The effect of intraumbilical fetal nutrition via a subcutaneously implanted port system on amino acid concentration by severe IUGR human fetuses

Objective: To determine if intrauterine intraumbilical supplementation with amino acids (AA) and glucose can improve neonatal outcome of severe growth restricted human fetuses (IUGR). Methods: Prospective pilot study of intrauterine treatment of severe IUGR fetuses [n = 14, 27 weeks of gestation (range 23–31)] with erebroplacental ratio < 1, with longterm intraumbilical AA and glucose supplementation (10% of feto-placental blood volume/day) using a perinatal port system alone (n = 5) or combined with hyperbaric oxygenation (n = 1, HBO) vs. control group (n = 8)

A Study of the Literature on Intrauterine Treatment Options for Chronic Placental Insufficiency with Intrauterine Growth Restriction Using Intrauterine Intravascular Amino Acid Supplementation

Background: Intrauterine growth retardation (IUGR) is a very serious prenatal condition with 3–5% incidence of all pregnancies. It results from numerous factors, including chronic placental insufficiency. IUGR is associated with an increased risk of mortality and morbidity and is considered a major cause of fetal mortality. Currently, treatment options are significantly limited and often result in preterm delivery. Postpartum, IUGR infants also have higher risks of disease and neurological abnormalities. Methods: The PubMed database was searched using the keywords “IUGR”, “fetal growth restriction”, “treatment”, “management” and “placental insufficiency” for the period between 1975 and 2023. These terms were also combined together. Results: There were 4160 papers, reviews and articles dealing with the topic of IUGR. In total, only 15 papers directly dealt with a prepartum therapy of IUGR; 10 of these were based on an animal model. Overall, the main focus was on maternal intravenous therapy with amino acids or intraamniotic infusion. Treatment methods have been tested since the 1970s to supplement the fetuses with nutrients lacking due to chronic placental insufficiency in various ways. In some studies, pregnant women were implanted with a subcutaneous intravascular perinatal port system, thus infusing the fetuses with a continuous amino acid solution. Prolongation of pregnancy was achieved, as well as improvement in fetal growth. However, insufficient benefit was observed in infusion with commercial amino acid solution in fetuses below 28 weeks’ gestation. The authors attribute this primarily to the enormous variation in amino acid concentrations of the commercially available solutions compared with those observed in the plasma of preterm infants. These different concentrations are particularly important because differences in the fetal brain caused by metabolic changes have been demonstrated in the rabbit model. Several brain metabolites and amino acids were significantly decreased in IUGR brain tissue samples, resulting in abnormal neurodevelopment with decreased brain volume. Discussion: There are currently only a few studies and case reports with correspondingly low case numbers. Most of the studies refer to prenatal treatment by supplementation of amino acids and nutrients to prolong pregnancy and support fetal growth. However, there is no infusion solution that matches the amino acid concentrations found in fetal plasma. The commercially available solutions have mismatched amino acid concentrations and have not shown sufficient benefit in fetuses below 28 weeks’ gestation. More treatment avenues need to be explored and existing ones improved to better treat multifactorial IUGR fetuses

Treatment of Classic Mid-Trimester Preterm Premature Rupture of Membranes (PPROM) with Oligo/Anhydramnion between 22 and 26 Weeks of Gestation by Means of Continuous Amnioinfusion: Protocol of a Randomized Multicentric Prospective Controlled TRIAL and Review of the Literature

Background: The classic mid-trimester preterm premature rupture of membranes (PPROM) is defined as a rupture of the fetal membranes prior to 28 weeks of gestation (WG) with oligo/anhydramnion; it complicates approximately 0.4–0.7% of all pregnancies and is associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacterial growth, chorioamnionitis and fetal inflammation. The repetitive amnioinfusion does not work because fluid is lost immediately after the intervention. The continuous amnioinfusion through the transabdominal port system or catheter in patients with classic PPROM shows promise by flushing out the bacteria and inflammatory components from the amniotic cavity, replacing amniotic fluid and thus prolonging the PPROM-to-delivery interval. Objective: This multicenter trial aims to test the effect of continuous amnioinfusion on the neonatal survival without the typical major morbidities, such as severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis one year after the delivery. Study Design: We plan to conduct a randomized multicenter trial with a two-arm parallel design. Randomization will be between 22/0 and 26/0 SSW. The control group: PPROM patients between 20/0 and 26/0 WG who will be treated with antibiotics and corticosteroids (from 22/0 SSW) in accordance with the guidelines of German Society of Obstetrics and Gynecology (standard PPROM therapy). In the interventional group, the standard PPROM therapy will be complemented with the Amnion Flush Method, with the amnioinfusion of Amnion Flush Solution through the intra-amnial catheter (up to 100 mL/h, 2400 mL/day). Subjects: The study will include 68 patients with classic PPROM between 20/0 and 26/0 WG. TRIAL-registration: ClinicalTrials.gov ID: NCT04696003. German Clinical Trials Register: DRKS00024503, January 2021

