193
Wallen bürg, Amniotic fluid. I.
Review article
•J. Perinat. Med.
5 (1977) 191
The amniotic fluid
L Water and electrolyte homeostasis
Henk C. S. Wallenburg
Department of Obstetrics and Gynecology, Erasmus University, Rotterdam, the
Netherlands
We know very little about the production and
disposal of the liquor amnii; the only sure fact is
that, in this country, nearly 2000 tons go down
the drain every year.
(D. C. A. BEVIS, 1968, Great-Britain)
l Introduction
Over the past two decades the development of new
sampling and analytical techniques together with
new possibilities for fetal diagnosis and treatment
have stimulated interest not only in the composition but also in the dynamics of amniotic fluid. It
has become evident that this fluid is neither a
passive accumulation of waste products such äs
fetal urine nor just a stagnant pool for fetal
recreation and protection, but a compartment of
rapidly exchanging water and electrolytes in a
dynamic equilibrium with the fetal and maternal
compartments.
In the following paragraphs it will be attempted
to present a brief review of some of the factors
involved in maintenance of fluid and electrolyte
homeostasis of the amniotic fluid.
l. l Outline of the problem
Many investigative approaches have been used,
including: morphologic studies on the histology
and ultrastructure of the placental and reflexed
membranes, the umbilical cord and the fetal skin;
in vivo experiments in various animals and in
J. Perinat. Med. 5 (1977)
Curriculum vitae
HENK C. S. WALLENBURG, M.D., Ph.D., born
in 1938. Received his M.D.
at the Free University,
Amsterdam, in 1961. Resident in Obstetrics and
Gynecology from 19651970, at the same University. In 1971 a Ph.D.
was obtained on a thesis
"Morphology and Pathogenesis of Placental Infarcts", at the Free University, Amsterdam. 19711972 A ssistant-Professor of
Ob-Gyn,
University
of
Pittsburgh, Medical School, Pittsburgh, Pa, U.S.A. 1972 present Associate-Professor of Ob-Gyn and Director of
the Department of Obstetrics, Erasmus University, Rotterdam.
Main fields of interest: Physiology and pathophysiology
ofuteroplacentalblood flow, and mechanisms of placental
transfer, in particularofflow-limited membrane transport.
humans; in vitro experiments on isolated membranes and umbilical cord.
Morphologic investigations can provide data which
may, to some extent, support or refute hypotheses
resulting from physiologic or clinical flndings.
Isolated morphologic data should be interpreted
with caution because of the very complex relationship between the many structures which might
contribute to the origin, exchange and composition
of the amniotic fluid.
14*
194
Wallenburg, Amniotic fluid. I.
In vivo experiments in humans are limited to intermittent sampling of amniotic fluid by means of
amniocentesis or after rupture of the membranes
during labor, and to studying the disappearance of
certain dyes, organic substances and isotopes
injected into the amniotic cavity. The recently
developed technique of in vivo measurement of
fetal urine production by means of ultrasound must
be regarded äs a major step forward to a better
understanding of the contribution of the fetal
kidneys to bulk changes in amniotic fluid. The use
of experimental animals, in which access can be
gained to the fetal and maternal compartments and
radioisotopes can be applied more freely, offers
possibilities for more extensive research. However,
the problem of valid extrapolation of the results to
man and the need for anesthesia introduce issues
Which should be carefully evaluated. In this respect,
the application of chronically instrumented models
in some species presents an important advantage
over acute preparations. Some of the problems
mentioned canbesolved by in vitro experimentation
in which one single system can be isolated and
many of the variables can be controlled. But here
another difficulty arises: how viable is the preparation and how comparable are the conditions
under which the experiments are performed with
those in the in vivo s täte.
It follows that there is no single experimental
method which could be called the "method of
choice" for the study of aiririiotic fluid production
and exchange. The results of each study have to be
evaluated against the background of the limitations
of the experimental method involved.
2 Possible pathways of amniotic fluid production
and exchange
The different types of epithelial structures which
line the amniotic cavity and the various fetal
organs which have direct Communications with the
amniotic fluid constitute possible sites of origin
and/or routes of exchange of amniotic fluid
(Fig. 1).
2. l The placental and reflexed membranes
The cells of the monolayered amniotic epithelium
are flattened in early pregnancy and become more
and more cuboidal or columnar with advancing
gestation. The free surface of the cells is covered
with microvilli, structures usually supposed to be
involved in exchange processes. All cells contain a
nucleus and, at least in early pregnancy, an extensive
rough endoplasmic reticulum, indicating ä capacity
for protein synthesis for use outside the cell. With
amniotic fluid
respiratory tract
gastro-intestinal
tract
u r m a r y tract
placental and
reflexed membranes
uterine wall
umbilical cord
fetal skin
Fig. 1. Possible pathways of amniotic fluid production and exchange.
J. Perinat. Med. 5 (1977)
195
Wallenburg, Amnioticfluid. I.
advancing gestation an increasing number of
"fibrillar" cells with fewer mitochondria and less
rough endoplasmic reticulum is found [35]. Lipid
is a prominent intracellular component of term
amniotic epithelium. The histology of the amniotic
epithelium suggests, therefore, that the amnion
cells are involved in exchange, synthesize protein,
and possibly secrete proteins and lipid. BEVIS [8]
showed that cultured cells from the placental
amnion and, in particular, from the area within a
5-cm radiusaround the cord insertion can synthesize
protein virtually identical with normal amniotic
fluid protein.
Some of the amnion cells are closely apposed but
many are separated by intercellular channels which
open directiy into the amniotic cavity. These intercellular channels explain the results of in vitro
experiments showing that bulk flow of water across
the term amnion in response to osmotic or hydraulic gradients is almost 100 times greater than
the transfer of isotopic water by simple diffusion
[33] (Tab. I). Such a bulk flow can only occur in
the presence of channels or spaces containing
water in unaltered solvent form.
The amnion, therefore, appears to function s a
molecular sieve. An average pore radius between
20 and 30 has been calculated on the basis of a
comparison between the hydraulic permeability
(Lp)* and the diffusional permeability (P)* to
water [28].
The in vitro transfer rates of solutes such s urea,
creatinine,glucose,sodium,potassium and chloride
are much lower than that of water. It has been
Tab. I. Definitions of bulk flow and diffusional flow.
Movement of water across
a porous membrane in
response to osmotic or
hydrostatic gradients
Bulk flow = nondiffusional
flow
Random movement of
water molecules across a
membrane to establish equal Diffusional flow
concentrations at both
sides
* Membrane hydraulic permeab ity (Lp) is derived from:
Jv = Lp.AP fpr ΔΤΓ = 0 (see equati n 1) and has the
dimensions of cm3.dynes"1.sec~1.
Diffusional permeability (P) is derived from J = P.AC for
ΔΡ = 0 and has the dimensions of cm.sec."1.
