The role of maternal age in fetal development

This study aimed to explore the relationship between fetal development and maternal age for women with a history of recurrent miscarriages.. Based on our findings, the relationship betwe

THE ROLE OF MATERNAL AGE IN FETAL DEVELOPMENT

Le Thi Anh Dao, Ta Thanh Van

Hanoi Medical University Maternal age is an important prognostic factor in the development of a fetus This study aimed to explore the relationship between fetal development and maternal age for women with a history of recurrent miscarriages This cross - sectional study was conducted at the National Hospital of Obstetrics and Gynecology in Viet-nam, from 1 st January 2012 to 1 st July 2014 A total of 301 newly pregnant patients who had experienced two or more consecutive miscarriages participated in the study The average age of participants was 29.08 ± 5.64 Based on our findings, the relationship between maternal age and the possibility of a baby being born alive can be described in the following equation: Possibility of pregnancy = e (3,760017 - 0,912499 x (mother’s age)). Here,

e = 2.71; the correlation coefficient R 2 = 0.0274 In the case of mothers under 20 years old, the possibility of

a baby being born alive was found to be 89 87% For mothers age 20 29, the percentage was 86 -72% For mothers age 36 to 40 years old, it was 57 - 47% and it decreased to 45 - 30% for those aged above 40 years old Thus, higher maternal age was associated with lower likelihood of giving birth to a live child.

Keywords: Recurrent miscarriages, Maternal age, Fetal development

Corresponding author: Le Thi Anh Dao, Hanoi Medical

University

E-mail: leanhdao1610@gmail.com

Received: 20 October 2016

Accepted: 10 December 2016

I INTRODUCTION

Maternal age is a major factor influencing

fetal conception and development In a

regis-ter - based study of 634,272 Danish pregnant

women who were hospitalized between 1978

and 1992, miscarriage rates were found to be

almost identical among women age 30 - 34

years with recurrent miscarriages and those

aged 35 - 39 with recurrent miscarriages (with

a rate of 38 - 40%), but increased to 70% in

women aged 40 - 44 [1] This would suggest

that the impact of age on miscarriage rates

among women with recurrent miscarriages is

quite modest until age 40, but beyond age 40,

age is the strongest prognostic factor of fetal

survival This assertion is also consistent with

previous findings [2; 3] According to Simpson,

the older a mother is, the more deteriorated the ovule quality and the more the endometrium changes in ways that are not conducive to conception [4] Therefore, higher maternal age is associated with higher risk of miscarriage and lower rates of normal pregnancies

Recurrent miscarriage is defined as 3

or more consecutive miscarriages when the fetus is under 22 weeks old, excluding cases

of ectopic pregnancy, hydatidiform mole and biochemical pregnancy [5] Finding and treat-ing the causes of recurrent miscarriages remains a major challenge for obstetricians Although there have been many advances in medical testing to study miscarriages, the causes of only about 50% of miscarriages can

be determined [6 - 8]

In cases where the exact cause of a mis-carriage can not be determined by traditional medical testing, doctors have to rely on other factors to predict what might have caused it

Maternal age is often mentioned in studies

looking at causes of miscarriages in other

parts of the globe, but the relationship

between maternal age and fetal development

has not been studied carefully in Vietnam Is

maternal age an independent factor that is

related to fetal development? If so, what is the

relationship between maternal age and fetal

well-being? The research was conducted to

determine the relationship between fetal

development and maternal age for

Vietnamese women with a history of recurrent

miscarriages

II SUBJECTS AND METHODS

1 Subjects

This study was conducted at the National

Hospital of Obstetrics and Gynecology in

Vietnam, from 1st January 2012 to 1st July

2014 Women who met the following selection

criteria were asked to participate:

Inclusion criteria

Women with a history of 2 or more

con-secutive miscarriages, where the fetus is 12

weeks or less when miscarriage occurs [9]

Newly pregnant women

Exclusion criteria

Women with a history of recurrent

miscarriage where the age of the fetus at

demise is greater than 12 weeks

Women with a history of miscarriages

which are not consecutive, or miscarriages

from ectopic pregnancies or hydatidiform

moles

2 Methods

A cross - sectional study was conducted A

minimum sample size of n = 254 participants was determined using the following equation:

- n: is the minimum sample size of patients with recurrent miscarriages to be obtained

- Z: is the reliability coefficient, at a prob-ability of 95%, Z = 1.96

- p: is the rate of antiphospholipid syndrome in recurrent miscarriage, p = 0.12, according to Balasch J [10]

- q: is the ratio of non antiphospholipid syndrome in recurrent miscarriage, q = 1 - p = 0.88

- d: is the desired accuracy, d = 0.04

Research Framework

Newly pregnant women with a history of recurrent miscarriage who were eligible for the study were recruited, and their age and preg-nancy outcome were recorded Patients were divided into four main groups, according to the World Health Organization: under 19; 20 - 29;

30 - 39 and above 40 years old The develop-ment of the fetus was tracked to the end of the pregnancy, noting whether infants were born dead or alive Women who had miscarriages received treatment and we attempted to deter-mine the cause of their miscarriage

3 Research ethics

Research subjects were informed about the goals of the study and voluntarily agreed

to participate in research All patient information was kept confidential and secure

n = Z2(1 - α/2)

pq

d2

III RESULTS

In this study, we surveyed 301 newly pregnant patients who had a history of two or more con-secutive miscarriages

