Introduction: For open fetal spina bifida (fSB) repair, a maternal laparotomy is required. Hence, enhanced maternal recovery after surgery (ERAS) is paramount. A revision of our ERAS protocol was made, including changes in operative techniques and postoperative pain management. This study investigates eventual benefits. Methods: Our study included 111 women with open fSB repair at our center. The old protocol group (group 1) either received a transverse incision of the fascia with transection of the rectus abdominis muscle (RAM) or a longitudinal incision of the fascia without RAM transection, depending on placental location. The new protocol required longitudinal incisions in all patients (group 2). Postoperative pain management was changed from tramadol to oxycodone/naloxone. Outcomes of the two different protocol groups were analyzed and compared regarding the primary endpoint, the length of hospital stay (LOS) after fetal surgery, as well as regarding the following secondary endpoints: postoperative pain scores, day of first mobilization, removal of urinary catheter, bowel movement, and the occurrence of maternal and fetal complications. Results: Out of 111 women, 82 (73.9%) were in group 1 and 29 (26.1%) were in group 2. Women in group 2 showed a significantly shorter LOS (18 [14–23] days vs. 27 [18–39] days, p = 0.002), duration until mobilization (3 [2–3] days vs. 3 [3–4] days, p = 0.03), and removal of urinary catheter (day 3 [3–3] vs. day 4 [3–4], p = 0.004). Group 2 less often received morphine subcutaneously (0% vs. 35.4%, p < 0.001) or intravenously (0% vs. 17.1%, p = 0.02) but more often oxycodone (69.0% vs. 18.3%, p < 0.001). No significant differences were seen regarding pain scores, bowel movement, and maternal and/or fetal complications. Conclusion: The new ERAS protocol that combined changes in surgical technique and pain medication led to better outcomes while reducing LOS. Continuous revisions of current ERAS protocols are essential to improve patient care continuously.

Fetal spina bifida (fSB) repair is performed in highly specialized fetal therapy centers according to strict protocols. It involves a multidisciplinary team that amongst others consists of fetal surgeons, feto-maternal specialists, obstetricians, anesthesiologists, midwifes, and nurses [1, 2]. The aim was to treat the fetus while minimizing maternal harm [3]. Since the access to the fetus leads through the womb of the mother, the mothers’ enhanced recovery after fetal surgery (ERAS) is a principal goal of the entire team. Since ERAS protocols are used in almost all surgical specialties to improve clinical outcomes, they were established at our center for fSB repair too and continuously adjusted in terms of pre-, intra-, and postoperative procedures to further optimize patient care [4‒6].

The surgical approach in open fSB repair normally depends on the location of the placenta. Traditionally, a transverse incision of the fascia with consecutive transverse transection of the rectus abdominis muscle (transverse incision) was performed in an anterior but not in a posterior located placenta. If the placenta was located at the posterior uterine wall, a longitudinal incision of the fascia without transection of the rectus abdominis muscle (longitudinal incision) was possible with direct access to the fetus via the anterior uterine wall [1]. With growing knowhow about open fSB repair, our team observed that women with transverse incision had more postoperative pain, and postoperative mobilization occurred later compared to women with longitudinal incision. Additionally, our obstetricians described insufficient or absent healing of the rectus abdominis muscles at cesarean delivery after transverse incision matching the findings of Vigneswaran et al. [7], who reported a higher rate of rectus abdominis muscle atrophy after transverse compared to longitudinal incision in nonpregnant patients. Thus, after having performed 88 fSB repairs at our center, our team decided to change the intraoperative approach to a longitudinal incision of the fascia without transection of the rectus abdominis muscle in all following cases, independently of the position of the placenta. Additionally, the postoperative pain medication was modified. Tramal® (tramadol) was replaced by Targin®, a combination of oxycodone and naloxone, which showed effective analgesia while improving bowel function in patients with moderate-to-severe pain and opioid-induced constipation [8, 9].

After the above-mentioned adaptations of our intra- and postoperative protocols, the aim of this study was to investigate the benefits of our changes. Primary endpoint was the length of hospital stay (LOS) after fetal surgery. Secondary endpoints were postoperative pain scores, day of first mobilization, removal of urinary catheter, and bowel movement as well as the occurrence of maternal and fetal complications.

