Medical Journal- Antenatal micronutrient supplements in Nepal

Publication date: 2005

Correspondence e-mail submissions to correspondence@lancet.com Antenatal micronutrient supplements in Nepal We have pooled the results of our two trials in the southern plains of Nepal,1,2 which examined the effect of maternal multiple micronutrient supplements on birthweight and other aspects of intra- uterine growth, and would like to report the potentially worrisome finding of an apparent association between multiple micronutrient supplementation and increased perinatal and neonatal death. The first trial1 randomised 4998 preg- nant women in Sarlahi district to receive one of five daily micronutrient supple- ments, including either a multiple micronutrient or an iron and folic acid (IFA) supplement, from early pregnancy to 3 months post partum. The second trial2 randomly allocated 1200 women at less than 20 weeks’ gestation who presented for antenatal care at Janakpur hospital to receive daily throughout pregnancy either an IFA supplement or a multiple micronutrient supplement of slightly different formulation from that used in Sarlahi. The primary outcome in both trials was birthweight assessed within 72 h of birth. In Sarlahi, mean birthweight was 64 g greater (95% CI 12–115) in the multiple micronutrient group than in the control group,1 and in Janakpur it was 77 g greater (24–130) in the multiple micronutrient group than in infants born to IFA-supplemented mothers.2 The respective relative risks for low birthweight (�2500 g) were 0·84 (0·74–0·99) and 0·75 (0·60–0·94). Maternal demographic and socioeco- nomic characteristics, and patterns of health-care use, varied across trial popu- lations: women from the entirely rural population of Sarlahi were older; of higher parity and lower socioeconomic standing with respect to education, asset ownership, and husband’s occu- pation; and less likely to have delivered in a health-care facility than women enrolled from the more urban setting in Janakpur. Despite these differences, baseline measurements of anthropo- metric and haematological status were similar across trials: participants were short, wasted, and prone to anaemia in both populations. Women in Janakpur weighed about 1·6 kg more and were nearly 5 weeks further along in gesta- tion at enrolment than those in Sarlahi. Within each trial, baseline characteristics were similar across randomised groups. In both trials, despite being associated with improved birthweight, multiple micronutrient supplementation was associated with a non-significant increase in perinatal mortality (stillbirths and neonatal deaths up to 7 days of age) and neonatal mortality (infant deaths up to 28 days of age) relative to groups that received IFA (table).2,3 The 95% CIs for the risk ratios in the individ- ual trials included unity, but once effect estimates from both trials were pooled, more stable relative risk estimates for each outcome emerged (table). Why antenatal micronutrient supple- mentation could increase the risk of perinatal mortality is unclear. Possibili- ties include differential effects on birth- weight across its distribution, with increased risk of asphyxia at the upper end,3 effects on uterine sensitivity to oxytocin,4,5 and increased survival of infants who might otherwise have suc- cumbed to stillbirth. It is unwise to generalise from our findings, since they arise from a pooled analysis of limited data. Policymakers are understandably interested to imple- ment interventions that improve health in countries where maternal undernutri- tion is common and is perpetuated by an intergenerational cycle of malnutri- tion which begins in utero. However, in the south Asian context, increased birthweight due to antenatal multiple micronutrient supplementation may not uniformly confer a survival benefit and may, on the basis of preliminary evi- dence from our two trials, increase mor- tality risk in some populations. Further investigation of the safety and efficacy of this intervention is urgently needed before broad policies are adopted in chronically undernourished south Asian populations. We declare that we have no conflict of interest. Parul Christian, David Osrin, Dharma S Manandhar, Subarna K Khatry, *Anthony M de L Costello, Keith P West Jr a.costello@ich.ucl.ac.uk Johns Hopkins Bloomberg School of Public Health, Department of International Health and Center for Human Nutrition, Baltimore, MD, USA (PC, KPW); International Perinatal Care Unit, Institute of Child Health, University College London, London WC1N 1EH, UK (DO, AMdeLC); Mother and Infant Research Activities, Kathmandu, Nepal (DSM); and Nepal Nutrition Intervention Project, Sarlahi, Nepal (SKK). 1 Christian P, Khatry SK, Katz J, et al. Effects of alternative maternal micronutrient supplements on low birth weight in rural Nepal: a double-blind randomized community trial. BMJ 2003; 326: 571–76. 2 Osrin D, Vaidya A, Shrestha Y, et al. Effects of antenatal multiple micronutrient supplementation on birthweight and www.thelancet.com Vol 366 August 27, 2005 711 Iron and folic acid Multiple micronutrients Relative risk Number Rate/1000 Number Rate/1000 (95% CI) Sarlahi Livebirths 773 ·· 872 ·· Stillbirths 29 36·2 47 51·1 ·· Perinatal deaths 50 62·3 80 87·0 1·40 (0·99–1·96) Neonatal deaths 28 36·2 47 53·9 1·49 (0·94–2·35) Janakpur Livebirths 550 ·· 556 ·· Stillbirths 18 31·7 15 26·3 ·· Perinatal deaths 23 40·5 28 49·0 1·21 (0·71–2·08) Neonatal deaths 11 20·0 17 30·6 1·53 (0·72–3·23) Combined Livebirths 1323 ·· 1428 ·· Stillbirths 47 34·3 62 41·6 ·· Perinatal deaths 73 53·3 108 72·5 1·36 (1·02–1·81) Neonatal deaths 39 29·5 64 44·8 1·52 (1·03–2·25) Table: Mortality outcomes by treatment group for individual studies and combined Correspondence gestational duration in Nepal: double-blind, randomised controlled trial. Lancet 2005; 365: 955–62. 3 Christian P, West KP Jr, Khatry SK, et al. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster- randomized trial in Nepal. Am J Clin Nutr 2003; 78: 1194–202. 