J. Perinat. Med. S (1977)
demonstrated that sodium is transferred across the
chorio-amnion by simple diffusion [21]. These in
vitro experiments provide Information on diffusional exchange and bulk flow of water which
cannot be obtained in in-vivo experiments with
radioisotopes and, therefore, are indispensable for
an understanding of the overall pattern of water
movement. In vivo evidence of a secretory and
absorptive function of the chorio-amnion for water
and solutes includes: the presence of amniotic
fluid very early in pregnancy, even in the absence
of a fetus; the experimental finding that fluid reaccumulates after removal of the fetus in the rhesus
monkey [7]; and the results of studies in the rhesus
monkey in which amniotic fluid was replaced with
solute free water [34].
In vivo transfer of water and solute is governed by
hydraulic, osmotic and electrochemical forces.
Water(volume)movement occurs s the result of a
net imbalance between differences in transmembrane hydraulic pressure and effective osmotic
pressures. This can be described by the following
relationship, obtained from linear non-equilibrium
thermodynamics
in which Jv = transmural volume flux
Lp = membrane hydraulic permeability
ΔΡ = transmembrane hydraulic pressure
difference
ΔτΓί = transmembrane osmotic pressure
difference due to solute i
σ^ = reflection coefficient of membrane
to solute i
The reflection coefficient σ is defined s the ratio
of membrane osmotic and hydraulic permeability
— which both have the dimensions of cm3.dynes"1.
sec"1 — and, therefore, σ has no dimension. The
enormous hydraulic permeability and the partial
permeability to many solutes give the chorioamnion
the characteristics of a "partially semi-permeable"
membrane, for which the reflection coefficient for
many solutes is less than unity. For instance, the
hydraulic permeability of tiie chorioamnion to
water is in the magnitude of 20 X l O"11 .cm3.dyn"1 .
sec"1 at physiologic transmembrane pressure differences [1], The osmotic permeability to water on
196
Wallenburg, Amniotic fluid. I.
the basis of an osmotic pressure difference due to
glucose isonly 12 Χ 10"12 cm3.dyn"1.sec""1, because
the chorioamnion is not completely impermeable
to glucose molecules. This yields a reflection
coefficient of 0.06 for glucose. Solutes with membrane a's less than one will exert less than their
calculated transmembrane osmotic pressure differences on water flux, whereas if σ of a membrane
to a solute is unity, that solute exerts the f ll
magnitude of its calculated "ideal" transmembrane
osmotic pressure on water flux. The osmotic
pressure difference Δπ of a solute can be described
by the VAN 'τ HOFF equation:
2.2 The umbilical cord
(2) ΔΤΓ = ψ
in which n = the number of moles of solute
particles, R = the universal gas constant, T = the
absolute temperature, and V = the volume of the
solution.
A biologically important consequence is that in a
non-equilibrium Situation net water transfer can
occur against a calculated osmotic pressure gradient
if the gradient results from solutes with significantly different reflection coefficients [26].
Example: Compartments l and 2 have identical
volumes and are separated by amnion. Compartment l contains 0.2 Moles of urea (aur = 0.02) and
compartment 2 contains 0.1 Moles of glucose
(°gi = 0.06). The transmembrane hy draulic pressure
difference is supposed to be zero. It follows from
equations (1) and (2) that:
1 2
- = L RT
the available data indicate that any net transfer
would appear to be from tfre amniotic fluid to the
mother.
Other factors which might play an important part
in thetransferof solutes across biological membranes
are that transport of one solute may be coupled
with transport of another solute (solute-solute
interaction), and the water-solute interaction.
At present there is no convincing evidence of the
existence of active transport — that is transport
dependent on an energy source — across the membranes.
Χ 0.1 - aur X 0.2)
J^ 2 =L P RT (0.006-0.004)
which under non-equilibrium conditions means a
net water flux from compartment l to compartment 2, whereas
The same phenomenon may be observed in a
three-compartment System if the compartments
are divided by two membranes — e.g. amnion and
chorion — with different reflection coefficients to
the same solute.
These phenomena might explain the transfer of
water from the maternal compartment to the
amniotic fluid which must take place but cannot
be explained by osmotic or hydraulic forces since
The epithelium consists of a single layer of cells
until approximately the 12th week when it becomes first bilaminar and later consists of three or
more layers. The cells of the term epithelium are
predominantly of the "fibrillar" type, suggesting
little synthetic or metabolic abilities [29]. Before
the 6th month of pregnancy the adjacent cell
membranes are fused but later intercellular channels
appear. It has been shown in in-vitro experiments
that inward and outward fluxes of 50 and 40 ml of
water per hour can be achieved between amniotic
fluid and cord blood [30], but these experiments
cannot provide Information about bulk flow. The
results of in vivo experiments with deuterated [2]
and tritiated water [17] also point to the umbilical
cord s a possible site of water transfer between
the amniotic fluid and the fetal circulation. These
data could be compatible with, the existence of
bulk flow which could be mediated by the intercellular channels, like in the chorioamnion.
2.3 The fetal skin
In early pregnancy the fetal epidermis is composed
of a few layers of cells interposed between a basal
and a superficial cell layer. The superficial cells
(periderm) gradually disappear by 17-20 weeks
and the underlying epithelium begins to keratinize.
A complete stratum corneum is present by approximately 25 weeks. Before keratinization occurs the
peridermal cells show microvilli, GOLGI apparatus,
ribosomes and an endoplasmic reticulum indicating
the possibility of functional activity. In vivo experiments have shown that urea, creatinine and
J. Perinat. Med. 5 (1977)
197
Wallenburg, Amniotic fluid. I.
electrolytes can be transferred across the fetal skin
in early midpregnancy [3]. In vitro experimentation
has confirmed the permeability of human fetal
skin to water and sodium [21] until keratinization
occurs. By approximately 25 weeks the keratinized
fetal skin appears to function no longer äs a pathway for exchange.
2.4 The gastrointestinal tract
The presence of epithelial cells, lanugo hairs and
vernix caseosa in the fetal stomach and in meconium
clearly indicates that the fetus can swallow in
utero. Radio-opaque dyeinjectedinto the amniotic
cavity of pregnant women at term is detected in
the fetal stomach and small bowel äs early äs 20
minutes following injection [25]. The fact that the
dye appears to become concentrated inside the
fetal stomach suggests that much .of the water is
absorbed. In an ingenious study PRITCHARD [31,
32] showed that the fetus swallows chromium
tagged maternal red cells injected into the amniotic
cavity. He found that a 16-week fetus swallowed
7 ml, a 20-21 week fetus 16 ml, a 28-week fetus
120 ml, and term fetuses between 210 and 760 ml
per 24 hours.
The data on fetal swallowing in midpregnancy
have been confirmed by means of injection of
radioactive colloidal gold into the amniotic sac [4].
In midpregnancy the percentage of the liquor
volume swallowed per 24 hoursis small, somewhere
between 2 and 5 %; at term, however, the fetus
may swallow per 24 hours half, or even more, of
the total amniotic fluid volume. Therefore, fetal
swallowing must be accepted to influence the
turnover of amniotic fluid water and solutes.
