Open Access

Original Article

Paternal factors in spontaneous

first trimester miscarriage
Riffat Jaleel1, Ayesha Khan2
ABSTRACT
Objectives: To determine whether paternal factors i.e., age, tobacco use and genital tract infection
increase the risk for spontaneous first trimester miscarriage.
Methodology: This case control study was conducted in the Department of Obstetrics & Gynaecology, Unit
V / IV, Dow Medical College & Lyari General Hospital, Dow University of Health Sciences, Karachi, Pakistan.
Duration of study was two and half years, from Nov, 2007 to Apr, 2010. Inclusion criteria were pregnant
women with age 20 – 35 years irrespective of parity. Exclusion criteria were known medical illness in either
partner, induced abortion and recurrent miscarriages. Studied paternal factors were age, tobacco use and
genital tract infection. Data was computed using SPSS version 16. Significance of paternal factors was
determined by Logistic Regression Analysis.
Results: Total cases studied were 200, while there were 400 controls. Mean maternal age was 27.6±4.9 years
in cases and 26.5±4.5 years in controls. Mean paternal age was 35.5±6.2 years in cases and 32.3±5.4 years
in controls. Paternal age was >35 years in 54.5% cases and 16.8% controls. Spearman Bivariate correlation
revealed paternal age > 35 years (p=0.000) and genital tract infection (p=0.043) as significant factors. Only
paternal age >35 years (p=0.000) remained significant in Final Model after entering into logistic regression.
Conclusion: Paternal age beyond 35 years was found to be significantly related to first trimester spontaneous
miscarriages.
KEY WORDS: Paternal age, Spontaneous miscarriage, Drug abuse, Male genital tract infection.
doi: http://dx.doi.org/10.12669/pjms.293.3388
How to cite this:
Jaleel R, Khan A. Paternal factors in spontaneous first trimester miscarriage. Pak J Med Sci 2013;29(3):748-752.
doi: http://dx.doi.org/10.12669/pjms.293.3388
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

INTRODUCTION miscarriages occurring in first trimester are

likely to be due to chromosomal abnormality.1
Spontaneous miscarriage is a common
Chromosomal abnormality in the zygote may
gynaecological condition creating an emotional
result from errors during gametogenesis, during
crisis for the family. Around half of the spontaneous
fertilization or during first cellular division. Thus
1. Dr. Riffat Jaleel, MBBS, FCPS, any such abnormality in the sperm could be a cause
Assistant Professor,
Ayesha Khan, MBBS, FRCOG, of spontaneous miscarriage. Advancing paternal
Professor, age is being increasingly identified as one of the
1, 2: Obstetrics & Gynaecology, Unit II,
Dow Medical College & Civil Hospital, possible causes for such defects.2-5
Dow University of Health Sciences, Trends towards increasing paternal age are being
Karachi, Pakistan.
observed in the UK as well as USA, due to delay in
Correspondence:
marriages for attaining better socio-economic sta-
Dr. Riffat Jaleel, bility.6 In England and Wales, mean age at child-
Address: C – 53, Block I, North Nazimabad,
Karachi – 74700. bearing rose from 26.4 years in 1974 to 29.3 years in
E-mail: [email protected] 2002.7 Since 1980, birth rates in United States have
* Received for Publication: January 16, 2013 increased by 40% for men aged 35 – 49 years.8
* Revision Received: May 5, 2013 Advancing paternal age has been shown to
* Accepted for Publication:* May 7, 2013 result in subfertility, adverse pregnancy outcomes

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 Paternal factors in spontaneous first trimester miscarriage

(miscarriage, late foetal death, preterm delivery, delivery beyond 24 weeks of gestation were taken
low birth weight), birth defects (cleft lip and as controls. Gestational age was calculated from
palate, congenital heart defects), achondroplasia, last menstrual period and confirmed by ultrasound,
osteogenesis imperfect , Apert’s syndrome, done from the Department of Radiology, Lyari
schizophrenia, childhood cancer (brain cancer, General Hospital. Exclusion criteria were known
retinoblastoma, acute lymphoblastic leukaemia) medical illness in either partner, induced abortion
and adult cancer (breast, prostate and nervous and history of recurrent miscarriages.
system).3 Possible mechanisms for these problems Data were collected on pre-designed proformas
include single gene mutations, autosomal by post-graduate trainees on duty. Information
dominant diseases, structural abnormalities in was obtained from the woman regarding her age,
sperm chromosomes (eg., reciprocal translocations) her husband’s age, parity, gestational age, ethnic
and multiple genetic / chromosomal defects. DNA group, husband’s occupation and income, tobacco
damage in sperm of men aged 36 – 57 years was / drug abuse by woman and husband and genital
found to be 3 times that of men less than 35 years.9 tract infection in husband (suggested by urethral
Male factors other than age e.g., occupation, discharge, urethral ulcer, premature ejaculation,
environmental exposure and smoking have dysuria).
also been shown to influence sperm quality and All data were entered and analyzed using SPSS
therefore, affect early embryo loss.10 Production of version 16. Means with standard deviations were
reactive oxygen species e.g., by excessive stress, calculated for numerical data, while frequencies
competitive sports, infection, alcohol, smoking, were calculated for categorical data. Paternal factors
nicotine and drug abuse may result in sperm DNA were studied using Spearman Bivariate Correlation.
fragmentation.11,12 Paternal age was divided into six categories i.e., 20
The effect of female factors on adverse – 25 (reference), 26 – 30, 31 – 35, 36 – 40 and > 45
reproductive outcome is well known. But having years. Maternal age, maternal tobacco / drug abuse
said this, in majority of cases of spontaneous were considered as confounders. Maternal age was
miscarriage the cause remains unidentified. Could divided into three categories i.e., 20 – 25 (reference),
paternal factors be responsible has not been studied 26 – 30 and 31 – 35 years. Factors found significant
in local population. This study, therefore, aimed were entered into logistic regression to construct
to study the possible link of these factors with the final model. Any result with p value < 0.05 was
spontaneous miscarriage. considered significant.

