Arch Gynecol Obstet DOI 10.1007/s00404-014-3469-0
MATERNAL-FETAL MEDICINE
The effects of maternal age and parity on maternal and neonatal outcome Michael S. Schimmel • Ruben Bromiker • Cathy Hammerman • Lila Chertman Alexander Ioscovich • Sorina Granovsky-Grisaru • Arnon Samueloff • Deborah Elstein
•
Received: 5 January 2014 / Accepted: 10 September 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Delayed childbearing is increasingly common; hence, concerns emerge regarding potential for additional risks of delivery at advanced maternal age (AMA; C35 years). In this study, we sought to assess impact of AMA and parity on maternal and perinatal outcomes. Methods In this retrospective single-center study (July 2005 to October 2011), we compared spontaneously-conceived singleton births of AMA mothers with spontaneously-conceived singletons of mothers aged 24–27 years. Maternal outcomes: incidence of diabetes, hypertension, and emergency cesarean sections (ECS). Neonatal outcomes: prematurity, birth weight, incidence of small or large for gestational age infants (SGA/LGA, respectively), low birth weight (LBW), and 50 -Apgar scores. Subgroupings of maternal age were 35–38, 39–42, or 43–47 years; prematurity as \34 or \37 weeks; AMA
parity as primiparous, 2–5 births, 6–9 births, or C10 births. Binary logistic regression was used for multivariate analyses. Results Of 24,579 eligible women, 11,243 were AMA (14.0 % total singleton births) and 13,336 were aged 24–27 years (16.7 % total singleton births) at delivery. There were no maternal or perinatal deaths. Incidence of maternal hypertension and diabetes was significantly greater in AMA, especially oldest AMA. AMA including primiparous had significantly more ECS than younger including primiparous controls, respectively, and were more likely to deliver LGA neonates. Primiparous AMA women did not have increased incidence of LGA babies but significantly increased incidence of SGA infants. Conclusion AMA, especially primiparous, has more adverse maternal and neonatal outcomes than younger women; however, these did not include mortality. Consistent antenatal care may explain this.
This paper was presented (in part) at the Annual Meeting, Society of Pediatric Research, May 2012, Boston, MA USA.
Keywords Advanced maternal age Adverse maternal outcome Adverse neonatal outcome Prematurity Primiparity
M. S. Schimmel R. Bromiker C. Hammerman Department of Neonatology, Shaare Zedek Medical Center, Affiliated with the Hebrew University, Hadassah Medical School, Jerusalem, Israel L. Chertman S. Granovsky-Grisaru A. Samueloff D. Elstein (&) Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Affiliated with the Hebrew University, Hadassah Medical School, P.O. Box 3235, 12 Bayit Street, 91031 Jerusalem, Israel e-mail: [email protected] A. Ioscovich Department of Anesthesiology, Shaare Zedek Medical Center, Affiliated with the Hebrew University, Hadassah Medical School, Jerusalem, Israel
Introduction In 2002, Astolfi and Zonta [1] estimated that by the year 2025 about 25 % of mothers will begin their child-bearing period at an ‘‘advanced age’’. In developed countries, this may be a reflection of improved social conditions and educational status. The question of whether delaying the age of childbearing increases the risk of adverse outcome is of importance to women who consider postponing childbearing as well as to women who continue to expand their families and to the physicians who care for them [2].
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Israel is a developed country where antenatal care is universally available via a National Health Care System. Women are generally compliant with pre-natal care. Both the phenomena of delayed childbearing and of grand multiparity extending into advanced maternal ages are common among Israeli women and are independent of socio-economic status. Reports from various countries [2–13] describe significantly increased pregnancy related risks among AMA mothers when compared to younger mothers. Recent reports highlight an increased incidence of maternal hypertension and gestational diabetes mellitus [14–17], of non-elective cesarean delivery [14, 18–23] and instrumental deliveries [21, 22], and of preterm delivery [14, 16, 19, 22]. Adverse neonatal outcomes in infants of AMA mothers have been reported to include intrauterine growth restriction (IUGR), low birth weight (BW), stillbirth, and intrauterine fetal death (IUFD) [17, 22, 23, 25]. However, increased neonatal adverse events among AMA women are not universally reported [15, 21, 26–29]. Primiparity among AMA women appears to be a determinant of adverse neonatal outcome in AMA [4, 6, 8, 19, 23, 24, 29, 30], while multiparity in AMA mothers seems to be correlated with a lesser risk than primiparity (assuming there were no adverse events in the first pregnancy), other than the greater incidence of macrosomia among grand multiparas [31–33]. Nevertheless, there is a report of increased Neonatal Intensive Care Units (NICU) admissions and of birth trauma [33], congenital malformations, and increased chromosomal abnormalities among the infants of multiparous AMA [35–37]. The objective of this study was to assess adverse maternal and neonatal outcomes in AMA mothers compared to outcomes in younger women. A secondary objective was to assess the effect of parity in addition to AMA women on incidence of these adverse events.
