FIG 11.4 (A) Kaplan-Meier curve for a cohort of subjects with congenital heart disease who underwent newborn surgery, demonstrating survival probability out to 70 months Note the significantly lower survival outcome for those with impaired maternal-fetal environment (B) Kaplan-Meier curve for a cohort of subjects with hypoplastic left heart syndrome (HLHS) who underwent newborn surgery, demonstrating survival probability out to 70 months Note the impact of an impaired maternal-fetal environment on surgical survival outcome (From Gaynor JW, Parry S, Moldenhauer JS, et al The impact of the maternal-fetal environment on outcomes of surgery for congenital heart disease in neonates Eur J Cardiothorac Surg 2018;54[2]:348–353.) Annotated References Barker DJP, Thornburg KL Placental programming of chronic diseases, cancer and lifespan: a review Placenta 2013;34(10):841– 845 Morphologic variations in normal placental development can predict a wide range of adultonset diseases, thought to be due to programming that later increases risk for diseases ranging from coronary artery disease to colorectal cancer Boyd HA, Basit S, Behrens I, et al Association between fetal congenital heart defects and maternal risk of hypertensive disorders of pregnancy in the same pregnancy and across pregnancies Circulation 2017;135(19) Pregnancies affected by fetal congenital heart disease are associated with early preeclampsia in the same pregnancy as well as in subsequent pregnancies unaffected by fetal CHD, suggesting a maternal etiology for both processes, such as angiogenic imbalance Gaynor JW, Parry S, Moldenhauer JS, et al The impact of the maternal-foetal environment on outcomes of surgery for congenital heart disease in neonates Eur J Cardiothorac Surg 2018;54(2):348–353 Impaired maternal-fetal environment, as indicated by preeclampsia, preterm birth or infants who are small for gestational age, is common in congenital heart disease and associated with decreased postoperative survival at 3 years Matthiesen NB, Henriksen TB, Agergaard P, et al Congenital heart defects and indices of placental and fetal growth in a nationwide study of 924 422 liveborn infants Circulation 2016;134(20):1546–1556 Placental weight is associated with measures of overall growth and cerebral growth in fetuses with CHD Rychik J, Goff D, McKay E, et al Characterization of the placenta in the newborn with congenital heart disease: distinctions based on type of cardiac malformation Pediatr Cardiol 2018 Placentas of neonates with congenital heart disease are disproportionally smaller than normal, with increased incidence of abnormal capillary proliferation, hypomature villi, thrombus and infarction