ABSTRACT Objective To develop and validate a new first‐trimester model for the prediction of gestational diabetes mellitus (GDM) based on maternal demographic characteristics and elements of medical history. Design Prospective cohort study. Setting Inner‐city hospital. Population 41 587 women with singleton pregnancies at 11 +0 –13 +6 weeks' gestation, including 4231 (10.2%) who subsequently developed GDM. Methods Logistic regression model for GDM was developed and fivefold cross‐validation was performed to assess the calibration and predictive performance of the model, assessed by the area under the receiver operating characteristic curve (AUROC) and detection rates (DRs) at different screen positive rates (SPRs). Main Outcome Measure GDM. Results In both parous women with a previous history of GDM and nulliparous women or parous women with no history of GDM, significant contributors to the prediction of GDM were maternal age, weight, height, ethnicity and family history of diabetes mellitus. In parous women with no previous history of GDM, there was a contribution from the birthweight z‐score of the previous pregnancy. There was good agreement between the predicted risk and observed incidence of GDM (intercept 0.000, 95% CI: −0.034, 0.034; slope 1.000, 95% CI: 0.967, 1.033). The AUROC curve was 0.757 (95% CI: 0.749, 0.765). The performance was higher for GDM treated with insulin versus metformin or diet alone. At SPR of 40%, the DR of the insulin, metformin and diet alone group was 87.2% (95% CI: 84.9, 89.3), 80.0% (77.8, 82.0) and 61.5% (59.2, 63.7), respectively. Conclusion Assessment of risk for GDM can be achieved in the first trimester based on maternal risk factors.

ABSTRACT Objective The objective of this study is to examine the association between dietary calcium intake (Ca) and pre‐eclampsia (PE). Design Cohort study. Setting Inner‐city hospital. Population A total of 2838 women with singleton pregnancies at 35 +0 –36 +6 weeks' gestation, including 96 (3.4%) who subsequently developed PE. Methods Online 24‐h dietary recall questionnaire was used to measure Ca intake. In the low (< 700 mg/d) vs. adequate (≥ 700 mg/d) Ca intake groups, we compared the prevalence of PE‐associated maternal risk factors and the incidence of PE. In multivariate regression, we examined the low Ca intake and PE relationship, adjusted for established PE risk factors (including blood pressure and angiogenic biomarkers) and any additional factors associated with low Ca intake specifically. Main Outcome Measure PE. Results Overall, 405 (14.3%) women had low Ca intake. Low (vs. adequate) Ca intake was associated with a higher incidence of PE (6.2% vs. 2.9%; odds ratio 2.2, 95% confidence interval 1.3–3.7), as well as more prevalent risk factors for PE, including Black ethnicity (34.1% vs. 11.8%), South Asian ethnicity (10.1% vs. 7.2%), high body mass index (29.8 vs. 28.3 kg/m 2 ) and more deprived index of multiple deprivation (54.3% vs. 35.5%). In multivariate regression adjusting for other PE risk factors, low Ca intake was no longer associated with PE (OR 1.7, 95% CI 0.9–3.2). Conclusions Although some contribution from low Ca to the development of PE cannot be ruled out, after accounting for maternal characteristics, medical history and deprivation, low Ca intake did not make an independent contribution to the development of PE in this population of mixed‐ethnicity women.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

ABSTRACT Background Pre-eclampsia (PE) and gestational hypertension (GH) identify women at increased risk of chronic hypertension (CH) and cardiovascular disease, but as efforts to prevent PE and GH advance, fewer women at increased cardiovascular risk will be identified. Methods Cohort of 26,511 women seen in two consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure (BP) at 11-13 weeks’ gestation, and development of PE or GH in the index pregnancy. Logistic regression models were fitted for prediction of development of future CH by the 20 th week of the subsequent pregnancy. Performance of screening and risk calibration of the model were assessed. Results 1560 (5.9%) women developed PE or GH (index pregnancy), and 215 (0.8%) developed future CH, a median of 3.0 years later. Predictors from the index pregnancy of development of future CH were: early pregnancy maternal age, weight and BP; Black or South Asian ethnicity; family history of PE; parity; and development of PE or GH. PE or GH accounted for 52.1% (95% confidence interval 45.2-58.9%) of future CH. At a screen-positive-rate of 10%, a model including terms for maternal characteristics and early pregnancy BP accounted for 67.9% (61.2-74.5) of future CH; addition of the development of PE or GH detected 73.5% (67.1-79.3) of future CH. Risks produced from the predictive model were well-calibrated and confirmed by five-fold cross-validation. Conclusion Early maternal characteristics and BP are effective in predicting development of future CH. As new interventions are expected to reduce the occurrence of PE and GH, our study results offer an alternative strategy for identifying women at increased risk of future CH and are applicable worldwide.

