A key issue to understand when selecting a gestational age estimation method for research purposes is that the choice may have implications, particularly in studies of pre- or post-term delivery as well as studies of outcomes that are closely related to length of pregnancy. To illustrate this issue, we used data from the Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS) to evaluate the effect of the choice of gestational age estimation method on the identification of risk factors for post-term delivery.20
The RADIUS was a randomised, clinical trial that was conducted from 1987 to 1991 to assess whether the administration of two routine obstetric ultrasound examinations reduces perinatal morbidity and mortality in a low-risk population. Eligibility criteria for participation included: aged 18 years or older, English speaking, date of first day of the LMP known within 1 week, regular menstrual cycles, free of chronic disease, no history of recent oral contraceptive use, and no history of stillbirth or history of delivering a small-for-gestational-age infant. Eligible women who provided informed consent to participate were randomised to receive either standard pregnancy management (routine prenatal care from her selected obstetrician) or two routine obstetric ultrasounds (scheduled for 15–22 and 31–35 weeks according to LMP) in addition to standard pregnancy management.
Among the 53 367 women screened for participation in the RADIUS trial, 21 050 (39%) were found to be eligible. RADIUS investigators randomised 15 530 women, 7812 to the intervention group and 7718 to the control group. We used data from the 7812 women randomised to the intervention group. We excluded 105 women who were lost to follow-up, 60 early pregnancy losses, 12 elective terminations, 68 multifetal pregnancies, 32 women who withdrew informed consent, 574 women who were missing fetal ultrasound measurements from either examination, and 178 women who were of a race/ethnicity other than non-Hispanic white or black. This left 6783 women available for analysis.
Menstrual-based pregnancy length in days was calculated by subtracting the date of the first day of the LMP from the date of delivery. Ultrasound-based gestational length was determined by calculating the estimated gestational age in days at the first routine ultrasound (according to ultrasound dating standards), and then adding the number of days between that date and delivery. Gestational age at the first routine ultrasound was calculated according to the multiple parameter formula of Hadlock et al., which used the head circumference, abdominal circumference, biparietal diameter and femur length measurements recorded during the first routine ultrasound.28 This formula has been shown to be the most accurate ultrasound-based gestational dating formula in studies of women with certain menstrual dates, as well as pregnancies achieved through assisted reproductive technologies. It has been shown to have a systematic error of less than 1 day.29
Post-term delivery was defined as delivery at 42 completed weeks of gestation or later according to three estimation methods: LMP, ultrasound and an obstetric estimate, in which the LMP estimate was replaced by the ultrasound measurement if they differed by more than 14 days.
The incidence of post-term delivery varied according to the gestational age estimation method. It ranged from a high of 5.4% [95% confidence interval (CI) 5.1, 5.7] when calculated according to LMP to a low of 2.5% [95% CI 2.3, 2.7] when calculated with ultrasound. The incidence of post-term delivery was 3.8% [95% CI 3.6, 4.1] using the obstetric estimate algorithm. The mean length of pregnancy calculated according to LMP was 279 days, 1.3 days longer than the ultrasound-based estimate.
These figures are similar in magnitude and direction to those reported by others. Between 1987 and 1989, Reuss and colleagues prospectively followed 1159 pregnant women for a study in which pregnancy length was a primary outcome of interest.46 They found that the incidence of post-term delivery was 9.7% when gestational age was calculated according to reliable LMP dates, compared with 2.8% based on ultrasound evaluations. Using data collected from 3655 women as part of the Pregnancy, Infection, and Nutrition study from October 1995 to May 2001, Savitz and colleagues found that the incidence of post-term delivery was 12.1% according to LMP and only 3.4% according to ultrasound. Further, they found that the LMP-based estimate of gestation was 2.8 days longer on average than the ultrasound-based estimate.47
We used unconditional logistic regression to identify risk factors for post-term delivery (Table 3). The factors that we examined included: maternal race (non-Hispanic white, non-Hispanic black); age (18–20, 21–30, 31 + years); education (less than high school, high school graduate, some college or college graduate, graduate school); smoking status at enrolment (non-smoker, smoker); maternal pre-pregnancy body mass index (BMI; kg/m2 classified as underweight, healthy, overweight or obese); parity (0, 1+); and infant sex (female, male). Variables were retained in the final model if they were found to be significantly associated with post-term delivery, or if they changed the estimate of another factor by more than ±10%.
