) 3 (5.7) 0.34 
Information regarding pain therapy received, N (%) 65 (97.0) 47 (88.7) 0.14 
Women’s involvement in pain therapy1,4 100 (82–100) 90 (79–100)4 0.34 
Satisfaction with pain therapy1 95 (78–100) 100 (80–100) 0.46 
History of pain, N (%) 4 (6.0) 7 (13.2) 0.21 
Intensity of historical pain1 32±27 49±22 0.28 
After fSB repair (N = 67)After C-section (N = 53)p value
Postoperative day of questionnaire fill out, days 4 (4–4)2 4 (4–7) 0.04 
Maximal pain1 68 (50–80)2 56±21 0.03 
Maximal pain, N (%) N = 66  0.13 
 Group 1: none 0 (0.0) 2 (3.8) 0.20 
 Group 2: slight 7 (10.6) 5 (9.4) 1.00 
 Group 3: moderate 26 (39.4) 29 (54.7) 0.10 
 Group 4: strong 25 (37.9) 15 (28.3) 0.33 
 Group 5: strongest 8 (12.1) 2 (3.8) 0.18 
Minimal pain1 0 (0–10) 2 (0–20) 0.31 
Minimal pain, N (%)  N = 51 0.15 
 Group 1: none 42 (62.7) 28 (54.9) 0.45 
 Group 2: slight 20 (29.9) 19 (37.3) 0.43 
 Group 3: moderate 5 (7.5) 1 (2.0) 0.23 
 Group 4: strong 0 (0.0) 2 (3.9) 0.18 
 Group 5: strongest 0 (0.0) 1 (2.0) 0.43 
Pain occurrence1 30 (11–49)2 30 (20–39)4 1.00 
Influence of pain on the following activities1 
 Lying in bed 51±26 51±25 0.91 
 Breathing, coughing 43±272 45 (20–70)4 0.73 
 Sleeping 40 (20–66) 30 (10–50)4 0.03 
 Mobilization 32 (20–60) 42±245 0.76 
Mobilization, N (%) 67 (100.0) 52 (98.1) 0.44 
Feelings1 
 Insecurity 30 (10–60) 20 (10–50) 0.18 
 Helplessness 30 (10–66) 29 (1–61) 0.38 
Side effects1 
 Nausea 10 (0–36) 0 (0–19) 0.67 
 Sedation 15 (0–45) 0 (0–24) 0.001 
 Itching 2 (0–20)2 0 (0–25) 0.79 
 Dizziness 20 (4–50) 10 (0–33) 0.08 
Pain relief due to pain therapy1 80 (70–90)3 79 (67–90)6 0.95 
Wish for additional pain therapy, N (%) 8 (11.9) 3 (5.7) 0.34 
Information regarding pain therapy received, N (%) 65 (97.0) 47 (88.7) 0.14 
Women’s involvement in pain therapy1,4 100 (82–100) 90 (79–100)4 0.34 
Satisfaction with pain therapy1 95 (78–100) 100 (80–100) 0.46 
History of pain, N (%) 4 (6.0) 7 (13.2) 0.21 
Intensity of historical pain1 32±27 49±22 0.28 

N (%), mean ± standard deviation; median with interquartile range (25%, 75%).

fSB, fetal spina bifida; C-section, caesarean section.

1According to a Likert scale (1–9: none/never; 10–39: slight/rarely; 40–69: moderate/sometimes; 70–99: strong/often; 100: strongest/always).

2N = 66,

3N = 65,

4N = 52,

5N = 51,

6N = 50; missing outcome data.

Fig. 3.

Maximal postoperative pain level after fetal fSB repair and C-section.

Fig. 3.

Maximal postoperative pain level after fetal fSB repair and C-section.

Close modal
Fig. 4.

Occurrence of different maximal postoperative pain levels after fSB repair and C-section.

Fig. 4.

Occurrence of different maximal postoperative pain levels after fSB repair and C-section.

Close modal

Results of the subgroup analysis comparing women with different MPS after fSB repair are shown in Table 3. No woman (0.0%) reported MPS of 1–9 (group 1), 7 (10.6%) reported MPS of 10–39 (group 2), 26 (39.4%) MPS of 40–69 (group 3), 25 (37.9%) MSP of 70–99 (group 4), and 8 (12.1%) MPS of 100 (group 5) (shown in Fig. 4). Apart from higher MPS in non-Caucasians (p = 0.003), no other significant differences existed among groups 1–5 in regard of baseline characteristics. MPS differed significantly among groups (p < 0.001). Likewise, pain occurrence differed significantly (p < 0.001) and increased from group 2 to group 5. Moderate pain scores (40–69 on Likert scale) as minimal postoperative pain were significantly more often reported in group 5 (p = 0.02). Significant differences existed among the groups regarding the pain impact while lying in bed (p = 0.007) and while being mobilized (p = 0.005). Dizziness as side effect from pain therapy differed significantly among groups (p = 0.02), with highest rates in group 4. Feelings of insecurity and satisfaction with pain therapy differed significantly among groups (p = 0.03, respectively) (shown in Fig. 5). Rates of insecurity feelings were highest and satisfaction with pain therapy was lowest in group 4. No significant differences were seen in regard of postoperative complications grade 1–5 according to the Zurich classification system.