2.5 The respiratory tract
There is no doubt that the respiratory tract of the
fetus secretes a special liquid that fills the future
air spaces. This liquid appears to reach the amniotic
fluid because the surface-active lecithins which it
contains can be demonstrated in amniotic fluid
samples. Nothing is known about the amount of
lungfluid producedinhuman fetuses, or how much
of it is passed into the amniotic fluid. Even if a
considerable amount of water would be secreted,
J. Perinat. Med. 5 (1977)
like in fetal lambs[6],much of it could be swallowed
before re achin g the amniotic cavity. Although fetal
ehest movements [9, 36] occur and may cause
some displacement of fluid, the existence in normal
fetuses of an inward flow of fluid to the tracheobronchial tree in late pregnancy remains disputed.
On the one hand, after Lipiodol amniography no
contrast medium is detected in the fetal or neonatal
lung [20] except in a few highly pathologic pregnancies, probably due to fetal gasping movements
äs aresponse tohypoxemia [10]. The small amount
of radioactivity found in fetal lungs after injection
of radioactive colloidal gold into the amniotic sac
in midpregnancy [4] also suggests that the lungs
play little part in the absorption of amniotic fluid.
On the other hand, the possibility of significant
absorption of amniotic fluid by the fetal lungs is
supported by the finding of polyhydramnios in
cases of aplasia of the trachea [16] naso-pharyngeal
teratoma [12] and multiple peripheral lung cysts
[19].
2.6 The urinary tract
The presence of urine in the bladder of fetuses
from 11 weeks to term leaves no doubt of the
existence of fetal renal activity. Actual proof of
fetalmicturition in utero and figures for the volumes
of urine passed into the amniotic cavity have only
recently been established by means of an ingenious
ultrasonic technique for in vivo nieasurement of
fetal bladder volume [11, 37]. The fetal bladder
can be demonstrated on a compound B-scan ultrasonogram of the maternal ab dornen and appears to
fill and empty at regulär intervals. The largest
sagittal diameter — from the bladder fundus to the
bladder neck —, the maximum transverse distance
and the largest antero-posterior dimension can be
measured and allow calculation of bladder volume.
The increase in bladder volume over a l hourperiod
of time during the process of filling allows computation of the fetal urine production rate per
hour. Fetal urine production rates in normal
pregnancies of 25—42 weeks duration show a rapid
and linear increase in mean fetal urine production from 3.5 ml per hour at 25 weeks to 26 ml
per hour at 39 weeks [37, 27]. After 40 weeks
there is a sharp fall in fetal urine production [27].
Wallenburg, Amniotic fluid. I.
198
It is striking that at term the amount of amniotic
fluid swallowed by the fetus is approximately equal
to the amount of urine produced (500-700 ml
per 24 hours). These data imply that like fetal
swallowing, fetal micturition also contributes to
the turnover of amniotic fluid. However, no direct
relationship was found between amniotic fluid
volume and fetal urine production between the
36th and42ndweek in 67 normal pregnancies [27].
Fetal urine is hypotonic compared with maternal
and fetal plasma, and amniotic fluid throughout
pregnancy. The fmding that in the third trimester
the concentrations of sodium and chloride in both
amniotic fluid and fetal urine decrease, whereas
the concentrations of urea and creatinine increase
in both fluids suggests that fetal urine could
significantly contribute to amniotic fluid compositon in the last part of gestation (Tab. II).
3 Behavior of amniotic fluid water and electroly tes
The foregoing paragraphs point to a number of
possible sites where water and solutes can enter
the amniotic cavity by means of continuous diffusional processes or bulk flow: the chorioamnion
and the cord, the fetal skin and the fetal respiratory
tract. Fetal urine is added intermittently to the
amniotic fluid. As possible pathways of continuous
outflow can be regarded the chorioamnion and the
cord, whereas fetal swallowing provides phasic
disposal of quantities of amniotic fluid. The
relative importance of these routes and mechanisms
— continuous versus phasic — of ingress into and
egress from the amniotic fluid appears to change
with advancing gestation. Also the importance of
the various sites of entry or removal may differ for
different constituents of the amniotic fluid. This
makes it extremely hazardous to derive general
conclusions about the dynamics of amniotic fluid
from observations on the behavior of a certain
constituent, such äs water, in a certain period of
gestation. In the followihg paragraphs we shall
nevertheless examine some observations relevant
to the dynamics of amniotic fluid water and
electrolytes, first in the first half of pregnancy,
and then in late pregnancy. For obvious reasons
little Information is available about mid-pregnancy
between approximately 20 and 30 weeks.
3. l First half of pregnancy
Water makes up the bulk of amniotic fluid volume.
Volume has been estimated at hysterotomy by
removing the intact sac and measuring the amount
of fluid obtained. At 12 weeks the mean volume is
58 ml (ränge 35-103). With an approximately
linear increase of 20—25 ml/ week a mean volume
of 170 ml (ränge 159-342 ml) is reached at 16
weeks, followed by a more rapid increase of
50—100 ml/week to reach a mean value of 500 ml
(ränge 226-515 ml) at 20 weeks. There appears to
be an enormous Variation in amniotic fluid volume s
between individuals, but good correlations exist
between amniotic fluid volume and fetal weight,
crown-rump length, placental weight and the
duration of the amenorrhea [5], The osmolality
äs well äs the concentrations of sodium, potassium
and chloride remain virtually constant during the
first half of pregnancy and are slightly lower than
the values in matemal and fetal plasma. Amniotic
fluid composition appears to be more closely
related to the extracellular fluid composition of
the fetus than to that of the mother [21 ], suggesting
that the fetus contributes to the composition of
amniotic fluid. Combining the few available data
on fetal swallowing and voiding with those of the
increase in amniotic fluid volume around the 20 th
week a tentative impression can be gained of the
Tab. II. Average production rate, osmolality, and electrolyte and urea concentrations of fetal urine at 20 and 38 weeks
of pregnancy [4, 24, 27 J.
duration of
pregnancy
(wks)
production
rate
(ml/24 hrs)
osmolality
(m.osm./l)
Na+
K+
(mEq/1)
er
urea
(mg/100 ml)
20
38
50
600
130 ·
137
60
44
3.0
4.7
64
41
20
102
J. Perinat. Med. 5 (1977)
199
Wallenburg, Amniotic fluid. L
importance of non-phasic shifts of water and
electrolytes. The daily increase in amniotic fluid
volume at this stage of pregnancy is approximately
16 ml and the same volume is swallowed by the
fetus. The few ultrasonic measurements of fetal
urine production around the 20th week of pregnancy indicate that the fetus voids about 50 ml
per day. This would mean that about 18 ml of
water has to be removed from the amniotic cavity
per 24 hours.
