Background Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. Methods The educational and medical records of all children born to mothers residing in five townships of Olmsted County, MN from 1976-1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). Results Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia N=193, and regional anesthesia N=304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia prior to age 4, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P=0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). Conclusion Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.

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We previously reported that hypoxia-mediated reductions in α-adrenoceptor sensitivity do not explain the augmented vasodilatation during hypoxic exercise, suggesting an enhanced vasodilator signal. We hypothesized that β-adrenoceptor activation contributes to augmented hypoxic exercise vasodilatation. Fourteen subjects (age: 29 ± 2 years) breathed hypoxic gas to titrate arterial O 2 saturation (pulse oximetry) to 80%, while remaining normocapnic via a rebreath system. Brachial artery and antecubital vein catheters were placed in the exercising arm. Under normoxic and hypoxic conditions, baseline and incremental forearm exercise (10% and 20% of maximum) was performed during control (saline), α-adrenoceptor inhibition (phentolamine), and combined α-and β-adrenoceptor inhibition (phentolomine/propranolol). Forearm blood flow (FBF), heart rate, blood pressure, minute ventilation, and end-tidal CO 2 were determined. Hypoxia increased heart rate (P < 0.05) and minute ventilation (P < 0.05) at rest and exercise under all drug infusions, whereas mean arterial pressure was unchanged. Arterial adrenaline (P < 0.05) and venous noradrenaline (P < 0.05) were higher with hypoxia during all drug infusions. The change (Δ) in FBF during 10% hypoxic exercise was greater with phentolamine (Δ306 ± 43 ml min −1 ) vs. saline (Δ169 ± 30 ml min −1 ) or combined phentolamine/propranolol (Δ213 ± 25 ml min −1 ; P < 0.05 for both). During 20% hypoxic exercise, ΔFBF was greater with phentalomine (Δ466 ± 57 ml min −1 ; P < 0.05) vs. saline (Δ346 ± 40 ml min −1 ) but was similar to combined phentolamine/propranolol (Δ450 ± 43 ml min −1 ). Thus, in the absence of overlying vasoconstriction, the contribution of β-adrenergic mechanisms to the augmented hypoxic vasodilatation is dependent on exercise intensity.

T he impact of obstetric anesthesia on short and long-term behavior and development of a neonate/child is not thoroughly understood. In animal studies, exposure of fetuses/neonates to anesthetics administered to the mother causes histopathologic changes in the brain; even single, relatively brief administrations may be associated with a diminished capacity to retain learned behavior and/or abnormal behaviors resembling autism. The significance of this in humans is not clear, but the authors of this study recently showed that repeated (not single) exposures to anesthesia before the age of 4 years may double the risk of learning disabilities (LD) in a child. Using data from the same population-based birth cohort, they examined the possible association between fetal exposure to anesthesia during cesarean delivery (CS) and the subsequent development of LD in the child.Records of all children born in Rochester, Minnesota, between January 1, 1976 and December 31, 1982 to women living in one county school district (n = 8548) were reviewed. Those still living in the district at 5 years of age (n = 5718) were identified for the cohort. School, medical, and Reading Center/ Dyslexia Institute records were used to identify those with a potential LD [n = 1510 (26%)]. Finally, children meeting criteria based on standard measures of intelligent quotient and/or achievement within the same calendar year and before the age of 19 years having at least 1 of 3 LD (reading, written language, and math disorders) were considered cases.From the total possible subjects, exclusion of 19 children with severe mental retardation and 379 with authorization issues left the cohort with 5320 children; 4823 (90.7%) delivered vaginally, 193 (3.6%) by CS with general anesthesia (most including sodium thiopental, nitrous oxide, and potent inhalational anesthetics), and 304 (5.7%) by CS with regional anesthesia. Mean exposures to anesthetics were: epidural, 63.5 minutes; spinal, 21 minutes; and general, 14 minutes. Among 921 (17.3%) actual LD cases, incidence for children whose mothers delivered vaginally was 20.8% versus 19.4% for children delivered through CS with general anesthesia and 15.4% for children born through CS with regional anesthesia. With unadjusted proportional hazard regression, the incidence of LD was not increased in children born through CS compared with those born through vaginal delivery (overall, P = 0.135). However, after adjusting for risk factors for LD, the data suggested the risk of LD may be decreased in children delivered through CS under regional anesthesia compared with those delivered vaginally. The authors concluded that these results suggest that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopment. As children born by CS under regional anesthesia had a lower incidence of LD than the other 2 groups, they hypothesize that regional anesthesia for CS may attenuate the neonatal stress response to delivery sufficiently to have significant effects on later neural development. Li...

Normotensive adults homozygous for glycine (Gly) of the Arg16/Gly beta2-adrenergic-receptor polymorphism have 1) greater forearm beta2-receptor mediated vasodilation and 2) a higher heart rate (HR) response to isometric handgrip than arginine (Arg) homozygotes. To test the hypothesis that the higher HR response in Gly16 subjects serves to maintain the pressor response [increased cardiac output (CO)] in the setting of augmented peripheral vasodilation to endogenous catecholamines, we measured continuous HR (ECG), arterial pressure (Finapres), and CO (transthoracic echocardiography) during isometric, 40% submaximal handgrip to fatigue in healthy subjects homozygous for Gly (n = 30; mean age +/- SE: 30 +/- 1.2, 13 women) and Arg (n = 17, age 30 +/- 1.6, 11 women). Resting data were similar between groups. Handgrip produced similar increases in arterial pressure and venous norepinephrine and epinephrine concentrations; however, HR increased more in the Gly group (60.1 +/- 4.3% increase from baseline vs. 45.5 +/- 3.9%, P = 0.03), and this caused CO to be higher (Gly: 7.6 +/- 0.3 l/m vs. Arg: 6.5 +/- 0.3 l/m, P = 0.03), whereas the decrease in systemic vascular resistance in the Gly group did not reach significance (P = 0.09). We conclude that Gly16 homozygotes generate a higher CO to maintain the pressor response to handgrip. The influence of polymorphic variants in the beta2-adrenergic receptor gene on the cardiovascular response to sympathoexcitation may have important implications in the development of hypertension and heart failure.