From December 2010 to July 2019, a total of 120 patients underwent open fSB repair at the Zurich Center for Fetal Diagnosis and Therapy. Data were prospectively collected in our registry using Research Electronic Data Capture (REDCap®) [10]. Inclusion criteria for fSB were published previously [11‒13]. Nine patients had to be excluded due to the following reasons: missing informed consent (N = 2), missing data (N = 1), impossibility for an epidural analgesia (EDA) (N = 2), cross-section of the fascia (N = 3), and delivery during fSB repair (N = 1) (shown in Fig. 1). The study was conducted in compliance with the Declaration of Helsinki and approved by the Local Ethics Committee Zurich (KEK Nr. 2015-0172). Written informed consent existed for all patients included in this study.

Fig. 1.

Flow diagram of women with fSB repair and their corresponding protocol group.

Fig. 1.

Flow diagram of women with fSB repair and their corresponding protocol group.

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The fSB repair was performed by fetal surgeons according to standardized operative techniques as reported in the Management of Myelomeningocele Study (MOMS) trial [1]. All patients received an EDA in addition to general anesthesia. A transverse skin incision was performed in all women. In the first 88 women, the further access to the uterus depended on the position of the placenta. In case of an anterior located placenta, a transverse incision was performed. If the placenta was located at the posterior uterine wall, a longitudinal incision was performed sparing the rectus abdominis muscle. After the first 88 fSB repairs, all women received a longitudinal incision. After fSB repair, women were monitored in an intermediate care unit for 2 days. Then, they were transferred to our prenatal care unit where they recovered. Peri- and postoperative tocolysis was performed as previously described [12]. Standard pain management consisted of an EDA for 3–5 days, paracetamol 4 × 1 g intravenously (i.v.) per day, and if necessary tramadol (Tramal®) 50–200 mg orally (p.o.) per day. After 82 patients, pain management was changed from tramadol to 5–20 mg oxycodone/naloxon 2.5/10 mg (Targin®) p.o. per day instead. This change was made since the combination of oxycodone and naloxone was reported to improve bowel function in patients with moderate-to-severe pain and opioid-induced constipation [8, 9]. Dependent on the women’s postoperative pain, they could additionally receive tramadol, oxycodone, or morphine. For regular pain assessment, the numeric rating scale (NRS) ranging from 0 “no pain” to 10 “the worst pain possible” was used at least three times per day. This scale has been shown to be valid, reliable, and appropriate for the use in clinical practice with good sensitivity [14]. The NRS scores were all documented in our clinical database. A NRS score of four was defined as a sufficient analgesia; therefore, the dose of tramadol or oxycodone/naloxone was halved in case of lower values. At a NRS score ≤2, tramadol or oxycodone/naloxone was completely stopped. The change in pain management defined our new protocol. Out of the total cohort of 111 women, 82 (73.9%) were treated according to the old protocol (group 1) and 29 (26.1%) according to the new protocol (group 2) (shown in Fig. 1, 2).

Fig. 2.

New enhanced recovery after fetal surgery (ERAS) protocol.

Fig. 2.

New enhanced recovery after fetal surgery (ERAS) protocol.

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To answer this study’s question, LOS, postoperative pain scores using the highest NRS score at rest at postoperative day 1, 3, 5, 7, 10, and 14, the day of first mobilization to upright standing, removal of the urinary catheter as well as first bowel movement were assessed. Criteria for removal of the urinary catheter were a prior removal of the EDA and prior problem-free mobilization. Additionally, maternal and fetal complications were analyzed according to the Zurich classification system, as previously described [15].

Furthermore, the following demographic, obstetric and clinical parameters were assessed: maternal age, maternal body mass index at fetal surgery, race/ethnicity, marital status, and smoking, history of previous uterine surgeries or prior abortion (<16 gestational weeks), parity, location of placenta, cervical length, type of incision, length of hysterotomy, total operative duration, day of EDA removal, type of postoperative pain medication, rate of postoperative bladder infections and pulmonary edema, gestational age at surgery and birth, fetal gender, and birth weight.

Outcome parameters were compared between group 1 and 2 to investigate the benefits of our adjustments on postoperative recovery. Additionally, to solely focus on the effect of the surgical technique, a subgroup analysis was performed in women who all received tramadol as pain medication. The previously defined primary and secondary endpoints were then compared according to their incision technique (transverse vs. longitudinal).

