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Acta Obstetricia et Gynecologica.

2007; 86: 783 787

ORIGINAL ARTICLE

Daily intake of 100 mg ascorbic acid as urinary tract infection


prophylactic agent during pregnancy

NDEZ2, GERSON JESU


S
GONZALO JAVIER OCHOA-BRUST1, ALMA ROSA FERNA
1
1
NDEZ3 &
VILLANUEVA-RUIZ , RAYMUNDO VELASCO , BENJAMIN TRUJILLO-HERNA
1
SQUEZ
CLEMENTE VA
1

Centro Universitario de Investigaciones Biomedicas y Facultad de Enfermera, Universidad de Colima, 2Coordinacion de


Investigacion, Servicios de Salud del Estado de Colima, and 3Unidad de Investigacion, Hospital General de Zona No. 1,
I.M.S.S. Colima, Colima, Mexico

Abstract
Objective. To evaluate the role a daily intake of 100 mg of ascorbic acid plays in urinary infection prophylaxis during
pregnancy. Methods and materials. A single-blind clinical trial was carried out on pregnant women randomly assigned to the
following treatment groups  Group A: oral treatment with ferrous sulphate (200 mg per day), folic acid (5 mg per day) and
ascorbic acid (100 mg per day) for 3 months, and Group B: oral treatment with ferrous sulphate (200 mg per day) and folic
acid (5 mg per day) for 3 months. All patients were clinically evaluated, and a urine culture was carried out each month for a
period of 3 months. The x2 and odds ratio were used to compare effects with and without ascorbic acid, and statistical
significance was considered at p B0.05. Results. Global frequency of urinary infections was 25%. The presence of urinary
infections in Group A (12.7%) was significantly lower than in Group B (29.1%), (p 0.03, OR 0.35, CI 95%0.13 
0.91). Conclusions. Daily intake of 100 mg of ascorbic acid played an important role in the reduction of urinary infections,
improving the health level of the gestating women. We recommend additional vitamin C intake for pregnant women in
populations which have a high incidence of bacteriuria and urinary infections.

Key words: Ascorbic acid, urinary infections, pregnancy


Abbreviations: OR: odds ratio, CI: confidence interval, UTI: urinary tract infection, DNA: deoxyribonucleic acid, CFU:
colony formation unit

Introduction
Urinary tract infections (UTI) are one of the most
frequent complications during pregnancy, especially
in adolescents. Between 8 and 23% of women
present with UTI during pregnancy (1), and of these
20 40% present with acute pyelonephritis. In our
population, UTI occupied ninth place in 1999, and
third place in 2000 (2). The combination of UTI
and poor hygiene increases the risk of uterine
contractility, provoking miscarriages and premature
births (3).
Ascorbic acid deficiency in pregnant women has
been associated with pre-eclampsia, premature

membrane rupture, collagen degradation in the


chorioamnion, and premature birth (4 11). Vegetable intake deficiency and the intake of foods low in
nutritional value during pregnancy play a role in the
presence of low seric levels of ascorbic acid in blood
plasma (concentrations B60 mg daily) (12,13).
Although the usefulness of ascorbic acid in UTI
prophylaxis has been known for some time, including reports during pregnancy (14), no studies
evaluating the importance of daily ascorbic acid
intake in UTI prevention during pregnancy in
populations with a high incidence of bacteriuria
and UTI were found in the revision of the available

Correspondence: C. Vasquez, Universidad de Colima, Centro Universitario de Investigaciones Biomedicas, Avenida 25 de julio # 965, Colonia Villa de San
Sebastian, 28040-Colima, Colima, Mexico. E-mail: clemvas@cgic.ucol.mx

(Received 28 September 2006; accepted 10 February 2007)


ISSN 0001-6349 print/ISSN 1600-0412 online # 2007 Taylor & Francis
DOI: 10.1080/00016340701273189

784

G.J. Ochoa-Brust et al.

