Prediction of complex gastroschisis: The evolution of therapeutic techniques and their relation with fetal sonographic features

Abstract

BACKGROUND:

To analyze prenatal ultrasound (US) markers to predict treatment and adverse neonatal outcome in fetal gastroschisis.

METHODS:

It was conducted a retrospective single-center study considering all pregnancies with isolated gastroschisis that were treated in our department between 2008 and 2020. 17 US markers were analyzed. Moreover, the association between prenatal ultrasound signs and neonatal outcomes was analyzed: need of bowel resection, techniques of reduction, type of closure, adverse neonatal outcomes, time to full enteral feeding, length of total parenteral nutrition and length of hospitalization.

RESULTS:

The analysis included 21 cases. We found significant associations between intestinal dilation (≥10 mm) appeared before 30 weeks of gestation and the need of bowel resection (p = 0.001), the length of total parenteral nutrition (p = 0,0013) and the length of hospitalization (p = 0,0017). Intrauterine growth restriction (IUGR) is a risk factor for serial reduction (p = 0,035). There were no signs significantly associated with the type of closure. Hyperbilirubinemia is related with gestational age (GA) at the diagnosis of intra-abdominal bowel dilation (IABD) (p = 0.0376) and maximum IABD (p = 0.05). All newborns with sepsis had echogenic loops in uterus (p = 0.026). The relation between the GA at delivery and the GA at the extra-abdominal bowel dilation (EABD)≥10 mm was r = 0.70.

CONCLUSION:

We showed the significant role of the early presence of bowel dilation in predicting intestinal resection and adverse outcomes. All IUGR fetuses needed staged reduction through the silo-bag technique. The echogenic bowel was related to neonatal sepsis, while IABD was associated with hyperbilirubinemia.

Keywords

Bowel dilation fetal sonographic gastroschisis intestinal resection silo-bag technique

1 Introduction

Gastroschisis is an abdominal wall defect associated with herniation of the bowel and more rarely of other organs, such as liver and spleen. The defect usually concerns the right side of the umbilical insertion and is characterized by the absence of the membrane covering the herniated organs, which therefore float in the amniotic fluid. It affects approximately one of every 5,000 newborns and data show an increasing trend [1]. Gastroschisis is usually associated with a good prognosis, however 20%of cases will be later defined as complex because they will have a complicated postnatal therapeutic process [2]. In addition, a third of these, will have consequences that will determine a significant reduction in quality of life: The short bowel syndrome [3].

Gastroschisis reduction and closure techniques have progressively become less invasive. The incoming silo closure, as well as the sutureless closure, have reduced the need for general anesthesia and the need for surgery. These reduction and closure techniques have also produced excellent aesthetic results, avoiding the previous large scars and deformities of the abdominal wall [4].

The initial diagnosis, usually made during the second trimester, can hardly predict the prognosis of each specific case because there are numerous prenatal aspects of the gastrointestinal tract which are often described with poor homogeneity due to the lack of commonly shared definitions and also due to the subjectivity of some definitions [5]. The main ultrasound markers that may potentially predict the adverse outcome are strongly influenced by the evolution of the clinical situation and they often show up only in the late third trimester [6].

Most of the prenatal studies have focused on the possibility of identifying the cases of complex gastroschisis. These cases lead to a greater risk of mortality and bowel morbidity [7 –12]. However, the evolution of therapeutic techniques would require a more accurate prenatal counseling based on the type of surgical treatment, the need for surgery and general anesthesia of the newborn.

The aim of this research was to take into consideration the possibility of identifying prenatal ultrasound features that could predict the type of surgical treatment and the adverse neonatal outcome.

2 Methods

A retrospective study was carried out from 2008 to 2020 concerning patients who were addressed to our third level Prenatal Diagnosis Center for suspected fetal gastroschisis, who later also gave birth in our hospital.

The exclusion criteria were: Abdominal wall defects other than gastroschisis, patients who decided to interrupt the pregnancy, multiple pregnancies, lack of data, incomplete follow-up, and cases of unconfirmed diagnosis.

