Transcript preterm birth

Dr. M.Moshfeghi
OBS&GYN
fellowship of perinatology
Shariati.Hospital ,TUMS
RUYAN INSTITUTE
INTRODUCTION
12% of births before 37 weeks and preterm.
20% of preterm are iatrogenic
IUGR preeclampsia, placenta previa,
80 % spontaneous,
related to preterm labor or PROM
PRETERM BIRTH
Classification .
By gestational age
Moderate preterm: 32 to <37 weeks
Late preterm: 34 0/7ths to 36 6/7ths weeks
Very preterm: 28 to <32 weeks
Extremely preterm: <28 weeks
Clinical manifestations
The clinical manifestations of true labor,
contractions and cervical change, are the
same whether labor occurs preterm or at
term.
Menstrual-like cramping
Mild, irregular contractions
Low back ache
Pressure sensation in the vagina
(ie, mucus plug, bloody show)
challenge of distinguishing
true labor
(contractions that result in cervical
change)
from false labor
(contractions that do not result in
cervical change).
The rate of cervical change
distinguishes cervical ripening, which occurs over
days to weeks,
from true labor, which occurs over minutes to
hours.
Transvaginal ultrasound is the most reliable
method for measuring cervical length.
In symptomatic and asymptomatic preterm
patients,
short cervix (<30 mm) is predictive of an increased
risk of preterm labor and birth;.
Diagnosis
generally based upon
clinical criteria of
regular painful uterine contractions
accompanied by cervical change
Approach to the patient with
suspected preterm labor
Initial evaluation
Maternal vital signs
fetal heart rate and contraction
Uterine contractions are evaluated continuously
using a contraction monitor, palpation, and
the patient’s subjective assessment
Examination of the uterus to assess firmness,
tenderness, fetal size, and fetal position.
Speculum examination.
swab for fetal fibronectin (Ffn)
we only send the swab if
CL
20 to 30 mm
A rectovaginal GBS culture should be performed
if not done within the previous five weeks;
antibiotic prophylaxis depends on the results
Screening for gonorrhea and chlamydia is
indicated for women
risk of these infections;
bacterial vaginosis and trichomoniasis is
indicated in women symptomatic.
Digital cervical
examination has limited reproducibility
between examiners,
TVS to evaluate the cervix in <34 weeks
when the diagnosis of labor is uncertain.
perform an obstetrical ultrasound
examination
, confirm the fetal presentation, assess
amniotic fluid volume, and estimate fetal
weight
Cervical dilation and effacement may be
assessed by digital examination
after
placenta previa and PPROM have been excluded
after
swabs for fFN
rectovaginal (GBS) culture
TVS examination has been performed.
When assessing cervical dilation and effacement
in the second trimester,
distinguish between patients whose membranes
have hour-glassed (prolapsed) through a
mildly dilated and effaced cervix (suggestive of
cervical insufficiency)
from those who are fully dilated and effaced as
a result of advanced labor.
Ultrasound imaging can distinguish between
these two diagnoses.
We obtain a urine culture,
since asymptomatic bacteriuria is
associated with an increased risk of
preterm labor and birth
We perform drug testing in patients with
risk factors for substance abuse, given
the link between cocaine use and
placental abruption
Triage based upon cervical length
no data
from large randomized trials to help determine
the optimal management of
symptomatic women with suspected preterm
labor and intact membranes.
As a general guideline,
preterm birth is highly unlikely in symptomatic
women
if cervix length is >30 mm unless abruption is
the cause of their symptoms,
and most likely
if cervical length <15 to 20 mm
Cervical length >30
mm
These women are at low risk of preterm birth,
regardless of fFN result,
so we do not send their swabs for fFN testing.
