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Preterm Birth & Labour what"s importnat.ppt
1. Preterm Labor and Birth
UNM Family Medicine Resident School
11/7/2018
Kira Paisley
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2. Learning Objectives
• Understand key Epidemiology
• Answer the question “Why do we care?”
• Identify who is at RISK for preterm delivery
• Identify evidence based PREVENTION strategies
• Confidently DIAGNOSE and MANAGE initial presentation of
Preterm Labor and PPROM
3. Outpatient
Management
Identify risks
Progesterone
Cervical length
screening
Cerclage
Diagnosis
Etiology
Prognosis: FFN,
Cervical length
Antenatal
Corticosteroids
Magnesium
Antibiotics
Tocolytics
PPROM
Neonatal care
Maternal care
OB Triage
Management
In-Patient
Management
Post Partum
Care
4. Definitions
• PRETERM LABOR: Contractions causing cervical change (dilation or
effacement) prior to 37.0 weeks
• Very early preterm – prior to 32 weeks
• Early preterm – 32 0/7 to 33 6/7 weeks
• Late preterm – 34 0/7 to 36 6/7 weeks
• PPROM – preterm premature (or pre-labor) rupture of membranes
• Premature Onset of Contractions – “POOC”, contractions without
cervical change
5. What causes Preterm Labor/Birth?
• ~50% of cases are spontaneous labor without rupture of
membranes
• ~25% are PPROM
• ~25 % are iatrogenic/indicated
Spontaneous Labor at preterm thought to be result of
infection or inflammation
Cytokines!
6. Epidemiology
• Preterm births decreased from 2007 -> 2014
• ACOG guidelines on prevention (ie: progesterone)
• Decrease in teen pregnancy
• Stricter guidelines on assisted reproductive technology (ie: fewer
multiples)
• Decline in medically non-indicated inductions prior to 39 weeks
• Preterm births are increasing from 2014 -> 2017
• Late preterm births are culprit
7.
8. Martin JA, Osterman MJK. Describing the increase in preterm births in the United States, 2014–2016. NCHS Data Brief, no 312. Hyattsville, MD: National Center for Health Statistics. 2018.
9. Source: Preterm birth rates are from the National Center for Health Statistics, 2017
final natality data. Grades assigned by March of Dimes Perinatal Data Center
10. Source: Preterm birth rates are from the National Center for Health Statistics, 2017 final natality data. Grades assigned by March of Dimes Perinatal Data Center
11. Source: Preterm birth rates are from the National Center for Health Statistics, 2017 final natality data. Grades assigned by March of Dimes Perinatal Data Center
12. Neonatal Outcomes – Why do we care?
Leading cause of infant mortality in the US
• Morbidity
• Respiratory disease: RDS, bronchopulmonary dysplasia
• Cognitive: Cerebral palsy, intraventricular hemorrhage, developmental delay
• GI: necrotizing enterocolitis
• Risk of preterm delivery when an adult!
Scott D. Grosse, Norman J. Waitzman, Ninee Yang, Karon Abe, Wanda D. Barfield. Employer-Sponsored Plan Expenditures for Infants Born Preterm. Pediatrics, 2017; e20171078 DOI: 10.1542/peds.2017-1078
Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes; Behrman RE, Butler AS, editors. Preterm Birth: Causes, Consequences, and Prevention. Washington (DC): National
Academies Press (US); 2007. 10, Mortality and Acute Complications in Preterm Infants.Available from: https://www.ncbi.nlm.nih.gov/books/NBK11385/
Cost: A new study estimates employer-sponsored health plans spent at least $6
billion extra on infants born prematurely in 2013
13. Shapiro-Mendoza CK, Barfield WD, Henderson Z, et al. CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth. MMWR Morb Mortal Wkly Rep 2016;65:826–830.
