Prognostic value of office and ambulatory blood pressure measurements in pregnancy

With the objective to assess the prognostic value of office values as compared with ambulatory monitoring in pregnancy, we analyzed 2430 blood pressure series systematically sampled from 403 untreated pregnant women for 48 consecutive hours every 4 weeks from the first visit to the hospital until delivery. Women were divided into 5 groups: "detected" gestational hypertension, women with office blood pressures >140/90 mm Hg after 20 weeks of gestation and hyperbaric index (area of blood pressure excess above the upper limit of a time-specified tolerance interval) consistently above the threshold for diagnosing hypertension in pregnancy; "undetected" gestational hypertension, office values <140/90 mm Hg but hyperbaric index above the threshold for diagnosis; normotension, both office values and hyperbaric index below the thresholds for diagnosis; white coat hypertension, women with recorded diagnosis of gestational hypertension but hyperbaric index consistently below the threshold for diagnosis; and preeclampsia, defined as gestational hypertension and proteinuria. Results indicate small and nonsignificant differences in 24-hour mean of ambulatory pressures between "detected" and "undetected" gestational hypertension at all stages of pregnancy, in contrast with highly significant differences between these two groups and normotensive pregnancies. Average office blood pressure values were similar for preeclampsia, "detected," and "undetected" gestational hypertension. The hyperbaric index was, however, significantly higher for women with preeclampsia after 20 weeks of gestation as compared with all other groups and higher for women with either "detected" or "undetected" gestational hypertension as compared with normotensive pregnant women. The incidence of preterm delivery and intrauterine growth retardation were similar for "detected" and "undetected" gestational hypertension but significantly lower for normotensive women. In pregnancy, the hyperbaric index derived from ambulatory monitoring is markedly superior to office measurements for diagnosis of what should be truly considered gestational hypertension, as well as for prediction of the outcome of pregnancy.     

Blood pressure changes during pregnancy in Nigerian women.

The purpose of this longitudinal study was to determine the pattern of blood pressure during pregnancy in Nigerian women. The blood pressure of 189 women from early pregnancy and up to term, during labor and 24 h after delivery were monitored. The mean systolic, diastolic and mean arterial blood pressure were computed and the blood pressure readings were correlated with parity and selected anthropometric and socioeconomic variables. The results showed a decline in blood pressure levels during the mid-trimester of pregnancy with a progressive increase towards term. The highest blood pressures were recorded during the third stage of labor. The mean (+/- 2 SD) of blood pressure was 130/80 mmHg. There was no significant correlation of blood pressure with parity but there was a significant positive correlation with maternal age and Quetelex index after 30 weeks of gestation. As compared to Caucasian women, Nigerian women showed higher levels of diastolic blood pressures. We conclude that: (1) the higher incidence of gestational hypertension in African women may be due to higher levels of resting baseline blood pressures in the women, and (2) pregnant women in our population with persistent elevation of blood pressures above 130/80 mmHg should be closely monitored.     

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

BACKGROUND: Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension. OBJECTIVE: To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the early-growth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations. DESIGN AND METHODS: Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography. RESULTS: Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited significant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring. CONCLUSIONS: The rat model of maternal dexamethasone treatment is established as a paradigm of 'programmed' hypertension in man. Our data show modification of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive fetal exposure to glucocorticoids could be a common early-life stimulus to the association between hyperinsulinaemia, hypertension and hyperleptinaemia often seen in individuals of low birthweight.     

