Preeclampsia In Twin Pregnancies Research Articles

The association between neonatal birthweight discordance and preeclampsia in twin pregnancy.

To investigate the association between neonatal birthweight (NBW) discordance and preeclampsia (PE) in twin pregnancy. This was a single-center retrospective cohort study. Women with two live births in the First Affiliated Hospital of Sun Yat-sen University from January 2011 to June 2020 were eligible. They were classified into four groups based on the quartiles of NBW discordance in monochorionic (MC) and dichorionic (DC) twin pregnancy. The relationship between NBW discordance and the risk of PE was assessed by logistic regression, subgroup analyses was further analyzed. A total of 1566 women were eligible for the final analysis, there were 445 MC cases and 1121 DC cases. No matter in monochorionic or dichorionic pregnancy, higher NBW discordance quartiles were associated with increased risks of PE. Compared with women in the lowest NBW discordance quartile, women in the highest NBW discordance quartile had approximately 3.6 and 6.0 times risk of PE in monochorionic and dichorionic pregnancy respectively. The association between quartiles of NBW discordance and the risk of PE were higher in dichorionic pregnancy than in monochorionic pregnancy. No matter in MC or DC pregnancy, no significant interaction effects were identified for maternal age, pregnancy body mass index, mode of conception and whether complicated with gestational diabetes mellitus. The increased NBW discordance quartile was related to an increased risk of PE. Assessing estimated fetal weight discordance by using ultrasound in clinical practice to predict PE remained to be further researched.

Impact factors and obstetric outcomes of preeclampsia in twin pregnancies by prepregnancy body mass index: a six-year retrospective cohort study

Objectives Among many risk factors for preeclampsia (PE), prepregnancy body mass index (BMI) is one of few controllable factors. However, there is a lack of stratified analysis based on the prepregnancy BMI. This study aimed to determine the influencing factors for PE and assess the impact of PE on obstetric outcomes in twin pregnancies by prepregnancy BMI. Methods This was a retrospective cohort study between January 1, 2017, and December 31, 2022, in Southwest China. Impact factors and associations between PE and obstetric outcomes were analyzed separately for twin pregnancies with prepregnancy BMI < 24kg/m2 (non-overweight group) and BMI ≥ 24kg/m2 (overweight group). Results In total, 3602 twin pregnancies were included, of which, 672 women were allocated into the overweight group and 11.8% of them reported with PE; 2930 women were allocated into the non-overweight group, with a PE incidence of 5.6%. PE had a negative effect on birthweight and increased the incidence of neonatal intensive care unit admission in both the overweight and non-overweight groups (43.0% vs. 28.0%, p = .008; 45.7% vs. 29.1%, p < .001). Among overweight women, PE increased the proportion of postpartum hemorrhage (15.2% vs. 4.4%, p < .001). After adjustments, multivariate regression analysis showed that excessive gestational weight gain (aOR = 1.103, 95% CI: 1.056–1.152; aOR = 1.094, 95% CI: 1.064–1.126) and hypoproteinemia (aOR = 2.828, 95% CI: 1.501–5.330; aOR = 6.932, 95% CI: 4.819–9.971) were the shared risk factors for PE in both overweight and non-overweight groups. In overweight group, in vitro fertilization was the other risk factor (aOR = 2.713, 95% CI: 1.183–6.878), whereas dichorionic fertilization (aOR = 0.435, 95% CI: 0.193–0.976) and aspirin use during pregnancy (aOR = 0.456, 95% CI: 0.246–0.844) were protective factors. Additionally, anemia during pregnancy (aOR = 1.542, 95% CI: 1.090–2.180) and growth discordance in twins (aOR = 2.451, 95% CI: 1.215–4.205) were connected with an increased risk of PE only in non-overweight twin pregnancies. Conclusions Both discrepancy and similarity of impact factors on developing PE were found between overweight and non-overweight twin pregnancies in this study. However, the dosage and initiation time of aspirin, as well as twin chorionicity on the occurrence of PE in two subgroups, are still debated.

