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VOL. 19, NO. 2, APRIL 2011
40 Thai J Obstet Gynaecol
Thai Journal of Obstetrics and Gynaecology
April 2011, Vol. 19, pp. 40-44 4216222-12
SPECIAL ARTICLE
Laryngopharyngeal Reux in Pregnancy
Worapong Vejvechaneyom MD.
Otolaryngologist-Head&Neck Surgeon, Samitivej Sukhumvit Hospital, Bangkok, Thailand
Introduction
Laryngopharyngeal reux (LPR) is the retrograde
movement of gastric contents (acid and enzymes such
as pepsin) in to the upper aerodigestive tract especially
the laryngopharynx leading to symptoms referable to
inammatory diseases of larynx/ hypopharynx/throat/
nose & paranasal sinuses/mouth/middle ears. Typical
symptoms of LPR include hoarseness, globus
pharyngeus (sensation of lump in the throat), cough,
excessive mucus in the throat with throat clearing, and
mild dysphagia. Sometime, the LPR patients including
the pregnant women with LPR also have the excessive
saliva and may occasionally complain of a sudden lling
of the throat with bitter or salty saliva (water brash).
LPR is related to gastroesophageal reux disease
(GERD), but is not identical to it. Patients with GERD
may have no LPR, and conversely, patients with LPR
may have no GERD. Most patients are relatively
unaware of LPR with only 30 percent reporting
heartburn.
(1)
There are no certain criteria that reliably
demonstrate a causal link between acid reux and LPR
symptoms. In fact, the validity of reux as a cause of
LPR symptoms, in the absence of symptoms of GERD,
has been called into question. Thus, it is likely that some
patients are mistakenly diagnosed with LPR, and
investigation of other causes of upper airway symptoms
(such as allergy, sinus, or other causes of cough, etc)
should be considered for patients who fail to respond
to LPR management.
Heartburn, the cardinal symptoms of GERD, is
a normal consequence of pregnancy. The predominant
etiology is the decrease in lower esophageal sphincter
pressure (LESP) caused by female sex hormones,
especially progesterone. Thus, GERD and LPR may be
ones of normal consequence of pregnancy. Most
patients begin to note their symptoms late in the rst
trimester or second trimester of pregnancy with
symptoms becoming more frequent and severe in the
latter months of gestation.
Epidemiology
There are relatively limited data on the prevalence
of LPR. It is difficult to determine the prevalence of LPR
in the population because there is no clear diagnostic
gold standard criteria to diagnose LPR. There are no
studies of the prevalence of LPR in pregnancy.
Pathophysiology
LPR can cause upper airway symptoms directly
or indirectly. The direct mechanism involves irritation of
upper aerodigestive mucosa by reuxate through the
action of caustic materials (ie, acid, pepsin etc.) on the
tissues. The indirect mechanism involves irritation of
distal esophagus by reuxate that does not reach the
upper aerodigestive mucosa, this irritation evokes the
vagally-mediated reexes that cause laryngeal and
bronchial reflexes (laryngospasm, apnea, cough,
asthma-like symptoms through bronchoconstriction
VOL. 19, NO. 2, APRIL 2011
41
Vejvechaneyom W. Laryngopharyngeal Reux in Pregnancy
etc.). Regardless of the pathway, factors such as the
resting tone of the upper and lower esophageal
sphincters (UES and LES) and the duration and
magnitude of increases in intraabdominal pressure are
important to the creation of the reuxate bolus.
In the rst trimester of pregnancy, basal (resting)
lower esophageal sphincter pressure (LESP) may not
change, but is less responsive to physiological stimuli
(i.e. pentagastrin, edrophonium chloride, methacholine
or a protein meal) that usually increase LESP
(2,3)
. In the
later two trimesters, LESP gradually falls approximately
33-50% of basal values reaching a nadir at 36 weeks
of gestation and rebounds to prepregnancy values 1-4
weeks postpartum
(4)
. Animal and human studies
reported that the increased circulating levels of
progesterone during pregnancy mediate the LES
relaxation (decreased LESP), but estrogen is
a necessary primer
(2)
. The role of increased
intraabdominal pressure because of the enlarging
gravid uterus is more controversial. All studies agreed
with the increasing intraabdominal pressure with the
increasing gestational age during pregnancy. It is
unknown whether the normal compensatory increasing
response of the LESP to these changes is impaired
during pregnancy
(2)
. Others have suggested that
abnormal gastric emptying or delayed small bowel
transit might contribute to reux in pregnancy. A limited
number of studies have examined the role of the LES,
esophageal motility, gastric emptying, and increased
intraabdominal pressure from the enlarged gravid uterus
in promoting reux during pregnancy.