Recent data on bulk flows through human amniochorion in vitro in combination with estimated invivo hydraulic and osmotic pressures are in agreement with such a flow outward from the amniotic
cavity [l]. Preliminary data suggest that movement
of water out of the amniotic sac could be enhanced
by a direct influence pf amniotic fluid prolactin
on the properties of the amnio-chorion [23]. Based
on concentrations pf electrolytes in amniotic fluid
and fetal urine [4] it can be estimated that the fetal
kidney already significanüy contributes to the
amniotic fluid composition at this stage of pregnancy. Virtually all of the K* and Cl~ needed can
be provided by fetal urine, only a small amount of
additional sodium has to be provided by other
sources (Tab. III).
All of these data indicate the existence of sizable
and independent shifts of electrolytes and bulk
flow of water between the intra-uterine and maternal compartments. An Impression of the magnitude
of these shifts can be derived from tracer exper-
iments. GILLIBRAND [13] demonstrated an
approximately linear increase in transfer rate of
water from the amniotic sac, from 120 ml/hr at 14
weeks to 350 ml/hr at 26 weeks. These results
show reasonable agreement withearlierexperimental
data [17, 18]. The average water transfer from
amniotic fluid to the mother at 12 weeks gestation
was calculated to be 64 ml/hr, from the amniotic
fluid to the fetus' 11 ml/hr and from the fetus to
the amniotic fluid only 2.5 ml/hr. At 20 weeks
there is a significant increase in the amount of
water r transferred from the fetus to the amniotic
fluid (101 ml/hr), showing that at this stage of
pregnancy the fetus is going to play a more
important part in water transfer to the amniotic
fluid. These figures, of course, include all possible
routes of diffusional exchange, bulk flow, fetal
swallowing and micturition. HUTCHINSON'S [17]
observations demonstrateslight differences between
the bidirectional fluxes suggesting the existence of
a net flux of water from mother to fetus to amniotic
fluid to mother. This would be in accordance with
the necessity of removing water added by fetal
voiding from the amniotic cavity. Though small
differences between these high rates of water turnovercannotbe demonstrated with much confidence,
the flnding that at term umbilical venous blood
contains more water than umbilical arterial blood
[15] seems to confirm the existence of a net flux
of water from the mother across the placenta to
the fetus.
Tab. III. Estimated net movements of electrolytes into the amniotic fluid necessary to maintain homeostasis at 20 and
38 weeks [14, 27,31].
Duiation pf
pregnancy
(wks)
concentration
in amniotic
fluid (mEq/1)
removed by
fetal swallowing
(mEq/24hrs)(l)
added with
fetal urine
(mEq/24 hrs) (2)
20
Na+ .
K*
133
4.0
105
2.1
0.06
1.7
3
0.15
3.2
38
Na+
K+
128
4.0
100
76
2.4'
60
26
2.8
25
er
er
(1) 16 and 600 ml/24 hrs at 20 and 38 weeks, respectively
(2) 50 ml and 600 ml/24 hrs at 20 and 38 weeks, respectively
(3) 16 ml/24 hrs at 20 weeks, none at 38 weeks
J Perinat. Med. 5 (1977)
mEq/24 hrs
needed for
increase in
volume (3)
mEq/24 hrs
to be provided
by another
mechanism
2.1
0.06
1.7
1.2
—
0.2
—
—
50
—
35
200
3.2 Late pregnancy
The volume of the amniotic fluid in the last trimester of pregnancy can be estimated by means of
a dilution technique, for which a variety of substances has been used. The reliability of these
measurements depends mainly on adequate mixing
of the indicator with the amniotic fluid. Most
investigators agree that amniotic fluid volume
increases to a peak volume of 500—1200 ml at
38-40 weeks and then declines to about 250 ml
by 43 weeks. Amniotic fluid osmolality decreases
progressively in the second half of pregnancy,
whereas maternal serum osmolality remains constant; between 38 and 44 weeks mean amniotic
fluid osmolality is 29 mOsm/kglower than that of
maternal serum [14].
Also the sodium concentration, which largely
\ietermines osmolality,falls äs pregnancy progresses;
between 38 and 44 weeks the mean amniotic fluid
deficit for sodium compared to matemal and fetal
serum is 8.8 mEq/1. A drop in chloride concentration also occurs in the last weeks before term
but this is far less marked than the fall in sodium.
Usually the concentration of chloride in amniotic
fluid at term is somewhat higher than in matched
samples of maternal plasma [22]. The weak correlation between the fall in sodium and that in chloride
concentration suggests that their exchange is at
least partiaUy independent. The potassium levels
in maternal serum and amniotic fluid do not significantly change with advancing gestation [14].
Though the fast rate of increase in water transfer
between the fetal and maternal compartments and
the amniotic fluid seems to slow down somewhat
äs pregnancy advances, water exchange reaches
enormous values in particular between mother and
fetus (3-4 liters/hr) [17].
Approximately 400—500 ml of water leave the
amniotic fluid per hour [13] of which about 150 ml
(30%) passthroughthe fetus, Sodium and potassium
leave the amniotic fluid at rates of 12.0 and 0.5
mEq/hour, respectively, independent of their concentration [18]. Accepting that water leaves the
amniotic fluid at term at a rate of 500 ml/hr, this
amount of solvent would carry with it about 65
mEq of sodium and 2 mEq of potassium (see Tab.
III). The experimentally determined much lower
transfer rates for these electrolytes demonstrate
Wallenburg, Amniotic fluid. I.
again that water and electrolytes are exchanged
independently at their own characteristic rates.
The drop in amniotic fluid sodium concentration
and osmolality with advancing gestation is generally
attributed to the fetus passing an increasing amount
of hypotonic urine into the amniotic cavity. The
phasic addition of urine water is approximately
balanced by removal of an equal amount of water
by fetal swallowing. Fetal swallowing, however,
removes considerable amounts of sodium and
chloride from the amniotic fluid which have to be
replenished by net movement of these electrolytes
back into the amniotic fluid (Tab. III). It has been
suggested that hydrochloric acid produced by the
fetal stomach might in late pregnancy play a part
in the necessary continuous addition of chloride
ions to the amniotic fluid.
The question arises how and why the amniotic
fluid maintains its osmolal deficit. There is no
obvious explänation äs to why amniotic fluid
sodium should not equilibrate with that of maternal and fetal serum. It is also obvious that the
increasing osmolal deficit would theoretically
tend to result in loss of water whereas amniotic
fluid volume steadily increases up until 38—40
weeks. It is possible that amniotic fluid osmolality
serves äs a factor in the control of fetal body water
and electrolyte homeostasis [14].
4 Control of amniotic fluid homeostasis.
It has been shown that amniotic fluid behaves äs a
separate compartment while rapidly exchanging
water and electrolytes with the fetus and the
mother. Which mechanisms control and maintain
the dynamic equilibrium of water and electrolytes
between the amniotic fluid, the fetus and the
mother? Phasic transport of water and solutes by
fetal swallowing and micturition certainly plays a
part in homeostasis but on the other hand creates
electrolyte deficits, in particular at term. This
necessitates net and independent movement of
sodium and chloride into the amniotic cavity.
