Pregnancy outcome at extremely advanced maternal age

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Pregnancy outcome at extremely advanced maternal age Yariv Yogev, MD; Nir Melamed, MD; Ron Bardin, MD; Kinneret Tenenbaum-Gavish, MD; Gadi Ben-Shitrit, MD; Avi Ben-Haroush, MD OBJECTIVE: The purpose of this study was to evaluate pregnancy outSTUDY DESIGN: We compared the condition of women aged ⱖ45 years (n ⫽ 177) in a 10:1 ratio (20-29, 30-39, and 40-44 years.). Subgroup analysis compared the condition of women aged 45-49 years with those women aged ⱖ50 years.

and OR, 3.5; 95% CI, 1.4 –9.0, respectively). The rates of cesarean delivery (OR, 31.8; 95% CI, 18.0 –56.1), placenta previa, postpartum hemorrhage, and adverse neonatal outcome were significantly higher among the study group. The risk for gestational diabetes mellitus, preeclampsia toxemia, preterm delivery, and neonatal intensive care unit admission was increased for women aged ⱖ50 years.

RESULTS: The rates of gestational diabetes mellitus and hypertensive

CONCLUSION: Pregnancy at extreme advanced maternal age is associ-

complications were higher for the study group, compared with the whole group (17.0% vs 5.6% and 19.7% vs 4.5%, respectively; P ⬍ .001), as was the rate of preterm delivery at ⬍37 and ⬍34 weeks of gestation (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2–3.6

ated with increased maternal and fetal risk.

come in women at extremely advanced maternal age (ⱖ45 years).

Key words: advanced maternal age, complication, neonatal, pregnancy

Cite this article as: Yogev Y, Melamed N, Tenenbaum-Gavish K, et al. Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol 2010;203:558.e1-7.

A

dvance maternal age is considered to maternal age of ⬎35 years at the estimated date of delivery. In the last decades, a trend of shifting family planning and childbearing towards advanced maternal age became more widespread. Moreover, more women defer pregnancy to the fifth decade of their life and even further by taking advantage of the artificial reproductive technologies. As a result, the live birth rate for women of advanced maternal age has increased steadily over the past years.1 The impact of advanced maternal age and delayed childbearing on perinatal outcome is equivocal. Some researchers have

From the Department of Obstetrics and Gynecology, Perinatal Division, Helen Schneider Hospital for Women, Rabin Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Received May 17, 2010; revised June 29, 2010; accepted July 22, 2010. Reprints not available from the authors. Authorship and contribution to the article is limited to the 6 authors indicated. There was no outside funding or technical assistance with the production of this article. 0002-9378/$36.00 © 2010 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2010.07.039

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suggested compromised pregnancy outcome2-4; other researchers have reported comparable outcome for this subgroup.5-9 Nevertheless, most studies have evaluated pregnancy outcome in women aged ⱖ35 years, and insufficient data exist concerning pregnancy outcome in women who conceive in the fifth and sixth decades of life.2-4 Thus, we aimed to determine whether these older mothers (⬎45 years old) constitute a specific and unique risk group that is distinct, in terms of magnitude of risks, from their younger counterparts.

M ETHODS The study sample consisted of women who were at least 45 years old at the time of delivery and who gave birth in our hospital between 2000 and 2008. For the purpose of comparison groups, data were compared with 3 control groups, which were matched by maternal age, in a 10:1 ratio (20-29, 30-39, and 40-44 years.). These groups were comprised of the next 10 deliveries for each of the 3 age subgroups after a delivery of a woman at ⱖ45 years old in the same time period. In addition, we further divided the study group to 2 subgroups that compared women who were 45-50 years old with those ⱖ50 years old at the time of delivery. Data for the study and

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control groups were obtained from the delivery room logbook and from a comprehensive perinatal database that is maintained in our institution. Eligibility for the study was limited to pregnancies that have reached at least 24 weeks of gestation. The local institutional review board approved the study. All pregnant women were screened for gestational diabetes mellitus (GDM) with a 50-g oral glucose challenge test between 24 and 28 weeks of gestation. Women with abnormal glucose challenge test (⬎140 mg/dL⫺) underwent a 3-hour oral glucose tolerance test with a 100-g oral glucose load. The diagnosis of GDM was made when ⱖ2 values exceeded the criteria of Carpenter and Coustan.10 Hypertension that was present at ⬍20 weeks of gestation that did not progress to preeclampsia toxemia was classified as chronic hypertension. After 20 weeks of gestation, hypertensive disorders in pregnancy were categorized according to the International Society for the Study of Hypertension in Pregnancy guidelines.11 Spontaneous preterm labor was defined as occurring ⬎24 and ⬍37 weeks of gestation in which the delivery was the result of spontaneous onset of delivery, premature rupture of membranes, or suspected cervical incompetence (painless dilation). Indicated preterm

