Estimating the effect of diuretics and inhaled corticosteroids for evolving bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Off-label treatment of extremely preterm infants with diuretics and inhaled corticosteroids (ICS) for evolving bronchopulmonary dysplasia (BPD) is common. Their effectiveness in reducing mortality or BPD severity, and optimal treatment timing, are unclear. OBJECTIVES: To determine whether diuretic treatment or ICS administration for infants with early evolving (between 10-27 days postnatal) and progressively evolving (28th-day-36th-week postnatal) BPD are independently associated with reduced mortality and moderate or severe BPD at 36-weeks postmenstrual age (PMA). METHODS: We examined neonates born before 28 weeks' gestation and admitted to neonatal intensive care units on postnatal Day 0 between 2006 and 2016 using data collected during routine care recorded within the Paediatric Health Information System (PHIS). An early evolving BPD cohort consisted of infants treated with oxygen, positive pressure or mechanical ventilation at 10 days postnatal. The progressively evolving BPD cohort consisted of infants treated with these modalities at 28 days. In new users, we evaluated the effect of diuretic and ICS treatment on mortality or BPD severity at 36 weeks PMA, adjusting for time-dependent confounding by respiratory status using marginal structural models. RESULTS: Early evolving BPD was present in 10,135 patients; progressively evolving BPD in 11,728. New diuretic exposure during early evolving BPD (adjusted risk ratio [aRR] 0.77, 95% confidence interval [CI] 0.65, 0.93) was associated with decreased mortality or moderate/severe BPD risk. New diuretics (aRR 0.86, 95% CI 0.75, 0.99) during progressively evolving BPD between 28-days-36-weeks PMA were less strongly associated with mortality or moderate/severe BPD reduction. There was no strong association for ICS in patients with early evolving (aRR: 1.40; 95% CI: 0.79, 2.51) or progressively evolving BPD (aRR 1.16, 95% CI 0.95, 1.49). CONCLUSION: Diuretics, but not ICS, for evolving BPD were associated with mortality and BPD risk reduction.

Associations of prenatal stress with 5-year-old children's executive function in a low socioeconomic status population.

Prenatal stress has a significant, but small, negative effect on children's executive function (EF) in middle and high socioeconomic status (SES) households. Importantly, rates and severity of prenatal stress are higher and protective factors are reduced in lower SES households, suggesting prenatal stress may be particularly detrimental for children's EF in this population. This study examined whether prenatal stress was linked to 5-year-old's EF in a predominantly low SES sample and child sex moderated this association, as males may be more vulnerable to adverse prenatal experiences. Participants were 132 mother-child dyads drawn from a prospective prenatal cohort. Mothers reported on their depression symptoms, trait anxiety, perceived stress, everyday discrimination, and sleep quality at enrollment and once each trimester, to form a composite prenatal stress measure. Children's EF was assessed at age 5 years using the parent-report Behavior Rating Inventory of Executive Function - Preschool (BRIEF-P) Global Executive Composite subscale and neuropsychological tasks completed by the children. Mixed models revealed higher prenatal stress was associated with lower BRIEF-P scores, indicating better EF, for females only. Higher prenatal stress was associated with lower performance on neuropsychological EF measures for both males and females. Results add to the limited evidence about prenatal stress effects on children's EF in low SES households.

Bacterial Vaginosis and Spontaneous Clearance of Chlamydia trachomatis in the Longitudinal Study of Vaginal Flora.

BACKGROUND: Up to 26% of urogenital Chlamydia trachomatis infections spontaneously resolve between detection and treatment. Mechanisms governing natural resolution are unknown. We examined whether bacterial vaginosis (BV) was associated with greater chlamydia persistence versus spontaneous clearance in a large, longitudinal study. METHODS: Between 1999 and 2003, the Longitudinal Study of Vaginal Flora followed reproductive-age women quarterly for 1 year. Baseline chlamydia screening and treatment were initiated after ligase chain reaction testing became available midstudy, and unscreened endocervical samples were tested after study completion. Chlamydia clearance and persistence were defined between consecutive visits without chlamydia-active antibiotics (n = 320 persistence/n = 310 clearance). Associations between Nugent score (0-3, no BV; 4-10, intermediate/BV), Amsel-BV, and chlamydia persistence versus clearance were modeled with alternating and conditional logistic regression. RESULTS: Of chlamydia cases, 48% spontaneously cleared by the next visit (310/630). Nugent-intermediate/BV was associated with higher odds of chlamydia persistence (adjusted odds ratio [aOR] = 1.89; 95% confidence interval [CI], 1.30-2.74), and the findings were similar for Amsel-BV (aOR 1.39; 95% CI, .99-1.96). The association between Nugent-intermediate/BV and chlamydia persistence was stronger in a within-participant analysis of 67 participants with both clearance/persistence intervals (aOR = 4.77; 95% CI, 1.39-16.35). BV symptoms did not affect any results. CONCLUSIONS: BV is associated with greater chlamydia persistence. Optimizing the vaginal microbiome may promote chlamydia clearance.