literature. The reports reviewed corresponded to the


short-term use of ascorbic acid in reducing urinary
infections in healthy individuals and in patients with
medular section (quadriplegics). Furthermore, some
of these studies were non-controlled clinical trials
(1517). The objective of the present study was to
determine whether or not there was a decrease in the
frequency of UTIs during pregnancy with a prophylactic administration of 100 mg of ascorbic acid/day
in populations with a high incidence of bacteriuria
and UTI.
Methods and materials
A single-blind clinical trial was carried out on
pregnant women receiving prenatal care in an urban
lvarez, Colima, Mexico.
Health Center in Villa de A
Women with a gestational period of 12 weeks or
more were selected. Those presenting with diabetes
mellitus, immunological diseases, any type of cancer,
arterial hypertension, cystocele or recurring urinary
infections (genitourinary tract malformations), or
those taking immunosuppressors or antimetabolytes,
were all excluded from the study. The study was
approved by the Health Center Ethics Committee
and all patients meeting the inclusion criteria were
invited to participate in the study. On signing a
written consent, patients were randomly assigned to
the following treatment groups:
Group A: patients receiving oral treatment with
ferrous sulphate (200 mg daily), folic acid (5 mg
daily) and ascorbic acid (100 mg daily) for 3 months.
Group B: patients receiving oral treatment with
ferrous sulphate (200 mg daily) and folic acid (5 mg
daily) for 3 months.
Randomisation was carried out based on a random number table. The even numbers were assigned
to Group A, and the odd numbers were assigned to
Group B.
The studied variables were: age, weight, height,
weeks of pregnancy, body mass index and urinary
pH. Three-monthly urine cultures were carried out
on all patients in order to evaluate UTI frequency.
UTI diagnosis was established when the urine
cultures were positive ( 1 105 CFU/ml).
Patients manifesting any desire to leave the study,
those missing two or more medical appointments,
those not taking the ascorbic acid regularly, those
having serious side effects from the medication
treatment, and those presenting with a pregnancy
complication, except that of UTI, were all excluded
from the study.
The urine culture was carried out in a blinded
manner at a private laboratory meeting established
validity and control standards. Each patient was

given the necessary amount of medication to be


taken for 1 month. At the end of every month, each
patient came in for a monthly check-up, and was
given the next months medication dose. A comparison of the number of patients presenting with UTI
in each group was carried out in order to determine
if ascorbic acid intake had reduced infection frequency. The physician carrying out the monthly
evaluations was blinded as to which group was
receiving the ascorbic acid. A different member of
the research group gave the monthly medication
dose to the participants of each group.
Side effects arising from the treatments were
registered.
The patients included in the study met the
following criteria: at least 12 weeks pregnant, no
other pathology present, and negative urine cultures
(when positive, patients received specific treatment
accompanied by an antibiogram until negativity was
achieved).
Patients developing UTI during the study were
treated for the infection, but they did not leave the
study. Treatment indication was determined by
positive cultures according to established criteria in
the literature. Patients experiencing infection recurrence were sent to the second level of medical
attention, and removed from the study. They were
counted as study failures, since their urinary infections had not been prevented.
Statistical analysis
Means and standard deviation were used for quantitative variable descriptive statistics. The Students
t-test was used for inferential statistics in verifying
equality of age, weight, height and weeks of pregnancy in both groups. Chi-square, OR and medical
parameters based on evidence (absolute risk reduction, relative risk reduction, necessary treatment
number of patients) were used to compare the
usefulness of ascorbic acid administration. Differences were considered significant at p B0.05.
Results
A total of 110 patients were studied, 55 women in
each group. Some 25% of the patients presented
with urinary infections at the start of the study.
Mean age was 21 years in both groups, with a
minimum age of 14 years and a maximum age of 43
years. The remaining demographic data on the
participating study population sample is presented
in Table I.
Ascorbic acid intake during pregnancy significantly reduced the amount of urinary infections in

Ascorbic acid prophylaxis in urinary infection


Table I. General characteristics of study patients

Age (years)
Weight (kg)
Height (m)
Weeks of pregnancy
Body Mass Index (%)
Urinary pH

Group A

Group B

22.395.9
58.999.8
1.590.1
19.195.8
25.194.1
6.190.5

23.195.5
61.1911.7
1.590.03
19.095.8
26.394.9
6.0590.45

0.79
0.26
0.46
0.92
0.15
0.5

Values represent means9standard deviation. p Values correspond


to the Students t -test.

patients. The infection percentage was 12.7% in


Group A, and 29.1% in Group B (p 0.03, OR 
0.35, CI 95% 0.13 0.91).
Three newborns had low birth weight with a
2250935 g mean. This complication was present
exclusively in Group B. There was no premature
membrane rupture in either group.
Three Group A patients reported pyrosis and
nausea, which went away with food intake or by
taking aluminum and magnesium hydroxide gel. It
was unclear whether these side effects were directly
caused by the ascorbic acid intake or if they were
part of the symptomatology common in patients
eating large quantities of foods which irritate the
gastric mucosa, or if they were a result of the
gestating uterus pressing on the stomach, or caused
by diminished gastric emptying from pressure on the
duodenum slowing the passage to the jejunum. No
patients were removed from the study for these or
any other complications.
Relative risk reduction was 56.5%, absolute risk
reduction was 16.3%, and the necessary treatment
number for patients in order to avoid an unfavourable event was 6.
Discussion
The frequency of urinary infections found in the
gestating women of our population (25%) was
greater than that presented on an international level.
Some studies mention an 813% prevalence of
infection, while other studies report a prevalence of
up to 23%.
Interestingly, the age limits of our patients were
from 14 to 43 years, showing gestation in women at
both extremes of reproductive life. There was an
increase in reproductive risk, in cesarean sections,
and in high risk pregnancies, suggesting the need for
health authorities to implement orientation programs.
The recommended daily amount of ascorbic acid
for women has varied over the years. In 2001,
the recommended dose was 90 mg for young
healthy women (18 20). Daily intake of ascorbic

