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Errol R. Norwitz, M.D., Ph.D.Associate Professor, Yale University School of Medicine Co-Director, Maternal-Fetal MedicineDirector, Maternal-Fetal Medicine Fellowship ProgramDirector, Ob/Gyn Residency ProgramDept of Obstetrics, Gynecology & Reprod SciencesYale-New Haven Hospital, New Haven, CT 06520

THE MANAGEMENT OF

POST-TERM PREGNANCY

POST-TERM PREGNANCY:RESCUE BY BIRTH

Case presentation

22-year-old G1 at 41-2/7 weeks complaining of decreased fetal movement.

Reactive NST.

Recommend discharge home to return in 3 days for “post-dates” testing.

She asks: “My sister’s baby died at 41 weeks. Why can’t you induce my labor now, Doctor?”

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Recognize the risks to both mother and fetus of pregnancy >40 weeks

Discuss the risks and benefits of induction of labor

Devise a clear and rational plan for the management of post-term pregnancy

Objectives

L

“Come on. Its almost time for Jeopardy!”

B&

Norwitz ER, et al. N Engl J Med 1999; 341:660-6

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Can we identify parturients atrisk of post-term pregnancy?

Risk factors for post-term pregnancy ...� Primiparity� Prior post-term pregnancy� Fetal anencephaly (without polyhydramnios)� Congenital adrenal hypoplasia (CAH)� Placental sulfatase deficiency (rare)� Male fetus

The majority of post-term pregnancies have no known cause

Population mix� % of primigravid women� % of women with high-pregnancies� Incidence of preterm birth

The incidence of post-termpregnancy depends on ….

Local Practice Patterns

� Rate of elective cesarean delivery� Rate of routine induction of labor� VBAC practices

2

4

6

8

% o

f all

deliv

erie

s

EDC

TermPost-term

(prolonged)

Gestational age (weeks)

10% (range, 3 14%)

4%(range, 2 7%)

What is the definitionof post-term pregnancy?

038 40 42 44

-

-

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Accurate dating

Menstrual history is often inaccurate→→→→ Especially if irregular cycles, on hormonal

contraception, or intermenstrual bleeding

Routine early ultrasound will ↓↓↓↓ incidence of post-term pregnancy from 10% to 1.5-5%→→→→ Not currently recommended in the U.S.

Warsof SL, et al. Clin Obstet Gynecol 1983; 10:445-7Bennett K, et al. Am J Obstet Gynecol 2004; 190:1077-81

Induction of labor is indicated when the benefits of delivery outweigh the benefits of continuing the pregnancy.

Basic obstetric tenant

� In high-risk pregnancy, the balance starts to shift in favor of delivery at around 38 weeks’ gestation.

Maternal FactorsPreeclampsiaChronic hypertensionDiabetes mellitus (including

gestational diabetes)

Which pregnancies shouldbe considered high-risk?

Cardiac diseaseChronic renal diseaseThromboembolic diseaseChronic pulmonary disease

Fetal Factors

Uteroplacental Factors

Non-reassuring fetal testingIntrauterine growth restrictionIsoimmunization

Premature rupture of membranesUnexplained oligohydramniosPrior “classical” hysterotomy

Placental abruptionPlacenta previaVasa previa

Previous stillbirthIntra-amniotic infectionFetal structural anomaly

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Basic obstetric tenant

However, when to recommend delivery in low-risk pregnancy is controversial

Review current management oflow-risk post-term pregnancy

Propose new recommendations formanagement of post-term pregnancy

Revisit the risks ofprolonged pregnancy

Revisit the risks/benefitsof induction of labor

What are the risks ofpost-term pregnancy?

“The post-mature infant has stayed too long

in intrauterine surroundings; he has remained

so long in utero that he has difficulty to be

born with safety to himself and his mother”

Ballentyne JW. J Obstet Gynaecol Br Emp 1902; 2:36

Fetal Risks

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Complication Incidence

•••• Perinatal death(stillbirth)

•••• Fetal macrosomia

•••• Meconium

•••• “Fetal distress”

•••• Uteroplacentalinsufficiency

4-fold ↑↑↑↑ at 43 wks and 5- to7-fold ↑↑↑↑ at 44 wks (vs 40 wks)

2.5-10% (vs 0.8-1% at 40 wks)

30-38% (vs 17% at 40 wks)

8% (vs 5% at term)

20-40%

Can you quantify the risk to the fetus?

Fetal dysmaturity syndrome?