Crossing Birth-Weight-Specific Mortality Curves: How a Puzzling Clinical Observation Led to an Important Advance in Epidemiologic Methods.

Throughout the second half of the 20th century, clinicians noted that although African-American neonates were more likely than White neonates to weigh less than 2,500 g at birth (low birth weight), among low-birth-weight infants African Americans were more likely than Whites to survive. However, when born at normal weight, African-American infants were substantially less likely to survive. The observation generated much physiological speculation, and several clever mathematical manipulations were devised to "uncross the mortality curves." With the development and dissemination of directed acyclic graphs in the early 2000s, methodologists focusing on perinatal epidemiology showed graphically, in an early use of directed acyclic graphs, that birth weight was a "collider" and that controlling for birth weight, whether by regression, stratification, or restriction, introduced confounding of the race-mortality association by all unmeasured common causes of birth weight and mortality. These investigations showed that the crossing curves could be explained as an artifact of a conceptually flawed analysis. These results have applicability beyond perinatal epidemiology, including applicability to the "obesity paradox."

The racial disparity of severe maternal morbidity across weeks of gestation: a cross-sectional analysis of the 2019 National Inpatient Sample.

BACKGROUND: Severe maternal morbidity is increasing in the United States. Black women experience the highest rates of severe maternal morbidity and also of preterm births, which are associated with severe maternal morbidity. The racial disparity of severe maternal morbidity across weeks of gestation has not been well-studied. OBJECTIVE: This study aimed to evaluate differences in severe maternal morbidity between Black and White birthing people by week of gestation. Differences may indicate periods of pregnancy when Black women are particularly vulnerable to severe maternal morbidity and may require additional interventions. STUDY DESIGN: This was a cross-sectional study using the National Inpatient Sample from 2019. We used International Classification of Diseases codes from Centers for Disease Control and Prevention guidelines to identify severe maternal morbidity from delivery hospitalizations. We examined the rates of severe maternal morbidity in Black vs White women by week of gestation to evaluate periods of pregnancy when Black women experience additional risks of severe maternal morbidity while adjusting for age, region, medical comorbidities, and Medicaid enrollment. Severe maternal morbidity was analyzed while both including and excluding cases for which blood transfusion was the only indicator of severe maternal morbidity. RESULTS: Overall, Black birthing people had twice the rate of severe maternal morbidity births compared with White birthing people (2.7% vs 1.3%; P<.0001) and were more likely to deliver preterm (14.7% vs 9.4%; P<.0001). The racial disparity of severe maternal morbidity was present throughout all weeks of gestation, with the largest gap observed at extremely and moderately preterm gestations (22-33 weeks). Rates of severe maternal morbidity for Black women peaked at 22 to 33 weeks' gestation and were lowest at term (≥37 weeks). Black women had a greater proportion of severe maternal morbidity cases due to blood transfusion (68.3% vs 64.5%; P<.01) and acute renal failure (11.1% vs 8.5%; P<.001). CONCLUSION: Black women experience a substantially higher rate of severe maternal morbidity at preterm gestations (22-36 weeks) in addition to higher rates of preterm delivery. Even when accounting for age, medical comorbidities, and social determinants, Black birthing people have higher odds of severe maternal morbidity throughout pregnancy.

Interpregnancy interval and preterm delivery: An empirical comparison of between-persons and within-sibship designs.

BACKGROUND: Short interpregnancy interval has been associated with increased risk of preterm delivery; recent studies employing within-sibship designs suggest that this risk may be exaggerated. There are unresolved issues regarding properties of this design. OBJECTIVES: To compare directly the results, for short intervals, of between-person and within-sibship analyses when applied to the same target population. METHODS: Cross-sectional data are from the National Survey of Family Growth, a statistically representative survey of women and men in the USA, 2006-2015. Participants provided a complete pregnancy history including outcome, duration and ending date, enabling calculation of interval. Conventional analysis employed log-linear regression, controlling survey design, early life events, demographic variables, pregnancy intendedness, breastfeeding of the previous birth and obstetric history. Within-sibship analyses, utilising conditional log-linear regression, controlled the same variables, except those remaining static within each participant. RESULTS: Among participants with at least three live- or stillbirths, the percentage of pregnancies in each interval, and the percent of deliveries that were preterm following that interval were 9.2%, 14.6% for <6, and 14.7%, 15.4% for 6-11, versus 12.2%, 14.7% for 18-23 months. Among participants with at least three live- or stillborn infants, those in the within-sibship analysis had a higher risk profile than comparably parous, ineligible participants. In a between-participant analysis, among those included in within-sibship models, the adjusted risk ratios (vs 18-23 months) for preterm delivery for intervals <6 and 6-11 months were 0.74 (95% CI 0.63, 0.88) and 0.85 (95% CI 0.74, 0.98). The corresponding risk ratios were 0.56 (95% CI 0.14, 2.30) and 0.49 (95% CI 0.13, 1.80) for those ineligible for the within-sibship models. CONCLUSIONS: When comparable analyses were employed, the association between interval and preterm delivery was similar between participants included in the within-sibship analysis and those ineligible for the within-sibship analysis, but differed from those in the full cohort, perhaps due to different target populations.

