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The incidence of giving low birth weight babies is 14 – 20% if the mother has poor weight gain. At the same time,increase in weight gain has the complications of fetal macrosomia,increase in operative deliveries & caesarean deliveries. Slide 3: CALORIES: Total calory requirement in pregnancy is 80000kcal.i.e 100 to 300 kcal/day needed per day.calorie accumulation maximum in last 20 weeks of pregnancy. Calorie is necessary for energy .If calorie is inadequate,the protein use is spared from fetal growth & development and it has been used for energy requirement. Slide 4: PROTEIN: Needed for growth of the fetus,placenta,uterus,breasts & increased maternal blood volume. Maximum in the second half of pregnancy. Almost all aminoacid levels falls except glutamic acid & alanine which rises in concentration. Good sources are eggs,cheese,poultry,fish, meat,milk Iron requirements : Iron requirements Haem iron Non haem iron Liver,meat,fish,poultry Cereals,greenleafy vegetables,nuts,legumes,oilseeds,jaggery,dried fruits Less bioavailability NORMA Total body iron is 2.5 – 5 gms.It is distributed in Hb - 66%,as ferritin & hemosederin is 25%,others 9%. The 100 ml blood₌15 g Hb₌50 mg of elemental iron.To raise the Hb level by 1 gm/dl –about 200 mg of iron needed Slide 7: Normal iron requirement in normal pregnancy 1000mg Placenta & fetus 300mg Normal excretion 200mg Erythrocytes 500mg In second half of pregnancy the requirement is 6 to 7 mg/ day.i.e 30mg/day of elemental iron orally needed. ABSORPTION OF IRON : ABSORPTION OF IRON Haem Fe+++ Fe++ Ferritin Tf Tf-Fe+++ Fe++ Fe++ Enterocyte Gut Slide 9: Absorbed from the duodenum & upper small intestine in the ferrous state. It combines with glycoprotein TRANSFERRIN,then transported into blood. Stored in mucosal cells as FERRITIN. Excreted mainly as exfoliated G.I.mucosal cells,RBC,in bile,desquamated skin,very little in urine . Slide 10: BODY IRON CYCLING Slide 11: The elemental iron content ¬ the quantity of the iron compound per dose unit should be taken into consideration. Sustained release preparations are not rationale because most of the iron is absorbed from upper intestine. A total of 200mg of elemental iron given thrice daily produces the maximal haemopoietic response. For antenatal mother the recommended iron supplementation dose is 60 mg of elemental iron /day(180 mg of ferrous sulphate). Eligible criteria:patients with Hb level 10 – 12 mg%. Duration : Daily administration until 2 to 3 months after Hb level has returned to normal.Again the Hb levels repeated at 3 to 4 months interval. Slide 12: Adverse effects : Common at therapeutic doses and are related to elemental iron content. Epigastric pain,nausea,vomiting,heart burn,staining of teeth,metallic taste. Constipation – more common due to astringent action of iron Diarrhoea _due to reflect irritant action Slide 13: PARENTERAL THERAPY: Indication: 1)Oral iron not tolerated 2)Failure to absorb the oral iron 3)Non –compliance 4)Severe deficiency Dose calculation: Iron requirement(mg)₌4.4×BW(kg)×Hb deficit(gm%) This formula gives the replenishment of iron stores.Rate of response with parenteral iron is not faster than oral iron.But stores can be replenished faster. Slide 14: Preparations: 1) Iron Dextran (imferon) 2) Iron sorbitol citric acid complex Test dose must be given to screen the sensitivity. I.M should be given deeply in the gluteal region to avoid staining of the skin. Local pain lasting for weeks may occur with higher dose. Iron Dextran (imferon) 2ml daily or alt days or 5ml on each side same day. I.V: Test dose 0.5 ml i.v over 5 – 10 mts followed by 2ml/day (or) Total calculated dose in 500 ml of saline over 6 to 8 hours. PREPARATION AND DOSES : PREPARATION AND DOSES ORAL PREPARATIONS Ferrous sulfate(hydrated salt 20%,exsicated salt 30 %iron) Ferrous gluconate(12% iron ) Ferrous fumarate(33%iron) Colloidal ferric hydroxide(50 % iron) Ferrous succinate Ferrous choline citrate Iron calcium complex (5% iron) Ferric ammonium citrate Ferrous amnioate( 10% iron) Ferric glycerophosphate Hemoglobin (0.33% iron) Slide 16: Ferrous sulfate 200mg tab Ferrous gluconate 300mg