Table 1 Causes of recurrent miscarriage

Uterine abnormalities

Double uterus 2/301

3.99 Uterine septum 1/301

Uterine Fibroids* 9/301 Chromosomal

abnormalities

Endocrine disorders

Thyroid Gland 7/301 2.33

Polycystic Ovarian Syndrome 6/301 1.99

Unidentified reasons 207/301 68.77%

The most common cause of recurrent miscarriage was antiphospholipid syndrome, responsi-ble for 11.29% of miscarriages among respondents

Table 2 Age of recurrent miscarriage among mothers, divided into those who were

suffering from APS and those who were not

Patients with recurrent

miscar-riages (n = 301) 29.08 ± 5.64 17 48

Patients with recurrent

mis-carriages who were suffering

from APS (n = 34)

27.65 ± 5.24 17 38

Patients with recurrent

miscar-riages who were not suffering

APS (n = 267)

29.27 ± 5.65 18 48

p > 0.05

The average age of women who were suffering from recurrent miscarriages was 29.08 ± 5.64 The average age of respondents in the group suffering from APS was 27.65 ± 5.24, while the

average age of respondents in the group not suffering APS was 29.27 ± 5.65 However, this age difference was not statistically significant (p > 0.05)

Graph 1 The relationship between maternal age and the likelihood

of giving birth to alive child

Graph 1 illustrates the relationship between maternal age and pregnancy outcomes among the participants The likelihood of a baby being born alive decreased in older mothers The likelihood

of a baby being born alive was 90% if the mother was 17 years old; this number fell to 30% when mothers were above 45 years old

In this study, we illustrated the relationship between maternal age and the possibility of babies being born alive through the following equation thank to logistics algorithm Possibility of preg-nancy = e (3.760017 - 0.912499 x (mother’s age)).In which, e = 2.71; correlation coefficient

R2= 0.0274

IV DISCUSSION

Among the 301 patients enrolled in this

study, there were 207 patients for whom the

cause of their recurrent miscarriages remained

unknown These patients accounted for

68.77% of the patients in the study For these

respondents, treatment of their miscarriages

was based on provider experience, and there

were no clear mechanisms to determine

whether their child would be born alive

In this study, maternal age was found to be

a significant prognostic factor for fetal develop-ment Higher maternal age was linked with a higher risk of miscarriage and lower rates of normal pregnancies The average age of the mothers in our study was 29 We found a negative correlation between maternal age and the likelihood of infants being born alive,

as shown in graph 3.1 Higher maternal age was associated with a lower chance of babies being born alive The figures in the chart show that in the case of mothers under 20 years old,

the possibility of babies being born alive was

87 - 89% With 20 - 29 year - old mothers, this

number decreased to 72 - 86% With 36 - 40

year - old mothers, it was 47 - 57% and it

de-creased to 45 - 30% for mothers above 40

years old In the case of the older mothers in

our study, the most common known cause of

miscarriage was chromosomal abnormalities

in the embryo According to Simpson, the

older the mother is, the more deteriorated the

oocyte quality is and the more the

endo-metrium changes in ways that are not

condu-cive to conception [4]

The results of our research are compatible

with the conclusions of Brigham and Conlon

Brigham and Conlon found that the possibility

of a successful pregnancy after three

con-secutive miscarriages due to unknown causes

was 90% for 20 - year - old mothers, whereas

for 45 years old mothers, the possibility of a

baby being born alive was 54% [11]

Among the 301 patients with recurrent

mis-carriages in this study, there were 34 patients

suffering from APS and 267 patients who were

not suffering from APS We wanted to find out

whether maternal age was an independent

factor affecting fetal development and whether

maternal age and APS interacted at all for

tho-se patients suffering from APS The average

age of the patients suffering from APS was

27.65, which was lower than that of the group

not suffering from APS, whose average age

was 29.27 However, this difference was not

statistically significant (p > 0.05) Thus, the

age of patients with recurrent miscarriages

suffering from APS in our study was the same

as that of patients with recurrent miscarriages

who were not suffering from APS

The rate of miscarriages due to unknown

causes among participants in our study, 68.77%, differs from the rate found in Dendrino’s study, where 52.63% of patients had recurrent miscarriages where the cause remained unknown [7] Dendrinos’ research was conducted on 323 patients with recurrent miscarriages Patients were divided into groups of causes: immunological disorders, uterine abnormalities, endocrine disorders, chromosome abnormalities and unknown cau-ses The average ages among the patients in each group were 32.2, 31.6, 32.1, 31.5 and 32.6, respectively [12] There were no signifi-cant differences among the average ages of patients in these five groups The average age

of patients in Dendrinos’ study was higher than the average age of patients in our study, which may be due to the fact that the repro-ductive age of women in Western societies is higher overall than that of Eastern societies

In this study, for most of the fetal miscarriages and non - developing fetuses that occurred at the first trimester, the placentas were not karyotyped We thus could not determine the rate of chromosome abnormalities in the embryo Therefore, the relation between maternal age and embryo quality should be further elucidated in future research by incorporating karyotyping into the analysis

V CONCLUSION

In summary, based on the results of our study, maternal age impacts the formation and development of fetus, likely by affecting ovule quality and egg nesting The relationship between maternal age and fetal development

is closely intertwined and non - linear Higher maternal age limits nesting and hinders development in the uterus, reducing the possibility of live birth

This research was supported by the

Ex-amination Department of the National Hospital

of Obstetrics and Gynecology in Vietnam

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