Table 3.

Subgroup analysis according to maximal pain scores after fSB repair

Group 2 (N = 7)Group 3 (N = 26)Group 4 (N = 25)Group 5 (N = 8)p values
Baseline characteristics 
Maternal age at fSB repair, years 31.0±5.1 32.9±4.3 32.2±5.1 34.1±5.4 0.60 
Maternal BMI at fSB repair, kg/m2 25.0 (21.6–46.5) 27.3 (24.2–31.2) 25.8 (23.8–29.8) 27.9 (26.0–34.2) 0.61 
Ethnicity, N (%)     0.003 
 Caucasian 7 (100.0) 26 (100.0) 25 (100.0) 5 (62.5) 0.002 
 Mediterranean 0 (0.0) 0 (0.0) 0 (0.0) 2 (25.0) 0.02 
 Afro-American 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) 0.23 
Maternal education, N (%)  N = 24   0.56 
 Elementary school 0 (0.0) 1 (4.2) 1 (4.0) 1 (14.3) 0.65 
 Vocation school 6 (85.7) 11 (45.8) 11 (44.0) 6 (85.7) 0.07 
 College 0 (0.0) 7 (29.2) 4 (16.0) 0 (0.0) 0.20 
 University, bachelor degree 1 (14.3) 3 (12.5) 5 (20.0) 0 (0.0) 0.82 
 University, master degree 0 (0.0) 2 (8.3) 2 (8.0) 0 (0.0) 1.00 
 University, doctor degree 0 (0.0) 0 (0.0) 2 (8.0) 0 (0.0) 0.69 
Primiparous, N (%) 3 (42.9) 15 (57.7) 12 (48.0) 4 (50.0) 0.88 
Previous open uterine surgery, N (%) 0 (0.0) 1 (3.8) 0 (0.0) 1 (12.5) 0.41 
Total operative time of fSB repair, min 145±30 129 (117–142) 138±24 125±18 0.50 
Length of hysterotomy, cm 6.1±0.9 6.5±0.8 6.6±1.5 6.0±1.2 0.06 
Location of Hysterotomy, N (%)     0.05 
 Anterior 2 (28.6) 6 (23.1) 15 (60) 3 (37.5)  
 Posterior 5 (71.4) 20 (76.9) 10 (40) 5 (62.5)  
Hysterotomy status at delivery, N (%) 
 Intact 3 (42.9) 7 (31.8) 6 (30.0) 1 (20.0) 0.56 
 Thin 3 (42.9) 13 (59.1) 14 (70.0) 3 (60.0) 0.89 
 Focal dehiscence 1 (14.3) 1 (4.5) 0 (0.0) 1 (20.0) 0.65 
 Complete dehiscence 0 (0.0) 1 (4.5) 0 (0.0) 0 (0.0) 0.12 
Fetal gender, N (%)     0.67 
 Male 2 (28.6) 12 (46.2) 12 (48.0) 5 (62.5)  
 Female 5 (71.4) 14 (53.8) 13 (52.0) 3 (37.5)  
GA at fSB repair, weeks 24.9±0.7 25.1±0.6 25.4±0.7 25.0±0.9 0.34 
GA at delivery, weeks 36.4 (31.7–37.3) 37.0 (35.7–37.0) 37.0 (34.9–37.0) 36.0 (33.1–37.0) 0.72 
Fetal weight at delivery, g 2,316±735 2,810 (2,550–2,970)5 2,640±4656 2,404±596 0.51 
Postoperative tocolysis, N (%) 7 (100.0) 26 (100.0) 25 (100.0) 7 (100.0)7  
Type of postoperative tocolysis, N (%) 
 Atosiban 7 (100.0) 26 (100.0) 25 (100.0) 7 (100.0)6  
 Gynipral 3 (42.9) 18 (69.2) 20 (80.0) 6 (85.7)6 0.24 
 Nifedipin 6 (85.7) 25 (96.2) 25 (100.0) 7 (100.0)6 0.40 
Duration of tocolysis, days 
 Atosiban 5 (4–5) 6.3±3.0 5 (3–7) 9±6 0.61 
 Gynipral 6.7±5.9 10 (7–15) 9 (7–13) 12±5 0.68 
 Nifedipin 70.8±15.6 73 (58–77) 67 (57–77) 50±25 0.24 
Outcome parameters1 
Postoperative day of questionnaire fill out, days 4.0 (4.0–6.0) 4.0 (4.0–4.5) 4.0 (4.0–4.0) 4.0 (4.0–4.0) 0.58 
Maximal pain2 23.9±6.3 50 (48–60) 80 (73–85) 100±0 <0.001 
Minimal pain2 0 (0–10) 0 (0–10) 5 (0–16) 5 (0–40) 0.44 
Minimal pain, N (%)     0.08 
 Group 1: none 5 (71.4) 19 (73.1) 13 (52.0) 4 (50.0) 0.37 
 Group 2: slight 2 (0.0) 6 (23.1) 11 (44.0) 1 (12.5) 0.29 
 Group 3: moderate 0 (0.0) 1 (3.8) 1 (4.0) 3 (37.5) 0.02 
 Group 4: strong 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)  
 Group 5: strongest 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)  
