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O r i g i na l

human _ ontogenetic s ­A r t i c l e

HUM ONTOGENET 3(1), 2009, 7–12

doi 10.1002/huon.200900001

A r t i c l e H i s to r y

received December 18, 2008

Determinants of birth weight in boys accepted January 29, 2009

published online March 18, 2009

and girls A f f i l i at i on :
1Dept. of Obstetrics and Gynecology,

Rikshospitalet Medical Centre; 2Dept. of

Biostatistics, Institute of Basic Medical


N a nn a V o l dn e r 1 , K a t h r i n e F r e y F r ø s l i e 1 , 2 ,
Science; 3Dept. of Medicine, Rikshospi-

K r i st i n G oda ng 3 , Jens Bollersle v3, talet University Hospital; University of

Oslo, Oslo, Norway


Tor e H e n r i k se n1
C o r r e s p ondence

Nanna Voldner,

Reg. Midwife, Candidate in Nursing

Science

Dept. of Obstetrics and Gynecology

Abstract Introduction Rikshospitalet Medical Centre

University of Oslo

Boys are heavier at birth than girls, but girls have high- Males and females may differ in the pathogenic path- 0027 Oslo, Norway

er fat mass at birth than boys. Insulin action may play ways leading to diabetes mellitus and insulin resist- Tel: +47 23 07 29 26 / +47 99 73 82 90
an important role of this different distribution. Ani- ance (Mittendorfer 2005). The current insight into insu- Fax: +47 23 07 26 50
mal models have shown that female offspring are more lin action is largely based on studies of male subjects. Email: nanna.voldner@rikshospitalet.no
sensitive to maternal feeding and glucose values during More recently, along with the increasing prevalence
pregnancy and weaning than male offspring. Newborn of obesity, the female population has been subjected
K e y wo r d s
girls have higher insulin and proinsulin concentrations to more studies. It seems that adult obese women are
Birth weight, sex differences, paternal
and total proinsulin-to-insulin ratios in cord blood more insulin sensitive compared with obese adult men
birth weight, intrauterine environment,
than boys, despite lighter birth weight. In a cohort of (Vistisen et al. 2008), and the prevalence of diabetes is
fasting glucose
522 newborn above 37 gestational weeks we split be- two to three times higher in men than in women, re-
tween the sexes and studied associations between birth spective of weight categories (Kuhl et al. 2005). Sheep
weights, parental anthropometrics and fasting mater- models show that restriction of fetal growth induced A bb r ev i at i on s

nal plasma glucose and insulin levels. Boys weighed by chronic restriction of placental growth results in BMI body mass index

184g more than girls, they were 1.1 cm longer and head features of the metabolic syndrome in adult male off- FPG fasting plasma glucose

circumference differed by 0.86 (all p values <0.01). spring, particularly impaired insulin action (Owens et al. FPI fasting plasma insulin
Multiple linear regressions showed that parity, ma- 2007). These authors suggested that ewes small at birth
ternal body mass index, gestational age and maternal also will develop the syndrome, but later than males
birth weight were associated with birth weight for both (Owens et al. 2007). The prevalence of insulin resistance
sexes, whereas maternal weight gain in pregnancy and has shown to vary between the sexes throughout pu-
maternal fasting plasma glucose at week 30-32 were berty. Rat offspring of mothers fed a junk food diet
significantly associated with birth weight for girls only. throughout pregnancy and lactation period, combined
The effect of fasting plasma glucose on birth weight in with feeding the offspring a junk food diet post-wean-
girls was twice as high as in boys (B=162, 95% CI 33.4- ing, show that male and female offspring were affected
291, p=0.01). Paternal birth weight was significantly differently in terms of plasma glucose and insulin lev-
associated with birth weight of boys, but no such asso- els. Increased adiposity was more enhanced in female
ciation was seen for girls. This supports the notion that than male rat offspring (Bayol et al. 2001). Boys at 19
there is a genetic regulation along the male line. Girls years of age have a higher lean body mass than girls at
may be more sensitive to intrauterine environment and the same age, but they also have higher prevalence of
maternal glucose values, as these have a stronger influ-
ence on birth weight of girls.
insulin resistance (Moran et al. 2006). Among children
at the age of five, girls have higher insulin resistance 7
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.humanontogenetics.com
human _ ontogenetic s V o l dne r , F r e y F r ø s l i e ,