DOI: http://dx.doi.org/10.15585/mmwr.mm6532a4
14. Outpatient
Management
Identify risks
Progesterone
Cervical length
screening
Cerclage
Diagnosis
Etiology
Prognosis: FFN,
Cervical length
Antenatal
Corticosteroids
Magnesium
Antibiotics
Tocolytics
PPROM
Neonatal care
Birth control
plan
OB Triage
Management
In-Patient
Management
Post Partum
Care
16. RISK factors for Preterm Delivery
Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372.
17. Ways to intervene?
• Tobacco Cessation programs can help
• Treatment of Asymptomatic bacteruria is successful
• Screening and treatment for BV controversial
• USPSTF says insufficient evidence
• If symptomatic, should treat
• Educate women on short interval pregnancy
• Preconception control of chronic disease
18. Progesterone
• Contributes to pregnancy in multiple ways:
• Functional withdrawal of progesterone
occurs around onset of labor
• Prevents apoptosis in fetal membrane explants under
pro-inflammatory conditions ?alteration of immune response
2013 – Data became overwhelming that Progesterone prevents Preterm Birth
19. Progesterone
• 2013 Meta-analysis with 39 randomized trials; treatment with
progesterone showed LOWER RISK for:
• Birth < 34 weeks, RR 0.31
• Birth < 37 weeks, RR 0.55
• Neonatal death, RR 0.45
• Use of assisted ventilation in neonate, RR 0.40
• Necrotizing enterocolitis in neonate, RR 0.30
• NICU admission, RR 0.24
20. Progesterone – Recommended!
For PREVENTION of Preterm Birth
Singleton pregnancy with prior preterm birth (<37 weeks) IM progesterone
recommended
17 Alpha-Hydroxyprogesterone Caproate) 250mg IM weekly
Requires a prior auth, so work with your RN
Home or in-clinic injections, can get through home health
Initiate between 16-24 weeks, until 36 weeks
Missed doses may increase risk of Preterm Birth – pts should be counseled prior to
starting
21. Cervical Length screening
• Risk of PTB is inversely
proportional to cervical length
Birth <35 weeks for:
• 30% in women with CL 20–24 mm
• 50% with CL 10–19 mm
• 90% with CL <10 mm
• Birth <35 weeks only 16% in women with
CL > 25 mm
Figure 3. Estimated Probability of
Spontaneous Preterm Delivery before 35
Weeks of Gestation from the Logistic-
Regression Analysis (Dashed Line) and
Observed Frequency of Spontaneous
Preterm Delivery (Solid Line) According to
Cervical Length Measured by Transvaginal
Ultrasonography at 24 Weeks.
Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development maternal
fetal medicine unit network. N Engl J Med. 1996;334:567–72.
Iams J. Identification of candidates for progesterone. Obstet Gynecol 2014;123:1317-1326
22. Cervical Length screening
• Society of Maternal-Fetal Medicine, ACOG recommendations
“Routine transvaginal cervical length screening for women with singleton
pregnancy and history of prior spontaneous preterm birth” Grade 1A
Routine screening = trans-vaginal, 16-22 weeks (q1-2 weeks)
Do NOT screen if:
- Cerclage in place - multiple gestations
- PPROM - Placenta previa
Society of Maternal Fetall Medicine, McIntosh, J., Feltovich, H, Berghella, V., Manuck, T. “SMFM Consult Series #40: The role of routine cervical length screening in selected high and low-risk women for
preterm birth prevention.” AJOG. 9/2016.
23. What about Vaginal Progesterone?
• Does NOT reduce risk of PTB in women with hx of PTB in absence of
short cervix
• OPPTIMUM and PROGRESS trial
Women with hx of PTB AND Cervical length <25mm
• 2018 Systemic review
• Reduced risk of PTB, Neonatal morbidity and mortality in singleton gestations
with CL <25mm
Romero, R. Conde-Agudelo, A. Da Fonseca, E. O’Brien, JM, Cetingoz, E. Creasy, GW. Hassan, SS. Nicolaides, KH. “Vaginal Progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short
cervix: a meta-analysis of individual patient data.” Am J Obstet Gynecol. 2018;218(2):161.