Since there is no evidence for the existence of active
transport of water or electrolytes across the membranes or the fetal skin, any net transfer from
mother or from fetus to amniotic fluid must take
place in response to osmotic or hydraulic forces.
J. Perinat. Med. 5 (1977)
Wailenburg, Amniotic fluid. L
The scanty Information thatisavailable on osmotic
gradients between the uterine and umbilical circulations, and between fetal and matemal extracellular fluids and amniotic fluid, suggests that they
are almost equal or would appear to exert a force
from the fetus to the mother, and from the
amniotic fluid to the fetus äs well äs to the mother.
However, äs discussed previously, the occurrence
of different concentrations of solutes with different
reflection coefflcients could result in osmotic water
shifts against apparent osmotic gradients.
Recent in vitro studies on guinea pig membranes
suggest that prolactin, cortisol and ADH, which
are normally present in amniotic fluid, could
influence the permeability of amnio-chorion to
water [23].
The hydrostatic pressure in the umbilical vessels is
higher than that prevailing in the intervillous spaces
and could therefore be expected to transfer water
from the fetus to the mother. On the other hand,
with advancing pregnancy increasing fetal hydro-
201
static pressure could force water and solutes into
the amniotic fluid through the cord.
The existence of a variety of clinical situations in
which pathologic alterations in amniotic fluid
volume — polyhydramnios and oligohydramnios —
are known to occur demonstrates that an imbalance
of amniotic fluid water exchange can be due to
many different fetal abnormalities and to maternal
disease. This suggests that there is not one single
factor which controls amniotic fluid volume but
that the relative efficiency of all of the discussed
pathwaysand mechanisms contributes to the maintenance of amniotic fluid homeostasis. But the
overall picture is far from clear. At present our
knowledge of the nature and the relative importance
of the biochemical and biophysical forces which,
together with fetal swallowing and voiding, control
the dynamics of the amniotic fluid and its constituents is too meager to be able to postulate a
theory which could link all available clinical and
experimental data.
Keywords: Amniotic fluid, amniotic fluid water and electrolytes, bulk flow, homeostasis, reflection coefficient,
amniotic epithelium, fetal micturition, oligohydramnios, polyhydramnios.
Zusammenfassung
Das Fruchtwasser. I. Wasser und Elektrolythomeostase
Viele Forschungsvorhaben konzentrierten sich auf das
Studium der Wasser-und Elektrolythomeostase im Fruchtwasser. Diese Untersuchungen beinhalteten morphologische Untersuchungen, in vivo Experimente bei Tier und
Mensch und in vitro Untersuchungen an isolierten Präparationen. Jede dieser Methoden hat ihre eigenen, spezifischen Vor- und Nachteile; es gibt keine Methode der
Wahl für das Studium der Fruchtwasserproduktion und
des Fruchtwasseraustausches.
Die verschiedenen epithelialen Strukturen, die die Fruchtwasserhöhle begrenzen, und die verschiedenen fetalen
Organe, die direkten Kontakt mit dem Fruchtwasser
haben, bilden die möglichen Ursprungsorte und/oder
Austauschwege des Fruchtwassers. Das Baugefüge der
Amnionzellen der Plazenta und die dazugehörigen Membranen lassen vermuten, daß sie an den Austauschprozessen
beteiligt sind, Proteine synthetisieren und möglicherweise
Proteine und Lipide abgeben. Das Vorhandensein von
Kannälchen mit einem mittleren Radius zw. 20 und 30 A
zwischen den Amnionzellen erklärt den Befund, daß die
Hauptmenge des Wasseraustausches durch die Eihäute am
Termin nahezu 100 mal größer ist als der einfache Transfer
von Wasser via Diffusion. Der Austausch von Wasser und
gelösten Bestandteilen wird in vivo durch hydraulische,
osmotische und elektrochemische Kräfte gesteuert. Auf
Grund der eingeschränkten Permeabilität des ChorioJ. Perinat. Med. 5 (1977)
amnions für viele Lösungsbestandteile können letztere
ihre osmotische Wirksamkeit auf den Wasseraustausch
durch die Membranen hindurch nicht in dem Maße ausüben, wie es rechnerisch zu erwarten wäre. Der Quotient
aus osmotischer und hydraulischer Membranpermeabilität
wird als Reflektionskoeffizient ( ) eines gelösten Stoffes
bezeichnet. Die Anwesenheit von Lösungsbestandteilen
mit signifikant verschiedenen Reflektionskoeffizienten in
zwei Kompartimenten, die durch eine semipermeable
Membran voneinander getrennt sind, vermag den Wassertransport gegen einen rechnerisch ermittelten osmotischen
Gradienten zu erklären. Dieses Phänomen könnte für den
Wassertransport vom mütterlichen Kompartiment in das
Fruchtwasser hinein verantwortlich sein, ein Transport,
der stattfinden muß, der jedoch auf der BAsis von berechneten osmotischen und hydraulischen Kräften bisher
schwer zu erklären ist.
Resultate der in vivo und in vitro Experimente weisen
darauf hin, daß die Hauptwassermenge auch durch die
interzellulären Kannälchen des Nabelschnurepithels hindurch erfolgen kann.
Bis zur vollen Keratinisiemng, die ungefähr in der 25.
Schwangerschaftswoche erfolgt, ist die fetale Haut für
Wasser und Elektrolyte durchlässig. Von diesem Zeitpunkt
an ist die fetale Haut nicht mehr als Austauschorgan
anzusehen. Am Termin verschluckt der Fetus innerhalb
von 24 Stunden ca. die Hälfte, oder sogar mehr, des
Fruchtwasservolumens.
202
Es muß daher angenommen werden, daß der fetale
Schluckakt den turnover von Fruchtwasser und seinen
gelösten Bestandteilen beeinflußt. Die Mehrzahl der verfügbaren Daten läßt vermuten, daß der fetale Respiration^·
trakt keine wichtige Rolle spielt beim Austausch von
Fruchtwasser und Elektrolyten. Kürzlich wurden Zahlen
bekannt über die Menge fetalen Urines, der in die Fruchtwasserhöhle abgegeben wird; diese Zahlen sind durch
Ultraschall-Messungen des fetalen Blasenvolumens über
eine gewisse Zeit hinweg gewonnen worden. Bei normalen
Schwangerschaften steigt die fetale Urinproduktion
rasch linear an, von ungefähr 3,5 ml/Std. in der 25. Woche
auf ungefähr 26 ml/Std. in der 39. Woche. Nach der 40.
Schwangerschaftswoche scheint die fetale Urinproduktion
wieder abzunehmen. Diese Daten und die Tatsache, daß
im dritten Schwangerschaftstrimester die Konzentration
an Natrium und Chlorid sowohl im Fruchtwasser wie im
fetalen Urin abnehmen, während Konzentrationen von
Harnstoff und Kreatinin in beiden Flüssigkeiten zunimmt, lassen vermuten, daß der fetale Urin die Fruchtwasserzusammensetzung signifikant beeinflußt, zumindest
in den letzten Phasen der Schwangerschaft.
