Human sex ratio at amniocentesis and at birth in Taiwan

Abstract

Objectives:
An increase in the proportion of male-to-female live births has raised concerns in Taiwan. Disclosure of fetal sex during prenatal screening is not allowed by the Taiwan government. Fetal sex annotation in clinical genetic reports is also prohibited. This study tested the hypothesis that the male-to-female sex ratio at amniocentesis should be lower than the sex ratio at birth, if a certain percentage of female fetuses are being selectively aborted after amniocentesis. Therefore, we examined the differences between fetal sex ratio at amniocentesis at a tertiary medical center in southern Taiwan and the nationwide sex ratio at birth in Taiwan from 1992 to 2011.

Materials and methods:
Data of normal male and female karyotypes during the study period were collected from the cytogenetic laboratory of the National Cheng Kung University Hospital (NCKUH) in southern Taiwan. Data of sex ratio at birth nationwide in Taiwan were obtained from the Department of Statistics, Ministry of the Interior, Taiwan. We calculated 95% binominal confidence intervals for the sex ratios and differences between fetal sex ratio at amniocentesis, and nationwide sex ratio at birth were tested by the χ(2) test and Bonferroni correction.

Results:
The nationwide sex ratio at birth ranged from 1.07 to 1.11 during the period from 1992 to 2011 in Taiwan, with the highest in 2004 and the lowest in 1993. The fetal sex ratio at amniocentesis at NCKUH ranged more widely (0.82-1.28), with the lowest in 1993 and the highest in 2007. After regression analysis, both trends of sex ratio at amniocentesis during midtrimester and at birth were not significantly increased by years. Furthermore, the sex distribution at amniocentesis during midtrimester did not differ significantly from the nationwide sex ratio at birth (1.113 vs. 1.092, p = 0.151).

Conclusions:
The results showed that sex ratio was already skewed toward male at midtrimester. Our data imply that artificial sex selection, if it were present, might have already emerged prior to the timing of amniocentesis. However, more large nationwide studies on sex ratios in Taiwan are warranted.

Full text

Original Article
Human sex ratio at amniocentesis and at birth in Taiwan
I-Wen Lee
a,b,c,e
, Yi-Chun Lai
a
, Pao-Lin Kuo
a,c,e,
**, Chia-Ming Chang
d,e,
*
a
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan, Taiwan
b
Institute of Biotechnology, National Cheng Kung University, Tainan, Taiwan
c
Cytogenetic Laboratory, Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan
d
Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
e
Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Accepted 2 March 2012
Abstract
Objectives: An increase in the proportion of male-to-female live births has raised concerns in Taiwan. Disclosure of fetal sex during prenatal
screening is not allowed by the Taiwan government. Fetal sex annotation in clinical genetic reports is also prohibited. This study tested the
hypothesis that the male-to-female sex ratio at amniocentesis should be lower than the sex ratio at birth, if a certain percentage of female fetuses
are being selectively aborted after amniocentesis. Therefore, we examined the differences between fetal sex ratio at amniocentesis at a tertiary
medical center in southern Taiwan and the nationwide sex ratio at birth in Taiwan from 1992 to 2011.
Materials and Methods: Data of normal male and female karyotypes during the study period were collected from the cytogenetic laboratory of
the National Cheng Kung University Hospital (NCKUH) in southern Taiwan. Data of sex ratio at birth nationwide in Taiwan were obtained from
the Department of Statistics, Ministry of the Interior, Taiwan. We calculated 95% binominal confidence intervals for the sex ratios and
differences between fetal sex ratio at amniocentesis, and nationwide sex ratio at birth were tested by the c
2
test and Bonferroni correction.
Results: The nationwide sex ratio at birth ranged from 1.07 to 1.11 during the period from 1992 to 2011 in Taiwan, with the highest in 2004 and
the lowest in 1993. The fetal sex ratio at amniocentesis at NCKUH ranged more widely (0.82e1.28), with the lowest in 1993 and the highest in
2007. After regression analysis, both trends of sex ratio at amniocentesis during midtrimester and at birth were not significantly increased by
years. Furthermore, the sex distribution at amniocentesis during midtrimester did not differ significantly from the nationwide sex ratio at birth
(1.113 vs. 1.092, p¼0.151).
