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.
CONCLUSIONS: 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.

Fetal supraventricular tachycardia can be difficult to manage and offers a challenging treatment course, particularly in refractory cases. The treatment course must balance maternal well-being with the health status of the fetus, all while racing against possible progression to hydrops fetalis or permanent cardiac dysfunction. We describe a case of fetal supraventricular tachycardia that demonstrates many of these concepts, as well as the importance of utilizing several treatment pathways in refractory cases.

BACKGROUND: Fetal hydrops is a serious condition difficult to manage, often with a poor prognosis, and it is characterized by the collection of fluid in the extravascular compartments. Before 1968, the most frequent cause was the maternal-fetal Rh incompatibility. Today, 90% of the cases are non-immune hydrops fetalis. Multiple fetal anatomic and functional disorders can cause non-immune hydrops fetalis and the pathogenesis is incompletely understood. Etiology varies from viral infections to heart disease, chromosomal abnormalities, hematological and autoimmune causes.
METHODS: A 38-year-old pregnant woman has neck lymphoadenomegaly, fever, cough, tonsillar plaques at 14 wk of amenorrhea and a rash with widespread itching. At 27.5 wk a fetal ultrasound shows signs of severe anemia and hydrops. Cordocentesis is performed with confirmation of severe fetal anemia and subsequent fetal transfusion. The karyotype is 46, XX, array-comparative genome hybridization (CGH) negative, and infectious tests are not conclusive. In the following days there is a progressive improvement of the indirect signs of fetal anemia. At 33.6 wk, for relapse of severe fetal anemia, further fetal transfusions are necessary and an urgent cesarean section is performed. On the day 12 of life, for the detection of anemia, the newborn is subjected to transfusion of concentrated red blood cells and begins treatment with erythropoietin. Later there is a normalization of blood chemistry values and the baby does not need new transfusions. A 29-year-old pregnant woman, with Sjogren\'s syndrome and positive Anti-Ro/SSA antibodies, is subjected to serial fetal ecocardio for branch block. At 26.5 wk there is a finding of fetal ascites. Infectious disease tests on amniotic fluid are negative as well as quantitative fluorescent polymerase chain reaction, Array CGH. At cordocentesis Hb is 1.3 mmol/L, consequently fetal transfusion is performed. Also in this case, due to continuous episodes of relapse of fetal anemia with consequent transfusions, at 29.4 wk a cesarean section is performed. On day 9 of life, a treatment with erythropoietin is started in the newborn, but the baby needs three blood transfusions. The search for autoantibodies in the baby found SS-A Ro60 positive, SSA-Ro52 positive and SS-B negative. The hemoglobin values normalized after the disappearance of maternal autoantibodies.
CONCLUSIONS: An attempt to determine the etiology of hydrops should be made at the time of diagnosis because the goal is to treat underlying cause, whenever possible. Even if the infectious examinations are not conclusive, but the pregnancy history is strongly suggestive of infection as in the first case, the infectious etiology must not be excluded. In the second case, instead, transplacental passage of maternal autoantibodies caused hydrops fetalis and severe anemia. Finally, obstetric management must be aimed at fetal support up to an optimal timing for delivery by evaluating risks and benefits to increase the chances of survival without sequelae.

