Severe Vitamin D Deficiency in Human Immunodeficiency Virus-Infected Pregnant Women is Associated with Preterm Birth.

Background Low maternal vitamin D has been associated with preterm birth (PTB). Human immunodeficiency virus (HIV)-infected pregnant women are at risk for PTB, but data on maternal vitamin D and PTB in this population are scarce. Methods In a cohort of Latin American HIV-infected pregnant women from the National Institute of Child Health and Human Development International Site Development Initiative protocol, we examined the association between maternal vitamin D status and PTB. Vitamin D status was defined as the following 25-hydroxyvitamin D levels: severe deficiency (< 10 ng/mL), deficiency (10-20 ng/mL), insufficiency (21-29 ng/mL), and sufficiency (≥30 ng/mL). PTB was defined as delivery at < 37 weeks' gestational age (GA). Logistic regression was used to assess the association between maternal vitamin D status and PTB. Results Of 715 HIV-infected pregnant women, 13 (1.8%) were severely vitamin D deficient, 224 (31.3%) were deficient, and 233 were (32.6%) insufficient. Overall, 23.2% (166/715) of pregnancies resulted in PTB (median GA of PTBs = 36 weeks [interquartile range: 34-36]). In multivariate analysis, severe vitamin D deficiency was associated with PTB (odds ratio = 4.7, 95% confidence interval: 1.3-16.8]). Conclusion Severe maternal vitamin D deficiency is associated with PTB in HIV-infected Latin American pregnant women. Further studies are warranted to determine if vitamin D supplementation in HIV-infected women may impact PTB.

Etiology, clinical characteristics, and risk factors associated with severe influenza-like illnesses in Mexican adults.

Objective: The aim of this study was to determine the risk factors associated with severe influenza-like illness (ILI) in Mexican adults that could be useful to clinicians when assessing patients with ILI. Methods: Data from adult patients enrolled from 2010 through 2014 in ILI002 - a prospective hospital-based observational cohort study - were analyzed. Etiology and clinical characteristics were compared between cases of severe ILI (defined as hospitalization and/or death) and cases of non-severe ILI. Results: Overall, 1428 (39.0%) out of a total 3664 cases of ILI were classified as severe. Adjusted analyses showed a higher risk of severe ILI associated with signs and symptoms related to lower tract infection, i.e. cough with sputum (odds ratio (OR) 2.037, 95% confidence interval (CI) 1.206-3.477; P = 0.008), dyspnea (OR 5.044, 95% CI 2.99-8.631; and shortness of breath (OR 5.24, 95% CI 3.0839.124; P < 0.001), and with increases in lactate dehydrogenase (OR 4.426, 95% CI 2.321-8.881; P < 0.001) and C-reactive protein (OR 3.618, 95% CI 2.5955.196; P < 0.001). Further, there was an increased risk of severe ILI with a longer time between symptom onset and inclusion (OR 1.108, 95% CI 1.049-1.172; P < 0.001) and with chronic steroid use (OR 14.324, 95% CI 8.059-26.216; P < 0.001). Conclusions: Respiratory viruses can cause severe ILI. The results of this study highlight the importance of evaluating data compatible with lower tract involvement and previous use of immunosuppressants at baseline, because patients meeting these conditions may develop severe illness.

Factors Associated with Lower Respiratory Tract Infections in HIV-Exposed Uninfected Infants.

To identify factors that predispose human immunodeficiency virus (HIV)-exposed uninfected infants (HEUs) to higher incidence of severe infections, hospitalization, and death in the first 6-24 months of life compared with HEUs with and without lower respiratory tract infection (LRTI) in the first 6 months of life. Nested case-control study of 107 LRTI+ infants enrolled in the International Site Development Initiative (NISDI) Perinatal and Longitudinal Study in Latin American Countries (LILAC) studies with and 140 LRTI- in the first 6 months, matched by date and place of birth. Infants and mothers had plasma antibodies measured against respiratory syncytial virus (RSV), parainfluenza (PIV) 1, 2, 3, influenza, and pneumococcus 1, 5, 6B, and 14. Compared with LRTI-, mothers of LRTI+ HEUs had lower years of education, lower CD4+ cells, and higher HIV plasma viral load at delivery, but similar use of antiretrovirals and cotrimoxazole and other sociodemographic characteristics. LRTI+ and LRTI- HEUs had similar demographic and hematological characteristics and antibody concentrations against respiratory pathogens at birth. At 6 months, the rates of seroconversions to respiratory pathogens and antibody responses to tetanus vaccine were also similar. However, antibody concentrations to RSV were significantly higher in LRTI+ compared with LRTI- HEUs and marginally higher to PIV1. Maternal factors associated with advanced HIV disease, but unrelated to the use of antiretrovirals, cotrimoxazole, or the level of maternal antibodies against respiratory pathogens, contribute to the increased risk of LRTI in HEUs. In HEUs, antiretroviral and cotrimoxazole use, exposure to respiratory pathogens and humoral immune responses were not associated with the incidence of LRTI.

