Policy and Strategy for Hepatitis C Virus Elimination at the National Level: Experience in Taiwan.

The estimated prevalence of anti-HCV was 3.1% in Taiwan. Studies have shown iatrogenic behavior was the major transmission route. It is highest in specific populations including patients with end stage renal disease (ESRD), human immunodeficiency virus infection, who inject drug (PWID), and under opioid substitution treatment. Approximately 405,160 patients were seropositive for HCV RNA and in need of treatment. Taiwan government claims to reach WHO's 2030 goal of HCV elimination by 2025 and works hard to resolve several barriers of HCV elimination including political commitment, sustainable financing, minimize reimbursement restrictions, instituted monitoring, and perform micro-elimination of specific populations. The last stage of HCV elimination is to accelerate the universal HCV screening program of populations aged 45-79 years and resolve the unawareness issue of HCV infection. Hopefully, we can achieve the targets of HCV elimination set by WHO and reach the goal earlier in 2025.

Atomic Imaging and Thermally Induced Dynamic Structural Evolution of Two-Dimensional Cr2S3.

In this study, facile salt-assisted chemical vapor deposition (CVD) was used to synthesize ultrathin non-van der Waals chromium sulfide (Cr2S3) with a thickness of ∼1.9 nm. The structural transformation of as-grown Cr2S3 was studied using advanced in situ heating techniques combined with transmission electron microscopy (TEM). Two-dimensional (2D) and quasi-one-dimensional (1D) samples were fabricated to investigate the connection between specific planes and the dynamic behavior of the structural variation. The rearrangement of atoms during the phase transition was driven by the loss of sulfur atoms at elevated temperatures, resulting in increased free energy. A decrease in the ratio of the (001) plane led to an overall increase in surface energy, thus lowering the critical phase transition temperature. Our study provides detailed insight into the mechanism of structural transformation and the critical factors governing transition temperature, thus paving the way for future studies on intriguing Cr-S compounds.

Polycystic ovary syndrome and risk of adverse pregnancy outcomes: a registry linkage study from Massachusetts.

STUDY QUESTION: Do women with polycystic ovary syndrome (PCOS) have a greater risk of adverse pregnancy complications (gestational diabetes, preeclampsia, cesarean section, placental abnormalities) and neonatal outcomes (preterm birth, small for gestational age, prolonged delivery hospitalization) compared to women without a PCOS diagnosis and does this risk vary by BMI, subfertility and fertility treatment utilization? SUMMARY ANSWER: Deliveries to women with a history of PCOS were at greater risk of complications associated with cardiometabolic function, including gestational diabetes and preeclampsia, as well as preterm birth and prolonged length of delivery hospitalization. WHAT IS KNOWN ALREADY: Prior research has suggested that women with PCOS may be at increased risk of adverse pregnancy outcomes. However, findings have been inconsistent possibly due to lack of consistent adjustment for confounding factors, small samples size and other sources of bias. STUDY DESIGN, SIZE, DURATION: Massachusetts deliveries among women ≥18 years old during 2013-2017 from state vital records linked to hospital discharges, observational stays and emergency department visits were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) and the Massachusetts All-Payers Claims Database (APCD). PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS was identified by ICD9 and ICD10 codes in APCD prior to index delivery. Relative risks (RRs) and 95% CI for pregnancy and delivery complications were modeled using generalized estimating equations with a log link and a Poisson distribution to take multiple cycles into account and were adjusted a priori for maternal age, BMI, race/ethnicity, education, plurality, birth year, chronic hypertension and chronic diabetes. Tests for homogeneity investigated differences between maternal pre-pregnancy BMI categories (<30, ≥30, <25 and ≥25 kg/m2) and between non-infertile deliveries and deliveries that used ART or had a history of subfertility (defined by birth certificates, SART CORS records, APCD or hospital records). MAIN RESULTS AND THE ROLE OF CHANCE: Among 91 825 deliveries, 3.9% had a history of PCOS. Women with a history of PCOS had a 51% greater risk of gestational diabetes (CI: 1.38-1.65) and a 25% greater risk of preeclampsia (CI: 1.15-1.35) compared to women without a diagnosis of PCOS. Neonates born to women with a history of PCOS were more likely to be born preterm (RR: 1.17, CI: 1.06-1.29) and more likely to have a prolonged delivery hospitalization after additionally adjusting for gestational age (RR: 1.23, CI: 1.09-1.40) compared to those of women without a diagnosis of PCOS. The risk for gestational diabetes for women with PCOS was greater among women with a pre-pregnancy BMI <30 kg/m2. LIMITATIONS, REASONS FOR CAUTION: PCOS was defined by ICD documentation prior to delivery so there may be women with undiagnosed PCOS or PCOS diagnosed after delivery included in the unexposed group. The study population is limited to deliveries within Massachusetts among most private insurance payers and inpatient or observational hospitalization in Massachusetts during the follow-up window, therefore there may be diagnoses and or deliveries outside of the state or outside of our sample that were not captured. WIDER IMPLICATIONS OF THE FINDINGS: In this population-based study, women with a history of PCOS were at greater risk of pregnancy complications associated with cardiometabolic function and preterm birth. Obstetricians should be aware of patients' PCOS status and closely monitor for potential pregnancy complications to improve maternal and infant perinatal health outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the NIH (R01HD067270). S.A.M. receives grant funding from NIH, AbbVie and the Marriot Family Foundation; payment/honoraria from the University of British Columbia, World Endometriosis Research Foundation and Huilun Shanghai; travel support for attending meetings for ESHRE 2019, IASP 2019, National Endometriosis Network UK meeting 2019; SRI 2022, ESHRE 2022; participates on the data safety monitoring board/advisory board for AbbVie, Roche, Frontiers in Reproductive Health; and has a leadership role in the Society for Women's Health Research, World Endometriosis Research Foundation, World Endometriosis Society, American Society for Reproductive Medicine and ESHRE. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Pregnancy outcomes among women with endometriosis and fibroids: registry linkage study in Massachusetts.