Conclusions: The results showed that sex ratio was already skewed toward male at midtrimester. Our data imply that artificial sex selection, if it
were present, might have already emerged prior to the timing of amniocentesis. However, more large nationwide studies on sex ratios in Taiwan
are warranted.
Copyright Ó2012, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
Keywords: prenatal sex determination; sex discrimination; sex ratio
Introduction
Sex ratio, defined as the ratio of males to females in
a population, is assumed to be close to 1:1. In humans, the
natural sex ratio at birth remains a controversial issue for
biologists. Considering the fact that male fetuses are more
vulnerable to life-threatening insults than females, it has
been postulated that the natural sex ratio at birth should be
slightly higher than 1. In reality, the worldwide sex ratio at
birth is approximately 105 boys per 100 girls [1e3].
However, statistics from a number of government databases
have shown that sex ratios at birth have been skewed
recently [4e7]. Human sex ratio after birth has also been
reported to be relevant to the variation of life expectancy
and mortality [8].
* Corresponding author. Department of Internal Medicine, National Cheng
Kung University Hospital, 138 Sheng-Li Road, Tainan 70403, Taiwan.
** Corresponding author. Division of Genetics, Department of Obstetrics and
Gynecology, National Cheng Kung University Hospital, 138 Sheng-Li Road,
Tainan 70403, Taiwan.
E-mail addresses: paolink@mail.ncku.edu.tw (P.-L. Kuo), cmchang@mail.
ncku.edu.tw,tw.charming@gmail.com (C.-M. Chang).
Available online at www.sciencedirect.com
Taiwanese Journal of Obstetrics & Gynecology 51 (2012) 572e575
www.tjog-online.com
1028-4559/$ - see front matter Copyright Ó2012, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
http://dx.doi.org/10.1016/j.tjog.2012.09.012

Generally, sex ratios at birth are lower than 1 in developed
countries at higher altitudes, such as the United States,
Canada, and Europe [4e7]. By contrast, sex ratios at birth are
consistently higher than 1 in developing countries with
cultural preferences that favor the birth of males over females.
In Asian countries, such as China, the predominant male-to-
female ratio at birth has been postulated as a result of selec-
tive abortion of female fetuses by prenatal sex determination
[9,10]. Skewed sex ratios have also been reported in immi-
grants from India to Norway [11]. However, the sample sizes
in that study were too small to draw definitive conclusions of
a preference for sex-selective abortion among mothers of
Indian origin [11].
Notably, in China, a country in which the birth of more than
one baby is prohibited by strict national policy, Zhu et al have
found that the ratio of boys to girls in rural areas of China was
as high as 120:100 [10]. Sex ratios in several countries have
also shown significant transitions in the past few decades [6],
and skewing of sex ratios at birth has been reported to be an
indicator of sex discrimination, which may violate basic
human rights [9].
An increase in the proportion of male-to-female live births
has raised concerns in Taiwan recently. Prenatal fetal sex
disclosure is strictly prohibited in all clinical settings by the
Taiwan government. Clinicians have been officially banned
from responding directly to parents who ask the question “Is it
a girl or a boy?” In addition, fetal sex annotation has also been
prohibited in all clinical genetic reports after August, 2011 [12].
In order to investigate the fetal sex ratio issue, the objective
of this study was to assess the difference between fetal sex
ratio at a tertiary medical center and the nationwide sex ratio
at birth in Taiwan. The null hypothesis of this study is that
fetal sex ratio at amniocentesis is not different to the sex ratio
at birth. On the contrary, the alternative hypothesis is that fetal
sex ratio at amniocentesis is different from the sex ratio at
birth, which implies a certain percentage of female fetuses are
being selectively aborted after fetal sex has been disclosed at
midtrimester.