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TABLE 1

Demographic and obstetric characteristics for the study and control groups Group 1: 20-29 y (n ⴝ 1770)

Overall (n ⴝ 5487)

Variable a

Maternal age, y

34.2 ⫾ 7.0

26.1 ⫾ 2.5

Group 2: 30-39 y (n ⴝ 1770) 33.7 ⫾ 2.6

Group 3: 40-44 y (n ⴝ 1770) 41.5 ⫾ 1.2

Group 4: >45 y (n ⴝ 177) 47.4 ⫾ 2.6

P value ⬍ .001 (4⫽3⫽2⫽1)

................................................................................................................................................................................................................................................................................................................................................................................ a

3.6 ⫾ 2.7

Gravidity

2.0 ⫾ 1.3

3.4 ⫾ 1.9

5.1 ⫾ 3.2

4.3 ⫾ 3.4

⬍ .001 (3⫽4⫽2⫽1)

................................................................................................................................................................................................................................................................................................................................................................................ a

1.3 ⫾ 1.1

Parity

0.4 ⫾ 0.8

1.0 ⫾ 0.9

2.4 ⫾ 1.6

2.2 ⫾ 2.0

⬍ .001 (3,4⫽2⫽1)

................................................................................................................................................................................................................................................................................................................................................................................

1287 (72.7)

⬍ .001

Nulliparity, n (%)

2895 (52.8)

954 (53.9)

585 (33.1)

69 (39)

Maternal obesity, n (%)

1139 (21)

336 (19)

354 (20)

407 (23)

42 (24)

.07

169 (3.1)

41 (2.3)

64 (3.6)

52 (2.9)

12 (6.8)

.004

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................

Multifetal gestations, n (%)

................................................................................................................................................................................................................................................................................................................................................................................

Oocyte donation, n (%)

NA

NA

NA

NA

141 (79)

246 (13.9)

375 (21.2)

................................................................................................................................................................................................................................................................................................................................................................................

91 (5.1)

40 (22.6)

⬍ .001

Previous cesarean delivery, n (%)

752 (13.8)

Chronic hypertension, n (%)

76 (1.4)

2 (0.1)

14 (0.8)

48 (2.7)

12 (6.8)

⬍ .001

Pregestational diabetes mellitus, n (%)

66 (1.2)

14 (0.8)

19 (1.1)

25 (1.4)

8 (4.5)

⬍ .001

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Gestational diabetes mellitus, n (%)

309 (5.6)

Gestational hypertension, n (%)

149 (2.7)

25 (1.4)

74 (4.2)

180 (10.2)

30 (17.0)

⬍ .001

................................................................................................................................................................................................................................................................................................................................................................................

36 (2.0)

41 (2.3)

56 (3.2)

16 (9.0)

⬍ .001

................................................................................................................................................................................................................................................................................................................................................................................

Preeclampsia toxemia, n (%)

99 (1.8)

Oligohydramnios, n (%)

145 (2.6)

12 (0.7)

26 (1.5)

42 (2.4)

19 (10.7)

⬍ .001

................................................................................................................................................................................................................................................................................................................................................................................

43 (2.4)

39 (2.2)

55 (3.1)

8 (4.5)

.04

................................................................................................................................................................................................................................................................................................................................................................................

NA, not applicable. a

Data are given as mean ⫾ SD.

Yogev. Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol 2010.

birth was defined as involving an infant born at ⬍37 weeks of gestation in which labor was induced or primary cesarean section delivery was performed because of fetal and/or maternal indications. Maternal obesity was defined as prepregnancy body mass index ⱖ 30 kg/m2. Gestational age at delivery was based on last menstrual period and, whenever available, confirmation by first-trimester ultrasound scans. For patients who underwent in vitro fertilization, gestational age was calculated from the date of the embryo transfer. Low birthweight was defined as ⬍2500 g; very low birthweight was defined as birthweight ⬍1500 g; small for gestational age was defined as birthweight below the 10th percentile for gestational age with the use of local, populationbased liveborn infant birthweight curves.12 Metabolic complications were defined by the presence of ⱖ1 of the fol-

lowing events: neonatal hypoglycemia (⬍40 mg/dL), erythrocytemia (hematocrit, ⬎60%), hyperbilirubinemia (⬎12 mg/dL), or hypocalcemia (⬍8 mg/dL). Comparisons between the groups and subgroups were performed with analysis of variance with Turkey’s multiple comparisons or Student t test for continuous data and with ␹2 or Fisher’s exact test for categoric data. A probability value of ⬍ .05 was considered significant. For the purpose of comparison, women who were 20-29 years old were referred as an odds ratio of 1.0. The odds ratio and 95% confidence interval were calculated where appropriate.