Antibiotic treatment of bacterial vaginosis to prevent preterm delivery: Systematic review and individual participant data meta-analysis.

BACKGROUND: Bacterial vaginosis (BV) increases preterm delivery (PTD) risk, but treatment trials showed mixed results in preventing PTD. OBJECTIVES: Determine, using individual participant data (IPD), whether BV treatment during pregnancy reduced PTD or prolonged time-to-delivery. DATA SOURCES: Cochrane Systematic Review (2013), MEDLINE, EMBASE, journal searches, and searches (January 2013-September 2022) ("bacterial vaginosis AND pregnancy") of (i) clinicaltrials.gov; (ii) Cochrane Central Register of Controlled Trials; (iii) World Health Organization International Clinical Trials Registry Platform Portal; and (iv) Web of Science ("bacterial vaginosis"). STUDY SELECTION AND DATA EXTRACTION: Studies randomising asymptomatic pregnant individuals with BV to antibiotics or control, measuring delivery gestation. Extraction was from original data files. Bias risk was assessed using the Cochrane tool. Analysis used "one-step" logistic and Cox random effect models, adjusting gestation at randomisation and PTD history; heterogeneity by I2 . Subgroup analysis tested interactions with treatment. In sensitivity analyses, studies not providing IPD were incorporated by "multiple random-donor hot-deck" imputation, using IPD studies as donors. RESULTS: There were 121 references (96 studies) with 23 eligible trials (11,979 participants); 13 studies (6915 participants) provided IPD; 12 (6115) were incorporated. Results from 9 (4887 participants) not providing IPD were imputed. Odds ratios for PTD for metronidazole and clindamycin versus placebo were 1.00 (95% CI 0.84, 1.17), I2  = 62%, and 0.59 (95% CI 0.42, 0.82), I2  = 0 before; and 0.95 (95% CI 0.81, 1.11), I2  = 59%, and 0.90 (95% CI: 0.72, 1.12), I2  = 0, after imputation. Time-to-delivery did not differ from null with either treatment. Including imputed IPD, there was no evidence that either drug was more effective when administered earlier, or among those with a PTD history. CONCLUSIONS: Clindamycin, but not metronidazole, was beneficial in studies providing IPD, but after imputing data from missing IPD studies, treatment of BV during pregnancy did not reduce PTD, nor prolong pregnancy, in any subgroup or when started earlier in gestation.

Association between Diabetes in Pregnancy and Shoulder Dystocia by Infant Birth Weight in an Era of Cesarean Delivery for Suspected Macrosomia.

OBJECTIVE: We estimated the association between diabetes and shoulder dystocia by infant birth weight subgroups (<4,000, 4,000-4,500, and >4,500 g) in an era of prophylactic cesarean delivery for suspected macrosomia. STUDY DESIGN: A secondary analysis from the National Institute of Child Health and Human Development U.S. Consortium for Safe Labor of deliveries at ≥24 weeks with a nonanomalous, singleton fetus with vertex presentation undergoing a trial of labor. The exposure was either pregestational or gestational diabetes compared with no diabetes. The primary outcome was shoulder dystocia and secondarily, birth trauma with a shoulder dystocia. We calculated adjusted risk ratios (aRRs) with modified Poison's regression between diabetes and shoulder dystocia and the number needed to treat (NNT) to prevent a shoulder dystocia with cesarean delivery. RESULTS: Among 167,589 assessed deliveries (6% with diabetes), pregnant individuals with diabetes had a higher risk of shoulder dystocia at birth weight <4,000 g (aRR: 1.95; 95% confidence interval [CI]: 1.66-2.31) and 4,000 to 4,500 g (aRR: 1.57; 95% CI: 1.24-1.99), albeit not significantly at birth weight >4,500 g (aRR: 1.26; 95% CI: 0.87-1.82) versus those without diabetes. The risk of birth trauma with shoulder dystocia was higher with diabetes (aRR: 2.29; 95% CI: 1.54-3.45). The NNT to prevent a shoulder dystocia with diabetes was 11 and 6 at ≥4,000 and >4,500 g, versus without diabetes, 17 and 8 at ≥4,000 and >4,500 g, respectively. CONCLUSION: Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered. Guidelines providing the option of cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights. KEY POINTS: · >Diabetes increased the risk of shoulder dystocia, even at lower birth weight thresholds than at which cesarean delivery is currently offered.. · Cesarean delivery for suspected macrosomia may have decreased the risk of shoulder dystocia at higher birth weights.. · These findings can inform delivery planning for providers and pregnant individuals with diabetes..