Material and methods
Feral sex ratio at amniocentesis
All prenatal karyotyping results obtained during the period
from 1992 to 2011 at the Cytogenetic Laboratory of the
National Cheng Kung University Hospital (NCKUH),
a tertiary medical center in southern Taiwan, were retrieved
and analyzed. Fetal sex ratios at amniocentesis were calculated
by dividing the number of fetuses with a normal male
karyotype (46,XY) by the number of fetuses with a normal
female karyotype (46,XX). Fetuses with aneuploidy or trans-
locations were excluded. Maternal and fetal characteristics
that were analyzed in this study included maternal age, indi-
cations for amniocentesis, date of amniocentesis, and gesta-
tional age of the fetus at the time of amniocentesis. This study
was approved by the institutional review boards from
NCKUH.
Sex ratio at birth
The sex ratio at birth in each year of the study period was
defined as the ratio of all boys to all girls aged <1 year
registered in the Department of Statistics, Ministry of the
Interior, Administrative Yuen, Taiwan, ROC.
Statistical analysis
We calculated the 95% binominal confidence intervals
(CIs) for the sex ratios by using the 95% CI for the proportion
of male births or fetuses with normal male karyotype (pf) with
a variance of pf (1 epf). The sex ratios and 95% binominal
CIs were determined with the quadratic formula as reported by
Spiegel (1961) for binomial CIs for proportions. Differences
between fetal sex ratio at amniocentesis and sex ratio at birth
were tested by the c
2
test and Bonferroni corrections [13].
Differences were considered statistically significant with a p
value <0.05.
Results
As illustrated in Fig. 1, the trends in sex ratio in Taiwan
during the period from 1992 to 2011 were examined by
regression analysis. First, the nationwide sex ratio at birth was
not increased or decreased for 20 years (y ¼0.0002x þ0.6253;
R
2
¼0.0334, NS). Second, the sex ratio at amniocentesis at
NCKUH during the 20 years was not significantly increased
(y ¼0.091x e17.108; R
2
¼0.2394, NS). Although the fetal sex
Fig. 1. Trends of sex ratio at amniocentesis and at birth. -The national sex
ratio at birth was defined as the ratio of all boys to all girls aged <1 year
registered in the Department of Statistics, Ministry of the Interior. Data were
retrieved from Statistical Year Book of Interior, published by Department of
Statistics, Ministry of the Interior, Executive Yuan, Taiwan, R.O.C., at http://
sowf.moi.gov.tw/stat/year/elist.htm, accessed on January 15, 2012. AFetal
sex ratios at amniocentesis were calculated by dividing the number of fetuses
with a normal male karyotype (46, XY) by the number of fetuses with
a normal female karyotype (46, XX). All prenatal karyotyping results were
obtained during the period 1990 to 2010 at the cytogenetic laboratory of the
National Cheng Kung University Hospital but fetuses with aneuploidy or
translocations were excluded. NS ¼not significant.
573I-W. Lee et al. / Taiwanese Journal of Obstetrics & Gynecology 51 (2012) 572e575

ratio at amniocentesis seemed to increase more than the human
sex ratio at birth nationwide during the study period of two
decades, the difference in both trends was not statistically
significant.
As shown in Table 1, the nationwide sex ratio at birth in
Taiwan remained constant at 1.08 during the period from 1992
to 2011, with the highest at 1.1057 in 2004 and the lowest at
1.0759 in 1993. Overall, there was no significant difference in
sex distribution between the NCKUH data and the nationwide
data (1.113 vs. 1.092, p¼0.110). Although the fetal sex ratios
at amniocentesis were significantly different to the nationwide
sex ratio at birth in 1994, 1997, and 2002, as tested by the c
2
test using the threshold of p0.05, all were nonsignificant
after Bonferroni correction using the corrected threshold of
p0.001.
In addition, the average maternal age at amniocentesis
ranged from 32.4 years to 35.33 years at NCKUH from 1992
to 2011, while the average maternal age ranged from 26.4
years in 1998 to 29.8 years in 2008. Of interest, the maternal
age at amniocentesis at NCKUH was higher than that
nationwide at birth because more than half the mothers
received amniocentesis due to advanced maternal age.
