ORIGINAL ARTICLE
Prolactin and amniotic fluid electrolytes NAMIKDEMIR',MURATCELILOGLU', PETERA. B. THOMASSEN', ATA ONVURAL' AND OKTAY ERTEN'
From the 'Department of Obstetrics and Gynecology, Dokuz Eylul University, School of Medicine, Izmir, Turkey, and the 'Department of Obstetrics and Gynecology, Karolinska Sjukhuset, Stockholm, Sweden
Acttr
Ohstet Gynecol Sccrtid 1992; 71: 197-200
Prolactin (PRL) levels and Na'. K', CI . Ca' concentrations in maternal serum and amniotic fluid from 64 women i n normal term pregnancy were measured by immuno+
enzymctric assay a n d flamc phorometry. The mean amniotic fluid PRL concentration wii5 597.7 (SE 31.5) ng/ml and the mean amniotic fluid Na', K', CI and Cd'+ lcvels were 125.6 (SE 0.9) mmolil, 4.5 (SE 0.1) mmol/l, 109.3 (SE 1.3) mmol/l and 2.0 (SE 7.5 E-02) mmol/l, respectively. There was no correlation between PRL levels in maternal scrum and amniotic fluid. and the electrolyte concentrations in amniotic fluid. A closc correlation was found between the concentrations of Na' and CI- in maternal serum and amniotic fluid. Thus, even though PRL may participate in the regulation of elcctrolytes in the amniotic fluid compartments, o u r findings provide indirect evidence for the
existence of othet- regulatory mechanisms. K c y words: prolactin; amniotic fluid: electrolytes; osmoregulator Submitted October 31, 1491 Accepted November 4, 1941
During the first half of pregnancy, the composition of amniotic fluid is similar to that of extracellular fluid, which explains why amniotic fluid may be considered an extension of the fetal extracellular space ( 1 ) . As pregnancy advances beyond the 20th week, the fetal kidneys become the major source of amniotic fluid production. Fetal swallowing and respiratory movements, the fetal skin and various hormones may participate in regulating volume and osmotic exchange in the amniotic fluid compartment (1,2). Prolactin (PRL) is a known osmoregulator and therefore may be one such factor (3,4). It is secreted by the fetal pituitary, maternal pituitary and the decidua during pregnancy, the part derived from the decidua being the main source of PRL in the amniotic fluid (5). Previous studies have shown that amniotic fluid PRL may regulate the passage of water across the chorioallantoic membranes and skin in the rhesus monkey and also, before cornification starts, in the human fetus (2.6). Moreover, i t has been known for several years past that PRL, when given in large doses, can reduce renal water and Na' excretion in the adult human (7).
It seems probable, therefore, that locally-produced PRL participates in the regulation of osmotic exchange in the amniotic fluid compartment. If this is the case, one would expect a correlation between the amniotic fluid PRL levels and certain electrolytes. In the present study, the P R L concentrations in maternal serum, cord blood and amniotic fluid were measured and Na+, K + , CI- and Caii. in the maternal serum and amniotic fluid were determined in order to ascertain a possible correlation between these levels.
Material and methods The study group consists of 64 healthy women at term who took no medication other than mineral and vitamin supplementation. Fifty-four (84.4%) o f them gave birth vaginally; in some of these cases. oxytocin was used for induction. Ten women undcrwent elective cesarean section because of fetopelvic disproportion. Amniotic fluid and blood specimens were taken within 24 h of delivery. The amniotic
198
Namik Demir et a / .
Table I.Mean values and normality of distribution of prolactin levels in maternal serum, umbilical cord and amniotic fluid Prolactin concentrations (ngiml) Mean (SE)
Maternal serum Cord serum Amniotic fluid
Range
Normal distribution Goodnessof-fit test p-values
230.0 (lY.6) 52-680 423.8 (23.9) 121-1058 597.7 (31.5) 123- 1082
-2. I E-07 6.2 E-03 0.07
fluid specimens were obtained by transabdominal or transcervical amniocentesis and placed in sterile test tubes. At the end of delivery, mixed umbilical cord blood was collected in sterile tubes. All blood samples and samples of amniotic fluid were centrifuged at 400 RPM for 10 min, after which serum and supernatant were separatcd and stored at -20°C for the subsequent determination of PRL and electrolytes. PRL levels were rneasurcd by the Tandem E PRL immunoenzymetric assay. Na', K', C1- and Ca++ion concentrations were determined in an Eppendorff FCM 6341 flame photometer. The normality of the distribution of values within each parameter was investigated by use of the normal distribution goodness-of-fit test. Data were analysed by descriptive statistics, Spearman rank correlation and regression analyses, using a Microstat software program in an IBM PC/2 computer. The normality of the distribution of the data collected for some of our parameters was nut suitable for paramctic statistical tests. For this reason, non-parametric tests for correlation analyses were carried out. A lcvel of p < 0.05 was considered significant.