Maternal antiretrovirals and hepatic enzyme, hematologic abnormalities among human immunodeficiency virus type 1-uninfected infants: the NISDI perinatal study.

OBJECTIVES: To assess hepatic enzyme (HE) and hematologic abnormalities among human immunodeficiency virus-1-uninfected infants according to maternal antiretroviral regimen during pregnancy. STUDY DESIGN: In a prospective cohort, HE and hematologic values of human immunodeficiency virus-1-uninfected, term infants with hospital discharge (HD) within 6 days after birth were evaluated. Maternal antiretroviral regimens were categorized as: 1 or 2 nucleoside reverse transcription inhibitors (NRTIs), highly active antiretroviral therapy (HAART)/protease inhibitor (PI), or HAART/non-NRTI. RESULTS: Among 503 infants, 63% and 24% had HE and hemoglobin abnormalities, respectively, at HD. Most or all HE and hemoglobin abnormalities (96-100%) were grade 1 or 2. At HD, infants with maternal HAART/PI or HAART/non-NRTI were more likely to have elevated HE [adjusted odds ratio (AOR): 1.9, 2.4, respectively] compared with infants whose mothers received 1 or 2 NRTIs. Infants with maternal HAART/PI were less likely to have abnormal hemoglobin values at HD (AOR, 0.5) when compared with those whose mothers received 1 or 2 NRTIs. Persistently abnormal hemoglobin and HE values decreased with time, such that <10% of infants had abnormalities at 6 months of age. CONCLUSIONS: Maternal receipt of HAART regimens was associated with an increased risk of HE abnormalities, and maternal HAART/PI was associated with a lower risk of abnormal hemoglobin values, at HD. Abnormalities of HE and hemoglobin were generally mild and transient.

Excess respiratory viral infections and low antibody responses among HIV-exposed, uninfected infants.

OBJECTIVE: HIV-exposed uninfected (HEUs) infants have frequent severe infection, hospitalization, and death. We performed a serologic investigation to determine the role of common childhood respiratory pathogens in the excess incidence of infections in HEUs. DESIGN: Prospective cohort study of mother-infant pairs. METHODS: Among 247 HEUs and 88 HIV-unexposed uninfected (HUU) infant-mother pairs, we measured maternal antibodies to respiratory syncytial virus (RSV) and pneumococcus (PNC 1, 5, 6B, 14); infant antibodies to RSV, influenza A (flu), parainfluenza viruses (1, 2, 3), and PNC 1, 5, 6B, and 14 were measured at 0 and 6 months, and antitetanus antibodies at 6 months. RESULTS: HIV-infected mothers had higher RSV and lower PNC antibody concentrations at delivery than uninfected mothers. Transplacental transfer of maternal antibodies, particularly for RSV, was lower in HEUs compared with HUUs. At birth, HEUs had higher concentrations of anti-RSV antibodies than HUUs, but lower antibodies to the other respiratory agents. At 6 months, HEUs had significantly higher proportions of seroconversions and higher antibody concentrations against parainfluenza viruses 1, 2, and 3. There were no significant differences in seroconversions to flu and RSV, but antibody concentrations to RSV were six-fold lower in HEUs versus HUUs at 6 months. Antibody responses to at least two doses of tetanus vaccine were also six-fold lower in HEUs compared with HUUs. CONCLUSION: Six-month-old HEUs had a higher incidence of respiratory viral infections than HUUs. In addition to the low passive protection from maternal antibodies, low antibody responses of HEUs may contribute to increased morbidity and mortality.