R ESULTS During the study period, 79,650 women gave birth in our hospital; 177 of these women (0.2%) were ⱖ45 years old at the time of delivery.

The demographic and obstetric characteristics for the study and the control groups are given in Table 1. Gravidity and parity and the rates of chronic hypertension and pregestational diabetes mellitus increased all through maternal age categories. The rates of GDM and preeclampsia toxemia in the study group were significantly higher in comparison with the overall rate in the control groups (17% vs 5.6% and 10.7% vs 1.8%, respectively; P ⬍ .01 for both). There were no maternal deaths within the study and the control groups. Delivery outcome is given in Table 2. The rate of preterm delivery (ⱕ37, ⬍34, and ⬍32 weeks of pregnancy) was higher for the study group in comparison with the control groups. Overall, the cesarean section delivery rate was increased significantly in the study group in comparison with the control groups (78.5% vs

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TABLE 2

Delivery outcome for the study and comparison groups Overall (n ⴝ 5487)

Variable a

Gestational age, wk

38.8 ⫾ 2.2

Group 1: 20-29 y (n ⴝ 1770) 39.2 ⫾ 2.0

Group 2: 30-39 y (n ⴝ 1770) 38.9 ⫾ 2.2

Group 3: 40-44 y (n ⴝ 1770)

Group 4: >45 y (n ⴝ 177)

38.5 ⫾ 2.4

b

37.6 ⫾ 2.5

P value ⬍ .001 (4⫽3⫽2,1)

.......................................................................................................................................................................................................................................................................................................................................................................

⬍37, n (%)

541 (10.3)

130 (7.7)

152 (9.1)

221 (12.8)

38 (21.5)

⬍ .001

⬍34, n (%)

149 (2.8)

27 (1.6)

49 (2.9)

62 (3.6)

11 (6.2)

⬍ .001

....................................................................................................................................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................................................................................................................................

⬍32, n (%)

76 (1.4)

15 (0.9)

23 (1.4)

34 (2.0)

4 (2.3)

.04

255 (47)

75 (58)

82 (54)

92 (42)

6 (15)

.01

................................................................................................................................................................................................................................................................................................................................................................................

Spontaneous preterm delivery (⬍37 wk), n (%)

................................................................................................................................................................................................................................................................................................................................................................................

Delivery mode, n (%)

.......................................................................................................................................................................................................................................................................................................................................................................

Normal vaginal delivery

3655 (66.6)

1384 (78.2)

1275 (72.0)

965 (54.5)

31 (17.5)

⬍ .001

255 (4.6)

113 (6.4)

87 (4.9)

49 (2.8)

6 (3.4)

⬍ .001

1587 (28.9)

277 (15.7)

412 (23.3)

759 (42.9)

139 (78.5)

⬍ .001

551 (37.5)

55 (21.6)

131 (35.5)

293 (41.5)

72 (51.8)

⬍ .001

....................................................................................................................................................................................................................................................................................................................................................................... b

Instrumental delivery

................................................................................................................................................................................................................................................................................................................................................................................

Cesarean delivery

.......................................................................................................................................................................................................................................................................................................................................................................

Elective cesarean delivery

................................................................................................................................................................................................................................................................................................................................................................................

Indication for cesarean delivery, n (%)

.......................................................................................................................................................................................................................................................................................................................................................................

Breech

265 (16.7)

55 (19.9)

79 (19.2)

101 (13.3)

30 (21.6)

.006

Multifetal gestation

75 (4.7)

13 (4.7)

28 (6.8)

26 (3.4)

8 (5.8)

.07

Dystocia

56 (3.5)

23 (8.3)

11 (2.7)

16 (2.1)

6 (4.3)

Nonreassuring fetal heart rate

79 (5.0)

14 (5.1)

13 (3.2)

40 (5.3)

12 (8.6)

.04

Placenta previa

35 (2.2)

2 (0.7)

10 (2.4)

20 (2.6)

3 (2.2)

.3

Previous cesarean delivery

461 (29.0)

43 (15.5)

127 (30.8)

268 (35.3)

23 (16.5)

⬍ .001

Macrosomia

114 (7.2)

....................................................................................................................................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................................................................................................................................

