Umbilical Cord Antisepsis in Low-Income Countries: Impact on Neonatal Mortality and Omphalitis

Transcription

1 Umbilical Cord Antisepsis in Low-Income Countries: Impact on Neonatal Mortality and Omphalitis James M. Tielsch, Ph.D. Department of International Health Johns Hopkins Bloomberg School of Public Health

2 Time Trends in Child Mortality Lawn J, et. al., Lancet 2005;365:

3 Distribution of Causes of Neonatal Death 7% 7% 23% Asphyxia 7% Preterm 3% Sepsis/Pnem Diarrhea Tetanus 26% 27% Congential Other Lawn J, et. al., Lancet 2005;365:

4 Background Multiple antiseptics used. Chlorhexidine widely used for cord cleansing in many settings since 1970 s WHO Recommendation (1998): dry cord care topical antiseptic may be used where infection and harmful practices are high* *WHO. Care of the umbilical cord. WHO. Geneva, WHO/RHT/MSM 98.4

5 Nepal Newborn Washing Study Design Cluster Randomization by Sector (n=413 Sectors) Placebo Wash (Sectors = 206) Chlorhexidine 0.25% Wash (Sectors = 207) Cord Care: Education Only (Sectors = 69) Cord Care: Soap/Water (Sectors = 69) Cord Care: Chlorhexidine (Sectors = 68) Cord Care: Education Only (Sectors = 69) Cord Care: Soap/Water (Sectors = 69) Cord Care: Chlorhexidine (Sectors = 69)

6 Nepal Study Site

7 NNIPS-NWS Study Site Sarlahi District, Nepal Sarlahi

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10 Cord Care Trial: Cord Infection Outcome Infection defined using three definitions: 1. Mild Infection: moderate or severe redness, with or without pus. 2. Moderate Infection: pus with moderate/severe redness, OR severe redness without pus. 3. Severe Infection: pus with severe redness Mullany LC et al. Arch Dis Child Fet Neonatal Ed. 2006; 91:

11 NNIPS-NWS Methods Pregnancies identified through weekly surveillance by local female staff (n=413). All women receive weekly vitamin A supplementation (7,000 RE). Enrolled ~ 6 th month of pregnancy Informed consent Clean delivery kits / cord & newborn care education Iron / folic-acid supplements Single-dose albendazole ASAP after delivery, local female workers deliver fullbody skin cleansing intervention. Cord intervention on days 1,2,3,4,6,8,10. Morbidity assessment on days 1,2,3,4,6,8,10,14,21,28.

12 Nepal Newborn Washing Study Methods Data analysis Cord Care Trial Neonatal omphalitis incidence estimated under three definitions of cord infection Stratified by early/late intervention time Stratified by full-body cleansing intervention to examine effect modification Neonatal mortality estimated as deaths per 1000 live births Generalized Estimating Equations to account for clustered design

13 Severity of Infection Cord Care Trial: Umbilical Cord Infection Chlorhexidine group compared to dry cord care, stratified by early/late intervention Early (<24 hours) RR (95% CI) Late (>=24 hours) RR (95% CI) Mild 0.65 ( ) 0.70 ( ) Moderate 0.42 ( ) 0.66 ( ) Severe 0.13 ( ) 1.06( ) No impact soap and H 2 O group. No interaction with skin cleansing.. Mullany LC et al. Lancet 2006; 367:

14 Cord Care Trial: Neonatal Mortality Chlorhexidine group compared to dry cord care, stratified by early/late intervention Early (<24 hours) Late (>=24 hours) RR (95% CI) RR (95% CI) NMR 0.66 ( ) 1.02 (0.54,1.92) 34% reduction in neonatal mortality No impact soap and H 2 O group, no effect modification. Mullany LC et al. Lancet 2006; 367:

15 S. Asia CHX Cord Cleansing Trials Southern Nepal: Mullany LC, et al. Lancet 2006; 367: Northeast Bangladesh: Arifeen SE, et al. Lancet 2012; 379: Sindh Province, Pakistan: Soofi S, et al, Lancet 2012; 379:

16 Overall Design and Context Nepal Bangladesh Pakistan Overall NMR 32 / / / 1000 % Home Births 92% 88% 80% No. Clusters (N) 413 (15,123) 133 (29,760) 187 (9,741) Eligibility All live births in study area All live births in study area All live births attended by TBAs Exclusion Not met within 10 days after birth Not met within 7 days after birth Birth defects, infection at birth, Not met within 3 Days after birth Imdad A, et al. (submitted).