Transection of aortic depressor nerve fails to raise blood pressure in spontaneously hypertensive rats

Although central resetting via the aortic depressor nerve (ADN) has been known to occur in spontaneously hypertensive rats, the function of the ADN is not yet clear in these animals. To determine whether a baroreflex via the ADN can act to regulate blood pressure during hypertension, blood pressures were measured following ADN transection in spontaneously hypertensive and normotensive rats, and the reflex changes of heart rate and the sympathetic nerve activity were recorded during the pressor response to phenylephrine infusions. Blood pressures were significantly raised 1 day after ADN transections in normotensive rats and continued so for 7 d. Blood pressures were not changed in sham operated rats. In spontaneously hypertensive rats, ADN transections did not alter blood pressures in comparison with sham operated controls. On the seventh day after transections, all rats were anaesthetised with urethane and pressor responses to phenylephrine were examined. Bradycardic and sympathoinhibitory responses to the elevation of blood pressure caused by phenylephrine infusions were significantly smaller in ADN transectioned normotensive rats than in sham operated controls. In spontaneously hypertensive rats, the bradycardic and sympatho-inhibitory responses were not reduced by ADN transections. These findings suggest that the impaired baroreflex via the ADN can contribute to the development of hypertension in the spontaneously hypertensive rat.     

Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring

Epidemiologic studies have demonstrated associations between low birth weight and increased rates of adult diseases such as hypertension and diabetes. Maternal iron restriction in the rat has been reported to both reduce birth weight and to elevate blood pressure at 40 days of age. The aim of the present study was to extend these findings to investigate the effects of maternal iron restriction on glucose tolerance and serum lipids, 2 important components of the metabolic syndrome, in adult offspring. Blood pressure, glucose tolerance, and serum lipids were measured in the 3-month-old offspring of iron-restricted dams. Rats were placed on control or iron-restricted diets 1 week before mating. At term, dams on the iron-restricted diet were anemic with decreased haemoglobin, red blood cell (RBC) count, hematocrit, and mean RBC volume compared with controls. Neonates from iron-restricted litters were more severely anemic than the dams. At birth, body weight was lower in the offspring of iron-restricted dams than in controls and was still decreased at 3 months of age. At this same age, systolic blood pressure was significantly elevated in the offspring of iron-restricted dams. Glucose tolerance was improved in the maternal iron-restricted group. Fasting serum insulin levels were not different between the control and maternal iron-restricted groups. Fasting serum triglyceride was decreased in the offspring of iron-restricted dams compared with controls. Fasting serum cholesterol and free fatty acid concentrations were similar in both groups. These results suggest that maternal iron restriction has long-term effects on physiology and metabolism in the offspring. Some of these findings are comparable to those reported for the maternal protein-restriction model. It is thus speculated that the long-term effects of maternal dietary restriction may result from common fetal metabolic responses to this restriction.     

Relations of Plasma Polyunsaturated Fatty Acids With Blood Pressures During the 26th and 28th Week of Gestation in Women of Chinese,Malay, and Indian Ethnicity

Observational and intervention studies have reported inconsistent results of the relationship between polyunsaturated fatty acids (PUFAs) and hypertension during pregnancy. Here, we examined maternal plasma concentrations of n-3 and n-6 PUFAs between the 26th and the 28th week of gestation in relation to blood pressures and pregnancy-associated hypertension.We used data from a birth cohort study of 751 Chinese, Malay, and Indian women. Maternal peripheral systolic blood pressure (SBP) and diastolic blood pressure (DBP) were taken from the brachial arm, and central SBP and pulse pressures (PPs) were derived from radial artery pressure waveforms between the 26th and the 28th week of gestation. Pregnancy-associated hypertension (including gestational hypertension and preeclampsia) was ascertained from medical records. Plasma phosphatidylcholine n-3 and n-6 PUFAs were measured by gas chromatography and expressed as percentage of total fatty acids.Peripheral SBP was inversely associated with total n-3 PUFAs [−0.51 (95% confidence interval, CI, −0.89 to −0.13) mm Hg] and long-chain n-3 PUFAs [−0.52 (CI −0.92 to −0.13) mmHg]. Similar but weaker associations were observed for central SBP and PP. Dihomo-γ-linolenic acid was marginally positively associated with peripheral SBP, central SBP, and PP, whereas linoleic acid and total n-6 PUFAs showed no significant associations with blood pressures. We identified 28 pregnancy-associated hypertension cases, and 1% increase in total n-3 PUFAs was associated with a 24% lower odds of pregnancy-associated hypertension (odds ratio 0.76; 95% CI 0.60 to 0.97). Maternal ethnicity modified the PUFAs–blood pressure relations, with stronger inverse associations with n-3 PUFAs in Chinese women, and stronger positive associations with n-6 PUFAs in Indian women (P values for interaction ranged from 0.02 to 0.07).Higher n-3 PUFAs at midgestation are related to lower maternal blood pressures and pregnancy-associated hypertension in Asian women, and the ethnicity-related variation between PUFAs and blood pressures deserves further investigation.     