The patients underwent a detailed ultrasound performed by fetal medicine specialists. All of them were offered both with an invasive procedure of prenatal diagnosis and a consultation with the pediatric surgeon.

Ultrasound evaluations were initially performed every 4 weeks up to 32 weeks of gestation, after that, they were performed weekly or every two weeks up to 37 weeks of gestation depending on the clinical evolution. At each control, fetal growth, amniotic fluid volume and umbilical artery’s Doppler velocimetry were checked. Also, the gastrointestinal tract was described, paying particular attention to intra-abdominal and herniated bowel loops. Measurements of the major transverse diameter of the dilated loops, the size of the stomach, the thickness of the intestinal walls in suspected thickening and the echogenicity of the intestinal loops were recorded. Fetal growth was analyzed with at least 2 weeks interval.

Delivery was scheduled approximately at week 37 of gestational age (GA) and delivery methods were assessed on a case-by-case basis, in agreement with the pediatric surgery and neonatal intensive care team. Data were collected based on the following prenatal characteristics: intra-abdominal bowel dilation (IABD) and extra-abdominal bowel dilation (EABD), defined by the specialist performing the ultrasound using a common cut-off of 10 mm, GA at the appearance of intestinal dilation, size of the hernial port at the first evaluation and the side of the abdominal defect with respect to the insertion of the umbilical cord, gastric dilation (above the 95th percentile for the gestational age) [13], “coffee bean” sign; thickening of the bowel wall and GA at the onset of thickening; hyperechogenicity of the dilated loops and GA at the appearance of hyperechogenicity; coexistence of 3 signs (dilatation, thickening and hyperechogenicity of the bowel loops), polyamnios - defined as a maximum pocket≥8 cm- and oligoamnios - defined as a single maximum pocket≤2 cm, fetal growth restriction (IUGR) - defined as an estimate fetal weight (EFW) lower than the 3rd percentile according to the Intergrowth reference curves [14] - presence of associated anomalies, alpha-fetoprotein value on amniotic fluid, anomalies of the fetal karyotype and of the Array CGH analysis.

All ultrasound characteristics were associated with the following neonatal results: Type of reduction of herniated organs (primary / serial reduction), type of wall defect closure (by sutures or sutureless), need for bowel resection, duration of parenteral nutrition and time to complete enteral feeding (TFEF).

Respiratory distress syndrome was diagnosed in case of respiratory distress sings, in addition to typical radiological changes and the need for oxygen therapy to maintain PaO2 > 50 mmHg [15]; sepsis diagnosis was defined based on a positive blood culture, in case of septic shock or in case of a radiological sign of infection in infants with clinical sepsis [16]; intraventricular hemorrhage was defined according to Papile’s criteria [17]; necrotizing enterocolitis was diagnosed on radiological findings [18]; bronchopulmonary dysplasia was defined based on the diagnostic criteria of Jobe and Bancalari [19]. Hyperbilirubinemia was defined by serum direct bilirubin values > 1 mg / dL [20]. In addition, the need for transfusion was considered. A composite adverse neonatal outcome was calculated as the sum of the neonatal complications listed above.

2.1 Data analysis

Numerical variables were described through med-ian and inter-quartile range. Categorical or dichotomous variables were described by absolute and relative frequencies (%). The association between dichotomous results and prenatal characteristics was investigated using Fisher’s exact test for categorical variables and Wilcoxon-Mann-Whitney test for continuous numerical variables. For numerical results such as time calculated through days or gestational age, the Wilcoxon-Mann-Whitney test was used for the association with categorical variables and the Spearman relation index for association with numerical variables.

Significant associations were graphed using box plots and scatter plots. In case of both dichotomous result and prenatal parameter, the predictive capacity of the parameter was assessed by calculating the indices of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. The statistical software which was used for the analysis was Stata version 13 (StataCorp, College Station, TX). Statistical significance is fixed for p < 0.05.

