Low birth weight infants do not have capillary rarefaction at birth: implications for early life influence on microcirculation

Low birth weight predicts adult essential hypertension and is linked to increased cardiovascular mortality in adult life. A reduction in capillary density (ie, rarefaction) is a hallmark of essential hypertension, and evidence suggests that rarefaction precedes the onset of the rise in blood pressure, because it is found in normotensive individuals at high risk of developing hypertension, suggesting that rarefaction is likely to be a primary structural abnormality. We hypothesized that low birth weight infants would have significant capillary rarefaction at birth. We studied 44 low birth weight infants born to normotensive mothers (33 were born preterm, birth weight: 1823±446 g; and 11 were born at term, birth weight: 2339±177 g) and compared them with 71 infants born at term with normal weight (birth weight: 3333±519 g). We used orthogonal polarized spectroscopy to measure basal (ie, functional) and maximal (ie, structural) skin capillary densities. Low birth weight infants, whether born preterm or at term, had significantly higher functional capillary density (mean difference of 10.5 capillaries per millimeter squared; 95% CI: 6.6-14.4 capillaries per millimeter squared; P<0.0001) and higher structural capillary density (mean difference of 11.1 capillaries per millimeter squared; 95% CI: 7.6-14.5 capillaries per millimeter squared; P<0.0001) when compared with normal weight term infants. We conclude that low birth weight infants born to normotensive mothers do not have capillary rarefaction at birth. These results contradict what might have been predicted from the concept of the intrauterine origins of adult disease and suggest that microcirculatory abnormalities observed in individuals of low birth weight occur in postnatal life rather than during their intrauterine existence.     

Ambulatory blood pressure in 12-year-old children born small for gestational age

An association between low birth weight and subsequent elevated blood pressure has been demonstrated in a large number of studies, but the number of subjects born small for gestational age in these studies has been negligible. The inverse relationship between birth weight and blood pressure in children has been evaluated previously with an ambulatory blood pressure device, but only in children with normal birth weights. In this prospective case-control study from birth to the age of 12, we evaluated the ambulatory blood pressures in 50 children born at term but small for gestational age and in 50 full-term children born appropriate for gestational age. Children born small for gestational age had similar mean+/-SD systolic (117.5+/-8.5 mm Hg versus 115.3+/-7.4 mm Hg, P=0.221), and diastolic (69.2+/-5.3 mm Hg versus 67.3+/-4.4 mm Hg, P=0.075) 24-hour ambulatory blood pressure compared with the values of the children born appropriate for gestational age. However, 24-hour systolic blood pressure in the small-for-gestational-age children was higher (3.90 mm Hg; 95% confidence interval, 0.65 to 7.15) after adjusting for current body mass index. The difference in current body mass index was the only determinant for the difference in systolic blood pressure between the groups. Birth weight had no direct association with the blood pressure values. Impaired fetal growth may have a relationship with higher later blood pressure, but in 12-year-old children, blood pressure differences between small for gestational age and appropriate for gestational age children are much more dependent on current body size.     

Growth in utero, adult blood pressure, and arterial compliance.

OBJECTIVES--To examine the relation between disproportionate fetal growth and adult blood pressure and to investigate whether arterial compliance in adult life is related to early development. DESIGN--A follow up study of a group of men and women whose birth weights and other measurements of body size had been recorded at birth. SETTING--Home and outpatient study. SUBJECTS--337 men and women born in the Jessop Hospital, Sheffield, between 1939 and 1940. MAIN OUTCOME--Adult systolic and diastolic blood pressures and arterial compliance as measured by pulse wave velocity in two arterial segments. RESULTS--Both systolic and diastolic blood pressures were higher in people whose birth weight was low, who were short or who had small abdominal or head circumferences at birth. Systolic blood pressure decreased by 2.7 mm Hg (95% CI 0.8 to 4.6) for each pound (454 g) gain in birth weight and by 3.4 mm Hg (95% CI 1.4 to 5.4) for each inch (2.54 cm) increase in crown-heel length. Diastolic pressure fell by 1.9 mm Hg (95% CI 0.9 to 2.9) for each pound (454 g) gain in birth weight and by 2.4 mm Hg (95% CI 1.4 to 3.5) for each inch (2.54 cm) increase in length. Systolic blood pressure was also higher in individuals whose mother's intercristal pelvic diameter was small or whose mother's blood pressure had been raised during pregnancy but these effects were statistically independent of the effects of low birth weight and other measurements that indicate fetal growth retardation. Arterial compliance was lower in those who had been small at birth. CONCLUSION--Impairment of fetal growth is associated with raised blood pressure in adult life and decreased compliance in the conduit arteries of the trunk and legs.     