Third trimester binge ethanol exposure results in fetal hypercapnea and acidemia but not hypoxemia in pregnant sheep

BACKGROUND: The mechanisms by which maternal ethanol abuse during pregnancy causes neurodevelopmental injury in the fetus are not well understood. The purpose of this study was to use a chronically instrumented fetal sheep model system to determine if a binge pattern of ethanol exposure administered throughout the third trimester reduced fetal arterial partial pressure of oxygen (PaO2); a positive finding would support the hypothesis that fetal hypoxemia may play a role in mediating ethanol-related birth defects. METHODS: Pregnant ewes received saline or 0.75, 1.25, 1.5, or 1.75 g/kg of ethanol intravenously over 1 hr beginning on day 109 of gestation (term = 145 days) for 3 consecutive days per week followed by 4 days without exposure. The fetuses were surgically instrumented on day 113, and experiments were performed on days 118 or 132, the 6th and the 12th ethanol exposure, respectively. RESULTS: Ethanol infusions resulted in peak blood ethanol concentrations of 80.8 +/- 6.5, 182.5 +/- 13.5, 224.4 +/- 13.9, and 260.6 +/- 20.0 mg/dl +/- SEM (maternal) and 70.0 +/- 5.9, 149.7 +/- 9.0, 216.9 +/- 14.0, and 233.3 +/- 19.8 mg/dl +/- SEM (fetal) in response to the 0.75, 1.25, 1.5, and 1.75 g/kg doses, respectively. Maternal and fetal heart rate and maternal blood pressure increased whereas fetal blood pressure decreased in a dose-dependent manner in response to ethanol infusions. Maternal and fetal arterial pH decreased and arterial partial pressures of carbon dioxide increased in response to ethanol infusions. Maternal PaO2 decreased whereas fetal PaO2 did not change in response to ethanol infusions. CONCLUSIONS: A binge ethanol exposure paradigm, three consecutive days per week throughout the third trimester at ethanol doses that created blood ethanol concentrations commonly achieved by human ethanol abusers, resulted in changes in maternal and fetal heart rate, changes in blood pressure, hypercapnea, acidemia, and maternal, but not fetal, hypoxemia. We conclude that in an ovine model system, ethanol doses that create blood ethanol concentrations as high as 260 mg/dl do not result in fetal hypoxemia. Remaining issues to address with this model system are whether neurodevelopmental injuries that are associated with maternal ethanol abuse are mediated by a reduction in fetal cerebral blood flow, fetal hypercapnea, or acidemia.     