2.2 Ethical approval

The study was approved by local the ethics committee and registered with the ID number NP 4794.

3 Results

3.1 Case selection

From 2008 to 2020, 32 patients have been taken into consideration due to a suspected gastroschisis, among these, 21 were included in the research (Fig. 1).

Fig. 1

Flow chart of patients included in the analysis.

3.2 Features of study subjects

The average women’s maternal age was 23 (IQR 7). The women had a pre-pregnancy BMI of 20.7 kg / m2, 85.7%(18/21) were nulliparous. 14 underwent an invasive diagnosis: Karyotype and array-CGH (when available) resulted normal in every case.

The average gestational age at delivery was 36.2 weeks (IQR: 1.4) and 90.4%(19/21) of patients delivered by caesarean section. The median age at diagnosis of gastroschisis was 19 weeks of gestation. In all the cases the first US evaluation was performed in the second trimester of pregnancy.

The main neonatal characteristics are summarized in Table 1.

Table 1
Neonatal features

Characteristic median (IQR)- n° (%)

Neonatal sex

Male 8 (38)

Female 13 (61,9)

Birthweight (g) 2145 (685)

Weight percentile

< 5°– 8 (38)

5°–10° 2 (9,5)

10°–90° 11 (52,3)

> 90° 0

APGAR 5’ minutes < 7 11 (52,3)

Respiratory distress at birth 9 (45)

Hole size at birth (cm) 2,7 (1,5)

other abdominal organs herniate 5 (23,8)

Time on TPN (days) 14 (26,2)

TFEF (days) 30 (16,5)

Complex Gastroschisis 5 (23,8)

Necrosis 2 (9,5)

Atresia 4 (19)

Perforation 1 (4,7)

Volvulus 1 (4,7)

Sepsis 4 (20)

RDS 1 (5)

IVH 0

BDP 0

NEC 1 (5)

Transfusion 10 (50)

Hyperbilirubinaemia 8 (40)

short bowel syndrome 2 (10)

Neonatal death 0

Weight at discharge (g) 3025 (177)

Composite adverse neonatal outcome 2 (1,25)

length of stay (d) 37 (32,5)

Primary reduction 10 (47,6)

Staged reduction 11 (52,3)

Time to abdominal wall closure (d) 0 (8)

Bowel resection 5 (23,8)

Sutureless closure 10 (47,6)

Characteristic	median (IQR)- n° (%)
Neonatal sex
Male	8 (38)
Female	13 (61,9)
Birthweight (g)	2145 (685)
Weight percentile
< 5°–	8 (38)
5°–10°	2 (9,5)
10°–90°	11 (52,3)
> 90°	0
APGAR 5’ minutes < 7	11 (52,3)
Respiratory distress at birth	9 (45)
Hole size at birth (cm)	2,7 (1,5)
other abdominal organs herniate	5 (23,8)
Time on TPN (days)	14 (26,2)
TFEF (days)	30 (16,5)
Complex Gastroschisis	5 (23,8)
Necrosis	2 (9,5)
Atresia	4 (19)
Perforation	1 (4,7)
Volvulus	1 (4,7)
Sepsis	4 (20)
RDS	1 (5)
IVH	0
BDP	0
NEC	1 (5)
Transfusion	10 (50)
Hyperbilirubinaemia	8 (40)
short bowel syndrome	2 (10)
Neonatal death	0
Weight at discharge (g)	3025 (177)
Composite adverse neonatal outcome	2 (1,25)
length of stay (d)	37 (32,5)
Primary reduction	10 (47,6)
Staged reduction	11 (52,3)
Time to abdominal wall closure (d)	0 (8)
Bowel resection	5 (23,8)
Sutureless closure	10 (47,6)

Abbreviations: TPN, total parenteral nutrition; TEFE, time to full enteral feeding; RDS, respiratory distress syndrome; IVH, intraventricular hemorrhage; BPD, broncho-pulmonary dysplasia; NEC, necrotising enterocolitis; IQR, interquartile range.

