Obstetrics-Preterm Birth

nianderthalNOTES

OBSTETRICS: Preterm Birth

PRETERM BIRTH: Definition of Terms

*with respect to size, a newborn may be appropriate, small or large for gestational age

Appropriate for gestational age -newborns whose birth weight is between 10th and the 90th percentile for

gestational age Small for gestational age -newborns whose birth weight is usually below the 10th percentile for

gestational age Large for gestational age -newborns whose birth weight is usually above the 90th percentile for

gestational age Low birth weight -neonates who are born too small weighing 500 to 2500 grams -Very Low birth weight: 500 to 1500 grams -Extremely Low birth weight: 500 to 1000 grams

PRETERM BIRTH: Definition of Terms

*with respect to gestational age, the newborn may be preterm, term or post-term.

Preterm or premature births

-neonates who are born too early before 37 completed weeks

-Late preterm births: delivery at 34 to 36 weeks of gestation

PRETERM BIRTH: Morbidity

-a variety of morbidities, largely due to system immaturity, are significantly increased in infants born before 37 weeks’ gestation compared with those delivered at term

-these infants also suffer long-term sequelae such as neurodevelopmental disability

PRETERM BIRTH: Threshold of Viability

-Births before 26 weeks, especially those weighing less than 750 grams are at the current threshold of variability

-It is considered appropriate not to initiate resuscitation for infants younger than 23 weeks or those whose birth weight is less than 400 grams

-Female gender, singleton pregnancy, corticosteroids given for lung maturation and higher gestational age improved the prognosis for infants born at the threshold of viability

PRETERM BIRTH: Threshold of Viability

-From an obstetrical standpoint, all fetal indications for cesarean delivery in more advaced pregnancies are practiced in women at 25 weeks

-Cesarean delivery is not offered for fetal indications at 23 weeks

-At 24 weeks, cesarean delivery is not offered unless the fetal weight is estimated at 750 grams or greater

PRETERM BIRTH: Late Preterm Birth

-Infants between 34 to 36 weeks account approximately 75% of all preterm births

-Approximately 80% of late preterm births were due to idiopathic spontaneous preterm labor or prematurely ruptured membranes while 20% of cases was due to complications such as hypertension or placental accidents

PRETERM BIRTH: Reasons for Preterm Delivery

There are four main direct reasons for preterm births in the US:

1. Delivery for maternal or fetal indications in which labor is induced or the infant is delivered by pre-labor cesarean delivery – 30-35%

2. Spontaneous unexplained preterm labor with intact membranes – 40-45%

3. Idiopathic preterm premature rupture of membranes – 30-35%

4. Twins and higher-order multifetal births


Maternal indications -Most common indications for medical intervention resulting in

preterm birth: 1. Preeclampsia 2. Fetal distress 3. Small for gestational age 4. Placental abruption -Less common causes: 1. Chronic hypertension 2. Placenta previa 3. Unexplained bleeding 4. Diabetes 5. Renal disease 6. Rh isoimmunization 7. Congenital malformations


Preterm Prematurely Ruptured Membranes (PPROM) -rupture of membranes before labor and prior to 37 weeks -Factors implicated: 1. Pathological mechanisms including intra-amniotic

infection 2. Low socioeconomic status 3. Low body mass index (BMI) – less than 19.8 4. Nutritional deficiencies 5. Cigarette smoking 6. Women with prior PPROM *HOWEVER, most cases of preterm rupture occur without risk

factors or are idiopathic


Spontaneous Preterm Labor -Most commonly, preterm birth, up to 45 % of cases – follows

spontaneous labor -Pathogenesis of Preterm labor are implicated on: 1. Progesterone withdrawal -as parturition nears, the fetal-adrenal axis becomes

more sensitive to adrenocorticotropic hormone, increasing the secretion of cortisol stimulation of 17-α-hydroxylase activity decrease progesterone secretion and increase estrogen production increased prostaglandin formation initiates a cascade that culminates in labor


-Pathogenesis of Preterm labor are implicated on: 2. Oxytocin initiation -because oxytocin increases the frequency and

intensity of uterine contractions, oxytocin is assumed to play a role in labor initiation

