1. Focus of Surgical Care of Ugandan Children Hospital-based Birth Defects Surveillance in Kampala, Uganda | 1 Linda Barlow-Mosha, MD MPH On behalf of the BD Surveillance Team Makerere University- Johns Hopkins University Research Collaboration Kampala-Uganda 28 Sep 2015 Metropole Hotel

2. Protocol Team MUJHU Philippa Musoke, MBChB, Ph.D. – Principal investigator Linda Barlow-Mosha, M.D., MPH Mulago Hospital Josephat Byamugisha, MBChB, MMed (OBS &GYN) PhD, Head of Department Christine Biryabarema, MBChB, MMed, Senior consultant Obstetrician & Gyanecologist Evelyn Nabunya, MBChB, MMed, Clinical Head, Dept. of Obstetrics and Gynaecology Jolly Nankunda, MBChB, MMed, Mulago Hospital, Uganda CDC Dhelia Williamson, Ph.D. Diana Valencia, Ph.D | 2

3. Background | 3 Globally 7.9 million children born with birth defects (BD) annually 3.3 million die annually from birth defects Limited data on the prevalence of birth defects in sub-Saharan Africa Purpose of this study: To establish a hospital-based birth defect surveillance system To conduct a nested case-control study to describe maternal risk factors associated with birth defects

4. Background In Uganda, HIV prevalence is 8% among pregnant women Initially EFV was not indicated for use in the first trimester – An increase risk of neural tube defects (NTD) was reported in animal studies and a few human case reports Preferred Antiretroviral regimen – EFV/TDF/XTC (Option B+) – In 2012, panel of experts reviewed evidence of safety for EFV in early pregnancy – Based on Antiretroviral Program Registry from developed countries and passively reported by physicians as well as a few studies – No increase risk of BD compared to other antiretrovirals – Need for more evidence of safety in developing countries with large numbers of women on EFV | 4

5. Why Uganda? | 5 Limited data on prevalence of birth defects in Uganda – Data that are available come from small studies* and March of Dimes Global Report on BD 2006 – Prevalence ranges from 20 to 60 per 1000 live births* 124,000 (7%)** of pregnant women in ANC are HIV positive 70% of HIV+ mothers received ARVs (including Option B+)** In preparation facilities identified with large number of deliveries Available resources – number of deliveries, staffing, hospital records/documentation, data collection, and patient flow *Simpkiss,1961; Ndibazza,2011; Ochieng,2011; **; HMIS,2013

6. Study Design | 6 Establish Hospital-based surveillance system – 4 participating hospitals in Kampala (48,000 births/ year) Mulago, Mengo, Nsambya and Rubaga Hospitals Represents 75% of births occurring in hospitals within Kampala Case-control study to determine if maternal use of ART (Option B+ regimen) or cotrimoxazole (concomitant medication) during early pregnancy is associated with higher risk of BD – Prospective enrollment: 1 case: 3 controls, matched by birth hospital – Duration 4 years (total of approximately 192,000 births)

7. Design Selected 10 major external birth defects – NTD (Spina bifida with and without hydrocephalus, encephalocoele, anencephaly) – Abdominal wall defects (Gastroschisis, Omphalocele) – Anotia/ Anopthalmia – Cleft lip/ and palate – Hypospadius – Talipes Equinovarus/ other Limb deficiencies Active case ascertainment | 7

8. Neural Tube Defects 8

9. Abdominal wall defects 9

10. Eye Defects - Anopthalmia Cryptophthalmos Coloboma 10

11. Ear Defects - Anotia/Microtia 11

12. Cleft Lip and Palate 12

13. Talipes Equinovarus 13

14. Limb Deficiencies Complete or partial absence of distal structures of a limb in a transverse plane at the point where the deficiency begins, with proximal structures being essentially intact Source: CDC-Beijing Medical University collaborative project Congenital complete absence of upper limbs/Amelia of upper limb (Q71.0) Congenital complete absence of lower limb/Amelia of lower limb (Q72.0) Congenital absence of both forearm and hand (Q71.2) Limb deficiencies | 4

15. Project Significance | 15 First birth defects surveillance program in Uganda Provides current data on baseline prevalence of birth defects in Uganda Identify potential risks associated with HIV treatment – Population reassurance and potential better ART adherence/compliance Evaluate effects of other medications on occurrence of adverse birth outcomes ( i.e., malaria, TB, and other new HIV drugs) Utilize findings to guide prevention, service provision, inform further studies, and expand surveillance to include other disorders present at birth

16. Lessons Learned so far….. | 16 Need to ensure sustainability beyond funding time frame Secure MOH’s interest in birth defects surveillance for the country – Involve in training/ stakeholder’s meetings/ birth defects awareness campaign Key elements - Piloting/Continuous improvement/ Patience

17. Lessons Learned Greatest challenges and how they were addressed – Examination of large number of deliveries in busy hospitals Hired surveillance midwives – Access to medical records/documentation Use of electronic data collection and real time quality control of data – Provision of referral services for affected children Create referral list for service provider Establish a link to pediatric surgeon to provide services for | 17

18. Update of Birth Defects Surveillance Piloting in Upper and Lower Mulago initiated in August 2015 Surveillance launched in Upper Mulago 20 August 2015 Lower Mulago to be launched in October 2015 Planned Stakeholder Meeting early 2016 Hospitals will receive quarterly updates on progress/ activties of the surveillance Present preliminary data from 2 months of piloting and surveillance activities | 18

19. Update on Birth Defects Piloting/Surveillance Type of Neural tube defects Number Spina bifida with hydrocephalus4 Spina bifida without hydrocephalus1 Encephalocoele2 Anencephaly4 Total11 | 19

20. Update on Birth Defects Piloting/Surveillance Other Types of Birth Defects Number Gastroschisis2 Eye & Ear defects3 Limb reduction defects2 Talipes Equinovarus8 Knee joint malformations3 Orofacial clefts1 Hypospadias2 Conjoined twins1 Amniotic band sequences1 Total23 | 20

22. | 22 Mwebale Nnyo Thank you