Maternal nutrition during gestation and blood pressure in later life

OBJECTIVE: To assess the link between maternal diet during pregnancy and blood pressure of the offspring. DESIGN: Follow-up study. SETTING: A university hospital in Amsterdam, The Netherlands. PARTICIPANTS: People born at term as singletons between November 1943 and February 1947. MAIN OUTCOME MEASURE: Blood pressure at adult age. RESULTS: Adult blood pressure was not associated with protein, carbohydrate or fat intake during any period of gestation. We found, however, after adjustment for sex that the systolic blood pressure decreased by 0.6 mmHg (0.1-1.1) for every 1% increase in protein/carbohydrate ratio in the third trimester. This association was present both in people who had been exposed to the famine during gestation as well as in those who had not been exposed. The association between protein/carbohydrate ratio in the third trimester and adult blood pressure was furthermore independent of maternal weight gain and final weight, and birth weight [increase for every 1% increase in protein/carbohydrate ratio 0.6 mmHg (0.0-1.2)]. Adjustment for adult characteristics such as body mass index, smoking and socio-economic status did not affect the observed association appreciably [adjusted increase 0.5 mmHg (0.0-1.0)]. CONCLUSION: Adult blood pressure seems to be affected by small variations in the balance of macro-nutrients in the maternal diet during gestation rather than by relatively large variations in the absolute amounts.     

Hypertension complicating diabetic pregnancies: pathophysiology, management, and controversies

Hypertensive disorders of pregnancy (HDP), including pre-existing hypertension, gestational hypertension, and preeclampsia, further complicate already high-risk pregnancies in women with diabetes mellitus (DM). Women with both pre-existing and gestational diabetes are at increased risk for HDP, leading to higher maternal and fetal morbidity. Further, particularly in diabetic women and women with a history of gestational diabetes, HDP significantly increases the risk for future cardiovascular events. For clinicians, women with hypertension and diabetes during pregnancy pose a management challenge. Specifically, preconception management should stress strict control of glycemia, blood pressure, and prevention of diabetic complications, specifically nephropathy, which specifically increases the risk for preeclampsia. During gestation, clinicians must be aware of potential maternal and fetal complications associated with various anti-hypertensive therapies, including known fetotoxicity of ACE inhibitors and ARBs when given in the 2nd or 3rd trimester, and the risks and benefits of expectant management versus delivery in cases of severe gestational hypertension or preeclampsia. Indeed, diabetic women must be followed closely prior to conception and throughout gestation to minimize the risk of HDP and its associated complications.     

Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis

ABSTRACT

Background: Conditions of excess androgen in women, such as polycystic ovary syndrome (PCOS), often exhibit intergenerational transmission. One way in which the risk for PCOS may be increased in daughters of affected women is through exposure to elevated androgens in utero. Hyperandrogenemic conditions have serious health consequences, including increased risk for hypertension and cardiovascular disease. Recently, gut dysbiosis has been found to induce hypertension in rats, such that blood pressure can be normalized through fecal microbial transplant. Therefore, we hypothesized that the hypertension seen in PCOS has early origins in gut dysbiosis caused by in utero exposure to excess androgen. We investigated this hypothesis with a model of prenatal androgen (PNA) exposure and maternal hyperandrogenemia by single-injection of testosterone cypionate or sesame oil vehicle (VEH) to pregnant dams in late gestation. We then completed a gut microbiota and cardiometabolic profile of the adult female offspring.

Results: The metabolic assessment revealed that adult PNA rats had increased body weight and increased mRNA expression of adipokines: adipocyte binding protein 2, adiponectin, and leptin in inguinal white adipose tissue. Radiotelemetry analysis revealed hypertension with decreased heart rate in PNA animals. The fecal microbiota profile of PNA animals contained higher relative abundance of bacteria associated with steroid hormone synthesis, Nocardiaceae and Clostridiaceae, and lower abundance of Akkermansia, Bacteroides, Lactobacillus, Clostridium. The PNA animals also had an increased relative abundance of bacteria associated with biosynthesis and elongation of unsaturated short chain fatty acids (SCFAs).

Conclusions: We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function.     

