Assessment of Red Blood Cell Aggregation in Preeclampsia by Microfluidic Image Flow Analysis-Impact of Oxidative Stress on Disease Severity.

Preeclampsia (PE) is a hypertensive disease characterized by proteinuria, endothelial dysfunction, and placental hypoxia. Reduced placental blood flow causes changes in red blood cell (RBC) rheological characteristics. Herein, we used microfluidics techniques and new image flow analysis to evaluate RBC aggregation in preeclamptic and normotensive pregnant women. The results demonstrate that RBC aggregation depends on the disease severity and was higher in patients with preterm birth and low birth weight. The RBC aggregation indices (EAI) at low shear rates were higher for non-severe (0.107 ± 0.01) and severe PE (0.149 ± 0.05) versus controls (0.085 ± 0.01; p < 0.05). The significantly more undispersed RBC aggregates were found at high shear rates for non-severe (18.1 ± 5.5) and severe PE (25.7 ± 5.8) versus controls (14.4 ± 4.1; p < 0.05). The model experiment with in-vitro-induced oxidative stress in RBCs demonstrated that the elevated aggregation in PE RBCs can be partially due to the effect of oxidation. The results revealed that RBCs from PE patients become significantly more adhesive, forming large, branched aggregates at a low shear rate. Significantly more undispersed RBC aggregates at high shear rates indicate the formation of stable RBC clusters, drastically more pronounced in patients with severe PE. Our findings demonstrate that altered RBC aggregation contributes to preeclampsia severity.

SARS-CoV-2 infection by trimester of pregnancy and adverse perinatal outcomes: a Mexican retrospective cohort study.

OBJECTIVE: Conflicting evidence for the association between COVID-19 and adverse perinatal outcomes exists. This study examined the associations between maternal COVID-19 during pregnancy and adverse perinatal outcomes including preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA) and fetal death; as well as whether the associations differ by trimester of infection. DESIGN AND SETTING: The study used a retrospective Mexican birth cohort from the Instituto Mexicano del Seguro Social (IMSS), Mexico, between January 2020 and November 2021. PARTICIPANTS: We used the social security administrative dataset from IMSS that had COVID-19 information and linked it with the IMSS routine hospitalisation dataset, to identify deliveries in the study period with a test for SARS-CoV-2 during pregnancy. OUTCOME MEASURES: PTB, LBW, SGA, LGA and fetal death. We used targeted maximum likelihood estimators, to quantify associations (risk ratio, RR) and CIs. We fit models for the overall COVID-19 sample, and separately for those with mild or severe disease, and by trimester of infection. Additionally, we investigated potential bias induced by missing non-tested pregnancies. RESULTS: The overall sample comprised 17 340 singleton pregnancies, of which 30% tested positive. We found that those with mild COVID-19 had an RR of 0.89 (95% CI 0.80 to 0.99) for PTB and those with severe COVID-19 had an RR of 1.53 (95% CI 1.07 to 2.19) for LGA. COVID-19 in the first trimester was associated with fetal death, RR=2.36 (95% CI 1.04, 5.36). Results also demonstrate that missing non-tested pregnancies might induce bias in the associations. CONCLUSIONS: In the overall sample, there was no evidence of an association between COVID-19 and adverse perinatal outcomes. However, the findings suggest that severe COVID-19 may increase the risk of some perinatal outcomes, with the first trimester potentially being a high-risk period.

Estimating Intervention Impact: Racial Disparities in Phthalate Exposure and Preterm Birth.

Pooling data from 16 studies, researchers estimated that, among Black and Hispanic/Latina participants, reducing disparities in phthalate exposure during pregnancy might also reduce preterm birth rates.

An evaluation of the quality, suitability and impact on equity of clinical practice guidelines relevant to preterm birth for use in Aotearoa New Zealand.

