Accepted Manuscript

Title: Effect of advanced maternal age on maternal and

neonatal outcomes in assisted reproductive technology
pregnancies

Authors: Amirhossein Moaddab, Frank A. Chervenak,

Laurence B. Mccullough, Haleh Sangi-Haghpeykar, Amir A.
Shamshirsaz, Amy Schutt, Sara E. Arian, Karin A. Fox, Gary
A. Dildy, Alireza A. Shamshirsaz

PII: S0301-2115(17)30363-9
DOI: http://dx.doi.org/doi:10.1016/j.ejogrb.2017.07.029
Reference: EURO 9999

To appear in: EURO

Received date: 14-4-2017

Revised date: 25-6-2017
Accepted date: 23-7-2017

Please cite this article as: Moaddab Amirhossein, Chervenak Frank A, Mccullough
Laurence B, Sangi-Haghpeykar Haleh, Shamshirsaz Amir A, Schutt Amy, Arian
Sara E, Fox Karin A, Dildy Gary A, Shamshirsaz Alireza A.Effect of advanced
maternal age on maternal and neonatal outcomes in assisted reproductive technology
pregnancies.European Journal of Obstetrics and Gynecology and Reproductive Biology
http://dx.doi.org/10.1016/j.ejogrb.2017.07.029

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 1

Category: Research Article

Title: Effect of advanced maternal age on maternal and neonatal outcomes in assisted

reproductive technology pregnancies

Running title: Assisted reproductive technologies in mid-life women

Amirhossein MOADDAB1 (M.D); Frank A CHERVENAK2 (M.D); Laurence B

MCCULLOUGH2 (Ph.D); Haleh SANGI-HAGHPEYKAR1 (Ph.D); Amir A SHAMSHIRSAZ1

(M.D); Amy SCHUTT1 (M.D); Sara E. ARIAN1 (M.D); Karin A. FOX1 (M.D.; M.Ed.); Gary A

DILDY1 (M.D); Alireza A SHAMSHIRSAZ1 (M.D)

1
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, United

States

2
Department of Obstetrics and Gynecology, Weill Medical College of Cornell University/New

York Presbyterian Hospital, New York, NY, United States

Corresponding author: Alireza A. Shamshirsaz, M.D.

Assistant Professor, Department of Obstetrics and Gynecology, Baylor College of Medicine

Address: F1040-04, 6621 Fannin St, Pavilion For Women, Houston, TX 77030

Email: shamshir@bcm.edu; alirezashamshirsaz@yahoo.com

Phone: 832-826-7470; Fax: 832-825-9351

 2

CONDENSATION

Advanced maternal age in pregnancies conceived with assisted reproductive technologies is

associated with an increased risk for maternal morbidities, even after adjusting for several

factors.

ABSTRACT

Effect of advanced maternal age on maternal and neonatal outcomes in assisted

Amirhossein MOADDAB; Frank A CHERVENAK; Laurence B MCCULLOUGH; Haleh

SANGI-HAGHPEYKAR; Amir A SHAMSHIRSAZ; Amy SCHUTT; Sara E. ARIAN; Karin A.

FOX; Gary A DILDY; Alireza A SHAMSHIRSAZ

Objectives: To compare maternal and neonatal outcomes between women with assisted

reproductive technologies pregnancy aged <40, 40-44, 45-49, and ≥50 years.

Study Design: In a population-level analysis study, all live births by ART identified on birth

certificate between 2011 and 2014 were extracted (n = 101,494) using data

from the Center for Disease Control and Prevention-National Center for Health Statistics (CDC-

NCHS). We investigated and compared maternal and neonatal outcomes based on conditions

routinely listed on birth certificates.

Results: Of 101,494 ART live births, 79,786 (78.6%), 16,186 (15.9%), 4,637 (4.6%), and 885

(0.9%) were delivered by women aged <40, 40-44, 45-49, and ≥50 years, respectively.