A comparative study of performance of first trimester FMF algorithm for prediction of preeclampsia in singleton and twin pregnancies in coastal Karnataka

Preeclampsia is one of the most common disorders of pregnancy known to complicate 5-10% of all the pregnancies, and it is a component of the deadly triad (along with haemorrhage and infection), that contributes greatly to maternal morbidity and mortality rates. The prevalence of preeclampsia in twin pregnancy is 3-4 fold compared to singleton pregnancy. Timely diagnosis and prevention of this condition is therefore critical. Multiple maternal factors and placental biomarkers have shown to predict preeclampsia in singleton pregnancies. Previous Studies have shown that the proposed algorithms for preeclampsia screening in singletons can also be applied in twins, but with slight modifications and lower accuracy. To study the various parameters included in FMF screening algorithm in first trimester for preeclampsia in singleton and twin pregnancies. To find diagnostic accuracy of screening parameters to predict preeclampsia later in second and third trimester. To study sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in singleton and twin pregnancy. This prospective observational cohort study conducted in department of Obstetrics and Gynecology, Kasturba Medial College, Hospital, Manipal. Patients were recruited from August 2021 to November 2022. A total of 295 pregnant women were included of which 255 were singleton gestation and 40 were twin gestation. All parameters mentioned in FMF algorithm were obtained between 11week to 13+6 weeks. Patients were followed until delivery for occurrence of pre-eclampsia. Individual parameters of first trimester FMF algorithm of pre-eclampsia screening were analyzed in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) in both singleton and twin study subjects and results were then compared among the groups. In this study a total of 295 pregnant women were recruited. 255 were single gestation of which 47 had preeclampsia and 40 were twin gestation of which 4 had preeclampsia. In the cohort of singleton pregnant women with pre-eclampsia, mean age was noted to be higher (32.77±4.27). They had higher BMI (mean 27.61±3.74) and first trimester MAP was also higher. Similarly, cohort of twin pregnancy with preeclampsia had higher mean of maternal age, BMI and MAP (30.33 ±4.46, 22.83 ± 2.93 and 90.40 ± 1.45 respectively). The Preeclampsia group in both singleton and twin subjects had lower serum concentration and lower MoM values of PAPP-A and PlGF while higher values of free beta HCG and uterine artery PI. Therefore the FMF algorithm for first trimester screening of preeclampsia was found to be a good predictor in both singleton and twin pregnancy. The first trimester FMF algorithm for preeclampsia screening had similar utility in the prediction of preeclampsia in both singleton and twin pregnancy with its individual parameters and combined risk model. However, its accuracy was slightly lesser among twins. Therefore, same screening model can be applicable in singleton and twin gestation.

Initial establishment and validation of a predictive model for preeclampsia in twin pregnancies based on maternal characteristics and echocardiographic parameters.

The primary objective of this study was to evaluate the association between maternal echocardiographic changes and the occurrence of preeclampsia (PE) in twin pregnancies. Additionally, we established and validated a prediction model for PE in twin pregnancies. The first part of this study was retrospective and included data from 854 twin pregnancies that received antenatal care at Peking University Third Hospital from April 2017 to April 2021 (training cohort). Overall, 159 women who underwent transthoracic echocardiography were included in the analysis. To build a predictive model, cardiac findings were compared between normotensive women and those with PE. The model was then validated in a prospective longitudinal cohort (test cohort) that included 109 women with twin pregnancies who underwent two consecutive transthoracic echocardiography examinations during the second and third trimesters. Fifty-four normotensive women and 105 women with PE were analyzed in the retrospective cohort that was used to build the model in which later preeclampsia was associated with higher left ventricular mass index (>61 g/m2 ), interventricular septal thickness (>7.87 mm), left atrial anteroposterior diameter (>33.5 mm), mitral inflow late diastolic velocity (A) (>0.685 m/s), ratio of early diastolic velocity (E) and peak early diastolic myocardial velocity of the lateral mitral annulus (>6.5), and lower peak early diastolic myocardial velocity (<13.1 cm/s). The optimized PE prediction model based on the interventricular septal thickness, left atrial anteroposterior diameter, A, peak early diastolic myocardial velocity and pre-pregnancy bodyweight index was then established (area under the curve [AUC] = 0.840, 95% CI 0.778-0.903, P < 0.001). The model was tested in the prospective cohort including 87 normotensive women and 22 women with PE; the validation test showed that the prediction model in the second (AUC = 0.801) and third (AUC = 0.811) trimesters had high discriminative ability and calibration. Maternal echocardiographic changes in twin pregnancies are associated with the development of preeclampsia. The model constructed, based on the echocardiographic parameters and body mass index, provides novel ideas for the prediction of PE.

Clinical utility of sFlt-1 and PlGF in screening, prediction, diagnosis and monitoring of pre-eclampsia and fetal growth restriction.

