Seminars in Fetal & Neonatal Medicine 22 (2017) 71e75

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Seminars in Fetal & Neonatal Medicine

journal homepage: www.elsevier.com/locate/siny

Water balance in the fetus and neonate

Julie B. Lindower
Division of Neonatology, University of Iowa Stead Family Children's Hospital, 8808 John Pappajohn Pavilion, Iowa City, IA, 52242, USA

a b s t r a c t
Keywords: Fetal water balance is dependent prenatally on the placental transfer of water from maternal to fetal
Watereelectrolyte balance circulation. Adequate amniotic fluid volume is one indicator of stable fetal status and development.
Fetus
Excessive or less than expected amniotic fluid volume may be a precursor to postnatal morbidity and
Newborn
mortality. Postnatal transition is marked by predictable changes in body water including contraction of
extracellular volume and insensible fluid loss, primarily across the skin barrier. The degree to which
these occur is determined by gestational and postnatal age. Neonatal complications and clinical condi-
tions associated with either retention or excessive loss of body water can occur. Fluid therapy in the
neonatal intensive care unit may be guided using three clinical indicators: change in body weight, serum
sodium concentration, and urine output.
© 2017 Elsevier Ltd. All rights reserved.

1. Fetal water balance
1.1. Amniotic fluid physiology
Amniotic fluid water balance is critical to fetal health. Amniotic
fluid supports normal fetal development and allows for unre-
stricted fetal movement. Inadequate or excessive amniotic fluid
volume is associated with fetal and neonatal conditions associated
with morbidity and mortality.
During fetal life, water is divided between the fetus, placenta,
chorionic and amniotic membranes, and amniotic fluid. Amniotic
fluid may be conceptualized as a fetal fluid compartment. It is
formed from either a transudate of fetal plasma through non-
keratinized skin or from maternal plasma across the uterine
decidua or placental surface. At term, the average fetus contains
~3000 mL of water, 350 mL of which is in the vascular compartment
[1].
The major sources of amniotic fluid water are fetal urine and
fetal lung fluid. Amniotic fluid is absorbed via fetal swallowing and
intramembranous flow [2]. During the first trimester, amniotic fluid
is isotonic with maternal plasma, but contains minimal protein [3].
As gestation advances, the osmolality and sodium content of am-
niotic fluid both decrease. This is due to fetal production of dilute
urine and isotonic fetal lung fluid secretion. By term the amniotic
fluid osmolality is about 85e90% of maternal serum osmolality. In
contrast, fetal urinary byproducts in amniotic fluid (urea,
E-mail address: julie-lindower@uiowa.edu.
creatinine, and uric acid) increase during the second half of
gestation to concentrations two to threefold higher than concen-
trations found in fetal plasma [4].
The amniotic fluid volume at term may vary from 500 to
>1200 mL [5] (Fig. 1).
Body water in the fetus may be conceptualized by dividing it
into the intracellular and extracellular compartments. Intracellular
water is defined as water present within cells. Extracellular water is
divided between the blood plasma, the interstitial space, and in
relatively smaller amounts bone, dense connective tissue, and
epithelial-lined spaces (transcellular fluid) including cerebrospinal
fluid, synovial fluid, and pleural fluid.
At 24 weeks of gestation fetal total body water is ~86% of body
weight, of which the majority (60%) is in the extracellular
compartment. At term, total body water is ~78% of body weight
with 44% in the extracellular compartment, 34% in the intracellular
compartment, and the remainder (22%) as solid body mass [6].
1.2. Homeostatic mechanisms
Under the current understanding of fetal water flow, water
moves from maternal to fetal circulation through the placenta,
possibly by formation of an osmotic gradient created by the active
transport of sodium. Transplacental water flow to the fetus occurs
through aquaporin water channels. The expression of these pro-
teins changes as gestation advances and with pathologic states
such as polyhydramnios and fetal acidosis [1].
Homeostatic control of amniotic fluid volume is thought to be

