Adverse pregnancy outcomes in Toxoplasma gondii seropositive Hispanic women.

AIMS: Chronic Toxoplasma gondii infection is not thought to affect pregnancy or birth outcomes, but there are few prospective studies. The study aims were T. gondii immunoglobulin G measurement and relationship of chronic T. gondii infection with gestational age at birth and adverse pregnancy outcomes in 690 Hispanic women in Tampa, Florida. METHODS: Hispanic women, born either in the United States or in Latin America or the Caribbean had a venous blood sample drawn to measure T. gondii IgG and T. gondii serotype at the first prenatal visit, along with collection of demographic and health-related measures. Seropositive and seronegative women were followed throughout their pregnancy. Gestational age, infant weights, and adverse pregnancy outcomes (miscarriages, preterm births) were compared in the two groups. RESULTS: There were 740 women of self-reported Hispanic ethnicity screened and enrolled in Tampa, Florida, with 690 having birth data extracted from the electronic health record (538 T. gondii negative and 152 T. gondii seropositive). T. gondii seropositivity was 22.4% and the majority (83%) had high avidity titers, indicating chronic infection. Compared to T. gondii seronegative Hispanic women, seroseropositive women had more smaller for gestational age infants and higher prevalences of miscarriages and preterm birth. CONCLUSION: This is one of the largest longitudinal cohort studies of women with chronic T. gondii infection followed through pregnancy. There was a higher percentages of adverse pregnancy outcomes in this group compared to T. gondii seronegative controls. The mechanism for this is unknown and warrants reexamination of the dogma that chronic T. gondii infection in pregnant women has no significant clinical consequences.

Homocysteine Levels Are not Related to Telomere Length in Cord Blood Leukocytes of Newborns.

Objective Elevated homocysteine (HC) levels and/or shortened telomere length (TL) are associated with adverse medical conditions. Our objective is to investigate the relationship between HC and TL in cord blood leukocytes of newborns. Study Design This is a nested study from a prospective cohort from 2011 to 2012 in pregnant women admitted for delivery at a university-affiliated hospital. Cord blood was collected at delivery and genomic DNA was analyzed using quantitative PCR. The telomere-to-single copy gene ratio method was employed to quantify TL. Newborn HC levels were measured. generalized linear regression modeling (GLM) and bootstrap statistical analyses were performed. Results Seventy-seven maternal-fetal dyads with a mean gestational age of 39 weeks were included. The distribution of the coefficient of homocysteine showed most values greater than zero demonstrating that homocysteine had a positive relationship with TL. In 915 of 10,000 (9.15%) iterations, the p-value was < 0.05 demonstrating a positive effect. Conclusion Increasing newborn concentrations of HC are not associated with decreasing TL. Larger, prospective studies are needed to confirm these findings and long-term implications.

Diabetic Retinopathy during pregnancy in Hispanic women with latent Toxoplasma gondii infection.

BACKGROUND: Retinal photography was performed in pregnancy and postpartum in pregnant Hispanic women with latent Toxoplasma gondii (TG) infection in order to screen for characteristic retinal lesions or the particular scars found in people with active T. gondii infection. A comparison group of TG negative women was included in the study but they did not have retinal photography. OBJECTIVE: The goal of the parent study was to assess for adverse pregnancy events and evidence for parasite reactivation in TG positive (TG + ) women, through examination of the eyes for characteristic lesions. Retinal photography, usually at prenatal visits 2 (17 +/- 3.35 weeks) and 3 (26.3+/-1.75) weeks, was done on TG + women. Fifty-six of these women also (43 %) had retinal photography at the postpartum visit. Health and demographic data were obtained at the first prenatal visit for all women. STUDY DESIGN: From the 690 recruited at the first prenatal visit, 128 TG- women and 158 TG + women were enrolled in a prospective study through pregnancy and the postpartum. All TG- women (n = 532) provided data at the first prenatal visit and throughout their pregnancy and birth through the EHR. This allowed comparison of health and outcome data for the TG + compared to a larger number of TG- Hispanic pregnant women. RESULTS: While there was no evidence of ocular toxoplasmosis during pregnancy, there was a surprisingly large number (42 %) of TG + women with diabetic retinopathy (DR). We also observed that TG + women had a 20 % incidence of gestational diabetes mellitus (GDM) compared to 11.3 % in the TG- women (p = 0.01). At postpartum (mean 5.6 weeks), 23 of 30 women with pregnancy DR showed no DR in the postpartum. CONCLUSIONS: No characteristic T. gondii lesions were discovered. Retinal photography serendipitously revealed DR in these T. gondii positive women. It was also found that latent TG infection was associated with increased incidence of GDM. Hispanic pregnant women's increased risk for latent TG infection, GDM and DR are underappreciated. Retinal photography may need to be considered an innovative approach to screening.

