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You Are What Your Mother Eats: Evidence for Maternal Preconception Diet Influencing Foetal Sex in Humans


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Facultative adjustment of sex ratios by mothers occurs in some animals, and has been linked to resource availability. In mammals, the search for consistent patterns is complicated by variations in mating systems, social hierarchies and litter sizes. Humans have low fecundity, high maternal investment and a potentially high differential between the numbers of offspring produced by sons and daughters: these conditions should favour the evolution of facultative sex ratio variation. Yet little is known of natural mechanisms of sex allocation in humans. Here, using data from 740 British women who were unaware of their foetus's gender, we show that foetal sex is associated with maternal diet at conception. Fifty six per cent of women in the highest third of preconceptional energy intake bore boys, compared with 45% in the lowest third. Intakes during pregnancy were not associated with sex, suggesting that the foetus does not manipulate maternal diet. Our results support hypotheses predicting investment in costly male offspring when resources are plentiful. Dietary changes may therefore explain the falling proportion of male births in industrialized countries. The results are relevant to the current debate about the artificial selection of offspring sex in fertility treatment and commercial 'gender clinics'.
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You are what your mother eats:
evidence for maternal preconception diet
influencing foetal sex in humans
Fiona Mathews
, Paul J. Johnson
and Andrew Neil
Hatherly Laboratories, School of Biosciences, University of Exeter, Prince of Wales Road, Exeter EX4 4PS, UK
Wildlife Conservation Research Unit, Department of Zoology, University of Oxford,
Tubney House, Tubney, Oxon OX13 5QL, UK
Division of Public Health and Primary Health Care, Institute of Health Sciences,
University of Oxford, PO Box 777, Oxford OX3 7LF, UK
Facultative adjustment of sex ratios by mothers occurs in some animals, and has been linked to resource
availability. In mammals, the search for consistent patterns is complicated by variations in mating systems,
social hierarchies and litter sizes. Humans have low fecundity, high maternal investment and a potentially
high differential between the numbers of offspring produced by sons and daughters: these conditions
should favour the evolution of facultative sex ratio variation. Yet little is known of natural mechanisms of
sex allocation in humans. Here, using data from 740 British women who were unaware of their foetus’s
gender, we show that foetal sex is associated with maternal diet at conception. Fifty six per cent of women
in the highest third of preconceptional energy intake bore boys, compared with 45% in the lowest third.
Intakes during pregnancy were not associated with sex, suggesting that the foetus does not manipulate
maternal diet. Our results support hypotheses predicting investment in costly male offspring when
resources are plentiful. Dietary changes may therefore explain the falling proportion of male births in
industrialized countries. The results are relevant to the current debate about the artificial selection of
offspring sex in fertility treatment and commercial ‘gender clinics’.
Keywords: sex ratio; nutrition; diet; mammal; fertility treatment; Trivers–Willard hypothesis
The ability of parents to influence their offsprings sex
should be favoured by natural selection (Trivers & Willard
1973; Myers 1978; Clutton-Brock 1991). Perhaps the best-
known evolutionary theory of sex ratio variation, the Trivers
and Willard hypothesis (1973), proposes that if increased
parental condition differentially enhances the reproductive
success of sons, then parents in good condition should
favour male offspring. Competing hypotheses have also
been proposed to explain differential sex ratio allocations in
relation to resource availability and local conditions.
Whether such models can be expected to apply to
modern-day humans might reasonably be disputed: not
only do we have complex social structures that govern
mating patterns but also resources are more readily
available to us than to most wild mammals. Yet the
technological age represents only a tiny fraction of the time
scale over which reproductive strategies have evolved:
phylogenetic inertia is therefore to be expected. In
industrialized, as well as traditional societies, tall men
and those of higher social status have greater reproductive
success (Pawlowski et al.2000; Fielder et al. 2005;
Hopcroft 2006). Similarly, men exhibit more risk-taking
behaviour than do women, particularly in young adult-
hood when sexual competitiveness is greatest (Daly &
Wilson 1985; Wilson & Daly 1997; Kruger & Nesse
2007); men have strong preferences for physical traits
associated with fertility (Buss et al. 1990); and they also
have a much greater desire for multiple partners and
short-term relationships than do women (Schmitt et al.
2001; Buss 2006). All of these traits are likely to have
evolved because they contributed to reproductive success
in an ancestral age. Human reproductive biology would be
expected to favour the evolution of parental control over
offspring sex, since there is low fecundity and high
maternal investment, and sons are more costly to produce
in both the short and long terms than daughters
(Clutton-Brock & Iason 1986; Frank 1987; Hrdy 1999;
Rickard et al. 2007; for further discussion of evolutionary
context, see electronic supplementary material).
Weak relationships between sex ratios and the nutri-
tional resources of mothers in late pregnancy and post-
natally have been reported (Gibson & Mace 2003; Tamimi
et al. 2003) but are controversial (Stein et al. 2003). Even if
real, they do not imply any maternal command over foetal
sex. Differential provisioning in late pregnancy or after
delivery may reflect either manipulation of maternal
metabolism and behaviour by the offspring, for example,
through the action of foetal testosterone, or alterations in
maternal behaviour due to knowledge of foetal sex (Shay
2003; Stein et al. 2003). The mechanism for controlling
the sex ratio at birth in mammals is likely to be the
differential conception and maintenance of male and
female embryos (McMillen 1979). If there is maternal
Proc. R. Soc. B (2008) 275, 1661–1668
Published online 22 April 2008
Electronic supplementary material is available at
1098/rspb.2008.0105 or via
* Author for correspondence (
Received 23 January 2008
Accepted 1 April 2008
1661 This journal is q 2008 The Royal Society
manipulation of sex ratios in response to resource
availability, then diet before and shortly after conception
should be correlated with offspring sex: in non-human
mammals, high resource availability around conception is
consistently linked with male-biased sex ratios, whereas
indices from later pregnancy or after birth produce contra-
dictory results (Cameron 2004). We explored whether high
resource availability around conception was linked with
differential investment in male offspring in a large cohort
of British women who were unaware of the sex of their
foetuses. Determining whether infant sex is ‘naturally
influenced by maternal conditions is of direct relevance to
the current debate about the artificial selection of an
embryo’s sex during fertility treatment and in commercial
‘gender clinics’, and may offer insights into the falling
proportion of male births in developed countries ( James
2000; Davis et al. 2007).
