Twenty-five years with HER2 targeted therapy.

The development of trastuzumab is among the most significant cancer drug development projects in the 20th century. Trastuzumab became a gamechanger for the treatment of human epidermal growth receptor 2 (HER2) positive breast cancer, with a significant positive impact on disease recurrence and survival. The development of trastuzumab was the beginning of a new era of cancer drug development, which showed us the importance of understanding the molecular pathophysiology and drug mechanism of action. The drug-diagnostic codevelopment model, in which the drug is developed in parallel with a predictive biomarker assay, has had a significant impact on today's cancer drug development, and we are indebted to trastuzumab when it comes to the clinical enrichment trial design. Trastuzumab is not the only drug developed to target the HER2 protein. Over the past few decades, several new HER2 targeted therapies have been developed, including small-molecule tyrosine kinase inhibitors (TKI), monoclonal antibodies, and antibody-drug conjugates (ADC). In particular, the ADC trastuzumab deruxtecan seems to pave new avenues when it comes to HER2 targeted treatment not only for breast cancer, but also for gastric cancer and non-small cell lung cancer. With the development of trastuzumab as a reference point, this article will provide a brief summary of the efficacy of HER2 targeted therapy, including testing for HER2 positivity, as it has evolved over the past 25 years.

Physical therapists' prognosis of outcomes after a hip or quadriceps exercise intervention in patients with patellofemoral pain: A secondary analysis of a randomized trial.

OBJECTIVE: Can physical therapists who are treating patients with Patellofemoral Pain (PFP) predict the outcome of a 12-week exercise intervention based on initial assessment, and what are the physical therapists' reasons for prediction? DESIGN: Secondary analysis of a randomized trial. METHODS: After the initial assessment, physical therapists were asked to predict the prognosis of 200 patients with PFP who were allocated to 12 weeks of quadriceps exercises (QE) or hip exercises (HE) on a 1-10 Likert scale, and to describe their reasoning for the prediction score. Outcome measures were changes from baseline to week 12 and 26 on the Anterior Knee Pain Scale (AKPS; range 0-100) and a transition questionnaire (TransQ). Linear mixed-effects models were used to assess the prediction. Secondly, we used a qualitative approach to summarize the physical therapists' reasoning (written notes) when predicting the outcome. RESULTS: There was no association between physical therapists' prognosis and changes in AKPS for QE or HE at week 12 and 26 (Slopes: -0.14 to -0.51 with wide 95% confidence intervals [CI]). There was no association between physical therapists' assessment of prognosis using TransQ for QE or HE at week 12 and 26 (OR: 0.99 to 1.17 with wide 95% CIs). physical therapists. CONCLUSION: Physical therapists' prognosis based on initial assessment was not associated with outcomes after weeks 12 of either quadriceps or hip exercise-therapy among patients with PFP. Physical therapists' prognoses were not useful as a source of information and to identify PFP patients with poor or good projected outcomes.

An umbrella review of systematic reviews on interventions of physical activity before pregnancy, during pregnancy, and postpartum to control and/or reduce weight gain.

BACKGROUND: The increasing prevalence of overweight and obesity worldwide represents a (chronic) complex public health problem. This is also seen among women of childbearing age despite increased efforts to promote physical activity (PA) interventions. Excessive gestational weight gain (GWG) is associated with negative health outcomes for both mothers and offspring. OBJECTIVES: To summarize current systematic reviews (SRs) on PA interventions during pregnancy and postpartum to prevent excessive GWG and identify the most effective approaches. SEARCH STRATEGY: A literature search was conducted on major electronic databases (MEDLINE/Pubmed, Cochrane, Web of Science, Epistemonikos) from inception to March 2023. SELECTION CRITERIA: This study included SRs and meta-analyses of studies involving women aged 18 years or older from diverse ethnic backgrounds, who were either in the preconception period, pregnant, or within 1 year postpartum and who had no contraindications for exercise. Women with chronic diseases, such as pre-existing diabetes (type 1 or type 2) were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from selected studies assessing the impact of PA in preconception, pregnancy, and postpartum. Methodologic quality was assessed with the AMSTAR-2 tool. A narrative summary of results addresses relationships between PA and weight before, during, and after pregnancy, informing future research priorities for preventing excessive weight gain. This study is registered on PROSPERO (CRD420233946666). MAIN RESULTS: Out of 892 identified articles, 25 studies were included after removing duplicates, unrelated titles, and screening titles and abstracts for eligibility. The results demonstrate that PA can help prevent excessive GWG and postpartum weight retention. Structured and supervised moderate-intensity exercise, at least twice a week, and each session lasting a minimum of 35 min seems to provide the greatest benefits. CONCLUSIONS: Women who comply with the PA program and recommendations are more likely to achieve adequate GWG and return to their pre-pregnancy body mass index after delivery. Further research is warranted to explore how preconception PA influences pregnancy and postpartum outcomes given the absence of identified preconception-focused interventions.