3. Decidual activation -seems to be mediated in part by fetal-decidual

paracrine system and through localized decrease in progesterone concentration

-decidual activation seems to arise in the context of intrauterine bleeding or occult intrauterine infection

PRETERM BIRTH: Contributing Factors to Preterm Birth

1. Threatened Abortion

-Vaginal bleeding in early pregnancy is associated with increased adverse outcomes later

-Both light and heavy bleeding were associated with subsequent preterm labor, placental abruption, and subsequent pregnancy loss prior to 24 weeks


2. Lifestyle Factors -Cigarette smoking, inadequate maternal weight gain, and

illicit drug use low-birth weight neonates -Overweight women had lower rates of preterm delivery

before 35 weeks than women with normal weight -Other maternal factors implicated include young or advanced

maternal age, poverty, short stature, vitamin C deficiency, and occupational factors such as prolonged walking or standing, strenuous working conditions, and long weekly work hours

-Psychological factors such as depression, anxiety, and chronic stress

-Women injured by physical abuse low birth weight and preterm birth


3. Racial and Ethnic Disparity

-Women classified as black, African-American, and Afro-Caribbean are consistently reported to be at higher risk

4. Work During Pregnancy

-Working long hours and hard physical labor are probably associated with increased risk


5. Genetic Factors

-Immunoregulatory genes may potentiate chorioamnionitis in cases of preterm delivery due to infection

6. Periodontal Disease

-Significantly associated with preterm birth—odds ratio 2.83 – but data not considered robust enough


7. Prior Preterm Birth

-A major risk factor for preterm labor is prior preterm delivery

-The risk of recurrent preterm delivery for women whose first delivery was preterm was increased threefold compared with that of women whose first neonate was born at term


8. Infection

-It is hypothesized that intrauterine infections trigger preterm labor by activation of the innate immune system.

-Microorganisms elicit release of inflammatory cytokines such as interleukins and tumor necrosis factor (TNF), stimulate the production of prostaglandin and/or matrix-degrading enzymes Prostaglandins stimulate uterine contractions, whereas degradation of extracellular matrix in the fetal membranes leads to preterm rupture of membranes.

-Intrauterine infection cause 25-40% of preterm births


8. Infection

-Potential routes of intrauterine infection:

a. Iatrogenic induction

b. Amnionic fluid infection

c. Choriodecidual infection

d. Salpingitis, Villitis or Funisitis

e. From either uterus, placenta, vagina or even the fetus


8. Infection -Two microorganisms, Ureaplasma urealyticum and

Mycoplasma hominis, have emerged as important perinatal pathogens

-Bacterial Vaginosis: condition where normal, hydrogen peroxide-producing, lactobacillus-predominant vaginal flora is replaced with anaerobes that include Gardnerella vaginalis, Mobiluncus species, and Mycoplasma hominis

- associated with spontaneous abortion, preterm labor, preterm rupture of membranes, chorioamnionitis, and amnionic fluid infection

- Causes: exposure to chronic stress, ethnic differences, and frequent or recent douching increased rates of the condition

PRETERM BIRTH: Diagnosis

Patient Symptoms Previously, The American Academy of Pediatrics and

the American College of Obstetricians and Gynecologists (1997) had earlier proposed the following criteria to document preterm labor:

-Contractions of four in 20 minutes or eight in 60 minutes plus progressive change in the cervix

-Cervical dilatation greater than 1 cm -Cervical effacement of 80 percent or greater. *Currently, however, such clinical findings are now

considered inaccurate predictors of preterm delivery


Patient Symptoms -In addition to painful or painless uterine contractions,

these symptoms are empirically associated with impending preterm birth:

-pelvic pressure -menstrual-like cramps -watery vaginal discharge -lower back pain *The signs and symptoms signaling preterm labor,

including uterine contractions may appear only within 24 hours of preterm labor


Cervical Changes Cervical Dilatation - Although women with dilatation and effacement in the third

trimester are at increased risk for preterm birth, detection does not improve pregnancy outcome

- Prenatal cervical examinations are neither beneficial nor harmful

Cervical Length - Mean cervical length at 24 weeks was approximately 35

mm - Women with progressively shorter cervices experienced

increased rates of preterm birth -Sonographic cervical length, funneling, and prior history of

preterm birth is correlated with delivery before 35 weeks.


