Diagnosis and outcome of first-trimester growth delay
- Joan M Mastrobattista, MD
Joan M Mastrobattista, MD
- Professor of Obstetrics & Gynecology
- Baylor College of Medicine
- Ultrasound Clinic Chief
- Division of Maternal-Fetal Medicine
- Deborah Levine, MD
Deborah Levine, MD
- Section Editor — Imaging
- Professor of Radiology
- Director of Ob/Gyn Ultrasound
- Department of Radiology
- Beth Israel Deaconess Medical Center
Prior to the widespread use of ultrasound in early pregnancy, first-trimester growth was thought to be uniform and under genetic control. Differences in fetal growth rates were not believed to manifest until the second half of pregnancy. However, these beliefs were challenged after analysis of data from thousands of first-trimester ultrasound examinations [1-5]. Early delay in fetal growth has been documented in pregnancies with precise gestational age dating, and appears to be predictive of subsequent adverse perinatal outcomes, such as fetal aneuploidy, growth restriction, and preterm birth. These perinatal outcomes can affect health and disease risks later in life.
In this discussion, the term "fetus" will be used regardless of gestational age, even though "embryo" is the biological term for early human life (ie, implantation through eight weeks postconception) and "fetus" is the biological term for human intrauterine life thereafter.
DIAGNOSIS OF FIRST-TRIMESTER GROWTH DELAY
The diagnosis of growth delay is based upon fetal size that is smaller than expected based on last menstrual period (LMP),early sonographic dating, or timing of embryo transfer in pregnancies resulting from assisted reproductive technology (table 1). Thus, it is crucial to have accurate information on the fetus' gestational age and the normal size range for fetuses of that age.
Pitfalls in determining gestational age
Use of last menstrual period — When clinicians date a pregnancy based on menstrual weeks (menstrual age), the first trimester of pregnancy is defined as the time interval beginning on the first day of the LMP and ending 130/7ths weeks later. However, this calculation can lead to errors in assessment of gestational age and, in turn, estimated delivery date (EDD) because:
●Many women do not have regular 28-day cycles and thus do not ovulate (or conceive) on day 14 of the cycle. The difference between the observed and expected size of embryos/fetuses is thus biased towards smaller than expected measurements since the timing of ovulation is skewed to the second half of the cycle.
- Salomon LJ, Bernard JP, Duyme M, et al. Revisiting first-trimester fetal biometry. Ultrasound Obstet Gynecol 2003; 22:63.
- Smith GC. First trimester origins of fetal growth impairment. Semin Perinatol 2004; 28:41.
- Deter RL, Buster JE, Casson PR, Carson SA. Individual growth patterns in the first trimester: evidence for difference in embryonic and fetal growth rates. Ultrasound Obstet Gynecol 1999; 13:90.
- Smith GC, Smith MF, McNay MB, Fleming JE. First-trimester growth and the risk of low birth weight. N Engl J Med 1998; 339:1817.
- Bukowski R, Smith GC, Malone FD, et al. Fetal growth in early pregnancy and risk of delivering low birth weight infant: prospective cohort study. BMJ 2007; 334:836.
- AIUM practice guidelines for the performance of obstetric ultrasound examinations. AIUM, Laurel, MD, 2007.
- Rossavik IK, Torjusen GO, Gibbons WE. Conceptual age and ultrasound measurements of gestational sac and crown-rump length in in vitro fertilization pregnancies. Fertil Steril 1988; 49:1012.
- Robinson HP. Sonar measurement of fetal crown-rump length as means of assessing maturity in first trimester of pregnancy. Br Med J 1973; 4:28.
- Robinson HP, Fleming JE. A critical evaluation of sonar "crown-rump length" measurements. Br J Obstet Gynaecol 1975; 82:702.
- Hadlock FP, Shah YP, Kanon DJ, Lindsey JV. Fetal crown-rump length: reevaluation of relation to menstrual age (5-18 weeks) with high-resolution real-time US. Radiology 1992; 182:501.
- Lasser DM, Peisner DB, Vollebergh J, Timor-Tritsch I. First-trimester fetal biometry using transvaginal sonography. Ultrasound Obstet Gynecol 1993; 3:104.
- Bovicelli L, Orsini LF, Rizzo N, et al. Estimation of gestational age during the first trimester by real-time measurement of fetal crown-rump length and biparietal diameter. J Clin Ultrasound 1981; 9:71.