Comparing to women aged<40 years, women aged 40-44, 45-49, and ≥50 years were at

increased risk for gestational hypertension (aRR: 1.26, 1.55, and 1.61, respectively), gestational

diabetes (aRR: 1.23, 1.40, and 1.31, respectively), eclampsia (aRR: 1.49, 1.51, and 2.37,

respectively), unplanned hysterectomy (aRR: 2.55, 4.05, and 3.02, respectively), and ICU

admission (aRR: 1.64, 2.06, and 2.04, respectively). The prevalence of preterm delivery was
 3

slightly higher in women aged 45 and older. (35%, 36.9%, and 40.2% in women aged <40 years,

45-49 years, and ≥50 years, respectively)

Conclusions: Advanced age ART was significantly associated with higher rates of maternal

morbidities. Except for preterm delivery, neonatal outcomes were similar between ART

pregnancies in women aged ≥45 years and younger women. These data should be interpreted

with caution because of potential confounding by potentially higher use of donor eggs by older

women, the exact rates for which we were unable to ascertain from the available data.

KEYWORDS: Assisted reproductive technology; Advanced maternal age; Pregnancy outcome;

In vitro fertilization

INTRODUCTION

The average woman’s age at the first birth increased between 2000 to 2014, with most of the

increase occurring from 2009 (25.2 years) to 2014 (26.3 years).1 Increasing age is associated

with reduced fecundity and fertility. This results in an increased demand for assisted

reproductive technology (ART) services by women who delayed their reproduction secondary to

a wide range of social and non-reproductive factors.2 In 2013, the American Society For

Reproductive Medicine (ASRM) published the updated committee opinion regarding

oocyte/embryo donation to women of advanced age. The ARSM stated that “the medical risks to

the mother and child are of paramount concern, but it will be many years before adequate data

are available to evaluate these issues.”3 At present, ARTs including in vitro fertilization (IVF)

and intracytoplasmic sperm injection (ICSI) are considered among the most promising and

practical infertility treatments. Despite this fact, many previously published studies established
 4

the high rate of adverse obstetric outcomes in ART pregnancies, compared to naturally

conceived pregnancies.4

As emphasized in the ASRM opinion, the data on maternal and neonatal outcomes in women of

advanced age remains scant.3 Previous research in small cohorts of women of advanced maternal

age has shown controversial results regarding the relationship between increased risk of

pregnancy complications and associated mortality in advanced aged women.5,6 Specifically, the

articles which have been cited in the ASRM opinion have been done on a limited number of

women with advanced age or are outdated.5,7–10 Moreover, some of these studies investigated the

outcomes in heterogeneous populations composed of both ART pregnancies and naturally

conceived pregnancies.

The increasing use of ART has generated the need to advance our knowledge regarding maternal

and neonatal outcomes of the ART pregnancies specific to women of advanced maternal age.

The ASRM committee opinion is focused more on women aged 50 years and above, [3] which

constitutes a minority of patients who are able to conceive. For the purposes of this study, we

considered age greater than 40 years as advanced maternal age. A majority of patients who

undergo ART do so because of subfertility or infertility – otherwise ART would be unnecessary.

From a clinical standpoint, women undergoing ART cannot “choose” to conceive naturally

(although a small proportion have spontaneous conception while preparing for ART), however

they can choose the age at which they will pursue ART based on anticipated outcomes.

Therefore, rather than compare maternal outcomes between these two groups, we aimed to

compare maternal and neonatal outcomes between women with ART pregnancy across various

age groups at the time of delivery: <40, 40-44, 45-49, and ≥50 years.

MATERIALS AND METHODS

 5

This study was exempt from human subject research regulatory and institutional review board

approval because we used publicly available data that does not contain any personal identifiers.

We utilized the live birth data from the Centers for Disease Control and Prevention’s National

Center for Health Statistics (NCHS) between 2011 and 2014, which is collected from the U.S.

Standard Certificates of Live Birth. Since 2010, some states have reported data on births

resulting from ART procedures. Despite the fact that births resulting from ART procedures are

underreported on the birth certificate11, publicly available U.S. birth certificate data provides a

reasonably large source of data from which to study the outcome of pregnancies conceived using

ART. These data represent all residents’ live births and non-residents’ live births registered in

the 50 States and the District of Columbia. By definition, “live birth means the complete

expulsion or extraction from its mother of a product of human conception, irrespective of the

duration of pregnancy, which, after such expulsion or extraction, breathes, or shows any other

evidence of life.”12

There is a general checkbox question about whether the pregnancy resulted from infertility

treatment. If the answer is “yes” (box checked) then the infertility treatments are grouped into

two separate categories: 1) Fertility enhancing drugs, artificial insemination, or intrauterine

insemination (IUI) and 2) Assisted reproductive technology (e.g. in vitro fertilization (IVF),

gamete intra-fallopian transfer (GIFT)). ART procedures are those in which both egg and sperm

are handled in the laboratory, e.g. in IVF and GIFT.12 For the purpose of this study, we included

only the second group.