Funneling

-bulging of the membranes into the endocervical canal and protruding at least 25 percent of the entire cervical length

Incompetent Cervix

Cervical incompetence

-a clinical diagnosis characterized by recurrent, painless cervical dilatation and spontaneous midtrimester birth in the absence of spontaneous membrane rupture, bleeding, or infection


Ambulatory Uterine Monitoring

-An external tocodynamometer belted around the abdomen and connected to an electronic waist recorder allows a woman to ambulate while uterine activity is recorded

-Women who used home monitoring had a significant increase in the number of unscheduled visits, and women with twins had increased use of tocolytic therapy


Fetal Fibronectin -Present in high concentrations in maternal blood and in

amnionic fluid -Play a role in intercellular adhesion during implantation and

in the maintenance of placental adhesion to uterine decidua

-Detected in cervicovaginal secretions in women who have normal pregnancies with intact membranes at term

-Reflect stromal remodeling of the cervix prior to labor -Measured using an enzyme-linked immunosorbent assay, and

values exceeding 50 ng/mL are considered positive *Positive even as early as 8 to 22 weeks, has been

found to be a powerful predictor of subsequent preterm birth

PRETERM BIRTH: Prevention

Progesterone Use -American College of Obstetricians and Gynecologists: progesterone

therapy should be limited to women with a documented history of a previous spontaneous birth at less than 37 weeks

Cervical Cerclage -Three circumstances when cerclage placement may be used to prevent

preterm birth: 1. History of recurrent midtrimester losses and who are diagnosed with

an incompetent cervix 2. Short cervix on sonographic examination 3.“Rescue" cerclage, done emergently when cervical incompetence is

recognized in the women with threatened preterm labor

PRETERM BIRTH: Management of Preterm Rupture of

Membranes and Preterm Labor American College of Obstetricians and

Gynecologists: Despite the numerous management methods proposed, the incidence of preterm birth has changed little over the past 40 years. Uncertainty persists about the best strategies for managing preterm labor


Membranes and Preterm Labor Diagnosis of Preterm Prematurely Ruptured Membranes

-A history of vaginal leakage of fluid, either as a continuous stream or as a gush should prompt a speculum examination to visualize gross vaginal pooling of amnionic fluid, clear fluid from cervical canal, or both.

-Confirmation of ruptured membranes is usually accompanied by sonographic examination to:

-Assess amnionic fluid volume

-Identify the presenting part

-Estimate gestational age


Membranes and Preterm Labor Diagnosis of Preterm Prematurely Ruptured

Membranes

*basis for frequently used pH testing for ruptured membranes

*blood, semen, antiseptics or bacterial vaginosis are also alkalinic and can give false-positive result

pH

AMNIONIC FLUID 7.1-7.3 (slightly alkalinic)

VAGINAL SECRETIONS 4.5-6.0 (acidic)


Membranes and Preterm Labor Natural History of Preterm Ruptured Membranes

-The time from preterm ruptured membranes to delivery is inversely proportional to the gestational age when rupture occurs


Membranes and Preterm Labor Expectant Management

-Tocolysis or expectant management did not improve perinatal outcomes

-Other considerations with expectant management involve the use of digital cervical examination and cerclage

-Risks of Expectant Management:

-No improved neonatal outcomes with expectant management beyond 33 weeks

-The volume of amnionic fluid remaining after rupture appears to have prognostic importance in pregnancies before 26 weeks


Membranes and Preterm Labor -Risks of Expectant Management: -Oligohydramnios - defined by the absence of fluid

pockets 2 cm or larger *all women with oligohydramnios delivered before

25 weeks, whereas 85 percent with adequate amnionic fluid volume were delivered in the third trimester