Exposure to environmental tobacco smoke and risk of antenatal depression: application of latent variable modeling.

This study sought to determine the impact of passive smoking on the risk for depressive symptoms during pregnancy. In this prospective study, 236 pregnant women were recruited at less than 20 weeks of gestation from a university-affiliated obstetric clinic from November 2009 through July 2011. Tobacco use/exposure was measured using questionnaire and confirmed by salivary cotinine analysis. The Edinburgh Perinatal Depression Scale (EPDS) was employed to capture perinatal depressive symptomatology. Traditionally, a cutoff of 13 is utilized to indicate depressive symptoms in the perinatal population. However, this approach is vulnerable to measurement errors that are inherent in assessing depression using cutoff points. Therefore, in this analysis, we apply a flexible approach (latent variable modeling) that accounts for measurement errors thereby reducing bias in the estimates of association. Significant differences were observed in the mean EPDS scores across non-smokers (mean ± SD = 4.8 ± 4.8), passive smokers (5.3 ± 5.5) and active smokers (7.4 ± 6.1) [p value = 0.02]. For each itemized response of the EPDS, passive smokers demonstrated an increased risk for depressive symptoms with the greatest risk exhibited by items 8 and 9 of the questionnaire (feeling sad or miserable and feeling unhappy [and]crying, respectively). In addition, for each item of the EPDS, a dose-response pattern was revealed with non-smokers having the least risk of depressive symptoms during pregnancy and active smokers having the greatest risk. Women who are exposed to secondhand smoke are at elevated risk for depressive symptoms during pregnancy.

Systematic review on sleep disorders and obstetric outcomes: scope of current knowledge.

OBJECTIVE: To assess the current state of knowledge regarding sleep disorders and their relationship to obstetric outcomes. STUDY DESIGN: A systematic literature review of the previous two decades (1991 to 2010) was conducted. The exposure was sleep disorders during pregnancy, and the outcomes of interest were feto-infant morbidity and maternal complications. RESULTS: Sleep apnea, snoring, and sleep quantity/duration were identified as the most frequently examined sleep disorders among pregnant women. Although our review found that studies examining the impact of sleep disorders on feto-infant outcomes were lacking, previous research indicates that such disorders may enhance the risk of preterm birth. Additionally, the current body of evidence suggests that sleep disorders adversely impact maternal health, increasing the likelihood of preeclampsia, and gestational diabetes. CONCLUSION: Existing research points to the potentially harmful effects of sleep disorders on obstetric outcomes. The limited research in this arena highlights the need for further studies regarding the nature and strength of this relationship. Given the multiple dimensions of sleep and pregnancy, multivariate research approaches that incorporate biological and psychosocial factors are warranted.

Previous cesarean section, gestational age at first delivery and subsequent risk of pre-eclampsia in obese mothers.

PURPOSE: We examine the association between prior C-section and subsequent pre-eclampsia; and describe the effect of gestational age at prior C-section, and obesity status on this association. METHODS: The study population included women with two subsequent singleton births in Missouri between 1998 and 2005. The risk for pre-eclampsia/eclampsia was assessed among women with and without prior cesarean delivery. The two groups were followed to their second pregnancy and the occurrence of pre-eclampsia was documented. Additionally, the history of pre-eclampsia, prior cesarean at preterm, and obesity status were examined for their differential effects on the risk of pre-eclamsia. RESULTS: Women with prior C-section were 28% more likely to have pre-eclampsia in their subsequent pregnancy [OR = 1.28; 95% CI = 1.20-1.37]. However, this result was not significant when women with pre-eclampsia in their first pregnancy were excluded. After this exclusion, a more than threefold increased risk for subsequent pre-eclampsia was observed in women with prior early C-section [OR = 3.15; 95% CI= 2.43-4.08], while the level of risk did not change in the prior late C-section group [OR = 0.90; 95% CI= 0.82-1.00]. Subgroup analysis suggested that obesity status modified the risk of prior early C-section but did not affect the risk for prior late C-section. CONCLUSION: Preterm C-section in the first pregnancy may be associated with subsequent pre-eclampsia regardless of prior pre-eclampsia status.