Body mass index z-scores in the first 2 years of life were associated with adverse metabolic and anthropometric outcomes at 3 years of age.

AIM: We investigated associations between body mass index (BMI) z-scores for children aged 0-2 years and the BMI z-scores, body fat percentage and metabolic risk factors at 3 years of age. METHODS: This was a secondary analysis of the Lifestyle in Pregnancy and Offspring randomised controlled trial, carried out at two university hospitals in Denmark. It comprised 149 mothers with BMI ≥30 kg/m2 who did or did not receive a lifestyle intervention during pregnancy and a reference group of 97 mothers with normal-weight, with follow-up of their 3-year-old offspring. The children in these three groups were pooled for the data analyses, due to similar characteristics between groups. The BMI z-scores were calculated at 5 weeks, 5 months and 1, 2 and 3 years, using Danish reference groups. Their anthropometrics and metabolic outcomes were examined at 3 years of age. RESULTS: BMI z-scores at 5 months to 2 years were associated with BMI z-scores and body fat percentage at 3 years of age and BMI z-scores were not associated with metabolic risk factors at 3 years. CONCLUSION: BMI z-scores from 5 weeks of age were associated with adverse anthropometric outcomes but not with metabolic risk factors at 3 years of age.

Increased contact activated endogenous thrombin potential in pregnant women with preeclampsia.

Preeclampsia is a worldwide contributor to maternal and fetal morbidity and mortality. Women with preeclampsia are in a hyper-coagulable state with increased risk of thromboembolic disease later in life compared with normal pregnant women. The contact system (CAS) in plasma can mediate thrombin generation and is an important contributor to thrombus growth, but the activation of CAS during pregnancy complicated by preeclampsia is not yet elucidated, and CAS may play a role in the pathophysiology of preeclampsia. Therefore, the aim of the study is to address thrombin generation, and in particular, the capacity of the CAS-mediated pathway in patients with preeclampsia compared with pregnant controls. One hundred and seventeen women with preeclampsia and matched controls were included. The project was registered at www.clinicaltrials.gov as NCT04825145. CAS and tissue factor induced thrombin generation, proteins C and S, antithrombin, and histidine-rich glycoprotein (HRG) were assessed. Women with preeclampsia had significantly increased CAS and tissue factor-induced endogenous thrombin potential (ETP), and HRG compared with controls, P  = 0.022, P  = 0.024, and P  = 0.02, respectively. The concentrations of protein C and antithrombin were significantly reduced in the preeclampsia group, P  = 0.024 and P  < 0.0001, respectively. No significant difference in the concentration of protein S was detected, P  = 0.06. This study demonstrates a significant increased CAS-induced ETP and an overall decrease of important regulators of coagulation in women with preeclampsia compared with controls. These aspects can contribute to the hyper-coagulable state characterizing preeclampsia.

High-Sensitivity Cardiac Troponin I Enhances Preeclampsia Prediction Beyond Maternal Factors and the sFlt-1/PlGF Ratio.

BACKGROUND: Preeclampsia shares numerous risk factors with cardiovascular diseases. Here, we aimed to assess the potential utility of high-sensitivity cardiac troponin I (hs-cTnI) values during pregnancy in predicting preeclampsia occurrence. METHODS: This study measured hs-cTnI levels in 3721 blood samples of 2245 pregnant women from 4 international, prospective cohorts. Three analytical approaches were used: (1) a cross-sectional analysis of all women using a single blood sample, (2) a longitudinal analysis of hs-cTnI trajectories in women with multiple samples, and (3) analyses of prediction models incorporating hs-cTnI, maternal factors, and the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio. RESULTS: Women with hs-cTnI levels in the upper quarter had higher odds ratios for preeclampsia occurrence compared with women with levels in the lower quarter. Associations were driven by preterm preeclampsia (odds ratio, 5.78 [95% CI, 2.73-12.26]) and remained significant when using hs-cTnI as a continuous variable adjusted for confounders. Between-trimester hs-cTnI trajectories were independent of subsequent preeclampsia occurrence. A prediction model incorporating a practical hs-cTnI level of detection cutoff (≥1.9 pg/mL) alongside maternal factors provided comparable performance with the sFlt-1/PlGF ratio. A comprehensive model including sFlt-1/PlGF, maternal factors, and hs-cTnI provided added value (cross-validated area under the receiver operator characteristic, 0.78 [95% CI, 0.73-0.82]) above the sFlt-1/PlGF ratio alone (cross-validated area under the receiver operator characteristic, 0.70 [95% CI, 0.65-0.76]; P=0.027). As assessed by likelihood ratio tests, the addition of hs-cTnI to each prediction model significantly improved the respective prediction model not incorporating hs-cTnI, particularly for preterm preeclampsia. Net reclassification improvement analyses indicated that incorporating hs-cTnI improved risk prediction predominantly by correctly reclassifying women with subsequent preeclampsia occurrence. CONCLUSIONS: These exploratory findings uncover a potential role for hs-cTnI as a complementary biomarker in the prediction of preeclampsia. After validation in prospective studies, hs-cTnI, alongside maternal factors, may either be considered as a substitute for angiogenic biomarkers in health care systems where they are sparce or unavailable, or as an enhancement to established prediction models using angiogenic markers.