(a) Study design and dietary assessment
Nulliparous white women with no medical problems
(including obesity) were recruited from a district general
hospital in the south of England at their first antenatal clinic
visit early in pregnancy (approx. 14 weeks gestation).
Regardless of their medical history, all pregnant women in
the region were referred to these clinics by their family
physician; stratified random sampling was used to ensure that
the proportion of smokers in the cohort represented that in
the local population. Full details of the study methods have
been reported elsewhere (Mathews et al. 1999). A total
of 740 women with normal singleton pregnancies kept a
prospective food diary of their diet in early pregnancy
(hereafter referred to as ‘early pregnancy’ data); of these,
721 gave a retrospective report of their usual diet in the year
prior to conception (‘preconception’ data) and 661 reported
their usual diet during pregnancy at approximately 28 weeks
gestation (‘later pregnancy’ data). Seventeen additional
women provided dietary data, but were excluded from the
analysis because they moved out of the district before giving
birth. The women were ‘blind’ to the sex of their offspring at
the time of completing their questionnaires: owing to hospital
policy, offspring sex was not disclosed at ultrasound scans.
The only mothers to know the sex of their infant during the
study were those who had amniocentesis (nZ25) or had
abnormality scans (nZ27): even here, the information was
available only later in gestation, after the preconception and
early pregnancy data had been obtained. All women provided
written informed consent and the study was approved by the
Research Ethics Committees of Portsmouth Hospitals and of
the University of Oxford Medical School.
Food frequency questionnaires are the most widely used
method of dietary assessment in epidemiological studies
(including previous work on maternal provisioning; Tamimi
et al. 2003), and substantial effort has been put into assessing
their repeatability and validity (Willett 1990). The time scale
for recall was relatively short (a matter of months) compared
with many studies, for example, those evaluating risks of
cancer or cardiovascular disease, which attempt to evaluate
dietary exposures experienced years ago. Those adopted for
this work have been used in large epidemiological studies in
Europe are based on the questionnaire used in the US Nurses
Health Study and have been validated (with comparable
intervals between food consumption and recall) against a
7-day food diary (Bingham et al. 1997). Food diaries, as used
in this project, are considered a ‘gold standard’ method of
dietary assessment (Willett 1990). Further details of the
methods used and their reliability are given in the electronic
supplementary material.
(b) Statistical analysis
We explored the differences between proportions using
-tests, and between means using Z-tests. Food and nutrient
intakes were measured on interval scales and were always
analysed as continuous variables. The groupings given in
figures for illustrative purposes are derived from splitting as
closely as possible to the tertiles; the unequal group size for
breakfast cereals is due to the large numbers of women who
habitually consumed cereal daily. Because intakes of different
nutrients are correlated, we used principal components
analysis (PCA; SAS FACTOR procedure) to summarize
dietary patterns: the computed factor scores were used in
further analyses. This method has been shown elsewhere to
be a good method of summarizing dietary patterns, and is
preferable to other methods such as cluster analysis, which
result in the formation of categorical rather than continuous
variables (Crozier et al. 2006). The joint effects of exposures
were investigated using logistic regression (SAS GENMOD
procedure). For the analyses of individual nutrient intakes
and foetal sex, the ranks of intakes were used for data derived
from the food frequency questionnaires. This was owing to
the difficulties in assessing absolute intakes using this method
and the technique reduces the leverage of outlying values. All
tests of significance were two-tailed. Given the multiplicity of
testing, we interpreted p-values conservatively for individual
nutrient items.
In the simple multivariate models (SAS GLM type 1
models; used because the predictors were correlated), the
coefficient for energy represents energy independent of
the other nutrients in the model. For example, for a model
including fat and energy, the term for energy represents
energy from sources other than fat, i.e. carbohydrate, protein
and alcohol. Alternatively, the residual method ( Willett
1990) can be used to adjust specific nutrients for energy
intakes. The relationships between the total energy intake
and outcome and the nutrient density and outcome can then
be analysed distinctly. Concordant results were obtained
with our data whichever method of analysis was used.
Nutritional patterns were summarized separately for
nutritional data from three time periods: usual intake
before conception (preconception); intake at approxi-
mately 16 weeks gestation (early pregnancy); and usual
intake between 16 and 28 weeks gestation (later
pregnancy). For each period, two derived factors
encapsulated a high proportion of the variability in the
data and can therefore be considered good summary
statistics (table 1). The factor-loading patterns in all
three time periods (correlations between the input
variables and the scores) indicated that high scores for
factor 1 described diets high in many nutrients including
protein, fat, vitamin C, folate and a range of minerals;
while high scores for factor 2, described diets high in the
vitamin A components and vitamin B
(table 1). The
factor scores for the three time periods were correlated
1662 F. Mathews et al. Preconceptional diet predicts foetal sex
Proc. R. Soc. B (2008)
(rZ 0.2, p!0.001), indicating some consistency in
individual women’s dietary intake over time.
Given the correlations between the dietary measures
across time, we first tested whether dietary patterns overall
were linked to offspring sex by using the factor scores from
the different times as multivariate responses (MANOVA)
and sex as a predictor. Factor 1 scores were influential
Z2.6, pZ0.051), but no models using
factor 2 were significant. Further, a profile analysis, using
the differences between the factor 1 scores in different time
periods, indicated that the difference varied significantly
across time (non-parallelism test: F
Z3.64, pZ0.03).