Es kann gefolgert werden, daß das Chorioamnion und die
'Nabelschnur die wichtigsten Austauschorgane für den
kontinuierlichen Wasser- und Elektrolytaustausch sind.
Der fetale Urin wird intermittierend in das Fruchtwasser
abgegeben, während das Verschlucken des Fruchtwassers
durch den Feten ein phasisches Entfernen von Fruchtwassermengen bedeutet. Die relative Wichtigkeit dieser
Austauschwege und -mechanismen verändert sich mit zunehmender Tragezeitdauer.
In der ersten Schwangerschaftshälfte scheint die Zusammensetzung des Fruchtwassers mehr der fetalen als
der mütterlichen extrazellulären Flüssigkeit zu gleichen.
In der 20. Schwangerschaftswoche beträgt die tägliche
Zunahme an Fruchtwasser ca. 16 ml; daselbe Fruchtwasservolumen wird vom Fetus verschluckt. Ultraschallmessungen der fetalen Urinproduktion zeigen, daß der Fet
zu diesem Gestationszeitpunkt um 50 ml pro Tag Urin abgibt. Diese Zahlen vermitteln uns einen Eindruck der
Wichtigkeit des nichtphasischen Wassertransportes. Ungefähr 18 ml Wasser müssen pro 24 Stunden aus der
Fruchtwasserhöhle entfernt werden. Vorläufige Daten
lassen vermuten, daß solche Wasserbewegungen aus dem
Amnionsack heraus beschleunigt wird durch Fruchtwasserprolaktin. In der ersten Hälfte der Schwangerschaft kann
praktisch alles Kalium und Chlorid des liquor amnii vom
fetalen Urin geliefert werden. Nur ein kleiner Anteü zusätzlichen Natriums muß aus anderen Quellen gedekct
Wallenburg, Amniotic fluid. I.
werden. Diese Daten belegen die Existenz meßbarer und
unabhängiger Verschiebungen von Elektrolyten und von
Wasser zwischen dem intrautejripen und dem mütterlichen
Kompartiment. Diese Auffassung wird gestützt durch Experimente mit markierten Substanzen.
Wählend der zweiten Schwangerschaftshälfte wird ein zunehmender Abfall der Osmolalität des Fruchtwassers beobachtet. Dies scheint vorwiegend durch einen Abfall der
Natriumkonzentration bedingt zu sein, die ihrerseits auf
den Feten zurückgeführt werden kann, der zunehmende
Mengen hypotonen Urins in die Amnionhöhle abgibt. Ein
Abfall der Chloridkonzentration erfolgt ebenfalls, ist jedoch weit weniger ausgeprägt als der Natriumabfall. Die
Kaliumspiegel bleiben praktisch unverändert. Die phasische
Wasserzufuhr durch den fetalen Urin wird durch das Verschlucken einer ungefähr gleich großen Fruchtwassermenge
durch den Fetus (zwischen 200 und 700 ml pro 24 Stunden am Termin) ausgeglichen. Andererseits wird durch das
fetale Verschlucken von Fruchtwasser eine erhebliche
Menge an Natrium udn Chlor aus dem Fruchtwasser entfernt. Es kann errechnet werden, daß am Termin ungefähr
50 mEq Natrium und ungefähr 35 mEq Chlor pro Tag ersetzt werden müssen durch reine Verschiebung an Elektrolyten in das Fruchtwasser hinein. Dies belegt erneut
den notwendigen, kontinuierlichen und unabhängigen
Austausch von Wasser und Elektrolyten.
Es gibt jedoch wenig Information darüber, welche Faktoren diesen Austausch im Gleichgewicht halten mit dem
phasischen Transport von Wasser und Lösungsbestandteilen
durch den fetalen Schlückakt und die Miktion. Die osmotischen Gradienten zwischen uteriner und umbilikaler
Zirkulation einerseits und zwischen fetalem und mütterlichem extrazellulären Raum und Fruchtwasser andererseits könnten möglicherweise Kräfte entfalten, die das
Wasser aus dem Fruchtwasser herausziehen. Wie jedoch
bereits besprochen, könnte die Anwesenheit von Lösungsbestandteilen verschiedener Konzentration mit unterschiedlichen Reflektionskoeffizienten zur Folge haben,
daß eine osmotische Wasserbewegung gegen osmotische
Gradienten erfolgt. Der mit fortschreitender Schwangerschaf t zunehmende fetale Blutdruck könnte ebenso Wasser
und Lösungsbeständteile durch die Nabelschnur hindurch
in das Fruchtwasser hineindrücken. Gegenwärtig sind
unsere Kenntnisse über die Natur und die relative Bedeutung dieser biochemischen und biophysikalischen Kräfte
zu beschränkt, um eine Theorie postuüeren zu können,
die alle klinisch verfügbaren und experimentell gewonnenen
Daten zusammenfassen könnte.
Schlüsselwörter: Amnionepithel, Elektrolyte, Fruchtwasser, Homeostasis, Miktion (fetale), Oligohydramnion, Polyhydramnion.
Resume
Le liquide amniotique. L Homoeostasis d'eau et d'electrolytes
De nombreuses etudes ont ete effectuees sur l'existence
d'homoeostasis liquide et electrolytique dans le liquide
amniotique. Ces etudes ont ete notamment d'ordre
morphologique: experimentations in vivo sur des etres
humains et des animaux, recherches in vitro sur des
systemes isoles. Chaque methode presente des avantages
et des limites specifiques et il n'en existe pas d'exclu-
sivement valable pour 1'examen de la production de
liquide amniotique et de ses echanges. Les differents types
de structures epitheliales qui bordent la cavite amniotique,
etlesdiversorganes foetaux qui communiquent diiectement
avecleliquideamniotiqueconstituentlessourceseventuelles
et:ou les voies d'echange du liquide amniotique. La
structure des cellules amniotiques du placenta et des
membranes reflexed permet de supposer qu'eiles sont
impliquees dans les processus d'echange, synthesent les
proteines et secretent eventuellement des proteines et des
J. Perinat. Med. 5 (1977)
Wallenburg, Amniotic fluid. L
lipides. La presence de canaux avec un rayon de pore
moyen de20-30° entre Icsccllulesamniotiquesexpliquent
les resultats trouves selon lesquels le principal flux d'eau
a travers Famnios a terme est presque 100 fois plusgrand
que le transfert d'eau par simple diffusion. In vivo, le
transfert d'eau et de solute est commande par hydraulise,
osmose et electrochimie. Etant donne la permeabilite
partielle du chorioamnios a beaucoup de solute s, ceux-ci
ne peuvent pas exercer leur pression osmotique transmembraneuse osmotique et hydraulique est defini par le
coefficient de reflection ( ) d'un solute. La presence de
solutes avec des coefficients de reflection tres differents
en deux compartiments, separes par une membrane semipermeable, peut expliquer l'apparition d'un net transfert
d'eau contre un gradient osmotique calcule.