Statistical analysis was performed using SPSS (version 29, IBM, USA). Shapiro-Wilk test was used to test for normal distribution. Data were analyzed using one of the following tests as appropriate: t test for independent variables, Mann-Whiney U test, Pearson’s χ2 test, or Fisher’s exact test. Additionally, regression analysis was performed to analyze the effect of operative technique, pain medication, and protocol type on LOS. Quantitative data are presented as mean ± standard deviation or median with interquartile range (25% and 75%) and categorical variables as numbers (N) with percentages (%). A p value <0.05 was defined as significant.

Baseline characteristics are shown in Table 1. Women in group 2 reported a significantly higher rate of previous uterine surgeries (41.4% vs. 19.8%, p = 0.03) as well as low-lying placentas (10.3% vs. 0%, p = 0.02). Beside the difference in incision type, no further significant differences were seen when comparing baseline characteristics among the groups.

Table 1.

Baseline characteristics

Group 1 (N = 82)Group 2 (N = 29)p values
Maternal age at fetal surgery, years 31.6±5.0 32.6±5.1 0.37 
Maternal BMI at fetal surgery, kg/m2 25.9 [23.2–30.5] 27.0±4.9 0.87 
Ethnicity1, N (%)   1.0 
 White 72 (88.9) 27 (93.1) 0.72 
 Black 2 (2.5) 0 (0.0) 1.0 
 Hispanic 3 (3.7) 1 (3.4) 1.0 
Other 4 (4.9) 1 (3.4) 1.0 
Marital status, N (%)   0.34 
 Single 1 (1.2) 2 (6.9) 0.17 
 Living with partner 25 (30.5) 6 (20.7) 0.35 
 Married 53 (65.6) 20 (69.0) 0.82 
 Divorced 2 (2.4) 1 (3.4) 1.0 
Widowed 1 (1.2) 0 (0.0) 1.0 
Smoking 3 (3.7)1 1 (3.4) 1.0 
History of prior uterine surgery, N (%) 16 (19.8)1 12 (41.4) 0.03 
History of prior abortion (<16 GW), N (%) 25 (30.5) 10 (34.5) 0.82 
Primiparous, N (%) 35 (42.7) 12 (41.4) 1.0 
Location of placenta2, N (%)   0.04 
 Anterior 44 (53.7) 14 (48.3) 0.67 
 Posterior 36 (43.9) 11 (37.9) 0.67 
 Right lateral 2 (2.4) 2 (6.9) 0.29 
 Low-lying 0 (0.0) 3 (10.3) 0.02 
Placenta previa 1 (1.2) 0 (0.0) 1.0 
Cervical length, mm 44±7 45±6 0.52 
Type of operative incision, N (%)   < 0.001 
 Transverse 44 (53.7) 0 (0.0)  
Longitudinal 38 (46.3) 29 (100.0)  
Length of hysterotomy, cm 7 [7–8] 7±1 0.99 
Total operative duration, min 138±22 142±22 0.39 
Fetal gender, N (%)   0.83 
 Male 37 (45.1) 12 (41.4)  
Female 45 (54.9) 17 (58.6)  
GA at surgery (GW) 25.2 [24.4–25.6] 25.0±0.8 0.94 
GA at birth (GW) 36.3 [34.8–37.0] 36.6 [34.3–37.0] 0.60 
Birth weight, g 2,670 [2,375–2,888] 2,665±484 0.35 
Group 1 (N = 82)Group 2 (N = 29)p values
Maternal age at fetal surgery, years 31.6±5.0 32.6±5.1 0.37 
Maternal BMI at fetal surgery, kg/m2 25.9 [23.2–30.5] 27.0±4.9 0.87 
Ethnicity1, N (%)   1.0 
 White 72 (88.9) 27 (93.1) 0.72 
 Black 2 (2.5) 0 (0.0) 1.0 
 Hispanic 3 (3.7) 1 (3.4) 1.0 
Other 4 (4.9) 1 (3.4) 1.0 
Marital status, N (%)   0.34 
 Single 1 (1.2) 2 (6.9) 0.17 
 Living with partner 25 (30.5) 6 (20.7) 0.35 
 Married 53 (65.6) 20 (69.0) 0.82 
 Divorced 2 (2.4) 1 (3.4) 1.0 
Widowed 1 (1.2) 0 (0.0) 1.0 
Smoking 3 (3.7)1 1 (3.4) 1.0 
History of prior uterine surgery, N (%) 16 (19.8)1 12 (41.4) 0.03 
History of prior abortion (<16 GW), N (%) 25 (30.5) 10 (34.5) 0.82 
Primiparous, N (%) 35 (42.7) 12 (41.4) 1.0 
Location of placenta2, N (%)   0.04 
 Anterior 44 (53.7) 14 (48.3) 0.67 
 Posterior 36 (43.9) 11 (37.9) 0.67 
 Right lateral 2 (2.4) 2 (6.9) 0.29 
 Low-lying 0 (0.0) 3 (10.3) 0.02 
Placenta previa 1 (1.2) 0 (0.0) 1.0 
Cervical length, mm 44±7 45±6 0.52 
Type of operative incision, N (%)   < 0.001 
 Transverse 44 (53.7) 0 (0.0)  
Longitudinal 38 (46.3) 29 (100.0)  
Length of hysterotomy, cm 7 [7–8] 7±1 0.99 
Total operative duration, min 138±22 142±22 0.39 
Fetal gender, N (%)   0.83 
 Male 37 (45.1) 12 (41.4)  
Female 45 (54.9) 17 (58.6)  
GA at surgery (GW) 25.2 [24.4–25.6] 25.0±0.8 0.94 
GA at birth (GW) 36.3 [34.8–37.0] 36.6 [34.3–37.0] 0.60 
Birth weight, g 2,670 [2,375–2,888] 2,665±484 0.35 