tab,400mg/15 ml syrup Ferrous fumarate 200mg tab Colloidal ferric hydroxide 200mg tab,400mg/5ml liquid There is no necessary to provide iron in first 4 months of pregnancy, because the requirement is less, and also to avoid the risk of aggravating symptoms of nausea & vomiting. Ingestion of iron at bed time or empty stomach will increase the absorption.The oral preparation should contain 60 mg of elemental iron.Once th anemia is detected the dose should be 200mg/day of elemental iron. Slide 18: PREGLAC KIT -ca carbonate 1.2mg ferrous fumarate 350mg folic acid 1.5mg, & B6,B12 EVA _ carbonyl iron 100mg(e.iron) folic acid 1.5 mg,& B12,zincsulphate SUPRAFER _ Ferrous ascorbate 100mg(e.iron) Folic acid 1.5 mg FEROMIRA _Ferrous bisglyconate equivalent to elemental iron of 100 mg,FA 1.5mg&B12,zincsulphate IROZORB _Ferrous ascorbate = to elemental iron of 100mg & FA 1.5mg SYP.FEROMIRA 5ml contains Ferric ammonium citrate 100 mg, B12,FA SYP.HAEM UP 5 ml contains Ferric ammonium citrate of 160mg & FA,B12 Slide 20: Adverse effects: Local:Pain at I.M site,Pigmentation of skin,sterile abcess. Systemic:Fever,headache,joint pain,flushing,palpitation,chest pain,dyspnoea,lymphnode enlargement,metallic taste for few hours,anaphylactoid reactions,death. Iron sorbitol contraindicated in kidney disease. Contraindications: Hemosiderosis, hemochromatosis. Iron compounds are also contraindicated in the treatment of anemia other than iron deficiency. E Slide 21: Liquid iron preparations may stain the teeth on continued use. Stains may be prevented to a large extent by taking the dose through a straw, first mixing it with water or fruit juice, and by following the dose with a drink of plain water or juice. Brushing the teeth with sodium bicarbonate or hydrogen peroxide 3% will usually remove existing stains. IRON ABSORPTION & REGULATION : IRON ABSORPTION & REGULATION Slide 23: Iron is brought into the cell through an active transport process involving the protein DMT-1 (divalent metal transporter-1), which is expressed on the apical surface of enterocytes in the initial part of the duodenum. DMT-1 is not specific to iron, and can transport other metal ions such as zinc, copper, cobalt, manganese, cadmium or lead. Once inside the enterocyte, there are two fates for iron: It may leave the enterocyte and enter the body via the basolateral transporter known as ferroportin. It can be bound to ferritin, an intracellular iron-binding protein. For the most part, iron bound to ferritin in the enterocyte will remain there. This iron will be lost from the body when the enterocyte dies and is sloughed off from the tip of the villus. Slide 26: Iron absorption & regulation: Only about 10% of dietary iron is absorbed. Absorption of iron is influenced by many factors including the form in which it is administered, the dose, the status of the patient's iron stores, the degree of erythropoiesis, and the patient's diet. Absorption will be increased in iron deficient individuals. Phytates are found in all kinds of grains, seeds, nuts, vegetables, roots (e.g., potatoes), and fruits,oats,wheat flour. Chemically, phytates are inositol hexaphosphate salts and are a storage form of phosphates and minerals. Phytates strongly inhibit iron absorption in a dose-dependent fashion and even small amounts of phytates have a marked effect. Slide 27: some of the phenolic compounds (mainly those containing galloyl groups) seem to be responsible for the inhibition of iron absorption . Tea, coffee, and cocoa are common plant products that contain iron-binding polyphenols. Many vegetables, especially green leafy vegetables (e.g., spinach), and herbs and spices contain appreciable amounts of galloyl groups, that strongly inhibit iron absorption. Consumption of betel leaves, common in areas of Asia, also has a marked negative effect on iron absorption. Calcium, consumed as a salt or in dairy products interferes significantly with the absorption of both heme and non-heme iron. The mechanism of action for absorption inhibition is unknown, but evidence strongly suggest that the inhibition is located within the mucosal cell itself at the common final transfer step for heme and non-heme iron. An