Pregnancy outcome following maternal use of zanamivir or oseltamivir during the 2009 influenza A/H1N1 pandemic: a national prospective surveillance study.

OBJECTIVE: To conduct enhanced surveillance for signals of teratogenesis following use of the neuraminidase inhibitors zanamivir and oseltamivir in the treatment or post-exposure prophylaxis of 2009 A/H1N1 influenza during pregnancy. DESIGN: Prospective cohort study, using national surveillance data collected by the UK Teratology Information Service (UKTIS) during the 2009 A/H1N1 pandemic. SETTING: United Kingdom. POPULATION: Pregnant women who were reported to UKTIS by healthcare professionals seeking advice about exposure to zanamivir and oseltamivir or to other non-teratogenic drugs. METHODS: Pregnancy outcomes were collected for prospectively reported pregnancies exposed to zanamivir (n = 180) or oseltamivir (n = 27), and compared with a reference group of 575 prospectively reported pregnancies exposed to non-teratogenic drugs over the same period. MAIN OUTCOME MEASURES: Rates of major congenital malformation, preterm delivery and low birth weight. RESULTS: No significant differences in overall rates of major malformation in live-born infants [adjusted odds ratios (aOR): zanamivir 0.37 (95% confidence interval 0.02-2.70); oseltamivir aOR 0.81 (0.05, 14.15)], preterm delivery [aOR: zanamivir 0.95 (0.45, 1.89); oseltamivir aOR 1.68 (0.38, 5.38)] or low birth weight [aOR: zanamivir 0.94 (0.25, 2.90); oseltamivir aOR 4.12 (0.59, 17.99)] were observed following exposure at any gestation. No major malformations were reported in 37 zanamivir or eight oseltamivir first trimester exposures. CONCLUSION: These surveillance data do not provide a signal that use of zanamivir or oseltamivir in pregnancy is associated with an increased risk of the adverse pregnancy outcomes studied but the data are too limited to state conclusively that there is no increase in risk.

Angiotensin-converting enzyme inhibition in adult hypertensive rats: a stereological study of renal filtration surface area.

1. Angiotensin-converting enzyme (ACE) inhibitor treatment leads to beneficial effects on kidney function. The aim of the present study was to determine whether ACE inhibition at high or low doses affects glomerular capillary surface area and length, glomerular number or total renal filtration surface area in rats with established hypertension and, if so, to determine whether these effects are mediated through bradykinin potentiation. 2. Spontaneously hypertensive rats (SHR) were treated with the ACE inhibitor perindopril at either 3 or 0.1 mg/kg per day (high and low doses, respectively) from 16 to 24 weeks of age. Some rats were concomitantly treated with the bradykinin B2 receptor antagonist S16118 (10 nmol/kg per day). Blood pressure was measured twice weekly during the treatment period. At 24 weeks of age, rats were perfusion fixed at 140 mmHg, the kidneys removed, embedded in resin and examined stereologically to estimate glomerular number and volume, length and surface area of glomerular capillaries and total renal filtration surface area. 3. High- and low-perindopril treatment significantly reduced systolic blood pressure compared with control SHR. However, the rats treated with low-dose perindopril were still considered hypertensive. Neither low-dose nor high-dose perindopril treatment had any observable effect on glomerular number (23 876 +/- 1201 vs 26 240 +/- 1465 glomeruli/kidney, respectively) or volume (2.25 +/- 0.21 and 1.96 +/- 0.06 x 10-3 mm3, respectively) compared with controls (glomerular number 25866 +/- 1210 glomeruli/kidney; glomerular volume 2.24 +/- 0.21 x 10-3 mm3). As a result, there was no significant difference in total renal filtration surface area between any of the experimental groups (8161.6 +/- 550.9, 8699.7 +/- 427.6, 9081.9 +/- 453.6, 8830.2 +/- 521.2 and 8559.4 +/- 341.4 mm2 for SHR, SHR low-dose perindopril, SHR low-dose perindopril + B2 antagonist, SHR high-dose perindopril and SHR high-dose perindopril + B2 antagonist, respectively). Coadministration of the bradykinin antagonist had no observable effect on any of the parameters studied. 4. In conclusion, because neither high-dose nor low-dose perindopril had any effect on total renal filtration surface area, the observed beneficial effects of ACE inhibition on kidney function are not the result of enhancement in glomerular capillary surface area.

Effect of angiotensin-converting enzyme inhibition on renal filtration surface area in hypertensive rats.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor treatment leads to protective effects on the cellular structure of the glomerulus and the kidney. The aim of this study was to determine whether ACE inhibition increases renal filtration surface area in the spontaneously hypertensive rat (SHR). METHODS: SHR were treated with the ACE inhibitor perindopril at a high dose (3 mg/kg/day) or a low dose (0.1 mg/kg/day) during the period of hypertension development, from 7 to 14 weeks of age. Some animals were treated concomitantly with the bradykinin B2 receptor antagonist, S16118. Tail-cuff systolic blood pressure and body weights were measured twice weekly. At termination of treatment, glomerular number and volume, length, and surface area of glomerular capillaries and renal filtration surface area were estimated using unbiased stereological techniques. RESULTS: There were significant dose-related reductions in blood pressure with high- and low-dose perindopril treatment. Neither low- nor high-dose perindopril treatment had any effect on glomerular number or size or glomerular capillary length and surface area. Hence, there was no significant difference in total renal filtration surface area between any of the experimental groups (8721 +/- 610 mm2 in untreated SHR and 7879 +/- 338 mm2 and 8767 +/- 437 mm2 in the low and high dose perindopril-treated groups, respectively). Coadministration of the bradykinin antagonist did not affect any of the glomerular parameters. CONCLUSIONS: ACE inhibition during the period of hypertension development does not lead to an enhanced glomerular capillary growth or increases in total renal filtration surface area in this model.