Eur J Pediatr Surg 2019; 29(04): 342-351
DOI: 10.1055/s-0039-1694746
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Gastroschisis: State of the Art in Translating Experimental Research to the Bedside

Lourenço Sbragia
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
,
Rebeca Lopes Figueira
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
,
Karina Miura da Costa
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
,
Fábio Perecim Volpe
1   Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
› Author Affiliations
Further Information

Publication History

24 June 2019

08 July 2019

Publication Date:
19 August 2019 (online)

Abstract

The survival rate of newborns with gastroschisis (GS) has been increasing in the past decades; however, the morbidity continues to be high, mainly related to the length of hospitalization due to disturbances of motility, absorption, and risk of intestinal infections. The development of basic research with the creation of experimental models has provided enormous advances in the understanding of the pathophysiology of the disease. These models allowed the study of the target genes involved in the embryology of the defect, the influence of the amniotic fluid, and the use of drugs and fetal therapies in an attempt to reduce the intestinal damage and to provide a rapid return of intestinal motility. Our aim was to describe the main GS models and the translational, historical impact of these research advances on the disease.

 
  • References

  • 1 O'Connell RV, Dotters-Katz SK, Kuller JA, Strauss RA. Gastroschisis: a review of management and outcomes. Obstet Gynecol Surv 2016; 71 (09) 537-544
  • 2 Skarsgard ED. Management of gastroschisis. Curr Opin Pediatr 2016; 28 (03) 363-369
  • 3 Eggink BH, Richardson CJ, Malloy MH, Angel CA. Outcome of gastroschisis: a 20-year case review of infants with gastroschisis born in Galveston, Texas. J Pediatr Surg 2006; 41 (06) 1103-1108
  • 4 Moore TC, Stokes GE. Gastroschisis; report of two cases treated by a modification of the gross operation for omphalocele. Surgery 1953; 33 (01) 112-120
  • 5 Sadler TW, Feldkamp ML. The embryology of body wall closure: relevance to gastroschisis and other ventral body wall defects. Am J Med Genet C Semin Med Genet 2008; 148C (03) 180-185
  • 6 Feldkamp ML, Carey JC, Sadler TW. Development of gastroschisis: review of hypotheses, a novel hypothesis, and implications for research. Am J Med Genet A 2007; 143A (07) 639-652
  • 7 Shaw A. The myth of gastroschisis. J Pediatr Surg 1975; 10 (02) 235-244
  • 8 Kapapa M, Rieg T, Henne-Bruns D. , et al. Risk factors for abdominal wall defects. Congenit Anom (Kyoto) 2019 Doi: 10.1111/cga.12336
  • 9 Sartori ALH, de Vilhena MFR, França GS. , et al. Histological and morphological study of the intestines of Wistar rat fetuses in a modified gastroschisis experimental model. Surg Sci 2016; 07: 72-81
  • 10 Srinathan SK, Langer JC, Blennerhassett MG, Harrison MR, Pelletier GJ, Lagunoff D. Etiology of intestinal damage in gastroschisis. III: morphometric analysis of the smooth muscle and submucosa. J Pediatr Surg 1995; 30 (03) 379-383
  • 11 Sydorak RM, Nijagal A, Sbragia L. , et al. Gastroschisis: small hole, big cost. J Pediatr Surg 2002; 37 (12) 1669-1672
  • 12 Singh SJ, Fraser A, Leditschke JF. , et al. Gastroschisis: determinants of neonatal outcome. Pediatr Surg Int 2003; 19 (04) 260-265