N (%), mean ± SD or median with interquartile range.

BMI, body mass index; GW, gestational weeks; GA, gestational age.

1Missing data of one woman in group 1.

2Including a women with placenta bipartite in both groups (N = 83 and N = 30).

In regard of the primary endpoint, the LOS (shown in Fig. 3 and Table 2), women in group 2 had a significantly shorter LOS compared to women in group 1 (18 [14–23] days vs. 27 [18–39] days, p = 0.002). Regarding secondary endpoints also depicted in Table 2, no difference was seen regarding postoperative pain scores (shown in Fig. 4). In both groups, pain scores were highest on the third postoperative day (NRS 3.5 ± 2.7 in group 2 vs. NRS 4 (2–6) in group 1, p = 0.40). The first day of mobilization was significantly earlier in group 2 compared to group 1 (3 [2–3] days vs. 3 [3–4] days, p = 0.03) and the same applies to the postoperative day of urinary catheter removal (day 3 [3–3] vs. day 4 [3–4], p = 0.004). Regarding the day of first bowel movement postoperatively, no significant differences were found when comparing the two groups (day 3 [3–3] in group 2 vs. day 3 [3–4] in group 1, p = 0.15). Group 2 significantly more often received enemas preoperatively compared to group 1 (96.6% vs. 57.3%, p < 0.001). Regarding maternal and fetal complications classified according to the Zurich classification system, no significant differences were seen between the two groups. The same applies for the maternal abdominal hernia rate that could be considered a long-term complication but did not differ among group 1 and 2 (7.7% vs. 4.2%, p = 1.0).

Fig. 3.

Length of hospital stay in days.

Fig. 3.

Length of hospital stay in days.

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Table 2.

