Baseline characteristics of the sample are presented in . Out of 221 pregnancies the number of discreet women included in this analysis was 183. Our final sample of 183 women was reached because of the following exclusions: 20 repeat deliveries; 2 twins; 5 births with incomplete delivery information; 4 abortions or miscarriages; 3 changed prenatal providers; and 4 incarcerations during the index pregnancy. The cohort was mostly African American (74.7%, n = 136) and single (86.7%, n = 157) with a mean age of 28.0 years (SD = 6.2). Educational attainment was low (high school or less; 63.4%, n = 116). A total of 69.1% (n = 123) of the women reported at least one birth prior to this pregnancy; 38.3% (n = 70) reported smoking during this pregnancy; 44.3% (n = 81) reported a history of ever using illicit drugs (majority of illicit drug use in this cohort was cocaine), and 18.0% (n = 33) reported using illicit drugs during the current pregnancy. The mean GA of the infant at the time the mother entered care was 14.6 weeks (SD = 7.5); the mean GA at outcome was 38 weeks (SD = 2.1). There were no significant differences of the GA at entry into prenatal care by SGA at the 10th percentile (14.8 weeks; SD = 7.4, P = 0.7029) or SGA at the 3rd percentile (13.2 weeks; SD = 3.7, P = 0.9630; ). The average duration of time since HIV diagnosis for the cohort was 4.3 years (SD = 4.3). The incidence of preeclampsia was 13.6% (n = 21/150).
Sociodemographic, behavioral, and medical characteristics of sample.
Socio-demographic, behavioral, and medical characteristics, by SGA at 10th percentile and SGA at 3rd percentile.
Two perinatal transmissions occurred in this cohort; neither were SGA. The first infant was 37 weeks gestation, 2952 grams. Maternal factors included ART of NRTI and NNRTI (nevirapine); CD4 count of 20; and viral load at the time of delivery, 98,500. The second infant was 42.2 week-gestation, 3430.3 grams. Maternal factors included ART of NRTI and PI combination (lopinavir/ritonavir); CD4 count of 626, viral load at time of delivery, 1000. It was suspected that transmission occurred during breastfeeding immediately following delivery.
CD4 T lymphocyte counts and HIV viral loads were recorded throughout pregnancy and at the time of delivery. The majority of women had CD4 counts greater than 200 copies/mm3
= 134, 73.2%); 55.2% (n
= 101) had viral loads greater than 1000
copies/mL at entry into prenatal care and 72.1% (n
= 132) were diagnosed with HIV prior to the index pregnancy. Disease severity as measured by CD4 at entry into care, and length of time of HIV diagnosis did not vary significantly between the women taking NNRTIs and those taking PIs. The number of women with CD4 counts greater than 200 and taking PIs (146) was 105 (71.9%) whereas the number of those taking NNRTIs (43) was 30 (60.8%), P
= 0.78. Average duration of time since HIV diagnosis for those taking PIs was 5.08 years (SD = 4.7) compared with 4.72 years (SD = 4.3; P
= 0.884) for those taking NNRTIs.
All women were taking ART during the pregnancy; 100% (n = 183) had nucleoside reverse transcriptase inhibitors (NRTIs) as part of their background regimen, with 14.8% (n = 27) taking NRTIs alone; 21.3% (n = 39) were taking nonnucleoside reverse transcriptase inhibitors (NNRTIs), and 63.9% (n = 117) were taking protease inhibitors (PIs). There were 11 (40.7%) women who were taking NRTI only and whose infants were SGA at the 10th percentile, as compared to all other women (on either a PI and NNRTI) whose infants were SGA at the 10th percentile (46, 29.5% P = 0.244). Four (14.8%) women were taking NRTI only whose infants were SGA at the 3rd percentile as compared to all others who were SGA at the 3rd percentile (19, 12.2% P = 0.703). Therefore, those women taking NRTI only did not have a higher rate of SGA at the 10th or 3rd percentiles.
Of the women taking NNRTIs, 1.1% (n = 2) were taking efavirenz, 16.9% (n = 31) were taking nevirapine, and 3.3% (n = 6) were taking etravirine. The following PIs were used in this cohort: amprenavir (2.7%, n = 5); atazanavir (15.8%, n = 29); darunavir (1.1%, n = 2); lopinavir/ritonavir (20.8%, n = 38); fosamprenavir (1.1%, n = 2); nelfinavir (23%, n = 42); and ritonavir (15.8%, n = 29). No participants were taking indinavir, raltegravir, or saquinavir. The majority of this sample (n = 137; 74.9%) was not taking ART prior to the index pregnancy and started the HIV medication regimen during the prenatal period.