Results Table 1 shows the mean maternal serum, umbilical cord and amniotic fluid PRL concentrations. Table
I1 shows the mean maternal and amniotic fluid electrolyte levels and ranges. Na+, K+ and Ca" concentrations were significantly higher in maternal serum than in amniotic fluid (pNa = 0.01; pK = 1.16 E-04; pCa = 5.19 E-05). Table 111 shows some of the analyses of the correlations between the P R L levels and the electrolytes. There was a significant positive correlation between cord serum PRL and amniotic fluid (CI-) (Fig. l ) , but no significant correlations between PRL levels and electrolyte concentrations in the amniotic fluid. Correlations were sought among the maternal and amniotic fluid electrolytes levels. A close correlation was found between maternal Na+ and amniotic fluid Na' (p = 1.05 E-04). The same correlation was found between maternal serum C1- and amniotic fluid CI- (p = 0.02).
Discussion Approximately 4 liters of water accumulates in the uterine compartments before term. Increases of 30 to 40 mliday near term far exceed anything possible from intra-uterine or fetal metabolic sources, which means that a substantial part of this increase must be transferred from the maternal compartment (1). Since amniotic fluid near term has a relatively constant tonicity between 255 and 270 mOsm/kg, it seems likely that the fetus is in a state of negative balance with respect to solute-free water and a fairly large amount of solute-free water must be reabsorbed from the amniotic cavity daily (8). The effect of intra-amniotic injections of PRL, vasopressin or oxytocin on the amniotic to maternal water flux has been studied in the ewe (4). Among those compounds, PRL seemed to play the principal role. Pullano et al. (9) determined the correlations between osmotic activity, hematocrit, total serum protein concentrations and total serum solids in maternal serum, amniotic fluid and cord serum and, on the other hand, the umbilical cord PRL in 94 women before term. They found a significant, positive cor-
Table II.Maternal and amniotic fluid electrolyte concentrations Na+ (mmol/l)
K' (rnmol/l)
CI -
Ca+i
(mmol/l)
(mmol/l)
Maternal scrum Mean (SE) h ) Rangc
138.4 (0.7) 113.0-149.0
5.5 (0.2) 1.2-9.5
115.4 (0.8) 95.0- 136.0
2.4 (0.03) 1.1-2.9
Amniotic fluid Mean (SE) h ) Range
125.6 (0.0) 108.0- 148.0
4.5 (0.1) 3.3-9.7
100.3 ( 1 3) 64.0- 127.0
2.0 (0.07) 0.8-4.5
o)
(1)
Actu Ohstel Gynecol Scotid 71 (1YY2)
Prolactin and amniotic fluid electrolytes
199
Table 111. Correlations between prolactin levels and electrolytes Independent variable. (nglml) Mean (SE)
Correl.
