Josefina Romaguera

Risk Factors and Opportunities for Prevention of Early-onset Neonatal Sepsis: A Multicenter Case-Control Study

Background. Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear. Methods. Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52 406 births; matched case-control study of risk factors for GBS and other sepsis. Results. Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births). GBS (1.4 cases per 1000 births) andEscherichia coli (0.6 cases per 1000 births) caused most infections. GBS sepsis less often occurred in preterm deliveries compared with other sepsis. Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2–13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1–8.0). An obstetric risk factor—preterm delivery, intrapartum fever, or membrane rupture ≥18 hours—was found in 49% of GBS cases and 79% of other sepsis. IAP had an adjusted efficacy of 68.2% against any early-onset sepsis. Ampicillin resistance was evident in 69% of E coliinfections. No deaths occurred among susceptible E coliinfections, whereas 41% of ampicillin-resistant E coliinfections were fatal. Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP. Conclusions. Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases. Sepsis caused by other organisms is more often a disease of prematurity. IAP seemed efficacious against early-onset sepsis. However, the severity of ampicillin-resistant E colisepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis.

Fetal lung maturation in congenital diaphragmatic hernia

OBJECTIVE Our purpose was to determine whether congenital diaphragmatic hernia is associated with abnormalities of fetal lung maturation. STUDY DESIGN We measured surfactant protein A and saturated phosphatidylcholine in amniotic fluid from 19 pregnancies with a prenatal diagnosis of congenital diaphragmatic hernia (gestational age 16 to 40 weeks) and 48 control pregnancies (gestational age 16 to 39 weeks). Results were compared by analysis of covariance. RESULTS Beyond 34 weeks of gestation there was a progressive rise in amniotic fluid surfactant protein A and saturated phosphatidylcholine in control pregnancies, whereas in most fetuses with prenatal diagnosis of congenital diaphragmatic hernia these values remained low (p < 0.01). Amniotic fluid surfactant protein A was lower in fetuses with congenital diaphragmatic hernia who died or required extracorporeal membrane oxygenation than in survivors treated with conventional management (4.9 +/- 2.9 vs 16.8 +/- 5.7 micrograms/ml surfactant protein A, respectively, p < 0.05 by Mann-Whitney U test). CONCLUSIONS There are decreased surfactant components in amniotic fluid in many pregnancies complicated by congenital diaphragmatic hernia, which may reflect fetal lung immaturity or hypoplasia.

Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine ☆

OBJECTIVES To assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine. METHODS V503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12-26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n=618) or saline placebo (n=306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA). RESULTS The frequency of injection-site AEs (days 1-5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1-15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV=0.5%; placebo=0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown. CONCLUSIONS Administration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12-26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.

Age at natural menopause and factors associated with menopause state among Puerto Rican women aged 40-59 years, living in Puerto Rico.

Objective:The timing of menopause is associated with multiple health outcomes in female populations including all-cause mortality, heart disease, breast cancer, and osteoporosis. Although research suggests that age at menopause varies in different ethnic groups, data on age at menopause among Hispanic women are limited. Design:The present cross-sectional study estimates age at natural menopause among a sample of 1,272 Puerto Rican women aged 40 to 59 years who participated in health fairs held in 22 municipalities of Puerto Rico between May 2000 and November 2001. Cox proportional hazard regression analysis was used to characterize age at natural menopause and its association with relevant covariates. Results:The overall adjusted median age at natural menopause was 51.3 years. Current employment (hazard ratio = 0.75, 95% CI: 0.59-0.95) and parity of two or three children as compared with having no children or one child (hazard ratio = 0.73, 95% CI: 0.54-0.98) were associated with a later menopause. Conclusions:This study provides a robust estimate of age at menopause for Puerto Rican women, which is similar to overall estimates previously reported for US populations, but higher than estimates for other Hispanic populations. Our results confirm attributes associated with age at menopause and provide information relevant to understanding the potential chronic disease burden of Puerto Rican women as they age.