- Lung hypoplasia has a threshold of development of 23 weeks or less

- Limb compression deformities - Umbilical cord prolapse – increased rate in women with

preterm ruptured membranes and noncephalic presentation, especially before 26 weeks


Membranes and Preterm Labor Clinical Chorioamnionitis:

- prolonged membrane rupture is associated with increased fetal and maternal sepsis

- If diagnosed, prompt efforts to effect delivery, preferably vaginally, are initiated

- Fever is the only reliable indicator for this diagnosis

-Temperature of 38°C or higher accompanying ruptured membranes implies infection

-During expectant management, monitoring for sustained maternal or fetal tachycardia, for uterine tenderness, and for a malodorous vaginal discharge is warranted


Membranes and Preterm Labor Clinical Chorioamnionitis:

- Associated with higher incidence of:

- sepsis

-respiratory distress syndrome

-early-onset seizures

-intraventricular hemorrhage

-periventricular leukomalacia

-vulnerable to neurological injury


Membranes and Preterm Labor Antimicrobial Therapy

- Only three of 10 outcomes were possibly benefited:

1. Fewer women developed chorioamnionitis 2. Fewer newborns developed sepsis

3. Pregnancy was more often prolonged 7 days in women given antimicrobials

*Neonatal survival was unaffected, as was the incidence of necrotizing enterocolitis, respiratory distress, or intracranial hemorrhage

-Amoxicillin-clavulanate regimen was not recommended with an increased incidence of necrotizing enterocolitis


Membranes and Preterm Labor Corticosteroids

- The National Institutes of Health Consensus Development Conference (2000) recommended a single course of antenatal corticosteroids for women with preterm membrane rupture before 32 weeks and in whom there was no evidence of chorioamnionitis

- American College of Obstetricians and Gynecologists:

-Single-dose therapy from 24-32 weeks

-No consensus regarding treatment between 32 and 34 weeks.

-Not recommended prior to 24 weeks


Membranes and Preterm Labor Membrane Repair

-Tissue sealants have been used for a variety of purposes in medicine and have become important in maintaining surgical hemostasis and stimulating wound healing


Membranes and Preterm Labor Recommended Management

Gestational Age Management by the American College of Obstetricians and Gynecologists

34 weeks or more -Proceed to delivery, usually by induction of labor -Group B streptococcal prophylaxis is recommended

32 weeks to 33 completed weeks

-Expectant management unless fetal pulmonary maturity is documented -Group B streptococcal prophylaxis is recommended -Corticosteroids—no consensus, but some experts recommend -Antimicrobials to prolong latency if no contraindications

24 weeks to 31 completed weeks

-Expectant management -Group B streptococcal prophylaxis is recommended -Single-course corticosteroids use is recommended -Tocolytics—no consensus -Antimicrobials to prolong latency if no contraindications

Before 24 weeks -Patient counseling -Expectant management or induction of labor -Group B streptococcal prophylaxis is not recommended -Corticosteroids are not recommended -Antimicrobials—there are incomplete data on use in prolonging latency

PRETERM BIRTH: Preterm Labor with Intact Membranes

-Women with signs and symptoms of preterm labor with intact membranes are managed much the same as those with preterm ruptured membranes

-The cornerstone of treatment is to avoid delivery prior to 34 weeks, if possible


Amniocentesis to Detect Infection

-The American College of Obstetricians and Gynecologists (2003) has concluded that there is no evidence to support routine amniocentesis to identify infection.


Corticosteroid Therapy to Enhance Fetal Lung Maturation - Corticosteroid therapy was effective in lowering the incidence of

respiratory distress and neonatal mortality rates if birth was delayed for at least 24 hours after initiation of betamethasone

- Lower dose had less severe effects on somatic growth without affecting cell proliferation in the fetal brain

- American College of Obstetricians and Gynecologists: single-course therapy for Corticosteroids

- Rescue Therapy: refers to administration of a repeated corticosteroid dose when delivery becomes imminent and more than 7 days have elapsed since the initial dose

*should not be routinely used and reserved for clinical trials -DEXAMETHASON vs BETAMETHASONE: These two drugs were

comparable in reducing the rates of major neonatal morbidities in preterm infants


