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DOI: 10.1111/1471-0528.12062 www.bjog.

org

Epidemiology

Pregestational body mass index is related to neonatal abdominal circumference at birtha Danish population-based study
M Tanvig,a,b S Wehberg,c CA Vinter,d JS Joergensen,d PG Ovesen,e H Beck-Nielsen,a DM Jensen,a,* HT Christesenb,*
a Department of Endocrinology, Odense University Hospital, Odense, Denmark b H.C. Andersen Childrens Hospital, Odense University Hospital, Odense, Denmark c Research Unit of Clinical Epidemiology, Centre for National Clinical Databases (South), University of Southern Denmark and Odense University Hospital, Odense, Denmark d Department of Gynaecology and Obstetrics, Odense University Hospital, Odense, Denmark e Department of Gynaecology and Obstetrics, Aarhus University Hospital, Skejby, Denmark Correspondence: M Tanvig, Department of Endocrinology, Odense University Hospital, Odense, Sdr. Boulevard 17, 5000 Odense C, Denmark. Email Mette.tanvig@ouh.regionsyddanmark.dk *These authors contributed equally to the study.

Accepted 1 October 2012. Published Online 12 November 2012.

Objectives To examine the impact of maternal pregestational body

mass index (BMI) and smoking on neonatal abdominal circumference (AC) and weight at birth. To dene reference curves for birth AC and weight in offspring of healthy, nonsmoking, normal weight women.
Design Population-based study. Setting Data from the Danish Medical Birth Registry. Population All live singletons without congenital malformations

in Denmark 200410. to 41+6 weeks+days of gestation were extracted and analysed using multivariate linear regressions.
Methods Data on 366 886 singletons at 35 Main outcome measures Birth AC and weight in relation
+0

Results Birth AC and weight increased with increasing pregestational BMI, and decreased with smoking (P < 0.0001). Reference curves were created for offspring of healthy, nonsmoking mothers with normal pregestational BMI. Mean AC ranged from 30.1 cm and 30.2 cm at 35 weeks of gestation to 33.9 cm and 34.1 cm at 41 weeks of gestation, for girls and boys, respectively. Mean birthweight ranged from 2581 and 2666 g at 35 weeks to 3705 and 3852 g at 41 weeks of gestation for girls and boys, respectively. Pregestational BMI correlated more to the Z score of birthweight than to the Z score of AC (P < 0.0001). Conclusion Birth AC and weight are affected by maternal smoking

status and pregestational BMI. Pregestational BMI correlated more to birthweight than to AC. Using data from healthy, nonsmoking mothers with normal pregestational BMI we have provided new reference curves for birth AC and birthweight.
Keywords Body mass index, neonatal anthropometry, obesity, pregnancy, smoking.

to pregestational maternal BMI, maternal smoking and medical conditions (any).

Please cite this paper as: Tanvig M, Wehberg S, Vinter C, Joergensen J, Ovesen P, Beck-Nielsen H, Jensen D, Christesen H. Pregestational body mass index is related to neonatal abdominal circumference at birtha Danish population-based study. BJOG 2013;120:320330.

Introduction
Physical parameters at birth may predict the risk of diseases in adulthood. Low birthweight is associated with cardiovascular disease, hypertension, glucose intolerance and type 2 diabetes in adulthood.13 Recent evidence suggests that high birthweight and a birthweight that is large-for-gestational-age are also associated with later adverse outcomes such as obesity and metabolic disease.46 U-shaped risk curves for type 2 diabetes and abdominal obesity in

adulthood are suggested for neonates born at both extremes of the birthweight spectrum.7,8 In adult life, excessive fat deposition, especially intrahepatic and central fat, is part of the metabolic syndrome.9 Data on later possible adverse effects of early life abdominal fat deposition are however limited. Maternal obesity is among the strongest predictors of high birthweight and of an infant being large for gestational age.1015 Likewise, the negative effects of maternal smoking on fetal growth are well-established.11,1618 At birth, term

