Clinical Obstetrics—A Case-based Approach Anjali Tempe, Pushpa Mishra, Niharika Dhiman
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Anemia in PregnancyCHAPTER 1

Ashok Kumar,
Ruchi Gupta,
Divya Arora
 
CASE SCENARIO
 
History of Present Complaints
  • Patient was a booked antenatal case in some private hospital in Sonipat since 4 months amenorrhea.
  • She got all her routine antenatal investigations done at 5 months amenorrhea and diagnosed with moderate hemoglobin.
  • She was non compliant with oral iron tablets and was transfused 6 doses of iron sucrose and with that her hemoglobin improved.
  • Again at 8 month of pregnancy she, became symptomatic and was referred to Lok Nayak Hospital (LNH) in view of severe anemia.
 
Course in the Hospital
  • She was admitted to labor room after her general, physical and abdominal examination.
  • Her blood sample [full blood count (FBC), blood group cross match, liver function test, kidney function test, serum electrolytes] was taken and patient was evaluated. She was diagnosed with moderate anemia with microcytic hypochromic picture in peripheral smear.
  • She was shifted to clean maternity ward, to be investigated and evaluated for the cause of anemia.
 
History of Present Pregnancy
Spontaneous conception, planned pregnancy.
 
First Trimester
  • Pregnancy was confirmed, at home by urine pregnancy test when she was overdue by 10 days.
  • She had no history of any bleeding or discharge per vaginum, pain lower abdomen, fever with rashes, bladder and bowel symptoms, self-medication or radiation exposure.
  • Folic acid (FA) was started once her pregnancy test came positive after she consulted in local dispensary. Her FA intake was occasional.
  • She reported mild symptoms of morning sickness and managed with dietary modification.
  • Ultrasonography was done in first trimester that showed positive cardiac activity.
 
Second Trimester
 
Amenorrhea Continued
  • Quickening felt at around 5 months. Iron and calcium started. FA not taken. Two doses of tetanus toxoid were received.
  • Blood and urine test were done and patient was diagnosed with moderate anemia. As she was noncompliant due to nausea and vomiting, i.e. intolerance after oral iron, injectable iron (six doses) was transfused. Her anemia got corrected. There is no history of any blood transfusion.2
  • Level II ultrasound was done in fifth month of pregnancy and was normal.
  • No history of breathlessness, easy fatigability, burning micturition, blood from any orifices, passage of worms in stools, swelling over feet, bleeding or leaking per vaginum or increased blood sugar was there.
  • She visited antenatal clinic thrice and her blood pressure was normal on all visits.
 
Third Trimester
 
Amenorrhea Continued
  • She was intolerant to oral iron. FA not taken. Calcium intake was normal.
  • She had breathlessness and fatigability at eighth month of amenorrhea. She was investigated and diagnosed with severe anemia.
  • She was referred to LNH in view of severe anemia and nonavailability of blood bank in dispensary.
 
Obstetric History
Married since 12 years, consanguineous marriage.
 
G3P2L1A0
  • G1—booked at Ambedkar hospital at 2 months amenorrhea, had preterm intrauterine demise (IUD) at 8 months, delivered by induction of labor 10 years back. Baby was female,1.8 kg birth weight, history of diabetes mellitus or hypertension was there, no morphological abnormality was detected in baby. Breast suppression was given, postnatal period was uneventful. Discharged in satisfactory condition on postpartum day 3.
  • G2—booked at LNH at four months amenorrhea. She had preterm lower segment cesarean section (LSCS) in view of severe preeclampsia with moderate hemoglobin with poor bishops score eight years back, baby was female 2 kg birth weight, admitted in nursery for 6 days. No history of PPH or any blood loss (surgical). Two units of packed cell transfused post-LSCS in view of severe anemia. SRC out on day 2, complete stitch removal on day 10. Uneventful postpartum period. Baby six months breastfed, is alive and healthy with normal milestones, immunized till date.
  • G4—present pregnancy.
 
Menstrual History
  • Menarche—14 years of age
  • LMP—13/10/2016
  • Estimated date of delivery (EDD)—20/07/2017
  • No history of dysmenorrhea, menorrhagia.
 
Medical History
No history of chronic hypertension, diabetes mellitus (DM), tuberculosis, asthma or any seizure disorder in past, or any chronic gastrointestinal complaints.
 
Surgical History
Not significant.
 
Family History
Not significant.
 
Personal History
  • She is a housewife with normal bowel and bladder pattern with normal sleep pattern.
  • Nonvegetarian, nonalcoholic and no other addictions.
 
Socioeconomic History
She lives in a nuclear family of four, pukka house, Municipal Corporation of Delhi (MCD) water supply with modern sanitation and electricity facilities. As per modified Kuppuswamy scale she belongs to lower middle class.
 
Dietery History
  • Patient takes approximately 2200 kcal.
  • Her protein intake is approximately 60 g.
 
Diagnosis on History
G3P2L1A0 with POG 30 week 2 days with moderate anemia with previous lower segment cesarean section (LSCS).
 
