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Animal models for preeclampsia are mostly determined by the experimental induction of hypertension, proteinuria and latterly, endogenous production of anti-angiogenic factors (sFlt-1). The focus on maternal outcome measures is more immediately obvious, with comparative and sequential data of blood pressure and urine protein excretion. In non-human primates, the data concerning birthweight requires a greater number of observations and thus will be accumulated over a longer period of time and a greater number of experimental protocols. The following represents the outcome of over 20 years of experimental preeclampsia (EPE) compared with normal pregnancy outcome data in baboons. MethodsThis data represents the outcomes from 91 pregnancies over the last 25 years at the Australian National Baboon Colony. These pregnancies are attributed to females who had experimental preeclampsia (EPE) and those within the general colony. EPE was induced at day 130 (of 182 days gestation length), and in some protocols, treatments such as inhibitory RNA or placental growth factor (PlGF) were tested. All studies were approved by the institutional Animal Welfare Committee. RESULTS: The overall neonatal birthweight was 697 g ± 115 g. The average birthweight for normal males was 770 ± 105 g; and for male offspring of animals with EPE, 680 ± 113 g; for normal females was 640 ± 95 g and females from EPE pregnancies, 690 ± 43 g. There was only a significant difference in weight for females compared to males overall (p = 0.002), and there was no significant difference in birthweight for males or females subjected to EPE. Correction for treated EPE did not change the outcome. CONCLUSIONS: These data indicate that in a non-human primate model of placental dysfunction through late pregnancy acute ischaemia, there is no measurable effect on baby birthweight compared to normal pregnancy, and no impact from a number of current experimental treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Accurate individualized assessment of preeclampsia risk enables the identification of patients most likely to benefit from initiation of low-dose aspirin at 12 to 16 weeks of gestation when there is evidence for its effectiveness, and enables the guidance of appropriate pregnancy care pathways and surveillance., Objective: The primary objective of this study was to evaluate the performance of artificial neural network models for the prediction of preterm preeclampsia (<37 weeks' gestation) using patient characteristics available at the first antenatal visit and data from prenatal cell-free DNA screening. Secondary outcomes were prediction of early-onset preeclampsia (<34 weeks' gestation) and term preeclampsia (≥37 weeks' gestation)., Methods: This secondary analysis of a prospective, multicenter, observational prenatal cell-free DNA screening study (SMART) included singleton pregnancies with known pregnancy outcomes. Thirteen patient characteristics that are routinely collected at the first prenatal visit and 2 characteristics of cell-free DNA (total cell-free DNA and fetal fraction) were used to develop predictive models for early-onset (<34 weeks), preterm (<37 weeks), and term (≥37 weeks) preeclampsia. For the models, the "reference" classifier was a shallow logistic regression model. We also explored several feedforward (nonlinear) neural network architectures with ≥1 hidden layers, and compared their performance with the logistic regression model. We selected a simple neural network model built with 1 hidden layer and made up of 15 units., Results: Of the 17,520 participants included in the final analysis, 72 (0.4%) developed early-onset, 251 (1.4%) preterm, and 420 (2.4%) term preeclampsia. Median gestational age at cell-free DNA measurement was 12.6 weeks, and 2155 (12.3%) had their cell-free DNA measurement at ≥16 weeks' gestation. Preeclampsia was associated with higher total cell-free DNA (median, 362.3 vs 339.0 copies/mL cell-free DNA; P<.001) and lower fetal fraction (median, 7.5% vs 9.4%; P<.001). The expected, cross-validated area under the curve scores for early-onset, preterm, and term preeclampsia were 0.782, 0.801, and 0.712, respectively, for the logistic regression model, and 0.797, 0.800, and 0.713, respectively, for the neural network model. At a screen-positive rate of 15%, sensitivity for preterm preeclampsia was 58.4% (95% confidence interval, 0.569-0.599) for the logistic regression model and 59.3% (95% confidence interval, 0.578-0.608) for the neural network model. The contribution of both total cell-free DNA and fetal fraction to the prediction of term and preterm preeclampsia was negligible. For early-onset preeclampsia, removal of the total cell-free DNA and fetal fraction features from the neural network model was associated with a 6.9% decrease in sensitivity at a 15% screen-positive rate, from 54.9% (95% confidence interval, 52.9-56.9) to 48.0% (95% confidence interval, 45.0-51.0)., Conclusion: Routinely available patient characteristics and cell-free DNA markers can be used to predict preeclampsia with performance comparable to that of other patient characteristic models for the prediction of preterm preeclampsia. Logistic regression and neural network models showed similar performance., (Copyright © 2024. Published by Elsevier Inc.)