All women who had any assisted reproductive technologies were excluded as were all women with multiple gestations. If there was more than one birth to a woman during the study period, only the first was included. The study was conducted in a single referral center and was exempt from Institutional Review Board approval because of its use of anonymized archival data. Maternal pregnancy-related health outcomes recorded included the incidence of diabetes [chronic diabetes mellitus type 2 and gestational diabetes (ICD code 648.0–648.04) were included as a single variable], hypertension [chronic and pregnancy-induced hypertension, HELLP syndrome (ICD code 014.2) and preeclampsia and preeclamptic toxemia (ICD codes 014.0 and 014.9) were included as a single variable], and emergency cesarean sections (ECS). For the purpose of the study, we defined any unplanned CS as emergency either due to suspected maternal or fetal compromise or dystocia of labor; etiologies included: bleeding with a low-lying placenta; placenta previa; cord presentation or prolapse; severe preeclamptic toxemia; severe pregnancy-induced hypertension; suspected uterine rupture; suspected placental abruption. Neonatal outcomes included prematurity (at least \37th week), birth weight, incidence of small or large for gestational age infants (SGA and LGA, defined respectively as \10th percentile and [90th percentile [38] for gestational age), low birth weight (LBW) infants (\2,500 g), and 50 Apgar scores. Advanced maternal age sub-groupings were further defined as follows: 35–38, 39–42, and 43–47 years; prematurity was further sub-divided as \34 weeks (early) or \37 weeks (late). AMA and control group parity were categorized as primiparous or multiparous. Neonatal admissions to the Intensive Care Unit (NICU) were not used as a measure of neonatal adverse outcome because of the variable and flexible criteria that were reflective of departmental policies over the study period, and also because of the institution of categorization into well-baby, intermediate, and NICU nurseries.
Materials and methods
Statistical analysis
We conducted a retrospective analysis of an electronic dataset of a single-center patient data from July 2005 to October 2011, in which we compared spontaneously-conceived singleton births of AMA women C35 years of age with similarly conceived singletons of mothers aged 24–27 years. This age range for the young controls was based on a consensus in the literature of an optimum 4-year range approximately one decade younger than the AMA group, but was also designed to exclude young gravida (\23 years of age) who have other unique adverse events because of their chronological age.
The Chi square test was used to compare frequencies of maternal complications across maternal age groups. Student’s t test and analysis of variance (ANOVA) were used to compare continuous variables within and between maternal age groups. Binary logistic regression was used for multivariable analyses of maternal and neonatal outcomes. Binary logistic regression was also used to analyze maternal and neonatal adverse outcome variables adjusted for parity, maternal hypertension, and diabetes (defined per coding in the hospital electronic computerized database). For the purpose of multivariable analyses of the whole
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cohort, in view of the large number of cases, all variables were included; in assessing primiparas only, since the numbers were much smaller, a multivariable model was built with only those variables which were significant (p \ 0.05) in the univariable analyses. A p value of \0.05 was considered significant. SPSS software was used.
Results During the study period 80,053 births were recorded, of which 24,579 women were potentially eligible for the study: 13,336 women aged 24–27 years constituted the control population (16.7 % of total singleton births) and 11,243 women aged C35 years constituted the AMA group (14.0 % of total singleton births). According to the intake records, all mothers had attended high school or beyond. All mothers had consistent antenatal care with follow-up of at least four antenatal visits according to the patient charts.