  • 13 Fitzsimmons J, Nyberg DA, Cyr DR, Hatch E. Perinatal management of gastroschisis. Obstet Gynecol 1988; 71 (6 Pt 1): 910-913
  • 14 Vegunta RK, Wallace LJ, Leonardi MR. , et al. Perinatal management of gastroschisis: analysis of a newly established clinical pathway. J Pediatr Surg 2005; 40 (03) 528-534
  • 15 Wilson RD, Johnson MP. Congenital abdominal wall defects: an update. Fetal Diagn Ther 2004; 19 (05) 385-398
  • 16 Schlatter M, Norris K, Uitvlugt N, DeCou J, Connors R. Improved outcomes in the treatment of gastroschisis using a preformed silo and delayed repair approach. J Pediatr Surg 2003; 38 (03) 459-464
  • 17 Pampfer S, Streffer C. Prenatal death and malformations after irradiation of mouse zygotes with neutrons or X-rays. Teratology 1988; 37 (06) 599-607
  • 18 Hillebrandt S, Streffer C. Protein patterns in tissues of fetuses with radiation-induced gastroschisis. Mutat Res 1994; 308 (01) 11-22
  • 19 Pampfer S, Streffer C. Increased chromosome aberration levels in cells from mouse fetuses after zygote X-irradiation. Int J Radiat Biol 1989; 55 (01) 85-92
  • 20 Müller WU, Streffer C. Lethal and teratogenic effects after exposure to X-rays at various times of early murine gestation. Teratology 1990; 42 (06) 643-650
  • 21 Muller WU, Streffer C, Knoelker M. A genetic characterization of differences in the sensitivity to radiation-induced malformation frequencies in the mouse strains Heiligenberger, C57BI, and Heiligenberger x C57BI. Radiat Environ Biophys 1996; 35 (01) 37-40
  • 22 Hillebrandt S, Streffer C, Müller WU. Genetic analysis of the cause of gastroschisis in the HLG mouse strain. Mutat Res 1996; 372 (01) 43-51
  • 23 Hillebrandt S, Streffer C, Montagutelli X, Balling R. A locus for radiation-induced gastroschisis on mouse chromosome 7. Mamm Genome 1998; 9 (12) 995-997
  • 24 Pils S, Müller WU, Streffer C. Lethal and teratogenic effects in two successive generations of the HLG mouse strain after radiation exposure of zygotes -- association with genomic instability?. Mutat Res 1999; 429 (01) 85-92
  • 25 Layne MD, Yet SF, Maemura K. , et al. Impaired abdominal wall development and deficient wound healing in mice lacking aortic carboxypeptidase-like protein. Mol Cell Biol 2001; 21 (15) 5256-5261
  • 26 Danzer E, Layne MD, Auber F. , et al. Gastroschisis in mice lacking aortic carboxypeptidase-like protein is associated with a defect in neuromuscular development of the eviscerated intestine. Pediatr Res 2010; 68 (01) 23-28
  • 27 Klück P, Tibboel D, van der Kamp AW, Molenaar JC. The effect of fetal urine on the development of the bowel in gastroschisis. J Pediatr Surg 1983; 18 (01) 47-50
  • 28 Tibboel D, Molenaar JC, Van Nie CJ. New perspectives in fetal surgery: the chicken embryo. J Pediatr Surg 1979; 14 (04) 438-440
  • 29 Tibboel D, Klück P, van der Kamp AW, Vermey-Keers C, Molenaar JC. The development of the characteristic anomalies found in gastroschisis--experimental and clinical data. Z Kinderchir 1985; 40 (06) 355-360
  • 30 Lopez de Torre B, Tovar JA, Uriarte S, Aldazabal P. Transperitoneal exchanges of water and solutes in the fetus with gastroschisis. Experimental study in the chick embryo. Eur J Pediatr Surg 1991; 1 (06) 346-352
  • 31 Aktuğ T, Erdağ G, Kargi A, Akgür FM, Tibboel D. Amnio-allantoic fluid exchange for the prevention of intestinal damage in gastroschisis: an experimental study on chick embryos. J Pediatr Surg 1995; 30 (03) 384-387
