CHAPTER I - INTRODUCTION

I.I. Overview
Preterm labor is defined as the presence of uterine contractions of sufficient frequency and
intensity to effect progressive effacement and dilation of the cervix prior to term gestation
(between 20 and 37 wk). Preterm labor precedes almost half of preterm births and preterm
birth occurs in approximately 12% of pregnancies and is the leading cause of neonatal
mortality in Asia. In addition, preterm birth accounts for 70% of neonatal morbidity,
mortality, and health care dollars spent on the neonate, largely due to the 2% of Average
women delivering very premature infants (< 32 wk).
Successful reduction of perinatal morbidity and mortality associated with prematurity may
require the implementation of effective risk identification and behavioral modification
programs for the prevention of preterm labor; these in turn require both an improved
understanding of the psychosocial risk factors, etiology, and mechanisms of preterm labor
and programs for accurate identification of pregnant women at risk for premature labor and
delivery. In fact, recent evidence suggests that early identification of at-risk gravidas with
timely referral for subspecialized obstetrical care may help identify women at risk for preterm
labor and delivery and decrease the extreme prematurity (< 32 wk) rate, thereby reducing the
morbidity, mortality, and expense associated with prematurity.

I.II. Goals of management

The focus of this article is the prevention, diagnosis, and treatment of preterm labor with
intact membranes. The management of preterm labor associated with ruptured membranes is
reviewed in Premature Rupture of Membranes; however, the overall goals of both
management schemes are similar.

Goals of obstetric patient management of preterm labor should include:

Early identification of risk factors associated with preterm birth.

Timely diagnosis of preterm labor.

Identifying the etiology of preterm labor.

Evaluating fetal well-being.

Providing prophylactic pharmacologic therapy to prolong gestation and reduce the

incidence of respiratory distress syndrome (RDS) and intra-amniotic infection (IAI).

Initiating tocolytic therapy when indicated.

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Establishing a plan of maternal and fetal surveillance with patient/provider education

to improve neonatal outcome.

CHAPTER II - DISCUSSION
II.I. Definition
Preterm or premature births are terms used to define neonates who are born too early (before
37 completed weeks, that is, < 8 months). This definition was based on a statistical analysis
of gestasional age distribution at birth (Steer, 2005). Infants born before term can be small or
large for gestational age but still fit the definition of preterm. Low birthweight refers to
neonates weighing 1500 to 2500 g; very low birthweight refers to those between 1000 and
1500 g; and extremely low birthweight refers to those between 500 and 1000 g.
It lacks a specific functional basis and should be clearly distinguished from the concept of
prematurity. Prematurity represents incomplete development of various organ systems at
birth. The lungs are particularly affected, leading to the respiratory distress syndrome.
Beginning, in 2005, in recognition that infants born between 34 weeks and 37 weeks
experience morbidities and mortality characteristic of premature infants, preterm births were
subdivided. Those before 34 weeks are labeled early preterm, and those occurring between
34 and 36 completed weeks late preterm.
Table 42-1 suggest that optimal pregnancy outcomes vis-a-vis prematurity are achived at 39
weeks gestation. These example suggest that shortened human gestation with regard to
prematurity is birth before 37 weeks rather than before 39 weeks.

