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587
Department of Epidemiology, bDepartment of Biostatistics and cCarolina Population Center, University of North Carolina at Chapel Hill, Chapel
Hill, NC, dHuman Studies Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency,
Research Triangle Park, NC, eDepartment of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY, fDepartment
of Obstetrics and Gynecology, Vanderbilt University School of Medicine, and gInstitute for Medicine and Public Health, Vanderbilt University
Medical Center, Nashville, TN, USA
Summary
Correspondence:
Dr Caroline Hoffman,
National Institute of
Environmental Health
Sciences, Division of
Extramural Research and
Training, P.O. Box 12233,
Research Triangle Park,
NC 27709, USA.
E-mail:
dilworthch@niehs.nih.gov
Hoffman CS, Messer LC, Mendola P, Savitz DA, Herring AH, Hartmann KE. Comparison of gestational age at birth based on last menstrual period and ultrasound during
the rst trimester. Paediatric and Perinatal Epidemiology 2008; 22: 587596.
Reported last menstrual period (LMP) is commonly used to estimate gestational age
(GA) but may be unreliable. Ultrasound in the rst trimester is generally considered a
highly accurate method of pregnancy dating. The authors compared rst trimester
report of LMP and rst trimester ultrasound for estimating GA at birth and examined
whether disagreement between estimates varied by maternal and infant characteristics.
Analyses included 1867 singleton livebirths to women enrolled in a prospective pregnancy cohort. The authors computed the difference between LMP and ultrasound GA
estimates (GA difference) and examined the proportion of births within categories of
GA difference stratied by maternal and infant characteristics. The proportion of births
classied as preterm, term and post-term by pregnancy dating methods was also
examined.
LMP-based estimates were 0.8 days (standard deviation = 8.0, median = 0) longer on
average than ultrasound estimates. LMP classied more births as post-term than ultrasound (4.0% vs. 0.7%). GA difference was greater among young women, non-Hispanic
Black and Hispanic women, women of non-optimal body weight and mothers of
low-birthweight infants. Results indicate rst trimester report of LMP reasonably
approximates gestational age obtained from rst trimester ultrasound, but the degree
of discrepancy between estimates varies by important maternal characteristics.
Keywords: gestational age, measurement, accuracy, LMP, ultrasound estimates, maternal
age, ethnic group, preterm, post-term, bias.
Introduction
Self-report of last menstrual period (LMP) is often used
to estimate gestational age in clinical care and epidemiological research. However, reported LMP may be
unreliable.1 Women may not recall LMP date accurately2,3 or misinterpret early pregnancy bleeding as
normal menses.4 In addition, the convention of assigning a 14-day interval between menstruation and ovulation, implicit in calculations of gestational age, will be
inaccurate for women with irregular menstrual cycles
or delayed ovulation.5,6 This presents the dilemma of
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
588
C. S. Hoffman et al.
Methods
Study design and population
Right from the Start (RFTS) is an ongoing, communitybased prospective cohort study. This analysis includes
participants in RFTS Phase I, conducted from 2000 to
2004. Women who were early in pregnancy (12
weeks gestation) or planning to become pregnant
were recruited from private and public prenatal care
clinics and the community at large (e.g. using information posters and brochures, advertisements placed in
community publications, targeted mailings) and followed until the end of pregnancy. Additional details of
site selection and recruitment are described elsewhere.20 The Institutional Review Boards at the University of North Carolina, University of Tennessee and the
University of Texas approved the study protocols; participants gave informed consent.
Pregnant women were enrolled after providing an
LMP date and date of their rst positive pregnancy test
(n = 2514). Women trying to become pregnant were
pre-enrolled and followed for up to 6 months with
free pregnancy test kits provided; those who conceived
were formally enrolled (n = 252). In all, 2766 pregnancies were enrolled and available for assessment. We
excluded 347 (12.5%) pregnancies that ended in a loss,
91 (3.3%) pregnancies lost to follow-up, 8 (0.3%) multigestational pregnancies and 16 (0.6%) repeat livebirths
to a RFTS participant. Additional exclusions were
made for pregnancies with no or incomplete baseline
interview (n = 259; 9.4%), incomplete LMP date (n = 18;
0.6%), no ultrasound data (n = 158; 5.7%) and missing
infant birth date (n = 2; 0.07%). This analysis includes
1867 singleton livebirths with complete baseline interview, LMP (month and day) and ultrasound data.