24. Cerclage placement
Who qualifies?
Women with CL <25mm before 24wks
AND
History of preterm birth <34 weeks
Work with OB colleague
American College of Obstetricians and Gynecologists ACOG practice bulletin no.142: cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014;123:372–379.
27. Outpatient
Management
Identify risks
Progesterone
Cervical length
screening
Cerclage
Diagnosis
Etiology
Prognosis: FFN,
Cervical length
Antenatal
Corticosteroids
Magnesium
Antibiotics
Tocolytics
PPROM
Neonatal care
Birth control
plan
OB Triage
Management
In-Patient
Management
Post Partum
Care
28. OB Triage Management
It’s your first shift as a 2nd year Night Float on MCH. You’re senior is
delivering their continuity in another room.
You get a page from triage:
“36 yo G1 at 34 wks contracting, she looks uncomfortable…”
29. Don’t panic
Assess the patient as soon as you can
Involve your Attending/Senior Resident early
Consider the following 5 key questions…
OB Triage Management
30. Other key thing:
- Scan to be sure VERTEX
QUESTION ASSESSMENT
1. Is she less than 37 weeks Confirm dating
2. Is she ruptured? SSE for pooling, nitrizine +, ferning, LVP
3. Is she in labor? SVE (if not ruptured!), monitor
contractions, eval for cervical change
4. Is there an infection? GBS culture, STD amp, wet mount/Vag
path, UA, UCx
5. What’s the likelihood she’ll delivery
preterm?
FFN, Cervical Length
Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372.
31. What is the likelihood she’ll delivery preterm?
• Fetal Fibronectin
- Negative predictive value 99% for delivery within 14 days
- Positive predictive value 13-30% for delivery in 7-10 days
- Can only be done if NOTHING in vagina in past 24hrs
- False positives with amniotic fluid, blood, vaginal infection
- Collect FIRST on your speculum exam
OB Triage Management
32. What is the likelihood she’ll deliver preterm?
Cervical Length can help stratify risk
- involve OB for imaging
- more reliable with FFN than either
alone
- Reassuring if >3cm
(1% delivery in 7 days in one study)
OB Triage Management
33. 36 yo G1 at 34 wks contracting, she looks uncomfortable…
You confirm her dating, she’s 34w1d
SSE, negative for SROM
FFN collected and sent
UA shows +nitrites, +LE, ketones
Toco shows contractions q3-5 min,
reactive NST
11:55PM -- SVE 1cm/50%/-2
QUESTIONS
1. Is she less than 37 weeks?
2. Is she ruptured?
3. Is she in labor?
4. Is there an infection?
5. What’s the likelihood she’ll
delivery preterm?
OB Triage Management
34. You give her 1L bolus of fluids
FFN comes back Negative
0230 AM: SSE 1/50%/-2
Her contractions are now q10 min, mild
Now what?
Send her home, treat for UTI
Premature onset of Contractions
without cervical change, “POOC”
- only 18% delivery before 37 wks
- only 3% delivery within 2 weeks
of triage visit
ACOG Practice Bulletin 171, October 2016. Management of Preterm Labor
OB Triage Management
35. Outpatient
Management
Identify risks
Progesterone
Cervical length
screening
Cerclage
Diagnosis
Etiology
Prognosis: FFN,
Cervical length
Antenatal
Corticosteroids
Magnesium
Antibiotics
Tocolytics
PPROM
Neonatal care
Birth control
plan
OB Triage
Management
In-Patient
Management
Post Partum
Care
36. In-Patient Management
It’s your second shift as a 2nd year Night Float on MCH. You’ve sent your
senior to go nap because you’re feeling confident.