Success of programming fetal growth phenotypes among obese women.

OBJECTIVE: To estimate the distribution and success of programmed fetal growth phenotypes among obese women. METHODS: This was a retrospective cohort study using the Missouri maternally linked cohort files (years 1978-1997). Maternal body mass index was classified as Normal (18.5-24.9) (referent group), Obese (class 1, 30.0-34.9; class 2, 35.0-39.9; and extreme or class 3, 40 or more). Fetal growth phenotypes were defined as large for gestational age (LGA), appropriate for gestational age (AGA), and small for gestational age (SGA). We used adjusted odds ratio with correction for intracluster correlation to estimate the risk of neonatal mortality for each fetal growth phenotype. RESULTS: As compared with normal weight mothers, obese gravidas tended to program LGA infants at a higher and increasing rate with ascending obesity severity. The opposite effect was observed with respect to AGA and SGA programming patterns. Neonatal mortality among LGA infants was similar for obese (6.2 in 1,000) and normal (4.9 in 1,000) weight mothers (OR 1.05, 95% confidence interval [CI] 0.75-1.48) and regardless of obesity subtype. By contrast, SGA and AGA infants programmed by obese mothers experienced greater neonatal mortality as compared with those born to normal weight mothers (AGA OR 1.45, 95% CI 1.32-1.59; SGA OR 1.72, 95% CI 1.49-1.98). CONCLUSION: Compared with normal weight mothers, obese women are least successful at programming SGA, less successful at programming AGA, and equally as successful at programming LGA infants. LEVEL OF EVIDENCE: II.

Folic Acid Intake, Fetal Brain Growth, and Maternal Smoking in Pregnancy: A Randomized Controlled Trial.

BACKGROUND: Folic acid supplementation during pregnancy plays an important role in fetal growth and development. To our knowledge, no experimental study has examined the effect of folic acid on fetal brain growth in women who smoke cigarettes during pregnancy. OBJECTIVES: The aim of this study was to investigate the efficacy of higher-dose compared with standard-dose folic acid supplementation on prenatal fetal brain growth, measured by head circumference, brain weight, and brain-body weight ratio (BBR). DESIGN: In this randomly assigned, double-blind, controlled clinical trial, we recruited 345 smoking pregnant women attending a community health center in Tampa, FL between 2010 and 2014. Participants were randomly assigned in a 1:1 ratio to receive either 0.8 mg folic acid/d (standard of care at the study center) or 4 mg folic acid/d (higher strength). Participants were also enrolled in a smoking cessation program. A 2-level linear growth model was used to assess treatment effect and factors that predict intrauterine growth in head circumference over time. Multiple linear regression analyses were conducted to estimate the effect of higher-strength folic acid on head circumference at birth, fetal brain weight, and fetal BBRs. RESULTS: Mothers who received the higher dose of folic acid had infants with a 1.18 mm larger mean head circumference compared with infants born to mothers who received the standard dose, but this difference was not statistically significant (P = 0.2762). Higher-dose folic acid also had no significant effect on brain weight. The BBR of infants of mothers who received higher-dose folic acid was, however, 0.33 percentage points lower than that for infants of mothers who received the standard dose of folic acid (P = 0.044). CONCLUSIONS: Infants of smokers in pregnancy may benefit from higher-strength maternal folic acid supplementation. We noted a decrease in the proportion of infants with impaired BBR among those on higher-dose folic acid. This trial was registered at clinicaltrials.gov as NCT01248260.

Hospital Variations in Unexpected Complications Among Term Newborns.