3.3 Subgroup analysis

Bowel resection 23.8%(5/21) of cases were classified as complex gastroschisis and required a bowel resection surgery, the most commonly encountered bowel complication was bowel atresia (4/5), and in one newborn both volvulus and bowel necrosis (1/5) occurred.

Taking into consideration the correlation with the ultrasound aspects it emerged that the only factor being significantly associated with the need for bowel resection was an occurring dilation≥10 mm before 30 weeks (p = 0.001). All 5 cases of complex gastroschisis had a≥10 mm dilation before 30 weeks, while 2 among the other cases had the same dilation (sensitivity 100%, specificity 87.5%, accuracy 90.5%, PPV = 5/7 = 71.4 %, VPN = 100%). In addition, compared to the other newborns, the ones who underwent bowel resection showed a significantly lower gestational age (less than 30 weeks) when dilation was≥10 mm (Table 2).

Table 2
Associations between prenatal markers of fetal gastroschisis and surgical outcomes

Simple n = 16 Complex n = 5

EGA at onset IABD (wks) 30 (27–33) 33 (28–34)

IABD at onset (mm) 13 (8–15) 9 (9–13)

EGA at onset EABD (wks) 31 (29–32) 28 (27–28)

EABD at onset (mm) 10 (7–14) 12 (11–14)

IABD max (mm) 17 (15–21) 16 (11–22)

EABD max (mm) 19 (17–20) 17 (17–25)

EGA IABD≥10 mm (wks) 32 (30–33) 34 (25–35)

EGA EABD≥10 mm (wks) 32 (32–32) 28 (27–28) ^*

EGA BD≥10 mm (wks) 32 (31–32) 27 (26–28) ^

BD≥10 mm 12 (75%) 5 (100%)

BD≥10 mm < 30 wks 2 (13%) 5 (100%) ^*

BD>25 mm 2 (13%) 2 (40%)

hole size at diagnosis (mm) 15 (10–15) 12 (12–14)

Left side of the umbilicus 2 (13%) 0 (0%)

Gastric dilation 0 (0%) 0 (0%)

Coffee bean sign 5 (31,2%) 3 (60%)

3 combined US markers 5 (31,2%) 3 (60%)

Polyhydramnios 0 (0%) 0 (0%)

Oligohydramnios 3 (18,7%) 0 (0%)

bowel wall thickness 6 (37,5%) 3 (60%)

EGA bowel wall thickness (wks) 31 (30–32) 34 (22–35)

Echogenic bowel 6 (37,5%) 4 (80%)

EGA echogenic bowel (wks) 31 (22–32) 24 (22–30)

IUGR 5 (31%) 0 (0%)

	Simple n = 16	Complex n = 5
EGA at onset IABD (wks)	30 (27–33)	33 (28–34)
IABD at onset (mm)	13 (8–15)	9 (9–13)
EGA at onset EABD (wks)	31 (29–32)	28 (27–28)
EABD at onset (mm)	10 (7–14)	12 (11–14)
IABD max (mm)	17 (15–21)	16 (11–22)
EABD max (mm)	19 (17–20)	17 (17–25)
EGA IABD≥10 mm (wks)	32 (30–33)	34 (25–35)
EGA EABD≥10 mm (wks)	32 (32–32)	28 (27–28) ^*
EGA BD≥10 mm (wks)	32 (31–32)	27 (26–28) ^**
BD≥10 mm	12 (75%)	5 (100%)
BD≥10 mm < 30 wks	2 (13%)	5 (100%) ^***
BD>25 mm	2 (13%)	2 (40%)
hole size at diagnosis (mm)	15 (10–15)	12 (12–14)
Left side of the umbilicus	2 (13%)	0 (0%)
Gastric dilation	0 (0%)	0 (0%)
Coffee bean sign	5 (31,2%)	3 (60%)
3 combined US markers	5 (31,2%)	3 (60%)
Polyhydramnios	0 (0%)	0 (0%)
Oligohydramnios	3 (18,7%)	0 (0%)
bowel wall thickness	6 (37,5%)	3 (60%)
EGA bowel wall thickness (wks)	31 (30–32)	34 (22–35)
Echogenic bowel	6 (37,5%)	4 (80%)
EGA echogenic bowel (wks)	31 (22–32)	24 (22–30)
IUGR	5 (31%)	0 (0%)