Page from triage:
22 yo G5 P1304 at 31 weeks is presenting with painful contractions…
37. • You don’t panic
• You alert your attending
• You go see the patient
• Evaluation:
• SSE neg pooling, no ferning, neg nitrizine; cervix looks slightly open
• GBS, FFN, STD Amp collected; UDS, Ucx and UA sent, UDATR sent
• Toco with q2-3 min contraction, reactive NST
• Vertex on US
In-Patient Management
38. • SVE (backed up by Attending)
3cm/50%/-2 at 0100
• You order IV fluids
• Her FFN comes back POSITIVE
• OB helps you do a cervical length and it’s 1.5cm
• Her UDATR comes back + for methamphetamines
1 hour later…
SVE – 3 cm/80%/-1 Admit to L&D for
Preterm Labor!
QUESTIONS
1. Is she less than 37 weeks
2. Is she ruptured?
3. Is she in labor?
4. Is there an infection?
5. What’s the likelihood she’ll
delivery preterm?
In-Patient Management
39. QUESTIONS TO CONSIDER
1. Does she need steroids?
2. Does she need IV Magnesium?
3. Does she need PCN?
4. Does she need tocolycis?
5. Does she need antibiotics for PPROM?
In-Patient Management
40. • 30% of preterm labor resolves spontaneously
• 50% of women admitted for PTL actually birth at term
Interventions must benefit the baby
- must be viable
- prolonging pregnancy is better than immediate delivery
In-Patient Management
41. Antenatal Corticosteroids
• Improves neonatal outcomes
• Decreases:
• Mortality
• Incidence and severity of RDS
• Intraventricular hemorrhage
• Necrotizing enterocolitis
• Single course 24.0-33.6 wks at risk of delivery within 7 days
• Betamethasone 12mg IM q24hrs x 2 doses
• Dexamethasone 6mg IM q12 hr x 4 doses
Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database
of Systematic Reviews 2017, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub3.
42. Rescue dose Steroids
• Studies have shown reduction in
Respiratory Distress Syndrome
ACOG recommends:
- Single repeat course of corticosteroids
- < 34 0/7 weeks
- At risk of delivery within 7 days
- Prior antenatal corticosteroid course was >14 days ago
In PPROM, rescue dose steroids is controversial
Garite TJ, Kurtzman J, Maurel K, Clark R. Impact of a ‘rescue course’ of antenatal corticosteroids: a multi-center randomized placebo-controlled trial. Obstetrix
Collaborative Research Network [published erratum appears in Am J Obstet Gynecol 2009;201:428]. Am J Obstet Gynecol 2009;200:248.e1–9. (Level I)
43. Late Preterm Steroids
• MFMU Network Antenatal Late Preterm Steroids trial
• Double-blind, placebo controlled RCT
• Excluded – multiple gestations, Pre-gestational diabetes,
previous steroids, chorio
• Tocolysis was not used
Primary outcome: decreased need for respiratory support
However – increased hypoglycemia in neonate
ACOG Committee Opinion from 2017 recommends
- Single course of Betamethasone for women 34 0/7 – 36 6/7 at risk
of preterm birth within 7 days
Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal betamethasone for women at risk for late preterm delivery. NICHD Maternal-Fetal Medicine Units Network. N Engl J
Med 2016;374:1311–20.
ACOG Committee Opinion, Number 713. August 2017. Antenatal Corticosteroid Therapy for Fetal Maturation.
44. Magnesium
Cochrane Review
Neuroprotection for delivery < 32 weeks
Outcomes - Reduction in cerebral palsy, RR 0.68
• No evidence for any specific regimen
• UNM 4g loading dose, then 1 g/hr infusion
• No evidence that IV Mg prolongs pregnancy
Shepherd E, Salam RA, Middleton P, Makrides M, McIntyre S, Badawi N, Crowther CA. Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic
reviews. Cochrane Database of Systematic Reviews 2017, Issue 8. Art. No.: CD012077. DOI: 10.1002/14651858.CD012077.pub2.
Costantine MM et al. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants. NICHD MFM Units Network Obstet Gynecol 2009;114:354-364.