Risk Factors and Opportunities for Prevention of Early-Onset Neonatal Sepsis: A Multicenter Case-Control Study

BACKGROUND Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear. METHODS Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52 406 births; matched case-control study of risk factors for GBS and other sepsis. RESULTS Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births). GBS (1.4 cases per 1000 births) and Escherichia coli (0.6 cases per 1000 births) caused most infections. GBS sepsis less often occurred in preterm deliveries compared with other sepsis. Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2-13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1-8. 0). An obstetric risk factor-preterm delivery, intrapartum fever, or membrane rupture >/=18 hours-was found in 49% of GBS cases and 79% of other sepsis. IAP had an adjusted efficacy of 68.2% against any early-onset sepsis. Ampicillin resistance was evident in 69% of E coli infections. No deaths occurred among susceptible E coli infections, whereas 41% of ampicillin-resistant E coli infections were fatal. Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP. CONCLUSIONS Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases. Sepsis caused by other organisms is more often a disease of prematurity. IAP seemed efficacious against early-onset sepsis. However, the severity of ampicillin-resistant E coli sepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis.

Factors associated with metabolic syndrome in a sample of women in Puerto Rico.

Objective: The aim of this study was to determine the association between metabolic syndrome (MetS) and demographic, health, and lifestyle characteristics in a sample of women living in Puerto Rico. Methods: The study group consisted of 214 women aged 36 to 82 years, residing in the metropolitan area of San Juan, Puerto Rico. Demographic, reproductive, lifestyle, and metabolic variables were assessed through an annual questionnaire and blood chemistries. MetS was defined according to the criteria set by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults/Adult Treatment Panel III (NCEP/ATP III) and the International Diabetes Federation (IDF). Results: The overall prevalence of MetS was 24% according to NCEP/ATP III criteria and 33% according to IDF criteria. When using the IDF criteria, 37% of participants older than 51 years have MetS, in contrast to 28% when using the NCEP/ATP III criteria. Obese women have an increased probability of MetS when adjusting for age, education level, menopause status, and/or alcohol use (IDF criteria: estimated odds ratio [OR], 2.68; 95% CI, 1.44-4.97; NCEP/ATP III criteria: estimated OR, 3.42; 95% CI, 1.71-6.84). A higher education level (estimated OR, 0.45; 95% CI, 0.23-0.92 [IDF criteria]) and alcohol consumption (estimated OR, 0.48; 95% CI, 0.23-0.99 [NCEP/ATP III criteria]) seem to provide a protective effect, when adjusting for confounders. Conclusions: Our study confirms obesity as an important risk factor associated with MetS in this sample of women in Puerto Rico. Alcohol consumption and a higher education level seem to decrease the prevalence of MetS. In view of this, patient counseling regarding weight reduction and lifestyle modification should be emphasized in the primary prevention and management of MetS. Additional studies are warranted to further characterize the effect of menopause status on MetS.

Prevalence of 21-hydroxylase-deficient nonclassic adrenal hyperplasia and insulin resistance among hirsute women from Puerto Rico

OBJECTIVE To determine the prevalence of 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) and insulin resistance in hirsute women from Puerto Rico. DESIGN Cross-sectional prospective study. SETTING Clinical research center. PATIENT(S) 100 consecutive untreated hirsute women. MAIN OUTCOME MEASURE(S) Fasting total T, free T, DHEAS, insulin, and glucose were measured, and a 60-minute acute ACTH-(1-24) stimulation for 17-hydroxyprogesterone (17-HP) was performed. A diagnosis of 21-OH-deficient NCAH was considered when the stimulated 17-HP level was >30.3 nmol/L. The glucose/insulin ratio was calculated as a measure of insulin resistance (normal value, > or =4.5). RESULT(S) Patients had a mean (+/-SD) age of 26.8+/-6.6 years; 82 were oligomenorrheic. Overall, 12%, 8%, and 60% of patients had elevated levels of DHEAS, total T, or free T, respectively. One patient was identified as having 21-OH-deficient NCAH. Eight women, none of whom had NCAH, were found to be hyperglycemic; four of these women had type 2 diabetes mellitus. Excluding hyperglycemic patients, a glucose/insulin ratio of <4.5, consistent with IR, was found in 51.7%. CONCLUSION(S) The prevalence of 21-OH-deficient NCAH among patients from Puerto Rico does not differ significantly from that reported for other non-Jewish, non-Hispanic white populations.

Human papillomavirus infection in women in Puerto Rico: agreement between physician-collected and self-collected anogenital specimens.