http://dx.doi.org/10.1016/j.siny.2017.01.002
1744-165X/© 2017 Elsevier Ltd. All rights reserved.
72 J.B. Lindower / Seminars in Fetal & Neonatal Medicine 22 (2017) 71e75
Fig. 1. Black dots refer to the mean amniotic fluid volume at a given gestational age
between 8 and 44 weeks. Percentiles along the distribution are shown on the right
vertical axis, with amniotic fluid volume in milliliters shown on the left vertical axis.
Grey shading indicates 2 standard deviations above and below the mean. Reproduced
with permission from Beall et al. [5].
mediated, at least in part, by small (28e30 kDa) membrane proteins
known as aquaporins. First discovered by Abre, these proteins allow
water molecules to pass across lipid membranes at a faster rate
than would be possible by diffusion alone, while excluding most
other molecules [7]. Thirteen aquaporins have been described,
numbered AQP0-12 [8]. Aquaporins contain four subunits, each
with an hourglass-shaped channel lined with charged chemical
groups. The charged groups interact with polar water molecules to
allow passage through the channel (Fig. 2). It has been shown that
five of these aquaporins (Aquaporins 1, 3, 8, 9, and 11) are expressed
Fig. 2. Aquaporin 1 (AQP1) structure. Reproduced with permission from Abre [8].
in the human fetalematernal membranes (amnion and chorion)
and are differentially expressed throughout gestation [9] (Fig. 3).
Pathologic states are associated with changes in aquaporin
expression on the membrane surface. For instance, in the setting of
polyhydramnios, Aquaporin 1 expression is markedly increased
(>30-fold), suggesting a regulatory function of these proteins [10].
1.3. Clinical relevance
Oligohydramnios is defined as amniotic fluid volume that is less
than expected for gestational age. This finding may be idiopathic, a
result of premature and/or prolonged rupture of membranes,
twinetwin transfusion syndrome (donor) or secondary to
decreased fetal urine production or flow. This condition may cause
fetal deformation, umbilical cord compression, and death [11].
Polyhydramnios is defined as an excessive volume of amniotic
fluid. This condition should be suspected when uterine size is large
for gestational age. It may also be idiopathic, a result of twinetwin
transfusion syndrome (recipient), maternal diabetes, fetal gastro-
intestinal tract obstruction, neural tube defect, or genetic condi-
tions such as trisomies. Even a relatively minor increase in daily
fetal urine production or decrease in fetal swallowing may result in
a marked increase in amniotic fluid volume [12]. This condition
carries a higher incidence of adverse perinatal outcomes, even
when cases of congenital anomalies are excluded [13].
Maternal dehydration with increased maternal osmolality
(excessive water loss from hot weather or diabetes insipidus, for
example) may be associated with reversible decreased fetal
compartment water and oligohydramnios [1].
Maternal overhydration (‘water intoxication’) during labor may
cause dangerous hyponatremia in both the mother and neonate
through transfer of water from hyponatremic maternal blood to the
fetus, who also develops hyponatremia. In severe cases this con-
dition may cause maternal and neonatal seizures [14].
Intrauterine growth restriction (IUGR) is associated with a
relatively higher proportion of total body water at birth as
compared to neonatal body composition resulting from expected
fetal growth. This is due to a decrease in body solids in growth-
restricted fetuses rather than an excess of water production or
retention [15].
2. Neonatal water balance
2.1. Neonatal transition
At birth, neonates must rapidly adapt to the extrauterine envi-
ronment. Body water content changes gradually from fetal to
neonatal life. Both total body water and extracellular fluid com-
partments decrease proportionately over time. Conversely, intra-
cellular fluid percentage increases at birth and peaks at three
months' postnatal age (Fig. 4).
After birth, notable changes in body water and composition take
place. Contraction of extracellular water occurs, with a corre-
sponding weight loss of between 7% and 15% of body weight by the
end of the first week. The degree of contraction of the extracellular
water compartment is inversely proportional to gestational age.
Term infants may exhibit a 5e7% weight loss during the first week
whereas preterm infants with birth weight <1500 g may exhibit a
10e15% weight loss [6].
2.2. Conditions determining water balance in the neonatal period
Gestational age, postnatal age, IUGR, prenatal steroid exposure,
total body surface area, ambient temperature and humidity, type of
heat source, and the neonate's activity all affect postnatal water
 J.B. Lindower / Seminars in Fetal & Neonatal Medicine 22 (2017) 71e75 73