Maternal antiretroviral drugs during pregnancy and infant low birth weight and preterm birth.

OBJECTIVE: To determine the relationship between maternal antiretroviral regimens during pregnancy and adverse infant outcomes [low birth weight (LBW) and preterm birth]. The a priori hypothesis was that protease inhibitor (PI)-containing regimens are associated with an increased risk of LBW and preterm birth. DESIGN: Prospective cohort study of HIV-1-infected women and their infants (NISDI Perinatal Study). METHODS: Data were analysed from 681 women receiving at least one antiretroviral drug [in order of increasing complexity: one or two nucleoside reverse transcriptase inhibitors (1-2 NRTI), two NRTI plus one non-nucleoside reverse transcriptase inhibitor (NNRTI) (HAART/NNRTI), or two NRTI plus one PI (HAART/PI)] for at least 28 days during pregnancy, and who delivered live born, singleton infants with known birth weight and gestational age by 1 March 2005. Multivariable logistic regression modeling was used to assess the relationship of maternal ART with LBW and with preterm birth, adjusting for covariates. RESULTS: The incidence of LBW and preterm birth, respectively, was 9.6% and 7.4% (1-2 NRTI), 7.4% and 5.8% (HAART/NNRTI), and 16.7% and 10.6% (HAART/PI). There was no statistically significant increased risk of LBW [adjusted odds ratio (AOR), 1.5; 95% confidence interval (95% CI), 0.7-3.2] or preterm birth (AOR, 1.1; 95% CI, 0.5-2.8) among women who received HAART/PI compared with women receiving 1-2 NRTI. CONCLUSIONS: Among a population of HIV-1-infected women in Latin America and the Caribbean, maternal receipt of PI-containing ART regimens during pregnancy was not associated with a statistically significant increase in risk of LBW or preterm birth.

Mode of delivery and postpartum morbidity in Latin American and Caribbean countries among women who are infected with human immunodeficiency virus-1: the NICHD International Site Development Initiative (NISDI) Perinatal Study.

OBJECTIVE: The purpose of this study was to test whether cesarean delivery before labor and before ruptured membranes is associated with a higher risk of postpartum morbidity than vaginal delivery among women who are infected with human immunodeficiency virus-1 in Latin America and the Caribbean. STUDY DESIGN: Data from a prospective cohort study (National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study) were analyzed. The study population consisted of women who were followed for > or = 6 to 12 weeks after delivery, who had singleton infants, and with a known mode of delivery. RESULTS: Of 819 enrollees, 697 women met inclusion criteria (299 vaginal deliveries, 260 cesarean deliveries before labor and before ruptured membranes, 138 cesarean deliveries after labor and/or after ruptured membranes); 36 women (5%) had postpartum morbidity (18 major, 18 minor). Mode of delivery was associated with postpartum morbidity (P = .02). Unadjusted odds ratios (95% CIs) for postpartum morbidity according to mode of delivery were cesarean delivery before labor and before ruptured membranes (odds ratio, 1.16 [95% CI, 0.5, 2.7]), cesarean delivery after labor and/or after ruptured membranes (odds ratio, 2.96 [95% CI, 1.3, 6.7]), and vaginal delivery (reference). These results did not differ appreciably with covariate adjustment. CONCLUSION: The rate of postpartum morbidity was low. Mode of delivery was associated with postpartum morbidity, possibly reflecting the larger proportion of minor postpartum morbidity events among those with cesarean delivery after labor and/or after ruptured membranes.

Low vitamin D status among pregnant Latin American and Caribbean women with HIV Infection.