⬍ .001

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................................................................................................................................

29 (10.5)

28 (6.8)

49 (6.5)

NA

NA

NA

8 (7.0)

.13

3 (1.1)

12 (2.9)

17 (2.2)

6 (4.3)

.18

444 (28.0)

95 (34.3)

104 (25.2)

222 (29.2)

23 (16.5)

.001

Placenta previa

49 (0.9)

3 (0.2)

11 (0.6)

25 (1.4)

10 (5.6)

Placental abruption

37 (0.7)

6 (0.3)

12 (0.7)

17 (1.0)

2 (1.1)

.13

3rd-4th degree vaginal tears

26 (0.7)

9 (0.6)

15 (1.1)

2 (0.2)

0

.054

Postpartum hemorrhage

76 (1.4)

18 (1.0)

21 (1.2)

30 (1.7)

7 (4.0)

.007

.......................................................................................................................................................................................................................................................................................................................................................................

Maternal request

NA

Preeclampsia

38 (2.4)

20 (14.4)

....................................................................................................................................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................................................................................................................................

Other

................................................................................................................................................................................................................................................................................................................................................................................

⬍ .001

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................

Blood transfusions

24 (0.4)

3 (0.2)

5 (0.3)

14 (0.8)

2 (1.1)

Postpartum fever

183 (3.3)

83 (4.7)

43 (2.4)

27 (1.5)

22 (12.5)

⬍ .001

.012

Prolonged hospitalization

111 (2.0)

23 (1.3)

36 (2.0)

40 (2.3)

12 (7.2)

⬍ .001

17 (1.0)

14 (0.8)

19 (1.1)

3 (1.7)

.1

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ c ................................................................................................................................................................................................................................................................................................................................................................................

Intensive care unit admission

53 (0.96)

................................................................................................................................................................................................................................................................................................................................................................................

NA, not applicable. a

Data are presented as mean ⫾ SD; b Vacuum extraction or forceps delivery; c Hospitalization for more than 4 or 7 days after vaginal or cesarean delivery, respectively.

Yogev. Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol 2010.

28.9%; P ⬍ .001). The indications for cesarean delivery are specified in Table 2. Of interest is that the rate of breech presentation was significantly higher in the study group (Table 2). Additionally, the rate of postpartum hemorrhage, the need for blood products transfusion, febrile complications, and prolonged hos558.e3

pitalization were increased in the study group (Table 2). Neonatal outcome is given in Table 3. The rate of low birthweight (⬍2500 g) was increased in the study group; however, the rate of very low birthweight (⬍1500 g), small for gestational age, 5-minute Apgar score, and neonatal

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intensive care unit (NICU) admission were similar among the studied groups (Table 3). Odds for adverse pregnancy outcome, with the 20-29 year old group as reference, are given in Table 4. The rate of preterm delivery at ⬍37 and ⬍34 weeks of gestation were increased significantly

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TABLE 3

Neonatal outcome for the study and comparison groups

Variable Birthweight, g

a

Overall (n ⴝ 5487)

Group 1: 20-29 y (n ⴝ 1770)

Group 2: 30-39 y (n ⴝ 1770)

Group 3: 40-44 y (n ⴝ 1770)

Group 4: >45 y (n ⴝ 177)

3164 ⫾ 595

3173 ⫾ 539

3196 ⫾ 595

3143 ⫾ 637

2961 ⫾ 642

P value ⬍ .001 (1⫽2,3,4)

.......................................................................................................................................................................................................................................................................................................................................................................

⬎4000, n (%)

286 (5.2)

75 (4.3)

90 (5.1)

114 (6.4)

7 (4.0)

⬍2500, n (%)

574 (10.5)

154 (8.7)

166 (9.4)

224 (12.7)

30 (16.9)

.026

.......................................................................................................................................................................................................................................................................................................................................................................

⬍ .001

.......................................................................................................................................................................................................................................................................................................................................................................

⬍1500, n (%)

92 (1.7)

18 (1.0)

36 (2.0)

35 (2.0)

3 (1.7)

.073

510 (9.7)

180 (10.7)

142 (8.5)

168 (9.8)

20 (11.3)

.15

................................................................................................................................................................................................................................................................................................................................................................................

Small for gestational age: ⬍10th percentile, n (%)

................................................................................................................................................................................................................................................................................................................................................................................

