Untitled

• Preterm delivery refers to delivery before 37 weeks of gestation.
• Preterm delivery occurs in 5% to 9% of pregnancies in developed countries.
• Preterm delivery accounts for 75% to 80% of all neonatal deaths and significant neonatal morbidity.
• The cost associated with preterm birth in the US was at least $26.2 billion.
• Racial/ethnic disparities exist in the frequency of preterm birth:
  • 9.0% of non-Hispanic whites
  • 13.8% of non-Hispanic blacks
  • 9.5% of Hispanics delivered preterm in 2015.
• Late preterm is defined as 34 0/7 to 36 6/7 completed weeks of gestation.
• Early preterm is defined as less than 34 completed weeks of gestation.
• The World Health Organization (WHO) identifies the frequency of preterm birth as a critical health issue.
• Worldwide, 15 million infants are born preterm annually.
• More than 60% of preterm births occur in Africa and South Asia, with Malawi having the highest rate at 18.1 per 100 live births.
• The global neonatal mortality rate is 19 per 1000 live births.

Definitions

• A preterm infant is born between 20 0/7 weeks and 36 6/7 weeks, inclusive, after the first day of the last menstrual period.
• ACOG defines peri-viable birth as birth between 20 weeks and 25 6/7 weeks gestation.
• Gestational age is difficult to determine without maternal history or first-trimester ultrasound.
• A low birth weight (LBW) does not necessarily mean the neonate was born preterm.
• Small for gestational age (SGA) newborns can have an LBW.
• An LBW neonate weighs less than 2500 g at birth, regardless of gestational age.
• A very low birth weight (VLBW) infant weighs less than 1500 g at birth.
• An extremely low birth weight (ELBW) infant weighs less than 1000 g at birth.

Classification of deliveries by gestational age:

• Extremely preterm: Less than 28 weeks
• Very preterm: 28 0/7 to 31 6/7 weeks
• Moderate preterm: 32 0/7 to 33 6/7 weeks
• Late preterm: 34 0/7 to 36 6/7 weeks
• Early preterm: 37 0/7 to 38 6/7 weeks
• Full term: 39 0/7 to 40 6/7 weeks
• Late term: 41 0/7 to 41 6/7 weeks
• Post term: 42 0/7 weeks and beyond

Neonatal Mortality

• Neonatal survival increases with birth weight and gestational age.
• Male infants have a higher mortality rate than female infants, controlled for gestational age and weight.
• There has been significant improvement in the survival rate for preterm infants in the past 3 decades.
• The greatest improvement is in the subgroup with a birth weight between 501 and 1250 grams.
• The neonatal survival rate is approximately 94% for infants born at 28 weeks gestation.
• Infants born at the threshold of viability (22 to 24 weeks gestation) continue to have the greatest risk for poor outcomes.
• Neonatal survival rates:
  • 9% at 22 weeks
  • 33% at 23 weeks
  • 65% at 24 weeks
  • 81% at 25 weeks
  • 87% at 26 weeks
• Most women received antenatal corticosteroids.
• Most neonates received exogenous surfactant.
• A delay of even 1 week in delivery can lead to significantly better outcomes and reduced costs.

Neonatal Morbidity

• 84% of preterm births occur between 32 0/7 and 36 6/7 weeks gestation.
• Morbidity is a greater concern in this gestational age range than mortality.
• Those born between 34 and 37 weeks gestation had lower scores regarding neurocognitive performance than those born after 37 weeks gestation.
• Morbidity decreases in frequency as gestational age increases.
• High-grade (III or IV) intraventricular hemorrhage incidence diminishes rapidly after 27 weeks gestation and is rare after 32 weeks gestation.

