Can changes in angiogenic biomarkers between the first and second trimesters of pregnancy predict development of pre-eclampsia in a low-risk nulliparous patient population?

OBJECTIVE: To determine if change in maternal angiogenic biomarkers between the first and second trimesters predicts pre-eclampsia in low-risk nulliparous women. DESIGN: A nested case-control study of change in maternal plasma soluble Flt-1 (sFlt-1), soluble endoglin (sEng) and placenta growth factor (PlGF). We studied 158 pregnancies complicated by pre-eclampsia and 468 normotensive nonproteinuric controls. SETTING: A multicentre study in 16 academic medical centres in the USA. POPULATION: Low-risk nulliparous women. METHODS: Luminex assays for PlGF, sFlt-1 and sEng performed on maternal EDTA plasma collected at 9-12, 15-18 and 23-26 weeks of gestation. Rate of change of analyte between first and either early or late second trimester was calculated with and without adjustment for baseline clinical characteristics. MAIN OUTCOME MEASURES: Change in PlGF, sFlt-1 and sEng. RESULTS: Rates of change of PlGF, sEng and sFlt-1 between first and either early or late second trimesters were significantly different in women who developed pre-eclampsia, severe pre-eclampsia or early-onset pre-eclampsia compared with women who remained normotensive. Inclusion of clinical characteristics (race, body mass index and blood pressure at entry) increased sensitivity for detecting severe and particularly early-onset pre-eclampsia but not pre-eclampsia overall. Receiver operating characteristics curves for change from first to early second trimester in sEng, PlGF and sFlt-1 with clinical characteristics had areas under the curve of 0.88, 0.84 and 0.86, respectively, and for early-onset pre-eclampsia with sensitivities of 88% (95% CI 64-99), 77% (95% CI 50-93) and 77% (95% CI 50-93) for 80% specificity, respectively. Similar results were seen in the change from first to late second trimester. CONCLUSION: Change in angiogenic biomarkers between first and early second trimester combined with clinical characteristics has strong utility for predicting early-onset pre-eclampsia

Association of Timing of Sexual Partnerships and Perceptions of Partners' Concurrency With Reporting of Sexually Transmitted Infection Diagnosis.

Importance: The timing of sexual partnerships is important for sexually transmitted infection (STI) transmission potential. Studies often measure timing as whether partnerships overlap in time (concurrency), but this measure does not account for how STI risk from previous partners can be carried forward into future partnerships even when there is a time gap between them (serial monogamy) if the infectious period is greater than this time gap. Objective: To examine the association of the timing of partnerships, measured as the time gap or time overlap between partners, and perceptions of partners' concurrency with STI transmission. Design, Setting, and Participants: This survey study that was conducted in 2017 included 8867 participants in Britain aged 16 to 44 years who reported 1 or more sexual partners in the 5 years before the interview. Data were collected from 2010 to 2012 from Britain's third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a large probability survey (response rate, 57.7%) designed to be broadly representative of the general population. Exposures: Gaps between participants' 3 or fewer most recent partners in the past 5 years were calculated from dates of the last sexual encounter with former partners and the first sexual encounter with subsequent partners. Negative gaps denote overlapping partnerships (concurrency); positive gaps denote serial monogamy. Participant perception of most recent partner concurrency was proxied by asking participants whether they knew or thought that their partners had had sex with other partners since their first sexual encounter together. Main Outcomes and Measures: Reported STI diagnosis in the past 5 years. Results: Of 8867 participants eligible for this analysis, 3509 (39.6%) were male and 5158 (58.2%) were female, with a mean age of 28 years. Overall, 48.1% of males and 39.5% of females reported 2 or more partners and 1 or more time gaps. The median time gap was 2 months (interquartile range, -3 months to 8 months). Although 67.0% of the time gaps were 1 month or more, many were sufficiently short time gaps for STI transmission. The time gap was independently associated with STI diagnosis, without a significant decrease in likelihood until the time gap was 4 months or more for females (adjusted odds ratio [OR]: 0.39, 95% CI, 0.19-0.81) and 6 months or more for males (adjusted OR: 0.42, 95% CI, 0.20-0.85) compared with time overlaps of 2 years or more. Participant perception of partners' concurrency (reported by half of the participants) was independently associated with STI diagnosis among females (reporting no partner concurrency vs reporting partner concurrency: adjusted OR, 0.32; 95% CI, 0.22-0.49). Conclusions and Relevance: The findings suggest that the gap between partners is often sufficiently small to permit STI transmission and that many people, although themselves monogamous, have partners who are not, which itself is associated with an increase in the risk of STI acquisition. Public health practitioners should communicate these epidemiological facts, and researchers should develop measures that better capture the risk of STI transmission from partners

Soluble fms-Like Tyrosine Kinase 1 (sFlt1), Endoglin and Placental Growth Factor (PlGF) in Preeclampsia among High Risk Pregnancies

