a presentation by Abdulkareeem Toyyib Oladimeji at the department of physiology, faculty of basic medical sciences, univeristy of ilorin teaching hospital, Ilorin, Kwara state, Nigeria.

1. Foetal Programming In Blood Pressure
Regulation
ABDULKAREEM, Toyyib Oladimeji
Presentation by:
Department of Physiology, Faculty of Basic Medical Sciences,
College of Health Sciences, University of Ilorin, Ilorin.

2. Outline
 Introduction
 Blood pressure
 Foetal programming
 Foetal programming in blood pressure regulation
 Summary
 Conclusion
 References
2

3. Definition of terms
 Blood Pressure = BP
 Systolic Blood Pressure = SBP
 Diastolic Blood Pressure = DBP
 Autonomic Nervous System = ANS
 World Health Organization = WHO
 Gestational Diabetes Mellitus = GDM
 Low Birth Weight = LBW
 Intrauterine Growth Restriction = IUGR
 Uteroplacental Insufficiency = UPI
 Peripheral Resistance = PR
 Metabolic Syndrome = MetS
 11-β-Hydroxysteroid Dehydrogenase type 2 = 11-Β-HSD2 3

4. INTRODUCTION
 Foetal programming
 may be defined as the phenomenon whereby a stimulus that occurs during a
critical window of development can bring about lifelong changes in bodily
structure and function (Blondeau et al., 2010).
 Insults during the foetal period predispose the offspring to various diseases and
anomalies.
 BP is the pressure exerted by circulating blood upon the walls of blood vessels
normal = 120/80 mmHg.
FIGURE 1: Dutch Famine of
1944 – Universiteit leiden
FIGURE 2: Biafra famine – Igbo focus
4

5. FOETAL PROGRAMMING
 The Barker Hypothesis, states that conditions during pregnancy will have long term
effects on adult health.
 Conditioning by a “Poor Start to Life”
 Conditioning by over nutrition - both maternal obesity and GDM have been
implicated in leading to a later risk of obesity and cardiometabolic disease risk in the
offspring (Lawlor et al., 2004; Reynolds et al., 2013).
FIGURE 3: Prof David JP Barker, 2012; lifecourse epidemiology.
5

6. PHYSIOLOGIC PATHWAYS
FIGURE 4: Physiological adaptive processes in developmental conditioning - Hanson and Gluckman,
2014; Early developmental conditioning of later health and disease: physiology or pathophysiology 6

7. PATHOPHYSIOLOGICAL PATHWAYS
FIGURE 5: Pathophysiological non-adaptive processes in developmental conditioning - Hanson
and Gluckman, 2014; Early developmental conditioning of later health and disease: physiology or pathophysiology 7

8. BLOOD PRESSURE
 BP is the pressure exerted by circulating blood upon the walls of blood vessels
 Age, sex, resistance, conductance, life style, blood vessels affects BP
 Mean arterial pressure = 1/3 SBP + 2/3 DBP, 93.33mmHg
TABLE 1: Various category of blood pressure
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9. MEASUREMENT OF BLOOD PRESSURE
 NONINVASIVE – palpation (carotid, femoral, radial pulses)
– auscultation (stethoscope and sphygmomanometer)
– oscillometric (oscillations of blood flow)
 INVASIVE - most accurately measured invasively through an arterial line.
FIGURE 6: Pulse palpation, Weinberg 2011,
Vascular medicine
FIGURE 7: Auscultatory technique for measuring blood pressure - Applegate, 2000
9

10. REGULATION OF BLOOD PRESSURE
 BARORECEPTOR REFLEX - A
baroreceptor is a sensory receptor that
responds to pressure.
Baroreceptor medulla ANS
(heart and PR)
 RENAL CONTROL - Rising pressure
causes the kidneys to excrete the excess
volume, thus returning the pressure back
toward normal and vice versa when
pressure falls.
 Hypothalamic pituitary adrenal (HPA)
axis – CRH, ACTH, Aldosterone release
 RENIN-ANGIOTENSIN-ALDOSTERONE
SYSTEM - raises arterial pressure in
several ways.
FIGURE 8: Renin-angiotensin vasoconstrictor
mechanism for arterial pressure control (Guyton and
Hall, Textbook of medical physiology, 2013, Saunders company).
10

11. ABNORMAL BLOOD PRESSURE
 HYPOTENSION - Blood pressure that is
too low is known as hypotension.
FIGURE 10: Effects of hypertension,
Harvard Health Publication
►HYPERTENSION - Hypertension is a
sustained elevation of blood
pressure.
FIGURE 9: Signs or Symptoms of hypotension,
National Heart Lung and Blood Institute, 2008. 11

12. FOETAL PROGRAMMING IN BLOOD PRESSURE REGULATION
 Prenatal influences on these have been explored as potential mechanisms
through which fetal nutritional insufficiency affects long-term blood
pressure.
 Offspring blood pressure is elevated by insults like;
- Fetal growth restriction (Langley-Evans et al., 1999; Vehaskari et al., 2001; Woods et al.,
2001; Battista et al., 2002)
- Administration of corticosteroids during pregnancy (Dodic et al., 2002)
- Manipulation of uterine blood supply (Alexander, 2003)
12
Foetus Insults
Adaptive and non-adaptive
changes in the foetus
Impairment of BP
regulation

