L’anémie ferriprive pendant la grossesse
• L’anémie ferriprive (AF) : La cause la plus fréquente d'anémie pendant la grossesse, affectant >
32 millions de grossesses par an dans le monde
• L'anémie pendant la grossesse est associée à un taux important de morbidité maternelle et néonatale, notamment une morbidité maternelle sévère (MMS), une septicémie, une
hémorragie post-partum et, chez la progéniture, à des problèmes cognitifs et comportementaux
• L'ACOG définit l'anémie pendant la grossesse comme un taux d'Hb inférieur à 11 g/dL au cours du 1 er trimestre et un taux d'Hb inférieur à 10,5 g/dL aux 2 ème et 3 ème trimestres ; les seuils varient selon les lignes directrices internationales.
• L'OMS définit l'anémie comme un taux d’Hb inférieur à 11 g/dL tout au long de la grossesse
• Anémie légère : Taux d’Hb inférieur à 9 - 10,9 g/dL
• Anémie modérée : Taux d’Hb entre 7 et 8,9 g/dL
• Anémie sévère : Taux d’Hb inférieur à 7 g/dL
• Les lignes directrices relatives à l'anémie post-partum varient entre des taux d'Hb inférieurs à 9 - 11 g/dL
• De nombreuses causes d'anémie : Physiologique, nutritionnelle, héréditaire, acquise, infectieuse - cependant, la carence en fer contribue à la majorité, > 70%, des cas d'anémie.
L’anémie ferriprive pendant la grossesse
Igbinosa I, et al. Curr Opin Obstet Gynecol. 2022; 34: 69-76. OMS : Organisation Mondiale de la Santé ; ACO : American College of Obstetricians and Gynecologists ; Hb : Hémoglobine ; g/dL : gramme par décilitre.
L’anémie ferriprive pendant la grossesse : Prise en charge
Igbinosa I, et al. Curr Opin Obstet Gynecol. 2022; 34: 69-76. Hb : Hémoglobine.
• Les lignes directrices actuelles préconisent une supplémentation de 27 mg de fer élémentaire par jour pendant la grossesse, une équivalence couramment retrouvée dans les vitamines prénatales en vente libre
• Le fer oral, principalement sous forme de sels ferreux (fumarate ferreux, sulfate ferreux, gluconate ferreux), constitue le traitement de 1 ère intention de l'AF. Les sels ferreux étaient administrés en doses fractionnées de 100 à 200 mg de fer élémentaire par jour
• L'efficacité du fer oral augmente lorsqu'il est pris le matin après une nuit de jeûne. Plus récemment, une dose unique quotidienne ou tous les deux jours semble être aussi efficace
• Les préparations orales sont moins chères, mais elles sont associées à des effets indésirables gastro-intestinaux, à la non- observance du traitement et à une moindre augmentation du taux d'Hb au moment de l'accouchement que les
préparations intraveineuses (IV)
• Une méta-analyse a conclu que 40 à 70% des femmes enceintes prenant du fer oral ont présenté un effet indésirable, impliquant principalement le système gastro-intestinal, avec le fer oral et que la moitié d'entre elles ont arrêté le traitement
• Les suppléments de fer à enrobage entérique améliorent la tolérance mais inhibent l'absorption
L’anémie ferriprive pendant la grossesse : Fer intraveineux
Adapté de : Igbinosa I, et al. Curr Opin Obstet Gynecol. 2022; 34: 69-76. Hb : Hémoglobine.