BACKGROUND: Endometriosis and uterine fibroids are common gynecologic conditions associated with a greater risk for infertility. Previous research has suggested that these conditions are associated with adverse pregnancy outcomes, potentially because of increased utilization of fertility treatments. OBJECTIVE: Our objective was to investigate whether women with a history of endometriosis or fibroids had a greater risk for adverse pregnancy outcomes and whether this risk varied by infertility history and fertility treatment utilization. STUDY DESIGN: Deliveries (2013-2017) recorded in Massachusetts' vital records were linked to assisted reproductive technology data, hospital stays, and all-payer claims database. We identified endometriosis and fibroids diagnoses via the all-payer claims database before index delivery. Adjusted relative risks for pregnancy complications were modeled using generalized estimating equations with a log link and Poisson distribution. The influence of subfertility or infertility and assisted reproductive technology was also investigated. RESULTS: Among 91,825 deliveries, 1560 women had endometriosis and 4212 had fibroids. Approximately 30% of women with endometriosis and 26% of women with fibroids experienced subfertility or infertility without utilizing assisted reproductive technology, and 34% of women with endometriosis and 21% of women with fibroids utilized assisted reproductive technology for the index delivery. Women with a history of endometriosis or fibroids were at a greater risk for pregnancy-induced hypertension, preeclampsia, or eclampsia (endometriosis relative risk, 1.17; fibroids relative risk, 1.08), placental abnormalities (endometriosis relative risk, 1.65; fibroids relative risk, 1.38), and cesarean delivery (endometriosis relative risk, 1.22; fibroids relative risk, 1.17) than women with no history of those conditions. Neonates born to women with a history of endometriosis or fibroids were also at a greater risk for preterm birth (endometriosis relative risk, 1.24; fibroids relative risk, 1.17). Associations between fibroids and low birthweight varied by fertility status or assisted reproductive technology (P homogeneity=.01) and were stronger among noninfertile women. CONCLUSION: Endometriosis or fibroids increased the risk for adverse pregnancy outcomes, possibly warranting differential screening or treatment.

History of cancer and fertility treatment outcomes: a registry linkage study in Massachusetts.