Antimicrobials

- Antimicrobial treatment of women with preterm labor for the sole purpose of preventing delivery is generally not recommended

- Fetal exposure to antimicrobials in this clinical setting was associated with an increased cerebral palsy rate at age 7 years compared with that of non-exposed infants


Emergency or Rescue Cerclage

- If cervical incompetence is recognized with threatened preterm labor, emergency cerclage can be attempted, albeit with an appreciable risk of infection and pregnancy loss

- Delivery delay was significantly greater in the cerclage group compared with that of bed rest alone—54 versus 24 days

- Nulliparity, membranes extending beyond the external cervical os, and cerclage prior to 22 weeks were associated with a significantly decreased chance of pregnancy continuation to 28 weeks or beyond


Inhibition of Preterm Labor

- The American College of Obstetricians and Gynecologists: Tocolytic agents do not markedly prolong gestation, but may delay delivery in some women for at least 48 hours.

*May facilitate transport to a regional obstetrical center and allow time for administration of corticosteroid therapy


Bed Rest

- One of the most often prescribed interventions during pregnancy, yet one of the least studied

- Bed rest in the hospital compared with bed rest at home had no effect on pregnancy duration in women with threatened preterm labor before 34 weeks

- Bed rest for 3 days or more increased thromboembolic complications

- Significant bone loss in pregnant women prescribed outpatient bed rest


β-Adrenergic Receptor Agonists

- A number of compounds react with β-adrenergic receptors to reduce intracellular ionized calcium levels and prevent activation of myometrial contractile proteins

- Ritodrine and terbutaline have been used in obstetrics

*only Ritodrine had been approved for preterm labor by the Food and Drug Administration


β-Adrenergic Receptor Agonists -Ritodrine: -neonates whose mothers were treated with ritodrine for threatened

preterm labor had lower rates of death and respiratory distress -may lead to Pulmonary edema -withdrawn by manufacturer in 2003 - Terbutaline - commonly used to forestall preterm labor - can cause pulmonary edema - terbutaline pumps cause sudden maternal death and a newborn with

myocardial necrosis after the mother used the pump for 12 weeks - oral terbutaline therapy to prevent preterm delivery has also not been

effective


Magnesium Sulfate

- Its role is presumably that of a calcium antagonist

- Intravenously administered magnesium sulfate—a 4-gram loading dose followed by a continuous infusion of 2 grams/hour—usually arrests labor

- Monitored closely for evidence of hypermagnesemia

- Parkland Hospital: "Time to Quit" on the use of magnesium sulfate for tocolysis on the basis that this therapy was ineffective and potentially harmful to infants


Magnesium Sulfate

- Neonatal effects:

- reduced incidence of cerebral palsy at 3 years

- minimize the inflammatory effects of infection

- Neuroprotection magnesium from 23 to 32 completed weeks

*A 6-gram loading dose is followed by an infusion of 2 gram per hour for at least 12 hours


Prostaglandin Inhibitors - Drugs that inhibit prostaglandins have been of

considerable interest because prostaglandins are intimately involved in contractions of normal labor

- Prostaglandin antagonists act by: -inhibiting prostaglandin synthesis -blocking prostaglandin action on target organs *A group of enzymes collectively termed prostaglandin

synthase is responsible for the conversion of free arachidonic acid to prostaglandins

-acetylsalicylate and indomethacin block this system


Prostaglandin Inhibitors -Indomethacin: -administered orally or rectally -50 to 100 mg dose is followed at 8-hour intervals

not to exceed a total 24-hour dose of 200 mg -Serum concentrations usually peak 1 to 2 hours

after oral administration,whereas levels after rectal administration peak slightly sooner.

-Limited usese to 24 to 48 hours because of concerns of oligohydramnios but is reversible with discontinuation of indomethacin.