Accurate identification of cohort study designs in perinatal research: a practical guide.

Study designs are often mischaracterized in the obstetrics literature; in particular, the designation of studies as retrospective (historical) cohorts is frequently in error to describe studies that are prospective cohorts. This is especially true for studies based on electronic health records, which often should be properly considered as prospective cohorts. Epidemiologic study designs were developed in earlier eras of research and healthcare when researchers directly contacted study participants or relied on data from paper medical records. Accordingly, standard epidemiologic study design definitions are difficult to apply to digitized data, which have become common in the modern era of healthcare and computing. In this article, we briefly review the characteristics of the 3 main types of cohort studies. Afterward, we build on existing definitions by proposing several subdesignations of prospective cohort studies that we believe will reduce the confusion in terminology. We provide illustrative examples from obstetrics to concretely demonstrate connections and distinctions among study designs. First, a prospective cohort study can be "active" (participants are deliberately and explicitly enrolled in a prospective research study) or "passive" (participants are followed up in real time for some nonresearch activity, such as clinical care or quality improvement). An active prospective cohort study never stops being a prospective cohort study; however, when reused to answer a new, secondary question, we propose that this should be called a "reused (active) prospective cohort." The de novo cohort study that answered the original question should be considered an "intended (active) prospective cohort." Lastly, when a randomized controlled trial is reused to study some new questions where the randomization variable is not under study, this is also a subtype of a prospective cohort study, a "repurposed randomized controlled trial." The use of more detailed descriptors to describe prospective cohort studies will enable more accurate identification of this study design going forward. It is likely that further refinements will be needed in the future, given the ongoing evolution of how we engage with patients or participants and how data are collected, stored, and linked.

Association between Prenatal Marijuana and Tobacco Smoke Exposures and Small for Gestational Age at Birth.

OBJECTIVE: The aim of this study was to determine the association of prenatal marijuana exposure with and without tobacco smoke exposure and small for gestational age (SGA) at birth. STUDY DESIGN: We conducted a secondary analysis of the prospective Lifestyle and Early Achievement in Families (LEAF) cohort enrolled from 2010 to 2015. We included singleton nonanomalous liveborn pregnancies. We assessed marijuana use inclusive of any pregnancy urine specimen with a Δ9-THC-COOH concentration of more than 15 ng/mL by mass spectrometry, self-report on questionnaire, and/or electronic health record; and self-reported maternal tobacco use. Because of the high co-frequency of marijuana with tobacco exposure in pregnancy and the known association between tobacco and fetal growth restriction, we modeled the exposure as: both marijuana and tobacco (hereafter "co-use"), only marijuana, only tobacco, and neither (reference). Incidence of SGA in each group was compared with the neither group. The primary outcome was SGA less than 10th percentile, and secondarily less than 5th percentile, using parity-specific definitions per 2017 US natality reference data. RESULTS: Among 325 assessed mothers, 46% had neither exposure, 11% had only prenatal marijuana exposure, 20% only tobacco exposure, and 23% co-use exposure. A third (33%) of infants were SGA less than 10th percentile and 20% SGA less than 5th percentile. Marijuana exposure only was associated with an increased risk of SGA less than 10th percentile (43 vs. 26%; adjusted relative risk [aRR]: 1.66; 95% confidence interval [CI]: 1.02-2.69), and SGA less than5th percentile (30 vs. 13%; aRR: 2.26; 95% CI: 1.15-4.47). Tobacco was not associated with SGA less than 10th percentile, but was with SGA less than 5th percentile (26 vs. 13%; aRR: 2.01; 95% CI: 1.13, 3.56). Co-use was not associated with increased SGA risk in multivariate analysis, but was in sensitivity analysis when tobacco use was defined using a cotinine assay rather than self-report (SGA <10th percentile, aRR: 1.97; 95% CI: 1.24-3.15) and (SGA <5th percentile, aRR: 2.03; 95% CI: 1.09-3.78). CONCLUSION: Prenatal marijuana exposure in addition to tobacco may increase the risk of SGA. Given the rising prevalence of marijuana use in pregnancy, further research is warranted to understand how in utero marijuana exposure may impact fetal growth and birth weight with and without tobacco exposure. KEY POINTS: · Marijuana and tobacco are commonly used together in pregnancy.. · Prenatal marijuana and tobacco exposure may increase the risk of a small for gestational age infant.. · Further research is warranted to understand how in utero marijuana exposure impacts fetal growth..

