Lauren Doyle

Prediction of preeclampsia utilizing the first trimester screening examination

OBJECTIVE To derive a prediction rule for preeclampsia and early onset preeclampsia requiring delivery <34 weeks using first trimester maternal, ultrasound, and serum markers. STUDY DESIGN Prospective cohort study of women enrolled at first trimester screening. Maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women with preeclampsia and normal outcome. The prediction rule was derived by Lasso logistic regression analysis. RESULTS In 2441 women, 108 (4.4%) women developed preeclampsia, and 18 (0.7%) early preeclampsia. Nulliparity, prior hypertension, diabetes, prior preeclampsia, mean arterial pressure, and the log pregnancy-associate pregnancy protein-A multiples of the median were primary risk factors. Prediction rules for preeclampsia/early preeclampsia had an area under the curve of 0.82/0.83 respectively. Preeclampsia was predicted with 49% sensitivity and early preeclampsia with 55% sensitivity for a 10% false positive rate. CONCLUSION First trimester prediction rules using parameters currently available at first trimester screening identify a significant proportion of women with subsequent preeclampsia.

First-trimester risk factors for preeclampsia development in women initiating aspirin by 16 weeks of gestation.

OBJECTIVE: The residual risk of preeclampsia in high-risk women on aspirin prophylaxis exceeds that of low-risk populations, and this study aimed to identify first-trimester maternal characteristics associated with aspirin prophylaxis failure. METHODS: This is a nested cohort study of prospectively enrolled women with verified initiation of risk-indicated aspirin prophylaxis by 16 weeks of gestation. First-trimester maternal history, demographics, anthropometry, ultrasound parameters, and serum analytes were compared between women who developed preeclampsia and those who did not. Blood pressure measurements were classified as prehypertension or hypertension according to the Joint National Committee on Hypertension guidelines. Chi square, nonparametric, and logistic regression analyses were used to determine the contributors to preeclampsia development. RESULTS: Six hundred fourteen women prospectively enrolled at 9–14 weeks of gestation initiated aspirin by 16 weeks of gestation. The 59 (9.6%) women who developed preeclampsia were more likely to have chronic hypertension, diabetes, and obesity and had higher first-trimester blood pressure and lower serum pregnancy-associated plasma protein-A concentrations (all P<.05). Having first-trimester Joint National Committee on Hypertension prehypertension or hypertension was associated with a 2.18-fold increased risk of developing preeclampsia, whereas normotension was associated with a reduction of risk of 56%. CONCLUSION: Women who develop preeclampsia while taking aspirin prophylaxis are more likely to have elevated first-trimester blood pressures. Conversely, first-trimester normotension is associated with a reduced risk of preeclampsia. LEVEL OF EVIDENCE: II

External validity of first‐trimester algorithms in the prediction of pre‐eclampsia disease severity

To compare disease features in women with pre‐eclampsia between those who are correctly identified (true positive) and those who are missed (false negative) when applying first‐trimester prediction algorithms for pre‐eclampsia to a prospectively enrolled population.

Second-trimester prediction of delivery of a small-for-gestational-age neonate: integrating sequential Doppler information, fetal biometry, and maternal characteristics.

The aim of this study was to investigate the predictive accuracy of second‐trimester ultrasound parameters, maternal characteristics, and sequential Doppler changes between first and second trimesters for the prediction of small‐for‐gestational‐age (SGA) infants (birth weight < 10th percentile).

First trimester prediction of maternal glycemic status

Abstract Objective: To predict gestational diabetes mellitus (GDM) or normoglycemic status using first trimester maternal characteristics. Methods: We used data from a prospective cohort study. First trimester maternal characteristics were compared between women with and without GDM. Association of these variables with sugar values at glucose challenge test (GCT) and subsequent GDM was tested to identify key parameters. A predictive algorithm for GDM was developed and receiver operating characteristics (ROC) statistics was used to derive the optimal risk score. We defined normoglycemic state, when GCT and all four sugar values at oral glucose tolerance test, whenever obtained, were normal. Using same statistical approach, we developed an algorithm to predict the normoglycemic state. Results: Maternal age, race, prior GDM, first trimester BMI, and systolic blood pressure (SBP) were all significantly associated with GDM. Age, BMI, and SBP were also associated with GCT values. The logistic regression analysis constructed equation and the calculated risk score yielded sensitivity, specificity, positive predictive value, and negative predictive value of 85%, 62%, 13.8%, and 98.3% for a cut-off value of 0.042, respectively (ROC-AUC – area under the curve 0.819, CI – confidence interval 0.769–0.868). The model constructed for normoglycemia prediction demonstrated lower performance (ROC-AUC 0.707, CI 0.668–0.746). Conclusions: GDM prediction can be achieved during the first trimester encounter by integration of maternal characteristics and basic measurements while normoglycemic status prediction is less effective.