Examination
Patient is conscious, oriented, sitting comfortably in bed, average built with normal gait, normal hair line, average orodental hygiene.
  • Gestational carrier (GC)—good
  • Weight—65 kg.
  • Height—150 cm.
  • Body mass index (BMI)—28.8 kg/m2 [according to prepregnancy weight]
  • Pallor—present, clinically 7-8 g%.
  • Icterus—absent.
  • Cyanosis—absent.
  • Clubbing—absent.3
  • Pedal edema—absent.
  • Pulse rate—90/min, regular, rhythmic, no radioradial or radiofemoral delay.
  • Blood pressure (BP)—110/80 mm Hg in right arm in sitting.
  • Respiratory rate—16/min.
  • Thyroid—normal
  • Lymph nodes—not palpable.
 
Respiratory System
Trachea centrally placed, no added sounds.
 
Cardiovascular System
S1, S2 normal with no abnormal sound.
 
Abdominal Examination
 
Inspection
  • Abdomen is uniformly distended with all quadrants moving with respiration.
  • Linea nigra and stria gravidarum present, transverse scar of previous LSCS present.
  • Umbilicus is central and everted, no herniation observed.
 
Palpation
  • Fundal height—30 weeks
  • Symphysio fundal height—28 cm
  • Abdominal girth—31.5 inches
  • Fundal grip—a soft broad ballotable structure felt at fundus, suggestive of breech
  • Lateral grip—smooth and curved structure felt on right lateral side of abdomen, suggestive of back
  • Multiple nobby parts felt on left side, suggestive of limbs
  • Pelvic grips—a hard, globular and smooth structure is felt on palpation, suggestive of head, was freely mobile and not engaged.
 
Auscultation
Fetal heart sounds were heard at right spinoumbilical line, 130 beats/min, regular.
 
Perineal Examination
  • External genitalia—normal
  • No bleeding and no leaking observed.
 
Per Speculum Examination
  • Os closed
  • Cervix long
  • No abnormal discharge or bleeding observed.
 
Diagnosis After Examination
G3P2L1A0 with POG 30 week 2 days with cephalic presentation with moderate anemia with previous LSCS, not in failure.
Her blood investigations are as follows:
  • Hemoglobin (Hb)—8 g%
  • Hematocrit (Hct)—30%
  • Mean corpuscular volume (MCV)—74 fL
  • Mean corpuscular hemoglobin (MCH)—24 pg
  • Mean corpuscular hemoglobin concentration (MCHC)—29%
  • Peripheral smear shows microcytic hypochromic red blood cells (RBCs) rest unremarkable
  • Nestroft—negative
  • High performance liquid chromatography (HPLC)—normal
  • Stool ova and cyst—not observed, no occult blood seen
  • Serum protein—6 g%
  • Lactate dehydrogenase (LDH)—320 IU/L
 
Treatment
As patient was intolerant to oral iron, injectable iron was given to her on alternate days for 8 doses calculated according to her prepregnancy weight. Patient was discharged on day 19 with Hb 10.1 g/dL.
Calculation of dose of iron (mg) = (2.4 ×[target Hb - actual Hb] × prepregnancy weight (kg)) + 10 mg/kg for stores replenishment.1
Q1. Define anemia and its epidemiology.
Anemia in pregnancy is defined by hemoglobin levels, trimester wise as:
  • First trimester <11.0 g/L
  • Second and third trimesters <10.5 g/L
  • Postpartum period <10.0 g/L.2
According to World Health Organization (WHO):
Hemoglobin of <11 g/dL, or hematocrit <33%, irrespective of trimesters.3
Center of disease control and prevention (CDC)—according to Hb and Hct:4
  • First and third trimesters—Hb <11 g/dL, Hct <33%
  • Second trimester—Hb <10.5 g/dL, hematocrit <32%.4
The WHO defines hemoglobin for all:
  • Severe hemoglobin Hb <7 g/dL
  • Very severe hemoglobin Hb <4 g/dL.5
National Family Health Survey IV
  • Non-pregnant female (15–49 years of age)—Hb <12 g%.6
  • Pregnant women (15–49 years of age)—Hb <11 g%.6
In India, prevalence of hemoglobin by WHO estimates was 65–75%. 50% of maternal deaths, worldwide due to anemia, occur in South Asian countries, 80% being contributed by India.7
Q2. How will you classify anemia according to severity?
The severity of anemia is based on the patient's Hb/hematocrit:5
Pregnancy state
Normal (g/dL)
Mild (g/dL)
Moderate (g/dL)
Severe (g/dL)
First trimester
11 or higher
10–10.9
7–7.9
Lower than 7
Second trimester
10.5 or higher
Third trimester
11 or higher
10–10.9
7–7.9
Lower than 7
Q3. What are the causes of anemia?
Causes of Anemia8
 
Acquired Causes
  • Iron deficiency anemia—dietary/chronic blood loss/worm infestation
  • Megaloblastic anemia—vitamin B12 and folic acid deficiency
  • Anemia of inflammation or malignancies, e.g. chronic renal disease, tuberculosis, etc.
  • Aplastic or hypoplastic anemia
  • Drug induced, e.g. alkylating agents like vincristine, chloramphenicol, anticonvulsants especially primidone, quinine, alpha methyldopa, etc.
  • Anemia caused by acute blood loss—postpartum hemorrhage (PPH)/ectopic/abortions, etc.
 