Exploration of Differences between Women Who Do and Do Not Disclose Their Marijuana Use during Pregnancy.

OBJECTIVE: This study aimed to explore demographic and health-related factors that may differentiate women who do and do not disclose their marijuana use during pregnancy. STUDY DESIGN: The current study is a secondary analysis of data from a prospective cohort of pregnant women identified as using marijuana during pregnancy via a variety of assessment tools including self-report, urine screen, and obstetrics record abstraction. The cohort included a convenience sample of women recruited from several antenatal clinics at The Ohio State University Wexner Medical Center (OSUWMC). To be eligible, women needed to be within the first or second trimester of their pregnancy, 16 to 50 years of age, able to communicate in English, and intended to deliver at OSUWMC. Chi-square, independent samples t-tests, and logistic regression analyses were used to explore differences between those who did and did not disclose their use in relation to physical and mental health diagnoses, adverse experiences, use of other substances, and demographics. RESULTS: Women who used marijuana during their pregnancy and had mental/physical health data available comprised the current sample (n = 109). Women who attended college were more likely to disclose their marijuana use compared with women who did not attend college (p < 0.001). Women who experienced homelessness (p < 0.01) or self-reported alcohol use during pregnancy (p < 0.001) were significantly more likely to disclose their marijuana use. CONCLUSION: Findings, suggesting disclosure of other substance use and adverse experiences, such as homelessness, may increase the likelihood that pregnant women will voluntarily disclose their marijuana use to providers. Findings did not reflect racial differences nor significant differences in mental/physical health status among women based on their disclosure. Future research with larger datasets is needed to build on these findings by confirming results, as well as exploring additional factors, that may more effectively differentiate women who are unlikely to disclose their prenatal marijuana use from those who do disclose their use. KEY POINTS: · Women with higher education were more likely to self-disclose their prenatal marijuana use.. · Women who experienced homelessness were more likely to self-disclose their prenatal marijuana use.. · Self-disclosure of prenatal alcohol use was related to self-disclosure of prenatal marijuana use.

Trends in Active Treatment of Live-born Neonates Between 22 Weeks 0 Days and 25 Weeks 6 Days by Gestational Age and Maternal Race and Ethnicity in the US, 2014 to 2020.

Importance: Birth in the periviable period between 22 weeks 0 days and 25 weeks 6 days' gestation is a major source of neonatal morbidity and mortality, and the decision to initiate active life-saving treatment is challenging. Objective: To assess whether the frequency of active treatment among live-born neonates in the periviable period has changed over time and whether active treatment differed by gestational age at birth and race and ethnicity. Design, Setting, and Participants: Serial cross-sectional descriptive study using National Center for Health Statistics natality data from 2014 to 2020 for 61 908 singleton live births without clinical anomalies between 22 weeks 0 days and 25 weeks 6 days in the US. Exposures: Year of delivery, gestational age at birth, and race and ethnicity of the pregnant individual, stratified as non-Hispanic Asian/Pacific Islander, non-Hispanic Black, Hispanic/Latina, and non-Hispanic White. Main Outcomes and Measures: Active treatment, determined by whether there was an attempt to treat the neonate and defined as a composite of surfactant therapy, immediate assisted ventilation at birth, assisted ventilation more than 6 hours in duration, and/or antibiotic therapy. Frequencies, mean annual percent change (APC), and adjusted risk ratios (aRRs) were estimated. Results: Of 26 986 716 live births, 61 908 (0.2%) were periviable live births included in this study: 5% were Asian/Pacific Islander, 37% Black, 24% Hispanic, and 34% White; and 14% were born at 22 weeks, 21% at 23 weeks, 30% at 24 weeks, and 34% at 25 weeks. Fifty-two percent of neonates received active treatment. From 2014 to 2020, the overall frequency (mean APC per year) of active treatment increased significantly (3.9% [95% CI, 3.0% to 4.9%]), as well as among all racial and ethnic subgroups (Asian/Pacific Islander: 3.4% [95% CI, 0.8% to 6.0%]); Black: 4.7% [95% CI, 3.4% to 5.9%]; Hispanic: 4.7% [95% CI, 3.4% to 5.9%]; and White: 3.1% [95% CI, 1.1% to 4.4%]) and among each gestational age range (22 weeks: 14.4% [95% CI, 11.1% to 17.7%] and 25 weeks: 2.9% [95% CI, 1.5% to 4.2%]). Compared with neonates born to White individuals (57.0%), neonates born to Asian/Pacific Islander (46.2%; risk difference [RD], -10.81 [95% CI, -12.75 to -8.88]; aRR, 0.82 [95% CI, [0.79-0.86]), Black (51.6%; RD, -5.42 [95% CI, -6.36 to -4.50]; aRR, 0.90 [95% CI, 0.89 to 0.92]), and Hispanic (48.0%; RD, -9.03 [95% CI, -10.07 to -7.99]; aRR, 0.83 [95% CI, 0.81 to 0.85]) individuals were significantly less likely to receive active treatment. Conclusions and Relevance: From 2014 to 2020 in the US, the frequency of active treatment among neonates born alive between 22 weeks 0 days and 25 weeks 6 days significantly increased, and there were differences in rates of active treatment by race and ethnicity.