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infants of obese and overweight mothers have increased fat mass compared with offspring of normal weight mothers.1923 Recently, Modi et al.24 have shown that increasing maternal body mass index (BMI) is associated with increasing abdominal and intrahepatocellular lipid content in the neonatal offspring, measured by magnetic resonance spectroscopy. In fetal life, accelerated growth of the abdominal circumference (AC) is a predictor of asymmetric growth and neonatal morbidity.25 Moreover, Ruckinger et al.17 have shown that BMI at 5 years was associated with the abdominal diameter of the fetus, measured in utero by abdominal ultrasound at 33 and 37 weeks of gestation and in childhood. Current AC has been shown to be an independent predictor of insulin resistance.26 One could speculate that excessive abdominal fat deposition at birth would be a better early predictor of later metabolic diseases than high birthweight. To further investigate this hypothesis, normal reference values for abdominal size at birth are needed, measured by AC, which reects central fat deposition.27 Existing reference curves for AC28,29 are based on small sample sizes and have not considered the possible inuence of maternal pregestational BMI or smoking. To our knowledge, reference curves for neonatal AC based on a population from a national birth registry, and birth AC curves adjusted for maternal factors, have not been published previously. Moreover, existing reference curves for birthweight based on populations from national birth registries3036 are not adjusted for maternal pregestational BMI or smoking. We aimed to examine the impact of maternal pregestational BMI and smoking on birth AC and birthweight after correcting for potentially inuencing factors such as parity, maternal medical conditions, age and height, in a population taken from a national birth registry; second, to dene normal reference curves for AC and birthweight in offspring of healthy, nonsmoking, normal-weight women; and third, to compare the impact of maternal BMI on the Z scores of AC and birthweight and on the ratio between AC and birthweight.

Methods
Data collection and handling
Nationwide data on Danish pregnant women and their offspring born between 1 January 2004 and 31 December 2010 were extracted from The Danish Medical Birth Registry.37 This registry has information on pregnancies and deliveries since 1973, including 99.8% of all Danish deliveries and with a high reliability and validity.38 Since 2004 the pregestational height and weight of the mother, as reported by her general practitioner, have been registered. The registry identied 454 032 children born between 2004 and 2010. We excluded neonates whose mothers did

not have a valid civil registration number (n = 13), stillborn children (n = 2949), children with congenital malformations (any kind, n = 33 316) and children from a multiple pregnancy (n = 16 904). Detailed description of the exclusion criteria can be seen in the Supplementary material, Table S1. For the remaining 400 850 children, we further restricted our analyses to those born in weeks 35+0 to 41+6 (weeks+days) of gestation, as the description of the more extreme gestational ages were outside the scope of this article. The gestation criterion was met by 366 886 children, who were included for further analyses (186 249 boys and 180 637 girls). For each mother and infant pair, the following variables were recorded: maternal pregestational weight and height, age, parity, smoking status, any medical condition, gestational age, sex, birthweight and AC. Pregestational BMI was calculated and women were grouped into the following ve categories: <18.5 kg/m2 (underweight), 18.5 24.9 kg/m2 (normal weight), 2529.9 kg/m2 (overweight), 3034.9 kg/m2 (obese) and >35 kg/m2 (severely obese) according to World Health Organization (WHO) denitions. Gestational age was expressed in weeks, dened as gestational weeks completed, i.e. the range from 35+0 to 35+6 was categorised as 35 weeks of gestation. According to national routine practice, all women were offered ultrasound scans in both the rst and the second trimester. In Denmark, gestational age is estimated from ultrasound scans in the rst trimester in over 90% of all pregnancies. Approximately another 8% of all pregnant women have scans performed in the second trimester before 20+6 weeks of gestation, which are then used for calculation. For the rest of the population the rst day of last menstrual period is used.39 Maternal and fetal diseases or complications were classied according to the International Classication of Diseases 10th revision. Infant anthropometrics were measured just after birth. Birthweight was obtained using a digitalised weight and Danish midwifes measured AC at the level of the umbilicus with a non-elastic band. Further information on the variables, their denitions and characteristics are shown in the Supplementary material, Table S2. To exclude biologically unrealistic values, the two outcome variables AC and birthweight were further restricted. Birthweight was dened as outlier and excluded if it exceeded 4 standard deviations (SD) from the mean of a comparable Scandinavian population, stratied by sex and gestational age (as read from ref. Niklasson A, Karlberg P40, see exact numbers in the Supplementary material, Table S3). This resulted in 997 additional missing values for birthweight across 35+0 to 41+6 weeks of gestation. Corresponding reference estimates of means and SDs for AC based on birth populations from a comparable population were not