Hereditary Causes
  • Thalassemia
  • Sickle cell hemoglobinopathy and hemoglobinopathies
  • Hereditary hemolytic anemia.
Q4. How will you diagnose iron deficiency clinically?
Symptoms and signs are usually nonspecific.
  • Symptoms—fatigue, weakness, headache, dizziness, palpitations, irritability, poor concentration, hair loss.
  • Signs—pallor, tachycardia, dyspnea, glossitis, stomatitis, restless leg syndrome, pica.911
Q5. Laboratory tests for diagnosis of iron deficiency anemia.
Full Blood Count (FBC)2
  • ↓Hb and Hct
  • ↓MCV
  • ↓MCH
  • ↓MCHC.
Blood Film
Microcytic hypochromic RBCs.
Serum Ferritin2,7
  • Earliest laboratory marker to become abnormal
  • Best test for iron deficiency anemia (IDA) with cut off of 30 µg/L.12 The values <15 µg/L indicates severe deficiency.
  • Sensitivity was 92% and specificity 98%.13
  • Serum ferritin initially rises followed by gradual fall till 32 weeks, slight increase is observed in third trimester.
Serum Iron (Fe) and Total Iron Binding Capacity (TIBC)
Unreliable indicators of tissue iron levels as fluctuation in levels observed with recent ingestion of Fe, diurnal rhythm and other.
Zinc Protoporphyrin (ZPP)
Unaffected by hemodilution. It increases with decrease in serum iron ZPP as zinc, is incorporated into the protoporphyrin ring in place of iron.
Reticulocyte Hemoglobin Content and Reticulocytes
It decreases in iron deficiency.
Soluble Transferrin Receptor (sTfR)
Sensitive marker13
A meta-analysis of ten studies of sTfR showed that it had a sensitivity of 86% and a specificity of 75%.14
Bone Marrow Iron2
Gold standard but clearly too invasive and not practical for any but can be done for most complicated cases in pregnancy.
Q6. What do you understand by trial of iron therapy?
  • In trial of iron therapy first we measure serum ferritin and rule out hemolysis with Nestroft.
  • If negative a trial of iron preparation either oral or injectable depending on period of gestation was given.5
  • Response to therapy was assessed by demonstrating a rise in Hb after 2 weeks. It is both diagnostic and therapeutic.
  • If no improvement is observed in Hb by 2 weeks, one should rule out other causes.3
Q7. Enumerate the factors influencing iron absorption.
Factors Inhibiting Iron Absorption
  • Foods rich in calcium
  • Tannins in tea
  • Phytates in cereals.
Factors Enhancing Iron Absorption
  • Heme iron
  • Ferrous iron
  • Ascorbic acid
  • Low iron stores.
Q8. What are the maternal and fetal effects of iron deficiency?
Effects of iron deficiency anemia have been described on:
Maternal Effects
  • Decrease immunity with increased susceptibility to infections15
  • Decrease work capacity and performance16
  • Postpartum emotional and cognition disturbances.17
Fetal Effects
  • Relatively unaffected.18
  • Impaired psychomotor and/or mental development.
  • Social emotional behaviour of infant is negatively affected.19
Effects on Pregnancy Outcome
Increase risk of preterm delivery,20 low birth weight,21 possibly placental abruption and increased peri-partum blood loss.22
Q9. Describe in brief the management of iron deficiency anemia.
Dietary Advice
  • Mothers should be advised to take food rich in iron
  • Due to very high requirement of iron, iron and folic acid should be given to all pregnant patients as prophylaxis to prevent anemia
  • To optimize absorption of iron, its intake should be spaced properly with meals rich in phytats, tannins, calcium
  • Maternal iron requirements are approximately 1000 mg in singleton pregnancies (500 mg for maternal hemoglobin, 300 mg for placenta and fetus, and 200 mg that is shed normally through gut, urine and skin)
  • Approximately 10 mg iron is absorbed from food, i.e. 15% of dietary iron
  • Pregnant women iron requirements are thrice as high as menstruating women23
  • Iron absorption increases by three-fold with progressive gestation, with iron requirements increasing from 1–2 mg to 6 mg per day in third trimester24
  • The main sources of dietary heme iron are from nonvegetarian foods like red meats, fish and poultry
  • Heme iron is 2- to 3-fold readily absorbed than nonheme iron sources which contributes approximately 95% of dietary iron25
  • Vitamin C markedly enhances iron absorption from non-heme foods26
  • Germinated and fermented food decreases phytate thereby improving bioavailability of nonheme iron
  • Tea and coffee (tannins) if taken with a meal or shortly after it decreases iron absorption
  • Deworming should be done in all patients
    • Tablet albendazole 400 mg single dose
    • Tablet mebendazole 500 mg single dose or 100 mg twice daily for 3 days.
Oral Iron Supplements
  • In pregnancy increased iron demands cannot be fulfilled by dietary changes alone and hence iron supplements are required
  • Ferrous iron salts cheap, effective, and safer way to replace iron and are the preparation of choice. The effective oral dose should be 100–200 mg of elemental iron daily.
Dose and elemental iron content per tablet of oral iron preparations:
Iron salt
Dose per tablet
Elemental iron
Ferrous ascorbate
500 mg
100 mg
Carbonyl iron
45 mg
Ferrous fumarate
200 mg
65 mg
Ferrous gluconate
300 mg
35 mg
Ferrous sulfate (dried)
200 mg
65 mg
Ferrous sulfate
300 mg
60 mg
Ferrous feredetate (Sytron)
190 mg/5 mL elixir
27.5 mg/5 mL elixir
Counseling should be done on how to take oral iron.
  • Preferably empty stomach
  • At least 1 hour prior meals
  • Along with vitamin C
  • Avoid other drugs like antacids.6
Q10. What are the Indications for oral iron supplementation?
  • All antenatal women should have a FBC taken at the booking and at 28 weeks [National Institute of Health and Clinical excellence (NICE), 2008]27
  • Trial of therapeutic iron replacement should be offered to women with a Hb <11 g% until 12 weeks or <10.5 g% beyond 12 weeks
  • In a women with hemoglobinopathy trial of iron therapy can be offered if the ferritin is <30 µg/L
  • The patient who are intolerant to oral iron, i.e. having excessive nausea and vomiting, lot of upper gastrointestinal (GI) discomfort to the extent patient avoid taking oral iron. Such patients are advised to take iron tablets after meals
  • To be given for 6 months in countries with prevalence <40% and additional 3 month postpartum where the prevalence >40%.
Q11. Enumerate non-anemic women with increased predisposition for anemia.
  • Inter-conceptional anemia
  • Frequent pregnancies ≤1 year interval in between
  • Vegetarians
