Infertility treatments and cyanotic congenital heart defects among livebirths in the USA: findings from a contemporary cohort.

STUDY QUESTION: Is there an elevated risk of cyanotic congenital heart defects (CCHD) among livebirths following infertility treatments? SUMMARY ANSWER: In this population-based study of single livebirths, infertility treatment (either ART or non-ART) was associated with a higher prevalence of CCHD among livebirths. WHAT IS KNOWN ALREADY: The use of infertility treatment has been on the rise over the past few decades. However, there are limited studies assessing the risk of major cardiac defects following infertility treatments. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of livebirth data from the National Vital Statistics System (NVSS) was conducted, comprising of 9.6 million singleton livebirths among first-time mothers aged 15-49 years from 2016 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Information on infertility treatment use and CCHD was obtained from the health and medical information section of birth certificates, which was completed by healthcare staff after reviewing medical records. Logistic regression models were used to estimate odds ratios (OR) and 95% CI. Entropy balancing weighting analysis and probabilistic bias analysis were also performed. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of births following infertility treatment increased from 1.9% (27 116) to 3.1% (43 510) during the study period. Overall, there were 5287 cases of CCHD resulting in a prevalence of 0.6 per 1000 livebirths. The prevalence was 1.2 per 1000 live births among infertility treatment users (ART: 1.1 per 1000 livebirths; non-ART: 1.3 per 1000 livebirths) while that for naturally conceived births was 0.5 per 1000 livebirths. Compared to naturally conceived births, the use of any infertility treatment (OR: 2.06, 95% CI: 1.82-2.33), either ART (OR: 2.02, 95% CI: 1.73-2.36) or other infertility treatments (OR: 2.12, 95% CI: 1.74-2.33), was associated with higher odds of CCHD after adjusting for maternal and paternal age, race and ethnicity, and education, as well as maternal nativity, marital status, source of payment, smoking status, and pre-pregnancy measures of BMI, hypertension and diabetes. This association did not differ by the type of infertility treatment (ART versus other infertility treatments) (OR: 1.04, 95% CI: 0.82-1.33, P = 0.712), and was robust to the presence of exposure and outcome misclassification bias and residual confounding. LIMITATIONS, REASONS FOR CAUTION: The findings are only limited to livebirths. We did not have the capacity to examine termination data, but differential termination by mode of conception has not been supported by previous studies designed to consider it. Infertility treatment use was self-reported, leading to the potential for selection bias and misclassification for infertility treatment and CCHD. However, the association persisted when systematic bias as well as exposure and outcome misclassification bias were accounted for in the analyses. Information on the underlying etiology of infertility relating to either maternal, paternal, or both factors, data on specific types of ART and other infertility treatments, as well as information on subtypes of CCHD, were all not available. WIDER IMPLICATIONS OF THE FINDINGS: In light of the increasing trend in the use of infertility treatment in the USA, and elsewhere, the finding of the current study holds significant importance for the clinical and public health of reproductive-aged individuals. The data show that the use of infertility treatment may expose offspring to elevated odds of severe congenital heart defects such as CCHD studied here. These findings cannot be interpreted causally. While our findings can assist in preconception counseling and prenatal care for pregnancies conceived by either ART or other infertility treatments, they also support some current recommendations that pregnancies resulting from infertility treatments undergo fetal echocardiography screening. STUDY FUNDING/COMPETING INTEREST(S): No funding was sought for the study. The authors declare that they have no conflict of interest. TRIAL REGISTRAION NUMBER: N/A.

Associations between hysterectomy and metabolic syndrome: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Metabolic syndrome is linked to an increased risk of incident cardiovascular disease and all-cause mortality. Notable associations exist between hysterectomy with bilateral salpingo-oophorectomy and metabolic syndrome. However, there is emerging evidence that even with ovarian conservation, hysterectomy may be independently associated with long-term cardiovascular disease risk. OBJECTIVE: To examine the associations between hysterectomy with ovarian preservation and metabolic syndrome risk in a multiethnic cohort. STUDY DESIGN: We studied 3367 female participants in the Multi-Ethnic Study of Atherosclerosis who had data on self-reported history of hysterectomy, oophorectomy, hystero-oophorectomy, and metabolic syndrome at baseline (2000-2002). We used adjusted logistic regression to assess the cross-sectional associations between hysterectomy and or oophorectomy subgroups and prevalent metabolic syndrome at baseline. Furthermore, we investigated 1355 participants free of baseline metabolic syndrome and used adjusted Cox regression models to evaluate incident metabolic syndrome from examinations 2 (2002-2004) to 6 (2016-2018). RESULTS: The mean age was 59.0±9.5 years, with 42% White, 27% Black, 19% Hispanic, and 13% Chinese American participants. 29% and 22% had a history of hysterectomy and oophorectomy, respectively. Over a median follow-up of 10.5 (3.01-17.62) years, there were 750 metabolic syndrome events. Hysterectomy (hazard ratio, 1.32 [95% confidence interval, 1.01-1.73]) and hystero-oophorectomy (hazard ratio, 1.40 [95% confidence interval, 1.13-1.74]) were both associated with incident metabolic syndrome compared with having neither hysterectomy nor oophorectomy. CONCLUSION: Hysterectomy, even with ovarian preservation, may be independently associated with a higher risk of metabolic syndrome. If other studies confirm these findings, screening and preventive strategies focused on females with ovary-sparing hysterectomies and the mechanisms underpinning these associations may be explored.

