936
June 1975 The Journal o f P E D I A T R I C S
Studies in calcium metabolism in infants with intrauterine growth retardation Serial serum Ca values in 47 infants with intrauterine growth retardation wereanalyzed in relation to clinical and biochemicalfactors. Serum Ca concentrations in IUGR infants fell within the 95% confidence limits for serum Ca in infants whose birth weights were appropriate for gestational age. Serum Ca concentrations in IUGR infants were significantly correlated with birth asphyxia and bicarbonate therapy for acidosis. Serum Ca concentration at 24 hours o f age was inversely correlated with serum P values. Thus the incidence o f neonatal hypocalcemia in 1UGR infants is not increased above the incidence expectedfrom their respective gestational ages. Infants with IUGR who are well at birth do not appear to develop neonatal hypocalcemia, but 1UGR infants who are asphyxiated at birth develop significant hypocalcemia.
R e g i n a l d C. T s a n g , M . B . B . S . , * M a r d i G i g g e r , B . A . , C i n c i n n a t i , Ohio, W i l l i a m O h , M . D . , P r o v i d e n c e , R . L, and David R. B r o w n , M . D . , C i n c i n n a t L Ohio
I N F A N T S with intrauterine growth retardation ("smallf o r - g e s t a t i o n a t - a g e i n f a n t s " or " s m a l l - f o r - d a t e s infants") often exhibit abnormal neuromuscular signs such as hyperirritability in the neonatal period, s, 2 In the clinical evaluation of abnormal neuromuscular activity in I U G R infants, hypocalcemia is often suspected, a, 4 There has been little information on the serum calcium changes in infants with IUGR. One recent study of infants with conditions "commonly associated with plac e n t a l i n s u f f i c i e n c y , ! ' i n c l u d i n g I U G R i n f a n t s , appeared to indicate lower serum concentrations of Ca in
such infants. 5 Thus it appeared important to examine serum Ca values in this group of infants, particularly in relation to clinical or biochemical factors. Recent publications have emphasized the important effects o f g e s t a t i o n a l age a n d b i r t h a s p h y x i a on neonatal calcium homeostasis. A direct positive correlation has been established between neonatal serum Ca values and both gestational age and one minute Apgar
From the Fels Division o f Pediatric Research, Newborn Division, Department o f Pediatrics, University of Cincinnati College o f Medicine; the Cincinnati Children's Hospital Research Foundation; the Michael Reese Hospital and Medical Center; and Brown University. Supported in part by National Institutes o f Health Research Grant Hd-O6-458-O1Al from the National Institute of Child Health and Human Development the Fels Institute o f Developmental Research, Yellow Springs, Ohio (Reginald C. Tsang), HD 3863-01 (William Oh, M.D.), 5TO1 HD 001683-03 (Reginald C. Tsang under Jaek Metcoff, M.D.), and HD 02912-01 (Dr. Metcoff ). *Reprint address:Children'sHospitaIReseareh Foundation, Elland and BethesdaA re., Cincinnati, Ohio45229.