13. Low Birth Weight and Blood Pressure Regulation
 LBW, defined as birth weight of <2500g by the WHO, may arise from IUGR, or
prematurity (Zandi-Nejad et al., 2006)
 Several animal models have demonstrated the inverse relationship between
LBW and hypertension (Manning et al., 2001; Poladia et al., 2006)
FIGURE 11: A comparison between normal and IUGR babies - Lausman et al., 2012; Screening, Diagnosis and
Management of IUGR; Journal of Obstetrics & Gynecology. 13

14. Glucocorticoids and programming of blood pressure
 A single course of antenatal corticosteroid is associated with higher
blood pressure in adolescence and decreased insulin sensitivity and
renal function in adulthood (Doyle et al., 2000; Seckl et al., 2007).
 This restricts fetal growth and program permanent changes in the
cardiovascular, endocrine, and metabolic systems (Edwards et al., 2001).
 11-β-HSD2 inactivates glucocorticoids to their inert 11-keto forms
(cortisone).
14

15. 15
FIGURE 12: Feotal programming and blood pressure - Norma et al., 2008; Role of Fetal
Programming in the Development of Hypertension, Future Cardiol.
Glucocorticoids and other insults

16. OTHER METHODS
 Sexual Dimorphism and blood pressure programming -
estrogen play a protective role (Ojeda et al., 2007).
males appear to be much more sensitive to insult in utero (Grigore et
al., 2008).
 Maternal health and blood pressure programming -
epidemiological studies have clearly identified maternal health
as a major factor for the development of MetS in offspring (Fetita et
al., 2006).
 Neonatal oxygen exposure and blood pressure
programming - premature newborns are more susceptible to
oxidative tissue damage (Hardy et al., 2000; Thebaud et al., 2005).
16

17. Summary
 Insults are bad for the unborn child. They cause the child to have
developmental changes including BP regulation.
 Numerous studies have largely supported blood pressure
programming and serve to illustrate complexity of the maternal-
fetal-environmental interaction.
Conclusion
 The goal of pregnancy is to have a healthy baby. People should be
be careful of insults as they can lead to impairment of BP
regulation in the unborn child.
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18. For Listening !!! 18

19. REFERENCES
 Alexander, B.T. (2003). Placental insufficiency leads to development of hypertension in
growth-restricted offspring. Hypertension 41:457–62.
 Bateson, P. and Gluckman, P. (2011). Plasticity, Robustness, Development and Evolution.
Cambridge, UK: Cambridge Univ. Press.
 Blondeau, B., Joly, B., Perret, C., Prince, S., Bruneval, P., Lelièvre-Pégorier,
M., Fassot, C. and Duong Van Huyen, J.P. (2011). Exposure in utero to maternal diabetes
leads to glucose intolerance and high blood pressure with no major effects on lipid
metabolism, Diabetes &amp; Metabolism Volume 37, n° 3 pages 245-251.
 Dodic, M., Moritz, K., Koukoulas, I. and Wintour, E.M. (2002). Programmed
hypertension: kidney, brain or both? Trends Endocrinol. Metab. 13:403–8.
 Edwards, L.J., Coulter, C.L., Symonds, M.E. and McMillen, I.C. (2001). “Prenatal under
nutrition, glucocorticoids and the programming of adult hypertension,” Clinical and
Experimental Pharmacology and Physiology, vol. 28, no. 11, pp. 938–941.
 Harding, J.E. (2001). The nutritional basis of the fetal origins of adult disease. Int. J.
Epidemiol. 30:15–23.
 Lawlor, D.A., Najman, J.M., Sterne, J., Williams, G.M., Ebrahim, S. and Davey, S.G.
(2004). Associations of parental, birth, and early life characteristics with systolic blood
pressure at 5 years of age: findings from the Mater-University study of pregnancy and its
outcomes. Circulation 110: 2417–2423. 19

20. REFERENCES
 Ojeda, N.B., Grigore D., Robertson E.B. and Alexander B.T. (2007). “Estrogen protects
against increased blood pressure in post pubertal female growth restricted offspring,”
Hypertension, vol. 50, no. 4, pp. 679–685.
 Poladia D.P., Kish K., Kutay B., Bauer J., Baum M., and Bates C.M. (2006). “Link between
reduced nephron number and hypertension: studies in a mutant mouse model,” Pediatric
Research, vol. 59, no. 4, pp. 489–493.
 Reynolds R.M., Allan K.M., Raja E.A., Bhattacharya S., McNeill G., Hannaford P.C.,
Sarwar N., Lee A.J., Bhattacharya S., and Norman J.E. (2013). Maternal obesity during
pregnancy and premature mortality from cardiovascular event in adult offspring: follow-up of
1 323 275 person years. BMJ 347: f4539.
 Seckl J.R. and Holmes M.C. (2007). Mechanisms of disease: glucocorticoids, their placental
metabolism and fetal ‘programming’ of adult pathophysiology. Nat Clin Pract Endocrinol
Metab. 3:479–488.
 Thebaud B., Ladha F., Michelakis E.D., Sawicka M., Thurston G., Eaton F., Hashimoto
K., Harry G., Haromy A., Korbutt G. and Archer S.L. (2005). Vascular endothelial growth
factor gene therapy increases survival, promotes lung angiogenesis, and prevents alveolar
damage in hyperoxia-induced lung injury: evidence that angiogenesis participates in
alveolarization. Circulation. 112:2477–2486.
 Vehaskari V.M., Aviles D.H., and Manning J. (2001). Prenatal programming of adult
hypertension in the rat. Kidney Int. 59: 238–45. 20