Médicament Fer
élémentaire
Dosage Grossesse et allaitement
Sécurité
Fer-saccharose 20 minutes Doses multiples de 200 à 300 ng Le fer IV le plus étudié dans la grossesse
Aucun effet indésirable chez les nourrissons allaités Derisomaltose ferrique
(également connu sous le nom d'Isomaltoside de fer)
100 mg/ml 500 mg/dose, max. 3 doses à 7 jours d'intervalle
ou
Dose unique de 20 mg/kg
Données limitées
Excrété dans le lait maternel
Fer dextran à faible poids moléculaire
50 mg/ml - Doses multiples de 100 mg ou
- dose unique de 1000 mg (dans 250 ml de saline normale) sur 1 heure - dose d’essai requise
Essais publiés présentant des résultats maternels/fœtaux négatifs rares
Excrétion minime dans le lait
Férumoxytol 30 mg/ml 510 mg/dose, max. 2 doses administrées à 3 - 8 jours d'intervalle
Étude de 164 patientes enceintes ayant des résultats obstétriques dans la norme
Avantages > risques
Remarque : également un agent de contraste Aucune étude rapportée sur l’allaitement Carboxymaltose ferrique 50 mg/ml 750 mg/dose, max. 2 doses Surveiller pour une hypophosphatémie
Excrété dans le lait maternel
L’anémie ferriprive pendant la grossesse : Conclusion
Igbinosa I, et al. Curr Opin Obstet Gynecol. 2022; 34: 69-76. AF : Anémie ferriprive ; IV : Intraveineux.
• Les lignes directrices nationales fournissent des recommandations variables sur le diagnostic et le traitement de l’AF pendant la grossesse
• Ferritine sérique : Un complément utile pour le diagnostic de l'AF
• Le fer, sous forme diététique, orale et intraveineuse, s'est révélé efficace pour résoudre l'anémie pendant la grossesse
• Le fer par voie orale reste une option thérapeutique ; l'absorption est améliorée avec une administration tous les deux jours et est efficace pour les patients capables de tolérer cette voie
• Il est raisonnable d'envisager les fers IV chez les patients présentant une anémie persistante, une intolérance au fer oral et une anémie grave pendant la grossesse
• Les nouvelles études sur les générations modernes de fer IV montrent des temps de perfusion plus courts et des profils de sécurité améliorés
• Les récentes lignes directrices britanniques envisagent une supplémentation universelle en fer IV pour le traitement de l'anémie au-delà de 34 semaines de grossesse
• Les femmes enceintes souffrant d'AF au cours du 3 ème trimestre sont plus susceptibles de bénéficier de fer IV
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C O
URRENTPINIONIron deficiency anemia in pregnancy
Irogue Igbinosaa, Caroline Berubeb, and Deirdre J. Lyella
Purpose of review
Anemia in pregnancy is associated with increased maternal and neonatal morbidity. There is increasing awareness amongst obstetricians about the need to screen for iron deficiency anemia (IDA), as well as growing literature on diagnosis and treatment. This review aims to summarize causes, consequences, treatment, and evaluation of IDA in pregnancy.
Recent Findings
National guidelines provide varying guidance on diagnosis and treatment of IDA in pregnancy. Serum ferritin is a helpful adjunct for the diagnosis of IDA. Oral iron remains an option for treatment; absorption is improved with every other day dosing and is effective for patients able to tolerate. Emerging studies on modern generations of intravenous (IV) iron demonstrate shorter infusion times and improved safety profiles.
Notably, recent UK guidelines provide consideration for universal IV iron supplementation for treatment of anemia beyond 34 weeks of pregnancy.
Summary
Iron, in dietary, oral, and IV forms, has been found effective in resolving anemia in pregnancy. Pregnant people with IDA in the third trimester are more likely to benefit from IV iron. Future studies designed and powered to assess maternal and perinatal morbidity indicators and blood transfusion rates can strengthen recommendations.
Keywords
anemia, iron, iron deficiency, pregnancy
INTRODUCTION
Iron deficiency anemia (IDA) is the most common cause of anemia in pregnancy, affecting more than 32 million pregnancies annually worldwide [1&&]. Ane- mia in pregnancy is linked to significant maternal and neonatal morbidity, including severe maternal morbidity (SMM), sepsis, postpartum hemorrhage, and in offspring, cognitive and behavioral issues [2,3]. Although thresholds differ among guidelines, the American College of Obstetricians and Gynecol- ogists (ACOG) defines anemia in pregnancy as hemo- globin below 11 grams per deciliter (g/dL) in the first trimester and hemoglobin below 10.5 g/dL in the second and third trimester; thresholds vary among international guidelines [4&&]. There are many causes of anemia – physiological, nutritional, hereditary, acquired, infectious – yet, iron deficiency contributes to the majority, more than 70% of anemias [5&].