OBJECTIVES: To examine contributing factors and potential reasons for hospital differences in unexpected newborn complication rates in Florida. METHODS: We conducted a population-based retrospective cohort study of linked birth certificate and hospital discharge records from 2004 to 2013. The study population included 1 604 774 term, singleton live births in 124 hospitals. Severe and moderate complications were identified via a published algorithm. Logistic mixed-effects models were used to examine risk factors for complications and to estimate the percentage of hospital variation explained by factors. Descriptive analyses were performed to explore reasons for the differences. RESULTS: Hospital total complication rates varied from 6.7 to 98.6 per 1000 births. No correlation between severe and moderate complication rates by hospital was identified. Leading risk factors for complications included medically indicated early-term delivery, no prenatal care, nulliparity, prepregnancy obesity, tobacco use, and delivery in southern Florida hospitals. Hospital factors such as geographic location, level of care or birth volume, and Medicaid births percentage explained 35% and 27.8% of variation in severe and moderate complication rates, respectively. Individual factors explained an additional 6% of variation in severe complication rates. Different complication subcategories (eg, infections, hospital transfers) drove the hospital factors that contributed to severe and moderate complications. CONCLUSIONS: Variation in unexpected complication rates is more likely to be related to hospital rather than patient characteristics in Florida. The high proportion of variation explained by hospital factors suggests potential opportunities for improvement, and identifying specific complication categories may provide focus areas. Some of the opportunities may be related to differences in hospital coding practice.

Physicians' human papillomavirus vaccine recommendations, 2009 and 2011.

BACKGROUND: Physician recommendation is a key predictor of human papillomavirus (HPV) vaccine uptake. Understanding factors associated with recommendation is important for efforts to increase current suboptimal vaccine uptake. PURPOSE: This study aimed to examine physician recommendations to vaccinate female patients aged 11-26 years, in 2009 and 2011, at 3 and 5 years postvaccine licensure, respectively. A second aim was to identify trends in factors associated with vaccine recommendation for ages 11 and 12 years. METHODS: Nationally representative samples of physicians practicing family medicine, pediatrics, and obstetrics and gynecology were randomly selected from the American Medical Association Physician Masterfile (n=1538 in 2009, n=1541 in 2011). A mailed survey asked physicians about patient and clinical practice characteristics; immunization support; and frequency of HPV vaccine recommendation ("always" ≥75% of the time vs other). Analyses were conducted in 2012. RESULTS: Completed surveys were received from 1013 eligible physicians (68% response rate) in 2009 and 928 (63%) in 2011. The proportion of physicians who reported always recommending HPV vaccine increased significantly from 2009 to 2011 for patients aged 11 or 12 years (35% vs 40%, respectively; p=0.03), but not for patients aged 13-17 years (53% vs 55%; p=0.28) or 18-26 years (50% vs 52%; p=0.52). Physician specialty, age, and perceived issues/barriers to vaccination were associated with vaccine recommendation for patients aged 11 or 12 in both years. CONCLUSIONS: Results suggest a modest increase in recommendations for HPV vaccination of girls aged 11 or 12 years over a 2-year period; however, recommendations remain suboptimal for all age groups despite national recommendations for universal immunization.

Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach.

AIMS: We used propensity scores matching techniques to assess the association between maternal cocaine abuse in pregnancy and the occurrence of placenta-associated syndromes (PAS). STUDY DESIGN: Mothers who abused cocaine (n=5026) were matched to controls (n=5026) from a sample of 1,693,197, unexposed mothers in Florida from 1998 to 2007. Cocaine abuse was identified using the ICD-9 principal and secondary diagnosis codes (304.2 for cocaine dependence and 305.6 for cocaine abuse). The outcome of interest, PAS, was identified as any indication in diagnosis field of ICD-9-CM codes for: placental abruption (641.2), oligohydramnios (658.0), placental infarction (656.7, 656.8, 656.9), gestational hypertension (642.3, 642.9), preeclampsia (642.4, 642.5, and 642.7) or eclampsia (642.6). RESULTS: Nearly 6% of mothers in the study sample experienced a condition associated with PAS prior to matching. Women who abused cocaine were 58% more likely to have PAS when compared to women who did not (OR=1.48, 95% confidence interval: 1.33, 1.66). Women who abused cocaine were at elevated odds for placental abruption, placenta infarction and preeclampsia with the most pronounced odds noted for placental abruption (OR=2.79, 95% confidence interval: 2.19, 3.55). CONCLUSIONS: These findings indicate that cocaine abuse during pregnancy is associated with more placenta-related disorders than previously reported.