Women retained for analysis were similar to all
enrolled participants with respect to maternal age, estimated gestational age at enrolment and parity, but
were slightly more likely to be White and to have completed 16 years of education.
Data collection
Information about LMP was obtained during screening
and enrolment telephone interviews, typically at 8
weeks gestation for women pregnant at initial screening and 5 weeks gestation for pre-enrolled women.
Women were informed they might need a calendar (or
diary) to answer certain questions and were invited to
obtain a calendar for the interview. Women were asked
What was the rst day of your last menstrual period?
If necessary, they were prompted to think of an event
that happened around the same time as their last
period (e.g. a holiday, vacation or weekend) to facilitate
recall. Additional maternal characteristics also were
collected by telephone interview.
First trimester endovaginal ultrasounds were conducted by clinical sonographers who were required to
have American Registry of Diagnostic Medical Sonog-
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
Statistical analysis
We compared the distributions of gestational age at
birth (in days) from LMP (date of birth date of LMP)
and ultrasound [date of birth - (date of ultrasound
estimated clinical age at assessment)]. Like the LMPbased estimate, the ultrasound estimated clinical age
includes an assumed 14-day interval between menses
and conception, rendering the two estimated methods
comparable.
The difference in days between the LMP and ultrasound estimates was calculated (LMP estimate ultrasound estimate, hereafter referred to as gestational age
589
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
590
C. S. Hoffman et al.
Results
The median estimated gestational age at birth was 276
days (39 weeks gestation) for both dating methods
(Fig. 1, left panel). Compared with LMP, ultrasoundderived gestational age was slightly shorter (mean of
273 vs. 274 days), less variable (standard deviation of
14 vs. 16 days), and had a narrower range (214307
days vs. 207315 days). A similar proportion of births
were classied as preterm (<37 weeks gestation) by
LMP than by ultrasound (proportions and associated
95% CIs were 10.0 [8.7, 11.5] vs. 8.9 [7.6, 10.3] respectively). The proportion of births classied as postterm (>41 weeks gestation) was notably higher
by LMP dating (4.0 [3.2, 5.0] vs. 0.7 [0.4, 1.3] %
respectively).
Gestational age difference was within +/-7 days for
80.8% of women and +/-30 days for 98.5% (Fig. 1,
right panel). The mean difference was 0.8 days
(SD = 8.0, median = 0 days) and ranged from -70 to 38
days. LMP-based estimates were somewhat more
likely to be higher (older) than ultrasound-based estimates when discrepant (gestational age difference was
zero for 10.5% of women, positive for 47.8% and negative for 41.7%).
Women <20 years old were more likely to have
both positive and negative differences (+8 days or
-8 days) than other age groups, while women 30
years old were less likely to have a positive gestational age difference (Table 1). Low education level
(completed high school or less), single marital status
and non-optimal BMI (<18.9 or >29.0 kg/m2) were
also associated with overall increased discrepancy.