Twenty-five years with companion diagnostics.

For decades, pharmacotherapy has been hampered by significant patient variability, and the inability to predict outcomes at the individual patient level has negatively affected its value. However, progress in molecular medicine has led to an increased understanding of the pathophysiology and mechanisms of action of drugs, thereby enabling the development of predictive biomarkers. Companion diagnostics (CDx) belongs to the group of predictive biomarkers, which the Food and Drug Administration (FDA) defines as an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product. In September 1998, 25 years ago, the FDA approved the first CDx assay, the HercepTest, an immunohistochemical (IHC) assay for the detection of HER2 protein expression. This assay is linked to the use of the monoclonal antibody trastuzumab in the treatment of HER2 positive breast cancer. The HercepTest is not the only CDx developed. Currently, more than 60 drugs or drug combinations, primarily in hematology and oncology, have been approved by the FDA, with CDx assays linked to their use. The current article briefly discusses the subject of CDx and provides an overview of its evolution over the past 25 years, with particular emphasis on the United States.

The Different Roles of MET in the Development and Treatment of Cancer.

This Special Issue features contributions from leading international researchers in the field of MET (hepatocyte growth factor (HGF) receptor) biology and therapeutics [...].

The Potential of Trastuzumab Deruxtecan as a Tissue Agnostic Drug.

BACKGROUND: Many modern anticancer drugs are designed to target specific molecular alterations harbored by the cancer. If a specific drug is able to target these alterations, regardless of the organ or tissue in which the cancer originates, it will often be characterized as a tissue- or tumor agnostic drug. According to the Food and Drug Administration (FDA), a tissue-agnostic drug refers to a drug that targets a specific molecular alteration across multiple cancer types, as defined by organ, tissue, or tumor type. SUMMARY: Over the last 6 years, the FDA has approved seven tissue-agnostic drugs, and more are anticipated in the future. One promising candidate for a tissue-agnostic classification is the antibody-drug conjugate trastuzumab deruxtecan (T-DXd). Currently, T-DXd is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive and HER2-low breast cancer, HER2-positive gastric or gastroesophageal junction adenocarcinoma, and non-small cell lung cancer with activating HER2 mutations. Ongoing clinical research is exploring the potential of T-DXd in various solid tumors that harbor specific HER2 molecular alterations, and encouraging results, including the interim data from the DESTINY-PanTumor02 trial, have been published, which suggest a tissue-agnostic potential. KEY MESSAGES: Published phase I data as well as the interim results from the phase II DESTINY-PanTumor02 trial indicates that patients with different HER2-positive advanced solid tumors may benefit from treatment with T-DXd. Based on the currently available data, it seems likely that T-DXd possesses pantumor activity. However, different clinical trials are ongoing, and it will be necessary to see the results from these trials before drawing a final conclusion. When discussing tissue-agnostic potential, it is important to add that for most of the patients enrolled in the DESTINY-PanTumor02 and other trials, few treatment alternatives seem to exist, and T-DXd might be able to cover an unmet medical need.

Prayer and meditation practices in the early COVID-19 pandemic: A nationwide survey among Danish pregnant women. The COVIDPregDK study.