Table 1 Univariable (%) and multivariable [OR (CI)] analysis of adverse maternal and neonatal outcome AMA group (n = 11,243) relative to control group (n = 13,336)
Univariable analyses Control (%)
Table 2 Univariable (%) and multivariable [OR (CI)] analysis of maternal and neonatal adverse outcome among primiparous AMA (n = 326; 2.4 %) relative to primiparous control (n = 3,004; 26.7 %)
p value
AMA [OR (CI)]
p value
4.7
6.1
0.0001
1.25 (1.11–1.40)
0.0001
Maternal diabetes
1.2
6.6
0.0001
5.96 (4.95–7.17)
0.0001
Multiparity ([1)
77.47
97.1
0.0001
9.86 (8.73–11.13)
0.0001
Intrauterine fetal demise
0.1
0.2
NS
1.45 (0.90–2.32)
NS
Instrumental delivery
5.2
3.0
0.0001
1.09 (0.93–1.27)
NS
Emergency cesarean section
0.3
0.8
0.0001
2.46 (1.65–3.67)
0.0001
Gestational age \37 weeks
4.0
5.0
0.006
1.10 (0.94–1.29)
NS
Gestational age \34 weeks
1.2
1.0
NS NS
5 -Apgar B3
1.2
1.3
NS
0.93 (0.74–1.17)
Small for gestational age
7.5
5.7
0.0001
0.94 (0.84–1.05)
NS
Large for gestational age
8.2
14.7
0.0001
1.64 (1.51–1.79)
0.0001
Univariable analyses Control (%)
AMA (%)
Multivariable analyses p value
Maternal hypertension
4.1
2.8
NS
Maternal diabetes
2.1
6.7
0.0001
Intrauterine fetal demise
0.2
0.6
NS
14.4
20.2
Instrumental delivery
NS not statistically significant
AMA (%)
Multivariable analyses
Maternal hypertension
0
NS not statistically significant
Although intake records include questions regarding the use of alcohol, illicit drugs, smoking, and concomitant medications for chronic conditions as well as use of prenatal vitamins, this information was not tabulated for this study. Table 1 presents the univariable and multivariable analyses of adverse maternal and neonatal outcomes in the AMA group relative to the young control group. The rates of intrauterine fetal death are low because many women who carry fetuses with diagnosed abnormalities are offered early elective abortions, and hence intrauterine death at term is distinctly rare in these women who are monitored at least four times before birth. Maternal hypertension and diabetes as well as the incidence of ECS and LGA neonates were significantly increased in AMA mothers. Table 2 presents the univariable and multivariable analyses of adverse outcomes among primiparas in the AMA group relative to the control group. There were 3,004 (26.7 %) primipara in the control population aged
0.007
AMA [OR (CI)]
p value
3.58 (2.09–5.79)
0.0001
1.59 (1.19–2.14)
0.002
Emergency cesarean section
0.2
1.5
0.004
4.03 (1.17–13.81)
0.026
Gestational age \37 weeks
4.2
8.3
0.002
1.36 (0.75–2.49)
0.30
Gestational age \34 weeks
1.1
2.5
NS
50 -Apgar B3
0.4
0.6
NS
Small for gestational age
11.3
18.4
0.0001
1.51 (1.06–2.16)
0.02
Large for gestational age Low birth weight
5.3 5.7
5.2 12.6
NS 0.0001
1.65 (0.98–2.77)
0.058
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Arch Gynecol Obstet Table 3 Univariable analysis of percent adverse maternal and neonatal outcome among the AMA sub-groups relative to control group
NS not statistically significant * \0.05, ** \0.0001
Outcome/maternal age
24–27 years (n = 13,336)
39–42 years (n = 3,214)
43–47 years (n = 694) 7.3**
Maternal hypertension
4.7
5.9**
6.4**
Maternal diabetes
1.2
5.2**
8.6**
11.7**
Intrauterine fetal demise
0.1
0.2 (NS)
0.2*
0.0 (NS)
Instrumental delivery
5.2
3.1
2.7
2.6**
Emergency cesarean section
0.3
0.7**
1.2**
0.9*
Gestational age \37 weeks
4.0
4.7*
5.6**
5.2**
Gestational age \34 weeks
1
1.2
1.3
0.7 (NS)
50 -Apgar B3
1.2
1.1 (NS)
1.8*
1.2 (NS)
Small for gestational age
7.5
5.8**
5.2**
6.6 (NS)
Large for gestational age
8.2
14.1**
15.7**
15.6**
24–27 years and 326 (2.4 %) primipara among the AMA women. The presence of diabetes was significantly increased among AMA primiparas relative to the control primiparas, as were ECS and the use of instrumental delivery. There was a significantly increased incidence of intrauterine growth retardation among babies born to primiparous AMA women relative to younger primiparas. Table 3 details univariable analysis of percent adverse maternal and neonatal outcomes among the AMA mothers sub-divided by age: 35–38 years (7,335; 65.2 %); 39–42 years (3,214; 28.6 %), and 43–47 years (694; 6.2 %) and compared to control group mothers. Maternal hypertension and diabetes were associated with increasing age. ECS deliveries, prematurity (\37 weeks), and the proportion of LGA infants were increased in each of the age subgroups relative to younger controls, but the increase was not progressive with advancing maternal age. The percent of neonates born SGA significantly decreased in the all the AMA age subgroups (7.5–5.8–5.2 %) as compared to the neonates of younger controls while the percent of LGA significantly increased across AMA age groups (8.2–14.1–15.7 %). The numbers of women with chronic hypertension or diabetes mellitus type 2, were included in the respective categories of hypertension and diabetes. When comparing all AMA to younger controls (Table 1), there was a significant difference in incidence of maternal hypertension (6.1 versus 4.7 %), but when comparing only primiparous AMA to primiparous controls (Table 2: 2.8 versus 4.1 %), there was no significant difference. The significant increase in incidence of maternal hypertension among the AMA was directly correlated with increasing age up to 7.3 % in the oldest AMA (Table 3). Similarly, there was a significant difference in incidence of maternal diabetes between
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35–38 years (n = 7,335)
all AMA and all younger controls (Table 1: 606 versus 1.2 %) but also between primiparous AMA and younger primiparous (Table 2: 6.7 versus 2.1 %) which again was seen to increase significantly across AMA groups (Table 3) up to 11.7 % among the oldest.
