In this open, randomized, multicenter trial involving extremely-low-birth-weight preterm infants, the use of a higher hemoglobin threshold for red-cell transfusion did not improve survival without ...neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity.
The objective of this review is to provide an integrated historical account of the complex, often convoluted events impacting milk hygiene and its resultant effect on infant mortality from 1875 to ...1925. Heat pasteurization of cow's milk is necessary for rendering this important nutrient source safe for humans-particularly infants. Developed by Louis Pasteur in 1864, pasteurization evolved from the commercially important parboiling of wine and beer when the Industrial Revolution was effecting rapid societal change in Western societies. In European and American societies of the early and mid-19th century, infant mortality rates were 30- to 60-fold higher than the current rates of five or six deaths per 1,000 live births per year. With proof of the germ theory of disease came convincing evidence of the role of microbes in the transmission of infections, which led to the discovery that microbial pathogens were transmissible via milk. Diseases caused by milkborne pathogens include human and bovine tuberculosis, brucellosis, salmonellosis, streptococcal infections, diphtheria, and "summer diarrhea." With pasteurization of milk, infectious diseases with their high infant mortality rates decreased by only half by the early 20th century, despite concurrent medical and dairy hygiene advances. To further mitigate unacceptably high infant mortality rates, social support providers-including public health nurses and midwives-encouraged breastfeeding, especially among socioeconomically disadvantaged mothers. Improvements in pulsating vacuum milking machines also favorably impacted food safety by providing a clean, enclosed environment. Currently, bottle feeding still competes with breastfeeding as the preferred method, and the sale of raw, unpasteurized milk remains a contentious issue. Informed and responsible food safety professionals, physicians, and public health officials currently view breastfeeding as the preferred feeding method and milk pasteurization as the safer and more prudent alternative.
Although many centers have introduced more restrictive transfusion policies for preterm infants in recent years, the benefits and adverse consequences of allowing lower hematocrit levels have not ...been systematically evaluated. The objective of this study was to determine if restrictive guidelines for red blood cell (RBC) transfusions for preterm infants can reduce the number of transfusions without adverse consequences.
We enrolled 100 hospitalized preterm infants with birth weights of 500 to 1300 g into a randomized clinical trial comparing 2 levels of hematocrit threshold for RBC transfusion.
The infants were assigned randomly to either the liberal- or the restrictive-transfusion group. For each group, transfusions were given only when the hematocrit level fell below the assigned value. In each group, the transfusion threshold levels decreased with improving clinical status.
We recorded the number of transfusions, the number of donor exposures, and various clinical and physiologic outcomes.
Infants in the liberal-transfusion group received more RBC transfusions (5.2 +/- 4.5 mean +/- SD vs 3.3 +/- 2.9 in the restrictive-transfusion group). However, the number of donors to whom the infants were exposed was not significantly different (2.8 +/- 2.5 vs 2.2 +/- 2.0). There was no difference between the groups in the percentage of infants who avoided transfusions altogether (12% in the liberal-transfusion group versus 10% in the restrictive-transfusion group). Infants in the restrictive-transfusion group were more likely to have intraparenchymal brain hemorrhage or periventricular leukomalacia, and they had more frequent episodes of apnea, including both mild and severe episodes.
Although both transfusion programs were well tolerated, our finding of more frequent major adverse neurologic events in the restrictive RBC-transfusion group suggests that the practice of restrictive transfusions may be harmful to preterm infants.
Critically ill preterm and term neonates are at high risk for negative iron balance due to phlebotomy that occurs with frequent laboratory monitoring, and the high iron demand of rapid growth. ...Understanding the prioritization of iron between red blood cells (RBCs) and brain is important given iron's role in neurodevelopment.
Ten neonatal twin lamb pairs (n = 20) underwent regular phlebotomy for 11 d. Lambs were randomized to receive no iron or i.v. daily iron supplementation from 1 to 5 mg/kg. Serum hemoglobin concentration and reticulocyte count were assayed, iron balance calculated, and iron content of RBCs, liver, brain, muscle, and heart measured at autopsy.
Among phlebotomized lambs: (i) liver iron concentration was directly related to net iron balance (r = 0.87; P < 0.001) and (ii) brain iron concentration was reduced as a function of net iron balance (r = 0.63) only after liver iron was depleted. In animals with negative iron balance, total RBC iron was maintained while brain iron concentration decreased as a percentage of the iron present in RBCs (r = -0.70; P < 0.01) and as a function of reticulocyte count (r = -0.63; P < 0.05).
Phlebotomy-induced negative iron balance limits iron availability to the developing brain.
Tissue hypoxia is the major stimulus of erythropoietin (EPO) synthesis in fetuses and adults. Since EPO does not cross the placenta and is not stored, fetal plasma and amniotic fluid levels indicate ...EPO synthesis and elimination. Acutely, the rate and magnitude of the increase in plasma EPO levels correlate with the intensity of hypoxia. Amniotic fluid EPO levels correlate with cord plasma levels in normal and abnormal pregnancies, with fetal plasma EPO levels in humans averaging 2.6 times higher than the corresponding amniotic fluid EPO levels. Recent experimental and clinical studies demonstrate that EPO has neuroprotective effects related to its anti-apoptotic and vascular growth-promoting properties. Although under basal conditions the fetal kidneys are the main site of EPO production, during hypoxia recent experimental data indicate an important role of the placenta. Amniotic fluid EPO levels have been shown to increase exponentially during fetal hypoxia in preeclamptic, diabetic and Rh-immunized pregnancies, to correlate inversely with cord blood pH, pO(2) and base excess and to predict neonatal morbidities and NICU admission. As an indicator of chronic intrauterine hypoxia, fetal EPO measurements have increased our knowledge about the pathogenesis and importance of intrauterine growth restriction, macrosomia, diabetic pregnancy, prolonged pregnancy, meconium staining, fetal hemorrhage, fetal anemia, maternal smoking and alcohol consumption, abnormal fetal heart rate and abnormal Doppler flow patterns. While the clinical utility of fetal amniotic fluid and plasma EPO measurements in the management of high-risk pregnancies and their offspring is promising, adequately powered clinical trials are urgently needed.
