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

NCT ID: NCT02596594

Last Updated: 2018-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2014-04-30

Brief 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.

Detailed 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.

Conditions

Intrauterine Growth Restriction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: SINGLE

Study Groups

Port intervention

The subcutaneous intraumbilical port-system will be implanted in IUGR patients with the cerebroplacental ratio less than 1 (cerebroplacental ratio= PI in the middle cerebral artery / PI umbilical artery) between 24/0 and 30/0 weeks of gestation.

The fetuses will receive AAs and glucose supplementation via a subcutaneously implanted intraumbilical perinatal port system till the delivery. Control by doppler and cardiotocogram

Group Type: EXPERIMENTAL

fetal nutrition port system

Intervention Type: DEVICE

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.

control

IUGR patients with the cerebroplacental ratio less than 1 (CPR= PI middle cerebral artery / PI umbilical artery) between 24/0 and 30/0 weeks of gestation.

Control by doppler and cardiotocogram

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Martin-Luther-Universität Halle-Wittenberg

OTHER

Sponsor Role: lead

Responsible Party

Michael Tchirikov MD, PhD

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Tchirikov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Martin-Luther University Halle-Wittenberg

References

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.

Reference Type: BACKGROUND

PMID: 20733317 (View on PubMed)

Other Identifiers

110; 3/15-08-2012

Identifier Type: -

Identifier Source: org_study_id