  • Teenagers
  • Women with bleeding disorders
  • Known hemoglobinopathy.
Q12. How will you assess response to oral iron supplementation?
Clinical improvement is assessed as:
  • Increased sense of well being
  • Increase in work capacity
  • Improvement of other symptoms.
Laboratory parameters:
  • Reticulocyte count—increase up to 5% in 5–7 days.
  • Hb—increase @ 0.8–1 g/dL/week after 2–3 weeks.
  • RBCs indices—improvement in MCV/MCH/MCHC after 2–3 weeks.
  • Peripheral smear—normocytic normochromic picture in 6–8 weeks.
Q13. Describe in brief regarding indications and contraindications of parenteral iron therapy.
Indications
  • Poor compliance to oral iron
  • Intolerance to oral iron therapy
  • Lack of response
  • Postpartum hemoglobin
  • Women with GI disorders that hampers oral iron absorption
  • Proven malnutrition.
Contraindications
  • Hypersensitivity to parenteral iron therapy
  • First trimester of pregnancy
  • Noniron deficiency hemoglobin
  • Active acute or chronic infection
  • Chronic liver disease.
Q14. Describe in brief various injectable iron preparations.
Injectable iron preparations available
Iron hydroxide dextran complex
Iron hydroxide sucrose complex
Iron carboxymaltose
Iron isomaltoside
Dose of elemental iron
50 mg/mL
20 mg/mL
50 mg/mL
100 mg/mL
Test dose
Yes
Yes
No
No
Routes of administration
Slow intravenous injection/
Intravenous infusion/
Intramuscular injection
Slow intravenous injection/
Intravenous infusion
Slow intravenous injection/
Intravenous infusion
Slow intravenous injection/
Intravenous infusion
Able to administer total
Dose
Yes (up to 20 mg/kg bodyweight over 4–6 h)
No
Yes [up to 20 mg/kg bodyweight
(maximum of 1000 mg/week)
over 15 min]
Yes (up to 20 mg/kg bodyweight over 1 h)
Dosage
100–200 mg per IV injection up to 3 times a week
Total IV single dose no more than 200 mg, can be repeated up to 3 times in 1 week
1000 mg by IV injection up to 15 mg/kg per week
100–200 mg per IV injection up to 3 times a week Total dose infusion up to 20 mg/kg body weight per week
Total dose infusion up to 20 mg/kg bodyweight over 4–6 h) (100 mg IM into alternate buttocks daily in active patients in bed ridden up to 3 times a week)
Total dose infusion up to 20 mg/kg bodyweight. Maximum weekly dose of 1000 mg, which can be administered over 15 min
Doses up to 10 mg/kg bodyweight can be administered over 30 min, doses >10 mg/kg body weight should be administered over 60 min
Adverse effects
5%
0.5–1.5%
3%
1%
7Q15. Describe fast-acting intravenous iron preparations.
Iron III Carboxymaltose
  • It facilitates controlled delivery of iron within the cells of the reticuloendothelial system
  • Followed by delivery to the iron binding proteins ferritin and transferrin.
Iron III Isomaltoside
This compound has strongly bound iron in spheroid iron-carbohydrate particles, allowing slow release of bioavailable iron to iron binding proteins thereby increasing reticulocyte count with in few days.
Q16. What are the recommendations for parenteral iron administrations and how to calculate the dose?2
Consider parenteral iron administration from second trimester onwards and postpartum period in case of failure or intolerance to oral iron.
  • The dose to be calculated on the basis of prepregnancy weight, with a target Hb of 11 g/mL.
  • Written informed consent should be there regarding potential side-effects.
Calculation of dose of iron (mg) =
  • [2.4 × (target Hb–actual Hb) × prepregnancy weight (kg)] + 10 mg/kg for stores replenishment.1
  • Iron (mg)–{weight (kg) × (14 – Hb) × (2.145)
C—concentration of elemental iron (mg/mL) in the product being used, e.g. iron sucrose 20 mg/mL.
Q17. Indications of blood transfusion in a women with anemia.
Royal College of Obstetrics and Gynecologists (RCOG) blood transfusion guideline recommends blood transfusion in labor or immediate postpartum period if Hb <7 g/dL.28
Indications of Blood Transfusion In Pregnancy29,30
Antepartum Period
  • Pregnancy <34 weeks
    • Hb <5 g/dL with/without signs of cardiac failure or hypoxia
    • 5–7 g/dL—in presence of impending heart failure.
  • Pregnancy >34 weeks
    • Hb <7 g/dL even without signs of cardiac failure or hypoxia
    • Severe anemia with decompensation.
  • Anemia not due to hematinic deficiency
    • Hemoglobinopathy or bone marrow failure syndromes
    • Hematologist should always be consulted.
  • Acute hemorrhage
    • Always indicated if Hb <6 g/dL
    • If the patient become hemodynamically unstable due to ongoing hemorrhage.
Intrapartum Period
  • Hb <7 g/dL (in labor)
  • Decision of blood transfusion depends on medical history or symptoms.
Postpartum Period
  • Anemia with signs of shock/acute hemorrhage with signs of hemodynamic instability
  • Hb <7 g/dL (postpartum): Decision of blood transfusion depends on medical history or symptoms.
Q18. Strategies for prevention of iron deficiency anemia.
A summary of recommendations by WHO and MoHFW:3133
During Pregnancy
Prophylaxis
Treatment
WHO
Daily 60 mg iron + 400 µg folic acid till term
Daily 120 mg iron + 400 µg folic acid—3 months
MoHFW
Daily 100 mg iron + 500 µg folic acid—6 months
Mild anemia—2 IFA tablets/day—100 days
Moderate anemia—IM iron therapy + oral folic acid
Severe anemia—IV sucrose
During Postpartum
WHO
Daily 60 mg iron and 400 µg folic acid—3 months
MoHFW
Daily 100 mg iron and 500 µg folic acid—6 months
Q19. What are the differential diagnosis of microcytic hemoglobin and how will differentiate them?
Differential diagnosis of various microcytic RBCs etiologies:34,35
Indicator
Iron deficiency hemoglobin (IDA)
Beta thalassemia (BT)
Dimorphic hemoglobin
Acute/chronic infections (ACI)
Hb
Decreased
Normal or decreased
Decreased
Decreased
Ferritin
Decreased
Normal
Decreased or normal
Normal or increased
Serum iron
Decreased
Normal or increased
Normal or decreased
Normal or decreased
TIBC
Increased
Normal
Increased
Slightly decreased8
TS
Decreased
Normal to increased
Normal or decreased
Normal to slightly decreased
sTfR
Increased in severe IDA
>100 mg/L
normal
Normal
FEP
Increased
Normal
Normal/increased
Increased
MCV
Decreased
Decreased
Normal/increased/decreased
Normal or decreased
RDW
Increased
Normal to increased
Increased
Normal
Reticulocytes
Decreased
-
Decreased
Normal or decreased
Abbreviations: TIBC, total iron binding capacity; sTfR, soluble transferrin receptor; FEP, free erythrocyte protoporphyrin; MCV, mean corpuscular volume; RDW, red cell distribution width
 