We found that ritonavir did not have the adverse outcome of an SGA infant as others have reported [13
]. There were 67 women on ritonavir-boosted regimens compared to 116 who were not exposed to ritonavir. A total of 22 (32.8%) women were taking ritonavir who also had SGA infants at the 10th versus 35 (30.2%) women not taking ritonavir who had SGA infants at the 10th (P
= 0.708). A total of 8 (11.9%) women taking ritonavir also had SGA at the 3rd versus 15 (12.9%) women not taking ritonavir with SGA infants at the 3rd percentile (P
= 0.846). The overall prevalence of SGA was high with 31.2% at the 10th percentile and 12.6% at the 3rd percentile. In bivariate analyses at the 10th percentile, newborns were less likely to be SGA if their mother was taking NNRTI medication compared to those newborns whose mothers were not taking NNRTI medication (12.3% versus 25.4%; P
= 0.045). Newborns were more likely to be SGA if their mother's first viral load was >1000 copies/mL (50.0% versus 66.7%; P
= 0.036. There were no significant differences in the rates of SGA in bivariate analyses for the following factors: the first available CD4 value dichotomized at 200 cells/mm3
; the rate of change of CD4 and viral load during the prenatal period; starting ART during pregnancy compared to starting ART prior to pregnancy or even starting ART later in pregnancy; taking a PI; length of time with HIV diagnosis; and viral load measurements at entry into the prenatal period and every trimester thereafter. There were no significant differences in those infants delivered preterm who were at the 10th percentile (n
= 15, 26.3%) compared to the non-SGA infants (n
= 19, 15.1%; P
= 0.070). As expected, the birth weight for those with SGA at the 10th percentile was significantly less than those without SGA (P
< 0.001). A higher percentage of the women with SGA infants had ever smoked cigarettes (P
= 0.057), though smoking at the time of the study (P
= 0.250) was not statistically significant for an SGA infant at the 10th percentile ().
The same comparisons were reevaluated using SGA at the 3rd percentile where the rate was shown to be 12.6% (). Education status was significantly associated with SGA at the 3rd percentile with a higher percentage of women with SGA infants having less than a high school education (P = 0.028). Current smoking status was close to significant (P = 0.056). CD4 counts >200 cells/mm3 at the first prenatal visit were significantly associated with a decreased risk of SGA at the 3rd percentile (P = 0.015). All other factors were not significantly associated with SGA at the 3rd percentile including HIV viral load measurements at entry into the prenatal period and every trimester thereafter, choice of ART (either NNRTI [P = 0.114] or PI [P = 0.287]), initiation of ART during the index pregnancy compared to those who started ART prior to the index pregnancy (P = 0.052), or starting ART in the third trimester. There were no significant differences in those infants delivered preterm at the 3rd percentile (n = 3, 13%) as compared to the non-SGA infants (n = 31, 19.4%; P = 0.465). As expected, the birth weight for those with SGA at the 3rd percentiles was significantly less than those without SGA (P < 0.001).
Cesarean delivery was the most prevalent mode of delivery for all infants, regardless of SGA status. Among the women for whom the mode of delivery was known (n = 193, 87%), 54% of the deliveries were cesarean births. SGA was not associated with an increased risk of cesarean delivery. The two SGA groups had comparable distribution of vaginal and cesarean deliveries. The modes of delivery of those infants at the 10th percentile were vaginal, 42.1% (n = 24); cesarean, 54.4% (n = 31); and unknown 3.5% (n = 2); for those at the 3rd percentile, vaginal deliveries were 39.1% (n = 9) and cesarean deliveries were 60.9% (n = 14).
The results of the logistic regression models are presented in . In the adjusted model for SGA at the 10th percentile, cigarette smoking was significantly associated with a higher likelihood of an SGA birth (OR 2.77; 95% CI, 1.28–5.97). Interestingly, even after adjustment, women taking NNRTI medications were significantly less likely to have an SGA birth at the 10th percentile (OR 0.28; 95% CI, 0.10–0.75) compared to those treated with other HIV regimens.
Logistic regressions predicting 10th percentile and 3rd percentile.
In the adjusted model for SGA at the 3rd percentile, current cigarette smoking was associated with a higher likelihood of an SGA birth (OR 3.64; 95% CI, 1.12–11.76). Those who had a CD4 value greater than 200 cells/mm3 at the first clinic visit were significantly less likely to have an SGA infant (OR 0.29, 95% CI, 0.10–0.86). As at the 10th percentile, after adjustment, women taking NNRTI medications were significantly less likely to have an SGA birth at the 3rd percentile (OR 0.16; 95% CI, 0.03–0.91) compared to those treated with other HIV regimens.
The rates of SGA in this cohort remained exceptionally elevated even when compared to a rate of 16% SGA births defined as less than the 10th percentile observed in a similar group of HIV-negative non-Hispanic black women from Philadelphia, PA. The comparison dataset was from a community-based study examining maternal stress and maternal and infant health and health-related behaviors [15
]. The women were recruited from a consortium of eight health centers run by the Philadelphia Department of Public Health. The sample used for comparison is a subsample of 3990 on whom SGA data were available.
When we formally compare the 183 to the 3990, we find the following differences: the HIV-infected cohort is significantly older (M
= 28.0; SD = 6.2) compared to the HIV negative comparison (M
= 24.1; SD = 5.7; P
< .001). The HIV-infected cohort has a significantly higher percentage of women who were African American (74.7% versus 67.1% P
= 0.03), and single (86.7%, 75.7% P
= 0.001), and HIV-infected women are more likely to have greater parity (more than 1 child: 69.1% versus 55.7% P
= 0.001) and higher rates of ever having smoked (50.8% versus 35.1%,P
= 0.001). In our sample of HIV-infected women the risk factors associated with SGA are more prevalent; however, when accounted for in the multivariate model, none except smoking was statistically significant.