Are birthweight and postnatal weight gain in childhood associated with blood pressure in early adolescence? Results from a Ugandan birth cohort

Fetal growth restriction (FGR), where a fetus fails to reach its genetic growth potential, affects up to 8% of pregnancies and is a major risk factor for stillbirth and adulthood morbidity. There are currently no treatments for FGR, but candidate therapies include the phosphodiesterase-5 inhibitor sildenafil citrate (SC). Randomized clinical trials in women demonstrated no effect of SC on fetal growth in cases of severe early onset FGR; however, long-term health outcomes on the offspring are unknown. This study aimed to assess the effect of antenatal SC treatment on metabolic and cardiovascular health in offspring by assessing postnatal weight gain, glucose tolerance, systolic blood pressure, and resistance artery function in a mouse model of FGR, the placental-specific insulin-like growth factor 2 (PO) knockout mouse. SC was administered subcutaneously (10 mg/kg) daily from embryonic day (E)12.5. Antenatal SC treatment did not alter fetal weight or viability but increased postnatal weight gain in wild-type (WT) female offspring ( P < 0.05) and reduced glucose sensitivity in both WT ( P < 0.01) and P0 ( P < 0.05) female offspring compared with controls. Antenatal SC treatment increased systolic blood pressure in both male (WT vs. WT-SC: 117 ± 2 vs. 140 ± 3 mmHg, P < 0.0001; P0 vs. P0-SC: 113 ± 3 vs. 140 ± 4 mmHg, P < 0.0001; means ± SE) and female (WT vs. WT-SC: 121 ± 2 vs. 140 ± 2 mmHg, P < 0.0001; P0 vs. P0-SC: 117 ± 2 vs. 144 ± 4 mmHg, P < 0.0001) offspring at 8 and 13 wk of age. Increased systolic blood pressure was not attributed to altered mesenteric artery function. In utero exposure to SC may result in metabolic dysfunction and elevated blood pressure in later life. NEW & NOTEWORTHY Sildenafil citrate (SC) is currently used to treat fetal growth restriction (FGR). We demonstrate that SC is ineffective at treating FGR, and leads to a substantial increase systolic blood pressure and alterations in glucose homeostasis in offspring. We therefore urge caution and suggest that further studies are required to assess the safety and efficacy of SC in utero, in addition to the implications on long-term health.

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Size at Birth and Blood Pressure in Early Adolescence: A Prospective Birth Cohort Study

American Journal of Epidemiology ◽

10.1093/aje/kwk031 ◽

2007 ◽

Vol 165 (6) ◽

pp. 611-616 ◽

Cited By ~ 26

Author(s):

A. M. B. Menezes ◽

P. C. Hallal ◽

B. L. Horta ◽

C. L. P. Araujo ◽

M. de Fatima Vieira ◽

...

Keyword(s):

Blood Pressure ◽

Cohort Study ◽

Birth Cohort ◽

Early Adolescence ◽

Birth Cohort Study ◽

Size At Birth ◽

Prospective Birth Cohort ◽

Prospective Birth Cohort Study

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Relationships of Urinary Adrenal Steroids at Age 8 Years with Birth Weight, Postnatal Growth, Blood Pressure, and Glucose Metabolism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0851 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4340-4345 ◽

Cited By ~ 14

Author(s):

John W. Honour ◽

Richard Jones ◽

Sam Leary ◽

Jean Golding ◽

Ken K. Ong ◽

...

Keyword(s):

Blood Pressure ◽

Weight Gain ◽

Birth Weight ◽

Waist Circumference ◽

Early Growth ◽

Adrenal Steroids ◽

Postnatal Weight Gain ◽

Hydroxy Steroid ◽

Steroid Dehydrogenase ◽

Cortisol Metabolites

Abstract Introduction: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids. Methods: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2–8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5α-androgen reduction of androgens and cortisol metabolites and 11β-hydroxy steroid dehydrogenase activity were calculated. Results: In both boys and girls, total urinary androgen and cortisol metabolites were positively related to current height, weight, BMI, and waist circumference. Girls had higher urine androgen metabolite levels and 5α-androgen indexes than boys, and in girls higher androgen metabolite excretion was associated with lower birth weight and faster postnatal weight gain. After adjustment for current BMI, total cortisol metabolites and 11β-hydroxy steroid dehydrogenase index were not related to birth weight or postnatal weight gain in either sex. Conclusions: These data confirm early growth associations in this cohort seen with plasma levels of adrenal androgens at age 8 yr, at least in girls. Larger studies and follow-up during puberty are needed to exclude the possibility of programming of cortisol metabolism by early growth.

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Excess early postnatal weight gain and blood pressure in healthy young children

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174418001149 ◽

2019 ◽

Vol 10 (5) ◽

pp. 563-569 ◽

Cited By ~ 1

Author(s):

M. A. C. Jansen ◽

C. S. P. M. Uiterwaal ◽

C. K. van der Ent ◽

D. E. Grobbee ◽

G. W. Dalmeijer

Keyword(s):

Blood Pressure ◽

Weight Gain ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Excess Weight ◽

Birth Size ◽

Standard Deviation Increase ◽

Excess Weight Gain ◽

Postnatal Weight Gain ◽

Length Gain

AbstractBlood pressure (BP) tracks from childhood to adulthood, and early BP trajectories predict cardiovascular disease risk later in life. Excess postnatal weight gain is associated with vascular changes early in life. However, to what extent it is associated with children’s BP is largely unknown. In 853 healthy 5-year-old children of the Wheezing-Illnesses-Study-Leidsche-Rijn (WHISTLER) birth cohort, systolic (SBP) and diastolic BP (DBP) were measured, and z scores of individual weight gain rates adjusted for length gain rates were calculated using at least two weight and length measurements from birth until 3 months of age. Linear regression analyses were conducted to investigate the association between weight gain rates adjusted for length gain rates and BP adjusted for sex and ethnicity. Each standard deviation increase in weight gain rates adjusted for length gain rates was associated with 0.9 mmHg (95% CI 0.3, 1.5) higher sitting SBP after adjustment for confounders. Particularly in children in the lowest birth size decile, high excess weight gain was associated with higher sitting SBP values compared to children with low weight gain rates adjusted for length gain rates. BMI and visceral adipose tissue partly explained the association between excess weight gain and sitting SBP (β 0.5 mmHg, 95% CI −0.3, 1.3). Weight gain rates adjusted for length gain rates were not associated with supine SBP or DBP. Children with excess weight gain, properly adjusted for length gain, in the first three months of life, particularly those with a small birth size, showed higher sitting systolic BP at the age of 5 years.

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