G odang , B o l l e r s l ev ,

H en r i k s en

Determinants of birth weight


in boys and girls

than boys. These girls also have more subcutaneous weight was obtained at the same time, both self re-
fat than boys, despite similar body weights (Murphy et ported.
al. 2004). This might be because prepubertal girls are
intrinsically more insulin resistant than boys, and that Independent variables
sex-linked genes may explain this difference.
Glucose was measured immediately in EDTA blood,
Girls have lower birth weight than boys, but the under- by Accu Check glucose test strips and glucometer
lying reasons have not been thoroughly investigated ­( Roche Diagnostics, Basel, Switzerland). Samples were
(Alexander et al. 1999, Skjaerven et al. 2000). Despite be- collected in 7 ml Vaccutainer tubes, centrifuged at
ing lighter, newborn girls display a lower proportion room temperature at 3000 RCF in 10 min. and serum
of fat-free mass and have a higher percent of body fat aliquoted and stored at -80 ºC until analyzed. Samples
than newborn boys (Catalano et al. 1995). for insulin were assayed in duplicate (RIA, DPC, Los
Angeles, CA, USA) and the intra- and inter-assay CV
Fetal insulin is strongly related to intrauterine growth, were 4.9% and 5.4%, respectively. All blood samples
and can be considered the true fetal growth hormone. were drawn an after overnight fast (from midnight
Insulin does not pass through the placenta, and ap- until 8.00 am). Maternal and paternal birth weight
pears to have no substantial effect on transplacental and maternal height was self-reported. Weight was
glucose transport. It acts indirectly by changing the measured on a digital scale at the first visit (week
transplacental glucose concentration gradient. Glucose 14-16).
appears to be one of the major physiological regulators
of insulin release in utero (Fowden 1989). Fetal hyper­ Statistical methods
glycaemia accelerates the developments of insulin se-
cretory mechanisms (Langer 2000). Descriptive statistics are presented as mean and
standard deviations (SD), or median and quartiles for
Measurements of cord insulin and insulin-related pep- skewed data. Comparisons of boys and girls were done
tides in newborns have shown that girls have higher by two-sample t-tests. The effects of predictor vari-
insulin and proinsulin concentrations and total proin- ables on birth weight in boys and girls were explored
sulin-to-insulin ratios in cord blood than boys, despite in univariate and multiple linear regression analyses.
lighter birth weight. No difference in cord glucose con- Also, logistic regression analyses with birth weight
centrations was found between newborn girls and boys above 4200 g as the response variable were done. Due
(Shields et al. 2007). to the low sample sizes (n=26 cases among girls and
n=58 cases among boys), the results presented from lo-
The aim of the present study was to examine whether gistic regression analysis were restricted to the univari-
parental anthropometric values and fasting mater- ate analyses. All models were checked for violations
nal plasma glucose and insulin levels influence birth from the model assumptions. A p value less than 0.05
weight differently in the two sexes. was considered statistically significant. All analyses
were done by SPSS 15.0.1.1.
Material and methods
Ethics
The population of the cohort that consists of 553
women and their newborn infants has been described The study was approved by the Regional Ethic Com-
in detail elsewhere (Voldner et al. 2008). Healthy women mittee and performed according to the Declaration of
with Scandinavian heritage were invited to participate. Helsinki and written informed consent obtained.
Exclusion criteria were multiple pregnancies, known
diabetes, fetal malformation or other severe maternal Results
illnesses.
Of the 553 children in the cohort, 522 were born after
The women came for four antenatal visits during preg- 37 gestational weeks (ultrasound based between weeks
nancy. At gestational weeks 14-16 and 30-32 fasting 17-19). Of these, 248 were female newborns (47.5 %).
plasma glucose values (FPG) were measured. Fasting Table 1 shows the distribution of maternal anthropo-
plasma insulin values (FPI) were measured at weeks metrics and fasting plasma glucose and insulin values
14-16, 22-24, 30-32 and 36-38. Weight was measured at weeks 14-16 and 30-32. The only significant dif-
on a digital scale at the first visit and height was self
reported. Information of maternal and paternal birth
ferences between boys and girls were gestational age,
the size, boys weighing 184g more, they were 1.21 cm 8
HUM ONTOGENET 3(1), 2009, 7–12, doi 10.1002/huon.200900001
human _ ontogenetic s V o l dne r , F r e y F r ø s l i e ,