Magnesium sulfate before anticipated preterm birth for neuroprotection. ACOG Committee Opinon 455. ACOG and SMFM.
45. Tocolytics
• Used to allow time to give steroids and magnesium, arrange transport
if needed
Contraindications
• Pre-viability
• IUFD
• Lethal anomaly
• Non reassuring fetal status
• Chorioamnionitis
• Pre-eclampsia with severe
features, eclampsia
• Hemodynamic instability of
mother
• PPROM
• Maternal contraindications
46. Tocolytics
• Reduces birth within 48hrs, but does not improve neonatal
outcomes
• No evidence of maintenance therapy outside 48-72 hr window
while inpatient and many risks
• Magnesium should not be used as a tocolytic
• When using for neuroprotection, be aware of interactions with
tocolytics
47. Tocolytics
Medication Dosage Maternal side
effects
Fetal or newborn
adverse effects
Contraindications
Nifedipine
(Calcium channel
blocker)
30mg -> 10-20mg
every 4-6 hours
Hypotension,
dizziness, increased
LFTs
None known Hypotension, pre-load
dependent cardiac
lesions
Indomethacin
(Prostoglandin
inhibiter, NSAID)
50-100mg loading
dose
25-50mg orraly q4-
6hrs
Not recommended
>48hrs
Nausea, GERD, emesis Constriction of ductus
arteriosus, oligo, NEC
in preterm infants
Platelet dysfunction,
Renal dysfunction,
hepatic dysfunction,
Asthma, PUD
Terbutaline
(Beta-adrenergic
receptor agonist)
0.25 subQ every 20-30
min
Alternative IV infusion
dose
Tachycardia,
hypotension, SOB,
Pulm edema, hypoK
and hyperglycemia
Fetal tachycardia Poorly controlled
diabetes
Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372.
48. Antibiotics
• Despite bacterial infections presumed cause for majority of preterm
births >32 weeks…
• There is no evidence antibiotic therapy prolongs pregnancy or reduces
neonatal morbidity or mortality
• And there may be some evidence of harm
King et al. Prophylactic antibiotics for inhibiting preterm labor with intact membranes. Cochrane Database 2002, Issue 4.
49. Antibiotics
• Meant for prevention of GBS sepsis in newborn only
• CDC Recommendations
• Penicillin G: 5 million units IV, then 2/5 million units IV q 4 hours until delivery
• “Adequate” treatment is >4hrs/2 doses
• Low risk PCN allergy: Cefazolin 2g IV, then 1gIV q 8 hours until delivery
• High risk PCN allergy, GBS susceptibilities known: Clindamycin 900mg IV q 8 hours until
delivery
• High risk PCN allergy, GBS susceptibilities unknown: Vancomycin 1g IV q 12 hours until
delivery
50. • 22 yo G5 P1304 at 31.0 wks
• Admitted for cervical change from 3/50/-2 3/80/-1
• Pregnancy has been otherwise complicated by amphetamine use, hx of UTI in
early pregnancy without confirmed TOC; no allergies to medications
• What interventions are indicated?
• Steroids!
• IV Mg for neuroprotection
• PCN for GBS prophylaxis
• Consider tocolysis to get her through steroid window
• NICU consult
In-Patient Management
51. • Your excellent Sub-I finds a scanned report of a 1st trimester US that
shows she’s actually 33w4d.
• Does this change your plans?
• Does not need IV Magnesium
In-Patient Management
52. Meanwhile in triage…
A 38 yo G4P2012 at 29w3d by 8wk US arrives due to a cat bite. While in
triage, the RN hears a “oh F***!” and runs into the room.
The patient is standing over a puddle of clear fluid.
They page you STAT…
In-Patient Management
53. • What do you do?
• SSE -- +pooling/nitrizine/+ferning
• You collect GBS, STD Amp swab, UA, UDATR
• FFN NOT INDICATED
• Cervix appears closed
• LVP 1.5cm, vertex
• Fetal heart tracing without decels, mod variability
In-Patient Management
Admit to L&D for
Preterm Labor!