Maternal blood pressures during pregnancy and the risk of delivering a small-for-gestational-age neonate.

ABSTRACT Objective: To determine the relationship between maternal blood pressures throughout pregnancy and the risk of delivering a small-for-gestational-age (SGA) neonate. Methods: Women were prospectively enrolled at 9–14 weeks and had serial blood pressure measurements throughout pregnancy. SGA prevalence was compared to maternal blood pressure at enrollment, average blood pressure during each trimester, and blood pressure trends throughout gestation. Blood pressure was categorized as normotension, prehypertension, or hypertension using Joint National Committee on Hypertension-7 (JNC-7) definitions. Information on preeclampsia prevalence was also obtained due to its frequent concurrence with SGA. Results: A total of 758 women had 8438 blood pressure measurements taken (average 11.1, range 3–14) and 65 (8.6%) delivered an SGA neonate. Forty-two of 514 (8.2%) normotensive women at enrollment and 23/244 (9.4%) women with enrollment prehypertension or hypertension delivered an SGA neonate. Women with persistent hypertensive range blood pressures had an SGA rate 2–3 times higher than other women (p = 0.272) as well as a significantly higher preeclampsia rate (p < 0.001). Women with elevated enrollment blood pressures did not have an increased SGA rate if their blood pressures improved throughout pregnancy. Logistic regression identified enrollment uterine artery Doppler, pregnancy-associated plasma protein-A levels, and ethnicity as primary contributors to SGA. Conclusion: Blood pressure improvement throughout pregnancy decreases the preeclampsia rate without increasing SGA frequency. Theoretical risks of fetal growth delay should not prevent investigations into improved maternal blood pressure control, possibly at thresholds lower than commonly used in obstetric practice, beginning in the first trimester of pregnancy.

First trimester maternal characteristics, Doppler parameters and serum analytes after preeclampsia

Objective: To evaluate the impact of prior preeclampsia on first trimester assessment in subsequent pregnancy. Methods: A total of 1283 parous patients were prospectively enrolled at 9–14 weeks of gestation. Maternal biophysical characteristics, ultrasound parameters and placental analytes were compared between women with and without prior preeclampsia. Results: There is no association between prior preeclampsia and the first trimester ultrasound parameters or placental analytes studied. The effects of prior preeclampsia in subsequent pregnancy are exaggerated by increasing parity and are predominantly blood pressure-related, independent of other cardiovascular risk factors. Conclusion: There is a potential role for lifestyle modification and stricter pregnancy blood pressure control in patients with prior preeclampsia.

QUAD versus cfDNA in an urban population in the second trimester for detection of trisomy 21: a cost sensitivity analysis.

Abstract Objective: To compare the unit cost of noninvasive prenatal testing (cell-free DNA [cfDNA]) in an urban population who did not have first-trimester screening as a primary screening tool for trisomy 21 (T21) to multiple marker screening (QUAD). Methods: Retrospective study of all QUAD screens performed at a single center from 2013 to 2015. All QUAD screen performed between 15 and 21 weeks were included in the study. Exclusion criteria were patients without anatomy scans or delivery information. Utilizing our population characteristics, we extrapolated to determine the cost of QUAD with additional screening (cfDNA and amniocentesis) versus QUAD for this entire population. Results: 590 QUAD screens were performed during the study time period. After ultrasound correction of gestational age, 5.9% (35) were screen positive. Within this cohort, 51.4% (18) patients underwent cfDNA and 11.4% (4) had invasive testing. No cases of T21 were identified. It would be cost equivalent to offer cfDNA as a primary screen for T21 at less than

A multidisciplinary approach to prenatal treatment of congenital long QT syndrome

360.54 to the entire population regardless of a priori risk status. Invasive procedures were reduced by 55.4%. Conclusions: cfDNA is an acceptable option for second-trimester screening and as a primary screen eliminates the need for multi-step screening preserving valuable healthcare resources.

First-trimester prediction of small-for-gestational age neonates incorporating fetal Doppler parameters and maternal characteristics

A 27‐week fetus evaluated for bradycardia and hydrops was found to have anti‐SSA‐negative 2° atrioventricular block and ventricular tachycardia. A presumptive diagnosis of fetal long QT syndrome was made. Transplacental pharmacotherapy with intravenous magnesium and lidocaine restored sinus rhythm. At 30 6/7 weeks, the infant was delivered due to premature labor. Despite postnatal treatment with mexiletine and propranolol, she developed torsades de pointes. Ultimately, a de novo KCNH2 G628S mutation was diagnosed. She received an implantable cardiac defibrillator at 5 months of age. Early diagnosis and a multidisciplinary approach allowed successful in utero treatment and anticipatory postnatal management.