5-Min Apgar score ⬍7, n (%)

12 (0.4)

2 (0.2)

4 (0.5)

5 (0.4)

1 (0.6)

.8

2778 (50.6)

879 (49.7)

909 (51.4)

897 (50.7)

93 (52.5)

.5

................................................................................................................................................................................................................................................................................................................................................................................

Male sex, n (%)

................................................................................................................................................................................................................................................................................................................................................................................ a

Hospitalization, d

4.1 ⫾ 7.1

3.3 ⫾ 4.2

3.9 ⫾ 6.5

5.0 ⫾ 9.3

6.6 ⫾ 9.2

⬍ .001 (1⫽2⫽3,4)

................................................................................................................................................................................................................................................................................................................................................................................

Neonatal intensive care unit admission, n (%)

384 (7.0)

111 (6.3)

130 (7.4)

152 (8.6)

19 (10.7)

.03

Hyperbilirubinemia, n (%)

533 (9.7)

142 (8.0)

137 (7.7)

233 (13.2)

21 (11.9)

⬍ .001

Metabolic complications, n (%)

100 (1.8)

19 (1.1)

23 (1.3)

50 (2.8)

8 (4.5)

⬍ .001

Major fetal anomalies, n (%)

127 (2.3)

44 (2.5)

37 (2.1)

42 (2.4)

4 (2.2)

.32

7.4

.16

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ b ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ c

Neonatal death, %

6.3

5.7

6.2

7.1

................................................................................................................................................................................................................................................................................................................................................................................ a

Data are presented as mean ⫾ SD; b Hypoglycemia, hypocalcemia, erythrocytemia; c Calculated up to 28 days for 1000 deliveries.

Yogev. Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol 2010.

in the study group, as were the rates of cesarean section delivery and postpartum hemorrhage. A subgroup analysis within the study group between women 45-49 years old compared with those women who were ⬎50 years old at delivery revealed that the rate of chronic hypertension, GDM, preterm delivery (⬍37, 34, and 32 weeks of gestation) were significantly higher in women who were ⱖ50 years old (Table 5).

C OMMENT Although it is generally uncommon, in the last 3 decades, the prevalence of delaying family planning after the age of 40 years old significantly increased.1 Moreover, because of enormous advances in reproductive medicine and oocyte donation, even postmenopausal women in their 5th and 6th decades of life may become pregnant. As a consequence, gravidity and parity in the last few decades created a unique group of pregnant women in the extreme advanced maternal age. Despite the fact that this issue

is under ethical controversy and is thought-provoking, limited evidencebased data are available concerning pregnancy outcome in this age group. The inconsistency, at least in part, may relate to the limitations of some of the available studies, which include a small sample size, comparison of only a small number of different maternal age groups, pooled data from several medical centers, and nonuniform definitions. In the current study, we focused on the group of pregnant patients at the extreme range of advanced maternal age (⬎45 years old at delivery), our main findings were (1) the rate of chronic maternal diseases (chronic hypertension, pregestational diabetes mellitus) and medical complications in pregnancy (GDM and preeclampsia toxemia) were increased; (2) the rates of cesarean delivery, postpartum hemorrhage, postpartum fever, blood transfusion, and prolonged hospitalization were increased; (3) the rate of preterm delivery, low birthweight, and NICU admission were increased for neonates who were born to

mothers in the extreme advanced maternal age group; and (4) pregnancy outcome was poorer for women ⱖ50 years old, compared with women 45-49 years old at delivery. The overall prevalence of childbearing after the age of 45 years in our cohort was relatively small (0.2%); yet, the rate of pregnancy complications among this age group was increased significantly. Surprisingly, the rate of nulliparity was only 40% among the studied group, which means that most women in the extreme advanced maternal age elected to deliver again in their 5th or 6th decade of life, even though they already had children. Similar observations were reported by other researcherss3,13; nevertheless, recently Simchen et al2 reported an increased rate of nulliparity in this age group. Similar to other recent studies, the extreme advanced age group was characterized with an increased rate of pregestational chronic medical complications such as type-2 diabetes mellitus and chronic hypertension.2,4,5-8,13 This may

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TABLE 4

Odds of adverse pregnancy outcome for women in the study and comparison groups, compared with the 20-29 years group Variable

Group 2: 30-39 y (n ⴝ 1770)

Group 3: 40-44 y (n ⴝ 1770)

Group 4: >45 y ( n ⴝ 177)

Delivery, wk

.......................................................................................................................................................................................................................................................................................................................................................................

⬍37

1.0 (0.7–1.3)

1.4 (1.1–1.8)

2.1 (1.2–3.6)

⬍34

1.6 (1.1–2.8)

1.8 (1.1–3.1)

3.5 (1.4–9.0)

....................................................................................................................................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................................................................................................................................

⬍32

1.4 (0.7–2.8)

2.1 (1.1–4.1)

Cesarean delivery

1.2 (1.0–1.4)

3.7 (3.1–4.6)

31.8 (18.0–56.1)

1.8 (0.4–83)

Placenta previa

3.8 (1.1–13.7)

5.7 (1.6–20.4)

13.4 (2.6–68.4)

Placental abruption

1.9 (0.7–5.3)

2.6 (0.9–7.5)

3.7 (0.5–24.4)

Postpartum fever

0.5 (0.3–0.7)

0.7 (0.3–1.4)

2.6 (1.4–4.8)

Prolonged maternal hospitalization

1.4 (0.8–2.5)

1.3 (0.8–2.4)

1.8 (0.5–5.9)

Postpartum hemorrhage

1.1 (0.6–2.1)

2.1 (1.2–3.9)

2.0 (0.5–8.0)

Blood transfusions

1.3 (0.3–5.9)

3.9 (1.1–14.5)

3.0 (0.2–44.5)

Low birthweight: ⬍2500 g

1.0 (0.7–1.2)

0.8 (0.6–1.1)

0.7 (0.3–1.4)

Very low birthweight: ⬍1500 g

1.7 (0.6–4.6)

0.8 (0.3–2.2)

0.1 (0.0–6.6)

5-Min Apgar score ⬍7

1.1 (0.2–7.4)

0.5 (0.1–3.9)

0.4 (0.1–14.6)

Neonatal intensive care unit admission

1.3 (0.6–1.1)

1.5(0.7–1.3)

1.6 (0.9–1.4)

Jaundice

0.9 (0.7–1.2)

1.5 (1.2–1.9)

2.0 (1.1–4.1)

Asphyxia

0.7 (0.4–1.3)

1.2 (0.7–2.2)

0.4 (0.1–1.4)

Metabolic complications

0.9 (0.5–1.7)

1.6 (0.8–2.8)

1.9 (0.6–5.8)

................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ b ................................................................................................................................................................................................................................................................................................................................................................................ b ................................................................................................................................................................................................................................................................................................................................................................................ b ................................................................................................................................................................................................................................................................................................................................................................................ b ................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ a ................................................................................................................................................................................................................................................................................................................................................................................ ac ................................................................................................................................................................................................................................................................................................................................................................................

Data is presented as odds ratio (95% confidence interval) of adverse outcome with group 1 (20-29 years) as the reference group: values reflect the results of multivariate logistic regression analysis that was controlled for the following variables: maternal age, parity, preeclampsia, chronic hypertension, pregestational diabetes mellitus, gestational diabetes mellitus, and multiple gestations. a

Analysis also controlled for gestational age at delivery; b Analysis also controlled for mode of delivery; c Hypoglycemia, hypocalcemia, erythrocytemia.

Yogev. Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol 2010.

explain, in part, the increased rate of preeclampsia and the need for indicated preterm delivery in the study group. This finding is supported most studies that have addressed this issue.2-8,13 Additionally, the fact that the rate of multifetal gestations was higher in the study group, largely because of artificial reproductive technologies, may explain the higher rates of preterm labor and cesarean section delivery (some of it, because of maternal request) in these women (Table 2).14 Although excessive prematurity (⬍32 weeks of gestation) was not significantly higher in the studied group, we found increased neonatal complications (prolonged hospitalization and metabolic complications) in this age group. These findings may indicate that neonatal complication are not unique to extremely premature neonates and that delivery at 32-37 gestational weeks carries 558.e5

significant risk for neonatal complications as well. Nearly 80% of the women in the studied group were delivered by cesarean section delivery (odds ratio, 31.8). The main contributors for this phenomenon are maternal request, higher rate of previous cesarean delivery, the presence of placenta previa, breech presentation, and increased rate of preterm delivery because of medical complications such as preeclampsia. We speculate that the caregivers are more prone to offer cesarean delivery in this extreme age group. This attitude towards higher rates of cesarean delivery was described earlier,2,4 which suggested that it is associated with age of at least 44 years, primiparity, and infertility treatment. Previous study suggested an increased rate of fetal and neonatal death with association to advanced maternal age.15 Although our study was not powered to find such a difference, we

