Professor, Department of Obstetrics and Gynecology University of Colorado School of Medicine, Aurora

Dr. Hobbins reports no financial relationships relative to this field of study.

SYNOPSIS: The NICHD Fetal Growth Studies – Singletons investigation recently yielded a new formula for determining gestational age based on standard biometric information. When compared to an often-used formula, it appeared to be more accurate after 21 weeks of gestation.

SOURCE: Skupski DW, Owen J, Kim S, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Developmental Fetal Growth Studies. Estimating gestational age from ultrasound fetal biometrics. Obstet Gynecol 2017;130:433-441.

When dating pregnancies, the clinician deals with two sources of information: patient history and ultrasound findings. The latter is certainly the most objective source, but there are inherent machine- and human-related drawbacks that affect the accuracy of these ultrasound dating methods.

Since equipment and user expertise have improved over the years, Skupski et al, using data generated under the support of the Eunice Kennedy Shriver National Institutes of Child Health and Human Development (NICHD), recently pitted a newly constructed formula for gestational age (the NICHD gestational age formula) against a formula published in 1984 (the Hadlock formula),¹ which the authors described as “being in common use today.” Both formulas use the same biometric variables: head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL).

The study involved 803 non-Hispanic black (28.6%), 781 Hispanic (27.9%), 751 non-Hispanic white (27.9%), and 467 Asian (16.7%) women. All women in the study had regular periods and first trimester ultrasound exams in which the crown rump lengths (CRLs) were within five days of the last menstrual period at 8/0 to 10/6 weeks, six days between 11/0 and 12/6 weeks, and seven days at 13/0 and 13/6. The menstrual dates were then considered as the true gestational age. The patients were followed with serial ultrasound exams through the second and third trimesters. Data from half of these patients were used to construct a gestational age equation, which then was applied to the other half of the study population. The idea was to see how close to the true gestational (menstrual) age the new formula performed, compared with the Hadlock formula. Since the splay in biological variation widens as pregnancy progresses, three gestational age windows were chosen for analysis: 14 to 20 weeks, 21 to 27 weeks, and 28 to 40 weeks. The authors also compared the performance of the new formula in each ethnic group and across various body mass indices (BMIs).

The NICHD formula performed no better than the Hadlock formula between 14 to 20 weeks (± 7 days). However, it was a little better at 21 to 27 weeks (± 10 days), with an average “estimation error” (EE) of 10.4 vs. 11.2 days. At 28 to 40 weeks (± 17 days), the EE was 17.0 vs. 19.8 days. It should be noted that after 34 weeks, the Hadlock formula was highly inaccurate. Interestingly, there were no statistical differences in accuracy between ethnic or BMI groups with either formula.

COMMENTARY

The authors made the point that more accurate dating will reduce the amount of unnecessary interventions for post-maturity and will enable clinicians to better identify true prematurity. However, it also must be noted that the diagnosis of two of the most vexing problems, fetal growth restriction and macrosomia, also depend on gestational age. So, anything we can do to get it right will help.

With the introduction of early screening with nuchal translucency (NT) and the growing desire for patients to have the earliest information available, first-trimester scans are being performed much more frequently, yielding CRL measurements that should trump any later biometric formula for gestational age. Skupski et al found that during the second window of opportunity (14 to 21 weeks), when many patients now have fetal anatomy scans, the new NICHD formula would provide little benefit over other commonly used formulas. Even the one- to two-day advantage of the new formula is of questionable benefit at 21 to 28 days. However, the new formula could make a difference in those showing up for their first scan after 28 weeks, when there would be about a week’s worth of advantage in accuracy over the Hadlock formula. The study data suggest that the Hadlock formula is virtually worthless after 34 weeks.

The nuances regarding ultrasound functions and formulas can be confusing. The new NICHD formula only deals with gestational age. With most ultrasound machines, users can choose their favorite formula or the formula, usually the Hadlock formula, loaded by the ultrasound manufacturer. The displayed result is labeled as the composite ultrasound age (CUA). In addition, the machine will automatically average all the biometric measurements (AC, BPD, FL, and HC), labeling the result as the arithmetic ultrasound age (AUA). In 1984, Hadlock et al compared their CUA formula with the AUA and found no significant differences between the two.¹ This has not been done with the new NICHD formula, but the CUA is likely to be very similar to the AUA.

The plot thickens when one attempts to determine the fetal size. There are more than 50 formulas to calculate fetal weight, using two to five biometric measurements. For example, the Hadlock formula for estimation of fetal weight (EFW) employs the HC, BPD, AC, and FL.² Not surprisingly, this is the one most often used.

The third step is to determine how a given fetus’s size matches up to what is expected, based on its assigned gestational age. This is done by plotting the EFW into a nomogram that best fits the population studied. Often, the user simply will apply the machine’s default nomogram (you guessed it, the Hadlock formula),² which was constructed from 392 Caucasian patients at sea level (Texas). This enables the EFW to be displayed as a percentile. This is the step that lends itself most to a customized approach, since this Texas cohort cannot be expected to be identical to, for example, a mixed ethnic population at 5,000 feet above sea level. To adjust for this, Gardosi et al developed the concept of a customized standard for each fetus.³ This and other formulas have been based on an individual patient’s historical factors, physique, ethnic background, parity, habits, etc. Tailor-made formulas tend to have a greater sensitivity for weight extremes and even have correlated better with perinatal mortality and morbidity in intrauterine growth restriction (IUGR) fetuses.⁴

Through the years, software engineers and researchers have attempted to make life better for clinicians by adding various new wrinkles in technology and algorithm formulations. While some of these endeavors have been helpful, others may have just confused some of the tasks at hand. Fine-tuning true gestational age certainly is worth tackling, but up until about 28 weeks, the benefit of the NICHD formula over existing formulas is underwhelming and represents the least important of the three steps. The last step is the most important regarding identifying small for gestational age and large for gestational age fetuses, but this devil’s advocate could point out that the customized formulas for EFW, while correlating best with some neonatal outcomes and diminishing false-positive results, may be missing deprived late IUGR fetuses with borderline EFWs who might develop neurological problems in childhood.⁵ Since these fetuses could be identified only by middle cerebral artery analysis alone, a case certainly could be made for casting a wider net with a more inclusive formula.

REFERENCES

1. Hadlock FP, Deter RL, Harrist RB, Park SK. Estimating fetal age: Computer-assisted analysis of multiple fetal growth parameters. Radiology 1984;152:497-501.
2. Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: A sonographic weight standard. Radiology 1991;18:129-133.
3. Gardosi J, Mongelli M, Wilcox M, Chang A. An adjustable fetal weight standard. Ultrasound Obstet Gynecol 1995;3:168-174.
4. Kase BA, Carreno CA, Blackwell SC. Customized estimated fetal weight: A novel antenatal tool to diagnose abnormal fetal growth. Am J Obstet Gynecol 2012;207:218.e1-5. doi: 10.1016/j.ajog.2012.06.014. Epub 2012 Jun 13.
5. Eixarch E, Mejer E, Iraola A, et al. Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution. Ultrasound Obstet Gynecol 2008;32:894-899.