4 Ninomiya-Alarcon JG, Hudson R, Reyes-Guerrero G, Barrera-Mera B, Guevara-Guzman R. Effect of photoperiod on the mechanical response of the pregnant rabbit uterus to oxytocin. Am J Physiol Regul Integr Comp Physiol 2004; 287: R174–80. 5 Ciosek J, Drobnik J. Vasopressin and oxytocin release and the thyroid function. J Physiol Pharmacol 2004; 55: 423–41. 712 www.thelancet.com Vol 366 August 27, 2005 American Psychological Association, 750 First Street NE, Washington, DC 20002, USA 1 Wilks M. A stain on medical ethics. Lancet 2005; 366: 429–31. 2 American Psychological Association. Report of the Presidential Task Force on Psychological Ethics and National Security. http://www.apa. org/releases/PENSTaskForceReportFinal.pdf (accessed Aug 10, 2005). resections4 shows very similar results to those of the CLASICC and COST trials (mortality 4·8%, conversion rate 20%). With the extension of the learning curve shown in the CLASICC trial, and indeed in our own experience, laparo- scopic surgery for rectal cancer with careful selection using MRI may result in similar outcomes to those seen in laparoscopically assisted colon cancer surgery. There do not seem to be suffi- cient data from the CLASICC trial to sug- gest otherwise. We declare that we have no conflict of interest. *T H A Arulampalam, R C T Austin, R W Motson laptan1@yahoo.co.uk Department of Minimal Access Surgery, Colchester General Hospital, Turner Road, Colchester CO4 5JL, UK 1 Guillou PJ, Quirke P, Thorpe H, et al. Short-term endpoints of conventional versus laparoscopic- assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet 2005; 365: 1718–26. 2 Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med 2004; 350: 2050–59. 3 Harinath G, Shah PR, Haray PN, Foster ME . Laparoscopic colorectal surgery in Great Britain and Ireland—where are we now? Colorectal Dis 2005; 7: 86–89. 4 Arulampalam THA, Austin RCT, Motson RW. Training the laparoscopic colorectal surgeon—a novel approach. European Association of Endoscopic Surgeons Annual Meeting; Venice, Italy; June 1–4, 2005. A stain on medical ethics In his Comment (Aug 6, p 429),1 Michael Wilks claims that the American Psychological Association (APA) and our Task Force on Psychological Ethics and National Security permits psycholo- gists to “dispense with any ethical responsibilities when their training and expertise is used outside a strictly thera- peutic context”. This statement is false. A central finding of the recent Task Force report2 and the position of the APA is that psychologists are always bound by the ethical responsibilities set forth in the APA ethics code—irrespec- tive of the work setting and irrespective of whether they are referred to as psy- chologists, behavioural consultants, sci- entists, or another term. Our code of ethics always applies—there are no exceptions. Wilks states that, according to certain reports, medical personnel have “failed to report evidence of torture, failed to intervene to stop it being repeated, and made available to interrogators infor- mation from confidential medical files”. The APA Task Force report states explic- itly that psychologists have an ethical obligation to report evidence of torture and other cruel, inhuman, or degrading treatment to appropriate authorities, and that it is unethical for psychologists to use information from a medical file to the detriment of an individual’s safety and wellbeing. Rhea Farberman, on behalf of the American Psychological Association rfarberman@apa.org MRC CLASICC trial The short term results of the MRC CLASICC trial, which compared laparo- scopically assisted surgery with open resection for colorectal cancer (May 14, p 1718)1 are similar to those of the US COST trial2 for colon cancer alone, with similar 30-day mortality, lymph-node harvest, and oncological clearance in both open and laparoscopic groups. The pathological data show similar longitudinal resection margins and lymph-node yield in both groups. Although circumferential resection- margin positivity was higher in the laparoscopic group, the difference was not significant. We are surprised that the authors chose a finding that did not reach significance as a principle conclu- sion of the study. Their conclusions are difficult to justify with regard to laparo- scopically assisted anterior resection which, we would suggest, confers many advantages. Even when pelvic dissec- tion proves to be difficult and requires conversion to open surgery, patients still have much to gain from laparo- scopic mobilisation of the splenic flex- ure and avoidance of a long midline incision. Our experience of more than 500 resections suggests that the con- version rate to open surgery can be as low as 11% for all laparoscopically assisted colorectal resections and 16% for anterior resection. The CLASICC trial authors discuss the training difficulties with regard to laparoscopy that result from the scarcity of surgeons who regularly do these operations for colorectal disease in the UK.3 Joint consultant operating may help circumvent these difficulties, and a prospective audit of 88 joint laparoscopically assisted colorectal The results of the MRC CLASICC trial1 on laparoscopic surgery for colorectal can- cers were long awaited and their publi- cation is welcome. However, as with the COST2 and Spanish3 trials, some flaws in the trial design do not allow us to state that laparoscopic surgery is formally val- idated for all colon cancers. What about right-sided cancers? Neither the CLASICC trial nor the other trials included a subgroup analysis: only overall results were reported. It is well known among laparoscopic surgeons that “laparoscopic” right colectomy can in fact mean three different kinds of procedure: a true or totally laparoscopic right colectomy (with both dissection and anastomosis done intracorpore- ally), laparoscopically assisted colec- Sc ie nc e Ph ot o Li br ar y Rights were not granted to include this image in electronic media. Please refer to the printed journal Antenatal micronutrient supplements in Nepal References

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