important player in this regulation is the recently discovered hormone hepcidin. Hepcidin is produced by hepatocytes when iron stores are full. Inflammation can also stimulate hepcidin production. Slide 28: Iron dextran complex Iron dextran injection, sterile liquid complex of ferric hydroxide and dextran. . Each mL contains 50 mg of elemental Fe (as an iron dextran complex.) Available as 50 mg/mL, 2-mL and 1-mL vials. A test dose (25 mg Fe) is required for 1st exposure and 1 hour observation. This should be diluted in 50-100 mL of NS and infused over 15-20 minutes. Iron dextran is not to be mixed with any other medication, and should only be diluted with NS. All other IV infusions should be stopped during iron dextran infusion. Recommended in 2 & 3 rd trimester. Slide 29: Sodium Ferric Gluconate A macromolecular complex of sodium ferric gluconate in an alkaline solution of 20% sucrose. It contains no ferrous ion (Fe++) and no dextran. Available as: 12.5 mg/mL, 5-mL ampules (62.5 mg per ampule).No test dose is required. The total Fe deficit (dose) is administered in small installments of 125 mg Fe or less. Each dose is diluted in 100 mL of NS and infused over 60 min. May also be administered undiluted as a slow IV injection at a rate not exceeding 12.5 mg/min (1 mL/min). Slide 30: Iron Sucrose Injection Composition : 100mg/5ml Indications : Iron deficiency, anemia of those patients suffering from chronic haemodialysis. Contraindications : Hypersensitivity, Iron overload Safety Profile : Caution required in pregnancy, safety has not been established to administer in nursing mother, children and geriatric. Adverse Effects : Hypotension, anaphylactoid reactions, musculoskeletal pain, diarrhoea, nausea vomiting, abdominal pain, pruritus, elevated liver enzymes, pain at injection site. Drug Interactions : Conocomitant use with oral iron preparation. Dosage :100mg (5ml) one to three times per week. Slide 31: Ferrous salt preparations (ferrous sulfate, ferrous gluconate, and ferrous fumarate) are equally tolerable. Controlled-release iron preparations cause less nausea and epigastric pain than conventional ferrous sulfate. Ferrous sulfate remains the standard first-line treatment of iron-deficiency anemia given its general tolerability, effectiveness, and low cost. The response to treatment doses of elemental iron is rapid.Reticulocyte count increases within 10 days of initiation 0.8 gm/dl/wk.If no clinical or hematological response is seen after 3 to 4 weeks of oral iron therapy diagnostic reevaluation is required. Slide 32: Side effects of Iron prophylaxis Iron supplementation may interfere with absorption of zinc.Zinc depletion may associated with fetal growth restriction. Iron supplementation in Iron replete woman does not increase the Hb level.The Hb level largely dependent on the increase in plasma volume.So ineffective plasma volume expansion increase the poor rate of poor pregnancy outcome. The excess iron result can result in production of free radicals & oxidative damage.May be implicated in CVS damage & cancer. Iron overloading in women with hemochromatosis also cconsidered. Slide 33: The goal of Iron supplementation in pregnancy is to maintain the maternal reserve during the time of increase demand & it also prevent anemia in infancy. Cochrane study shown that no improvement in Hb levels with iron prophylaxis & it does not appear to benefit fetal growth or pregnancy outcome. But some studies shown that Iron supplementation may prevent reduced or absent iron stores after pregnancy & reduce the risk of iron deficiency in subsequent pregnancy. SELECTIVE IRON SUPPLEMENTATION: Based on the ferritin levels in pregnancy.A s.ferritin level <50 mcg/L in early pregnancy is the indication of iron supplements. S.Ferritin normal value is 50 – 200mcg/L. T.Saturation normal value is 30 -50% Slide 34: The WHO recommends universal Iron supplementaion with 60 mg elemental iron daily for 6 months in pregnancy in areas where the prevalence of iron deficiency is less than <40%. In areas where the prevalence is greater than >40% the recommendation is to continue the supplementation for 3 months postpartum. FOLIC ACID : FOLIC ACID FOLIC