For 2011-2014, a subset of the revised state reporting area reported information on the type of

infertility treatment used. These subsets includes 27 states and the District of Columbia,

representing 67 percent of 2011 births, 29 states and the District of Columbia, representing 71.2
 6

percent of 2012 births, 34 states and the District of Columbia, representing 78.7 percent of 2013

births, and 43 states and the District of Columbia, representing 88.9 percent of 2014.12–15

We investigated and compared maternal and neonatal outcomes among study groups based on

conditions that appear on the birth certificates. Maternal characteristics, early adverse maternal

outcomes, and complications included: gestational hypertension, gestational diabetes, method of

delivery, chorioamnionitis, uterus rupture, unplanned hysterectomy, transfusion, and admission

to ICU. Neonatal characteristics and outcomes included: gestational age (GA) at delivery, birth

weight (BW), APGAR at 5 and 10 minutes, assisted ventilation immediately after birth, assisted

ventilation >6 hours, neonatal intensive care unit (NICU) admission, antibiotic therapy, and

seizures. We also assessed the rate of chromosomal disorders and congenital anomalies including

anencephaly, gastroschisis, spina bifida/meningomyelocele, omphalocele, congenital

diaphragmatic hernia, and cyanotic congenital heart disease.

The risk of various maternal and neonatal outcomes was compared among ART pregnancies in

women aged <40 years to women aged 40-44, 45-49, and ≥50 years. Pregnancies conceived

using fertility enhancing druges, artificial insemination or IUI were excluded. Relative risks for

the outcomes were computed using generalized mixed models (proc GENMOD in SAS). The

GENMOD procedure fits a generalized linear model to the data by maximum likelihood

estimation. Confounders were assessed and controlled for by including them in the model

(adjusted RR), and corresponding 95% confidence intervals (CI) were provided. P<.05 was

considered significant. All analyses were performed in SAS statistical software (version 9.4,

Cary, NC)

RESULTS
 7

From 2011 to 2014, there were 15,826,688 reported live births in the U.S., of which 101,494

(.64%) were identified as products of ART conception based on available birth certificate data.

The rate of ART live births in 2011, 2012, 2013, and 2014 was 0.62%, 0.68%, 0.73%, and

0.79%, respectively. Among ART pregnancies, 79,786 (78.6%), 16,186 (15.9%), 4,637 (4.6%),

and 885 (0.9%) live infants were delivered by mothers aged <40, 40-44, 45-49, and ≥50 years,

respectively. Demographic, lifestyle, health, and socioeconomic characteristics for ART live

births with regards to maternal age are demonstrated in Table 1. The majority of live births

secondary to ART procedures occurred in multiparous women. The overall prevalence of early

adverse maternal outcomes, medical, and obstetric complications are shown in Table 2.

The risk for gestational hypertension, gestational diabetes, eclampsia, unplanned hysterectomy,

ICU admissions, and maternal transfusion increased with advancing maternal age. As

demonstrated in Table 3, the risk for these conditions remained significantly higher even after

adjusting for several potential confounders including demographic, lifestyle, health, and

socioeconomic characteristics.

The prevalence of early neonatal outcomes and medical complications are shown in Table 4.

Although the risk for NICU admission was slightly higher for offspring of women aged 50 years

and more, the risk of assisted ventilation imnmediately after delivery and assisted ventilation >6h

were not higher when compared to offspring of younger women. (Table 5) Advanced maternal

age at the time of ART was not associated with an increased risk of chromosomal disorders,

anencephaly, Down’s syndrome, gastroschisis, neural tube defects, omphalocele, congenital

heart defects, or cyanotic heart defects.