Non-Hispanic Black women were more likely to have
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
591
Table 1. Difference in LMP and ultrasound-based estimates of gestational age at birth by selected maternal and infant characteristics,
livebirths (n = 1867) to participants in the RFTS study, 200004
GA difference (in days): LMP US estimate
All participants
Maternal age (years)
<20
2024
2529
3034
35
Mean (SD)
<-14
-14 to -8
+8 to +14
>+14
1867
0.8 (8.0)
2.0%
4.5%
80.8%
8.6%
4.1%
P-valuea
<0.001
107
426
610
528
196
1.7
0.5
1.5
0.6
-0.6
(12.2)
(9.8)
(7.4)
(6.4)
(6)
2.8%
2.8%
1.5%
2.3%
1.0%
10.3%
5.6%
3.8%
2.8%
5.6%
65.4%
75.6%
81.2%
85.8
85.7%
12.2%
11.3%
8.7%
6.6%
6.1%
9.4%
4.7%
4.9%
2.5%
1.5%
Race/ethnicity
Non-Hispanic White
Non-Hispanic Black
Hispanic
Other
Missing
1109
520
176
59
3
1.2
-0.5
1.3
2.5
(6.5)
(9.7)
(9.3)
(10.1)
1.3%
3.3%
3.4%
1.7%
3.4%
7.7%
3.4%
0%
84.1%
76.5%
75.0%
72.9%
8.3%
7.7%
11.9%
13.6%
2.9%
4.8%
6.3%
11.9%
Education level
High school or less
Some college
4+ years of college
496
417
954
0.8 (10.8)
0.6 (7.1)
0.9 (6.5)
3.2%
1.9%
1.5%
5.7%
4.8%
3.8%
73.2%
80.6%
84.8%
11.9%
9.8%
6.4%
6.1%
2.9%
3.6%
<0.001
1298
568
1
1.1 (6.9)
0.1 (10.1)
1.6%
3.0%
3.4%
7.0%
83.4%
74.8%
8.0%
9.9%
3.5%
5.3%
<0.001
192
956
253
418
48
1.5
0.8
0.2
0.8
(7.6)
(7.5)
(8.0)
(9.0)
0.5%
1.4%
3.6%
2.9%
6.8%
4.0%
4.0%
5.0%
77.1%
84.0%
80.6%
76.6%
9.4%
7.2%
8.3%
10.8%
6.3%
3.5%
3.6%
4.8%
0.026
1275
367
137
48
40
0.5
0.6
3.1
2.1
(7.2)
(8.7)
(11)
(12.9)
1.7%
2.7%
2.9%
4.2%
3.7%
6.8%
5.1%
8.3%
84.2%
76.6%
66.4%
56.3%
7.8%
9.3%
13.1%
14.6%
2.6%
4.6%
12.4%
16.7%
0.014b
153
1714
1236
323
147
8
3
0.6
-0.3
1.4
0.6
(6.8)
(8.1)
(8.3)
(11.4)
(8.2)
0%
2.2%
1.7%
4.0%
2.0%
0.7%
4.8%
3.4%
9.3%
6.8%
83.7%
80.5%
82.6%
74.9%
76.2%
9.8%
8.5%
9.3%
6.2%
7.5%
5.9%
3.9%
3%
5.6%
7.5%
<0.001
104
959
557
245
2
0.9
1.0
0.6
0.2
(10.0)
(8.4)
(7.2)
(7.2)
4.8%
2.2%
1.4%
1.6%
2.9%
5.4%
4.3%
2.0%
74.0%
77.9%
84.2%
86.9%
12.5%
9.9%
6.6%
6.5%
5.8%
4.6%
3.4%
2.9%
0.022
Marital status
Married
Not married
Missing
Pre-pregnancy BMI (kg/m2)
<19.8
19.825.9
26.029.0
>29.0
Missing
0.024b
a
P-value corresponds to two-sided Pearson chi-square test for independence of maternal/infant characteristics and categories of GA difference
unless otherwise specied.
b
P-value corresponds to two-sided Fishers Exact test for independence of maternal/infant characteristics and categories of GA difference.
c
Participants that were pregnant at enrolment were further subdivided into three categories: those who reported they had not used contraceptives
in the past year or had stopped using contraceptives to become pregnant, those who reported they became pregnant during a gap or break in
contraceptive use, and those who reported they became pregnant owing to contraceptive failure.
BMI, body mass index; GA, gestational age; LMP, last menstrual period; RFTS, Right from the Start; SD, standard deviation; US, ultrasound.