We discuss the current indications, technical variation and procedure-related complications of percutaneous umbilical cord blood sampling (PUBS). The term PUBS is commonly used in the United States. Cordocentesis and funipuncture are equivalent terms. A needle guided by ultrasound is introduced into a blood vessel (usually the vein) of the umbilical cord to collect fetal specimen in PUBS. We conducted a literature search in PubMed indexed journals and analyzed all related articles on PUBS and cordocentesis. We chose this subject because it is a relatively new but convenient method that has both diagnostic and therapeutic value in fetal medicine. At present the only procedure that provides direct access to fetal circulation is PUBS. The most common clinical indication for PUBS is suspected fetal anemia. Other major indications for PUBS are the diagnosis of congenital infections, cytogenetic analysis, metabolic disorders, fetal growth restriction and hematologic disorders. Therapeutic applications of cordocentesis or puncture of the umbilical cord are in utero transfusions for rhesus alloimmunization and medication administration. PUBS also provides a direct assessment of fetal thyroid function diagnosing fetal thyroid disorders and helps administer therapy in utero.  Literature demonstrates a low incidence of complications associated with percutaneous umbilical blood sampling. For PUBS, the true complication rate related to the method of sampling remains unclear. A few cases reported complications conducted PUBS for therapeutic purposes which naturally has a higher accident rate compared to diagnostic purposes. Although life-threatening complications are rare, there are potential risks that include bleeding from the puncture site, fetal bradycardia, vertical transmission of maternal infection. Therefore, PUBS should be performed at perinatal care centers by experienced physicians and the best time is between 17 to 40 weeks of gestation. There are three methods used to approach the umbilical cord that includes direct, indirect and free puncture. Anteriorly placed placenta allows an easier approach to the umbilical cord. The danger of abruption of placenta must be kept in mind while using this technique. The number of punctures should be limited to a maximum of 3 to reduce complications. According to a case series report, the mean time required for the procedure was 4 minutes with a fall in duration seen with increased experience. In conclusion, percutaneous blood sampling allows direct access to fetal circulation thus opening up new areas of prenatal diagnosis and therapy. PUBS is now a well-codified procedure. It is clear from our literature review that risks directly related to the technique are small. The indication of the procedure must be carefully chosen as the risk of complications of umbilical cord puncture is directly related to the severity of the condition. Complications such as bleeding and hematoma formation are related to duration and number of punctures which are operator-dependent. Thus, only highly trained personnel should conduct the procedure. The list of indications is extensive and growing. Nevertheless, this technique shows potential to open up new realms in the area of fetal medicine.

Genes involved in the regulation of metabolism, adipose tissue deposition, inflammation, and the appetite-satiety axis may play an important role in fetal development, and possibly induce permanent metabolic changes and fat accumulation. In this study we investigated: (1) obesity-related gene expression in maternal and cord blood of overweight/obese and normal-weight pregnant women; (2) associations between obesity-related gene expression in maternal and cord blood; and (3) associations of gene expression in each of maternal and cord blood with newborn adiposity.
Twenty-five overweight/obese and 32 normal-weight pregnant women were selected from the Araraquara Cohort Study according to their pre-pregnancy BMI. Maternal and cord blood gene expression of LEPR, STAT3, PPARG, TLR4, IL-6, IL-10, FTO, MC4R, TNF-α, and NFκB were investigated by relative real-time PCR quantification. The body composition of the newborns was assessed by air displacement plethysmography. Associations between maternal and cord blood gene expression and markers of newborn adiposity (weight, BMI, and fat mass%) were explored by linear regression models controlling for maternal age, pre-pregnancy BMI, maternal gestational weight gain, gestational age, and newborn sex.
There was higher TLR4, NFκB, and TNF-a expression, and lower IL-6 expression, in overweight/obese pregnant women and their respective newborns compared with normal-weight women and their newborns (p < 0.001). Maternal PPARG gene expression was associated with both weight and fat mass % of the newborns, and cord blood IL-10 expression was associated with BMI and fat mass %, controlling for confounders.
To our knowledge, this is the first study to evaluate the relationship of maternal and cord blood gene expression with adiposity markers of the newborn. Our results provide evidence for the contribution of maternal and cord blood gene expression-particularly maternal PPARG and TLR4 expression, and cord blood IL-10 expression-to newborn weight, BMI, and fat mass %.

Environmental factors can induce detrimental consequences into adulthood life. In this study, we examined the epigenetic effects induced by in utero chlordecone (CD) exposure on human male cord blood as well as in blood-derived Ke-37 cell line. Genome-wide analysis of histone H3K4me3 distribution revealed that genes related to chromosome segregation, chromatin organization, and cell cycle have altered occupancy in their promoters. The affected regions were enriched in ESR1, SP family, and IKZF1 binding motifs. We also observed a global reduction in H3K9me3, markedly in repeated sequences of the genome. Decrease in H3K9me3 after CD exposure correlates with decreased methylation in LINE-1 promoters and telomere length extension. These observations on human cord blood were assessed in the Ke-37 human cell line. H3K4me3 and the expression of genes related to immune response, DNA repair, and chromatin organization, which were affected in human cord blood were also altered in CD-exposed Ke-37 cells. Our data suggest that developmental exposure to CD leads to profound changes in histone modification patterns and affects the processes controlled by them in human cord blood.