Aims To determine if maternal cardiovascular and metabolic indices before conception were different in women who in a subsequent singleton pregnancy developed gestational diabetes mellitus (GDM), compared to those without GDM. Methods This was a prospective observational study in women attending for infertility treatment in an in vitro fertilization clinic. This visit included recording of maternal demographic characteristics and medical history, assessment of maternal cardiovascular function by echocardiography and examination of metabolic profile. The inclusion criteria were attendance of the infertility clinic before the onset of treatment and subsequent singleton pregnancy delivering a non-malformed live birth. The pre-pregnancy results in women who developed GDM were compared to those without GDM. Results The study population of 287 women included 75 (26.1%) who developed GDM. In the GDM, compared to the non-GDM group, there was a higher mitral valve E/e’ (6.24[5.93, 6.55] vs 5.83[5.69, 5.93], mean intima media thickness(0.51[0.51,0.51] vs 0.49[0.49, 0.49] mm and left ventricular global longitudinal systolic strain (-19.9[-20.4, -19.6] vs -20.8[-21.1, -20.6]% and lower apolipoprotein A (113[105, 121] vs 136[121,134]mg/dl). In multivariable analysis, after accounting for differences in maternal characteristics, there was persistence of significant differences in E/e’ and apolipoprotein A. However, the performance of screening for GDM achieved by the use of maternal risk factors was not improved by the addition of cardiovascular and metabolic indices. Conclusion Women at risk to develop GDM during pregnancy have an adverse risk factor profile before conception. Further studies are needed to confirm whether optimization of cardiovascular and metabolic risk factors prior to conception might be beneficial in reducing the risk for subsequent development of GDM.

Objective: To investigate the validity of the conclusion from Cochrane reviews and meta-analyses that treatment with calcium supplementation during pregnancy reduces the risk for pre-eclampsia by 55%, which has been influential in international guidelines and future research. Design: Sensitivity analysis of data from Cochrane reviews of trials evaluating high-dose calcium supplementation (of at least 1 g/day) for reduction of pre-eclampsia risk. Setting: Systematic review and meta-analysis. Population: The Cochrane reviews and meta-analyses included 13 trials enrolling a total of 15730 women. Random-effects meta-analysis of these studies resulted in a mean risk ratio (RR, calcium/placebo) of 0.45 (95% confidence interval [CI] 0.31-0.65; p < 0.0001). Methods: We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size. Main outcome measures: pre-eclampsia. Results: In the three largest studies, accounting for 13 815 (88%) of total recruitment, mean RR was 0.92 (95% CI 0.80-1.06) and there was no evidence of heterogeneity between studies (I-2 = 0). With inclusion of the smaller studies, mean RR decreased to 0.45 and I-2 increased to 70%. Conclusions: In assessment of the effect of calcium supplementation on pre-eclampsia risk, the naive focus on the mean of the random-effects meta-analysis in the presence of substantial heterogeneity is highly misleading.

Preeclampsia is a serious complication of pregnancy, and efforts have been made to increase the ability to predict when an individual will develop the condition. Guidelines from the National Institute for Health and Care Excellence (NICE) are based on risk factor scoring, with high-risk women having either 1 major risk factor or 2 moderate risk factors.