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II.II. Risk Factors

The exact mechanism(s) of preterm labor is largely unknown but is believed to include
decidual hemorrhage, (eg, abruption, mechanical factors such as uterine overdistension from
multiple gestation or polyhydramnios), cervical incompetence (eg, trauma, cone biopsy),
uterine distortion (eg, mllerian duct abnormalities, fibroid uterus), cervical inflammation
(eg, resulting from bacterial vaginosis [BV], trichomonas), maternal inflammation/fever (eg,
urinary tract infection), hormonal changes (eg, mediated by maternal or fetal stress), and
uteroplacental insufficiency (eg, hypertension, insulin-dependent diabetes, drug abuse,
smoking, alcohol consumption).
Although prediction of preterm delivery remains inexact, a variety of maternal and obstetric
characteristics are known to increase the risk, presumably via one of these mechanisms.
Finally, the fetus plays a role in the initiation of labor. In a simplistic sense, the fetus
recognizes a hostile intrauterine environment and precipitates labor by premature activation
of a fetal-placental parturition pathway.
Risk factors for preterm birth include demographic characteristics, behavioral factors, and
aspects of obstetric history such as previous preterm birth. Demographic factors for preterm
labor include nonwhite race, extremes of maternal age (< 17 y or >35 y), low socioeconomic
status, and low prepregnancy weight. Preterm labor and birth can be associated with stressful
life situations (eg, domestic violence; close family death; insecurity over food, home, or
partner; work and home environment) either indirectly by associated risk behaviors or
directly by mechanisms not completely understood. Many risk factors may manifest in the
same gravida.
Methods used for predicting preterm birth include home uterine activity monitoring
(HUAM), assessments of salivary estriol, fetal fibronectin (FFN), the presence of BV, and
cervical length assessment.

While hospital tocodynamometry has been effective for monitoring uterine

contractions to evaluate preterm labor, HUAM has not been proven valuable in
detecting or preventing preterm birth and is not currently recommended for use.

The proposed use of salivary estriol measurements in detecting preterm labor was
based on the belief that the adrenal gland production of dehydroepiandrosterone
increases before the onset of labor, which results in an increase of maternal estriol.
Unfortunately, maternal estriol levels show diurnal variation, peaking at night, and are
suppressed by betamethasone administration, thereby decreasing the predictive value
of salivary estriol in the detection of preterm delivery risk.

FFN is a basement membrane protein that helps bind placental membranes to the
decidua. While a negative FFN is helpful in predicting women who are not destined to
deliver preterm, a positive FFN has limited value in predicting women who will

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deliver preterm. Nevertheless, FFN has a predictive value in identifying patients who
will or will not deliver within the subsequent 1-2 weeks.

While the presence of BV has been associated with the risk of preterm delivery,
prospective treatment trials eradicating asymptomatic BV failed to reduce the risk of
preterm delivery.

Longer term prediction of the risk of preterm delivery is achieved by cervical length
measurements. A short cervical length in the early or late second trimester has been
associated with a markedly increased risk of preterm labor and delivery. The
prediction of preterm delivery may potentially be improved by combining FFN testing
with measurements of cervical length.

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Preconceptual evaluation
While the risk for preterm birth in nulliparous patients is hard to determine, past obstetric
experience and personal behavior may provide significant insight into future pregnancy
outcome in multiparous women. Identifying at-risk patients preconceptually may allow
additional treatment options. Women who seek birth control have a 30% chance of becoming
pregnant in the next 2 years, suggesting that these women represent one potential opportunity
for intervention. The presence of the following risk factors should be addressed prior to
pregnancy.

Cervical trauma
The most common etiologies for cervical injury are elective abortion, surgeries to treat
cervical dysplasia, and injury occurring at delivery. A single uncomplicated elective abortion
at less than 10 weeks gestation does not increase the risk of midtrimester loss or preterm
birth unless the cervix has been forcibly dilated to more than 10 mm at the time of the
abortion. However, patients with a history of multiple first-trimester elective terminations or
one or more second-trimester elective abortions may be at increased risk for preterm delivery.
Cervical dilatation with laminaria or cervical ripening agents, such as misoprostol, appears to
be less traumatizing to the cervix than mechanical dilation.
Cervical dysplasia should be treated appropriately whenever diagnosed. However the
incidence of preterm birth and cervical incompetence may be increased 200-300% after
preconceptual surgical treatment (eg, cold knife cone, cryoconization, laser cone, LEEP) of
cervical intraepithelial neoplasia (CIN). The risk of subsequent preterm delivery may be
proportional to the amount of cervical tissue removed during surgery. Surprisingly, the ease
of performing LEEP for relatively minor abnormalities may have paradoxically led to more
cervical injury than was observed with the relatively more invasive cone biopsy.
Obstetric trauma may be underestimated as a risk for midtrimester loss or preterm birth.
While women may relate a history of cervical laceration, often they are unaware of the injury
and the obstetric records of the previous delivery may be misleading as to the extent of the
cervical injury. Therefore, visual inspection of the cervix is important to assess the degree of
injury and risk. Defects that involve more than 50% of the cervical length may indicate a
higher risk for midtrimester loss. The accuracy of transvaginal ultrasonic measurements to
determine risk of cervical incompetence, specifically in the presence of a history of cervical
trauma, has yet to be determined.