CASE SCENARIO
 
History of Presenting Complaints
  • Patient was a booked antenatal case of same hospital
  • She complained of easy fatigability and breathlessness on exertion since 1 month
  • No history of any blood loss from any site
  • No history of any cardiac illness in present or past
  • No history of any respiratory disorders
  • No complains of any bleeding or leaking per vaginum.
 
Course in the Hospital
  • She was admitted to the labor room after her general and abdominal examinations.
  • Her blood samples [full blood count (FBC), blood group cross match, liver function test, kidney function test, serum electrolytes] was taken and patient was evaluated. She was diagnosed with moderate anemia with macrocytic normochromic picture in peripheral smear.
  • She was shifted to clean maternity ward, investigated and evaluated for the cause of anemia.
 
History of Present Pregnancy
Spontaneous conception, planned pregnancy.
 
First Trimester
  • Pregnancy was confirmed, at home by urine pregnancy test when she was overdue by 20 days
  • No intake of folic acid in first trimester. Rest unremarkable.
 
Second Trimester
Unremarkable.
 
Third Trimester
  • Amenorrhea continued and patient develops gradual onset weakness, fatigability, and breathlessness over a period of 1 month
  • Her iron intake was occasional, folic acid not taken.
 
Obstetric History
  • Married since 11 years
  • Non-consanguinous marriage.
 
G4P2L1A1
  • G1—was a supervised pregnancy at LNH, had full-term emergency LSCS in view of fetal distress, 9 years back
  • G2—was a supervised pregnancy at LNH, had full-term vaginal delivery, 4 year back
  • Baby was male, 2.6 kg birth weight, cried after birth
  • Died at 6 month of age due to drowning
  • G3—spontaneous abortion
  • G4—present pregnancy.
 