Pre-eclampsia (PE) is characterized by placental and maternal endothelial dysfunction, and associated with fetal growth restriction (FGR), placental abruption, preterm delivery and stillbirth. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are altered in pregnancies complicated by placenta-related disorders. In this Review, we summarize the existing knowledge, examining the performance of maternal PlGF, sFlt-1 and the sFlt-1/PlGF ratio for screening PE, predicting development of PE in the short term, diagnosing PE, monitoring established PE and predicting other placenta-related disorders in singleton pregnancy. We also discuss the performance of PlGF and the sFlt-1/PlGF ratio for predicting PE in twin pregnancy. For first-trimester screening in singleton pregnancy, a more accurate way of identifying high-risk women than current practice is to combine maternal PlGF levels with clinical risk factors and ultrasound markers. Later in pregnancy, the sFlt-1/PlGF ratio has advantages over PlGF because it has a higher pooled sensitivity and specificity for diagnosing and monitoring PE. It has clinical value because it can rule out the development of PE in the 1-4-week period after the test. Once a diagnosis of PE is established, repeat measurement of sFlt-1 and PlGF can help monitor progression of the condition and may inform clinical decision-making regarding the optimal time for delivery. The sFlt-1/PlGF ratio is useful for predicting FGR and preterm delivery, but the association between stillbirth and the angiogenic factors is unclear. The sFlt-1/PlGF ratio can be used to predict PE in twin pregnancy, although different sFlt-1/PlGF ratio cut-offs from those for singleton pregnancy should be applied for optimal performance. In summary, PlGF, sFlt-1 and the sFlt-1/PlGF ratio are useful for screening, diagnosing, predicting and monitoring placenta-related disorders in singleton and twin pregnancy. We propose that tests for these angiogenic factors are integrated more fully into clinical practice.© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Low-dose aspirin in the prevention of preeclampsia in twin pregnancies: A real-world study.

The use of low-dose aspirin for women with twin pregnancies remains controversial. This study was to describe the frequency of preeclampsia and aspirin use in twin pregnancies in real practice. This retrospective cohort study based on real-world data was conducted in the Obstetrics and Gynecology Hospital of Fudan University between 2013 and 2020. Women with twin pregnancies who received prenatal care before 20 weeks of gestational age were included. They were divided into those using low-dose aspirin (LDA group) and those not using aspirin group (N-LDA group). The primary outcome was the frequency of preeclampsia, and secondary outcomes included early-onset and preterm mild and severe preeclampsia. A total of 2,946 women had twin pregnancies, and 241 were excluded due to missing information. Of 2,705 eligible women, 291 (10.75%) were administered aspirin and the other 2,414 (89.25%) did not. The patients in the LDA group were significantly more likely to be older, have a higher rate of use of ART, have a previous history of hypertension, and have gestational diabetes (p < 0.05). In the LDA group, aspirin compliance ≥50% was relatively low (14.43%, 42/291). Preeclampsia occurred in 106 of 291 participants (36.43%) in the LDA group, as compared to 449 of 2,411 (18.62%) in the N-LDA group (OR: 2.15, 95% CI: 1.62-2.82; p < 0.01). The association was confirmed (OR: 1.74, 95% CI: 1.26-2.4; p < 0.01) in the 1:2 case-matched analysis. Higher odds of ratio in the LDA group were demonstrated (aORs > 1, p < 0.01), except for early-onset and preterm mild preeclampsia (p > 0.05). This association was confirmed in a subgroup analysis of methods of conception (aORs ≥ 1, p > 0.05). Aspirin prescription of 75 to 100 mg in twin pregnancies was associated with no significant reduction of preeclampsia, which may be due to poor compliance with the aspirin used. Further randomized controlled or prospective cohort studies are required.

Optimal cutoffs of growth discordance for the risk of preeclampsia in twin pregnancies: A single-center retrospective cohort study.