Comment Delaying the onset of child-bearing is becoming an increasingly popular choice for contemporary women. As a result, concern has arisen as to whether older women in a first pregnancy pose an increased risk for maternal and neonatal pregnancy-related complications relative to younger primiparas. While most AMA (C35 years) women with a spontaneous singleton pregnancy have an uncomplicated outcome, several recent studies show that compared to younger women, pregnant AMA women have significantly higher risks of hypertension and gestational diabetes. Our study corroborates these findings and additionally shows that the older the woman, the greater the risk of developing each of these morbidities. Primiparous AMA women were also at greater risk for gestational diabetes but not for hypertension than the control group. Neonatal outcomes were not significantly affected by maternal age other than the increased incidence of LGA infants among AMA mothers. Although it could be argued that large infants may merely reflect co-morbidity with maternal diabetes and multiparity [31, 34], the increased LGA incidence remained significant after adjusting for the latter two variables in the multivariable analyses. Therefore, our data indicate that the birth of an LGA infant is independently associated with AMA.
Arch Gynecol Obstet
The secondary objective was to study the contribution of primiparity among the AMA mothers to adverse pregnancy-related events. Interestingly, while the incidence of LGA infants was increased overall in the older women, among AMA primiparous women in our population, as compared to younger primiparas, there were more SGA neonates. This was true despite the fact that the incidence of gestational diabetes was increased in the primiparous AMA women as it was in the general AMA population. This finding has heretofore not been reported. The current study shows differential maternal outcomes and fetal morbidities that are increasingly based on increasing maternal age but partly on primiparity. Moreover, the relative good maternal outcome, particularly that there were no maternal deaths or near-misses, or severe maternal outcomes, is in sharp contrast to the results seen in a very recent report by the WHO Multicountry Survey on Maternal and Newborn Health [39] where 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East were surveyed for maternal and fetal outcome in 308,149 AMA women (C35 years) of whom 12.3 % had a singleton pregnancy compared to younger women with a singleton pregnancy. Their findings included maternal mortality and severe maternal outcome in addition to perinatal deaths and stillbirths [38]. Thus, the percent of AMA was comparable as was the study design, yet in our survey, there were no maternal or neonatal deaths, and the adverse outcomes were confined to morbidities. One possible explanation for these relatively benign outcomes as described in the current study might be good prenatal care and consistent monitoring enjoyed by all Israeli women (it is free to all Israeli citizens and hence compliance is high); in addition, periodic antenatal follow-up visits facilitate early decision making in cases of diagnosis of major fetal abnormalities. These latter point-of-care opportunities to monitor and provide early counseling in the cases of maternal and/or fetal complications may be the underlying explanation of the differences seen in the WHO countries and in our Jerusalem center. In summary, in addition to noting an increased incidence of maternal diabetes and hypertension, an increased incidence of LGA infants and emergency cesarean sections was seen in AMA women. Primiparous AMA women were also at greater risk for gestational diabetes than their younger counterparts but, unlike multiparous AMA women who had an increased risk of LGA babies, primiparous AMA women were at risk for SGA babies. Acknowledgments The authors would like to acknowledge the technical assistance of Ms. Rivka Farkash and Mr. Maymone Dahan of the SZMC Computer Services Department in accessing the archival material.
Conflict of interest None of the authors have any conflicts of interest to report. No special funding was received for the performance of this study.