G odang , B o l l e r s l ev ,

H en r i k s en

Determinants of birth weight


in boys and girls

T ab l e 1 .
Girls Boys
Characteristics of girls and boys
n Mean or SD or Range n Mean or SD or Range p
248 mediana Q1-Q3* 274 mediana Q1-Q3* at birth. Maternal characteris-

Gestational age (weeks) 248 40.1 1.2 37.3–43.1 274 40.4 1.2 37.4–42.7 <0.01 tics were obtained throughout

Maternal age (year) 248 31.3 4.2 21–42 274 31 3.9 19–41 0.46 pregnancy. Data are presented as

Para 0 125 143 0.68 means and standard deviations


(SD), or medians and quartiles (Q)
Maternal birth weight (g) 237 3446 0.6 1470–5400 259 3414 0.6 1200–4910 0.54
for skewed data.
Paternal birth weight (g) 212 3547 0.5 1880–5190 242 3620 0.6 1970–5490 0.15
Maternal height (cm) 242 168.7 5.6 150–183 267 168.5 5.5 152–182 0.75
Maternal BMI (kg/m2) week 14–16 241 25.05 4.2 17.6–44.0 260 24.8 4 17.5–42.3 0.44
Maternal weight gain (kg)
week 14–16 to 30–32 230 10.5 3.9 –0.8–29.4 256 10.6 3.7 –1.2–27.7 0.85
Fasting plasma glucose week
14–16 (mmol/l) 240 4.18 0.5 3.02–5.6 262 4.20 0.5 2.63–5.6 0.59
Fasting plasma glucose week
30–32 (mmol/l) 235 4.44 0.5 3.18–6.8 265 4.43 0.5 3.07–6.03 0.12
Fasting insulin week 14–16 (pmol/l) 240 28.0a 28–36a 259 27.0a 27–41a 8–160 0.71
Fasting insulin week 30–32 (pmol/l) 237 46.0a 46–62a 267 41.0a 41–58a 8–323 0.06
Birth weight (g) 248 3593 498 2325–5420 274 3777 467 2785–5140 <0.01
Length (cm) 244 50.5 2 44.0–58.0 267 51.7 1.9 47–57 <0.01
Head circumference (cm) 245 34.7 1.4 29.5–38.4 273 35.6 1.4 32.0–39.5 <0.01

longer and head circumference differed by 0.86 cml (all association between birth weight and maternal FPG
p values <0.01). and FPI.