Abbreviation: EGA, estimate gestational age; IABD, intra-abd-ominal bowel dilatation; EABD, extra-abdominal bowel dilatation; BD, bowel dilation; US, ultrasound; IUGR, intrauterine growth restriction. ^*0.003; ^**0.002; ^***; 0.001.

3.4 Techniques of reduction

It was possible to make a primary reduction of herniated viscera in 10 newborns, while 11 patients required a staged reduction through the use of a “silobag”. The prenatal diagnosis of IUGR was a risk factor for the multi-step reduction of herniated viscera (p = 0.035), none of the patients who got primary reduction was previously diagnosed with IUGR (0/10). All the IUGR fetuses were in “staged reduction” group (5/11) (P = 0.035).

3.5 Techniques of closure

In 47.6%(10/21) sutureless delayed closure techniques were used. No prenatal aspect was significantly associated with this type of closure. Only, the group of newborns that got sutureless delayed closure seemed to show a lower EABD than the other groups, however it does not reach statistical significance (10 vs 14; p = 0.07).

Gestational age at delivery: The connection between the GA at delivery and the GA at diagnosis of the EABD≥10 mm has a strong degree and tends to be linear (r = 0.70) (Fig. 2).

Fig. 2

Correlation between EGA at BD≥10 mm and EGA at delivery (scatter plot).

3.6 Neonatal sepsis

In the 20%(4/21) of newborns postnatal period was complicated by sepsis. All newborns who developed sepsis had hyperechogenicity of the bowel loops in the prenatal period (31%vs 100%p = 0.026), sensitivity 100%, specificity 68.8%, NPV = 100%, PPV = (4/9) 44.4%, accuracy = (15/20) 75%. Furthermore, the group diagnosed with sepsis was at a lower gestational age when hyperechogenicity appeared, compared to the other group (32 w vs 22 w, p = 0.027) (Fig. 3).

Fig. 3

Correlation between EGA at Echogenic bowel and sepsis (Box-plot).

3.7 Composite adverse neonatal outcome

The composite outcome is available for 20 out of 21 patients and ranges from a minimum of 0 to a maximum of 5. The average value is 2.

Cases showing≥10 mm dilation before 30 weeks and those showing hyperechogenicity result in a significantly higher composite outcome (p = 0.014) (Table 3).

Table 3
Associations between ultrasound markers and neonatal outcomes

Lenght of stay (days, IQR) Time on TPN (days, IQR) TFEF (days, IQR) Composite adverse neonatal outcome (IQR)

BD≥10 mm

Yes 43 (31–72) 14 (10–38) 31 (29–47) 2 (1–3)

No 27 (24–34) 15 (10–19) 27 (22–34) 1,5 (1–2)

BD≥10 mm < 30w

Yes 77 (54–90) 45 (36–60) 47 (44–71) 2,5 (2–3)

No 31 (24–38) ^* 12 (9–15) ^* 30 (23–71) 1 (0–2)

^* ^ ^* ^

BD≥25 mm

Yes 57 (33–91) 25 (12–58) 37 (26–72) 1,5 (01–3)

No 34 (30–57) 14 (10–30) 30 (25–43) 2 (1–2)

Left side of the umbilicus

Yes 48 (36–60) 25 (11–39) 42 (31–52) 3,5 (2–5)

No 35 (30–70) 14 (10–36) 30 (25–43) 2 (0–2)

Coffè bean sign

Yes 57 (31–82) 25 (11–56) 30 (29–71) 2 (2–3)

No 34 (24–48) 14 (9–22) 31 (23–40) 1,5 (0–2)

3 combined US markers

Yes 60 (30–90) 39 (10–60) 41 (29–71) 2 (1–3)