To explore the optimal cutoffs of growth discordance for the risk of preeclampsia in twin pregnancies. A retrospective cohort study in a university hospital which included twins delivered from February 2013 to September 2020. Restrictive cubic spline (RCS) model was applied to the trend of intertwin birthweight difference (BWD) with the risk of preeclampsia. Logistic regression and subgroup analysis were performed to find the cut-off with statistical significance and clinical meaningfulness. A total of 2,631 women pregnant with twins were enrolled. RCS showed a nonlinear upward trend of preeclampsia with BWD, and the BWD of 15% was the initial rising point. With the confounders adjusted, only the group with BWD ≥ 25% was found to be significantly associated with an increased risk of preeclampsia (adjusted odds ratio [aOR], 2.44; 95% confidence interval [CI]: 1.74-3.42). Additionally, subgroup analysis showed that both monochorionic (MC) and small for gestational age (SGA) twins were more likely to complicate with preeclampsia. The growth discordance of 15% during pregnancy may be the preventive point of preeclampsia, and 25% may be the interventional point.

Prevalence and risk factors of gestational hypertension and preeclampsia in twin pregnancies: population based study

Prevalence and risk factors of gestational hypertension and preeclampsia in twin pregnancies: population based study

双胎妊娠中影响子痫前期的因素预测

双胎妊娠中影响子痫前期的因素预测

Intertwin growth discordance throughout gestation and hypertensive disorders of pregnancy

Previous studies have established the association between intertwin birthweight discordance and hypertensive disorders of pregnancy. However, longitudinal fetal size discordance concerning gestational hypertension or preeclampsia remains unclear. This study aimed to compare the patterns of estimated fetal weight discordance throughout gestation among normotensive women, women with gestational hypertension, and women with preeclampsia and to evaluate the association between crown-rump length discordance at 11 to 14 weeks of gestation and hypertensive disorders of pregnancy. This was a retrospective cohort study of women with twin pregnancies who had antenatal care visits and delivered at a tertiary hospital between January 2013 and June 2021. The crown-rump length was measured at 11 to 14 weeks of gestation. Estimated fetal weight was calculated based on ultrasound examinations of fetal biometrics at 16 to 18, 20 to 24, 28 to 32, and ≥34 weeks of gestation, respectively. Crown-rump length and estimated fetal weight discordances were calculated: (larger crown-rump length- smaller crown-rump length)/larger crown-rump length× 100% and (larger estimated fetal weight- smaller estimated fetal weight)/larger estimated fetal weight× 100%, respectively. Multiple imputation was used to handle missing data, and all models accounted for the imputation. Multilevel model analysis was used to compare the differences in estimated fetal weight discordances throughout gestation among normotensive women, women with gestational hypertension, and women with preeclampsia. Generalized linear models were used to evaluate the association between crown-rump length discordance and hypertensive disorders of pregnancy, assuming a Poisson distribution. The possible nonlinear relationship between continuous crown-rump length discordance and hypertensive disorders of pregnancy was examined by generalized additive models. All analyses were stratified by chorionicity. Of the 3280 women with twin pregnancies who met the inclusion criteria, 187 (5.7%) developed gestational hypertension, and 436 (13.3%) developed preeclampsia, including 125 (3.8%) early-onset preeclampsia and 311 (9.5%) late-onset preeclampsia. In women with dichorionic twin pregnancies, compared with normotensive women, a substantial progression of estimated fetal weight discordance throughout pregnancy was identified in women who developed preeclampsia, and a large progression of estimated fetal weight discordance in late pregnancy was identified in women who developed gestational hypertension. In women with monochorionic twin pregnancies, estimated fetal weight discordances were more progressive from 20 to 24 weeks of gestation onward in women who developed preeclampsia than in normotensive women. Crown-rump length discordance at 11 to 14 weeks of gestation was associated with an increased risk of preeclampsia (relative risk, 1.03; 95% confidence interval, 1.00-1.05), particularly early-onset preeclampsia (relative risk, 1.09; 95% confidence interval, 1.04-1.13). A crown-rump length discordance of ≥10% had 1.2 times the increased risk of developing early-onset preeclampsia (relative risk, 2.27; 95% confidence interval, 1.28-4.03). This association was identified in dichorionic twins, but not in monochorionic twins. Our study demonstrated distinct growth discordant patterns among normotensive women, women with gestational hypertension, and women with preeclampsia in twin pregnancies. Intertwin crown-rump length discordance at 11 to 14 weeks of gestation was associated with an increased risk of preeclampsia, especially early-onset preeclampsia in dichorionic twin pregnancies, with a dose-response pattern.

Screening for preeclampsia in twin pregnancies.