Background: The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes., Objective: This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes., Study Design: This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction., Results: In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30])., Conclusion: Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation., Methods: This was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies., Results: A total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%., Conclusion: Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes., Competing Interests: Conflict of Interest All site principal investigators (Pe’er Dar, Bo Jacobsson, Fergal Malone, Ronald J. Wapner, Ashley S. Roman, Asma Khalil, Revital Faro, Rajeevi Madankumar, Sina Haeri, Robert M. Silver, Nidhi Vohra, Jon Hyett, Cora MacPherson, and Mary E. Norton) received institutional research support from the funding sponsor (Natera). Melissa Egbert, Zachary Demko, and Matt Rabinowitz are employed by the study’s funding sponsor (Natera) and hold stock or options to hold stock. Kimberly Martin is a consultant to the funding sponsor (Natera) and holds stock and options to hold stock. Jon Hyett has an ongoing research collaboration that includes financial support for biochemical analytes from Perkin Elmer; has earned honoraria and/or given talks that were not compensated from Natera, Roche, and Canon; and has participated in Asian/Australasian expert consultancies for Natera and Roche. Bo Jacobsson collaborated in the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) study where Roche, Perkin Elmer, and Thermo Fisher provide reagents to Placental Growth Factor (PLGF) analyses. Ronald J. Wapner receives research funding from National Institute of Child Health and Human Development and support from Illumina for research reagents. Mary E. Norton is a consultant to Luna Genetics. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy., Objective: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed., Results: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate., Conclusion: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported., Objective: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome., Study Design: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome., Results: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P<.001) and a positive predictive value of 52.6% (10/19; 95% confidence interval, 28.9-75.6)., Conclusion: Noninvasive cell-free DNA prenatal screening for 22q11.2 deletion syndrome can detect most affected cases, including smaller nested deletions, with a low false positive rate., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Maternal nutrition is associated with epigenetic and cardiometabolic risk factors in offspring. Research in humans has primarily focused on assessing the impact of individual nutrients., Objectives: We sought to assess the collective impact of maternal dietary MUFAs, PUFAs, and SFAs on epigenetic aging and cardiometabolic risk markers in healthy newborn infants using a geometric framework approach., Methods: Body fatness (n = 162), aortic intima-media thickness (aIMT; n = 131), heart rate variability (n = 118), and epigenetic age acceleration (n = 124) were assessed in newborn infants. Maternal dietary intake was cross-sectionally assessed in the immediate postpartum period via a validated 80-item self-administered FFQ. Generalized additive models were used to explore interactive associations of nutrient intake, with results visualized as response surfaces., Results: After adjustment for total energy intake, maternal age, gestational age, and sex there was a 3-way interactive association of MUFAs, PUFAs, and SFAs (P = 0.001) with newborn epigenetic aging. This suggests that the nature of each fat class association depends upon one another. Response surfaces revealed MUFAs were positively associated with newborn epigenetic age acceleration only at proportionately lower intakes of SFAs or PUFAs. We also demonstrate a potential beneficial association of omega-3 (n-3) PUFAs with newborn epigenetic age acceleration (P = 0.008). There was no significant association of fat class with newborn aIMT, heart rate variability, or body fatness., Conclusions: In this study, we demonstrated an association between maternal dietary fat class composition and epigenetic aging in newborns. Future research should consider other characteristics such as the source of maternal dietary fatty acids., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP 2 ) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters., Study Design: Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months., Main Outcome Measures: Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change., Secondary Outcomes: maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change., Conclusions: BP 2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP., (Copyright © 2020 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Preterm birth, defined as a delivery before 37 weeks' gestation, continues to affect 8-15% of all pregnancies and is associated with significant neonatal morbidity and mortality. Effective prediction of timing of delivery among women identified to be at significant risk for preterm birth would allow proper implementation of prophylactic therapeutic interventions. This paper aims first to develop a model that acts as a decision support system for pregnant women at high risk of delivering prematurely before having cervical cerclage. The model will predict whether the pregnancy will continue beyond 26 weeks' gestation and the potential value of adding the cerclage in prolonging the pregnancy. The second aim is to develop a model that predicts the timing of spontaneous delivery in this high risk cohort after cerclage. The model will help treating physicians to define the chronology of management in relation to the risk of preterm birth, reducing the neonatal complications associated with it. Data from 274 pregnancies managed with cervical cerclage were included. 