Inspection of the within-time period factor score pattern
showed that the diet difference was greatest for the
preconception diet, whereas there was not a significant
difference for either early or later pregnancy (Wald
%0.22, pR0.47). Factor 1 score was a significant
predictor of foetal sex preconception (Wald c
pZ0.00095), with male offspring being more frequent
among women with high scores. Factor 2 was not
associated with foetal sex (Wald c
Z0.22, pZ0.64).
Having established the existence of relationships
between preconceptional nutritional patterns and foetal
sex, we went on to examine individual nutrients in more
detail. As would be predicted from the factor pattern,
factor 1 scores were highly correlated with energy intake
(rZ0.87, p!0.001): in logistic regression, energy intake
gave a similar model fit to factor 1 (Wald c
pZ0.023). In support of the prediction that mothers with
more resources before conception would have more sons,
mothers of males had higher intakes of macronutrients and
a range of micronutrients at this time than did mothers of
females, when individual nutrients were used in the
analyses (table 2). The proportions of male offspring born
to women in different thirds of energy intake are illustrated
in figure 1: the odds ratio for having a male infant was 1.5
for women in the highest third of energy intake compared
with those in the lowest third (95% CI 1.1, 2.2).
The relationships between nutritional exposures and
outcome variables may be analysed either in terms of
absolute intakes, or in relation to total energy intake
(intakes of many nutrients are positively correlated with
total energy intake, and some, e.g. the macronutrients, are
metabolized in proportion to total energy consumption;
Willett 1990). After adjusting for energy in simple multi-
variate models, no other nutrient was independently
associated with infant sex. Thus, an increased prevalence
of male foetuses was associated with high maternal nutrient
intakes, but not with high-nutrient density. Although the
associations with energy are compatible with predictions
from evolutionary approaches to sex ratio variation, it is
possible that the causal mechanism involves other nutri-
ents. In forward stepwise regression, potassium intake was
selected as the predictor of offspring sex ( pZ0.004) and no
other variable was selected for inclusion in the model after
adjusting for the effect of potassium.
No socio-demographic or anthropometric charac-
teristic was a significant predictor of foetal sex (table 3).
Nor was smoking status or caffeine intake prior to, or
during, pregnancy (table 3). We also tested whether
offspring sex was a nonlinear function of body mass index
(BMI) to allow for the possibility that an optimum
‘condition exists on this continuum. There was no
evidence for this (a quadratic function of BMI was not a
significant predictor of offspring sex).
We then examined whether there is differential
postconception investment in the foetus according to
sex, possibly induced by the foetus itself. Nutrient intakes
in early pregnancy, but beyond the period when most
foetal losses occur—approximately 16 weeks gestation
were not associated with foetal sex (table 2). The same was
true for later pregnancy (see electronic supplementary
material). Thus, the additional energetic cost of producing
a male infant, males being approximately 100 g heavier
than females, does not appear to be met via detectable
differences in maternal nutritional intake.
Table 1. PCA factor loadings for daily dietary intakes, and proportion of variability in data encapsulated by the factors at each
time point. (Notes. Because sodium is difficult to measure accurately with any dietary method due to variation between brands of
processed food, and addition of table salt to food and cooking, it was not included in the PCA. Italics indicate PCA factor
loadings with absolute values R 0.70 which by convention indicate that the variables are excellent components of the factors
(Comfrey & Lee 1992).)
preconception early pregnancy later pregnancy
factor 1 factor 2 factor 1 factor 2 factor 1 factor 2
fat 0.73 0.25 0.84 0.07 0.90 0.11
protein 0.88 0.26 0.74 0.50 0.79 0.48
carbohydrate 0.60 K0.08 0.03 0.76 0.13 0.76
vitamin C 0.85 0.18 0.61 0.42 0.81 0.33
vitamin E 0.70 0.18 0.41 0.10 0.60 0.39
b-carotene 0.50 K0.13 0 0.59 0.10 0.67
retinol 0.01 0.91 0.67 K0.13 0.83 0.04
vitamin B
0.25 0.82 0.62 0.24 0.18 0.57
folate 0.82 0.11 0.36 0.80 0.47 0.77
iron 0.84 0.28 0.50 0.60 0.61 0.62
zinc 0.86 0.29 0.67 0.53 0.79 0.44
calcium 0.74 0.19 0.67 0.41 0.81 0.24
potassium 0.89 0.13 0.56 0.70 0.71 0.58
proportion of variability
encapsulated by factor (%)
55.40 11.00 48.80 10.50 59.60 10.20
Preconceptional diet predicts foetal sex F. Mathews et al. 1663
Proc. R. Soc. B (2008)
Table 2. Daily dietary intakes
by foetal sex.