Dependent variable
p
Coeff. (mmol/l)
Mean (SE)
Amniotic fluid prolactin 597.7 (31.5)
AMN AMN AMN AMN
125.6 4.5 109.3 2.0
(0.9) (0.1) (1.2) (0. I )
0.05 0.02 -0.17 -0. 15
0.68 0.90 0.18 0.24
Maternal serum prolactin 230.0 (19.6)
MTRN N a + MTRN K' MTRN CIMTRN Ca+' AMN Na' AMN C1-
138.4 5.5 111.4 2.37
(0.8) (0.2) (0.9) (0.0)
-0.11 0.02
0.39
-0.09
0.47 0.18 0.36 0.22
AMN Na' AMN K + AMN C1-
125.6 (0.9) 4.5 (0.1) 109.3 (1.2)
Cord blood prolactin 421.8 (23.9)
Na' Kf C1Ca'+
relation between cord serum PRL and amniotic fluid N a ' a s well as a significant correlation between PRL and Nat in cord serum when the PRL levels were less than 230 &I. In the study group, Na', K + and C a t + values were significantly higher in maternal serum than in amniotic fluid. In this respect, the present results are in agreement with those of Johnell & NiIsson (10). A close correlation was found between maternal serum and amniotic fluid Na' and CI- @Na = 0.001; pCI = 0.019). This must be the result of diffusion between the intra-uterine compartments. Our findings suggest that. besides factors such as osmotic and hydrostatic pressures as well as PRL, more refined regulatory mechanisms may be involved in the water transport acro branes. One such factor may be atrial natriuretic factor (ANF). which is a class of diuretic and natriuretic peptides secreted by mammalian cardiac atria ( 1 I ) . A N F has. indeed, been found in uteroplacental tissue, and it has been shown that the concentration of ANF in the membranes declines after the onset of labor (12). Other compounds. such as asperginevasopressin, have also been thought to play a role in water and electrolyte transport across the fetal membranes (1 3 ) . In conclusion, even though PRL may participate in the regulation of osmotic exchange in the amniotic fluid compartments, our findings provide indirect evidence for the existence of other, more important regulatory mechanisms.
-0.17 -0.11 0.16
0.02 0.23 0.36
0.90
0.90 0.07
0.003
References 1. Brace R A . Amniotic fluid dynamics. In: Creasy RK.
2.
3.
4.
5.
6.
7.
8.
9,
10.
Resnik E. eds. Maternal and fetal medicine. principles and practice. Philadelphia: WB Saunders. 1989; 128-35. Leontic E A , Schrueffer J J . Andereassen B, Pinto H. Tyson JE. Further evidence for the role o f prolactin on human fetoplacental osmoregulation. Am J Obstet Gynecol 1979; 133: 435-8. Leontic E A . Tyson J E . Prolactin and fetal osmorcgulation: water transport across isolated human amnion. Am J Physiol 1977; 232: R124. Ross M G , Erwin MG. Lcakc R D . Oakes G. Hobel C, Fisher D A . Bulk flow of amniotic fluid water i n response to maternal osmotic challenge. Am J Obstet Gynecol 1983; 147: 697-701. McCoshen J A , Barc J . Prolactin bioactivity following decidual synthesis and transport by aniniochorion. Am J Obstet Gynecol 1985; 153: 217-23. Josimovich JB. Merisko K. Bocella L. Amniotic prolactin control over amniotic and fctal cxtracellular fluid water and electrolytes in the rhesus monkcy. Endocrinology 1977; 100: 564-70. Horrobin DF, Lloyd JJ, Lipton A. Burstyn PG. Durkin N. Muriuri KL. Actions of prolactin on human renal functions. Lancet 1971; ii: 3 5 2 4 . Seeds A E . Water dynamics in the amniotic fluid. In: Fairweather DVI, Eskes TKAB. cds. Amniotic fluid. Research and clinical application. 2nd edn. Amsterdam: Excerpta Medica. 1978: 51-7. Pullano JG, Addad NC, Apuzzio JJ. Ganesch VL. Josirnovich JB. Water and salt conservation in the human fetus and newhorn. 1. Evidence for ii role o f fctal prolactin. J Clin Endocrinol Metah I98Y; 69: 1 IX(l-6. Johnell H E , Nilsson BA. Oxygen tcnsion. acid-base status and electrolytes in human amniotic fluid. Acta Obstet Gynecol Scand 1971; SO: 183-92.
200
Nurnik Demir et al.
1 1 . Dc Bold AJ. Atrial natriuretic factor: a hormone produced by the heart. Science lY85; 230: 767-7(1. 12. Caatio C. Arora C, Hobel C. Atrial natriuretic factor in uteroplacental tissues. Am J Ohstet Gynecol 1991; 164: 263. 1.7. Ross MG, Ervin MG, Lam R W , Leake R D , Fisher DA. Fetal atrial natriuretic factor and arginine, vasopressin responses to hyperosmolality and hypervolemia. Pediatr Res 19x8: 24: 318-21.
