Pedro J. Garcia

Association of intimate partner physical and sexual violence with unintended pregnancy among pregnant women in Peru.

To examine the associations between lifetime physical and/or sexual intimate partner violence (IPV) with pregnancy intent among pregnant women in Lima, Peru.

Correlates of cervical Mycoplasma genitalium and risk of preterm birth among Peruvian women.

Background: Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease in nonpregnant women. We investigated associations between cervical M genitalium, demographic and behavioral risk factors for sexually transmitted infection and preterm birth among low-income Peruvian women. Methods: This case-control study, conducted at the Instituto Nacional Materno Perinatal, Lima, Peru, included 661 cases with a spontaneous preterm birth at <37 weeks and 667 controls who delivered at ≥37 weeks. Within 48 hours after delivery, subjects underwent interviews, medical record review, and collection of cervicovaginal specimens for M. genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae by nucleic acid amplification testing, and Trichomonas vaginalis by culture. Odds ratios and 95% confidence intervals were calculated for associations between M. genitalium, other genital infections and risk factors, and preterm birth. Multivariable logistic regression was used to adjust for potential confounders. Results: Cervical M. genitalium was detected in 3% of subjects and was significantly associated with C. trachomatis infection (P < 0.001) and preterm birth (4% vs. 2%; adjusted odds ratio: 2.5, 95% confidence interval: 1.2–5.0, P = 0.014), and marginally associated with T. vaginalis (P = 0.05). M. genitalium detection was also associated with younger maternal age (P = 0.003) but not with other risk factors for preterm birth. The association between cervical M. genitalium detection and preterm birth remained significant after adjustment for maternal age and coinfection with C. trachomatis or T. vaginalis. Conclusions: Cervical M. genitalium detection was independently associated with younger maternal age and preterm birth, suggesting that this organism may be an infectious correlate of spontaneous preterm birth.

Association of Childhood Physical and Sexual Abuse with Intimate Partner Violence, Poor General Health and Depressive Symptoms among Pregnant Women

Objective We examined associations of childhood physical and sexual abuse with risk of intimate partner violence (IPV). We also evaluated the extent to which childhood abuse was associated with self-reported general health status and symptoms of antepartum depression in a cohort of pregnant Peruvian women. Methods In-person interviews were conducted to collect information regarding history of childhood abuse and IPV from 1,521 women during early pregnancy. Antepartum depressive symptomatology was evaluated using the Patient Health Questionnaire-9. Multivariable logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Results Any childhood abuse was associated with 2.2-fold increased odds of lifetime IPV (95%CI: 1.72–2.83). Compared with women who reported no childhood abuse, those who reported both, childhood physical and sexual abuse had a 7.14-fold lifetime risk of physical and sexual IPV (95%CI: 4.15–12.26). The odds of experiencing physical and sexual abuse by an intimate partner in the past year was 3.33-fold higher among women with a history of childhood physical and sexual abuse as compared to women who were not abused as children (95%CI 1.60–6.89). Childhood abuse was associated with higher odds of self-reported poor health status during early pregnancy (aOR = 1.32, 95%CI: 1.04–1.68) and with symptoms of antepartum depression (aOR = 2.07, 95%CI: 1.58–2.71). Conclusion These data indicate that childhood sexual and physical abuse is associated with IPV, poor general health and depressive symptoms in early pregnancy. The high prevalence of childhood trauma and its enduring effects of on women’s health warrant concerted global health efforts in preventing violence.

Risk of placental abruption in relation to maternal depressive, anxiety and stress symptoms.

