The Effect of Advanced Maternal Age on Pregnancy Outcomes: A Prospective Study
Conditions: Advanced Maternal Age Pregnancy
Sponsor: Mansoura University

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
 
 
Mansoura University 
Faculty of medicine 
Obstetrics and Gynecology Department 
The effect of advanced maternal age on pregnancy outcomes: 
A prospective study 
Protocol of thesis 
Submitted for partial fulfillment of a master degree in 
Obstetrics and Gynecology 
By 
Rana Magdy Ibrahim El-Gharbawy (Rana M. Ibrahim) 
(M.B.B.CH., 2015) 
Resident of obstetrics and gynecology at Kafr El-sheikh general hospital 
Supervised by 
Prof. Dr. Mohamed Alaa El-Deen Mosbah Mohamed (Alaa Mosbah) 
Professor of Obstetrics and Gynecology 
Faculty of Medicine – Mansoura University 
{Principal supervisor} 
DR. Abdelhady Abdelhady Zayed (Abdelhady A. Zayed) 
Assistant Professor of Obstetrics and Gynecology 
Faculty of Medicine – Mansoura University 
Dr. Maher El-Esawy Kamel El-Esawy (Maher E. Kamel) 
Lecturer of Obstetrics and Gynecology 
Faculty of Medicine – Mansoura University 
2021 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
Introduction 
Advanced maternal age (AMA) is mostly defined as a pregnancy in women 
≥35 years of age or more during their pregnancy or time of delivery (1). It grows 
trending in high-income countries, which is most commonly seen in older 
primigravida women who delay child bearing by life style choice or due to 
underlying subfertility, but also includes multiparous women continuing 
childbearing. Approximately 18% of all united states birth in 2018 were to women 
with advanced maternal age compare with approximately 5% before, much of this 
shift due to delayed first births, the rate of first births increased seven-fold among 
women aged 35 to 39 y and five-fold among women aged 40 to 44 y between 1985 
and 2018 (2). 
In England, the incidence of births to women aged 35y increased from 6% to 
20% at 2013. Pregnancy at advanced maternal age is associated with different 
adverse neonatal outcomes. It is associated with stillbirth and also complicated by 
intrauterine fetal death (IUFD) and neonatal death (3 & 4). Advanced maternal age is 
reported to be associated with a range of pregnancy complications including: fetal 
growth restriction (FGR), preeclampsia (PE), placental abruption, pre-term birth 
(PTB) and stillbirth (5). 
Perinatal adverse outcomes like preterm birth, early neonatal death, low birth 
weight, neonatal intensive care unit (NICU) admission and APGAR score of less than 
seven at five minutes are significantly associated with pregnancy at advanced 
maternal age (6). The adverse outcomes result from inadequate cardiovascular 
adaptation during pregnancy, which impedes the hemodynamic changes for 
supporting the fetus (7). This may explain occurrence of intrauterine growth 
restriction and placental abruption at advanced maternal age (8). 
 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
 
Early pregnancy outcomes associated with advanced maternal age include: 
Ectopic pregnancy which increase a four- to eight-fold in women more 35 years 
increasing maternal mortality and morbidity (9). Epidemiological studies show an 
association between advanced maternal and paternal ages and the risk of autism  
spectrum disorders in the offspring, also advanced maternal age is a risk factor for 
congenital malformation and Down syndrome (10). 
Risk of spontaneous abortion between 6 to 14 weeks of pregnancy increased 
with increasing maternal age (11). Late pregnancy outcomes including Gestational 
DM and preeclampsia which increasing up to 10% in women more 40 years of age 
and higher up to 35% in women more than 50 years of age which may cause intra 
uterine growth retardation and stillbirth (12). 
Advanced maternal age is also linked to a higher prevalence of placenta 
praevia and placental abruption, both of which cause bleeding in late pregnancy (after 
about 20 weeks) especially in multipara (13). Women more than 40 years of age 
showed an eight-fold increased risk of amniotic fluid embolism due to increased 
incidence of caesarian section and a three-fold increased risk of obstetric shock 
compared with women age 25–29 years (14). 
According to the royal college of obstetricians and gynecologists, the optimum 
period for child bearing is between 20 and 35 years of age to decrease maternal and 
neonatal complications (15). 
 
