In this paper, we have used 1999 and 2000 United States nationwide Natality databases to generate multiple reference percentiles for birth weight at each completed week of gestation. Birth weight rose in a non-linear pattern as gestational age increased. In concordance with published data, at each gestational age birth weights were higher among boys than girls, and among non-firstborn infants than firstborns. Near term, infants born to non-Hispanic white mothers were larger than those born to non-Hispanic blacks. Our more detailed data correspond well with the limited percentiles published by Alexander et al. (Figure ), which have been used as a reference standard within the United States.[10
] Our data should prove useful to investigators working to understand both the determinants and the sequelae of fetal growth. The electronic publication of these data allows for dissemination and widespread use of such a detailed reference.
Previous studies have been hampered by the lack of a continuous measure of birth weight independent of gestational age. We first consider previous approaches for the use of fetal growth as an outcome. The interactions among fetal, maternal, and environmental factors that influence fetal growth remain poorly understood. Removing the contribution of gestational age to birth weight is a first step in understanding the roles of these factors in determining fetal growth.[20
] Many researchers have attempted to remove the influence of gestational age when studying predictors of birth weight by using the categories small- (SGA), large- (LGA), and appropriate-for-gestational age (AGA). [22
] However, this categorization reduces the power to detect small associations between fetal exposures and birth weight, unless there is a change in the relationship exactly at the arbitrary cutpoint. This is a particular problem when the size of the association is small in magnitude. Additionally, comparing SGA or LGA with AGA infants inhibits study of variation within the majority of babies that are AGA.
Others have used various methods to control for gestational age when investigating determinants of fetal growth. One procedure has been to use a "birth weight ratio." This measure is calculated by dividing an infant's birth weight by a reference median birth weight at the given gestational age.[16
] However the reference median is chosen, this ratio will assume a linear relationship between birth weight and its influences across the range of birth weights, which may not be correct.
Another approach has been to include gestational age in a multiple regression equation along with other potential predictors of birth weight. This strategy has been used to generate a predicted weight, against which an individual baby's weight can be compared.[16
] Like the birth weight ratio, regression analysis also typically assumes a linear relationship between birth weight and gestational age. This assumption may or may not be appropriate, but in any case is not required by our method, which is based on actual data.
In addition to examining determinants of fetal growth, adjusting birth weight for gestational age is also needed to understand the influence of fetal growth on later outcomes. While birth weight alone may predict risk for adult diseases,[8
] most published data emanate from an era when few premature babies survived until adulthood. Future studies of the early life origins of adult disease will require disentangling the effects of length of gestation from fetal growth. A continuous measure is needed since many studies in this field suggest associations that span the entire range of birth weight, and are not limited to birth weight extremes.
For use of fetal growth as a predictor variable, previously published methods either assume a normal distribution of birth weights at each completed week of gestation,[20
] or include both birth weight and gestational age in multivariable regression models. [28
] However, these approaches are limited because they assume either no relationship or a linear relationship between birth weight and gestational age.
Our method provides comprehensive reference values from broadly based nationwide data without making parametric, functional, or other modeling assumptions. It is useful whether fetal growth is used as an outcome or as an exposure (predictor). These results are not intended to assign a percentile to an individual infant for clinical use. Rather, this approach should help researchers investigate the factors associated with infants born at, for example, the 20th as compared with the 40th, 60th, or 80th percentile, as well as the sequelae of such differences in fetal growth.
We have trimmed the dataset prior to analysis following the methods of Alexander et al.[10
] This procedure primarily excludes infants with implausibly high birth weights at the younger gestational ages, likely because of inaccurate dating. Investigators might therefore wish to consider whether study subjects well beyond the 99.5th
percentile at the youngest gestational ages have accurately recorded weights and gestational ages, prior to inclusion in any analyses. Additionally, some infants with inaccurate gestational ages may remain in the dataset despite trimming, which would tend to inflate values for percentiles above the median.
Several limitations should be considered. One is that relatively low numbers of births at the earlier gestational ages may make percentile estimates for these infants less stable. However, our major percentiles are quite consistent with the combined 1994–1996 data even at the earliest gestational ages (Figure ).[10
] We were not able to account for altitude, although few infants in the US are born at high altitude. In addition, infants born before term may have different growth patterns from those remaining in utero. These curves thus represent cross-sectional weights at birth rather than longitudinal fetal growth.
The Natality dataset calculates gestational age from last menstrual period. Some studies suggest that prenatal ultrasound may provide more accurate dates, even when the last menstrual period is recalled with apparent certainty.[31
] Thus, some investigators advocate use of ultrasound to generate birth weight norms.[25
] Nevertheless, the use of ultrasound reference data has several problems. Because prenatal ultrasounds are not universally performed, these reference datasets are generally regional.[26
] Additionally, data are available only for the subset of women who receive early ultrasounds, and may not include women seeking prenatal care late in pregnancy, or those who choose not to have an ultrasound. Further, different institutions may use different methods to estimate gestational age for a fetus of a given size. Thus, the United States Natality data remain most representative of pregnancies throughout the United States, and appropriate for use as reference.
In addition to calculating reference percentiles for all newborns, we have presented percentiles stratified by infant sex, birth order, and maternal race. Other researchers have advocated further adjusting estimates for factors such as maternal height and weight, [16
] and even for weights of prior infants born to the same mother.[19
] We fear that an overly stratified reference may obscure important predictors of birth weight. While sex and birth order are immutable, the other factors likely serve as surrogates for a combination of maternal exposures such as stress, socioeconomic position, and nutrition, and thus are not permanently bound to differences in fetal growth for future populations.
In conclusion, we have presented a United States national reference standard for size at birth over a broad range of birth weight percentiles from 22 through 44 completed weeks of gestation. Advances in computer technology now permit manipulation of such large data sets as well as electronic publication of multiple reference percentiles for widespread use. These data should prove useful for researchers investigating the determinants and sequelae of altered fetal growth.