BACKGROUND Little is known about the influence of psychiatric factors on the etiology of placental abruption (PA), an obstetrical condition that complicates 1-2% of pregnancies. We examined the risk of PA in relation to maternal psychiatric symptoms during pregnancy. METHODS This case-control study included 373 PA cases and 368 controls delivered at five medical centers in Lima, Peru. Depressive, anxiety and stress symptoms were assessed using the Patient Health Questionnaire (PHQ-9) and the Depression Anxiety Stress Scales (DASS-21). Multivariable logistic regression models were fit to calculate odds ratios (aOR) and 95% confidence intervals (CI) adjusted for confounders. RESULTS Depressive symptoms of increasing severity (using the DASS depression subscale) was associated with PA (p for trend=0.02). Compared with women with no depressive symptoms, the aOR (95%CI) for PA associated with each level of severity of depression symptoms based on the DASS assessment were as follows: mild 1.84 (0.91-3.74); moderate 1.25 (0.67-2.33); and severe 4.68 (0.98-22.4). The corresponding ORs for mild, moderate, and moderately severe depressive symptoms based on the PHQ assessment were 1.10 (0.79-1.54), 3.31 (1.45-7.57), and 5.01 (1.06-23.6), respectively. A positive gradient was observed for the odds of PA with severity of anxiety (p for trend=0.002) and stress symptoms (p for trend=0.002). LIMITATIONS These cross-sectionally collected data may be subject to recall bias. CONCLUSIONS Maternal psychiatric disorders may be associated with an increased occurrence of AP. Larger studies that allow for more precise evaluations of maternal psychiatric health in relation to PA risk are warranted.

Generation C: Prevalence of and Risk Factors for Chlamydia trachomatis among Adolescents and Young Women in Lima, Peru

OBJECTIVE Adolescent and young adult women in urban, socioeconomically disadvantaged areas are at high risk of contracting sexually transmitted infections (STIs). We assessed associations of Chlamydia trachomatis (CT) infection with both traditional STI risk factors, and partner and partnership-related factors among low-income women in Lima, Peru, by age group. METHODS In a cross-sectional analysis of CT infection among 1290 postpartum women, cervical swabs were collected for CT polymerase chain reaction (PCR) within 48 h after delivery, and a structured interview was completed. Multivariate logistic regression was used to evaluate risk factors for CT, with separate models stratified by age: adolescents (12-19 years), young women (20-24 years), and older women (>or=25 years). RESULTS CT was detected in 9.6% of adolescents, 9.0% of young women, and 5.4% of older women (p = 0.03). Among adolescents, history of drug use (odds ratio [OR] = 5.62, 95% confidence interval [CI] 1.03-30.6) and short duration of current partnership (OR = 2.6, 95% CI 1.14-5.93) were the strongest predictors of CT infection. Among young women, younger age at coitarche (OR = 0.74 for each year older, 95% CI 0.60-0.91) and low income (OR = 2.40, 95% CI 1.04-5.55) were associated with CT, while self-report of ever using condoms was protective (OR = 0.22, 95% CI 0.08-0.61). Among older women, only younger age at coitarche was related to CT (OR = 0.85, 95% CI 0.75-0.97). CONCLUSIONS Risk factors for CT among women in Lima, Peru, differed for adolescents, young women, and older women, which may reflect differences in biology and/or immunology of CT as well as variability in the occurrence of specific risk behaviors by age group.

Childhood abuse and early menarche among Peruvian women

PURPOSE Childhood abuse has been associated with age of menarche in some studies, but not all, and few have assessed the independent associations of sexual and physical abuse with early menarche. We examined the association between childhood abuse and early menarche among pregnant women in Lima, Peru. METHODS Multinomial logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for early menarche (≤11 years) in relation to any physical or sexual childhood abuse, physical abuse only, sexual abuse only, and both physical and sexual abuse in a cohort of 1,499 pregnant (first trimester) women. RESULTS Approximately 69% of participants reported experiencing physical or sexual abuse in childhood. The frequencies of physical abuse only, sexual abuse only, and both physical and sexual abuse were 37.4%, 7.7%, and 24.5%, respectively. Compared with women who reported no childhood abuse, those who reported any childhood abuse had a 1.38-fold increased odds of early menarche (95% CI, 1.01-1.87). Compared with no abuse, the odds of early menarche was 1.60-fold among women with childhood sexual abuse only (OR, 1.60; 95% CI, .93-2.74) and 1.56-fold for those with both physical and sexual abuse (OR, 1.56; 95% CI, 1.07-2.25) during childhood. Isolated physical abuse was weakly associated with early menarche (OR, 1.23; 95% CI, .87-1.74). There was no clear evidence of association of childhood abuse with late menarche (≥15 years). CONCLUSIONS Childhood abuse, particularly joint physical and sexual abuse, is associated with early menarche. Our findings add to an expanding body of studies documenting the enduring adverse health consequences of childhood abuse.

Genetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies.

INTRODUCTION Accumulating epidemiological evidence points to strong genetic susceptibility to placental abruption (PA). However, characterization of genes associated with PA remains incomplete. We conducted a genome-wide association study (GWAS) of PA and a meta-analysis of GWAS. METHODS Participants of the Placental Abruption Genetic Epidemiology (PAGE) study, a population based case-control study of PA conducted in Lima, Peru, were genotyped using the Illumina HumanCore-24 BeadChip platform. Genotypes were imputed using the 1000 genomes reference panel, and >4.9 million SNPs that passed quality control were analyzed. We performed a GWAS in PAGE participants (507 PA cases and 1090 controls) and a GWAS meta-analysis in 2512 participants (959 PA cases and 1553 controls) that included PAGE and the previously reported Peruvian Abruptio Placentae Epidemiology (PAPE) study. We fitted population stratification-adjusted logistic regression models and fixed-effects meta-analyses using inverse-variance weighting. RESULTS Independent loci (linkage-disequilibrium<0.80) suggestively associated with PA (P-value<5e-5) included rs4148646 and rs2074311 in ABCC8, rs7249210, rs7250184, rs7249100 and rs10401828 in ZNF28, rs11133659 in CTNND2, and rs2074314 and rs35271178 near KCNJ11 in the PAGE GWAS. Similarly, independent loci suggestively associated with PA in the GWAS meta-analysis included rs76258369 near IRX1, and rs7094759 and rs12264492 in ADAM12. Functional analyses of these genes showed trophoblast-like cell interaction, as well as networks involved in endocrine system disorders, cardiovascular diseases, and cellular function. CONCLUSIONS We identified several genetic loci and related functions that may play a role in PA risk. Understanding genetic factors underlying pathophysiological mechanisms of PA may facilitate prevention and early diagnostic efforts.

Abruptio Placentae Risk and Genetic Variations in Mitochondrial Biogenesis and Oxidative Phosphorylation: Replication of a Candidate Gene Association Study