Selected outcomes for extremely preterm infants (22 – 24 weeks gestation):

• Use of antenatal therapy:
  • Maternal corticosteroid admin: 64%
  • Maternal antibiotic admin: 66%
• Cesarean Delivery: 38%
• Male gender: 52%
• Multiple birth: 27%
• Surfactant therapy after birth: 66%
• Death before discharge: 64%
• Survival without neurodevelopmental impairment: 20%
• Survival without neurosensory impairment: 29%

Preterm Labor - Risk Factors

• Significant risk factors:
  • History of preterm delivery
  • Non-Hispanic black race
  • Multiple gestation
• Normal parturition involves:
  • Increased uterine contractility
  • Cervical ripening
  • Membrane/decidual activation
  • The fetus also plays a role
• Causes of preterm delivery:
  • Preterm premature rupture of membranes (PPROM): ~25%
  • Spontaneous preterm labor: ~45%
  • Maternal or fetal indications for early delivery: ~30%
• "Spontaneous" causes do not have a uniform pathophysiology.
  • Preterm labor is a syndrome with multiple causes: genetic, biologic, biophysical, psychosocial, and environmental factors.
• Factors of interest regarding initiation of myometrial contractility: infection and uterine distention.
• Infection is thought to be present in up to 40% of preterm deliveries.
• Approximately 50% of preterm deliveries occur in women with no apparent risk factors.
  • Subclinical infection may precipitate preterm labor.
  • Infection compounds with increased rates of neurologic injury.
• Multiple gestation accounts for 21.6% of all preterm births.
• In the past three decades, the incidence of multiple gestation has risen.
  • Attributed to a shift toward older maternal age at conception and increased use of assisted reproductive technology (ART).
• The twinning rate rose 76% from 1980 to 2009 (from 18.9 to 33.2 per 1000).
  • Recently, rates of multifetal pregnancies have started to decline.
• The twin birth rate peaked at 33.9 twins per 1000 births in 2014.
  • Decreased to 33.4 in 2016.
• The triplet and higher-order multiple birth rate has fallen 48% since the 1998 peak (193.5) to a rate of 101.4 multiples per 100,000 births in 2016.
• Modification in ART may contribute to changes in the preterm birth rate and recent declines in multiple gestation.
• In 2015, ART contributed to 1.7% of all infants born in the United States:
  • 17.0% of all multiple-birth infants:
    • 16.8% of all twin infants
    • 22.2% of all triplets and higher-order infants.
• The risk for preterm birth is elevated even for singleton pregnancies conceived by ART.
• Placenta previa, gestational diabetes, pre-eclampsia, and neonatal intensive care unit admission were also more prevalent in the patients that made use of ART system.

Factors associated with spontaneous preterm labor:

• Demographic & Medical Characteristics:
  • Non-Caucasian race
  • Extremes of age (less than 17 or greater than 35)
  • Low socioeconomic status
  • Low pre-pregnancy body mass index
  • History of preterm delivery
  • Periodontal disease
  • Abnormal uterine anatomy
  • Trauma
  • Abdominal surgery during pregnancy
• Behavioral Factors:
  • Tobacco use
  • Substance abuse
• Obstetric Factors:
  • Previous preterm birth
  • Vaginal bleeding
  • Infection (systemic, genital tract, periodontal)
  • Short cervical length
  • Multiple gestation
  • Assisted reproductive technologies
  • Preterm premature rupture of membranes
  • Polyhydramnios

Preterm Labor - Prediction

• Preventing spontaneous preterm birth would be more practical if one could intervene prophylactically.
• Prophylactic and treatment practices require the ability to accurately predict which asymptomatic patients will go on to have spontaneous preterm delivery.
• Short cervical length, as assessed by transvaginal ultrasonography, is associated with a greater risk for preterm delivery.
• A history of cervical surgery (conization and loop electrosurgical excision procedure) has been a traditional risk factor for preterm birth.
  • However, this relationship may be related to environmental/behavioral factors that underlie the progression of cervical dysplasia.

