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DOI: 10.1055/s-0031-1271708
© Georg Thieme Verlag KG Stuttgart · New York
Induction of Fetal Diuresis with Intraamniotic Furosemide Injection Reduces Intestinal Damage in a Rat Model of Gastroschisis
Publication History
received November 22, 2010
accepted after revision January 6, 2011
Publication Date:
21 February 2011 (online)

Abstract
Background/Purpose: Contact with amniotic fluid causes intestinal damage (ID) in fetuses with gastroschisis. Intraamniotic meconium has been shown to be responsible for ID, and ID has been shown to correlate with intraamniotic meconium concentrations. ID can be prevented by lowering the intraamniotic meconium concentration. A new method to lower intraamniotic meconium concentration might consist in the induction of fetal diuresis with intraamniotic diuretic injection. This hypothesis was tested in a rat model.
Materials and Method: There were 4 experimental groups.
Control group: Rat fetuses without any manipulation. Fetuses were harvested by cesarean section for examination at E21.5 (Term).
Sham group: On E18.5, the hind limb of the rat fetuses were exteriorized by hysterotomy and replaced in the uterus.
Gastroschisis group: Gastroschisis was surgically created in rat fetuses on E18.5, under a dissection microscope (16×).
Gastroschisis+furosemide group: After surgical creation of gastroschisis on E18.5, intraamniotic furosemide (5 mg/kg) was administered to the fetuses on E20. All fetuses were harvested on E21.5.
Results: There was no significant difference between intestinal serosal thicknesses of the control and sham groups. The serosal thickness was significantly higher in the gastroschisis group compared to the control group. In the gastroschisis+furosemide group, the intestinal serosal thickness was found significantly decreased compared with the gastroschisis group.
Conclusion: Intraamniotic furosemide injection caused a substantial decrease in ID encountered in gastroschisis. The induction of fetal diuresis with intraamniotic furosemide injection seems promising as a prenatal treatment modality.
Key words
gastroschisis - amniotic fluid - intestinal damage - intraamniotic furosemide injection - prenatal treatment
References
- 1
Haller JA, Kehrer BH, Shaker JI. et al .
Studies of the pathophysiology of gastroschisis in fetal sheep.
J Pediatr Surg.
1974;
9
627-632
Reference Ris Wihthout Link
- 2
Klück P, Tibboel D, van der Kamp AWM. et al .
The effect of fetal urine on the development of bowel in gastroschisis.
J Pediatr Surg.
1983;
18
47-50
Reference Ris Wihthout Link
- 3
Tibboel D, Klück P, van der Kamp AWM. et al .
The development of the characteristic anomalies found in gastroschisis: experimental
and clinical data.
Z Kinderchir.
1985;
40
355-360
Reference Ris Wihthout Link
- 4
Tibboel D, Vermey-Keers C, Klück P. et al .
The natural history of gastroschisis during fetal life: development of the fibrous
coating on bowel loops.
Teratology.
1986;
33
267-272
Reference Ris Wihthout Link
- 5
Tibboel D, Raine P, McNee M. et al .
Development aspects of gastroschisis.
J Pediatr Surg.
1986;
21
865-869
Reference Ris Wihthout Link
- 6
Albert A, Julia MV, Morales L. et al .
Gastroschisis in the partially extraamniotic fetus: Experimental study.
J Pediatr Surg.
1993;
28
656-659
Reference Ris Wihthout Link
- 7
Bealer JF, Graf J, Bruch SW. et al .
Gatroschisis increases small bowel nitric oxide synthase activity.
J Pediatr Surg.
1996;
31
1043-1046
Reference Ris Wihthout Link
- 8
Aktuğ T, Hosgör M, Akgür FM. et al .
End results of experimental gastroschisis created by abdominal wall defect versus
umbilical cord defect.
Pediatr Surg Int.
1997;
12
583-586
Reference Ris Wihthout Link
- 9
Heffez DS, Aryanpur J, Hutchins GM. et al .
The paralysis associated with myelomeningocele: Clinical and experimental data implicating
a preventable spinal cord injury.
Neurosurgery.
1990;
26
987-992
Reference Ris Wihthout Link
- 10
Olguner M, Akgür FM, Özdemir T. et al .
