Arch Iranian Med 2006; 9 (2): 144 147

Original Article

THE INFLUENCE OF MATERNAL KETONURIA ON FETAL

WELL-BEING TESTS IN POSTTERM PREGNANCY
Kobra Hamdi MD*, Parvin Bastani MD*, Roya Gafarieh MD*, Hadi Mozafari MD**,

Seyed-Hassan Hashemi MD***, Mohammad-Hamed Ghotbi MD MPH

Background: Although it is well-known that postterm pregnancies are associated with the risk
of perinatal morbidity and mortality, a comprehensive study on its management is lacking.
The aim of present study was to determine whether ketonuria is associated with abnormal fetal
test results in pregnancies >40 weeks of gestation.
Methods: In this analytical cross sectional study, a total of 360 pregnant women with
gestational age of >40 weeks were evaluated in two hospitals during 2003 2004. For each woman,
urinary ketones, glucose, pH, proteins, and specific gravity were measured by total screen LSG
tapes (Rapignost); in addition, biophysical profile test was recorded and the amniotic fluid index
was assessed by ultrasonography.
Results: Ketonuria was found in 34 women (9.44%). Statistical analyses showed that maternal
ketonuria was associated with oligohydramnios, abnormal fetal tests, and a significant increase in
fetal heart rate decelerations.
Conclusion: Patients with clinically-detectable ketonuria have higher risk for abnormal fetal
tests in comparison with those without the disease.
Archives of Iranian Medicine, Volume 9, Number 2, 2006: 144 147.

Keywords: Ketonuria management oligohydramnios postterm

Introduction

erinatal morbidity and mortality increase

significantly as a pregnancy progresses
beyond term. Approximately, 18.5% of
all pregnancies continue up to 41 weeks of
gestation, and 4% to 10% continue until 42 weeks
or more. Although, the risks associated with
prolonged pregnancy have been well-chronicled,
the management of this common condition still
remains controversial.1
Current strategies for managing postterm
pregnancies are either induction of labor or assessing fetal status repeatedly (expectant management).
Authors affiliations: *Department of Obstetrics and Gynecology,
Al-Zahra Hospital, **Department of Internal Medicine, Tabriz
University of Medical Sciences, Tabriz, ***Department of
Pathology, Sina Hospital, Department of Digestive Research
Center, Tehran University of Medical Sciences, Tehran, Iran.
Corresponding author and reprints: Mohammad-Hamed
Ghotbi MD MPH, Department of Digestive Research
Center, Shariati Hospital, Kargar Shomali Ave., Tehran 14114,
Iran. Telefax: +98-21-88012992, E-mail: ghotbi@ams.ac.ir.
Accepted for publication: 30 November 2005

144 Archives of Iranian Medicine, Volume 9, Number 2, April 2006

Since labor induction at any stage of gestation is

associated with a higher risk for cesarean section,
expectant management is more favorable. In the
latter case, we use nonstress test (NST),
ultrasonographic evaluation of amniotic fluid
volume, amniotic fluid index (AFI), and
biophysical profile test (BPP) to assess the fetal
well-being continuously. These would continue
until we encounter a nonreassuring NST,
oligohydramnios, or abnormal BPP, when delivery
could be induced by an obstetrician.
Accelerated starvation is a term referring to the
propensity to exaggerated ketone-body generation
during fasting in pregnancy.2 This process occurs
as a result of a relative insulin-deficiency state
incurred because of increased nutrient flux to the
fetus and because of the lipolytic and antiinsulin
nature of some gestational hormones.3 5
Detection of urinary ketones, an inexpensive
test, is easily performed in any outpatient settings.
Ketonuria during pregnancy is a common transient
phenomenon. It may signal a variety of maternal

K. Hamdi, P. Bastani, R. Gafarieh, et al

100
90

90.6

80
Percentage

70
60
50
40
30
20
10

7.5
1.3

0
Negative

Small

Moderate

0.6
Large

Degree of ketonuria

Figure 1. The prevalence of different degrees of ketonuria.

metabolic derangements including dehydration,

caloric restriction, and diabetic ketosis.1
Previous studies have shown that ketones elicit
alterations in amniotic fluid volume and
composition in sheep6 and also elicit potentially
detrimental changes in the neurologic status of
human.7
The aim of our study was to assess the
association between ketonuria, a commonly
assessed urinary marker of maternal starvation and
dehydration, with the results of some fetal tests
such as NST, AFI, BPP, FHR, and ultrasonographic evaluation of amniotic fluid volume in
pregnancies >40 weeks of gestation. Results of this
study would help us to evaluate the potential
benefits of treating ketonuria to improve fetal tests.

Patients and Methods

This study was performed on 360 full-term
pregnant women who were referred to Al-Zahra
and Taleghani Hospitals, Tabriz, Iran, during 2003
2004. In this research considered postterm
pregnancies as pregnancies >40 weeks of gestation
determined according to the last normal menstrual
period (LNMP) date or early ultrasonography, or
both. The exclusion criteria were diabetes,
vomiting, diarrhea, multiple pregnancies, history of
renal disease, hypertension, uncertain gestational

age, incomplete delivery data, and high-risk

pregnancies. The Ethics Committee of Tabriz
University of Medical Sciences approved this
study and a written informed consent was obtained
from each woman.
All the patients were evaluated by taking
medical history, physical examination, and
urinalysis. Urinalysis was performed by Rapignost
tapes (Total Screen LSG) which measured glucose,
ketones, protein, and specific gravity of maternal
urine, simultaneously. Ketonuria was classified as
follows: negative (0 mg/dL), small amounts of
ketones (1 30 mg/dL), moderate amounts (30
40 mg/dL), and large amounts (>40 mg/dL). All
observations were performed by experienced
registered nurses and were recorded directly into
the database at the time of assessment.
Fetal well-being was assessed by FHR, NST,
BPP, and AFI. The NST result was considered
abnormal in the presence of recurrent FHR
variable decelerations, late decelerations, or 120
minutes of nonreactivity. Amniotic fluid volume
was quantified by means of the four-quadrant
method
described
by
Phelan
et
al.8
Oligohydramnios was defined as an amniotic fluid
index of <5.0 cm. Patients were referred for labor
induction in the presence of oligohydramnios or an
abnormal FHR tracing.
Statistical analyses were performed by Chi-

Table 1. Characteristics of women with or without ketonuria.