scores.6, 7 Since many I U G R infants are gestationally m a t u r e , t h o u g h low in b i r t h weight, a " p r o t e c t i v e " effect for serum Ca might be envisioned. Conversely, since I U G R infants m a y be born with birth asphyxia, neonatal serum Ca values m a y be adversely affected. A s t u d y o f s e r u m Ca c o n c e n t r a t i o n s in I U G R infants would require a close examination of the two variables of gestational age and Apgar scores. The present report on serum Ca changes in infants with I U G R demonstrates that the incidence of neonatal hypocalcemia in I U G R infants is not increased beyond t h e i n c i d e n c e e x p e c t e d f r o m t h e i r g e s t a t i o n a l ages. Furthermore, infants with I U G R who are well at birth
Vol. 86, No. 6, pp. 936-941
Abbreviations used IUGR: intrauterine growth retardation AGA: appropriate for gestational age
Volume 86 Number 6
Studies in calcium metabolism with IUGR
937
Table I. Clinical associations for 47 infants with intrauterine growth retardation*
Maternal hypertension ( ~ I30190)
Maternal age
Placental abnormalities
Young ~< 17 years
(3)
Toxemia
(6)
Older ~ 35 years
(5)
Chronic hypertension
(2)
Abruptio Necrosis-infarct Retained placenta
Other (2) (1) (1)
(10) (2) (23)
Twins Gestational diabetes None of above
*Twenty-fourof 47 IUGR infants had one or more clinicalfactors commonlyassociatedwith intrauterinegrowth retardation. Table II. Gestational ages and birth asphyxia in I U G R and A G A infants
Appropriate for gestational age
Intrauterine growth retardation Gestational age
Birth asphyxia
No asphyxia
Total groups 31 32 33 34 35 36 37
1 2 2 1 3 6 2
0 0 0 3 5 10 9
Totals
17
27
I [
I
No asphyxia
Incomplete record
14 3 1 4 0 0 0
15 6 10 7 6 1 0
0 2 0 1 0 0 0
22
45
Incomplete record
Birth asphyxia
0 0 0 1 0 1 1 3
3
70
47 14 matched infant pairs
31 32 33 34 35 36
1 2 1 1 0 0
0 0 0 3 5 1
Totals
5
9 14
do not appear to develop neonatal hypocalcemia, while those I U G R infants with birth asphyxia can develop significant hypocalcemia. MATERIALS
AND METHODS
Infants were chosen from a study of low-birth-weight infants of 2,000 gm or less and admitted to a Special Care Nursery. Their clinical care has been previously described. 8 Gestational ages were determined in all infants by direct questioning of the mother for the date of her last menstrual period, and corroborated by the clinical characteristics of the infants at birth. 6If there was a question regarding the accuracy of the date of the last normal menstrual period, or if a discrepancy of more than two weeks was apparent between the calculated gestational
1
0
2
0
1 1
0 3
0 0
5 1
5
9 14
age by dates and the clinical assessment, the infant was e x c l u d e d from the study. Study i n f a n t s with birth weights less t h a n the t e n t h p e r c e n t i l e on the intrauterine growth chart of Lubchenco and associates 9 were said to have IUGR. Infants with birth weights between the tenth & ninetieth percentile were considered appropriate for gestational age. Using these criteria, 47 infants with I U G R were identified (Table I). Twenty-four of the 47 I U G R infants had one or more clinical factors commonly associated with i n t r a u t e r i n e growth retardation: y o u n g or old m o t h e r s , m a t e r n a l h y p e r t e n s i o n , placental a b n o r malities, and twinning. Their clinical course was compared with 70 A G A infants (Table II). Seventeen of 44 i n f a n t s (39%) with I U G R had b i r t h asphyxia (one minute Apgar score of 6 or less, or respiratory assist-
938
Tsang et aL
The Journal of Pediatrics June 1975
Table III, Clinical factors and symptoms in hypocalcemia of I U G R infants
Neonatal hypocalcemia (n =10) Clinical factors* Birth asphyxiat a. Bicarbonate therapy b. No bicarbonate Bicarbonate therapy for acidosis Respiratory distress
6/10 (60%) 6/10 (60%)
Neurologic signs and symptoms* Jitteriness a. With hypoglycemia b. Without hypoglycemia Twitching of extremity a. With hypoglycemia b. Without hypoglycemia Convulsion Hypert0nicity Hypotonicity High-pitched cry
4/10 3 1 1/10 1 0 0/10 3/10 2/10 3/10
Hypoglycemia
3/10 (30%)
7/9 (78%)* 6 1
(40%) (10%)
(0%) (30%) (20%) (30%)
Non hypoealeemic (n =37)
Ch# square
I
P value
10/35 (29%)* 2 8
5.38
June 1975 The Journal o f P E D I A T R I C S
Studies in calcium metabolism in infants with intrauterine growth retardation Serial serum Ca values in 47 infants with intrauterine growth retardation wereanalyzed in relation to clinical and biochemicalfactors. Serum Ca concentrations in IUGR infants fell within the 95% confidence limits for serum Ca in infants whose birth weights were appropriate for gestational age. Serum Ca concentrations in IUGR infants were significantly correlated with birth asphyxia and bicarbonate therapy for acidosis. Serum Ca concentration at 24 hours o f age was inversely correlated with serum P values. Thus the incidence o f neonatal hypocalcemia in 1UGR infants is not increased above the incidence expectedfrom their respective gestational ages. Infants with IUGR who are well at birth do not appear to develop neonatal hypocalcemia, but 1UGR infants who are asphyxiated at birth develop significant hypocalcemia.