Adress f o r correspondencc:
Namik Demir, M . D . Department of Obstetrics and Gynecology Dokuz Eylul University School of Medicine. 35340 - Inciralti lzmir Turkey
Prolactin and amniotic fluid electrolytes NAMIKDEMIR',MURATCELILOGLU', PETERA. B. THOMASSEN', ATA ONVURAL' AND OKTAY ERTEN'
From the 'Department of Obstetrics and Gynecology, Dokuz Eylul University, School of Medicine, Izmir, Turkey, and the 'Department of Obstetrics and Gynecology, Karolinska Sjukhuset, Stockholm, Sweden
Acttr
Ohstet Gynecol Sccrtid 1992; 71: 197-200
Prolactin (PRL) levels and Na'. K', CI . Ca' concentrations in maternal serum and amniotic fluid from 64 women i n normal term pregnancy were measured by immuno+
enzymctric assay a n d flamc phorometry. The mean amniotic fluid PRL concentration wii5 597.7 (SE 31.5) ng/ml and the mean amniotic fluid Na', K', CI and Cd'+ lcvels were 125.6 (SE 0.9) mmolil, 4.5 (SE 0.1) mmol/l, 109.3 (SE 1.3) mmol/l and 2.0 (SE 7.5 E-02) mmol/l, respectively. There was no correlation between PRL levels in maternal scrum and amniotic fluid. and the electrolyte concentrations in amniotic fluid. A closc correlation was found between the concentrations of Na' and CI- in maternal serum and amniotic fluid. Thus, even though PRL may participate in the regulation of elcctrolytes in the amniotic fluid compartments, o u r findings provide indirect evidence for the
existence of othet- regulatory mechanisms. K c y words: prolactin; amniotic fluid: electrolytes; osmoregulator Submitted October 31, 1491 Accepted November 4, 1941
During the first half of pregnancy, the composition of amniotic fluid is similar to that of extracellular fluid, which explains why amniotic fluid may be considered an extension of the fetal extracellular space ( 1 ) . As pregnancy advances beyond the 20th week, the fetal kidneys become the major source of amniotic fluid production. Fetal swallowing and respiratory movements, the fetal skin and various hormones may participate in regulating volume and osmotic exchange in the amniotic fluid compartment (1,2). Prolactin (PRL) is a known osmoregulator and therefore may be one such factor (3,4). It is secreted by the fetal pituitary, maternal pituitary and the decidua during pregnancy, the part derived from the decidua being the main source of PRL in the amniotic fluid (5). Previous studies have shown that amniotic fluid PRL may regulate the passage of water across the chorioallantoic membranes and skin in the rhesus monkey and also, before cornification starts, in the human fetus (2.6). Moreover, i t has been known for several years past that PRL, when given in large doses, can reduce renal water and Na' excretion in the adult human (7).
It seems probable, therefore, that locally-produced PRL participates in the regulation of osmotic exchange in the amniotic fluid compartment. If this is the case, one would expect a correlation between the amniotic fluid PRL levels and certain electrolytes. In the present study, the P R L concentrations in maternal serum, cord blood and amniotic fluid were measured and Na+, K + , CI- and Caii. in the maternal serum and amniotic fluid were determined in order to ascertain a possible correlation between these levels.
Material and methods The study group consists of 64 healthy women at term who took no medication other than mineral and vitamin supplementation. Fifty-four (84.4%) o f them gave birth vaginally; in some of these cases. oxytocin was used for induction. Ten women undcrwent elective cesarean section because of fetopelvic disproportion. Amniotic fluid and blood specimens were taken within 24 h of delivery. The amniotic
198
Namik Demir et a / .
Table I.Mean values and normality of distribution of prolactin levels in maternal serum, umbilical cord and amniotic fluid Prolactin concentrations (ngiml) Mean (SE)
Maternal serum Cord serum Amniotic fluid
Range
Normal distribution Goodnessof-fit test p-values
230.0 (lY.6) 52-680 423.8 (23.9) 121-1058 597.7 (31.5) 123- 1082
-2. I E-07 6.2 E-03 0.07
fluid specimens were obtained by transabdominal or transcervical amniocentesis and placed in sterile test tubes. At the end of delivery, mixed umbilical cord blood was collected in sterile tubes. All blood samples and samples of amniotic fluid were centrifuged at 400 RPM for 10 min, after which serum and supernatant were separatcd and stored at -20°C for the subsequent determination of PRL and electrolytes. PRL levels were rneasurcd by the Tandem E PRL immunoenzymetric assay. Na', K', C1- and Ca++ion concentrations were determined in an Eppendorff FCM 6341 flame photometer. The normality of the distribution of values within each parameter was investigated by use of the normal distribution goodness-of-fit test. Data were analysed by descriptive statistics, Spearman rank correlation and regression analyses, using a Microstat software program in an IBM PC/2 computer. The normality of the distribution of the data collected for some of our parameters was nut suitable for paramctic statistical tests. For this reason, non-parametric tests for correlation analyses were carried out. A lcvel of p < 0.05 was considered significant.