Primary and secondary outcome parameters

Group 1 (N = 82)Group 2 (N = 29)p values
LOS, days 27 [18–39] 18 [14–23] 0.002 
Postoperative pain scores (NRS) 
 Day 1 2.5 [1.4–5.0] 2.0 [0.0–3.5] 0.13 
 Day 3 4.0 [2.0–6.3] 3.5±2.7 0.40 
 Day 5 3.0 [1.0–5.0] 2.0 [1.0–3.8] 0.19 
 Day 7 1.5 [0.0–3.0] 1.0 [0.0–5.0] 0.75 
 Day 10 1.0 [0.0–3.0] 1.0 [0.0–3.5] 0.81 
Day 14 0.0 [0.0–3.0] 0.0 [0.0–1.0] 0.33 
Postoperative day of first mobilization 3 [3–4] 3 [2–3] 0.03 
Postoperative day of urinary catheter removal 4 [3–4] 3 [3–3] 0.004 
Postoperative day of first bowel movement 3 [3–4] 3 [3–3] 0.15 
Maternal complications, N (%)   0.70 
 Grade 1 43 (52.4) 16 (55.2) 0.83 
 Grade 2 29 (35.4) 8 (27.6) 0.50 
 Grade 3 19 (23.2) 9 (31.0) 0.46 
 Grade 4 6 (7.3) 1 (3.4) 0.67 
Grade 5 0 (0.0) 0 (0.0)  
Fetal complications, N (%)   0.46 
 Grade 1 40 (48.8) 10 (34.5) 0.20 
 Grade 2 10 (12.2) 6 (20.7) 0.36 
 Grade 3 8 (9.8) 1 (3.4) 0.44 
 Grade 4 1 (1.2) 0 (0.0) 1.0 
Grade 5 0 (0.0) 0 (0.0)  
Long-term complication, N (%) 
 Maternal hernia 4 (7.7)1 1 (4.2)2 1.0 
Group 1 (N = 82)Group 2 (N = 29)p values
LOS, days 27 [18–39] 18 [14–23] 0.002 
Postoperative pain scores (NRS) 
 Day 1 2.5 [1.4–5.0] 2.0 [0.0–3.5] 0.13 
 Day 3 4.0 [2.0–6.3] 3.5±2.7 0.40 
 Day 5 3.0 [1.0–5.0] 2.0 [1.0–3.8] 0.19 
 Day 7 1.5 [0.0–3.0] 1.0 [0.0–5.0] 0.75 
 Day 10 1.0 [0.0–3.0] 1.0 [0.0–3.5] 0.81 
Day 14 0.0 [0.0–3.0] 0.0 [0.0–1.0] 0.33 
Postoperative day of first mobilization 3 [3–4] 3 [2–3] 0.03 
Postoperative day of urinary catheter removal 4 [3–4] 3 [3–3] 0.004 
Postoperative day of first bowel movement 3 [3–4] 3 [3–3] 0.15 
Maternal complications, N (%)   0.70 
 Grade 1 43 (52.4) 16 (55.2) 0.83 
 Grade 2 29 (35.4) 8 (27.6) 0.50 
 Grade 3 19 (23.2) 9 (31.0) 0.46 
 Grade 4 6 (7.3) 1 (3.4) 0.67 
Grade 5 0 (0.0) 0 (0.0)  
Fetal complications, N (%)   0.46 
 Grade 1 40 (48.8) 10 (34.5) 0.20 
 Grade 2 10 (12.2) 6 (20.7) 0.36 
 Grade 3 8 (9.8) 1 (3.4) 0.44 
 Grade 4 1 (1.2) 0 (0.0) 1.0 
Grade 5 0 (0.0) 0 (0.0)  
Long-term complication, N (%) 
 Maternal hernia 4 (7.7)1 1 (4.2)2 1.0 

N (%), mean ± SD or median with interquartile range.

LOS, length of hospital stay; NRS, numeric rating scale.

1N = 52; 2N = 24; missing data of other women.

Fig. 4.

Postoperative pain scores on a numeric rating scale (NRS) from 0 “no pain” to 10 “the worst pain possible.”

Fig. 4.

Postoperative pain scores on a numeric rating scale (NRS) from 0 “no pain” to 10 “the worst pain possible.”

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When analyzing additional parameters depicted in Table 3, results showed that group 2 significantly more often received oxycodone/naloxone as pain medication (100.0% vs. 8.5% in group 1, p < 0.001), and significantly less often tramadol (3.4% vs. 86.6% in group 1, p < 0.001). One woman in group 2 and five women in group 1 received both tramadol and oxycodone/naloxone (3.4% vs. 6.1%, p = 1.0). When analyzing in more detail, the additional pain medications used, results showed that women in group 2 compared to group 1 significantly less often received morphine subcutaneously (s.c.) (0% vs. 35.4%, p < 0.001), or morphine i.v. (0% vs. 17.1%, p = 0.02). On the other hand, group 2 was significantly more often treated with additional oxycodone (69% vs. 18.3%, p < 0.001).

Table 3.

