Some patients require transfusion of blood products, and most benefit from corticosteroid therapy. In this supplement, Rush (2) questions the benefit of routine iron supplementation in relation to the evidence of the harm or burden of anemia on reproductive outcomes. Use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, and mineralocorticoid receptor antagonists should be avoided in pregnancy. In poor areas, the usual diet often consists mainly of unprocessed grain products that are relatively high in phytate, which is a known inhibitor of iron absorption. The pathogenesis of HELLP syndrome remains unclear. Evidence does not suggest that this association is causal; it could be better attributed to hypertensive disorders of pregnancy and to preeclampsia. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. These conditions of increased red blood cell production share the one basic feature of increased red cell mass with normal or increased total blood volume. The other is cigarette smoking, which causes part of the hemoglobin to become nonfunctional as a result of binding with carbon monoxide (30). The Hemminki trial was of selective compared with routine iron use [Murray MJ, Murray AB, Murray MB, et al. These patients do not require transfusion unless the platelet count drops to less than 20,000 per mm3 (20 109 per L). Additionally, because many possible causes of anemia exist, such statistics-based anemia criteria provide only a guideline for establishing the probability of specific health and nutritional causes of anemia for a given population. The relation between hemoglobin and blood viscosity is linear when the hematocrit is <0.50 (equivalent to a hemoglobin value of 160 g/L). Hookworm infection and anemia: an approach to prevention and control. Hemoglobin in the first half of pregnancy was 12.61 (1.06) g/dL and average hematocrit in the first half of pregnancy was 38.19 (3.07) grams percent. When multiple factors contribute to the severity of anemia, iron deficiency is always a major factor (evidence of deficiency) (23). Ray Yip, Significance of an abnormally low or high hemoglobin concentration during pregnancy: special consideration of iron nutrition, The American Journal of Clinical Nutrition, Volume 72, Issue 1, July 2000, Pages 272S279S, https://doi.org/10.1093/ajcn/72.1.272S. First, if iron deficiency anemia was more common in the 1930s and 1920s than it is now, we should have seen a fall in deaths from hemorrhage and we did not. In the later group we found increased erythrocyte aggregation and a higher hematocrit than in normal patients of comparable gestational age.Erythrocyte aggregation correlated well with plasma fibrinogen levels (r = 0.74) but other high molecular weight proteins such . This obstruction leads to periportal necrosis and, in severe cases, intrahepatic hemorrhage, subcapsular hematoma formation or hepatic rupture. Direct evidence showing that a reduction in anemia will lead to fewer adverse birth outcomes (evidence of benefit) is lacking. For individuals with this condition, any extra iron will contribute to their iron burden, including iron supplementation during pregnancy. When the syndrome was first described, prompt delivery was recommended.1 Recent research suggests that morbidity and mortality do not increase when patients with HELLP are treated conservatively.18 The treatment approach should be based on the estimated gestational age and the condition of the mother and fetus (Figure 1).19. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. However, right upper quadrant tenderness is present in as many as 90 percent of affected women.2 Edema is not a useful marker because swelling is a factor in up to 30 percent of normal pregnancies.3 Hypertension and proteinuria may be absent or mild. HELLP, a syndrome characterized by hemolysis, elevated liver enzyme levels and a low platelet count, is an obstetric complication that is frequently misdiagnosed at initial presentation. These issues are discussed below. The clinical significance of low or high hemoglobin concentrations that are less extreme has more to do with underlying conditions that cause abnormally high or low hemoglobin concentrations. In the less severe range, however, the evidence that anemia is a direct cause of poor reproductive outcomes is not clear. Improving iron status through diet: the application of knowledge concerning dietary iron bioavailability in human populations. In the study by Pritchard et al (34), the average hematocrit for women with preeclampsia was 0.405, compared with a mean of 0.374 for women with a normal pregnancy. In: Rudolph . Peeters, L., Verkeste, C., Saxena, P. et al. In maternal anemia and iron deficiency, the anemia itself is often regarded as an adverse outcome. The rates of chronic hypertension are increasing and are predicted to continue because of obesity and older maternal age. Iron supplementation during pregnancyexperiences of a randomized trial relying on health services personnel. Dr Fleming: The study Mr Alnwick refers to showed an increase of mortality when the hemoglobin was <80 g/L and the blood loss was >500 mL without transfusion. The justification for controlling maternal anemia can be based on the undesirable effects of anemia other than poor birth outcomes and harmful health consequences beyond that of anemia alone. A third trimester hemoglobin of 130 or 140 g/L can be induced by oral iron supplements. He questions whether efforts to prevent anemia through iron supplementation can put some women at risk by placing their hemoglobin in a higher range that is associated with poor pregnancy outcomes. Because of the serious associated