OBJECTIVE To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre-eclampsia and examine the impact of aspirin in the prevention of PTB. DESIGN Secondary analysis of data from the SPREE study and the ASPRE trial. SETTING Multicentre studies. POPULATION In SPREE, women with singleton pregnancies had screening for preterm pre-eclampsia at 11-13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. METHODS Comparison of performance of FMF method and NICE guidelines for pre-eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. MAIN OUTCOME MEASURE Spontaneous PTB (sPTB), iatrogenic PTB for pre-eclampsia (iPTB-PE) and iatrogenic PTB for reasons other than pre-eclampsia (iPTB-noPE). RESULTS Estimated incidence rates of sPTB, iPTB-PE and iPTB-noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. CONCLUSION Prediction of sPTB and iPTB-noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB-noPE was reduced substantially by aspirin.

Background: Most preeclampsia occurs at term. There are no effective preventative strategies. We aimed to identify the optimal preeclampsia screening and timing of birth strategy for prevention of term preeclampsia. Methods: This secondary analysis was of data from a prospective nonintervention cohort study of singleton pregnancies delivering at ≥24 weeks, without major anomalies, at 2 United Kingdom maternity hospitals. At routine visits at 11 to 13 weeks’ (57 131 pregnancies screened, 1138 term preeclampsia developed) or 35 to 36 weeks’ gestation (29 035 pregnancies screened, 619 term preeclampsia), with patient-specific preeclampsia risks determined by: United Kingdom National Institute for Health and Care Excellence guidance, and the Fetal Medicine Foundation competing-risks model. For each screening strategy, timing of birth for term preeclampsia prevention was evaluated at gestational time points that were fixed (37, 38, 39, 40 weeks) or dependent on preeclampsia risk by the competing-risks model at 35 to 36 weeks. Main outcomes were proportion of term preeclampsia prevented, and number-needed-to-deliver to prevent one term preeclampsia case. Results: The proportion of term preeclampsia prevented was the highest, and number-needed-to-deliver lowest, for preeclampsia screening at 35 to 36 (rather than 11–13) weeks. For delivery at 37 weeks, fewer cases of preeclampsia were prevented for National Institute for Health and Care Excellence (28.8%) than the competing-risks model (59.8%), and the number-needed-to-deliver was higher (16.4 versus 6.9, respectively). The risk-stratified approach (at 35–36 weeks) had similar preeclampsia prevention (by 57.2%) and number-needed-to-deliver (8.4), but fewer women would be induced at 37 weeks (1.2% versus 8.8%). Conclusions: Risk-stratified timing of birth at term may more than halve the risk of term preeclampsia.

BACKGROUND: Triplet pregnancies are high risk for both the mother and the infants. The risks for infants include premature birth, low birthweight, and neonatal complications. Therefore, the management of triplet pregnancies involves close monitoring and may include interventions, such as fetal reduction, to prolong the pregnancy and improve outcomes. However, the evidence of benefits and risks associated with fetal reduction is inconsistent. OBJECTIVE: This study aimed to compare the outcomes of trichorionic triplet pregnancies with and without fetal reduction and with nonreduced dichorionic twin pregnancies and primary singleton pregnancies.STUDY DESIGN: All trichorionic triplet pregnancies in Denmark, including those with fetal reduction, were identified between 2008 and 2018. In Denmark, all couples expecting triplets are informed about and offered fetal reduction. Pregnancies with viable fetuses at the first -trimester ultrasound scan and pregnancies not terminated were included. Adverse pregnancy outcome was defined as a composite of miscarriage before 24 weeks of gestation, stillbirth at 24 weeks of gestation, or intrauterine fetal death of 1 or 2 fetuses. RESULTS: The study cohort was composed of 317 trichorionic triplet pregnancies, of which 70.0% of pregnancies underwent fetal reduction to a twin pregnancy, 2.2% of pregnancies were reduced to singleton preg- nancies, and 27.8% of pregnancies were not reduced. Nonreduced triplet pregnancies had high risks of adverse pregnancy outcomes (28.4%), which was significantly lower in triplets reduced to twins (9.0%; difference, 19.4%, 95% confidence interval, 8.5%-30.3%). Severe preterm de-liveries were significantly higher in nonreduced triplet pregnancies (27.9%) than triplet pregnancies reduced to twin pregnancies (13.1%; difference, 14.9%, 95% confidence interval, 7.9%-21.9%). However, triplet pregnancies reduced to twin pregnancies had an insignificantly higher risk of miscarriage (6.8%) than nonreduced twin pregnancies (1.1%; difference, 5.6%; 95% confidence interval, 0.9%-10.4%). CONCLUSION: Triplet pregnancies reduced to twin pregnancies had significantly lower risks of adverse pregnancy outcomes, severe preterm deliveries, and low birthweight than nonreduced triplet pregnancies. However, triplet pregnancies reduced to twin pregnancies were potentially associated with a 5.6% increased risk of miscarriage.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in women. Pregnancy is an ideal period to implement cardiovascular prevention strategies as women seek medical help. We aimed to develop a predictive model to identify women at increased risk for chronic hypertension (CH) based on information collected in the index pregnancy. METHODS: Cohort of 26 511 women seen in 2 consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure at 11 to 13 weeks’ gestation, and the development of preeclampsia or gestational hypertension (GH) in the index pregnancy. Logistic regression models were fitted for the prediction of the development of future CH by the 20th week of the subsequent pregnancy. The performance of screening and risk calibration of the model were assessed. RESULTS: In this study 1560 (5.9%) women developed preeclampsia or GH (index pregnancy), and 215 (0.8%) developed future CH, with a median of 3.0 years later. Predictors of development of future CH were maternal age, weight, and blood pressure; Black and South Asian ethnicity; family history of preeclampsia; parity; and development of preeclampsia or GH. Preeclampsia or GH detected 52.1% (45.2%–58.9%) of future CH. At a screen-positive rate of 10%, a model including maternal characteristics, early pregnancy blood pressure, and development of preeclampsia or GH detected 73.5% (67.1–79.3) of future CH. CONCLUSIONS: Early pregnancy maternal characteristics, blood pressure, and development of preeclampsia or GH identify three-fourths of women at risk for future CH. Our results offer an important preventative strategy for identifying women at increased risk of future CH, which is applicable worldwide.