preconception early pregnancy
median (lower, upper quartile) c
p-value median (lower, upper quartile) c
male foetus (nZ360) female foetus (nZ361) male foetus (nZ372) female foetus (nZ368)
energy (kcal) 2413 (1986, 2912) 2283 (1781, 2720) 4.80 0.029 2033 (1763, 2283) 2061 (1730, 2326) 1.06 0.304
total fat (g) 87.0 (70.7, 112.0) 85.5 (67.3, 106.2) 2.20 0.138 84.2 (69.6, 98.0) 84.8 (70.4, 101.3) 0.16 0.692
% energy from fat 33.5 (30.6, 37.0) 34.2 (31.0, 37.4) 0.59 0.441 37.6 (34.5, 40.7) 37.9 (34.7, 41.2) 1.43 0.232
protein (g) 95.9 (77.3, 113.9) 91.3 (73.7, 109.8) 7.25 0.007 71.7 (62.0, 84.2) 74.6 (61.8, 85.2) 0.68 0.409
% energy from protein 15.9 (14.3, 17.7) 15.7 (14.1, 17.6) 0.49 0.484 14.5 (12.9, 16.1) 14.6 (13.2, 16.0) 0.19 0.663
carbohydrate (g) 342 (281, 406) 323 (259, 384) 4.46 0.035 257.3 (220.5, 292.4) 255.2 (214.3, 293.1) 2.43 0.119
% energy from carbohydrate 52.8 (49.0, 56.1) 52.4 (49.0, 56.1) 0.08 0.784 47.4 (44.7, 50.5) 47.2 (43.6, 50.3) 1.51 0.219
vitamin C (mg) 111 (78, 72) 103 (72, 140) 2.29 0.130 76.5 (49.0, 109.8) 71.0 (46.0, 107.0) 0.72 0.397
vitamin E (mg) 8.0 (6.3, 10.4) 7.7 (6.0, 9.6) 2.75 0.097 8.0 (5.8, 11.3) 8.2 (6.0, 11.2) 0.03 0.872
b-carotene (mg) 1658 (998, 2564) 1479 (999, 2560) 0.00 0.975 897 (449, 1542) 869 (481, 1345) 0.83 0.360
retinol (mg) 469 (321, 888) 433 (302, 832) 0.14 0.708 406 (311, 503) 417 (317, 532) 0.62 0.432
vitamin B
(mg) 7.2 (4.8, 10.9) 6.8 (4.5, 10.5) 0.02 0.875 3.7 (2.8, 4.7) 3.6 (2.8, 4.6) 0.02 0.879
folate (mg) 396 (321, 479) 367 (293, 460) 3.76 0.052 240 (189, 279) 236 (192, 292) 0.96 0.327
iron (mg) 14.6 (11.8, 18.3) 13.5 (11.1, 16.8) 4.14 0.042 10.2 (8.4, 12.2) 10.0 (8.7, 11.9) 1.04 0.308
zinc (mg) 12.0 (9.5, 14.9) 11.3 (9.1, 13.9) 4.45 0.035 8.0 (6.5, 9.5) 8.1 (6.7, 9.6) 0.02 0.880
sodium (mg)
4267 (3445, 5105) 3944 (3226, 4807) 8.73 0.003 2976 (2534, 3553) 2971 (2522, 3547) 1.57 0.209
calcium (mg) 1246 (970, 1572) 1154 (905, 1437) 7.41 0.006 896 (725, 1103) 903 (721, 1129) 0.52 0.437
potassium (mg) 4630 (3952, 5492) 4342 (3646, 5190) 3.97 0.046 2952 (2516, 3390) 2967 (2462, 3478) 0.76 0.382
Diet before conception was assessed using a food frequency questionnaire, and in early pregnancy using a 7-day food diary. The absolute values for intakes are therefore not directly comparable due to the
methodological differences, but good agreement is obtained for the ranking of subjects (see electronic supplementary material).
Sodium intake is difficult to measure accurately with any dietary method due to variation between brands of processed food and addition of table salt to food and cooking.
1664 F. Mathews et al. Preconceptional diet predicts foetal sex
Proc. R. Soc. B (2008)
We went on to test whether particular foods were
associated with infant sex. Data of the 133 food items from
our food frequency questionnaire were analysed, and we
also performed additional analyses using broader food
groups. Prior to pregnancy, breakfast cereal, but no other
item, was strongly associated with infant sex (Wald
Z8.2, pZ0.004). Women producing male infants
consumed more breakfast cereal than those with female
infants (figure 1). The odds ratio for a male infant was
1.87 (95% CI 1.31, 2.65) for women who consumed at
least one bowl of breakfast cereal daily compared with
those who ate less than or equal to one bowlful per week.
No other foods were significantly associated with infant
sex (given the multiplicity of testing, p%0.01 was
considered significant), and was also true for the broader
food categories. During later pregnancy, breakfast cereal
consumption remained considerably higher among
mothers of males (Wald c
Z4.0, pZ0.04). There were
no differences for any other foods. Our data did not permit
us to examine the consumption of breakfast per se, but
breakfast cereal is the main food eaten for breakfast in the
UK and is only rarely consumed at other times of day.
We have provided evidence of facultative selection of
offspring sex by individual women according to environ-
mental cues experienced around conception. The results
fit into evolutionary frameworks developed with other
species where, as in humans, males have greater potential
lifetime reproductive success and are also more costly to
produce ( Trivers & Willard 1973; Myers 1978; Clutton-
Brock 1991; see also electronic supplementary material).
The overall sex ratio in our population was close to
50 : 50, but individual mothers had a greater chance of
bearing male offspring if their nutrient intake was high
prior to conception. The consumption of breakfast cereals
was also strongly associated with having a male infant. The
effect sizes in our study are striking even though our
cohort was relatively well nourished. Parity is the main
factor consistently associated with sex ratio in humans
(Novitski & Kimball 1958; Rostron & James 1977). The
difference in sex ratio between women in the highest and
lowest tertiles of energy intake is approximately 10 times
more than that reported between women with first and
third births, and is comparable with differences found in
classic experimental manipulations of maternal nutrition
in animals (e.g. Sachdeva et al. 1973; Labov et al. 1986).
The lack of dietary differences between mothers of sons
and daughters during pregnancy itself is consistent with
well-established observations that the very slow growth rate
of the human foetus generates a lower incremental
nutritional stress than in any other mammal: additional
energy requirements, for example, are met via metabolic
and behavioural energy-sparing mechanisms rather than
increased intakes (Prentice et al.1995). The marginally
significant greater energy intake among pregnant mothers of
males reported by one previous study (Ta m im i et al.2003)
may have been due to maternal knowledge of foetal sex, or
because preconceptional dietary patterns were carried over
into pregnancy to a greater extent than in our cohort.
Although strong associations were seen for energy
consumption, it is possible that any of the other correlated
nutrients may be important in the aetiological pathway.