Calcium Channel Blockers -Myometrial activity is directly related to cytoplasmic free

calcium, and a reduction in its concentration inhibits contractions

-Act to inhibit, by a variety of mechanisms, the entry of calcium through channels in the cell membrane

-Although nifedipine treatment reduced births of neonates weighing less than 2500 g, significantly more of these were admitted for intensive care

-Combination of nifedipine with magnesium for tocolysis is potentially dangerous since nifedipine enhances neuromuscular blocking effects of magnesium that can interfere with pulmonary and cardiac function


Atosiban -Nonapeptide oxytocin analog is a competitive antagonist of

oxytocin-induced contractions -Failed to improve relevant neonatal outcomes and was

linked with significant neonatal morbidity Nitric Oxide Donors -potent smooth-muscle relaxants affect the vasculature, gut,

and uterus -Nitroglycerin administered orally, transdermally, or

intravenously was not effective or showed no superiority to other tocolytics

-Maternal hypotension was a common side effect


Summary of Tocolytic Use for Preterm Labor

-Tocolytics stop contractions temporarily but rarely prevent preterm birth

-Although delivery may be delayed long enough for administration of corticosteroids, treatment does not result in improved perinatal outcome

-Tocolytic therapy can prolong gestation, but that β-agonists are not better than other drugs and pose potential maternal danger.

-There are no benefits of maintenance tocolytic therapy


Summary of Tocolytic Use for Preterm Labor

-As a general rule, if tocolytics are given, they should be given concomitantly with corticosteroids.

-The gestational age range for their use is debatable, but because corticosteroids are not generally used after 33 weeks and because the perinatal outcomes in preterm neonates are generally good after this time, most practitioners do not recommend use of tocolytics at or after 33 weeks

PRETERM BIRTH: Recommended Management of

Preterm Labor The following considerations should be given to women in preterm labor: 1. Confirmation of preterm labor 2.For pregnancies less than 34 weeks in women with no maternal or fetal

indications for delivery, close observation with monitoring of uterine contractions and fetal heart rate is appropriate. Serial examinations are done to assess cervical changes

3. For pregnancies less than 34 weeks, corticosteroids are given for

enhancement of fetal lung maturation 4. Consideration is given for maternal magnesium sulfate infusion for 12

to 24 hours to afford fetal neuroprotection

PRETERM BIRTH: Recommended Management of

Preterm Labor The following considerations should be given to women in preterm labor: 5. For pregnancies less than 34 weeks in women who are not in advanced

labor, some practitioners believe it is reasonable to attempt inhibition of contractions to delay delivery while the women are given corticosteroid therapy and group B streptococcal prophylaxis.

*Although tocolytic drugs are not used at Parkland Hospital, they are given at University of Alabama at Birmingham Hospital

6. For pregnancies at 34 weeks or beyond, women with preterm labor are

monitored for labor progression and fetal well-being 7. For active labor, an antimicrobial is given for prevention of neonatal

group B streptococcal infection

PRETERM BIRTH: Intrapartum Management

-In general, the more immature the fetus, the greater the risks of labor and delivery

-Labor: -Whether labor is induced or spontaneous, abnormalities of

fetal heart rate and uterine contractions should be sought -Continuous electronic monitoring -Fetal tachycardia, especially with ruptured membranes, is

suggestive of sepsis -Intrapartum acidemia (umbilical artery blood pH less than

7.0) may intensify some of the neonatal complications usually attributed to preterm delivery—more severe respiratory disease in preterm neonates

-Group B streptococcal infections are common and dangerous in the preterm neonate - prophylaxis should be provided


-Delivery: -In the absence of a relaxed vaginal outlet, an

episiotomy for delivery may be necessary once the fetal head reaches the perineum

-Perinatal outcome data do not support routine forceps delivery to protect the "fragile preterm fetal head"

-Staff proficient in resuscitative techniques commensurate with the gestational age and fully oriented to any specific problems should be present at delivery


-Prevention of Neonatal Intracranial Hemorrhage:

-Cesarean delivery did not lower the risk of mortality or intracranial hemorrhage

-Avoidance of active-phase labor is impossible in most preterm births because the route of delivery cannot be decided until the active phase of labor is firmly established

Health & Medicine

Obstetrics-Preterm Birth