54. PPROM Management
• Preterm Pre-labor (Premature) Rupture of Membranes
• Cause of ~25% of Preterm births
• At least 50% of patients with PPROM birth within 1 week
How does management differ?
ACOG Practice Bulletin. Prelabor Rutpure of Membranes. Number 188, January 2018.
55. PPROM Management
• Avoid SVE due to increased risk of infection
• Confirm vertex and collect GBS swab (culture)
• Management depends on gestational age
• Late Preterm (34 0/7 – 36 6/7) -> Proceed to delivery, GBS prophylaxis as
indicated
• Preterm (24 0/7 – 33 6/7) -> EXPECTANT management
• Evaluate for infection, abruption, fetal distress or labor
56. PPROM Management
• EXPECTANT Management 24 0/7 – 33 6/7 weeks
• Latency Antibiotics
• Single-course corticosteroids
• GBS prophylaxis as indicated
• Magnesium IV for neuroprotection if <32 0/7 weeks
Latency antibiotics
Ampicillin 2g IV q6hr and azithromycin 500mg IV q24 hrs x 48 hrs
Then amoxicillin 250mg PO q8 hrs and erythromycin 333mg PO q 8 hrs x 5
days
57. • The 33.4wk who you admitted earlier is suddenly feeling a lot of
pressure…
• SVE is 9.5cm/100%/+1
• Fetal tracing still ok
Now what?!!
In-Patient Management
58. Delivery Management of Preterm Birth
• At UNM, < 36 weeks delivery in OR (for NICU team access)
• No vacuums <34 weeks
• Delayed cord clamping! 1-2 minutes
• Less need for transfusion
• Less hypotension
• Less anemia
• Less IVH
• Milking cord is an option if NICU intervention critical
Timing of Umbilical Cord Clamping. ACOG Practice Bulletin 543, December 2012.
59. Outpatient
Management
Identify risks
Progesterone
Cervical length
screening
Cerclage
Diagnosis
Etiology
Prognosis: FFN,
Cervical length
Antenatal
Corticosteroids
Magnesium
Antibiotics
Tocolytics
PPROM
Neonatal care
Birth control
plan
OB Triage
Management
In-Patient
Management
Post Partum
Care
60. Post Partum Care
• Neonatal care
• < 36 weeks admit to ICN3 vs NICU
• >36 weeks to MBU
• Preterm infants (even late preterm) struggle with:
• Temperature regulation
• Hypoglycemia
• Breast feeding (coordination of suckling, energy)
• Hyperbilirubinemia (remember, will moderate risk on bili tool!)
• Consider early Lactation involvement, breast pump at bedside,
supplementation earlier
61. Post Partum Care
• Education of family and mother regarding risk of recurrence
• Discussion of avoiding short interval pregnancy
• Woman may be at increased risk of Post Partum
depression
Vigod S, Villegas L, Dennis C-L, Ross L. Prevalence and risk factors for postpartum depression among women with preterm and low-birth-weight infants: a systematic review. BJOG 2010;117:540–550.
63. REFERENCES
1. Vigod S, Villegas L, Dennis C-L, Ross L. Prevalence and risk factors for postpartum depression among women with preterm and low-birth-weight infants: a systematic review. BJOG 2010;117:540–550.
2. Shapiro-Mendoza CK, Barfield WD, Henderson Z, et al. CDC Grand Rounds: Public Health Strategies to Prevent Preterm Birth. MMWR Morb Mortal Wkly Rep 2016;65:826–830.