Statistical error in calculating fetal risk (wrong denominator)

This error has resulted in a significant under representation of the risk of stillbirth for post term pregnancies

Revisiting the fetal risksof post-term pregnancy

--

Baird D, et al. J Obstet Gynaecol Br Empire 1954;61:433-8Gibson GB. Br Med J 1955;II:715-9

Yudkin P, et al. Lancet 1987; 8543:1192-4

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Risks of post-term pregnancy are far higher than appreciated

Study No. ResultsYudkin P, et al.1987

n=4,635 4-fold ↑↑↑↑ risk at 41 weeks (vs nadir at 33 weeks)

Cotzias CS, et al.1999

n=171,527 Risk recalculated at each GA Propose induction at 41 weeks

Hilder L, et al.1998

n=171,527 8-fold ↑↑↑↑ risk when including infant mortality (0.7/1000 at 37weeks →→→→ 5.8/1000 at 43 weeks)

Smith GCS.2001

n=700,878 Perinatal death is lowest at38 weeks (1.7/1,000 births)

Yudkin P, et al. Lancet 1987; 8543:1192-4

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r 1,

000

unde

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ed

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

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29 31 33 35 37 39 41

Unexplained stillbirths

Overall stillbirths

Hilder L, et al. Br J Obstet Gynaecol 1998; 105:169-73 Rand L, et al. Obstet Gynecol 2000; 96:779-83

Stillbirth

Infant mortality

Stillbirth

Infant mortality

PNMR per 1,000 live births PNMR per 1,000 ongoing pregnancies

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Smith GCS. Am J Obstet Gynecol 2001; 184:489-96

Nulliparous

Multiparous

35 161,638 48 0.30 (0.23-0.37) 1:3,33236 159,723 62 0.39 (0.31-0.46) 1:2,53637 155,791 47 0.30 (0.23-0.37) 1:3,33238 147,631 77 0.52 (0.44-0.60) 1:1,92239 126,448 62 0.49 (0.40-0.58) 1:2,03940 93,539 81 0.87 (0.80-0.96) 1:1,14841 39,245 50 1.27 (0.94-1.60) 1:78642 10,305 16 1.55 (0.93-2.78) 1:64443 1,874 4 2.13 (0.28-3.99) 1:486

Gestation(weeks)

No. of ongoingpregnancies

No. of stillbirths

Risk of stillbirthin ensuing week

Risk of stillbirth/1,000ongoing pregnancies

RR (95% CI)

Prospective risk of stillbirth by week of gestation for singleton pregnancies in North East Thames region, 1989-1991

Hilder L, et al. Br Med J 2000; 320:444-5

Likely due to uteroplacental dysfunction

Speaks to the limitations of antepartum fetal testing

Why does risk of stillbirth increase after 40 weeks?

May reflect our failure to identify risk factors for stillbirth …� AMA� Infertility� Multiple pregnancy� Low blood pressure

� IUGR� Prior SGA, IUGR,

or preterm infant� Elevated MS-AFP

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Feldman GB. Obstet Gynecol 1992; 79:547-53

25-34 years

<25 years

>35 years

Jackson RA, et al. Obstet Gynecol 2004; 103:551-63

Kahn B, et al. Obstet Gynecol 2003; 102:685-92

Singletonpregnancies(n=10,695,767)

Twinpregnancies

(n=291,792)

Tripletpregnancies

(n=15,108)

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Friedman EA, et al. JAMA1978; 239:2249-51

Steer PJ, et al. Br Med J2004; 329:1312-7

Total

+ Proteinuria

p<0.01

Also increased risk of perinatal morbidity

Clausson B, et al. Obstet Gynecol 1999; 94:758-62(n=510,029 singleton births: 92% term vs 8% post-term)

3.6 (1.5-8.7)SGA

2.0 (1.5-2.5)AGAApgar score<4 at 5 min

1.6 (0.5-5.0)SGA

3.0 (2.6-3.7)AGAMeconium aspiration

3.4 (1.5-7.6)SGA

1.5 (1.6-3.4)AGAConvulsions

Odds Ratio (95% CI)Complications

Preconceptional factors Antepartum factors

• Increased maternal age

• Unemployed, unskilled laborer• No private health insurance• Family history of seizures

and neurological disorders• Infertility treatment

• Maternal thyroid disease

• Severe preeclampsia• Bleeding in pregnancy• Viral illness in pregnancy

• Post-term pregnancy• Fetal restriction in the fetus

• Placental abnormalities

Antepartum risk factorsfor newborn encephalopathy

Badawi N, et al. Br Med J 1998; 317:1549-53

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Quantifying the risk of newborn encephalopathy by gestational age

37 39 41

Gestational age (weeks)

OR 13.2

OR 2.35

4238 400

3

6

9

12

Odd

s ra

tio

15

36

Badawi N, et al. Br Med J 1998; 317:1549-53

Does post-term pregnancy pose any risk to the mother?