We discharge the patients home
after an observational period of four to six
hours
during which we confirm fetal well-being (eg,
reactive nonstress test),
R/O of an acute precipitating event
(eg, abruption or overt infection), and
assure ourselves that the cervix is not
progressively dilating or effacing
We arrange
follow-up in one to two weeks
and give the patient instructions
to call if
she experiences additional signs or
symptoms of preterm labor,
CL
20 to 30 mm
increased risk
but most of these women do not deliver
preterm.
send the swab for fFN testing.
If the test is positive (fFN level greater than 50
ng/mL),
we actively manage the pregnancy in an
attempt to prevent morbidity associated with
preterm birth.
Cervical length <20 mm
at high risk of preterm birth
regardless of the fFN result.
we do not send swabs for fFN testing
we actively manage the patient in an
attempt to prevent morbidity
associated with preterm birth
Management
We hospitalize women diagnosed
with preterm labor <34 w
initiate the following treatments
A course of betamethasone
Tocolytic for up to 48 hours to delay delivery so that
betamethasone can achieve its maximum fetal effect
Antibiotics for GBS chemoprophylaxis, when appropriate
Appropriate antibiotics to women with positive urine
culture results
Magnesium sulfate for pregnancies at 24 to 32 weeks.
provides neuroprotection
Preterm labor itself is not an indication for
antibiotic prophylaxis or treatment in the
absence of documented infection or GBS
prophylaxis
There is no role for progesterone
supplementation in the treatment of acute
preterm labor
Gestational age limits for tocolytic therapy
Lower limit
not indicated prior to neonatal viability
Upper limit
Thirty-four weeks
attempting to inhibit contractions after a selflimited event
Contraindications to tocolysis
Women with preterm contractions without
cervical change, especially those with a
cervical dilation of <2 cm,
generally should not be treated with tocolytics
Established contraindications to labor
inhibition :
Intrauterine fetal demise
Lethal fetal anomaly
Nonreassuring fetal status
Severe preeclampsia or eclampsia
Maternal hemorrhage with hemodynamic
instability
Intraamniotic infection
Maternal contraindications to the tocolytic drug
fetal pulmonary maturity is not an absolute
contraindication to tocolysis, as there are
nonpulmonary morbidities associated with
preterm birth.
As an example, a 30-week fetus with a mature
amniotic fluid fetal lung maturity test is still at
risk for intraventricular hemorrhage, sepsis,
hyperbilirubinemia, and other morbidities
unrelated to respiratory distress syndrome.
Inhibition of preterm is less likely to be
successful when cervical dilation is
greater than 3 cm.
Tocolysis can still be considered in
these cases, especially when the goal
is to administer antenatal
corticosteroids
or safely transport the mother to a
tertiary care center
TOCOLYTIC OPTIONS
24 to 32 weeks
indomethacin as first-line
. 32 to 34 weeks
nifedipine for initial treatment
for adverse fetal effects with indomethacin
use at this gestational age.
32 to 34 weeks
For second-line therapy
we suggest a beta-adrenergic receptor
agonist
Maternal side effects with indomethacin
nausea,
esophageal reflux,
gastritis, and emesis
, Platelet dysfunction
indomethacin and other COX inhibitors
Fetal side effects
constriction of the ductus arteriosus
oligohydramnios.
in which the duration of indomethacin exposure
exceeded 48 hours
Oligohydramnios
use of indomethacin or ibuprofen for greater
than 72 h
Neonatal effects
associated with in utero indomethacin
exposure
bronchopulmonary dysplasia,
necrotizing enterocolitis,
patent ductus arteriosus,
periventricular leukomalacia,
intraventricular hemorrhage
Contraindications
Maternal contraindications to COX
inhibitors include
platelet dysfunction or bleeding disorder,
hepatic dysfunction,
gastrointestinal ulcerative disease,
renal dysfunction, and asthma
Dose
The dose of indomethacin for labor inhibition
50 to 100 mg loading dose (may be given per
rectum),
followed by 25 mg orally every four to six hours
Monitoring
If indomethacin longer than 48 hours,
sonographic evaluation for oligohydramnios
and narrowing of the fetal ductus arteriosus
is
warranted at least weekly
Evidence of oligohydramnios or ductal
constriction should prompt discontinuation of
this therapy.