DOI: http://dx.doi.org/10.15585/mmwr.mm6532a4
3. Scott D. Grosse, Norman J. Waitzman, Ninee Yang, Karon Abe, Wanda D. Barfield. Employer-Sponsored Plan Expenditures for Infants Born Preterm. Pediatrics, 2017; e20171078 DOI: 10.1542/peds.2017-1078
4. Institute of Medicine (US) Committee on Understanding Premature Birth and Assuring Healthy Outcomes; Behrman RE, Butler AS, editors. Preterm Birth: Causes, Consequences, and Prevention. Washington (DC): National
Academies Press (US); 2007. 10, Mortality and Acute Complications in Preterm Infants.Available from: https://www.ncbi.nlm.nih.gov/books/NBK11385/
5. Timing of Umbilical Cord Clamping. ACOG Practice Bulletin number 543, December 2012
6. Prelabor Rupture of Membranes. ACOG Practice Bulletin number 188, January 2018.
7. King et al. Prophylactic antibiotics for inhibiting preterm labor with intact membranes. Cochrane Database 2002, Issue 4
8. Rundell K, Panchal B. Preterm labor: prevention and management. Am. Fam. Physician. 2017;95:366–372
9. Shepherd E, Salam RA, Middleton P, Makrides M, McIntyre S, Badawi N, Crowther CA. Antenatal and intrapartum interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews. Cochrane
Database of Systematic Reviews 2017, Issue 8. Art. No.: CD012077. DOI: 10.1002/14651858.CD012077.pub2.
10. Costantine MM et al. Effects of antenatal exposure to magnesium sulfate on neuroprotection and mortality in preterm infants. NICHD MFM Units Network Obstet Gynecol 2009;114:354-364.
11. Magnesium sulfate before anticipated preterm birth for neuroprotection. ACOG Committee Opinon 455. ACOG and SMFM.
12. Gyamfi-Bannerman C, Thom EA, Blackwell SC, Tita AT, Reddy UM, Saade GR, et al. Antenatal betamethasone for women at risk for late preterm delivery. NICHD Maternal-Fetal Medicine Units Network. N Engl J Med
2016;374:1311–20.
13. Antenatal Corticosteroid Therapy for Fetal Maturation. ACOG Committee Opinion, Number 713. August 2017.
14. Garite TJ, Kurtzman J, Maurel K, Clark R. Impact of a ‘rescue course’ of antenatal corticosteroids: a multi-center randomized placebo-controlled trial. Obstetrix Collaborative Research Network [published erratum appears in
Am J Obstet Gynecol 2009;201:428]. Am J Obstet Gynecol 2009;200:248.e1–9. (Level I)
15. Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD004454.
DOI: 10.1002/14651858.CD004454.pub3.
16. Management of Preterm Labor. ACOG Practice Bulletin 171, October 2016.
17. American College of Obstetricians and Gynecologists ACOG practice bulletin no.142: cerclage for the management of cervical insufficiency. Obstet Gynecol. 2014;123:372–379.
18. Romero, R. Conde-Agudelo, A. Da Fonseca, E. O’Brien, JM, Cetingoz, E. Creasy, GW. Hassan, SS. Nicolaides, KH. “Vaginal Progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with
a short cervix: a meta-analysis of individual patient data.” Am J Obstet Gynecol. 2018;218(2):161.
19. Martin JA, Osterman MJK. Describing the increase in preterm births in the United States, 2014–2016. NCHS Data Brief, no 312. Hyattsville, MD: National Center for Health Statistics. 2018.
20. Source: Preterm birth rates are from the National Center for Health Statistics, 2017 final natality data. Grades assigned by March of Dimes Perinatal Data Center
21. Society of Maternal Fetall Medicine, McIntosh, J., Feltovich, H, Berghella, V., Manuck, T. “SMFM Consult Series #40: The role of routine cervical length screening in selected high and low-risk women for preterm birth
prevention.” AJOG. 9/2016.
22. Iams JD, Goldenberg RL, Meis PJ, Mercer BM, Moawad A, Das A, et al. The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development maternal fetal
medicine unit network. N Engl J Med. 1996;334:567–72.
23. Iams J. Identification of candidates for progesterone. Obstet Gynecol 2014;123:1317-1326