David, AL, Peebles, D. Gene therapy for the fetus: Is there a future? Best Pract Res Clin Obstet Gynaecol 2008;22(1):203–18.Google Scholar

Mattar, CN, Waddington, SN, Biswas, A, Davidoff, AM, Choolani, M, Chan, JKY, et al. The case for intrauterine gene therapy. Best Pract Res Clin Obstet Gynaecol 2012;26(5):697–709.CrossRefGoogle ScholarPubMed

Gene Therapy Advisory Committee. Report on the potential use of gene therapy in utero. Health Departments of the United Kingdom, November 1998. Hum Gene Ther 1999;10(4):689–92.Google Scholar

U. S. National Institutes of Health. Recombinant DNA Advisory Committee. Prenatal gene transfer: Scientific, medical, and ethical issues: A report of the Recombinant DNA Advisory Committee. Hum Gene Ther 2000;11(8):1211–29.Google Scholar

Lyall, F, Robson, SC, Bulmer, JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: Relationship to clinical outcome. Hypertension 2013;62(6):1046–54.CrossRefGoogle ScholarPubMed

Konje, JC, Howarth, ES, Kaufmann, P, Taylor, DJ. Longitudinal quantification of uterine artery blood volume flow changes during gestation in pregnancies complicated by intrauterine growth restriction. BJOG 2003;110(3):301–5.Google Scholar

Ginn, SL, Alexander, IE, Edelstein, ML, Abedi, MR, Wixon, J. Gene therapy clinical trials worldwide to 2012 – an update. J Gene Med 2013;15(2):65–77.Google Scholar

Coutelle, C, Waddington, SN. Vector systems for prenatal gene therapy: Choosing vectors for different applications. Methods Mol Biol 2012;891:41–53.Google Scholar

Khare, R, Chen, CY, Weaver, EA, Barry, MA. Advances and future challenges in adenoviral vector pharmacology and targeting. Curr Gene Ther 2011;11(4):241–58.CrossRefGoogle ScholarPubMed

Katayama, K, Furuki, R, Yokoyama, H, Kaneko, M, Tachibana, M, Yoshida, I, et al. Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector Biomaterials 2011;32(17):4185–93.CrossRefGoogle ScholarPubMed

Al-Hendy, A, Salama, S. Gene therapy and uterine leiomyoma: A review. Hum Reprod Update 2006;12(4):385–400.CrossRefGoogle ScholarPubMed

Stribley, JM, Rehman, KS, Niu, H, Christman, GM. Gene therapy and reproductive medicine. Fertil Steril 2002;77(4):645–57.CrossRefGoogle ScholarPubMed

Ahmed, A, Dunk, C, Ahmad, S, Khaliq, A. Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) and soluble Flt-1 by oxygen – a review. Placenta 2000;21 Suppl A:S16–24.CrossRefGoogle ScholarPubMed

Olsson, AK, Dimberg, A, Kreuger, J, Claesson-Welsh, L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol 2006;7(5):359–71.Google Scholar

Savvidou, MD, Yu, CK, Harland, LC, Hingorani, AD, Nicolaides, KH. Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular endothelial growth factor in women with abnormal uterine artery Doppler and in those with fetal growth restriction. Am J Obstet Gynecol 2006;195(6):1668–73.Google Scholar

Herraiz, I, Droge, LA, Gomez-Montes, E, Henrich, W, Galindo, A, Verlohren, S. Characterization of the soluble fms-like tyrosine kinase-1 to placental growth factor ratio in pregnancies complicated by fetal growth restriction. Obstet Gynecol 2014;124(2 Pt 1):265–73.CrossRefGoogle ScholarPubMed

Roberts, CT, Owens, JA, Sferruzzi-Perri, AN. Distinct actions of insulin-like growth factors (IGFs) on placental development and fetal growth: Lessons from mice and guinea pigs. Placenta 2008;29 Suppl A:S42–7.CrossRefGoogle ScholarPubMed

Forbes, K, Westwood, M. The IGF axis and placental function. A mini review. Horm Res 2008; 69(3):129–37.Google Scholar

David, AL, Torondel, B, Zachary, I, Wigley, V, Abi-Nader, K, Mehta, V, et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Ther 2008;15(19):1344–50.Google Scholar

Mehta, V, Abi-Nader, KN, Peebles, DM, Benjamin, E, Wigley, V, Torondel, B, et al. Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A(165) in the uterine arteries of pregnant sheep. Gene Ther 2012;19(9):925–35.CrossRefGoogle ScholarPubMed