Genital tract infection

The young gynecology patient diagnosed with gonorrhea, chlamydia, or trichomoniasis has
an approximate 25% risk of reinfection during the subsequent 12 months, but a clear

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association between these organisms and preterm delivery has not been established. BV is a
vaginal syndrome associated with an alteration of the normal vaginal flora rather than an
infection specific to any one organism and a lack of vaginal inflammation is evident when
compared with vaginitis. The diagnosis of BV should be suspected with a positive Gram stain
result or the presence of 3 of 4 traditional diagnostic signs (homogenous gray-white
discharge, >20% clue cells on saline wet smear, positive whiff test, and a vaginal pH >4.50)
Patients should be treated per the US Centers for Disease Control and Prevention guidelines,
with test-of-cure sampling and subsequent treatment if necessary.

Preterm labor/birth history

A history of prior preterm deliveries places the patient in the high-risk category. Of the
predictors of preterm birth, past obstetric history may be one of the strongest predictors of
recurrent preterm birth. Given a baseline risk of 10-12%, the risk of recurrent preterm birth
after 1, 2, and 3 consecutive preterm births may be increased to approximately 15%, 30%,
and 45%, respectively. Preconceptual counseling should help encourage patients to make
informed decisions concerning future pregnancy in light of prematurity risk in the presence of
previous preterm delivery. Often the best time to counsel the patient is at her 4- to 6-week
postpartum check after a preterm delivery.
Lykke et al found that spontaneous preterm delivery, preeclampsia, or fetal growth deviation
in a first singleton pregnancy predisposes women to those complications in their second
pregnancy, especially if the complications were severe.
The optimal method of preterm birth in multiple gestations has yet to be proven. Cervical
cerclage, prophylactic bed rest, and empiric use of tocolytics have not been successful. Most
recently, a randomized controlled trial by Lim et al suggests that the use of 17hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in
multiple pregnancies.

Midtrimester loss
Midtrimester loss has many etiologies, including infection (eg, syphilis), antiphospholipid
syndrome, diabetes, substance abuse, genetic disorders, congenital mllerian abnormalities,
cervical trauma, and cervical incompetence. Unfortunately, many midtrimester losses remain
unexplained. A complete workup (see History of midtrimester loss) may be of value in
selected patients following a midtrimester loss.

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II.III. Etiology
Pathway to Preterm Labor
Pregnancy with intact fetal membranes and spontaneous preterm labor must be distinguished
from those complicated by preterm prematurely ruptured membranes. Even so, those with
spontaneous preterm labor do not constitute a homogeneous group characterized singularly
by early initiation of parturition (American College of Obstetricians and Gynecologists,
2012b). This certainly is one reason why preventative therapies and clinical tools to assess the
risks for preterm birth have been difficult to identify. Among the more common associated
findings are multifetal pregnancy, intrauterine infection, bleeding, placental infarction,
premature cervical dilatation, cervical insufficiency, hydramnions, uterine fundal
abnormalities, and fetal anomalies. Severe maternal illness as a resullt of infections,
autoimmune diseases, and gestational hypertension also increases preterm labor risks.
Although there are unique aspects to each cause of preterm labor, these diverse processes
culminate in a common end point, which is premature cervical dilatation and effacement and
premature activation of uterine contractions. It seems important to emphasize that actual
process of preterm labor should be considered a final step one that results from progressive
or acute changes that could be initiated days or even weeks before labor onset. Indeed many
forms of spontaneous preterm labor that result from premature initiation of phase 2 of
parturition.
Diverse pathways to instigate parturition exist and are dependent on the etiology of preterm
birth. Identification of both common and uncommon factors has begun to explain the
physiological processes of human parturition at term and preterm.