Twin pregnancies are an important risk factor for preeclampsia, a hypertensive disorder of pregnancy that is associated with a significant risk of maternal and perinatal morbidity. Given the burden of preeclampsia, the identification of women at high risk in early pregnancy is essential to allow for preventive strategies and close monitoring. In singleton pregnancies, the risk factors for preeclampsia are well established, and a combined first-trimester prediction model has been shown to adequately predict preterm disease. Furthermore, intervention with low-dose aspirin at 150mg/day in those identified as high-risk reduces the rate of preterm preeclampsia by 62%. In contrast, risk factors for preeclampsia in twin pregnancies are less established, the proposed screening models have shown poor performance with high false-positive rates, and the benefit of aspirin for the prevention of preeclampsia is not clearly demonstrated. In this review, we examine the literature assessing prediction and prevention of preeclampsia in twin pregnancies.

The correlation between maternal serum sST2, IL‐33 and NT‐proBNP concentrations and occurrence of pre‐eclampsia in twin pregnancies: A longitudinal study

The primary objective of this study was to determine the longitudinal profile of serum sST2 (soluble suppression of tumorigenicity 2), IL-33 (interleukin-33) and NT-proBNP (N-terminal pro-brain natriuretic peptide) concentrations in twin pregnancies with pre-eclampsia (PE) and those normotensive twins. The secondary objective was to test whether the change of serum sST2,IL-33 and NT-proBNP is related to PE in twin pregnancies. This is a longitudinal nested case-control study and all 156 dichorionic (DC) pregnancies were from a prospective cohort of twin pregnancies who received antenatal care and gave two live births at Peking University Third Hospital between October 2017 and September 2020. Four to five milliliters of peripheral blood of each pregnant woman were collected during the following three intervals: (1) 6-11+6 weeks; (2) 24-27+6 weeks; (3) 28-31+6 weeks. We found that sST2 and NT-proBNP levels increased as pregnancy progressed in normotensive twin pregnancies and further increased in PE group, while no differences were found in IL-33 levels throughout pregnancy. Then the correlation of biomarker levels with the occurrence of PE was assessed. Our results indicated that combining maternal serum sST2 and NT-proBNP levels yielded the highest predictive value on the occurrence of PE significantly higher than the predictive value of any markers alone. Interestingly, the predictive value of second trimester (AUC=0.876, 95%CI 0.824-0.928, LR-0.338, LR+7.67, p<0.001)was higher than that of early-third trimester (AUC=0.832, 95%CI 0.769-0.896, LR-0.29, LR+3.845, p<0.001). Serum sST2 and NT-proBNP concentrations during second and early-third trimester were associated with the occurrence of PE in twin pregnancies.

The Maternal-Neonatal Outcomes of Twin Pregnancies with Preeclampsia and Their Association with Assisted Reproductive Technology: A Retrospective Study.

Objective: This study aimed to investigate the maternal–neonatal outcomes of twin pregnancies of mothers with preeclampsia and their association with assisted reproductive technology (ART). Methods: A retrospective study on the clinical and maternal–neonatal outcome data of 698 women with twin pregnancies who delivered in our hospital from December 2013 to September 2021 was conducted. Continuous variables were analyzed using a Student’s t-test or Wilcoxon rank-sum test. Categorical variables were analyzed using the Chi-square test. The risk factors of twin pregnancies with preeclampsia were analyzed by logistic regression. Results: The rate of twin pregnancy complicated by preeclampsia was 17.62% (123/698). Logistic regression analysis showed that ART increased the risk of preeclampsia in twin pregnancies (AOR: 1.868, 95% CI: 1.187–2.941). Mothers with preeclampsia carrying twins conceived with ART had a higher rate of delivery at gestational week < 34 (29.9% vs. 12.5%) and asphyxia of the neonate at 5 min after delivery (13.4% vs. 1.8%) than those with preeclampsia conceived without ART (p < 0.05). Conclusions: ART increases the risk of preeclampsia in twin pregnancies and the rate of adverse maternal–neonatal outcomes for twin pregnancies with preeclampsia. The policy of single embryo transfer is a method to reduce the adverse pregnancy outcomes of ART.

