Preterm Birth

Medical Paper Presentation

Aditiawan, Fitriyani
OBSTETRICS AND GYNECOLOGY CLERKSHIP
TARUMANAGARA UNIVERSITY
RSUD CIAWI, BOGOR
Period February 2nd 2015 - April 11st 2015

Definition
Preterm labor is defined as the
presence
of
contractions
of
sufficient strength and frequency to
effect progressive effacement and
dilatation of the cervix between 20
and 37 weeks gestation

(Williams Obstetric, 24ed)

Incidence
Overall incidence of PTL : 6 % - 10 %
Spontaneous

: 40 50 %

PROM

: 25 40 %

Obstetrically indicated

: 20 25 %

)Slattery and Morrison 2002 )

Survival in Premature
Infants
26 wks 80%
27 wks 90%
28-31 wks 90 to
95%
32-33 wks 95%
34-36 wks
approaches term
survival rates

Complications of
Prematurity
RDS
Intraventricular
Hemorrhage of the
new born
Necrotizing
enterocolitis
Apnea
PDA
Infection
Jaundice
Hypothermia
Neurobehavioral
Anemia

Risk Factors
I-Maternal factors :
Previous preterm delivery .
Low socioeconomic status .
Maternal age <18 years or >40 years .
Preterm premature rupture of the membranes .
Multiple gestation .
second-trimester abortions .
Maternal complications )medical or obstetric) .
Lack of prenatal care .
Smoking.
)Murphy.2007)

Risk Factors
II-Uterine causes :
Uterine septum .
Bicornuate uterus .
Cervical incompetence .
III-Fetal causes :
Intrauterine fetal death .
Intrauterine growth retardation .
Congenital anomalies .
IV-Placental causes :
Abnormal placentation

)Murphy.2007)

Risk Factors
V- Infectious factors :
Genital :
* Bacterial vaginosis )BV)
* Chlamydia
* Group B streptococcus
* Mycoplasmas
Intra-uterine :
* Ascending )from genital tract)
* Transplacental )blood-borne)
* Transfallopian )intraperitoneal)
* Iatrogenic )invasive procedures)
Extra-uterine :
* Malaria
* Typhoid fever
* Listeria

* Pneumonia
* Asymptomatic bacteriuria
)Jane Norman.2005)

The Challenge:
Identification
Labor = regular, painful uterine
contractions that produce cervical
dilation and/or effacement
Uterine contractions are seen in
normal pregnancies at early
gestational ages
Up to 50% of women hospitalized for
PTL go on to deliver at term

Prediction of preterm labor

1. Risk factors .
2. Cervical ultrasonography )Cx. Length assessment) .
3. Salivary estriol .
4. Screening for bacterial vaginosis )BV) .
5. Screening for fetal fibronectin )fFN) .
) Edwin and Sabaratnam. 2005)

Fetal Fibronectin
99% negative
predictive value for
delivery within 2 wks
Positive predictive
value worse, about
30%
22 to 35 weeks
Sample collection
issues

Changes in Cervical Morphology

Normal Cervix

Short and Funneled Cervix

Reprinted with permission from Berghella V. Contemporary Ob/Gyn . 2004;49:26-34.

Fetal fibronectin testing

Sample :
from the posterior fornix of the vagina
Indications:
1- Symptomatic preterm labour 24 - 36 weeks
2- Intact membranes and
3- Cervical dilatation less than 3 cm
Contraindications:
1- Ruptured membranes
2- Vaginal bleeding
3- Cervical cerclage insitu
Relative Contraindications:
1- After the use of lubricants or disinfectants
2- Within 24 hours of coitus or vaginal examination
)The Royal Australian and New Zealand College of Obstetricians and Gynaecologists 2008)

Prevention of premature labor

Primary prevention :
Aim :
lower the prevalence of premature labor by improving maternal health in
general and by avoiding risk factors before or during pregnancy
Measures :
1- Smoking cessation .
2- Nutritional counseling .
3- lower workload for women with stressful jobs
) Flood and Malone ,2012 )

Prevention of premature labor

Secondary prevention :
Aim :
Early identification of pregnant women at a risk of preterm labor and helped them to carry their
pregnancies to term.
Measures :
1- Self-measurement of the vaginal pH for B.V. )Bitzer.,et al.2011)
2- Cervix length measurement by TVS . ) Crane and hutchens ,2008)
(The accepted cutoff value for cervix length is 25 before GW 24 (

3- Cerclage and complete closure of the birth canal )Berghella.,et al.2011 )