BACKGROUND: Preterm birth is a leading cause of perinatal morbidity and mortality and a defining event for pregnant people, infants, and whanau (extended families). Recommendations have been made for a national preterm birth prevention initiative focusing on equity in Aotearoa New Zealand, including the development of a national best practice guide. An understanding of the number and quality of guidelines, and consideration of their suitability and impact on equity is required. METHODS: Guidelines were identified through a systematic literature search, search of professional bodies websites, and invitation to regional health services in Aotearoa New Zealand. Obstetric and midwifery clinical directors were invited to report on guideline use. Identified guidelines were appraised by a 23-member trans-disciplinary Review Panel; quantitatively using the AGREE-II instrument and qualitatively using modified ADAPTE questions. The quality of guidelines available but not in use was compared against those in current use, and by health services by level of maternity and neonatal care. Major themes affecting implementation and impact on equity were identified using Braun and Clarke methodology. RESULTS: A total of 235 guidelines were included for appraisal. Guidelines available but not in use by regional health services scored higher in quality than guidelines in current use (median domain score Rigour and Development 47.5 versus 18.8, p < 0.001, median domain score Overall Assessment 62.5 versus 44.4, p < 0.001). Guidelines in use by regional health services with tertiary maternity and neonatal services had higher median AGREE II scores in several domains, than those with secondary level services (median domain score Overall Assessment 50.0 versus 37.5, p < 0.001). Groups identified by the Review Panel as experiencing the greatest constraints and limitations to guideline implementation were rural, provincial, low socioeconomic, Maori, and Pacific populations. Identified themes to improve equity included a targeted approach to groups experiencing the least advantage; a culturally considered approach; nationally consistent guidance; and improved funding to support implementation of guideline recommendations. CONCLUSIONS: We have systematically identified and assessed guidelines on preterm birth. High-quality guidelines will inform a national best practice guide for use in Taonga Tuku Iho, a knowledge translation project for equity in preterm birth care and outcomes in Aotearoa.

Global, regional, and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021.

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378-521), affecting 3·40 billion (3·20-3·62) individuals (43·1%, 40·5-45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7-26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6-38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5-32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7-2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. FUNDING: Bill & Melinda Gates Foundation.

Structural gendered racism and preterm birth inequities in the United States.

Structural gendered racism - the "totality of interconnectedness between structural racism and sexism" - is conceptualized as a fundamental cause of the persistent preterm birth inequities experienced by Black and Indigenous people in the United States. Our objective was to develop a state-level latent class measure of structural gendered racism and examine its association with preterm birth among all singleton live births in the US in 2019. Using previously-validated inequity indicators between White men and Black women across 9 domains (education, employment, poverty, homeownership, health insurance, segregation, voting, political representation, incarceration), we conducted a latent profile analysis to identify a latent categorical variable with k number of classes that have similar values on the observed continuous input variables. Racialized group-stratified multilevel modified Poisson regression models with robust variance and random effects for state assessed the association between state-level classes and preterm birth. We found four distinct latent classes that were all characterized by higher levels of disadvantage for Black women and advantages for White men, but the magnitude of that difference varied by latent class. We found preterm birth risk among Black birthing people was higher across all state-level latent classes compared to White birthing people, and there was some variation of preterm birth risk across classes among Black but not White birthing people. These findings further emphasize the importance of understanding and interrogating the whole system and the need for multifaceted policy solutions.

Do women living in a deprived neighborhood have higher maternity care costs and worse pregnancy outcomes? A retrospective population-based study.