Amniotic fluid exchange for the prevention of neural tissue damage in myelomeningocele:
An alternative minimally invasive method to open in utero surgery.
Pediatr Neurosurg.
2000;
33
252-256
Reference Ris Wihthout Link
- 11
Akgür FM, Özdemir T, Olguner M. et al .
An experimental study investigating the effects of intraperitoneal human neonatal
urine and meconium on rat intestines.
Res Exp Med.
1998;
198
207-213
Reference Ris Wihthout Link
- 12
Olguner M, Akgür FM, Api A. et al .
The effects of intraamniotic human neonatal urine and meconium on intestines of chick
embryo with gastroschisis.
J Pediatr Surg.
2000;
35
458-461
Reference Ris Wihthout Link
- 13
Correia-Pinto J, Tavares ML, Baptista MJ. et al .
Meconium dependence of bowel damage in gastroschisis.
J Pediatr Surg.
2002;
37
31-35
Reference Ris Wihthout Link
- 14
Api A, Olguner M, Hakgüder G. et al .
Intestinal damage in gastroschisis correlates with the concentration of intraamniotic
meconium.
J Pediatr Surg.
2001;
36
1811-1815
Reference Ris Wihthout Link
- 15
Aktuğ T, Erdağ G, Kargı A. et al .
Amnio-allantoic fluid exchange for the prevention of intestinal damage in gastroschisis:
an experimental study on chick embryos.
J Pediatr Surg.
1995;
30
384-387
Reference Ris Wihthout Link
- 16
Aktuğ T, Uçan B, Olguner M. et al .
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
308-311
Reference Ris Wihthout Link
- 17
Aktuğ T, Uçan B, Olguner M. et al .
Amnio-allantoic fluid exchange for prevention of intestinal damage in gastroschisis
III: Determination of the waste products removed by exchange.
Eur J Pediatr Surg.
1998;
8
326-328
Reference Ris Wihthout Link
- 18
Aktuğ T, Demir N, Akgür FM. et al .
Intrauterine pretreatment of gastroschisis with transabdominal amniotic fluid exchange.
Obstet Gynecol.
1998;
91
821-823
Reference Ris Wihthout Link
- 19
Dommergues M, Ansker Y, Aubry MC. et al .
Serial transabdominal amnioinfusion in the management of gastroschisis with severe
oligohydramnios.
J Pediatr Surg.
1996;
31
1297-1299
Reference Ris Wihthout Link
- 20
Luton D, de Lagausie P, Guibourdenche J. et al .
Effect of amnioinfusion on the outcome of prenatally diagnosed gastroschisis.
Fetal Diagn Ther.
1999;
14
152-155
Reference Ris Wihthout Link
- 21
Luton D, de Lagauise 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
224-228
Reference Ris Wihthout Link
- 22
Sapin E, Mahieu D, Borgnon J. et al .
Transbdominal amnioinfusion to avoid fetal demise and intestinal damage in fetuses
with gastroschisis and severe oligohydramnios.
J Pediatr Surg.
2000;
35
598-600
Reference Ris Wihthout Link
- 23
Hakgüder G, Ateş O, Olguner M. et al .
Induction of fetal diuresis with intraamniotic furosemide increases the clearance
of intraamniotic substances: An alternative therapy aimed at reducing intraamniotic
meconium concentration.
J Pediatr Surg.
2002;
37
1337-1342
Reference Ris Wihthout Link
- 24
Hakgüder G, Ateş O, Olguner M. et al .
Is induction of fetal diuresis with intraamniotic furosemide effective for the removal
of intestinal waste products from amniotic fluid?.
Eur J Pediatr Surg.
2002;
12
293-298
Reference Ris Wihthout Link
- 25
Gilbert WM, Newman PS, Brace RA.
Potential route for fetal therapy: Intramembranous absorbtion of intraamnioticly injected
furosemide.
Am J Obstet Gynecol.
1995;
172
1471-1476
Reference Ris Wihthout Link
- 26
Correia-Pinto J, Tavares ML, Baptista MJ. et al .
A new fetal rat model of gastroschisis: Development and early characterization.
J Pediatr Surg.
2001;
36
213-216
Reference Ris Wihthout Link
- 27
Olguner M, Hakgüder G, Ateş O. et al .
Urinary trypsin inhibitor present in fetal urine prevents intraamniotic meconium induced
intestinal damage in gastroschisis.
