Anna Kistner

Prenatal Dexamethasone Causes Oligonephronia, Sodium Retention, and Higher Blood Pressure in the Offspring

Recent reports have shown that low birth weight infants have a higher incidence of adult hypertension. These observations have stimulated a number of studies designed to evaluate the mechanisms of this phenomenon. In this study, fetal growth retardation was induced by treating pregnant rats with dexamethasone. After birth, pups whose mothers were treated with dexamethasone had a lower body and kidney weight and a lower number of glomeruli than control pups. Immunohistochemistry on treated kidneys demonstrated a marked reduction in the number of cells undergoing mitosis in the cortical nephrogenic zone. In the treated group, body and kidney weight normalized by 60 d of age, but blood pressure was significantly higher compared with controls (130 ± 4 versus 107 ± 1 mm Hg). In addition, GFR was significantly lower, albuminuria was higher, urinary sodium excretion rate and fractional sodium excretion were lower, and sodium tissue content was higher. In contrast, when pregnant rats were treated with a natural glucocorticoid (hydrocortisone) which is metabolized by the placenta, fetal development and adult blood pressure were normal. In conclusion, we found that high levels of maternal glucocorticoids impair renal development and lead to arterial hypertension in offspring. Even though renal mass eventually normalizes, glomerular damage as well as sodium retention occur and these factors may contribute to the development of hypertension.

Increased blood pressure but normal renal function in adult women born preterm

Abstract It has been suggested that children born small for gestational age may develop hypertension and renal dysfunction in adulthood due to impaired fetal kidney development. Very little information on this issue is available on children born preterm. The objective of this study was to investigate the relationship between birth weight, blood pressure, and kidney function in adult subjects who were born preterm or born small for gestational age (SGA). Study design: Subjects (n=50), all women born between 1966 and 1974, were evaluated at a mean age of 26±1.9 years. They were allocated to three groups: (1) born before gestational week 32 (n=15), (2) born full term with birth weight <2600 g (n=18) (SGA), and (3) controls, born full term with appropriate birth weight (n=17). Casual blood pressure, ambulatory 24-h blood pressure (ABPM), glomerular filtration rate (GFR), renal plasma flow (ERPF) and urinary albumin excretion were determined. Results: Preterms had significantly higher casual systolic and mean arterial blood pressure levels compared to controls (123±13 vs 110±7 mmHg, P<0.01, and 87±9 vs 79±6 mmHg, P<0.005, respectively). ABPM was not significantly different between the groups. When the number of systolic recordings >130 mmHg/subject during ABPM was calculated, the preterms had significantly more recordings above this value (P<0.05) as well as a significantly increased area under the curve >130 mmHg and >140 mmHg systolic (P<0.05) compared to the controls. SGA subjects were not significantly different from controls. There were no significant differences in GFR, ERPF or urinary albumin excretion between the three groups. Conclusion: Women born preterm seem to have a disturbance in blood pressure regulation in adulthood, a finding that is not observed for those born small for gestational age. Kidney function in early adulthood seems to be normal in subjects born preterm or small for gestational age.

Low Gestational Age Associated with Abnormal Retinal Vascularization and Increased Blood Pressure in Adult Women

The objective was to investigate any possible relationship between functional and structural vascular changes in women with low gestational age and/or low birth weight by analyzing the retinal vascular pattern in women with thoroughly documented blood pressure. Retinal vessel morphology was evaluated by digital image analysis of ocular fundus photographs in 47 subjects, aged 23–30 y. The women were allocated into three groups: 1) those born preterm and appropriate for gestational age (AGA), with a median gestational age at birth of 30 wk and a median birth weight of 1250 g (n = 14); 2) those born small for gestational age (SGA) but full term (median 40 wk), with a median birth weight of 2130 g (n = 17), and 3) those born full term, AGA, and with a median birth weight of 3640 g (n = 16). Women born preterm had significantly higher length index for arterioles compared with the other two groups (median 1.11 and 1.08, respectively, p = 0.005). In addition, the preterm-born women had significantly fewer number of vascular branching points compared with the controls (median 27 and 30, respectively, p = 0.03). The abnormal retinal vascularization observed in ex-preterm women together with an increased casual blood pressure observed in these subjects suggests that being born preterm does have effects on the vascular system that persist into adult life. In addition, it demonstrates that preterm birth seems to affect the vascular system both functionally and structurally, which, in adulthood, could result in a lower threshold for the development of vascular disease.

IGFBP-1 levels in adult women born small for gestational age suggest insulin resistance in spite of normal BMI

Objective.  Impaired fetal development may contribute to decreased insulin sensitivity. This study was designed to characterize serum markers of insulin resistance in adults born small for date or born prematurely.

Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age

Objective To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA). Study design In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than −2.0 SDS using the Swedish reference and as BW below the 10th percentile using the Canadian reference charts. Results Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDSCanada (p<0.001), and SGACanada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDSSweden, OR = 0.80 vs 0.56; and BWSDSCanada, OR = 0.72 vs 0.41). Conclusions Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infants degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.