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available. We therefore used an alternative rule dening outliers as AC below 10% centile minus 1.5 times the interquartile range, or above 90% centile plus 1.5 times the interquartile range. These outliers were set to missing (exact numbers given in Table S3). Application of this rule resulted in 1334 additional missing values for AC across 35+0 to 41+6 weeks of gestation.

The study was conducted according to the Helsinki Protocol and it was approved by the Danish Data Protection Agency.

Results
The study included 333 618 healthy singletons born at 35+0 to 41+6 weeks of gestation and their mothers. An overview of sample sizes in the different analyses is given in Table 1. In a population of nonsmoking mothers with no medical conditions, maternal pregestational BMI was directly associated with mean birth AC and birthweight, and across all BMI categories both outcomes increased signicantly (P < 0.0001) estimated by linear regression analyses. Sexspecic curves for mean birth AC and birth weight, stratied by maternal pregestational BMI according to gestational age are shown in Figure 1. Corresponding single reference curves, stratied by sex and each maternal pregestational BMI category, are given in the Supplementary material, Figures S1S4 and statistics can be seen in the Supplementary material, Tables S4S23. In adjusted analysis, every increase in pregestational BMI of 1 kg/m2 was associated with an increase in AC of 0.5 mm (95% condence interval [95% CI] 0.50.5 mm) and an increase in birthweight of 14.2 g (95% CI 13.914.5 g) (Table 2). An increase in gestational week was associated with an increase in abdominal circumference of 5.0 mm (95% CI 5.05.1 mm) and an increase in birthweight of 162.2 g (95% CI 161.1163.3 g). In this model, increasing gestational age had the highest positive impact and smoking had the largest negative impact on both AC and birthweight. Increasing parity and maternal height were also positively associated with both outcomes, whereas sex (girls), advancing maternal age and maternal medical condition (any) were negatively associated. Based on these results, we excluded smokers and women with medical conditions from further analyses aiming to establish healthy, normative references for birth AC and birthweight. Sex-specic normative curves for birth AC and birthweight by gestational age, based on offspring of healthy, nonsmoking, normal-weight mothers are presented in Figures 2 and 3 Corresponding statistics are shown in the Supplementary material, Tables S5, S10, S15 and S20. Mean AC ( 2 SD) ranged from 30.1 cm (25.934.3 cm) at 35 weeks of gestation to 33.9 cm (30.137.7 cm) at 41 weeks (girls); and from 30.2 cm (25.834.6 cm) at 35 weeks to 34.1 cm (30.3 37.9 cm) at 41 weeks (boys). Mean birthweight ranged from 2581 g (18313332 g) at 35 weeks of gestation to 3705 g (28644546 g) at 41 weeks (girls); and from 2666 g (1924 3407 g) at 35 weeks to 3852 g (29714734 g) at 41 weeks (boys). Finally, using a regression model, we addressed the question whether birth AC or birthweight had the strongest

