The Declaration of Helsinki, adopted by the World Medical Association's General Assembly in 1964, is the most important set of guidelines about research on human participants. It both reflects and shapes the ethos of international research ethics. It is a living instrument and is reviewed and revised regularly. Its latest revision was in 2013. There are four substantial changes, reflected in the new Paragraph 15 (which deals with compensation for trial related injuries), Paragraph 33 (relating to placebos), Paragraph 20 (relating to vulnerable groups) and the new Paragraph 34 (relating to post-trial provisions). This article analyses these changes, and asks whether they indicate any shift in the overall philosophy of the Declaration. We conclude that these changes, though significant, are not tectonic. They accord with the spirit that has motivated the Declaration through all its iterations, and indicate a steady, incremental evolution towards a holistic code of research ethics for research on human participants. Patient autonomy, though crucial, is no longer the only concern of the Declaration; distributive justice and beneficence are motivating forces too. While the Declaration is aware of the need to facilitate research, it is equally aware of the need to protect the vulnerable, and of the practical difficulties involved in that protection.

The occurrence of IUGR increased with low maternal and cord concentrations of folate and high maternal levels of tHcy. Further studies on the effects of vitamin B supplementation through pregnancy are warranted.

Although intrauterine growth retardation (IUGR) is a major risk factor for increased neonatal mortality and morbidity, the mechanisms behind it are not clear. We analyzed cytokine gene expression and gene polymorphisms in infants with and without IUGR in Pakistan, where IUGR is very common. 45 IUGR and 55 control mother/infant pairs were studied. mRNA for IL-10, IL-8, TNF-␣, TGF-␤, IL-6, IL-4, IL-1␤, IL-12, IFN-␥ and GAPDH was quantified with RT-PCR from placenta. Cytokine and cytokine receptor gene polymorphisms for -1087IL10, -308TNFA, -174IL6, ϩ915TGFB1, intron 2 IL1RN, ϩ36TNFR1, 150V IL4RA and -159CD14 were determined from genomic DNA. The serum levels of IL-1␤, IL-6, IL-8, IL-10, IL-12, TNF-␣ and TGF-␤ were measured.There was a significant decrease of IL-10 and IL-12, but increase of TGF-␤ in the decidua and similarly decrease of IL-10, but increase of TGF-␤ in the trophoblasts of the IUGR placentas compared with the non-IUGR placentas. We found significantly lower levels of IL-1␤ in serum from the mothers of the IUGR infants and of TGF-␤ in serum of the infants with IUGR compared with the non-IUGR infants. We note that the IL-10 mRNA expression in the decidua was down-regulated, but the TGF-␤ mRNA up-regulated in IUGR placentas of mothers from a population with multiple risk factors for IUGR. We propose that the low IL-10 in the placenta may be involved in the pathogenesis of IUGR and might possibly be treatable. (Pediatr Res 59: 254-258, 2006)

The occurrence of IUGR increased with low maternal and cord concentrations of folate and high maternal levels of tHcy. Further studies on the effects of vitamin B supplementation through pregnancy are warranted.