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Hypertensive disorders during pregnancy and health outcomes in the offspring: a systematic review

  • T. V. Pinheiro (a1), S. Brunetto (a1), J. G. L. Ramos (a2), J. R. Bernardi (a1) and M. Z. Goldani (a1) (a3)...

Abstract

The hypertensive disorders of pregnancy complicate up to 10% of pregnancies worldwide and are a leading cause of maternal, foetal, and neonatal morbidity and mortality. The aim of this study was to present an overview of recent studies addressing offspring’s medium and long-term health outcomes after intrauterine exposure to maternal hypertension. A search on PubMed/MEDLINE and Bireme databases was conducted to identify observational studies that reported any offspring outcome measured after the 6th month of life. The search was limited to studies published after May 2008. Forty-five articles were included and categorized into four groups of outcomes: cardiovascular, immune, metabolic and behavioural/neurological effects. According to our findings, hypertensive disorders of pregnancy had an overall negative impact on offspring’s cardiovascular, immune and neurological health, although not all parameters analysed in each group had consistent results among studies. The most prominent and reliable associations were verified between gestational hypertension and higher offspring’s blood pressure and between preeclampsia and offspring’s lower cognitive functioning. In the metabolic outcomes, body composition had conflicting results among papers, while all studies that examined blood biomarkers showed no evidence that preeclampsia or gestational hypertension could be associated with an alteration of this metabolic outcomes. Most included studies were highly heterogeneous regarding the measure of outcomes and covariables used for adjustments. Future studies should consider using the same protocols and cut-off points already published so that results can be better compared and summarized.

This review was registered in PROSPERO. Registration number: CRD42015020838

Copyright

Corresponding author

*Address for correspondence: T. V. Pinheiro, Department of Paediatrics, Universidade Federal do Rio Grande do Sul, R. Ramiro Barcelos, 2350 – Santa Cecilia, Porto Alegre, Rio Grande do Sul 90035-903, Brazil. (Email tanaravogel@gmail.com)