Birth weight is inversely correlated to adult systolic blood pressure and pulse pressure in type 1 diabetes

In the general population, there is an inverse relationship between birth weight and adult systolic blood pressure. Because blood pressure in diabetic patients at least in part seems to be regulated by different mechanisms than in nondiabetic subjects, it is not known whether a similar correlation exists in diabetic individuals. Therefore, we obtained data on birth weight from original birth certificates in 1543 type 1 diabetic patients. Blood pressure was measured auscultatorily on a single occasion. In the 1225 patients born at term (after 37 weeks of gestation), the age- and sex-adjusted regression coefficients between systolic blood pressure and birth weight was -1.90 mm Hg/kg (95% confidence interval [CI], -3.71 to -0.09). The finding remained unchanged after adjustment for body mass index, current smoking, duration of diabetes, social class, antihypertensive therapy, glomerular filtration rate, glycemic control, and elevated albuminuria. The regression coefficient between birth weight and pulse pressure was of a similar magnitude. The age-adjusted regression coefficient between systolic blood pressure and birth weight seemed stronger in females (-3.34 mm Hg/kg; 95% CI, -6.06 to -0.62) than in males (-0.42 mm Hg/kg; 95% CI, -2.80 to 1.95), although this difference was not statistically significant. As a new finding, we report an inverse relationship between weight at birth and systolic blood pressure and pulse pressure in adult type 1 diabetic patients. Given the deleterious effects of elevated arterial blood pressure in diabetes, the impact of intrauterine growth retardation on the development of end-organ damage needs to be clarified.     

Low birth weight predicts higher blood pressure but not dermal capillary density in two populations

The association between low birth weight and high blood pressure is well established, but underlying mechanisms remain undefined. Vascular rarefaction, which may elevate peripheral vascular resistance, has been observed in capillaries of young men at risk for hypertension and men who had low birth weight. We looked for evidence that capillary rarefaction explains the association of low birth weight with high blood pressure in two cohorts. Participants in study 1 included 107 healthy boys aged 6 to 16 years recruited at random from a single school. Study 2 included 61 members of a cohort recruited at birth and studied at age 24 years. Measurements included indices of current size, blood pressure by automated sphygmomanometer, and dermal capillary density by video capillaroscopy of dorsal index finger skin after 10 minutes of venous occlusion. Lower birth weight predicted higher systolic blood pressure in both studies: in study 1, 3.57 mm Hg/kg birth weight (after adjustment for current height, 95% confidence interval 0.38 to 6.75, P<0.05); in study 2, 122+/-12 mm Hg in low birth weight (<2 kg) versus 115+/-9 in controls (P<0.05). Dermal capillary density was not associated in either group with birth weight or systolic blood pressure. We have found no evidence in these 2 cohorts that reduced capillary density explains the associations between lower birth weight and higher blood pressure.     

Early life factors and blood pressure at age 31 years in the 1966 northern Finland birth cohort

Data on the birth weight-blood pressure relationship are inconsistent. Although an inverse association has been suggested in several large studies, interpretation is complicated by publication and other biases. Few data are available on the relationship between other early growth measures and blood pressure. We examined the shape and size of association between determinants of fetal growth, size at birth, growth in infancy, and adult systolic and diastolic blood pressure at 31 years in the prospective northern Finnish 1966 birth cohort of 5960 participants. Birth weight, birth length, gestational age, ponderal index, and birth weight relative to gestational age showed a significant inverse association with blood pressure at age 31. Rapid growth in infancy ("change-up") was positively associated with blood pressure. Adjusted regression coefficients for birth weight indicated systolic/diastolic blood pressure lower by -1.7 (95% confidence interval [CI], -2.5, -1.0)/-0.7 (95% CI, -1.4, -0.02) mm Hg for 1 kg higher birth weight. The significant inverse association between birth weight and systolic blood pressure persisted without adjustment for adult body mass index for males. Among females, gestational age showed a stronger association with blood pressure than birth weight: gestational age higher by 7 weeks (equivalent to an average of 1 kg higher birth weight) among singletons associated with -2.9 (95% CI, -4.7, -1.1) mm Hg lower systolic blood pressure. Our results support the concept that birth weight, other birth measures, and infant growth are important determinants of blood pressure and hence cardiovascular disease risk in later life.     

