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DATE. 5/10/78
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/ A very interesting paper showing elevation in FEP in infants is related { to iron deficiency.
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FROM:
E. S. JACOBS
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Pet. Lab. . Ext. 2702
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May 1978
The Journal o/PEDIATRICS
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Free erythrocyte porphyrins in cord blood
Red cellfree erythrocyte porphyrin determinations were performed on cord blood specimensfrom 236 term infants and on capillary blood specimensfrom 63 preterm infants weighing less than 1,500 gm, .during the first week of life. These results were contrasted with those obtainedfrom 398 normal infants and children ages 1 to 6years. The mean FEP valuefor the infants was significantly higher than that observed in the normal control subjects. In 10.5% of the. term infants and 15,9% of the preterm infants, values in excess of 120 pg/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values werefound to have lower serum iron and transferrin saturation values than did infants with low FEP values. Thesefindings suggest that elevations in cord blood FEP values may indicate a state ofrelative iron deficiency present at birth.
Michael A. Gottuso,* Barbara F. Oski, and Frank A. Oski, Syracuse, N. Y,
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Th e me a s u r e me n t of.free-erythrocyte porphyrin is now widely used as a sensitive screening test for the detection of both lead poisoning and iron deficiency anemia.1" Several studies*" * have demonstrated that some infants may be bom with elevated cord blood lead levels. A study was initiated to screen cord blood specimens for the presence of intrauterine lead! poisoning, utilizing FEP determinations. Many newborn infants had FEP values higher than those ofnormal children, and these elevations did not appear to reflect lead poisoning. The purpose of this communication is to describe our efforts to find an explanation for the elevated FEP values observed in newborn infants.
MATERIALS AND MET HODS
Cord blood specimens were collected at the time of delivery from infants born at Community General Hospital and St. Joseph's Hospital, both, in Syracuse, New York. Two cord blood specimens were collected from each infant, one in a heparinized tube and one in a tube with no anticoagulant (Vacutainer, Becton, Dickinson & Co., Rutherford, NJ 07070). FEP determinations were performed on 20 lambda specimens by the method of Piomelli1" employing- an Aminco-Bowman spectrofluoromcter. Blood lead levels were measured bv atomic
From the Department of Pediatrics, State University of New York, Upstate Medical Center, *Repritu address: Department of Pediatrics. State University Hospital, 750 E. Adams St.. Syracuse, NY 13210.
Vol 92, No. 5, pp. 810-812
absorption spectrofluorometry'* in the New York State Laboratories. Serum iron and percentage of transferrin saturations were determined by the method of Jung and Parekh1- by means of a Dupont Automatic Clinical. Analyzer. Serum ferritin assays were performed through the courtesy of Dr. Peter Dallman of the University of California, San Francisco.
Abbreviations used FEP; free erythrocyte porphyrin RBC:' red blood cells
RESULTS .
Initially, cord blood samples from 236 term infants were analyzed for FEP levels and contrasted with concur rent samples obtained from infants and children I to 6 years of age and from 63 preterm infants during the first week oflife (Table I). AH infants and children (I to 6 years of age) classified as normal had blood lead values of less than 30 pg/dl and were not iron deficient. All preterm infants Had birth weights of less than 1,500 gm.
The mean FEP values in both the term and preterm infants were significantly higher than those observed in normal infants and children in the 1- to 6-year age range. Although the mean FEP value observed in the preterm infants was higher than that of the term infants, the difference was not statistically significant. It was found that 10.5% of the term infants and 15.9% of the preterm infants had FEP values above the highest value, 120 pg/dl
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RBC, that was recorded in the normal population of older
infants and children.
Blood lead determinations were performed on 14
infants with the lowest FEP values and contrasted with
similar determinations in 13 term infants with the highest
FEP values {Table II). The mean blood lead values in
these two groups were identical.
The FEP values of infants with low cord blood hema
tocrits were contrasted with those of normal infants
(Table III). Considerable overlap in FEP values existed
and there was no significant difference between these two
groups.
After the initial study failed to reveal any relationship
between either blood lead or hematocrit and elevations in
FEP, ioO more infants were studied. Ten infants with FEP
values in excess of 125 pg/dl RBC were identified. Serum
iron and percentage of transferrin saturation values were
contrasted with those of 20 infants with low FEP values
(Table IV). This comparison revealed that infants with
elevated FEP values had significantly lower values for
both serum iron and percentage of transferrin saturation.
Serum iron values' in the high FEP group averaged 127
pg/dl. This is normal by conventional standards applied
to older infants, children, and adults, but is well below the
mean observed for the low FEP group. The value of 177 in
this latter group is in close agreement with the. mean
values of 173 and 193 reported by Hagberg'-' and Stur
geon,^ respectively.
Similarly, the transferrin saturation of 43.4% observed
in the infants with the elevated FEP values would be
considered normal by standards applied to older infants
and children but is significantly lower than the value of
72.1% observed in the infatns with the normal FEP levels.
Cord blood transferrin saturation has been reported to
range normally between 65 and 80% in other investiga-
tions.15- M
" The total iron binding capacity averaged 316 jtg/dl in
the infante with elevated FEP values as contrasted with a
value of 240 pg/dl in the infante with normal FEP values
(Table IV).