No 36 (30–40) 13 (10–20) 30 (25–37) 2 (0–2)

Oligohydramnios

Yes 70 (54–74) 23 (13–52) 43 (30–71) 2 (0–3)

No 31 (30–44) 12 (10–36) 30 (24–41) 2 (1–2)

bowel wall thickness

Yes 51 (31–82) 27 (11–56) 35 (29–71) 2 (0–2)

No 34 (27–49) 13 (9–22) 30 (24–40) 2 (1–3)

Echogenic bowel

Yes 60 (31–80) 37 (11–52) 39 (30–62) 2 (2–3)

No 31 (24–44) 13 (7–20) 30 (23–37) 1 (0–2)

^*

IUGR

Yes 60 (38–70) 20 (13–39) 37 (30–52) 2 (2–3)

No 31 (24–54) 12 (10–36) 30 (23–43) 2 (0–2)

	Lenght of stay (days, IQR)	Time on TPN (days, IQR)	TFEF (days, IQR)	Composite adverse neonatal outcome (IQR)
BD≥10 mm
Yes	43 (31–72)	14 (10–38)	31 (29–47)	2 (1–3)
No	27 (24–34)	15 (10–19)	27 (22–34)	1,5 (1–2)
BD≥10 mm < 30w
Yes	77 (54–90)	45 (36–60)	47 (44–71)	2,5 (2–3)
No	31 (24–38) ^*	12 (9–15) ^*	30 (23–71)	1 (0–2)
	^*	^**	^***	^****
BD≥25 mm
Yes	57 (33–91)	25 (12–58)	37 (26–72)	1,5 (01–3)
No	34 (30–57)	14 (10–30)	30 (25–43)	2 (1–2)
Left side of the umbilicus
Yes	48 (36–60)	25 (11–39)	42 (31–52)	3,5 (2–5)
No	35 (30–70)	14 (10–36)	30 (25–43)	2 (0–2)
Coffè bean sign
Yes	57 (31–82)	25 (11–56)	30 (29–71)	2 (2–3)
No	34 (24–48)	14 (9–22)	31 (23–40)	1,5 (0–2)
3 combined US markers
Yes	60 (30–90)	39 (10–60)	41 (29–71)	2 (1–3)
No	36 (30–40)	13 (10–20)	30 (25–37)	2 (0–2)
Oligohydramnios
Yes	70 (54–74)	23 (13–52)	43 (30–71)	2 (0–3)
No	31 (30–44)	12 (10–36)	30 (24–41)	2 (1–2)
bowel wall thickness
Yes	51 (31–82)	27 (11–56)	35 (29–71)	2 (0–2)
No	34 (27–49)	13 (9–22)	30 (24–40)	2 (1–3)
Echogenic bowel
Yes	60 (31–80)	37 (11–52)	39 (30–62)	2 (2–3)
No	31 (24–44)	13 (7–20)	30 (23–37)	1 (0–2)
				^*****
IUGR
Yes	60 (38–70)	20 (13–39)	37 (30–52)	2 (2–3)
No	31 (24–54)	12 (10–36)	30 (23–43)	2 (0–2)

Abbreviation: TPN, total parenteral nutrition; TEFE, time to full enteral feeding; BD, bowel dilation, IUGR, intrauterine growth restriction; IQR, interquartile range. ^*0.0017, ^** 0.0013, ^***0.003, ^****0.0142, ^*****0.0140.

3.8 Time to total parenteral nutrition and time to full enteral feeding

The duration of total parental nutrition is significantly associated with the presence of a dilation≥10 mm before week 30 of GA (12 vs 45 p = 0.0013). Duration of TPN is also positively related to the dilation of the EABD (r = 0.5067), to the presence of a dilation≥10 mm (r = –0.5228) and inversely related to the GA of its appearance (Table 3).

The complete enteral feeding time (TFEF) is also associated with dilation≥10 mm before 30 weeks [30 (range 20–52) VS 47 (range 43–100) p = 0.0030]. Furthermore, the TFEF is inversely related to both the GA of appearance and the thickening (r = –0.4865).