CAUSES OF ANEMIA
Iron, a critical component of oxygen-heme metab- olism, functions to support the demands of the maternal-fetal-placental triad [6]. Physiologically, increases in maternal blood volume (50%) and
red blood cell mass (35%) contribute to a tempo- rary dilutional effect on hemoglobin concentra- tions. As iron metabolism efforts grow, iron deficiency (a state of decreased iron) precedes IDA (low iron plus anemia) [7]. Iron utilization increases from 2 mg/day in early pregnancy to approximately 5–6 mg/day by the third trimester [8]. Over 1000 mg elemental iron is required for the average term singleton pregnancy, and iron requirements are amplified nearly two-fold in multifetal pregnancies [9]. The remaining causes of anemias in pregnancy range from nutritional (acquired B12 and folate deficiency) anemias, hemoglobinopathies (i.e.
sickle cell anemia and thalassemia), infection (HIV, malaria), and chronic diseases [10].
aStanford University, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine and bStanford University, Department of Medicine, Division of Hematology, Stanford, California, USA
Correspondence to Irogue Igbinosa, MD, Stanford University, Depart- ment of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Stanford, California, USA. Tel: +650 725 5720;
e-mail: iiigbi@stanford.edu
Curr Opin Obstet Gynecol2022, 34:69–76 DOI:10.1097/GCO.0000000000000772
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REVIEW
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DEFINITION OF ANEMIA
International variance exists on ideal cutoffs to define anemia in pregnancy. The Centers for Disease Control and Prevention and ACOG define anemia as hemoglobin/hematocrit below 11 g/dL/33% in the first and third trimester and below 10.5 g/dL/32.5%
in the second trimester [11]. Notably, the British Society of Hematology defines anemia as hemoglo- bin below 10.5 g/dL beyond 12 weeks and less than 10 g/dL postpartum [12&&]. The World Health Orga- nization (WHO) defines anemia as hemoglobin below 11.0 g/dL throughout pregnancy [1&&]. Mild anemiais defined by hemoglobin below 9–10.9,mod- erate anemiaby 7–8.9, andsevere anemiaby less than 7 g/dL [2]. Guidelines for postpartum anemia vary between hemoglobin levels less than 9.0–11.0 g/dL
[12&&,13]. Recent research challenges the applicability
of the hemoglobin cutoffs to more diverse popula- tions; a follow-up consensus statement from the WHO is pending at the time of this writing [14].
PREVALENCE AND CAUSES
Anemia in pregnancy affects more than 40 percent- age of pregnancies globally [1&&]. In the United States, underrepresented communities are particu- larly at risk for antenatal anemia, with the highest rates seen among Black women, 2–3-fold greater than White women even after excluding hereditary anemias (e.g., sickle cell anemia) [11,15].
Epidemiologic surveys underscore the impor- tant roles access to nutrition, socioeconomics, and social determinants of health play in addressing the public health challenge of anemia in pregnancy.
IDA risk factors include multiparity, interpregnancy interval less than one-year, adolescent pregnancy, and chronic medical illness [16]. Diets low in iron- rich/fortified foods (i.e. vegan, vegetarian) or high in foods diminishing iron absorption (i.e., coffee, tea) may contribute nutritional-related anemias [8,17].
Hemoglobin concentrations are also affected by
high altitudes (1000m above sea level) and smoking, which reduce heme oxygen carrying capacity [18].
MATERNAL CONSEQUENCES OF ANEMIA Common pregnancy symptoms often overlap with IDA symptoms and can cloud recognition of ane- mia. IDA contributes to fatigue, malaise, insomnia, chest pain, shortness of breath, and restless legs [19].
Physical exam findings of the skin or conjunctival pallor, flow murmurs, tachycardia, and decreased blood pressure should prompt evaluation for ane- mia [20&,21]. Infection, preterm delivery, cesarean delivery, preeclampsia, and severe maternal mortal- ity are seen more frequently with IDA, as are post- partum depression and decreased breastfeeding at six and twelve months.
