Biol. Neonate 29: 187-193 (1976)
Serotonin Metabolism in Normal and Abnormal Infants during the Perinatal Period Jun-bi Tu and Ching- Yee Wong Department of Pediatrics, Queen’s University, Kingston, Ont.
Key Words. Serotonin • Perinatal • Fetal blood • Toxemia Abstract. The concentration of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in various body fluids was measured during the perinatal period in two groups of infants bom with normal and pathological conditions, respectively. Evidence was obtained showing that fetal blood 5-HT level was relatively stable, uninfluenced by maternal or fetal factors, and was about half the value of the maternal blood. High levels of 5-HIAA and evidence of an active decomposition of 5-HT were found in the amniotic fluid. These findings suggest that 5-HT in utero is subjected to a very active metabolic turnover. The origin of the fetal blood 5-HT and the significance of the placenta in the control of intra uterine 5-HT metabolism is discussed. There was no clear evidence of abnormal 5-HT metab olism in toxemic pregnancies, premature babies, and an infant with Down’s syndrome in the perinatal period.
Introduction
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Serotonin, chemically known as 5-hydroxytryptamine (5-HT), is increas ingly considered to be an important biogenic amine which plays a significant role in the function of many organ systems, notably the central nervous system {Page, 1968). In recent years, many investigators have come to believe that fundamental knowledge of the function of this amine might be obtained by studying its metabolism in early embryogenesis and developing tissue {Baker and Quay, 1969). The assay of 5-HT and its metabolites in human placental and fetal tissues {Fahim and Botros, 1964; Karen et aL, 1965), amniotic fluids {Brzezinski et aL, 1962; Loose and Paterson, 1966; Emery et aL, 1972), umbilical cord blood {Fahim and Botros, 1964; Sadayuki, 1969), and newborn infant blood
Tu/Wong
188
{Berman et al., 1965 \liazra et al, 1965), have yielded some interesting results, but most of these studies were limited to the observation of a few isolated specimens without systematic elaboration. No general consensus has emerged concerning the metabolism of 5-HT in the human fetus. This study is an attempt to fill this gap by a study of 5-HT and its metabolites in all related body fluids during the perinatal period in normal as well as pathological conditions.
Methods The subjects formed two major groups: (1) Forty-three healthy and mature infants; mean maternal age 25 years. The majority of mothers had certain medical or obstetrical complications requiring special care and management; these included mild degrees of anemia, edema, elevation of the blood pressure, toxemia and so forth. (2) Fourteen abnormal infants; ten were born prematurely, with or without associated low birth weight and four cases had congenital anomaly including one case of trisomy 21 (Down’s syndrome). The average maternal age was 21 years. All the maternal venous blood and amniotic fluid samples were collected at the time of delivery, but the umbilical cord and placental blood were collected immediately after deliv ery and kept frozen until analysis. The newborn urine samples were collected from a separate group of babies immediately after birth and throughout the first 10 days of the neonatal period. The control urines were the first morning samples collected from a group of normal healthy school children, ranging in age from 6 10 years. As described elsewhere (Partington et al., 1971 and 1973), a series of modified meth ods were adopted for the analysis of whole blood 5-HT, and 5-H1AA in the amniotic fluid and newborn urine specimens. Total 5-HI in the amniotic fluid were measured by slightly modifying the method proposed by Ashcroft et al. (1964).
The 5-HI levels found in the various body fluids are summadzed in table I. As the values of 5-HT in the cord artery, cord vein and placenta were practically identical, the three values were combined under one item, cord blood, which represents portions of the fetal circulation. Despite differences in gestational history and physical status, both groups of pregnancies gave very similar results. The most remarkable finding was the great difference of 5-HT levels between the maternal and fetal blood. The mean fetal level was about half that of the maternal value. The levels of 5-HI and 5-HT in the cord and placental blood, measured respectively by the different methods, agreed quite well. There was no detectable 5-HIAA in the cord blood. In contrast to fetal blood, 5-HIAA was the main component of total 5-HI in the amniotic fluid. It accounted for approximately 65 % of the total 5-HI. Although other components in the amniotic fluids still remain to be identified,
Downloaded by: University of New England 132.174.255.223 - 1/13/2019 2:05:44 AM
Results
Serotonin Metabolism during the Perinatal Period
189
Maternal blood 5-HT
Umbilical cord blood 5-HT
Placental blood 5-HT
Amniotic fluid 5-HIAA
5-HI
Normal infants Number Mean SE Range
42 147 6 90-217
20 83 6 32-131
34 83 5 41-160
18 99 10 32-168
19 178 19 63-398
Abnormal infants Number Mean SE Range
12 156 15 50-260
5 57 12 32-100
11 70 8 41-126
8 112 23 12-208
8 161 35 24-329
All infants Number Mean SE Range
54 149 6 50-260
25 77 6 32-131
45 79 4 41 160
26 103 10 12-208
27 173 17 24-398
our preliminary bioassay revealed some biological activity similar to that of authentic 5-HT. Table II shows the levels of 5-HI in the various body fluids of infants born to toxemic mothers. These included both the normal and abnormal groups. In spite of the slight elevation of 5-HI AA in the amniotic fluid, there was no significant difference between values of the toxemic and the non-toxemic group shown in table I. Table III shows the correlations between the 5-HI levels of various body fluids and fetal body weight during the perinatal period. Since no significant difference was found between the normal and abnormal infant groups, the data was combined into one group for the purpose of statistical analysis. A possible correlation was found between the levels of 5-HIAA and 5-HI in the amniotic fluid (p < 0.001). All the remaining paired values showed no significant correla tion. The infant with Down’s syndrome showed no evidence of abnormality of 5-HT metabolism in utero. The maternal and cord blood 5-HT levels were found to be 175 and 70 ng/ml, respectively. The amniotic fluid contained 156 ng/ml of 5-HIAA and 244 ng/ml of total 5-HI.