Calcium channel blockers
Efficacy
no large randomized trials directly
comparing the efficacy of calcium channel
blockers with placebo for treatment of
preterm labor.
Maternal side effects
Nifedipine is a peripheral vasodilator,
nausea, flushing, headache, dizziness, and
palpitations.
Fetal side effects
blood sampling has not shown any clear
evidence of fetal hypoxia or acidosis
when these agents were used
Contraindications
Calcium channel blockers
hypotension, or preload-dependent cardiac
lesions
with caution in women with left ventricular
dysfunction or congestive heart failure
The concomitant use of a calcium-channel
blocker and magnesium sulfate result in
respiratory depression
Dose
initial loading dose 20 mg orally,
followed by
20 mg orally in 90 minutes.
If contractions persist,
20 mg can be given orally every 3 to 8 hours
for up to 72 hours, with a maximum dose of
180 mg/day.
(ACOG) suggests a 30 mg loading dose and then
10 to 20 mg every four to six hours
Beta-adrenergic receptor agonists
ritodrine and terbutaline
Salbutamol have also been evaluated,
but data are sparse
ritodrine is the only drug approved by (FDA) for
the treatment of preterm labor,
Target cells become desensitized to the
effect of beta-adrenergic receptor
agonists,
thereby decreasing efficacy with
prolonged use
.
Maternal side effects
causes peripheral vasodilation, diastolic
hypotension, and bronchial relaxation.
tachycardia, palpitations, and lower blood
pressure
. Pulmonary edema
metabolic effects, including hypokalemia
Hyperglycemia
lipolysis
Myocardial ischemia is a rare complication.
Contraindications
cardiac disease
hyperthyroidism poorly controlled
poorly controlled diabetes mellitus
In diabetic women, hourly blood glucose
monitoring and an intravenous insulin drip are
usually required to maintain euglycemia.
FDA oral terbutaline should not be used for
prevention or any treatment of preterm labor
The FDA
injectable terbutaline should not be used in
pregnant women for prevention or prolonged
treatment (beyond 48 to 72 hours) of preterm
labor in either the hospital or outpatient
setting
terbutaline is the most commonly used beta-adrenergic
receptor agonist for labor inhibition.
subcutaneously by intermittent injection. The dose is
variable: 0.25 mg can be administered every 20 to 30
minutes for up to four doses or until tocolysis is
achieved. Once labor is inhibited, 0.25 mg can be
administered every three to four hours until the uterus
is quiescent for 24 hours.
It can also be administered as a continuous intravenous
infusion. We suggest the infusion be started at 2.5 to 5
mcg/min; this can be increased by 2.5 to 5 mcg/min
every 20 to 30 minutes to a maximum of 25 mcg/min,
or until the contractions have abated.
At this point, the infusion is reduced by decrements of 2.5
to 5 mcg/min to the lowest dose that maintains uterine
quiescence.
48 to 72 hours
Monitoring
During beta-adrenergic agonist
fluid intake, urine output, and maternal symptoms,.
We suggest the drug be withheld if the maternal
heart rate exceeds 120 beats/min.
Glucose and potassium monitored every four to six
hours during parenteral drug administration,
since hyperglycemia and hypokalemia commonly
occur.
Significant hypokalemia should be treated to
minimize risk of arrhythmias. Significant
hyperglycemia can be treated with insulin.
Oxytocin receptor antagonists
atosiban should be more effective at later
gestational ages
as effective as beta-adrenergic receptor agonists
FDA declined to approve the use of atosiban for
tocolysis because of concerns about the drug's
safety when used in fetuses less than 28
weeks of gestation
Dose
Atosiban
is administered intravenously
beginning with a bolus of 6.75 mg
followed by a 300 mcg/min infusion for three
hours,
and then 100 mcg/min for up to 45 hours
Magnesium sulfate
magnesium sulfate was neither more nor less
effective than other s
decrease in baseline FHR and fetal heart rate
variability
. biophysical profile score and nonstress test
reactivity are not significantly altered.