Bacterial Vaginosis and Behavioral Factors Associated With Incident Pelvic Inflammatory Disease in the Longitudinal Study of Vaginal Flora.

BACKGROUND: Pelvic inflammatory disease (PID) leads to long-term reproductive consequences for cisgender women. Bacterial vaginosis (BV) and behavioral factors may play a role in PID pathogenesis. We assessed associations between BV, behavioral factors, and incident PID. METHODS: We analyzed participants (N = 2956) enrolled in the National Institutes of Health Longitudinal Study of Vaginal Flora, a cohort of nonpregnant cisgender women followed quarterly for 12 months. PID was defined by at least 1 of the following: cervical motion tenderness, uterine tenderness, or adnexal tenderness (160 cases). We tested associations between BV (measured using Nugent and Amsel criteria) and PID at the subsequent visit. Sociodemographic factors, sexual behaviors, and Chlamydia trachomatis (CT), untreated at baseline and concurrent with BV, were covariates in Cox proportional hazards models. Adjusting for the few Neisseria gonorrhoeae and Trichomonas vaginalis cases did not alter results. RESULTS: In multivariable modeling, Nugent-BV (adjusted hazard ratio [aHR], 1.53 [95% confidence interval {CI}, 1.05-2.21]), symptomatic Amsel-BV (aHR, 2.15 [95% CI, 1.23-3.75]), and vaginal douching (aHR, 1.47 [95% CI, 1.03-2.09]) were associated with incident PID. CONCLUSIONS: BV was associated with incident PID in a large prospective cohort, controlling for behavioral factors and sexually transmitted infections (STIs). Larger studies on how BV, STIs, behaviors, and host responses interactively affect PID risk are needed.

Perceived Stress and Molecular Bacterial Vaginosis in the National Institutes of Health Longitudinal Study of Vaginal Flora.

Vaginal microbiota provide the first line of defense against urogenital infections primarily through protective actions of Lactobacillus species Perceived stress increases susceptibility to infection through several mechanisms, including suppression of immune function. We investigated whether stress was associated with deleterious changes to vaginal bacterial composition in a subsample of 572 women in the Longitudinal Study of Vaginal Flora, sampled from 1999 through 2002. Using Cox proportional hazards models, both unadjusted and adjusted for sociodemographic factors and sexual behaviors, we found that participants who exhibited a 5-unit-increase in Cohen's Perceived Stress Scale had greater risk (adjusted hazard ratio (HR) = 1.40, 95% confidence interval (CI): 1.13, 1.74) of developing molecular bacterial vaginosis (BV), a state with low Lactobacillus abundance and diverse anaerobic bacteria. A 5-unit increase in stress score was also associated with greater risks of transitioning from the L. iners-dominated community state type (26% higher) to molecular-BV (adjusted HR = 1.26, 95% CI: 1.01, 1.56) or maintaining molecular-BV from baseline (adjusted HR = 1.23, 95% CI: 1.01, 1.47). Inversely, women with baseline molecular-BV reporting a 5-unit stress increase were less likely to transition to microbiota dominated by L. crispatus, L. gasseri, or L. jensenii (adjusted HR = 0.81, 95% CI: 0.68, 0.99). These findings suggest that psychosocial stress is associated with vaginal microbiota composition, inviting a more mechanistic exploration of the relationship between psychosocial stress and molecular-BV.

Underdiagnosis of obesity in pediatric clinical care settings among children born preterm: a retrospective cohort study.

