Differing prevalence of microcephaly and macrocephaly in male and female fetuses

Amalia M Brawley; Eric W Schaefer; Elizabeth Lucarelli; Serdar H Ural; Cynthia H Chuang; Wenke Hwang; Ian M Paul; Carrie Daymont

doi:10.3389/fgwh.2023.1080175

Differing prevalence of microcephaly and macrocephaly in male and female fetuses

Front Glob Womens Health. 2023 Feb 24:4:1080175. doi: 10.3389/fgwh.2023.1080175. eCollection 2023.

Authors

Amalia M Brawley¹, Eric W Schaefer², Elizabeth Lucarelli¹, Serdar H Ural¹, Cynthia H Chuang^{2

3}, Wenke Hwang², Ian M Paul^{2

4}, Carrie Daymont^{2

4}

Affiliations

¹ Department of Obstetrics and Gynecology, Penn State College of Medicine, Hershey, PA, United States.
² Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, United States.
³ Department of Medicine, Penn State College of Medicine, Hershey, PA, United States.
⁴ Department of Pediatrics, Penn State College of Medicine, Hershey, PA, United States.

Abstract

Objective: To compare the proportion of female and male fetuses classified as microcephalic (head circumference [HC] < 3rd percentile) and macrocephalic (>97th percentile) by commonly used sex-neutral growth curves.

Methods: For fetuses evaluated at a single center, we retrospectively determined the percentile of the first fetal HC measurement between 16 and 0/7 and 21-6/7 weeks using the Hadlock, Intergrowth-21st, and NICHD growth curves. The association between sex and the likelihood of being classified as microcephalic or macrocephalic was evaluated with logistic regression.

Results: Female fetuses (n = 3,006) were more likely than male fetuses (n = 3,186) to be classified as microcephalic using the Hadlock (0.4% male, 1.4% female; odds ratio female vs. male 3.7, 95% CI [1.9, 7.0], p < 0.001), Intergrowth-21st (0.5% male, 1.6% female; odds ratio female vs. male 3.4, 95% CI [1.9, 6.1], p < 0.001), and NICHD (0.3% male, 1.6% female; odds ratio female vs. male 5.6, 95% CI [2.7, 11.5], p < 0.001) curves. Male fetuses were more likely than female fetuses to be classified as macrocephalic using the Intergrowth-21st (6.0% male, 1.5% female; odds ratio male vs. female 4.3, 95% CI [3.1, 6.0], p < 0.001) and NICHD (4.7% male, 1.0% female; odds ratio male vs. female 5.1, 95% CI [3.4, 7.6], p < 0.001) curves. Very low proportions of fetuses were classified as macrocephalic using the Hadlock curves (0.2% male, < 0.1% female; odds ratio male vs. female 6.6, 95% CI [0.8, 52.6]).

Conclusion: Female fetuses were more likely to be classified as microcephalic, and male fetuses were more likely to be classified as macrocephalic. Sex-specific fetal head circumference growth curves could improve interpretation of fetal head circumference measurements, potentially decreasing over- and under-diagnosis of microcephaly and macrocephaly based on sex, therefore improving guidance for clinical decisions. Additionally, the overall prevalence of atypical head size varied using three growth curves, with the NICHD and Intergrowth-21st curves fitting our population better than the Hadlock curves. The choice of fetal head circumference growth curves may substantially impact clinical care.

Keywords: biometry; growth; macrocephaly; microcephaly; ultrasound.

Grants and funding

Funding was received from the Children's Miracle Network at Penn State Children's Hospital. Children's Miracle Network had no role in study design, data collection or analysis, writing of report, or decision to submit for publication. The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR002014 and Grant UL1 TR00045. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.