The appropriate use of antenatal corticosteroids improves neonatal outcomes, including decreased severity and/or frequency of respiratory distress syndrome (RDS), intracranial hemorrhage, necrotizing enterocolitis and death. Antenatal corticosteroids, when appropriate, are administered in a clinical setting where patients are at risk for preterm delivery within 7 days, irrespective of membrane status and fetal number.
Clinical Actions:
Risk of preterm delivery within 7 days
Between 24w0d to 33w6d – ‘Recommended’
Single course of corticosteroids
Between 22w0d and 23w6d – ‘May be Considered’
23w0d to 23w6d
Single course of corticosteroids
22w0d to 22w6d
Single course of corticosteroids
Note: ACOG and SMFM revised recommendation states
Antenatal corticosteroids may be considered at 22 0/7 weeks to 22 6/7 weeks of gestation if neonatal resuscitation is planned and after appropriate counseling
Some families may choose to forgo resuscitation and support after appropriate counseling
Between 20w0d and 21w6d – ‘Not Recommended’
Antenatal corticosteroids are not recommended due to lack of data suggesting benefit
Late preterm (34w0d – 36w6d)
ACOG
If no previous corticosteroids
Single course of betamethasone
Not indicated in women diagnosed with clinical chorioamnionitis
SMFM
Single course of betamethasone in specific populations
Population included in ALPS trial: Recommended
Nonanomalous singleton gestation
High risk for preterm delivery (medically indicated or spontaneous)
No prior antenatal steroids
Select populations not in the original ALPS trial: Suggest consideration for use in the following clinical scenarios
Multiple gestations reduced to a singleton gestation ≥14w0d
Fetal anomalies
Expected to deliver in less than 12 hours
Low likelihood of delivery <37 weeks: Recommend against
Pregestational diabetes: Recommend against due to risk for worsening neonatal hypoglycemia
Repeat or Rescue Courses
Regularly scheduled repeat courses or serial (> 2) courses
Not recommended
If a patient has received one prior course of corticosteroids > 14 days ago, is less than 34w0d gestation and is at risk of preterm delivery within 7 days
a single repeat course of corticosteroids should be considered (change from previous ‘may’)
Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario (based on Cochrane meta-analysis)
Preterm prelabor rupture of membranes (PPROM)
There is insufficient evidence to make a recommendation for or against repeat or rescue courses
Dose and Regimen: give first dose even if 2nd dose unlikely
ACOG Guidance Update: Diagnosis and Management of PROM (Prelabor Rupture of Membranes)
SUMMARY:
ACOG guidance on Prelabor Rupture of Membranes (PROM) addresses current literature especially related to management of late preterm PROM (34w0d to 36w6d). Following appropriate counseling, expectant management or delivery is appropriate. The use of ‘prelabor’ is in keeping with reVITALize terminology (see ‘Related ObG Topics’ below) and is defined as the ‘spontaneous rupture of membranes that occurs before the onset of labor’.
IV ampicillin [2 g every 6 hours] and erythromycin [250 mg every 6 hours] for 48 hours followed by oral amoxicillin [250 mg every 8 hours] and erythromycin base [333 mg every 8 hours] for an additional 5 days (7 days total)
Azithromycin (e.g., 1 g single dose) “is a suitable alternative” to replace erythromycin if unavailable or poorly tolerated
Amoxicillin–clavulanic acid
Not recommended due to increased risk for necrotizing enterocolitis
Allergy to β-lactam antibiotics
“May be reasonable to consider another agent against GBS” | Choice based on severity of allergic reaction and susceptibility profiling
Unclear as to whether cerclage should be removed or retained but if retained, antibiotic therapy should not be extended beyond 7 days
Note: There are multiple regimens in use | There is no evidence to support a single optimal regimen for latency antibiotics
Patients with PROM before 32w0d and imminent delivery are candidates for fetal neuroprotective treatment with magnesium sulfate (if no contraindications)
Obtain vaginal/rectal swab for GBS | Administer GBS prophylaxis as indicated
HSV infection and Preterm PROM
Risk of vertical transmission is 30-50% with primary HSV and 3% with recurrent HSV
Recurrent active HSV
Expectant management is recommended <34w0d
Initiate HSV therapy
Corticosteroids | Antibiotics | Magnesium sulfate per indications
Cesarean section is indicated if active disease or prodromal symptoms are present at time of delivery
Primary HSV
Management less clear due to high risk of vertical transmission
HSV therapy is recommended
Cesarean delivery recommended if active lesions are present
HIV infection and Preterm PROM
Optimal management is uncertain due to concern of vertical transmission with PROM
Management should include a physician with expertise in the management of HIV in pregnancy and standard HIV guidelines should be followed
Most recent data suggest that vertical transmission risk my not be increased if the patient is on highly active antiretroviral therapy with a low viral load and has received antepartum and intrapartum zidovudine
Management should be individualized
If gestational age is early, but patient is on appropriate therapy with a low viral load expectant management may be appropriate
Late Preterm (34w0d to 36w6d)