Sodium-blood pressure interrelationship in pregnancy

In non-pregnant individuals, a strong positive association of sodium intake with blood pressure has been established, but the relationship between sodium intake and blood pressure in human pregnancy remains obscure up to date. The aim of this prospective observational cohort study was to assess the relationship between urinary sodium excretion (as a measure for intake) and blood pressure from the early second trimester onwards throughout pregnancy. The study group consisted of 667 low-risk women with singleton pregnancies, of whom 350 were nulliparous and 317 parous. Blood pressure was measured in a standardised fashion at predetermined intervals from the first antenatal visit prior to 16 weeks gestation until delivery. Urinary sodium excretion was measured in 24-h urine collections on at least four occasions between 16 and 38 weeks gestation. Main outcome measures were the coefficients of correlation between changes in urinary sodium output and changes in blood pressure during six different gestational epochs. No significant correlations were found between changes in urinary sodium output and changes in blood pressure. Correlation coefficients were alike for nulliparous and parous women and for different gestational intervals. Prior to 32 weeks gestation, no differences were observed in sodium excretion between women who remained normotensive and those who developed gestational hypertension. These results suggest that changes in sodium intake are not associated with blood pressure changes in low-risk pregnant women. Blood pressure increases as observed in the second half of normotensive and hypertensive pregnancies are unlikely to be caused by changes in renal sodium handling.     

Risk of Pregnancy-Related Hypertension Within 5 Years of Exposure to Drinking Water Contaminated With Escherichia coli O157:H7

J Clin Hypertens(Greenwich). 2010;12:613–620. © 2010 Wiley Periodicals, Inc. The authors evaluated the risk for pregnancy-related hypertension among previously healthy women who conceived within 5 years of exposure to drinking water contaminated with Escherichia coli O157.H7 in Walkerton, Canada (2000). Chronic hypertension was defined as systolic/diastolic blood pressure ≥140/90 mm Hg before 20 weeks gestation; gestational hypertension was defined as new onset systolic/diastolic blood pressure ≥140/90 mm Hg ≥20 weeks gestation. The incidence of hypertension was compared between women who were asymptomatic during the outbreak to those who experienced acute gastroenteritis. Blood pressure data were available for 135 of 148 eligible pregnancies. The adjusted relative risks for chronic and gestational hypertension were 1.5 (95% confidence interval [CI]: 0.3–7.7) and 1.0 (95% CI: 0.4–2.5), respectively. Mean arterial pressure before 20 weeks gestation was 2.7 mm Hg higher in women who had acute gastroenteritis (95% CI: 0.05–5.4). A trend toward higher chronic hypertension and mean arterial pressure in early pregnancy was observed among women who experienced gastroenteritis after exposure to bacterially-contaminated drinking water.     

Programmed hypertension: kidney, brain or both?

The results from numerous epidemiological studies suggested that there was a link between low birth weight (low for gestational age) and development of high blood pressure in adulthood. More recently, it has been shown that one important determinant is the early exposure of the developing fetus to excess glucocorticoid (GC). Hypertension develops in adult sheep and rats that are exposed to excess GC at a stage in gestation when both kidney and brain are still extremely primitive organs. Here, we propose that permanent changes in gene expression and function of these two organs could be crucial in the development of adult-onset hypertension as a result of prenatal GC exposure.     

Maternal educational level and risk of gestational hypertension: the Generation R Study

We examined whether maternal educational level as an indicator of socioeconomic status is associated with gestational hypertension. We also examined the extent to which the effect of education is mediated by maternal substance use (that is smoking, alcohol consumption and illegal drug use), pre-existing diabetes, anthropometrics (that is height and body mass index (BMI)) and blood pressure at enrollment. This was studied in 3262 Dutch pregnant women participating in the Generation R Study, a population-based cohort study. Level of maternal education was established by questionnaire at enrollment, and categorized into high, mid-high, mid-low and low. Diagnosis of gestational hypertension was retrieved from medical records using standard criteria. Odds ratios (OR) of gestational hypertension for educational levels were calculated, adjusted for potential confounders and additionally adjusted for potential mediators. Adjusted for age and gravidity, women with mid-low (OR: 1.52; 95% CI: 1.02, 2.27) and low education (OR: 1.30; 95% CI: 0.80, 2.12) had a higher risk of gestational hypertension than women with high education. Additional adjustment for substance use, pre-existing diabetes, anthropometrics and blood pressure at enrollment attenuated these ORs to 1.09 (95% CI: 0.70, 1.69) and 0.89 (95% CI: 0.50, 1.58), respectively. These attenuations were largely due to the effects of BMI and blood pressure at enrollment. Women with relatively low educational levels have a higher risk of gestational hypertension, which is largely due to higher BMI and blood pressure levels from early pregnancy. The higher risk of gestational hypertension in these women is probably caused by pre-existing hypertensive tendencies that manifested themselves during pregnancy.     

