Correcting for measurement error in assessing gestational age in a low-resource setting: a regression calibration approach

Abstract

Introduction: Measurement error in gestational age (GA) may bias the association of GA with a health outcome. Ultrasound-based GA is considered the gold standard and is not readily available in low-resource settings. We corrected for measurement error in GA based on fundal height (FH) and date of last menstrual period (LMP) using ultrasound from the sub-cohort and adjusted for the bias in associating GA with neonatal mortality and low birth weight (< 2,500 grams, LBW).

Methods: We used data collected from 01/2015 to 09/2019 from pregnant women enrolled at two public hospitals in Siaya county, Kenya (N = 2,750). We used regression calibration to correct for measurement error in FH- and LMP-based GA accounting for maternal and child characteristics. We applied logistic regression to associate GA with neonatal mortality and low birth weight, with and without calibrating FH- and LMP-based GA.

Results: Calibration improved the precision of LMP (correlation coefficient, $\rho$ from 0.48 to 0.57) and FH-based GA ($\rho$ from 0.82 to 0.83). Calibrating FH/LMP-based GA eliminated the bias in the mean GA estimates. The log odds ratio that quantifies the association of GA with neonatal mortality increased by 29% (from -0.159 to -0.205) by calibrating FH-based GA and by more than twofold (from -0.158 to -0.471) by calibrating LMP-based GA.

Conclusion: Calibrating FH/LMP-based GA improved the accuracy and precision of GA estimates and strengthened the association of GA with neonatal mortality/LBW. When assessing GA, neonatal public health and clinical interventions may benefit from calibration modeling in settings where ultrasound may not be fully available.

Keywords: attenuation; fundal height; gestational age; last menstrual period; measurement error; preterm; regression calibration.