BACKGROUND: Living in a deprived neighborhood is associated with poorer health, due to factors such as lower socio-economic status and an adverse lifestyle. There is little insight into whether living in deprived neighborhood is associated with adverse maternity care outcomes and maternity health care costs. We expect women in a deprived neighborhood to experience a more complicated pregnancy, with more secondary obstetric care (as opposed to primary midwifery care) and higher maternity care costs. This study aimed to answer the following research question: to what extent are moment of referral from primary to secondary care, mode of delivery, (extreme or very) preterm delivery and maternity care costs associated with neighborhood deprivation? METHODS: This retrospective cohort study used a national Dutch database with healthcare claims processed by health insurers. All pregnancies that started in 2018 were included. The moment of referral from primary to secondary care, mode of delivery, (extreme or very) preterm delivery and maternity care costs were compared between women in deprived and non-deprived neighborhoods. We reported descriptive statistics, and results of ordinal logistic, multinomial and linear regressions to assess whether differences between the two groups exist. RESULTS: Women in deprived neighborhoods had higher odds of being referred from primary to secondary care during pregnancy (adjusted OR 1.49, 95%CI 1.41-1.57) and to start their pregnancy in secondary care (adjusted OR 1.55, 95%CI 1.44-1.66). Furthermore, women in deprived neighborhoods had lower odds of assisted delivery than women in non-deprived neighborhoods (adjusted OR 0.73, 95%CI 0.66-0.80), and they had higher odds of a cesarean section (adjusted OR 1.19, 95%CI 1.13-1.25). On average, women in a deprived neighborhood had higher maternity care costs worth 156 euros (95%CI 104-208). CONCLUSION: This study showed that living in a deprived neighborhood is associated with more intensive maternal care and higher maternal care costs in the Netherlands. These findings support the needs for greater attention to socio-economic factors in maternity care in the Netherlands.

Homelessness in Pregnancy and Increased Risk of Adverse Outcomes: A Retrospective Cohort Study.

Limited data indicates that homelessness during pregnancy is linked to adverse outcomes for both mothers and newborns, but there is an information gap surrounding pregnant individuals struggling with homelessness. In a landscape of increasing healthcare disparities, housing shortages and maternal mortality, information on this vulnerable population is fundamental to the creation of targeted interventions and outreach. The current study investigates homelessness as a risk factor for adverse obstetrical, neonatal, and postpartum outcomes. We reviewed more than 1000 deliveries over 1 year at a large public hospital in New York City, comparing homeless subjects to a group of age-matched, stably housed controls. Multiple outcomes were assessed regarding obstetrical, neonatal, and postpartum outcomes along with social stressors. Homeless pregnant individuals were more likely to experience numerous adverse outcomes, including cesarean delivery and preterm delivery. Their neonates were more likely to undergo an extended stay in the intensive care unit and evaluation by the Administration for Children's Services, suggesting that they may be at an increased risk for family separation. After delivery, patients were less likely to exclusively breastfeed or return for their postpartum visit. Regarding personal history, they were more likely to endorse a history of violence or abuse, use illicit substances, and carry a psychiatric diagnosis. These findings indicate that homelessness is linked to numerous adverse obstetrical, neonatal, and postpartum outcomes that worsen health indices and exacerbate pre-existing disparities. Initiatives must focus on improved outreach and care delivery for homeless pregnant individuals.

Immediate postnatal prediction of death or bronchopulmonary dysplasia among very preterm and very low birth weight infants based on gradient boosting decision trees algorithm: A nationwide database study in Japan.

INTRODUCTION: Bronchopulmonary dysplasia (BPD) poses a substantial global health burden. Individualized treatment strategies based on early prediction of the development of BPD can mitigate preterm birth complications; however, previously suggested predictive models lack early postnatal applicability. We aimed to develop predictive models for BPD and mortality based on immediate postnatal clinical data. METHODS: Clinical information on very preterm and very low birth weight infants born between 2008 and 2018 was extracted from a nationwide Japanese database. The gradient boosting decision trees (GBDT) algorithm was adopted to predict BPD and mortality, using predictors within the first 6 h postpartum. We assessed the temporal validity and evaluated model adequacy using Shapley additive explanations (SHAP) values. RESULTS: We developed three predictive models using data from 39,488, 39,096, and 40,291 infants to predict "death or BPD," "death or severe BPD," and "death before discharge," respectively. These well-calibrated models achieved areas under the receiver operating characteristic curve of 0.828 (95% CI: 0.828-0.828), 0.873 (0.873-0.873), and 0.887 (0.887-0.888), respectively, outperforming the multivariable logistic regression models. SHAP value analysis identified predictors of BPD, including gestational age, size at birth, male sex, and persistent pulmonary hypertension. In SHAP value-based case clustering, the "death or BPD" prediction model stratified infants by gestational age and persistent pulmonary hypertension, whereas the other models for "death or severe BPD" and "death before discharge" commonly formed clusters of low mortality, extreme prematurity, low Apgar scores, and persistent pulmonary hypertension of the newborn. CONCLUSIONS: GBDT models for predicting BPD and mortality, designed for use within 6 h postpartum, demonstrated superior prognostic performance. SHAP value-based clustering, a data-driven approach, formed clusters of clinical relevance. These findings suggest the efficacy of a GBDT algorithm for the early postnatal prediction of BPD.