Fetal associative learning mediated through maternal alcohol intoxication

BACKGROUND: The aim of the present study was to analyze whether alcohol as an unconditioned stimulus is capable of supporting associative learning in near-term fetuses. METHODS: In experiment 1, we determined pharmacokinetic profiles of alcohol and of an aromatic substance (cineole) in amniotic fluid and maternal blood during late gestation. The results obtained through gas chromatographic analysis allowed a second experiment in which we explicitly paired peak levels of cineole with peak levels of alcohol in amniotic fluid and blood, by intragastrically administering cineole and ethanol to the dams during gestational days 17 through 20 (paired condition). Control groups were dams given cineole 4 hr before commencement of an acute state of alcohol intoxication (long-delay group) or were only exposed to water administrations (water control group). The progeny were evaluated during postnatal day 16 in terms of behavioral responsiveness to intraorally infused solutions (cineole or alcohol presented in milk vehicle, or milk alone). RESULTS: Mouthing responsiveness to cineole was strongly affected by the nature of prenatal treatments. Pups in the paired prenatal condition mouthed significantly less than did long-delay and water controls. Physical and behavioral measures allowed us to reject the possibility that these effects were due to teratogenic effects of alcohol during late gestation. CONCLUSIONS: These results indicate that before birth, rat fetuses are capable of acquiring associative memories supported by the unconditioned properties of alcohol. This associative memory can be expressed during infancy through a significant reduction in mouth movements in the presence of the specific orosensory cue explicitly paired with alcohol interoceptive effects in utero.     

Effect of Maternal Ethanol Consumption on Maternal and Fetal Calcium Metabolism

Alcohol consumption can have deleterious effects on both adult and developing bone. The mechanism(s) by which alcohol affects bone, however, is unknown. This study investigated the possibility that alcohol affects bone by alterations in calcium (Ca) metabolism. Female rats were fed lab chow ad libitum (C, Control) or a liquid diet with (E, Ethanol) or without (PF, Pair-Fed) ethanol. After 2 weeks on their respective diets, the rats were bred and the experimental diets continued throughout gestation. Blood (dams only) and tissue were collected on day 21 of gestation. The Ca content of maternal bone showed a trend toward a decrease in E and PF compared with C dams. Ionic Ca (iCa) levels were decreased in the blood of the E compared with PF and C dams. Serum parathyroid hormone levels were elevated in the E compared with C dams, consistent with the low iCa levels. Serum levels of 1,25(OH)₂D, however, were elevated only in the PF dams. Mean fetal body weight and fetal skeletal ossification were reduced in the E compared with PF and C groups, but no group differences were found in fetal Ca content. These results indicate that maternal ethanol consumption compromised the ability of the dam to regulate her blood iCa levels, possibly partly due to a failure to increase 1,25(OH)₂D levels. The delays in skeletal development observed in the ethanol exposed fetuses, however, do not appear to result from impaired placental Ca transfer.     