BACKGROUND: Neonatal care of preterm infants may include dietary approaches such as high calorie formulas to promote physical growth. However, continuing growth-promoting strategies beyond the point of necessity, coupled with poverty and food insecurity which are more common among families of children born preterm, may increase the risk of obesity. Because children born preterm tend to have more pressing health conditions that require ongoing care, obesity may go undiagnosed by providers. METHODS: This retrospective cohort study included 38,849 children (31,548 term, 7301 preterm) born from 2010 to 2015, who received clinical care at a large pediatric medical center (Ohio, USA). Electronic medical record data, linked to Ohio birth certificates, were used to identify children with measured obesity (≥2 weight-for-length values ≥95th percentile before 24 months of age or BMI values ≥95th percentile at or after 24 months of age). Children were considered to have diagnosed obesity if their medical record had an obesity-related phrase or billing code recorded. Modified Poisson regression was used to compare risk of obesity undiagnosis among obese children born preterm versus at term. RESULTS: In total, 13,697 children had measured obesity, 10,273 (75%) of which were undiagnosed. Children born preterm with measured obesity were 8% more likely to be undiagnosed compared to children born at term (adjusted relative risk = 1.08 95% CI 1.05, 1.11). The risk was slightly higher for preterm children born to white women or born to women with higher educational attainment. For both groups, Primary Care and subspecialist clinics were the most common settings for undiagnosed obesity (74.9% and 16.8% of undiagnosed cases, respectively). CONCLUSIONS AND RELEVANCE: Preterm birth was associated with increased risk of undiagnosed obesity in early childhood. This highlights the need to enhance obesity screening in the preterm population and to further explore reasons for this disparity.

Moms in motion: weight loss intervention for postpartum mothers after gestational diabetes: a randomized controlled trial.

BACKGROUND: Up to 50 % of women with gestational diabetes mellitus (GDM) will receive a diagnosis of type 2 diabetes mellitus (T2DM) within a decade after pregnancy. While excess postpartum weight retention exacerbates T2DM risk, lifestyle changes and behavior modifications can promote healthy postpartum weight loss and contribute to T2DM prevention efforts. However, some women have difficulty prioritizing self-care during this life stage. Efficacious interventions that women can balance with motherhood to reduce T2DM risk remain a goal. The objective of the Moms in Motion study is to evaluate the efficacy of a simple, novel, activity-boosting intervention using ankle weights worn with daily activities during a 6-month postpartum intervention among women with GDM. We hypothesize that women randomized to the 6-month intensity-modifying intervention will (1) demonstrate greater weight loss and (2) greater improvement in body composition and biomarker profile versus controls. METHODS: This study will be a parallel two-arm randomized controlled trial (n = 160). Women will be allocated 1:1 to an ankle weight intervention group or a standard-of-care control group. The intervention uses ankle weights (1.1 kg) worn on each ankle during routine daily activities (e.g., cleaning, childcare). Primary outcomes include pre- and post-assessments of weight from Visit 2 to Visit 3. Secondary outcomes include body composition, glycemia (2-h, 75 g oral glucose tolerance test), and fasting insulin. Exploratory outcomes include energy expenditure, diet, and psychosocial well-being. DISCUSSION: Beyond the expected significance of this study in its direct health impacts from weight loss, it will contribute to exploring (1) the mechanism(s) by which the intervention is successful (mediating effects of energy expenditure and diet on weight loss) and (2) the effects of the intervention on body composition and biomarkers associated with insulin resistance and metabolic health. Additionally, we expect the findings to be meaningful regarding the intervention's effectiveness on engaging women with GDM in the postpartum period to reduce T2DM risk. TRIAL REGISTRATION: The ClinicalTrials.gov Identifier, is NCT03664089 . The trial registration date is September 10, 2018. The trial sponsor is Dr. Sarah A. Keim.

Marijuana Use during Pregnancy and Preterm Birth: A Prospective Cohort Study.

OBJECTIVE: The aim of this study is to estimate the association between marijuana use during pregnancy and total, spontaneous and indicated preterm birth. STUDY DESIGN: Prospective cohort study of women receiving antenatal care at The Ohio State University from 2010 to 2015. Marijuana use was assessed by questionnaire, record abstraction, and urine toxicology. Women were followed through the end of pregnancy. Relative risks were assessed with Poisson regression and time to delivery with proportional hazard models. RESULTS: Of 363 eligible women, 119 (33%) used marijuana in pregnancy by at least one measure. In this high-risk cohort, preterm birth occurred to 36.0% of users and 34.6% of nonusers (p = 0.81). The unadjusted relative risk of all preterm birth was 1.06 (95% confidence interval [CI]: 0.76-1.47); the adjusted relative risk was similar 1.04 (95% CI: 0.72-1.50). Spontaneous preterm birth was nonsignificantly elevated among users before 1.32 (95% CI: 0.89-1.96), and after 1.21 (95% CI: 0.76-1.94) adjustment. Indicated preterm birth was nonsignificantly reduced before 0.52 (95% CI: 0.22-1.23) and after 0.75 (95% CI: 0.29-2.15) adjustment. The unadjusted hazard ratio (HR) for time to preterm birth was 1.26 (95% CI: 0.84-2.00); the adjusted HR was 1.32 (95% CI: 0.80-2.07). Both unadjusted 1.77 (95% CI: 1.06-2.93) and adjusted 2.16 (95% CI: 1.16-4.02) HRs for spontaneous preterm birth were significantly elevated, primarily due to an increased risk of spontaneous birth <28 weeks among users. The unadjusted and adjusted HRs for time to indicated preterm birth were 0.69 (95% CI: 0.33-1.43) and 0.58 (95% CI: 0.23-1.46). CONCLUSION: Marijuana use was not associated with total preterm birth in this cohort, suggesting that among women already at high risk of preterm birth, marijuana does not increase risk further. However, there was a suggestion that pregnant women who use marijuana may deliver earlier, particularly from spontaneous preterm birth, than women who do not use marijuana. KEY POINTS: · Marijuana was not associated with risk of all preterm birth.. · Marijuana was not associated with reduced time to delivery.. · However, users had reduced time to spontaneous preterm birth..