Statistical analysis
For all analyses we used STATA 12 software (StataCorp, College Station, TX, USA). As an initial analysis, two separate linear regression models (analysis of variance) were used to estimate the relation of AC and birthweight to different categories of maternal pregestational BMI in a normal population of nonsmoking mothers without medical conditions. Next, to quantify the effect of smoking and pregestational BMI, a multivariate linear regression model was estimated for both AC and birthweight, accounting also for sex, gestational age, maternal age, height, parity and any medical condition. For construction of normative curves for AC and birthweight only offspring of nonsmoking, healthy mothers with normal pregestational BMI category (18.524.9 kg/m2) were included. Normative curves were produced for gestational weeks 35 to 41, covering gestational ages from 35+0 until 41+6 weeks. Descriptive statistics (mean and SD) for the normative curves were calculated point-wise, i.e. separately, for each gestational week and sex. This means that 35+0 weeks of gestation was treated the same as 35+6 weeks of gestation, and a separate model was tted for each entire week. In the corresponding curves, the point-wise estimates were connected by lines and as such, gave a linear extrapolation. In addition, we used multivariate linear regressions to analyse whether AC or birthweight had the strongest association with maternal pregestational BMI. Standardised Z scores (SDS) of AC and birthweight from our established healthy reference curves were used instead of their raw values. Analyses were performed on all observations with complete data on both AC and birthweight. The following covariates were included in the model: maternal pregestational BMI (continuous), sex, gestational age (35 41 weeks, continuous), smoking (yes/no), maternal medical condition (yes/no), height (continuous), parity (categorical) and age (continuous). Furthermore, we tested the difference between the two estimated regression coefcients, BMI on AC, and BMI on birthweight. The methods used for testing equality of the two regression coefcients are further explained in detail by the StataCorp.41 Finally, we examined the ratio between AC and birthweight and the impact of maternal pregestational BMI on this parameter. For this analysis we only used data on offspring of nonsmoking mothers with no medical conditions.

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Table 1. Overview of the number of motherchild pairs contributing to the different analyses. All analyses are based on data from 35+0 to 41+6 weeks of gestation

Abdominal circumference

134 521

160 541

160 202

134 521

87 114

Girls

association to maternal pregestational BMI, adjusted for smoking, maternal medical conditions, age, parity and height. Z scores were calculated from our newly established normative values. For every increase of 1 kg/m2 in pregestational BMI, birth AC Z score (95% CI) increased by 0.02 (0.020.03), whereas birthweight Z score increased by 0.03 (0.030.03). The difference was statistically signicant (P < 0.0001), implying that birthweight was more strongly associated with maternal pregestational BMI than birth AC. In accordance with these results, the ratio between AC and birthweight decreased with increasing maternal pregestational BMI. For every increase of 1 kg/m2 in pregestational BMI, the AC: birthweight ratio decreased by 0.02 cm/kg (95% CI 0.02 to 0.02, P < 0.0001).

279 169

333 618

324 673 160 202 164 471 324 673

Birthweight

137 515

164 246

181 487

141 654

169 372

272 346

325 352

177 085

272 346

Total

137 825

92 424

Boys

134 521

89 063

Girls

272 346

Total

137 825

164 811

164 471

137 825

89 971

Boys

Discussion
Based on nationwide data on pregnant women and their offspring we found that, maternal smoking and pregestational BMI correlates not only to birthweight, but also to birth AC, even after correction for other potentially inuencing factors such as parity, maternal medical conditions, age and height. After establishing reference curves for AC and birthweight based on offspring of nonsmoking, healthy mothers with a normal pregestational BMI, we have shown that maternal pregestational BMI is more closely associated with the Z score of birthweight than the AC Z score and, consequently, that the ratio between AC and birthweight decreases as pregestational BMI increases. We nd that the biggest novelty of this paper is the new reference values for AC. In general, AC is an anthropometric index of both abdominal visceral size and fat stores. In nonhuman primates, maternal obesity induces epigenetic changes in genes regulating liver metabolism, resulting in increased liver lipid content and nonalcoholic fatty liver disease in the offspring.42 Also in humans, maternal BMI is linked to both infant liver lipid content and abdominal adiposity. Our data should stimulate further investigations of the correlation between neonatal abdominal adiposity and later metabolic health.