  • 32 Aktuğ T, Uçan B, Olguner M, Akgür FM, Ozer E. Amnio-allantoic fluid exchange for prevention of intestinal damage in gastroschisis II: effects of exchange performed by using two different solutions. Eur J Pediatr Surg 1998; 8 (05) 308-311
  • 33 Aktuğ T, Uçan B, Olguner M. , et al. Amnio-allantoic fluid exchange for the prevention of intestinal damage in gastroschisis. III: determination of the waste products removed by exchange. Eur J Pediatr Surg 1998; 8 (06) 326-328
  • 34 Olguner M, Akgür FM, Api A, Ozer E, Aktuğ T. The effects of intraamniotic human neonatal urine and meconium on the intestines of the chick embryo with gastroschisis. J Pediatr Surg 2000; 35 (03) 458-461
  • 35 Dilsiz A, Gündogan AH, Aktan M, Duman S, Aktug T. Nitric oxide synthase inhibition prevents intestinal damage in gastroschisis: a morphological evaluation in chick embryos. J Pediatr Surg 1999; 34 (08) 1248-1252
  • 36 Kanmaz T, Yağmurlu A, Aktuğ T, Gökçora H. The effect of amnio-allantoic fluid pH on the intestines: an experimental study in the chick embryo gastroschisis model. J Pediatr Surg 2001; 36 (09) 1341-1345
  • 37 Api A, Olguner M, Hakgüder G, Ateş O, Ozer E, Akgür FM. Intestinal damage in gastroschisis correlates with the concentration of intraamniotic meconium. J Pediatr Surg 2001; 36 (12) 1811-1815
  • 38 Sencan A, Gümüştekin M, Gelal A, Arslan O, Ozer E, Mir E. Effects of amnio-allantoic fluid exchange on bowel contractility in chick embryos with gastroschisis. J Pediatr Surg 2002; 37 (11) 1589-1593
  • 39 Yu J, Gonzalez-Reyes S, Diez-Pardo JA, Tovar JA. Local dexamethasone improves the intestinal lesions of gastroschisis in chick embryos. Pediatr Surg Int 2004; 19 (12) 780-784
  • 40 Denli O, Barlas M, Bingol-Kologlu M. , et al. The effect on the intestines of continuous release of methylene blue from a drug delivery system: an experimental study in a chick embryo gastroschisis model. Pediatr Surg Int 2004; 20 (08) 609-613
  • 41 Ozdamar A, Topcu K, Gumustekin M. , et al. Erythropoietin restores bowel damage and hypoperistalsis in gastroschisis. J Pediatr Surg 2006; 41 (02) 352-357
  • 42 Olguner M, Hakgüder G, Ateş O, Cağlar M, Ozer E, Akgür FM. Urinary trypsin inhibitor present in fetal urine prevents intraamniotic meconium-induced intestinal damage in gastroschisis. J Pediatr Surg 2006; 41 (08) 1407-1412
  • 43 Karakuş OZ, Ateş O, Murat N. , et al. Intra-amniotic administration of urinary trypsin inhibitor preserves intestinal contractility in meconium induced intestinal damage in chick embryos with gastroschisis. J Pediatr Surg 2013; 48 (07) 1495-1498
  • 44 Karakuş OZ, Solmaz B, Ateş O. , et al. Effect of meconium on the contractility of the superior mesenteric artery: a clue to intestinal damage in gastroschisis. Eur J Pediatr Surg 2015; 25 (04) 373-376
  • 45 Vargun R, Aktug T, Heper A, Bingol-kologlu M. Effects of intrauterine treatment on interstitial cells of Cajal in gastroschisis. J Pediatr Surg 2007; 42 (05) 783-787
  • 46 Cağlar M, Hakgüder G, Ateş O. , et al. Amniotic fluid ferritin as a marker of intestinal damage in gastroschisis: a time course experimental study. J Pediatr Surg 2007; 42 (10) 1710-1715
  • 47 Caglar M, Karaguzel G, Gokhan-Ocak G. , et al. Multidirectional and simultaneous evaluation of gastroschisis-related intestinal damage in chick embryos. J Pediatr Surg 2014; 49 (11) 1577-1584
