DRAFT

SOOCA III – English Case

Friday, 12th Januari 2018

RISK FACTORS AND MANAGEMENT IN

PREGNANCY WITH PREMATURE HISTORY

Presented by:
dr. Amarendra Nandiwardhana

Moderator:
dr. Astri Novianti

Resource Person :
dr. Windi Nurdiawan SpOG M.Kes

OBSTETRICS AND GYNECOLOGY DEPARTMENT

FACULTY OF MEDICINE UNIVERSITAS PADJADJARAN
DR. HASAN SADIKIN HOSPITAL
BANDUNG
2018
I. INTRODUCTION

Preterm birth is defined as childbirth that occurring at gestational age less

than 37 (259 days) from the first day of last menstruation. Preterm birth is still a
major cause of morbidity and mortality in perinatal.1 Babies born prematurely
have increased risks of neurological developmental disorders such as severe
cerebral palsy, mental retardation, sensory disturbances (impaired vision, hearing
impairment) and hydrocephalus, or problems like learning difficulties, language,
impaired concentration or attention, hyperactivity, motor disabilities, and
cognitive problems. About one fifth of babies born under 32 weeks of age cannot
survive the first year compared with 1% of deaths of infants born at the age of 33
- 36 weeks and only about 0.3% of infant deaths when the birth was at sufficient
months.2,3 The incidence of preterm birth varies. Blencowe, H. et al., reported that
in 2010 the number of preterm birth worldwide reached 15 million, with 11
countries in the world that has a number of preterm births more than 15 per 100
live births. In Europe, the figure ranges between 5% - 11%.3 In the USA, one of
the nine infants was born preterm (11.9%) as a result of spontaneous labor and
maternal indications, and in Australia it happened about 7%.4 Although in
developed countries early detection, prevention, management of preterm birth are
well managed, however there has been a little increase in incidence as due to the
increase of female labor force in the last decade; in which currently happening in
Indonesia. In developing countries, the incidence is much higher, about 30% in
India, 15% in South Africa, 31% in Sudan and 10% in Malaysia. Indonesia ranks
fifth country with the highest preterm birth in the world after India, China,
Nigeria, and Pakistan.4 In Indonesia, the record of the incidence of preterm birth
nationwide is not yet available, but the incidence of babies with low birth weight
(LBW) might reflect a rough indication of preterm births; hospitals nationwide
figure is 27.9%, the provincial rate varies from 7.2% to 16.8% with the average
rate of 10.2%, while West Java is 10.8%.5 The cause of preterm birth is complex
and multifactorial. Several factors are expected to increase the risk of the
incidence of premature birth, including maternal age, education, parity, pregnancy

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interval, preterm birth history, history of abortion, premature rupture of
membranes (PROM), antepartum hemorrhage, antenatal care, and maternal
diseases, for example hypertension, anemia and even some of preterm births that
occurred spontaneously did not show apparent risk factors.6 Knowledge of risk
factors is crucial for predicting the incidence of preterm birth in order to reduce
the incidence of premature childbirth.
II. CASE REPORT
2.1 Patient Identity
Name : Mrs. W
Age : 19 years old
Address : Kp Cipaku Hilir RT/ RW 10 Ciaro Nagreg
Education : Junior High School
Employment : Housewife
Medical Record Number : 000160xxx
Hospital Admission : 6th December 2017 at 12.49

2.2 Anamnesis
Referred from : RSUD Cicalengka
Refferal note : G3P2A0 preterm parturien First latent phase

Anamnesis:
G3P2A0 felt 7.5 months of pregnancy, came with chief complaint of
abdominal pain for eight hours before hospital admission. Watery discharge from
birth canal was denied by the patient. Patient still felt fetal movement. Complain
of leukorea and dysuria was denied. Because of her complaint, the patient went
Nagreg Primary health Care and then referred to RSUD Cicalengka, because
NICU room was full, patient reffered to RSHS.

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2.3 Obstetric History
Pregnancy Place of Outcome Delivery Sex Year of
birth type birth
1 Shaman Preterm Spontan Male 2015 (+)
1700 gram
2 Home Preterm Spontan Female IUFD;
600 gram 2016
3 This pregnancy

Additional data
Marriage : ♀, 17 years old, Junior High School, Housewife
♂, 21 years old, Junior High School, Laborer
Last contraception : No contraception were used
Last menstrual period : 04/5/2017 (Regular cycle, 28 days)
Due date : 11/2/2018
Prenatal care : Midwife 6x

2.4 Vital signs:

General condition : Compos mentis
Blood Pressure : 100/70 mmHg
Heart Rate : 86 x/menit
Respiratory Rate : 20 x/menit
Temperature : 36,4oC
Cor : Regular, murmur (-) gallop (-)
Lung : VBS right=left, Rh -/-, Wh -/-
Reflex : Physiologic (+/+)
Edema : -/-
Spleen and liver : hard to assess

2.5 Obstetrics examination

Abdomen : Convex, soft

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Fundal height : 45 cm
Abdominal circumference : 128 cm
Fetal lie : Cephalic lie; back on the left side
Fetal heart rate : 148-152 bpm
Uterine contraction : 3-4x/10’/40’Strong
Body weight : 52 kg
Body height : 154 cm
Internal examination
Vulva/ vagina: within normal limit
Portio: thin, soft
Cervical opening: 3-4 cm
Amniotic membrane: (-) Intake
Head station 0, left occiput anterior

2.6 Ultrasonography
Singleton pregnancy, cephalic lie, equals to 31-32 weeks of pregnancy, placenta
at posterior corpus. Amniotic fluid Normal, EFW: 1470 grams

2.7 Laboratory Findings:

Hb : 9.7 gr/dL Leukosit : 16.136 /mm3
Ht : 27,7 % Trombosit : 295.000 /mm3
Eritrosit : 4.30 x 106 MCV : 79.1
MCH : 26.3 MCHC : 33.2
Leukosit esterase : + 3

2.8. Diagnosis
G3P2A0 31-32 weeks parturien; stage I active phase; anemia

2.9Care Plan
- Admission test
- Complete blood count, Urinalisis

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 - MgSO4 20% 4 grams in 100 cc Ringer Lactate for 15 minutes
- MgSO4 20% 8 grams in 500 cc Ringer Lactate  20 drops per minute
- Spontaneous delivery
- Informed consent
- Observation of general condition, vital sign, uterine contraction, and fetal
heart rate

Observation
Blood Heart
Contractio FHR Respiratory
Time Pressure Rate Note
n (bpm) Rate (bpm)
(mmHg) (bpm)
13.00 - 3-4x/10’/40 148- 120/80 84 20 (-)
14.00 Strong 152
14.00 - 3-4x/10’/40 144- 120/70 86 20
15.00 Strong 148
15.00 - 3-4x/10’/40 144- 120/80 86 20
16.00 Strong 148
16.00 - 3-4x/10’/40 140- 120/80 88 20
16.10 Strong 144