Four major causes of spontaneous preterm labor, include:

Uterine distention
Maternal fetal stress
Premature cervical changes
Infection

There are four main direct reasons for preterm births, these include:
Spontaneous unexplained preterm labor with intact membranes
Idiopathic preterm prematur rupture of membrane (PPROM)
Delivery for maternal or fetal indications
Twins and higher order multifetalbirths

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Of all preterm births, 30 to 35 percent are indicated, 40 to 45 percent are due to spontaneous
preterm labor, and 30 to 35 percent follow preterm membrane rupture (Goldenberg, 2008).
Reasons for preterm birth have multiple, of interacting, antecedents and contributing factors.

II.IV. Diagnosis
Contractions of sufficient frequency and intensity to effect progressive effacement and
dilation of the cervix at 24-37 weeks gestation are indicative of active preterm labor. If the
diagnosis of preterm labor is suspected, but not confirmed, it may be prudent to first obtain a
vaginal fetal fibronectin (FFN) sample before pelvic cervical examination. If the diagnosis of
preterm labor becomes obvious after the pelvic examination, the FFN specimen can be
subsequently discarded. However, if the diagnosis remains in doubt, the FFN specimen can
be sent to the lab for analysis.
Criteria that indicate consideration of tocolytic therapy include more than 6 contractions per
hour resulting in a demonstrated cervical change or presumed prior cervical change
(transvaginal cervical length < 2.5 cm, >50% cervical effacement, or cervical dilation 2 cm).
If contractions are present without cervical change, management options include continued
observation or therapeutic sleep (eg, morphine sulphate 10-15 mg subcutaneous).
When using strict criteria in women at 24 0/7 to 33 6/7 weeks gestation for false preterm
labor (one contraction or less in 10 min, cervical dilation < 2 cm, and no evidence of
cervical change over 2 h of observation), Chao et al demonstrated that these patients had a
greater incidence of late preterm (34-36 weeks gestation) but not early preterm delivery (<
34 weeks gestation), compared with a control obstetric population. However, those patients
with cervical dilation of 1 cm were more likely to delivery prior to 34 weeks gestation.
Although this study provides some guidance as to management, a negative FFN result and/or
evidence of abated contractions may be of additional value in discharging patients with false
preterm labor. In addition, measures of absolute or change in cervical length (effacement), in
addition to dilation, may be of value in discriminating true versus false preterm labor.

Symptoms
Early differentiation between true and false labor is difficult before there is demonstrable
cervical effacement and dilatation. Uterine activity alone can be misleading because of
Braxton Hicks contractions. These contractions, described as irregular, no rhythmical, and
either painful or painless, can cause considerable confusion in the diagnosis of true preterm
labor. Not infrequently, women who deliver before term have uterine activity that is attributed
to Braxton Hicks contractions, prompting an incorrect diagnosis of false labor.
Accordingly, the American Academy of Pediatrics and the American College of Obstetricians
and Gynecologists (2012) define preterm labor to be regular contractions before 37 weeks
that are associated with cervical change. In addition to painful or painless uterine
contractions, symptoms such as pelvic pressure, menstrual-like cramps, watery vaginal
discharge, and lower back pain have been empirically associated with impending preterm

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birth. Iams and coworkers (1994) found that the signs and symptoms signaling preterm labor,
including uterine contractions, appeared only within 24 hours of preterm labor.