METHODOLOGY RESULTS

This case control study was conducted in the Total Gynaecology admissions during the study
Department of Obstetrics and Gynaecology, Unit period were 687. Total number of miscarriages was
V / IV, Dow Medical College and Lyari General 363, out of which 349 (96.1%) were spontaneous
Hospital, Karachi. Duration of study was two and miscarriages. Upon further sorting, number of first
half years, from November, 2007 to April, 2010. trimester spontaneous miscarriages was 240 (69%),
Convenient sampling was used. We studied 200 out of which 200 cases met inclusion and exclusion
cases against 400 controls. Our inclusion criteria criteria. They were compared with 400 controls.
were pregnant women between the age of 20 – 35 Table-I shows descriptive baseline data of
years, with any parity, admitted in the Department. patients. Mean maternal as well as paternal age was
Women with spontaneous first trimester miscarriage higher amongst the cases as compared to controls,
were taken as cases, while those admitted for while parity was comparable. Mean gestational age

Table-I: Baseline data.

Cases Controls p 95% Confidence Interval
Mean ± SD Mean ± SD Lower Upper
Maternal age (years) 27.6 4.9 26.5 4.5 0.008 - 1.868 - 0.282
Parity (n) 2.5 2.1 2.7 1.9 0.176 - 0.103 + 0.563
Paternal age (years) 35.5 6.2 32.3 5.4 0.000 - 4.131 - 2.204
Income (Pakistani Rupees) 5816.5 2685 6777.5 3030 0.000 464.3 1457
Gestational age (weeks) 10.6 1.8 37.5 1.7 0.000 26.661 27.249

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Riffat Jaleel et al.

Table-II: Factors associated with spontaneous miscarriage (Spearman Bivariate Correlation).

Cases Controls p
No % No %
Paternal Age (Years) 1(REF)= 20 - 25 9 4.5 46 11.5 0.000
2= 26 - 30 47 23.5 143 35.8
3= 31 - 35 35 17.5 144 36
4= 36 - 40 88 44 48 12
5= 41 - 45 18 9 14 3.5
6= > 45 3 1.5 5 1.2
Maternal Age (Years) 1(REF)= 20 - 25 82 41 198 49.5 0.027
2= 26 - 30 73 36.5 136 34
3= 31 - 35 45 22.5 66 16.5
Paternal tobacco / drug abuse 136 68 273 68 0.249
Maternal tobacco / drug abuse 104 52 188 47 0.951
Genital Tract Infection 13 6.5 12 3 0.043

