Collaborative Studies in Fetal DevelopmentRobin Ohls, MD

Department of Pediatrics

Infants born prematurely suffer from numerous problems affecting every organ system

Premature adaptation from the in utero environment to the extra-uterine environment creates significant developmental stressors which are managed differently by each system

Blood (AoP)

GI System (NEC)

Eye (ROP)

Heart (PDA)

Developing GI Tract and NEC: Necrotizing Enterocolitis

Life threatening GI disease in preterm infants

Involves severe inflammatory response to mucosal injury

Cause of NEC is unknown; thought to be due to ischemia, bacterial invasion, and increased gut response to inflammatory cells

mucosal tolerance to bacterial products developmentally regulated, deficient in the preterm intestine

TGF-2 attenuates macrophage inflammatory responses in the developing intestine In collaboration with Akhil Maheshwari, University of Alabama-Birmingham

Vascular Growth in Developing Eye: Retinopathy of Prematurity

Vascular overgrowth/scarring of the retina that occurs during maturation

Associated risk factors for development of ROP:

prematurity

Hyperoxia/hypoxia

Prevention of ROP might include evaluation of vascular growth factors such as Epo or VEGF

Measure of vascular growth factors in developing human eye

1

2

3

Stage 3 ROP

0

5

10

15

20

25

30

12-14 15-17 18-20 21-24

vitreousserum

Weeks gestation

Epo mU/mL

In collaboration with Shrena Patel, University of Utah

Developing Circulation and PDA: Patent Ductus Arteriosus

Ductus arteriosus allows for in utero communication between the pulmonary artery and the aorta; major morbidity for preterm infants if it persists after birth

Link between Epo administration and PDA closure

Epo stimulates Endothelin production

Epo receptors present in fetal sheep DA; receptor number increases with increasing gestation

What role do Epo receptors and other vascular growth factor receptors play in developing human DA?

Right PA

Pulm. trunk

Left PA

Ductus Arteriosus

Aorta

3 mm

In collaboration with Ron Clyman, UCSF

Other Projects

• Vascular growth factors involved in fetal skin development and wound healing (Epo, VEGF, PPAR, PGC-1)

• Impact of early CMV infection on developing brain inflammatory cells and developing cochlear cells

• Identification of Rh positive and negative fetuses through measurement of fetal DNA in maternal circulation

• Endothelial progenitor cells in the developing circulation