Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation.
BACKGROUND
Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities.


METHODS
HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling.


RESULTS
HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 g, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells.


CONCLUSIONS
Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases.
Divisions of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Helen N
HN
Jones
Divisions of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Stephanie K
SK
Olbrych
The Division of Maternal Fetal Medicine, Good Samaritan Hospital, Cincinnati, OH, USA.
Kathleen L
KL
Smith
Divisions of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
James F
JF
Cnota
Divisions of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; The Division of Maternal Fetal Medicine, Good Samaritan Hospital, Cincinnati, OH, USA; The Fetal Care Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Mounira
M
Habli
Divisions of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Osniel
O
Ramos-Gonzales
Divisions of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kathryn J
KJ
Owens
The Division of Maternal Fetal Medicine, Good Samaritan Hospital, Cincinnati, OH, USA.
Andrea C
AC
Hinton
The Division of Maternal Fetal Medicine, Good Samaritan Hospital, Cincinnati, OH, USA; The Fetal Care Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
William J
WJ
Polzin
Divisions of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Louis J
LJ
Muglia
Divisions of Cardiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: bingrbh@icloud.com.
Robert B
RB
Hinton
D001724:Birth Weight; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000378:metabolism / Q000473:pathology*; D020738:Leptin / Q000378:metabolism*; D009929:Organ Size; D010920:Placenta / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020738:Leptin; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D054411:Receptors, Leptin; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D005337:Fibrin; D040301:Vascular Endothelial Growth Factor Receptor-2
Angiogenesis; Congenital heart disease; Vascular biology