Hemostatic Profile of Intrauterine Growth-Restricted Neonates: Assessment with the Use of NATEM Assay in Cord Blood Samples.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples. METHODS: During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE). RESULTS: IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT. CONCLUSION: IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables.

Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature.

Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.

Hemostasis in Neonates with Perinatal Hypoxia-Laboratory Approach: A Systematic Review.

Birth asphyxia, with an estimated prevalence of 1 to 6 per 1,000 live births, may lead to multiorgan dysfunction due to impaired oxygen and/or blood supply to various organ systems, including the hemostatic system. Coagulopathy, a common complication of perinatal asphyxia, has been described since the 1960s. The aim of this study was to systematically review the literature for records on the use of hemostasis tests in the evaluation of coagulation disorders, in neonates who had suffered from perinatal hypoxia or asphyxia. We identified published studies by searching PubMed and Scopus, up until April 2022. The literature search retrieved 37 articles fulfilling the inclusion criteria of the review. According to the bibliography, thrombocytopenia is commonly associated with perinatal hypoxia/asphyxia. The thrombocytopenia is usually described as mild and platelets return to normal levels by the 10th day of life. Additionally, hypoxic neonates usually present with a hypocoagulable profile, as reflected by the prolongation of standard coagulation tests, including prothrombin time, activated partial thromboplastin time, and international normalized ratio, findings commonly associated with disseminated intravascular coagulation, and by the reduction of the levels of the physiologic inhibition of coagulation system. A few studies thus far using ROTEM/TEG in hypoxic neonates have come to the same conclusion as well; hypoxic newborns seem to be characterized by a hypocoagulable profile compared with healthy neonates. It should be emphasized, however, that standard coagulation tests provide only a rough estimation of the true bleeding or thrombotic risk of hypoxic neonates. On the contrary, viscoelastic methods seem to be more precise in the early detection of hemostasis disorders in the neonatal population. However, until now, there was uncertainty as to the most appropriate coagulation assays for diagnosis and management of coagulation derangement in neonates with perinatal hypoxia indicating the need for further research on this field.

Reference Values of Thromboelastometry Parameters in Healthy Term Neonates Using NATEM in Cord Blood Samples.

Background: ROTEM assay has gained increasing acceptance as a method for rapid and specific coagulation pathway assessment. However, its use in the neonatal population remains limited since reference ranges have not yet been established. Aims: (1) to determine reference ranges for healthy term neonates of ROTEM parameters using non-activated assay (NATEM) in cord blood samples; (2) to assess whether delivery mode, gender, gestational age, birth weight and blood group (ABO and Rhesus) of the neonate, coagulation disorder and anticoagulant medication of the mother have an impact on NATEM parameters. Methods: NATEM assay was conducted in cord blood samples of 189 term neonates without any medical history. Results: Reference ranges (2.5th and 97.5th percentiles) are established for clotting time (CT), clot formation time (CFT), α-angle, clot amplitude at 5, 10 and 20 min (A5, A10, A20), maximum clot firmness (MCF), lysis index at 30 and 60 min (LI30, LI60, %) and maximum clot elasticity (MCE). Reference ranges for NATEM are CT 182-499 s, CFT 63-176 s, α-angle 58-78°, A5 28-52 mm, A10 37-61 mm, A20 42-66 mm, MCF 43-67 mm, LI30 97-100%, LI60 87-98% and MCE 75-203. Male neonates appear to be more hypocoagulable than females. Conclusions: We demonstrate reference ranges for healthy term neonates in NATEM assay that could be used as a reference group for future studies of neonates with an underlying pathology.

Mothers in Need of Lactation Support May Benefit from Early Postnatal Galactagogue Administration: Experience from a Single Center.

BACKGROUND: Galactagogues are substances that promote lactation, although data on their effects on humans remain limited. We investigated the efficacy of Silitidil to increase milk supply and duration of breastfeeding of a specific subgroup of mothers in need of lactation support. METHODS: 161 mothers from November 2018 until January 2021 were the study subjects in this retrospective study; during their hospitalization, due to neonatal or maternal factors that inhibited lactation, they were prescribed galactagogues. Mothers were surveyed by telephone interview via a 13-item questionnaire. RESULTS: 73.91%, were primigravidas, 78.26% gave birth by cesarean section (CS) and 72.05% continued to take galactagogues after hospital discharge. Of the neonates, 24.22% were preterm ≤37 weeks of gestation, and 55.9% had birth weight (BW) between 2500 and 3500 g. With respect to breastfeeding rates, 100% were breastfed during their first week, 98.8% breastfed during the first month, 87% during the first 4 months, dropping to 56.5% at 6 months, 41% at 1 year and 19.3% over 1 year of age. CONCLUSIONS: This study demonstrates that administration of a galactagogue containing Silitidil (Piulatte-Humana) improves breastfeeding rates at from 1 until 12 months of life in mothers with low milk supply during their hospital stay. Further studies are needed to generate evidence-based strategies to improve breastfeeding outcomes.