American Journal of Obstetrics & Gynecology DECEMBER 2010

did demonstrate higher neonatal death through maternal age categories. Puerperal complications that included postpartum fever, prolonged hospitalization, and the need for blood transfusion were more common in the study group. Some of the immediate puerperal complications might be the result of the increased rate of cesarean delivery by itself or the background of an increased rate of medical complications. When pregnancy outcome was compared in patients with advanced maternal age who conceived after oocyte donation or after in vitro fertilization with autologous oocytes, Henne et al16 found an increased risk for preterm labor, preeclampsia, and protracted labor that required cesarean delivery in the first group. Additionally, Simchen et al17 showed that pregnancy in advanced-aged pregnant women (⬎40 years old) after oocyte donation who were carrying twins is associated with sig-

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TABLE 5

Pregnancy outcome in the study group: subgroup analysis Group 4 45-49 y (n ⴝ 150)

Variable Oocyte donation, n (%)

>50 y (n ⴝ 27)

P value

114 (76)

27 (100)

.01

Chronic hypertension, n (%)

8 (5.3)

4 (14.8)

.07

Pregestational diabetes mellitus, n (%)

8 (5.3)

0

.47

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................

Gestational diabetes mellitus, n (%)

22 (14.7)

8 (29.6)

.01

Preeclampsia/pregnancy-induced hypertension, n (%)

25 (16.7)

9 (33.3)

.04

Gestational age, wks

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ a

37.8 ⫾ 2.3

36.3 ⫾ 3.1

.006

⬍37, n (%)

28 (18.7)

10 (37.0)

.03

⬍34, n (%)

7 (4.7)

4 (14.8)

.04

⬍32, n (%)

2 (1.3)

2 (7.4)

.04

....................................................................................................................................................................................................................................................................................................................................................................... ....................................................................................................................................................................................................................................................................................................................................................................... .......................................................................................................................................................................................................................................................................................................................................................................

................................................................................................................................................................................................................................................................................................................................................................................

Cesarean delivery, n (%)

116 (77.3)

23 (85.2)

.36

Placenta previa, n (%)

9 (6.0)

1 (3.7)

.6

Postpartum hemorrhage, n (%)

7 (4.7)

0

.25

Blood transfusions, n (%)

2 (1.3)

0

.54

Postpartum fever, n (%)

23 (15.3)

7 (25.9)

.17

9 (6.4)

3 (11.5)

.35

................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ ................................................................................................................................................................................................................................................................................................................................................................................ b

Prolonged hospitalization, n (%)

................................................................................................................................................................................................................................................................................................................................................................................ a

3001 ⫾ 625

Birthweight, g

2737 ⫾ 697

.04

.......................................................................................................................................................................................................................................................................................................................................................................

⬍2500, n (%)

23 (15.3)

7 (25.9)

.17

2 (1.3)

1 (3.7)

.38

16 (10.1)

3 (11.1)

.10

1 (3.7)

.8

.......................................................................................................................................................................................................................................................................................................................................................................

⬍1500, n (%)

................................................................................................................................................................................................................................................................................................................................................................................

Neonatal intensive care unit admission, n (%)

................................................................................................................................................................................................................................................................................................................................................................................ c

Metabolic complications, n (%)

7 (4.7)

................................................................................................................................................................................................................................................................................................................................................................................ a

Data are given as mean ⫾ SD; Hospitalization for ⬎4 or 7 days after vaginal or cesarean delivery, respectively; Hypoglycemia, hypocalcemia, erythrocytemia. b

c

Yogev. Pregnancy outcome at extremely advanced maternal age. Am J Obstet Gynecol 2010.

nificant maternal and fetal complications, with increased risks of prematurity and lower birthweight in comparison with nonoocyte donated twins and singleton fetuses for the same maternal age. In our study group, most multifetal pregnancies were the result of oocyte donation. Possibly, the aged uterus is less suitable for carrying a multifetal pregnancy than a younger uterus. Moreover, the fact that pregnancy was achieved from a young oocyte donor does not guarantee enhanced pregnancy outcome. Therefore, the alternative of transferring a single, good-quality embryo should be the preferred option, especially in this age group of women. We further compared pregnancy outcome within the study group. We found that women who were ⬎50 years old had an increased risk for GDM, preeclampsia toxemia, preterm delivery, and NICU

admission in comparison with women who were 45-49 years old. This finding supports the concept that there is a significant increment in the risk for pregnancy complication, even with moderate increase in maternal age in the extremely advanced maternal age. This finding is supported by others as well.2,4,5,13,18,19 Importantly, we excluded pregnancies that ended before viability (⬍24 weeks of gestation) because we aimed to evaluate pregnancy outcome, especially shortterm neonatal outcome in the extremely advanced age group. We speculate that early and late abortions are more prevalent in this age group, which contributes to higher overall pregnancy complications. Moreover, we present data that are limited to the immediate postpartum period; thus, reliable long-term medical and sociologic outcomes are lacking.