Menstrual History
  • Menarche—14 years of age
  • LMP—17/09/2016
  • Estimate date of death delivery (EDD)—24/06/2017.
  • No history of dysmenorrhea, menorrhagia.9
 
Medical History/Surgical History/Family History/Personal History
Unremarkable.
 
Socioeconomic History
Unremarkable.
 
Dietery History
  • Patient takes approximately 1,700 kcal as per 24 hour recall method.
  • Her protein intake is approximately 40 g. Her calorie deficit was 500 kcal and her protein deficit was 20 g. Diet modification to include increase protein and calories explained.
 
Diagnosis on History
G4P2L1A1 with POG 32 weeks 4 days with moderate anemia with previous one LSCS not in failure.
 
Examination
Patient is conscious, oriented, sitting comfortably in bed, average built with normal gait, normal hair line, average orodental hygiene.
  • GC—good
  • Weight—50 kg
  • Height—150 cm
  • BMI—22.2 kg/m
  • Pallor—present, clinically 7–8 g%
  • Rest unremarkable
  • Systemic examination—unremarkable.
 
Abdominal Examination
 
Inspection
Unremarkable.
 
Palpation
  • Fundal height—32 weeks
  • Symphysio fundal height—30 cm
  • Abdominal girth—32.3 inches
  • Grips—unremarkable.
 
Auscultation
Fetal heart sounds were heard at right spino umbilical line, 140 beats/min, regular.
 
Perineal Examination
Unremarkable.
 
Per Speculum Examination
Unremarkable
 
Diagnosis after Examination
G4P2L2A0 with period of gestation (POG) 32 week 4 days with cephalic presentation with moderate anemia with previous LSCS not in failure.
Her blood investigations are as follows:
  • Hb—7.2 g%
  • Hct—24%
  • Mean corpuscular volume (MCV)—106 fl
  • Mean corpuscular hemoglobin (MCH)—21 pg
  • Mean corpuscular hemoglobin concentration (MCHC)—27%.
Peripheral smear shows macrocytic normochromic RBCs with anisopoikilocytosis, macro-ovalocytes, with hypersegmented neutrophils.
  • Nestroft—negative
  • HPLC—normal.
 
