Helena Martin

Impaired Endothelial Function and Increased Carotid Stiffness in 9-Year-Old Children With Low Birthweight

BackgroundLow birthweight (LBW) has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and loss of arterial elasticity are early markers of hypertension and atherosclerosis. We studied the prevalence of these markers in 44 healthy, prepubertal (age 9±1.3 years) children, 22 with LBW for age. Methods and ResultsEndothelial function in skin was tested with the local application of acetylcholine (inducing endothelium-dependent vasodilation) and nitroglycerin (endothelium-independent vasodilation), and local perfusion changes were measured with the laser Doppler method. The elastic properties of the abdominal aorta and common carotid artery were measured with an ultrasonic vessel-wall tracking system. Endothelium-dependent vasodilation was lower in children with LBW (88±33 perfusion units [PU]) than in normal-birthweight controls (133±34 PU, P <0.001). There was no difference in aortic or carotid elasticity between the 2 groups, but a negative correlation was found between birthweight and stiffness of the carotid artery wall (r =−0.45, P <0.01). Endothelium-independent vasodilation and blood pressure were similar in the 2 groups. ConclusionsSchoolchildren with a history of LBW show impaired endothelial function and a trend toward increased carotid stiffness. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

Preterm birth contributes to increased vascular resistance and higher blood pressure in adolescent girls.

Preterm birth might induce permanent changes in vascular structure and function as well as in blood pressure. To elucidate this hypothesis and underlying mechanisms in girls born before term, the authors correlated neonatal data, including estradiol levels, with vascular function and structure and with blood pressure after puberty. In a case-control study design, 34 girls born before term and 32 gender- and age-matched control infants born at term were included. Pulse wave analysis was used to determine aortic pressure profiles and overall arterial compliance. Stiffness of the carotid artery and abdominal aorta was measured with ultrasonography. Pulse wave velocity in the forearm was measured with photoplethysmography. A laser Doppler technique was used to determine skin perfusion before and after transdermal delivery of acetylcholine, an endothelium-dependent vasodilator. It was found that preterm girls had significantly higher brachial and aortic blood pressure, a narrower but less stiff abdominal aorta, and lower peripheral skin blood flow than did control infants. Augmentation index, carotid stiffness, pulse wave velocity, endothelium-dependent vasodilatation, and heart rate were similar in the two groups. In the preterm group, blood pressure and vascular functions showed no association with intrauterine growth retardation or neonatal estradiol levels. In conclusion, preterm girls have higher blood pressure and an increased resistance in the vascular tree after puberty. These findings may have implications for future cardiovascular risk in the growing adult population surviving preterm birth.

Intrathecal sufentanil, fentanyl, or placebo added to bupivacaine for cesarean section

We compared the effects of intrathecal sufentanil 2.5 and 5 micro g, fentanyl 10 micro g, and placebo when administered together with hyperbaric bupivacaine 0.5% 12.5 mg for cesarean section. The study was performed in a randomized, double-blind fashion in 80 (20 per group) healthy, full-term parturients presenting for elective cesarean section. Postoperative pain was assessed using the visual analog scale (VAS). Duration of complete analgesia was defined as the time from the intrathecal injection to VAS score >0. Duration of effective analgesia was defined as the time to VAS score >or=to4. No patient experienced intraoperative pain. Complete analgesia was prolonged in all groups receiving opioids. Effective analgesia was prolonged and the 0- to 6-h intravenous opioid requirements were lower in the groups receiving sufentanil compared with those receiving fentanyl and placebo. The need for intraoperative antiemetic medication was greater in the placebo group. Pruritus was a frequent and dose-related side effect in the groups receiving sufentanil. There were no differences in umbilical cord blood gases or neonatal Apgar scores and neurological and adaptive capacity scores among the groups. In conclusion, the addition of sufentanil or fentanyl improved the quality of subarachnoid block compared with placebo. The duration of action was longer for sufentanil than fentanyl. Implications: Small doses of fentanyl or sufentanil (synthetic opioids) added to bupivacaine (local anesthetic) for spinal anesthesia for cesarean section reduce the need for intraoperative antiemetic medication and increase the duration of analgesia in the early postoperative period compared with placebo. (Anesth Analg 1997;85:1288-93)

Impaired acetylcholine-induced vascular relaxation in low birth weight infants: implications for adult hypertension?

Low birth weight is associated with an increased risk of adult hypertension. To elucidate whether this association reflects altered vascular physiology already at birth, we studied acetylcholine-induced vasodilation. Forty newborn infants and their mothers were studied 3 d after delivery. Vasodilation in skin was induced by local application of acetylcholine and local heating to 44°C. Perfusion changes were measured with the laser Doppler technique. In response to acetylcholine, the mean skin perfusion increased by 240% in low birth weight infants compared with 650% in normal birth weight controls (p < 0.001). In contrast, mothers of low birth weight infants showed a mean increase in perfusion of 1100% after acetylcholine administration compared with 680% in mothers of control infants (p < 0.05). The perfusion increase at 44°C local skin temperature did not differ between the two groups of infants or between their mothers. Blood pressure was normal in all subjects. We conclude that low birth weight infants show signs of endothelial dysfunction at birth. Such findings may help us understand the link between low birth weight and adult hypertension.