Congenital parvovirus B19 infection is a rare but serious condition that can result in hydrops fetalis and fetal death. Due to the virus\' cytotoxic effect on fetal red blood cell precursors, postnatal infection can cause a neonatal viremia and secondary pure red cell aplasia. Here, we describe a case of congenital parvovirus infection in a preterm infant complicated by hydrops fetalis and chronic anaemia that responded to postnatal treatment with intravenous immunoglobulin administered on day of life 44. After treatment, the anaemia resolved as the neonate exhibited interval increases in haemoglobin, haematocrit and reticulocyte count with no subsequent need for red blood cell transfusions.

Prenatal Diagnosis (PND) forms an important part of primary preventive management for families having a child affected with primary immunodeficiency. Although individually sparse, collectively this group of genetic disorders represents a significant burden of disease. This paper discusses the prenatal services available for affected families at various centers across the country and the challenges and ethical considerations associated with genetic counseling. Mutation detection in the index case and analysis of chorionic villous sampling or amniocentesis remain the preferred procedures for PND and phenotypic analysis of cordocentesis sample is reserved for families with well-characterized index case seeking PND in the latter part of the second trimester of pregnancy. A total of 112 families were provided PND services in the last decade and the presence of an affected fetus was confirmed in 32 families. Post-test genetic counseling enabled the affected families to make an informed decision about the current pregnancy.

Human Vγ9Vδ2 T cells respond to several diverse pathogens by sensing microbial cholesterol intermediates. Unlike CD4 T cells, they are poised for rapid Th1-like responses even before birth, which allows them to play a key role in the first line of defense against pathogens in early life. However, their regulation and functional maturation during infancy (in particular the acquisition of cytotoxic potential) remain understudied. We thus characterized their responses to cholesterol intermediates and Bacille Calmette-Guérin in a cohort of African neonates and 12-month-old infants. Infant Vδ2 lymphocytes exhibited intermediate or adult-like expression of markers associated with differentiation or function, intermediate proliferative responses, and adult-like cytotoxic potential. The enhancement of Vδ2 cell cytotoxic potential coincided with decreasing PD-1 and increasing NKG2A expression. Our results are consistent with the hypothesis that switching from a PD-1+ to a NKG2A+ phenotype during infancy indicates a shift in mechanisms regulating Vδ2 T cell function.

Iron stores at birth are essential to meet iron needs during the first 4-6 months of life. The present study aimed to investigate iron stores in normal birth weight, healthy, term neonates. Umbilical cord blood samples were collected from apparently normal singleton vaginal deliveries (n=854). Subjects were screened and excluded if C-reactive protein (CRP) > 5 mg/l or α1-acid glycoprotein (AGP) > 1 g/l, preterm (<37 complete weeks), term < 2500g or term > 4000g. In total, 762 samples were included in the study. Serum ferritin, soluble transferrin receptor (sTfR), hepcidin, and erythropoietin (EPO) were measured in umbilical cord blood samples; total body iron (TBI) (mg/kg) was calculated using sTfR and ferritin concentrations. A total of 19.8% newborns were iron deficient (ferritin 35 μg/l) and an additional 46.6% had insufficient iron stores (ferritin < 76 μg/l). There was a positive association between serum ferritin and sTfR, hepcidin, and EPO. Gestational age was positively associated with ferritin, sTfR, EPO, and hepcidin. In conclusion, we demonstrate a high prevalence of insufficient iron stores in a Chinese birth cohort. The value of cord sTfR and TBI in the assessment of iron status in the newborn is questionable, and reference ranges need to be established.