Pain occurrence2 4 (0–29) 20 (10–32) 42±24 52±31 <0.001 
Influence of pain on the following activities2 
 Lying in bed 24.6±20.6 49.2±20.8 62.0±25.5 43±33 0.007 
 Breathing, coughing 21.6±13.9 44.5±25.3 49.1±28.0 40±31 0.10 
 Sleeping 21.4±15.7 40.7±26.7 51.8±28.3 45±35 0.09 
 Mobilization 15±17.2 30 (25–55) 49.8±22.7 46±34 0.005 
Mobilization, N (%) 7 (100.0) 26 (100.0) 25 (100.0) (100.0)  
Feelings2 
 Insecurity 17.3±16.9 28.5±22.1 47.6±30.3 36±24 0.03 
 Helplessness 14±10.9 30 (8–67) 45.3±32.8 45±42 0.17 
Side effects2 
 Nausea 0 (0–2) 0 (0–40) 20 (10–55) 5 (0–38) 0.06 
 Sedation 5.6±6.8 15 (0–33) 20 (10–59) 20 (3–58) 0.06 
 Itching 0 (0–5)4 2 (0–20) 4 (0–25) 19±22 0.42 
 Dizziness 1 (0–5) 25.7±21.7 30 (15–61) 15 (3–28) 0.02 
Pain relief due to pain therapy2 90 (73–98)4 80 (70–90) 77 (66–80) 65±33 0.28 
Wish for additional pain therapy, N (%) 0 (0.0) 1 (3.8) 5 (20.0) 2 (25.0) 0.14 
Information regarding pain therapy received, N (%) 7 (100.0) 24 (92.3) 25 (100.0) 8 (100.0) 0.70 
Women’s involvement in pain therapy2 100 (90–100) 100 (88–100) 90 (80–100) 100 (93–100) 0.13 
Satisfaction with pain therapy2 100 (100–100) 100 (89–100) 80 (68–100) 90 (40–100) 0.03 
History of pain, N (%) 1 (14.3) 2 (8.0)5 0 (0.0) 1 (12.5) 0.23 
Postoperative complications3, N (%) N = 18 N = 44 N = 35 N = 15 0.62 
 Grade 1 5 (27.8) 22 (50.0) 13 (37.1) 6 (40.0) 0.41 
 Grade 2 9 (50.0) 14 (31.8) 16 (45.7) 6 (40.0) 0.50 
 Grade 3 3 (16.7) 8 (18.2) 6 (17.1) 3 (20.0) 1.00 
 Grade 4 1 (5.6) 0 (0.0) 0 (0.0) 0 (0.0) 0.30 
 Grade 5 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)  
Group 2 (N = 7)Group 3 (N = 26)Group 4 (N = 25)Group 5 (N = 8)p values
Baseline characteristics 
Maternal age at fSB repair, years 31.0±5.1 32.9±4.3 32.2±5.1 34.1±5.4 0.60 
Maternal BMI at fSB repair, kg/m2 25.0 (21.6–46.5) 27.3 (24.2–31.2) 25.8 (23.8–29.8) 27.9 (26.0–34.2) 0.61 
Ethnicity, N (%)     0.003 
 Caucasian 7 (100.0) 26 (100.0) 25 (100.0) 5 (62.5) 0.002 
 Mediterranean 0 (0.0) 0 (0.0) 0 (0.0) 2 (25.0) 0.02 
 Afro-American 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) 0.23 
Maternal education, N (%)  N = 24   0.56 
 Elementary school 0 (0.0) 1 (4.2) 1 (4.0) 1 (14.3) 0.65 
 Vocation school 6 (85.7) 11 (45.8) 11 (44.0) 6 (85.7) 0.07 
 College 0 (0.0) 7 (29.2) 4 (16.0) 0 (0.0) 0.20 
 University, bachelor degree 1 (14.3) 3 (12.5) 5 (20.0) 0 (0.0) 0.82 
 University, master degree 0 (0.0) 2 (8.3) 2 (8.0) 0 (0.0) 1.00 
 University, doctor degree 0 (0.0) 0 (0.0) 2 (8.0) 0 (0.0) 0.69 
Primiparous, N (%) 3 (42.9) 15 (57.7) 12 (48.0) 4 (50.0) 0.88 
Previous open uterine surgery, N (%) 0 (0.0) 1 (3.8) 0 (0.0) 1 (12.5) 0.41 
Total operative time of fSB repair, min 145±30 129 (117–142) 138±24 125±18 0.50 
Length of hysterotomy, cm 6.1±0.9 6.5±0.8 6.6±1.5 6.0±1.2 0.06 
Location of Hysterotomy, N (%)     0.05 
 Anterior 2 (28.6) 6 (23.1) 15 (60) 3 (37.5)  
 Posterior 5 (71.4) 20 (76.9) 10 (40) 5 (62.5)  
Hysterotomy status at delivery, N (%) 
 Intact 3 (42.9) 7 (31.8) 6 (30.0) 1 (20.0) 0.56 
 Thin 3 (42.9) 13 (59.1) 14 (70.0) 3 (60.0) 0.89 
 Focal dehiscence 1 (14.3) 1 (4.5) 0 (0.0) 1 (20.0) 0.65 