Although gastric acid is common to both LPR
and GERD, there are many differences making LPR a
distinct clinical entity. The majority of GERD patients
have signs of esophagitis on biopsy, while only 25
percents of LPR patients do
(5)
. GERD is felt to be a
problem of the LES and mainly occurs in a supine
position. In contrast, LPR is seen as primarily an UES
problem that mainly occurs in the upright position during
periods of physical exertion (eg, bending over, Valsalva,
exercise)
(5)
. There appears to be a lower incidence of
esophageal dysmotility in LPR versus GERD.
CLINICAL MANIFESTATIONS
LPR is ubiquitous and associated with many
upper airway symptoms and diagnoses. In some cases,
the symptoms are the diagnosis, for example, LPR can
cause sore throat, chronic cough, globus pharyngeus,
and laryngospasm. Alternately, LPR can be associated
with specic histopathologic lesions, for example, vocal
process granulomas. LPR can be the sole cause or an
etiologic cofactor in the development of many disorders
of the upper airway.
The common LPR symptoms are dysphonia or
hoarseness, cough, globus pharyngeus, excessive
mucus in the throat/throat clearing, and mild
dysphagia. Even though the symptoms and nding of
LPR have been described, the clinical diagnosis is
sometimes elusive. Symptoms can occur in the
absence of conclusive physical ndings, and they can
be nonspecic symptoms. There are many factors
possible contributing the symptoms similar to LPR, such
as postnasal drip, allergic rhinitis, upper respiratory
infections, habitual throat clearing, tobacco or alcohol
use, excessive voice use, temperature or climate
change, emotional issues, environmental irritants, etc.
In addition to typical LPR symptoms, reflux-
induced respiratory symptoms are also common. The
association between LPR and asthma has been well
documented. Asthma can predispose a patient to have
reflux. Also, LPR can exacerbate asthma.
Microaspiration of gastric refluxate and resultant
bronchiectasis can also occur. Some investigators have
found strong associations between LPR and airway
stenosis, sleep apnea, laryngospasm, and nasal
congestion
(5)
. Although the etiology of these disorders
is multifactorial, LPR as a sole cause or as a cofactor
should be routinely considered in the differential
diagnosis of subglottic stenosis, asthma, laryngospasm,
bronchiectasis , chronic rhinitis, and sleep-disordered
breathing.
Diagonosis in The Pregnant Patients
There is significant controversy over the
appropriate way to diagnose LPR and there is no test
that is both easy to perform and highly reliable. Most
patients are diagnosed clinically based on symptoms
associated with LPR. In patients who are seeing an
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42 Thai J Obstet Gynaecol
otolaryngologist, the clinical history is generally
augmented with a laryngoscopic examination.
However, the lake of standardized criteria for the
diagnosis of LPR and the relatively poor correlation
between symptoms and endoscopic ndings of LPR
have been cited as a rationale against the use of
endoscopic techniques to diagnose LPR
(6,7)
.
The initial diagnosis of LPR in pregnancy can
reliably be made based on symptoms alone. Any
radiographs are not necessary and should be avoided
because of radiation exposure to the fetus. Esophageal
manometry and pH monitoring studies, as in the non-
pregnant patient, are rarely necessary during pregnancy
but can be performed safely. Endoscopic examination
(laryngoscopy or transnasal esophagoscopy) is the
procedure of choice to evaluate intractable LPR
symptoms.
Treatment of LPR During Pregnancy
The challenge of treatment during pregnancy is
the potential teratogenicity of common antireflux
medications. Diets and lifestyle modication is the key
for treating mild symptoms. Smaller meals, not eating
late at night, elevation of the head of the bed and sleep
by the left side, and avoiding foods and medications
causing reux usually relieve the mild symptoms seen
in early pregnancy. Chewing gum stimulates the salivary
gland can help neutralize acid by salivary bicarbonate.
Abstinence from alcohol and tobacco are encouraged
to reduce reux symptoms and to avoid fetal exposure
to these harmful substances.
For more troubling reux symptoms, the doctor
must discuss with the patient about benets versus the
risk of drug therapy. Informed consent is appropriate.
Nearly all medications are not tested in randomized-
controlled studies in pregnant women because of ethical
and medicolegal concerns. Most recommendations on
drug safety arise from case reports and cohort studies
by doctors, pharmaceutical companies or the FDA.
Voluntary reporting by the manufacturers suffers from
unknown duration of follow-up, absence of appropriate
controls and possible reporting bias
(8)
.