Ethnic differences in the association of birth weight and blood pressure: the Georgia cardiovascular twin study

BACKGROUND: African Americans (AAs) not only have higher blood-pressure levels, but also an increased risk of low weight at birth, compared with European Americans (EAs). In light of fetal programming theories, it has been suggested that ethnic differences in blood pressure originate in utero. However, most previous studies in biethnic samples have not found a significant inverse association between birth weight and blood pressure in AAs. METHODS: In 562 EA and 465 AA adolescent twins of the Georgia Cardiovascular Twin Study, we investigated the potential ethnic difference in the association of blood pressure and birth weight, with the ability to control for potential confounding by familial factors. RESULTS: Blood-pressure levels were significantly higher in AAs compared to EAs, independent of birth weight (P < .01). After adjustment for parental factors and body mass index, the difference in systolic blood pressure per kg birth weight was -1.1 mm Hg (95% confidence interval, -2.7 to 0.48, P = .17) in EAs, and -2.5 mm Hg (95% confidence interval, -4.7 to -0.40, P = .02) in AAs. A significant ethnic interaction was revealed in paired analysis, where the inverse association remained in AAs, but not in EAs. Associations with diastolic blood pressure were generally weaker and nonsignificant. CONCLUSIONS: We showed that low birth weight was associated with an elevated systolic blood pressure in AAs, independent of familial factors. The results also suggest that the association between birth weight and blood pressure may be more pronounced in AAs in adolescence.     

Immediate postnatal growth is associated with blood pressure in young adulthood: the Barry Caerphilly Growth Study

There is a consistent inverse association between birth weight and systolic blood pressure; however, few studies have been able to examine the immediate postnatal period. We have examined whether accelerated postnatal growth predicts adult systolic and diastolic blood pressure. We followed up participants from the Barry Caerphilly Growth Study. Blood pressure data were obtained on 679 of the original 951 subjects (73%) aged approximately 25 years. Both multivariable linear regression and spline models were used to examine the association among weight, length, and growth velocities with systolic blood pressure and diastolic blood pressure. Both statistical approaches showed that birth weight was inversely associated with systolic blood pressure. Only the spline models found that immediate (0 to 5 months) weight gain (beta coefficient: 1.29 mm Hg; 95% CI: 0.36 to 2.23; P=0.007) and weight gain between 1 year and 9 months to 5 years (beta coefficient: 1.44 mm Hg; 95% CI: 0.31 to 2.57; P=0.01) were independently associated with systolic blood pressure, whereas only immediate weight gain (beta coefficient: 0.74 mm Hg; 95% CI: 0.08 to 1.41; P=0.03) was associated with diastolic blood pressure. This is the first study to demonstrate that only immediate postnatal growth predicts diastolic blood pressure in term births, whereas it adds further evidence that both birth weight and postnatal growth are associated with systolic blood pressure in support of both the fetal origins and growth acceleration hypotheses.     

Effect of postnatal catch-up growth on blood pressure in children at 3 years of age

Size at birth and early postnatal growth rates appear to be important determinants of cardiovascular diseases. We examined whether intrauterine growth restriction or the subsequent catch-up postnatal weight gain leads to higher blood pressure in early life to confirm that size at birth and early postnatal growth rates appear to be important determinants of blood pressure changes in early life. Of 407 children born between December 2001 and November 2002 in hospital based-birth cohorts, 102 were followed up at 3 years of age (24.2%) at Ewha Womans University Hospital in Seoul, Korea. At 3 years of age, those who had a low birth weight still belonged in the lower-weight group than the others. The subjects' systolic blood pressure was correlated with their current weight (r=0.41) and weight gain (r=0.39), but not with their birth weight. Those with a higher current weight and higher weight gain based on birth weight (conditional weight gain) had the highest blood pressure. Systolic blood pressure increased by 0.2 mm Hg for every 100-g increase in weight at 3 years and, independently, by 1.5 mm Hg for every 100-unit increase in conditional weight gain. This study suggests that birth weight is not directly associated with blood pressure, but accelerated growth, which occurs mostly in those born with a low birth weight, seems to affect blood pressure in early life.     