Signs
Asymptomatic cervical dilatation after midpregnancy is suspected to be a risk factor for
preterm delivery, although some clinicians consider it to be a normal anatomical variant.
Moreover, study results have suggested that parity alone is not sufficient to explain cervical
dilation discovered early in the third trimester. Cook (1996) longitudinally evaluated cervical
status with transvaginal sonography between 18 and 30 weeks in both nulliparous and parous
women who all subsequently gave birth at term. Cervical length and diameter were identical
in both groups throughout these critical weeks. In a study from Parkland Hospital, routine
digital cervical examinations were performed between 26 and 30 weeks in 185 women.
Approximately 25 percent of women whose cervix was dilated 2 or 3 cm delivered before 34
weeks.
Knowledge of antenatal cervical dilatation did not affect any pregnancy outcome related to
preterm birth or the frequency of interventions for preterm labor. The investigators also
reported that cervical examination were not related to preterm membrane rupture. At this
time, it seems that prenatal cervical examinations are neither beneficial nor harmful.
Iams and associates (2002) analyzed data from almost 35.000 hours of daily home monitoring
and verifed that no contraction pattern efficiently predicted preterm birth. The American
College of Obstetricians and Gynecologists (2012a) does not recommend home monitoring
uterine activity monitoring.
Lockwood (1991) reported that fibronectin detection in cervicovaginal secretions before
membrane rupture was a possible marker for impending preterm labor. Values exceeding 50
ng/ml are considered positive. Sample contamination by amniotic fluid and maternal blood
should be avoided. Interventional studies based on the use of fetal fibronectin screening in
asymptomatic women have not demonstrated improved perinatal outcomes (Andrews, 2003;
Grobman, 2004). The American College of Obstetricians and Gynecologists (2012b) does not
recommend screening with fetal fibronectin tests.

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II.V. Prevention
Prevention of preterm birth has been an elusive goal. Recent reports, however, suggest that
prevention in selected populations may be achieveable.

Cervical cerclage, indication:

-

History of recurrent midtrimester losses and who are diagnosed with cervical
insufficiency
- Women that identified during sonographic examination to have a short cervix
- rescue cerclage, done emergently when cervical incompetence is recognized in
women with threatened preterm labor.

Cerclage for sonographically detected short cervix alone has not been found to be beneficial.
In contrast, women with a very short cervix, that is, < 15 mm, and a history of prior preterm
birth may be benefit.

Progestin compunds
Progesterone level in most mammals fall rapidly before the onset of labor. This is termed
progesterone withdrawal and is considered to be a parturition-triggering event. During
human parturition , however, maternal, fetal, and amnionic fluid progesterone levels
remain elevated with no decline. It has been proposed that human parturition involves
functional progesterone withdrawal mediated by decreased progesterone activity of
progesterone receptors (Ziyan, 2010). It follows conceptually that the administration of
progesterone to maintain uterine quiscence may block preterm labor.

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II.VI. Management
Preterm labor may be difficult to diagnose and a potential exists for overtreatment of uterine
irritability. Tocolytic agents, while generally safe in appropriate dosages with proper clinical
monitoring, have potential morbidity and should only be used after consideration of the risks
and benefits of such use. Neonatal morbidity and mortality are greatly affected by gestational
age, especially when the pregnancy is less than 28 weeks gestation. Tocolysis should be used
with caution when the fetus is previable because the expected prolongation of the pregnancy
is limited, and the neonate has a minimal chance of survival at less than 23 weeks. The
likelihood of survival is further reduced in the presence of significant medical complications,
such as intra-amniotic infection (IAI) at these ages.
On the other hand, the risk of neonatal mortality and morbidity is low after 34 completed
weeks of gestation; although a trial of acute tocolysis may be initiated, aggressive tocolytic
therapy is generally not recommended beyond 34 weeks, due to potential maternal
complications. Between 24 and 33 weeks gestation, benefits of tocolytic therapy are
generally accepted to outweigh the risk of maternal and/or fetal complications and these
agents should be initiated provided no contraindications exist. Although aggressive tocolysis
is not typically used beyond 34 weeks gestation, clinicians are advised not to deliver patients
at this gestation without indication because of a higher risk of neonatal morbidity in infants
born at 34-36 weeks gestation compared with deliveries at 37-40 weeks gestation.