Background: Differences in circulating concentrations of antiangiogenic factors sFlt1 and soluble endoglin (sEng) and the pro-angiogenic growth factor PlGF are reported to precede the onset of preeclampsia weeks to months in low-risk pregnant women. The objective of this study was to investigate whether similar changes can be detected in pregnant women at high-risk to develop the syndrome. Methods: This study is a secondary analysis of the NICHD MFMU trial of aspirin to prevent preeclampsia in high-risk pregnancies. Serum samples were available from 194 women with pre-existing diabetes, 313 with chronic hypertension, 234 with multifetal gestation, and 252 with a history of preeclampsia in a previous pregnancy. Samples collected across pregnancy were analyzed in a blinded fashion for sFlt1, sEng and PlGF. Results: The odds of developing preeclampsia were significantly increased among women with multiple fetuses for each 2- fold elevation in sFlt1, sEng and the ratio of angiogenic factors (e.g. OR 2.18, 95% CI 1.46-3.32), and significantly decreased for each 2-fold elevation in circulating PlGF (OR 0.50, 95% CI 0.30-0.82) between 7 and 26 weeks' gestation. Cross-sectional analysis of the angiogenic factors across gestation showed significant differences during the third trimester in women who develop preeclampsia compared with appropriate controls in all high-risk groups. However, when data were examined in relation to the gestational week when preeclampsia was diagnosed only sFlt1 was significantly higher 2 to 5 weeks before the clinical onset of preeclampsia and only in women with previous preeclampsia. Conclusions: The pattern of elevated concentrations of sFlt1 and sEng, and low PlGF in high-risk pregnant subjects who develop preeclampsia is similar to that reported in low-risk pregnant women. However, differences in these factors among high-risk women who do and do not develop preeclampsia are modest, and do not appear to be clinically useful predictors in these high-risk pregnant women

Laboratory Abnormalities in Pregnancy-Associated Hypertension: Frequency and Association With Pregnancy Outcomes

To estimate the frequency of abnormal laboratory test results in pregnancy-associated hypertension and relationship with pregnancy outcomes

Effect of Smoking on Circulating Angiogenic Factors in High Risk Pregnancies

Objective: Changes in maternal concentrations of the anti-angiogenic factors, soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng), and the pro-angiogenic placental growth factor (PlGF) precede the development of preeclampsia in healthy women. The risk of preeclampsia is reduced in women who smoke during pregnancy. The objective of this study was to investigate whether smoking affects concentrations of angiogenic factors (sFlt1, PlGF, and sEng) in women at high risk for developing preeclampsia. Study Design: We performed a secondary analysis of serum samples from 993 high-risk women (chronic hypertension, diabetes, multifetal gestation, and previous preeclampsia) in a preeclampsia prevention trial. sFlt1, sEng and PlGF were measured in serum samples obtained at study entry, which was prior to initiation of aspirin (median 19.0 weeks' [interquartile range of 16.0-22.6 weeks']). Smoking status was determined by self-report. Results: sFlt1 was not significantly different in smokers from any high-risk groups compared to their nonsmoking counterparts. PlGF was higher among smokers compared to nonsmokers among diabetic women (142.7 [77.4-337.3] vs 95.9 [48.5-180.7] pg/ml, p = 0.005) and women with a history of preeclampsia (252.2 [137.1-486.0] vs 152.2 [73.6-253.7] pg/ml, p = 0.001). sEng was lower in smokers with multifetal gestations (5.8 [4.6-6.5] vs 6.8 [5.5-8.7] ng/ml, p = 0.002) and trended lower among smokers with diabetes (4.9 [3.8-5.6] vs 5.3 [4.3-6.3] ng/ml, p = 0.05). Smoking was not associated with a lower incidence of preeclampsia in any of these groups. Conclusions: In certain high-risk groups, smoking is associated with changes in the concentrations of these factors towards a pro-angiogenic direction during early pregnancy; however, there was no apparent association between smoking and the development of preeclampsia in our cohort

Pregnancy Outcomes With Weight Gain Above or Below the 2009 Institute of Medicine Guidelines

To evaluate pregnancy outcomes according to 2009 Institute of Medicine (IOM) gestational weight gain guidelines

First-Trimester Prediction of Preeclampsia in Nulliparous Women at Low Risk

To identify clinical characteristics and biochemical markers in first-trimester samples that would possibly predict the subsequent development of preeclampsia

VITAMIN C AND E SUPPLEMENTATION TO PREVENT SPONTANEOUS PRETERM BIRTH

Evidence suggests an association between maternal vitamin C levels and preterm premature rupture of membranes (PROM) or preterm labor. The objective of this study was to estimate whether maternally administered vitamins C and E lowers the risk of spontaneous preterm birth (SPB)

The Utility of Uterine Artery Doppler Velocimetry in Prediction of Preeclampsia in a Low-Risk Population:

The underlying pathophysiology of preeclampsia is thought to be abnormal trophoblast invasion of the spiral arteries, leading to maldevelopment of uteroplacental perfusion. We estimated whether uterine artery Doppler measurements made in the early second trimester would predict the subsequent development of preeclampsia

Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19)

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race–ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2–11%) incidence of venous thromboembolism among those with severe–critical illness compared with 0.2% in mild–moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe–critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30–1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18–2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42–5.14) compared with asymptomatic patients. Mild–moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. CONCLUSION: Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe–critical COVID-19, but not those with mild–moderate COVID-19, were at increased risk of perinatal complications