Preterm Labor - Prevention

• Few, if any, interventions reduce the incidence of preterm labor and delivery.
• Examined interventions:
  • Detection and suppression of uterine contractions
  • Antimicrobial therapy
  • Prophylactic cervical cerclage
  • Maternal nutritional supplements
  • Reduction of maternal stress
• Prophylactic cervical cerclage in the early second trimester has been used to prevent preterm birth (typically for women with a history of mid-trimester pregnancy loss).
  • Evidence supporting the efficacy of this practice is weak.
• Prophylactic antibiotics are unsupported in asymptomatic women at risk.
• Prophylactic beta-adrenergic receptor agonists are unsupported to prevent preterm labor in high-risk women.
• Progesterone therapy may be effective in reducing the rate of preterm birth in some patient populations.
• Progesterone therapy has also been shown to be beneficial in reducing the incidence of preterm delivery in women with a sonographically identified short cervix.
• Recent meta-analysis: vaginal progesterone may be beneficial in twin pregnancy (studies compared progesterone (vaginally & intramuscularly), pessary, and cervical cerclage).

Preterm Labor - Diagnosis

• Determining whether a woman is in early preterm labor or in false labor is often difficult.
• Criteria for preterm labor:
  • Gestational age between 20 0/7 and 36 6/7 weeks gestation
  • Regular uterine contractions accompanied by a change in cervical dilation, effacement, or both
  • Initial presentation with regular contractions and cervical dilation of 2 cm or more.
• Less than 10% of women with the clinical diagnosis of preterm labor give birth within 7 days of presentation.

Preterm Labor - Assessment & Therapy

• Initial assessment:
  • Physical examination
  • External monitoring of contractions with a tocodynometer
  • Monitor fetal heart rate if indicated by gestational age
• Consider acute conditions e.g., infection and placental abruption.
• In many women, preterm uterine contractions will cease spontaneously.
• The obstetric care provider must decide whether intervention is warranted once preterm labor is established.
• Antenatal corticosteroids for fetal lung maturation and magnesium sulfate for fetal neuroprotection leads to improved neonatal outcomes.
• Acute tocolytic therapy is used (although widely used before 34 weeks gestation).
• Tocolysis is currently recommended between 24- and 34 weeks gestation.
• There is no consistent evidence that the use of acute tocolysis reduces the chance of preterm birth or improves neonatal outcomes.
• Acute tocolysis has been associated with a short (approximately 48-hour) prolongation of pregnancy.
  • It may be used to facilitate the transfer of the patient to a tertiary care facility.
• A short course of tocolytic therapy may delay delivery for 24 to 48 hours.
  • Maternal corticosteroid administration to accelerate fetal lung maturity
  • Antibiotic therapy to prevent neonatal group B streptococcal infection.
• ACOG supports the use of acute tocolysis to allow for the administration of a complete course of antenatal corticosteroids but discourages the continued use of tocolysis after corticosteroid administration is complete.
• Criteria for tocolytic therapy:
  • Gestational age after viability (23 weeks) and before 34 weeks gestation
  • Reassuring fetal status
  • No overt clinical signs of infection

Contraindications to tocolytic therapy for preterm labor:

• Fetal death
• Fetal anomalies incompatible with life
• Nonreassuring fetal status
• Chorioamnionitis
• Severe hemorrhage

Preterm Labor - Corticosteroids

• Neonatal benefit of corticosteroid administration before preterm delivery has been demonstrated.
• Antenatal corticosteroid treatment reduces the incidence of neonatal respiratory distress syndrome, intraventricular hemorrhage, and neonatal death in all subgroups of the population.
• Reduction in neonatal morbidity and mortality from corticosteroid administration is additive to the reduction observed with the use of neonatal surfactant alone.
• Corticosteroids after 34 weeks but before 37 weeks gestation results in a significantly lower incidence of severe neonatal respiratory morbidity.
• Antenatal Corticosteroid Therapy*
• Betamethasone: 12 mg IM every 24 H X 2
• Dexamethasone: 6 mg IM every 12 H X 4