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
592
C. S. Hoffman et al.
Table 2. Odds of having a difference of more than 7 days between LMP and US-based estimates of gestational age at birth by selected
maternal and infant characteristics: livebirths to participants in the RFTS study, 200004
GA difference +8 vs. -7 to +7a
+8
n
Maternal age (years)
<20
23
2024
68
2529
83
3034
48
35
15
P-value
Race/ethnicity
Non-Hispanic White
124
Non-Hispanic Black
65
Hispanic
32
15
Otherd
Missing
1
P-value
Education level
High school or less
89
Some college
53
4+ years of college
95
P-value
Marital status
Married
150
Not married
86
Missing
1
P-value
Pre-pregnancy BMI (kg/m2)
<19.8
30
19.825.9
102
26.029.0
30
>29.0
65
Missing
10
P-value
Certainty of LMP date
Very sure
133
Pretty sure
51
Somewhat sure
35
Very uncertain
15
Missing
3
P-value
Infant birthweight (g)
<2500
19
25003499
139
35003999
56
4000
23
Missing
0
P-value
+/-7
n
Unadjusted
OR [95% CI]
Adjustedc
OR [95% CI]
-8
n
+/-7
n
Unadjusted
OR [95% CI]
Adjustedc
OR [95% CI]
70
322
495
453
168
14
36
32
27
13
70
322
495
453
168
933
398
132
43
2
1.0 Reference
1.2 [0.9, 1.7]
1.8 [1.2, 2.8]
2.6 [1.4, 4.9]
1.0 Reference
0.8 [0.6, 1.2]
1.2 [0.7, 1.9]
2.3 [1.2, 4.5]
52
57
12
1
0
933
398
132
43
2
1.0 Reference
2.6 [1.7, 3.8]
1.6 [0.8, 3.1]
1.0 Reference
1.8 [1.1, 2.9]
1.4 [0.7, 2.9]
0.002
0.033
<0.001
0.057
363
336
809
44
28
50
363
336
809
1083
425
0
1.0 Reference
1.5 [1.1, 1.9]
1.0 Reference
1.0 [0.7, 1.5]
65
57
0
1083
425
0
1.0 Reference
2.2 [1.5, 3.2]
1.0 Reference
1.3 [0.8, 2.3]
0.010
0.995
<0.001
0.275
0.025
0.077
0.156
0.413
1.0 Reference
1.5 [1.0, 2.1]
3.1 [2.0, 4.8]
4.5 [2.3, 8.6]
1.0 Reference
1.5 [1.0, 2.1]
2.9 [1.8, 4.6]
3.3 [1.6, 6.9]
1.0 Reference
1.9 [1.3, 3.0]
1.9 [1.0, 3.7]
3.5 [1.4, 8.6]
1.0 Reference
1.9 [1.2, 3.0]
1.8 [0.9, 3.6]
2.2 [0.7, 6.6]
<0.001
<0.001
0.002
0.018
0.005
0.014
0.065
0.382
148
803
204
320
33
1073
281
91
27
36
77
747
469
213
2
14
51
19
33
5
69
35
11
6
1
8
73
32
9
0
148
803
204
320
33
1073
281
91
27
36
77
747
469
213
2
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
Discussion
Findings from this study suggest that early report of
LMP results in similar gestational age dating as that
obtained from early ultrasound. Over 90% of women
were concordantly classied as preterm, term or postterm by LMP and ultrasound. However, the LMP estimate of gestational age tended to be greater than
gestational age based upon ultrasound when discrepant (by approximately 1 day, on average) and resulted
in a higher proportion of births classied as post-term.
In addition, the degree of difference between LMP and
ultrasound-based estimates varied by important maternal characteristics.
No feasible gold standard currently exists for estimating the gestational age of spontaneously conceived
pregnancies in large-scale epidemiological studies.
From a clinical perspective, rst trimester crown-rump
measurement is considered the most accurate method
of dating pregnancies.13 The validity of rst trimester
ultrasound assessment has been empirically demonstrated in studies of women undergoing in vitro fertilization, which have found high concordance between
known time of embryo transfer (oocyte retrieval + 14
days) and gestational age from rst trimester ultra-
593
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
594
C. S. Hoffman et al.
Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works
Acknowledgements
This study was funded jointly by the Awwa Research
Foundation (AwwaRF) and the U.S. Environmental
Protection Agency (USEPA) under Cooperative
Agreement Nos. CR825625-01, CR827268-01 and
CR828216-01, a grant from the National Institute
of Environmental Health Sciences (P30ES10126), and
the NHEERL-DESE Cooperative Training grant in
Environmental Sciences Research (EPA CT8229471
and CR83323601).
595
Disclaimer
The information in this document has been funded, in
part, by the US Environmental Protection Agency. It
has been subjected to review by the National Health
and Environmental Effects Research Laboratory and
approved for publication. Approval does not signify
that the contents reect the views of the Agency, nor
does mention of trade names or commercial products
constitute endorsement or recommendation for use.
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Paediatric and Perinatal Epidemiology, 22, 587596. Journal Compilation 2008 Blackwell Publishing Ltd. No claim to original US government works