 Complete dehiscence 0 (0.0) 1 (4.5) 0 (0.0) 0 (0.0) 0.12 
Fetal gender, N (%)     0.67 
 Male 2 (28.6) 12 (46.2) 12 (48.0) 5 (62.5)  
 Female 5 (71.4) 14 (53.8) 13 (52.0) 3 (37.5)  
GA at fSB repair, weeks 24.9±0.7 25.1±0.6 25.4±0.7 25.0±0.9 0.34 
GA at delivery, weeks 36.4 (31.7–37.3) 37.0 (35.7–37.0) 37.0 (34.9–37.0) 36.0 (33.1–37.0) 0.72 
Fetal weight at delivery, g 2,316±735 2,810 (2,550–2,970)5 2,640±4656 2,404±596 0.51 
Postoperative tocolysis, N (%) 7 (100.0) 26 (100.0) 25 (100.0) 7 (100.0)7  
Type of postoperative tocolysis, N (%) 
 Atosiban 7 (100.0) 26 (100.0) 25 (100.0) 7 (100.0)6  
 Gynipral 3 (42.9) 18 (69.2) 20 (80.0) 6 (85.7)6 0.24 
 Nifedipin 6 (85.7) 25 (96.2) 25 (100.0) 7 (100.0)6 0.40 
Duration of tocolysis, days 
 Atosiban 5 (4–5) 6.3±3.0 5 (3–7) 9±6 0.61 
 Gynipral 6.7±5.9 10 (7–15) 9 (7–13) 12±5 0.68 
 Nifedipin 70.8±15.6 73 (58–77) 67 (57–77) 50±25 0.24 
Outcome parameters1 
Postoperative day of questionnaire fill out, days 4.0 (4.0–6.0) 4.0 (4.0–4.5) 4.0 (4.0–4.0) 4.0 (4.0–4.0) 0.58 
Maximal pain2 23.9±6.3 50 (48–60) 80 (73–85) 100±0 <0.001 
Minimal pain2 0 (0–10) 0 (0–10) 5 (0–16) 5 (0–40) 0.44 
Minimal pain, N (%)     0.08 
 Group 1: none 5 (71.4) 19 (73.1) 13 (52.0) 4 (50.0) 0.37 
 Group 2: slight 2 (0.0) 6 (23.1) 11 (44.0) 1 (12.5) 0.29 
 Group 3: moderate 0 (0.0) 1 (3.8) 1 (4.0) 3 (37.5) 0.02 
 Group 4: strong 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)  
 Group 5: strongest 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)  
Pain occurrence2 4 (0–29) 20 (10–32) 42±24 52±31 <0.001 
Influence of pain on the following activities2 
 Lying in bed 24.6±20.6 49.2±20.8 62.0±25.5 43±33 0.007 
 Breathing, coughing 21.6±13.9 44.5±25.3 49.1±28.0 40±31 0.10 
 Sleeping 21.4±15.7 40.7±26.7 51.8±28.3 45±35 0.09 
 Mobilization 15±17.2 30 (25–55) 49.8±22.7 46±34 0.005 
Mobilization, N (%) 7 (100.0) 26 (100.0) 25 (100.0) (100.0)  
Feelings2 
 Insecurity 17.3±16.9 28.5±22.1 47.6±30.3 36±24 0.03 
 Helplessness 14±10.9 30 (8–67) 45.3±32.8 45±42 0.17 
Side effects2 
 Nausea 0 (0–2) 0 (0–40) 20 (10–55) 5 (0–38) 0.06 
 Sedation 5.6±6.8 15 (0–33) 20 (10–59) 20 (3–58) 0.06 
 Itching 0 (0–5)4 2 (0–20) 4 (0–25) 19±22 0.42 
 Dizziness 1 (0–5) 25.7±21.7 30 (15–61) 15 (3–28) 0.02 
Pain relief due to pain therapy2 90 (73–98)4 80 (70–90) 77 (66–80) 65±33 0.28 
Wish for additional pain therapy, N (%) 0 (0.0) 1 (3.8) 5 (20.0) 2 (25.0) 0.14 
Information regarding pain therapy received, N (%) 7 (100.0) 24 (92.3) 25 (100.0) 8 (100.0) 0.70 
Women’s involvement in pain therapy2 100 (90–100) 100 (88–100) 90 (80–100) 100 (93–100) 0.13 
Satisfaction with pain therapy2 100 (100–100) 100 (89–100) 80 (68–100) 90 (40–100) 0.03 
History of pain, N (%) 1 (14.3) 2 (8.0)5 0 (0.0) 1 (12.5) 0.23 
Postoperative complications3, N (%) N = 18 N = 44 N = 35 N = 15 0.62 
 Grade 1 5 (27.8) 22 (50.0) 13 (37.1) 6 (40.0) 0.41 
 Grade 2 9 (50.0) 14 (31.8) 16 (45.7) 6 (40.0) 0.50 
 Grade 3 3 (16.7) 8 (18.2) 6 (17.1) 3 (20.0) 1.00 
 Grade 4 1 (5.6) 0 (0.0) 0 (0.0) 0 (0.0) 0.30 
 Grade 5 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)  