OBJECTIVE:To assess differences in cardiac morphology and function at midgestation in fetuses from pregnancies that subsequently developed preeclampsia (PE) or gestational hypertension (GH). METHODS:This was a prospective study in 5,801 women with singleton pregnancies attending for a routine ultrasound examination at midgestation, including 179 (3.1%) who subsequently developed PE and 149 (2.6%) who developed GH. Conventional and more advanced echocardiographic modalities, such as speckle-tracking, were used to assess fetal cardiac function in the right and left ventricle. The morphology of the fetal heart was assessed by calculating the right and left sphericity index. RESULTS:In fetuses from the PE group (vs the no PE or GH group) there was a significantly higher left ventricular global longitudinal strain and lower left ventricular ejection fraction that could not be accounted for by fetal size. All other indices of fetal cardiac morphology and function were comparable between groups. There was no significant correlation between fetal cardiac indices and uterine artery pulsatility index multiple of the median or placental growth factor multiple of the median. CONCLUSION:At midgestation, fetuses of mothers at risk of developing PE, but not those at risk of GH, have mild reduction in left ventricular myocardial function. Although absolute differences were minimal and most likely not clinically relevant, these may suggest an early programming effect on left ventricular contractility in fetuses of mothers who develop PE.

Importance:Fetuses in women with gestational diabetes (GD) compared with those without GD show evidence of subclinical cardiac functional and morphological changes. However, it is uncertain whether glycemia or the adverse maternal underlying risk factor profile is the main driver for fetal cardiac remodeling.Objective:To assess cardiac morphology and function at midgestation in fetuses of mothers prior to development of GD and compare them with those of unaffected controls.Design, Setting, and Participants:During this prospective nonintervention screening study at 19 to 23 weeks' gestation, fetal cardiac morphology and function were assessed in all participants. Pregnancy complications were obtained from the medical records of the women. Fetal cardiac morphology and function were assessed in all participants at Harris Birthright Research Institute at King's College Hospital, London, United Kingdom. Participants included pregnant women with singleton pregnancy who attended their routine fetal ultrasound examination at midgestation and agreed to participate in the Advanced Cardiovascular Imaging Study in pregnancy.Main Outcome and Measures:Comparison of fetal cardiac morphology and function between mothers who subsequently developed GD and those who did not develop GD.Methods:This was a prospective nonintervention screening study of 5620 women with singleton pregnancies at 19 to 23 weeks' gestation. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricle. The morphology of the fetal heart was assessed by calculating the right and left sphericity index.Results:The 5620 included patients had a mean age of 33.6 years. In 470 cases, the women were diagnosed with GD after the midgestation echocardiographic assessment (8.4%). Women with GD, compared with the non-GD group, were older, had higher BMI, higher prevalence of family history of diabetes, non-White ethnicity, chronic hypertension, and GD in a previous pregnancy. In fetuses of the GD group compared with the non-GD group, there was mild increase in interventricular millimeter thickness (0.04; 95% CI, 0.03-0.06 mm) and left atrial area (0.04; 95% CI, 0.04-0.05), whereas left and right functional indices were comparable between groups with the exception of left ventricular ejection fraction, which was marginally improved in the GD group (0.02; 95% CI, 0.03-0.03).Conclusions and Relevance:This study demonstrates that prior to development of GD, there was mild alteration in fetal cardiac morphology without affecting cardiac function. This suggests that the adverse maternal risk factor profile and not only the glycemia might contribute to cardiac remodeling noted in fetuses of women with GD.

