Detecting congenital malformations - Lessons learned from the Mpepu study, Botswana.
BACKGROUND
A large and increasing number of HIV-infected women are conceiving on antiretroviral treatment (ART). While most antiretrovirals are considered safe in pregnancy, monitoring for rare pregnancy and infant adverse outcomes is warranted.


METHODS
We conducted a retrospective secondary analysis nested within a clinical trial of infant cotrimoxazole vs. placebo prophylaxis in Botswana (the Mpepu Study). Infants were examined at birth, and at least every 3 months through 18 months of age. Abnormal physical findings and diagnostic testing revealing malformations were documented. Post hoc, a geneticist classified all reported malformations based on available documentation. Structural malformations with surgical, medical or cosmetic importance were classified as major malformations. We present a descriptive analysis of identified malformations.


RESULTS
Between 2011 and 2014, 2,933 HIV-infected women who enrolled in the Mpepu study delivered 2,971 live-born infants. Study staff conducted 2,944 (99%) newborn exams. One thousand eighty-eight (38%) women were taking ART at conception; 1,147 (40%) started ART during pregnancy; 442 (15%) received zidovudine monotherapy; and 223 (7%) received no antiretroviral during pregnancy. Of 33 reported anomalies, 25 (76%) met congenital malformations criteria, 10 (30%) were classified as major malformations, 4 (40%) of which were identified after the birth exam.


CONCLUSIONS
Our results highlight the importance of staff training on identification of congenital malformations, programmatic monitoring beyond the birth examination and the value of geneticist involvement in the malformations classification process in resource-limited settings. These elements will be important to fully define antiretroviral drug safety in pregnancy.


CONCLUSIONS
Surveillance systems for monitoring the safety of antiretroviral use during pregnancy among HIV-infected women in resource-limited setting are lacking. The World Health Organization's published programmatic recommendations for such surveillance systems represents the gold standard. We employed data from a clinical trial in Botswana, a country with a generalized HIV epidemic and high antiretroviral uptake by HIV-infected women, to highlight practical opportunities to strengthen congenital malformation surveillance systems in these settings where over 1 million HIV infected pregnant women reside.


BACKGROUND
Clinical Trials.gov NCT01229761.
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Gbolahan
http://orcid.org/0000-0002-5408-4823
G
Ajibola
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.|Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Rebecca
R
Zash
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
Roger L
RL
Shapiro
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Oganne
O
Batlang
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Kerapetse
K
Botebele
Bennett Statistical Consulting, Inc., Ballston Lake, New York, United States of America.
Kara
K
Bennett
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Florence
F
Chilisa
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Erik von
EV
Widenfelt
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.
Joseph
J
Makhema
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.|Infectious Disease Unit, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
Shahin
S
Lockman
Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.
Lewis B
LB
Holmes
Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.|Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.|Global Health, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.
Kathleen M
KM
Powis
D000014:Abnormalities, Drug-Induced / Q000175:diagnosis*; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001902:Botswana; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy; D012189:Retrospective Studies; D015215:Zidovudine / Q000009:adverse effects* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine