Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial
- Peter Aaby1,
- Henrik Ravn2,
- Adam Roth2,3,
- Amabelia Rodrigues1,
- Ida Maria Lisse4,
- Birgitte Rode Diness1,
- Karen Rokkedal Lausch1,
- Najaaraq Lund1,
- Julie Rasmussen1,
- Sofie Biering-Sørensen1,
- Hilton Whittle5,
- Christine Stabell Benn2
- 1Bandim Health Project, Bissau, Guinea-Bissau
- 2Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark
- 3Department of Medical Microbiology, Lund University, Malmö, Sweden
- 4Department of Pathology, Herlev University Hospital, Copenhagen, Denmark
- 5MRC Laboratories, Fajara, Gambia
- Correspondence to Peter Aaby, Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark;
Contributors CSB and PA were the chief investigators and are guarantors. CSB, AdR, HW, IML and PA designed the studies. CSB, PA and AdR initiated the studies. AdR, AmR, CSB and PA were responsible for the recruitment and follow-up of participants. BRD, KRL, NL, JR and SBS supervised data collection in different periods. HR was responsible for the statistical analysis and PA wrote the first draft of the paper. All authors contributed to and approved the final version of the paper.
- Received 6 July 2011
- Accepted 18 January 2012
- Published Online First 13 February 2012
Background Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants.
Methods 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit.
Results Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls.
Conclusion Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.
Funding The study was funded by the EU (ICA4-CT-2002-10053), March of Dimes and the Danish National Research Foundation. The Bandim Health Project received support from DANIDA. PA holds a research professorship grant from the Novo Nordisk Foundation.
Competing interests None.
Ethics approval The protocol was approved by the Danish Central Ethics Committee and the Guinean Ministry of Health's Research Coordination Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
This paper is freely available online under the BMJ Journals unlocked scheme, see http://adc.bmj.com/info/unlocked.dtl