29 of the procedures involved multiple pregnancies. To build the first model, a data balancing technique called SMOTE was applied to overcome the problem of highly imbalanced class distribution in the dataset. After that, four classification models, namely Decision Tree, Random Forest, K-Nearest Neighbors (K-NN), and Neural Network (NN) were used to build the prediction model. The results showed that Random Forest classifier gave the best results in terms of G-mean and sensitivity with values of 0.96 and 1.00, respectively. These results were achieved at an oversampling ratio of 200%. For the second prediction model, five classification models were used to predict the time of spontaneous delivery; linear regression, Gaussian process, Random Forest, K-star, and LWL classifier. The Random Forest classifier performed best, with 0.752 correlation value. In conclusion, computational models can be developed to predict the need for cerclage and the gestation of delivery after this procedure. These models have moderate/high sensitivity for clinical application., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Epigenetic aging is associated with higher risk of cardiovascular disease, cancer, and all-cause mortality and may be a mechanistic link between early-life exposures, such as maternal dietary characteristics during pregnancy, and risk of adult disease., Objectives: We sought to determine the early-life risk factors for newborn epigenetic aging, specifically maternal dietary macronutrient intake, and whether epigenetic aging is associated with cardiovascular health markers in the newborn., Methods: Epigenetic age acceleration of 169 newborns was measured from saliva using the Horvath age calculator. Maternal diet during pregnancy was assessed using food-frequency questionnaires., Results: Newborns with positive age acceleration were more likely to be female and have greater body fatness. Maternal intakes of saturated fat [6.2 wk epigenetic age acceleration (95% CI: 1.0, 11.3) per 5% of energy; P = 0.02] and monounsaturated fat [12.4 wk (95% CI: 4.2, 20.5) per 5% of energy; P = 0.003] were associated with higher epigenetic age acceleration in the newborn. The strongest association of individual fatty acids were for palmitoleic acid (25.3 wk; 95% CI: 11.4, 39.2; P = 0.0004), oleic acid (2.2 wk; 95% CI: 0.8, 3.6; P = 0.002), and palmitic acid (2.9 wk; 95% CI: 1.0, 4.9; P = 0.004) per 1% of energy intake. Vitamin D supplementation was associated with lower epigenetic age acceleration (-8.1 wk; 95% CI: -14.5, -1.7; P = 0.01). Epigenetic age acceleration was associated with aortic intima-media thickness in preterm infants [1.0 µm (95% CI: 0.2, 1.8) per week of epigenetic age acceleration; P = 0.01], but not among those born at term (P = 0.78). Epigenetic age acceleration was not associated with heart rate variability in either preterm or term born infants (both P > 0.2)., Conclusions: This study provides evidence of maternal dietary characteristics that are associated with epigenetic aging in the offspring. Prospective intervention studies are required to determine whether such associations are causal., (Copyright © The Author(s) 2020.)

Podocalyxin is expressed on endothelial surface throughout the body and is likely released into the circulation during pregnancy in association with vessel remodeling. We have recently reported that serum podocalyxin is significantly increased in preeclampsia at disease presentation. In this study we investigated whether serum podocalyxin is altered prior to clinical presentation of preeclampsia. At 11-13 weeks of gestation, serum podocalyxin was significantly elevated in women who subsequently developed preeclampsia. Multi-factorial analysis suggests that combination of serum podocalyxin with the long isoform of HtrA3 and mean arterial pressure, may provide effective detection of late-onset preeclampsia at 11-13 weeks of pregnancy., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objectives: To determine if home blood pressure measurement (HBPM) provides comparable results to clinic blood pressure (BP) measurement., Study Design: A prospective, single-centre study of 37 pregnant and early post-partum women with a hypertensive pregnancy or at high-risk of developing a hypertensive pregnancy were asked to perform HBPM for a minimum period of one week. This was subsequently compared to clinic BP measurement both before and after the period of home measurement., Main Outcome Measures: The accuracy of HBPM compared to clinic measurement, and the acceptability by patients for HBPM., Results: The HBPM was comparable to clinic measurements [for the systolic blood pressure (SBP), the mean home reading was 123.4mmHg (122.0-124.9mmHg) versus 123.9mmHg (121.3-126.5mmHg) for the clinic reading (p=0.69); for the diastolic blood pressure (DBP) the mean home reading was 81.6mmHg (80.4-82.8mmHg) versus 84.4mmHg (82.6-86.2mmHg) for the clinic (p<0.01)]. There were no reported issues associated with the use of HBPM, but it did lead to 5 women contacting health care professionals for management of their BP between clinic visits., Conclusions: HBPM provides comparable results to the clinic BP measurement. It is also an acceptable technique for pregnant and early post-partum women. However, it should be used as an adjunct to clinic measurement, and cannot at this present stage replace clinic visits or clinic BP measurement., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure restricts the use of fetal lung maturity assessment., Objective: The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis of the fetal lung (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries., Study Design: This was a prospective multicenter study conducted in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks of gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated., Results: A total of 883 images were collected, but 17.3% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, positive and negative predictive values of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively., Conclusion: The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique., (Copyright © 2017. Published by Elsevier Inc.)