PURPOSE: To investigate assisted reproductive technology (ART) outcomes among adolescent and young-adult female cancer survivors. METHODS: The Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to the Massachusetts Cancer Registry for 90,928 ART cycles in Massachusetts to women ≥ 18 years old from 2004 to 2013. To estimate relative risks (RR) and 95% confidence intervals (CI), we used generalized estimating equations with a log link that accounted for multiple cycles per woman and a priori adjusted for maternal age and cycle year. The main outcomes of interest were ART treatment patterns; number of autologous oocytes retrieved, fertilized, and transferred; and rates of implantation, clinical intrauterine gestation (CIG), live birth, and pregnancy loss. RESULTS: We saw no difference in number of oocytes retrieved (aRR: 0.95 (0.89-1.02)) or proportion of autologous oocytes fertilized (aRR: 0.99 (0.95-1.03)) between autologous cycles with and without a history of cancer; however, cancer survivors required a higher total FSH administered (aRR: 1.12 (1.06-1.19)). Among autologous cycle starts, cycles in women with a history of cancer were less likely to result in CIG compared to no history of cancer (aRR: 0.73 (0.65-0.83)); this relationship was absent from donor cycles (aRR: 1.01 (0.85-1.20)). Once achieving CIG, donor cycles for women with a history of cancer were two times more likely to result in pregnancy loss (aRR: 1.99 (1.26-3.16)). CONCLUSIONS: Our analysis suggests that cancer may influence ovarian stimulation response, requiring more FSH and resulting in lower CIG among cycle starts.

Early-life cancer, infertility, and risk of adverse pregnancy outcomes: a registry linkage study in Massachusetts.

PURPOSE: Investigate the relationship between history of cancer and adverse pregnancy outcomes according to subfertility/fertility treatment. METHODS: Deliveries (2004-2013) from Massachusetts (MA) Registry of Vital Records and Statistics were linked to MA assisted reproductive technology data, hospital discharge records, and Cancer Registry. The relative risks (RR) and 95% confidence intervals of adverse outcomes (gestational diabetes (GDM), gestational hypertension (GHTN), cesarean section (CS), low birth weight (LBW), small for gestational age (SGA), preterm birth (PTB), neonatal mortality, and prolonged neonatal hospital stay) were modeled with log-link and Poisson distribution generalized estimating equations. Differences by history of subfertility/fertility treatment were investigated with likelihood ratio tests. RESULTS: Among 662,630 deliveries, 2,983 had a history of cancer. Women with cancer history were not at greater risk of GDM, GHTN, or CS. However, infants born to women with prior cancer had higher risk of LBW (RR: 1.19 [1.07-1.32]), prolonged neonatal hospital stay (RR: 1.16 [1.01-1.34]), and PTB (RR: 1.19 [1.07-1.32]). We found clinically and statistically significant differences in the relationship between cancer history and SGA by subfertility/fertility treatment (p value, test for heterogeneity = 0.02); among deliveries with subfertility or fertility treatment, those with a history of cancer experienced a greater risk of SGA (RRsubfertile: 1.36 [1.02-1.83]). CONCLUSIONS: Women with a history of cancer had greater risk of some adverse pregnancy outcomes; this relationship varied by subfertility and fertility treatment.

Risk factors for emergency room use and rehospitalization among opioid-exposed newborns in Massachusetts.

OBJECTIVE: To determine the risk factors for receipt of emergency room (ER) care and rehospitalization among opioid-exposed newborns in Massachusetts. DESIGN/METHODS: We analyzed two linked data sets from 2002 to 2010: (a) Massachusetts Pregnancy to Early Life Longitudinal Data System and (b) Massachusetts Bureau of Substance Abuse Services Management Information System. Generalized estimating equations were used to assess the independent association of maternal and infant characteristics with ER use and rehospitalization in the first year of life. RESULTS: Four thousand and five hundred and twenty-four maternal-infant dyads affected by OUD were included in the analysis. In adjusted analysis, risk factors for receipt of ER care included Hispanic ethnicity (aOR 1.63 [95% CI 1.30-2.05]), lower education levels (aOR 1.54-1.69 [95% CI 1.12-2.31]), nonprivate insurance (aOR 1.44 [95% CI 1.11-1.86]), and presence of maternal chronic conditions (aOR 1.14 [95% CI 1.01-1.29]). Risk factors for rehospitalization included prematurity (aOR 1.44 [95% CI 1.14-1.82]), low birthweight (aOR 2.02 [95% CI 1.63-2.49]), and nonprivate insurance (aOR 1.58 [95% CI 1.13-2.22]). Prolonged infant birth hospitalization was protective against both ER use (aOR 0.84 [95% CI 0.73-0.96]) and rehospitalization (aOR 0.63 [95% CI 0.53-0.75]). CONCLUSIONS: Clinical and sociodemographic characteristics are risk factors for receipt of ER care and rehospitalization among opioid-exposed newborns in Massachusetts.

