This neonatal case presentation involves a 16 day old infant admitted to the NICU with jaundice since birth and vomiting for 1 day. Investigations revealed severe anemia, indirect hyperbilirubinemia, increased reticulocyte count, and elevated LDH. The infant received a PRBC transfusion and was discharged with improved Hb. The clinical picture is suggestive of hemolytic anemia, possibly due to fetomaternal hemorrhage given the maternal history of blood transfusions in the second trimester.

1. Neonatal Case Presentation

2. • 16 day old child was admitted to NICU on
04/03/17 with
-h/o Yellowish discoloration of skin from D1 of life.
-h/o Vomiting 2-3 episodes from 1 day.
• Has shown to local doctor for yellowish
discoloration on D3 and D8 and no treatment was
advised.
• No h/o convulsions,high pitched cry or arching.
• Vomiting from last 1 day-contains milk and
immediately after feeding.
• No h/o bilious vomiting, abdominal distension ,
constipation , poor feeding ,dark colored urine ,
clay colored stools.

3. Antenatal History:G2P1L1,Spontaneosuly concieved.
ML-4 yrs,NCM.
MBG-O positive.
Had regular ANC.Antenatal USG –Normal.
No maternal h/o GDM,PE.
Not on medication except nutritional supplements.
Maternal h/o receiving 2 pint of BT on 5th and 6th month
of gestation.(Hb6gm%)
Birth History: Delivered via LSCS,Indcn-Non progression of
labour.
Baby Cried immediately after birth.
Birth weight-3.25kg.
Breast fed within a hour.
Family history:No h/o blood transfusions,jaundice in
family.
Elder sibling 2 yrs old female apparently healthy

4. On examination:
-PR-142/min N volume,regular. -Normothermic
-RR-42/min.
-SpO2-94% in room air
-CRT:2 sec.
Anthropometry:Wt-3.2kg,Length-49cm,HC-
35.5cm.
Head to toe examination:Icterus Zone- 4
Pallor +.
No dysmorphic features.

5. Systemic Examination:
P/A: soft non distended,no organomegaly.bowel
sounds heard.
CVS: S1,S2 heard .No murmur.
R/S:clear,AE adequate.
CNS:CRAT- good,AF at level.Moro-complete.

6. TERM /AGA/S/MCH/PROLONGED
JAUNDICE FOR EVALUATION?BREAST
MILK JAUNDICE.

7. Investigations:
CBC:
Hg-5.1gm%,HCT-18.4%
RBC-1.5 million/cumm
MCV-121.1fl (105-125fl)
MCH-33.6pg (35-38pg)
MCHC-27.7gm/dl (32-34gm/dl)
Nucleated RBC-3030cells/cumm
Reticulocyte-3%
TLC-17,310/cumm(N-30%,L-61%)
Plt-7.15 lakh/cumm

8. Periphreal smear:
RBC
-severe anisopoikilocytosis,majority are
macrocytic with severe hypochromasia,good
no of microcytes,oval,elongated,pencil shaped
cells.
-No inclusions seen.
-Normoblasts 6/100 WBC (3-10/100 WBC)
-No parasites seen.
Impression:Dimorphic anemia with Leucocytosis

9. • MBG-O positive, ICT-Negative
• BBG- O positive, DCT-Negative.
• RFT ,Electrolytes-Normal.
• TSB-Total-13.7mg/dl,D-11.4,I-2.1mg/dl.
• Thyroid profile-Normal

10. • G -6-PD:Present,No deficiency.
• Vitamin B12,Folic acid-WNL.
• Serum LDH-863 IU/L (N 80-285IU/L).
• Hb Electrophoresis:HbF-74%,HbA-27%.
Normal for age.
• CT Brain-No e/o IC bleed.

11. • 16D old T/AGA Mch with severe anemia and
jaundice.
• No features HSM,CCF,dysmphorphology.
• Maternal h/o BT in 2nd trimester.
• Investigation-
- Severe anemia with indirect hyperbilirubinemia.
- Increased reticulocyte count
- Negative coombs test
- Smear examination-Dimorphic anemia
- Eleveated LDH

12. TERM/AGA/S/M/Severe anemia
? Hemolytic anemia.
?Feto-maternal Hemorrhage

13. Course in Hospital:
• Feeds started on admission.
• Received PRBC transfusion 20ml/kg.
• Discharge: Hb-10.1gm%
• On follow up baby thriving well, planned for
repeat CBC at 3 months and repeat
electrophoresis at 6 months.