BACKGROUND: The emergence of the COVID-19 pandemic and the derived changes in maternity care have created stress and anxiety among pregnant women in different parts of the world. In times of stress and crisis, spirituality, including spiritual and religious practices, may increase. OBJECTIVE: To describe if the COVID-19 pandemic influenced pregnant women's considerations and practises of existential meaning-making and to investigate such considerations and practices during the early pandemic in a large nationwide sample. METHODS: We used survey data from a nationwide cross-sectional study sent to all registered pregnant women in Denmark during April and May 2020. We used questions from four core items on prayer and meditation practices. RESULTS: A total of 30,995 women were invited, of whom 16,380 participated (53%). Among respondents, we found that 44% considered themselves believers, 29% confirmed a specific form of prayer, and 18% confirmed a specific form of meditation. In addition, most respondents (88%) reported that the COVID-19 pandemic had not influenced their responses. CONCLUSION: In a nationwide Danish cohort of pregnant women, existential meaning-making considerations and practices were not changed due to the COVID-19 pandemic. Nearly one in two study participants described themselves as believers, and many practised prayer and/or meditation.

Gender bias in shared decision-making among cancer care guidelines: A systematic review.

BACKGROUND: In cancer care, the promotion and implementation of shared decision-making in clinical practice guidelines (CPG) and consensus statements may have potential differences by gender. OBJECTIVE: To systematically analyse recommendations concerning shared decision-making in CPGs and consensus statements for the most frequent cancers exclusively among males (prostate) and females (endometrial). SEARCH STRATEGY: We prospectively registered the protocol at PROSPERO (ID: RD42021241127). MEDLINE, EMBASE, Web of Science, Scopus and online sources (8 guideline databases and 65 professional society websites) were searched independently by two reviewers, without language restrictions. INCLUSION CRITERIA: CPGs and consensus statements about the diagnosis or treatment of prostate and endometrial cancers were included from January 2015 to August 2021. DATA EXTRACTION AND SYNTHESIS: Quality assessment deployed a previously developed 31-item tool and differences between the two cancers analysed. MAIN RESULTS: A total of 176 documents met inclusion criteria, 97 for prostate cancer (84 CPGs and 13 consensus statements) and 79 for endometrial cancer (67 CPGs and 12 consensus statements). Shared decision-making was recommended more often in prostate cancer guidelines compared to endometrial cancer (46/97 vs. 13/79, 47.4% vs. 16.5%; p < .001). Compared to prostate cancer guidelines (mean 2.14 items, standard deviation 3.45), compliance with the shared-decision-making 31-item tool was lower for endometrial cancer guidelines (mean 0.48 items, standard deviation 1.29) (p < .001). Regarding advice on the implementation of shared decision-making, it was only reported in 3 (3.8%) endometrial cancer guidelines and in 16 (16.5%) prostate cancer guidelines (p < .001). DISCUSSION AND CONCLUSIONS: We observed a significant gender bias as shared decision-making was systematically more often recommended in the prostate compared to endometrial cancer guidelines. These findings should encourage new CPGs and consensus statements to consider shared decision-making for improving cancer care regardless of the gender affected. PATIENT OR PUBLIC CONTRIBUTION: The findings may inform future recommendations for professional associations and governments to update and develop high-quality clinical guidelines to consider patients' preferences and shared decision-making in cancer care.

The safety of phthalate-containing medications used during pregnancy.

INTRODUCTION: Phthalates freely cross the placenta and have the potential to influence pregnancy outcomes, with evidence of an increased incidence of preterm birth, low birth weight, pregnancy loss, and gestational diabetes. There is no regulation of phthalate concentrations in medications, which is often found in enteric coatings. Ingestion of phthalate containing medication during pregnancy may result in materno-fetal harm. AREAS COVERED: Phthalate subtypes, sources of phthalate exposure, mechanisms of phthalate toxicity, associations between phthalate exposure and incidence of preterm birth, low birth weight, fetal growth, gestational diabetes, and placental development. EXPERT OPINION: There is robust evidence to link exposure to phthalates in medical products including preterm birth, gestational diabetes, pregnancy-induced hypertension, and miscarriage. Nevertheless, future studies need to address standardization to avoid the heterogeneity of current studies. In future, the use of naturally occurring biopolymers may be safer, and the role of vitamin D as an immune modulator also has promise.

Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

INTRODUCTION: We identified risk factors and outcomes associated with SARS-CoV-2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS-CoV-2 during pregnancy in national health registers in Denmark. MATERIAL AND METHODS: Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS-CoV-2 test during pregnancy with non-infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID-19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS-CoV-2 diagnosis in pregnancy in the registers. RESULTS: SARS-CoV-2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28-2.07). Risk factors for severe COVID-19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04-1.09), asthma (RR 7.47, 95% CI 3.51-15.90) and gestational age at the time of infection (gestational age 28-36 vs < 22: RR 3.53, 95% CI 1.75-7.10). SARS-CoV-2-infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04-1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00-1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01-5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01-2.19) and small-for-gestational age children (aHR 1.28, 95% CI 1.05-1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS-CoV-2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9-100.0) and a positive predictive value of 82.1 (95% CI 80.4-83.7). CONCLUSIONS: Women infected with SARS-CoV-2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS-CoV-2 infection during pregnancy.