Optimizing the control group for evaluating ART outcomes: can outpatient claims data yield a better control group?

PURPOSE: We previously developed a subfertile comparison group with which to compare outcomes of assisted reproductive technology (ART) treatment. In this study, we evaluated whether insurance claims data in the Massachusetts All Payers Claims Database (APCD) defined a more appropriate comparison group. METHODS: We used Massachusetts vital records of women who delivered between 2013 and 2017 on whom APCD data were available. ART deliveries were those linked to a national ART database. Deliveries were subfertile if fertility treatment was marked on the birth certificate, had prior hospitalization with ICD code for infertility, or prior fertility treatment. An infertile group included women with an APCD outpatient or inpatient ICD 9/10 infertility code prior to delivery. Fertile deliveries were none of the above. Demographics, health risks, and obstetric outcomes were compared among groups. Multivariable generalized estimating equations were used to calculate adjusted relative risk (aRR) and 95% confidence intervals (CI). RESULTS: There were 70,726 fertile, 4,763 subfertile, 11,970 infertile, and 7,689 ART-treated deliveries. Only 3,297 deliveries were identified as both subfertile and infertile. Both subfertile and infertile were older, and had more education, chronic hypertension, and diabetes than the fertile group and less than the ART-treated group. Prematurity (aRR = 1.15-1.17) and birthweight (aRR = 1.10-1.21) were increased in all groups compared with the fertile group. CONCLUSION: Although the APCD allowed identification of more women than the previously defined subfertile categorization and allowed us to remove previously unidentified infertile women from the fertile group, it is not clear that it offered a clinically significantly improved comparison group.

The epidemiological profile of chronic hepatitis C with advanced hepatic fibrosis regarding virus genotype in Taiwan: A nationwide study.

BACKGROUND/PURPOSE: This study aims at investigating the epidemiological profile of chronic hepatitis C (CHC) regarding hepatitis C virus (HCV) genotype in Taiwan. METHODS: A total of 29,087 CHC patients with advanced fibrosis who received direct-acting antivirals (DAAs) therapy under Taiwan's National Health Insurance (NHI) during 2017-2018 were recruited. The HCV genotype distribution and its association with patients' demographic factors including age, gender, and geographical areas were examined. RESULTS: The most common genotypes were 1b (59.5%) and 2 (30.1%) with characteristics of older age (mean ± standard deviation (SD): 66.5 ± 10.7 years and 67.3 ± 10.9 years) and female gender predominant (57.1% and 59.4%), which were associated with iatrogenic infection decades ago. Most of patients with genotype 1a (5.9%) and 6 (3.7%) infection were relatively younger (59.2 ± 12.0 years and 60.0 ± 13.8 years) and male gender predominant (59.1% and 61.1%), except Liujia and Liuying districts in southern Taiwan. The youngest group (53.2 ± 11.8 years) and most male gender predominant (74.3%) was genotype 3 (0.37%). These genotypes with characteristics of being younger and male gender predominant were highly related to injection drug use in recent years. The number of genotype 4 patients were extremely rare (n = 25) and efficacy of genotype-4-specific-DAA was significantly poorer than non-genotype-4-specific DAA (P value = 0.0411). CONCLUSION: The significant differences in demographic characteristics among CHC patients with different HCV genotypes found in this study suggest HCV genotype was highly associated with transmission pattern and may be used as a reference for HCV control.

The Association of Concomitant Maternal Marijuana Use on Health Outcomes for Opioid Exposed Newborns in Massachusetts, 2003-2009.