- Drumm JE, Clinch J, MacKenzie G. The ultrasonic measurement of fetal crown-rump length as a method of assessing gestational age. Br J Obstet Gynaecol 1976; 83:417.
- Nelson LH. Comparison of methods for determining crown-rump measurement by real-time ultrasound. J Clin Ultrasound 1981; 9:67.
- Pedersen JF. Fetal crown-rump length measurement by ultrasound in normal pregnancy. Br J Obstet Gynaecol 1982; 89:926.
- Selbing A. Gestational age and ultrasonic measurement of gestational sac, crown-rump length and biparietal diameter during first 15 weeks of pregnancy. Acta Obstet Gynecol Scand 1982; 61:233.
- MacGregor SN, Tamura RK, Sabbagha RE, et al. Underestimation of gestational age by conventional crown-rump length dating curves. Obstet Gynecol 1987; 70:344.
- Vollebergh JH, Jongsma HW, van Dongen PW. The accuracy of ultrasonic measurement of fetal crown-rump length. Eur J Obstet Gynecol Reprod Biol 1989; 30:253.
- Evans J. Fetal crown-rump length values in the first trimester based upon ovulation timing using the luteinizing hormone surge. Br J Obstet Gynaecol 1991; 98:48.
- Silva PD, Mahairas G, Schaper AM, Schauberger CW. Early crown-rump length. A good predictor of gestational age. J Reprod Med 1990; 35:641.
- Koornstra G, Wattel E, Exalto N. Crown-rump length measurements revisited. Eur J Obstet Gynecol Reprod Biol 1990; 35:131.
- Kustermann A, Zorzoli A, Spagnolo D, Nicolini U. Transvaginal sonography for fetal measurement in early pregnancy. Br J Obstet Gynaecol 1992; 99:38.
- Dickey RP, Gasser RF. Ultrasound evidence for variability in the size and development of normal human embryos before the tenth post-insemination week after assisted reproductive technologies. Hum Reprod 1993; 8:331.
- Grisolia G, Milano K, Pilu G, et al. Biometry of early pregnancy with transvaginal sonography. Ultrasound Obstet Gynecol 1993; 3:403.
- Lohr PA, Reeves MF, Creinin MD. A comparison of transabdominal and transvaginal ultrasonography for determination of gestational age and clinical outcomes in women undergoing early medical abortion. Contraception 2010; 81:240.
- Grange G, Pannier E, Goffinet F, et al. Dating biometry during the first trimester: accuracy of an every-day practice. Eur J Obstet Gynecol Reprod Biol 2000; 88:61.
- Goldstein SR, Wolfson R. Endovaginal ultrasonographic measurement of early embryonic size as a means of assessing gestational age. J Ultrasound Med 1994; 13:27.
- Hadlock FP. Sonographic estimation of fetal age and weight. Radiol Clin North Am 1990; 28:39.
- Bhide A, Sankaran S, Sairam S, et al. Relationship of intertwin crown-rump length discrepancy to chorionicity, fetal demise and birth-weight discordance. Ultrasound Obstet Gynecol 2009; 34:131.
- Salomon LJ, Cavicchioni O, Bernard JP, et al. Growth discrepancy in twins in the first trimester of pregnancy. Ultrasound Obstet Gynecol 2005; 26:512.
- Becker S, Ural S, Fehm T, Bienstock J. Fetal gender and sonographic assessment of crown-rump length: implications for multifetal pregnancy reduction. Ultrasound Obstet Gynecol 2004; 24:399.
- Pölzlberger E, Hartmann B, Hafner E, et al. MATERNAL HEIGHT AND PRE-PREGNANCY WEIGHT STATUS ARE ASSOCIATED WITH FETAL GROWTH PATTERNS AND NEWBORN SIZE. J Biosoc Sci 2016; :1.
- Parker AJ, Davies P, Newton JR. Assessment of gestational age of the Asian fetus by the sonar measurement of crown-rump length and biparietal diameter. Br J Obstet Gynaecol 1982; 89:836.
- Mahendru AA, Daemen A, Everett TR, et al. Impact of ovulation and implantation timing on first-trimester crown-rump length and gestational age. Ultrasound Obstet Gynecol 2012; 40:630.
- Bahado-Singh RO, Lynch L, Deren O, et al. First-trimester growth restriction and fetal aneuploidy: the effect of type of aneuploidy and gestational age. Am J Obstet Gynecol 1997; 176:976.