ACID - B9 : FOLIC ACID - B9 Chemically it is Pteroyl glutamic acid consisting of pteridine & paraaminobenzoic acid & glutamic acid. Sources:Liver,green leafy vegetables(spinach)egg,meat,milk Daily requirement:RDA is 0.2 mg/day.During pregnancy 0.4 mg – 0.8 mg/day is required. Stored in liver as polyglutamates. Total body store is 5-10 mg. Normally the excretion is trace.But when pharmacological doses are given 50 – 90% of the dose is excreted in urine. Slide 39: FOLIC ACID(POLYGLUTAMATE) GLUTAMATES DHFA THFA METHYLENE –THFA VARIOUS METABOLISM Slide 40: METHYLATION CYCLE &DNA SYNTHESIS Slide 41: FETAL RISK OF FOLATE DEFICIENCY Folate acts as a cofactor for enzymes involved in DNA and RNA biosynthesis and methylation cycle Mechanism of NTD and Folic acid The cause of most NTDs is unknown Interruption of DNA biosynthesis or methylation reactions could prevent the proper closure of the neural tube. Such inhibition could be caused by simple deficiency of either folic acid or vitamin B12. or may be indirectly due to the high homocysteine levels. Folate depletion associated with high homocysteine levels. Whether the folate depletion or the high homocysteine levels or the both causes NTD is contraversial. Slide 42: Inborn errors of folate and homocysteine metabolism may be involved in the etiology of NTDs. Although some cases of NTDs are induced by hyperhomocysteinemia resulting from genetic polymorphism of a thermolabile enzyme. mutations in the methylenetetrahydrofolate reductase gene represent genetic risk factors for NTDs . There are additional folate-related genes that contribute to NTD pathogenesis, including mutant forms of folate receptors (FR) such as FR. Genetic associations between molecular variations of the FR gene and NTDs have been documented, suggesting that this gene may be a risk factor for human NTD : Why is the neural tube so sensitive to maternal folate or homocysteine? Other developing organ systems can also be seriously affected, but probably to somewhat lesser extents. One possible mechanism relates to the important role of folate for one carbon metabolism in nucleic acid and amino acid biosynthesis in rapidly dividing cells. Another theory implicates impaired cellular remodeling (apoptosis) of the neural tube in folate-associated NTDs. Slide 44: The anti folate drugs like trimethoprim, triamterene, methotrexate, aminopterin and sulfasalazine causes NTD by inhibiting enzyme DHFRedutase when the administered in first trimester. Folate deficiency may also be related to other serious birth defects,like urinary tract and cardiovascular congenital abnormalities and congenital limb deficiencies , orofacial cleftings, cleft lip and cleft palate, omphalacele Slide 45: Supplementation of folate in a periconceptional (atleast one month prior to conception) dose of 0.4 mg/day can prevent the first occurrence >80% . Up to 85% of recurrent neural tube defects can be prevented ,If the 4mg FA supplementation started one month prior & first 3 months of pregnancy. WOMEN WHO HAVE HAD A PREVIOUS NTD-AFFECTED PREGNANCY the recurrence risk is 2% to 3% in subsequent pregnancies. In folate-resistant NTDs, inositol can cure such defects. This is believed to be occur by the up-regulation of the retinoic acid receptor in the underlying hindgut endoderm, correcting a proliferation defect. Slide 47: MATERNAL RISK: Megaloblastic anemia: Always secondary to folate deficiency. Diagnosis: peripheral smear: oval macrocytes,hypersegmented neutrophil Red cell folat level:normal is 6 to 20 ng/ml.values ≤4ng/ml considered as folate deficiency. Folate dficiency in pregnancy is not always accompanied by hematological changes.In the absence of changes when the expected response to adequate iron therapy is not achieved,megaloblastic hemopoiesis is suspected. VitB12 & folicacid: The routine supplementation of FA is the risk to women with B12 deficiency.Because it worsens the neuropathy.But the risk is low in Slide 48: pregnancy because,pernicious anemia is the disease of the elderly & patients with severe deficiency are usually infertile. WHO RECOMMENDATIONS(prophylaxis): Folate intake of upto 400mcg daily with 60mg iron for 6 months during pregnancy & continuing for 3 months postpartum in areas of world with poor nutrition. Estabilished folate deficiency: Folic acid 5mg once daily continued for several weeks postpartum. Anticonvulsants: They interfere with folate metabolism by inhibiting the enzyme THFR.Interferece of epilepsy control by folate supplementation may be overestimated.FA supplementation should be continued in this patients. CALCIUM & VIT D3 : CALCIUM & VIT D3 Total calcium in human body is 1 – 1.5 kg.99% of which is seen in bone. Milk is a good source of calcium.cow’s milk 100mg/100ml and in human milk 30mg/dl.other sources are fish egg,vegetables. Daily requirement: Adult – 500mg/day child -1200mg/day pregnancy and lactation _1500mg/day Normal S.calcium level is 9 -11 mg/day Slide 51: Absorption from the 1st & 2nd part of duodenum. Excreted mostly in stools and also by urine. Vit D3: Naturally derived from 7- dehydrocholestrol by the action of UV rays.It is isomerised to form Vitamin D3 (OR) cholecalciferol. 7- dehydrocholestrol uv ray Cholecalciferol(D3) ergocalciferol (D2) Commercially the vitamine derived from fungus,ergot. Vit D3 is a prohormone. Slide 52: Liver kidney cholecalciferol Action of VIT D3: Increases the absorption of Ca from intestine by fascilitating the synthesis of calbindin, a ca binding protein.It binds with ca ,and increases the absorption in brush border cells. Increases the absorption of ca in brush border cells. Requirement: Adult 5 to 10 mcg/day ; pregnancy & lactation 10 mcg/day [ 1 mcg= 40I.U] sources: sunlight,fish oil,fish & egg yolk sac 25OH CC 1,25 OH CC(CALCITRIOL) Pharmacological preparations : Pharmacological preparations Ca chloride(27% of ca): Ca gluconate(9% ca): Ca lactate (13% ca) Ca dibasicphospate(23% ca) Ca carbonate (40%) Ca citrate (21%) Side effects: g.i side effects like constipation,bloating RDA:Adult – 1 g:pregnant & lactating women – 1.2 – 1.5 g/day:Older age – 1.5 g/day Slide 54: SHELCAL: ca carbonate 1.25 gms:Vit D3 250 I.U SUPRACAL:Ca citrate 1g,vit D3-200I.U MACZORB: Ca asparate 560 mg CALMIGEN:Ca citrate 1g :vitD3 200 I.U SYP.CALCIMAX: 5 ml Caco3 625 mg ,VIT D3 200I.U SYP. Osteocalcium : 5 ml - vit D3 200 I.U,caphosphate 82 mg Efforts to prevent preeclampsia using calcium supplementaion have not proven efficacious.and it is not recommended in routiene pregnancy. Slide 55: Calcium Carbonate Absorption: Calcium Carbonate is alkaline based, it requires extra stomach acid for better absorption, Calcium Content: Calcium Carbonate is the most prevalent calcium supplements in the market . It provides more elemental calcium than Calcium Citrate. calcium carbonate is 40% calcium and the citrate form is 21% calcium. Calcium Gluconate and Calcium Lactate: These types of calcium supplements contain low content of elemental calcium. Slide 56: Calcium Citrate : Absorption: Calcium is best absorbed in an acidic environment, hence calcium citrate is the best absorbed supplemental form of calcium. It does not require extra stomach acid for absorption, Calcium content: Calcium Citrate usually provides less elemental calcium per pill than Calcium Carbonate, therefore one may need to take a relatively more numbers of pills per day to meet the needs. : ZINC: Severe congenital zinc deficiency causes acrodermatitis enteropathica and this deficincy causes poor appetite,suboptimal growth,impaired wound healing,dwarfism,hypogonadism. RDA is 12mg/day Maternal plasma zinc concentration in the third trimester can suggest mothers at risk of having IUGR baby. IODINE: Severe iodine deficincy causes congenital cretinism.In subclinical deficiency it causes neurodevelopmental defect .RDA is 220mcg/day in lactation, & 290mcg /day in lactation Slide 58: SELENIUM: Important defensive component in free radical damage.severe deficiency causes fatal cardiomyopathy in children and women of child bearing age. Slide 59: The highest estimated prevalence of dietary inadequacy in early &late half of pregnancy is Iron 93%,Zinc 80-88%,folate74 -87%,calcium82-86%.. VIT A:2 forms Beta carotene & retinoids .Doses higher than RDA 5000I.U should be avoided in pregnancy. Slide 60: THANK YOU You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.