This population-based study showed that maternal opioid plus marijuana use during pregnancy was associated with increased odds of prematurity and low birth weight but lower odds of neonatal abstinence syndrome and prolonged hospitalization compared with opioid exposure without marijuana use. Further research should evaluate the biologic mechanisms responsible for these outcomes.

Hospitalization before and after delivery in fertile, subfertile, and ART-treated women.

PURPOSE: Pre-pregnancy and post-delivery hospitalizations were compared as markers for health among women who conceived using assisted reproductive technology (ART), non-ART medically assisted reproduction (MAR), no treatment (unassisted subfertile), and who were fertile. METHODS: We analyzed hospital discharge data linked to Massachusetts birth certificates from 2004 to 2013 within 5 years prior to pregnancy and 8-365 days post-delivery. ART deliveries were linked from a national ART database; MAR deliveries had fertility treatment but not ART; unassisted subfertile women had subfertility but no ART or MAR; and fertile women had none of these. Prevalence of diagnoses during hospitalization was quantified. Multivariable logistic regression models with fertile deliveries as reference were adjusted for maternal age, race, education, year, and plurality (post-delivery only) with results reported as adjusted odds ratios (AORs) and 95% confidence intervals (CI). RESULTS: Of 170,605 privately insured, primiparous deliveries, 10,458 were ART, 3005 MAR, 1365 unassisted subfertile, and 155,777 fertile. Pre-pregnancy hospitalization occurred in 6.8% and post-delivery in 2.8% of fertile women. Subfertile groups had more pre-pregnancy hospitalizations (AOR, 95% CI: 1.84, 1.72-1.96 ART; 1.41, 1.24-1.60 MAR; 3.02, 2.62-3.47 unassisted subfertile) with endometriosis, reproductive organ disease, ectopic pregnancy/miscarriage, and disorders of menstruation, ovulation, and genital tract being common. Post-delivery hospitalizations were significantly more frequent in the ART (AOR 1.19, 95% CI 1.05-1.34) and unassisted subfertile (1.59, 1.23-2.07) groups with more digestive tract disorders, thyroid problems, and other grouped chronic disease conditions. CONCLUSIONS: Greater likelihood of hospitalization in the ART, MAR, and unassisted subfertile groups is largely explained by admissions for conditions associated with subfertility.

Birth outcomes of singleton vaginal deliveries to ART-treated, subfertile, and fertile primiparous women.

PURPOSE: To determine whether differences in birth outcomes among assisted reproductive technology (ART)-treated, subfertile, and fertile women exist in primiparous women with, singleton, vaginal deliveries. METHODS: Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to Massachusetts vital records and hospital discharges for deliveries between July 2004 and December 2010. Primiparous women with in-state vaginal deliveries, adequate prenatal care, and singleton birth at ≥ 20 weeks (n = 117,779) were classified as ART-treated (linked to ART data from SART CORS, n = 3138); subfertile (not ART-treated but with indicators of subfertility, n = 1507); or fertile (neither ART-treated nor subfertile, n = 113,134). Outcomes of prematurity (< 37 weeks), low birthweight (< 2500 g), perinatal death (death at ≥ 20 weeks to ≤ 7 days), and maternal prolonged length of hospital stay (LOS > 3 days) were compared using multivariable logistic regression. RESULTS: Compared to fertile, higher odds were found for prematurity among ART-treated (adjusted odds ratio [AOR] 1.40, 95% confidence interval [CI] 1.25-1.50) and subfertile (AOR 1.25, 95% CI 1.03-1.50) women, low birthweight among ART-treated (AOR 1.41, 95% CI 1.23-1.62) and subfertile (AOR 1.40, 95% CI 1.15-1.71) women, perinatal death among subfertile (AOR 2.64, 95% CI 1.72-4.05), and prolonged LOS among ART-treated (AOR 1.33, 95% CI 1.19-1.48) women. Differences remained despite stratification by young age and absence of pregnancy/delivery complications. CONCLUSIONS: Greater odds of prematurity and low birthweight in ART-treated and subfertile, and perinatal death in subfertile deliveries are evident among singleton vaginal deliveries. The data suggest that even low-risk pregnancies to ART-treated and subfertile women be managed for adverse outcomes.