Folate, vitamin B12, and homocysteine levels in South Asian women with growth- retarded fetuses

Objective.  To investigate whether intrauterine growth retardation (IUGR) and preterm delivery in a poor population of South Asia was associated with altered maternal and fetal levels of folate, vitamin B12, and homocysteine.

Preterm Birth Attenuates Association Between Low Birth Weight and Endothelial Dysfunction

Background—Low birth weight predisposes to later coronary disease. To further elucidate the mechanisms behind this association and their timing, vascular endothelial function—a key factor in early pathophysiology of atherosclerosis—was studied in 54 infants born either before the third trimester or at term. Methods and Results—All subjects were studied at 3 months of postnatal age. A laser-Doppler technique was used to measure skin perfusion before and after transdermal iontophoresis of acetylcholine (ACh; an endothelium-dependent vasodilator). In infants born at term (n=19; birth weight range: 2230 to 4205 g), maximum perfusion after ACh was 109±8 perfusion units (PU, mean±SEM) in normal–birth weight controls compared with 56±13 PU among those who had been small for gestational age at birth (P <0.01). In infants born preterm (n=35; birth weight range, 722 to 1868 g), ACh induced similar perfusion responses among subjects appropriate for gestational age (113±16 PU) and in those small for gestational age at birth (109±19 PU). Conclusions—Impairment in human endothelial function associated with low birth weight occurs or emerges late in pregnancy. Very preterm birth attenuates this association. Different gene–environment interactions in the third trimester may contribute to this finding.

Lower skin capillary density, normal endothelial function and higher blood pressure in children born preterm

Abstract.  Bonamy A‐KE, Martin H, Jörneskog G, Norman M (Karolinska Institutet, Stockholm, Sweden). Lower skin capillary density, normal endothelial function and higher blood pressure in children born preterm. J Intern Med 2007; 262: 635–642.

Endothelial Function in Newborn Infants Is Related to Folate Levels and Birth Weight

OBJECTIVE. Low maternal folate levels during pregnancy correlate with low birth weight, a perinatal risk factor for later cardiovascular disease. We studied relationships between red blood cell folate levels, birth weight, and vascular endothelial function (a key factor in the early pathophysiologic processes of heart disease) in newborn infants. METHODS. We included 82 infants (30 low birth weight) and their mothers. A laser Doppler technique was used to measure skin perfusion during transdermal iontophoresis of acetylcholine (an endothelium-dependent vasodilator). Red blood cell folate, vitamin B12, and homocysteine levels were determined. RESULTS. The perfusion response to acetylcholine was lower in low birth weight infants than in normal birth weight control subjects (mean: 35 vs 76 perfusion units). The neonatal acetylcholine response correlated with red blood cell folate levels in both infants and their mothers. The folate levels of low birth weight and control infants did not differ significantly (mean: 1603 vs 1795 nmol/L), but mothers of low birth weight infants had lower folate levels than did mothers of control infants (mean: 805 vs 1109 nmol/L). In multivariate analysis, low birth weight and red blood cell folate levels contributed independently to endothelial function in newborn infants. The levels of vitamin B12 and homocysteine were similar in the 2 groups and did not correlate with endothelial function. CONCLUSION. The data presented here provide the first evidence for a relationship between folate levels and vascular endothelial function in newborn infants.

Preterm birth and carotid diameter and stiffness in childhood

Background and Aim: Low birthweight, either as a result of poor foetal growth or preterm birth, is a risk factor for stroke in adult life. Carotid stiffening, an early marker of atheromatous disease, has been found in low‐birthweight children born at term. We hypothesized that carotid artery growth and dynamic properties are permanently affected by preterm birth.

Skin microcirculation before and after local warming in infants delivered vaginally or by caesarean section.

To elucidate early postnatal changes in skin microcirculation, term newborn infants were studied at 2,6 and 24 h after vaginal delivery (VD, n= 20) or elective caesarean section (CS, n= 10). Laser Doppler technique was used to measure perfusion, rhythmical perfusion changes, i.e. vasomotion, and reactive hyperaemia of the dorsal hand, before and after local warming of the skin to 37°C. The skin perfusion and the magnitude of reactive hyperaemia (mean 85%) remained essentially unchanged, while vasomotion increased from 0–5 to 2–8 cycles/min (p < 0.001) during the first day of life. Local warming of the skin promoted microcirculation slightly at 2 h and more markedly at 24 h postnatal age. The CS group showed a higher degree of skin perfusion, vasomotion and reactive hyperaemia than did VD infants at 2 h postnatal age. Our findings most likely reflect skin microcirculatory effects of birth‐related events, such as a drop in body temperature, sympathoadrenal activation and placental transfusion.