Clinical and economic burden of respiratory syncytial virus in children aged 0-5 years in Italy.

BACKGROUND: Respiratory syncytial virus (RSV) is among the leading causes of hospitalization due to lower respiratory tract infections (LRTIs) in children younger than 5 years worldwide and the second cause of infant death after malaria. RSV infection occurs in almost all the infants before the second year of life with variable clinical severity, often requiring medical assistance. This analysis investigated patients aged 0-5 years with RSV infection focusing on epidemiology, clinical features, and economic burden of RSV-associated hospitalizations in a setting of Italian real clinical practice. METHODS: An observational retrospective analysis was conducted on administrative databases of healthcare entities covering around 2.6 million residents of whom 120,000 health-assisted infants aged < 5 years. From 2010 to 2018, pediatric patients were included in the presence of hospitalization discharge diagnosis for RSV infections, and RSV-related acute bronchiolitis or pneumonia. Epidemiology, demographics, clinical picture and costs were evaluated in RSV-infected patients, overall and stratified by age ranges (0-1, 1-2, 2-5 years) and compared with an age-matched general population. RESULTS: Overall 1378 RSV-infected children aged 0-5 years were included. Among them, the annual incidence rate of RSV-related hospitalizations was 175-195/100,000 people, with a peak in neonates aged < 1 year (689-806/100,000). While nearly 85% of infected infants were healthy, the remaining 15% presented previous hospitalization for known RSV risk factors, like preterm birth, or congenital heart, lung, and immune diseases. The economic analysis revealed that direct healthcare costs per patient/year were markedly higher in RSV patients than in the general population (3605€ vs 344€). CONCLUSIONS: These findings derived from the real clinical practice in Italy confirmed that RSV has an important epidemiological, clinical, and economic burden among children aged 0-5 years. While the complex management of at-risk infants was confirmed, our data also highlighted the significant impact of RSV infection in infants born at term or otherwise healthy, demonstrating that all infants need protection against RSV disease, reducing then the risk of medium and long-term complications, such as wheezing and asthma.

The Association Between Adverse Childhood Experiences and Preterm Delivery: A Latent Class Approach.

Background: Racial and socioeconomic status (SES) disparities in preterm delivery (PTD) have existed in the United States for decades. Disproportionate maternal exposures to adverse childhood experiences (ACEs) may increase the risk for adverse birth outcomes. Moreover, racial and SES disparities exist in the prevalence of ACEs, underscoring the need for research that examines whether ACEs contribute to racial and SES disparities in PTD. Methods: We examined the relationship between ACEs and PTD in a longitudinal sample of N = 3,884 women from the National Longitudinal Study of Adolescent to Adult Health (1994-2018). We applied latent class analysis to (1) identify subgroups of women characterized by patterns of ACE occurrence; (2) estimate the association between latent class membership (LCM) and PTD, and (3) examine whether race and SES influence LCM or the association between LCM and PTD. Results: Two latent classes were identified, with women in the high ACEs class characterized by a higher probability of emotional abuse, physical abuse, sexual abuse, and foster care placement compared with the low ACEs class, but neither class was associated with PTD. Race and SES did not predict LCM. Conclusions: Our findings suggest that ACEs may not impact PTD risk in previously hypothesized ways. Future research should assess the impact of ACEs on the probability of having live birth pregnancies as well as the role of potential protective factors in mitigating the impact of ACEs on PTD.