785

acid (100 mg) over a 3-month period was shown in


our study to be adequate for diminishing urinary
infection frequency. Only 7 out of 55 patients
presented with UTI in the group receiving ascorbic
acid, while 16 out of 55 patients presented with UTI
in the group not receiving ascorbic acid.
It is important to emphasise that in the group not
receiving ascorbic acid, 3 infants had low birth
weight (mean: 2250935 g), while there were no
infants with low birth weight in the group receiving
ascorbic acid. There was no premature membrane
rupture in either group.
Some studies have reported controversy as to the
benefits of ascorbic acid in relation to urinary
problems. This is perhaps due to the fact that
many of the studies on the reduction of urinary
infection frequency included completely healthy
volunteers with a minimum risk factor for urinary
infections or, at the other extreme, they included
patients having sequela from different pathologies
which could propitiate recurring UTIs (15 17).
The observed benefit from additional ascorbic
acid intake leads us to believe that perhaps gestating
women do not regularly receive ascorbic acid in their
diets, or if they do, the quantities are insufficient, as
has previously been reported (12,13).
The efficacy of ascorbic acid intake at a dose of
100 mg can be explained by its absorption. Some
90% of low doses of ascorbic acid is absorbed in the
intestine by active transport, whereas only 16% is
absorbed with high doses (19). Tetrafolate oxidation
is also avoided, and, therefore, folic acid and iron are
protected. Another intervening factor is ascorbic
acid elimination, since it is carried out in active
form. It is not excreted in the urine until adequate
saturation has been reached, which is the case with
100 mg daily. At this dose, there is also more
adequate tissue saturation. No adverse effects have
been reported with doses up to 1,000 mg daily
(19,20).
Ascorbic acid is important in cellular respiration
reduction. It protects folic acid reductase, favouring
erithropoyesis, and it plays an important role in
collagen synthesis, steroid hormone production and
lipid metabolism. Cardiac, hematologic and skeletal
problems in fetuses can all be avoided when the
pregnant woman ingests ascorbic acid (21,22).
Ascorbic acid toxicity in the mother (alterations in
DNA) and/or in the fetus has not been reported
(23,24). Supplementation with 100 mg/daily of
ascorbic acid allows for the conservation of ascorbate
leukocyte concentration 18 mg/108 cells from the
24th week of gestation, and effectively prevents
premature membrane rupture (25).

786

G.J. Ochoa-Brust et al.

On the other hand, it has been observed that when


Escherichia coli and Pseudomonas aeruginosa are
exposed to the combination of acidified urine (pH
55.5) and nitrites, ascorbic acid increases the
antibacterial effect. This action is related to nitric
oxide production and other toxic reactive nitrogen
intermediates (26,27).
Although vitamin C intake during pregnancy has
been described since the late 1950s and early 1960s
(14), it is important to point out that ascorbic acid is
not included in the Mexican Health Secretariats
complementary provision outline for pregnant women. Studies, such as this, are important in procuring ascorbic acid distribution for the pregnant
population in populations with a high incidence of
bacteriuria and UTI, or a high incidence of antimicrobial resistance. It is probable that this phenomenon is present in other developing countries as well.
When comparing the nutrition and health of
mothers in Japan and the Philippines, the total
dietary score averages were lower for pregnant
Philippine women than for pregnant Japanese women (28).
Relatively low folate intake and the small proportion of women taking folate supplements is of
concern even in developed countries, because of
the association between inadequate amounts of
folate in the diet and neural tube defects (29). The
quality of diet during pregnancy decreases when
financial difficulties affect the affordability of foods
(30).
It is also worth mentioning that the results from
the present study indicated that only 6 patients were
needed in order to observe the benefits obtained
from the additional daily intake of 100 mg of
ascorbic acid.

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In areas with a high incidence of bacteriuria, UTI,


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beginning at the 12th week of gestation, in order to
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Conclusions

Ascorbic acid prophylaxis in urinary infection


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