Table 2 shows the results from univariate linear re- In multiple linear regression models shown in Table
gression analyses. Gestational age, maternal BMI in 3, we found that parity, maternal BMI, gestational age
early pregnancy and maternal birth weight were sig- and maternal birth weight were associated with birth
nificantly associated with birth weight for both girls weight for both sexes, whereas maternal weight gain
and boys. Maternal height and weight gain throughout in pregnancy and maternal FPG at week 30-32 were
pregnancy was only associated with birth weight of the significantly associated with birth weight for girls
girls, whereas paternal birth weight were significantly only. The adjusted effect of FPG at week 30-32 on
associated with birth weight of the boys. We found sig- birth weight in boys was positive, but not significant
nificant differences between the sexes in term of the (B=79.4, 95% CI -45-204, p=0.21). In contrast, the ef-

T ab l e 2 .
Girls Boys
B p CI CI B p CI CI Results from univariate linear re-
lower upper lower upper gression analyses on birth weight.
Gestational age (weeks) 198 <0.01 152 244 110 <0.01 65 154 The analyses were stratified by
Maternal age (year) 12 0.12 –3.2 26.8 4 0.59 –10.5 18.4 fetal sex. For both sexes, results
Maternal birth weight (kg) 215 <0.01 108.5 322 200 <0.01 101 298
are given as the crude regression
Paternal birth weight (kg) 93 0.15 –32.6 219 183 <0.01 76 289
coefficient B, 95 % confidence
Parity (0 – 1+) 256 <0.01 135 376 200 <0.01 92 309
intervals (CI) for B and p-values.
Maternal BMI (week 14–16) 24 <0.01 9.1 39 33 <0.01 19.4 46.6
Maternal variables considered to
Weight gain week 14 to 36 (kg) 24 <0.01 7 40 7 0.40 –8.8 22
be relevant covariates were ob-
Maternal height (cm) 27 <0.01 15.9 37.6 9 0.08 –1.2 19.1
tained throughout pregnancy.
Fasting glucose weeks 14–16 (mmol/l) 191 <0.01 54.4 328 –9 0.88 –130 112
Fasting glucose weeks 30–32 (mmol/l) 297 <0.01 177 417 92 0.13 –26.2 210
Fasting glucose diff. weeks 30–32 to 14–16 (mmol/l) 168 0.02 31.5 304 110 0.06 –4.6 226
Fasting insulin week 14–16 (pmol/l)
Fasting insulin week 30–32 (pmol/l)
6
3
<0.01
<0.01
2.5
0.1 4.7
9 2
2
0.30
0.10
–1.3
–0.3
4.2
3.4 9
HUM ONTOGENET 3(1), 2009, 7–12, doi 10.1002/huon.200900001
human _ ontogenetic s V o l dne r , F r e y F r ø s l i e ,

G odang , B o l l e r s l ev ,

H en r i k s en

Determinants of birth weight


in boys and girls

T ab l e 3 .
Female Male
Adjusted models. Results from
B p 95% CI B p 95% CI
multiple linear regression analyses
Gestational age (weeks) 184 <0.01 1367 231 111 <0.01 61.7 160
on birth weight. The analyses
Maternal age (year) –11.7 0.14 –27 3.7 –13.4 0.09 –29 2.3
were stratified by fetal sex. For
Maternal birth weight (kg) 184 <0.01 87 280 148 <0.01 51 243
both sexes, results are given as the
Paternal birth weight (kg) 40.5 0.46 –67.4 149 184.4 <0.01 85 283
Parity (0–1+) 286 <0.01 163 409 257 <0.01 137 378 adjusted regression coefficients B,

Maternal BMI week 14–16 (kg/m2) 21 0.02 4 38 20 0.01 4.1 36 95 % confidence intervals (CI) for

Weight gain week 14 to 36 (kg) 26.7 <0.01 11.6 42 11 0.16 –4.3 26 B and p-values. Maternal variables

Fasting glucose week 30–32 (mmol/l) 162 0.01 33.4 291 79.4 0.21 –45 204 considered to be relevant covari-

Fasting insulin week 30–32 (pmol/l) –0.1 0.93 –2 1.8 –0.8 0.5 –3 1.5 ates were obtained throughout
pregnancy.