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Preterm prematurely ruptured membranes

A history of vaginal leakage of fluid, either as a continuous stream or as a gush, should
prompt a speculum examination to visualize gross vaginal pooling of amnionic fluid, clear
fluid from the cervical canal, or both. Confirmation of ruptured membranes is usually
accompanied by sonographic examinationto assess amnionic fluid volume, to identify the
presenting part, and if not previously determined, to estimate gestational age. Amnionic fluid
is slightly alkaline (pH 7,1 7,3) compared with vaginal secretions (pH 4,5 6,0). This is the
basis of frequently used pH testing for ruptured membranes. Blood, semen, antiseptics, or
bacterial vaginosis, however, are all also alkaline and can give false positive results.

Preterm labor with intact membranes

Women with sign and symptoms of preterm labor with intact membranes are managed much
the same as described above for those with preterm ruptured membranes. If possible, delivery
before 34 weeks is delayed. Drugs used to abate or suppress preterm uterine contractions are
subsequently discussed.

Assessment prior to tocolytic therapy

One should always attempt to determine gestational age by first identifying the first day of
the last menstrual period (LMP) and confirming it by one or more of the following:

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Positive pregnancy test (home or clinic) prior to the expected date of the second
missed period

Uterine size determined by bimanual examination prior to 12 weeks' gestation

Doppler fetal heart tones noted prior to 12 weeks' gestation

Ultrasonographic estimation of gestational age (ie, first trimester within 1 wk, second
trimester within 2 wk, and third trimester within 3 wk)

When the LMP is not reliable, the gestational age is determined by the first ultrasonography.
Following gestational age determination, assessment of fetal well-being, fetal growth, and
evaluation of congenital anomaly should be conducted. Subspecialist consultation (MFM) is
recommended in the presence of suspected fetal anomalies because tocolytics are generally
contraindicated for any congenital anomaly incompatible with life. Tocolytics are not
indicated in patients with either suspected or confirmed IAI. Use of tocolytics is relatively
contraindicated when evidence of a hostile intrauterine environment exists, such as the
following:

Oligohydramnios

Nonreactive nonstress test results

Positive contraction stress test results

Absent or reversed diastolic flow upon Doppler examination of umbilical blood flow

Repetitive severe variable decelerations

Significant vaginal bleeding consistent with abruption, unless patient is stable and
fetal well being established

Evaluate for the presence of genital tract infection

Tocolytics are contraindicated in the presence of symptomatic IAI. The definition of IAI
infection (ie, chorioamnionitis) includes a temperature greater than 38.0C (100.0F) and 2 of
the 5 following signs:

WBC count greater than 15,000 cells/mm 3

Maternal tachycardia greater than 100 beats per minute (bpm)

Fetal tachycardia greater than 160 bpm

Tender uterus

Foul-smelling discharge

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In situations in which the diagnosis remains unclear, an amniocentesis for fluid culture
(aerobic/anaerobic bacteria), Gram stain (bacteria present if Gram stain is positive or if WBC
count is >50 cells/mm3), glucose level (positive if < 15 mg/dL), or leukocyte esterase
evaluation may be considered. However, amniocentesis may result in a false-positive FFN
test result if the FFN is performed after amniocentesis.