BACKGROUND: Preeclampsia is associated with increased risks of life-threatening,-altering, and-ending complications. Assessment of risk for preeclampsia at 35 to 36 weeks' gestation by the Fetal Medicine Foundation 36-week competing-risk model identifies approximately 75% of women who will develop term preeclampsia, at a 10% screen-positive rate.OBJECTIVE: This study aimed to assess whether the Fetal Medicine Foundation 36-week model can provide personalized guidance to women about the probable timing of their delivery, whether or not they develop pregnancy hypertension.STUDY DESIGN: In this prospective nonintervention screening study at 2 maternity hospitals in England, women who did not have preeclampsia (American College of Obstetricians and Gynecologists definition) and were attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation underwent assessment of risk for preeclampsia, including maternal de-mographic characteristics, medical history, mean arterial pressure, and serum placental growth factor and soluble fms-like tyrosine kinase-1. Fetal Medicine Foundation 36-week model risk categories for subse-quent preeclampsia were defined as: A, >0.500; B, 0.20 to 0.499; C, 0.05 to 0.199; D, 0.020 to 0.049; and E, <0.020. Obstetrical records were examined for all women to identify their gestational age at delivery, and whether they experienced a spontaneous onset of labor (irrespective of mode of delivery) or had a medically indicated birth (either induction of labor or unlabored cesarean delivery). The cumulative incidence of delivery and risk ratios, for all deliveries and for spontaneous deliveries, was assessed.RESULTS: Among 29,035 women with singleton pregnancies, 1.0%, 2.9%, 3.3%, 5.0%, 9.9%, and 77.9% were in A, B, C, D, and E risk strata, respectively. In the A (vs E) stratum, 71.95% (vs 33.52%) of births were medically indicated. Compared with women in stratum E, women in higher risk strata were more likely to deliver, and to deliver following spontaneous labor, before their due date. For example, of the women in stratum A (vs E), 14.2% (vs 1.1%; risk ratio, 12.5 [95% confidence interval, 9.45-15.35]), 48.5% (vs 5.1%; risk ratio, 8.47 [7.48-9.35]), 69.6% (vs 15.5%; risk ra-tio, 3.86 [3.59-4.08]), and 90.1% (vs 44.8%; risk ratio, 6.72 [4.53-9.95]) gave birth before 37 0/7, 38 0/7, 39 0/7, and 40 0/7 weeks, respectively. For women in stratum A (vs E), when censored for medically indicated births, spontaneous labor occurred more commonly before 37 0/7 (risk ratio, 4.31 [1.99-6.57]), 38 0/7 (risk ratio, 3.71 [2.48-4.88]), 39 0/7 (risk ratio, 2.87 [2.22-3.46]), and 40 0/7 (risk ratio, 1.42 [1.14-1.77]) weeks.CONCLUSION: Women in higher-risk strata gave birth earlier, and more frequently following medically indicated delivery, compared with those in lower-risk strata. Importantly, the proportion of women who gave birth following spontaneous onset of labor before their due date was also greater in higher-risk than in lower-risk women. The Fetal Medicine Foundation 36-week competing-risk model incorporates biomarkers of placental aging, including angiogenic imbalance; these results imply that a fetoplacental response to placental aging may be an important trigger for the onset of labor at term.