Neuroprotective effects
The minimum duration of administration that
results in neuroprotection is not known,
but is less than 24 hours.
Contraindications
Magnesium sulfate
myasthenia gravis.
women with known myocardial compromise
or cardiac conduction defects
Dose
Magnesium sulfate
6 g intravenous load over 20 minutes,
followed by a continuous infusion of 2 g/hour
1 g per hour
no maintenance dose if the serum creatinine is
greater than 2.5 mg/dL
If the first tocolytic not successfully inhibit
preterm labor,
discontinuing it
beginning therapy with a second agent
avoiding multiple tocolytics concurrently in
patients who fail therapy with a single agent
INEFFECTIVE APPROACHES
Antibiotic therapy
Although subclinical genital tract
infection clearly contributes to the
pathogenesis of preterm birth,
there is no evidence-based role for
antibiotic therapy in the prevention of
prematurity
Progesterone supplementation
no evidence that progesterone
supplementation is effective in
women with acute preterm labor,
Bedrest, hydration, and sedation
There is no high quality evidence of
the efficacy of bedrest, hydration, or
sedation for prevention or treatment
of preterm labor in singleton
pregnancy
ineffectiveness of bedrest on preterm
birth
Women at risk of preterm birth
Women with twin pregnancies
Women with arrested preterm labor in index
pregnancy
MANAGEMENT
AFTER
CESSATION OF CONTRACTIONS
If a second episode of acute preterm labor
occurs, the indications for retreatment
are the same as for a primary episode
. corticosteroids is generally not repeated,
except for one course of salvage (rescue)
PREVENTION
with proven efficacy for prevention
Smoking cessation
Progesterone supplementation (in asymptomatic
women with previous preterm birth or in
asymptomatic women with no history of preterm
birth but a short cervix in the current pregnancy)
Reduction of multiple gestation by limiting the
number of embryo transfers in ART
Cerclage (in women with previous preterm birth
and a short cervix in current pregnancy)
Management of pregnant women
after inhibition of acute preterm
labor
The optimal management of pregnancies after
resolution of an acute episode of preterm
labor (PTL)
is unknown.
PHYSICAL ACTIVITY
Is hospitalization useful?
— We suggest outpatient management for
stable patients
Unstable patient
Advanced cervical dilatation,
vaginal bleeding,
nonreassuring fetal status,
a long travel time to a hospital with appropriate
levels of obstetric and neonatal care services
Is bed rest indicated?
no evidence that bed rest is
effective for prevention of
spontaneous preterm birth in
singletons or twins
Bed rest has potential harms
Should exercise and work be
avoided?
Most trials of exercise in pregnancy
have excluded women at risk for PTL
or who develop PTL during the trial;
therefore,
it is difficult to assess the effect of
exercise on these women.
reasonable to suggest
modification of activities
avoid working more than 40 hours per week,
night work,
prolonged standing (more than a total of eight
hours or
more than four continuous hours per 24-hour
period),
Should sexual activity be avoided?
Both prostaglandins in semen and orgasm can
contribute to increases in myometrial activity
discuss with patients that contractions may
occur with greater frequency and
intensity aft er intercourse
We suggest patients avoid demanding physical
activity and sexual intercourse,
Should travel be avoided?
While it is unlikely that travel will
cause PTL or preterm birth, women
who wish to travel need to consider
the risk of pregnancy complications
away from their usual source of
medical care,
MONITORING
Fetal fibronectin testing
Home uterine activity monitoring
ACOG
Fetal fibronectin testing and home uterine
activity monitoring are not useful for
monitoring women with an episode of
arrested preterm labor
MEDICATION
Maintenance tocolysis
does not support the use of maintenance
tocolytic for prevention
Maintenance tocolysis may have a role in
providing symptomatic relief with respect to
intensity and frequency of contractions
Progesterone supplementation
In the absence of another indication for
progesterone supplementation
(eg, prior spontaneous preterm birth,
sonographic short cervix),
we recommend not using progesterone as an
adjunct to tocolysis nor as part of
maintenance therapy after an arrested
episode of PTL
Repeated courses of antenatal corticosteroids
do not prevent PTL.