4- Progesterone supplementation . ) Romero.,etal.2012)

Assessment and management of

PTL

Secondary prevention :
Aim :
Early identification of pregnant women at a risk of preterm labor and helped them to
carry their pregnancies to term.
Measures :
1- Self-measurement of the vaginal pH for B.V.
2- Cervix length measurement by TVS .
(The accepted cutoff value for cervix length is 25 before GW 24 (

3- Cerclage and complete closure of the birth canal

4- Progesterone supplementation

Queensland Maternity and Neonatal Clinical Guideline )2009)

Treatment of premature
labor
Inhibition of uterine contractions with tocolysis
Corticosteroids to induce fetal lung maturation
Treatment of infection with antibiotics
Bed rest and hospitalization.
)Schleuner.2013)

Goals of Treatment of PTL

Tocolysis often halts contractions
only temporarily
Allow 48 hr+ for steroids to be given
Allow for transport to delivery
location with NICU capability
Allow for correction of reversible
causes

Tocolysis
Aim of tocolysis :
Suppress uterine contractions and delay preterm delivery to :
1-allow in-utero transfer to an appropriate level facility .
2-allow for the administration of corticosteroids.
)King .,et al.2003)

Tocolysis
Contraindications :
Gestation > 34 weeks
Labour is too advanced
In utero fetal death
Lethal fetal anomalies
Suspected fetal compromise
Placental abruption
Suspected intra-uterine infection
Maternal hypotension: BP < 90 mmHg systolic
Relative contraindications :
pre-eclampsia
. Multiple pregnancy
placenta praevia
. Rupture of membrane
)Di Renzo et al., 2007)

Tocolysis
Tocolytic drugs that are used in clinical practice
Calcium antagonists . ) Nifedipine )
Oxytocin-receptor antagonists . ) Atosiban )
Inhibitors of prostaglandin synthesis . ) Indomethacin )
NO donors . ) Nitroglycerin)
Betamimetics . ) Terbutaline & Ritodrine )
Magnesium sulfate . ) MgSO4 )

Tocolysis

Mechanisms of action of tocolytic drugs

(Schleuner 2013)

Calcium channel blockers

(Nifedipine(
Dosage and administration :
30 mg loading dose,|then 1020 mg every 46 h.

Contraindications :
. Cardiac disease .

. Renal disease .
. Maternal hypotension )< 90/50 mm Hg) .
. Avoid concomitant use with magnesium sulphate .

Maternal side effects :

. Flushing, headache .
. Transient hypotension .

. Nausea .
. Transient tachycardia .

Fetal and neonatal side effects :

. Sudden fetal death .

. Fetal distress .
)Conde et al.,2011)

Atosiban (Tractocile)
Dosage and administration :
Initial bolus dose 6.75 mg over one minute, followed by an
Infusion of 18 mg/h for 3 h and then 6 mg/h for up to 45 h.

Contraindications :
. None .

Maternal side effects :

. Nausea .
. Allergic reaction .
. Headache .

Fetal and neonatal side effects :

. None
) De Heus et al.,2009 )

Prostaglandin synthetase inhibitors

( Indomethacin (
Dosage and administration :

loading dose of 50 mg rectally or 50-100 mg orally, then

25-50 mg orally every 6 hr 48 hr.
Contraindications :
. Renal or Hepatic impairment
Maternal side effects :
. Nausea, heartburn gastritis
. Increased PPHge

. Renal impairment function

. Headache, dizziness

Fetal and neonatal side effects :

. Constriction of ductus arterious
. Oligohydramnios,
. Hyperbilirubinemia,

. Pulmonaryhypertension
. Intraventricularhemorrhage
. Necrotizing enterocolitis
) Haas et al.,2009 )

Nitric oxide donors

Dosage and administration :
10 mg patch for every 12 hr continuing until contraction
cease up to 48 hours
Contraindications :
. Headache
Maternal side effects :
. Headache .
. Hypotension .
Fetal and neonatal side effects :
. Neonatal hypotension
) Smith et al.,2007 )

Betamimetics
Dosage and administration :
1-Terbutaline 0.25 mg subcutaneously every 20 min. to 3 hr .
2-Ritodrine initial dose of 50-100 g/min i.v., increase 50 g/min
every 10 min until contractions cease or side effects develop,
maximum dose = 350 g/min
Contraindications :
. Uncontrolled thyroid desease, & diabetes mellitus
. Cardiac arrythmias
)Anotayanonth et al.,2010 )
Maternal side effects :
. Hypokalemia
. Pulmonary edema

