van Uden Lisa, Tchirikov Michael
University Clinic of Obstetrics and Prenatal Medicine, Center of Fetal Surgery, University Medical Center Halle (Saale), Martin Luther University Halle-Wittenberg, Ernst-Grube Strasse 40, 06120 Halle (Saale), Germany.
Life (Basel). 2023 May 23;13(6):1232. doi: 10.3390/life13061232.
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.
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.
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.
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.
宫内生长受限（IUGR）是一种非常严重的产前疾病，在所有妊娠中发病率为3%至5%。它由多种因素引起，包括慢性胎盘功能不全。IUGR与死亡率和发病率增加相关，被认为是胎儿死亡的主要原因。目前，治疗选择非常有限，且常常导致早产。产后，IUGR婴儿患疾病和神经异常的风险也更高。
在PubMed数据库中使用关键词“IUGR”、“胎儿生长受限”、“治疗”、“管理”和“胎盘功能不全”检索1975年至2023年期间的文献。这些术语也进行了组合检索。
有4160篇论文、综述和文章涉及IUGR主题。总共只有15篇论文直接涉及IUGR的产前治疗；其中10篇基于动物模型。总体而言，主要重点是母体静脉输注氨基酸或羊膜腔内输注。自20世纪70年代以来，已经通过各种方式测试了治疗方法，以补充因慢性胎盘功能不全而缺乏的胎儿营养物质。在一些研究中，给孕妇植入皮下血管内围产期端口系统，从而持续给胎儿输注氨基酸溶液。实现了延长孕周以及改善胎儿生长。然而，对于孕周小于28周的胎儿，输注商业氨基酸溶液观察到的益处不足。作者将此主要归因于市售溶液中氨基酸浓度与早产儿血浆中观察到的浓度相比存在巨大差异。这些不同的浓度尤为重要，因为在兔模型中已证明代谢变化会导致胎儿大脑产生差异。IUGR脑组织样本中的几种脑代谢物和氨基酸显著减少，导致脑容量减小，神经发育异常。
目前只有少数研究和病例报告，病例数相应较少。大多数研究涉及通过补充氨基酸和营养物质进行产前治疗，以延长孕周并支持胎儿生长。然而，没有一种输注溶液的氨基酸浓度与胎儿血浆中的浓度相匹配。市售溶液的氨基酸浓度不匹配，并且在孕周小于28周的胎儿中未显示出足够的益处。需要探索更多的治疗途径并改进现有方法，以更好地治疗多因素IUGR胎儿。