14. Approachto Neonatal Anemia

15. Definition:
• Defined as Hb>2 SD, below mean for postnatal
age.
• Anemia in 1st week is defined as Hb<14gm/dl.
• Any significant fall in Hb ,even if within normal
range.Eg:Birth-18.5gm% and 1st week-14gm%.
• Failure of Hb to raise during first few hours of life
–may first clue for hemolysis or hemmorage.

16. Fetal Erythropoesis:
• Erythropesis in fetus sequentially in different
sites-
-Yolk sac: maximal btw 2-10 wks
-Liver : By 6-8 wks liver is primary erytropoetic
organ
-Bone marrow:Begins at 18th week & at 30th
week is major EP organ
• Fetal EP is independent from mother.
• EPO (produced in liver)plays role in hepatic
and BM phase.

17. Fetal Erythrocyte:
• Fetal RBC-Higher O2 affinity.(no interaction 2,3 –DPG)
• Types of Hb:
- Embryonic Hb: Gower-1: ζ2 ε2
Gower-2: α2 ε2
Portland: ζ2 γ2
-Fetal Hb: Hb F: α2γ2
-Adult Hb: Hb A : α2 β2
Hb A1: α2 δ2
• Hb,HCT,and RBC count increase throuh fetal life.
• Large RBCs with increased Hb in early fetal life,size and
content decrease through gestation.
• MCV-180fl in embryo
-130fl mid gestation.
-110fl at term .

18. Neonatal Erythrocyte:
• Life span of the red blood cell (RBC) at birth is lower
than that in adult 60-70 days (preterm 35-50 days).
• Larger MCV and lower MCHC, and are more
susceptible to oxidant-induced injury mainly due to a
deficiency in phosphofructokinase activity.
• High frequency of dysmorphology of RBC in term
neonates14% are spherocytes and poikilocytes
compared to 3% in adults, more in preterm neonates.
• Rate of haemoglobin synthesis and RBC production
decreases sharply during the first few days after
delivery due to decrease in EPO in the plasma

19. Normal Values in Newborn period:
Hb and Hematocrit:
• Term infant ranges from 15.7-17.9gm/dl.
• Rises shortly(15%) after birth-absolute and
relative.
• Normal Hct:51-56% rises during few hours and
reaches original value by 1 week

20. Reticulocyte count:
Term Newborn
-At birth-3-7%
-4th day-1-3%
-7th day < 1%
• PT infants reticulocyte count is higher 6-10%
remains higher for longer period.
Nucleated RBC:
• Term infants has 0-24
NRBC/100leukocytes.(higher in PT)
• Disappear 3-4 days in Term and 7-10days in PT

21. RBC count:
4.6-5.2 million/cumm at birth,rises and returns
to normal value by 1 week
RBC indices:
MCV:105-125fl,<95fl-microcytes
MCH:35-38pg,<34pg-hypochromia

22. Etiology:
• Anemia in neonatal period is due to three
distinct causes:
1. Hemorrhage: Acute/chronic,
prenatal/postnatal
2. Hemolysis: Immune/nonimmune
3. Failure of red cell production.

23. Hemmorage:
• Prenatal Blood Loss-
-Placental –placenta previa,abruptio,vasa previa
-fetomaternal blood loss
-Retroplacental Bleed
-Twin-to-Twin Transfusion
• Postnatal Blood Loss
-skipped ligature of cord
-traumatic delivery leading to subgalel or
intrabdominal bleed.
-Iatrogenic Anemia(sampling)

25. Hemolysis:
Anemia with reticulocytosis,Unconjugated
hyperbilirubinemia and hemoglobinuria without any
evidence of Hemorrhage.
1. Immune Mediated
-Rh hemolytic disease
-ABO incompatibilty.
2. Non Immune mediated
-Red cell membrane defects :Hereditary
spherocytosis, elliptocytosis,stomatocytosis
-Hemoglobinopathies:Alpha thalassemia , Gamma
thalassemia
-RBC enzyme abnormalities:G6PD deficiency , pyruvate
kinase deficiency, 5’ nucleotidase deficiency and glucose
phosphate isomerase deficiency.
-Infection:TORCH,Malaria