The relationship between gestational age, systolic blood pressure and pulse pressure in children

This cross-sectional study investigates the relationship between gestational age and systolic blood pressure and pulse pressure in childhood. Blood pressure was measured in 483 schoolchildren, free from cardiovascular disease, aged between 6 and 16 years. Pulse pressure was estimated as the difference between the 24-h mean systolic and diastolic blood pressure values. Linear regression showed an inverse relationship between gestational age and mean 24-h systolic blood pressure (adjusted regression coefficient mm Hg per week gestation -0.631, 95% confidence interval (CI) -1.21 to -0.04, P=0.036). Further, linear regression showed a significant negative association between gestational age and log-transformed pulse pressure (adjusted antilog regression coefficient mm Hg per week of gestation -1.39, 95% CI -2.96 to -0.3, P=0.013), which after gender-specific analyses was found to be restricted to the girls in the study. The results of the present study suggest that low gestational age is associated with elevated systolic blood pressure and pulse pressure in childhood, the latter particularly in girls. This observation provides some support for the developmental origins of adult disease hypothesis-that adverse events in early life may have long-term consequences for cardiovascular health. However, as gestational age itself is unlikely to be the causal event in determining blood pressure control, further investigation is required, particularly with regard to the nutritional, physiological and molecular mechanisms that explain such epidemiological observations.     

Effects of Ethanol on Reproduction and Arterial Hypertension in Spontaneously Hypertensive and Normotensive Rats: a Preliminary Communication

Ethanol consumption and spontaneous (essential) hypertension are important fetal and maternal risk factors. Alone, they contribute to embryopathy (fetal alcohol syndrome) or maternal organ pathology and fetal loss in hypertensive pregnancies. Combined, the effects of ethanol consumption on the progress of a hypertensive pregnancy have not been adequately investigated. In the present study, groups of O-A strain genetic hypertensive (SHR: groups 1 and 2) and Wistar-Kyoto normotensive (WKY: groups 3 and 4) pregnant rats were given 20 ml/kg of distilled water by gavage to serve as controls [groups 1 (SHR) and 3 (WKY)] or 3.2 g/kg of ethanol [groups 2 (SHR) and 4 (WKY)] from days 6 to 15 of gestation. During acclimation, hypertension developed in SHR rats (WKY pressures were 105 to 114 mm Hg; SHR pressures were 137 to 148 mm Hg). From day 6 to 15 of gestation, ethanol-consuming rats (groups 2 and 4) had higher arterial pressures than controls (groups 1 and 3). Pregnant SHR rats given ethanol did not experience a prebirthing hypotension. On gestation day 20, most offspring (84%, group 2; 86%, group 4) of alcoholic dams were dead or malformed. Intrauterine growth retardation occurred in group 4. Hydrocephalus, microphthalmia, and mild hydronephrosis and hydroureter were common in live offspring of group 2 dams. Hydronephrosis and hydroureter were increased in group 4 pups. Variant cranial ossification was noted in group 2 and 4 pups. These preliminary data suggest an altered hypertensive response during pregnancy in alcohol-consuming rats and confirm the embryopathic effects of relatively high levels of ethanol consumed during the critical period of organogenesis in two additional strains of rats.     

Prenatal dexamethasone programs hypertension and renal injury in the rat

Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.     

Blood pressure in the child and the adolescent. Effect of age, sex, height, weight and heart rate

6,391 school children in the department of Seine-Saint-Denis were studied to determine the normal limits of blood pressure, its variations with age and sex, and its correlations with height, weight and heart rate. Blood pressure has a nearly perfect Gaussian distribution. Average blood pressures increase linearly with age according to sex. Boys have higher systolic blood pressures after the age of 14 and higher diastolic blood pressures after the age of 16. The estimated incidence of hypertension was 3,1% systolic hypertension and 2.2% diastolic hypertension. There was a very close relationship between systolic and diastolic blood pressure. Average systolic and diastolic blood pressures increased very significantly with height and weight, in both sex. Heart rate decreased with age. The average blood pressure was not related to heart rate. Blood pressure charts, related to age, sex, height and weight, allow follow-up of arterial blood pressure as children grow up and may lead to a better understanding of the mechanism of hypertension.