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

Not Applicable
Completed
Conditions
Intrauterine Growth Restriction
Interventions
Device: fetal nutrition port system
Registration Number
NCT02596594
Lead Sponsor
Martin-Luther-Universität Halle-Wittenberg
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
14
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Port interventionfetal nutrition port systemThe 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
Primary Outcome Measures
NameTimeMethod
The mean interval from diagnosis of brain sparing of severe IUGR fetuses to deliverythrough study completion, up to 2 years

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.

Secondary Outcome Measures
NameTimeMethod
fetal weight gainthrough study completion, up to 2 years

the difference (g) between estimated by ultrasound fetal weight and neonatal weight at delivery

blood gas analysis in the umbilical arterythrough study completion, up to 2 years

the blood gas analysis in the umbilical artery will be performed after the delivery

neonatal weightthrough study completion, up to 2 years

the neonates' weight will be estimated after the delivery

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