Impact of being underweight before pregnancy on preterm birth by race/ethnicity and insurance status in California: an analysis of birth records.

BACKGROUND: The US still has a high burden of preterm birth (PTB), with important disparities by race/ethnicity and poverty status. There is a large body of literature looking at the impact of pre-pregnancy obesity on PTB, but fewer studies have explored the association between underweight status on PTB, especially with a lens toward health disparities. Furthermore, little is known about how weight, specifically pre-pregnancy underweight status, and socio-economic-demographic factors such as race/ethnicity and insurance status, interact with each other to contribute to risks of PTB. OBJECTIVES: The objective of this study was to measure the association between pre-pregnancy underweight and PTB and small for gestational age (SGA) among a large sample of births in the US. Our secondary objective was to see if underweight status and two markers of health disparities - race/ethnicity and insurance status (public vs. other) - on PTB. STUDY DESIGN: We used data from all births in California from 2011 to 2017, which resulted in 3,070,241 singleton births with linked hospital discharge records. We ran regression models to estimate the relative risk of PTB by underweight status, by race/ethnicity, and by poverty (Medi-cal status). We then looked at the interaction between underweight status and race/ethnicity and underweight and poverty on PTB. RESULTS: Black and Asian women were more likely to be underweight (aRR = 1.0, 95% CI: 1.01, 1.1 and aRR = 1.4, 95% CI: 1.4, 1.5, respectively), and Latina women were less likely to be underweight (aRR = 0.7, 95% CI: 0.7, 0.7). Being underweight was associated with increased odds of PTB (aRR = 1.3, 95% CI 1.3-1.3) and, after controlling for underweight, all nonwhite race/ethnic groups had increased odds of PTB compared to white women. In interaction models, the combined effect of being both underweight and Black, Indigenous and People of Color (BIPOC) statistically significantly reduced the relative risk of PTB (aRR = 0.9, 95% CI: 0.8, 0.9) and SGA (aRR = 1.0, 95% CI: 0.9, 1.0). The combined effect of being both underweight and on public insurance increased the relative risk of PTB (aRR = 1.1, 95% CI: 1.1, 1.2) but there was no additional effect of being both underweight and on public insurance on SGA (aRR = 1.0, 95% CI: 1.0, 1.0). CONCLUSIONS: We confirm and build upon previous findings that being underweight preconception is associated with increased risk of PTB and SGA - a fact often overlooked in the focus on overweight and adverse birth outcomes. Additionally, our findings suggest that the effect of being underweight on PTB and SGA differs by race/ethnicity and by insurance status, emphasizing that other factors related to inequities in access to health care and poverty are contributing to disparities in PTB.

Lifetime Upward Economic Mobility and US-Born Latina Women's Preterm Birth Rates.

OBJECTIVES: To determine whether Latina women's upward economic mobility from early-life residence in impoverished urban neighborhoods is associated with preterm birth (< 37 weeks, PTB) . METHODS: Multivariate logistic regression analyses were performed on the Illinois transgenerational birth-file with appended US census income information for Hispanic infants (born 1989-1991) and their mothers (born 1956-1976). RESULTS: In Chicago, modestly impoverished-born Latina women (n = 1,674) who experienced upward economic mobility had a PTB rate of 8.5% versus 13.1% for those (n = 3,760) with a lifelong residence in modestly impoverished neighborhoods; the unadjusted and adjusted (controlling for age, marital status, adequacy of prenatal care, and cigarette smoking) RR equaled 0.65 (0.47, 0.90) and 0.66 (0.47, 0.93), respectively. Extremely impoverished-born Latina women (n = 2,507) who experienced upward economic mobility across their life-course had a PTB rate of 12.7% versus 15.9% for those (n = 3,849) who had a lifelong residence in extremely impoverished neighborhoods, the unadjusted and adjusted RR equaled 0.8 (0.63. 1.01) and 0.95 (0.75, 1.22), respectively. CONCLUSIONS FOR PRACTICE: Latina women's upward economic mobility from early-life residence in modestly impoverished urban neighborhoods is associated with a decreased risk of PTB. A similar trend is absent among their peers with an early-life residence in extremely impoverished areas.

