PRETERM LABOR AND BIRTH

FAHAD ZAKWAN

DEFINITION

• Preterm birth is birth before a gestational age of 37 complete weeks.(i.e. btw 28 & 37 completed wks)

• In the normal human fetus, several organ systems mature between 34 and 37 weeks, and the fetus reaches adequate maturity by the end of this period.

• One of the main organs greatly affected by premature birth is the lungs

RISK FACTORS FOR PTD

• Previous PTB

• Multiple gestation

• Polyhydramnios

• Uterine anomalies

• Infection

• Placental pathology

• Smoking

• Substance abuse

• Maternal age extremes

• Anemia

• Low BMI

• Hx cervical surgery

• Hx 2nd TM loss

• Severe stressors

• Short interpregnancy interval

History of preterm birth

•odds ratio 5.1for delivery <34 wks

•increase risk of <37 wk birth from 9% to 22%

Multifetal gestation

•preterm birth incidence (<37 wks) 50 % in twins, higher in triplets

Cervical surgery

•cervical conization OR 3.23, CI 2.29-4.55

•cryotherapy, laser vaporization, laser minicone, LEEP not associated with preterm birth

Uterine malformation

•unicornuate uterus 17% risk of preterm birth

• large uterine fibroid >5cm may increase preterm birth risk

Smoking

•daily consumption of

•1-9 cig OR 1.1(1.1-1.2) PTB<36wks and OR1.3(1.2-1.5) PTB<32 wks

• >10 cig/d OR 1.4(1.3-1.4) PTB<36 wks and OR 1.6 PTB<32wks

Substance abuse

•hard to separate from other risk factors

• cocaine positive urine samples gives 3-6 fold increased risk preterm labor

Interpregnancy interval• in two separate

epidemiologic studies, birth interval <18 months or >59 months increases risk of preterm birth than birth intervals between 18 and 59 months.

Others: •physical activity (+/-),

socioeconomic status, anemia, adolescence, prior terminations, periodontal disease, delayed ovulation.•No role for diet or

paternal risk factors

• History of preterm delivery

• History of diethylstilbestrol exposure

• History of second trimester abortion

• Young age<18 years

• Low socioeconomic status

• Acute or chronic systemic disease

• Trauma

• Abdominal surgery during pregnancy

• Infections: Untreated syphilis, Neisseria gonorrhoeae, asymptomatic group B streptococcus, acute pyelonephritis, cervicovaginal infections

• Smoking

• Drug abuse

MATERNAL FACTORS

•Overdistention of cavity: multiple gestation, polyhydramnios

•Abnormal cavity: uterine anomaly, fibroids

•Foreign body: intrauterine device

•Cervical incompetence

•Trauma to cervix

UTERINE & CERVICAL CAUSES

•Faulty placentation: placenta previa, placental abruption

•Genetic abnormality

•IUFD

•PROM

•Iatrogenic-50%

OTHER CAUSES

•20%-25% Preterm deliveries don’t follow preterm labor

• Elective delivery:

• Severe preeclampsia

•Non reassuring fetal heart rate

OTHER CONSIDERATION

Preterm Birth•Spontaneous preterm labor 30-50%

•Multiple gestation 10-30%

•PPROM 5-40%

•Preeclampsia/eclampsia 12%

•Antepartum bleeding 6-9%

•Fetal growth restriction 2-4%

•Other 8-9%

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

• ↑Survival rate with ↑gestational age and birth weight

• 70%-80% survival in infants weighing 750 to 1000 gms

• High mortality rate with weight < 750 gms

• 24 weeks-Survival 43%

• 25 weeks-Survival 74%

• 26 weeks-Survival 83%

• Greatest gain achieved by prolonging pregnancy beyond 24 weeks gestation

NEONATAL MORTALITY

• Survival exceeds 90% by 30 weeks gestation

• 90% Preterm births: 30-36 weeks gestation

• Morbidity primary concern at this gestational age

• ↓ Morbidity from RDS > 36 weeks gestation

• ↓ Morbidity from IVH (grade III and IV) > 27 weeks gestation

• ↓ Morbidity from necrotizing enterocolitis and patent ductus arteriosus > 32 weeks gestation

NEONATAL MORBIDITY

PATHOGENESIS4 PRIMARY AETIOLOGIES RECOGNISED

1. Premature activation of maternal or fetal HPA axis

2. Decidual hemorrhage

3. Inflammation/infection

4. Pathological uterine distention

HPA axis activation

• in the mother can result from stress, psychological or physical

• in the fetus can result from stressors such as uteroplacental vasculopathy, preeclampsia, nonreassuring heart rate patterns, and hypoxemia.

• Markers of HPA activation are corticotropin releasing hormoneand maternal estrogens (primarily synthesized by the fetus!)

• clinical assays for serum CRH and salivary estriol have been validated but don’t add to clinical diagnosis

INFECTION

• including bacterial vaginosis, chlamydia, GC, group B strep, ureaplasma vaginally or chorioamnionitis

• increase risk for spontaneous preterm birth through inflammatory mediators such as interleukin-6 (IL-6) or prostaglandin E2 or F2.