Mehta, V, Abi-Nader, KN, Shangaris, P, Shaw, SW, Filippi, E, Benjamin, E, et al. Local over-expression of VEGF-DDeltaNDeltaC in the uterine arteries of pregnant sheep results in long-term changes in uterine artery contractility and angiogenesis. PloS One 2014; 9(6):e100021.Google Scholar

Wallace, JM, Luther, JS, Milne, JS, Aitken, RP, Redmer, DA, Reynolds, LP, et al. Nutritional modulation of adolescent pregnancy outcome – a review. Placenta 2006;27 Suppl A:S61–8.Google Scholar

Robinson, JS, Kingston, EJ, Jones, CT, Thorburn, GD. Studies on experimental growth retardation in sheep. The effect of removal of a endometrial caruncles on fetal size and metabolism. J Dev Physiol 1979; 1(5):379–98.Google Scholar

Wallace, JM, Aitken, RP, Milne, JS, Hay, WW, Jr. Nutritionally mediated placental growth restriction in the growing adolescent: Consequences for the fetus. Biol Reprod 2004;71(4):1055–62.Google Scholar

Wallace, JM, Milne, JS, Matsuzaki, M, Aitken, RP. Serial measurement of uterine blood flow from mid to late gestation in growth restricted pregnancies induced by overnourishing adolescent sheep dams. Placenta 2008;29(8):718–24.Google Scholar

Wallace, JM, Bourke, DA, Aitken, RP, Palmer, RM, Da, Silva, P, Cruickshank, MA. Relationship between nutritionally-mediated placental growth restriction and fetal growth, body composition and endocrine status during late gestation in adolescent sheep. Placenta 2000;21(1):100–8.Google Scholar

Carr, DJ, Aitken, RP, Milne, JS, David, AL, Wallace, JM. Fetoplacental biometry and umbilical artery Doppler velocimetry in the overnourished adolescent model of fetal growth restriction. Am J Obstet Gynecol 2012; 207(2):141.Google Scholar

Redmer, DA, Aitken, RP, Milne, JS, Reynolds, LP, Wallace, JM. Influence of maternal nutrition on messenger RNA expression of placental angiogenic factors and their receptors at midgestation in adolescent sheep. Biol Reprod 2005;72(4):1004–9.CrossRefGoogle ScholarPubMed

Redmer, DA, Luther, JS, Milne, JS, Aitken, RP, Johnson, ML, Borowicz, PP, et al. Fetoplacental growth and vascular development in overnourished adolescent sheep at day 50, 90 and 130 of gestation. Reproduction 2009;137(4):749–57.CrossRefGoogle ScholarPubMed

Lea, RG, Wooding, P, Stewart, I, Hannah, LT, Morton, S, Wallace, K, et al. The expression of ovine placental lactogen, StAR and progesterone-associated steroidogenic enzymes in placentae of overnourished growing adolescent ewes. Reproduction 2007; 133(4):785–96.Google Scholar

Carr, DJ, Aitken, RP, Milne, JS, David, AL, Wallace, JM. Ultrasonographic assessment of growth and estimation of birthweight in late gestation fetal sheep. Ultrasound Med Biol 2011;37(10):1588–95.Google Scholar

Smith, GC, Smith, MF, McNay, MB, Fleming, JE. The relation between fetal abdominal circumference and birthweight: Findings in 3512 pregnancies. BJOG 1997;104(2):186–90.CrossRefGoogle ScholarPubMed

Carr, DJ, Aitken, RP, Milne, JS, Peebles, DM, Martin, JM, Zachary, IC, et al. Prenatal Ad.VEGF gene therapy – a promising new treatment for fetal growth restriction. Hum Gene Ther 2011;22(10):A128.Google Scholar

Carr, DJ, Aitken, RP, Milne, JS, Peebles, DM, Martin, JM, Zachary, IC, et al. Maternal delivery of Ad.VEGF gene therapy increases fetal growth velocity in an ovine paradigm of fetal growth restriction. Reprod Sci 2011; 18(3 suppl):269A.Google Scholar

Carr, DJ, Aitken, RP, Milne, JS, Peebles, DM, Martin, JM, Zachary, IC, et al. Alterations in postnatal growth and metabolism following prenatal treatment of intrauterine growth restriction with Ad.VEGF gene therapy in the sheep. Arch Dis Child Fetal Neonatal Ed 2011;96:Fa7.CrossRefGoogle Scholar