Treating Mild Chronic Hypertension During Pregnancy: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the cost effectiveness of targeting a blood pressure of less than 140/90 mm Hg compared with 160/105 mm Hg. METHODS: A decision-analytic model was constructed to compare the treatment of chronic hypertension in pregnancy at mild-range blood pressures (140/90 mm Hg) with the treatment of chronic hypertension before 20 weeks of gestation at severe-range blood pressures (160/105 mm Hg) in a theoretical cohort of 180,000 patients with mild chronic hypertension. Probabilities, costs, and utilities were derived from literature and varied in sensitivity analyses. Primary outcomes included incremental cost per quality-adjusted life-year (QALY), cases of preeclampsia, preeclampsia with severe features, severe maternal morbidity (SMM), preterm birth, maternal death, neonatal death, and neurodevelopmental delay. The cost-effectiveness threshold was $100,000 per QALY. RESULTS: Treating chronic hypertension in a population of 180,000 pregnant persons at mild-range blood pressures, compared with severe-range blood pressures, resulted in 14,177 fewer cases of preeclampsia (43,953 vs 58,130), 11,835 of which were cases of preeclampsia with severe features (40,530 vs 52,365). This led to 817 fewer cases of SMM (4,375 vs 5,192), and 18 fewer cases of maternal death (102 vs 120). Treating at a lower threshold also resulted in 8,078 fewer cases of preterm birth (22,000 vs 30,078), which led to 26 fewer neonatal deaths (276 vs 302) and 157 fewer cases of neurodevelopmental delay (661 vs 818). Overall, treating chronic hypertension at a lower threshold was a dominant strategy that resulted in decreased costs of $600 million and increased effectiveness of 12,852 QALYs. CONCLUSION: Treating chronic hypertension at a threshold of mild-range blood pressures is a dominant (lower costs, better outcomes) and cost-effective strategy that results in fewer neonatal and maternal deaths compared with the standard treatment of treating at severe range blood pressures.

Prenatal phthalate exposure and adverse birth outcomes in the USA: a prospective analysis of births and estimates of attributable burden and costs.

BACKGROUND: Phthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs. METHODS: In this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery. FINDINGS: We identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log10 increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion). INTERPRETATION: In a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class. FUNDING: National Institutes of Health.

Contractions of the lower uterine segment during transvaginal ultrasound cervical length: incidence, significance, proper measurement, and management.

An accurate transvaginal ultrasound cervical length is paramount to obtain the best prediction for preterm birth. Transvaginal ultrasound cervical length should be optimally obtained when a lower uterine segment contraction is not seen. For universal transvaginal ultrasound cervical length screening at approximately 20 weeks of gestation, the options are to do the transvaginal ultrasound soon after bladder void (lower uterine segment contractions present in 16%-43% of this approach) or to wait until the end of the anatomy scan (ideally within 30 minutes after bladder voiding) to decrease the chance of a lower uterine segment contraction. If the lower uterine segment contraction persists even after waiting up to 20 minutes or more, only the true transvaginal ultrasound cervical length should be reported. In particular, in patients with a previous spontaneous preterm birth, if the lower uterine segment contraction persists, the transvaginal ultrasound cervical length can be repeated in ≤7 days even in the presence of a normal (>25 mm) cervical length. Similar to a blood pressure cuff that must be of the right size for proper blood pressure measurement and a glucometer that must be properly calibrated, screening with transvaginal ultrasound cervical length should only be performed following a proper and standardized technique, including avoiding as much as feasible the presence of lower uterine segment contractions.

Cost-effectiveness of universal routine sonographic cervical-length measurement at 19 to 25 weeks' gestation.