Comparison of birth AC and weight Z score with pregestational BMI, adjusted for maternal smoking, height, age, parity and medical conditions Relation of AC/birthweight ratio to pregestational BMI

Relation of birth AC and weight to pregestational BMI, maternal smoking status, medical conditions, height, age and parity

Nonsmokers; no medical condition; all BMI categories Both smokers and nonsmokers, all BMI, age, height and age categories, medical condition Nonsmokers; no medical condition; BMI category 18.524.9 kg/m2 Smoking status, height, age, parity, BMI, birth AC and weight none missing Nonsmokers; no medical condition; all BMI categories, birth AC and weight none missing

Inclusion criteria

Reference values for AC


To our knowledge, the impact of maternal BMI on birth abdominal size has never been investigated on a population level. However, birth AC reference values have previously been reported based on small studies.28,29,43,44 None of these studies excluded smokers or mothers with medical diseases, nor were the results stratied by maternal pregestational BMI, parity, age or height. The Danish neonates had higher mean birth AC values at 40 weeks of gestation than those reported from Spain28 and China29; boys, +1.3 cm and +1.1 cm; girls, +1.4 cm and +1.2 cm, respectively. In Swedish term neonates, mean AC values were 2.0 cm, and

Analysis

Normative curves, stratied by sex

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Figure 1. (A) Mean abdominal circumference by maternal pregestational BMI and gestational age, separately for boys and girls (P < 0.0001). (B) Mean birthweight by maternal pregestational BMI and gestational age, separately for boys and girls (P < 0.0001).

1.5 cm higher, compared with our values for 40 weeks of gestation, boys and girls, respectively.43 This may suggest a different proportion of included women with obesity and smoking status in the other studies. Comparisons between studies are, however, hampered by the use of different measurement methods. We measured AC at the umbilicus level, whereas AC was measured at the mid-point between the xiphoid and umbilical cord in two studies28,29 or at an unspecied position.43 In accordance with our ndings, fetal midabdominal diameter (MAD, measured in utero by ultrasound) has previously been correlated to maternal weight, smoking,

parity and height.45 Ruckinger et al.17 found smoking to be correlated with a reduction in MAD of 1.8 mm at 37 weeks of gestation. In our multivariate regression model, smoking was associated with an almost 5-mm reduction of AC, which corresponds to 1.6 mm in MAD (= AC 9 p).

Reference values for birthweight


Despite the fact that maternal obesity is a well-known risk factor for macrosomia1215,46 and that maternal smoking has long been recognised as being negatively associated with fetal growth,11,1618 reference values for birthweight, based on populations from national birth registries have, to our

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Table 2. Factors associated with birth AC and weight in multivariate regression analysis (n = 333 618 motherchild pairs) Abdominal circumference (cm) Coefcient (95% CI) 0.05 0.50 0.20 0.45 0.08 0.65 0.73 0.01 0.04 (0.050.05) (0.500.51) (0.22 to 0.19) (0.47 to 0.43) (0.12 to 0.01) (0.630.66) (0.710.75) (0.01 to 0.01) (0.040.05) Birthweight (g) Coefcient (95% CI) 14.2 162.2 133.2 172.7 17.4 153.2 182.8 2.5 13.8 (13.914.5) (161.1163.3) (136.0 to 130.4) (176.8 to 168.5) (.7 to 5.2) (150.0156.4) (178.6187.1) (2.8 to 2.1) (13.514.0)

Covariate Maternal BMI (continuous)* Gestational week (3541, continuous)** Sex (girls versus boys) Smoking (yes versus no) Any medical condition, mother (yes versus no) Parity 1*** Parity 2 or more*** Maternal age (continuous) **** Maternal height (continuous)***** *Every increase in pregestational BMI of 1 kg/m2. **Every increase in gestational week. ***Compared with rst time pregnancies. ****Every increase in maternal age of 1 year. *****Every increase in maternal height of 1 cm.