Background: Preeclampsia and fetal growth restriction are major causes of perinatal death and handicap in survivors. Randomized clinical trials have reported that the risk of preeclampsia, severe preeclampsia, and fetal growth restriction can be reduced by the prophylactic use of aspirin in high-risk women, but the appropriate dose of the drug to achieve this objective is not certain., Objective: We sought to estimate the impact of aspirin dosage on the prevention of preeclampsia, severe preeclampsia, and fetal growth restriction., Study Design: We performed a systematic review and meta-analysis of randomized controlled trials comparing the effect of daily aspirin or placebo (or no treatment) during pregnancy. We searched MEDLINE, Embase, Web of Science, and Cochrane Central Register of Controlled Trials up to December 2015, and study bibliographies were reviewed. Authors were contacted to obtain additional data when needed. Relative risks for preeclampsia, severe preeclampsia, and fetal growth restriction were calculated with 95% confidence intervals using random-effect models. Dose-response effect was evaluated using meta-regression and reported as adjusted R 2 . Analyses were stratified according to gestational age at initiation of aspirin (≤16 and >16 weeks) and repeated after exclusion of studies at high risk of biases., Results: In all, 45 randomized controlled trials included a total of 20,909 pregnant women randomized to between 50-150 mg of aspirin daily. When aspirin was initiated at ≤16 weeks, there was a significant reduction and a dose-response effect for the prevention of preeclampsia (relative risk, 0.57; 95% confidence interval, 0.43-0.75; P < .001; R 2 , 44%; P = .036), severe preeclampsia (relative risk, 0.47; 95% confidence interval, 0.26-0.83; P = .009; R 2 , 100%; P = .008), and fetal growth restriction (relative risk, 0.56; 95% confidence interval, 0.44-0.70; P < .001; R 2 , 100%; P = .044) with higher dosages of aspirin being associated with greater reduction of the 3 outcomes. Similar results were observed after the exclusion of studies at high risk of biases. When aspirin was initiated at >16 weeks, there was a smaller reduction of preeclampsia (relative risk, 0.81; 95% confidence interval, 0.66-0.99; P = .04) without relationship with aspirin dosage (R 2 , 0%; P = .941). Aspirin initiated at >16 weeks was not associated with a risk reduction or a dose-response effect for severe preeclampsia (relative risk, 0.85; 95% confidence interval, 0.64-1.14; P = .28; R 2 , 0%; P = .838) and fetal growth restriction (relative risk, 0.95; 95% confidence interval, 0.86-1.05; P = .34; R 2 , not available; P = .563)., Conclusion: Prevention of preeclampsia and fetal growth restriction using aspirin in early pregnancy is associated with a dose-response effect. Low-dose aspirin initiated at >16 weeks' gestation has a modest or no impact on the risk of preeclampsia, severe preeclampsia, and fetal growth restriction. Women at high risk for those outcomes should be identified in early pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A number of groups are currently examining the potential of screening for pre-eclampsia and gestational diabetes at 12 weeks' gestation. This can be performed at the time of combined first-trimester screening for aneuploidy using a similar method of regression analysis to combine multiple demographic and investigative factors. At present, research into the prediction of pre-eclampsia is more robust and is associated with the potential for therapeutic intervention that can reduce the prevalence of early-onset pre-eclampsia and improve maternal and neonatal outcomes., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

Sonographic assessment of fetal nuchal translucency (NT) thickness is the cornerstone of screening for chromosomal abnormality at 11-13(+6) weeks gestation. This marker was first recognized in pregnancies being karyotyped for advanced maternal age, but its underlying pathophysiology remains to be fully determined. Although increased NT is clearly associated with changes in both lymphatic and cardiac development, neither is an obvious causative agent. The association with cardiac defects has now being subjected to a significant amount of research, with a large body of evidence showing that this marker is also a screening tool for major cardiac defects - although it performs more modestly than for chromosomal abnormality. The field continues to change rapidly. Recent evidence that uses a combination of increased NT, tricuspid regurgitation and abnormal flow in the 'a' wave of the ductus venosus can provide an effective screening strategy to predict many