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30. Lisonkova S, Janssen PA, Sheps SB, Lee SK, Dahlgren L (2010) The effect of maternal age on adverse birth outcomes: does parity matter? J Obstet Gynaecol Can 32(6):541–548 31. Juntunen KS, La¨a¨ra¨ EM, Kauppila AJ (1997) Grand grand multiparity and birth weight. Obstet Gynecol 90(4 Pt 1):495–499 32. Sacks DA (2007) Etiology, detection, and management of fetal macrosomia in pregnancies complicated by diabetes mellitus. Clin Obstet Gynecol 50:980–989 33. Akin Y, Co¨mert S, Turan C, Pic¸ak A, Ag˘zikuru T, Telatar B (2010) Macrosomic newborns: a 3-year review. Turk J Pediatr 52(4):378–383 34. Kaplan B, Harel L, Neri A, Rabinerson D, Goldman GA, Chayen B (1995) Great grand multiparity—beyond the 10th delivery. Int J Gynaecol Obstet 50:17–19 35. Schimmel MS, Eidelaman AI, Hammerman C, Zdaka P, Kornblut E (1997) Increased parity and risk of trisomy-21: review of 37,110 live births. BMJ 314:720–721 36. Doria-Rose VP, Kim HS, Augustine ET, Edwards KL (2003) Parity and the risk of Down’s syndrome. Am J Epidemiol 158(6):503–508 37. Materna-Kiryluk A, Wie˛ckowska B, Wis´niewska K, BorszewskaKornacka MK, Godula-Stuglik U, Limon J et al (2011) Maternal reproductive history and the risk of isolated congenital malformations. Paediatr Perinat Epidemiol 25(2):135–143 38. Lubchenco LO, Hansman C, Dressler M, Boyd E (1963) Intrauterine growth as estimated from liveborn birth-weight data at 24 to 42 weeks of gestation. Pediatrics 32:793–800 39. Laopaiboon M, Lumbiganon P, Intarut N, Mori R, Ganchimeg T, Vogel JP et al (2014) Advanced maternal age and pregnancy outcomes: a multicountry assessment. Br J Obstet Gynecol 121(Suppl 1):49–56
MATERNAL-FETAL MEDICINE
The effects of maternal age and parity on maternal and neonatal outcome Michael S. Schimmel • Ruben Bromiker • Cathy Hammerman • Lila Chertman Alexander Ioscovich • Sorina Granovsky-Grisaru • Arnon Samueloff • Deborah Elstein
•
Received: 5 January 2014 / Accepted: 10 September 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Purpose Delayed childbearing is increasingly common; hence, concerns emerge regarding potential for additional risks of delivery at advanced maternal age (AMA; C35 years). In this study, we sought to assess impact of AMA and parity on maternal and perinatal outcomes. Methods In this retrospective single-center study (July 2005 to October 2011), we compared spontaneously-conceived singleton births of AMA mothers with spontaneously-conceived singletons of mothers aged 24–27 years. Maternal outcomes: incidence of diabetes, hypertension, and emergency cesarean sections (ECS). Neonatal outcomes: prematurity, birth weight, incidence of small or large for gestational age infants (SGA/LGA, respectively), low birth weight (LBW), and 50 -Apgar scores. Subgroupings of maternal age were 35–38, 39–42, or 43–47 years; prematurity as \34 or \37 weeks; AMA
parity as primiparous, 2–5 births, 6–9 births, or C10 births. Binary logistic regression was used for multivariate analyses. Results Of 24,579 eligible women, 11,243 were AMA (14.0 % total singleton births) and 13,336 were aged 24–27 years (16.7 % total singleton births) at delivery. There were no maternal or perinatal deaths. Incidence of maternal hypertension and diabetes was significantly greater in AMA, especially oldest AMA. AMA including primiparous had significantly more ECS than younger including primiparous controls, respectively, and were more likely to deliver LGA neonates. Primiparous AMA women did not have increased incidence of LGA babies but significantly increased incidence of SGA infants. Conclusion AMA, especially primiparous, has more adverse maternal and neonatal outcomes than younger women; however, these did not include mortality. Consistent antenatal care may explain this.
This paper was presented (in part) at the Annual Meeting, Society of Pediatric Research, May 2012, Boston, MA USA.
Keywords Advanced maternal age Adverse maternal outcome Adverse neonatal outcome Prematurity Primiparity
M. S. Schimmel R. Bromiker C. Hammerman Department of Neonatology, Shaare Zedek Medical Center, Affiliated with the Hebrew University, Hadassah Medical School, Jerusalem, Israel L. Chertman S. Granovsky-Grisaru A. Samueloff D. Elstein (&) Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Affiliated with the Hebrew University, Hadassah Medical School, P.O. Box 3235, 12 Bayit Street, 91031 Jerusalem, Israel e-mail: [email protected] A. Ioscovich Department of Anesthesiology, Shaare Zedek Medical Center, Affiliated with the Hebrew University, Hadassah Medical School, Jerusalem, Israel
Introduction In 2002, Astolfi and Zonta [1] estimated that by the year 2025 about 25 % of mothers will begin their child-bearing period at an ‘‘advanced age’’. In developed countries, this may be a reflection of improved social conditions and educational status. The question of whether delaying the age of childbearing increases the risk of adverse outcome is of importance to women who consider postponing childbearing as well as to women who continue to expand their families and to the physicians who care for them [2].