Internal examination
Vulva/ vagina: within normal limit
Cervical opening: fully dilated
Amniotic membrane: (-) clear fluid
Head station +3, left occiput anterior

D/ G3P1A1 parturien 31-32 weeks stage II; anemia

Th/ lead the patient to bear down
Informed consent
Consult perinatology
Observation of general condition, vital sign, his, fetal heart rate

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 On 16.15 Patient was lead to beardown
On 16.20 Born baby girl
FW 1325 grams; FL 39 cm; APGAR 1’: 8 5’: 9
Active management stage III of labour
Injected oxytocin 10 IU intramuscular
Controlled cord traction
Sign of detachment of placenta (+)
On 16.25 Born placenta with controlled cord traction
Weight 300 gr, size 16x15x1 cm
Bleeding ± 200 cc
Diuresis ± 150 cc

Diagnosis/ P3A0 preterm spontaneous delivery ; anemia

Follow Up
Date/Time NOTE INSTRUCTION
6/12/2017 Post Partum Follow Up P :
17.00 S : Complaint : - - Cefadroxil 2 x 500 mg PO
O : GC : Compos mentis - Mefenamic Acid 3x500 mg
BP : 120/70 mmHg RR : 20 x/mnt PO
HR : 84 x/mnt T : 36.7oC - Observation of general
Abdomen: flat, soft condition, vital signs and
Fundus palpable 3 fingers bleeding
below umbilicus, good
contraction
Vaginal bleeding (-)
Micturition (+)
A : P3A0 preterm spontaneous delivery ;
anemia
7/12/2017 Follow Up P :

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Date/Time NOTE INSTRUCTION
06.00 S : Complaint : - - Allowed to discharged
O : GC : Compos mentis
BP : 110/70 mmHg RR : 20 x/mnt
HR : 88 x/mnt T : 36.7oC
Abdomen: flat, soft
Fundus palpable 3 fingers
below umbilicus, good
contraction
Vaginal bleeding (-)
Micturition (+)
A : P3A0 preterm spontaneous delivery ;
anemia

III. PROBLEMS
1. What are the risks to be considered in this pregnancy?
2. How prevention and treatment in this case ?
IV. DISCUSSION
1. What are the risks to be considered in this pregnancy?
1.1 Definitions Preterm birth (PTB)
Refers to the birth of a baby that occurs before 37 completed weeks of
gestation. PTB can be further sub-categorized as late preterm delivery- 34 to
36 completed weeks gestation, moderately preterm- 32 to 34 completed
weeks, very preterm- less than 32 weeks, and extremely preterm- less than 28
weeks gestation.6 Preterm birth can also be defined by birth weight: low birth
weight- less than 2500g, very low birth weight- 1500g, and extremely low
birth weight- less than 1000g.6
1.2 Significance
Preterm birth is an increasingly common complex condition with multiple
risk factors and has substantial medical, psychological, economic and social

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 impacts.7 It is the leading cause of infant mortality in the United States.
Compared with term neonates, mortality rates for preterm (less than 37 weeks)
and very preterm infants (less than 32 weeks) are 15-fold and 75-fold higher
respectively .8 The organs most commonly affected by preterm delivery are
the lungs, as the lungs are one of the last organs to develop in utero. Preterm
birth is also the most important determinant of short and long term morbidity
in infants and children, and can have serious long term health consequences,
such as cerebral palsy, blindness, developmental difficulties, including
cognitive, sensory, learning and language deficits. The younger the gestation,
the greater the risk of severe morbidity. The EPIPAGE study group reported a
twofold increased prevalence of hyperactivity, inattention and peer problems
in very preterm birth children at school ages when compared to children born
at term9.
1.3 Incidence
Significant progress has been made in the care of premature infants, but
not in reducing the prevalence of preterm birth. In the United States, there has
been a 21% rise in the rate of preterm births since 1990, which peaked in 2006
with 12.8% of all 4 million annual live births born at less than 37 weeks of
gestation. The incidence in Europe and other developed countries lies between
5-9%.10 East Asian and Hispanic women typically have a low pre-term birth
rate. However, the incidence of preterm birth continues to rise. Part of this
escalation is due to the increased www.intechopen.com 74 Preterm Birth -
Mother and Child indicated preterm delivery of artificially conceived multiple
pregnancies, which account for 15-20% of all pre-term births.10 Preterm birth
is the principal cause of infant mortality in developed countries. One in 8
births in the United States in 2005 were preterm, compared to 1 in 18 births in
Ireland and Finland. The infant mortality rate in Ireland in 2010 was 3.89 per
1000 live births and in the United States 6.8 per 1000 live births. The main
cause of the United States' high infant mortality rate when compared with
Europe is the very high percentage of preterm births in the United States, the
period when infant mortality is greatest.11

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2. Risk factors
Several studies have been conducted to investigate the risk factors of
preterm birth, however, there were several factors that did not contribute to the
overall risk. There were cases of idiopathic preterm birth with no clear risk
factors.
A. Risk factors of preterm birth12
1. Idiopathic
2. Iatrogenic (elective)
3. Sociodemographic
4. Maternal factors
5. Medical history and pregnancy condition
6. Infection
7. Genetic
1. Idiopathic
In the past, 50% of preterm birth had unknown causes. In the present, however,
the idiopathic cause is deemed overestimated due to multiple risk factors of
preterm birth that have been discovered. This cause of preterm birth will only be
considered if all other risk factors have been ruled out.
2. Iatrogenic
Advances in medical technology and ethics had placed fetus as an individual
with the rights of life (Fetus as a patient). If the continuation of pregnancy may
harm the fetus, expulsion may be necessary due to the outside environment may
be deemed safer for the fetus. On the contrary, if the pregnancy may harm the life
of the mother, the physician may choose to force the fetus out of the mother’s
womb in order to save both the mother and the fetus.13
Such conditions may require artificial preterm birth / iatrogenic (elective
preterm birth)
a. Maternal conditions that may require elective preterm birth:
 Severe preeclampsia and eclampsia
 Antepartum bleeding
 Chorioamnionitis

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  Severe heart / lung / kidney disease
b. Fetal conditions that may require elective preterm birth:
 Fetal emergency (anemia, hypoxia, acidosis, or congenital heart defects)
 Intrauterine infections
 Intra-uterine growth restriction
 Rhesus isoimmunization
 Cord entanglement on monochorionic twins
3. Sociodemographic factors
a. Psychosocial factors (anxiety, depression, stress, emotional response,
social support, occupation, behavior, sexual activity, and willingness to
be pregnant)
b. Demographic factors (maternal age, marital status, socioeconomical
factors, race, ethnic)
a. Psychosocial Factors
1) Anxiety and Depression
An earlier study by Gorsuch and Key investigated the psychosocial effects
on preterm birth, specifically regarding anxiety and depression. The study
suggested that anxiety is often accompanied with depression. From 11 prospective
studies that investigated the correlation between anxiety and preterm birth
prevalence, 9 studies had concluded that there was significant correlation between
anxiety and prematurity, while 2 studies had concluded that anxiety correlated
with fetal growth disorders and only found in Caucasians.
Dole et al had devised a scoring system for anxiety and found that only
pregnant women that had anxiety combined with inadequate weight gain were
correlated with preterm birth. In Indonesia, there are no multicenter studies that
correlate the effects of anxiety and depression with gestational age at birth.
2) Stress
Stress is a physiological arousal caused by external or internal factors that
may cause disorder on individuals’ life balance. Stress may be defined as a
condition where an individual is demanded to respond adaptively.