The severity of anemia correlates with out- comes. In one study, blood transfusion odds increased with moderate anemia (2.45 OR, 95% CI 12.2–37.3) and severe anemia (84.1 OR, 95% CI 26.4–267.9) [2]. A rare consequence of anemia, severe anemia was associated with 1.86 odds (95%
CI, 1.39–2.49) of maternal death [22].
FETAL AND CHILDHOOD CONSEQUENCES OF ANEMIA
Fetal well-being is also affected by maternal anemia.
Fetal growth restriction (1.9% vs. 0.3%, p 0.006), preterm delivery (10.2% vs. 6.1%, p 0.009), and rarely neonatal anemia are associated with maternal IDA [23,24]. Neurocognitive dysfunction, such as reduced recognition memory [25], difficulty processing [26], slower processing speed [27,28&], and autism spec- trum disorders [29], have been associated with severe IDA. The hippocampus is highly metabolically active and develops more extensively after28 weeks. It is critical for memory, spatial and fact learning and is vulnerable to the lack of critical substrates such as iron [28&]. Less complex dendritic structure has been associated with severe maternal anemia [28&]. New- borns absorb iron poorly, and IDA that is established during pregnancy, a time when fetal ’iron loading’ is critical, can be difficult to overcome.
DIAGNOSIS OF IRON DEFICIENCY ANEMIA IN PREGNANCY
Anemia in pregnancy
The historical gold standard diagnosis for IDA is bone marrow aspiration with hemosiderin staining, though its invasiveness precludes widespread practice [30]. IDA is often the late stage of iron deficiency, or depleted iron stores in the absence of
KEY POINTS
Serum ferritin is a helpful adjunct for the diagnosis of IDA.
Oral iron remains an option for treatment; absorption is improved with every other day dosing and is effective for patients able to tolerate.
Intravenous iron can be used in obstetric populations;
guidelines provide consideration for use in patients with oral iron intolerance and anemia(less than 10 g/dl) beyond 34 weeks of pregnancy.
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anemia [31,32].Iron deficiency anemiareflects hemo- globin less than 11 g/dl plus evidence of iron defi- ciency. A complete blood count is the most common initial screening tool, with hemoglobin and hematocrit indices less than 11 g/dL or 33%
frequently prompting additional workup.
Peripheral blood smear
Morphologically, IDA findings on microscopy of peripheral smears are microcytosis and hypochro- mia of red cells [30]. Reticulocytes are decreased, consistent with decreased erythropoiesis. Platelets can be increased in IDA and normalized after reple- tion [30,33].
Mean corpuscular volume
In nonpregnant populations, microcytosis (mean corpuscular volume (MCV) less than 80 femtoliters (fL) suggests IDA [30]. However, pregnancy is asso- ciated with higher MCV values [12&&]. Thus, a nor- mal MCV does not exclude IDA [34]. Microcytosis may also be seen with thalassemia minor or sickle beta thalassemia, and macrocytosis points toward folate or vitamin B12 deficiency.
Serum ferritin
Serum ferritin, an intracellular protein crucial for iron storage, is a marker of IDA. Thresholds for defining IDA vary in the literature from serum ferri- tin less than 12–15 micrograms per milliliter (mg/L) to less than 20–30mg/L [35]. The specificity for serum ferritin approaches 98% for both cutoffs [36,37]. Serum ferritin cutoffs at less than 30mg/L are more efficient at identifying IDA; sensitivity, meaning that patients with IDA will be identified, is 25% at serum ferritin of 12–15mg/L vs. 92% at less than 30mg/L [38]. Serum ferritin is also an acute- phase reactant that can be increased by inflamma- tion, infection, stress, liver disease, and neoplastic conditions. In the absence of confounders, serum ferritin can reliably diagnose IDA [37].
Serum iron
Serum iron is a nonspecific marker of IDA [6]. In studies comparing serum iron to serum ferritin as control, the sensitivity of serum iron was 63.5% and specificity, 38.6% [12&&,20&,39]. Normal serum iron level does not rule out IDA.