Maternal size at birth and the development of hypertension during pregnancy: a test of the Barker hypothesis.

BACKGROUND: Whether individuals who were small at birth are at increased risk of developing cardiovascular disease (the Barker hypothesis) is a topic of great controversy. Although an increased risk has been suggested by several reports, the reports have been criticized for being based on ill-defined populations, for the large numbers of subjects who were unavailable for follow-up, and for inadequate control of socioeconomic status. OBJECTIVE: To determine whether a woman's weight and gestational age at birth predict the development of hypertension during her subsequent pregnancies. DESIGN: Prospective observational study. SUBJECTS: Women born in Copenhagen, Denmark, as subjects in the Danish Perinatal Study (1959-1961) were traced through the Danish Population Register. Information was obtained on their pregnancies from 1974 to 1989. MAIN OUTCOME MEASURES: Onset of hypertension in pregnancy, defined by the presence of a systolic blood pressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hg or greater on 2 visits at or after 140 days' gestation. RESULTS: Hypertension developed in 11.3% of the pregnant women who were small for gestational age at birth, compared with 7.2% of the pregnant women who were not small for gestational age at birth (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.1-2.6), and in 9.4% of the pregnancies in women who were preterm at birth, compared with 7.6% of pregnancies in women who were not preterm at birth (OR, 1.3; 95% CI, 0.8-2.0). After adjustment for adult body mass index, smoking, birth order, and hypertension in the subjects' own mothers, the ORs for small-for-gestational-age women and preterm women to develop hypertension during pregnancy were 1.8 (95% CI, 1.1-2.8) and 1.5 (95% CI, 0.96-2.5), respectively. CONCLUSION: These results support the Barker hypothesis, while addressing many of the methodological criticisms of previous investigations.     

Blood pressure in adults after prenatal exposure to famine

BACKGROUND: Many studies have shown that low birth weight is associated with high blood pressure. The composition of the diet of pregnant women has also been found to affect blood pressure in their children. We assessed the effect of prenatal exposure to the Dutch famine of 1944-1945, during which the caloric intake from protein, fat and carbohydrate was proportionally reduced, on blood pressures in adults now aged about 50 years. METHODS AND RESULTS: We measured blood pressures at home and in the clinic among people born at term in one hospital in Amsterdam, The Netherlands, between November 1 1943 and February 28 1947, for whom we had detailed birth records. Blood pressures of people exposed to famine during late (n = 120), mid-(n = 109) or early gestation (n = 68) were compared with those of people born in the year before or conceived in the year after the famine (unexposed subjects, n = 442). No effect of prenatal exposure on systolic and diastolic blood pressure was observed. The mean systolic blood pressure taken in the clinic in those exposed in late gestation, and adjusted for sex and age, was 1.3 mmHg higher than in the unexposed group (95% confidence interval -1.9 to 4.4). The mean systolic blood pressure differed by -0.6 mmHg (95% confidence interval -3.9 to 2.7) for those exposed in mid-gestation and -1.7 mmHg (95% confidence interval -5.6 to 2.2) for those exposed in early gestation. People who were small at birth had higher blood pressures. A 1 kg increase in birth weight was associated with a decrease of 2.7 mmHg (95% confidence interval 0.3 to 5.1) in systolic blood pressure. Analyses of blood pressures measured at home gave similar results. CONCLUSION: High blood pressure was not linked to prenatal exposure to a balanced reduction of macronutrients in the maternal diet. However, it was linked to reduced fetal growth. We postulate that it might be the composition rather than the quantity of a pregnant woman's diet that affects her child's blood pressure in later life.     

Association of the growth hormone receptor d3-variant and catch-up growth of preterm infants with birth weight of less than 1500 grams

BACKGROUND: Preterm infants with very low birth weight frequently exhibit impaired longitudinal growth during the first years of life. Recently, the d3-isoform (genomic deletion of exon 3) of the GH receptor (GHR) has been linked to an increased responsiveness to GH. OBJECTIVE: Our objective was to test whether the GHRd3 isoform is associated with postnatal catch-up growth in very low birth weight preterm infants. DESIGN AND PATIENTS: We compared the postnatal growth pattern of 77 otherwise healthy preterm infants (mean gestational age, 28.5 wk; range, 23-35 wk) with a birth weight below 1500 g (mean birth weight, 941 g) to their GHR exon 3 genotype, which was analyzed by multiplex PCR. On examination, mean age of the children was 6.0 yr (range, 4.2-8.0 yr). RESULTS: Children homozygous or heterozygous for the GHRd3 allele showed a significantly higher rate of postnatal catch-up, compared with those homozygous for the full-length allele. CONCLUSIONS: Our results define the GHR exon 3 genotype as a predictor for the postnatal growth pattern of very low birth weight preterm infants. Those who carry at least one GHRd3 allele are more likely to catch-up.     

