Intraumbilical Amino Acids and Glucose Supplementation Via Port by Severe IUGR in Human Fetuses

Intrauterine Growth Restriction Clinical Trial

— port-IUGR  

Official title:

Intraumbilical Amino Acids and Glucose Supplementation Via Subcutaneously Implanted Port System by Severe IUGR Human Fetuses

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02596594
• Other study ID #: 110; 3/15-08-2012
• Status: Completed
• Phase: N/A
• First received: October 12, 2015
• Last updated: January 24, 2018
• Start date: January 2010
• Est. completion date: April 2014

Study information

• Verified date: January 2018
• Source: Martin-Luther-Universität Halle-Wittenberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Placental insufficiency is responsible for fetal loss in about 40% of all stillbirths and long term neurological deficits. The mean interval from diagnosis of brain sparing of severe IUGR fetuses to delivery has been recently identified by only seven days (Flood K et al, Am J Obstetrics and Gynecology 2014).

The critical placental player in the active amino acids (AA) transport from the mother to the fetus is the trophoblast, which is irreversibly changed in severe IUGR fetuses caused by placental insufficiency. Thus, a logical partial solution of IUGR could be the direct supply of AAs and glucose to the fetus, in order to improve the fetal growth, normalize the fetal programming and to prolong the pregnancy.

The aim of this prospective pilot study is to further test the efficacy of the administration of AAs and glucose supplementation with hyperbaric oxygenation (HBO), via a subcutaneously implanted intraumbilical perinatal port system, as a treatment option for severe IUGR human fetuses with brain sparing.

Description:

Placental insufficiency is the main source of the development of intrauterine growth restriction (IUGR) caused by one of a variety of factors including chronic placental infections, many maternal diseases, abnormal genome and intravascular trophoblast invasion impairment. Placental insufficiency is responsible for fetal loss in about 40% of all stillbirths and long term neurological deficits. The reduction of blood flow resistance of cerebral arteries in severe IUGR conditions with reduced pulsatility index (PI) in the medial cerebral artery predicts the 11 fold increased risk of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. The mean interval from diagnosis of brain sparing of severe IUGR fetuses to delivery has been recently identified by only seven days (ranging 2-15 days).

The amino acids (AA) concentration of fetal plasma is many times higher than in mother because of active transplacental transport of AA and additional AA synthesis in the placenta.

The critical placental player in the active AA transport from the mother to the fetus is the trophoblast, which is irreversibly changed in severe IUGR fetuses caused by placental insufficiency. Thus, a logical partial solution of IUGR could be the direct supply of AAs and glucose to the fetus, in order to improve the fetal growth, normalize the IUGR changed fetal programming and to prolong the pregnancy. Additional oxygen supply of fetal tissues could also be important in improving the uptake of injected nutritional supplements and may avoid the development of lactate acidosis in IUGR fetuses.

The aim of this prospective pilot study was to further test the efficacy of the administration of AAs and glucose supplementation with hyperbaric oxygenation (HBO), via a subcutaneously implanted intraumbilical perinatal port system, as a treatment option for severe IUGR human fetuses with brain sparing.

Study design - IUGR was defined in this study as an estimated fetal weight of < 5%, combined with increased resistance in both uterine arteries with pulsatility index (PI) > 95%. Fetuses with morphological and/or chromosomal abnormalities were not included in the final analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. clinical diagnosis of severe intrauterine growth restricted fetuses with the cerebroplacental ratio less than 1 (CPR= PI middle cerebral artery / PI umbilical artery)

2. gestational age between 24/0 and 30/0 weeks

3. single pregnancy

4. anterior or lateral location of the placenta

Exclusion Criteria:

1. multiple pregnancy

2. fetal genetic anomalities,

3. fetal morphologic anomalities

4. BMI > 35

5. placenta praevia

6. vaginal bleeding

7. uterine contractions

8. vasa praevia

9. posterior location of the placenta

10. severe maternal morbidities

11. Infections

12. preliminary rupture of the membranes

Related Conditions & MeSH terms

• Fetal Growth Retardation
• Intrauterine Growth Restriction

Intervention

Device:
• fetal nutrition port system
Under local anesthesia a subcutaneous pouch for the port capsule was prepared using a pair of scissors. The umbilical vein was punctured with a 18 gauge needle under ultrasound control and the catheter was inserted into the umbilical vein. Note the amniotic cavity remained intact. A 25 gauge port needle was used to enter the port system. The treatment course included daily infusions of AA solution (Fresenius Kabi, Bad Homburg, Germany) with a 10% glucose solution. The investigators limited the volume of the intraumbilical infusion to 10% of the estimated feto-placental blood volume per day. On average, the AA/glucose-infusion was below 50 ml/kg.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Martin-Luther-Universität Halle-Wittenberg

References & Publications (1)

Tchirikov M, Kharkevich O, Steetskamp J, Beluga M, Strohner M. Treatment of growth-restricted human fetuses with amino acids and glucose supplementation through a chronic fetal intravascular perinatal port system. Eur Surg Res. 2010;45(1):45-9. doi: 10.1159/000318859. Epub 2010 Aug 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The mean interval from diagnosis of brain sparing of severe IUGR fetuses to delivery	The mean interval from diagnosis of brain sparing of severe IUGR fetuses to delivery will be documented (days). The timing of delivery by caesarean section will be decided by the lead clinician managing each case based on doppler and cardiotocogram clinical evaluations.	through study completion, up to 2 years
Secondary	neonatal weight	the neonates' weight will be estimated after the delivery	through study completion, up to 2 years
Secondary	fetal weight gain	the difference (g) between estimated by ultrasound fetal weight and neonatal weight at delivery	through study completion, up to 2 years
Secondary	blood gas analysis in the umbilical artery	the blood gas analysis in the umbilical artery will be performed after the delivery	through study completion, up to 2 years