Maternal Substance Use Disorders and Infant Outcomes in the First Year of Life among Massachusetts Singletons, 2003-2010.

OBJECTIVE: To determine the association of maternal substance use disorders (SUDs) during pregnancy with adverse neonatal outcomes and infant hospital re-admissions, observational stays, and emergency department utilization in the first year of life. STUDY DESIGN: We analyzed 2 linked statewide datasets from 2002 to 2010: the Massachusetts Pregnancy to Early Life Longitudinal data system and the Massachusetts Bureau of Substance Abuse Services Management Information System. Generalized estimating equations were used to assess the association of maternal SUDs and neonatal outcomes and infant hospital-based care in the first year of life, controlling for maternal and infant characteristics. RESULTS: Maternal SUDs increased from 19.4 per 1000 live births in 2003 to 31.1 per 1000 live births in 2009. In the adjusted analysis, exposed neonates were more likely to be born preterm (aOR 1.85; 95% CI 1.75-1.96) and low birthweight (aOR 1.94; 95% CI 1.80-2.09). After controlling for maternal characteristics and preterm birth, SUD-exposed neonates were more likely to have intrauterine growth restriction, cardiac, respiratory, neurologic, infectious, hematologic, and feeding/nutrition problems, prolonged hospital stay, and higher mortality (aOR range 1.26-3.80). Exposed infants were more likely to be rehospitalized (aOR 1.10; 95% CI 1.04-1.17) but less likely to have an observational stay (aOR 0.90; 95% CI 0.82-0.99) or use the emergency department (aOR 0.87; 95% CI 0.83-0.90) in the first year of life. CONCLUSIONS: Infants born to mothers with SUD are at higher risk for adverse health outcomes in the perinatal period and are also more likely to be rehospitalized in the first year of life.

Preconception and perinatal hospitalizations as indicators of risk for severe maternal morbidity in primiparas.

BACKGROUND: Severe maternal morbidity includes unexpected outcomes of labor and delivery that result in significant short- or long-term consequences to a woman's health. A statewide longitudinally linked database was used to examine hospitalization during and before pregnancy for birthing people with severe maternal morbidity at delivery. OBJECTIVE: This study aimed to examine the association between hospital visits during pregnancy and 1 to 5 years before pregnancy and severe maternal morbidity at delivery. STUDY DESIGN: This study was a retrospective, population-based cohort analysis of the Massachusetts Pregnancy to Early Life Longitudinal database between January 1, 2004, and December 31, 2018. Nonbirth hospital visits, including emergency department visits, observational stays, and hospital admissions during pregnancy and 5 years before pregnancy, were identified. The diagnoses for hospitalizations were categorized. We compared medical conditions leading to antecedent, nonbirth hospital visits among primiparous birthing individuals with singleton births with and without severe maternal morbidity, excluding transfusions. RESULTS: Of 235,398 birthing individuals, 2120 had severe maternal morbidity, a rate of 90.1 cases per 10,000 deliveries, and 233,278 did not have severe maternal morbidity. Compared with 4.3% of patients without severe maternal morbidity, 10.4% of patients with severe maternal morbidity were hospitalized during pregnancy. In multivariable analysis, there was a 31% increased risk of hospital admission during the prenatal period, a 60% increased risk of hospital admission in the year before pregnancy, and a 41% increased risk of hospital admission in 2 to 5 years before pregnancy. Compared with 9.8% of non-Hispanic White birthing people, 14.9% of non-Hispanic Black birthing people with severe maternal morbidity experienced a hospital admission during pregnancy. For those with severe maternal morbidity, prenatal hospitalization was most common for those with endocrine (3.6%) or hematologic (3.3%) conditions, with the largest differences between those with and without severe maternal morbidity for musculoskeletal (relative risk, 9.82; 95% confidence interval, 7.06-13.64) and cardiovascular (relative risk, 9.73; 95% confidence interval, 7.26-13.03) conditions. CONCLUSION: This study found a strong association between previous nonbirth hospitalizations and the likelihood of severe maternal morbidity at delivery.

