802 - Perinatal inflammation and postnatal head circumference growth from birth to 36 months: A prospective cohort study in rural Bangladesh

Publication Number: 802.6308

Sara Cherkerzian, Harvard Medical School, Boston, MA, United States; Lian V. Folger, Duke University School of Medicine, Durham, NC, United States; Salahuddin Ahmed, Projahnmo Research Foundation, Dhaka, Dhaka, Bangladesh; Rasheda Khanam, Johns Hopkins University, Baltimore, MD, United States; Anne CC. Lee, The Warren Alpert Medical School of Brown University, Wayland, MA, United States

Background: Perinatal inflammation is a major risk factor for adverse neurodevelopmental outcomes, particularly in low- and middle-income countries (LMICs) where the disease burden of both perinatal infection and neurodevelopmental impairment is high. Head circumference (HC) measurement during infancy and childhood may be a valuable tool to monitor brain growth and child development in LMICs.

Objective: To examine associations between cord blood inflammatory markers measured at birth and HC growth trajectories to 36 months in a cohort of children in rural Bangladesh.

Design/Methods: In Sylhet, Bangladesh, we consecutively enrolled 299 pregnancies and collected prenatal data and umbilical cord dried blood spots at birth. Cord blood was analyzed for interleukin (IL)-1α, IL-1β, IL-6, IL-8, and C-reactive protein (CRP). HC for age/sex Z scores (HCAZ) at birth were calculated using the Intergrowth-21 standard; postnatal measures were calculated using the WHO growth standards. The association between high inflammatory marker status (>75% vs <=75%), and HCAZ at 36 months was modeled using linear regression adjusted for gestational age (GA), sex, and birth head circumference. Subgroup analyses further examined this association among small for gestational age infants (SGA; birthweight < 10th%ile for GA/sex).

Results: There were 262 (87.6%) infants with HCAZ at birth and at least one postnatal measurement. Among them, the mean birth GA was 39.1 ± 1.7 weeks; 9.1% were preterm, 25.9% low birthweight ( < 2500 g), 44.9% SGA, and 44.9% male (Table 1). In the full cohort, HCAZ was normal at birth (-0.08±1.14), but HC growth faltered postnatally, and by 36 months, mean HCAZ was -1.53±0.86. There were no significant associations between inflammatory biomarkers at birth and postnatal HC trajectories in the full cohort (Table 2). Among SGA infants, HCAZ was lower at birth (-0.47±1.13), and mean HCAZ at 36 months was -1.85±0.88 (Figure 1a). There was a greater decrease in HCAZ among SGA infants with elevated IL-8 at birth (β = -0.35; 95% CI: -0.68, -0.01; p = 0.04) compared to SGA infants with non-elevated levels (Figure 1b, Table 2).

Conclusion(s): In a cohort of Bangladeshi infants, HCAZ significantly declined from birth to 36 months. Among infants born SGA, HCAZ was smaller at birth than for those appropriate for gestational age (AGA). In SGA infants exposed to inflammation, specifically higher IL-8 at birth, there was a greater rate of decline in head size from birth to 36 months.

Table 1. Descriptive statistics of demographic and clinical characteristics, n = 262 infants
Table 1_HC_110424.pdf1.Statistics presented as mean ± SD unless stated otherwise
2. Abbreviations: Interquartile range (IQR)


Figure 1. Trajectories of head circumference z scores from birth to 36 months by SGA status (SGA v. appropriate for gestational age (AGA)) (A) and among SGA infants by elevated cord blood IL-8 status (> 75th%ile v. <= 75th %ile)(B)
Figure 1_HC_110424.pdf

Table 2. Linear regression: Associations between elevated cord blood immune biomarkers (> 75%ile v. <= 75%ile) and size (z score) at 36 months
Table 2_HC_110424.pdf1. Z scores for birth size calculated using the Intergrowth-21 standard; postnatal measures were calculated using the WHO growth standards.
2. All models adjusted for birth size z score. Adjusted model controlled for gestational age and sex