major cardiac defects at this early stage of pregnancy., (Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Our purpose was to compare the biochemical composition of the fluid contained in pathologic and physiologic cavities in early pregnancy., Study Design: The level of urea, creatinine, electrolytes, enzymes, total protein, and alpha-fetoprotein and the affinity of alpha-fetoprotein for concanavalin A Sepharose was measured in samples of vesicular fluid from complete (n=2) and partial (n=1) mole, nuchal fluid (n=4), and cystic hygroma fluid (n=4). For comparison samples of maternal serum (n=32), amniotic fluid (n=32), coelomic fluid (n=15), and fetal blood (n=13) were obtained from normal pregnancies at 10 to 16 weeks' gestation., Results: Urea concentration was lower, whereas sodium, potassium, and total protein concentrations were higher in vesicular fluid than in amniotic and coelomic fluid. Urea, creatinine, sodium, potassium, chloride, and beta2-microglobulin concentrations did not vary between nuchal or cystic hygroma fluid and amniotic fluid or fetal serum. The concentration of total protein in nuchal and hygroma fluid was significantly lower than in fetal serum and significantly higher than in amniotic fluid. The amniotic fluid contained extremely high tau-glutamyltransferase concentration compared with the other fluids and fetal serum. Alkaline phosphatase and amylase were not detectable in coelomic fluid, fetal serum, or nuchal and hygroma fluid. The nuchal and hygroma fluid composition was similar except for total protein and alpha-fetoprotein concentrations, which were significantly higher in nuchal than in hygroma fluid. The vesicular fluid from the partial mole, fetal serum, and nuchal and hygroma fluid contained extremely high alpha-fetoprotein concentrations, which were significantly higher that those found in amniotic fluid. In complete mole alpha-fetoprotein molecules were of the yolk sac type, whereas they were of the liver type in nuchal and hygroma fluid., Conclusions: The composition of vesicular fluid in complete mole reflects a possible origin from the maternal plasma, yolk sac, and trophoblast, whereas the composition of nuchal and cystic hygroma fluid suggests a leakage from the fetal circulation.

Placental pregnancy-associated plasma protein-A (PAPP-A) mRNA expression, placental PAPP-A protein concentration and maternal serum levels of PAPP-A were examined in pregnancies affected by trisomy 21 (n=8), trisomy 18 (n=7) and 15 normal controls at 12-15 weeks of gestation. The maternal serum concentration of PAPP-A in the trisomic group of pregnancies was significantly lower than in the normal controls. However there were no significant differences between the three groups in PAPP-A mRNA expression or PAPP-A protein concentration in the placental tissues. There was no significant association between the level of placental mRNA and either placental protein or maternal serum PAPP-A concentrations in the normal or trisomic pregnancies. There was however a significant association between placental protein and maternal serum PAPP-A concentrations in the normal and trisomy 21 pregnancies but not in those affected by trisomy 18. These findings suggest that the decrease in maternal serum PAPP-A in trisomic pregnancies is due to alternations in post-translational events such as protein stability, alterations in the release mechanism of the protein, impaired protein transport across the placenta or modified serum stability of PAPP-A.

Objective: Our purpose was to determine the incidence of cardiac septal defects in fetuses with trisomy 21 diagnosed by increased nuchal translucency thickness at 10 to 13 weeks' gestation., Study Design: Pathologic examination of the fetal heart was performed in 36 fetuses with trisomy 21 after suction termination of pregnancy at 12 to 15 weeks' gestation. The diagnosis of trisomy 21 was made by chorion villus sampling because of increased (> or = 3 mm) fetal nuchal translucency thickness detected at routine first-trimester ultrasonographic examination., Results: Perimembranous ventricular and atrioventricular septal defects were detected in 20 of 36 fetal hearts. A septal defect was observed in 1 of the 11 fetuses with nuchal translucency thickness of 3 mm and in 19 of the 25 with translucency > or = 4 mm (p < 0.001)., Conclusion: The incidence of ventricular and atrioventricular septal defects is much higher in fetuses with trisomy 21 and increased nuchal translucency thickness at 10 to 13 weeks' gestation than in live-born infants with this chromosomal abnormality. The incidence of cardiac septal defects increases with nuchal translucency thickness.