R e g i n a l d C. T s a n g , M . B . B . S . , * M a r d i G i g g e r , B . A . , C i n c i n n a t i , Ohio, W i l l i a m O h , M . D . , P r o v i d e n c e , R . L, and David R. B r o w n , M . D . , C i n c i n n a t L Ohio
I N F A N T S with intrauterine growth retardation ("smallf o r - g e s t a t i o n a t - a g e i n f a n t s " or " s m a l l - f o r - d a t e s infants") often exhibit abnormal neuromuscular signs such as hyperirritability in the neonatal period, s, 2 In the clinical evaluation of abnormal neuromuscular activity in I U G R infants, hypocalcemia is often suspected, a, 4 There has been little information on the serum calcium changes in infants with IUGR. One recent study of infants with conditions "commonly associated with plac e n t a l i n s u f f i c i e n c y , ! ' i n c l u d i n g I U G R i n f a n t s , appeared to indicate lower serum concentrations of Ca in
such infants. 5 Thus it appeared important to examine serum Ca values in this group of infants, particularly in relation to clinical or biochemical factors. Recent publications have emphasized the important effects o f g e s t a t i o n a l age a n d b i r t h a s p h y x i a on neonatal calcium homeostasis. A direct positive correlation has been established between neonatal serum Ca values and both gestational age and one minute Apgar
From the Fels Division o f Pediatric Research, Newborn Division, Department o f Pediatrics, University of Cincinnati College o f Medicine; the Cincinnati Children's Hospital Research Foundation; the Michael Reese Hospital and Medical Center; and Brown University. Supported in part by National Institutes o f Health Research Grant Hd-O6-458-O1Al from the National Institute of Child Health and Human Development the Fels Institute o f Developmental Research, Yellow Springs, Ohio (Reginald C. Tsang), HD 3863-01 (William Oh, M.D.), 5TO1 HD 001683-03 (Reginald C. Tsang under Jaek Metcoff, M.D.), and HD 02912-01 (Dr. Metcoff ). *Reprint address:Children'sHospitaIReseareh Foundation, Elland and BethesdaA re., Cincinnati, Ohio45229.