..
..
Serum ferritin values were obtained in additional term
infants with high and low FEP values (Table V). Only one
infant wa$ found with a ferritin level in the range
considered diagnostic of iron deficiency. This value was
less than 10 ng/ml and was observed in the infant with the
highest FEP value.
DISCUSSION
Previous studies have suggested that porphyrin values may rise in red cells when iron supply is inadequate to meet the demands of intense erythropoiesis.17-'-'" The level of free erythrocyte porphyrin has been shown to be
Free erythrocyte porphyrins 811
Table I. Free erythrocyte porphyrin values in preterm infants. Full-term infants, and norma} subjects between I and 6 years of age
Group
A'o. of subjects
. FEP (Hg/dl RBC)
Mean* Rouge
%of group with
values in excess of 120 jigidl
RBC
Preterm infants
63 933 * 48 46-306
Term infants
236 813 a: 28 33-200
Normal children 398 54.0 * 20 8-120
(1-6 years of
age)
15.9 10.5 0.0
Values expressed as mean I SD.
Table II, Comparison of blood lead values in irifanls with "high" and "low" cord blood FEP values
Group No.
Low" "High"
. 14 13
FEP (pg/dl BBC)
Mean
Range
57 45-64 146 125-199
Blood lead -<K'dl)
Mean Range
. 1U 12.0
7-13 . 10-15
Table III, Comparison of cord blood FEP values in infante with "high" and "low" hematocrits .
Hematocrit
Hemet-
<%)
tocrit
No. Mean
Range
"Low" 20 42
"High" 20
58
39-44 56-62
PEP (ag/dlRBC)
Mean Range
77.4 48-137 92.9 49-181
increased in children with blood lead values In excess of 30 pg/dl.'- -' In addition, children 1 to 6 years of age and adults with reduced serum iron values and transferrin saturations of less than 16%'-7 usually have elevations in FEP. The measurement of serum iron and transferrin saturation alone, however, may not always be suitable for making judgments regarding iron sufficiency under such circumstances. The finding of .elevated FEP values in newborn infants with seemingly adequate serum levels of iron may be ari example of such a situation. The fact that serum iron values and transferrin saturations in infants with elevated EEP levels were significantly lower than those of normal infants is consistent with such an inter pretation. The etevation in total iron binding capacity also supports the hypothesis that the elevated FEP reflects a form of relative iron deficiency rather than chronic intrauterine infection. FEP values may rise in chronic
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The Journal of Pediatrics May 1978
Table IV. Iron status of infants with "high" and "low" cord blood FEP values
FEP
FEP
RBC)
groP So. Mean Range
Senim iron
(V-g/dl)
Transferrin saturation
Mean Range Mean Range
"Low" .20 "High" 10
44 33-54 177 128-257 72.1 49-92
40.3
19
156 126-200 127 94-182 43.4 5-70
30.2
20
Table V. Serum ferritin values in infants'with "high" and "low" cord blood FEP values
"High" FEP
Subject
FEP
Ferritin
No. (tig/dlRBQ (Pg/!)
1 2 3 4 5 Mean
156 177 178 231 376 224
110 77 89 151 5.9 86.6
"Lon" FEP
FEP
Ferritin
(pg/dl RBC) in'1)
' 38 48 52 73
. 77 58
>200 175 68 . 53 91 117.5
inflammatory states,5' -55 but in such situations the
decrease in serum iron concentration is usually
accompanied by a fall in the transferrin level.
In states of iron deficiency the levels ofserum ferritin
are low.111- The failure in our study to find significant
differences in. serum ferritin values between a small
number ofinfants with high and iow FEP values indicates
the need for further studies to determine the clinical
significance of an elevated cord blood FEP, Serial evalu
ation of such infants with respect to iron status may
provide an answer.
-
REFERENCES
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2. Piomelli S, and Davidow B: Free erythrocyte protopor phyrin concentration: A promising screening test for lead poisoning. Pediatr Res 6:366, 1972.
3. Piomelli S, Davidow B, Quince VF, et al: The FEP (free erythrocyte porphyrins) test: A screening mjeromethod for lead poisoning. Pediatrics 51:254, 1973. '
4. Kammholz LP, Thatcher LG, Blodgett FM, and Good TA: Rapid protoporphyrin quantitation for detection of lead poisoning, Pediatrics 50:625, 1972.
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screening technique for increased lead absorption in young children, J Pe d iat r 84:490, 1974. 6. Koening HM. and Lightsey AL; The micromeasurement of free erythrocyte porphyrin (FEP) as a means of differen tiating alpha-thalassemia trait from iron deficiency anemia, Pediatr Res 8:404. 1974. . 7. Piomelli S, Gay G. and Young P: Rapid diagnosis of Fe
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'
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DaggJH, Goldberg A, and Lochhead A: Value of erythro
cyte protoporphyrin in the diagnosis of latent iron defi ciency, Br J Haematol 12:236, 1966. 20. Langer EE, Hauling RG, Labbe RF, Jacobs P, Crosby EF, and Finch CA: Etythroeyle protoporphyrins. Blood 40:112, 1972. 21. Cartwright GE, Lauritsen MA. Jones PJ, et al: Anemia of
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