Characteristic
Mean SD age (yr)
Mean SD height (cm)
Mean SD weight (kg)
Nulliparity (%)

Ketonuria
Present
25 5.52
160.23 5.03
71.23 7.73
52.9

Absent
25 4.84
159.86 5.42
70.88 12.34
49.7

P value
0.884
0.701
0.870
0.929

Archives of Iranian Medicine, Volume 9, Number 2, April 2006 145

Maternal ketonuria affects fetal tests

Table 2. Different manifestations in women with or without ketonuria.

Ketonuria

Manifestation

Present
1030 540
26.3%

Mean SD urine specific gravity

Nausea

Absent
1025 600
25.2%

square, Students t-, Mann-Whitney, and one-way

ANOVA tests. A P value of <0.05 was considered
statistically significant.

P value
0.603
0.300

Previous studies provide preliminary evidence

to support the hypothesis that ketone bodies passed
from mother to fetus may elicit alterations in FHR
reactivity and amniotic fluid volume.1, 2, 4 Maternal
ketonemia resulting in ketonuria is a hyperosmolar
state.9 Studies in sheep have shown that maternal
conditions involving hyperosmolarity, such as
maternal dehydration, result in a diminution in
fetal amniotic fluid volume from decreased fetal
urination.10 This is likely originated from a
decrease in fetal production of atrial natriuretic
peptide.6 Likewise, several human studies have
shown that maternal hydration leads to a
significant increase in the amniotic fluid volume.11
13
It has been shown that oligohydramnios is
associated with neonates birth weight rather than
redistribution of renal perfusion14 and this creates

Results
Out of 360 women studied, 34 (9.4%) showed
different degrees of ketonuria (Figure 1).
General characteristics of the women with or
without ketonuria, with regard to age, height,
weight, and parity were not statistically different
(Table 1). Urine specific gravity and the frequency
of nausea were also not statistically different
(Table 2). The perinatal fetal tests performed (i.e.,
FHR, NST, AFI) were significantly different
between women with ketonuria and those without
(Table 3).

Table 3. Results of perinatal fetal tests in women with or without ketonuria.

Ketonuria
Present
Absent
8.38 3.9
10.8 3.1
17.6%
2.5%
29.4%
5.8%
51.9%
11.0%
7.53 1.48
9.06 1.32

Fetal Tests
Mean SD AFI
Oligohydramnios
Spontaneous FHR deceleration
Nonreactive NST
Mean SD biophysical profile

P value
0.001*
0.01**
<0.001**
<0.01**
<0.001***

* = Students t-test; ** = Chi-square test; *** = Mann-Whitney U-test.

Finally, we evaluated the association of

different fetal tests and the degrees of ketonuria.
Because of few numbers of patients with large
amounts of ketonuria, those with moderate and
large amounts of ketonuria were combined for
statistical analyses (Table 4), which showed that all
these tests have significant association with
degrees of ketonuria.

another hypothesis which states that when there is

hypovolemia in mother, the fetus might also
develop hypovolemia and consequent diminished
renal perfusion. In such condition oligohydramnios
might be due to the mothers hypovolemia rather
than mothers ketonemia.
Fetus commonly shows different physiologic
responses due to alterations in nutritional status of
mother. Nutritional deprivation of the mothers
might alter neurologic status of the fetus by
ketogenesis. Pyrimidine synthesis in fetal brain
decreases in presence of ketone bodies.15 Onyeije
and Divon hypothesized that the presence of a
nonreactive NST is an early manifestation of these

Discussion
We found that ketonuria in pregnant women
with gestational age of >40 weeks is associated
with abnormal perinatal BPP, AFI, NST, and FHR.

Table 4. Association between fetal tests and ketonuria.

Fetal test
Oligohydramnios
FHR deceleration
Nonreactive NST
BPP <8
Mean SD AFI (cm)

Negative
2.5%
5.8%
11.0%
5.8%
10.89 3.13

Amounts of ketonuria
Small
Moderate and large
14.8%
28.6%
29.6%
28.6%
51.9%
85.7%
29.6%
28.6%
8.48 3.66
8.00 5.13

* = Chi-square test; ** = one-way ANOVA.

146 Archives of Iranian Medicine, Volume 9, Number 2, April 2006

P value
<0.001*
<0.001*
<0.001*
<0.001*
<0.001**

K. Hamdi, P. Bastani, R. Gafarieh, et al

neurologic alterations in some fetuses.1 In our

study, we showed that nonreactive NST was
associated with degrees of ketonuria as well as
other fetal tests (Table 4), which supports this
hypothesis. Nonetheless, some studies suggest that
maternal ketonuria is possibly because of
dehydration and hypovolemia, in which case, there
would be a chance for development of
hypovolemia in fetus too. These findings might
describe the alterations of these tests. But by using
retrospective studies there would be lots of
unwanted bias and, therefore, we could not be able
to accept neither of these hypotheses per se. So, for
better understanding of this situation and better
management of full-term pregnancy, we should
consider other types of prospective surveys such as
cohort study or controlled clinical trials.

10

11

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