Public Health

Neonatology

Global Neonatal & Children's Health

Basic Science Pathway

Cross-Disciplinary Pathway

Clinical Research Pathway

Individualized Neonatal Care: Sex-Specific Approach Matters!

Chair(s)

• 

  Pradeep Alur, MD

  Associate Professor
  University of Mississippi Medical center
  Brandon, Mississippi, United States

The biological differences between the sexes manifest quite early during fetal life. The crown-rump length is larger in male fetuses compared to females in the first trimester. Placentae of male and female fetuses have different protein and gene expressions, especially in adverse conditions. Even within the intrauterine milieu, the same extracellular micro RNA may show upregulation in females and downregulation in male fetuses. There appears to be a natural survival advantage for females. Maternal glucocorticoids (GC) play a key role in fetal growth and organ maturation. However, excess glucocorticoids can not only affect growth, but the response may be sex-specific and probably mediated through glucocorticoid receptors (GR) in the placenta. Mild pre-eclampsia and asthma are associated with normal growth patterns in males, but in female fetuses, they are associated with a slowing of growth rate without causing IUGR, probably as an adaptive response for future adverse events. Thus, female fetuses survive while male fetuses exhibit IUGR, preterm delivery, and even death in the face of another adverse event.

There is growing evidence that maternal pre-pregnancy overweight or obesity status is directly associated with a higher risk of obesity in a male child, but not in a female child, at one year of age. It is fascinating that male and female fetuses respond differently to the same intrauterine environment, and this suggests a fundamental biological variation most likely at the cellular and molecular level.

It is well-known that weight, length, and head circumferences are greater in male preterm infants at all gestational ages. We have sex-specific growth charts such as Fenton-2013 for the preterm infants starting from 22 weeks of gestation. It is intuitive to wonder if growth rates are different between male and female ELBW infants, then their nutritional requirements would also be different. There is some preliminary clinical evidence suggesting the same. Poindexter et al., in their “early vs. late amino acid initiation study,” noted that males in the late amino acid administration group had increased odds of having a suboptimal head circumference at 18 months corrected gestational age.

There are sex-specific differences in the outcomes associated with birth asphyxia. Males have poorer neurodevelopmental outcomes for a similar degree of hypoxic-ischemic encephalopathy. Pharmacologic studies in a traumatic brain injury piglet model have shown striking differences between males and females. A subset analysis of the multicenter randomized controlled trial in extremely low-birth-weight infants found that the prophylactic use of indomethacin prophylaxis slightly favored males regarding the development of severe IVH (grades III and IV) and on long-term outcomes.

Yet, many large perinatal studies have not explored if there were any sex-specific differences in the outcomes. Caffeine for Apnea of Prematurity trial showed gross motor functions were not different in those exposed to caffeine versus controls. Though animal studies have shown that neonatal caffeine exposure has sex-specific benefits; However, as the sex-specific analysis is not performed, any specific sex-related benefits of therapy may have been masked.

We, therefore, believe that bringing awareness about sex-specific analysis of the data in all the neonatal studies may help us all understand the therapeutic options better in the future. This session involves basic science and animal research scientists, as well as perinatal clinical scientists, to discuss the Cross-Disciplinary Spotlight on this hot topic.

Presentations:

• 1:00 PM - 1:15 PM US CT

  Sex Differences in the Developmental Origins of Diseases
  

  Presenter: Norma B. Ojeda, MD – University of Mississippi
• 1:15 PM - 1:30 PM US CT

  Sex differences in neonatal vulnerability to and recovery from neurologic insult
  

  Presenter: R. Holly Fitch, PhD – University of Connecticut
• 1:30 PM - 1:50 PM US CT

  Differences in neonatal response and recovery to therapeutic interventions for hypoxic neurologic injury
  

  Presenter: Ted S. Rosenkrantz, MD – University of Connecticut School of Medicine
• 1:50 PM - 2:10 PM US CT

  Sex Differences in Neonatal Nutrition-What Evidence Do We have?
  

  Presenter: Pradeep Alur, MD – University of Mississippi Medical center
• 2:10 PM - 2:30 PM US CT

  Impact of Gender in Provision of Nutrition to Optimize Growth Outcomes
  

  Presenter: Brenda Poindexter, MD, MS, FAAP – Emory University and Children's Healthcare of Atlanta
• 2:30 PM - 3:30 PM US CT

  Break
  

  Presenter: Belinda Thomas
• 3:30 PM - 4:00 PM US CT

  Click for Live Q&A: Individualized Neonatal Care: Sex-Specific Approach Matters!
  

  Presenter: Belinda Thomas