References

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1. Barker, DJ, Winter, PD, Osmond, C, Margetts, B, Simmonds, SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2, 577580.
2. Barker, DJ, Osmond, C, Forsen, TJ, Kajantie, E, Eriksson, JG. Trajectories of growth among children who have coronary events as adults. N Engl J Med. 2005; 353, 18021809.
3. Roberts, JM, August, PA, Bakris, G, et al. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ task force on hypertension in pregnancy. Obstet Gynecol. 2013; 122, 11221131.
4. Rugolo, LMSdS, Bentlin, MR, Trindade, CEP, et al. Effect on the fetus and newborn. NeoReviews. 2011; 12, 198206.
5. Brown, MA, Lindheimer, MD, de Swiet, M, Van Assche, A, Moutquin, JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2001; 20, 914.
6. Ip, S, Chung, M, Raman, G, et al. Breastfeeding and maternal and infant health outcomes in developed countries. Evid Rep Technol Assess (Full Rep). 2007; 153, 1186.
7. Ehrenstein, V, Rothman, KJ, Pedersen, L, Hatch, EE, Sorensen, HT. Pregnancy-associated hypertensive disorders and adult cognitive function among Danish conscripts. Am J Epidemiol. 2009; 170, 10251031.
8. Kajantie, E, Eriksson, JG, Osmond, C, Thornburg, K, Barker, DJ. Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study. Stroke. 2009; 40, 11761180.
9. Geelhoed, JJ, Fraser, A, Tilling, K, et al. Preeclampsia and gestational hypertension are associated with childhood blood pressure independently of family adiposity measures: the Avon Longitudinal Study of Parents and Children. Circulation. 2010; 122, 11921199.
10. Lawlor, DA, Macdonald-Wallis, C, Fraser, A, et al. Cardiovascular biomarkers and vascular function during childhood in the offspring of mothers with hypertensive disorders of pregnancy: findings from the Avon Longitudinal Study of Parents and Children. Eur Heart J. 2012; 33, 335345.
11. Fraser, A, Nelson, SM, Macdonald-Wallis, C, Sattar, N, Lawlor, DA. Hypertensive disorders of pregnancy and cardiometabolic health in adolescent offspring. Hypertension. 2013; 62, 614620.
12. Miettola, S, Hartikainen, AL, Vaarasmaki, M, et al. Offspring’s blood pressure and metabolic phenotype after exposure to gestational hypertension in utero. Eur J Epidemiol. 2013; 28, 8798.
13. Lazdam, M, de la Horra, A, Pitcher, A, et al. Elevated blood pressure in offspring born premature to hypertensive pregnancy: is endothelial dysfunction the underlying vascular mechanism? Hypertension. 2010; 56, 159165.
14. Palmsten, K, Buka, SL, Michels, KB. Maternal pregnancy-related hypertension and risk for hypertension in offspring later in life. Obstet Gynecol. 2010; 116, 858864.
15. Mamun, AA, Kinarivala, MK, O’Callaghan, M, et al. Does hypertensive disorder of pregnancy predict offspring blood pressure at 21 years? Evidence from a birth cohort study. J Hum Hypertens. 2012; 26, 288294.
16. Oglaend, B, Forman, MR, Romundstad, PR, Nilsen, ST, Vatten, LJ. Blood pressure in early adolescence in the offspring of preeclamptic and normotensive pregnancies. J Hypertens. 2009; 27, 20512054.
17. Lazdam, M, de la Horra, A, Diesch, J, et al. Unique blood pressure characteristics in mother and offspring after early onset preeclampsia. Hypertension. 2012; 60, 13381345.
18. Fugelseth, D, Ramstad, HB, Kvehaugen, AS, et al. Myocardial function in offspring 5-8 years after pregnancy complicated by preeclampsia. Early Hum Dev. 2011; 87, 531535.
19. Jayet, PY, Rimoldi, SF, Stuber, T, et al. Pulmonary and systemic vascular dysfunction in young offspring of mothers with preeclampsia. Circulation. 2010; 122, 488494.
20. Keski-Nisula, L, Heinonen, S, Remes, S, Pekkanen, J. Pre-eclampsia, placental abruption and increased risk of atopic sensitization in male adolescent offspring. Am J Reprod Immunol. 2009; 62, 293300.
21. Byberg, KK, Ogland, B, Eide, GE, Oymar, K. Birth after preeclamptic pregnancies: association with allergic sensitization and allergic rhinoconjunctivitis in late childhood; a historically matched cohort study. BMC Pediatr. 2014; 14, 101.