Additional outcome parameters

Group 1 (N = 82)Group 2 (N = 29)p values
Day of EDA removal 3 [3–4] 3 [3–3] 0.08 
Type of pain medication, N (%)    
 Tramadol 71 (86.6) 1 (3.4) <0.001 
 Oxycodone/naloxone 7 (8.5) 29 (100.0) <0.001 
 Morphine PCA 20 (24.4) 3 (10.3) 0.12 
 Morphine s.c. 29 (35.4) 0 (0.0) <0.001 
 Morphine i.v. 14 (17.1) 0 (0.0) 0.02 
Oxycodone 15 (18.3) 20 (69.0) <0.001 
Bladder infection, N (%) 8 (9.8) 0 (0.0) 0.11 
Pulmonary edema, N (%) 1 (1.2) 0 (0.0) 1.00 
Group 1 (N = 82)Group 2 (N = 29)p values
Day of EDA removal 3 [3–4] 3 [3–3] 0.08 
Type of pain medication, N (%)    
 Tramadol 71 (86.6) 1 (3.4) <0.001 
 Oxycodone/naloxone 7 (8.5) 29 (100.0) <0.001 
 Morphine PCA 20 (24.4) 3 (10.3) 0.12 
 Morphine s.c. 29 (35.4) 0 (0.0) <0.001 
 Morphine i.v. 14 (17.1) 0 (0.0) 0.02 
Oxycodone 15 (18.3) 20 (69.0) <0.001 
Bladder infection, N (%) 8 (9.8) 0 (0.0) 0.11 
Pulmonary edema, N (%) 1 (1.2) 0 (0.0) 1.00 

N (%), median with interquartile range.

EDA, epidural analgesia; PCA, patient controlled analgesia; s.c., subcutaneously; i.v., intravenously; MRI, magnetic resonance imaging.

Furthermore, in group 2 no cases of bladder infections were reported, whereas group 1 reported 8 cases (0% vs. 9.8%, p = 0.11). Regarding the occurrence of postoperative pulmonary edema, no significant differences were seen in group 2 compared to group 1 (0% vs. 1.2%, p = 1.0).

Subgroup analysis, focusing on the surgical technique in women who all received tramadol as pain medication, showed the following significant differences in regard to our primary and secondary endpoints: women with longitudinal incision compared to the ones with transverse incision had a significantly earlier removal of the urinary catheter (day 4 [3–4] vs. day 4 [4–4], p = 0.04) and higher rate of maternal complications grade 1 (71% vs. 37%, p = 0.007), which, however, did not need any intervention. No other significant differences were seen (shown in Table 4).

Table 4.

Subgroup analysis: Women with different incision technique and tramadol as pain medication

Transverse incision (N = 35)Longitudinal incision (N = 31)p values
LOS, days 26 [18–52] 21 [16–33]5 0.28 
Postoperative pain scores (NRS) 
 Day 1 2.5 [1.0–4.0] 3.0±2.0 0.66 
 Day 3 4.0 [0.0–7.0] 4.6±2.7 0.31 
 Day 5 4.0 [1.0–5.3]1 2.0 [0.0–5.0]5 0.16 
 Day 7 2.0 [0.0–3.0]2 1.0 [0.0–4.5]6 0.98 
 Day 10 1.0 [0.0–2.0]3 2.0 [0.0–4.0]7 0.37 
Day 14 0.0 [0.0–1.8]4 1.0 [0.0–3.0]8 0.44 
Postoperative day of first mobilization 3 [3–4] 3 [3–3] 0.44 
Postoperative day of urinary catheter removal 4 [4–4] 4 [3–4] 0.04 
Postoperative day of first bowel movement 3 [3–5] 3 [3–4] 0.51 
Maternal complications, N (%)   0.21 
 Grade 1 13 (37.1) 22 (71.0) 0.007 
 Grade 2 13 (37.1) 9 (29.0) 0.60 
 Grade 3 6 (17.1) 10 (32.3) 0.25 
 Grade 4 1 (2.9) 5 (16.1) 0.09 
Grade 5 0 (0.0) 0 (0.0)  
Fetal complications, N (%)   0.53 
 Grade 1 17 (48.6) 14 (45.2) 0.81 
 Grade 2 4 (11.4) 4 (12.9) 1.00 
 Grade 3 2 (5.7) 5 (16.1) 0.24 
 Grade 4 0 (0.0) 1 (3.2) 0.47 
 Grade 5 0 (0.0) 0 (0.0)  
Transverse incision (N = 35)Longitudinal incision (N = 31)p values
LOS, days 26 [18–52] 21 [16–33]5 0.28 
Postoperative pain scores (NRS) 
 Day 1 2.5 [1.0–4.0] 3.0±2.0 0.66 
 Day 3 4.0 [0.0–7.0] 4.6±2.7 0.31 
 Day 5 4.0 [1.0–5.3]1 2.0 [0.0–5.0]5 0.16 
 Day 7 2.0 [0.0–3.0]2 1.0 [0.0–4.5]6 0.98 
 Day 10 1.0 [0.0–2.0]3 2.0 [0.0–4.0]7 0.37 
Day 14 0.0 [0.0–1.8]4 1.0 [0.0–3.0]8 0.44 
Postoperative day of first mobilization 3 [3–4] 3 [3–3] 0.44 
Postoperative day of urinary catheter removal 4 [4–4] 4 [3–4] 0.04 
Postoperative day of first bowel movement 3 [3–5] 3 [3–4] 0.51 
Maternal complications, N (%)   0.21 
 Grade 1 13 (37.1) 22 (71.0) 0.007 
 Grade 2 13 (37.1) 9 (29.0) 0.60 
 Grade 3 6 (17.1) 10 (32.3) 0.25 
 Grade 4 1 (2.9) 5 (16.1) 0.09 
Grade 5 0 (0.0) 0 (0.0)  
Fetal complications, N (%)   0.53 
 Grade 1 17 (48.6) 14 (45.2) 0.81 
 Grade 2 4 (11.4) 4 (12.9) 1.00 
 Grade 3 2 (5.7) 5 (16.1) 0.24 
 Grade 4 0 (0.0) 1 (3.2) 0.47 
 Grade 5 0 (0.0) 0 (0.0)  