Results Table 1 shows the mean maternal serum, umbilical cord and amniotic fluid PRL concentrations. Table
I1 shows the mean maternal and amniotic fluid electrolyte levels and ranges. Na+, K+ and Ca" concentrations were significantly higher in maternal serum than in amniotic fluid (pNa = 0.01; pK = 1.16 E-04; pCa = 5.19 E-05). Table 111 shows some of the analyses of the correlations between the P R L levels and the electrolytes. There was a significant positive correlation between cord serum PRL and amniotic fluid (CI-) (Fig. l ) , but no significant correlations between PRL levels and electrolyte concentrations in the amniotic fluid. Correlations were sought among the maternal and amniotic fluid electrolytes levels. A close correlation was found between maternal Na+ and amniotic fluid Na' (p = 1.05 E-04). The same correlation was found between maternal serum C1- and amniotic fluid CI- (p = 0.02).
Discussion Approximately 4 liters of water accumulates in the uterine compartments before term. Increases of 30 to 40 mliday near term far exceed anything possible from intra-uterine or fetal metabolic sources, which means that a substantial part of this increase must be transferred from the maternal compartment (1). Since amniotic fluid near term has a relatively constant tonicity between 255 and 270 mOsm/kg, it seems likely that the fetus is in a state of negative balance with respect to solute-free water and a fairly large amount of solute-free water must be reabsorbed from the amniotic cavity daily (8). The effect of intra-amniotic injections of PRL, vasopressin or oxytocin on the amniotic to maternal water flux has been studied in the ewe (4). Among those compounds, PRL seemed to play the principal role. Pullano et al. (9) determined the correlations between osmotic activity, hematocrit, total serum protein concentrations and total serum solids in maternal serum, amniotic fluid and cord serum and, on the other hand, the umbilical cord PRL in 94 women before term. They found a significant, positive cor-
Table II.Maternal and amniotic fluid electrolyte concentrations Na+ (mmol/l)
K' (rnmol/l)
CI -
Ca+i
(mmol/l)
(mmol/l)
Maternal scrum Mean (SE) h ) Rangc
138.4 (0.7) 113.0-149.0
5.5 (0.2) 1.2-9.5
115.4 (0.8) 95.0- 136.0
2.4 (0.03) 1.1-2.9
Amniotic fluid Mean (SE) h ) Range
125.6 (0.0) 108.0- 148.0
4.5 (0.1) 3.3-9.7
100.3 ( 1 3) 64.0- 127.0
2.0 (0.07) 0.8-4.5
o)
(1)
Actu Ohstel Gynecol Scotid 71 (1YY2)
Prolactin and amniotic fluid electrolytes
199
Table 111. Correlations between prolactin levels and electrolytes Independent variable. (nglml) Mean (SE)
Correl.
