BAB I

Preterm delivery before 37 gestational weeks is a major challenge in perinatal

health care. Over the past 30, the incidence of preterm delivery in most developed
countries has been about 7–10% of live births. Some evidence shows that this
incidence has increased slightly in the past few years, but the rate of birth before 32
weeks’ gestation is almost unchanged, at 1-2%. Several factors have contributed to
the overall rise in the incidence of preterm delivery. The cause of preterm birth is
often multi factorial in origin, with a large number of risk factors identified. These
include maternal ethnicity, previous preterm birth, short time interval between
pregnancies, low maternal body mass index, maternal smoking, multiple pregnancy,
maternal stress. Neonates born preterm are at increased risk of both short-term
complications, attributed to immaturity of multiple organ systems.1

IUGR is defined as fetus that fails to achieve his growth potential. Antenatal
small for gestational age (SGA) is defined as fetus with weight <10th percentile.
IUGR is multifactorial in origin and occurs in 4–10% of all term pregnancies. In
developing countries, the major cause of IUGR is maternal undernutrition whereas in
developed countries the majority of IUGR pregnancies are the result of placental
insufficiency which leads to fetal hypoxia and hypoglycaemia and subsequent fetal
growth restriction.4

Progesterone is the key hormone maintaining pregnancy. Numerous

progesterone effects can be demonstrated by laboratory studies involving every tissue
of the reproductive tract, the myometrium, decidua, cervix, and fetal membranes.
Presumably, progesterone may alter the rate of cervical stromal degradation via
altering secretion of matrix metalloproteases by diminishing prostaglandin and nitric
oxide synthesis and minimizing neutrophil recruitment. A substantial part of
unexplained preterm deliveries might be attributable to a deleterious immune
response of the mother toward the fetus. A growing body of evidence suggests that
progesterone might play a significant role in establishing an adequate immune
environment during the early stages of pregnancy.
2.1.1 Definition Preterm

Preterm birth is defined as regular uterine contractions accompanied by

progressive cervical dilation and/or effacement at less than 37 weeks.1 Preterm
birth is a major determinant of neonatal mortality and morbidity and has long-
term adverse consequences for health. Children who are born prematurely
have higher rates of cerebral palsy, sensory deficits, learning disabilities and
respiratory illnesses compared with children born at term.2

2.2.2 Etiology and Risk Factor of Preterm

Preterm delivery may be secondary to preterm premature rupture of

membranes, spontaneous Preterm delivery with intact membranes and
indications for preterm delivery. The most common indications for a preterm
birth are gestational hypertension, abnormal fetal monitoring findings,
intrauterine growth restriction, placental abruption, intrauterine demise and
chorioamnionitis.

Risk Assessment for preterm labour and preterm birth are history of
spontaneous pre term birth, preterm pre-labour rupture of membranes in
current pregnancy, antepartum hemorrhage, uterine overdistension due to
multifetal gestation or polyhydramnios, incompetent cervix or uterine
abnormality, fetal anomaly, second trimester bleeding, infection
(chorioamnitis, bacteriuria, periodontal disease, current bacterial vaginosis
with a prior preterm birth), drugs, smoking more than 10 cigarettes per day,
lifestyle, stress, domestic violence, maternal age <18 years and >35 years,
maternal weight <55 kg.
2.2.1 Definition IUGR

IUGR is defined as fetus that fails to achieve his growth potential.

The term IUGR has been used interchangeably with small for gestational age
(SGA). SGA is a term commonly used for the neonate with birth weight
<10 %.3

2.2.2 Etiology and Risk Factor of IUGR

The causes of IUGR are broadly described under three main categories
are maternal, fetal, and placental. Several maternal demographic factors have
been associated with IUGR. Woman with young age are at increased risk for
IUGR. Beside that Maternal race, lower socioeconomic status, and living in a
developing country also increase risk of IUGR. Woman with lower
socioeconomic status commonly have poor nutritional status, maternal
anemia, and poor prenatal care and substance abuse problem, which affect
fetal growth. Several environmental and behavioral risk factors are known to
cause IUGR. Women residing in high altitude areas are exposed to chronic
hypoxia, which results in low birth weight. Smoking in pregnancy especially
in third trimester is associated is 3.5 fold increased risk of SGA compared
with nonsmokers. Exposure to various medications, such as warfa- rin,
anticonvulsants, antineoplastic agents, and folic acidantagonists (such as
trimethoprim-sulfamethoxazole, phenobarbital), can result in IUGR. Several
other maternal disease conditions are associated with IUGR. These maternal
causes of IUGR commonly are related to reduced uteroplacental blood flow,
reduced oxygen-carrying capacity, or decreased nutrition to the fetus.