Prolongation of Pregnancy in Patients with HELLP Syndrome Using Methylprednisolone: A Retrospective Multicentric Analysis

Background: Immediate delivery is an established concept for preventing life-threatening complications in mothers with HELLP syndrome; however, it is associated with preterm births. Methods: Cases of HELLP syndrome diagnosed at the university hospitals of Halle and Magdeburg (Germany) were analyzed retrospectively. Each patient of the treatment group was administered 64 mg of methylprednisolone (MP) intravenously for 10 days, with the dosage being reduced by 50% every other day in patients from Halle (n = 65). Almost immediate delivery was performed in the control groups (n = 45, Halle; n = 28, Magdeburg). Results: Pregnancies in the treatment group were prolonged by 4 days (median 1–55 days). The platelet counts increased from 76,060 ± 22,900/μL to 117,430 ± 39,065/μL in the MP group compared with an increase from 66,500 ± 25,852/μL to 83,430 ± 34,608/μL in control group 1 and from 78,890 ± 19,100/μL to 131,080 ± 50,900/µL in control group 2 (p p < 0.05): sepsis, 9.25% vs. 24%; ventilation, 44.6% vs. 46.5%; and infant death, 1.6% vs. 8.6%. Conclusions: In a selected collective of patients with HELLP syndrome, prolongation of pregnancy using MP treatment improved maternal and neonatal outcomes

Hyperbaric oxygenation and glucose/amino acids substitution in human severe placental insufficiency

In the first case, the AA and glucose were infused through a perinatal port system into the umbilical vein at 30 weeks' gestation due to severe IUGR. The patient received daily hyperbaric oxygenation (HBO, 100% O2) with 1.4 atmospheres absolute for 50 min for 7 days. At 31+4 weeks' gestation, the patient gave birth spontaneously to a newborn weighing 1378 g, pH 7.33, APGAR score 4/6/intubation. In follow‐up examinations at 5 years of age, the boy was doing well without any neurological disturbance or developmental delay. In the second case, the patient presented at 25/5 weeks' gestation suffering from severe IUGR received HBO and maternal AA infusions. The cardiotocography was monitored continuously during HBO treatment. The short‐time variations improved during HBO from 2.9 to 9 msec. The patient developed pathologic CTG and uterine contractions 1 day later and gave birth to a hypotrophic newborn weighing 420 g. After initial adequate stabilization, the extremely preterm newborn unfortunately died 6 days later. Fetal nutrition combined with HBO is technically possible and may allow the prolongation of the pregnancy. Fetal‐specific amino‐acid composition would facilitate the treatment options of IUGR fetuses and extremely preterm newborn

Treatment of mid-trimester preterm premature rupture of membranes (PPROM) with multi-resistant bacteria-colonized anhydramnion with continuous amnioinfusion and meropenem: a case report and literature review

Purpose!#!Treatment of mid-trimester classic preterm premature rupture of membranes (PPROM) with systemic antibiotics has limited success in the prevention of chorioamnionitis, funisitis and fetal inflammatory response syndrome because of very low transplacental passage.!##!Methods!#!Here we report a case of PPROM at 18 weeks gestation with anhydramnion colonized by multi-resistant Escherichia coli (E. coli). A catheter system was implanted at 23/2nd weeks gestation, enabling long-term continuous lavage of the amniotic cavity with Amnion Flush Solution (100 ml/h combined with intraamniotic meropenem application).!##!Results!#!The patient gave birth to a preterm male infant at 28/3rd without any signs of infection. In a follow-up examination at 24 months, there was no neurological disturbance or developmental delay.!##!Conclusion!#!The classic PPROM with multi-resistant E. coli colonization could be treated with continuous amnioinfusion and meropenem

Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants

Cohort Profile: The LoewenKIDS Study - life-course perspective on infections, the microbiome and the development of the immune system in early childhood.

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