COMMENT
 8

In this population-level analysis of ART pregnancies, advanced maternal age was associated

with a significantly higher risk for maternal morbidities. There was no statistically significant

difference in early neonatal outcomes between ART pregnancies in women aged <40 years and

their older counterparts.

Other studies have found that pregnancy in women aged 45 years and older is associated with

and increased risk of maternal morbidity and mortality including: cesarean delivery, transfusion,

myocardial infarction, cardiac arrest, deep vein thrombosis, death, and fetal demise when

compared to their younger peers.16,17 Evidence of the odds for maternal and neonatal morbidity

in advanced age women conceived with ART is unequivocal.6,18,19 Our study supports the

findings of Kenny et al6 that even after adjusting for several health characteristics, socio-

economic, and setting-related factors, the odds for maternal morbidities in older women is still

higher than that for younger women. It is unknown that to what extent an established health care

center with high-quality care may reduce or mitigate ART risk in this population.

Although this study has important strengths, several limitations must be considered when

interpreting study findings. Previous studies chose different cut-off points ranged from 43 to 50

years as what usually called “advanced-age”.5,8–10,20 The ASRM committee opinion focuses on

women aged 50 years and more.3 For the purpose of this study, we categorized maternal age into

4 groups including <40, 40-44, 45-49, and ≥50 years, to permit evaluation of risk over a

spectrum of time. This methodology has the potential to provide a better clinical insight into the

trends of maternal and neonatal trends across different maternal age groups.

The study population was diverse in terms of age, race, socio-economic characteristics and

includes a large national dataset that provides the ability to identify ART-conceived pregnancies,

which provides generalizability. However, despite improvements in the birth certificate form,
 9

considerable limitations remain inherent to any study using birth certificate data. The

homogeneity, accuracy, and quality of the data collected, including the reporting about the

specific form of ART used during pregnancy may not be as robust as with a chart review.21,22

Women over 40 are more prone to use oocyte donation than younger women. In 2013, 38% and

73% of cycles in women aged 43-44 years and women aged >44 years used donor eggs or

embryos, respectively.23 There is no data regarding the use of donor eggs or whether embryos

were transferred fresh or frozen listed on the birth certificate data. Data regarding prenatal

genetic screening (PGS) or termination was also unavailable. It possible that our findings that

age at time of ART was not associated with an increased risk of neonatal chromosomal and

congenital anomalies reflect selection of chromosomally normal embryos or termination of

pregnancies.

Comparing ART live birth rates based on the birth certificate and numbers from the National

ART Surveillance System (NASS), shows that about half of ART live births are not reported on

birth certificates.24,25 In order to minimize the effects of underreported ART pregnancies and the

problem of dealing with an inaccurate control group consisting of a mixed group of ART and

non-ART pregnancies, we limited our analysis to only live births that were identified as ART

pregnancies in CDC data.

Our study showed higher risk for preterm delivery in women aged 45-49 years and ≥50 years;

other neonatal outcomes were similar among different age groups. However, we should consider

the study limitations in that ART pregnancies which resulted in miscarriage, termination,

intrauterine fetal demise or neonatal death are either not included or cannot be deduced from the

birth certificate data. Advanced maternal age accounts for an increased risk of spontaneous

abortion and poor long-term neonatal outcomes (e.g. dominant autism spectrum disorders) in
 10

offspring.2 In addition, with regards to some variables like anencephaly, the number of

diagnosed and reported cases was too small to perform an accurate analysis.

The higher prevalence of cesarean delivery (CD) among older women may be secondary to a

higher prevalence of the history of previous CD or placenta accreta or an increased need for

emergency CD due to the development of maternal-fetal complications like preeclampsia.

Considering maternal outcomes, there were no data available regarding maternal mortality and

long-term follow-up of older women conceived with ART. A better understanding of the long-

term outcomes following ART and the impact on the quality of life of women conceived with

ART at advanced age is required to better counsel patients, particularly younger women who are

considering family planning and their reproductive options.