N (%), mean ± standard deviation, median with interquartile range (25%, 75%).

fSB, fetal spina bifida; BMI, body mass index; GA, gestational age.

1Parameters assessed after fSB repair.

2According to a Likert scale (1–9: none/never; 10–39: slight/rarely; 40–69: moderate/sometimes; 70–99: strong/often; 100: strongest/always).

3According to the Zurich classifications system.

4N = 6,

5N = 25,

6N = 22,

7N = 7; missing outcome data of other women.

Fig. 5.

Subgroup analysis: classification of women according to their maximal pain level after fetal fSB repair into groups 2 to 5 and analysis of: feelings of insecurity; feelings of helplessness; satisfaction with pain therapy.

Fig. 5.

Subgroup analysis: classification of women according to their maximal pain level after fetal fSB repair into groups 2 to 5 and analysis of: feelings of insecurity; feelings of helplessness; satisfaction with pain therapy.

Close modal

This comparative study showed that postoperative MPS after open fSB repair were higher compared to C-section, as to be expected; however, satisfaction with pain therapy did not differ. Adequate postoperative pain management after fSB repair is essential for enhanced recovery and early mobilization, as well as important to ensure emotional stability of the mother. Thus, these findings deserve some more detailed considerations.

Although women after fSB repair received opioids and therefore a stronger pain medication, MPS were still higher compared to C-section. Explanations might be the higher tension on the hysterotomy wound in a still pregnant and growing uterus, as well as fetal bumps and knocks against a fresh surgical site. Furthermore, the hysterotomy position might influence postoperative pain. A lower segment transverse uterine incision was performed during the C-section, whereas the incision was higher up in the anterior or posterior uterine body during fSB repair. Since no other studies analyzed postoperative pain after fSB repair in more detail, no data exist to support or disprove these assumptions. Optimal pain management is undoubtedly essential for rapid recovery and reduction of complications. It represents one cardinal element of enhanced recovery after surgery (ERAS) protocols, which consist of numerous pre-, intra-, and postoperative interventions that all aim at reducing negative impacts caused by surgery [4, 6]. ERAS protocols were therefore also established at our center. Nevertheless, the impact of such protocols on postoperative recovery and outcomes needs to be further evaluated, just as specific studies are needed to evaluate the optimal pain management after fSB repair.

However, when comparing the results with a previous study we performed that analyzed postoperative pain in a cohort of 60 women after C-section but no prior fSB repair, maximal postoperative pain levels were interestingly lower in this current study, both after fSB repair (68 [50–80]) and after the following C-section (56 ± 21). Women after C-section without prior fSB repair reported a mean maximal pain of 7.3 ± 1.6 on a numeric rating scale from 0 for “no pain” to 10 for “strongest pain,” although pain management after C-section in the current and previous study did not substantially differ. This effect might be due to positive psychological aspects of finally knowing the newborn baby is safely delivered. After weeks of stress and anxiety for the wellbeing of the unborn child in the period after fSB, the mothers experience an enormous relief after C-section. Although we have no data for proofing this effect, we consider this a potential explanation for the lower perception of the pain compared to standard C-section.