Recurrent versus isolated pre-eclampsia and risk of feto-infant morbidity outcomes: racial/ethnic disparity.

OBJECTIVE: We examined the association between recurrent versus isolated pre-eclampsia and feto-infant morbidity outcomes. STUDY DESIGN: This is a population-based retrospective study on Florida hospital discharge data linked to the birth cohort files from 1998 through 2007. The study population comprised women with singleton first and second births who experienced pre-eclampsia in both pregnancies, and a comparison group consisting of women who were normotensive during their first pregnancy but developed pre-eclampsia in their second pregnancy. Feto-infant morbidities (low birth weight, very low birth weight, preterm, very preterm and small for gestational age) were the outcome of interest. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between recurrent pre-eclampsia and feto-infant morbidity outcomes were obtained from logistic regression models. RESULT: Women who experienced recurrent pre-eclampsia were at elevated risk for low birth weight, very low birth weight, preterm and very preterm. The risk was most pronounced for preterm infants (OR=1.58 CL=1.42-1.76). Subgroup analysis demonstrated that infants born to black mothers with recurrent pre-eclampsia experienced the most elevated risk across all the racial/ethnic subgroups and this was most pronounced for very low birth weight and very preterm with a more than three-fold increase in risk (OR=3.77, 95% CI=2.77-5.13 and OR=3.66, 95% CI=2.66-5.03, respectively) as compared to the referent category (white mothers who were normotensive in first pregnancy but developed pre-eclampsia in their second pregnancy). CONCLUSION: Pre-eclampsia is very severe when it recurs and black women are affected more than white or Hispanic women.

Phase 1 randomized trial of the vaginal safety and acceptability of SPL7013 gel (VivaGel) in sexually active young women (MTN-004).

OBJECTIVES: The study was designed to assess the safety, adherence, acceptability, and effect on vaginal microflora of 3% SPL7013 Gel (VivaGel), a novel dendrimer topical microbicide that inhibits HIV, herpes simplex virus-2, and human papillomavirus in vitro and in animal models. DESIGN: Phase 1, randomized, double-blind, placebo-controlled study on sexually active women. METHODS: Sixty-one sexually active women aged 18-24 years were recruited from three sites in the United States. Participants were randomized 1: 1: 1 to receive VivaGel, VivaGel placebo, or a hydroxyethylcellulose (HEC) placebo twice daily for 14 consecutive days. Safety endpoints included genitourinary and/or other adverse events. Changes in vaginal flora were determined from Gram-stained vaginal smears and quantitative vaginal culture. RESULTS: No serious adverse events or withdrawals due to adverse events were reported. Genitourinary symptoms were reported as follows: VivaGel (n = 17/22; 77.3%), VivaGel placebo (n = 14/21; 66.7%), and HEC (n = eight of 18; 44.4%; not significant, P = 0.1). The incidence of abnormal pelvic examination findings was similar across all gel arms of the study. Using pairwise comparison, women in the VivaGel arm had a significantly higher incidence of related genitourinary adverse events compared with women in the HEC gel arm (0.297 versus 0.111 per 100 person-years, respectively; P = 0.003). Exposure to VivaGel and VivaGel placebo resulted in minor shifts in the vaginal microflora, but there was no overall impact on incidence of bacterial vaginosis as assessed by Nugent score. CONCLUSION: VivaGel was generally well tolerated and comparable with the VivaGel placebo, although there was a higher incidence of low-grade related genital adverse events compared to the HEC placebo gel.

Missed clinical opportunities: provider recommendations for HPV vaccination for 11-12 year old girls are limited.