Total iron-binding capacity
Total iron-binding capacity (TIBC) reflects the avail- ability of the iron transport protein transferrin in serum [40]. Generally, low levels of TIBC correspond to an iron-rich state, and high levels, to an iron-poor environment. The sensitivity of TIBC is 64.5%, and
specificity is 42.85%, identifying it as a less helpful marker for IDA [41].
Serum transferrin saturation
Serum transferrin saturation (TSAT) is the ratio of serum iron to TIBC. TSAT cutoffs to diagnose IDA are less than 16% in absence of inflammation vs. 20%
with inflammation [42]. Given limitations in diag- nosing inflammation, some guidelines use the 20%
cutoff [34].
Hepcidin
Hepcidin is a small peptide that is the main regula- tor of intestinal iron absorption and the release of iron from the macrophages [43]. Secreted by the liver and cleared by the kidney, hepcidin is low in iron deficiency states. Hepcidin levels indicative of iron deficiency precede anemia. Studies are under- way to evaluate thresholds for hepcidin as a single marker of IDA in pregnant women [43,44].
Screening for iron deficiency anemia
Universally, guidelines recommend screening for anemia in pregnancy with the initiation of prenatal care. WHO supports the evaluation of hemoglobin levels with each trimester [12&&]. ACOG recom- mends repeat screening at 24–28 weeks’ gestation;
UK guidelines recommend 28 weeks’ gestation
[4&&,12&&]. Patient signs/symptoms, risk factors,
and medical and surgical history may also warrant additional testing; for example, patients with inflammatory bowel disorders, chronic diseases, pri- mary micronutrient deficiencies, bariatric surgery, or prior surgery impairing gastrointestinal (GI) absorption should undergo interval hemoglobin screening in pregnancy [45,46].
Once anemia is confirmed, serum ferritin levels of less than 30 micrograms per milliliter diagnose IDA in the absence of concomitant inflammation
[12&&,35,48]. Transferrin saturation less than 20%
also diagnoses IDA. Guidelines do not support uni- versal screening for iron deficiency in the absence of anemia in pregnancy; this is a critical gap in the literature and warrants further exploration [47].
Empirical treatment of presumed IDA without definitive diagnosis is optional [4&&,12&&]. However, a workup is indicated if rising hemoglobin indices are not evident within 2–4 weeks of treatment. Ideally, confirmation of IDA with serum ferritintransferrin saturation is recommended prior to treatment [35].
Accurate IDA diagnosis is essential for patients with concomitant hemoglobinopathies, increased bleed- ing risk, and those who decline blood products
[4&&,12&&]. Inconclusive workups warrant referral to a
specialist (i.e., maternal-fetal medicine; hematology).
Iron deficiency anemia in pregnancyIgbinosaet al.
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Management of iron deficiency anemia in pregnancy
Current guidelines support supplementation with 27 mg of elemental iron daily in pregnancy, an equivalency commonly found in over-the-counter prenatal vitamins [48]. Dietary sources of iron are also encouraged (see Table 1). Counseling on diet optimization is important; nevertheless, for most patients presenting with anemia later in pregnancy –diet alone is insufficient.
Oral iron, primarily in the form of ferrous salts (ferrous fumarate, ferrous sulfate, ferrous gluco- nate), is the first-line treatment for IDA [49]. Ferrous salts used to be administered in fractionated dosing of 100–200 mg of elemental iron daily.
Oral iron efficacy increases when taken in the morning after an overnight fast. More recently, single dose daily or every other day appear to be as effective [50,51].
Oral preparations are cheaper, though associ- ated with adverse GI side effects, noncompliance, and less increase in hemoglobin at the time of delivery compared to intravenous (IV) preparations.
A meta-analysis concluded that 40–70% of pregnant people taking oral iron experienced an adverse side effect, largely GI, with oral iron and approximately half discontinued treatment [50]. Iron supplements with enteric coating improve tolerance but inhibit absorption [50].