Discussion
The trends in sex ratio at birth in Taiwan during the period
from 1992 to 2011 remained constant at 1.08. Our result shows
that the fetal male-to-female sex ratio at amniocentesis
increased no more than the sex ratio of newborn babies in
Taiwan. In addition, the mothers who underwent prenatal
diagnosis were older. Our findings imply that the so-called
selective abortion of female fetuses after amniocentesis is
not true; at least at a tertiary medical center in southern
Taiwan, where people are considered to be more traditional
and conservative than northern Taiwan.
Changes in sex ratio at birth have been attributed to many
different factors, including maternal age at menarche, parental
ages, birth order, race, and preference of boys or girls
[3,5,7,14e16]. By contrast, data from most countries in
Europe and North America show that the male-to-female ratio
of second-order births is lower than that of first-order births
[4,6]. Globally, the differences in human natal sex ratio are
positively correlated with life expectancy, indicating that the
natal sex ratio is influenced by existing environmental condi-
tions and perceived future survival [8,17]. Advocates and
governments seeking to reverse this imbalance have prohibited
sex detection tests and/or sex-selective abortion [9] in the hope
that these measures would reverse the trend. Such policies
have been difficult to enforce, however, and have met with
only limited success [18,19].
Taiwan is located off the coast of southeastern China and
shares a Han Chinese heritage. One of the most distinguishing
culture features of the Han Chinese, both in China and in
Taiwan, is the existence of a patrilineal society in which
married daughters belong to the husband’s family, and fami-
lies tend to prefer boys to girls. In some instances, in China as
well as in countries with low fertility rates, data on sex ratio at
birth are affected by generalized and systematic under-
Table 1
Comparison of sex ratio at amniocentesis and at birth.
Year Maternal age at
amniocentesis
(y; mean SD)
Numbers of karyotype reports of fetus Boys/girls <1 y old in national population in Taiwan
a
46,XY 46,XX Sex ratio at amniocentesis
(95% CI
c
)
Boys born Girls born Sex ratio at birth
(95% CI)
b
pvalue
1992 34.45 4.25 47 50 0.94 (0.63e1.40) 160,372 147,360 1.09 (1.08e1.10) 0.471
1993 33.65 4.80 71 87 0.82 (0.60e1.12) 159,265 148,027 1.08 (1.07e1.08) 0.083
1994 32.46 6.48 117 137 0.85 (0.67e1.09) 153,609 140,085 1.10 (1.09e1.11) 0.047
c
1995 32.50 4.94 150 155 0.97 (0.77e1.21) 157,466 145,612 1.08 (1.07e1.09) 0.332
1996 32.40 4.93 312 273 1.14 (0.97e1.34) 158,284 145,553 1.09 (1.08e1.10) 0.549
1997 32.65 5.01 455 357 1.28 (1.11e1.46) 160,299 147,107 1.09 (1.08e1.10) 0.027
c
1998 32.40 5.15 568 520 1.09 (0.97e1.23) 132,759 122,017 1.09 (1.08e1.10) 0.949
1999 32.87 4.87 848 784 1.08 (0.98e1.19) 141,105 129,112 1.09 (1.09e1.10) 0.835
2000 33.12 4.88 983 918 1.07 (0.98e1.17) 153,054 139,670 1.10 (1.09e1.10) 0.616
2001 32.40 5.13 1019 905 1.13 (1.03e1.23) 128,338 118,043 1.09 (1.08e1.10) 0.445
2002 32.43 5.11 1024 849 1.21 (1.10e1.32) 123,895 112,792 1.10 (1.09e1.11) 0.045
c
2003 32.62 5.10 904 799 1.13 (1.03e1.24) 114,018 103,438 1.10 (1.09e1.11) 0.593
2004 32.61 5.03 989 888 1.11 (1.02e1.22) 108,663 98,273 1.11 (1.10e1.12) 0.876
2005 32.74 5.52 936 870 1.08 (0.98e1.18) 101,864 93,467 1.09 (1.08e1.10) 0.785
2006 33.28 5.11 1025 932 1.10 (1.01e1.20) 100,859 92,028 1.10 (1.09e1.11) 0.939
2007 35.33 1.15 1278 1,109 1.15 (1.06e1.25) 100,434 91,587 1.10 (1.09e1.11) 0.229
2008 NA 1268 1,164 1.09 (1.01e1.18) 98,038 89,530 1.10 (1.09e1.11) 0.899
2009 33.54 4.33 1318 1,136 1.16 (1.07e1.26) 94,987 87,612 1.08 (1.07e1.09) 0.096
2010 33.49 4.61 1301 1,189 1.09 (1.01e1.18) 82,126 75,156 1.09 (1.08e1.10) 0.974
2011 33.68 4.13 1310 1,232 1.06 (0.98e1.15) 101,943 94,684 1.08 (1.07e1.09) 0.755
Total 15,923 14,354 1.11 (1.08e1.13) 788,014 722,337 1.09 (1.09e1.09) 0.151
CI ¼confidence interval; NA ¼not available.