26. Failure of Red Cell Production
1. Congenital
-Pure red cell aplasia (Diamond-Blackfan
anemia),
-Aase syndrome and
-Fanconi’s anemia
2. Anemia of premaurity

27. Diagnostic Approach:
• History and physical examination can give a lead to the cause
of anemia in a newborn.
• Family history of anemia, cholelithiasis, unexplained jaundice
and splenomegaly - Hereditary hemolytic anemia.
• Obstetric history of difficult labor,instrumentation, bleeding or
placental abnormalities - Hemorrhagic anemia.
• The age at which anemia manifest also is of diagnostic
importance.
-Significant anemia at birth is due to blood loss or
alloimmunization.
- After 24 hours, internal hemorrhage and other causes of
hemolysis manifest.
-Anemia of prematurity, hypoplastic anemia and abnormalities
of synthesis of hemoglobin chain generally appear several
weeks after birth.

28. • Coombs test, reticulocyte count, mean
corpuscular volume, MCH and blood smear
are the key investigative tools for diagnosing
the cause of anemia in newborn.

29. Management:
Transfusion:
• Hypovolemic shock d/t acute blood loss- 10-20
ml/kg of whole blood, cross matched with
mother transfused immediately.
• Remaining situations, the decision to transfuse
takes into consideration a combination of
clinical signs and laboratory parameters.
• Transfusion products for neonatal transfusions
should be leukocyte-depleted, irradiated for
infants weighing <1200 g and from selected
donors to limit donor exposure.

30. Transfusion Guidelines:
Roseff SD, Luban NL, Manno CS. Guidelines for assessing appropriateness of
pediatric transfusion. Transfusion 2002;42:1398e412

31. Transfuion guidelines in PT :

32. The Premature Infants in Need of Transfusion
(PINT) study:

33. PINT trial:

34. Transfusion in anemia of prematurity:
Whyte RK, Jefferies AL, Canadian Paediatric Society, Fetus and Newborn
Committee. Red blood cell transfusion in newborn infants. Paediatr Child
Health 2014;19:213e22.

35. Erythropoietin:
• Transitory reduction in EPO production in the first
few months after birth.
• Early administration of EPO reduces the use of RBC
transfusions, the volume transfused, number of
donor- limited clinical importance and significant
increase in ROP,reduce or increase any important
adverse outcomes including mortality,
intraventricular hemorrhage and NEC.
• Late EPO does not significantly reduce or increase
any clinically important adverse outcomes except for
a trend in increased risk for ROP
Aher SM, Ohlsson A. Late erythropoietin for preventing red blood cell transfusion
in preterm and/or low birth weight infants. Cochrane Database Syst
Rev 2014;(4):CD004868

36. Prevention:
• Delivery room practices:delayed cord clumping,milking or
striping of the umbilical cord, and drawing all NICU baseline
laboratory blood tests from fetal blood in the placenta.
• Measures to reduce blood loss: limiting phlebotomy losses for
blood testing; returning the dead space volume after sampling
an arterial catheter; microtechnique laboratory procedures;
and the development of non-invasive monitoring
• Adopting transfusion guidelines and locally adapted
transfusion criteria.
• EPO Early administration might be considered in selected
circumstances, but should not be routinely recommended.
• Iron supplementation:2010 AAP recommends iron for
breastfed term infants at 4month.
-Preterm start supplementation at 4-6wks.
• Vitamin E(5-25IU)daily upto 40 wks.

37. References:
• Colombatti et al. Anemia and transfusion in the
neonate/ Seminars in Fetal & Neonatal Medicine 21
(2016) 2e9.
• Neha rastogi et el,Anemia in Newborn.In:Practical
Pediatric Hematology 2nd ed.2006 ;pp 35-40.
• E.Henry et al.Reference intervals in Neonatal
Hematology/Clinics in Perinatology 42(2015) 483-487.
• Matthews et al.Erythrocyte disorders in
Infancy.In:Avery’s Diseases of Newborn 7th ed;p1080-
88.
• Asimenia et al.Anemia.In:Cloherty’s Manual of
Neonatal Care 8th ed;p537-45