 
 
 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
 
 
 
Aim of work 
This study to evaluate the effect of advanced maternal age on the outcomes of 
pregnancy which include: maternal, obstetric, fetal and perinatal outcomes. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

O B S T E T RI C A N D G Y N E C OL O G Y  D E P A R T M E N T,  M A N S O U R A 
U NI V E R SI T Y  H O S PI T AL  
0 5/ 2 5/ 2 0 2 1 
 
 
 
P atie nt a n d met h o ds  
St u d y Desi g n & Are a:  
  A pr os pecti ve  c o h ort st u d y  of  pre g na nt  w o me n  recr uite d  fr o m  De part me nt  of 
O bstetrics a n d G y nec ol o g y, Ma ns o ura U ni versit y H os pitals d uri n g J u ne 2 0 2 1 u ntil 
J u ne  2 0 2 2  a n d ma y be e xte n de d if nee de d . 
 T he h os pital o perates A nte natal cli nics si x h o urs e ver y da y e xce pt Fri da y.  
 Ma ns o ura U ni versit y H os pital is Referral teac hi n g h os pital, l ocate d i n Ma ns o ura, 
E g y pt . 
 
St u d y p o p ul ati o n:  
T he st u d y gr o u p will be re prese nte d b y  5 0  pri mi gra vi da w o me n a ge d 3 5 y  or 
m ore  d uri n g  t heir  pre g na nc y  a n d  t he  c o ntr ol gr o u p  will  be  re prese nte d  b y  5 0  
pri mi gra vi da w o me n a ge d 2 0 -3 4  y d uri n g t heir  pre g na nc y till t he ti me of deli ver y. 
 
A.  I ncl usi o n criteri a: 
- Pri mi gra vi da W o me n wit h  si n glet o n  pre g na ncies  a ge d  2 0  t o  3 4  years  i n  c o ntr ol 
gr o u p a n d a ge d 3 5  y or m ore i n case gr o u p, nat ural c o nce pti o n or wit h usi n g A R T, 
w h o see ki n g f or r o uti ne a nte natal care t o t he u ni versit y h os pital a n d w h o will  acce pt 
t he st u d y pr ot oc ol. 
 
B.  E xcl usi o n criteri a : 
-  Patie nt s a ge d less t ha n 2 0 y will be e xcl u de d fr o m t he st u d y . 
- Patie nt s wit h me dical dis or ders  (a nti p h os p h oli pi d s y n dr o me, c hr o nic h y perte nsi o n,  
pre -e xisti n g dia betes, a ut oi m m u ne diseases,  t hr o m b o-e m b olic disease).  
-  Multi para . 
 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
Sample size 
Sample size was calculated by PASS 15 Power Analysis and Sample Size 
Software (2017). NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/pass. 
Based on previous studies including Yogev et al. (2010), the authors 
hypothesize an overall poor outcome in 20% of young pregnant group vs. 60% in 
elderly pregnant group with a prevalence of elderly pregnant ladies of 25% vs. 75% 
of young pregnant ladies. 
A logistic regression of a binary response variable (Y) on a binary independent 
variable (X) with a sample size (N) of 80 observations (of which 50% are in the 
group X=0 [40 young pregnant ladies] and 50% are in the group X=1 [40 elderly 
pregnant ladies]) achieves 94% power at a 0.050 significance level to detect a change 
in Prob (Y=1) from the baseline value of 0.200 to 0.600. This change corresponds to 
an odds ratio of 6.000.A two-sided Wald test is used. 
Considering a possible dropout rate (DR) of 20%, the expected number of 
dropouts will be 20, and the dropout-inflated enrollment sample size (N') will be 100 
participants (50 young, and 50 elderly) where N' = N / (1 – DR). 
- We will have 2 groups: the first group will be represented by 50 women aged 35 y 
or more and the second group will be represented by 50 women aged from 20 to 34 
y.  
- The first group will be also divided into 2 subgroups:  group (1A) aged from 35y 
to 40 y, the group (1B) aged above 40 y and we will compare between the outcomes 
in the 2 groups which include maternal, obstetric, fetal and perinatal outcomes. 
-  We will also compare between those with spontaneous pregnancy and those with 
ART. 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
 