a
Data retrieved from http://sowf.moi.gov.tw/stat/year/elist.htm; accessed January 15, 2012.
b
95% CI for the proportion of male births (pf) with a variance of pf (1 epf).
c
All were nonsignificant after Bonferroni correction.
574 I-W. Lee et al. / Taiwanese Journal of Obstetrics & Gynecology 51 (2012) 572e575

reporting of female births and, in some cases, even mis-
reporting of the sex [20,21]. Previous studies suggest
a growing imbalance in China’s sex ratio at birth, which is
most likely due to an increase in sex-selective abortion [20].
Contrary to China with its strict one-child policy, people in
Taiwan are encouraged to have two or more children, espe-
cially if a girl is born first. In Taiwan, the fertility rate, defined
as the number of babies born every year divided by the
number of women during childbearing age, has gradually
decreased from 7.045 in the 1940s to 1.030 in 2010 [22].In
fact, the decision by parents not to have another child if their
first child is a boy may more accurately explain the higher sex
ratio than sex-selection abortion as a result of fetal sex
detection [18]. A couple, therefore, might choose to have only
one baby if they already have a boy, whereas a couple whose
first child is a girl might attempt to have a son in the following
pregnancy [23].
Our data obtained from individuals with a cultural prefer-
ence for boys show that sex ratio is already skewed at
amniocentesis at midtrimester. The data imply that artificial
sex selection, if it were present, might occur prior to
amniocentesis.
To the best of our knowledge, no previous reports on the
prenatal human sex distribution issue have been published in
Taiwan. Our series might be the first one to investigate the sex
ratio at amniocentesis and at birth. Our data showed no
difference between the sex ratio at amniocentesis and that at
birth. However, our study had some limitations. First, the sex
ratio at birth might vary with maternal age, and the mothers in
the prenatal group at NCKUH were markedly older than the
mothers in the general population in Taiwan. Second, the
cytogenetic database does not include information on the birth
order or the sex of babies previously born in the same families.
In conclusion, we present the trends of sex ratios at the
midtrimester and at birth in Taiwan from 1992 to 2011. The
results show no difference between the sex ratios at amnio-
centesis at NCKUH and at birth in Taiwan for two decades.
From this series, we conclude that the annotation of fetal sex
by prenatal cytogenetic reports has no effect on the sex ratio at
birth. Further studies are required to draw a definite conclusion
between these links.
Acknowledgments
Special thanks to Professor Fong-Ming Chang, Department
of Obstetrics and Gynecology, National Cheng Kung Univer-
sity Hospital and College of Medicine, for his critical review
and suggestions for this manuscript.
References
[1] Bloom DE. 7 billion and counting. Science 2011;333:562e9.
[2] Catalano R, Bruckner T. Male lifespan and the secondary sex ratio. Am J
Human Biol 2006;18:783e904.