- Kuhn P, Brizot ML, Pandya PP, et al. Crown-rump length in chromosomally abnormal fetuses at 10 to 13 weeks' gestation. Am J Obstet Gynecol 1995; 172:32.
- Leelapatana P, Garrett WJ, Warren PS. Early growth retardation in the first trimester: is it characteristic of the chromosomally abnormal fetus? Aust N Z J Obstet Gynaecol 1992; 32:95.
- Drugan A, Johnson MP, Isada NB, et al. The smaller than expected first-trimester fetus is at increased risk for chromosome anomalies. Am J Obstet Gynecol 1992; 167:1525.
- Baken L, van Heesch PN, Wildschut HI, et al. First-trimester crown-rump length and embryonic volume of aneuploid fetuses measured in virtual reality. Ultrasound Obstet Gynecol 2013; 41:521.
- Morin I, Morin L, Zhang X, et al. Determinants and consequences of discrepancies in menstrual and ultrasonographic gestational age estimates. BJOG 2005; 112:145.
- van Uitert EM, Exalto N, Burton GJ, et al. Human embryonic growth trajectories and associations with fetal growth and birthweight. Hum Reprod 2013; 28:1753.
- Smith GC, Stenhouse EJ, Crossley JA, et al. Early-pregnancy origins of low birth weight. Nature 2002; 417:916.
- Leung TY, Sahota DS, Chan LW, et al. Prediction of birth weight by fetal crown-rump length and maternal serum levels of pregnancy-associated plasma protein-A in the first trimester. Ultrasound Obstet Gynecol 2008; 31:10.
- Mercer BM, Merlino AA, Milluzzi CJ, Moore JJ. Small fetal size before 20 weeks' gestation: associations with maternal tobacco use, early preterm birth, and low birthweight. Am J Obstet Gynecol 2008; 198:673.e1.
- Thorsell M, Kaijser M, Almström H, Andolf E. Expected day of delivery from ultrasound dating versus last menstrual period--obstetric outcome when dates mismatch. BJOG 2008; 115:585.
- Mook-Kanamori DO, Steegers EA, Eilers PH, et al. Risk factors and outcomes associated with first-trimester fetal growth restriction. JAMA 2010; 303:527.
- Bromley B, Harlow BL, Laboda LA, Benacerraf BR. Small sac size in the first trimester: a predictor of poor fetal outcome. Radiology 1991; 178:375.
- Dickey RP, Olar TT, Taylor SN, et al. Relationship of small gestational sac-crown-rump length differences to abortion and abortus karyotypes. Obstet Gynecol 1992; 79:554.
- Papaioannou GI, Syngelaki A, Maiz N, et al. Ultrasonographic prediction of early miscarriage. Hum Reprod 2011; 26:1685.
- Reljic M. The significance of crown-rump length measurement for predicting adverse pregnancy outcome of threatened abortion. Ultrasound Obstet Gynecol 2001; 17:510.
- Choong S, Rombauts L, Ugoni A, Meagher S. Ultrasound prediction of risk of spontaneous miscarriage in live embryos from assisted conceptions. Ultrasound Obstet Gynecol 2003; 22:571.
- Mukri F, Bourne T, Bottomley C, et al. Evidence of early first-trimester growth restriction in pregnancies that subsequently end in miscarriage. BJOG 2008; 115:1273.
- Abuelghar WM, Fathi HM, Ellaithy MI, Anwar MA. Can a smaller than expected crown-rump length reliably predict the occurrence of subsequent miscarriage in a viable first trimester pregnancy? J Obstet Gynaecol Res 2013; 39:1449.
- Jaddoe VW, de Jonge LL, Hofman A, et al. First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study. BMJ 2014; 348:g14.
- D'Antonio F, Khalil A, Pagani G, et al. Crown-rump length discordance and adverse perinatal outcome in twin pregnancies: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2014; 44:138.
- DIAGNOSIS OF FIRST-TRIMESTER GROWTH DELAY
- Pitfalls in determining gestational age
- - Use of last menstrual period
- - Use of mean sac diameter
- - Use of crown rump length
- RISK OF ANEUPLOIDY
- RISK OF OTHER ADVERSE OUTCOMES
- Growth restriction, low birth weight, and preterm birth
- Pregnancy loss
- Cardiovascular risk
- DISCORDANT TWINS
- Aneuploidy risk
- Risk of pregnancy loss
- SUMMARY AND RECOMMENDATIONS