Urine excretion of C3dg and sC5b-9 coincide with proteinuria and development of preeclampsia in pregnant women with type-1 diabetes.

OBJECTIVE: Pregnant women with type-1 diabetes have an increased risk of preeclampsia with kidney injury and cardiovascular complications. Urine excretion of plasmin and soluble membrane attack complex (sC5b-9) is elevated in severe preeclampsia. We hypothesized a coupling between these events and that active plasmin promotes intratubular complement activation and membrane deposition. METHODS: Stored urine and plasma samples from pregnant women with type-1 diabetes (n = 88) collected at gestational weeks 12, 20, 28, 32, 36 and 38 were used. In the cohort, 14 women developed preeclampsia and were compared with 16 nonpreeclampsia controls. RESULTS: Urine C3dg and sC5b-9-associated C9 neoantigen/creatinine ratios increased and were significantly higher in women who developed preeclampsia. Plasma concentrations did not change with gestation. Urine plasmin(ogen) correlated to urine C3dg (r = 0.51, P < 0.001) and C9 neoantigen (r = 0.68, P < 0.001); urine albumin correlated to C3dg (r = 0.44, P < 0.001) and C9 (r = 0.59, P < 0.001). Membrane-associated C3dg and C9 neoantigen was detected in urinary extracellular vesicles from patients but not controls at 36 weeks. Receiver operating characteristic curves showed that C3dg and C9 neoantigen were inferior to albumin as predictive biomarkers for preeclampsia. CONCLUSION: In preeclampsia, urinary excretion of activated complement relates significantly to albuminuria and to plasmin(ogen) but not to activation in plasma. Intratubular complement activation in preeclampsia is a postfiltration event tightly related to proteinuria/plasminogenuria and a possible mechanistic link to cellular damage and kidney injury.

Fibrinolytic Changes in Women with Preeclampsia.

OBJECTIVES: Preeclampsia (PE) is a serious complication of pregnancy. The fibrinolytic system play crucial roles regarding placentation and evolution of PE. AIM: To study comprehensively components of the fibrinolytic system and fibrin lysability in women with PE. DESIGN AND METHODS: 117 women with PE and matched controls were included. Tissue type plasminogen activator (t-PA), plasminogen, PAI-1, plasmin inhibitor (PI), D-dimer, the fibrinolytic potential of dextran sulphate euglobulin fraction (DEF), PAI-2, polymere PAI-2, fibrin clot lysability, thrombin activatable fibrinolysis inhibitor (TAFI) and fibrinogen were assessed. RESULTS: Women with PE had significantly increased concentrations of t-PA and PAI-1, whereas the plasma concentration of PAI-2 was significantly lower compared to controls, p < 0.0001. Polymere PAI-2 was detected in both groups. DEF, TAFI and fibrinogen were not different between the groups. D-dimer was significantly increased and plasminogen/PI together with fibrin clot lysability time decreased in the PE-group, p = 0.0004 p = 0.04, p = 0.03, p < 0.0001 respectively. CONCLUSION: This study demonstrates that PE is associated with an affected t-PA/PAI-1 system, decreased PAI-2 and increased fibrin lysability. Furthermore, PAI-2 has the potential to polymerize during pregnancy.

[Predictive biomarkers in medical treatment].

Use of predictive biomarkers plays a promising role in stratifying patients to a more effective medical treatment with less side effects. This review provides a brief overview in a Danish context of the potential of applying pharmacogenomics (PGx) including companion diagnostics (CDx) in daily clinical practice based on the current knowledge and regulation from the FDA and EMA, Summary of Product Characteristics (SPC), PharmGKB (pharmacogenomics knowledge resource providing clinical dosing guidelines) and partly promedicin.dk. Also, the barriers to more widespread use are being addressed.

Elevated blood pressure in pregnant women with gestational diabetes according to the WHO criteria: importance of overweight.

OBJECTIVE: Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester. METHODS: We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28-30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval. RESULTS: Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22-2.70) mmHg higher SBP and 1.04 (0.07-2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05-5.25) mmHg higher SBP and 1.94 (0.42-3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance. CONCLUSION: GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women.