Figure 2. Normative curves for abdominal circumference by gestational age, for healthy singletons of nonsmoking mothers with normal pregestational BMI.

knowledge, never been published for healthy nonsmoking, normal weight mothers only. Previous reference charts for Danish children have been based on measurements made in the 1970s with no exclusion of smokers or mothers with abnormal BMI.47 Since then it has become clear that birthweight of Danish children has increased48 and secular increases in birthweight have been shown in a number of studies.35,49,50 Compared with Danish children from the 1970s, our normative values at 40 weeks of gestation were 284.4 g (boys) and 263.2 g (girls) higher.

An explanation for the substantially increased birthweight could relate to our exclusion of smokers (14.8%, Table S2). The percentage of smokers among Danish pregnant women in the 1970s is unknown but probably high, as 47% of all Danish women were smokers.51 Data from 1991 showed that the proportion of smokers among pregnant women was 30.6%,48 compared with 40% among all Danish women.51 National Norwegian data from the 1980s were based on all singleton neonates, without exclusion of mothers with medical illness, smoking or abnormal BMI.35 The

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5500 5000 4500 4000

Girls

5500 5000 4500 4000

Boys

Weight (g)

3500 3000 2500 2000 1500 1000 35 37 39 41

Weight (g)

3500 3000 2500 2000 1500 1000 35 37 39 41

Gestational age (weeks)


Mean 1 SD 2 SD 3 SD Mean

Gestational age (weeks)


1 SD 2 SD 3 SD

Figure 3. Normative curves for birthweight by gestational age, for healthy singletons of nonsmoking mothers with normal pregestational BMI.

Norwegian birthweight values were comparable with our normative values at 40 weeks (the Norwegians being 10.6 and 1.8 g heavier, boys and girls, respectively). Compared with the most recent Swedish study, our mean birthweight values were higher; 64.4 (boys) and 73.2 g (girls).40 The population in that particular study was not described in detail, suggesting that smokers, mothers with medical illness or mothers with abnormal BMI were not excluded. In 2006, WHO proposed a new growth reference comprising term neonates and older children from various countries.52 WHO only included healthy, nonsmoking mothers and their offspring, but did not stratify by each week of gestation or maternal BMI and the study was based on smaller populations. Our Danish neonates were substantially heavier at 40 weeks of gestation compared with the WHO standard, 368.4 (boys) and 341.2 g (girls). In the UK, a UK-WHO growth chart has been made by merging postnatal growth data from the WHO with English birth data from ve different studies from the 1990s, with no exclusion of smokers and unhealthy mothers and without stratication for maternal pregestational BMI.53 Compared with these data, the normative values of the Danish newborns were also higher; 154.4 (boys) and 163.2 g (girls). Likewise, compared with Canadian national references, the Danish newborns were bigger; 87 (boys) and 90 g (girls).33 Again, the Canadian references were not corrected for BMI, smoking or medical disease. In conclusion, our healthy birthweight reference values were generally considerably higher, even when compared with other Caucasian populations, suggesting a strong need to re-evaluate other national and international

birthweight reference values with exclusion of mothers with abnormal pregestational BMI, medical conditions and smoking status.

The impact of maternal obesity


Our results showed that pregestational BMI correlated with both birthweight and AC but most strongly with birthweight. In accordance, the ratio between AC and birthweight, which to some extent is a measure of the degree of abdominal obesity in relation to weight, decreased with increasing maternal BMI. It is suggested that maternal obesity results in a general weight gain of the fetus rather than just fat accumulation around the abdomen. However, another explanation for the closer association between maternal BMI and birthweight than with AC is the difference in accuracy of the measurement methods. Values of AC are often rounded to whole centimetres and lack precision, whereas birthweight is reported in smaller units and with more accuracy. Despite the closer correlation between BMI and birthweight, our ndings do not tell us whether birth AC is a weaker or better predictor of future obesity or metabolic syndrome than birthweight. In older children, waist circumference has proven to be a better predictor for metabolic syndrome than other anthropometric measures such as BMI,54,55 and intrauterine abdominal diameter was more correlated to BMI at 5 years of age than birthweight.17 We therefore hypothesise that the easy and cheap birth AC measure may be a useful predictor of later obesity and metabolic syndrome, allowing for a more precise early intervention. With our normative birth AC and weight reference curves we have provided a research tool for