  • 48 Ulusoy O, Karakuş OZ, Ateş O. , et al. The intestinal damage induced by lipid soluble meconium subfraction is profound compared to the intestinal damage induced by water soluble meconium subfraction. J Pediatr Surg 2016; 51 (08) 1303-1306
  • 49 Şiyve S, Ulusoy O, Karakuş OZ. , et al. The role of water-soluble meconium subfraction and lipid-soluble meconium subfraction on the superior mesenteric artery vasoconstriction in chick embryos. J Pediatr Surg 2017; 52 (03) 481-483
  • 50 Mortell A, Montedonico S, Puri P. Animal models in pediatric surgery. Pediatr Surg Int 2006; 22 (02) 111-128
  • 51 Haller Jr JA, Kehrer BH, Shaker IJ, Shermeta DW, Wyllie RG. Studies of the pathophysiology of gastroschisis in fetal sheep. J Pediatr Surg 1974; 9 (05) 627-632
  • 52 Langer JC, Longaker MT, Crombleholme TM. , et al. Etiology of intestinal damage in gastroschisis. I: Effects of amniotic fluid exposure and bowel constriction in a fetal lamb model. J Pediatr Surg 1989; 24 (10) 992-997
  • 53 Langer JC, Bell JG, Castillo RO. , et al. Etiology of intestinal damage in gastroschisis, II. Timing and reversibility of histological changes, mucosal function, and contractility. J Pediatr Surg 1990; 25 (11) 1122-1126
  • 54 Luton D, de Lagausie P, Guibourdenche J. , et al. Influence of amnioinfusion in a model of in utero created gastroschisis in the pregnant ewe. Fetal Diagn Ther 2000; 15 (04) 224-228
  • 55 de Lagausie P, Guibourdenche J, de Buis A. , et al. Esophageal ligature in experimental gastroschisis. J Pediatr Surg 2002; 37 (08) 1160-1164
  • 56 Roelofs LAJ, Eggink AJ, Hulsbergen-van de Kaa CA. , et al. Fetal abdominal wall repair with a collagen biomatrix in an experimental sheep model for gastroschisis. Tissue Eng Part A 2008; 14 (12) 2033-2040
  • 57 Kohl T, Tchatcheva K, Stressig R, Gembruch U, Kahl P. Is there a therapeutic role for fetoscopic surgery in the prenatal treatment of gastroschisis? A feasibility study in sheep. Surg Endosc 2009; 23 (07) 1499-1505
  • 58 Stephenson JT, Pichakron KO, Vu L. , et al. In utero repair of gastroschisis in the sheep (Ovis aries) model. J Pediatr Surg 2010; 45 (01) 65-69
  • 59 Bergholz R, Krebs T, Wenke K. , et al. Fetoscopic management of gastroschisis in a lamb model. Surg Endosc 2012; 26 (05) 1412-1416
  • 60 Kahl P, Buettner R, Tchatcheva K, Stressig R, Gembruch U, Kohl T. Macroscopic and histopathologic findings in a laparoschisis model in fetal sheep: comparisons with gastroschisis in human fetuses and implications for prenatal interventions. Arch Gynecol Obstet 2012; 285 (01) 15-19
  • 61 Krebs T, Boettcher M, Schäfer H. , et al. Gut inflammation and expression of ICC in a fetal lamb model of fetoscopic intervention for gastroschisis. Surg Endosc 2014; 28 (08) 2437-2442
  • 62 Obayashi J, Tanaka K, Koike J. , et al. Does a large abdominal wall defect affect lung growth?. J Pediatr Surg 2016; 51 (12) 1972-1975
  • 63 Sherman NJ, Asch MJ, Isaacs Jr H, Rosenkrantz JG. Experimental gastroschisis in the fetal rabbit. J Pediatr Surg 1973; 8 (02) 165-169
  • 64 Albert A, Julia MV, Morales L, Parri FJ. Gastroschisis in the partially extraamniotic fetus: experimental study. J Pediatr Surg 1993; 28 (05) 656-659
  • 65 Shaw K, Buchmiller TL, Curr M. , et al. Impairment of nutrient uptake in a rabbit model of gastroschisis. J Pediatr Surg 1994; 29 (03) 376-378
  • 66 Guo W, Swaniker F, Fonkalsrud EW, Vo K, Karamanoukian R. Effect of intraamniotic dexamethasone administration on intestinal absorption in a rabbit gastroschisis model. J Pediatr Surg 1995; 30 (07) 983-986
