Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana


BACKGROUND: After reporting a possible association between neural tube defects (NTDs) and exposure to dolutegravir (DTG) from conception in 2018, yearly updates from the Tsepamo study have been increasingly reassuring. We report updated data collected through March 2022.
METHODS: The Tsepamo Study conducts birth outcomes surveillance study at government hospitals throughout Botswana, covering ~70% of all births. Midwives perform surface examinations of all live births and stillbirths and describe abnormalities. Research assistants photograph major abnormalities after maternal consent, which are reviewed by a birth defects expert blinded to exposures. Prevalence of NTDs was determined by maternal HIV and antiretroviral (ARV) exposure status (95% CI by Wilson method) and the primary analysis evaluated prevalence differences by exposure status (95% CI by Newcombe method).
RESULTS: Since April 2021, 32,819 additional births were recorded, including 3,780 additional DTG conception exposures. Since August 2014, there have been a total of 224,251 deliveries; 223,797 (99.8%) had an evaluable infant surface exam, with 156 (0.07%, 95% CI 0.06%, 0.08%) NTDs identified (100 with photo, 56 by description only). Among women on DTG at conception, 10/5860 NTDs occurred (0.11%; 95%CI 0.06%, 0.19%): 4 myelomeningoceles, 2 anencephaly, 3 encephaloceles, and 1 iniencephaly. In comparison, NTDs occurred in 25/23,664 (0.11%; 95%CI 0.07%, 0.16%) women on any non-DTG ARVs from conception, 11/14,432 (0.08%; 95%CI 0.04%, 0.14%) on efavirenz from conception, 4/6,551 (0.06%; 95%CI 0.02%, 0.16%) on dolutegravir started in pregnancy, and 108/170,723 (0.07%; 95%CI 0.05, 0.08%) among women without HIV. NTD prevalence did not differ between DTG and any non-DTG ARVs from conception (0.00% difference; 95%CI -0.07%, 0.10%).
Table. Prevalence Difference of Neural Tube Defects by ARV and HIV Exposure Categories

Exposure group vs. comparison groupPrevalence difference (%) (95% CI)
DTG at conception vs. Non-DTG at conception
0.00 (-0.07, 0.10)
DTG at conception vs. EFV at conception0.03 (-0.05, 0.12)
DTG at conception vs. DTG started in pregnancy0.04 (-0.06,0.14)
DTG at conception vs. non-DTG started in pregnancy0.04 (-0.07,0.13)
DTG at conception vs. women without HIV0.04 (-0.01, 0.13)

CONCLUSIONS: The prevalence of NTDs among infants born to women on DTG at conception has declined to 0.11% and does not substantially differ from other exposure groups.

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