There is tremendous interest in popular literature and the
media about a possible link between dietary mineral intake
(particularly calcium, sodium and potassium) and off-
spring sex (e.g. Chesterman-Phillips 2005). This is despite
there being only scant support for the mechanism
operating in humans (Papa et al. 1983) or animals (Cluzan
et al. 1965; Bird & Contreras 1986). Doubt has also been
cast on the mechanism of altered blood and vaginal pH
linking offspring sex with mineral intake (Roche & Lee
2007). Although all of these nutrients did show highly
significant associations with foetal sex in our study, we are
cautious in the interpretation of the data until further
research is available: the associations for sodium and
potassium were in the predicted direction, but the
association for calcium was not.
In general, the mechanisms of sex allocation in
mammals are not well understood; however, a pathway
has been proposed that could explain our associations of
foetal sex with energy intake and breakfast cereal
consumption around conception. In vitro,glucose
enhances the growth and development of male con-
ceptuses while inhibiting that of females (Larson et al.
2001). Skipping breakfast extends the normal period of
nocturnal fasting, depresses circulating glucose levels
and may be interpreted by the body as indicative of poor
environmental conditions. A range of sequelae has
previously been reported, including elevated risks of
chronic diseases, such as non-insulin-dependent Diabetes
mellitus, and abnormal blood glucose levels ( Lecomte
et al.2002).
Various non-nutritional factors have been associated
with sex allocation in humans, and these may act in
concert with nutritional factors or may be confounded
with them. These factors include environmental tempera-
ture (Helle et al. 2008); variations in hormonal profiles in
women at around the time of conception according to
their status and ‘stress’ levels (James 1990; Grant 2007);
and the timing of insemination relative to ovulation (which
is closely correlated with coital frequency since fertili-
zation early in the cycle is more likely if there is frequent
insemination; James 1971; Guerrero 1974; Harlap 1979).
energy cereal
percentage of males
240 240 241 216 205 300
Figure 1. Relationship between usual maternal intakes of
energy and breakfast cereal prior to pregnancy, split at
approximate tertiles, and the proportion of male infants
(Cs.e.m.). Comparisons of the numbers of males and females
across the groups were made using c
-test for linear
association. The numbers above each bar indicate the
numbers of women in each category of intake. For energy,
the bars represent the low (open), moderate (filled) and
high ( hatched) thirds of intake; c
Z5.83, pZ0.016. For
breakfast cereal, the bars represent less than one bowl per
week (open), two to six bowls per week (filled) and one or
more bowl per day (hatched); c
Z13.96, p!0.001.
Preconceptional diet predicts foetal sex F. Mathews et al. 1665
Proc. R. Soc. B (2008)
Attention has focused particularly on the latter, with
conceptions earlier in the oestrus cycle apparently being
more likely to be male, and there being greater
maintenance of male blastocysts if they are in synchrony
with uterine ripeness (Krackow 1995). However, more
recent clinical studies dispute these associations ( Wilcox
et al. 1995; Reubinoff & Schenker 1996). It remains to be
seen whether women with greater nutritional intakes, and
higher frequency of breakfast cereal consumption, prior to
conception are also those with more active sex lives.
All methods of dietary assessment are prone to some
degree of error. However, it is highly unlikely that these
errors (formally, the within-subject differences between
true and measured intakes) would produce spurious
associations. Rather they will attenuate the observed
associations between the outcome and exposure measures,
depressing odds ratios towards zero: the generation of
artefactual relationships would generally require differ-
ential misreporting of diet by women carrying male rather
than female foetuses ( Willett 1990; Clayton & Gill 1991;
see electronic supplementary material). Given that the
women in this study did not know the sex of their foetus,
the latter possibility is unlikely.
Since all of the women in the study were white and
nulliparous, we avoided the potentially confounding
effects of race and birth order, both of which are associated
with sex ratio ( Novitski & Kimball 1958; Rostron & James
1977). Maternal age has not generally been associated
with sex ratio independent of parity ( Teitelbaum &
Mantel 1971; Rostron & James 1977), and accordingly
we found no association between any maternal age and sex
ratio. Weight and condition measures are poor predictors
of offspring sex in non-human mammals (Cameron 2004;
Sheldon & West 2004), and we found no associations in
our study. The measures are relatively weak indicators of
resource availability, reflecting a combination of basal
metabolic rate (a variable practically impossible to
measure in large-scale studies), frame size and long-term
levels of physical activity and dietary intake. Of these
factors, variation in physical activity appears to be a major
determinant of differences between individuals in energy
expenditure, and is likely to explain why obesity is only
poorly correlated with energy intake in epidemiological
studies ( Willett 1990). Although BMI (weight/height
widely used as an index of body fat, it is error prone due to
the large variation in lean body mass among people of the
same height. Even in Ethiopia, a country with marked
regional variations in the prevalence of maternal under-
nutrition, the associations between such indices and infant
sex are questionable (Shay 2003; Stein et al. 2003): from
an evolutionary perspective, there is no reason to assume
that body fat indices—reflecting historical imbalances
between energy intake and expenditure—should be a good
marker of resources currently available. For many
nutrients, circulating levels are highly dependent on recent
intakes and not on stored fat reserves. This is the case, for
example, with water-soluble vitamins, and circulating
glucose levels are influenced by the glycaemic index of
foods. The recent finding that change in condition indices
is more predictive of sex ratio than is condition per se
(Roche et al. 2006; Cameron & Linklater 2007) further
supports our contention that sex ratio is linked more
directly to diet than to maternal condition.
Over the past 40 years, there have been small, but
highly consistent, declines in the proportion of male
infants born in industrialized countries (James 2000).
This has caused considerable concern, and is regarded as a
health sentinel, possibly of exposure to toxins (Davis et al.
1998; James 2000). However, population-level changes in
the diets of young women may explain the pattern. Trends
of declining mean energy intake over time among adults
and children are reported by most (Heini & Weinsier
Table 3. Maternal characteristics and foetal sex.
