Inflated Denominators, Selection In Utero, and the Black Male Neonatal Death Paradox.

Area of Science:

• Perinatal epidemiology
• Reproductive health disparities
• Neonatal outcomes research

Background:

• Epidemiologists hypothesize that elevated fetal death rates among males born to non-Hispanic Black (NHB) women in the USA may explain the lower-than-expected neonatal death rates for extremely preterm (ePTB) NHB males.
• This 'selection in utero' hypothesis is supported by findings that conception cohorts with higher sex ratios (male:female) of NHB stillbirths show greater NHB advantages in ePTB male neonatal death rates.
• However, skeptics suggest this association may be an artifact due to inflated denominators in neonatal death rates within highly stressed populations.

Purpose of the Study:

• To investigate if the observed association between NHB stillbirth sex ratios and NHB male neonatal death advantage persists after accounting for potential denominator inflation.
• To rigorously test the 'selection in utero' hypothesis by examining the relationship between NHB stillbirth sex ratios and NHB ePTB male neonatal death rates across conception cohorts.

Main Methods:

• Utilized US vital statistics for NHB and non-Hispanic white (NHW) singleton ePTB infants born between 1995-2018, aggregated into 282 monthly conception cohorts.
• Addressed potential denominator inflation by using a 'NHB share of burden' variable, defined as the NHB proportion of neonatal deaths among NHB and NHW ePTB males per conception cohort.
• Employed Box-Jenkins methods to analyze the relationship between high sex ratios of NHB stillbirths and the NHB share of ePTB male neonatal deaths within these cohorts.

Main Results:

• Findings align with the 'selection in utero' hypothesis.
• Cohorts with unusually high sex ratios of NHB stillbirths demonstrated a 7% lower-than-expected NHB share of neonatal deaths among ePTB males.

Conclusions:

• Stillbirth acts as a selective process, removing less fit males from conception cohorts and influencing the composition of subsequent birth cohorts.
• This selection bias, driven by differential fetal mortality, likely contributes to observed paradoxes, such as the lower neonatal death rates among extremely preterm non-Hispanic Black males.
• Further research is needed to explore the clinical manifestations and broader implications of this in utero selection bias on neonatal outcomes.