A New Model for the Predicting the Risk of Preeclampsia in Twin Pregnancy

ObjectiveWe aimed to develop an effective nomogram model for predicting the risk of preeclampsia in twin pregnancies.MethodsThe study was a retrospective cohort study of women pregnant with twins who attended antenatal care and labored between January 2015 and December 2020 at the Fujian Maternity and Child Health Hospital, China. We extracted maternal demographic data and clinical characteristics. Then we performed the least absolute shrinkage and selection operator regression combined with clinical significance to screen variables. Thereafter, multivariate logistic regression was used to construct a nomogram that predicted the risk of preeclampsia in twin pregnancies. Finally, the nomogram was validated using C-statistics (C-index) and calibration curves.ResultsA total of 2,469 women with twin pregnancies were included, of whom 325 (13.16%) had preeclampsia. Multivariate logistic regression models revealed that serum creatinine, uric acid, mean platelet volume, high-density lipoprotein, lactate dehydrogenase, fibrinogen, primiparity, pre-pregnancy body mass index, and regular prenatal were independently associated with preeclampsia in twin pregnancies. The constructed predictive model exhibited a good discrimination and predictive ability for preeclampsia in twin pregnancies (concordance index 0.821).ConclusionThe model for the prediction of preeclampsia in twin pregnancies has high accuracy and specificity. It can be used to assess the risk of preeclampsia in twin pregnancies.

Spontaneous twin pregnancy in uterus bicornis unicollis complicated with preeclampsia: A case report

Introduction and importanceBicornuate uterus is a uterine malformation caused by abnormal Müllerian fusion, often leading to multiple obstetric complications. A twin pregnancy in this condition is extremely rare.Case presentationA 27-year-old patient (Gravida 3, Para 0) with a previous history of two spontaneous early miscarriages was diagnosed with uterus bicornis unicollis (unicervical bicornuate uterus). She presented with spontaneous twin pregnancy complicated with preeclampsia at 34 weeks + 6 days. Thus, she underwent cesarean section with two separate lower-segment incisions. Consequently, healthy twins were delivered successfully.Clinical discussionBicornuate uterus is a rare congenital uterine malformation, and only 16 cases of twin pregnancy associated with uterus bicornis unicollis have been reported worldwide. This uterine malformation can be discovered spontaneously in imaging or during obstetric complications such as spontaneous abortions, premature labor, premature rupture of membranes, malpresentations, and intrauterine growth restriction.In addition, the risk for preeclampsia in twin pregnancies is twice higher than singleton gestations.ConclusionTwin pregnancy in a bicornuate uterus is extremely rare; this phenomenon is yet to have guidelines for monitoring pregnancy and the mode of delivery.

Predictive value of the sFlt-1/PlGF ratio for preeclampsia in twin pregnancies: a retrospective study

ABSTRACT Objective: This study aimed to investigate the efficiency of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in predicting preeclampsia (PE) within 4 weeks in twin pregnancies. Methods: Seventy-eight women with serum angiogenic markers measured at 28 + 0 to 30 + 6 weeks of gestation were enrolled. A receiver-operating characteristic curve was used to determine the sFlt-1/PlGF ratio threshold to predict PE. Results: A cutoff value for the sFlt-1/PlGF ratio of 22.2 predicted PE presence within 4 weeks. Conclusion: An sFlt-1/PlGF ratio of ≤22.2 is potentially indicative of PE absence within 4 weeks in twin pregnancies.

P-027. The prognostic role of maternal angiogenic markers in suspected pre-eclampsia in twin pregnancies

Alzheimer’s disease (AD) is a complex age-related neurodegenerative disease, associated with central and peripheral metabolic anomalies, such as impaired glucose utilization and insulin resistance. These observations led to a considerable interest not only in lifestyle-related interventions, but also in repurposing insulin and other anti-diabetic drugs to prevent or treat dementia. Body temperature is the oldest known metabolic readout and mechanisms underlying its maintenance fail in the elderly, when the incidence of AD rises. This raises the possibility that an age-associated thermoregulatory deficit contributes to energy failure underlying AD pathogenesis. Brown adipose tissue (BAT) plays a central role in thermogenesis and maintenance of body temperature. In recent years, the modulation of BAT activity has been increasingly demonstrated to regulate energy expenditure, insulin sensitivity and glucose utilization, which could also provide benefits for AD. Here, we review the evidence linking thermoregulation, BAT and insulin-related metabolic defects with AD, and we propose mechanisms through which correcting thermoregulatory impairments could slow the progression and delay the onset of AD.