22. Wu, CS, Nohr, EA, Bech, BH, et al. Health of children born to mothers who had preeclampsia: a population-based cohort study. Am J Obstet Gynecol. 2009; 201, 269 e1269 e10.
23. Liu, X, Olsen, J, Agerbo, E, et al. Maternal preeclampsia and childhood asthma in the offspring. Pediatr Allergy Immunol. 2015; 26, 181185.
24. Kulak, W, Sobaniec, W, Okurowska-Zawada, B, Sienkiewicz, D, Paszko-Patej, G. Antenatal, intrapartum and neonatal risk factors for cerebral palsy in children in Podlaskie Province. Neurologia Dziecięca. 2009; 18, 1924.
25. Kulak, W, Okurowska-Zawada, B, Sienkiewicz, D, Paszko-Patej, G, Krajewska-Kulak, E. Risk factors for cerebral palsy in term birth infants. Adv Med Sci. 2010; 55, 216221.
26. Strand, KM, Heimstad, R, Iversen, AC, et al. Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study. BMJ. 2013; 347, f4089.
27. Mann, JR, McDermott, S, Griffith, MI, Hardin, J, Gregg, A. Uncovering the complex relationship between pre-eclampsia, preterm birth and cerebral palsy. Paediatr Perinat Epidemiol. 2011; 25, 100110.
28. Tronnes, H, Wilcox, AJ, Lie, RT, Markestad, T, Moster, D. Risk of cerebral palsy in relation to pregnancy disorders and preterm birth: a national cohort study. Dev Med Child Neurol. 2014; 56, 779785.
29. Beaino, G, Khoshnood, B, Kaminski, M, et al. Predictors of cerebral palsy in very preterm infants: the EPIPAGE prospective population-based cohort study. Dev Med Child Neurol. 2010; 52, e119e125.
30. Tuovinen, S, Raikkonen, K, Kajantie, E, et al. Hypertensive disorders in pregnancy and intellectual abilities in the offspring in young adulthood: the Helsinki Birth Cohort Study. Ann Med. 2012; 44, 394403.
31. Tuovinen, S, Raikkonen, K, Kajantie, E, et al. Hypertensive disorders in pregnancy and cognitive decline in the offspring up to old age. Neurology. 2012; 79, 15781582.
32. Tuovinen, S, Eriksson, JG, Kajantie, E, et al. Maternal hypertensive disorders in pregnancy and self-reported cognitive impairment of the offspring 70 years later: the Helsinki Birth Cohort Study. Am J Obstet Gynecol. 2013; 208, 200.e1200.e9.
33. Morsing, E, Marsal, K. Pre-eclampsia- an additional risk factor for cognitive impairment at school age after intrauterine growth restriction and very preterm birth. Early Hum Dev. 2014; 90, 99101.
34. van Wassenaer, AG, Westera, J, van Schie, PE, et al. Outcome at 4.5 years of children born after expectant management of early-onset hypertensive disorders of pregnancy. Am J Obstet Gynecol. 2011; 204, 510.e1510.e9.
35. Whitehouse, AJ, Robinson, M, Newnham, JP, Pennell, CE. Do hypertensive diseases of pregnancy disrupt neurocognitive development in offspring? Paediatr Perinat Epidemiol. 2012; 26, 101108.
36. Heikura, U, Hartikainen, AL, Nordstrom, T, et al. Maternal hypertensive disorders during pregnancy and mild cognitive limitations in the offspring. Paediatr Perinat Epidemiol. 2013; 27, 188198.
37. Tuovinen, S, Raikkonen, K, Kajantie, E, et al. Depressive symptoms in adulthood and intrauterine exposure to pre-eclampsia: the Helsinki Birth Cohort Study. BJOG. 2010; 117, 12361242.
38. Tuovinen, S, Raikkonen, K, Pesonen, AK, et al. Hypertensive disorders in pregnancy and risk of severe mental disorders in the offspring in adulthood: the Helsinki Birth Cohort Study. J Psychiatr Res. 2012; 46, 303310.
39. Tuovinen, S, Aalto-Viljakainen, T, Eriksson, JG, et al. Maternal hypertensive disorders during pregnancy: adaptive functioning and psychiatric and psychological problems of the older offspring. BJOG. 2014; 121, 14821491.
40. Wade, M, Jenkins, JM. Pregnancy hypertension and the risk for neuropsychological difficulties across early development: a brief report. Child Neuropsychol. 2014; 22, 18.
41. Robinson, M, Mattes, E, Oddy, WH, et al. Hypertensive diseases of pregnancy and the development of behavioral problems in childhood and adolescence: the Western Australian Pregnancy Cohort Study. J Pediatr. 2009; 154, 218224.
42. Robinson, M, Oddy, WH, Whitehouse, AJ, et al. Hypertensive diseases of pregnancy predict parent-reported difficult temperament in infancy. J Dev Behav Pediatr. 2013; 34, 174180.