%(n) or mean [s.d.]
male foetus (nZ372) female foetus (nZ368) test statistic
current smoker
39.0 (145) 42.4 (156) 0.89 0.35
cigarettes yesterday (n)
0 73.9 (275) 69.8 (257) 1.72 0.27
1–8 14.8 (55) 17.4 (64)
9–16 8.6 (32) 9.2 (34)
17 or more 2.7 (10) 3.5 (13)
folic acid used prior to conception 34.4 (128) 34.2 (126) 0.002 0.96
!O level 23.1 (86) 19.6 (72) 1.40 0.50
O level 51.1 (190) 53.5 (197)
OO level 25.8 (96) 26.9 (99)
age ( years) 25.8 [5.0] 25.8 [4.9] 0.01 0.92
weight prior to conception ( kg)
62.8 [11.7] 62.6 [15.0] 0.06 0.80
weight at booking ( kg)
67.2 [12.5] 66.2 [12.3] 1.16 0.28
height (cm) 164.3 [6.5] 164.3 [6.6] 0.01 0.91
body mass index prior to conception
(kg m
23.2 [4.0] 23.2 [5.3] 0.06 0.81
body mass index at first antenatal clinic
(kg m
24.9 [4.3] 24.5 [4.3] 1.18 0.28
Wald c
-test for continuous and categorical predictors in logistic models.
Defined by self-report or by a serum cotinine concentration greater than 14 ng ml
in self-reported ‘non-smokers’.
Data missing from medical records for 18 (4.8%) mothers of boys and 11 (3.0%) mothers of girls.
Data missing from medical records for 9 (2.4%) mothers of boys and 11 (3.0%) mothers of girls.
1666 F. Mathews et al. Preconceptional diet predicts foetal sex
Proc. R. Soc. B (2008)
1997; Troiano et al. 2000; Fletcher et al. 2004) though not
all ( Nielsen et al. 2002) large-scale studies, with the
current obesity epidemic being ascribed to declines in
physical activity and alterations in the distribution of
energy intakes. At the same time, there is good evidence
that the prevalence of breakfast skipping is increasing,
particularly among younger age groups: for example, in
the USA, the proportion of adults consuming breakfast
fell from 86 to 75% between 1965 and 1991, and for
adolescent girls, the decline was from 85 to 65% (Haines
et al. 1996; Siega-Riz et al. 1998). More work using
biomarkers of nutrient status pre-pregnancy is warranted
to further explore the relationship between infant sex and
maternal resources.
All women provided written informed consent and the
study was approved by the Research Ethics Committees of
Portsmouth Hospitals and of the University of Oxford
Medical school.
We thank the women who participated in the project, and
the staff of St Mary’s Hospital, Portsmouth. We are grateful
to the European Prospective Investigation of Cancer
(EPIC) for permission to use their dietary questionnaires.
Lin McRoberts and Linda Willis helped with data
collection and management. The project was funded by
the Sir Jules Thorn Charitable Trust. F.M. was a Royal
Society Dorothy Hodgkin Research Fellow. The manuscript
was improved by discussion with John Clarke, Ben Sheldon
and Tom Tregenza.
None of the authors has any competing interest.
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Proc. R. Soc. B (2008)
... Indeed, in high-income countries, higher intakes have been observed among mothers of sons compared with daughters, both preconceptually and during pregnancy (Mathews et al., 2008;Tamimi et al., 2003). In Chile, fetal growth of boys was affected by maternal nutritional status whereas that of girls was not. ...
... The nutrient adequacy of their diet is lower than their male household head despite some improvements in equity of intake associated with trial interventions . In contrast to observations of greater intake by mothers of sons in high-income settings (Mathews et al., 2008;Tamimi et al., 2003), diets were similar in mothers of sons and daughters in our sample. The increases in BMI and MUAC in the final month of pregnancy suggest that there may have been higher energy intakes in late pregnancy in the main study sample, however, we were not able to detect any difference in energy intake, perhaps due to the small number of still-pregnant women enrolled in the trial at study endpoint. ...
Full-text available
Objective: On average, boys grow faster than girls in early life but appear more susceptible to undernutrition. We investigated sex differences in early child growth, and whether maternal nutritional status and diet differed by offspring sex during and after pregnancy in an undernourished population. Methods: We analyzed longitudinal data from a cluster-randomized trial from plains Nepal, stratifying results by child or gestational age. Children's outcomes (0-20 months) were weight, length, and head circumference and their z-scores relative to WHO reference data in 2-monthly intervals (n range: 24837 to 25 946). Maternal outcomes were mid-upper arm circumference (MUAC), and body mass index (BMI) during pregnancy (12-40 weeks) (n = 5550 and n = 5519) and postpartum (n = 15 710 and n = 15 356), and diet in pregnancy. We fitted unadjusted and adjusted mixed-effects linear and logistic regression models comparing boys with girls. Results: Boys were larger than girls, however relative to their sex-specific reference they had lower length and head circumference z-scores from birth to 12 months, but higher weight-for-length z-scores from 0 to 6 months. Mothers of sons had higher MUAC and BMI around 36 weeks gestation but no other differences in pregnancy diets or pregnancy/postpartum maternal anthropometry were detected. Larger sex differences in children's size in the food supple-mentation study arm suggest that food restriction in pregnancy may limit fetal growth of boys more than girls. Conclusions: Generally, mothers' anthropometry and dietary intake do not differ according to offspring sex. As boys are consistently larger, we expect that poor maternal nutritional status may compromise their growth more than girls.
... 10 On the other hand, Mathews et al. found that the SRB increased in women who had a higher energy intake during their preconceptional period. 11 It is also observed that the pre-pregnancy body weight of the mother influences SRB. In this regard, Cagnacci et al. 12 reported that mothers with the lowest quartile of body weight ( < 54.6 kg) before pregnancy had a lower SRB than those of the other three quartiles of pregnancy (p < 0.01). ...