We do not recommend routine weekly
courses of antenatal corticosteroid therapy
Antibiotic prophylaxis
no
There is
proven benefit to use of
prophylactic broad-spectrum antibiotics
to delay delivery in the setting of PTL with
intact membranes
FOLLOW-UP
singleton and twin
scheduled on a weekly basis to review signs
and symptoms of PTL and to evaluate
whether there has been further cervical
change.
Typically, this evaluation is performed
by digital examination
and/or sterile speculum inspection of the cervix
After acute labor inhibition,
do not routinely recommend
a specific strategy of
antenatal fetal assessment
or serial ultrasound examinations for fetal
growth assessment
.
Efforts to delay delivery
largely unsuccessful.
SO
, much attention
focused on prevention
Risk factors for preterm birth
Supplemental progesterone
in women with a history of prior preterm birth
or a short cervix on ultrasound examination.
It may be effective after an episode of
arrested preterm labor, but the evidence is
less robust
. There is no evidence that progesterone
supplementation is beneficial in other settings
multiple gestation, PROM.
We suggest
intramuscular injections of
17-alpha- hydroxyprogesterone caproate rather
than vaginal progesterone
beginning (16 to 20 weeks) and continuing
through the 36 th week
.
250 mg weekly
Routine progesterone to preventing
preterm birth in multiple gestations. NO
twin pregnancies and a previous spontaneous
preterm birth, the author prescribes 17-alphahydroxyprogesterone caproate .
twin pregnancies and a short cervix in the
current pregnancy, the author prescribes
vaginal progesterone.
Routine progesterone supplementation in
the setting of PROM NO
after an arrested preterm labor NO
.
women with a positive fetal fibronectin
test. unclear
The effect in women with a cerclage is
unclear
Recommendations for progesterone
supplementation to prevent preterm birth
Singleton pregnancy, prior spontaneous
singleton preterm birth,
normal cervical
length
yes
250 mg intramuscularly weekly between 16 and
20 weeks continuing through 36 weeks
or until delivery and monitor cervical length.
Short (<25 mm) cervix → perform cerclage
Progesterone supplementation
indicated?
Singleton pregnancy, prior spontaneous twin
preterm birth, normal cervical length
Possibly
250 mg
between 16 and 20 weeks
continuing through 36 weeks or until delivery
and monitor cervical length.
Short (<25 mm) cervix → perform cerclage
Progesterone supplementation
indicated?
Singleton pregnancy, no prior spontaneous
preterm birth,
short cervix (≤20 mm) Yes
Progesterone suppository 90 to 200 mg vaginally
each night from time of diagnosis through 36
weeks of gestation.
• .
Progesterone supplementation
indicated?
Multiple pregnancy (twins or triplets) without
prior preterm birth, normal cervical length
No
No progesterone, no cerclage
Progesterone supplementation
indicated?
Twins,
short cervix
Possibly
Vaginal progesterone,
no cerclage
Progesterone supplementation
indicated?
Preterm premature rupture of membranes
No
Positive fetal fibronectin test
No
Undelivered after an episode of preterm labor
Unclear –
•
Uterine anomaly or ART
There are no data on the effectiveness of
progesterone t for prevention of preterm birth
in women with uterine malformations or who
conceive with ART
. Standard contraindications to progesterone
administration
hormone-sensitive cancer,
liver disease,
or uncontrolled hypertension.
• Placement of a pessary has also been
reported to be useful for reducing the risk of
preterm birth in women with a short cervix.