In our study, the rate of singleton pregnancies was higher in women aged <40 years. (<.0001)

Previous studies demonstrated that older women undergo a higher number of embryo transfer

procedures that put them at higher risk for multiple gestations.26 In addition, IVF and multiple

gestations significantly increase the risk for several morbidities such as CD and preterm

delivery.8

ART pregnancies secondary to oocyte donation are at a higher risk for development of

preeclampsia which is compatible with our results, and may account for some of the increased

risk we identified. 20,23 In more than 70% and more than 95% of autologous ART births to

women ≥45 years and women ≥50 years, frozen oocytes or embryos were used, respectively.27

This study documents the risks of maternal morbidities, about which patients of advanced

maternal age should be routinely informed. The low absolute and relative risks of maternal

morbidity do not, however, support making a recommendation against ART. In the informed
 11

consent process, the patient should be informed about the clinical benefits and risks of clinical

management. Shared decision making should therefore be employed with the goal of a well-

informed decision by the patient.28 Further studies are needed to investigate the role of

preconception maternal health characteristics in increasing the odds for maternal morbidity and

mortality and long-term adverse outcome in the offspring of women who conceive via ART.

CONFLICTS OF INTEREST: None

AUTHORSHIP: All authors have met the criteria for authorship and contributed to the present

study.

ACKNOWLEDGEMENTS: None
 12

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(24) Moaddab A, Bateni ZH, Dildy G, Clark SL. Poor compliance and lack of improvement in

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(25) Cohen B, Bernson D, Sappenfield W, Kirby RS, Kissin D, Zhang Y, et al. Accuracy of

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[Epub ahead of print]

 16

TABLES

Table 1. Demographic, lifestyle, health, and socioeconomic characteristics for ART live births

with regards to maternal age, United States, 2011-2014

Characteristic Maternal Maternal age Maternal Maternal

age<40 40-44 age 45-49 age≥50***

Total number of pregnancies 79,786 (78.6) 16,186 (15.9) 4,637 (4.6) 885 (0.9)

Maternal age (years) 33.3±3.7 41.6±1.4 46.4±1.3 50.0

Father’s age (years) 38.1±12.5 47.4±16.3 51.9±17.6 57.2±18.3

BMI (kg/m2) 27.8±14.3 28.5±15.4 28.4±15.6 30.3±18.6

Race Non- 42,018 (52.7) 8,086 (50.0) 2,132 (46.0) 345 (39.0)

Hispanic

White

Non- 4,252 (5.3) 1,039 (6.4) 324 (7.0) 8 (9.0)

Hispanic

Black

Hispanic 25,488 (32.0) 4,981 (30.8) 1,386 (30.0) 239 (27.0)

Other races 7,009 (8.8) 1,614 (10.0) 481 (10.4) 122 (13.8)

Unknown 1,019 (1.2) 466 (2.8) 314 (6.6) 99 (11.2)

Nulliparous 43,042 (53.9) 8,030 (49.6) 2,017 (43.5) 290 (32.8)

Unmarried mother 4,275 (5.4) 1,927 (11.9) 801 (17.3) 166 (18.8)

Mother’s Less than 909 (1.1) 109 (0.7) 46 (1.0) 9 (1.0)

education 12th grade

 17

12th grade 4,675 (5.9) 684 (4.2) 214 (4.6) 53 (6.0)

More than 72,560 (90.9) 14,664 (90.6) 3,911 (84.3) 633 (71.5)

12th grade

Unknown 1,642 (2.1) 729 (4.5) 466 (10.1) 190 (21.5)

Father’s Less than 1,198 (1.5) 137 (0.8) 61 (1.3) 6 (0.7)

education 12th grade

12th grade 7,449 (9.3) 1,001 (6.2) 321 (6.9) 59 (6.7)

More than 66,803 (83.8) 13,119 (81.1) 3,439 (74.2) 573 (64.8)

12th grade

Unknown 4,336 (5.4) 1,929 (11.9) 816 (17.6) 247 (27.8)

Smoking 643 (0.6) 72 (0.4) 6 (0.1) 2 (0.2)

Diabetes 677 (0.9) 190 (1.2) 50 (1.1) 13 (1.5)

Chronic hypertension 1,826 (2.3) 613 (3.8) 231 (5.0) 45 (5.1)

Previous Cesarean delivery 9,130 (11.4) 2,656 (16.4) 917 (19.8) 202 (22.8)