Fig. 3. Aquaporin protein expression in human term fetal membranes and the WISH cell line: AQP1 (AeC), AQP3 (DeF), AQP8 (GeI), AQP9 (JeL), and AQP11 (MeO) immuno-
histochemistry and immunocytochemistry (green labeling) was performed on human term amnion (A, D, G, J, M, and P), human term chorion (B, E, H, K, N, and Q), and the WISH cell
line (C, F, I, L, O, and R). Cell nuclei were visualized by Hoescht (blue) staining. Primary antibody-free incubations (P, Q, and R) are presented as negative controls. Original
magnification 3400. Reproduced with permission from Prat et al. [9].

Fig. 4. Fetal and neonatal body water content changes with respect to time. TBW, total body water; ECF, extracellular fluid; ICF, intracellular fluid. Illustration supplied courtesy of
Istvan Seri, MD, PhD.

balance. 2.2.2. Insensible fluid loss

Water (i.e. fluid) loss may be sensible (related to the body's
intrinsic physiologic functions) or insensible (related to the body's
interaction with the extrinsic environment). Sensible fluid losses in
neonates occur through voiding and stooling. Insensible fluid losses
occur from the skin and the respiratory tract.
2.2.1. Sensible fluid loss
In extremely low birth weight preterm infants, mean urine
output is 1.6 mL/kg/h on day 1 and 5.4 mL/kg/day on day 3 of life. In
preterm infants between 30 and 34 weeks, mean urine output is
3.75 and 6.25 mL/kg/h on days 1 and 3, respectively [16]. Factors
influencing urine output include renal blood flow, glomerular
filtration rate and functional maturity of the renal tubules.
In preterm infants stool output is around 7 mL/kg/day and
10 mL/kg/day in term infants [17]. Stool output depends upon the
maturation of gut motility, mucosal function, and type of diet
(breastmilk or formula).
The majority of neonatal water loss occurs through the skin
(transepidermal). The transepidermal water loss of a 24-week
appropriate-for-gestational age (AGA) infant is 10e15 times
higher than that of a term neonate during the first day of life [18].
As gestational and postnatal age advance, transepidermal water
loss decreases (Fig. 5).
Although the difference in transepidermal water loss diminishes
with age, it is still twice as high in a former 24-week AGA infant
compared to that of a former term neonate on the 28th day of life
[20].
The respiratory tract is also a source of insensible fluid loss. The
temperature and humidity of inspired air affect the degree of res-
piratory fluid loss. Warmed, humidified inspired air leads to
decreased respiratory insensible fluid loss in ventilated patients
[19]. The newborn's respiratory rate and corresponding minute
ventilation are directly proportional to insensible respiratory fluid
loss.
74 J.B. Lindower / Seminars in Fetal & Neonatal Medicine 22 (2017) 71e75
Fig. 5. Mean insensible water loss through the skin in appropriate for gestational age
infants in 50% relative ambient humidity. Reproduced with permission from Ham-
marlund et al. [18].
Intrauterine growth restriction leading to small for gestational
age status predicts a relative decrease in postnatal weight loss than
that seen in appropriate for gestational age (AGA) infants [24].
Prenatal steroid exposure in very low birth weight infants is asso-
ciated with a decrease in insensible water loss and higher urine
output [20].
The higher the total body surface area, the higher the insensible
water loss. The cooler and drier the environmental conditions, the
greater the insensible water loss. Radiant heat sources are associ-
ated with increased insensible water loss as compared to in-
cubators [21]. Increased activity also leads to an increase in
insensible fluid loss. Phototherapy in thermally stable newborns
does not appear to cause an increase in insensible fluid loss [22].
2.3. Physiologic controls of water balance in the neonate
In neonates, the hormonal response to excess and deficient body
water is triggered by changes in plasma osmolality sensed by pi-
tuitary hypophyseal osmoreceptors. This leads to secretion or