All women in this study will be subjected to the following: 
I. History: 
a. Personal (age, duration of marriage, educational level, special habits). 
b. Menstrual: LMP to detect Gestational age expressed in weeks which calculated 
from first day of LMP. For patients who underwent in vitro fertilization, gestational 
age will be calculated from the date of the embryo transfer. 
c. Obstetric history: all patients will be primigravida. 
d. Past history: of any medical disease or surgical operation. 
e. Family history: of any hereditary or non-hereditary disease. 
c. Present history: of any symptoms during pregnancy, analysis of any complain, 
investigations will be done and treatment will be given during pregnancy. 
 
II. Clinical examination: General, abdominal and local examination. 
General examination: include blood pressure, pulse, temperature, height and weight 
to calculate body mass index (BMI) to determine maternal obesity. 
- Blood pressure to exclude the hypertensive patients. We will measure blood 
pressure in each antenatal visit to diagnose the cases which may develop 
gestational hypertension or preeclampsia after 20 weeks of gestations which 
will be screened and diagnosed clinically by the obstetricians, according to 
guidelines (16). 
Abdominal examination: include obstetric grips. 
Local examination: when indicated. 
 
 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
III. Investigations: 
- All pregnant women will undergo routine investigations at the first antenatal visit 
which include: CBC, RH grouping, blood grouping, urine analysis, fasting and 
postprandial blood glucose. 
-All pregnant women will be 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) will undergo a 3-hour oral glucose 
tolerance test with a 100-g oral glucose load. The diagnosis of GDM will be made 
when levels of blood glucose are fasting plasma glucose above 95 mg/dL, 1 hour 
postprandial above 130-140 mg/dL, and 2 hours postprandial above 120mg/dL 
according to The American College of Obstetricians and Gynecologists (ACOG) 
recommendations (17). 
- All pregnant women will undergo a monthly ultrasound examination until delivery. 
- All obstetrical and clinical data will be recorded and collected in an appropriate 
database. 
-Obstetric outcomes will be recorded regarding pregnancy induced hypertension, 
gestational 
diabetes 
mellitus 
(GDM), 
anemia, 
antepartum 
hemorrhage, 
oligohydraminos or polyhydraminos, obtetretric shock and intrapartum hemorrhage. 
-Maternal outcomes will be recorded regarding mode of delivery “ceaserean or 
vaginal delivery”, premature rupture of membranes, preterm birth which is defined as 
delivery of an infant before 37 weeks of gestation and will be classified into late 
preterm (from 34 to less than 37 weeks of gestation) and early preterm birth (delivery 
from 28 to 34 weeks of gestation), obstructed labor and prolonged labor. 
 
-Fetal outcomes will be recorded regarding congenital malformations, intrauterine 
growth restriction, intrauterine fetal death and stillbirth. 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
- Perinatal outcomes will be recorded regarding birth weight which will be classified 
into low birth weight (less than 2500 g), very low birth weight (less than 1500 g) and 
macrosomia (more than 4000 g), birth asphyxia, meconium aspiration syndrome, 
NICU admission, neonatal hypoglycemia, Hyperbilirubinemia, 5-Min Apgar score 
less than 7 and neonatal death. 
 
Ethical Consideration 
- Agreement for this study will be obtained from the hospital's ethical committee. 
- Study protocol will be submitted for approval by IRB. 
- Informed consent will be obtained from pregnant women after adequate provision 
of information regarding the study requirements and purpose. 
- Personal privacy will be respected in all levels of the study. Collected data will not 
be used for any other purpose. 
 
Statistical analysis 
Data will be entered and analyzed using IBM-SPSS software (IBM Corp. Released 
2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.) 
Qualitative data will be presented as Number and percent, Quantitative data will be 
tested for normality using Shapiro-Wilk’s test then described as mean and standard 
deviation for normally distributed data and median and range for non-normally 
distributed. The appropriate statistical test will be applied according to data type with 
the following suggested tests: Chi-Square for categorical variable. 
 
 

OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
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OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
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OBSTETRIC AND GYNECOLOGY DEPARTMENT, MANSOURA 
UNIVERSITY HOSPITAL 
05/25/2021 
 
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