  • 67 Bealer JF, Graf J, Bruch SW, Adzick NS, Harrison MR. Gastroschisis increases small bowel nitric oxide synthase activity. J Pediatr Surg 1996; 31 (08) 1043-1045
  • 68 Langer JC, Bramlett G. Effect of prokinetic agents on ileal contractility in a rabbit model of gastroschisis. J Pediatr Surg 1997; 32 (04) 605-608
  • 69 Albert A, Sancho MA, Juliá V, Díaz F, Bombí JA, Morales L. Intestinal damage in gastroschisis is independent of the size of the abdominal defect. Pediatr Surg Int 2001; 17 (2-3): 116-119
  • 70 Albert BA, Margarit J, Julia V. , et al. Morphology and mucosal biochemistry of gastroschisis intestine in urine-free amniotic fluid. 2003; 38 (08) 1217-1220
  • 71 Till H, Muensterer O, Mueller M. , et al. Intrauterine repair of gastroschisis in fetal rabbits. Fetal Diagn Ther 2003; 18 (05) 297-300
  • 72 Santos MM, Tannuri U, Maksoud JG. Alterations of enteric nerve plexus in experimental gastroschisis: is there a delay in the maturation?. J Pediatr Surg 2003; 38 (10) 1506-1511
  • 73 Biard JM, Lu HQ, Vanamo K. , et al. Pulmonary effects of gastroschisis in a fetal rabbit model. Pediatr Pulmonol 2004; 37 (02) 99-103
  • 74 Oyachi N, Lakshmanan J, Ross MG, Atkinson JB. Fetal gastrointestinal motility in a rabbit model of gastroschisis. J Pediatr Surg 2004; 39 (03) 366-370
  • 75 Ross MG, Lakshamanan J. Effects of gastroschisis on gastric dilation. Am J Obstet Gynecol 2005; 192 (03) 985-986
  • 76 Ashrafi M, Hosseinpour M, Farid M, Sanei MH. Evaluation of diluted amniotic fluid effects on histological changes of intestine of rabbit fetus with gastroschisis. Pediatr Surg Int 2008; 24 (04) 421-424
  • 77 Ayele T, Zuki AB, Noorjahan BM, Noordin MM. Tissue engineering approach to repair abdominal wall defects using cell-seeded bovine tunica vaginalis in a rabbit model. J Mater Sci Mater Med 2010; 21 (05) 1721-1730
  • 78 Feng C, Graham CD, Shieh HF. , et al. Transamniotic stem cell therapy (TRASCET) in a leporine model of gastroschisis. J Pediatr Surg 2017; 52 (01) 30-34
  • 79 Correia-Pinto J, Tavares ML, Baptista MJ, Estevão-Costa J, Flake AW, Leite-Moreira AF. A new fetal rat model of gastroschisis: development and early characterization. J Pediatr Surg 2001; 36 (01) 213-216
  • 80 Akgür FM, Ozdemir T, Olguner M, Aktuğ T, Ozer E. An experimental study investigating the effects of intraperitoneal human neonatal urine and meconium on rat intestines. Res Exp Med (Berl) 1998; 198 (04) 207-213
  • 81 Correia-Pinto J, Tavares ML, Baptista MJ. , et al. Meconium dependence of bowel damage in gastroschisis. J Pediatr Surg 2002; 37 (01) 31-35
  • 82 Vannucchi MG, Midrio P, Flake AW, Faussone-Pellegrini MS. Neuronal differentiation and myenteric plexus organization are delayed in gastroschisis: an immunohistochemical study in a rat model. Neurosci Lett 2003; 339 (01) 77-81
  • 83 Vannucchi MG, Midrio P, Zardo C, Faussone-Pellegrini MS. Neurofilament formation and synaptic activity are delayed in the myenteric neurons of the rat fetus with gastroschisis. Neurosci Lett 2004; 364 (02) 81-85
  • 84 Midrio P, Faussone-Pellegrini MS, Vannucchi MG, Flake AW. Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells. J Pediatr Surg 2004; 39 (10) 1541-1547
  • 85 Midrio P, Vannucchi MG, Pieri L, Alaggio R, Faussone-Pellegrini MS. Delayed development of interstitial cells of Cajal in the ileum of a human case of gastroschisis. J Cell Mol Med 2008; 12 (02) 471-478
