Objective: To determine the association between treatment of persistent BV in pregnancy and risk for spontaneous preterm birth (sPTB). Design: The retrospective data from IBM® MarketScan® Commercial Database was analyzed. Setting: United States outpatient data. Population or Sample: Women aged 12–55 years with a singleton gestation. Methods: Women were linked to an outpatient medications database and medications taken during the pregnancy were analyzed. Treatment of BV in pregnancy was defined as a diagnosis of BV and treatment with Metronidazole and/or Clindamycin, and persistent treatment of BV was defined as BV in more than 1 trimester or BV requiring more than 1 antibiotic prescription. Odds ratios were calculated comparing sPTB in those with BV and persistent BV to women without BV in pregnancy. Survival analysis using Kaplan-Meier curves for the gestational age at delivery was also performed. Main outcome measures: sPTB Results: Among a cohort of 2,538,606 women, 216,611 had an associated ICD-9 or ICD-10 code for diagnosis of BV alone, and 63,817 had BV and were treated with either metronidazole and/or clindamycin. The sPTB rate among women treated with BV was 7.5% compared with 5.7% for women without BV who did not receive antibiotics. Relative to those without BV in pregnancy, odds ratios for sPTB were highest in those treated for BV in both the first and second trimester (1.66 [95% CI 1.52, 1.81]) or those with 3 or more prescriptions in pregnancy (1.48 [95% CI 1.35, 1.63]. Conclusions: Treatment of persistent BV is associated with increased sPTB risk.

Objective To evaluate whether longitudinal measurements of serological adipokines and sphingolipids can predict preeclampsia early in gestation. Design Retrospective multi-omics discovery and longitudinal validation. Setting Maternity units in two US hospitals. Methods A multi-omics approach integrating genomic and lipidomic discoveries was employed to identify leptin (Lep) and ceramide (Cer) as novel PE early gestational biomarkers. The levels of placental growth factor (PlGF), soluble fms-like tyrosine kinase (sFlt-1), Lep, and Cer in maternal sera were then determined by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. Main outcome measures Interval from positive prediction to confirmative diagnosis. Results Genomic meta-analysis compiled six PE placental cohorts with 78 PE and 95 non-PE control placentas. The Testing Cohort included sera from 7 non-PE and 8 PE women collected at confirmatory diagnosis. The Validation Cohort included sera from 20 non-PE and 20 PE women collected longitudinally through gestation. Our findings revealed a marked elevation of maternal serum Leptin/Ceramide (d18:1/25:0) ratio from early gestation (a median of 23 weeks) when comparing later PE-complicated with uncomplicated pregnancies. The maternal Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting PE for sensitivity (85% vs. 40%), positive predictive value (89% vs. 42%), and AUC (0.92 vs. 0.52) from 5 to 25 weeks of gestation. Conclusions Non-invasive longitudinal assessment by serological evaluation of Lep/Cer (d18:1/25:0) ratio can case find early pregnancies at risk of preeclampsia, outperforming sFlt-1/PlGF ratio test. Tweetable abstract Non-invasive longitudinal assessment by serological evaluation of Lep and Cer ratio can predict preeclampsia early in gestation.