Ce phenomene peut etre ä Porigine du transfert net d'eau
du compartiment maternel au liquide amniotique qui
s'opere sans aucun doute bien qu'on puisse difficilement
l'expliquer par les forces calculees d'osmose et d'hydraulise.
Les resultats des experimentations in vivo et in vitro indiquent que le flux principal d'eau pourrait aussi se faire
par les canaux intercellulaires de Fepithelium du cordon
ombilical.
La peau du foetus est permeable ä l'eau et l'electrolyse
jusqu'a keratinisation.complete est survenue aux alentours
de la 25eme semaine, moment auquel la peau foetale ne
finctionne plus comme voie d'echange. Au terme de la
grossesse, le foetus absorbe environ la moitie ou meme plus
du volume du liquide amniotique par 24 heures. En consequence, Fabsorption foetale doit etre consideree comme
influencant le transfert de l'eau et des solutes du liquide
amniotique. La plupart des donnees obtenues laissent
supposer que la voie respiratorie du foetus ne joue pas
un role important dans Fechange d'eau et d'electrolytes
du liquide amniotique.
Depuis peu, les donnees recueillies pour les volumes
d'urine foetale passee dans la cavite amniotique peuvent
etre mesurees par le calcul ultrasonique de l'accroissement
du volume de la vessie foetale pendant un certain laps de
temps. Dans les grossesses normales, la production d'urine
foetale augmente de faqon rapide et continue a raison
d'environ 3,5 ml par h. a la 25eme semaine jusqu'a
environ 26 ml par h. a la 39eme semaine. Apres la 40eme
semaine, la production d'urine foetale semble diminuer.
Ces donnees ainsi que Fobservation faite selon laquelle, au
3 emetrimestre de la grossesse, les concentrations de sodium
et de chlorures diminuent dans le liquide amniotique et
l'urine foetale, tandis qu'y augmentent les concentrations
d'uree et de creatinine, semblent prouver que l'urine du
foetus represente sans doute un element important du
liquide amniotique, au moins dans la derniere partie de la
grossesse.
On peut en deduire que le chorioamnios et le cordon
constituent les principales voies d'echange continu d'eau
et de solutes. L'urine foetale s'additionne par intermittence
au liquide amniotique, tandis que l'absorption foetale
fournit phasiquement des quantites de liquide amniotique.
L'importance relative de ces voies et mecanismes evolue
selon le stade de la grossesse. Dans la premiere moitie de
la grossesse, la composition du liquide amniotique semble
se rapprocher davantage du liquide extracellulaire foetal
203
que maternel. A la 20eme semaine de grossesse, l'augmentation quotidicnne du volume de liquide amniotique
est approximativement de 16 ml et le meme volume est
absorbe par le foetus. La mesure ultrasonique de la production d'urine foetale indique que le foetus elimine
environ 50 ml par jour ä cette periode de grossesse. Ces
donnees nous livrent une idee de l'importance du transfert
d'eau non-phasique. 18 ml d'eau environ doivent etre
evacues de la cavite amniotique toutes les 24 h. Des
resultatspreliminairesfont supposer qu'une teile evacuation
d'eau en dehors du sac amniotique est probablement accrue
par une prolactine du liquide amniotique. Dans la premiere
moitie de la grossesse, l'urine foetale peut pratiquement
fournir la total i te du potassium et des chlorures du
liquide amniotique. Seule, une faible quantite de sodium
supplementaire doit provenir d'autres sources. Ces
donnees indiquent l'existence de transferts mesurables et
independants d electrolytes et de flux principal d'eau
entre les compartiments intra-uterin et maternel, ainsi que
ie confirment les resultats des experiences enregistrees.
Dans la seconde moitie de la grossesse, on observe une
baisse progressive dans l'osmolalite du liquide amniotique.
II semble que cela soit du en grande partie a une baisse
de la concentration de sodium qui peut etre attribuee au
foetus passant un volume croissant d'urine hypotonique
dans la cavite amniotique. Une diminution de la concentration de chlorures s'opere donc, mais sans etre aussi
forte que la chute du sodium. Les niveaux de potassium
ne changent pratiquement pas. L'addition phasique d'eau
urinaire foetale se trouve a peu prcs equilibree par le
transfert d'un volume egal d'absorption foetale (entre
200 et 700 ml/24 h. au terme de la grossesse). Par
ailleurs, l'absorption foetale retire du liquide amniotique
des quantites considerables de sodium et de chlorures.
On peut estimer ä 50 mEq et 35 mEq les quantites
respectives et approximatives de sodium et de chlorures
par 24 h. qui doivent etre redomrees au liquide amniotique
par un mouvement net de ces electrolytes, au terme de la
grossesse. Ceci prouve a nouveau Fechange necessairement
continu et independant d'eau et d'electrolytes.
On ne connait pas encore bien, cependant, les facteurs qui
maintiennent ces echanges en equilibre avec le transfert
d'eau et de solutes par absorption et micturition foetales.
Des gradients osmotiques entre les circulations uterine et
ombilicale et entre les liquides extracellulaires foetäux et
maternels et le liquide amniotique semblent devoir
exercer des forces qui retirent l'eau de la cavite amniotique.
Comme il a ete discute plus haut cependant, l'apparition
de concentrations differentes de solutes avec des coefficients
de reflection differents pourraient conduire a des transferts osmotiques d'eau contre des gradients osmotiques
apparents. La pression sanguine hydrostatique foetale,
augmentant en meme temps qu'avance la grossesse,
pourrait donc amener l'eau et les solutes ä passer dans le
liquide amniotique a travers le cordon. Notre connaissance
de la nature et de l'importance relative de ces forces biochimiques et biophysiques est encore trop limitee actuellement pour nous permettrc de postuler une theorie qui
resume et synthese toutes les donnees cüniques et
experimentales enregistrees.
Mots-cles: Liquide amniotique, eau et electrolytes du liquide amniotique, flux principal, homoeostasis, coefficient de
reflection, epithelium amniotique, micturition foetale, oligohydramnios, polyhydramnios.
J. Perinat. Med. 5 (1977)
204
Wallenburg, Amniotic fluid. I.
Bibliograph/
[1] ABRAMOVICH, D. R., K. R. PAGE, L. JANDIAL:
Bulk flows through human fetal membranes. Gynecol.
Invest. 7 (1976) 157
[2] ABRAMOVICH, D. R., K. R. PAGE: Pathways of
water transfer between liquor amnii and the fetoplacental unit at term. Europ. J. Obstet. Gynec.
Reprod.Biol. 3(1973)155
[3] ABRAMOVICH, D. R., B. HEATON, K. R. PAGE:
Transfer of labelled urea, creatinine and electrolytes
between liquor amnii and the fetoplacental unit in
midpregnancy. Europ. J. Obstet. Gynec. Reprod.