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Stress is a condition that demanded individual response to adapt. It may cause
increase worry, tension, anxiety, headache, muscle tension, sleep disorders, blood
pressure, irritability, fatigue, or changes (increase or decrease) in appetite and
depression.
Maternal stress may cause increased catecholamine and cortisol secretion
that activate placental corticotrophin releasing hormone and precipitate labor
through biological pathways. Stress may also adversely affect immunity that may
cause inflammatory response or intraamniotic infection that may trigger labor
prematurely. Moutquin has investigated several stressors that may be associated
with preterm birth, such as death or sickness in the family, household violence, or
financial problems.14
3) Occupation
The rate of preterm birth was lower on mothers that do not work compared
to the mothers who worked during pregnancy. Maternal occupation may cause
increased risk of preterm birth due to fatigue or workplace-related stress. Several
workplace-related factors that may increase the risk of preterm birth were long
work hours, heavy physical activity, and workplace-related stress (such as
customer service) or financial problem associated with work.
According to EUROPOP Case Control Survey conducted by Saurel-
Cibizoles et al that involved pregnant workers that worked until 3rd trimester of
pregnancy, there were 2,369 cases of preterm birth and 4,098 term birth. The rate
of preterm birth had increased 1.3 times compared to mothers that did not work.
The workplace-related factors for preterm birth were working more than 42 hours
per week, standing more than 6 hours per day, and low job satisfaction. Newman
et al concluded that the increased rate of premature rupture of membranes on
strenuous occupation may be caused by 5 factors: posture, factory worker,
physical exertion, mental stress, and environmental stress. The study had found 2
times the risk of preterm birth compared to general population for mothers that
experienced 4 of 5 of these indicators.

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 Pregnant workers may cause workplace burden and often asked to take a
maternity leave in order to not disrupt the workflow although the majority of
pregnant mother were still able to work efficiently by gauging her work capacity.
4) Maternal behaviors
Several behavioral factors associated with preterm birth were smoking,
alcohol consumption, drug usage, eating patterns, and sexual activity.
Smoking
Smoking during pregnancy is strongly correlated with placental abruption,
low birth weight (LBW) and fetal death. Direct effects on preterm birth was only
observed on mothers that kept smoking until the 3rd trimester of pregnancy. On
mothers who stopped smoking soon after pregnancy or during 1st trimester, no
adverse birth outcomes were observed.
The risk for preterm birth on smokers are 1.2 times higher compared to the
general population. Active and passive smokers during pregnancy had no
significant difference in for the risk. Pregnant passive smokers (with partner
smoking or working in smokers’ environment) may experience difficulty in
sleeping and difficulty in breathing compared to pregnant women that were not
exposed to cigarette smoke.
Alcohol
Alcohol consumption during pregnancy is strongly correlated with growth
and congenital fetal disorders and preterm birth. Marijuana and cocaine are the
most studied and correlated drugs with the prevalence of preterm birth. Cocaine
users have 2 time the risk of preterm birth compared to the general population.
The current possible cause for growth restriction was vasoconstriction although
other causes must be considered as well. First, pregnant women that used drugs
tend to consume alcohol as well, that may cause infection or malnutrition. Second,
cocaine usage differs from individuals that may bring different effects as well.
Although behavior is a modifiable risk factor, current studies regarding behavioral
change are mostly retrospective and thus the results may have had recall bias or
there was a significant stigma associated with drug use and/or alcohol
consumption.

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Body weight before pregnancy
Body weight before pregnancy is not directly a behavioral factor, although
it is associated with dietary patterns. Several studies had indicated that low body
weight before pregnancy was associated with increased rate of preterm birth.
Preterm Prediction Study had discovered the relative risk of 1.5 on mothers with
low body mass index (BMI). Hendler had found 2.5 relative risk on mothers with
low BMI and increased rates of spontaneous preterm birth on overweight women.
However, Honest et al had conducted a meta-analysis study and no association
between BMI and preterm birth was found.
Body weight gain during pregnancy
Weight gain during pregnancy and BMI before pregnancy is associated
with preterm birth. Berkowitz and Papiernik had found an association between
preterm birth and low pregnancy weight gain; specifically, on non-obese women
with relative risk of 1.5 – 2.5. Mothers with low BMI (< 19.8) and low pregnancy
weight gain (< 0.5 kg/week) may have 3 times higher risk for preterm birth
compared to mothers with normal BMI (19.8 – 26) with low pregnancy weight
gain. Conversely, the risk increases 6 times compared to pregnant women with
normal BMI and pregnancy weight gain.
Pregnancy weight gain is not only caused by increased calorie intake or fat
deposit during pregnancy, but also fluid retention. Therefore, hydration is an
important aspect to reduce the rate of preterm birth.
Dietary patterns
Diet reflects individual choices and lifestyle; therefore, it would be
difficult to gauge the effects of individual micronutrients and its effects on the
rates of preterm birth.
Several studies conducted in 1970s shown that there were no association
between increased calorie intake with decreased rate of preterm birth. Concurrent
results from random clinical trials were found in developed and developing
countries that shown diet supplementation have not prevented preterm birth.
Protein intake has not yet been proven to decrease the risk of preterm birth. There