Fetal erythropoietin (EPO), in addition to regulating erythropoiesis, has also tissue-protective properties based on its anti-inflammatory, anti-apoptotic, antioxidant, and neurotrophic effects. ...Notably, EPO concentrations needed for tissue protection are 100-1000 times higher than concentrations needed for regulating erythropoiesis. This dual effect of EPO is based on EPO-receptor (EPO-R) isoforms, which differ structurally and functionally. We hypothesize in this Integrated Mechanism Review that during severe fetal hypoxia the observed, but poorly understood, marked increases of fetal plasma EPO concentrations occur to protect the brain, heart, and other vital fetal organs. We further hypothesize that the concurrent marked increases of EPO in the amniotic fluid during fetal hypoxia, occur to protect newborn infants from necrotizing enterocolitis. This review presents experimental and clinical evidence in support of these hypotheses and points out unknown or poorly understood functions of EPO in the fetus. If these novel hypotheses are correct, the importance of fetal EPO as an antenatal hypoxia biomarker will become apparent. It will also likely point the way to important diagnostic and therapeutic fetal and neonatal interventions.
The development of anemia after birth in very premature, critically ill newborn infants is a universal well-described phenomenon. Although preventing anemia in this population, along with efforts to ...establish optimal red blood cell (RBC) transfusion and pharmacologic therapy continue to be actively investigated, the present review focuses exclusively on nonpharmacological approaches to the prevention and treatment of neonatal anemia. We begin with an overview of topics relevant to nonpharmacological techniques. These topics include neonatal and fetoplacental hemoglobin levels and blood volumes, clinical and laboratory practices applied in critically ill neonates, and current RBC transfusion practice guidelines. This is followed by a discussion of the most effective and promising nonpharmacological blood conservation strategies and techniques. Fortunately, many of these techniques are feasible in most neonatal intensive care units. When applied together, these techniques are more effective than existing pharmacotherapies in significantly decreasing neonatal RBC transfusions. They include increasing hemoglobin endowment and circulating blood volume at birth; removing less blood for laboratory testing; and optimizing nutrition.
IMPORTANCE: Thrombocytopenia and intraventricular hemorrhage (IVH) are common among very-low-birth-weight (VLBW) infants. Survey results suggest that US neonatologists frequently administer platelet ...transfusions to VLBW infants with mild to moderate thrombocytopenia. OBJECTIVES: To characterize platelet transfusion practices in US neonatal intensive care units (NICUs), to determine whether severity of illness influences platelet transfusion decisions, and to examine the association between platelet count (PCT) and the risk for IVH in the first 7 days of life. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, retrospective cohort study included 972 VLBW infants treated in 6 US NICUs, with admission dates from January 1, 2006, to December 31, 2007. Data were collected from all infants until NICU discharge or death (last day of data collected, December 4, 2008). Data were entered into the central database, cleaned, and analyzed from May 1, 2009, to February 11, 2016. INTERVENTION: Platelet transfusion. MAIN OUTCOMES AND MEASURES: Number of platelet transfusions and incidence of IVH. RESULTS: Among the 972 VLBW infants (520 53.5% male; mean SD gestational age, 28.2 2.9 weeks), 231 received 1002 platelet transfusions (mean SD, 4.3 6.0 per infant; range, 1-63 per infant). The pretransfusion PCT was at least 50 000/μL for 653 of 998 transfusions (65.4%) with this information. Two hundred eighty-one transfusions (28.0%) were given during the first 7 days of life. During that period, platelet transfusions were given on 35 of 53 days (66.0%) when the patient had a PCT less than 50 000/μL and on 203 of 436 days (46.6%) when the patient had a PCT of 50 000/μL to 99 000/μL. At least 1 marker of severe illness was present on 198 of 212 patient-days (93.4%) with thrombocytopenia (PCT, <100 000/μL) when a platelet transfusion was given compared with 113 of 190 patient-days (59.5%) with thrombocytopenia when no platelet transfusion was given. Thrombocytopenia was a risk factor for intraventricular hemorrhage during the first 7 days of life (hazard ratio, 2.17; 95% CI, 1.53-3.08; P < .001). However, no correlation was found between severity of thrombocytopenia and risk for IVH. After controlling for significant clinical factors and thrombocytopenia, platelet transfusions did not have a significant effect on the incidence of IVH (hazard ratio, 0.92; 95% CI, 0.49-1.73; P = .80). CONCLUSIONS AND RELEVANCE: A large proportion of platelet transfusions were given to VLBW infants with PCT greater than 50 000/μL. Severity of illness influenced transfusion decisions. However, the severity of thrombocytopenia did not correlate with the risk for IVH, and platelet transfusions did not reduce this risk.
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