  • 86 Auber F, Danzer E, Noché-Monnery M-E. , et al. Enteric nervous system impairment in gastroschisis. Eur J Pediatr Surg 2013; 23 (01) 29-38
  • 87 França WM, Langone F, de la Hoz CL. , et al. Maturity of the myenteric plexus is decreased in the gastroschisis rat model. Fetal Diagn Ther 2008; 23 (01) 60-68
  • 88 Franchi-Teixeira AR, Weber Guimarães Barreto M, Nogueira B, Bittencourt D, Violin L, Sbragia L. Aminiotic fluid and intrauterine growth restriction in a gastroschisis fetal rat model. Fetal Diagn Ther 2005; 20 (06) 494-497
  • 89 Yu J, Gonzalez-Reyes S, Diez-Pardo JA, Tovar JA. Effects of prenatal dexamethasone on the intestine of rats with gastroschisis. J Pediatr Surg 2003; 38 (07) 1032-1035
  • 90 Bittencourt DG, Barreto MWG, França WMG, Gonçalves A, Pereira LA, Sbragia L. Impact of corticosteroid on intestinal injury in a gastroschisis rat model: morphometric analysis. J Pediatr Surg 2006; 41 (03) 547-553
  • 91 Gonçalves FL, Bittencourt DG, Velloso LA, Schmidt AF, Gallindo RM, Sbragia L. Corticosteroid effect upon intestinal and hepatic interleukin profile in a gastroschisis rat model. Acta Cir Bras 2013; 28 (Suppl. 01) 8-12
  • 92 Sbragia L, Schmidt AF, Moraes S. , et al. Inflammatory response in a rat model of gastroschisis is associated with an increase of NF-kappaB. Braz J Med Biol Res 2010; 43 (02) 160-165
  • 93 Bueno MP, Gonçalves FL, Guadagnini D. , et al. The role of gut-liver axis in the restriction of intrauterine growth in a model of experimental gastroschisis. Acta Cir Bras 2013; 28 (Suppl. 01) 3-7
  • 94 Gonçalves FL, da Silva R, Schmidt AF, de Oliveira MG, Sbragia L. Hydrogel protection: a novel approach to reduce bowel inflammation in experimental gastroschisis. Eur J Obstet Gynecol Reprod Biol 2010; 148 (01) 35-39
  • 95 Gonçalves FL, de Souza GFP, Schmidt AF, Regis AC, de Oliveira MG, Sbragia L. Evaluation of nitric oxide (NO) and nitric oxide synthases (NOS) in the amniotic fluid in an experimental gastroschisis rat model. Eur J Pediatr Surg 2011; 21 (06) 362-365
  • 96 Gonçalves FL, Bueno MP, Schmidt AF, Figueira RL, Sbragia L. Treatment of bowel in experimental gastroschisis with a nitric oxide donor. Am J Obstet Gynecol 2015; 212 (03) 383.e1-383.e7
  • 97 Régis AC, Rojas-Moscoso JA, Gonçalves FL. , et al. The cholinergic response is increased in isolated ileum from gastroschisis rat model. Pediatr Surg Int 2011; 27 (09) 1015-1019
  • 98 Cavalcante MB, de Lima FJ, Okoba W. , et al. Gastric contractility in experimental gastroschisis. J Pediatr Surg 2013; 48 (02) 326-332
  • 99 Hakguder G, Olguner M, Gürel D, Akgür FM, Flake AW. Induction of fetal diuresis with intraamniotic furosemide injection reduces intestinal damage in a rat model of gastroschisis. Eur J Pediatr Surg 2011; 21 (03) 183-187
  • 100 Caporossi C, Nogueira PL, Marques JC, Assis RM, Aguilar-Nascimento JE. Validation of the gastroschisis experimental model and the influence of the mother's diet enriched with glutamine in the fetal morphology. Acta Cir Bras 2014; 29 (03) 158-165
  • 101 Feng C, Graham CD, Connors JP. , et al. Transamniotic stem cell therapy (TRASCET) mitigates bowel damage in a model of gastroschisis. J Pediatr Surg 2016; 51 (01) 56-61
  • 102 Callejas GH, Figueira RL, Gonçalves FLL. , et al. Maternal administration of cannabidiol promotes an anti-inflammatory effect on the intestinal wall in a gastroschisis rat model. Braz J Med Biol Res 2018; 51 (05) e7132