“Either expectant management or immediate delivery is a reasonable option”
Data suggests when comparing these 2 options
No difference in neonatal sepsis
Newborn: Increased respiratory distress, mechanical ventilation, ICU stay in the immediate group
Maternal: Increased hemorrhage and infection in expectant management group
Administer single-course corticosteroids if
Not previously given
Delivery expected in >24 hours and ≤7 days
No chorioamnionitis
Screen for GBS and administer prophylaxis as indicated
Chorioamnionitis: Treat and plan for delivery
ACOG states (PB 831)
Care should be individualized through shred decision making, and expectant management should not extend beyond 37 0/7 weeks of gestation
Outside the scenario of unknown GBS status, latency antibiotics are not appropriate in this setting
Term (≥37w0d)
Induction is recommended vs expectant management | Short period of expectant management (12 to 24 hours) “may be appropriately offered”
If no spontaneous labor, induce labor with oxytocin
Allow adequate time (12-18 hours) for latent phase to progress before performing a cesarean section for failed induction of labor
Induction with prostaglandins equally as effective as oxytocin but may have higher rates of chorioamnionitis
Insufficient data to recommend for or against cervical ripening with mechanical methods such as a Foley balloon
Insufficient evidence to recommend antibiotic prophylaxis beyond GBS indications
If a patient declines delivery and requests expectant management, counsel regarding risks and benefits
If fetal and maternal status are reassuring, expectant management ‘may be acceptable’
Screen for GBS and administer prophylaxis as indicated
Chorioamnionitis: Treat and plan for delivery
Key Points:
PROM-Related Risks
Preterm birth
50% of patients will deliver within 1 week
Risks associate with prematurity include RDS, sepsis, IVH and NEC
Infection
Preterm PROM and intrauterine inflammation are associated with increased risk of neurologic injury
Intraamniotic infection (15-25%)
Postpartum infection (15-20%)
Abruption (2-5%)
Infection and umbilical cord accidents are associated with a 1 to 2% chance for fetal demise
Additional Clinical Considerations
Membranes may reseal spontaneously leading to good outcomes
Hospital admission is recommended if the fetus is viable to monitor for signs of infection, abruption and fetal compromise
Acceptable strategy includes periodic ultrasound for fetal growth and FH monitoring (precise timing not established)
No clinical utility evidence for the use of serial WBC counts or other infectious markers
Use of tocolysis
Tocolytic therapy is not recommended at 34w0d to 36w7d gestation
Can be considered for steroid benefit at earlier gestational age and during maternal transport
GBS as per standard protocol
GBS prophylaxis should be given based on prior culture results or intrapartum risk factors if cultures not performed or unavailable
PROM Following Amniocentesis
Risk of PROM following amniocentesis is 1%
Outpatient, expectant management
Monitor regularly with ultrasound and counsel patients to watch for signs of infection, bleeding and/or miscarriage
Contrary to spontaneous PROM, good outcomes have been reported
AF fluid reaccumulated within 1 month in 72% of patients
Perinatal survival rate was 91%
Preterm PROM and Future Pregnancies
Increased risk of recurrent PROM and preterm birth
Offer progesterone supplementation starting at 16-24 weeks
Can Azithromycin Be Used in Place of Erythromycin for Preterm PROM?
BACKGROUND AND PURPOSE:
Finneran et. al. (American Journal of Perinatology, 2017) assessed the impact of substituting a single dose of azithromycin in place of the standard erythromycin regimen used to prolong pregnancy in preterm PROM (PPROM)
METHODS:
Retrospective cohort study of 162 women with PPROM between 22 and 33 6/7 weeks
Subjects were categorized as:
Received standard antibiotic regimen (7 days of erythromycin and ampicillin/amoxicillin)
Received a single oral dose of azithromycin substituted for erythromycin in this regimen
Primary outcome
latency from PPROM to delivery defined as the time of first antibiotic administration to delivery
Secondary outcomes included
rates of cesarean delivery, intrauterine infection (chorioamnionitis or funisitis), Apgar scores, positive neonatal blood cultures, respiratory distress syndrome, necrotizing enterocolitis, and neonatal death
RESULTS:
Tocolytic therapy was more frequent in the azithromycin group compared with erythromycin group (33.3 vs. 16.7%, P = 0.01); otherwise, there were no differences in baseline characteristics
Tocolytic exposure was included in multivariate analysis
When comparing erythromycin to azithromycin
There was no difference median latency from PPROM to delivery (6.37 days vs 5.86 days, P = 0.67)
There was a higher rate of cesarean delivery (48.8 vs. 29.5%, P = 0.01)
There was an increased risk of neonatal sepsis (4.1 vs. 13.6%, P = 0.05)
Based on pathogens, unlikely to be related to antibiotic exposure
CONCLUSION:
There was no difference in latency when azithromycin was substituted for erythromycin
Ease of single dose regimen and cost effectiveness may make azithromycin a good alternative to erythromycin in PPROM
This study by Lorthe et al. (AJOG, 2017) explores if tocolytic therapy following preterm PROM (PPROM) is associated with improved neonatal or obstetric outcomes.