scores.6, 7 Since many I U G R infants are gestationally m a t u r e , t h o u g h low in b i r t h weight, a " p r o t e c t i v e " effect for serum Ca might be envisioned. Conversely, since I U G R infants m a y be born with birth asphyxia, neonatal serum Ca values m a y be adversely affected. A s t u d y o f s e r u m Ca c o n c e n t r a t i o n s in I U G R infants would require a close examination of the two variables of gestational age and Apgar scores. The present report on serum Ca changes in infants with I U G R demonstrates that the incidence of neonatal hypocalcemia in I U G R infants is not increased beyond t h e i n c i d e n c e e x p e c t e d f r o m t h e i r g e s t a t i o n a l ages. Furthermore, infants with I U G R who are well at birth
Vol. 86, No. 6, pp. 936-941
Abbreviations used IUGR: intrauterine growth retardation AGA: appropriate for gestational age
Volume 86 Number 6
Studies in calcium metabolism with IUGR
937
Table I. Clinical associations for 47 infants with intrauterine growth retardation*
Maternal hypertension ( ~ I30190)
Maternal age
Placental abnormalities
Young ~< 17 years
(3)
Toxemia
(6)
Older ~ 35 years
(5)
Chronic hypertension
(2)
Abruptio Necrosis-infarct Retained placenta
Other (2) (1) (1)
(10) (2) (23)
Twins Gestational diabetes None of above
*Twenty-fourof 47 IUGR infants had one or more clinicalfactors commonlyassociatedwith intrauterinegrowth retardation. Table II. Gestational ages and birth asphyxia in I U G R and A G A infants
Appropriate for gestational age
Intrauterine growth retardation Gestational age
Birth asphyxia
No asphyxia
Total groups 31 32 33 34 35 36 37
1 2 2 1 3 6 2
0 0 0 3 5 10 9
Totals
17
27
I [
I
No asphyxia
Incomplete record
14 3 1 4 0 0 0
15 6 10 7 6 1 0
0 2 0 1 0 0 0
22
45
Incomplete record
Birth asphyxia
0 0 0 1 0 1 1 3
3
70
47 14 matched infant pairs
31 32 33 34 35 36
1 2 1 1 0 0
0 0 0 3 5 1
Totals
5
9 14
do not appear to develop neonatal hypocalcemia, while those I U G R infants with birth asphyxia can develop significant hypocalcemia. MATERIALS
AND METHODS
Infants were chosen from a study of low-birth-weight infants of 2,000 gm or less and admitted to a Special Care Nursery. Their clinical care has been previously described. 8 Gestational ages were determined in all infants by direct questioning of the mother for the date of her last menstrual period, and corroborated by the clinical characteristics of the infants at birth. 6If there was a question regarding the accuracy of the date of the last normal menstrual period, or if a discrepancy of more than two weeks was apparent between the calculated gestational
1
0
2
0
1 1
0 3
0 0
5 1
5
9 14
age by dates and the clinical assessment, the infant was e x c l u d e d from the study. Study i n f a n t s with birth weights less t h a n the t e n t h p e r c e n t i l e on the intrauterine growth chart of Lubchenco and associates 9 were said to have IUGR. Infants with birth weights between the tenth & ninetieth percentile were considered appropriate for gestational age. Using these criteria, 47 infants with I U G R were identified (Table I). Twenty-four of the 47 I U G R infants had one or more clinical factors commonly associated with i n t r a u t e r i n e growth retardation: y o u n g or old m o t h e r s , m a t e r n a l h y p e r t e n s i o n , placental a b n o r malities, and twinning. Their clinical course was compared with 70 A G A infants (Table II). Seventeen of 44 i n f a n t s (39%) with I U G R had b i r t h asphyxia (one minute Apgar score of 6 or less, or respiratory assist-
938
Tsang et aL
The Journal of Pediatrics June 1975
Table III, Clinical factors and symptoms in hypocalcemia of I U G R infants
Neonatal hypocalcemia (n =10) Clinical factors* Birth asphyxiat a. Bicarbonate therapy b. No bicarbonate Bicarbonate therapy for acidosis Respiratory distress
6/10 (60%) 6/10 (60%)
Neurologic signs and symptoms* Jitteriness a. With hypoglycemia b. Without hypoglycemia Twitching of extremity a. With hypoglycemia b. Without hypoglycemia Convulsion Hypert0nicity Hypotonicity High-pitched cry
4/10 3 1 1/10 1 0 0/10 3/10 2/10 3/10
Hypoglycemia
3/10 (30%)
7/9 (78%)* 6 1
(40%) (10%)
(0%) (30%) (20%) (30%)
Non hypoealeemic (n =37)
Ch# square
I
P value
10/35 (29%)* 2 8
5.38