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Israel is a developed country where antenatal care is universally available via a National Health Care System. Women are generally compliant with pre-natal care. Both the phenomena of delayed childbearing and of grand multiparity extending into advanced maternal ages are common among Israeli women and are independent of socio-economic status. Reports from various countries [2–13] describe significantly increased pregnancy related risks among AMA mothers when compared to younger mothers. Recent reports highlight an increased incidence of maternal hypertension and gestational diabetes mellitus [14–17], of non-elective cesarean delivery [14, 18–23] and instrumental deliveries [21, 22], and of preterm delivery [14, 16, 19, 22]. Adverse neonatal outcomes in infants of AMA mothers have been reported to include intrauterine growth restriction (IUGR), low birth weight (BW), stillbirth, and intrauterine fetal death (IUFD) [17, 22, 23, 25]. However, increased neonatal adverse events among AMA women are not universally reported [15, 21, 26–29]. Primiparity among AMA women appears to be a determinant of adverse neonatal outcome in AMA [4, 6, 8, 19, 23, 24, 29, 30], while multiparity in AMA mothers seems to be correlated with a lesser risk than primiparity (assuming there were no adverse events in the first pregnancy), other than the greater incidence of macrosomia among grand multiparas [31–33]. Nevertheless, there is a report of increased Neonatal Intensive Care Units (NICU) admissions and of birth trauma [33], congenital malformations, and increased chromosomal abnormalities among the infants of multiparous AMA [35–37]. The objective of this study was to assess adverse maternal and neonatal outcomes in AMA mothers compared to outcomes in younger women. A secondary objective was to assess the effect of parity in addition to AMA women on incidence of these adverse events.
All women who had any assisted reproductive technologies were excluded as were all women with multiple gestations. If there was more than one birth to a woman during the study period, only the first was included. The study was conducted in a single referral center and was exempt from Institutional Review Board approval because of its use of anonymized archival data. Maternal pregnancy-related health outcomes recorded included the incidence of diabetes [chronic diabetes mellitus type 2 and gestational diabetes (ICD code 648.0–648.04) were included as a single variable], hypertension [chronic and pregnancy-induced hypertension, HELLP syndrome (ICD code 014.2) and preeclampsia and preeclamptic toxemia (ICD codes 014.0 and 014.9) were included as a single variable], and emergency cesarean sections (ECS). For the purpose of the study, we defined any unplanned CS as emergency either due to suspected maternal or fetal compromise or dystocia of labor; etiologies included: bleeding with a low-lying placenta; placenta previa; cord presentation or prolapse; severe preeclamptic toxemia; severe pregnancy-induced hypertension; suspected uterine rupture; suspected placental abruption. Neonatal outcomes included prematurity (at least \37th week), birth weight, incidence of small or large for gestational age infants (SGA and LGA, defined respectively as \10th percentile and [90th percentile [38] for gestational age), low birth weight (LBW) infants (\2,500 g), and 50 Apgar scores. Advanced maternal age sub-groupings were further defined as follows: 35–38, 39–42, and 43–47 years; prematurity was further sub-divided as \34 weeks (early) or \37 weeks (late). AMA and control group parity were categorized as primiparous or multiparous. Neonatal admissions to the Intensive Care Unit (NICU) were not used as a measure of neonatal adverse outcome because of the variable and flexible criteria that were reflective of departmental policies over the study period, and also because of the institution of categorization into well-baby, intermediate, and NICU nurseries.
Materials and methods
Statistical analysis
We conducted a retrospective analysis of an electronic dataset of a single-center patient data from July 2005 to October 2011, in which we compared spontaneously-conceived singleton births of AMA women C35 years of age with similarly conceived singletons of mothers aged 24–27 years. This age range for the young controls was based on a consensus in the literature of an optimum 4-year range approximately one decade younger than the AMA group, but was also designed to exclude young gravida (\23 years of age) who have other unique adverse events because of their chronological age.
The Chi square test was used to compare frequencies of maternal complications across maternal age groups. Student’s t test and analysis of variance (ANOVA) were used to compare continuous variables within and between maternal age groups. Binary logistic regression was used for multivariable analyses of maternal and neonatal outcomes. Binary logistic regression was also used to analyze maternal and neonatal adverse outcome variables adjusted for parity, maternal hypertension, and diabetes (defined per coding in the hospital electronic computerized database). For the purpose of multivariable analyses of the whole
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cohort, in view of the large number of cases, all variables were included; in assessing primiparas only, since the numbers were much smaller, a multivariable model was built with only those variables which were significant (p \ 0.05) in the univariable analyses. A p value of \0.05 was considered significant. SPSS software was used.
Results During the study period 80,053 births were recorded, of which 24,579 women were potentially eligible for the study: 13,336 women aged 24–27 years constituted the control population (16.7 % of total singleton births) and 11,243 women aged C35 years constituted the AMA group (14.0 % of total singleton births). According to the intake records, all mothers had attended high school or beyond. All mothers had consistent antenatal care with follow-up of at least four antenatal visits according to the patient charts.