of patients was 10.6 weeks, while controls were at Kleinhaus K conducted a case control study and
term. concluded that odd ratio for spontaneous miscar-
Paternal age was more than 35 years in 54.5% riage was 1.6 (95% CI = 1.2 – 2.0, p = 0.003), for
cases versus 16% controls and was more than 45 fathers aged 40 years or more. This risk was inde-
years in 1.5% and 1.2%, respectively. Majority of pendent of maternal age and multiple other fac-
husbands in both groups were labourers, with tors.13 Report from Reproductive Endocrinology &
income less than Rs. 5000/=. Commonest ethnic Infertility Committee & Collaborators states that
group was Balochi in more than 50%, followed by advanced paternal age appears to be associated
Pathans. Drug abuse history was difficult to obtain, with increased risk of spontaneous miscarriage and
but a substantial number of women and their some autosomal dominant conditions, autism spec-
husbands were using tobacco in various forms, trum disorder and schizophrenia. They recommend
alone or in combination (Gutka, Hukka, Pan, Beeri counselling of men more than 40 years of age when
and Cigarette). seeking pregnancy.14,15 Iwayoma and colleagues
Table-II shows the factors studied by Spearman from Japan also found link between increasing
Bivariate Correlation. Maternal age, paternal age paternal age and higher incidence of spontaneous
and genital tract infection were found to be signifi- miscarriage.16 Similar results have been reported by
cant risk factors. Final model (Table-III) revealed Veles de la Calle JF, Belloc S and Fisch H.12,17,18
both maternal age group 31 – 35 years and paternal Dane L published a systematic review on effect of
age > 35 years as independent risk factors. paternal age on assisted reproductive outcomes.19
Majority of studies in this review failed to show a
DISCUSSION correlation between paternal age and spontaneous
miscarriage when adjusted for maternal age, except
The present study has demonstrated that the
for one study by Frattarelli et al.20 They concluded
paternal age more than 35 years was an independent
that overall pregnancy loss rate significantly in-
risk factor associated with spontaneous first
creased with paternal age, 41.5% for > 50 years old
trimester miscarriages. In order to eliminate the
and 24.4% for less than or equal to 50 years (p <
effect of maternal age, which is itself a known risk
0.01; RR, 0.61; 95% CI, 0.45 – 0.84).
factor, we selected women between the age of 20
– 35 years, as this is considered to be ideal age for Table-III: Final model (Logistic Regression).
child bearing. Slama R, et al studied influence of p OR 95% CI
paternal age on spontaneous miscarriage. They Lower Upper
inducted women in early pregnancy and followed
Maternal
them to detect outcome. They found that the risk
Age 31-35 Years 0.003 0.360 0.185 0.702
of spontaneous miscarriage with paternal age 35 or
Paternal
more years was 1.26 times higher (95% CI = 1.00,
Age 36-40 Years 0.000 16.44 6.612 40.896
1.60). The result was independent of maternal age,
41 – 45 Years 0.000 13.738 4.376 43.127
maternal tobacco, alcohol, caffeine and paternal
> 45 Years 0.026 7.042 1.269 39.090
tobacco use.1

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 Paternal factors in spontaneous first trimester miscarriage

We selected the cutoff of 35 years for paternal residents from Lyari town, where nicotine use
age. Interestingly, none of the husbands in our in various forms is very common, in addition to
study was less than 20 years, while more than 45 other abuse drugs, in men and women. However,
years were very few. Different authors have used only history of tobacco use could be retrieved,
different paternal ages. Kleinhaus K et al have stud- and none of the patients committed the use of
ied various age groups and have found father’s alcohol or other abuse drugs by herself or husband.
age more than 40 years to be significantly associ- As tobacco use was almost equally common in
ated with spontaneous miscarriage.13 Slama R has both genders, therefore, any possible effect on
also studied age ranges and have found that risk of spontaneous miscarriage has been nullified. Bellver
spontaneous miscarriage showed linear increase in J and colleagues in their study have reported that
the hazard of spontaneous miscarriage in male age the number of cigarettes smoked by healthy men
between 20 and 45 years. They also observed that was 0 – 3 per day as compared to 0 – 20 per day in
hazard ratio was highest with male age > 45 years recurrent spontaneous miscarriage.33
compared with 18 – 24 years (HR = 1.87, 95% CI, Reactive oxygen species can also be formed
1.01 – 3.44).1 Others have used paternal age between in inflammatory processes. So we studied
30 to more than 50 years. whether genital tract infection could also result in
Studies on paternal age and fertility suggest that possible sperm damage and thereby spontaneous
male biological clock does exist. Similar to women, miscarriage. Male genital tract infection was
advancing paternal age results in negative effects supposed to be present on the basis of history stated
on reproductive outcomes. Reduced semen volume, by the wife and any confirmation of diagnosis could
decline in sperm concentration, reduced sperm mo- not be made. We found positive result on bivariate
tility and morphology and reduced motile sperm correlation, which did not sustain its significance on
count have been observed with increasing men’s logistic regression. According to Aitken RJ’s study,
age.20-25 Moreover, Luna M et al reported decline male genital tract infection can result in DNA
in implantation rate after assisted reproductive damage in male germ cells and therefore, increase
techniques in men > 60 years old, while Frattarelli the rates of miscarriage.32
et al and Klonoff-Cohen et al found deteriorating
embryo quality.20,23,26 Klonoff-Cohen also found de- CONCLUSION
creasing pregnancy rate with male age. Pregnancy Paternal age more than 35 years was found to
rate was 53% for men less than or equal to 35 years, be an independent risk factor in spontaneous first
35% for 36 – 40 years and 13% for men > 40 years. trimester miscarriages.
Another observation that suggests sperm
abnormalities with increasing age is the higher ACKNOWLEDGEMENT
incidence of mutations in offsprings of aging men. We are extremely thankful to Professor Nazeer
Advanced paternal age is linked with poor neuro- Khan, PhD, Head of Department of Research and
cognitive scores, Apert’s syndrome, schizophrenia Biostatistics, Dow University of Health Sciences,
and autism.27-30 Ji-Yeob Choi et al in a case control Karachi, Pakistan, for helping us in data analysis.
study report the risk of breast cancer 1.6 fold high in
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