morbidity and mortality, family physicians who provide maternity care need to be aware of HELLP syndrome so that they can identify it early. This deficit, or excess, of iron prejudices the mother-child wellbeing. In such settings, improving iron nutrition is a necessarybut not a sufficientmeasure for the reduction of anemia. . There is no evidence to support the proposition that iron supplementation during pregnancy can cause abnormally high hemoglobin concentrations, beyond the optimal level for an individual or population. However, a clinician must be particularly watchful in treating a pregnant dengue-infected patient as physiologic hematology changes provide greater volume compensation and . Because of the variable nature of the clinical presentation, the diagnosis of HELLP syndrome is generally delayed for an average of eight days.7 Many woman with this syndrome are initially misdiagnosed with other disorders, such as cholecystitis, esophagitis, gastritis, hepatitis or idiopathic thrombocytopenia.3 In one retrospective chart review of patients with HELLP syndrome, only two of 14 patients entered the hospital with the correct diagnosis.7. Could you comment on that possible interaction and, also, whether there is a larger literature outside women and pregnancy just relating anemia to the risk of blood loss from X, Y, and Z in men and women? The decision of whether to treat chronic hypertension at lower blood pressure levels should be based on a discussion with the patient as well as the presence of comorbid conditions that might warrant lower blood pressure. Rarely, patients with refractory HELLP syndrome require plasmapheresis. Does iron supplementation make a difference? High hemoglobin concentrations are often mistaken as adequate iron status; however, high hemoglobin is independent of iron status and is often associated with poor health outcomes. For women, a hemoglobin concentration >170 g/L can perhaps be regarded as a moderately elevated value. Primiparas have very little immunity to malaria. Mr Alnwick: There was a multicenter trial in the United States with 2000 adult male and female patients, all of whom elected not to have a blood transfusion after surgery for all causes. Mandani G, Branson HE. We did not recommend routine iron supplementation in pregnancy in the United States. Throughout normal pregnancy, blood volume expands by an average of 50% compared with the nonpregnant state (33). These observations raised the issue of whether we should be concerned about high hemoglobin concentrations during pregnancy. Hypertension, hypovolemia, and poor placenta perfusion are all part of the physiologic disturbances of preeclampsia (39). There is no evidence that the observed low birth weight of infants from mothers who smoke is due to elevated hemoglobin. Antihypertensive therapy should be initiated if blood pressure is consistently greater than 160/110 mm Hg despite the use of magnesium sulfate. In addition, several iron supplementation studies of children and women showed that the resulting mean hemoglobin concentration, or the hemoglobin distribution, never exceeded that of the reference populations who were iron replete (43, 44). Hemoconcentration. Another reason for supplementation is that anemia caused by iron deficiency alone or in combination with other factors, eg, folate deficiency, vitamin A deficiency, and malaria, has been implicated as having several negative effects on maternal and fetal health. This reduces the risk of maternal cerebral hemorrhage, placental abruption and seizure. A more recent study, however, did not show that the risk of malaria justifies the withholding of iron (50). HELLP syndrome occurs in approximately 0.2 to 0.6 percent of all pregnancies.3 In comparison, preeclampsia occurs in 5 to 7 percent of pregnancies.3 Superimposed HELLP syndrome develops in 4 to 12 percent of women with preeclampsia or eclampsia.3 When preeclampsia is not present, diagnosis of the syndrome is often delayed.4. The effect of very low or very high hemoglobin concentrations on the cardiovascular system and resulting compromised delivery of oxygen to tissues can directly cause severe morbidity or mortality. https://journals.lww.com/greenjournal/fulltext/2019/01000/ACOG_Practice_Bulletin_No__203_Summary__Chronic.43.aspx. This is regarded as indirect evidence because epidemiologic findings of an association cannot distinguish whether the relation is causal. One study20 found that pregnancy was prolonged by an average of 15 days when conservative management (i.e., bed rest, fluids and close observation) was used in patients who were at less than 32 weeks of gestation. The three chief abnormalities found in HELLP syndrome are hemolysis, elevated liver enzyme levels and a low platelet count. Regarding the high-end hemoglobin issue, let us assume the population mean hemoglobin concentration is 140 g/L. (29). Relationship between Maternal Hemodynamics and Hematocrit and Hemodynamic Effects of Isovolemic Hemodilution and Hemoconcentration in the Awake Late . Because of reported potentiation of effect, care should be taken when nifedipine and magnesium sulfate are given concurrently.22 Diuretics may compromise placental perfusion and therefore are not used to control blood pressure in patients with HELLP syndrome. The acronym HELLP was coined in 1982 to describe a syndrome consisting of h emolysis, e levated l iver enzyme levels and l ow p latelet count. Patients who develop DIC generally do so in the setting of well-developed HELLP syndrome. The peripheral smear may reveal spherocytes, schistocytes, triangular cells and burr cells. Midwives' perceptions of and attitudes