A study by Romero et al indicated that IAI can be quickly and accurately diagnosed with
polymerase chain reaction assay with electrospray ionization time-of-flight mass
spectrometry (PCR/ESI-MS). In the study, amniotic fluid from 142 women with preterm
labor with intact membranes underwent culturing and PCR/ESI-MS testing. Standard
culturing techniques detected microbial invasion of the amniotic cavity in 7% of these
patients, while PCR/ESI-MS detected it in 12% of them. Compared with women in whom
both tests were negative, those patients who had negative cultures but positive PCR/ESI-MS
results had a significantly greater incidence of intra-amniotic inflammation and acute
histologic chorioamnionitis, as well as a shorter time to delivery and offspring with a greater
perinatal mortality risk.[23]

Patients with preterm labor may be assessed for the presence or absence of lower genital tract
infection, such as:

Sterile speculum examination for ruptured membranes

Endocervical sampling for gonorrhea and chlamydia

Vaginal fluid pH

Wet smear for BV and trichomonal infection if indicated

GBS culture

Urinalysis and culture

Positive results are treated with appropriate antibiotics.

Assess for medical contraindications to tocolysis

Tocolytics should be used with considerable caution in pregnant patients with cardiac disease,
especially those who require medication or have a history of congestive heart failure, cardiac
surgery, significant pulmonary disease, renal failure, or maternal infection (ie, pneumonia,
appendicitis, pyelonephritis). In these cases, it may be prudent to consult with an MFM
specialist.
Specific tocolytic agents should not be used whenever known allergies exist. Indomethacin is
contraindicated in the presence of aspirin-induced asthma, coagulopathy, or significant liver

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disease. Magnesium sulfate should not be used in conjunction with select medications, such
as calcium channel blockers, or when myasthenia gravis or neuromuscular disorders exist.
Beta-mimetics (eg, terbutaline) may be contraindicated in the presence of cardiac arrhythmia,
valvular disease, and ischemic heart disease and may alter glucose homeostasis in patients
with diabetes.

Fetal therapy
The administration of glucocorticoids is recommended in the absence of clinical infection
whenever the gestational age is between 24 and 34 weeks. An attempt should be made to
delay delivery for a minimum of 12 hours to obtain the maximum benefits of antenatal
steroids. However, a randomized clinical trial by Porto et al showed that treatment with
corticosteroids at 34-36 weeks of pregnancy does not reduce the incidence of respiratory
disorders in newborn infants.
The recommended dosage of betamethasone consists of two 12 mg doses 24 hours apart
while four doses of 6 mg of dexamethasone should be administered at 6-hour intervals.
Whenever the following clinical conditions exist, the glucocorticoid regimen may require
modification:

In the presence of insulin-dependent or gestational diabetes, the provider should be

prepared for control of blood sugars.

In the event of an acutely distressed fetus, indicative of fetal hypoxia, the use of
prophylactic steroids should not delay the delivery of an acutely distressed fetus.

Although the use of repeated doses of glucocorticoids remains controversial, a meta-analysis

concluded that repeated doses of prenatal corticosteroids in women who remained at risk for
preterm birth 7 or more days after an initial course reduced the risk of their infants
developing respiratory distress syndrome and reduced serious infant outcomes (relative risk
0.83 and 0.84, respectively). Treatment with repeat doses was associated with a reduction in
mean birthweight of approximately 76 g; however, no differences in growth assessments or
disabilities at early childhood were noted in follow-up. In view of these conclusions, the
authors suggest that the clinician consider use of a single repeated dose of glucocorticoids if
the patient remains at significant risk for preterm delivery within the next 7 days, at a
gestational age less 34 weeks.

Group B streptococci prophylaxis

All patients in preterm labor should be considered at high risk for neonatal GBS sepsis.
Patients in preterm labor with the potential to deliver should receive prophylactic antibiotics
against GBS, unless GBS culture is negative. Prophylactic antibiotics should be administered
when the diagnosis of preterm labor is made and should be continued until delivery or for a
minimum of 72 hours. Patients should be re-treated if preterm labor recurs or when the
patient enters labor at term depending upon culture results.