Perinatal outcomes in twin pregnancies complicated by gestational diabetes

Gestational diabetes in singleton pregnancies increases the risk for large for gestational age infants, hypertensive disorders of pregnancy, and neonatal morbidity. Compared with singleton gestations, twin gestations are at increased risk for fetal growth abnormalities, hypertensive disorders, and neonatal morbidity. Whether gestational diabetes further increases the risk for these outcomes is unclear. We sought to determine the relationship between gestational diabetes and the risk for preeclampsia, fetal growth abnormalities, and neonatal intensive care unit admissions in a large cohort of women with twin pregnancies. We used a retrospective cohort of all twin gestations that were delivered at our institution from 1998 to 2013. We excluded pregnancies delivered before 24 weeks' gestation, monochorionic-monoamniotic twins, and patients with preexisting diabetes for a final cohort of 2573 twin deliveries. Gestational diabetes was defined as 2 abnormal values on a 100 g, 3-hour glucose challenge test as defined by the Carpenter-Coustan criteria or a 1-hour value of 200 mg/dL after a 50 g glucose test. Multivariable Poisson regression models were used to estimate the associations between gestational diabetes and preeclampsia, small for gestational age infants, large for gestational age infants, and admission to the neonatal intensive care unit after adjusting for prepregnancy body mass index, maternal race, maternal age, parity, use of in vitro fertilization, prepregnancy smoking status, and chronic hypertension as confounders. The unadjusted incidence of gestational diabetes was 6.5% (n=167). Women with gestational diabetes were more likely to be aged 35 years or older, living with obesity, and have conceived via in vitro fertilization than women without gestational diabetes. Preeclampsia was more common among women with twin pregnancies complicated by gestational diabetes (31%) than among women with twin pregnancies without gestational diabetes (18%) (adjusted risk ratio, 1.5; 95% confidence interval, 1.1-2.1). A diagnosis of small for gestational age infant was less common among women with gestational diabetes (17%) than among women without gestational diabetes (24%), although the results were imprecise (adjusted risk ratio, 0.8; 95% confidence interval, 0.5-1.1). There was no association between gestational diabetes and the incidence of large for gestational age neonates or neonatal intensive care unit admissions. Among women with gestational diabetes who reached 35 weeks' gestation, 62% (n=60) required medical management. Gestational diabetes is a risk factor for preeclampsia among women with twin pregnancies. Close blood pressure monitoring and patient education are critical for this high-risk group. The association between gestational diabetes and neonatal outcomes among women with twin pregnancies is less precise, although it may reduce the incidence of small for gestational age infants. Prospective studies to determine if glycemic control decreases the risk for preeclampsia in twin pregnancies with gestational diabetes are needed.

Clinical risk factors for preeclampsia in twin pregnancies.

BackgroundPreeclampsia is a common obstetric complication. The rate of preeclampsia is increased in twin pregnancies. The aim of this study was to assess the clinical risk factors for developing preeclampsia in twin pregnancies.MethodsA case-control study was carried out among women with twin pregnancies who delivered at gestational age more than 23 weeks at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, from 2003 to 2019. The data were retrieved from electronic medical records. Multivariate logistic regression analysis was used to find the risk factors.ResultsA total of 1,568 twin pregnancies were delivered during the study period and 182 cases (11.6%) developed preeclampsia. 172 cases with preeclampsia and 516 controls were selected for analysis. After certain variables were adjusted in the multivariate logistic regression analysis, the clinical factors associated with preeclampsia in twin pregnancies were nulliparity (adjusted odds ratio (OR) 1.57, 95% confidence interval (CI) 1.02–2.41) and chronic hypertension (adjusted OR 6.22, 95%CI 1.98–19.57). Low gestational weight gain was a significant protective factor against the development of preeclampsia (adjusted OR 0.50; 95%CI 0.32–0.77).ConclusionThe clinical risk factors for developing preeclampsia in twin pregnancies were nulliparity and chronic hypertension. These risk factors are of value to identify twin pregnant women at risk for preeclampsia and in implementing primary prevention.

Biomarkers of angiogenesis in twin gestations and the risk of preeclampsia — review of the current literature

Twin pregnancy is one of the key risk factors for the development of preeclampsia. Soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin are molecules involved in the process of angiogenesis with a proven role in the pathogenesis of preeclampsia. The aim of the review was to summarize available data on maternal serum levels of the biomarkers of angiogenesis and their usefulness in predicting preeclampsia in twin pregnancies. Most of available data suggest biomarkers concentrations differ between singleton and twin gestation and are related to chorionicity of twin pregnancy. Several algorithms including biomarkers of angiogenesis in prediction of PE in twin pregnancy are available and seem promising, however more large prospective surveys are necessary to assess their usefulness in general clinic use.