Hyperbilirubinemia is associated with GA at diagnosis of IABD [33 (range 24.8–35.2) vs 25.6 (range 21.6–30.1) p = 0.0376] and with the maximum dilation of the intra-abdominal loops [15 (range 9–20) vs 21 (range 12–23) p = 0.05] (Fig. 4).

Fig. 4

Correlation between IABD (mm) and neonatal hyperbilirubinemia.

3.9 Length of hospitalization

The presence of≥10 mm dilation before 30 weeks of gestation is related to the length of hospitalization in the neonatal intensive care unit (NICU) [77 vs 31 p = 0.0017]. Newborns with≥10 mm dilation before 30 weeks stayed in NICU approximately 46 days longer. In addition, the hospitalization in the NICU is inversely related to the gestational age of the appearance of dilation > 10mm (r = –0.48), in particular for the EABD (r = –0.48) (Table 3).

4 Discussion

Isolated gastroschisis is usually correlated with a good prognosis which has shown a progressive improvement over the years. In our study, 23%of newborns had intestinal complications, in particular atresia, but only 10%was diagnosed with a short bowel syndrome.

To our knowledge, this is the first study that has analyzed the relation between prenatal ultrasound features and postnatal surgical treatment choice, introducing the possibility of predicting the surgical procedure.

In fact, the presence of an intestinal dilation ≥10 mm at a GA earlier than 30 weeks, has been associated with complex gastroschisis and therefore there is a high probability that an intestinal resection will be needed after birth (in more than 70%of the cases). Furthermore, IUGR diagnosis is a risk factor for a multi-step reduction of the herniated organs.

Many studies attempted to identify prenatal predictors of adverse postnatal outcomes on fetuses with gastroschisis, focusing mainly on the prediction of complex gastroschisis. The traits that were usually analyzed are: IABD and EABD, intestinal wall thickening, intestinal peristalsis, gastric dilation and herniation through the abdominal defect. Specifically, the IABD is reported as the most frequent predictor of complications and adverse outcomes [8 , 21–23]. However, most of the studies provide limited sources and different definitions of bowel dilation. In our experience, all cases of complex gastroschisis showed a dilation larger than 10 mm before 30 weeks of GA regardless its localization. Moreover, dilation≥10 mm before 30 weeks was associated with a significantly higher neonatal composite outcome, a longer duration of total parenteral nutrition, lasting approximately 30 days, a longer time to achieve complete enteral nutrition and, therefore, a longer permanence in the neonatal intensive care unit. This study supports the predictive value of the time of appearance of bowel dilation in predicting neonatal outcomes, rather than focusing on its localization (extra or intra-abdominal). Lato et al. were among the first to introduce the concept of dilation’s GA at diagnosis and they demonstrated how dilation≥10 mm before 30 weeks of GA was the strongest predictor of postnatal intestinal complications [24]

Our results contrast with Langer who suggested that the only presence of dilation can be a prenatal marker of intestinal damage in fetuses with gastroschisis, especially when it occurs in late gestational periods [25]. Due to the small size of our series, the observations found cannot be presented as definitive statements, as the subgroups analyzed were composed of a few patients, but the rarity of the condition makes our result remarkable.

Over the last few decades, the increase of the incidence and the introduction of progressively less invasive surgical techniques lead to the need of an even more accurate medical counseling.

With respect to the surgical strategy we not only predicted the need for a bowel resection but we also assessed the need for the type of herniated organs reduction (primary / staged) and the type of abdominal wall closure (sutured immediate/sutureless delayed). It has emerged that intrauterine fetal growth reduction is a risk factor for staged reduction. In newborns with a small abdomen for the GA it will be more difficult the reduction of the whole herniates bowel in one single attempt. Regarding the abdominal defect’s type of closure, we did not detect ultrasound signs significantly associated, perhaps because it depends on several factors, such as the experience of the surgeon. Overall, we observed an increasing use of suture-free techniques over the years [4]. These less invasive closure techniques, as reported in recent series, reduce both the need for general anesthesia and the access to surgery rooms and they can also minimize the increase in abdominal pressure guaranteeing excellent aesthetic results.