Consequently, some women will require paren- teral iron. Newer preparations of IV iron have been well tolerated with low anaphylaxis-type reactions and fewer adverse side effects than older formula- tions [34]. IV iron sucrose in pregnancy is efficacious in addressing anemia in late pregnancy, yet draw- backs include dosing (max 200 mg/dose), frequency (average of 4–5 infusions), and duration (1-2 h each) [52–55]. Modern IV irons available include ferric carboxymaltose (FCM), ferric derisomaltose, feru- moxytol, iron polymaltose, and low molecular weight dextran (LMWD) [5&,56]; availability may
vary by country (see Table 1). Advantages include single- and two-dose administrations, shorter infu- sion times, and better safety profiles [56–58]. Nota- ble disadvantages include medication costs, ancillary procedures (peripheral IV placement, monitoring pre, and postinfusion), and evidence on best dosing regimens in pregnancy [59]. Current practices utilize the Ganzoni formula or modified weight-based regimens [60]. Most guidelines sup- port IV iron as a therapeutic option for IDA in patients intolerant of oral iron. UK guidelines sup- port IV iron administration for pregnant patients presenting beyond 34 weeks of pregnancy with hemoglobin below 10ug/L [12&&].
Summary of intravenous irons (Table 2)
Ferric carboxymaltose
FCM, a newer generation of IV iron, allows for rapid infusion [61–63]. FCM shows similar efficacy when compared to other IV iron formulations [64–66].
Adverse reactions such as pruritis, rash, urticaria, and hypotension occurred in less than 1.5%, and serious adverse events, i.e., severe anaphylaxis, occurred in 0.1% (2/1775) [59,67]. In the general population, FCM-induced hypophosphatemia lead- ing to musculoskeletal compromise in association with FCM transfusion is a rising concern [68,69].
Pregnant people may be at increased risk for severe hypophosphatemia after FCM transfusion [70];
there is limited understanding on maternal or fetal implications of hyperphosphatemia.
Ferumoxytol
Ferumoxytol is a ’superparamagnetic iron oxide’
that creates an iron-carbohydrate complex with ele- mental iron permitting rapid infusion [71]. Feru- moxytol is Food and Drug Administration (FDA) approved for adults with IDA [71]. Animal studies have not shown teratogenic effects at human doses, and a clinical trial of 131 pregnant patients had no serious adverse effects [72].
Low molecular weight dextran
LMWD has the advantage of being administered in a single dose. LMWD requires a test dose before infu- sion and has a lower rate of anaphylaxis than its predecessor, high molecular weight iron dextran (HMWD) [73,74]. HMWD is no longer on the market.
Ferric derisomaltose
Ferric derisomaltose, composed of iron hydroxide and derisomaltose, was approved by the FDA in 2020 [75,76]. In clinical trials conducted in nonpregnant Table 1. Common iron rich foods
Meat and eggs Starch Vegetables
-Beef -Lentils -Spinach
-Lamb -Beans -Sweet potatoes
-Ham - Iron fortified cereal (varies) -Peas
-Turkey - Tofu -String beans
-Chicken - Almonds -Collards
-Veal - Baked potato -Kale
-Eggs -Cashews -Chard
Source of Information: USDA National Nutrient Database.
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Table2.IntravenousIron DrugTrade nameElemental IronDosingAnimalstudies[62]Pregnancy&Lactation SafetySerioushypersensitivity reactions[42,59,63] Ironsucrose[53]Venofer20mg/mlMultipledosesof200–300ngNoadverseeffectsMoststudiedIVironin pregnancy Noadversereactionsin nursinginfants
21per100,00 (95%CI,15–26) Ferricderisomaltose [75] (alsoknownasiron Isomaltoside)
Monferric100mg/ml500mg/dose,max3doses 7daysapart Or Singledose20mg/kg Skeletalanomaliesat 0.1–0.3timeshuman dosing
Limiteddata Excretedintobreastmilk0.3%(6in2008)inonetrial Lowmolecularweight irondextran[73]INFeD50mg/ml-Multipledosesof100mgor -singledoseof1000mg(in 250mlnormalsaline)over 1h -testdoserequired
Teratogenicityat3times humandosingPublishedtrialswithrare adversematernal/fetal outcomes Minimallyexcretedinmilk
82per100,000(95%CI, 71–93)–includesHMWD 1.3per100,000[63] FerumoxytolFeraheme30mg/ml510mg/dose,max2doses given3–8daysapartNoeffectsathuman dosing;fetal malformationsat6times humandosing
Studyof164pregnant patientsobstetricoutcomes withinnormal Benefits>risks Note:alsoacontrastagent Noreportedstudieson lactation
34per100,000(95%CI, 23–50) FerricCarboxymaltoseInjectafer50mg/ml750mg/dose,max2dosesTeratogenic0.13–25times humandoseMonitorforhypophosphatemia Excretedinbreastmilk6per100,000[63] SeeBibliographyforcorrespondingreferences.