Biol. 4 (1974) 143
[4] ABRAMOVICH, D. R.: Fetal factors influencing the
volume and composition of liquor amnii. J. Obstet.
Gynaec. Brit. Cwlth. 77 (1970) 865
[5] ABRAMOVICH, D. R.: The volume of amniotic fluid
in early pregnancy. J. Obstet. Gynaec. brit. Cwlth.
75 (1968)728
. [6] ADAMS, F. H., D. T. DES1LETS, B. TOWERS:
Control of flow of fetal lung fluid at the laryngeal
outlet. Resp. Physiol. 2 (1967) 302
[7] BEHRMAN, R. E., J. T. PARER,C. W. DE LANNOY:
Placental growth and the formation of amniotic
fluid. Nature 214 (1967) 678
[8] BEVIS, D. C. A.: Errors arising from amniocentesis
and the origin of the liquor amnii. J. Obstet. Gynaec.
Brit. Cwlth. 75 (1968) 1214
[9] BODDY, K., C. D.MANTELL: Observationsof foetal
breathing movements transmitted through maternal
abdominal wall. Lancet II (1972) 1219
[10] BODDY, K., G. S. DAWES, R. FISHER: Foetal
respiratory movements, electrocorticai and cardiovascular responses to hypoxaemia and hypercapnia
in sheep. J. Physiol. 243 (1974) 599
[11] CAMPBELL, S., J. W. WLADIMIROFF, C. J. DEWHURST: The antenatal measurement of fetal urine
production. J. Obstet. Gynaec. Brit. Cwlth. 80 (1973)
680
[12] CHARLES, D.: Fetal lung pathology and hydramnios.
Obstet. Gynec. 16 (1960) 495
[13] GILLIBRAND, P. N.: The rate of water transfer from
the amniotic sac with advancing pregnancy. J. Obstet.
Gynaec. Brit. Cwlth. 76 (1969) 530
[14] GILLIBRAND, P. N.: Changes in the electrolytes,
urea and osmolality of the amniotic fluid with advancing pregnancy. J. Obstet. Gynaec. Brit. Cwlth.
76(1969)898
[15] HARBERT,G.M.,R.G.BRAME,H.S.MCGAUGHEY,
W. N. THORNTON: Fetomaternal water exchange.
Obstet. Gynec. 32 (1968) 232
[16] HOPKINSON, J. M.: Congenital absence of the
trachea. J. Pathol. 107 (1972) 63
[17] HUTCHINSON, D. L., M. J. GRAY, A. A. PLENTL,
H.
ALVAREZ,
R.
CALDEYRO-BARCIA,
B. KAPLAN, J. LIND: The role of the fetus in the
water exchange of the amniotic fluid of normal and
hydramniotic patients. J. Clin. Invest. 38 (1959) 971
[18] HUTCHINSON,D.L.,C. B.'HUNTER^.D.NESLEN,
A. A. PLENTL: The exchange of water and electrolytes in the mechanism of amniotic fluid formation
and the relationship to hydramnios. Surg. Gynec.
Obstet. 100(1955)391
[19]IZZO, C., P. P. RICKHAM: Neonatal pulmonary
hamartoma. J. Pediat. Surg. 3 (1968) 77
[20] LILEY, A. W.: Disorders of amniotic fluid, in:
ASSALI, N. S.: Pathophysiology of Gestation,
volume II. Academic Press, New York & London
1972
[21] LIND, T., A. KENDALL, F. E. HYTTEN: The role
of the fetus in the formation of amniotic fluid. J.
Obstet. Gynec. Brit. Cwlth. 79 (1972) 289
[22] LIND, T.: The biochemistry of amniotic fluid. In:
FAIRWEATHER, D. V. L, T. K. A. B. ESKES:
Amniotic Fluid. Excerpta Medica, Amsterdam 1973
[23] MANKU, M. S., J. P. MTABAJI, D. F. HORROBIN:
Effectof cortisol, prolactin and ADH on the amniotic
membrane. Nature 258 (1975) 78
[24]MCCANCE, R. A., E. M. WIDDOWSON: Renal
function before birth. Proc. roy. Soc. Lond. 141 .
(1953)488
[25] MCLAIN, JR., C. R.: Amniographic studies of the
gastro-intestinal motility of the human fetus. Amer.
J. Obstet. Gynec. 86 (1963) 1079
[26] MESCHIA, G., I. SETNIKAR: Experimental study
of osmosis through a collodion membrane. J. gen.
Physiol. 42 (1958) 429
[27] OTTERLO, L. C. VAN, J. W. WLADIMIROFF,
H. C. S. WALLENBURG: Relationship between
fetal urine production and amniotic fluid volume
in normal pregnancy and pregnancy complicated by
diabetes. Brit. J. Obstet. Gynaec. 7 84 (1977) 205
[28] PAGE, K. R., D. R. ABRAMOVICH, M. R. SMITH:
Water transport across isolated term human amnion.
J. Membrane Biol. 18 (1974) 49
[29] PARRY, E. W., D. R. ABRAMOVICH: Some observations on the surface layer of full-term human
umbilical cord epithelium. J. Obstet. Gynec. Brit.
Cwlth., 77 (1970) 878
[30] PLENTL, A. A.: Transfer of water across perfused
umbüical cord. Proc. Soc. Exp. Biol. Med. 107 (1961)
622
[31] PRITCHARD, J. A.: Deglutition by normal and anencephalic fetuses. Obstet. Gynecol. 25 (1965) 289
[32] PRITCHARD, J. A.: Fetal swallowing and amniotic
fluid volume. Obstet. Gynec. 28 (1966) 606
[33] SEEDS, A. E.: Water transfer across the human
amnion in response to osmotic gradients. Amer. J.
Obstet. Gynec. 98 (1967) 568
[34] SCHRUEFER, J. J. P., A. E. SEEDS, R. E. BEHRMAN, A. E. HELLEGERS, P. BRUNS: Changes in
amniotic fluid volume and total solute concentration
in the rhesus monkey following replacement with
distüled water. Amer. J. Obstet. Gynec. 112 (1972)
807
[35] THOMAS, C. E.: The ultrastructure of human
amnion epithelium. J. Ultrastruct. Res. 13 (1965) 65
J. Perinat. Med. 5 (1977)
Wallenbuig, Amniotic fluid. L
[361 WLADIMIROFF, J. W.f C. M. LIGHTVOET, J. A.
SPERMON: Combined one- and two-dimensional
ultrasound system for monitoring fetal breathing
movemcnts. Brit. Med. J. 2 (1976) 975
[37J WLADIMIROFF, J. W., S. CAMPBELL: Fetal urineproduction rates in normal and complicatcd prcenancy. Lancet l (1974) 151
Henk C. S. Wallenbuig, M.D.. Ph.D.
Department Ob-Gynt
AZR - Dijkzigt.
Dr. Molewaterplesn 40.
Rotterdam - 3002,
The Netherlands.
l l*«»*»«»