THE MANAGEMENT OF POST-TERM PREGNANCY

Errol R. Norwitz, M.D., Ph.D.

Associate Professor, Yale University School of Medicine Co-Director, Maternal-Fetal Medicine Director, Maternal-Fetal Medicine Fellowship Program Director, Ob/Gyn Residency Program Dept of Obstetrics, Gynecology & Reprod Sciences Yale-New Haven Hospital, New Haven, CT 06520

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 sisters baby died at 41 weeks. Why cant you induce my labor now, Doctor?

Objectives
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

L&B

Come on. Its almost time for Jeopardy!

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

Can we identify parturients at risk 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

The incidence of post-term pregnancy depends on .

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

Local Practice Patterns

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

What is the definition of post-term pregnancy?

% of all deliveries
8 6 4 2 0

Term
EDC

Post-term (prolonged)
(range, 3 -14%)

10%

(range, 2 -7%)

4%

38

40

42

44

Gestational age (weeks)

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

Basic obstetric tenant

Induction of labor is indicated when the benefits of delivery outweigh the benefits of continuing the pregnancy.
In high-risk pregnancy, the balance starts to shift in favor of delivery at around 38 weeks gestation.

Which pregnancies should be considered high-risk?

Maternal Factors
Preeclampsia Chronic hypertension Diabetes mellitus (including gestational diabetes) Cardiac disease Chronic renal disease Thromboembolic disease Chronic pulmonary disease

Fetal Factors
Non-reassuring fetal testing Intrauterine growth restriction Isoimmunization Previous stillbirth Intra-amniotic infection Fetal structural anomaly

Uteroplacental Factors
Premature rupture of membranes Unexplained oligohydramnios Prior classical hysterotomy Placental abruption Placenta previa Vasa previa

Basic obstetric tenant

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

Review current management of low-risk post-term pregnancy

Revisit the risks of prolonged pregnancy Revisit the risks/benefits of induction of labor Propose new recommendations for management of post-term pregnancy

What are the risks of post-term pregnancy?

Fetal Risks
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

Can you quantify the risk to the fetus?

Complication
Perinatal death (stillbirth) Fetal macrosomia Meconium Fetal distress Uteroplacental insufficiency

Incidence
4-fold at 43 wks and 5- to 7-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%

Fetal dysmaturity syndrome?

Revisiting the fetal risks of post-term pregnancy

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
Baird D, et al. J Obstet Gynaecol Br Empire 1954;61:433-8 Gibson GB. Br Med J 1955;II:715-9 Yudkin P, et al. Lancet 1987; 8543:1192-4

Risks of post-term pregnancy are far higher than appreciated

Study
Yudkin P, et al. 1987 Hilder L, et al. 1998 Cotzias CS, et al. 1999 Smith GCS. 2001

No.
n=4,635 n=171,527

Results
4-fold risk at 41 weeks (vs nadir at 33 weeks) 8-fold risk when including infant mortality (0.7/1000 at 37 weeks 5.8/1000 at 43 weeks) Risk recalculated at each GA Propose induction at 41 weeks Perinatal death is lowest at 38 weeks (1.7/1,000 births)

n=171,527 n=700,878

2 1.8 Rate per 1,000 undelivered 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 29 31 33 35 37 39 41

Overall stillbirths

Unexplained stillbirths

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

PNMR per 1,000 live births

PNMR per 1,000 ongoing pregnancies

Infant mortality

Infant mortality

Stillbirth

Stillbirth

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

Nulliparous

Multiparous

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

Prospective risk of stillbirth by week of gestation for singleton pregnancies in North East Thames region, 1989-1991
Gestation No. of ongoing No. of Risk of stillbirth/1,000 (weeks) pregnancies stillbirths ongoing pregnancies RR (95% CI) 35 36 37 38 39 40 41 42 43 161,638 159,723 155,791 147,631 126,448 93,539 39,245 10,305 1,874 48 62 47 77 62 81 50 16 4 0.30 (0.23-0.37) 0.39 (0.31-0.46) 0.30 (0.23-0.37) 0.52 (0.44-0.60) 0.49 (0.40-0.58) 0.87 (0.80-0.96) 1.27 (0.94-1.60) 1.55 (0.93-2.78) 2.13 (0.28-3.99) Risk of stillbirth in ensuing week 1:3,332 1:2,536 1:3,332 1:1,922 1:2,039 1:1,148 1:786 1:644 1:486

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

Why does risk of stillbirth increase after 40 weeks?