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is a possibility that increasing protein intake, alongside vitamin supplementation,
may increase the risk of preterm birth instead.
Iron deficiency anemia may increase the risk of preterm birth although
iron deficiency is not a direct cause for preterm birth due to serum ferritin
reflecting infection and inflammation processes instead of iron intake. Therefore,
iron intake is beneficial in reducing the risk of preterm birth.
Folic acid is frequently studied regarding its effects on congenital disorders,
although some studies had suggested an increase of folic acid was associated with
a decrease of preterm birth rates. Other studies had indicated there were no
association between folic acid supplementation and preterm birth.
An observational studied performed recently had suggested that low
vitamin C intake may increase the risk of preterm premature rupture of membrane
that may lead to preterm birth.
The association between zinc and preterm birth on pregnant women with low BMI
had been conducted in United States. Pregnant women with low BMI that
consumed zinc supplementation had babies with higher birth weight compared to
those who did not. On the other hand, zinc supplementation did not affect the birth
weight of babies with overweight mothers.
A case series had suggested that high consumption of fish with high
polyunsaturated fatty acid content may prevent preterm birth and aid in fetal
growth. Olsen et al had investigated fish consumption with gestational age and
birth weight, although no significant correlation was found between fish
consumption and gestational age and birth weight. If the population were to be
specified into non-smoker pregnant women, however, fish consumption is
associated with increase of gestational age and birth weight.
Sexual activity
A study in 1980s had shown that sexual activity may be associated with
preterm birth due to direct effects of semen on initiation of labor or due to the
encroachment of vaginal pathogenic microflora upwards during coitus.
On pregnant women with genital tract infection 9trichiomoniasis or bacterial
vaginosis) sexual activity may increase the risk of preterm birth, however recent

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studies conducted by Sayle et al suggested that sexual activity was not related to
increased incidence of premature birth.
Vaginal irrigation is thought to increase the incidence of premature rupture
of the membranes followed by premature labor. Pregnant women rarely do
vaginal irrigation, so research more often connects vaginal irrigation before
pregnancy with the incidence of prematurity. Bruce et al, reported no association
between vaginal irrigation before pregnancy with the incidence of prematurity
with an Odd Ratio of 0.7-1.1. In a small group of pregnant women who do vaginal
irrigation during pregnancy, the incidence of preterm labor is found 1.9 times
higher.14
b. Demographic Factors
The various socio-demographic characteristics of the mother that are
associated with an increase in the incidence of preterm labor includes maternal
age, marital status, socio-economic conditions, race and ethnic factors.
1) Maternal age
Teenage pregnancies aged <16 years, especially those with a young
gynecological history (adolescents who get their first period <2 years before their
pregnancy) will increase the incidence of preterm labor at <33 weeks gestation.
Women aged >35 years are also at increased risk of preterm labor. Astolfi and
Zonta received an 64% increase in the incidence of preterm labor in an Italian
female population aged 35 years or older, especially in the first pregnancy (old
primi). The reason for this increase is unknown, further research is still needed to
explain how this relationship occurs. 13
2) Marital status
Preterm delivery to unmarried mothers increases in all ethnic groups and
all age groups of mothers. The exact cause is unknown, presumably related to
psychosocial factors (anxiety, stress), environmental support and socio-economic
factors. In the USA, 40% of preterm labor occurs in mothers who are not married
but has a partner living together with them (cohabitation), as well as elsewhere in
the world, the cohabitation outside of marriage increases the incidence of preterm
labor. 12

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3) Socio-economic conditions
The differences in the incidence of preterm labor based on socioeconomic
conditions have long been known, not only in the USA, but also in European
countries, Canadia, Finland, Scotland and Spain, which generally have a
population with a fairly good socioeconomic level. This relates to other factors
that can occur in such conditions such as the tendency to conceive at a young age,
the mother’s unmarried status, bigger stress, less nutrition, unability to utilize
health services, smoking or drug usage, and physical violence.
4) Race-ethnicity
In the USA there are differences in the incidence of prematurity in various
races. Data from Santa Clara County Public Health Department, Birth Records
2005, show differences in incidence of prematurity among white ethnicity
(10%); black (16%); Hispanic (12%); Asian/pacific Islander (11%); and Indian
Americans (19%). This difference has been going on for about 2 decades, and has
not changed. The cause is associated with racial differences, stress, lifestyle,
maternal habits, infection and genetics.
These inter-ethnic differences are not influenced by education or socio-
economic status increases, meaning that even in higher education and better
status, differences in ethnic-based premality occur. 15
4. Maternal Factors
a. Cervical Incompetence
Cervical incompetence is clinically diagnosed when there is a cervical
opening during pregnancy (without uterine contractions). Some studies
incorporate these risk factors into uterine abnormalities. The exact incidence rate
is difficult to recognize, and it is very likely to be preterm labor when triggered by
ascending infection propagation that will lead to rupture or release of
prostaglandins and cause uterine contractions. Premature labor can also take place
because the fetus with amniotic fluid is too heavy to be propped up by the uterus
with an incompetent cervix; the amniotic fluid may soon be ruptured or preceded
by uterine contractions.

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 In some cases, cervical incompetence occurs due to operative interventions
on the cervix, for example a history of abortion, a cervical dilatation procedure
that results in tearing, or a congenital aberration in the cervix.
In pregnancy, cervical incompetence can be diagnosed by sonographic
examination. Funneling as a predictor of preterm labor can be detected
transvaginally but is often not seen when transabdominal examination is
performed. 16
b. Reproductive History
1) Never had premature labor
Mothers with a history of one previous preterm birth will have increased
risk of a repeat preterm labor by 2.2 fold; and if she has had 3 preterm births the
risk increases to 4.9 fold. Other studies found a 3-fold incidence of preterm labor
in women with a history of preterm labor. The younger the gestational age in
preterm labor, the more rapid prematurity in subsequent pregnancies.
2) History of premature rupture of membranes (PROM)
The risk of preterm delivery in women with a history of PROM during a
<37 weeks pregnancy (PPROM, preterm premature rupture of membrane) was 34-
44%, whereas the risk for having repeat PPROM was about 16-32%.
3) History of miscarriage (Abortion)
Most studies have found that history of abortion or termination in the first
trimester is not directly related to the incidence of preterm labor, but other
researchers have found an increase in the incidence of prematurity by 1.3 times in
women with two abortions.
Incidence of miscarriage in second trimester pregnancies increases the
likelihood of abortion, premature labor, fetal growth disorders and fetal death in
utero in subsequent pregnancies.
4) Pregnancy interval
Several studies have proven that there is an inverse relationship between
the pregnancy interval (the distance between the last labor and early pregnancy)
with the incidence of preterm labor. The risk of preterm labor in a <32 weeks

