Evidence of genetic regulation of fetal longitudinal growth
Introduction
Genetic as well as environmental factors are important determinants of fetal growth. Studies including fathers can provide information on the nature of these genetic factors but to date studies including fathers have been limited. Strong support for genetic regulation is provided by the correlation of paternal birth weight with offspring birth weight, which remains after correcting for maternal birth weight [1], [2], [3], [4].
Paternal anthropometry has been associated with birth weight but the size of this and nature of this association is controversial. Kramer in his review of the determinants of low birth weight in 1987 [5], identifies the association between paternal height and paternal weight with offspring birth weight, but suggests that the influence is minimal, with the sample size weighted magnitude of height effect estimated as 1.6 g/cm, and for weight as 3.3 g/kg. Subsequent studies have reported a greater association with paternal height and birth weight, ranging from 6.8 to 10 g/cm. These associations are present after correction for maternal height [6], [7], [8], but frequently corrections were not made for other confounders such as social class. The paternal height studies have been mainly undertaken on Caucasian populations, but similar trends have been noted in the Chinese [9] and Indian [10] populations. Paternal weight was associated with birth weight but this association was lost when adjusted for paternal height in most [6], [7], but not all cases [10]. Birth weight is an overall measure of fetal growth and it is uncertain which components of fetal growth are associated with paternal height. A link with skeletal development would seem logical and this was supported by Godfrey and colleagues [11], [12] as paternal height was associated with both fetal crown heel length, and bone mineral content. Further studies are needed to confirm this.
Our study aimed to define the relationship of paternal anthropometry and size at birth in normal singleton delivery. We report our results from 567 parents and children who were studied prospectively using research measurements.
Section snippets
Research design and methods
The Exeter Family Study of Childhood Health (EFSOCH) was set up to study fetal and early post natal growth, by investigating the role of genes and genetic factors [13] within a normal Caucasian population. This is an ongoing, prospective, community based study, within a specific area of central Exeter, as defined by postcode. The detailed study protocol is available [14]. Ethical approval was given by the North and East Devon local ethics committee [15]. We report data from the first 600
Inclusion and exclusion criteria
All white Caucasian families (both partners) living in central Exeter (postcode EX1-4), who were registered on the obstetric database of the Royal Devon and Exeter Hospital, were invited to participate in EFSOCH. Diabetic mothers and multiple pregnancies were excluded. Those families where both the pregnant mother and the father of her child agreed to participate were visited at home when the mother was 28 weeks gestation. Written consent was obtained from both parents prior to any data
Paternal anthropometric measurements
Anthropometry was measured by one of three specially trained research midwives. Each measurement was taken three times on the non-dominant side, and the mean value was used in analysis.
Inter- and intra-rater reliability studies were undertaken to ensure reproducibility [16]. Inter-rater coefficient of variation (CV) for weight and skeletal measures (height and head circumference) was < 1%, and for skinfolds measurements < 5%. Intra-rater CVs for all measurements were < 1%. Measurements included
Blood measurements
Fasting venous blood samples were collected in appropriate tubes and spun to separate plasma within 2 h. Haematological, biochemical and hormonal measurements were made on these samples. DNA was extracted from leucocytes and stored for genetic analysis.
Socio-economic status (SES)
We assigned Socio-economic status (SES) by Townsend Scores based on Enumeration Districts by postcode [17]. A Townsend score of 0 indicates the average for the UK, with positive scores indicating more deprivation, and negative scores representing more affluence.
Gestation
Gestation was calculated from last menstrual period (LMP) in women who had regular periods and were confident of the date of their last period. Where there was doubt about the LMP, or if the ultrasound-dating scan differed from LMP by 10 or more days, gestation was calculated by the “dating scan”, done early in pregnancy (12.6 ± 1.6 weeks gestation). Of the 600 pregnancies, 311 were thus dated by LMP, and 289 by ultra sound scan date.
Antenatal follow up and delivery details
Following routine antenatal care, the women delivered locally, and delivery details were recorded on the local maternity unit database.
Neonatal anthropometry
Babies were measured within 24 h of birth, by one of the three research midwives. Measurements included length (to nearest 0.1 cm using the Harpenden stadiometer), weight was taken from delivery room records (to nearest 0.1 kg, using Soehnle scales), skinfold measurements taken on the left side of the body (to the nearest 0.2 mm, using Holtain skinfold calipers), and head and mid-arm circumference (to nearest 0.1 mm using appropriate sized fibreglass, nonstretching tape.) Inter- and intrarater
Statistics
Data are summarized as means and standard deviations, except where the data were not normally distributed, when they are presented as median and interquartile range. Relationships between parental variables and birth measurements were estimated using partial correlations (Pearson), in all cases adjusting for sex, gestational age and parity. The known potential confounders of SES, maternal glucose and maternal smoking were corrected for independently and together. Multiple linear regression
Study cohort (Fig. 1)
Of the 600 couples studied, 5 were excluded as the partner was found to be nonwhite Caucasian, 1 woman was found to be diabetic, 2 families moved away and delivered elsewhere (Fig. 1). There was 1 intrauterine death. 591 live singleton babies were born. 21 babies were born premature (gestation < 37 weeks), 2 babies had severe growth problems, and one had cerebral palsy. Thus we report on 567 singleton, full term, healthy babies delivered in the EFSOCH study.
Characteristics of study population (Table 1)
Mothers were on average 30 years old,
Discussion
Our study has clearly shown that paternal anthropometry influences size at birth. The strongest paternal influence on fetal growth is fathers' height and this predominantly influences length and linear growth of the baby. In contrast to maternal obesity the degree of paternal obesity does not influence birth weight. This work suggests that there is genetic regulation of skeletal growth. Our study is consistent with the earlier studies that have also shown that paternal height influences birth
Acknowledgements
This study was funded by South West NHS Research and Development, Exeter NHS Research and Development, and the Darlington Trust.
ATH is a Wellcome Trust Research Leave fellow.
BK holds an NHS Research and Development studentship.
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