17 Intervention Provided Nepal Bangladesh Pakistan Comparison Group Dry Cord Care Dry Cord Care Dry Cord Care Intervention Groups 1. Multiple CHX 2. Soap/H 2 O 1. Multiple CHX 2. Single CHX 1. Multiple CHX 2. Hand Washing 3. HW + CHX CHX Concentration 4.0% 4.0% 4.0% Freq of Multiple App 1,2,3,4,6,8,10 1,2,3,4,5,6,7 Daily for 14 days Intervention Provider Local project staff Local project staff TBA to caretaker Imdad A, et al. (submitted).

18 Impact on Cord Infection In all studies Multiple CHX reduced cord infection Nepal: 32% 75% reduction Bangladesh: 22% 65% reduction Pakistan: 54% 78% reduction *Single cleansing in Bangladesh and Soap/H20 in Nepal did not reduce infection Imdad A, et al. (submitted).

19 Pooled Analysis Neonatal Mortality Imdad A, et al. (submitted).

20 How to Scale Up in S. Asia? Who should provide / apply the CHX? When / where distributed or obtained? When / how often should it be applied? Develop effective IEC/BCC materials. Which formulations are acceptable and effective?

21 Other Lessons Learned from Operations Research Who applies Mother, TBA, or Facility Provider When/Where Distributed? Outreach home visits during pregnancy, private sector (packaged in CDK or stand-alone) Acceptable, and willing to pay Development of BCC materials Pictorial and combination materials helpful Our best experience has been through demonstration Formulations? Context-specific: gel / aqueous / lotion / nozzle

22 Light-weight Gel Formulation Lomus Pharmaceuticals, Kathmandu, Nepal

23 Translation to Programs & Policy Nepal MOH&P incorporated CHX cord care into national essential newborn care package. Being considered in Bangladesh and Pakistan. WHO Consultation on Postnatal Care met last week. Their conclusions:

24 WHO Recommendations 1998 In hospitals it is probably best to apply a topical antimicrobial to the cord stump For home deliveries.. application of an antiseptic is not required. In areas at high risk where harmful practices are prevalent, an antimicrobial can be recommended Daily chlorhexidine 4% application to the umbilical cord stump and first week of life is recommended for newborns who are born at home in settings with high NMR greater than 30 per 1000.

25 Conclusions on CHX CHX cord cleansing can save lives in S. Asia CHX is safe, acceptable, low-cost CHX can have various formulations, packaging, distribution models CHX cord cleansing should be included in MNH programs in South Asia Two on-going trials in Zanzibar and Zambia The policy development process can be mysterious

26 Nepal Newborn Washing Study Colleagues and Support Colleagues Ramesh Adhikari Gary Darmstadt Joanne Katz Subarna Khatry Steven LeClerq Luke Mullany Support NICHD/NIH Bill & Melinda Gates Foundation USAID Procter & Gamble Co. (commodity support)

27 Partners and Support for Pooled Analysis Nepal: NNIPS, JHU, IOM-Tribhuvan University, NICHD, Bill & Melinda Gates Foundation, USAID, Proctor and Gamble, MoHP, Nepal Family Health Project Bangladesh: MoH, ICDDR,B, JHU, Shimantik, DSH, SNL/Save The Children (USA), USAID Pakistan: Aga Khan University, John Snow Inc, Pakistan MoH

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29 After wipe, upper level staff notified to initiate 28 day follow-up.

30 Infants in the chlorhexidine and soap and water groups received umbilical cord cleansing on Days 1,2,3,4,6,8, and

31 At each visit, axillary temperature and respiratory rate of the newborn were recorded.

32 Photo of umbilical cord showing extensive redness around the base of cord stump (redness=3, approximately 72 hours after birth)

33 Photo of umbilical cord showing redness extending to the skin around the base of the cord (redness=2, approximately 96 hours after birth)

34 Photo of umbilical cord showing pus discharge, redness extending to the skin around the base of the cord stump, and moderate swelling (pus=1, redness=3, swelling=2, approximately 72 hours after birth)

35 Kaplan-Meier Survival Curve, 2500 gms Time to Event CHX Placebo Logrank χ 2 = 0.79, p = 0.37

36 Kaplan-Meier Survival Curve, <2500 gms Time to Event CHX Placebo Logrank χ 2 = 5.26, p = 0.02