Dependent variable
p
Coeff. (mmol/l)
Mean (SE)
Amniotic fluid prolactin 597.7 (31.5)
AMN AMN AMN AMN
125.6 4.5 109.3 2.0
(0.9) (0.1) (1.2) (0. I )
0.05 0.02 -0.17 -0. 15
0.68 0.90 0.18 0.24
Maternal serum prolactin 230.0 (19.6)
MTRN N a + MTRN K' MTRN CIMTRN Ca+' AMN Na' AMN C1-
138.4 5.5 111.4 2.37
(0.8) (0.2) (0.9) (0.0)
-0.11 0.02
0.39
-0.09
0.47 0.18 0.36 0.22
AMN Na' AMN K + AMN C1-
125.6 (0.9) 4.5 (0.1) 109.3 (1.2)
Cord blood prolactin 421.8 (23.9)
Na' Kf C1Ca'+
relation between cord serum PRL and amniotic fluid N a ' a s well as a significant correlation between PRL and Nat in cord serum when the PRL levels were less than 230 &I. In the study group, Na', K + and C a t + values were significantly higher in maternal serum than in amniotic fluid. In this respect, the present results are in agreement with those of Johnell & NiIsson (10). A close correlation was found between maternal serum and amniotic fluid Na' and CI- @Na = 0.001; pCI = 0.019). This must be the result of diffusion between the intra-uterine compartments. Our findings suggest that. besides factors such as osmotic and hydrostatic pressures as well as PRL, more refined regulatory mechanisms may be involved in the water transport acro branes. One such factor may be atrial natriuretic factor (ANF). which is a class of diuretic and natriuretic peptides secreted by mammalian cardiac atria ( 1 I ) . A N F has. indeed, been found in uteroplacental tissue, and it has been shown that the concentration of ANF in the membranes declines after the onset of labor (12). Other compounds. such as asperginevasopressin, have also been thought to play a role in water and electrolyte transport across the fetal membranes (1 3 ) . In conclusion, even though PRL may participate in the regulation of osmotic exchange in the amniotic fluid compartments, our findings provide indirect evidence for the existence of other, more important regulatory mechanisms.
-0.17 -0.11 0.16
0.02 0.23 0.36
0.90
0.90 0.07
0.003
References 1. Brace R A . Amniotic fluid dynamics. In: Creasy RK.
2.
3.
4.
5.
6.
7.
8.
9,
10.
Resnik E. eds. Maternal and fetal medicine. principles and practice. Philadelphia: WB Saunders. 1989; 128-35. Leontic E A , Schrueffer J J . Andereassen B, Pinto H. Tyson JE. Further evidence for the role o f prolactin on human fetoplacental osmoregulation. Am J Obstet Gynecol 1979; 133: 435-8. Leontic E A . Tyson J E . Prolactin and fetal osmorcgulation: water transport across isolated human amnion. Am J Physiol 1977; 232: R124. Ross M G , Erwin MG. Lcakc R D . Oakes G. Hobel C, Fisher D A . Bulk flow of amniotic fluid water i n response to maternal osmotic challenge. Am J Obstet Gynecol 1983; 147: 697-701. McCoshen J A , Barc J . Prolactin bioactivity following decidual synthesis and transport by aniniochorion. Am J Obstet Gynecol 1985; 153: 217-23. Josimovich JB. Merisko K. Bocella L. Amniotic prolactin control over amniotic and fctal cxtracellular fluid water and electrolytes in the rhesus monkcy. Endocrinology 1977; 100: 564-70. Horrobin DF, Lloyd JJ, Lipton A. Burstyn PG. Durkin N. Muriuri KL. Actions of prolactin on human renal functions. Lancet 1971; ii: 3 5 2 4 . Seeds A E . Water dynamics in the amniotic fluid. In: Fairweather DVI, Eskes TKAB. cds. Amniotic fluid. Research and clinical application. 2nd edn. Amsterdam: Excerpta Medica. 1978: 51-7. Pullano JG, Addad NC, Apuzzio JJ. Ganesch VL. Josirnovich JB. Water and salt conservation in the human fetus and newhorn. 1. Evidence for ii role o f fctal prolactin. J Clin Endocrinol Metah I98Y; 69: 1 IX(l-6. Johnell H E , Nilsson BA. Oxygen tcnsion. acid-base status and electrolytes in human amniotic fluid. Acta Obstet Gynecol Scand 1971; SO: 183-92.
200
Nurnik Demir et al.
1 1 . Dc Bold AJ. Atrial natriuretic factor: a hormone produced by the heart. Science lY85; 230: 767-7(1. 12. Caatio C. Arora C, Hobel C. Atrial natriuretic factor in uteroplacental tissues. Am J Ohstet Gynecol 1991; 164: 263. 1.7. Ross MG, Ervin MG, Lam R W , Leake R D , Fisher DA. Fetal atrial natriuretic factor and arginine, vasopressin responses to hyperosmolality and hypervolemia. Pediatr Res 19x8: 24: 318-21.
Adress f o r correspondencc:
Namik Demir, M . D . Department of Obstetrics and Gynecology Dokuz Eylul University School of Medicine. 35340 - Inciralti lzmir Turkey