BACKGROUND Preeclampsia (PE) is an independent risk factor for adverse maternal cardiovascular outcomes. The role of maternal cardiac function in the pathophysiology of PE remains unclear. OBJECTIVES This study sought to describe differences in cardiac function at midgestation between women who develop PE and those with uncomplicated pregnancy and to establish whether routine cardiac assessment at midgestation can improve performance of screening for PE achieved by established biomarkers. METHODS Mean arterial pressure was measured, medical history was obtained, and left ventricular (LV) systolic and diastolic functions were assessed using standard echocardiography and speckle tracking imaging. Uterine artery pulsatility index and serum placental growth factor and soluble fms-like tyrosine kinase-1 were measured. RESULTS In 4,795 pregnancies, 126 (2.6%) developed PE. Following multivariable analysis, peripheral vascular resistance was significantly higher and LV global longitudinal systolic strain, ejection fraction, cardiac output, and left atrial area were mildly lower in women who developed PE compared to those who did not. There was a weak association between maternal cardiovascular indices and biomarkers of placental perfusion and function. Cardiac indices did not improve the performance of screening for PE on top of maternal risk factors, mean arterial pressure, and biomarkers of placental perfusion and function. CONCLUSION Women who develop PE have an increase in peripheral vascular resistance and a mild reduction in LV functional cardiac indices long before PE development. However, cardiac indices do not improve the performance of screening for PE; thus, their routine clinical use is not advocated. (C) 2022 by the American College of Cardiology Foundation.

BACKGROUND: Twin pregnancies carry a higher risk of congenital and structural malformations, and pregnancy complications including miscarriage, stillbirth, and intrauterine fetal death, compared with singleton pregnancies. Carrying a fetus with severe malformations or abnormal karyotype places the remaining healthy fetus at an even higher risk of adverse outcome and pregnancy complications. Maternal medical conditions or complicated obstetrical history could, in combination with twin pregnancy, cause increased risks for both the woman and the fetuses. To our knowledge, no previous studies have evaluated and compared the outcomes of all dichorionic twin pregnancies and compared the results of reduced twins with those of nonreduced and primary singletons in a na-tional cohort. These data are important for clinicians when counseling couples about fetal reduction and its implications. OBJECTIVE: This study aimed to describe and compare the risks of adverse pregnancy outcomes, including the risk of pregnancy loss, in a national cohort of all dichorionic twins-reduced, nonreduced, and pri-mary singletons. In addition, we examined the implications of gestational age at fetal reduction on gestational age at delivery. STUDY DESIGN: This was a retrospective cohort study of all Danish dichorionic twin pregnancies, including pregnancies undergoing fetal reduction and a large proportion of randomly selected primary singleton pregnancies with due dates between January 2008 and December 2018. The primary outcome measures were adverse pregnancy outcomes (defined as miscarriage before 24 weeks, stillbirth from 24 weeks, or single intrauterine fetal death in non -reduced twin pregnancies), preterm delivery, and obstetrical pregnancy complications. Outcomes after fetal reduction were compared with those of nonreduced dichorionic twins and primary singletons. RESULTS: In total, 9735 dichorionic twin pregnancies were included, of which 172 (1.8%) were reduced. In addition, 16,465 primary singletons were included. Fetal reductions were performed between 11 and 23 weeks by transabdominal needle-guided injection of potassium chloride, and outcome data were complete for all cases. Adverse pregnancy outcome was observed in 4.1% (95% confidence interval, 1.7%-8.2%) of reduced twin pregnancies, and 2.4% (95% confidence interval, 0.7%-6.1%) were delivered before 28 weeks, and 4.2% (95% confi-dence interval, 1.7%-8.5%) before 32 weeks. However, when fetal reduction was performed before 14 weeks, adverse pregnancy outcomes occurred in only 1.4% (95% confidence interval, 0.0%-7.4%), and de-livery before 28 and 32 weeks diminished to 0% (95% confidence interval, 0.0%-5.0%) and 2.8% (95% confidence interval, 0.3%-9.7%), respectively. In contrast, 3.0% (95% confidence interval, 2.7%-3.4%) of nonreduced dichorionic twins had an adverse pregnancy outcome, and 1.9% (95% confidence interval, 1.7%-2.1%) were delivered before 28 weeks, and 7.3% (95% confidence interval, 6.9%-7.7%) before 32 weeks. Adverse pregnancy outcomes occurred in 0.9% (95% confidence interval, 0.7%-1.0%) of primary singletons, and 0.2% (95% confidence interval, 0.1%-0.3%) were delivered before 28 weeks, and 0.7% (95% confidence interval, 0.6%-0.9%) before 32 weeks. For reduced twins, after taking account of maternal factors and medical history, it was demonstrated that the later the fetal reduction was performed, the earlier the delivery occurred (P<.01). The overall risk of pregnancy complications was significantly lower among reduced twin pregnancies than among nonreduced dichorionic twin pregnancies (P1/4.02). CONCLUSION: In a national 11-year cohort including all dichorionic twin pregnancies, transabdominal fetal reduction by needle guide for fetal or maternal indication was shown to be safe, with good outcomes for the remaining co-twin. Results were best when the procedure was performed before 14 weeks.

