To the editor
HIV-infected youth are reaching child-bearing age due to treatment with highly active antiretroviral therapy (HAART)1. We hypothesized that given different risk behaviors, vertically-infected youth (VIY) may have differences in pregnancy rates and adverse outcomes compared to behaviorally-infected youth (BIY).
Methods
This was a retrospective study of all VIY HIV-infected female youth age 13-24 , and all BIY females (from clinic enrollment through age 24) followed between January 1997 and May 2009 at 4 high-volume, urban, academic pediatric clinics in the HIV Research Network (HIVRN)2. Median age of first inclusion was 13 (IQR 13-13) for VIY and 17.4 years (IQR 13.8-20.1) for BIY. We examined pregnancies occurring in the setting of known HIV; 7 pregnancies where HIV was diagnosed concurrently were excluded. All sites have Institutional Review Board approval. The main outcome measures included pregnancy incidence, delivery outcomes (live birth, spontaneous abortion (SAB), therapeutic abortion (TAB)) and adverse pregnancy outcomes (prematurity and stillbirth). Poisson regression was used to compare pregnancy incidence rates. Logistic regression was used to compare groups in terms of pregnancy outcomes of live and stillbirths among non-TAB pregnancies and pre-term delivery among live births. Clustering by patient adjusted for multiple pregnancies per patient.
Results
181 (130 VIY, 51 BIY) HIV-infected female youth were followed for 637.2 patient years (PY); median 8.9 (range: 5.7, 10.3) PY/patient for VIY and 1.6 (range: 0.4, 3.2) PY/patient for BIY. Overall, 66 youth had 96 pregnancies (34 VIY, 62 BIY). Twenty-eight (21.5%) VIY vs. 38 (74.5%) of BIY had ≥ 1 pregnancy (p<0.001). Incidence rates were 52.3 pregnancies/1000 patient-years (PY) among VIY and 372.9 pregnancies/1000 PY among BIY (p<0.001). Of the 66 who became pregnant, 72.7% had 1, 15.1% had 2, 9.1% had 3 and 3.0% had ≥4 pregnancies. Behaviorally-infected youth tended to have >1 pregnancy compared to VIY (36.8% vs. 14.3%, p=0.04).
The median age at first pregnancy was 18 in VIY vs. 19.5 in BIY (p=0.06) (Table 1). Pregnant VIY were more likely than BIY to have CD4<200 cells/mm3 as pre-pregnancy nadir (35.7% vs. 7.5%, p=0.01) and at delivery (28.6% vs. 5.0%, p=0.04), respectively. Prenatal HAART use and HIV-1 RNA levels were similar between BIY and VIY pregnancies. No other differences were associated with incident pregnancy between the groups (Table 1).
Table 1.
Demographic and Clinical Characteristics of Pregnant VIY and BIY females, N=66
| VIY n=28 |
BIY n=38 |
p-value | |
|---|---|---|---|
| Median age at first pregnancy (IQR) | 18 (16, 20) | 19.5 (18, 21) | 0.06 |
|
| |||
| Race, n (%)* | 0.76 | ||
| Black, not Hispanic | 18 (64.3) | 25 (67.5) | |
| Caucasian, not Hispanic | 5 (17.9) | 9 (22.5) | |
| Hispanic | 5 (17.9) | 4 (10.0) | |
|
| |||
| Nadir CD4 prior to 1st pregnancy, n (%) | 0.01 | ||
| <200 cells/mm3 | 10 (35.7) | 3 (7.5) | |
| ≥200 cells/mm3 | 14 (50.0) | 27 (72.5) | |
| Missing† | 4 (14.3) | 8 (20.0) | |
|
| |||
| Reported substance use during 1st pregnancy, n(%) | 0.68 | ||
| None noted | 15 (53.6) | 21 (55.2) | |
| Ever‡ | 7 (25.0) | 13 (36.8) | |
| Tobacco | 4 (14.3) | 10 (26.3) | |
| Alcohol | 3 (10.7) | 0 | |
| Marijuana | 5 (17.9) | 7 (18.4) | |
| Cocaine | 0 | 2 (5.3) | |
| Heroin | 0 | 1 (2.6) | |
| Unknown† | 6 (21.4) | 4 (10.5) | |
|
| |||
| STI diagnosis during 1st pregnancy, n (%) | 0.64 | ||
| None noted | 24 (85.7) | 34 (89.5) | |
| Yes | 4 (14.3) | 4 (10.5) | |
Analyzed as Black, not Black (Caucasian + Hispanic). Race/ethnicity was self-identified and abstracted from the medical record; it was not assigned by the investigators. Race and ethnicity were assessed in order to examine potential differences in the demographic characteristics of pregnant VIY and BIY.