METHODS:
Multi-center, prospective, population-based cohort study
RESULTS:
803 women with PPROM at 24-32 weeks’ gestation and singleton pregnancies were included in the study. 73.45% patients received tocolysis. There was no difference in neonatal survival without severe morbidity between women who received tocolysis and those who did not (86.7% vs. 83.9% respectively). When adjusting for confounders, primarily bias due to indication for treatment, tocolysis was not associated with increase survival without severe morbidity (odds ratio, 1.01 [95% CI 0.94-1.09]), latency of ≥48 hours to delivery (1.03 [95% CI 0.95-1.11]), or histological chorioamnionitis (1.03 [95% CI 0.92-1.17]). The choice of tocolytic medication (oxytocin receptor antagonists or calcium-channel blockers) had no impact on outcomes. The authors conclude that at present, there does not appear to be any clinical benefit for the use of tocolytic drugs in the setting of PPROM.
What is the Best Course of Action Following PPROM Between 24 and 37 Weeks?
PURPOSE:
This study by Bond et al. (Cochrane Database Systematic Review, 2017) compared planned early birth vs. expectant management following preterm pre-labor rupture of the membranes (PPROM) between 24 and 37 weeks gestation.
METHODS:
Systematic Review and meta-analysis
RESULTS:
This update of a 2010 Cochrane review included 12 randomized controlled trials, with analyses on a total of 3,617 women and 3,628 infants.
Primary outcomes:
There was no significant difference in rates of neonatal sepsis or proven neonatal infection
Early birth was associated with
Increased rate of RDS (Relative Risk 1.26, 95% CI 1.05 to 1.53)
Increased rate of c-section (Relative Risk 1.26, 95% CI 1.11 to 1.44)
Secondary outcomes:
There was no significant difference in rates of overall perinatal mortality or intrauterine deaths between the two groups
Early birth was associated with the following maternal outcomes
Decreased rate of chorioamnionitis (Relative Risk 0.50, 95% CI 0.26 to 0.95)
Decreased hospital stay with a mean difference of -1.75 days (95% CI -2.45 to -1.05)
Increased rate of endometritis (Relative Risk 1.61, 95% CI 1.00 to 2.59)
Early birth was associated with the following neonatal outcomes
Higher rates of neonatal death (Relative Risk 1.26, 95% CI 1.11 to 1.44)
Higher rates of ventilation (Relative Risk 1.27, 95% CI 1.02 to 1.58)
Delivery at lower gestational ages with a mean difference of -0.48 weeks (95% CI -0.57 to -0.39)
Higher rates of NICU admission (Relative Risk 1.16, 95% CI 1.08 to 1.24)
Subgroup analyses:
Improved maternal and infant outcomes in expectant management greater than 34 weeks gestation for RDS and maternal infections
Antibiotics reduce maternal infections in the expectant management group
Authors’ conclusions:
If there are no contraindications, overall the expectant management group with careful monitoring had better outcomes for mother and baby
Further research needed for subgroup analysis as to who would not benefit from expectant management
Long term neurodevelopment was not addressed in this study
Vasa previa is defined as fetal vessels that run through the fetal membranes, over or near the endocervical os (2 cm or less) and are unprotected by placenta or umbilical cord.
CLINICAL ACTIONS:
Deliver by cesarean section before the onset of labor and before rupture of membranes
Scheduled delivery 34w0d to 37w0d
Deliver by cesarean section in the case of PPROM and viability
Antenatal corticosteroids 28 to 32 weeks gestation
SMFM guidance states to consider hospitalization at 30 to 34 weeks
Benefit is unproven and there have been good outcomes reported with outpatient management
When considering hospitalization, individualize based on the following
Symptoms
History of preterm birth
Logistics in getting to hospital with transfusion capabilities
Patients with normal cervical lengths are the best candidates for possible outpatient management
Repeat ultrasound in the third trimester is suggested if vasa previa is suspected in the second trimester, as approximately 20% of apparent vasa previa will resolve by the late third trimester
SYNOPSIS:
Vasa previa occurs in 1/2500 to 1/5000 pregnancies and is associated with an increased risk of preterm birth and the associated complications of prematurity. There is a 97% survival rate when diagnosed by prenatal ultrasound and a 44% survival rate when the diagnosis is made intrapartum.
KEY POINTS:
Risk factors:
Velamentous cord insertion (Type 1 vasa previa)
Succinturate or bilobed placenta connecting vessels (Type 2 vasa previa)
Placenta previa or low lying placenta in the second trimester
Multiple gestation
IVF (1/250 risk of Type 1 vasa previa)
In cases of low lying placenta, bilobed placenta, succinturate placenta or velamentous cord insertion, a targeted ultrasound for vasa previa should be performed
Screening possible at 2nd trimester fetal anatomy ultrasound
If detected on 2nd trimester ultrasound, 20% will resolve
Document cord insertion site if possible
Diagnosis is made by ultrasound, ideally with transvaginal and color flow Doppler
Ultrasound findings include a linear tubular echolucent body overlying the endocervical os with color flow doppler demonstrating flow through the structure and pulsed doppler showing fetal vascular wave forms
Risk of perinatal loss due to fetal exsanguination – watch for sinusoidal pattern on FHT tracing
Plan for delivery at a center that can perform neonatal transfusion if required
Note: Center should have negative blood available for neonate in case rapid transfusion is necessary
Chlamydia: CDC Recommendations for Diagnosis and Treatment
CLINICAL ACTIONS:
Annual screening of all sexually active women aged <25 years for chlamydia is recommended, as is screening of older women at increased risk for infection (e.g., those who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STD).
To diagnose a chlamydia infection:
Obtain nucleic acid amplification testing (NAAT), which detects genetic material of C. trachomatis
Highly sensitive in first-catch urine samples and endocervical or vaginal swabs
Can be collected by a provider or a self-collected vaginal swab
Certain NAATs have been FDA-cleared for use on liquid-based cytology specimens (collected for Pap smears), however sensitivity may be lower than swabs
SYNOPSIS:
Chlamydial infection is the most frequently reported infectious disease in the United States, and prevalence is highest in persons aged ≤24 years. Several sequelae can result from C. trachomatis infection in women, the most serious of which include PID (pelvic inflammatory disease), ectopic pregnancy, and infertility. Some women who receive a diagnosis of uncomplicated cervical infection already have subclinical upper-reproductive–tract infection.
KEY POINTS:
Chlamydia treatment should be provided promptly for all persons testing positive for infection; treatment delays have been associated with complications
Recommended Regimens
Azithromycin 1 g orally in a single dose or
Doxycycline 100 mg orally twice a day for 7 days
Alternative Regimens
Erythromycin base 500 mg orally four times a day for 7 days or
Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days or
Levofloxacin 500 mg orally once daily for 7 days or
Ofloxacin 300 mg orally twice a day for 7 days
Routine pharyngeal screening for chlamydia is not recommended, but if C. trachomatis is detected in an oropharyngeal specimen treat with azithromycin or doxycycline
Directly observe patient receiving therapy when single dose therapy is given
To minimize disease transmission to sex partners, persons treated for chlamydia should be instructed to abstain from sexual intercourse for 7 days after single-dose therapy or until completion of a 7-day regimen and resolution of symptoms if present
To minimize risk for reinfection, patients also should be instructed to abstain from sexual intercourse until all of their sex partners are treated
Persons who receive a diagnosis of chlamydia should be tested for HIV, gonococcal infection, and syphilis
Test-of-cure to detect therapeutic failure is not advised unless therapeutic adherence is in question, symptoms persist, or reinfection is suspected
Chlamydial NAATs at <3 weeks after completion of therapy is not recommended because the continued presence of nonviable organisms can lead to false-positive results
Retest after 3 months
Recurrence may not be treatment failure but rather reinfection
In States where legally allowed (see ‘Related OBG Topics’ below), consider Expedited Partner Therapy (EPT) which allows the patient herself to provide medications to her partner when there are limited public health services to treat a partner, or concern that the partner will not have access to treatment
Treat women with HIV with the same recommended regimen
PREGNANCY AND CHLAMYDIAL INFECTION
Risks in pregnancy include preterm labor, premature rupture of membranes and low birth weight with neonates at risk for conjunctivitis (ophthalmia neonatorum) and pneumonia. It is therefore imperative to screen and treat pregnant women with the following:
Recommended Regimens
Azithromycin 1 g orally in a single dose
Alternative Regimens
Amoxicillin 500 mg orally three times a day for 7 days or
Erythromycin base 500 mg orally four times a day for 7 days or
Erythromycin base 250 mg orally four times a day for 14 days or
Erythromycin ethylsuccinate 800 mg orally four times a day for 7 days or
Erythromycin ethylsuccinate 400 mg orally four times a day for 14 days
Test-of-cure (preferably by NAAT) recommended at 3 to 4 weeks after completion of therapy and again after 3 months
Diagnosis code: Chlamydia: A74.9 (pregnant) or A56.02 (nonpregnant)
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