17
pregnancy will increase by 30-90% in mothers with a pregnancy interval <6
months compared with mothers who had 12 months gestational interval.
5) Parity (number of deliveries)
Preterm delivery is more common in the first pregnancy. The incidence
will decrease with the increase in the number of parity up to the fourth
parity. Studies in large populations in Abu Dhabi show no difference in the
number of paritiy with the incidence of preterm labor up to the 5th birth, but at
parity more than 10 it turns out that the incidence of preterm labor is increased.
c. Multiple Pregnancy/Twins
Twin pregnancies is an important cause of premature inflammation. The
average of twin pregnancies reaches only 35 weeks gestation, about 60% are
preterm labor at 32 weeks gestation to <37 weeks and 12% are delivered before
32 weeks gestation.
In a triplet pregnancy (3 babies) the average pregnancy will only reach
32.2 weeks, quadriplets (5 babies) will only reach 29.9 weeks and quintuplets (5
babies) will 100% be born prematurely at gestational age <29 weeks if no
intervention is done.
The number of preterm births of twin pregnancies account for about 12%
of all premature labor events. In the United States report by the CDC in 2005,
only 39.5% of twins were born full term.
d. Assisted Reproduction Techniques
The ART-Assisted Reproduction Techniques has been known sice 20-30
years ago in both developed and developing countries, including Indonesia.
Due to induction of ovulation, or other ART procedures, the incidence of twins
has increases. The use of Clomiphene preparations for ovulation induction has
been known since 1966 in the United Kingdoms, and in 1995 >60,000 doctors
prescribed this preparation. Similarly, prescription of other ovulation induction
preparations and in other countries has been noted.
In line with the progress of ovulation induction drugs, the incidence of
twins has increased, this is because the use of ovulation induction drugs will cause
multiple ovulations, as well as the ART procedure that will embed several

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embryos in one individual. In the USA about 39% of twin pregnancies occur due
to ART, in Europe 26%, while in Canada 21% of all twin pregnancies are due to
IVF program.17
e. Gestation of the Uterus
Benign uterine tumors (myomas), especially submucosal or subplasental
myomas, congenital uterine abnormalities such as septus uterus, bicornic uterus
and incompetent cervix are a risk for premature labor. The incidence of preterm
labor may increase between 7-29 times in women with Müller's congenital
aberration.
f. Pregnancy test
Pregnant women who do not get a pregnancy test, are not given a quality
pregnancy service or at an inadequate quantity, are at an increased risk for preterm
labor. In the USA, studies of more than 14 million pregnancies suggest that in
both white and black ethnicity, pregnant women without prenatal examination has
an increased incidence of preterm labor by 2.8 times. The cause is unclear,
perhaps in pregnant women who perform pregnancy checks, other risk factors are
detected early and intervention can be done.
g. Risk Scoring
The many risk factors for preterm labor, Creasy et al (quoted by Greer,
200%) grouped it into a scoring system. A pregnancy is said to be low risk for
preterm labor if the risk scores are between 1-5;moderate risk at a score of 6-9 and
a high risk if the score is 10 or more.
Table: Creasy Risk Scoring System
Scoring Maternal Obstetric Habits Current pregnancy
characteristics history
1 Two children Abortion < 1 Working Physical exhaustion
Low socio- year ago
economic status
2 <20 years of age 2 abortion Smokes > Body weight increase <
10 13 kg in 32 weeks

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 cigarettes
per day
3 Very low socio- 3 abortions Heavy labor Breech at 32-week
economic status work pregnancy
Lost 2 kg of body
weight
Engaged head
Fever
4 <18 years od Bleeding before 12
age weeks
Cervical bleeding
Uterine irritability
Placenta previa
5 Abortion at Uterine anomaly
2nd trimester Hydramnion
DES exposure
10 Abortion at Multiple pregnancies
3rd trimester Abdominal surgery
Repeat
preterm labor
Hisroty of
preterm labor

h. Medical Disease and Pregnancy Condition

Various maternal diseases, conditions and medical treatment will affect the
state of pregnancy and are related or increases the incidence of preterm
labor. Systemic diseases especially those involving the circulatory system,
oxygenation or maternal nutrition can cause impaired placental circulation which
will reduce the nutrients and oxygen to the fetus.

20
These diseases can cause impaired growth of the fetus in the womb and increase
the incidence of preeclampsia/eclampsia which is also often the cause of induced
lifesabing preterm births.
Maternal illnesses known to cause the above are:
 Chronic hypertension and hypertension in pregnancy
 Systemic Erythmatous Lupus
 Restrictive lung disease
 Hyperthyroidism
 Pregestational and gestational diabetes mellitus
 Heart diseases
 Kidney diseases
Maternal pregnancy conditions that can increase the incidence of preterm
labor are;
 Hydramnion
 Fetus with congenital abnormalities
 Severe anemia
5. Infections
Urinary tract and birth canal (urogenital tract) infections are strongly
associated with preterm labor. These infections typically represent bacterial
infections that propagate by ascending from the lower genital tract; whereas
viral infection has never been implied as a significant cause of preterm labor.
Sources of indications related to the incidence of preterm labor are:
 Genital infections:
o Bacterial vaginosis
o Group B Streptococcus
o Chlamydia trachomatis
 Intrauterine infection:
o The genital tract infection
o Through the placenta
o Through blood (blood borne)

21
 o Through the Fallopian tubes (Transfallopian,
intraperiotoneal)
o Iatrogenic (due to invasive procedures)
 Extr uterine infections:
o Kidney inflammation (pyelonephritis)
o Asymptomatic bacteriuria
o Periodontitis
o Malaria
o Pneumonia
6. Genetic Factors
The mechanisms of preterm delivery are not yet known. There are
currently five paths that will trigger premature labor through a series of:
 Inflammatory response
 Uteroplasental
 Hormonal balance
 Response to stress
 Fetal factor
Due to the vagueness of the delivery mechanism, attempts are made to
find the cause of preterm labor through a genetic approach. There is some
evidence of genetic predisposition and the existence of gene-environment
interactions associated with preterm labor, as well as some evidence of familial
and intergenerational influences on preterm labor. In these patients found risk
factors that are likely to cause prematurity are anemia, urinary tract infections,
young mothers who are under 20 years of age and previous premature birth
history.
Maternal age factor has a significant relationship to preterm birth. Patirn
with age under 20 y= years are 1589 times likely to experience preterm birth. The
result are consistent with the reseacrh conducted by kozuki et al., which women
with age under 20 years is the category thathas the high risk for the occurence of
labor premature. Pregnancies at young age are more likely to experience
complication during pregnancy and childbirth because young women often have
22
limited knowledge about pregnanancy or lack of information on how to acces the
health care system. At this age, they also ahve not reached physical maturty,
mental and reproductive organs function to be the prospective mother. The
likehood of stress on pregnant women at young age is vey high, thus the level
cathecolamine and cortisol level could increase which then enable the placental
cortichropin releasing hormone and precipitate labor through biological
pathway.19
The history of premature birth is significantly associated with the
incidence of preterm birth and as a risk factor. Results in this study are consistent
with the research conducted by G.C. Di Renzo et al., stating that patients with a
history of previous preterm delivery have amounted to 3412 times of the
possibility to experience preterm birth compared to patients without a history of
premature birth.11 Anemia has a significant relationship with the occurrence of
preterm birth as a risk factor. This is consistent with studies conducted by Yi,
Han, & Ohrr in Korea which conclude that anemia in pregnant women contributes
1.53 times against premature birth. In pregnant women with anemia, disruption
delivery of oxygen and nutrients from the mother to the placenta and fetus,
affecting the function of the placenta. Anemia in pregnant women other than can
lead to impaired fetal growth, can also cause abortion, obstructed labor, puerperal
sepsis, prematurity and maternal, even fetus mortality.12 During pregnancy, the
mother’s body undergoes many changes one of which is the relationship between
blood supply and the body’s response. Total number of plasma in pregnant
women and the number of red blood cells increased from the initial needs, but the
increase in the volume of plasma is greater than the increase in the mass of red
blood cells. This causes a decrease in hemoglobin concentration, thus affecting
the levels of O2 into the network. This situation may cause tissue hypoxia that
will then produce cortisol and prostaglandins, which trigger preterm birth in
women with anemia.19