Carr, DJ, Aitken, RP, Milne, JS, Peebles, DM, Martin, JF, Zachary, IC, et al. Prenatal gene therapy increases fetal growth velocity and expression of VEGF receptors in an ovine paradigm of fetal growth restriction. Reprod Sci 2012;19(3):78A.Google Scholar

Carter, AM. Animal models of human placentation – a review. Placenta 2007;28 Suppl A:S41–7.CrossRefGoogle ScholarPubMed

Mess, A. The Guinea pig placenta: Model of placental growth dynamics. Placenta 2007;28(8–9):812–15.CrossRefGoogle ScholarPubMed

Roberts, CT, Sohlstrom, A, Kind, KL, Earl, RA, Khong, TY, Robinson, JS, et al. Maternal food restriction reduces the exchange surface area and increases the barrier thickness of the placenta in the guinea-pig. Placenta 2001;22(2–3):177–85.Google Scholar

Mehta, V, Boyd, M, Martin, J, Zachary, I, Peebles, DM, David, AL. Local administration of Ad.VEGF-A165 to the uteroplacental circulation enhances fetal growth and reduces brain sparing in an FGR model of guinea pig pregnancy. Reprod Sci 2012;19(3):78A.Google Scholar

Sferruzzi-Perri, AN, Owens, JA, Pringle, KG, Robinson, JS, Roberts, CT. Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth. Endocrinology 2006;147(7):3344–55.CrossRefGoogle ScholarPubMed

Sferruzzi-Perri, AN, Owens, JA, Standen, P, Taylor, RL, Heinemann, GK, Robinson, JS, et al. Early treatment of the pregnant guinea pig with IGFs promotes placental transport and nutrient partitioning near term. Am J Physiol Endocrinol Metab 2007;292(3):E668–76.Google Scholar

Sohlstrom, A, Fernberg, P, Owens, JA, Owens, PC. Maternal nutrition affects the ability of treatment with IGF-I and IGF-II to increase growth of the placenta and fetus, in guinea pigs. Growth Horm IGF Res 2001; 11(6):392–8.Google Scholar

Eremia, SC, de Boo, HA, Bloomfield, FH, Oliver, MH, Harding, JE. Fetal and amniotic insulin-like growth factor-I supplements improve growth rate in intrauterine growth restriction fetal sheep. Endocrinology 2007;148(6):2963–72.Google Scholar

Wali, JA, de Boo, HA, Derraik, JG, Phua, HH, Oliver, MH, Bloomfield, FH, et al. Weekly intra-amniotic IGF-1 treatment increases growth of growth-restricted ovine fetuses and up-regulates placental amino acid transporters. PloS One 2012;7(5):e37899.CrossRefGoogle ScholarPubMed

Miller, AG, Aplin, JD, Westwood, M. Adenovirally mediated expression of insulin-like growth factors enhances the function of first trimester placental fibroblasts. J Clin Endocrinol Metab 2005; 90(1):379–85.Google Scholar

Jones, H, Crombleholme, T, Habli, M. Regulation of amino acid transporters by adenoviral-mediated human insulin-like growth factor-1 in a mouse model of placental insufficiency in vivo and the human trophoblast line BeWo in vitro. Placenta 2014; 35(2):132–8.Google Scholar

Jones, HN, Crombleholme, T, Habli, M. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms. PloS One 2013;8(9):e74632.Google Scholar

Habli, M, Jones, H, Aronow, B, Omar, K, Crombleholme, TM. Recapitulation of characteristics of human placental vascular insufficiency in a novel mouse model. Placenta 2013;34(12):1150–8.Google Scholar

David, AL, Ashcroft, R. Placental gene therapy. Obstet Gynaecol Reprod Med 2009;19(10):296–8.Google Scholar

Sheppard, MK, Spencer, RN, David, AL, Ashcroft, R. Evaluation of the ethics and social acceptability of a proposed clinical trial using maternal gene therapy to treat severe early-onset fetal growth restriction in pregnant women. Hum Gene Ther 2014:A98.Google Scholar

Hedman, M, Muona, K, Hedman, A, Kivela, A, Syvanne, M, Eranen, J, et al. Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer. Gene Ther 2009; 16(5):629–34.Google Scholar