towards prevention of mother-to-child-transmission of HIV. From the perspective of reproductive health outcomes, however, the evidence is not clear that anemia or iron deficiency are direct risk factors (2). Early diagnosis is critical because the morbidity and mortality rates associated with the syndrome have been reported to be as high as 25 percent. Pregnant women presenting with blood pressures higher than 160 mm Hg systolic or 110 mm Hg diastolic for 15 minutes should be given an antihypertensive medication as soon as possible, but at least within one hour. Once the lifelong accumulation of excess iron reaches a critical leveloften by middle agetissue and organ damage can result (48). Women with chronic hypertension requiring medication or who have comorbidities that could affect fetal outcomes, fetal growth restriction, or superimposed preeclampsia are recommended for antenatal fetal testing, although evidence is lacking on timing of testing. The most common types of iron-loading disease in developing areas are the severe form of hereditary anemia, eg, thalassemia major, and the iron overloading is often the result of repeated transfusion (47). Additionally, because of the poor blood flow, the risk of thromboembolism increases substantially (21). Approximately 90 percent of patients present with generalized malaise, 65 percent with epigastric pain, 30 percent with nausea and vomiting, and 31 percent with headache.3 Because early diagnosis of this syndrome is critical, any pregnant woman who presents with malaise or a viral-type illness in the third trimester should be evaluated with a complete blood cell count and liver function tests.6. The use of inappropriate evaluative hemoglobin criteria during pregnancy can result in misinterpretation of the relation between anemia and resulting health outcomes. Pain relief with intravenous narcotics and local anesthesia is acceptable but certainly not optimal for pain control. Existing evidence does not support the hypothesis that high hemoglobin concentrations during pregnancy, within a range not classified as high, result in poor pregnancy outcomes. The challenge of improving iron nutrition: limitations and potentials of major intervention approaches. A placebo-controlled trial is unlikely. I do not think that making a blanket statement that iron unmasks malaria is possible. Dr Johnston: One risk that you did not mention was that of unmasking malaria, especially in pregnant women. The finding of a decreased serum haptoglobin level may confirm ongoing hemolysis when the hematocrit is normal.8 The serum transaminase levels may be elevated to as high as 4,000 U per L, but milder elevations are typical. The measured beneficial effect under controlled research conditions is known as efficacy, which is the maximum achievable effect under ideal conditions. In addition to poor intakes of bioavailable iron, which is a common problem in developing countries and is related to low intakes of heme iron from animal sources, hookworm infection is prevalent in many tropical areas (24). There is thus some support for not obligating iron supplements during pregnancy. 1 The syndrome has been considered a variant of. There is a supported opinion about the increased adverse pregnancy outcomes both with low and high hemoglobin levels. When blood transfusion became widely available to the public, which was during World War II, hemorrhage-related deaths also fell. The adverse effect of iron repletion on the course of certain infections. Hemoquant determination of hookworm-related blood loss and its role in iron deficiency in African children, Iron status and inflammatory processes in anaemic children, Not only supplementation with iron but also with vitamin A is necessary to combat nutritional anemia in pregnant women in West Java, Indonesia, Some clinical aspects of life at high altitudes, The effect of cigarette smoking on hemoglobin levels and the diagnosis of anemia, Polycythemia vera: stem cell and probable clonal origin of the disease, Changes in the blood volume during pregnancy and delivery, The Parkland Memorial Hospital protocol for treatment of eclampsia: evaluation of 245 cases, High hemoglobin levels during pregnancy and fetal risk, Increased 2nd trimester hemoglobin concentration in pregnancies later complicated by hypertension and growth retardation: early evidence of reduced plasma volume, The significance, diagnosis, and treatment of maternal hypovolemia as associated with fetal maternal illness, Gender differences and low birth weight with maternal smokeless tobacco use in pregnancy, Assessment of the prevalence and the nature of iron deficiency for populations: the utility of comparing hemoglobin distributions, Hemoglobin as a predictor of response to iron therapy and its use in screening and prevalence estimates, The role of malaria in nutritional anemia, The effect of iron supplementation during pregnancy, given by traditional birth attendants, on prevalence of anemia and malaria. Therefore, HELLP syndrome should be suspected in any patient who shows a significant drop in the platelet count during the antenatal period.10 A positive D-dimer test in the setting of preeclampsia has recently been reported to be predictive of patients who will develop HELLP syndrome.11 The D-dimer is a more sensitive indicator of subclinical coagulopathy and may be positive before coagulation studies are abnormal. Evaluations of large-scale programs have found that the reduction of anemia is often limited because of a breakdown in the chain of events required to ensure proper functioning of programs (3, 4).
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