OBJECTIVE: To evaluate the prevalence and predictors of low vitamin D status among pregnant women with HIV infection. METHODS: The present cross-sectional study analyzed repository specimens collected at 12-34 weeks of pregnancy among women enrolled across 17 sites in Latin America and the Caribbean between 2002 and 2009. Logistic regression modeling was used to identify factors associated with low vitamin D status (25-hydroxyvitamin D <30 ng/mL). RESULTS: Among 715 women, 218 (30.5%) were vitamin D deficient (<20 ng/mL) and 252 (35.2%) were insufficient (21- /mL). Factors associated with low vitamin D status included residence in subtropical latitudes (adjusted odds ratio [aOR] 1.97, 95% confidence interval [CI] 1.35-2.88), assessment during non-summer seasons (autumn: aOR 1.85, 95% CI 1.20-2.86; spring: 4.3, 2.65-6.95; winter: 10.82, 5.74-20.41), employment (aOR 1.56, 95% CI 1.06-2.38), and assessment before 20 weeks of pregnancy (aOR 1.89, 95% CI 1.18-3.06). Factors protective against low vitamin D status were CD4 count below 200 cells per mm(3) (aOR 0.45, 95% CI 0.26-0.77) and protease inhibitors (aOR 0.62, 95% CI 0.40-0.95). CONCLUSION: Low vitamin D status was prevalent among pregnant women with HIV infection. Further studies are warranted to identify the impact of low maternal vitamin D status.

Clinical characteristics and outcomes of influenza and other influenza-like illnesses in Mexico City.

BACKGROUND: Influenza-like illnesses (ILI) are estimated to cause millions of deaths annually. Despite this disease burden, the etiologic causes of ILI are poorly described for many geographical regions. METHODS: Beginning in April 2010, we conducted an observational cohort study at five hospitals in Mexico City, enrolling subjects who met the criteria for ILI. Evaluations were conducted at enrollment and on day 28, with the collection of clinical data and a nasopharyngeal swab (or nasal aspirate in children). Swabs were tested by multiplex PCR for 15 viral pathogens and real-time PCR for influenza. RESULTS: During the first year, 1065 subjects were enrolled in this study, 55% of whom were hospitalized; 24% of all subjects were children. One or more pathogens were detected by PCR in 64% of subjects, most commonly rhinovirus (25% of all isolates) and influenza (24% of isolates). Six percent of subjects died, and of those, 54% had no pathogen identified. Rhinovirus was the most common pathogen among those who died, although it did not have the highest case fatality rate. CONCLUSIONS: Multiple respiratory viruses beyond influenza are associated with significant morbidity and mortality among adults and children in Mexico City. Detection of these agents could be useful for the adjustment of antibiotic treatment in severe cases.

Infectious disease morbidity among young HIV-1-exposed but uninfected infants in Latin American and Caribbean countries: the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study.

OBJECTIVE: The goal was to describe the frequency, characteristics, and correlates of infectious disease morbidity during the first 6 months of life among HIV-1-exposed but uninfected infants. METHODS: The study population consisted of infants enrolled in the National Institute of Child Health and Human Development International Site Development Initiative Perinatal Study who were HIV-1 uninfected and had follow-up data through the 6-month study visit. Definitive and presumed infections were recorded at study visits (birth, 6-12 weeks, and 6 months). RESULTS: Of 462 HIV-1-uninfected infants with 11,644 child-weeks of observation, 283 experienced > or = 1 infection. These 283 infants experienced 522 infections (1.8 infections per infant). The overall incidence rate of infections was 4.5 cases per 100 child-weeks of observation. Overall, the most common infections were skin or mucous membrane infections (1.9 cases per 100 child-weeks) and respiratory tract infections (1.7 cases per 100 child-weeks). Thirty-six percent of infants had > 1 respiratory tract infection (1.8 cases per 100 child-weeks). Incidence rates of upper and lower respiratory tract infections were similar (0.89 cases per 100 child-weeks and 0.9 cases per 100 child-weeks, respectively). Cutaneous and/or oral candidiasis occurred in 48 neonates (10.3%) and 92 older infants (19.3%). Early neonatal sepsis was diagnosed in 12 infants (26.0 cases per 1000 infants). Overall, 81 of 462 (17.5%) infants were hospitalized with an infection. Infants with lower respiratory tract infections were hospitalized frequently (40.7%). The occurrence of > or = 1 neonatal infection was associated with more-advanced maternal HIV-1 disease, tobacco use during pregnancy, infant anemia, and crowding. Lower maternal CD4+ cell counts, receipt of intrapartum antibiotic treatment, and country of residence were associated with postneonatal infections. CONCLUSIONS: Close monitoring of HIV-1-exposed infants, especially those who are anemic at birth or whose mothers have more-advanced HIV-1 disease or who smoked during pregnancy, remains important.