The incidence of major fetal malformations in the
general population ranges between 1% and 3%. The
US FDA divides the safety of drugs during pregnancy
into ve categories (A, B, C, D and X) based on systemic
absorption and reports of congenital defects in animals
or humans (Table 1)
Table 1. US FDA Classication of Drugs for Pregnancy
(2)
FDA classication Denition
Category A Well controlled studies in humans show no fetal risk
Category B
Animal studies show no risks, but human studies inadequate or animal studies show some
risk not supported by human studies
Category C
Animal studies show risk but human studies are inadequate or lacking or no studies in
humans or animals
Category D Denite fetal abnormalities in human studies but potential benets may outweigh the risks
Category X
Contraindicated in pregnancy, fetal abnormalities in animals or humans. Risks outweigh
benets
Table 2. summarizes the drugs used for reux diseases in pregnancy.
VOL. 19, NO. 2, APRIL 2011
43
Vejvechaneyom W. Laryngopharyngeal Reux in Pregnancy
Table 2. FDA Classication of Drugs Used for Reux Diseases in Pregnancy (modied from Ref.2)
Drugs FDA class Comments
Antacids
Aluminium-, calcium- or
magnesium-containing
antacids
None Most are safe for use during pregnancy and for aspiration prophylaxis
during labour because of minimal absorption
Magnesium trisilicates None Avoid long-term, high-dose therapy in pregnancy
Sodium bicarbonate None Not safe for use in pregnancy as causes uid overload and metabolic
alkalosis
Mucosal protectant
Sucralfate B No teratogenicity in animals. Generally regarded as acceptable for
human use because of minimal absorption
Histamine
2
-receptor antagonist (H
2
RA)
Ranitidine B Ranitidine is the only H
2
RA whose efficacy during pregnancy has
been established
Promotility agents
Metoclopramide B No teratogeneic effects in animals or humans reported
Proton-pump inhibitors
Omeprazole C Embryotoxic and fetotoxic in animals. Case reports in human suggest
similar concerns. Acceptable for use for aspiration prophylaxis in
labour
Lansoprazole B No fetal teratogenicity or harm. Limited human pregnancy data. Use
is acceptable for aspiration prophylaxis during pregnancy
Rabeprazole B No fetal teratogenicity or harm. Limited human pregnancy data. Use
is acceptable for aspiration prophylaxis during pregnancy
Pantoprazole B No fetal teratogenicity or harm. Limited human pregnancy data.
Use is acceptable for aspiration prophylaxis during pregnancy
Esomeprazole B No fetal teratogenicity or harm. Limited human pregnancy data.
Use is acceptable for aspiration prophylaxis during pregnancy
Alginates (Gaviscon ) from a strong, non-systemic
barrier in the stomach, preventing reux of stomach’s
contents (acid, pepsin, and foods) in to the esophagus
(acts as the “antireuxant”).
The H2RAs are the most commonly used and
safest medications for the pregnant woman with reux
not responding to lifestyle modification and non-
absorbable medication. The H2RAs are category B
drugs for pregnancy. Ranitidine has no antiandrogenic
activity in animal
(10)
. Neither H2RA has reports of
human sexual defects in infants.
Proton-pump inhibitors (PPIs) are the most
effective drug therapy for symptom control and healing
of reflux esophagitis. The PPIs have not been as
extensively used in pregnancy as the H2RAs, or is their
efficacy proven in pregnancy, and the data about total
safety are more limited. However, unlike the non-
pregnant patients, PPIs should only be used during
pregnancy in women with well-dened complicated
reux diseases, not responding to lifestyle modication,
antacid, mucosal protectants, promotility drugs, and
H2RAs.
VOL. 19, NO. 2, APRIL 2011
44 Thai J Obstet Gynaecol
Unlike the non-pregnant patient, step-up therapy
is preferred (diets and lifestyle modication à antacids
à mucosal protectants à alginate compoundsà
promotility drugs à H2RAs à PPIs) in pregnant patients.
CONCLUSION
There are no studies of the prevalence of LPR
in pregnancy, but LPR may be one of normal
consequence of pregnancy. The predominant cause is
a decrease in LESP caused by female sex hormones,
especially progesterone. Serious reux complications
during pregnancy are uncommon; therefore upper
endoscopy and other diagnostic tests are usually not
needed. Symptomatic pregnant patient should be
managed with a step-up algorithm beginning with diets
and lifestyle modication. Antacids or sucralfate are
considered the rst-line medical therapy. If symptoms
persist, alginate compounds or promotility drugs or any
of the H2RAs can be used. PPIs are reserved for women
with intractable symptoms or complicated reux disease.
Most drugs are excreted in breast milk. Of the systemic
absorbed agents, only ranitidine is safe to use during
lactation.
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