• Treatment of asymptomatic bacteriuria, bacterial vaginosis in high risk patients, and gonorrhea reduces risk of preterm birth

• Treatment of GBS, chlamydia, or syphilis is aimed at preventing transmission, as preterm birth risk is not reduced

DECIDUAL HEMORRHAGE

•increases risk of PTL and premature rupture of membranes (PROM)

•vaginal bleeding in more than one trimester increase risk of PROM sevenfold.

UTERINE DISTENSION

• It is due to multifetal gestation, polyhydramnios, and others increase risk of preterm birth•note on cervical incompetence: dilation of cervix unrelated to labor. Likely due to one of these four processes at a time when myometrium resistant to uterotonics.

Complications of Prematurity

• RDS

• IVH

• Feeding difficulties/NEC

• Apnea

• PDA

• Infection

• Jaundice

• Hypothermia

• Neurobehavioral

• ROP

• Anemia

Criteria: PRETERM LABOUR

Clinical diagnosis with all of the following

GESTATION AGE: ≥ 28 wks 37 wks

CONTRACTIONS ≥ 3 in 30 minutes

CERVIX DILATATION: ≥ 2 cm

EFFACEMENT: ≥ 80%

Augment your diagnosis with cervical length by ultrasound following data from 24 and 28 week

series

•10th% = 25mm (20 to 30 wks gestation)

•80-100% of women who deliver early have cervix <30mm

•15 mm or less = 50% delivery rate within one week

Augment your diagnosis withfetal fibronectin:• requires intact fetal membranes, cervical dilatation < 3cm,

gest age between 24 wks and 35 wks.

• Collected from posterior fornix or cervical os during speculum exam

• false positives can result from manipulation of the cervix--digital or ultrasound exam, or coitus within 24 hrs.--or from vaginal lubricants or medications

• fFN concentration>50 ng/ml considered positive.

Fetal Fibronectin

•99% negative predictive value for delivery within 2 wks•Positive predictive value

worse, about 30%•22 to 35 weeks• Sample collection issues

• Physical examination

• Intravenous hydration

• Bed rest

• Fetal heart rate monitoring

• Ultrasonography for gestational age and weight

• Amniocentesis for fetal lung maturity and to rule out infection

• Speculum examination to rule out PPROM

ASSESSMENT AND THERAPY

Goals of Treatment of PTL

Tocolytics

•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

Review meds

Steroids• Reduce incidence of RDS, IVH, NEC, sepsis, and mortality by about

50%

• administer to all women at high risk for preterm delivery unless ‘immediate’ (<1 hour) delivery is anticipated

• GA 24-34 weeks with intact membranes

• PPROM: 24-32 weeks GA

• betamethasone 12 mg IM q 24 hrs. x 2 doses or dexamethasone6mg IM q 12 hrs. x 4

•Reduced incidence of respiratory distress syndrome

•Reduced incidence of intraventricular hemorrhage

•Reduction of neonatal morbidity and mortality

benefits of steroid before preterm delivery

Tocolysis• Tocolysis 24-34 weeks, earlier for elective cerclage or abdominal

surgery

• contraindications include:

• IUFD, • lethal fetal anomaly, • nonreassuring fetal assessment, • severe IUGR, chorioamnionitis, •maternal hemorrhage with hemodynamic

instability, • severe preeclampsia or eclampsia

• β-adrenergic agents:

Ritodrine*

Terbutaline

• Magnesium sulfate

• Prostaglandin synthetase inhibitor:

Indomethacin• Calcium channel blockers:

Nifedipine* Ritodrine is only FDA approved tocolytic, however, terbutaline, magnesium

sulfate, nifedipine and indomethacin are widely used in US.

TOCOLYTIC AGENTS:

Tocolytics…..

Nifedipine

•Efficacy based on comparison to ritodrine or any agent, no placebo controlled trials

•dose 30 mg orally followed by 20 mg orally in 90 min

•mild side effects make it number one for maintenance, 10-30 tid or ER 60-90/d

Tocolysis…..

• Beta agonists (ritodrine, terbutaline)• Tachycardia, hypotension, tremor, palpitations, chest discomfort,

hypokalemia, hyperglycemia

• Magnesium sulfate• Nausea, flushing, fatigue, diaphoresis, loss of DTRs, respiratory depression,

cardiac arrest

• Indomethacin• Maternal GI SE, premature closure of ductus, oligohydramnios

• Atosiban• Possible increase in fetal/neonatal morbidity/mortality; not available in US

Terbutaline• prolongs pregnancy in RCT’s, insignificant trend towards

reduction in low birth weight and RDS

• contraindicated in women with heart disease due to inotropy

• iv dose 2.5-5 micrograms/min, increase q 20-30 minutes to max of 25 micrograms/minute