The results of our study could help in planning the neonatal surgical strategy. This allows us to organize counseling with the couple regarding the postnatal therapeutic process. In fact, the possibility of predicting staged reduction and bowel resection allows to identify a subgroup of cases who will be informed for a probable longer duration of hospitalization, the possibility of major surgery for intestinal complications.

The average delivery’s GA was 36.2 weeks like what is reported in literature [26].

It should be observed that in our cases emerged a strong and linear relation between the delivery’s gestational age and the gestational age of the EABD diagnosis (r = 0.70).

It is known that the amniotic fluid of fetuses with gastroschisis shows higher levels of pro-inf-lammatory cytokines, interleukin 8 and other inflammatory markers such as total protein, ferritin, amylase and lipase which could explain the higher incidence of preterm labor in these pregnancies [26, 27]. The dilation of the intestinal loops is related to an injury of that intestinal tract, so we could hypothesize that the earlier this dilation occurs, the faster the release of pro-inflammatory cytokines is, especially for what regards the extra-abdominal loops floating in the amniotic liquid. Regarding the short-term neonatal outcomes, sepsis was diagnosed in the 20%of cases. In all newborns who developed sepsis, bowel loops hyperechogenicity was observed in the prenatal period. Also, the GA at diagnosis of hyperechogenicity was lower in these cases. Only a few studies had previously analyzed the role of intestinal hyperechogenicity in gastroschisis; Grignon et al. hypothesized that hyperechogenicity is a sign of temporary bowel obstruction probably related to ischemic vascular damage [28]. If the hyperechogenicity of the dilated loops, as stated by these authors, is related to an ischemic bowel injury, newborns could be exposed to a greater septic risk. Indeed, our study reveals that fetuses with hyperechogenic bowel showed a worse composite outcome.

Another common finding was hyperbilirubinemia which affected 40%of newborns. Both cholestasis and hepatic dysfunction are well known complications of protracted parenteral nutrition [29].

Hyperbilirubinemia has been associated with the gestational age at diagnosis of IABD and with the maximum intra-abdominal dilation. The relationship between the maximum IABD and the GA of its appearance makes us hypothesize a possible and temporary compressive effect on the biliary tract during fetal life. In 2005, Teoh had already reported cases of newborns with abdominal wall defects and jaundice due to a mechanical obstruction of the bile duct [30]. According to D’Antonio’s meta-analysis, polyhydramnios was associated with both an increasing risk of bowel atresia and gastric dilatation with a consequent neonatal death [10]. In our experience, no cases reported gastric dilatation or polyamnios and no neonatal deaths occurred.

The strength of our research was the use of homogeneous definitions and management criteria; it is also the first work connecting the ultrasound data to neonatal surgical strategy.

On the contrary, we acknowledge as weaknesses and limitations of our study, the retrospective and single center nature of the study, the small size of the sample over 12 years.

5 Conclusion

This study highlights the importance of the early onset of bowel dilation as a predictor of neonatal outcomes. Fetuses with intrauterine growth restriction have a higher probability to undergo a multistep reduction of the herniated organs through the silo-bag technique. The hyperechogenicity of the loops is a risk factor for neonatal sepsis while IABD is associated with an increased risk of hyperbilirubinemia. The information that emerged can be useful in counselling couples over the postnatal surgical treatment, in preparing neonatologists and paediatric surgeons for neonatal care and in stressing the value of multidisciplinarity in the management of this cases. Further studies will be useful for validate our findings and to determine whether timing of appearance of bowel dilatation can improve prenatal prediction of surgical treatment.

The authors received no specific funding for this work

Footnotes

Acknowledgments

The authors received no specific funding for this work.

Disclosure statements

The authors have no conflict of interest to report.

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