Table 1 Univariable (%) and multivariable [OR (CI)] analysis of adverse maternal and neonatal outcome AMA group (n = 11,243) relative to control group (n = 13,336)
Univariable analyses Control (%)
Table 2 Univariable (%) and multivariable [OR (CI)] analysis of maternal and neonatal adverse outcome among primiparous AMA (n = 326; 2.4 %) relative to primiparous control (n = 3,004; 26.7 %)
p value
AMA [OR (CI)]
p value
4.7
6.1
0.0001
1.25 (1.11–1.40)
0.0001
Maternal diabetes
1.2
6.6
0.0001
5.96 (4.95–7.17)
0.0001
Multiparity ([1)
77.47
97.1
0.0001
9.86 (8.73–11.13)
0.0001
Intrauterine fetal demise
0.1
0.2
NS
1.45 (0.90–2.32)
NS
Instrumental delivery
5.2
3.0
0.0001
1.09 (0.93–1.27)
NS
Emergency cesarean section
0.3
0.8
0.0001
2.46 (1.65–3.67)
0.0001
Gestational age \37 weeks
4.0
5.0
0.006
1.10 (0.94–1.29)
NS
Gestational age \34 weeks
1.2
1.0
NS NS
5 -Apgar B3
1.2
1.3
NS
0.93 (0.74–1.17)
Small for gestational age
7.5
5.7
0.0001
0.94 (0.84–1.05)
NS
Large for gestational age
8.2
14.7
0.0001
1.64 (1.51–1.79)
0.0001
Univariable analyses Control (%)
AMA (%)
Multivariable analyses p value
Maternal hypertension
4.1
2.8
NS
Maternal diabetes
2.1
6.7
0.0001
Intrauterine fetal demise
0.2
0.6
NS
14.4
20.2
Instrumental delivery
NS not statistically significant
AMA (%)
Multivariable analyses
Maternal hypertension
0
NS not statistically significant
Although intake records include questions regarding the use of alcohol, illicit drugs, smoking, and concomitant medications for chronic conditions as well as use of prenatal vitamins, this information was not tabulated for this study. Table 1 presents the univariable and multivariable analyses of adverse maternal and neonatal outcomes in the AMA group relative to the young control group. The rates of intrauterine fetal death are low because many women who carry fetuses with diagnosed abnormalities are offered early elective abortions, and hence intrauterine death at term is distinctly rare in these women who are monitored at least four times before birth. Maternal hypertension and diabetes as well as the incidence of ECS and LGA neonates were significantly increased in AMA mothers. Table 2 presents the univariable and multivariable analyses of adverse outcomes among primiparas in the AMA group relative to the control group. There were 3,004 (26.7 %) primipara in the control population aged
0.007
AMA [OR (CI)]
p value
3.58 (2.09–5.79)
0.0001
1.59 (1.19–2.14)
0.002
Emergency cesarean section
0.2
1.5
0.004
4.03 (1.17–13.81)
0.026
Gestational age \37 weeks
4.2
8.3
0.002
1.36 (0.75–2.49)
0.30
Gestational age \34 weeks
1.1
2.5
NS
50 -Apgar B3
0.4
0.6
NS
Small for gestational age
11.3
18.4
0.0001
1.51 (1.06–2.16)
0.02
Large for gestational age Low birth weight
5.3 5.7
5.2 12.6
NS 0.0001
1.65 (0.98–2.77)
0.058
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Arch Gynecol Obstet Table 3 Univariable analysis of percent adverse maternal and neonatal outcome among the AMA sub-groups relative to control group
NS not statistically significant * \0.05, ** \0.0001
Outcome/maternal age
24–27 years (n = 13,336)
39–42 years (n = 3,214)
43–47 years (n = 694) 7.3**
Maternal hypertension
4.7
5.9**
6.4**
Maternal diabetes
1.2
5.2**
8.6**
11.7**
Intrauterine fetal demise
0.1
0.2 (NS)
0.2*
0.0 (NS)
Instrumental delivery
5.2
3.1
2.7
2.6**
Emergency cesarean section
0.3
0.7**
1.2**
0.9*
Gestational age \37 weeks
4.0
4.7*
5.6**
5.2**
Gestational age \34 weeks
1
1.2
1.3
0.7 (NS)
50 -Apgar B3
1.2
1.1 (NS)
1.8*
1.2 (NS)
Small for gestational age
7.5
5.8**
5.2**
6.6 (NS)
Large for gestational age
8.2
14.1**
15.7**
15.6**
24–27 years and 326 (2.4 %) primipara among the AMA women. The presence of diabetes was significantly increased among AMA primiparas relative to the control primiparas, as were ECS and the use of instrumental delivery. There was a significantly increased incidence of intrauterine growth retardation among babies born to primiparous AMA women relative to younger primiparas. Table 3 details univariable analysis of percent adverse maternal and neonatal outcomes among the AMA mothers sub-divided by age: 35–38 years (7,335; 65.2 %); 39–42 years (3,214; 28.6 %), and 43–47 years (694; 6.2 %) and compared to control group mothers. Maternal hypertension and diabetes were associated with increasing age. ECS deliveries, prematurity (\37 weeks), and the proportion of LGA infants were increased in each of the age subgroups relative to younger controls, but the increase was not progressive with advancing maternal age. The percent of neonates born SGA significantly decreased in the all the AMA age subgroups (7.5–5.8–5.2 %) as compared to the neonates of younger controls while the percent of LGA significantly increased across AMA age groups (8.2–14.1–15.7 %). The numbers of women with chronic hypertension or diabetes mellitus type 2, were included in the respective categories of hypertension and diabetes. When comparing all AMA to younger controls (Table 1), there was a significant difference in incidence of maternal hypertension (6.1 versus 4.7 %), but when comparing only primiparous AMA to primiparous controls (Table 2: 2.8 versus 4.1 %), there was no significant difference. The significant increase in incidence of maternal hypertension among the AMA was directly correlated with increasing age up to 7.3 % in the oldest AMA (Table 3). Similarly, there was a significant difference in incidence of maternal diabetes between
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35–38 years (n = 7,335)
all AMA and all younger controls (Table 1: 606 versus 1.2 %) but also between primiparous AMA and younger primiparous (Table 2: 6.7 versus 2.1 %) which again was seen to increase significantly across AMA groups (Table 3) up to 11.7 % among the oldest.