Behavioral and Cognitive Differences in Early Childhood related to Prenatal Marijuana Exposure.

Prenatal marijuana exposure (PME) negatively impacts child development and behavior; however, few studies have examined these associations at early ages among children exposed to today's highly potent marijuana. Using a prospective prenatal cohort (Columbus, Ohio, USA), PME was determined from maternal self-report, medical chart abstraction, and urine toxicology from prenatal visits and delivery. At age 3.5 years, 63 offspring children completed tasks assessing executive function (EF), visual spatial ability, emotion regulation, and aggressive behavior. Caregivers reported on children's EF and problem behaviors. Logistic regressions and analyses of covariance controlling for key variables were used to examine associations between PME and child outcomes. Compared to non-exposed children, children with PME had more sleep-related problems, withdrawal symptoms, and externalizing problems, including aggressive behaviors and oppositional defiant behaviors. Children with and without PME did not differ in terms of executive functioning. Findings suggest behavioral problems associated with PME may manifest by age 3.5.

Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia.

BACKGROUND: Pulmonary hypertension (PH) in patients with bronchopulmonary dysplasia (BPD) results from vasoconstriction and/or vascular remodeling, which can be regulated by mitogen-activated protein kinases (MAPKs). MAPKs are deactivated by dual-specificity phosphatases (DUSPs). We hypothesized that single-nucleotide polymorphisms (SNPs) in DUSP genes could be used to predict PH in BPD. METHODS: Preterm infants diagnosed with BPD (n = 188) were studied. PH was defined by echocardiographic criteria. Genomic DNA isolated from patient blood samples was analyzed for 31 SNPs in DUSP genes. Clinical characteristics and minor allele frequencies were compared between BPD-PH (cases) and BPD-without PH (control) groups. Biomarker models to predict PH in BPD using clinical and SNP data were tested by calculations of area under the ROC curve. RESULTS: In our BPD cohort, 32% (n = 61) had PH. Of the DUSP SNPs evaluated, DUSP1 SNP rs322351 was less common, and DUSP5 SNPs rs1042606 and rs3793892 were more common in cases than in controls. The best fit biomarker model combines clinical and DUSP genetic data with an area under the ROC curve of 0.76. CONCLUSION: We identified three DUSP SNPs as potential BPD-PH biomarkers. Combining clinical and DUSP genetic data yields the most robust predictor for PH in BPD.

Lifestyle and Early Achievement in Families (LEAF) study: Design of an ambidirectional cohort study of prenatal marijuana exposure and child development and behaviour.

BACKGROUND: Marijuana is the most-used illicit substance during pregnancy in the USA, but only two cohort studies, begun over 30 years ago, were specifically established to assess the association of pregnancy use with childhood outcomes. They found use to be associated with specific deficits in executive function at 8+ years, but did not focus on these outcomes earlier in life when intervention may be more successful. Two general purpose cohorts found increased aggression in exposed female toddlers and increased behavioural problems and tic disorders in exposed school-age children. OBJECTIVES: The Lifestyle and Early Achievement in Families (LEAF) study assesses the association of in utero marijuana exposure, documented prospectively by biomarker, self-report, and medical records, with executive function and aggression at age 3½-7 years. METHODS: This ambidirectional cohort (historical cohort with continued follow-up) includes women enrolled in the Perinatal Research Repository during prenatal care at Ohio State University Wexner Medical Center and their children, recontacted 3½-7 years post-birth. Children complete 1-2 study visits including cognitive testing, behavioural observation, and maternal and teacher report of behaviour. Family and social environmental factors are assessed. RESULTS: Child follow-up began in September 2016; visits continue through August 2020. There are 362 eligible children; 32% had mothers who used marijuana during pregnancy, 10% of mothers completed college, and 23% did not complete high school. Mean maternal age at study registration in pregnancy was 26.4 years, and 63% of mothers were African American. To date, 268 children have completed at least 1 study visit. CONCLUSIONS: The LEAF Study will document the association of prenatal marijuana exposure with development and behaviour in the current era when marijuana is more potent than when previous cohorts were studied. The results may inform policy and interventions to counsel reproductive-aged women about the risks of use during pregnancy and guide prevention and treatment of adverse effects among children.