Sex Differences Between Female and Male Newborn Piglets During Asphyxia, Resuscitation, and Recovery

Abstract

Background: Male and female newborns have differences in their fetal development, fetal-to-neonatal transition, and postnatal morbidity. However, the cardiovascular fetal-to-neonatal adaption is similar between sexes. No study has examined sex differences in newborns during hypoxia, asphyxia, cardio-pulmonary resuscitation, or post-resuscitation recovery. Methods: Secondary analysis (two previous publications and two studies currently under peer-review) of 110 term newborn mixed breed piglets (1-3 days of age, weighing 2.0 ± 0.2 kg), which were exposed to 30 min normocapnic hypoxia followed by asphyxia until asystole, which was achieved by disconnecting the ventilator and clamping the endotracheal tube. This was followed by cardio-pulmonary resuscitation. For the analysis piglets were divided into female and male groups. Cardiac function, carotid blood flow, and cerebral and renal oxygenation were continuously recorded throughout the experiment. Results: A total of 35/41 (85%) female and 54/69 (78%) male piglets resuscitated achieved ROSC (p = 0.881). The median (IQR) time to achieve return of spontaneous circulation in females and males was 111 (80-228) s and 106 (80-206) s (p = 0.875), respectively. The 4-h survival rate was similar between females and males with 28/35 (80%) and 49/54 (91%) piglets surviving (p = 0.241), respectively. Conclusions: No difference between female and male newborn piglets was observed during hypoxia, asphyxia, resuscitation, and post-resuscitation recovery.

Keywords: asphyxia; chest compressions; infants; neonatal resuscitation; newborn; sex differences.

Figure 1

Kaplan-Meier survival curve.

Figure 2

Changes in (A) heart rate [beats per minute (bpm)], (B) mean arterial blood pressure (mmHg), (C) carotid blood flow (mL/min), and (D) cerebral oxygen saturation (%) during hypoxia, asphyxia, and post-resuscitation (solid circle represents male and open circle represents female).

Figure 3

Proinflammatory cytokines in lung tissue. Concentrations of TNF-α, interleukin (IL)-1β, IL-6, and IL-8 in lung tissue homogenates, expressed relative to lung protein concentration, in sham female (n = 5) and male piglets (n = 13) and female (n = 28) and male (n = 49) piglets receiving resuscitation. Results represent the median (solid bar), IQR (box margin), and 95% confidence interval.

Figure 4

Concentrations of IL-1β, IL-6, and IL-8 in frontoparietal cortex homogenates, expressed relative to protein concentration, in sham female (n = 5) and male piglets (n = 13) and female (n = 28) and male (n = 49) piglets receiving resuscitation. Results represent the median (solid bar), IQR (box margin), and 95% confidence interval. Asterisk (*) indicates a significant difference between groups (p < 0.05).

Figure 5

Concentrations of IL-1β, IL-6, and IL-8 in thalamus homogenates, expressed relative to protein concentration, in sham female (n = 5) and male piglets (n = 13) and female (n = 28) and male (n = 49) piglets receiving resuscitation. Results represent the median (solid bar), IQR (box margin), and 95% confidence interval.