N (%), mean ± SD or median with interquartile range.

LOS, length of hospital stay; NRS, numeric rating scale from 0 for “no pain” to 10 for “the worst pain possible”.

1N = 34; 2N = 32; 3N = 23; 4N = 20; 5N = 30; 6N = 27; 7N = 22; 8N = 15; missing data of other women.

The additionally performed linear regression analysis confirmed the positive influence of the new protocol on reducing LOS (p = 0.02). When specifically analyzing the effect of the operative technique (longitudinal vs. transverse), as well as the pain management (tramadol vs. oxycodone/naloxone) on LOS, only the operative technique, namely longitudinal incisions showed to reduce LOS (p = 0.02). However, when combining these factors in a multivariate regression analysis no significant results were found.

Results of this study showed that women undergoing fSB repair benefit from the new ERAS protocol, thanks to the replacement of transverse incisions with only longitudinal incisions as operative technique, as well as the change in pain medication from tramadol to oxycodone/naloxone. In the following, the main findings and considerable differences between group 1 and group 2 are discussed.

One benefit of the new protocol was the significantly shorter LOS in group 2. A recent study by Patino et al. [16] analyzing the effect of their novel ERAS program in comparison to their traditional management also showed a significant reduction in LOS (p = 0.01) due to optimization of their patient management in a cohort of 30 women having had fetoscopic fSB repair. As in our study, their new protocol was equally not able to reduce pain scores significantly [16].

Postoperative pain scores did not significantly differ. In both groups, the highest pain scores were reported on the third postoperative day. One explanation might be the fact that the EDA catheter mostly was also removed on the third postoperative day in both groups, potentially causing higher pain scores after removal. However, results show that further studies focusing on the optimal pain management are needed to improve pain scores in patients undergoing fSB repair.

A further benefit of the new protocol was the significant earlier postoperative mobilization in group 2 (p = 0.03) [17‒19]. This is another relevant benefit since postoperative immobilization increases the risk for pulmonary complications as well as thromboembolic events [20]. The latter still represent one of the main reasons for maternal morbidity and mortality [21]. An early postoperative mobilization is therefore essential and our results showed that this was possible in women treated according to the new protocol without increasing the pain scores on the other hand.

Additionally, our results showed a significantly earlier postoperative removal of the urinary catheter in group 2 (p = 0.004). This is a clear benefit since a later removal is associated with higher rates of symptomatic and asymptomatic urinary bladder infections and a delayed mobilization [17‒19]. Tambyah et al. [22] reported that the prevalence of bacteriuria even increases by 3–10% with every day a urinary catheter stays in place.