Preterm Labor - Antibiotic Therapy

• The use of prophylactic antibiotic therapy in the management of preterm labor in patients with intact membranes is not supported.
• There was an increase in cerebral palsy in children born to mothers in preterm labor with intact membranes who received any prophylactic antibiotics.
• ACOG does NOT recommend empirical antibiotic therapy in this patients.
• Prophylactic antibiotic administration remains appropriate for women who are positive for group B streptococcus (GBS).
• Antimicrobial therapy prolongs pregnancy and reduces both maternal and neonatal morbidity in patients with PPROM.
  • ACOG recommends a 7-day course of antimicrobial therapy when PPROM is diagnosed.
• Several clinical trials have provided evidence that maternal magnesium sulfate provides fetal neuroprotection when given to women at risk for preterm delivery.
• Magnesium sulfate reduced the rate of substantial gross motor dysfunction and reduced the combined rate of death or substantial gross motor dysfunction.
• ACOG states that magnesium sulfate, given before anticipated early preterm birth, reduces the risk of cerebral palsy in surviving infants.
• Physicians should develop specific guidelines based on the protocols given by ACOG, given that the best regimen for administering is unclear.

Preterm Labor - Rescue Cerclage

• Prophylactic cervical cerclage is typically performed when the cervix is closed.
• A rescue cerclage (emergency or physical exam-indicated cerclage is) used in women with cervical dilation and or prolapsed membranes.
• Its efficacy and safety remain controversial.
• Contraindications include:
  • Established preterm labor w/ impending preterm birth
  • Chorioamnionitis
  • Heavy Vagnial bleeding
  • Preterm PROM
  • Fetal demise
  • Major fetal anomalies
  • Fetal death
• Prolapsing membranes should be replaced when placing the cerclage, reducing the risk for iatrogenic PROM.
• Purse-string sutures are placed around the circumference of the cervix.
• Only one small randomized controlled trial has compared rescue cerclage and bed rest.
• Improved outcomes with cerclage:
  • Prolonged gestation by 4 weeks
  • Reduced NICU and neonatal rates of mortality

Preterm Labor - Cerclage Removal

• Cerclage removal does not routinely precipitate the labor process
• Recommend removal when virginal delivery is planned at week 36-37 of the gestation period
• It is important to defer removal in cases with a planned cesarean delivery period removal date to when labor has started, in cases where that occurs.
• If patients patient demonstrates cervical change, painful contractions, or vaginal bleeding then the procedure must be urgently performed .
• Current evidence suggest to not retain or remove the cerclage in cases with PROM unless the patient has received antibiotics

Preterm Labor - Cerclage Removal procedure

• Cerclage removal procedure is straightforward.
• With the patient in the dorsal lithotomy position, a speculum is inserted.
• rings grasp and suture is transected with scissors.
• If not during active labour, the procedure may be performed is an ofice setting
• Neuraxial anesthesia may be if stitch it too embedded for easier dissection and removal.

Preterm Labor - Tocolysis

• Once the obstetrician has decided to tocolytic therapy.
• beta-adrenergic receptor agonists
• calcium entry-blocking agents, magnesium sulfate, and nonsteroidal anti-inflammatory drugs.
• Magnesium sulfate is not efficacious and should not be used

Preterm Labor - Tocolysis contraindications

• For the following drug contraindications please consult the table below. |Drug| Contraindication|Maternal Side Effects| Fetal Side Effects| |----|----|---|---| |Calcium entry-blocking agents|Cardiac disease Renal disease Maternal hypotension|>Transient hypotension, >flushing, headache, dizziness, nausea|None identified.| |Cyclooxygenase inhibitotors
  (NSAIDs) |Significant renal/hepatic
  impairmentActive PUDCoagulation disorders Thrombocytopenia
  NSAID-sensitive AsthmaOther NSAID sensitivities| Nausea
  >Heartburn|Constriction of the ductus arteriosus
  Pulmonary hypertension

Reversible renal dysfunction Intraventricular hemorrhage Hyperbilirubinemia
Necrotizing enterocolitis|