In summary, pregnancy at extreme advanced maternal age is associated with significant increased maternal and fetal risk. Our findings suggest that this age group is a distinct obstetric high-risk entity; this information may be used for more accurate consultation with women who are contemplating pregnancy in this age group. Because we chose to concentrate on this special subgroup of extremely advanced maternal age, our findings might shed some more light on the consequences of pregnancy at theses ages and might be taken into consideration by the woman and her treating physician when she is planning a pregnancy. f REFERENCES 1. Krieg SA, Henne MB, Westphal LM. Obstetric outcomes in donor oocyte pregnancies

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compared with advanced maternal age in in vitro fertilization pregnancies. Fertil Steril 2008; 90:65-70. 2. Simchen MJ, Yinon Y, Moran O, Schiff E, Sivan E. Pregnancy outcome after age 50. Obstet Gynecol 2006;108:1084-8. 3. Dulitzki M, Soriano D, Schiff E, Chetrit A, Mashiach S, Seidman DS. Effect of very advanced maternal age on pregnancy outcome and rate of cesarean delivery. Obstet Gynecol 1998;92:935-9. 4. Callaway LK, Lust K, McIntyre HD. Pregnancy outcomes in women of very advanced maternal age. Aust N Z J Obstet Gynecol 2005;45:12-6. 5. Dildy GA, Jackson GM, Fowers GK, Oshiro BT, Varner MW, Clark SL. Very advanced maternal age: pregnancy after age 45. Am J Obstet Gynecol 1996;175:668-74. 6. Bianco A, Stone J, Lynch L, Lapinski R, Berkowitz G, Berkowitz RL. Pregnancy outcome at age 40 and older. Obstet Gynecol 1996;87:917-22. 7. Jacobsson B, Ladfors L, Milsom I. Advanced maternal age and adverse perinatal outcome. Obstet Gynecol 2004;104:727-33.

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www.AJOG.org 8. Berkowitz GS, Skovron ML, Lapinski RH, Berkowitz RL. Delayed childbearing and the outcome of pregnancy. N Engl J Med 1990; 322:659-64. 9. Fretts RC, Schmittdiel J, McLean FH, Usher RH, Goldman MB. Increased maternal age and the risk of fetal death. N Engl J Med 1995; 333:953-7. 10. Carpenter MW, Coustan DR. Criteria for screening tests for gestational diabetes. Am J Obstet Gynecol 1982;144:768-73. 11. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001; 20:ix-xiv. 12. Dollberg S, Haklai Z, Mimouni FB, Gorfein I, Gordon ES. Birthweight standards in the liveborn population in Israel. Israel Med Assoc J 2005;7:311-4. 13. Salihu HM, Shumpert MN, Slay M, Kirby RS, Alexander GR. Childbearing beyond maternal age 50 and fetal outcomes in the United States. Obstet Gynecol 2003;102:1006-14.

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14. Ohel I, Sheiner E. Does oocyte donation equal cesarean delivery? J Matern Fetal Neonatal Med 2009;22:776-9. 15. Hoffman MC, Jeffers S, Carter J, Duthely L, Cotter A, González-Quintero VH. Pregnancy at or beyond age 40 years is associated with an increased risk of fetal death and other adverse outcomes. Am J Obstet Gynecol 2007;196: e1-3. 16. Henne MB, Zhang M, Paroski S, Kelshikar B, Westphal LM. Comparison of obstetric outcomes in recipients of donor oocytes vs women of advanced maternal age with autologous oocytes. J Reprod Med 2007;52:585-90. 17. Simchen MJ, Shulman A, Wiser A, Zilberberg E, Schiff E. The aged uterus: multifetal pregnancy outcome after ovum donation in older women. Hum Reprod 2009;24:2500-3. 18. Sauer MV, Paulson RJ, Lobo RA. Pregnancy in women 50 or more years of age: outcomes of 22 consecutively established pregnancies from oocyte donation. Fertil Steril 1995;64:111-5. 19. Paulson RJ, Boostanfar R, Saadat P, et al. Pregnancy in the sixth decade of life: obstetric outcomes in women of advanced reproductive age. JAMA 2002;288:2320-3.