Downloaded by: University of New England 132.174.255.223 - 1/13/2019 2:05:44 AM
Table I. Levels of 5-hydroxyindoles (ng/ml) in various body fluids during perinatal period
190
Tu/Wong
Table II. Levels of 5-hydroxyindoles (ng/ml) in maternal blood, amniotic fluids and placental blood in toxaemia of pregnancy Maternal blood 5-HT
Placental blood 5-HT
Amniotic fluid 5-HIAA
5-H1
1 2 3 4 5 6 7
180 95 90 156 145 110 165
130 90 73 53
_
_
168 108
264 398
-
-
Mean ± SE
134 ± 14
Case No.
—
120
155
90 41
—
-
-
-
80 ± 13
132
272
Infant
normal normal normal normal normal abnormal abnormal
Number of pairs r P
Maternal blood 5-HT versus
Fetal blood 5-HT versus
fetal blood 5-HT
amniotic fluid
amniotic fluid
5-HIAA
5-HI
fetal body weight
5-HIAA
5-HI
Amniotic fluid 5-HIAA versus amniotic fluid 5-HI
48 + 0.277 >0.05
24 + 0.014 >0.05
24 + 0.123 >0.05
51 + 0.220 >0.05
21 -0.022 >0.05
21 -0.084 >0.05
21 + 0.804
Serotonin Metabolism in Normal and Abnormal Infants during the Perinatal Period Jun-bi Tu and Ching- Yee Wong Department of Pediatrics, Queen’s University, Kingston, Ont.
Key Words. Serotonin • Perinatal • Fetal blood • Toxemia Abstract. The concentration of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in various body fluids was measured during the perinatal period in two groups of infants bom with normal and pathological conditions, respectively. Evidence was obtained showing that fetal blood 5-HT level was relatively stable, uninfluenced by maternal or fetal factors, and was about half the value of the maternal blood. High levels of 5-HIAA and evidence of an active decomposition of 5-HT were found in the amniotic fluid. These findings suggest that 5-HT in utero is subjected to a very active metabolic turnover. The origin of the fetal blood 5-HT and the significance of the placenta in the control of intra uterine 5-HT metabolism is discussed. There was no clear evidence of abnormal 5-HT metab olism in toxemic pregnancies, premature babies, and an infant with Down’s syndrome in the perinatal period.
Introduction
Downloaded by: University of New England 132.174.255.223 - 1/13/2019 2:05:44 AM
Serotonin, chemically known as 5-hydroxytryptamine (5-HT), is increas ingly considered to be an important biogenic amine which plays a significant role in the function of many organ systems, notably the central nervous system {Page, 1968). In recent years, many investigators have come to believe that fundamental knowledge of the function of this amine might be obtained by studying its metabolism in early embryogenesis and developing tissue {Baker and Quay, 1969). The assay of 5-HT and its metabolites in human placental and fetal tissues {Fahim and Botros, 1964; Karen et aL, 1965), amniotic fluids {Brzezinski et aL, 1962; Loose and Paterson, 1966; Emery et aL, 1972), umbilical cord blood {Fahim and Botros, 1964; Sadayuki, 1969), and newborn infant blood
Tu/Wong
188
{Berman et al., 1965 \liazra et al, 1965), have yielded some interesting results, but most of these studies were limited to the observation of a few isolated specimens without systematic elaboration. No general consensus has emerged concerning the metabolism of 5-HT in the human fetus. This study is an attempt to fill this gap by a study of 5-HT and its metabolites in all related body fluids during the perinatal period in normal as well as pathological conditions.