The sex ratio (ratio of boys to girls) at birth (SRB) is about 1.05 (about 105 males to 100 females) under normal conditions and could be an indicator for monitoring demographic changes. Generally, in comparison with female fetuses, the male fetus is biologically weaker and more vulnerable to prenatal events. SRB is influenced by various factors, such as maternal malnourishment. Remarkably, maternal malnourishment and less energy intake are pivotal factors for declining SRB in humans. As estimates, the SRB is below the normal range in sub-Saharan Africa (1.03) than the normal range (1.05). On the other hand, both malaria and helminth infections are hyperendemic in sub-Saharan Africa and both diseases are associated with maternal malnourishment. Hence, an important question arises, could declining SRB in sub-Saharan Africa be influenced by malaria and helminth infections? Cumulative evidence suggests that malaria and helminth infections could influence SRB by induction of maternal malnourishment. This hypothesis provides new ideas about the variation of SRB in some regions of the world where helminths and malaria are endemic.
... Fewer males were born to mothers affected by anorexia and bulimia nervosa and more males were born to those with binge eating disorder and eating disorder not otherwise specified (Bulik et al., 2008). A British longitudinal study of the diets of 740 women from pre-conception through pregnancy confirmed the hypothesis that gender ratio is in part influenced by the pre-conception nutritional status (Mathews, Johnson, & Neil, 2008). There was a higher proportion of conception of male fetuses when the maternal diet was rich in energy, protein and carbohydrate (supporting an evolutionary theory that when nutritional resources are poor the species needs more females). ...
Objective: To establish any health outcomes for infants to age one, associated with their mother having a diagnosis of an active eating disorder during pregnancy or the 12-month postnatal period. Method: A qualitative systematic literature review of numerous databases (Medline, PsycINFO, CINAHL, Scopus, Cochrane Library, MedNar, PsycExtra, National Institute for Health and Care Excellence and Open Grey) was performed examining any infant health outcomes. Results: This resulted in 22 included studies (17 cohort, 3 cross-sectional, 1 case controlled and 1 mixed methods study). A range of adverse infant outcomes including poor birth, growth and interactional feeding outcomes were identified. Discussion: Antenatal identification and treatment for women with an eating disorder during the perinatal period and their infants are vital. Optimizing pregnancy nutrition, maternal eating disorder symptoms and feeding interactions appear particularly important.
... In Kwon et al.' [14] also showed no differences in calcium concentration between male and female infants. A few country studies [23,34] revealed that the calcium concentration in human milk differed from infant sex. In the case of Korean women, there was no differences in calcium levels according to infant sex because of insufficient calcium intake and low levels of calcium in human milk. ...
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This study aimed to identify the relationship between selected trace elements in human milk and depression, breastfeeding self-efficacy, sleep satisfaction, and the demographic and obstetric characteristics of lactating mothers. Forty lactating mothers recovering after birth in two postpartum care centers located in Changwon, South Korea, were studied. Calcium, sodium, iron, and selenium concentrations in human milk were analyzed using inductively coupled plasma mass spectrometry at the analysis center of Kyungnam University. Data were analyzed using descriptive statistics, the Kruskal-Wallis test, the Mann-Whiney U test, and Spearman's correlation coefficients using an SPSS 23.0 program. There were no significant differences in concentration of selected trace elements (calcium, sodium, iron, and selenium) in human milk according to demographic and obstetric characteristics. Sodium concentration was negatively correlated with breastfeeding self-efficacy (r = −0.51, CI = −0.71 to −0.24). Selenium concentration was negatively correlated with calcium concentration (r = −0.34, CI = −0.58 to 0.38). Postpartum depression was negatively correlated with sleep satisfaction (r = −0.46, CI = −0.67 to −0.17) and with breastfeeding self-efficacy (r = −0.41, CI = −0.64 to −0.11). Breastfeeding self-efficacy was positively correlated with sleep satisfaction (r = 0.48, CI = 0.20 to 0.69). This study suggests that sodium concentration in human milk is associated with breastfeeding self-efficacy.
... As a result, mothers do not invest more than indispensable in their offspring growth, as a preventive strategy for safeguarding their own energetic balance during and after pregnancy and even for future gestations [81,82]. Evolutionary biology traditionally views males as the "most expensive and less useful" sex, so may therefore not be energy efficient for a mother to heavily invest in male offspring when the investment in adequate development and homeostasis of female progeny would guarantee the chances to reproduce and maintain the species through gene transmission to future generations [83,84]. ...
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The present study aimed to assess the importance of offspring genotype on postnatal development, independently of confounding factors related to prenatal environment and postnatal lifestyle, using a translational model of obesity and metabolic syndrome (the Iberian pig). Hence, we compared two genotypes (purebred Iberian and crossbreds Iberian × Large White), produced in one single maternal environment (pure Iberian mothers) through artificial insemination of Iberian sows with Iberian and Large White heterospermic semen and maintained in the same conditions during postnatal development. The results indicate that, under same pre- and postnatal environments, the interaction genotype-by-sex has a determinant role on offspring phenotype (i.e., growth and development, metabolic and antioxidant status and fatty acid composition of different tissues). These results may set the basis for future preclinical and clinical research on the differences in the metabolic phenotype among genotypes.
... However, these findings are not consistent across all studies (Sheldon and West 2004). Furthermore, nutritional factors also affect offspring sex, with female mice with higher systemic glucose concentrations having more male pups (Cameron et al. 2008) and different mineral intake in women affecting offspring sex ratio (Mathews et al. 2008;Noorlander et al. 2010). In the present study, there was a tendency for more male embryos to be recovered from mares that were administered oral urea, but the majority of DEGs resulting from sex or urea treatment were different and presented a different pattern of regulation (up-or downregulation) (Fig. S1). ...