Fetal factors can vary from genetic causes, congenital malformations,

fetal infection, or other causes, including multiple pregnancies. Genetic causes
can contribute to 5-20 % of IUGR, especially for early onset growth restricted
fetuses. Congenital malformations, including congenital heart disease,
diaphragmatic hernia, abdominal wall defects like omphalocele, gastroschisis,
renal agenesis or dysplasia, anencephaly, and single umbilical artery, are
associated with IUGR. Infections accounts for less than 5 % of IUGR fetuses.
Common infections are viral rubella, CMV, herpes, varicella, herpes zoster,
 HIV and parasitic infections like toxoplasmosis, syphilis, malaria. The most
common infectious etiology of IUGR in developed countries is CMV. The
mechanism of the impairment of fetal growth in CMV results from direct
cytol- ysis and loss of cell function in various organ system in the fetus.
Malaria infection in the pregnancy results in low birth weight and IUGR
secondary to poor oxygen and nutrient transfer to the fetus from the
destruction of red blood cells and placental malaria, which results from
plasmodium infected RBC causing vascular obstruction. Bacterial infections
are associated with direct cell damage or transplacental passage causing fetal
infection, or placental vascular insufficiency.

Multiple pregnancies are known to have fetal growth restriction as one

of the common complications, and account for up to 3% of all cases of IUGR.
Multiple pregnancies are at fivefold to tenfold higher risk of IUGR compared
with singleton pregnancies with 15-30 % incidence of fetal growth restriction
in twins. The risk of fetal growth restriction depends on a variety of factors,
including number of fetuses, chorionicity, presence of congenital anomaly or
umbilical cord abnormalities, such as velamentous cord insertion or two-vessel
cord, unequal placenta sharing with selective IUGR, presence of twin-twin
transfusion syndrome, conjoint twin, acardia, and maternal under nutrition.

2.2.3 Progesterone and Preterm

The exact mechanism of the onset of both term and preterm labor in
humans is a complex interaction of many different hormonal pathways,
culminating in coordinated uterine contractile. Before birth, coordinated
uterine activity is associated with connective tissue changes resulting in
cervical ripening and dilatation. Progesterone has an essential role in
maintaining pregnancy, primarily through establishing uterine quiescence.
This is achieved through suppression of the calcium-calmodulin-myosin light
chain kinase system, reducing calcium ux and altering the resting potential of
smooth muscle.

In humans, the progesterone receptor (PR) has two major subtypes PR-
A and PR-B. Binding of progesterone to PR-A, the short form of the receptor,
not thought to be associated with intra-cellular pathway mechanisms, prevents
the actions of progesterone mediated by PR-B. An increase in the myometrial
PR-A to PR-B expression ratio occurs at the onset of labor at term, resulting in
an increase in myometrial PR-A, and in effect a functional withdrawal of
progesterone with increasing sensitivity to contractile stimuli.

Progesterone can alter the response to cytokines, inhibit prostaglandin

and nitric oxide synthesis, reduce corticotrophin-releasing hormone (CRH)
synthesis, block cervical stromal degradation, and induce cervical stromal
matrix protein secretion. By altering both the mechanical and physiologic
functions of the cervix, cervical performance may be substantially enhanced
by these agents. Presumably, progesterone may alter the rate of cervical
stromal degradation via altering secretion of matrix metalloproteases by
diminishing prostaglandin and nitric oxide synthesis and minimizing
neutrophil recruitment. (hindawi)

Evidence from randomized controlled trials and systematic reviews

indicates a potential bene cial effect in the use of progesterone for some
women considered to be at increased risk of preterm birth, primarily in the
reduction in the risk of preterm birth before 34 weeks gestation. However, it
remains unclear if the observed prolongation of pregnancy translates into
improved health outcomes for the infant, as to date there is more limited
information available about neonatal and longer term infant health.
DAFTAR PUSTAKA

1. https://www.glowm.com/pdf/AIP%20Chap15%20Preterm%20Labour%20Preterm%20Bi
rth.pdf
2. http://www.who.int/reproductivehealth/publications/monitoring/who_bulletin_88.pdf
3. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.660.4636&rep=
rep1&type=pdf
4. https://link.springer.com/article/10.1007/s13669-013-0041-z
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2971700/pdf/ijwh-1-
073.pdf