[3] Allan BB, Brant R, Seidel JE, Jarrell J. Declining sex ratios in Canada.
CMAJ 1997;156:37e41.
[4] Fukuda M, Fukuda K, Shimizu T, Nobunaga M, Grete Byskov A, Yding
Andersen C. The sex ratio of offspring is associated with the mothers’
age at menarche. Hum Rep 2011;26:1551e4.
[5] Branum AM, Parker JD, Schoendorf KC. Trends in US sex ratio by
plurality, gestational age and race/ethnicity. Hum Rep 2009;24:2936e44.
[6] Mathews TJ, Hamilton BE. Trend analysis of the sex ratio at birth in the
United States. Natl Vital Stat Rep 2005;53:1e17.
[7] Smith D, Von Behren J. Trends in the sex ratio of California births, 1960-
1996. J Epidemiol Community Health 2005;59:1047e53.
[8] Dama MS. Sex ratio at birth and mortality rates are negatively related in
humans. PLoS One 2011;6:e23792.
[9] Jha P, Kesler MA, Kumar R, Ram F, Ram U, Aleksandrowicz L, et al.
Trends in selective abortions of girls in India: analysis of nationally
representative birth histories from 1990 to 2005 and census data from
1991 to 2011. Lancet 2011;377:1921e8.
[10] Zhu WX, Lu L, Hesketh T. China’s excess males, sex selective abortion,
and one child policy: analysis of data from 2005 national intercensus
survey. BMJ 2009;338:1211.
[11] Singh N, Pripp AH, Brekke T, Stray-Pedersen B. Different sex ratios of
children born to Indian and Pakistani immigrants in Norway. BMC
Pregnancy Childbirth 2010;10:40.
[12] Department of Health Order: number 1000200809, published by the
Executive Yuan, Taiwan, R.O.C. Available at: http://gazette.nat.gov.tw/
EG_FileManager/eguploadpub/eg017011/ch08/type1/gov70/num17/Eg.
htm [accessed 15.12.11].
[13] Spiegel MR. Schaum’s outline of theory and problems of statistics
(’Schaum’s outline series). 2nd ed. New York: McGraw-Hill; 1989.
[14] Cramer JS, Lumey LH. Maternal preconception diet and the sex ratio.
Hum. Biol 2010;82:103e7.
[15] Marcus M, Kiely J, Xu F, McGeehin M, Jackson R, Sinks T. Changing
sex ratio in the United States, 1969e1995. Fertil Steril 1998;70:270e3.
[16] Scherb H, Voigt K. The human sex odds at birth after the atmospheric
atomic bomb tests, after Chernobyl, and in the vicinity of nuclear
facilities. Environ Sci Pollut Res Int 2011;18:697e707.
[17] Liu Y, Zhi M, Li X. Parental age and characteristics of the offspring.
Ageing Res Rev 2011;10:115e23.
[18] Egan JF, Campbell WA, Chapman A, Shamshirsaz AA, Gurram P,
Benn PA. Distortions of sex ratios at birth in the United States; evidence
for prenatal gender selection. Prenat Diagn 2011;31:560e5.
[19] Ganatra B. Maintaining access to safe abortion and reducing sex ratio
imbalances in Asia. Reprod Health Matters 2008;16:90e8.
[20] Hvistendahl M. Demography. China’s population growing slowly,
changing fast. Science 2011;332:650e1.
[21] Hvistendahl M. Demography. Has China outgrown the one-child policy?
Science 2010;329:1458e61.
[22] Satistical Year Book of Interior. published by Innitary Department,
Administary Yuen, Available at: http://sowf.moi.gov.tw/stat/year/elist.
htm [accessed 15.01.12].
[23] Manchanda S, Saikia B, Gupta N, Chowdhary S, Puliyel JM. Sex ratio at
birth in India, its relation to birth order, sex of previous children and use
of indigenous medicine. PLoS One 2011;6:e20097.
575I-W. Lee et al. / Taiwanese Journal of Obstetrics & Gynecology 51 (2012) 572e575