Likely due to uteroplacental dysfunction Speaks to the limitations of antepartum fetal testing 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

>35 years 25-34 years

<25 years

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

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

Singleton pregnancies

(n=10,695,767)

Twin pregnancies
(n=291,792)

Triplet pregnancies
(n=15,108)

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

+ Proteinuria

p<0.01

Total

Friedman EA, et al. JAMA 1978; 239:2249-51

Steer PJ, et al. Br Med J 2004; 329:1312-7

Also increased risk of perinatal morbidity

Complications
Convulsions Meconium aspiration Apgar score <4 at 5 min AGA SGA AGA SGA AGA SGA

Odds Ratio (95% CI)

1.5 (1.6-3.4) 3.4 (1.5-7.6) 3.0 (2.6-3.7) 1.6 (0.5-5.0) 2.0 (1.5-2.5) 3.6 (1.5-8.7)

(n=510,029 singleton births: 92% term vs 8% post-term)

Clausson B, et al. Obstet Gynecol 1999; 94:758-62

Antepartum risk factors for newborn encephalopathy

Preconceptional factors
Increased maternal age Unemployed, unskilled laborer No private health insurance Family history of seizures and neurological disorders Infertility treatment

Antepartum factors
Maternal thyroid disease Severe preeclampsia Bleeding in pregnancy Viral illness in pregnancy Post-term pregnancy Fetal restriction in the fetus Placental abnormalities

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

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Quantifying the risk of newborn encephalopathy by gestational age

15

OR 13.2

Odds ratio

12 9 6 3 0 36 37 38 39 40 41 42

OR 2.35

Gestational age (weeks) Badawi N, et al. Br Med J 1998; 317:1549-53

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

Complication
Labor dystocia Cesarean delivery Severe perineal injury Postpartum hemorrhage

Incidence
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 quantify the risk to the mother?

Study
Campbell MK, et al. Obstet Gynecol 1997 Treger M, et al. J Matern Fetal Med 2002 Alexander JM, et al. Obstet Gynecol 2000

Patients
n=65,796 (c/w 379,445 term controls) n=36,160

Results
Maternal complications in post-term vs term deliveries Complications with advancing gestational age from 39 to 43 weeks Labor complications from 40 to 41 to 42 weeks in low-risk pregnancies

n=56,317

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Management
ACOG 1989, 1997
Induction of labor for low-risk pregnancy sometime during the 43rd week of gestation.

Management relies on good dating.

Current guidelines
ACOG 2004
No specific guidelines were given as regards the timing of delivery in low-risk post-term pregnancies

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

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What fetal testing?

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

What fetal testing?

Caveats about fetal testing Never been shown to perinatal mortality Insufficient evidence for testing 40-42 wks Most authorities recommend twice weekly fetal testing (with evaluation of AFV on at least one occasion) starting approximately 41 weeks gestation

There are two risks of induction of labor ...

(Iatrogenic prematurity) Failed induction leading to cesarean
Commonly believed that routine induction of labor increases cesarean delivery rate Newer studies suggest that induction of labor at 41 weeks does not increase overall cesarean delivery rate

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Effect of induction of labor on cesarean delivery rate ...

The ideal study has not been performed
To demonstrate a statistical difference in perinatal outcome, 150,000 post-term pregnancies would need to be randomized to induction or expectant management Likely unattainable
Grant JM. Br J Obstet Gynaecol 1995; 102:849

How good is the data?

Study
Yeast et al, 1999

Design
Review n=18,055

Results
Induction rate 32% to 43% over 7 years, but no increase in cesarean rate Cesarean rate in spont. labor = induction 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)

Herabutya et al, 1992 McNellis et al, 1994 Hannah et al, 1992

RCT* At 42 weeks n=108 RCT* At 41 weeks n=440 RCT* At 41+ weeks n=3,407

* non - blinded

How good is the data?

Study
Yeast et al, 1999

Design
Review n=18,055

Results
Induction rate 32% to 43% over 7 years, but no increase in cesarean rate Cesarean rate in spont. labor = induction 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)

Herabutya et al, 1992 McNellis et al, 1994 Hannah et al, 1992

RCT* At 42 weeks n=108 RCT* At 41 weeks n=440 RCT* At 41+ weeks n=3,407

* non - blinded

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