J Pediatr Surg.
2006;
41
1407-1412
Reference Ris Wihthout Link
- 28
el Maradny E, Kanayama N, Halim A. et al .
Urinary trypsin inhibitor has a protective effect on amnion.
Gynecol Obstet Invest.
1994;
38
169-172
Reference Ris Wihthout Link
- 29
Karakus OZ, Ateş O, Murat N. et al .
The protective effect of urinary tripsin inhibitor on intestinal motility of chick
embryos with gastroschisis.
Presented at the 9th European Congress of Pediatric Surgery, Istanbul, Turkey, June
18–21
2008;
Reference Ris Wihthout Link
- 30
Morrison JJ, Klein N, Chitty LS. et al .
Intra-amniotic inflammation in human gastroschisis: possible aetiology of postnatal
bowel dysfunction.
Br J Obstet Gynaecol.
1998;
105
1200-1204
Reference Ris Wihthout Link
- 31
de Beaufort AJ, Pelikan DM, Elferink JG. et al .
Effect of interleukin 8 in meconium on in-vitro neutrophil chemotaxis.
Lancet.
1998;
352
102-105
Reference Ris Wihthout Link
- 32
Kanayama N.
Intrauterine defensive mechanism of amniotic fluid and fetal membranes.
Acta Obst Gynaec Jpn.
1994;
46
673-685
Reference Ris Wihthout Link
- 33 Crooney DR. Defects of the abdominal wall. In: O’Neill JA, Rowe MI, Grosfeld JL, Fonkalsrud EW, Coran AG, (eds): Pediatric Surgery. St Louis, MO: Mosby; 1998: 1045-1069
Reference Ris Wihthout Link
- 34
Deans KJ, Mooney DP, Meyer MM. et al .
Prolonged intestinal exposure to amniotic fluid does not result in peel formation
in gastroschisis.
J Pediatr Surg.
1999;
34
975-976
Reference Ris Wihthout Link
- 35
Brace RA.
Physiology of amniotic fluid volume regulation.
Clin Obstet Gynecol.
1997;
40
280-289
Reference Ris Wihthout Link
- 36
Kanayama N, Yamazaki T, Naruse H. et al .
Determining zinc coproporphyrin in maternal plasma: a new method for diagnosing amniotic
fluid embolism.
Clin Chem.
1992;
38
526-529
Reference Ris Wihthout Link
- 37
Usta IM, Sibai BM, Mercer BM. et al .
Use of maternal plasma level of zinc coproporphyrin in the prediction of intrauterine
passage of meconium: a pilot study.
J Matern Fetal Med.
2000;
9
201-203
Reference Ris Wihthout Link
- 38
Brace RA.
Fetal blood volume, urine flow, swallowing and amniotic fluid volume responses to
long-term intravascular infusion of saline.
Am J Obstet Gynecol.
1989;
161
1049-1054
Reference Ris Wihthout Link
- 39
Kelly TF, Moore TR, Brace RA.
Hemodynamic and fluid responses to furosemide infusion in the ovine fetus.
Am J Obstet Gynecol.
1993;
168
260-268
Reference Ris Wihthout Link
- 40
Verbeeck RK, Patwardhan RV, Villeneuve JP. et al .
Furosemide disposition in cirrhosis.
Clin Pharmacol Ther.
1982;
31
719-725
Reference Ris Wihthout Link
- 41
Anandakumar C, Biswas A, Chew SS. et al .
Direct fetal treatment for hydrops secondary to congenital atrioventricular heart
block.
Obstet Gynecol.
1996;
87
835-837
Reference Ris Wihthout Link
- 42
Anandakumar C, Biswas A, Chua TM. et al .
Direct intrauterine fetal therapy in a case of bronchopulmonary sequestration associated
with non-immune hydrops fetalis.
Ultrasound Obstet Gynocol.
1999;
13
263-265
Reference Ris Wihthout Link
Correspondence
Dr. Gulce Hakguder
Dokuz Eylul University School
of Medicine
Department of Pediatric
Surgery
Dokuz Eylul Universitesi tıp
fakultesi
35340 Izmir
Turkey
Phone: +90 232 412 3005
Fax: +90 232 279 2101
Email: gulce.hakguder@deu.edu.tr