Excluded from analysis
Not mutually exclusive; no difference in analysis of all substance use vs. use of cocaine and heroin
Pregnant VIY were more likely than BIY to electively terminate (41.2% vs. 9.7%, p=0.001). There were no differences in adverse pregnancy outcomes between the groups (Table 2). One-third of live births were premature (29.4% VIY, 36.3% BIY), 13.5% of pregnancies ended in SAB (5.9% VIY, 17.7% BIY) and 2.1% ended in stillbirth (2.9% VIY, 1.6% BIY). Vertical transmission occurred in 1 live birth in a BIY despite prenatal HAART.
Table 2.
Comparison of pregnancy outcomes between the VIY and BIY pregnancies (N=96)
| Pregnancy outcomes, n (%)1 |
VIY (n=34) |
BIY (n=62) |
Total (n=96) |
OR (95% CI) |
| Spontaneous abortion | 2 (5.9) | 11 (17.7) | 13 (13.5) | 0.4 (0.1, 1.8) |
| Therapeutic abortion | 14 (41.2) | 6 (9.7) | 20 (20.8) | 6.5 (2.2, 19.2) |
| Stillbirth | 1 (2.9) | 1 (1.6) | 2 (2.1) | 2.9 (0.2, 51.4) |
| Live birth | 17 (50.0) | 44 (71.0) | 61 (63.5) | 1.3 (0.4, 4.5) |
|
| ||||
| Delivery mode of live births (n=61), n (%) | ||||
| Cesarean section | 10 (58.8) | 23 (56.1) | 33 (54.1) | 1.3 (0.4, 4.1) |
| Vaginal | 7 (41.2) | 21 (51.2) | 28 (45.9) | |
|
| ||||
| Gestational age of live births (n=61), n (%) | ||||
| < 37 weeks | 5 (29.4) | 16 (36.3) | 21 (34.4) | 0.7 (0.2, 2.8) |
| ≥ 37 weeks | 12 (70.6) | 25 (56.8) | 39 (63.9) | |
| Unknown2 | 0 | 3 (6.8) | 3 (4.9) | |
Univariate logistic regression analysis of pregnancy outcome among all pregnancies (n=96) and for pregnancies resulting in live births (n=61). Multiple pregnancies in the same individual were clustered by unique patient identifiers. Odds ratio refers to likelihood of VIY vs. BIY to have a particular outcome
Excluded from analysis
Comment
In the HIVRN cohort, we observed high pregnancy incidence among VIY and BIY. The rate in BIY was, 5 and 2.5 times that in the general population age 15-19 and 20-24, respectively3. The reasons for the observed rates, particularly among BIY may be multi-factorial. BIY may have other characteristics that were not studied (e.g., pregnancy desire) that increased pregnancy risk. Compared to nationally observed data in youth, there were higher rates of premature births (34.4% vs. 21.5%) and SAB (13.5% vs. 8.9%) 4,5. Vertically-infected youth were more likely than BIY to electively terminate pregnancy.
Our findings are not generalizable to all clinics caring for HIV-infected youth. The study is limited by its retrospective nature, small numbers, and limited follow-up time for BIY.
Early risk reduction to prevent unplanned pregnancies among HIV-infected youth is critical. Studies to understand differences in reproductive attitudes, and decision-making between VIY and BIY are vital to optimizing counseling and medical care for this population.
ACKNOWLEDGMENTS
Drs. Gebo and Agwu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. We would like to acknowledge Robert Warford, P.A. for his diligence in verifying the data from his site and Dr. John Fleishman for his careful review of the manuscript.