23
2. How prevention and treatment in this case ?

Efforts to reduce the incidence of preterm birth cannot yet be called successful
but have produced sufficient information to justify management suggestions for
clinicians, not only for strategies that do not work but also for those that do. The
quality and number of clinical trials of interventions intended to reduce the
incidence and/or morbidity of preterm birth has risen substantially in recent years,
yielding data that can improve care for women at risk.

Prediction of preterm labor Up to 75% of preterm labor occurs either

spontaneously or following PPROM and many attempts have been made to
develop methods that may help us to predict the onset of preterm labor so that
measures could be taken to prevent its occurrence. These include:

1. Risk markers
2. Salivary estriol
3. Screening for bacterial vaginosis (BV)
4. Screening for fetal fibronectin (fFN)
5. Cervical ultrasonography (cervical length assessment)

Risk markers

A previous history of preterm labor is the strongest risk marker. It has

been estimated that the incidence of preterm labor in subsequent pregnancies after
one preterm birth rises to 14.3% and after two preterm births to 28% . Other risk
markers include multiple pregnancy, cigarette smoking, cervical incompetence or
uterine anomalies, uterine over-distension (polyhydraminos, macrosomia,
fibroids), previous cervical surgery , using smokeless tobacco , bleeding in early
pregnancy , bacterial vaginosis, poor socioeconomic or educational status, and
young or advanced maternal age. Pre-conceptional multivitamin treatment was
inversely associated with both early and late preterm birth . There is now evidence
to support an association between severe periodontal disease and spontaneous
preterm labor . Short interval between pregnancies (less than 12 months) has been

24
found to increase the risk of recurrent preterm birth . Recently, domestic violence,
especially injury due to physical abuse, was found to be significantly associated
with both preterm birth and low birth weight10. Unfortunately, 119 most of these
risk markers are poor predictors of preterm labor as they have variable
sensitivities (35-60%) and positive predictive values (15-30%)20.

Salivary estriol

Studies on the physiology of parturition in sheep have demonstrated the

role of fetal hypothalamo-pituitary-adrenal (HPA) axis and the resultant increase
in the production of estriol from the placenta at the onset of labor. Extrapolated to
the human pregnancy, premature activation of HPA axis in preterm labor may
increase the serum and salivary levels of estriol in the mother and this may predict
the onset of preterm labor early. Two prospective trials showed that salivary
estriol was more effective in predicting preterm labor than traditional risk
assessment. However, this test has very poor sensitivity and specificity and has a
very high false positive rate, which may increase the cost of prenatal care due to
unnecessary intervention. There is a diurnal variation of the maternal salivary
estriol level and it has been reported that administration of betamethasone to
effect surfactant production may suppress maternal salivary estriol levels . Both
these factors may pose difficulties in interpretation of the results. 21

Screening for bacterial vaginosis (BV)

Infection is closely associated with PPROM, which accounts for almost

one third of preterm labor. Abnormal genital tract flora at 26-32 weeks of
gestation was associated with preterm birth with an odds ratio (OR) of 1.4 to 2 .
Routine screening for Group B streptococcus (GBS) in the antenatal population
for GBS carrier status prior to 32 weeks of gestation may not identify women at
high risk of preterm rupture of membranes or of preterm labor 17. Attempts have
been made to screen for bacterial infections in the vagina so that antibiotic
treatment can be instituted to prevent PPROM and hence, preterm labor. Such an

25
approach would potentially reduce the incidence of preterm births by about 25%.
BV refers to the alteration of normal bacterial flora of the vagina, in which normal
lactobacilli are replaced by anerobic organisms. BV may be present in up to 10-
25% of pregnant women 18 and up to 64% of women attending sexually
transmitted diseases (STD) clinic. Half of these women with BV are
asymptomatic. An association has been found between BV and preterm labor and
it has been found to increase the risk of preterm labor by two-fold 19. However,
many studies have been done in mixed populations disregarding the fact that BV
is more common in Afro-Caribbean than in white women. Results have been
largely inconclusive and the benefit of screening for BV with the aim of
predicting the onset of preterm labor is still unclear especially in low risk
community .22

Screening for fetal fibronectin (fFN)

Fetal fibronectin (fFN) is a basement membrane protein produced by the

fetal membranes and functions as an ‘adhesion binder’. It facilitates the
attachment of the placenta and membranes to the uterine decidua and is normally
detectable in cervical secretions until 16-20 weeks of gestation. Appearance of
fFN in cervical secretions after 24 weeks of gestation may indicate disruption of
the normal adhesion between chorioamnion and the underlying decidua. Hence, it
may be a marker of inflammation of the fetal membrane / decidual inter-phase,
with or without infection, that often heralds the onset of preterm labor. Many
studies have shown an increased risk of preterm birth, if fFN is positive after 24
weeks and decreased risk if this protein is negative in cervical secretion. A meta-
analysis of 40 studies revealed a very high negative predictive value for fFN in
predicting the onset of preterm birth in the next 3 weeks 21. The specificity of
fFN test for predicting preterm delivery within 1 and 2 weeks was 89%, whereas
for delivery within 3 weeks it was 92%. The sensitivity of the test in predicting
the onset of preterm labor within 1 week and 3 weeks was 71% and 59%,
respectively. It appears that a negative fFN test is useful in ruling out an imminent
preterm delivery, whereas the implication of a positive test is uncertain. It can be
26
recommended in highrisk women who fulfill the criteria of intact membranes,
minimal cervical dilatation (< 26 mm, < 22 mm and < 13 mm, respectively at 28
weeks of gestation. The results of various studies using cervical length assessment
as a predictor of preterm delivery were not always reliable or reproducible. There
is also a wide variation in predictive values. A systemic review of 35 studies
involving cervical length assessment revealed a very wide variation in sensitivity
(68-100%) and specificity (44-79%).23 Hence, currently there is no strong
evidence to support routine cervical assessment using ultrasound between 24-28
weeks for the purpose of predicting preterm delivery.

However, it may have a place in high-risk pregnancies or in combination

with fFN assessment. Combination of fFN and cervical ultrasonography Cervical
length assessment in conjunction with fFN estimation in cervicovaginal secretions
in women with high risk of preterm delivery may be useful. A study to determine
the risk of recurrence of spontaneous preterm delivery in women with prior
preterm birth reported a risk of 65% if the cervical length is less than 25 mm and
the fFN is positiuve 24. However, if the fFN is negative, the risk of preterm
delivery was only 25%. As shown in Table 1, the risk of recurrent preterm
delivery in women with cervical length > 35 mm and negative fFN was only 7%.
Hence, a combination of cervical length assessment using ultrasound scan and
estimation of fFN may help predict the recurrence of preterm delivery in high-risk
women. 24

Table 1. Combination of cervical length assessment and fetal fibronectin fFN

in predicting recurrent risk of preterm delivery.
Recurrent risk of preterm delivery

Cervical length fFN Positive fFN Negative

< 25 mm 65% 25%

26 – 25 mm 45% 14%\

27
 > 35 mm 25% 7%

The treatment of premature labor

The goal of all interventions is not just to prolong pregnancy per se, but
rather to give the newborn infant the best chance of surviving with as few
complications as possible. Thus, depending on the particular clinical situation, the
treatment of choice might be either to prolong the pregnancy or to deliver the
baby. As a rule, however, prolongation of pregnancy by at least 48 hours is an
important objective, so that the pregnant woman can be transferred to a high-level
perinatal care center, and fetal lung maturation can be induced with
glucocorticoids. These two measures have been demonstrated to improve survival
in babies born before Gestational weeks (GW ) 34.

Premature labor is treated with the following measures:

● inhibition of uterine contractions with drugs—
tocolysis (for its indications and contraindi- cations, see Box)
● glucocorticoid administration to induce fetal
lung maturation
● treatment of local or systemic infection with antibiotics
● avoidance of physical exertion—bed rest and hospitalization

Inhibition of uterine contractions with drugs—tocolysis

Any decision to inhibit uterine contractions when fetal viability is
considered borderline (before GW 24) should be taken only after the pregnant
woman has been thoroughly informed of the high risk of neonatal morbidity and
after informed consent has been documented in writing. According to the German
guidelines, the decision to intervene or not must always serve the interests of the
child, while taking the parents’ interests into account as well. After GW 34,
careful weighing of the benefits and risks generally leads to the conclusion that
prolonging pregnancy with drugs is not indicated.

28
 Tocolytic therapy should be given for as short a time as possible and
promptly terminated once contractions have ceased. There is no indication in
routine clinical practice for continuing tocolytic therapy for more than 48 hours.
Tocolysis for more than 48 hours and after the cessation of contractions is
indicated only in exceptional cases (e.g., placenta previa hemorrhage, amniotic
sac prolapse). Individualized therapy consists of the selection of the tocolytic
agent that is most effective for each patient, and that has the least side effects,
from among the agents discussed in the following paragraphs, which are also
listed in Table 2. There is no single tocolytic agent of first choice. Betamimetics
are the best-studied tocolytic drugs; they inhibit myometrial contractions by
raising the intracellular concentration of cAMP (Figure 4). Fenoterol has been
approved for this purpose only in Germany and Austria, where it is used in 95%
of hospitals. In other countries, ritodrine and ter - butaline are used. According to
a recent Cochrane meta-analysis of eleven placebo-controlled trials of ritodrine
and terbutaline, these drugs prolong pregnancy by two and seven days,
respectively, but do not lower perinatal mortality. Because these drugs activate the
sympathetic nervous system, nearly all patients who take them suffer from
tachycardia, sweating, tremulousness, nausea, or headaches in the first few hours
of use.25
Betamimetics have the highest side-effect rates of all tocolytic drugs. Their
maternal side effects can be severe, including cardiac arrhythmia and pulmo - nary
edema, and fatalities have been reported . Even though fenoterol has been used as
a tocolytic for decades in 95% of all German hospitals, often as the sole tocolytic
agent in the hospital, the foreign guidelines no longer recommend the use of
betamimetics. If they are used at all, then preferably as bolus tocolysis, which has
fewer side effects .
Oxytocin antagonists (atosiban) bind competitively to the oxytocin receptor,
thereby inhibiting the oxytocin-mediated rise of the intracellular calcium
concentration that induces muscle contraction (Figure 4). According to a current
meta-analysis of nine randomized trials, atosiban is as effective as betamimetics
with respect to the prolongation of pregnancy and neonatal development, and its

29
side-effect rate is less than 1%. No fetal side effects have been reported; the
maternal side effects are mild (headache, nausea, vomiting). A follow-up study of
infants born after tocolysis with atosiban revealed no ill effect on their
psychosocial and motor development up to the age of two years26

Table 2.
Tocolytic drugs that are used in clinical practice
Substance class Active substances
Calcium antagonists* Nifedipine
Oxytocin-receptor Atosiban
antagonists
Inhibitors of Indomethacin
prostaglandin
synthesis*
NO donors* Nitroglycerin
Betamimetics Fenoterol, terbutaline,
ritodrine
Magnesium*

Calcium antagonists are preferred above all other tocolytic agents in the
Royal College guidelines because of their effectiveness and tolerabilit, and they
are being used increasingly often in Germany as well. They inhibit both the direct
influx of calcium into myocytes and the release of intracellular calcium (Figure
4). A Cochrane meta-analysis of twelve randomized and controlled trials revealed
that nifedipine, the most commonly used calcium antagonist, is superior to
betamimetics with respect to the prolongation of pregnancy by seven days and
past the 34th week of gestation. The administration of nifedipine lowers the
frequency of neonatal intraventricular hemorrhage (OR 0.53, 95% CI 0.34–0.84),
respi - ratory distress syndrome (OR 0.63, 95% CI 0.46–0.86), and necrotizing
enterocolitis (OR 0.21, 95% CI 0.05–0.94). Its side effects, including nausea,
flushing, headache, palpitations, and (often) reflex tachycardia, are less severe
than those of betamimetics.