Blood pressure, arterial compliance, and left ventricular mass: no relation to small size at birth in south Indian adults

OBJECTIVE: To determine whether reduced fetal growth leads to raised blood pressure, reduced arterial compliance, and increased left ventricular mass in an Indian population. DESIGN: A retrospective cohort study of men and women (age range 40-61 years) whose weight, length, and head circumference at birth were recorded. SETTING: The Holdsworth Memorial Hospital, Mysore, South India. SUBJECTS: 435 men and women born in the hospital between 1934 and 1953. MAIN OUTCOME MEASURES: Systolic and diastolic blood pressures; compliance in four arterial segments derived from pulse wave velocity, measured by a non-invasive optical method; and left ventricular mass measured using M mode echocardiography. RESULTS: Small size at birth was not associated with increased adult blood pressure or left ventricular mass, or with reduced arterial compliance. Systolic blood pressure and left ventricular mass were higher in subjects who were greater in length at birth, rising by 1.64 mm Hg (95% confidence interval (CI) -0.08 to +3.37 mm Hg) and 1.63 g/m(2) (95% CI 0.13 to 3.13 g/m(2)), respectively, per one inch (2.5 cm) increase in birth length, independently of adult size. Arterial compliance was reduced in people whose mothers were lighter and had smaller pelvic (external conjugate) diameters. CONCLUSIONS: The higher prevalence of coronary heart disease in Indian men and women of lower birth weight, shown in an earlier study of the same cohort, cannot be explained by changes in blood pressure, arterial compliance, and left ventricular mass. The association of raised blood pressure and left ventricular mass with longer birth length suggests that the way in which the intrauterine environment influences coronary heart disease differs between Indian and Western populations.     

Evidence for genetic factors explaining the birth weight-blood pressure relation. Analysis in twins

Epidemiological studies have consistently shown an inverse association between birth weight and systolic blood pressure in later life after adjustment for current size. To examine whether this association is explained by intrauterine or genetic factors, we investigated birth weight and blood pressure data in 53 dizygotic and 61 monozygotic adolescent twin pairs. Birth weight was obtained from the mothers. Blood pressure measurements were performed 6 times at rest and during mental stress. The dizygotic but not the monozygotic twins with the lowest birth weight from each pair had a systolic blood pressure measured at rest and during the reaction time experiment that was higher compared with their cotwins with the highest birth weight (dizygotic twins: blood pressure at rest, 119. 4+/-9.7 mm Hg versus 117.3+/-8.5 mm Hg, P=0.07, and during a reaction time task, 126.2+/-10.8 versus 123.6+/-9.5, P=0.09; monozygotic twins: blood pressure at rest, 117.4+/-6.4 versus 118. 4+/-9.0, P=0.4, and during a reaction time task, 122.9+/-8.4 versus 124.2+/-10.8, P=0.2). The differences in blood pressure between the cotwins with the lowest and the cotwins with the highest birth weight were different in dizygotic compared with monozygotic twin pairs (for blood pressure at rest, P=0.05; for blood pressure during reaction time, P=0.03). After adjustment for differences in current weight, intrapair differences in birth weight were negatively and significantly associated with differences in systolic blood pressure at rest and during the reaction time task in dizygotic twins (regression coefficient, -5.7 mm Hg/kg [95% confidence interval, -10.4 to -1.0] and -6.3 [-12.7 to 0], respectively) but not in monozygotic twins (-0.1 [-5.4 to 5.2] and +3.5 [-1.8 to 8.8], respectively). Interaction analysis indicated that the associations were different between dizygotic twins and monozygotic twins (P=0.1 and P<0.05, respectively). These data suggest that genetic factors may play an important role in the association between birth weight and blood pressure.     