Apart from improvements in pain management, alternative surgical techniques, like fetoscopic fSB repair, might reduce postoperative pain and improve emotional well-being as this was reported in women undergoing laparoscopic compared to open hysterectomy [16]. Of note, in this context, a more differentiated consideration is mandatory since different fetoscopic approaches exist. The laparotomy-assisted fetoscopic approach still requires a large maternal laparotomy because the uterus must also be exteriorized [17]. On the other hand, the percutaneous fetoscopic approach does not need a maternal laparotomy but faces other challenges like high rates of leakage, preterm premature rupture of membranes, and preterm birth [18]. The percutaneous/mini-laparotomy fetoscopic approach tries to combine the two previously mentioned approaches and requires only a small maternal abdominal incision of 2–3 cm [19]. Chmait et al. [19] described lower postoperative pain and reduced need for postoperative tocolysis in the two latter approaches compared to open maternal-fetal and laparotomy-assisted fetoscopic fSB repair. One explanation for this finding might be the rising thrombin production with increase in hysterotomy size that promotes uterine activity [20]. Another factor influencing the risk for preterm contractions is inadequate pain control [5]. Maternal and fetal pain causes an activation of stress response triggering increased production of cortisol and activation of hormonal pathways leading to labor [5]. Although fetoscopic surgery seems promising in reducing postoperative pain and preterm contractions after fSB repair, it bears other risks like bleeding and/or leakage at the trocar sites leading to increased rates of preterm premature rupture of membranes [18, 21]. Approaches reducing postoperative pain, therefore, always need to be seen in a larger context.

Side effects of pain therapy were generally low, with dizziness being to most commonly reported side effect after fSB repair and after C-section. Sedation was significantly more often reported after fSB repair (p = 0.001). A tenable explanation is that opioids were regularly given after fSB repair but not after C-section. It is therefore not surprising that women who regularly received opioids after fSB repair, also reported higher rates of sedation, a well-known side effect of opioids [22].

The subgroup analysis, comparing women with different MPS after fSB repair, revealed highest pain scores in non-Caucasians. This finding is consistent with a systematic literature review analyzing the effect of race, sex, and socioeconomic status on postoperative pain showing higher levels in Afro-Americans and Hispanics compared to Caucasians [23]. The authors furthermore found that Caucasians were more often prescribed and more frequently used opioids and stated that racial disparities may result from physician bias [23]. This assumption was supported by a study of Felder et al. [24] who did not find any racial differences after implementing an ERAS protocol, but it contrasts our findings, since we treated all women according to ERAS protocols. However, this finding needs to be considered with caution since the sample sized was generally small and 96% of the cohort consisted of Caucasians.

A further reason for the lower pain score after C-section might be the fact that skin nerves were already cut during the initial laparotomy for the fSB. The period between fSB repair and C-section does not seem long enough for sensibility to recover [25]. Further research in testing skin sensitivity in the operation field prior to fSB and prior to the subsequent C-section could be performed for a follow-up research project.

In contrast to current evidence suggesting lower postoperative pain with higher socioeconomic status [23], we did not find a significant correlation between maternal education and postoperative pain. The higher MPS in group 4 and 5 were accompanied by higher rates of feelings of insecurity. It has been shown that acute pain is a risk factor for mood disorders and vice-versa [26]. Also, a study by Eisenach et al. [8] showed that women with severe acute postpartum pain did not only have a 3-fold increased risk for postpartum depression, but also a 2.5-fold increased risk for persistent pain, independent of the mode of delivery. Additionally, Sibbern et al. [27] reported patients’ decreasing motivation to participate in the recovery process if symptoms like pain, nausea, or weakness were present. On the other hand, professional support helped patients feel secure, comply with their postoperative regimen, and recover faster [27]. Taken together, the above findings compellingly suggest care of patients with higher pain scores should be intensified.

Finally, findings of this study should be seen in the context of the Swiss health-care system, where women are generally treated as inpatients for about 2 weeks after fSB repair and 3–4 days after C-section. Results might look different in other health-care systems, where earlier discharge is required or fewer nurses per patient are available.

Strength and Weaknesses

To our knowledge, this is the first study analyzing pain after open fSB repair in detail and comparing it with pain after C-section in the same patients, and thus contributes to a better understanding of pain and emotional experiences in these special situations. This knowledge is essential for the counseling of women undergoing fSB repair and for optimizing pain management and patient care. The response rate of questionnaires was good after fSB repair, with 74%, but worse after C-section, with only 58%. Additionally, there might be a recall bias since questionnaires were filled out significantly earlier after fSB repair compared to C-section, most probably because women were absorbed/distracted while caring for their newborns after C-section. Initially, the questionnaire was only available in German. Nevertheless, there were only 2 women, unable to return the questionnaire due to missing German skills. Further limitations of this study are the retrospective study design and relatively small sample size. Ultimately, postoperative pain scores after these two surgeries are not completely comparable since first of all the uterus stays exposed to stress after fSB repair, whereas it does not after C-section, and second the delivery of the child during C-section represents a moment of happiness potentially downgrading feelings of pain.

This cohort analysis showed that MPS after fSB repair were significantly higher than after the subsequent C-section. Yet, women were equally satisfied with pain management after both surgeries. Higher MPS after fSB repair were associated with greater pain occurrence and more feelings of insecurity. Clearly, our findings emphasize the importance of adequate postoperative pain management and psychological support after fSB repair.