Interval since No previous 30,535 (54.6) 4,757 (43.8) 1,138 (39.8) 174 (33.3)

last pregnancy pregnancy

<12 month 1,988 (3.5) 370 (3.4) 73 (2.6) 12 (2.3)

12-23 7,881 (14.1) 1,956 (18.0) 424 (14.8) 60 (11.5)

24-35 5,600 (10.0) 1,243 (11.5) 345 (12.1) 76 (14.6)

35-47 3,701 (6.6) 823 (7.6) 234 (8.2) 47 (9.0)

≥48 6,275 (11.2) 1,703 (15.7) 643 (22.5) 153 (29.3)

Number of Less than 10 13,309 (16.7) 2,666 (16.5) 780 (16.9) 162 (18.3)

prenatal visits 10 or more 63,222 (79.2) 12,832 (79.3) 3,667 (79.1) 686 (77.5)
 18

Unknown 3,255 (4.1) 688 (4.2) 190 (4.0) 37 (4.2)

Gestation Singleton 43,485 (54.5) 9,830 (60.7) 2,571 (55.4) 470 (53.1)

Twin 33,376 (41.8) 5,996 (37.1) 1,980 (42.7) 399 (45.1)

Triplet or 2,925 (3.7) 360 (2.2) 86 (1.9) 16 (1.8)

more

Weight gain <11 3,822 (4.8) 796 (4.9) 302 (6.5) 67 (7.6)

(pound) 11-20 8,673 (10.9) 2,135 (13.2) 645 (13.9) 141 (15.9)

21-30 19,680 (24.7) 4,338 (26.8) 1,297 (28.0) 244 (27.6)

31-40 20,967 (26.3) 4,184 (25.9) 1,082 (23.3) 178 (20.1)

41-98 23,190 (29.1) 3,907 (24.1) 1,058 (22.8) 187 (21.1)

Unknown 3,453 (4.2) 826 (5.1) 253 (5.5) 68 (7.7)

Payment Medicaid 3,054 (3.8) 388 (2.4) 215 (4.6) 38 (4.3)

source Private 72,787 (91.2) 15,037 (92.9) 4,153 (89.6) 776 (87.7)

Self-pay 925 (1.2) 222 (1.4) 110 (2.4) 31 (3.5)

Other 2,069 (2.6) 343 (2.1) 97 (2.1) 31 (3.5)

governmental

Unknown 951 (1.2) 196 (1.2) 62 (1.3) 9 (1.0)

* Data are reported as number (proportion) and mean ± standard deviation.

**All relationships are significant (P<.001) except for diabetes (.07) and prenatal visits (.21).

*** Maternal age for births to women aged 50 to 64 years was documented as 50 years.
 19

Table 2. Early maternal outcomes, medical, and obstetrics complications for ART pregnancies

with regards to maternal age, United States, 2011-2014

Characteristic Maternal Maternal age Maternal age Maternal

age<40 40-44 45-49 age≥50

Gestational hypertension 8,343 (10.5) 2,061 (12.7) 724 (15.6) 149 (16.8)

Gestational diabetes 7,635 (9.6) 1,919 (11.9) 645 (13.9) 119 (13.5)

Eclampsia 423 (0.5) 123 (0.8) 36 (0.8) 11 (1.2)

Chorioamnionitis 1,843 (2.3) 336 (2.1) 105 (2.3) 12 (1.4)

Method of Spontaneous 28,787 4,385 (27.1) 923 (19.9) 173 (19.6)

delivery vaginal (36.1)

Operative 3,241 (4.1) 566 (3.5) 134 (2.9) 18 (2.0)

vaginal

Cesarean 47,685 11,218 (69.3) 3,577 (77.1) 694 (78.4)

(59.7)

Unknown 73 (0.1) 17 (0.1) 3 (0.1) 0

Ruptured uterus 30 (0.04) 10 (.06) 2 (0.04) 1 (0.11)

Unplanned hysterectomy 134 (0.2) 71 (0.4) 35 (0.8) 6 (0.7)

ICU admission 362 (0.5) 120 (0.7) 47 (1.0) 9 (1.0)

Maternal transfusion 1,065 (1.3) 234 (1.5) 94 (2.0) 18 (2.1)

* Data are reported as number (proportion) and mean ± standard deviation.