High blood urea nitrogen (BUN) in cows and ewes has a negative effect on embryo development; however, no comparable studies have been published in mares. The aims of the present study were to evaluate the effects of high BUN on blastocoele fluid, systemic progesterone and Day 14 equine embryos. When a follicle with a mean (±s.e.m.) diameter of 25±3mm was detected, mares were administered urea (0.4g kg−1) with sweet feed and molasses (n=9) or sweet feed and molasses alone (control; n=10). Blood samples were collected every other day. Mares were subjected to AI and the day ovulation was detected was designated as Day 0. Embryos were collected on Day 14 (urea-treated, n=5 embryos; control, n=7 embryos). There was an increase in systemic BUN in the urea-treated group compared with control (P<0.05), with no difference in progesterone concentrations. There were no differences between the two groups in embryo recovery or embryo size. Urea concentrations in the blastocoele fluid tended to be higher in the urea-treated mares, with a strong correlation with plasma BUN. However, there was no difference in the osmolality or pH of the blastocoele fluid between the two groups. Differentially expressed genes in Day 14 embryos from urea-treated mares analysed by RNA sequencing were involved in neurological development, urea transport, vascular remodelling and adhesion. In conclusion, oral urea treatment in mares increased BUN and induced transcriptome changes in Day 14 equine embryos of genes important in normal embryo development.
The sex ratio at birth (SRB) is the ratio of male-to-female births. This ratio is slightly skewed toward males (about 105 males to 100 females). However, several studies mostly in experimental animals have raised the question of whether the sex ratio in humans may be modified by certain nutritional and nonnutritional factors. The aim of this literature review is to explore the influence of maternal nutritional factors on sex ratio at birth in various animals and humans. We used Google Scholar, Research Gate, ProQuest, Scopus, Cochrane, and PubMed databases to collect appropriate articles for the review without limiting the publication period. Of the different nutritional approaches in animals the most frequent manipulations are controlling the energy intake and, to a lesser extent, the composition of the diet in terms of macronutrients and micronutrients is most likely to influence the sex ratio at birth in animals. The data on these factors affecting sex ratio at birth are sparse and offer little promise of influencing sex at birth in humans.
Fetal responses to adverse pregnancy environments are sex-specific. In fetal guinea pigs (GPs), we assessed morphology and messenger RNA (mRNA) expression in fetal growth-restricted (FGR) tissues at midpregnancy. Female GPs were assigned either an ad libitum diet (C) or 30% restricted diet (R) prior to pregnancy to midpregnancy. At midpregnancy, a subset of R females underwent ultrasound-guided nanoparticle (NP) injection to enhance placental function. Five days later, fetuses were sampled. Fetal brain, heart, and liver were assessed for morphology (hematoxylin and eosin), proliferation (Ki67), and vascularization (CD31), as well as expression of inflammatory markers. R fetuses were 19% lighter with reduced organ weights and evidence of brain sparing compared to controls. No increased necrosis, proliferation, or vascularization was found between C and R nor male or female fetal organs. Sexual dimorphism in mRNA expression of Tgfβ and Ctgf was observed in R but not C fetal brains: increased expression in females. NP treatment increased fetal brain mRNA expression of Tgfβ and Ctgf in R males, abolishing the significant difference observed in untreated R fetuses. Sex-specific differences in mRNA expression in the fetal brain with FGR could impart a potential survival bias and may be useful for the development of treatments for obstetric diseases. Male and female fetuses respond differently to adverse pregnancy environments. Under fetal growth restriction conditions, inflammatory marker mRNA expression in the fetal brain was higher in females compared to males. Differences in gene expression between males and females may confer a selective advantage/disadvantage under adverse conditions. Better characterization of sexual dimorphism in fetal development will aid better development of treatments for obstetric diseases.
Full-text available
This paper reexamines the relationship between status and reproductive success (at the ultimate and proximate levels) using data on sex frequency and number of biological children from representative samples of the U.S. population. An ordered probit analysis of data from the 1989–2000 General Social Survey (GSS) shows that high-income men report greater frequency of sex than all others do. An OLS regression of data from the 1994 GSS shows that high-income men have more biological children than do low-income men and high-income women. Furthermore, more educated men have more biological children than do more educated women. Results also show that intelligence decreases the number of offspring and frequency of sex for both men and women.
Reprint requests: Josef G. Schenker, M.D., Department of Obstetrics and Gynecology, Hadassah University Hospital, Ein-Kerem, P.O. Box 12000, Jerusalem 91120, Israel (FAX: 972434434).
The key problem in epidemiological studies is the identification of relevant exposures and outcomes, and the relationship (and error modelling) between observed and relevant measures, and between relevant measures and relevant outcomes. Measurement errors and bias undermine the ability to detect diet-disease relationships, and the problem is particularly acute in nutritional epidemiological studies because of the difficulties of measuring relevant dietary exposures accurately, and the particular problem of differential misclassification (i.e., the differences in bias in the measurements between individuals, or between one subset of a sample and another). Correcting for measurement error is a controversial topic, but the chapter provides illustrations of the extent of attenuation or misrepresentation of diet-disease associations. © Barrie M. Margetts, Michael Nelson, and the contributors listed on p. ix, 1997. All rights reserved.
Contents: Preface to the First Edition. Preface to the Second Edition. Introduction. The Factor Analytic Model. Factor Extraction by the Centroid Method. Methods of Factor Extraction. Orthogonal Hand Rotations. Oblique Hand Rotations. Simple Structure and Other Rotational Criteria. Planning the Standard Design Factor Analysis. Alternate Designs in Factor Analysis. Interpretation and Application of Factor Analytic Results. Development of the Comrey Personality Scales: An Example of the Use of Factor Analysis. Confirmatory Factor Analysis. Structural Equation Models. Computer Programs.