OBJECTIVE: The purpose of this study was to determine the prevalence of physician recommendation of human papillomavirus (HPV) vaccination in early (ages 11-12), middle (13-17), and late adolescent/young adult (18-26) female patients by physician specialty, and to identify factors associated with recommendation in early adolescents. METHODS: A 38-item survey was conducted April 2009 through August 2009 among a nationally representative random sample of 1538 Family Physicians, Pediatricians, and Obstetricians and Gynecologists obtained from the American Medical Association Physician Masterfile. A multivariable model was used to assess factors associated with frequency of physician recommendation of HPV vaccination ("always"=76-100% of the time vs. other=0-75%) within the past 12 months. RESULTS: Completed surveys were received from 1013 physicians, including 500 Family Physicians, 287 Pediatricians, and 226 Obstetricians and Gynecologists (response rate=67.8%). Across the specialties, 34.6% of physicians reported they "always" recommend the HPV vaccine to early adolescents, 52.7% to middle adolescents, and 50.2% to late adolescents/young adults. The likelihood of "always" recommending the HPV vaccine was highest among Pediatricians for all age groups (P<0.001). Physician specialty, age, ethnicity, reported barriers, and Vaccines for Children provider status were significantly associated with "always" recommending HPV vaccination for early adolescents. CONCLUSIONS: Findings suggest missed clinical opportunities for HPV vaccination, and perceived barriers to vaccination may drive decisions about recommendation. Results suggest the need for age and specialty targeted practice and policy level interventions to increase HPV vaccination among US females.

Pre-eclampsia in the first pregnancy and subsequent risk of stillbirth in black and white gravidas.

OBJECTIVE: To examine the association between prior pre-eclampsia and subsequent stillbirth in black women and white women. STUDY DESIGN: This is a population-based retrospective study of Missouri maternally linked birth cohort files from 1989 to 2005. We analyzed singleton first and second births to mothers in the state of Missouri. The study population comprised women who experienced pre-eclampsia in their first pregnancy and a comparison group consisting of women who did not. The two groups were followed to their second pregnancy to document stillbirth occurrence. Adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prior pre-eclampsia and subsequent stillbirth were obtained from logistic regression models. RESULTS: Women who experienced prior pre-eclampsia had a 43% increased risk of subsequent stillbirth [OR=1.43; 95% CI=1.08-1.89]. Whereas women with a history of late-onset pre-eclampsia had no elevated risk for subsequent stillbirth, those whose first pregnancy resulted in early-onset pre-eclampsia had a more than 4-fold increased risk of stillbirth in their second pregnancy [OR=4.07; 95% CI=2.32-7.14]. When sub-analysis was performed on the two main racial groups in the State, we found that elevated risk for subsequent stillbirth in a second pregnancy was observed among black women with prior early-onset pre-eclampsia (OR=8.21; 95% CI=4.03-16.70) but not in whites (OR=1.95; 95% CI=0.72-5.26). CONCLUSION: Initiation of pregnancy with pre-eclampsia elevates the risk for subsequent stillbirth. The risk elevation is most pronounced in black women with early-onset pre-eclampsia in their first pregnancy. This information is valuable for inter-pregnancy counseling of affected women.

Prepregnancy obesity and risk of stillbirth in viable twin gestations.

We sought to estimate the impact of prepregnancy obesity on demise of one or both fetuses in twin gestations. We performed a retrospective cohort study using the Missouri maternally linked cohort files (years 1989-2005). Prepregnancy obesity was defined as a BMI >or=30. Outcomes of interest were stillbirth (intrauterine fetal death at >or=20 weeks' gestation) and demise of one (partial loss) or both (complete loss) fetuses, regardless of the cause. We used Cox Proportional Hazards with correction for intracluster correlation to obtain risk estimates. The overall stillbirth rate for twin gestations was 15.5/1,000 (18.4/1,000 vs. 14.5/1,000 in obese and normal weight mothers, respectively; P = 0.02). The rate for complete fetal loss was higher in obese mothers (8.3/1,000 vs. 5.6/1,000; P = 0.01) but was comparable for partial fetal loss (19.1/1,000 for obese vs. 16.3/1,000 for normal weight mothers; P = 0.1). Adjusted estimates confirmed these findings (adjusted hazards ratio (AHR) and 95% confidence interval (CI) = 1.31 (1.02-1.68) for stillbirth; AHR = 1.59; CI = 1.01-2.51) for complete loss; and AHR = 1.21; CI = 0.91-1.62) for partial loss. Subanalysis conducted on stillbirth showed that the risk associated with obesity was only elevated for same-sex (AHR = 1.54; CI = 1.15-2.04) but not opposite-sex twins (0.99; CI = 0.56-1.75). Our findings may find utility in counseling of obese women with twin gestations.