Treatment
Diagnosis of megaloblastic anemia is made based on examination and laboratory investigations. Injectable iron is also given along as there is increased requirement during erythropoisis.
7 doses of injection elderwit (B12—2500 μmg, 0.7 mg folic acid, 150 mg vitamin C/1.5 mL) given alternately with injection iron sucrose. Patient was discharged on 17th day with Hb 9.5 g/dL.
Q1. How will you confirm the diagnosis of megaloblastic hemoglobin?
Peripheral smear and FBC will suggest type of anemia followed by serum B12 and folate levels measurement for confirmation.
  • Serum B12 level <100 pg/mL suggest B12 deficiency.
  • Serum folate level <2 ng/mL suggests folate deficiency anemia.
  • Fasting serum folate level <6 µg/L and RBC folate <165 µg/L are diagnostic of folate deficiency.
Q2. Causes of megaloblastic hemoglobin?
Megaloblastic hemoglobin is usually caused by a deficiency of folic acid or vitamin B12.10
Other less common causes are:36
  • Alcohol abuse
  • HIV infection
  • Certain inherited disorders
  • Atrophic gastritis and achlorhydria
  • Pernicious hemoglobin
  • Pancreatic insufficiency
  • Zollinger-Ellison syndrome
  • Inflammatory bowel syndrome
  • Tropical sprue
  • Blind loop syndrome
  • Drugs that affect DNA, such as chemotherapy drugs
  • Leukemia
  • Myelodysplastic syndrome
  • Myelofibrosis
  • The anticonvulsant drug dilantin.
Q3. Describe the pathophysiology of megaloblastosis?
Due to deficiency of B12 and folic acid, a defect in DNA synthesis in rapidly dividing cells with RNA and protein causes megaloblastosis.
Arrest in nuclear maturation causes unbalanced cell growth and impaired cell division.
It causes intramedullary hemolysis.37,38
Q4. What are the symptoms and signs of megaloblastic hemoglobin?
Symptoms39
  • Weakness, fatigue
  • Gastrointestinal—loss of appetite, weight loss, nausea, constipation
  • Neurological—numbness, pain, tingling, and burning in a patient's hands and feet stocking or glove neuropathy.
Signs41
  • Lemon color complexion
  • Palpitations, glossitis
  • Hyperpigmentation of skin and abnormal hair pigmentation
  • Peripheral neuropathy, psychosis, abnormal gait, speech impairment, loss of propioceptive and vibratory senses
  • Weight loss, abdominal distension, diarrhea, and steatorrhea.
Q5. Enumerate the dietary sources of vitamin B12 and folic acid.
The primary sources of cobalamin (Clb), a cobalt-containing vitamin, are meat, fish, and dairy products and not vegetables and fruit.
The folate is found in fresh vegetables, fruits, and animal protein. Dietary folic is usually conjugated, polyglutamate folates, and are converted to dihydrofolic acid, so they can be absorbed.
Q6. What are the daily requirement of folic acid and vitamin B12 during pregnancy?
  • Daily 400 µg of folic acid.40
  • Daily vitamin B12 2.6 μg.
Q7. Enumerate the differential diagnosis of macrocytic picture in peripheral smear.
Serum and vitamin B12 deficiency
  • Hypothyroidism
  • Liver disease
  • Myelodysplasia
  • Hydroxyurea
  • Alcoholism
  • Lesch-Nyhan syndrome
  • Homocystinuria.
Q8. What are the maternal and fetal effects of folate and cobalamin deficiency.
Folic acid deficiency increases risk of neural tube defects (NTDs), low birth weight, and small for gestational age (SGA).
  • Maternal vitamin B12 status affects fetal growth and development.
  • Low cobalamin increases risk of fetal low lean mass and excess adiposity, increased insulin resistance and impaired neurodevelopment.
  • Maternal risks include fatigue, pallor, tachycardia, poor exercise tolerance and suboptimal work performance.
  • Depleted blood reserves during delivery may increase the need for blood transfusion, preeclampsia, placental abruption, cardiac failure and related death.
Q9. How will you treat B12 deficiency in pregnant women?
  • Oral: 1000 μg of vitamin B12, daily should be given to patient with serum levels to be monitored to ensure adequate repletion.
  • Sublingual: For patients with absorption disorder, i.e. bariatric surgery, steatorrhea, malabsorption syndromes.
  • Parenteral: Non-responders and patients with neurological features.
Treatment of clinical vitamin B12 deficiency has traditionally been accomplished by intramuscular injection 11of crystalline vitamin B12 at a dosage of 1 mg weekly for eight weeks, followed by 1 mg monthly for life.41
Q10. What is the difference in response to oral and intramuscular treatment with B12?
In a 2005 Cochrane review, patients who received high dosages of oral vitamin B12 (1–2 mg daily) for 90–120 days had an improvement in serum vitamin B12similar to patients who received intramuscular injections of vitamin B12.42
Q11. How will you treat a folate deficiency?
As little as 1 mg of folic acid administered once daily, produces a striking hematological response by 4–7 days after beginning of treatment. The reticulocyte count increases with leukopenia and thrombocytopenia correction.
Q12. How will you monitor response of the treatment?
Clinically improvement assessed as:
  • Increased sense of well being
  • Improved working capacity
  • Improvement of glossitis
  • Improvement of depigmentation
  • Improvement of neurological symptoms.
Laboratory parameters to assess improvement are:
  • Decrease in LDH levels by 3–4 days
  • Increase in reticulocyte count by 5–7 days
  • Increase in hemoglobin 0.8–1 g/dL/week
  • Peripheral smear shows normocytic normochromic RBCs.
Q13. Any counseling do you want to give to folate deficiency patients for prevention of NTDs in next pregnancy?
Preconceptional folic acid 4 mg daily is advised for 3 months and should be continued in first trimester.
 
CASE SCENARIO
 
History of Presenting Complaints
  • She was a booked antenatal case in government hospital, Najafgarh, New Delhi
  • She had breathlessness since 2 months. It was gradual in onset and increased progressively
  • She had palpitations since 1 month
  • She had weakness which was gradual in onset and markedly increased since 10 days
  • She had no history of any cardiac disorder in present or past
  • She had no history of any respiratory illness in present or past
  • She had no history of bleeding per vaginum or blood loss from any other orifices.
 
Course in the Hospital
  • She was admitted to labor room after her general physical and abdominal examination which showed severe pallor, PR 100/min, RR 18/min, hemic murmur on cardiovascular system (CVS) examination with bilateral chest clear and presence of abdominal wall edema with pedal edema, rest unremarkable.
  • She was evaluated again in labor room, propped up, oxygen saturation done (100%), continued oral intake with monitoring of vitals, input, output, chest auscultation to detect earliest symptoms and signs of cardiorespiratory failure.
  • Intermittent oxygen by mask continued.
  • Fetal monitoring continued as routine (NST at admission, DFMC, intermittent auscultation)
  • Her blood samples [full blood count (FBC), blood group cross match, liver function test, kidney function test, serum electrolytes] was taken and patient was evaluated. She was diagnosed with severe anemia with microcytic hypochromic picture in peripheral smear.
  • All other reports normal except serum proteins 5 g/dL.
  • Patient was evaluated and investigated and diagnosed with severe hemoglobin not in failure.
Her blood investigations on 7/5/17 are as follows:
  • ABO Rh—B+
  • Hb—5.1 g/dL
  • Hct—14.9%
  • MCV—57 Fl
  • MCH—14.8 pg
  • MCHC—26.1%
  • RDW—16.7
  • TLC—14900/cumm
  • Platelet—1.69/cumm12
  • Serum total bilirubin—1.6
  • Aspartate transaminase (AST)—10
  • Alanine transaminase (ALT)—22
  • Serum proteins—5 g/dL
  • Blood urea—22 mg/dL
  • Serum creatinine—1.2 mg/dL
  • Prothrombin time (PT)—14.4
  • International normalized ratio (INR)—1.12
  • Hepatitis B surface antibody (HBsAg)—Nonreactive
  • Venereal disease research laboratory (VDRL)—nonreactive
  • Human immunodeficiency virus (HIV)—nonreactive.
Decision of packed cell transfusion is made. Patient was transfused 3 units of packed RBCs under lasix cover. Her post-BT Hb was 8 g/dL. She went into labor two days after that and was delivered vaginally uneventfully. Her post-natal Hb was 7.6 g/dL. She was given 5 doses of iron sucrose in view of postnatal hemoglobin.
She was discharged on 24/5/17.
 