. Hyperglycemia
. Arrhythmias

Fetal and neonatal side effects :

. Tachycardia.
. Hyperinsulinemia

. Hypotension
. Myocardial ischemia

. Hyperglycemia

Magnesium sulfate
Dosage and administration :
Loading dose: 4g MgSO4 as a SLOW BOLUS over 15-30 minutes
Maintenance dose: 1g/hr. for 24/hr.
( Stop infusion if: RR<12 ,Hypotension ,loss of Patellar reflexes & UOP<100ml in 4hours )

Contraindications :
1- Hypersensitivity .
2- Hypermagnesemia & Hypercalcemia .
3- Myocardial damage, Diabetic coma, Heart block .
Side effects :
Magnesium toxicity include :
1- Hypotension & Hypothermia .
2- Cardiac and Central nervous system depression
3- Respiratory paralysis .
( Overdose is treated with 10ml of 10% Calcium Gluconate i.v. over 10 minutes )
(Lowes 2013)

Steroids
Reduce incidence of RDS, IVH, NEC,
sepsis, and mortality by about 50%
Intact membranes: 24-34 weeks GA
PPROM: 24-32 weeks GA
Betamethasone 12 mg q 24 hr x 2
Dexamethasone 6 mg q 12 hr x 4

Management after Tocolysis

If maternal and fetal conditions are
stable, can be managed at home
Avoid excessive physical activity;
most advocate pelvic rest
Continued tocolytics have not shown
definite benefit

Latest Review
There is no clear evidence that tocolytic drugs
improve outcome and therefore it is reasonable
not to use them. However, tocolysis should be
considered if the few days gained would be
put to good use, such as completing a course
of corticosteroids or in utero transfer.
)Royal Colege of Obstetricians & Gynaecologist. Green-top
Guideline No. 1B, Feb 2011)

Latest Review
Nifedipine and atosiban have comparable
effectiveness in delaying birth for up to seven
days.
Compared with beta-agonists, nifedipine is
associated with improvement in neonatal
outcome, although there are no long-term data.
)Royal Colege of Obstetricians & Gynaecologist. Green-top Guideline No. 1B,
Feb 2011)

Latest Review
The suggested dose of nifedipine is an initial
oral dose of 20 mg followed by 1020 mg
three to four times daily, adjusted according to
uterine activity for up to 48 hours. A total dose
above 60mg appears to be associated with a
three- to four-fold increase in adverse events.
)Royal Colege of Obstetricians & Gynaecologist. Green-top Guideline No. 1B, Feb
2011)

Latest Review
Beta-agonists have a high frequency of adverse
effects. Nifedipine, atosiban and the COX inhibitors
have fewer types of adverse effects, and they occur
less frequently than for beta-agonists but how they
compare with each other is unclear.
Using multiple tocolytic drugs appears to be
associated with a higher risk of adverse effects and so
should be avoided.
)Royal Colege of Obstetricians & Gynaecologist. Green-top Guideline No. 1B, Feb 2011)

Latest Review
Fetal fibronectin is a promising predictive test. )Honest et al.,2009) but it may have limited
accuracy in predicting preterm birth within 7 days for women with symptoms of
preterm labour .
)Sanchez-Ramos et al.,2009)

Ultrasound assessment of cervical length is also a promising predictive test for

symptomatic women . ) Crane and hutchens .2008)

Latest Review
There is no indication in routine clinical practice for continuing tocolytic therapy for

more than 48 hours. Except in some cases )e.g., placenta previa hemorrhage, amniotic
sac prolapse).

)Schleuner.2013)

Using multiple tocolytic drugs associated with a higher risk of adverse effects and
should be avoided.

)De Heus et al.,2009)

Latest Review
FDA warns against magnesium sulfate injections to pregnant women for more than 5-7
days to stop preterm labor, as this agent can lead to hypocalcemia and bone abnormalities
in the fetus.
)Lowes.2013)

Antenatal corticosteroid therapy should be initiated between 24 and 34 weeks gestation to

reduce fetal morbidity.
)Porto et al.,2011)

Latest Review
Routine administration of antibiotics in premature labor

without

premature

rupture

of

the

membranes

is

not

recommended .because the rate of maternal infection is lower ,

but pregnancy is not prolonged, nor reduction of the neonatal
complications .

)Subramaniam et al.,2012)

There is no evidence that bed rest actually lowers the rate of

preterm birth.

)Crowther and Han. 2012)