Seminars in Fetal & Neonatal Medicine最新文献

Iron deficiency is a highly prevalent nutritional deficiency and the most common cause of anemia worldwide. Pregnant individuals are particularly susceptible due to increased demands to support expanding maternal blood volume and fetal growth. Iron deficiency and iron deficiency anemia are associated with maternal and neonatal morbidity, including preterm birth, preeclampsia, postpartum hemorrhage, and low birth weight. Iron is essential to support the rapidly growing fetal brain. Maternal iron deficiency is linked to cognitive delays, motor impairment, and neuropsychiatric disease in the offspring with effects lasting beyond childhood. Despite its high prevalence and profound clinical implications, it remains underdiagnosed and undertreated in pregnancy. This is potentiated by a lack of consensus regarding laboratory diagnosis and recommendations for screening and treatment. Here, we review the physiology, clinical implications, diagnosis, and treatment of iron deficiency in pregnancy.

Necrotizing enterocolitis (NEC) is a catastrophic inflammatory bowel necrosis of premature infants. The etiology is unknown, but 25-40 % of cases have a history of red blood cell (RBC) transfusions in the preceding 48 h. This association has been noted in retrospective case/case-control studies, and many meta-analyses, and in a murine model. However, we still need human studies with larger, adequately powered cohorts to confirm this association and determine the operant mechanisms. The murine model shows that severe anemia leads to macrophage infiltration in the gut mucosa. Subsequent RBC transfusions containing free hemoglobin, activate nuclear factor-kappa B-mediated inflammatory changes and cause NEC-like mucosal injury. This review summarizes current human and experimental data to evaluate ta-NEC and hitherto unanswered mechanistic questions. If a causal relationship between transfusions and NEC is proven, these data could help develop effective therapeutic strategies.

Hemostatic derangements are common in critically ill and premature neonates. Nevertheless, hemostasis assessment in neonates is still challenging. The hemostatic system undergoes age-related physiological changes during its maturation and exhibits quantitative and qualitative differences between infants and adults. Conventional coagulation tests are mainly responsive to procoagulant factors, regardless of the contribution of cellular elements, anticoagulants and fibrinolytic contributors and, therefore, their role in predicting bleeding in neonatal acquired coagulopathy is somewhat limited. Viscoelastic coagulation tests offer a promising alternative, enabling a bedside and real-time assessment of the entire hemostatic process in short turn-around times with a limited amount of blood. These tests allow a targeted hemostatic monitoring and a tailored management of blood products and anticoagulation. The routine use of VCTs in the NICU remains limited, especially for premature infants, due to the lack of established normative ranges. In this review we will provide an overview of the main evidence related to the clinical application of viscoelastic monitoring in the neonatal setting.

Nearly half a century ago, granulocyte transfusions were trialed in critically ill, septic, neutropenic neonates and showed improved survival when used concurrently with antimicrobials. Benefits were particularly noteworthy for Gram-negative and fungal infections. The introduction of granulocyte colony-stimulating factor into clinical medicine in 1991 and inherent problems associated with granulocyte procurement for transfusion caused granulocyte transfusions to become nearly extinct for this patient population. Simultaneous technological and clinical management advancements have enabled the survival of younger neonates, who are at the highest risk for neutropenia and neonatal sepsis. These infants have well-documented developmental deficiencies in the number and functional capabilities of their neutrophils compared to older patients. A continued surge in antimicrobial resistance and an increasing number of Gram-negative infections have created an urgent need for clinicians to rethink old therapies and consider new ones. This review details the evolution of granulocyte transfusions and whether they should be resurrected in neonatal patients.

Hemolytic disorders in neonates, once exceedingly common causes of infant mortality, have become increasingly rare and now largely non-fatal. Global advancements in neonatal care and deeper understanding of the mechanisms of neonatal hemolysis have significantly improved survival outcomes, particularly among those in high-income countries. However, regional disparities persist due to non-equitable healthcare access. Their long-lasting health consequences have been attributed to social, demographic factors that are most likely amenable to healthcare governance. In this review, we focus our attention to neonatal hemolytic disorders to i) analyze data resourced from the Global Burden of Disease (GBD) 2021 report; ii) study the trends in infant mortality rates (IMR) as related to hemolytic disorders including its severe complication, extreme hyperbilirubinemia (EHB-IMR); iii) evaluate geospatial disparities among GBD super regions; and iv) examine these trends in relation to the socio-demographic index (SDI) of the countries that comprise the "super-regions". From 1991 to 2021, global EHB-related IMR has declined significantly, from 73 to 25 per 100,000 live births. By 2021, EHB and kernicterus accounted for only 0.7 % of all under-five deaths. High-income countries have dramatically minimized hemolytic disease fatalities, but matched progress eludes regions like South Asia and sub-Saharan Africa. The inverse relationship between SDI and EHB-IMR highlight these national disparities to manifest as slower decline in IMR. In order to achieve equitable healthcare access for all regions, an improved understanding of the societal risk factors would guide re-engineering solutions that are also empowered by audited resource utilization to evaluate remedial governance policies.

The WHO recently revised their classification schema for G6PD gene variants. Notably, the previously separate Class II (severe enzyme deficiency; <10 % normal) and Class III (moderate enzyme deficiency; 10-60 % normal) variant groups are now combined into a single new category designated as Class B. Class B variants exhibit G6PD enzymatic activity in the <45 % of normal range. This welcome and prudent reclassification far better aligns with the neonatal hyperbilirubinemia risk reported in neonates with i) former "less severe" Class III variants including G6PD A- and ii) female neonates heterozygous for deficient alleles.

Infants born preterm or with other perinatal risk factors are at added risk for both iron deficiency and overload. Insufficient iron supplementation in the perinatal period is associated with long-term neurodevelopmental effects. Based on this, iron supplements must be targeted to infants' individual iron needs to avoid the adverse effects of both iron deficiency and overload. Enteral iron supplements have been the gold standard in iron supplementation of neonates for many years. However, emerging parenteral formulations may provide an alternative for some infants, such as those who are unable to tolerate oral supplements or who are refractory to enteral supplementation. Optimal dosing and timing of supplementation is an area of ongoing research. In this review, we will summarize available enteral and parenteral iron formulations, review iron measurement parameters, and identify outstanding questions and ongoing research.

In neonatal patients, bleeding is a multifactorial event in which several factors may play a pathogenic role. Among these, thrombocytopenia is often considered a risk factor for bleeding, although a causal relationship has never been demonstrated. In fact, major bleeding mainly occurs in non-thrombocytopenic newborns and thrombocytopenic newborns rarely experience major bleeding. Therefore, parameters other than platelet count might better assess the hemostatic function and define bleeding risk. Historically, neonatologists aimed to reduce the risk of bleeding by administering platelet transfusions. However, recent studies demonstrated that transfusing newborns at higher threshold is associated with an increased risk of death, bleeding, bronchopulmonary dysplasia and neurodevelopmental impairment. The mechanism behind this association is not known and various hypotheses have been proposed, including the non-hemostatic effects of adult-derived platelets transfused into neonates. Alternatively, the rapid volume expansion caused by a platelet transfusion might cause hemodynamic instability and cardiocirculatory overload. Guidelines about platelet transfusions should now include this recent evidence and adopt more stringent thresholds. Future research should focus on finding alternative or improved transfusion products more suitable for newborns.