43. Mann, JR, McDermott, S. Maternal pre-eclampsia is associated with childhood epilepsy in South Carolina children insured by Medicaid. Epilepsy Behav. 2011; 20, 506511.
44. Grace, T, Bulsara, M, Pennell, C, Hands, B. Maternal hypertensive diseases negatively affect offspring motor development. Pregnancy Hypertens. 2014; 4, 209214.
45. Miettola, S, Hovi, P, Andersson, S, et al. Maternal preeclampsia and bone mineral density of the adult offspring. Am J Obstet Gynecol. 2013; 209, 443 e1443 e10.
46. Kvehaugen, AS, Andersen, LF, Staff, AC. Anthropometry and cardiovascular risk factors in women and offspring after pregnancies complicated by preeclampsia or diabetes mellitus. Acta Obstet Gynecol Scand. 2010; 89, 14781485.
47. Washburn, L, Nixon, P, Russell, G, Snively, BM, O’Shea, TM. Adiposity in adolescent offspring born prematurely to mothers with preeclampsia. J Pediatr. 2013; 162, 912.e1917.e1.
48. Hannam, K, Lawlor, DA, Tobias, JH. Maternal preeclampsia is associated with reduced adolescent off-spring hip bone mineral density in a UK population based birth cohort. J Bone Miner Res. 2015; 30, 16841691.
49. Tuovinen, S, Eriksson, JG, Kajantie, E, Raikkonen, K. Maternal hypertensive pregnancy disorders and cognitive functioning of the offspring: a systematic review. J Am Soc Hypertens. 2014; 8, 832.e1847.e1.
50. Davis, E, Lazdam, M, Lewandowski, A, et al. Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review. Pediatrics. 2012; 129, 15521561.
51. Roberts, JM, Redman, CW. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet. 1993; 341, 14471451.
52. Burton, GJ, Jauniaux, E. Placental oxidative stress: from miscarriage to preeclampsia. J Soc Gynecol Investig. 2004; 11, 342352.
53. Rees, S, Harding, R. Brain development during fetal life: influences of the intra-uterine environment. Neurosci Lett. 2004; 361, 111114.
54. Zucchi, FC, Yao, Y, Ward, ID, et al. Maternal stress induces epigenetic signatures of psychiatric and neurological diseases in the offspring. PLoS One. 2013; 8, e56967.
55. Jaenisch, R, Bird, A. Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nature Genetics. 2003; 33, 245254.
56. Challis, JR, Sloboda, D, Matthews, SG, et al. The fetal placental hypothalamic-pituitary-adrenal (HPA) axis, parturition and post natal health. Mol Cell Endocrinol. 2001; 185, 135144.
57. McCalla, CO, Nacharaju, VL, Muneyyirci-Delale, O, Glasgow, S, Feldman, JG. Placental 11 beta-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies. Steroids. 1998; 63, 511515.
58. Seckl, JR, Meaney, MJ. Glucocorticoid programming. Ann N Y Acad Sci. 2004; 1032, 6384.
59. Cottrell, EC, Holmes, MC, Livingstone, DE, Kenyon, CJ, Seckl, JR. Reconciling the nutritional and glucocorticoid hypotheses of fetal programming. FASEB J. 2012; 26, 18661874.
60. Doridot, L, Houry, D, Gaillard, H, et al. miR-34a expression, epigenetic regulation, and function in human placental diseases. Epigenetics. 2014; 9, 142151.
61. Huang, Q, Chen, H, Li, J, et al. Epigenetic and non-epigenetic regulation of syncytin-1 expression in human placenta and cancer tissues. Cell Signal. 2014; 26, 648656.
62. Tsankova, N, Renthal, W, Kumar, A, Nestler, EJ. Epigenetic regulation in psychiatric disorders. Nat Rev Neurosci. 2007; 8, 355367.
63. Vatten, L, Skjaerven, R. Is pre-eclampsia more than one disease? BJOG. 2016; 111, 298302.
64. Lewandowski, A, Leeson, P. Preeclampsia, prematurity and cardiovascular health in adult life. Early Hum Dev. 2014; 90, 725729.
65. Seckl, JR. Glucocorticoid programming of the fetus; adult phenotypes and molecular mechanisms. Mol Cell Endocrinol. 2001; 185, 6171.
66. Bell, MJ. A historical overview of preeclampsia-eclampsia. J Obstet Gynecol Neonatal Nurs. 2010; 39, 510518.

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Hypertensive disorders during pregnancy and health outcomes in the offspring: a systematic review

  • T. V. Pinheiro (a1), S. Brunetto (a1), J. G. L. Ramos (a2), J. R. Bernardi (a1) and M. Z. Goldani (a1) (a3)...

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