NO donors—Nitric oxide (NO) is the most important mediator of smooth-

muscle relaxation. During pregnancy, contractions of the myometrium are

30
inhibited by an NO-mediated rise in intracellular cGMP synthesis and a resulting
efflux of calcium from the myocytes (Figure 4). In eleven randomized trials, the
transdermal application of an NO donor was found to be at least as effective as
betamimetics for tocolysis lasting 48 hours or seven days, with a significantly
better maternal side-effect profile. A placebo-controlled trial demonstrated a
significant reduction of severe neonatal complications (OR 0.29, 95% CI 0.09–
1.00). Women with known migraine or recurrent headaches should not take NO,
as it causes headache in as many as two-thirds of all patients taking it. Other
potential side effects include myalgia, contact dermatitis from the adhesive in the
patch, and hypotension and/or orthostatic dysregulation at the start of treatment.
No fetal side effects or teratological effects have been described. In a follow-up
study, children born after nitroglycerin tocolysis were found to be neu rologically
normal 18 months later.

Inhibitors of prostaglandin synthesis block the inducible cyclo-oxygenase

COX-2 and thereby affect the number of myometrial gap junctions and the release
of intracellular calcium (Figure 4). Indo - methacin is the best-tested agent in this
class, but selective COX-2 inhibitors are also used. A recent meta-analysis
concluded that prostaglandin inhibitors are superior to all other tocolytic agents
with respect to both efficacy and safety and are thus the drugs of first choice for
premature labor before the 32nd week of gestation. Maternal side effects are few
as long as these agents are used for a short time only, and as long as no
contraindicating conditions are present (gastro intestinal ulcers, bronchial asthma,
coronary heart disease). Indomethacin crosses the placenta and can cause serious
fetal complications if it is used for more than 48 hours or after GW 32; these
range from a reduction of the volume of amniotic fluid to persistent fetal anuria
and, in up to 50% of fetuses, constriction of the ductus arteriosus. A meta-analysis
of neonatal complications after indomethacin tocolysis revealed no association
with neonatal respiratory distress syndrome or with intraventricular hemorrhage,
but it did reveal an elevated risk of periventricular leukomalacia (OR 2.0, 95% CI
1.3–3.1) and early necrotizing enterocolitis (OR 2.2, 95% CI 1.1–4.2).

31
 Magnesium sulfate non-specifically and competitively displaces calcium
from the voltage-dependent calcium channels of myometrial cell membranes
(Figure 4). A Cochrane meta-analysis of 23 trials on a total of 2036 patients failed
to document efficacy for the prolongation of pregnancy by 48 hours, to the end of
GW 34, or to the end of GW 37 (30). The meta-analysis did, however, reveal a
2.82-fold elevation of perinatal mortality when high-dose magnesium sulfate was
given for more than 24 hours. It was concluded that magnesium sulfate cannot be
recommended as a treatment for premature labor because of its lack of tocolytic
efficacy, increased perinatal mortality, and considerable maternal side effects (1,
5). Despite this, another recent meta-analysis documented a 31% reduction in the
frequency of severe cerebral hemorrhage through the use of magnesium sulfate.
This finding conflicts, however, with the findings of an evaluation by the German
Neonatology Network (GNN) of 1965 preterm neonates weighing less than 1500
grams: In this cohort, the combination of fenoterol and magnesium sulfate was
found to be associated with the highest rate of cerebral hemorrhage of all the
tocolytic drugs and drug combinations that were analyzed.28 Off-label use -
Despite their well-documented efficacy and therapeutic safety, most of the
tocolytic drugs discussed here have not been approved for this indication in
Germany, with the exception of beta - mimetics and the oxytocin antagonist
atosiban. Lack of approval of effective medications is common in many branches
of pediatrics. All of these medications, however, are commercially available in
Germany, and physicians are free to use them for tocolysis as long as they obtain
the patient’s explicit informed consent. Special patient information forms
explaining the tocolytic effect of these drugs, their side effects, and the
medicolegal situation have been found useful in routine clinical practice. It is also
wise for each obstetrical service to have its own internal guidelines regarding the
drugs that are to be used to treat premature labor; such guidelines enable
individual physicians to take decisions more confidently and with less concern
about the potential legal repercussions, even in difficult situations.

32
 FIGURE 4

contractility
cGMP
cAMP myosin light chain kinase
ATP Ca2+
G protein
Ca2+-channel
Ca2+-calmodulin Ca2+ Ca2+
complex

inositol
phospate

Antibiotic treatment

Vaginal infections are considered to be the main cause of premature labor

and premature rupture of the membranes. It thus seems reasonable to treat vaginal
infections with antibiotics in order to prevent preterm birth. For women with
premature rupture of the membranes, a meta-analysis of 22 studies with a total of
6800 women demonstrated the benefit of antibiotics both for lowering the
frequency of chorioamnionitis (OR 0.66, 95% CI 0.46–0.96) and for preventing
preterm birth within 48 hours (OR 0.71, 95% CI 0.58–0.87) or seven days (OR
0.79, 95% CI 0.71–0.89) (35). When antibiotics are given for preterm labor
without premature rupture of the membranes, the rate of maternal infection is
lower (OR 0.74, 95% CI 0.64–0.87), but pregnancy is not prolonged, nor is there
any reduction of the rate of neonatal complications. For these reasons, the routine
administration of antibiotics in premature labor is currently not recommended.29

Bed rest Although clinical experience suggests that restricting physical

exertion may help women at high risk of premature labor, or for women who are
already in premature labor, there is no evidence that this actually lowers the rate
of preterm birth. There has not been any randomized trial of bed rest in the
prevention or treatment of premature labor in single pregnancy, and a trial of bed

33
rest in twin pregnancies revealed no benefit. The greater the degree of
immobilization, the higher the risk of maternal complications such as thrombosis
and muscle atrophy.30

34
V. CONCLUSION

 Preterm birth refers to birth of the fetus before the completion of the 37th week
of gestation and/or < 2500 gr of the birth weight.
 Preterm birth has numerous risk factors, according to fetal factors, maternal
factors, maternal environment. Those factors, including maternal age and the
history of preterm birth, collaborately contributing to preterm birth.
 Previous preterm birth is the strongest risk factor for repeated preterm delivery
and recurrences of often-occur at similar gestational age.
 The effort to reduce the incidence of preterm birth today merely giving
information to justify the management, yet have not been successful to reduce
its rate.
 The predictors of preterm labor are risk markers, salivary estriol, screening for
bacterial vaginosis, screening for fetal fibronectin, and cervical
ultrasonography (cervical length assessment).
 The inhibition of uterine contraction should be taken only after the pregnant
woman has been thouroughly informed of the high risk of neonatal morbidity
and written informed consent has been obtained.

VI. SUGGESTION

 Numerous risk factors have been known to be correlated with preterm birth;
Thus, physician shoul be aware of the risk factor and apply a tighter control on
patients with high risk for preterm birth. Those factors included the maternal
age and the history of preterm birth.
 It is necessary in the future to do reseach on the prevention of preterm birth to
reduce its incidence rate.
 It is necessary to do total examination including preterm birth predictor to
ensure the maternal condition and chance for unintentional preterm birth.

35
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