Sponsorship: Supported by the Agency for Healthcare Research and Quality (AHRQ) (290-01-0012). AHRQ was not responsible for the design and conduct of the study; collection, management, analysis, interpretation of the data; preparation, review, or approval of the manuscript. The views expressed in this paper are those of the authors. No official endorsement by the Agency for Healthcare Research and Quality or NCCR is intended or should be inferred.
Sponsorship: Susie Jang was supported by a grant from the Doris Duke Charitable Foundation to Johns Hopkins University School of Medicine. This project was supported by the National Institutes of Aging (R01 AG026250) (Dr. Gebo). Dr. Agwu was supported by the National Center for Research Resources (NCCR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research (1KL2RR025006-01). Dr. Korthuis is supported by the National Institute on Drug Abuse (K23-DA019809).
Footnotes
Financial Disclosure: Dr. Gebo has received research funding from Tibotec.
Participating Sites Alameda County Medical Center, Oakland, California (Howard Edelstein, M.D.)
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania (Richard Rutstein, M.D.)
Community Health Network, Rochester, New York (Roberto Corales, D.O.)
Drexel University, Philadelphia, Pennsylvania (Jeffrey Jacobson, M.D., Sara Allen, C.R.N.P.)
Johns Hopkins University, Baltimore, Maryland (Kelly Gebo, M.D., Richard Moore, M.D., Allison Agwu M.D.)
Montefiore Medical Group, Bronx, New York (Robert Beil, M.D., Carolyn Chu, M.D.)
Montefiore Medical Center, Bronx, New York (Lawrence Hanau, M.D.)
Nemechek Health Renewal, Kansas City, Missouri (Patrick Nemechek, M.D.)
Oregon Health and Science University, Portland, Oregon (P. Todd Korthuis, M.D.)
Parkland Health and Hospital System, Dallas, Texas (Gary Sinclair, M.D., Laura Armas-Kolostroubis, M.D.)
St. Jude’s Children’s Hospital and University of Tennessee, Memphis, Tennessee (Aditya Gaur, M.D.)
St. Luke’s Roosevelt Hospital Center, New York, New York (Victoria Sharp, M.D.)
Tampa General Health Care, Tampa, Florida (Charurut Somboonwit, M.D.)
University of California, San Diego, La Jolla, California (Stephen Spector, M.D.)
University of California, San Diego, California (W. Christopher Mathews, M.D.)
Wayne State University, Detroit, Michigan (Jonathan Cohn, M.D.)
Sponsoring Agencies Agency for Healthcare Research and Quality, Rockville, Maryland (Fred Hellinger, Ph.D., John Fleishman, Ph.D., Irene Fraser, Ph.D.)
Health Resources and Services Administration, Rockville, Maryland (Robert Mills, Ph.D.)
Data Coordinating Center
Johns Hopkins University (Richard Moore, M.D., Jeanne Keruly, C.R.N.P.,Kelly Gebo, M.D., Cindy Voss, M.A., Bonnie Cameron, M.S.)
Reference List
- (1).Gortmaker SL, Hughes M, Cervia J, et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med. 2001;345:1522–1528. doi: 10.1056/NEJMoa011157. [DOI] [PubMed] [Google Scholar]
- (2).Fleishman JA, Gebo KA, Reilly ED, et al. Hospital and outpatient health services utilization among HIV-infected adults in care 2000-2002. Med Care. 2005;43:III40–III52. doi: 10.1097/01.mlr.0000175621.65005.c6. [DOI] [PubMed] [Google Scholar]
- (3).Ventura SJ, Abma JC, Mosher WD, Henshaw SK. Estimated pregnancy rates by outcome for the United States, 1990-2004. Natl Vital Stat Rep. 2008;56:1–25. 28. [PubMed] [Google Scholar]
- (4).Chen XK, Wen SW, Fleming N, Demissie K, Rhoads GG, Walker M. Teenage pregnancy and adverse birth outcomes: a large population based retrospective cohort study. Int J Epidemiol. 2007;36:368–373. doi: 10.1093/ije/dyl284. [DOI] [PubMed] [Google Scholar]
- (5).Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000;320:1708–1712. doi: 10.1136/bmj.320.7251.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]