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evaluation of this hypothesis. In a clinical setting, the curves can be used for comparison of a given neonates size at birth against what it might have been if the mother was healthy and had a normal BMI. Furthermore, clinicians can use data in the supplementary material for comparison with others in the same abnormal BMI category. If for instance the neonate is smaller or larger than would be expected from references within the same BMI category, it might be at greater risk of having intrauterine growth restriction or being large for gestational age.

Contribution to authorship
MT, SW, CV, JSJ, PGO, HBN, DMJ and HTC conceived and designed the research, interpreted the results and undertook critical revision of the manuscript. MT was responsible for the data acquisition. MT and SW undertook the data analyses. MT, SW, DMJ and HTC drafted the manuscript and DMJ and HTC were responsible for handling, funding and supervision.

Details of ethics approval


The study was conducted according to the Helsinki Protocol and it was approved by the Danish Data Protection Agency. Further ethics approval was not obtained because this study did not involve human or animal participants or medical records. The data came from a national database and did not contain patient ID numbers.

Strengths and limitations


With the use of the Danish national birth registry, which contains a vast amount of information on pregnancies, deliveries and outcome, our data are unique because of the size of the cohort, the high validity of the data and the possibility to stratify for smoking, BMI and diseases. Moreover, the population in Denmark is relatively homogeneous with more than 90% Caucasians and all citizens have free access to health services on an equal term. Our study could not give data on inter-observer and intra-observer reproducibility of AC and birthweight. The AC may be rounded into whole centimetres and lack precision. The quality of the birthweight measure may also vary substantially and be subjected to gross imprecision. Trained healthcare professionals have, however, an acceptable reliability and reproducibility of both measures.56 Moreover, systematic biases affecting the associations studied are not suggested. The registry did not allow us to subcategorise smoking (binary data only) and we had no information on ethnicity or gestational weight gain, only pregestational height and weight as reported by the general practitioner.

Funding
This study was supported by Odense University Hospital. MT was funded by University of Southern Denmark, Region of Southern Denmark and The Danish PhD School of Molecular Metabolism.

Supporting Information
Additional Supporting Information may be found in the online version of this article: Figure S1. Reference curves for abdominal circumference by gestational age, separately for categories of maternal pregestational BMI, girls (mothers are nonsmokers and have no medical illness). Figure S2. Reference curves for abdominal circumference by gestational age, separately for categories of maternal pregestational BMI, boys (mothers are nonsmokers and have no medical illness). Figure S3. Reference curves for birthweight by gestational age, separately for categories of maternal pregestational BMI, girls (mothers are nonsmokers and have no medical illness). Figure S4. Reference curves for birthweight by gestational age, separately for categories of maternal pregestational BMI, boys (mothers are nonsmokers and have no medical illness). Table S1. Detailed description of exclusion criteria. A denition of variables can be found at www.sst.dk/ Indberetning%20og%20statistik/Sundhedsstyrelsens% 20registre/Foedselsregister.aspx (accessed 2 December 2011). An explanation of codes can be found at www.medinfo.dk/ sks/brows.php (accessed 2 December 2011). Table S2. Denition and characteristics (minimum, 25% centile, median, 75% centile, maximum) of relevant variables.

Conclusion
We have shown that both maternal pregestational BMI and smoking are strongly associated not only with birthweight but also with birth AC. We therefore constructed reference curves for birthweight and AC based on a population of nonsmoking, healthy mothers with a normal BMI. Our birthweight reference means were substantially higher than in most other references, suggesting a strong importance of the use of our exclusion criteria. Using our reference data, increasing pregestational BMI was associated with a higher increase of birthweight Z score than birth AC Z score and with a decrease in AC: ratio. Birth AC Z score may, however, be an important tool for future research in early predictors of obesity and metabolic syndrome.

Disclosure of interests
None of the authors have a conict of interests.

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Table S3. Lower (LL) and upper limits (UL) as well as resulting numbers of nonmissing values (n) for abdominal circumference and birthweight by gender and gestational week (GW). To compare methods, lower and upper limits for birthweight as well as resulting number of nonmissing values (n), when the outlier rule were the same as for abdominal circumference (i.e. lower limit = 10% centile 1.5*interquartile range (IQR); upper limit = 90% centile + 1.5*IQR) are also displayed (birthweight, other method). In addition, the difference in nonmissing numbers (Diff) between n (birthweight, method used) and n (birthweight, other method) is presented in the last column. Table S4. Descriptive statistics for abdominal circumference by gestational age, BMI category 1418.4 kg/ m2, girls (mothers are nonsmokers and have no medical illness). Table S5. Descriptive statistics for abdominal circumference by gestational age, BMI category 18.5 24.9 kg/m2, girls (mothers are nonsmokers and have no medical illness). Table S6. Descriptive statistics for abdominal circumference by gestational age, BMI category 2529.9 kg/ m2, girls (mothers are nonsmokers and have no medical illness). Table S7. Descriptive statistics for abdominal circumference by gestational age, BMI category 3034.9 kg/ m2, girls (mothers are nonsmokers and have no medical illness). Table S8. Descriptive statistics for abdominal circumference by gestational age, BMI category 35 kg/m2, girls (mothers are nonsmokers and have no medical illness). Table S9. Descriptive statistics for abdominal circumference by gestational age, BMI category 1418.4 kg/ m2, boys (mothers are nonsmokers and have no medical illness). Table S10. Descriptive statistics for abdominal circumference by gestational age, BMI category 18.5 24.9 kg/m2, boys (mothers are nonsmokers and have no medical illness). Table S11. Descriptive statistics for abdominal circumference by gestational age, BMI category 2529.9 kg/ m2, boys (mothers are nonsmokers and have no medical illness). Table S12. Descriptive statistics for abdominal circumference by gestational age, BMI category 3034.9 kg/ m2, boys (mothers are nonsmokers and have no medical illness). Table S13. Descriptive statistics for abdominal circumference by gestational age, BMI category 35 kg/m2, boys (mothers are nonsmokers and have no medical illness). Table S14. Descriptive statistics for birthweight by gestational age, BMI category 1418.4 kg/m2, girls (mothers are nonsmokers and have no medical illness).

Table S15. Descriptive statistics for birthweight by gestational age, BMI category 18.524.9 kg/m, girls (mothers are nonsmokers and have no medical illness). Table S16. Descriptive statistics for birthweight by gestational age, BMI category 2529.9 kg/m2, girls (mothers are non-smokers and have no medical illness). Table S17. Descriptive statistics for birthweight by gestational age, BMI category 3034.9 kg/m2, girls (mothers are nonsmokers and have no medical illness). Table S18. Descriptive statistics for birthweight by gestational age, BMI category 35 kg/m2, girls (mothers are nonsmokers and have no medical illness). Table S19. Descriptive statistics for birthweight by gestational age, BMI category 1418.4 kg/m2, boys (mothers are nonsmokers and have no medical illness). Table S20. Descriptive statistics for birthweight by gestational age, BMI category 18.524.9 kg/m2, boys (mothers are nonsmokers and have no medical illness). Table S21. Descriptive statistics for birthweight by gestational age, BMI category 2529.9 kg/m2, boys (mothers are nonsmokers and have no medical illness). Table S22. Descriptive statistics for birthweight by gestational age, BMI category 3034.9 kg/m2, boys (mothers are nonsmokers and have no medical illness). Table S23. Descriptive statistics for birthweight by gestational age, BMI category 35 kg/m2, boys (mothers are nonsmokers and have no medical illness). &

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