History of Present Pregnancy
Spontaneous conception, unplanned pregnancy.
 
First Trimester
Unremarkable.
 
Second Trimester
Blood and urine test were done and patient was diagnosed with moderate anemia. As she was intolerant to oral iron. Rest unremarkable.
 
Third Trimester
  • Amenorrhea continued.
  • She was intolerant to oral iron. FA not taken. Calcium intake was normal.
  • She had breathlessness and fatigability at eighth month of amenorrhea. She was investigated and diagnosed with severe anemia.
  • She was referred to LNH in view of severe anemia and nonavailability of blood bank in Najafgarh hospital.
 
Obstetric History
 
G3P1L1E1
  • G1—was a supervised pregnancy at LNH, had full-term emergency LSCS in view of Naval Physical and Oceanographic Laboratory (NPOL) distress, 10 years back. Baby was female, 2.8 kg birth weight 6 months breastfed. SRC out on day 2rd, stitch removal on day 7. Discharged satisfactory on day 7th.
  • G2—diagnosed with unruptured left tubal ectopic pregnancy. Treated medically at LNH, 7 year back.
  • G3—present pregnancy.
 
Menstrual History
History of menorrhagia present. 7–8 days of bleeding, every 24–25 days with 6–7 pads soaked daily for 5–6 days.
 
Dietery History
Patient takes approximately 1500 kcal as per 24 hour recall method.
Her protein intake is approximately 35 g. Her calorie deficit was 700 kcal and protein deficit was 25 g. Dietary advice given.
 
Diagnosis on History
G3P1L1E1 with POG 37 week 4 days with severe anemia with hypoproteinemia with previous one LSCS, not in failure.
 
Examination
Patient is conscious, oriented, average built with normal gait, normal hair line, average orodental hygiene.
 
General Condition
  • GC—good
  • Weight—50 kg
  • Height—150 cm
  • BMI—22.2
  • Pallor—present, clinically 3–4 g%
  • Icterus—absent
  • Cyanosis—absent
  • Clubbing—absent
  • Pedal edema—present
  • Pulse rate—104/min, regular, rhythmic, no radioradial or radiofemoral delay
  • BP—110/80 mm Hg in right arm in sitting
  • Respiratory rate—22/min
  • Cardiovascular examination—S1, S2 normal, hemic murmur heard.
 
Abdominal Examination
 
Inspection
Unremarkable.
 
Palpation
  • Fundal height—40 weeks
  • Symphysiofundal height—34 cm
  • Abdominal girth—35.46 inches
  • Presentation—cephalic.13
 
Auscultation
Fetal heart sounds were heard at right spinoumbilical line, 150 beats/min, regular.
 
Perineal Examination
Unremarkable.
 
Per Speculum Examination
Unremarkable.
 
Diagnosis after Examination
G3P1L1E1 with POG 37 weeks 4 days with cephalic presentation with severe anemia with previous LSCS not in failure.
Q1. How will you manage the patient of severe anemia in labor?
1st Stage
  • Patient should be propped up
  • Intermittent oxygen should be given
  • High-risk consent
  • The patient should be in bed preferably in position comfortable to her
  • Send urgent hemogram with BGCM
  • Arrange and transfuse adequate packed cell
  • Intermittent chest auscultation
  • Strict asepsis should be followed
  • Fluid restriction (IV fluid)
  • Watch for symptoms and sign of cardiac failure.
2nd Stage
  • Partogram to be maintained
  • Concentrated oxtytocin should be given if required.
3nd Stage
  • Active management of third stage of labor (AMSTL)
  • Avoid postpartum hemorrhage (PPH).
  • Avoid any genital trauma. Prophylactic episiotomy to be given, if required.
4nd Stage
  • Patient should be kept in observation for at least 6 hours postpartum
  • Prophylactic antibiotics can be considered to prevent sepsis
  • Iron and folic acid should be continued 6 month postpartum
  • Contraception advice
  • Barrier methods
  • POPs
  • Sterilization if family completed.
Q2. How will you manage hypoproteinemia?
Hypoproteinemia is characterized by low protein level. It causes fluid loss from intravascular to interstitial space resulting in edema.
Causes
  • Malnutrition as part of nutritional anemia
  • Hypertensive disorders
  • Deranged blood sugars/hyperglycemias
  • Infections
  • Liver diseases
  • Renal diseases
  • Nutritional deficiency
  • Malabsorption
  • Septicemia
Diagnosis
Serum protein-albumin and globulin.
Treatment
  • Nonspecific: Dietary protein supplementation irrespective of cause is the most common way of treatment.
  • Specific: Treating underlying cause.
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