We thank all families who participated in this research. We also thank the Spina Bifida Study Group. Without its contributions, this research would not be possible. From the University Children’s Hospital, this includes Barbara Casanova, Thomas Dreher, Ruth Etter, Patrice Grehten, Domenic Grisch, Annette Hackenberg, Cornelia Hagmann, Maya Horst Luethy, Raimund Kottke, Niklaus Krayenbuehl, Claudia M. Kuzan-Fischer, Markus A. Landolt, Bea Latal Hajnal, Andreas Meyer-Heim, Theres Moehrlen, Svea Muehlberg, Beth Padden, Silke Quanz, Brigitte Seliner, Mithula Shellvarajah, Sandra P. Toelle, Julia Velz, Alexandra Wattinger, and Noemi Zweifel. From the University Hospital Zurich, our study group consists of Dirk Bassler, Salome Meyer, and Christian Schaer. Additionally, we thank the Clinical Trial Center, University Hospital Zurich, for hosting the REDCap® Database.

This study protocol was reviewed and approved by the Local Ethic Commission Zurich (KEK-ZH, No. 2021-01101). The study was carried out in compliance with the Declaration of Helsinki and written informed consent was given by all participants.

None of the authors has any conflict of interest to declare.

This study had no funding sources.

J.Z., N.S., and N.O. designed the study outline. J.Z. and N.S. performed data collection and data quality control. J.Z. conducted the data analyses and wrote the manuscript. J.Z., N.S., L.V., L.R., F.K., L.M., M.M., U.M., T.M., L.K., and N.O. contributed to drafting and/or revising of the manuscript and contributed to its intellectual content. All mentioned authors approved the final version of the manuscript prior to publication.

Study data are not publicly available for reasons of privacy protection but can be requested from the corresponding author upon reasonable request.