fect of FPG on birth weight in girls was twice as high, dependently correlated with birth weight. The authors
and significant (B=162, 95% CI 33.4-291, p=0.01). suggested that skeletal growth is genetically regulated,
Paternal birth weight was significantly associated with while the maternal environment predominantly alters
birth weight of boys, with an increase in birth weight of the adiposity of the fetus (Knight et al. 2005). Our find-
180g per kg change in paternal birth weight (p<0.01), ing that paternal birth weight has a significant influ-
but no such association was seen for girls. ence on birth weight of boys, but not for girls, supports
the notion that there is a genetic regulation along the
Macrosomia is defined as birth weight above 4200g, male line. These genes may either be associated with
this is in relation to the 90th percentile of the Nor- the y-chromosome or subjected to sex-dependent im-
wegian birth cohort (Skjaerven et al. 2000, Voldner et al. printing (Hager et al. 2008). As far as we know, paternal
2008). Of the 84 (15%) newborns in our cohort with birth weight has previously not been studied in relation
birth weight above 4200g, 58 (69%) were boys and 26 to birth weight and infant sex. The present results add
(31%) were girls. new information by the finding that the father’s own
birth weight influence that of the male offspring only.
By performing the same analyses using a univariate lo-
gistic regression model, with birth weight above 4200g FPG in third trimester and weight gain were positively
as dependent variable, similar results were found (data associated with birth weight of females only. Growth
not shown). of the fetus is generally a result of both placental prop-
erties and inherent growth potentials of the fetus. The
Discussion observed sex-specific effects may therefore be caused
by sex-dependent differences in “sensitivity” of the
Our findings, that gestational age, parity, maternal placental and/or fetal tissue to fasting plasma glucose
birth weight and BMI independently influence birth or factors associated with weight gain. Such sex-de-
weight for both boys and girls is in accordance with pendent differences in “sensitivity” may, for example,
previous reports (Catalano et al. 1998, Shields et al. 2006). include placental transport capacity of glucose or fe-
However, after adjusting for these variables, paternal tal growth response to a given supply of glucose. Our
birth weight had a significant effect on birth weight of findings are summarized in Figure 1.
boys but not for girls. Furthermore, maternal weight
gain from early to late pregnancy and FPG at weeks These findings are in accordance with a previous study
30-32 was independently associated with birth weight which found girls to be intrinsically more insulin re-
of girls but not for boys. It has previously been shown sistance than boys at birth (Shields et al. 2007). Despite
that modifiable variables like fasting glucose, pre-preg- weighing less at birth, the girls had significantly higher
nant BMI, low level of pre-pregnant physical activity insulin and proinsulin concentrations in cord blood
independently influence fetal macrosomia (Voldner than boys, whereas there was no difference in cord
et al. 2008). glucose concentrations between girls and boys. The
same study also found that girls had significantly more
A previous Norwegian study reported that paternal subcutaneous fat measured by triceps and subscapular
birth weight contributed independently to offspring skinfold thicknesses (Shields et al. 2007).
birth weight (Magnus et al. 2001). In a UK study it was
found that paternal height, but not paternal BMI, in- 10
HUM ONTOGENET 3(1), 2009, 7–12, doi 10.1002/huon.200900001
human _ ontogenetic s V o l dne r , F r e y F r ø s l i e ,

G odang , B o l l e r s l ev ,

H en r i k s en

Determinants of birth weight


in boys and girls

F i gu r e 1

Fasting glucose Fasting insulin week Effects of paternal and maternal


week 30-32 30-32 birth weight, maternal anthropo-
metry, fasting plasma and glucose
values on birth weight of boys
Maternal and girls.
birth weight

U -

Paternal birth
Maternal weight
weight gain
Maternal
BMI

Associations (p < 0.05)

No associations

We preferred not to use relative birth weight in the Faculty of Medicine, Thematic Research Area, Univer-
present work. This is based on findings indicating that sity of Oslo, Norway
among newborn anthropometric parametres birth
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