Complication Incidence

•••• Labor dystocia

•••• Cesarean delivery

•••• Severe perineal injury

•••• Postpartum hemorrhage

9-12% (vs 2-7% at term)

1.5- to 2-fold ↑↑↑↑

3.3% (vs 2.6% at term)

10% (vs 8% at term)

Can you quantifythe risk to the mother?

Study Patients Results

Treger M, et al. J Matern Fetal Med2002

n=36,160 Complications ↑↑↑↑ withadvancing gestational age from 39 to 43 weeks

Alexander JM, et al.Obstet Gynecol2000

n=56,317 Labor complications ↑↑↑↑from 40 to 41 to 42 weeksin low-risk pregnancies

Campbell MK, et al. Obstet Gynecol1997

n=65,796(c/w 379,445term controls)

Maternal complications↑↑↑↑ in post-term vs termdeliveries

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Management

ACOG 1989, 1997

Management relies on good dating.

Induction of labor for low-risk pregnancy sometime during the 43rd week of gestation.

Current guidelines

ACOG 2004

No specific guidelines were given as regards the timing of delivery in low-risk post-term pregnancies

If the plan is to continue expectant management into the post-term period (after 42-0/7 weeks), you should initiate fetal testing

Fetal testing

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NST, BPP, AFV (mod BPP), CST (OCT)

No single test is better than any other→→→→ Doppler velocimetry is not recommended

No firm guidelines about frequency of testing

AFV decreases by 30-50% from 40-42 weeks

What fetal testing?

Bleisher N, et al. Am J Obstet Gynecol 1969; 103:496Phelan JP, et al. J Reprod Med 1987; 32:601-4

Caveats about fetal testing→→→→ Never been shown to ↓↓↓↓ perinatal mortality→→→→ Insufficient evidence for testing 40-42 wks

Most authorities recommend twice weeklyfetal testing (with evaluation of AFV on atleast one occasion) starting approximately41 weeks’ gestation

What fetal testing?

There are two risks of induction of labor ...

(Iatrogenic prematurity)

� Commonly believed that routine induction oflabor increases cesarean delivery rate

� Newer studies suggest that induction of labor at 41 weeks does not increase overall cesarean delivery rate

Failed induction leading to cesarean

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Effect of induction of laboron cesarean delivery rate ...

The ideal study has not been performed…

� To demonstrate a statistical differencein perinatal outcome, 150,000 post-term pregnancies would need to be randomized to induction or expectant management

Grant JM. Br J Obstet Gynaecol 1995; 102:849

� Likely unattainable

Induction rate ↑↑↑↑ 32% to 43% over 7 years,but no increase in cesarean rate

Cesarean rate in spont. labor = induction

How good is the data?Study Design ResultsYeast et al, 1999

Reviewn=18,055

McNellis et al, 1994

RCT*At 41 weeksn=440

Hannah et al, 1992

RCT*At 41+ weeksn=3,407

Herabutya et al, 1992

RCT*At 42 weeksn=108

Cesarean rate of 47% in both expectant management and induction groups

Inadequate power

No significant difference in cesarean rate(18% expectant management group; 22%PGE induction; 18% placebo induction)

Lower cesarean rate in induction group (21.2% vs 24.5% expectant management)

* non blinded -

Induction rate ↑↑↑↑ 32% to 43% over 7 years,but no increase in cesarean rate

Cesarean rate in spont. labor = induction

How good is the data?Study Design ResultsYeast et al, 1999

Reviewn=18,055

McNellis et al, 1994

RCT*At 41 weeksn=440

Hannah et al, 1992

RCT*At 41+ weeksn=3,407

Herabutya et al, 1992

RCT*At 42 weeksn=108

Cesarean rate of 47% in both expectant management and induction groups

Inadequate power

No significant difference in cesarean rate(18% expectant management group; 22%PGE induction; 18% placebo induction)

Lower cesarean rate in induction group (21.2% vs 24.5% expectant management)

* non blinded -