**All relationships are significant (P<.001).

 20

Table 3. Crude and adjusted relative risks of the association between maternal age and early

maternal outcomes, medical, and obstetrics complications for ART pregnancies, United States,

2011-2014

Characteristic Maternal age 40-44 Maternal age 45-49 Maternal age≥50

RR Adjusted RR Adjusted RR (95% Adjusted

(95% RR (95% (95% RR (95% CI) RR (95%

CI) CI) CI) CI) CI)

Gestational 1.22 1.26 (1.19- 1.49 1.55 (1.45- 1.61 1.70 (1.74-

hypertension (1.64- 1.31) (1.39- 1.67) (1.39- 1.97)

1.27) 1.60) 1.87)

Gestational diabetes 1.24 1.23 (1.18- 1.45 1.40 (1.29- 1.41 1.31 (1.11-

(1.18- 1.30) (1.35- 1.50) (1.19- 1.55)

1.30) 1.57) 1.66)

Eclampsia 1.43 1.49 (1.22- 1.46 1.51 (1.10- 2.34 2.37 (1.30-

(1.17- 1.83) (1.04- 2.12) (1.29- 4.31)

1.75) 2.06) 4.25)

Chorioamnionitis 0.90 0.93 (0.83- 0.98 1.04 (0.85- 0.59 0.63 (0.36-

(0.80- 1.04) (0.81- 1.27) (0.33- 1.10)

1.01) 1.19) 1.03)

Method Operative 1.13 1.16 (1.06- 1.25 1.31 (1.12- 0.93 0.99 (0.65-

of vaginal (1.04- 1.26) (1.07- 1.55) (0.60- 1.56)

delivery 1.23) 1.47) 1.45)

 21

Cesarean 1.15 1.03 (1.02- 1.28 1.04 (1.03- 1.28 1.03 (1.02-

(1.14- 1.04) (1.26- 1.05) (1.24- 1.04)

1.17) 1.30) 1.33)

Ruptured uterus 1.64 1.69 (0.72- 1.15 - 3.02 -

(0.80- 3.04) (0.28- (0.41-

3.36) 4.81) 22.08)

Unplanned 2.61 2.55 (1.91- 4.51 4.05 (2.76- 3.02 3.02 (1.32-

hysterectomy (1.96- 3.42) (3.12- 5.95) (1.79- 6.94)

3.48) 6.52) 9.15)

ICU admissions 1.64 1.64 (1.33- 2.24 2.06 (1.51- 2.25 2.04 (1.05-

(1.33- 2.01) (1.65- 2.81) (1.16- 3.96)

2.01) 3.03) 4.34)

Maternal 1.08 1.12 (0.97- 1.52 1.55 (1.26- 1.53 1.56 (0.98-

transfusion (0.94- 1.29) (1.23- 1.92) (0.96- 2.48)

1.25) 1.84) 2.42)

⃰ Adjusted for mother’s race, education, smoking, marital status, weight gain, previous

cesarean, and interval since last pregnancy.

 22

Table 4. Early neonatal outcomes, medical, and obstetrics complications for ART pregnancies

with regards to maternal age, United States, 2011-2014 ⃰

Characteristic Maternal Maternal Maternal Maternal

age<40 age 40-44 age 45-49 age≥50

Gestational age at ≤28 3,101 (3.9) 447 (2.8) 140 (3.0) 27 (3.1)

delivery (weeks) 28<GA<34 7,775 (9.8) 1,367 (8.5) 467 (10.1) 114 (12.9)

34≤GA<37 16,962 3,385 (20.9) 1,101 (23.8) 214 (24.2)

(21.3)

≥37 51,888 10,977 (67.9) 2,926 (63.1) 530 (59.9)

(65.1)

Mean gestational age at delivery 36.9±0.1 37.2±0.1 36.9±0.1 36.5±0.1

(weeks)

Birth weight <1500 5373 (6.8) 833 (5.2) 250 (5.4) 76 (8.6)

(grams) 1500-2499 19,286 3,662 (22.7) 1,195 (25.8) 229 (25.9)

(24.3)

2500-3999 50,778 10,766 (66.3) 2,966 (64.1) 541 (61.1)

(63.8)

≥4000 4,109 (5.2) 897 (5.6) 220 (4.8) 39 (4.4)