Bone and fat mass in relation to postnatal levels of insulin-like growth factors in prematurely born children at 4 y of age

Background:Children born prematurely may be at risk of developing osteopenia. This study investigated whether insulin-like growth factors (IGFs) in the early postnatal period influence bone mass and body composition in prematurely born children.Methods:A total of 74 control (gestational age >36 wk; n = 37) and preterm (gestational age <32 wk; n = 37) infants were investigated (mean age ± SD: 4.59 ± 0.31 y). Bone mineral density, body composition, and markers of bone and mineral metabolism were investigated in relation to postnatal IGF levels.Results:After adjusting for confounders, we found no differences in bone mass, but significantly less lean mass, increased fat mass, and increased osteocalcin levels in ex-preterm infants. Forward stepwise multiple analysis revealed that higher late postnatal IGF-II levels predict lumbar spine bone mineral content (P < 0.05) and lean mass (P < 0.05). When the birth weight standard deviation score was included in the analysis, higher early postnatal IGF-I levels predicted both lumbar spine bone mineral density and bone mineral content (P < 0.05). Higher early postnatal IGF binding protein-3 (P < 0.01) predicted increased fat mass at 4-y follow-up.Conclusion:Ex-preterm children have normal bone mass but different body composition compared with full-term controls. Higher early IGF-I and late postnatal IGF-II concentrations are positive predictors of lumbar spine bone mass.

Preterm born 9-year-olds have elevated IGF-1 and low prolactin, but levels vary with behavioural and eating disorders.

This study examined the relationship between hypothalamic‐associated hormones and behavioural and eating disorders in children with low birthweight.

Neonatal IGF-1/IGFBP-1 axis and retinopathy of prematurity are associated with increased blood pressure in preterm children

Preterm children are at risk of developing increased blood pressure (BP). We evaluated possible associations between BP, early insulin‐like growth factor‐1 (IGF‐1) and IGF‐binding protein‐1 (IGFBP‐1) levels and retinopathy of prematurity (ROP) in preterm children.

Leptin may enhance hepatic insulin sensitivity in children and women born small for gestational age

Objective Children born small for gestational age (SGA) are at risk for developing type 2 diabetes. Lipodystrophy leads to early type 2 diabetes and leptin reverses the metabolic consequences of the disease. Low IGF-binding protein 1 (IGFBP1) can predict the development of type 2 diabetes. The aim of this study was to determine leptin, insulin, and IGFBP1 in children and adult women born preterm or SGA to evaluate the role of leptin as a compensatory mechanism in insulin resistance development. Methods Seventy-six children (8.5–10 years, 41 girls and 35 boys) and 45 women (23–30 years) were studied. The children comprised subjects born appropriate for gestational age (<30 gestational weeks) (n=22), born SGA at term (n=23), and full-term normal-weight controls (n=31). Among the women, the corresponding figures were, n=10, n=18, and n=17 respectively. Fasting levels of IGFBP1, leptin, insulin, and IGF1 were determined and total adiponectin only in women. Results In girls and women, term SGA subjects had higher leptin levels in relation to BMI SDS (P=0.042 and P=0.03 respectively). More than half of IGFBP1 variability was explained by leptin and insulin in children. In term SGA women, IGFBP1 level was lower compared with controls (P=0.012) and the regression line of IGFBP1 on insulin was suppressed below −1 s.d. of a reference material. Conclusion Leptin levels were elevated in term SGA girls and women, in particular in adult women, but not found in preterm girls and women. IGFBP1 was lower in term SGA women. In children, leptin and insulin were strong suppressors of IGFBP1. We speculate that higher leptin levels could be a protective event to enhance hepatic insulin sensitivity.

Fetal Growth Retardation Correlates with Small Kidneys and Higher Blood Pressure in Adulthood • 1847

It has been suggested that impaired fetal kidney development may contribute to the onset of hypertension. This study was designed to investigate the outcome of adult subjects who were born preterm or growth retarded. Subjects(mean age± SEM 26±1 years, n=34) were randomly selected from the neonatal clinical records. They were allocated in 3 groups: born full term with approporiate birth weight, born full term with birth weight median. Gestational age was positively correlated to adult ERPF (r = 0.35, p median. All pathological 24-hours pressure profiles were in the group with renal volume < median. IGF-1 was lowest in the adults born full term but with low birth weights (207±73) and highest in the adults born preterm(258±40) (control adults: 231±21). No correlation was found between gestational age, birth weight or kidney volume with other variables. In conclusion, this study shows a weak but significant correlation between fetal growth retardation and renal function in adulthood. Adult renal volume and GFR are lower in adults who were born prematurely or small for age. Small renal volume in adulthood may be associated to the early onset of hypertension.