The impact of birth weight and gestational age on blood pressure in adult life: A population-based study of 49-year-old men

The impact of birth weight and gestational age on blood pressure in adult life was studied in a population of 49-year-old men born in 1926–27 who took part in a screening investigation of blood pressure performed in 1975–76 in Göteborg, Sweden. Birth records were traced in 430 subjects and compared with screening records. The adult systolic blood pressure (SBP) was not correlated with birth weight but was inversely correlated with gestational age in the whole study group (r = −0.10, P = .04; n = 430). The correlation between adult blood pressure and gestational age was stronger in preterm subjects, ie, those with a gestational age less than 38 weeks (for SBP, r = −0.46, P = .001 and for diastolic blood pressure [DBP], r = −0.44, P = .01; n = 44), and these correlations were independent of birth weight. There was, however, no correlation between adult blood pressure and gestational age in subjects born at term (between 38 and 41 complete weeks of gestation) or postterm (more than 42 weeks of gestation).The inverse correlation between adult SBP and gestational age was stronger in low-birth-weight subjects (≤ 2500 g; r = −0.86, P < .001; n = 14). After adjustment for birth weight, in this group an increase by 1 week of gestation was associated with a decrease in adult SBP of 7.2 mm Hg (95% CI, 10.1–4.2). In the whole study group, a positive correlation was found between adult blood pressure and adult body mass index (BMI) (r = 0.30, P < .001 for SBP and r = 0.33, P < .001 for DBP). In preterm subjects, however, no such correlation was found, but in subjects born at term or postterm, adult blood pressure was significantly correlated with BMI (for SBP at term, r = 0.34, P < .001 and postterm, r = 0.47, P < .001 and for DBP at term, r = 0.36, P < .001 and postterm, r = 0.30, P < .05).This study indicates that adult blood pressure appears to be related to different variables in different ranges of gestation. In preterm subjects, gestational age appears to have a great impact on adult blood pressure. In subjects born at term or later, however, adult blood pressure was not associated with factors related to birth, but only to the adult BMI.     

Childhood growth and adult hypertension in a population of high birth weight

Low birth weight has consistently been associated with increased adult blood pressure. The relative importance of childhood growth is, however, less well established. This study examined sex-specific associations between childhood growth and adult blood pressure in 2120 subjects born from 1921 to 1935 in Reykjavik who were recruited into a longitudinal study in 1967-1991. Size at birth and growth at regular intervals between 8 and 13 years were collected from national archives. Hypertensive males did not differ from normotensive males at birth but were increasingly taller and of higher body mass index between 8 and 13 years. No differences in adult height were observed between hypertensive and normotensive males. For boys, growth-velocity (change in growth per year) for body mass index and height between 8 to 13 years was positively associated (P<0.05) with adult blood pressure. The association for body mass index-velocity was fully accounted for by concurrent body size, whereas height-velocity was independent of birth weight and concurrent body size. Males in the highest compared with the lowest tertile in the height-velocity distribution had 66% increased risks of hypertension (95% CI: 15% to 139% increased risks of hypertension) corresponding with 5.0 mm Hg increase (95% CI: 1.5 to 8.5 mm Hg increase) and 3.1 mm Hg increase (95% CI: 1.1 to 5.0 mm Hg increase) in systolic and diastolic blood pressures, respectively. Hypertensive females weighed less at birth but did not differ markedly from normotensive girls between 8 and 13 years, and no association was observed for growth-velocity. In conclusion, rapid linear growth between 8 and 13 years predicts elevated adult blood pressure in boys. This association is likely to reflect relatively early onset of puberty among hypertensive males.     

Celiac disease and risk of adverse fetal outcome: a population-based cohort study