suppression of arginine vasopressin (AVP) [23]. Both preterm and
term neonates generally have the capacity to regulate intravascular
volume within a range of fluid intakes. Both preterm and term
neonates are also able to excrete dilute urine. However, preterm
infants are only able to concentrate urine to ~600 and ~700 mOsm/L
at term [24]. By comparison, adults can concentrate urine to ~1300
mOsm/L.
2.4. Clinical relevance
Arginine vasopressin (also called ADH, antidiuretic hormone)
levels rise after birth. AVP secretion is increased in response to
events such as birth, perinatal depression, respiratory distress
syndrome, positive pressure ventilation, pneumothorax or intra-
cranial hemorrhage. SIADH (syndrome of inappropriate ADH
secretion) may occur in the neonatal conditions listed above,
leading to water retention and low serum sodium levels. This
condition is generally treated with assessment and therapy for the
underlying cause, fluid restriction in euvolemic patients, and
administration with close monitoring of rate of correction of
hyponatremia in hypovolemic patients [25].
Diabetes insipidus (DI) is due either to deficient secretion of AVP
by the pituitary gland (central or neurogenic DI) or renal tubular
unresponsiveness to AVP (nephrogenic DI).
For central/neurogenic DI, the treatment of choice is the syn-
thetic ADH analogue desmopressin (1-deamino-8-D-arginine
vasopressin [DDAVP]). Other potentially useful medications include
chlorpropamide and thiazide diuretics. Nephrogenic DI cannot be
effectively treated with DDAVP because renal receptor sites are
unresponsive to AVP. Thiazide diuretics, amiloride, indomethacin,
or aspirin may be useful therapies for nephrogenic DI when
coupled with a low-solute diet [26].
Information to consider when calculating a neonate's fluid goals
and intake include the following [20]:
1. Daily alteration in body weight: Lack of postnatal weight loss or
immediate postnatal weight gain is indicative of fluid excess
caused by impaired sodium and/or water excretion.
2. Serum sodium: Hyponatraemia suggests water excess. Hyper-
natraemia suggests water deficit. The frequency of serum so-
dium determinations in a given neonate depends on gestational
age, postnatal age, and response to current therapy.
3. Urine output: Urine volume <1 mL/kg/h requires investigation.
Output of 2e4 mL/kg/h suggests normal hydration. Higher
output of 6e7 mL/kg/h suggests impaired concentrating ability
or excess fluid administration.
In conclusion, the regulation and maintenance of fetal water
balance involves complex interactions between the fetus, fetal
membranes, and maternal circulation. The estimated amniotic fluid
volume varies significantly throughout normal gestation, especially
during the third trimester. Both oligohydramnios and poly-
hydramnios may contribute to, or be a result of, fetal pathology,
which in turn affects neonatal outcome. The movement of water
across the chorion and amnion is mediated and likely regulated by
transmembrane proteins known as aquaporins.
After birth, the percent total body water gradually decreases,
primarily as a result of decreasing extracellular fluid. Intracellular
fluid proportionately increases postnatally. The degree of contrac-
tion of the extracellular water compartment is inversely propor-
tional to gestational age. Neonates exhibit both sensible and
insensible water loss. Transepidermal insensible fluid loss is most
pronounced in extremely low birth weight neonates, decreasing
with increasing gestational age at birth as well as with postnatal
age. Osmoreceptors in the hypophyseal region sense changes in
body fluid status. This allows for increased or decreased secretion of
arginine vasopressin in order to maintain body fluid homeostasis.
When calculating the fluid needs of hospitalized neonates, critical
analysis of the daily change in body weight, serum sodium, and
urine output is useful.
Conflict of interest statement
None declared.
Funding sources
None.
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