Mean birth weight (grams) 2,841±7 2,916±13 2,844±29 2,746±54

Apgar at 5 min <7 3,075 (3.9) 524 (3.2) 145 (3.1) 26 (2.94)

Apgar at 10 min <7 1,049 (1.3) 136 (0.8) 40 (0.9) 10 (1.1)

Immediately assisted ventilation 8,215 (10.3) 1,439 (8.9) 405 (8.8) 84 (9.5)

Assisted ventilation>6h 4,010 (5.0) 645 (4.0) 194 (4.2) 41 (4.6)

 23

NICU admission 20,768 3,903 (24.2) 1,279 (27.7) 276 (31.2)

(26.1)

Antibiotics 5,854 (7.4) 969 (6.0) 295 (6.4) 53 (6.0)

Seizures 48 (0.06) 4 (0.02) 0 0

* Data are reported as number (proportion) and mean ± standard deviation.

**All relationships are significant (P<.001).

*** Maternal age for births to women aged 50 to 64 years was documented as 50 years.
 24

Table 5. Crude and adjusted relative risks of the association between maternal age and early

neonatal outcomes, medical, and obstetrics complications for ART pregnancies, United States,

2011-2014 ⃰

Characteristic Maternal age 40- Maternal age 45- Maternal age≥50

44 49

RR Adjusted RR Adjusted RR Adjusted

(95% RR (95% (95% RR (95% (95% RR (95%

CI) CI) CI) CI) CI) CI)

Gestational ≤28 0.69 0.70 0.80 0.80 0.86 0.85

age at (0.63- (0.63- (0.69- (0.68- (0.60- (0.59-

delivery 0.77) 0.77) 0.96) 0.95) 1.24) 1.22)

(weeks) 28<GA<34 0.85 0.88 1.06 1.11 1.36 1.47

(0.81- (0.83- (0.97- (1.02- (1.15- (1.24-

0.90) 0.93) 1.15) 1.22) 1.61) 1.73)

34≤GA<37 0.96 0.98 1.11 1.15 1.17 1.21

(0.93- (0.93- (1.05- (1.09- (1.04- (1.09-

0.99) 1.02) 1.69) 1.21) 1.39) 1.36)

Adjusted mean gestational 37.2±0.1 37.0±0.1 36.5±0.1

age at delivery (weeks)

Adjusted mean birth weight 2,973±7 2,896±13 2,794±29

(grams)
 25

Apgar at 5 <7 0.84 0.86 0.81 0.83 0.76 0.80

min (0.77- (0.78- (0.69- (0.70- (0.52- (0.55-

0.92) 0.94) 0.96) 0.98) 1.12) 1.17)

Apgar at 10 <7 0.64 0.65 0.66 0.66 0.86 0.87

min (0.57- (0.54- (0.48- (0.48- (0.74- (0.74-

0.76) 0.77) 0.90) 0.91) 1.60) 1.62)

Immediately assisted 0.86 0.89 0.85 0.88 0.92 0.99

ventilation (0.82- (0.84- (0.77- (0.80- (0.75- (0.80-

0.91) 0.94) 0.94) 0.97) 1.13) 1.21)

Assisted ventilation>6h 0.79 0.81 0.83 0.86 0.92 0.98

(0.73- (0.75- (0.72- (0.74- (0.68- (0.72-

0.86) 0.86) 0.96) 0.99) 1.24) 1.32)

NICU admission 0.43 0.94 1.06 1.09 1.20 1.24

(0.90- (0.92- (1.01- (1.04- (1.09- (1.13-

0.95) 0.97) 1.11) 1.14) 1.32) 1.34)

Antibiotics 0.82 0.84 0.87 0.92 0.82 0.89

(0.76- (0.79- (0.78- (0.82- (0.63- (0.69-

0.87) 0.90) 0.97) 1.03) 1.06) 1.16)

Seizures 0.41 0.42 - - - -

(0.15- (0.15-

1.14) 1.17)
 26

⃰ Adjusted for mother’s race, education, smoking, marital status, weight gain, previous cesarean,

interval since last pregnancy, gestational hypertension, gestational diabetes, eclampsia, method

of delivery, and chorioamnionitis.