• SQ dose .25 mg q 20-30 minutes x 4 doses

• watch pulmonary edema, myocardial ischemia in moms

Magnesium sulfate • despite lack of evidence that pregnancy is prolonged, used locally as

more efficacious than terbutaline

• toxicity related to level

• 8-10 loss of DTR’s

• 10-15 respiratory paralysis

• 15-20 cardiac arrest

• Contraindicated in myasthenia gravis

• dose 4-6 gm. IV load over 20 min,

• follow with infusion 2-4 gms/hr

Indocin

•efficacy based on small trials• fetal side effects of oligo and premature closure of

ductus arteriosus(DA) limit use•dose 50-100 mg loading dose, followed by 25 mg

QID• if given >48 hours, evaluate sonographically for oligo

and narrowing of DA at least weekly

• ABSOLUTE:

• Fetal death

• Fetal anomalies incompatible with life

• Fetal distress warranting immediate delivery

• Chorioamnionitis / fever of unknown origin

• Severe hemorrhage

• Severe chronic HTN and/or PIH

• RELATIVE:

• Cervical dilation > 4 cm

• Ruptured membranes

CONTRAINDICATIONS TO TOCOLYTIC THERAPY

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

PREVENTION OF PTB•Reduce/eliminate risk factors, if possible•Not proven to be effective: •bed rest, •home uterine monitoring,•prophylactic tocolytics, •prophylactic antibiotics, •abstinence

PREVENTION OF PRETERM BIRTH

•Supplemental progesterone•Women with previous spontaneous preterm delivery at less than 34 weeks gestation•Weekly 17OHprogesterone IM or daily vaginal progesterone suppositories•Start at 16-20 wks gestation, continue through 36 weeks

Want some more???????????

• During labor and delivery, preterm infant at high risk of acidosis and has high incidence of intracranial hemorrhage

• High incidence of CD due to fetal distress

• Preterm infant more sensitive to depressant effects of analgesic and anesthetic drugs.

• Regional anesthesia technique of choice to avoid depressant effects of anesthetic drugs.

• Epidural prevents precipitous vaginal delivery and rapid decompression of vulnerable fetal head

ANESTHETIC CONSIDERATIONS

• Ritodrine and terbutaline commonly used agents

• May delay delivery for 24-48 hrs; however, not in substantial prolongation of pregnancy

• Contraindicated in severe cardiac or pulmonary disease

• Reported incidence of side effects vary from 0.54% to 9% as per different studies

• Side effects include hypotension, tachycardia, cardiac arrhythmias, myocardial ischemia, pulmonary edema, hyperglycemia, hypokalemia and fetal tachycardia

• Side effects dose related

• Consider delaying administration of anesthesia where feasible until maternal side effects have subsided

BETA-ADRENERGIC AGONISTS

• Extensive experience for use of seizure prophylaxis in preeclamptic women

• Little scientific evidence of efficacy of MgSO4 for tocolysis

• Many clinicians consider MgSO4 to be tocolytic of choice in patients at high risk of bleeding (P. Previa)

• Less frequent and less severe side effects than β-adrenergic agents

• Side effects include chest pain, palpitations, nausea, transient hypotension, blurred vision, sedation and pulmonary edema

• Can attenuate compensatory response to hemorrhage

• Some concern about possible increase in perinatal mortality

• May increase risk of hypotension

MAGNESIUM SULFATE

• Loading dose 4 gm over 15-20 min

• Followed by infusion at 1-4 gm/hr

• Serum levels of 5-7 mg/dl required for tocolysis

• 8-10 mg/dl; loss of tendon reflexes

• 10-15 mg/dl: respiratory depression

• >10-15 mg/dl: cardiac conduction defects

• Potentiates both depolarizers and non-depolarizers

• Causes sedation, ↓MAC and ↓analgesic requirements

• Modest prolongation of bleeding time due to effect on platelet aggregation by antagonizing the effects of Ca++

MAGNESIUM SULFATE

• Acts by inhibiting cyclo-oxygenase

• Dose: 50 mg PO followed by 25 mg PO 4-6 hr

• Limit course of therapy to less than 72 hr and administer only before 32 week gestation to minimize neonatal side effects

• No cardiovascular side effects like other agents

• ↓ thromboxane A2 →↓platelet aggregation

• Does not necessitate assessment of coagulation status prior to regional due to transient reversible effect on platelet function

• Can cause premature closure of ductus arteriosus in utero resulting in persistent fetal circulation if administered after 32 weeks gestation

• Other side effects include oligohydramnios and neonatal necrotizing enterocolitis

INDOMETHACIN

• Reduced side effect profile compared to β-adrenergic agonists

• Some investigators suggest as first line tocolytic compared to others

• Can arrest labor for 48 hrs or longer

• Can be administered orally or sublingually

• Dose: 10-20 mg PO every 4-6 hours

• More effective with fewer side effects than

β-adrenergic agents and better neonatal outcome

• However, adverse fetal effects as per some animal studies

• Usually mild maternal side effects like flushing

• Potential to cause vasodilatation, hypotension, myocardial depression and conduction defects when used in combination with volatile agents

NIFEDIPINE