title: Influence of maternal angiogenic factors during pregnancy on microvascular structure in school-age children.
abstract: Reduced placental growth factor (PlGF) levels and higher soluble fms-like tyrosine kinase (sFlt-1) levels in mothers during pregnancy may have persistent effects on vascular structures in their offspring. We examined whether angiogenic factors during pregnancy also affect childhood retinal microvasculature in a population-based prospective cohort study among 3505 mothers and their children. We measured maternal PlGF and sFlt-1 in the first and second trimester of pregnancy. At the age of 6, we measured childhood retinal arteriolar and venular calibers from digitized retinal photographs. We performed multiple linear regression models, taking maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, and childhood current body mass index and blood pressure into account. We observed that first trimester maternal PlGF and sFlt-1 levels were not associated with childhood retinal arteriolar caliber. Lower second trimester maternal PlGF levels, but not sFlt-1 levels, were associated with narrower childhood retinal arteriolar caliber (difference: -0.09 SD score [95% confidence interval, -0.16 to 0.01], per SD score decrease in PlGF). This association was not explained by maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, or childhood current body mass index and blood pressure. Maternal PlGF and sFlt-1 levels in the first or second trimester were not associated with childhood retinal venular caliber. Our results suggest that lower maternal second trimester PlGF levels affect the microvascular development in the offspring, leading to narrower retinal arteriolar caliber in childhood. Further studies are needed to confirm these findings and to explore the underlying mechanisms and long-term cardiovascular consequences.
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Olta
authors.initials: O
authors.lastname: Gishti
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.). v.jaddoe@erasmusmc.nl.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Janine F
authors.initials: JF
authors.lastname: Felix
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Irwin
authors.initials: I
authors.lastname: Reiss
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: From the Generation R Study Group (O.G., V.W.V.J., J.F.F., R.G.), and Departments of Pediatrics (O.G., V.W.V.J., I.R., R.G.), Epidemiology (O.G., V.W.V.J., J.F.F., A.H., R.G.), Ophthalmology (M.K.I.), Obstetrics and Gynecology (E.A.P.S.), and Neonatology (I.R.), Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Singapore Eye Research Institute and Duke-NUS Graduate Medical School, National University of Singapore, Singapore, Singapore (M.K.I.); and Memory Aging & Cognition Centre (MACC), National University of Health System, Singapore, Singapore (M.K.I.).
authors.forename: Romy
authors.initials: R
authors.lastname: Gaillard
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D002196:Capillaries / Q000166:cytology*; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011379:Prognosis; D011446:Prospective Studies; D012171:Retinal Vessels / Q000166:cytology*; D012307:Risk Factors; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor
keywords: epidemiology; microcirculation; pediatrics