1.
Adzick
NS
,
Thom
EA
,
Spong
CY
,
Brock
JW
3rd
,
Burrows
PK
,
Johnson
MP
, et al
.
A randomized trial of prenatal versus postnatal repair of myelomeningocele
.
N Engl J Med
.
2011
;
364
(
11
):
993
1004
.
2.
Moehrlen
U
,
Ochsenbein
N
,
Vonzun
L
,
Mazzone
L
,
Horst
M
,
Schauer
S
, et al
.
Fetal surgery for spina bifida in Zurich: results from 150 cases
.
Pediatr Surg Int
.
2021
;
37
(
3
):
311
6
.
3.
Mohrlen
U
,
Ochsenbein-Kolble
N
,
Mazzone
L
,
Kraehenmann
F
,
Husler
M
,
Casanova
B
, et al
.
Benchmarking against the MOMS trial: Zurich results of open fetal surgery for spina bifida
.
Fetal Diagn Ther
.
2020
;
47
(
2
):
91
7
.
4.
Scott
MJ
,
Urman
RD
.
Concepts in physiology and pathophysiology of enhanced recovery after surgery
.
Int Anesthesiol Clin
.
2017
;
55
(
4
):
38
50
.
5.
Myers
LB
,
Bulich
LA
,
Hess
P
,
Miller
NM
.
Fetal endoscopic surgery: indications and anaesthetic management
.
Best Pract Res Clin Anaesthesiol
.
2004
;
18
(
2
):
231
58
.
6.
Kehlet
H
.
Postoperative pain, analgesia, and recovery—bedfellows that cannot be ignored
.
Pain
.
2018
;
159
(
Suppl 1
):
S11
6
.
7.
Gray
G
,
Nelson-Piercy
C
.
Thromboembolic disorders in obstetrics
.
Best Pract Res Clin Obstet Gynaecol
.
2012
;
26
(
1
):
53
64
.
8.
Eisenach
JC
,
Pan
PH
,
Smiley
R
,
Lavand’homme
P
,
Landau
R
,
Houle
TT
.
Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum depression
.
Pain
.
2008
;
140
(
1
):
87
94
.
9.
Noll
FZJ
,
Zingg
J
,
Schliessbach
J
,
Krähenmann
F
,
Macrea
L
,
Ochsenbein-Kölble
N
.
Pain assessment after cesarean section with a standardized pain questionnaire
.
Austin J Obstet Gynecol
.
2021
;
8
(
8
).
10.
Harris
PA
,
Taylor
R
,
Thielke
R
,
Payne
J
,
Gonzalez
N
,
Conde
JG
.
Research electronic data capture (REDCap): a metadata-driven methodology and workflow process for providing translational research informatics support
.
J Biomed Inform
.
2009
;
42
(
2
):
377
81
.
11.
Ochsenbein-Kolble
N
,
Krahenmann
F
,
Husler
M
,
Meuli
M
,
Moehrlen
U
,
Mazzone
L
, et al
.
Tocolysis for in utero surgery: atosiban performs distinctly better than magnesium sulfate
.
Fetal Diagn Ther
.
2018
;
44
(
1
):
59
64
.
12.
Vonzun
L
,
Winder
FM
,
Meuli
M
,
Moerlen
U
,
Mazzone
L
,
Kraehenmann
F
, et al
.
Prenatal sonographic head circumference and cerebral ventricle width measurements before and after open fetal myelomeningocele repair: prediction of shunting during the first year of life
.
Ultraschall Med
.
2020
;
41
(
5
):
544
9
.
13.
Moehrlen
U
,
Ochsenbein-Kolble
N
,
Stricker
S
,
Moehrlen
T
,
Mazzone
L
,
Krahenmann
F
, et al
.
Prenatal Spina Bifida Repair: defendable trespassing of MOMS criteria results in commendable personalized medicine
.
Fetal Diagn Ther
.
2023
;
50
(
6
):
454
63
.
14.
Meuli
M
,
Meuli-Simmen
C
,
Mazzone
L
,
Tharakan
SJ
,
Zimmermann
R
,
Ochsenbein
N
, et al
.
In utero plastic surgery in Zurich: successful use of distally pedicled random pattern transposition flaps for definitive skin closure during open fetal spina bifida repair
.
Fetal Diagn Ther
.
2018
;
44
(
3
):
173
8
.
15.
Vonzun
L
,
Kahr
MK
,
Noll
F
,
Mazzone
L
,
Moehrlen
U
,
Meuli
M
, et al
.
Systematic classification of maternal and fetal intervention-related complications following open fetal myelomeningocele repair: results from a large prospective cohort
.
BJOG
.
2021
;
128
(
7
):
1184
91
.
16.
Kotani
Y
,
Murakami
K
,
Fujishima
R
,
Kanto
A
,
Takaya
H
,
Shimaoka
M
, et al
.
Research Article Quality of life after laparoscopic hysterectomy versus abdominal hysterectomy
.
BMC Womens Health
.
2021
;
21
(
1
):
219
.
17.
Belfort
MA
,
Whitehead
WE
,
Shamshirsaz
AA
,
Bateni
ZH
,
Olutoye
OO
,
Olutoye
OA
, et al
.
Fetoscopic open neural tube defect repair: development and refinement of a two-port, carbon dioxide insufflation technique
.
Obstet Gynecol
.
2017
;
129
(
4
):
734
43
.
18.
Kabagambe
SK
,
Jensen
GW
,
Chen
YJ
,
Vanover
MA
,
Farmer
DL
.
Fetal surgery for myelomeningocele: a systematic review and meta-analysis of outcomes in fetoscopic versus open repair
.
Fetal Diagn Ther
.
2018
;
43
(
3
):
161
74
.
19.
Chmait
RH
,
Monson
MA
,
Pham
HQ
,
Chu
JK
,
Van Speybroeck
A
,
Chon
AH
, et al
.
Percutaneous/mini-laparotomy fetoscopic repair of open spina bifida: a novel surgical technique
.
Am J Obstet Gynecol
.
2022
;
227
(
3
):
375
83
.
20.
Elovitz
MA
,
Saunders
T
,
Ascher-Landsberg
J
,
Phillippe
M
.
Effects of thrombin on myometrial contractions in vitro and in vivo
.
Am J Obstet Gynecol
.
2000
;
183
(
4
):
799
804
.
21.
Sanz Cortes
M
,
Chmait
RH
,
Lapa
DA
,
Belfort
MA
,
Carreras
E
,
Miller
JL
, et al
.
Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium
.
Am J Obstet Gynecol
.
2021
;
225
(
6
):
678 e1
1
.
22.
Benyamin
R
,
Trescot
AM
,
Datta
S
,
Buenaventura
R
,
Adlaka
R
,
Sehgal
N
.
Opioid complications and side effects
.
Pain Physician
.
2008
;
2s;11
(
3;2s
):
S105
20
.
23.
Thurston
KL
,
Zhang
SJ
,
Wilbanks
BA
,
Billings
R
,
Aroke
EN
.
A systematic review of race, sex, and socioeconomic status differences in postoperative pain and pain management
.
J Perianesth Nurs
.
2023
;
38
(
3
):
504
15
.
24.
Felder
L
,
Cao
C
,
Konys
C
,
Weerasooriya
N
,
Mahmood
S
,
Dayaratna
S
, et al
.
404 ERAS protocol to improve racial and ethnic disparities in pain management following cesarean delivery
.
Am J Obstet Gynecol
.
2021
;
224
(
2
):
S261
.
25.
Wang
ML
,
Rivlin
M
,
Graham
JG
,
Beredjiklian
PK
.
Peripheral nerve injury, scarring, and recovery
.
Connect Tissue Res
.
2019
;
60
(
1
):
3
9
.
26.
Michaelides
A
,
Zis
P
.
Depression, anxiety and acute pain: links and management challenges
.
Postgrad Med
.
2019
;
131
(
7
):
438
44
.
27.
Sibbern
T
,
Bull Sellevold
V
,
Steindal
SA
,
Dale
C
,
Watt-Watson
J
,
Dihle
A
.
Patients’ experiences of enhanced recovery after surgery: a systematic review of qualitative studies
.
J Clin Nurs
.
2017
;
26
(
9–10
):
1172
88
.