BACKGROUND: Abruptio placentae is a complex multifactorial disease that is associated with maternal and neonatal death and morbidity. Abruptio placentaes high recurrence rate, high prevalence of heritable thrombophilia among women with abruptio placentae, and aggregation of cases in families of women with the disease support the possibility of a genetic predisposition. Previous genome‐wide and candidate gene association studies have identified single nucleotide polymorphisms in mitochondrial biogenesis and oxidative phosphorylation genes that potentially are associated with abruptio placentae risk. Perturbations in mitochondrial biogenesis and oxidative phosphorylation, which results in mitochondrial dysfunction, can lead to the impairment of differentiation and invasion of the trophoblast and to several obstetrics complications that include abruptio placentae. OBJECTIVE: The purpose of this study was to determine whether the results of a candidate genetic association study that indicated a link between DNA variants (implicated in mitochondrial biogenesis and oxidative phosphorylation) and abruptio placentae could be replicated. STUDY DESIGN: The study was conducted among participants (507 abruptio placentae cases and 1090 control subjects) of the Placental Abruption Genetic Epidemiology study. Weighted genetic risk scores were calculated with the use of abruptio placentae risk‐increasing alleles of 11 single nucleotide polymorphisms in 9 mitochondrial biogenesis and oxidative phosphorylation genes (CAMK2B, NR1H3, PPARG, PRKCA, THRB, COX5A, NDUFA10, NDUFA12, and NDUFC2), which previously was reported in the Peruvian Abruptio Placentae Epidemiology study, a study with similar design and study population to the Placental Abruption Genetic Epidemiology study. Logistic regression models were fit to examine associations of weighted genetic risk scores (quartile 1, <25th percentile; quartile 2, 25–50th percentile; quartile 3, 50–70th percentile, and quartile 4, >75th percentile) with risk of abruptio placentae, adjusted for population admixture (the first 4 principal components), maternal age, infant sex, and preeclampsia. The weighted genetic risk score was also modeled as a continuous predictor. To assess potential effect modification, analyses were repeated among strata that were defined by preeclampsia status, maternal age (≥35 vs 18–34 years), and infant sex. RESULTS: Abruptio placentae cases were more likely to have preeclampsia, shorter gestational age, and lower infant birthweight. Participants in quartile 2 (score, 12.6–13.8), quartile 3 (score, 13.9–15.0) and quartile 4 (score, ≥15.1) had a genetic risk score of 1.45‐fold (95% confidence interval, 1.04–2.02; P=.03), a 1.42‐fold (95% confidence interval, 1.02–1.98; P=.04), and a 1.75‐fold (95% confidence interval, 1.27–2.42; P=7.0E‐04) higher odds of abruptio placentae, respectively, compared with those in quartile 1 (score,<12.6; P‐for trend=.0003). The risk of abruptio placentae was 1.12‐fold (95% confidence interval, 1.05–1.19; P=3.0×1004) higher per 1‐unit increase in the score. Among women with preeclampsia, those in quartile 4 had a 3.92‐fold (95% confidence interval, 1.48–10.36; P=.01) higher odds of abruptio placentae compared with women in quartile 1. Among normotensive women, women in quartile 4 had a 1.57‐fold (95% confidence interval, 1.11–2.21; P=.01) higher odds of abruptio placentae compared with those in quartile 1 (P‐for interaction=.12). We did not observe differences in associations among strata defined by maternal age or infant sex. CONCLUSION: In this study, we replicated previous findings and provide strong evidence for DNA variants that encode for genes that are involved in mitochondrial biogenesis and oxidative phosphorylation pathways, which confers risk for abruptio placentae. These results shed light on the mechanisms that implicate DNA variants that encode for proteins in mitochondrial function that are responsible for abruptio placentae risk. Therapeutic efforts to reduce risk of abruptio placentae can be enhanced by improved biologic understanding of maternal mitochondrial biogenesis/oxidative phosphorylation pathways and identification of women who would be at high risk for abruptio placentae.

Childhood Abuse and Early Menarche Among Peruvian Women

The aim of this study was to determine the prevalence of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolated from urinary tract and bloodstream infections in a rural hospital in Manhiça, Mozambique. ESBLs were investigated among ceftriaxone-non-susceptible K. pneumoniae clinical isolates recovered between 2004 and 2009. Characterisation of blaCTX-M, blaSHV, blaOXA and blaTEM genes was performed by PCR and sequencing. Epidemiological relationships were established by phylogenetic analysis, repetitive extragenic palindromic PCR (REP-PCR), pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST), whilst plasmid transferability was evaluated by conjugation. In addition, the presence of class 1 and 2 integrons was studied. A total of 19 K. pneumoniae were analysed. The blaCTX-M-15 gene was found in all strains. Other ESBL genes were found concomitantly, including blaSHV-5, blaSHV-2, blaSHV-2A, blaSHV-12 and blaSHV-38. In addition, other β-lactamases such as blaTEM-1 and blaOXA-30 were also detected. REP-PCR identified 15 different epidemiological profiles. MLST analysis also showed great variability of sequence types. The blaCTX-M-15 gene showed a high transfer capacity. The presence of class 1 integrons was high. High levels of multidrug resistance were also found. In conclusion, these data show the dominance of the CTX-M-type ESBL, particularly CTX-M-15, supporting its worldwide dissemination, including in areas with limited access to third-generation cephalosporins. This finding is a matter of concern for clinical management as third-generation cephalosporins are an alternative for treating severe cases of multidrug-resistant infections in this community.