BACKGROUND & AIMS: Studies of maternal celiac disease (CD) and fetal outcome are inconsistent, and low statistical power is likely to have contributed to this inconsistency. We investigated the risk of adverse outcomes in women with CD diagnosed prior to pregnancy and in women who did not receive a diagnosis of CD until after the delivery. METHODS: A national register-based cohort study restricted to women aged 15-44 years with singleton live born infants was used. We identified 2078 offspring to women who had received a diagnosis of CD (1964-2001): 1149 offspring to women diagnosed prior to birth and 929 offspring to women diagnosed after infant birth. Main outcome measures were: intrauterine growth retardation, low birth weight (<2500 g), very low birth weight (<1500 g), preterm birth (<37 gestational weeks), very preterm birth (<30 gestational weeks), and caesarean section. RESULTS: Undiagnosed CD was associated with an increased risk of intrauterine growth retardation (OR = 1.62; 95% CI: 1.22-2.15), low birth weight (OR = 2.13; 95% CI: 1.66-2.75), very low birth weight (OR = 2.45; 95% CI: 1.35-4.43), preterm birth (OR = 1.71; 95% CI: 1.35-2.17), and caesarean section (OR = 1.82; 95% CI: 1.27-2.60). In contrast, a diagnosis of CD made before the birth was not associated with these adverse fetal outcomes. CONCLUSIONS: Undiagnosed maternal CD is a risk factor for unfavorable fetal outcomes, but the risks are reduced when CD has been diagnosed. CD diagnosed prior to pregnancy does not constitute a great a risk as undiagnosed CD.     

Salt sensitivity of children with low birth weight

Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.     

Association between birth weight and blood pressure is robust, amplifies with age, and may be underestimated

Data on the early life origins of adult hypertension have been widely reported: however, recent research shows that the strength of association between small size at birth and higher blood pressure weakens as study size increases. In this article, we retest the association between birth weight and systolic blood pressure in a large cohort, examine whether age interacts with birth weight to predict blood pressure, and explore reasons why birth weight-blood pressure associations tend to weaken with increasing study size. Measurements from 25874 employees of a large United Kingdom company (mean [SD] age: 38.0 [7.9] years), undertaking voluntary occupational health screening, were available. Using linear regression analysis, we observed that systolic blood pressure changed -0.8 (95% CI: -1.1 to -0.5) mmHg per 1-kg increase in birth weight (P<0.001) adjusted for age and sex and -1.1 (95% CI: -1.3 to -0.8) mmHg/kg (P<0.001) after further adjustment for body size. This inverse association amplified with age (age/birth weight interaction term P<0.001). In participants reporting birth weight from hospital records (n=744), systolic blood pressure changed -1.4 (95% CI: -3.1 to 0.2) mmHg/kg compared with -0.8 (95% CI: -1.0 to -0.5) mmHg/kg in all of the other participants. Finally, the data show evidence of "fixed-category blood pressure allocation," where participants are allocated certain blood pressure values, such as 120/80 mmHg, independent of actual blood pressure. Although the association between birth weight and systolic blood pressure was weaker than observed in smaller studies, recalled birth weight and fixed blood pressure measurement error may generate a trend toward weaker associations in larger studies.     

Arterial blood pressure and arterial stiffness in adolescents are related to gestational age

BACKGROUND: Recent studies show that low birth weight (LBW) infants are at risk of increased arterial blood pressure (BP) in adulthood. Previous work from our centre and others suggests that arterial stiffness (AS) is increased in such patients. However, the respective roles of preterm birth and of intrauterine growth restriction (IUGR) are unclear. AIM: To characterize AS and BP in adolescents who were: born at term with an appropriate birth weight for gestational age (GA) (group 1, n=41); born preterm with an appropriate birth weight for GA (group 2, n=25); born at term and small for GA (group 3, n=24). PATIENTS AND METHODS: Systemic BP was measured with an automated oscillometric device. AS was assessed by measuring pulse wave velocity (PWV) between carotid and radial arteries. RESULTS: 90 adolescents were studied at a mean (SD) age of 13.9 (1.2) years. Subjects from group 2 were born with a 33.6 (1.5) GA. Systolic BP, mean BP, and PWV were significantly increased in group 2 subjects in comparison to both group 1 (123 +/- 11 vs. 117 +/- 11 mmHg, p = 0.04; 88 +/- 7 vs. 83 +/- 7 mmHg, p = 0.03; 7.7 +/- 1.0 vs. 7.0 +/- 0.9 m/s, p = 0.02 respectively) and to group 3 (114 +/- 15 mmHg, p = 0.03: 79 +/- 8 mmHg, p = 0.001; 6.8 +/- 0.9 m/s, p = 0.005 respectively) subjects. Systolic BP, mean BP, and PWV were similar in group 1 and group 3 subjects. CONCLUSION: BP and AS are increased during adolescence in subjects born with a LBW due to preterm birth, while they are not altered in subjects when LBW is related to IUGR. It may be speculated that such changes predispose to long term hypertension and that preterm birth is involved in the early programming of arterial diseases in adulthood.