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Tocolytic Agents
The most common tocolytic agents used for the treatment of preterm labor are magnesium
sulfate (MgSO4), indomethacin, and nifedipine. In the past, beta-mimetic agents, such as
terbutaline or ritodrine, were the agents of choice, but in recent years their use has been
significantly curtailed due to maternal and fetal side effects, such as maternal tachycardia,
hyperglycemia, and palpitations The use of these agents can lead to pulmonary edema,
myocardial ischemia, and cardiac arrhythmia.
Tocolytic agents have not proven to be efficacious in preventing preterm birth or reducing
neonatal mortality or morbidity. The primary purpose of tocolytic therapy today is to delay
delivery for 48 hours to allow the maximum benefit of glucocorticoids to decrease the
incidence of RDS. While tocolytics can be successful for 48 hours when membranes are
intact, some clinical studies suggest that the effectiveness of tocolytics is only slightly better
than bedrest and hydration, both of which have fewer adverse effects than tocolytic therapy.

Magnesium sulfate
Magnesium sulfate is widely used as the primary tocolytic agent because it has similar
efficacy to terbutaline with far better tolerance. Common maternal side effects include
flushing, nausea, headache, drowsiness, and blurred vision. The mother should be monitored
for toxic effects, such as respiratory depression or even cardiac arrest that can occur at
supratherapeutic levels. In addition, magnesium sulfate readily crosses the placenta and may
lead to respiratory and motor depression of the neonate.

Indomethacin
Indomethacin is an appropriate first-line tocolytic for the pregnant patient in early preterm
labor (< 30 wk) or preterm labor associated with polyhydramnios. A more significant
inflammatory response in the membranes and decidua is observed at gestational ages less
than 30 weeks compared with 30-36 weeks. Indomethacin reduces prostaglandin synthesis
from decidual macrophages. The fetal renal effects of indomethacin may be beneficial to
reduce polyhydramnios.

Nifedipine
Nifedipine, a calcium channel blocker, is commonly used to treat high blood pressure and
heart disease because of its ability to inhibit contractility in smooth muscle cells by reducing
calcium influx into cells. Consequently, nifedipine has emerged as an effective and safe
alternative tocolytic agent for the management of preterm labor. Despite its unlabeled status,
several randomized studies have shown that the use of nifedipine in comparison with other
tocolytics is associated with a more frequent successful prolongation of pregnancy, resulting
in significantly fewer admissions of newborns to the neonatal intensive care unit, and may be

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associated with a lower incidence of RDS, necrotizing enterocolitis, and intraventricular

hemorrhage.

II.VII. Complications
The following table depicts survival, major short-term morbidity, and intact long-term
survival by gestational age.

On shorts we can pull a red string that the older we can deliver the newborn, better outcome
will ensure to follow.

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Medical Papers (Referat) Preterm Labor RSUD Ciawi Aditiawan & Fitriyani (FK UNTAR)

REFERENCES
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Gynaecology, 7th ED. Blackwell Publishing. United States of America. 2007.
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ACOG practice bulletin. Management of preterm labor. Number 43, May 2003.
Int J Gynaecol Obstet. Jul 2003;82(1):127-35.
RCOG. Tocolysis for Women in Preterm Labour. No. Ib, February 2911. Greetop Guideline. Feb 2011.
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Chao TT, Bloom SL, Mitchell JS, McIntire DD, Leveno KJ. The diagnosis and
natural history of false preterm labor. Obstet Gynecol. Dec 2011;118(6):13018.
Cheng Y, Kaimal A, Bruckner T, Hallaron D, Caughey A. Perinatal morbidity
associated with late preterm deliveries compared with deliveries between 37
and 40 weeks of gestation. BJOG. Nov 2011;118(12):1446-1454.
Porto AM, Coutinho IC, Correia JB, Amorim MM. Effectiveness of antenatal
corticosteroids in reducing respiratory disorders in late preterm infants:
randomised clinical trial. BMJ. Apr 12 2011;342:d1696.

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Medical Papers (Referat) Preterm Labor RSUD Ciawi Aditiawan & Fitriyani (FK UNTAR)