Regarding the first day of bowel movement, we did not see any significant difference between the groups. The first bowel movement happened on average on the third postoperative day in both groups, a prolonged postoperative constipation was not seen in either group. Several studies reported the positive effects of oxycodone/naloxone regarding opioid-induced constipation via selectively blocking enteric µ-opioid receptors, while providing effective analgesia [8, 9, 23]. However, Leng et al. [9], who conducted a study comparing prolonged-release oxycodone/naloxone to solely prolonged-release oxycodone, reported significant improvements in bowel function only after a couple of weeks of treatment, potentially explaining the non-significant differences among our groups. Additionally, no significant differences were seen regarding postoperative ileus (included within maternal complications) affecting two women in group 1 and one woman in group 2. These few cases might be due to our proactive perioperative management consisting of intake of oral laxatives for 2 days preoperatively and postoperatively, as well as an enema on the night before surgery. These measures were reported to improve postoperative defecation [24, 25]. Due to the postulated positive effect of preoperative enema application, this procedure was standardized over time, although prolonged postoperative constipation was not regularly seen before [24]. Therefore, enema application was reported significantly more often in group 2 (p < 0.001). However, since this study did not show any difference regarding bowel movement among the groups and the new pain management should be in favor of good bowel function, enema application could be reconsidered.

Due to the change in protocol, group 2 significantly more often received oxycodone/naloxone as pain relief (p < 0.001), whereas group 1 was significantly more often treated with tramadol (p < 0.001). Results furthermore showed that the need for additional pain medication like morphine i.v. or s.c. was significantly higher in group 1 (p = 0.02 [i.v.] and p < 0.001 [s.c.]). On the other hand, women in group 2 significantly more often received oxycodone as additional pain medication (p < 0.001). Taken together, women in both groups needed additional pain relief in most cases, while the type of additional medication was most likely influenced by current protocols/preferences. However, as pain scores in both groups were low this supports that postoperative pain management has been working well since starting with open fSB repair at our center in 2010. An adequate postoperative pain relief is essential since pain causes a physical and psychological stress response of the body, deteriorates sleep, limits mobilization, and causes insufficient inspiratory performance that increases the risk for pulmonary infections [26, 27].

The subgroup analysis revealed significantly earlier removal of urinary catheter in women with longitudinal incision. However, no significant difference was seen regarding LOS between women with longitudinal compared to transverse incision. This finding emphasizes on the added positive effect of change in pain medication from tramadol to oxycodone in the new ERAS protocol since the combination of a longitudinal incision with oxycodone as pain medication led to significantly shorter LOS, apart from earlier removal of urinary catheter. Furthermore, subgroup analysis showed a higher maternal complication grade 1 rate in women with longitudinal incision (not needing any intervention). However, no differences were seen when comparing the old to the new ERAS protocol. This finding may be explained by the increasing experience of the team over time. Results of this study emphasize that constant improvements of ERAS protocols are vital in optimizing patient care while potentially reducing health-care costs.

Strength and Weaknesses

This is the first study focusing on ERAS protocol in open fSB repair and to our knowledge only the second one regarding fetal surgery in general. In our center, a multidisciplinary team consisting of always the same members performs patient care around fetal surgery as well as the subsequent cesarean delivery. This practice allows for accurate evaluation of the whole management and consequently led to the revision of our ERAS protocol that now showed to improve patient care.

Nevertheless, this study has some limitations like the retrospective study design. Furthermore, there might be an inevitable bias as increasing knowhow regarding, e.g., operative technique, importance of early mobilization for postoperative recovery, other elements of pain management not looked at in this study, patient care and eventually psychological assistance over time could have influenced the better outcomes in group 2.

The study demonstrates clear-cut benefits of our new ERAS protocol, consisting of a change in operative incision techniques and pain management that together with generally growing knowhow, lead to a significant reduction in LOS, significantly earlier postoperative mobilization, as well as significantly earlier removal of the urinary catheter postoperatively. ERAS protocols are important to improve clinical outcomes and thus should more commonly be implemented in the field of fetal surgery. Additionally, constant evaluation of current protocols is essential to improve patient care continuously.

The authors want to first thank all families who participated in this research. In addition, we thank our contributing study group without whom 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 und Noemi Zweifel. From the University Hospital Zurich, our study group consists of Dirk Bassler, Lukas Kandler, 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 Ethics Commission Zurich (KEK-ZH, Nr. 2015-0172). The study was carried out in compliance with the Declaration of Helsinki and written informed consent was obtained by all participants.

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

This study had no funding sources.

A.Z. and N.O. designed the study outline. N.S. and A.Z. performed data collection and data quality control. J.Z. conducted the data analyses and wrote the manuscript. J.Z., A.Z., L.V., L.R., F.K., N.S., L.M., M.M., U.M., and N.O. participated in the 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.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author upon reasonable request.

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