Objective To examine the effect of self-declared race on serum placental growth factor (PlGF) and sFlt-1/PlGF ratio and the impact on pre-eclampsia (PE) prediction. Design Prospective observational study. Setting Two UK maternity hospitals. Population 29 035 women with singleton pregnancies attending a routine 35(+0) to 36(+6) weeks' gestation hospital visit, including 654 (2.3%) who subsequently developed PE. Methods The predictive performance of PlGF and sFlt-1/PlGF for PE in minority racial groups (versus white) was examined. Main outcome measure Delivery with PE. Results Compared with white women, mean PlGF was higher and sFlt-1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut-off corresponding to a screen-positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut-off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut-off in sFlt-1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient-specific risks. Conclusion Screening for PE with fixed cut-offs in PlGF or sFlt-1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.

BACKGROUND:There is good evidence that first-trimester assessment of the risk for preterm preeclampsia and treatment of the high-risk group with aspirin reduces the incidence of preterm preeclampsia. Furthermore, there is evidence that aspirin is associated with an increased risk of maternal and neonatal hemorrhagic complications. Against this background, there are ongoing debates whether aspirin should be recommended for all women or to a subpopulation of women predicted to be at increased risk of developing preeclampsia. Moreover, if a strategy of the prediction and prevention of preterm preeclampsia is to be used, what method should be used for the prediction, and what risk cutoff should be used to decide on who to treat?OBJECTIVE:This study aimed to compare the policies of universal treatment, stratified treatment, and no treatment with aspirin.STUDY DESIGN:Decisions about aspirin prophylaxis were considered from the perspective of the Bayesian decision theory. Using this approach, the treatment policies were evaluated for risks of preterm preeclampsia, effects of aspirin, and trade-offs between the harms and benefits of the treatment. Evidence on the risk of preterm preeclampsia was taken from the Screening programme for pre-eclampsia study, which was a first-trimester screening study for the prediction of preeclampsia. Evidence of the effect of aspirin was taken from the Aspirin for Evidence-Based Preeclampsia Prevention trial, which was a trial of aspirin vs placebo in the prevention of preterm preeclampsia. The trade-off between the benefits and harms of aspirin was specified by addressing the question, "What is the maximum number of women that should be treated to prevent 1 case of preterm preeclampsia?" The number can be considered as an exchange rate between the harms and benefits of using aspirin to prevent preterm PE. Given the uncertainty about the harms associated with aspirin, the treatment policies were compared across a wide range of exchange rates.RESULTS:For exchange rates between 10 and 1000 women treated with aspirin to prevent 1 case of preterm preeclampsia, the net benefit achieved from the risk assessment and targeted treatment of women at high risk of preterm preeclampsia was higher than that from women with no treatment or women with universal treatment with aspirin.CONCLUSION:Universal treatment with aspirin should be avoided. Risk-based screening should be used, and the cutoff for taking aspirin should be determined from the consideration of the trade-off between the benefits and harms and detection, false-positive, and screen-positive rates.