Objective This study aimed to describe the prevalence and concordance between cervical and anal human papillomavirus (HPV) infection and compare cervicovaginal and anal self-collection methods for HPV testing between physician and self-collected specimens in women in Puerto Rico. Materials and Methods Specimens for HPV-DNA testing were obtained from 100 women aged 18 to 34 years attending a general gynecology clinic for a routine Pap smear. Human papillomavirus testing was performed using polymerase chain reaction MY09/MY11 primers. Positive samples were typed for 39 genotypes. Agreement between sampling methods was determined by percent agreement and the &kgr; statistic. Results For the 39 genotypes evaluated, 38.4% (38/99) of cervicovaginal and 33.7% (30/89) of anal physician-collected samples were HPV+, whereas 35.1% (34/97) of cervicovaginal and 32.0% (31/97) of anal self-collected samples were positive. Human papillomavirus type 16 was the most common type identified in the cervix (8.3%, 8/97) and the anus (5.6%, 5/89) of physician-collected samples, with similar prevalence in self-collected samples. Concordance between cervical and anal HPV infection was high (>90%) for all types evaluated. There was a strong percent agreement between physician- and self-collected cervicovaginal and anal samples (>95% for all HPV types) and good to excellent agreement (&kgr; > 0.60) for most HPV types. Conclusions The clinic-based prevalence of anal and cervicovaginal HPV infection was high, with a strong concordance between cervical and anal infection and good to excellent agreement between physician- and self-collected samples. This study supports the feasibility of using cervical and anal self-sampling methods in future population-based studies of HPV infection in Puerto Rico and as an HPV screening method in women.

Correlates of the Metabolic Syndrome Among a Sample of Women in the San Juan Metropolitan Area of Puerto Rico

BACKGROUND The metabolic syndrome is an interaction of risk factors that may lead to cardiovascular disease and type 2 diabetes. METHODS Given the need for data in Puerto Rico, this cross-sectional study aimed to determine the association between demographic, lifestyles, and reproductive characteristics and the metabolic syndrome among a sample of women (N = 564) in the San Juan Metropolitan Area. The metabolic syndrome was defined based on the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. RESULTS In multivariate logistic regression models, women aged 40-59 and 60-79 years were 3.03 [95% confidence interval (CI), 1.70, 5.40] and 7.05 (95% CI, 3.69, 13.49) times more likely, respectively, to have the metabolic syndrome as compared to those aged 21-39 years. A dose-response relationship was also observed between body mass index (BMI) and metabolic syndrome. Physical activity reduced the odds for metabolic syndrome [prevalence odds ratios (POR) = 0.64; 95% CI, 0.41, 1.01]; however, this association was marginally significant (P = 0.05). Among reproductive characteristics, only women who had a history of gestational diabetes (GDM) were 2.14 (95% CI, 1.02, 4.51) times more likely to have metabolic syndrome. CONCLUSIONS Consistent with previous studies, increased age and BMI, physical inactivity, and GDM are associated with the metabolic syndrome in this population. This information is relevant for the development of preventive interventions for the metabolic syndrome.

Amniotic fluid epidermal growth factor concentrations:The effect of intra-amniotic thyroxine for acceleration of fetal maturation

Intra‐amniotic thyroxine (200–500 ug) was administered weekly to 29 women in the third trimester to enhance fetal maturation. Lecithin‐sphingomyelin ratio (L/S) and epidermal growth factor (EGF) were measured in amniotic fluid (AF) before (n = 58) and after (n = 92) administration of thyroxine. The AF L/S ratio and EGF concentration increased linearly with increasing gestational age both before (r = 0.76, p > 0.0001; r = 0.41, p > 0.001, respectively) and after (r = 0.62, p > 0.0001; r = 0.43, p > 0.001 respectively) initiation of thyroxine treatment. The slopes of gestational age vs L/S (0.07) and EGF (0.004) before T4 increased significantly after initiation of T4 therapy (L/S:0.23, p > 0.001; EGF:0.015, p > 0.01, respectively). L/S ratios correlated with AF EGF levels before (r = 0.77, p > 0.001) and after (r = 0.63, p > 0.001) initiation of T4 therapy. These results demonstrate that intra‐amniotic thyroxine accelerates not only the progression of the amniotic fluid L/S ratio, but the appearance of EGF.