Ideal Cardiovascular Health and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the association between ideal cardiovascular health (CVH) and adipokine levels. Adipokines are hormones implicated in obesity and its cardiometabolic consequences. The concept of ideal CVH was introduced to promote 7 key health factors and behaviors in the general population. Previous studies have found strong associations between obesity and ideal CVH. However, existing literature on the link between CVH and adipokines is scarce. METHODS: We studied 1842 Multi-Ethnic Study of Atherosclerosis participants free of cardiovascular disease who had 7 CVH metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting blood glucose) measured at baseline and serum adipokine levels measured at a median of 2.4 years later. Each CVH metric was assigned a score of 0 (poor), 1 (intermediate), or 2 (ideal), and all scores were summed for a total CVH score (0-14). The total CVH scores of 0 to 8, 9 to 10, and 11 to 14 were considered inadequate, average, and optimal, respectively. We used multivariable linear regression models to assess the nonconcurrent associations between the CVH score and log-transformed adipokine levels. RESULTS: The mean age was 62.1 ± 9.8 years; 50.2% of participants were men. After adjusting for sociodemographic factors, a 1-unit higher CVH score was significantly associated with 4% higher adiponectin and 15% and 1% lower leptin and resistin levels. Individuals with optimal CVH scores had 27% higher adiponectin and 56% lower leptin levels than those with inadequate CVH scores. Similar trends were observed for those with average versus inadequate CVH scores. CONCLUSION: In a multi-ethnic cohort free of cardiovascular disease at baseline, individuals with average and optimal CVH scores had a more favorable adipokine profile than those with inadequate CVH scores.

The Diabetes-Cardiovascular Connection in Women: Understanding the Known Risks, Outcomes, and Implications for Care.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) complications constitute about 50-70% of mortality in people with diabetes. However, there remains a persistently greater relative increase in CVD morbidity and mortality in women with diabetes than in their male counterparts. This review presents recent evidence for the risks, outcomes, and management implications for women with diabetes. RECENT FINDINGS: Compared to men, women have higher BMI and more adverse cardiovascular risk profile at time of diabetes diagnosis with greater risk for coronary heart disease, stroke, vascular dementia, and heart failure. Pregnancy-specific risk factors of gestational diabetes and pre-eclampsia are associated with future type 2 diabetes (T2D) and CVD. Women with T2D may experience greater benefits than men from GLP-1 receptor agonists. Women with diabetes are at greater relative risk for CVD complications than men, with poorer outcomes, superimposed on preexisting gender disparities in social determinants of health, lower likelihood of being offered cardioprotective interventions, and enrollment in trials. Further research and the utilization of SGLT-2 inhibitors, GLP-1 receptor agonists, and other CVD prevention strategies will help reduce morbidity and mortality.

Adipokines and incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established. OBJECTIVES: To examine whether adipokines are associated with increased risk of incident VTE. METHODS: We studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE. RESULTS: The mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area. CONCLUSION: Higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.

Migration-Related Weight Changes among African Immigrants in the United States.

(1) Background: people who migrate from low-to high-income countries are at an increased risk of weight gain, and excess weight is a risk factor for cardiovascular disease. Few studies have quantified the changes in body mass index (BMI) pre- and post-migration among African immigrants. We assessed changes in BMI pre- and post-migration from Africa to the United States (US) and its associated risk factors. (2) Methods: we performed a cross-sectional analysis of the African Immigrant Health Study, which included African immigrants in the Baltimore-Washington District of the Columbia metropolitan area. BMI category change was the outcome of interest, categorized as healthy BMI change or maintenance, unhealthy BMI maintenance, and unhealthy BMI change. We explored the following potential factors of BMI change: sex, age at migration, percentage of life in the US, perceived stress, and reasons for migration. We performed multinomial logistic regression adjusting for employment, education, income, and marital status. (3) Results: we included 300 participants with a mean (±SD) current age of 47 (±11.4) years, and 56% were female. Overall, 14% of the participants had a healthy BMI change or maintenance, 22% had an unhealthy BMI maintenance, and 64% had an unhealthy BMI change. Each year of age at immigration was associated with a 7% higher relative risk of maintaining an unhealthy BMI (relative risk ratio [RRR]: 1.07; 95% CI 1.01, 1.14), and compared to men, females had two times the relative risk of unhealthy BMI maintenance (RRR: 2.67; 95% CI 1.02, 7.02). Spending 25% or more of life in the US was associated with a 3-fold higher risk of unhealthy BMI change (RRR: 2.78; 95% CI 1.1, 6.97). (4) Conclusions: the age at immigration, the reason for migration, and length of residence in the US could inform health promotion interventions that are targeted at preventing unhealthy weight gain among African immigrants.

Blood biomarkers for neonatal hypoxic-ischemic encephalopathy in the presence and absence of sentinel events.

OBJECTIVE: To determine if neonatal serum biomarkers representing different pathways of injury differ for cases of HIE of unknown cause to gain insight into timing and mechanism of injury. STUDY DESIGN: In this cohort of all neonates with HIE admitted to our NICU, newborns with sentinel events were compared to those without during the 1st 3 days of life. Discard neonatal blood during the 1st 3 days of life was used for analysis. RESULTS: Of 277 babies with HIE treated with whole-body hypothermia, 190 (68.6%) had blood available for biomarker analysis. In total, 71 (37.4%) were born within our system, and 119 (62.6%) were transferred in from outside hospitals. Of these babies, 77 (40.5%) had a sentinel event and 113 (59.6%) had no sentinel event. Although the degree of metabolic acidosis was similar, repeated measures analysis showed that during the initial 3 days of life neonates born with HIE in the absence of sentinel events had 41.4% decreased VEGF (p = 0.027) and 62.5% increased IL-10 serum concentrations (p = 0.005). CONCLUSION: These changes indicate that neonatal HIE in the absence of sentinel events is not related to an unrecognized acute intrapartum event and is possibly related to chronic hypoxia of lower severity or recovery from a remote event.