Intraumbilical Amino Acids and Glucose Supplementation Via Port by Severe IUGR in Human Fetuses (port-IUGR)

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

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.

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.

Intraumbilical amino acid and glucose suplementation of human fetuses with a severe IUGR via a subcutaneously implanted port system

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

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

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.

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.

Inclusion Criteria: clinical diagnosis of severe intrauterine growth restricted fetuses with the cerebroplacental ratio less than 1 (CPR= PI middle cerebral artery / PI umbilical artery) gestational age between 24/0 and 30/0 weeks single pregnancy anterior or lateral location of the placenta Exclusion Criteria: multiple pregnancy fetal genetic anomalities, fetal morphologic anomalities BMI > 35 placenta praevia vaginal bleeding uterine contractions vasa praevia posterior location of the placenta severe maternal morbidities Infections preliminary rupture of the membranes

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.