BACKGROUND: National second-trimester scanning of cervical length was introduced in Israel in 2010, and in the decade thereafter, a significant systematic reduction in preterm birth and in the delivery of low birthweight babies was found among singletons. OBJECTIVE: In this study, we sought to estimate the cost-effectiveness of a national policy mandating second-trimester cervical length screening by ultrasound, followed by vaginal progesterone treatment for short cervical length in comparison with no screening strategy. STUDY DESIGN: We constructed a decision model comparing 2 strategies, namely (1) universal cervical length screening, and (2) no screening strategy. This study used the national delivery registry of Israel's Ministry of Health. All women diagnosed with a second-trimester cervical length <25 mm were treated with vaginal progesterone and were monitored with a bimonthly ultrasound scan for cervical dynamics and threat of early delivery. Preterm birth prevalence associated with short cervical length, the efficacy of progesterone in preterm birth prevention, and the accuracy of cervical length measurements were derived from previous studies. The cost of progesterone and bimonthly sonographic surveillance, low birthweight delivery, newborn admission to intensive care units, the first-year costs of managing preterm birth and low birthweight, and instances of handicaps and the cost of their follow-up were extracted from the publicly posted registry of Israel's Ministry of Health and Israel Social Securities data. Monte Carlo simulations decision tree mode, Tornado diagrams, and 1- and 2-way sensitivity analyses were implemented and the base case and sensitivity to parameters that were predicted to influence cost-effectiveness were calculated. RESULTS: Without cervical length screening, the discounted quality-adjusted life years were 30.179, and with universal cervical length screening, it increased to 30.198 (difference of 0.018 quality-adjusted life years). The average cost of no screening for cervical length strategy was $1047, and for universal cervical length screening, it was reduced to $998. The calculated incremental cost-effectiveness ratio was -$2676 per quality-adjusted life year (dividing the difference in costs by the difference in quality-adjusted life years). Monte Carlo simulation of cervical length screening of 170,000 singleton newborns (rounded large number close to the number of singleton newborns in Israel) showed that 95.17% of all babies were delivered at gestational week ≥37 in comparison with 94.46% of babies with the no screening strategy. Given 170,000 singleton births, the national savings of screening for short cervical length when compared with no cervical length screening amounted to $8.31M annually, equating to $48.84 for a base case, and the incremental cost-effectiveness ratio for each case of low birthweight or very low birthweight avoided was -$14,718. A cervical length <25 mm was measured for 30,090 women, and of those, 24,650 were false positives. The major parameters that affected the incremental cost-effectiveness ratio were the incidence of preterm birth, the specificity of cervical length measurements, and the efficacy of progesterone treatment. At a preterm birth incidence of <3%, universal screening does not lead to a cost saving. CONCLUSION: National universal cervical length screening should be incorporated into the routine anomaly scan in the second trimester, because it leads to a drop in the incidence of preterm birth and low birthweight babies in singleton pregnancies, thereby saving costs related to the newborn and gaining quality-adjusted life years.

[The comparative analysis of health care systems].

Within the framework of the national development goal of the Russian Federation "preservation of population, health and well-being of people" the target indicator "the increase of life expectancy up to 78 years" is to be achieved by 2030. The achievement of this value is also directly affected by functioning of of health care system. In 2015, the United Nations, within the framework of the Sustainable Development Goals for the period up to 2030, formulated the task that implies ensuring of universal health services coverage "including financial risk security, access to qualitative essential medical and sanitary services and access to safe, effective, qualitative and inexpensive essential medications and vaccines for all". In the course of the study, methodology was developed that permitted to calculate values of performance indicators of main health care systems (financial support and infrastructure development) and to conduct comprehensive comparative analysis with values of particular public health indicators. The study results confirmed possibility of such comparisons. The stable direct relationship between such indicators as "current health expenditure (CHE) per capita", "current health expenditure (CHE) as percentage of gross domestic product (GDP)", "UHC Service Coverage Index", "life expectancy" was revealed. The inverse dependency between such indicators as "out-of-pocket expenditure as percentage of current health expenditure (CHE)" and "UHC Service Coverage Index" as well as between "UHC Service Coverage Index" and "total NCD mortality rate" and "probability of premature dying from non-infectious diseases" was determined.