Rosengart, TK, Bishawi, MM, Halbreiner, MS, Fakhoury, M, Finnin, E, Hollmann, C, et al. Long-term follow-up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease. Hum Gene Ther 2013;24(2):203–8.CrossRefGoogle ScholarPubMed

Heikkila, A, Hiltunen, MO, Turunen, MP, Keski-Nisula, L, Turunen, AM, Rasanen, H, et al. Angiographically guided utero-placental gene transfer in rabbits with adenoviruses, plasmid/liposomes and plasmid/polyethyleneimine complexes. Gene Ther 2001; 8(10):784–8.Google Scholar

Brownbill, P, Desforges, M, Sebire, N, Greenwood, S, Sibley, CP, David, A. Human placental ex vivo studies to support an adenovirus-mediated vascular endothelial growth factor (VEGF) gene medicine for the treatment of severe early onset fetal growth restriction (FGR). Hum Gene Ther 2014;25(11):A60.Google Scholar

Woo, YJ, Raju, GP, Swain, JL, Richmond, ME, Gardner, TJ, Balice-Gordon, RJ. In utero cardiac gene transfer via intraplacental delivery of recombinant adenovirus. Circulation 1997;96(10):3561–9.Google Scholar

Turkay, A, Saunders, T, Kurachi, K. Intrauterine gene transfer: Gestational stage-specific gene delivery in mice. Gene Ther 1999;6(10):1685–94.CrossRefGoogle ScholarPubMed

Xing, A, Boileau, P, Cauzac, M, Challier, JC, Girard, J, Hauguel-de Mouzon, S. Comparative in vivo approaches for selective adenovirus-mediated gene delivery to the placenta. Hum Gene Ther 2000; 11(1):167–77.CrossRefGoogle ScholarPubMed

Senoo, M, Matsubara, Y, Fujii, K, Nagasaki, Y, Hiratsuka, M, Kure, S, et al. Adenovirus-mediated in utero gene transfer in mice and guinea pigs: tissue distribution of recombinant adenovirus determined by quantitative TaqMan-polymerase chain reaction assay. Mol Genet Metab 2000;69(4):269–76.CrossRefGoogle ScholarPubMed

Katz, AB, Keswani, SG, Habli, M, Lim, FY, Zoltick, PW, Midrio, P, et al. Placental gene transfer: Transgene screening in mice for trophic effects on the placenta. Am J Obstet Gynecol 2009;201(5):499.e1–8.Google Scholar

Mehta, V, Peebles, DM, Boyd, M, Zachary, I, Martin, J, David, AL. Gene targeting to the utero-placental circulation of pregnant guinea pigs. Society for Gynaecologic Investigation 58th Annual Meeting: Reproductive Sciences; 2011. p. 332A.Google Scholar

Mok, M, Heidemann, B, Dundas, K, Gillespie, I, Clark, V. Interventional radiology in women with suspected placenta accreta undergoing caesarean section. Int J Obstet Anesth 2008;17(3):255–61.Google Scholar

Carnevale, FC, Kondo, MM, de Oliveira Sousa, W, Jr., Santos, AB, da Motta Leal Filho, JM, Moreira, AM, et al. Perioperative temporary occlusion of the internal iliac arteries as prophylaxis in cesarean section at risk of hemorrhage in placenta accreta. Cardiovasc Intervent Radiol 2011;34(4):758–64.Google Scholar

Alfirevic, Z, Sundberg, K, Brigham, S. Amniocentesis and chorionic villus sampling for prenatal diagnosis. Cochrane Database Syst Rev 2003(3):CD003252.Google Scholar

Wing, DA, Powers, B, Hickok, D. U.S. Food and Drug Administration drug approval: Slow advances in obstetric care in the United States. Obstet Gynecol 2010;115(4):825–33.Google Scholar

European Medicines Agency. Guideline on the Non-clinical Studies Required before First Clinical Use of Gene Therapy Medicinal Products (EMEA/CHMP/GTWP/125459/2006). London: European Medicines Agency; 2008.Google Scholar

European Medicines Agency. ICH Harmonised Tripartite Guideline E6: Note for Guidance on Good Clinical Practice (PMP/ICH/135/95). London: European Medicines Agency; 2002.Google Scholar

European Medicines Agency. Detection of Toxicity to Reproduction for Medicinal Products and Toxicity to Male Fertility (CPMP/ICH/386/95). London: European Medicines Agency; 1994.Google Scholar