Iron deficiency anemia in pregnancyIgbinosaet al.
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adults, efficacy was comparable to iron sucrose.
Research on use in pregnancy is limited.
Pregnancy and lactation safety
As a precaution, IV irons are not recommended in the first trimester during organogenesis [34]. The FDA updated labeling for pregnancy and lactation list provides consideration for IV iron use in the second/third trimester [77].
Safety of intravenous irons
Anaphylactic allergic reactions to IV iron are extremely rare, with approximately 1 death per 5 million doses of IV iron [57,73]. Minor reactions of flushing, and chest/flank myalgias may occur sec- ondary to temporary complement activation [73].
Premedication with diphenhydramine is not recom- mended as it may precipitate a Fishbane reaction (transient flushing, chest pain or myalgias) [21,78].
Most minor reactions resolved with pausing and resuming the infusion at a slower rate. Patients with multiple medication allergies may benefit from methyl-prednisone prior to IV iron infusion [72,79]. Institutes/centers desiring to utilize IV iron should identify treatment algorithms to assess and manage reactions [80].
Blood transfusion
Blood transfusions are reserved for severely anemic pregnant patients with active bleeding, hemody- namically instability, and signs of cardiac decom- pensation [12&&,75]. Red cell alloimmunization, infection and allergic reactions, although minor, pose additional consequences for women of child- bearing age.
Postpartum anemia
Postpartum anemia cutoffs vary from 9 to 11 g/dL [13]. A meta-analysis of 15 randomized control trials on postpartum anemia found IV iron increased hemoglobin by 0.9 g/dL more than oral iron at six weeks postpartum (P<0.05) [81]. This rise is similar to the effect seen after transfusion of one unit of red blood cell., IV iron presents as an likely alternative in preventing blood transfusions [81,82].
LITERATURE GAPS/FUTURE DIRECTIONS We have identified several gaps in the literature from the lens of screening, management and out- comes reported. Guidelines and recommendations for anemia in pregnancy reflect a broad spectrum of practice. Several systematic reviews and meta-anal- yses have demonstrated that treatment of IDA can
improve the individual hemoglobin and hematocrit indices. However, it is assumed though not demon- strated if treatment of IDA decreases SMM and improves perinatal/neonatal outcomes. Future stud- ies designed and powered to assess maternal and perinatal morbidity indicators and blood trans- fusion rates can strengthen recommendations.
Research on patient-reported perspectives regarding response to iron therapy and quality of life is also limited. Longitudinal studies on mother–infant are also needed. Global differences in the prevalence of IDA and implications of social determinants of health imply that more understanding of the causes and risk factors for IDA are needed.
SUMMARY
IDA in pregnancy is a known risk factor for SMM and mortality. Screening, management, and treatment guidelines for IDA in pregnancy have the potential to improve adverse pregnancy outcomes. Oral iron with alternate dosing may produce the same effects as daily dosing with less adverse effects. IV irons are reasonable to consider for patients with persistent anemia, intolerance to oral iron, and severe anemia in pregnancy.
Acknowledgements None.
Financial support and sponsorship None.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
& of special interest
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This review provides updated guidance for management of anemia in pregnancy in the United States. Notable changes include removal of race-based hemoglobin cutoffs for the diagnosis of anemia in pregnancy.
Maternal fetal medicine
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