Methods The subjects formed two major groups: (1) Forty-three healthy and mature infants; mean maternal age 25 years. The majority of mothers had certain medical or obstetrical complications requiring special care and management; these included mild degrees of anemia, edema, elevation of the blood pressure, toxemia and so forth. (2) Fourteen abnormal infants; ten were born prematurely, with or without associated low birth weight and four cases had congenital anomaly including one case of trisomy 21 (Down’s syndrome). The average maternal age was 21 years. All the maternal venous blood and amniotic fluid samples were collected at the time of delivery, but the umbilical cord and placental blood were collected immediately after deliv ery and kept frozen until analysis. The newborn urine samples were collected from a separate group of babies immediately after birth and throughout the first 10 days of the neonatal period. The control urines were the first morning samples collected from a group of normal healthy school children, ranging in age from 6 10 years. As described elsewhere (Partington et al., 1971 and 1973), a series of modified meth ods were adopted for the analysis of whole blood 5-HT, and 5-H1AA in the amniotic fluid and newborn urine specimens. Total 5-HI in the amniotic fluid were measured by slightly modifying the method proposed by Ashcroft et al. (1964).
The 5-HI levels found in the various body fluids are summadzed in table I. As the values of 5-HT in the cord artery, cord vein and placenta were practically identical, the three values were combined under one item, cord blood, which represents portions of the fetal circulation. Despite differences in gestational history and physical status, both groups of pregnancies gave very similar results. The most remarkable finding was the great difference of 5-HT levels between the maternal and fetal blood. The mean fetal level was about half that of the maternal value. The levels of 5-HI and 5-HT in the cord and placental blood, measured respectively by the different methods, agreed quite well. There was no detectable 5-HIAA in the cord blood. In contrast to fetal blood, 5-HIAA was the main component of total 5-HI in the amniotic fluid. It accounted for approximately 65 % of the total 5-HI. Although other components in the amniotic fluids still remain to be identified,
Downloaded by: University of New England 132.174.255.223 - 1/13/2019 2:05:44 AM
Results
Serotonin Metabolism during the Perinatal Period
189
Maternal blood 5-HT
Umbilical cord blood 5-HT
Placental blood 5-HT
Amniotic fluid 5-HIAA
5-HI
Normal infants Number Mean SE Range
42 147 6 90-217
20 83 6 32-131
34 83 5 41-160
18 99 10 32-168
19 178 19 63-398
Abnormal infants Number Mean SE Range
12 156 15 50-260
5 57 12 32-100
11 70 8 41-126
8 112 23 12-208
8 161 35 24-329
All infants Number Mean SE Range
54 149 6 50-260
25 77 6 32-131
45 79 4 41 160
26 103 10 12-208
27 173 17 24-398
our preliminary bioassay revealed some biological activity similar to that of authentic 5-HT. Table II shows the levels of 5-HI in the various body fluids of infants born to toxemic mothers. These included both the normal and abnormal groups. In spite of the slight elevation of 5-HI AA in the amniotic fluid, there was no significant difference between values of the toxemic and the non-toxemic group shown in table I. Table III shows the correlations between the 5-HI levels of various body fluids and fetal body weight during the perinatal period. Since no significant difference was found between the normal and abnormal infant groups, the data was combined into one group for the purpose of statistical analysis. A possible correlation was found between the levels of 5-HIAA and 5-HI in the amniotic fluid (p < 0.001). All the remaining paired values showed no significant correla tion. The infant with Down’s syndrome showed no evidence of abnormality of 5-HT metabolism in utero. The maternal and cord blood 5-HT levels were found to be 175 and 70 ng/ml, respectively. The amniotic fluid contained 156 ng/ml of 5-HIAA and 244 ng/ml of total 5-HI.
Downloaded by: University of New England 132.174.255.223 - 1/13/2019 2:05:44 AM
Table I. Levels of 5-hydroxyindoles (ng/ml) in various body fluids during perinatal period
190
Tu/Wong
Table II. Levels of 5-hydroxyindoles (ng/ml) in maternal blood, amniotic fluids and placental blood in toxaemia of pregnancy Maternal blood 5-HT
Placental blood 5-HT
Amniotic fluid 5-HIAA
5-H1
1 2 3 4 5 6 7
180 95 90 156 145 110 165
130 90 73 53
_
_
168 108
264 398
-
-
Mean ± SE
134 ± 14
Case No.
—
120
155
90 41
—
-
-
-
80 ± 13
132
272
Infant
normal normal normal normal normal abnormal abnormal
Number of pairs r P
Maternal blood 5-HT versus
Fetal blood 5-HT versus
fetal blood 5-HT
amniotic fluid
amniotic fluid
5-HIAA
5-HI
fetal body weight
5-HIAA
5-HI
Amniotic fluid 5-HIAA versus amniotic fluid 5-HI
48 + 0.277 >0.05
24 + 0.014 >0.05
24 + 0.123 >0.05
51 + 0.220 >0.05
21 -0.022 >0.05
21 -0.084 >0.05
21 + 0.804