Table 3. Predictors of post-term delivery by method of estimation of gestational age, Routine Antenatal Diagnostic Imaging with Ultrasound Study (RADIUS)
| Non-Hispanic white||96.2||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| Non-Hispanic black||3.8||0.9 [0.5, 1.7]||0.9 [0.5, 1.5]||0.5 [0.1, 1.4]||0.3 [0.1, 1.2]||0.7 [0.3, 1.5]||0.7 [0.3, 1.4]|
|Maternal age (years)|
| 18–20||4.1||1.6 [1.0, 2.5]||1.3 [0.8, 2.1]||1.0 [0.5, 2.3]||0.8 [0.4, 1.9]||1.6 [0.9, 2.6]||1.2 [0.7, 2.0]|
| 21–30||67.5||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| 31+||28.4||0.7 [0.5, 0.9]||0.8 [0.6, 1.0]||1.2 [0.8, 1.6]||1.6 [1.1, 2.3]||0.8 [0.6, 1.0]||1.0 [0.7, 1.3]|
| Less than high school||3.4||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| High school graduate||25.7||0.9 [0.5, 1.5]||0.9 [0.5, 1.5]||1.9 [0.6, 6.2]||1.7 [0.5, 5.5]||0.8 [0.4, 1.4]||0.8 [0.4, 1.5]|
| College||61.8||0.8 [0.5, 1.4]||0.8 [0.5, 1.4]||2.0 [0.6, 6.2]||1.6 [0.5, 5.4]||0.7 [0.4, 1.3]||0.7 [0.4, 1.4]|
| Graduate school||9.1||0.7 [0.4, 1.4]||0.7 [0.4, 1.4]||2.4 [0.7, 8.1]||1.7 [0.5, 6.2]||0.6 [0.3, 1.2]||0.6 [0.3, 1.3]|
|Maternal smoking status|
| Non-smoker||87.1||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| Smoker||12.9||1.3 [1.0, 1.8]||1.3 [0.9, 1.7]||1.0 [0.6, 1.5]||1.0 [0.6, 1.7]||1.2 [0.9, 1.7]||1.1 [0.8, 1.6]|
|Maternal body mass index|
| Underweight||6.0||1.1 [0.7, 1.8]||1.1 [0.7, 1.6]||1.2 [0.6, 2.3]||1.3 [0.7, 2.4]||1.3 [0.8, 2.1]||1.2 [0.7, 2.0]|
| Healthy||71.6||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| Overweight or obese||22.4||1.4 [1.1, 1.7]||1.4 [1.1, 1.7]||1.5 [1.1, 2.1]||1.6 [1.1, 2.3]||1.3 [1.0, 1.8]||1.3 [1.0, 1.8]|
| 0||45.6||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| 1+||54.4||0.6 [0.5, 0.8]||0.7 [0.5, 0.8]||0.3 [0.2, 0.4]||0.3 [0.2, 0.4]||0.5 [0.4, 0.6]||0.5 [0.4, 0.6]|
| Female||48.9||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference||1.0 Reference|
| Male||51.1||0.9 [0.7, 1.1]||0.9 [0.7, 1.1]||1.4 [1.0, 1.8]||1.3 [1.0, 1.8]||0.8 [0.6, 1.1]||0.8 [0.6, 1.1]|
When pregnancy length was estimated according to LMP, maternal age, smoking status, maternal pre-pregnancy BMI and parity were found to be statistically significantly associated with post-term delivery in the univariable analyses. In the adjusted analyses, overweight and obese women had a 40% increased odds of post-term delivery compared with healthy-weight women, while the odds of post-term delivery was 30% lower among multiparae compared with primiparae.
When pregnancy length was based on ultrasound, maternal pre-pregnancy BMI and parity were statistically significantly associated with post-term delivery in the univariable analyses. In the adjusted analyses, overweight or obese women had a 50% increased odds of delivering post-term compared with healthy-weight women. Multiparae, in contrast, had a 70% decreased odds of delivering post-term compared with primiparae.
As expected, the results in which pregnancy length was calculated using the obstetric estimate algorithm were somewhat intermediate to the LMP and ultrasound findings. The two factors that were found to be significantly predictive of post-term delivery were maternal pre-pregnancy BMI and parity. In the adjusted analyses, overweight or obese women had a 30% increased odds of post-term delivery compared with healthy-weight women, while the odds of post-term delivery was decreased by approximately 50% in multiparae compared with primiparae.
Given that the choice of method of gestational age estimation has a clear impact on the identification of risk factors for post-term delivery, it is likely that most of the observed associations are artifacts rather than evidence that the factors are in some way involved in the aetiology of post-term delivery. In the LMP-based analyses, factors associated with longer or more irregular menstrual cycles were associated with post-term delivery; however, in the ultrasound-based analyses, identified factors were related to fetal growth. It has been well documented that there is systematic bias in the assessment of LMP and ultrasound-based gestational age for some subgroups of the population.48–50 These biases often result in somewhat large (>7 days) discrepancies between LMP and ultrasound-based estimates of gestation, which can lead to spurious associations between certain covariates and outcomes related to length of pregnancy, depending on the gestational age estimation method that is chosen.
One important issue to note is that while the impact of a given factor on the estimate of pregnancy length may be small, the joint effect of systematic errors could be quite large for certain subgroups of the population.48 For instance, overweight or obese women have longer and more irregular menstrual cycles compared with normal-weight women, which influences the accuracy of LMP-based gestational age estimates.51,52 In addition, overweight or obese women are more likely to carry larger fetuses, resulting in systematic error in the ultrasound-based estimate of pregnancy length.53
Regardless of the gestational age estimation method chosen, multiparae appear to be less likely than primiparae to deliver a post-term infant. This is consistent with previous work that indicates the mean length of pregnancy is somewhat shorter among multiparae.12 While the odds ratios for post-term delivery were comparable when gestation was calculated using LMP or the clinical-based estimate, the odds ratio for post-term delivery appears to be reduced even further when ultrasound-based estimates are used.