Comment Delaying the onset of child-bearing is becoming an increasingly popular choice for contemporary women. As a result, concern has arisen as to whether older women in a first pregnancy pose an increased risk for maternal and neonatal pregnancy-related complications relative to younger primiparas. While most AMA (C35 years) women with a spontaneous singleton pregnancy have an uncomplicated outcome, several recent studies show that compared to younger women, pregnant AMA women have significantly higher risks of hypertension and gestational diabetes. Our study corroborates these findings and additionally shows that the older the woman, the greater the risk of developing each of these morbidities. Primiparous AMA women were also at greater risk for gestational diabetes but not for hypertension than the control group. Neonatal outcomes were not significantly affected by maternal age other than the increased incidence of LGA infants among AMA mothers. Although it could be argued that large infants may merely reflect co-morbidity with maternal diabetes and multiparity [31, 34], the increased LGA incidence remained significant after adjusting for the latter two variables in the multivariable analyses. Therefore, our data indicate that the birth of an LGA infant is independently associated with AMA.
Arch Gynecol Obstet
The secondary objective was to study the contribution of primiparity among the AMA mothers to adverse pregnancy-related events. Interestingly, while the incidence of LGA infants was increased overall in the older women, among AMA primiparous women in our population, as compared to younger primiparas, there were more SGA neonates. This was true despite the fact that the incidence of gestational diabetes was increased in the primiparous AMA women as it was in the general AMA population. This finding has heretofore not been reported. The current study shows differential maternal outcomes and fetal morbidities that are increasingly based on increasing maternal age but partly on primiparity. Moreover, the relative good maternal outcome, particularly that there were no maternal deaths or near-misses, or severe maternal outcomes, is in sharp contrast to the results seen in a very recent report by the WHO Multicountry Survey on Maternal and Newborn Health [39] where 359 health facilities in 29 countries in Africa, Asia, Latin America, and the Middle East were surveyed for maternal and fetal outcome in 308,149 AMA women (C35 years) of whom 12.3 % had a singleton pregnancy compared to younger women with a singleton pregnancy. Their findings included maternal mortality and severe maternal outcome in addition to perinatal deaths and stillbirths [38]. Thus, the percent of AMA was comparable as was the study design, yet in our survey, there were no maternal or neonatal deaths, and the adverse outcomes were confined to morbidities. One possible explanation for these relatively benign outcomes as described in the current study might be good prenatal care and consistent monitoring enjoyed by all Israeli women (it is free to all Israeli citizens and hence compliance is high); in addition, periodic antenatal follow-up visits facilitate early decision making in cases of diagnosis of major fetal abnormalities. These latter point-of-care opportunities to monitor and provide early counseling in the cases of maternal and/or fetal complications may be the underlying explanation of the differences seen in the WHO countries and in our Jerusalem center. In summary, in addition to noting an increased incidence of maternal diabetes and hypertension, an increased incidence of LGA infants and emergency cesarean sections was seen in AMA women. Primiparous AMA women were also at greater risk for gestational diabetes than their younger counterparts but, unlike multiparous AMA women who had an increased risk of LGA babies, primiparous AMA women were at risk for SGA babies. Acknowledgments The authors would like to acknowledge the technical assistance of Ms. Rivka Farkash and Mr. Maymone Dahan of the SZMC Computer Services Department in accessing the archival material.
Conflict of interest None of the authors have any conflicts of interest to report. No special funding was received for the performance of this study.
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