Prior Hospitalization, Severe Maternal Morbidity, and Pregnancy-Associated Deaths in Massachusetts From 2002 to 2019.

OBJECTIVE: To examine demographic and clinical precursors to pregnancy-associated deaths overall and when pregnancy-related deaths are excluded. METHODS: We conducted a retrospective cohort study based on a Massachusetts population-based data system linking data from live birth and fetal death certificates to corresponding delivery hospital discharge records and a birthing individual's nonbirth hospital contacts and associated death records. Exposures included maternal demographics, severe maternal morbidity (without transfusion), hospitalizations in the 3 years before pregnancy, comorbidities during pregnancy, and opioid use. In cases of postpartum deaths, hospitalization between delivery and death was examined. The primary outcome measure was pregnancy-associated death , defined as death during pregnancy or up to 1 year postpartum. RESULTS: There were 1,291,626 deliveries between 2002 and 2019, of which 384 were linked to pregnancy-associated deaths. Pregnancy-associated but not pregnancy-related deaths (per 100,000 deliveries) were highest for birthing people with opioid use before pregnancy (498.3), severe maternal morbidity (387.3), a comorbidity (106.3), or a prior hospitalization (88.9). In multivariable analysis, the adjusted risk ratios associated with severe maternal morbidity (9.37, 95% CI, 6.14-14.31) and opioid use (6.49, 95%, CI, 3.71-11.35) were highest. Individuals with pregnancy-associated deaths were also more likely to have been hospitalized before or during pregnancy (2.30, 95% CI, 1.62-3.26). Among postpartum deaths, more than two-thirds (69.9%) of birthing people had a hospital contact after delivery and before their death. CONCLUSION: Severe maternal morbidity and opioid use disorder were precursors to pregnancy-associated deaths. Individuals with pregnancy-associated but not pregnancy-related deaths experienced a history of hospital contacts during and after pregnancy before death.

The impact of single-step and sequential embryo culture systems on obstetric and perinatal outcomes in singleton pregnancies: the Massachusetts Outcomes Study of Assisted Reproductive Technology.

OBJECTIVE: To compare the obstetric and perinatal outcomes of deliveries conceived with embryos from single-step vs. sequential culture media systems. DESIGN: Historical cohort of Massachusetts vital records linked to assisted reproductive technology clinic data from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System and laboratory embryology data from two large academic hospital fertility centers. SETTING: Not applicable. PATIENTS: Patients with singleton live birth deliveries between 2004 and 2017 conceived with autologous assisted reproductive technology cycles with fresh blastocyst transfer using either single-step (n = 1,058) or sequential (n = 474) culture media systems. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Associations of single-step vs. sequential culture with obstetric outcomes (mode of delivery, placental abnormalities, pregnancy-induced hypertension, and gestational diabetes) and perinatal outcomes (preterm birth, low birthweight, small-for-gestational-age, and large-for-gestational-age [LGA]) were assessed with multivariate logistic modeling, adjusted for maternal age, race/ethnicity, education, parity, insurance type, protein supplementation, oxygen concentration, fertilization method, and number of transferred embryos. RESULTS: Compared with sequential culture, single-step culture was associated with increased odds of LGA (adjusted odds ratio 2.1, 95% confidence interval 1.04-4.22). There were no statistically significant differences between single-step and sequential culture media systems in the odds of placental abnormalities, pregnancy-induced hypertension, gestational diabetes, prematurity, small-for-gestational-age, or low birthweight. CONCLUSIONS: Single-step culture is associated with increased odds of LGA, indicating that embryo culture media systems may affect perinatal outcomes.

Using Longitudinally Linked Data to Measure Severe Maternal Morbidity.

OBJECTIVE: To assess whether application of a standard algorithm to hospitalizations in the prenatal and postpartum (42 days) periods increases identification of severe maternal morbidity (SMM) beyond analysis of only the delivery event. METHODS: We performed a retrospective cohort study using data from the PELL (Pregnancy to Early Life Longitudinal) database, a Massachusetts population-based data system that links records from birth certificates to delivery hospital discharge records and nonbirth hospital records for all birthing individuals. We included deliveries from January 1, 2009, to December 31, 2018, distinguishing between International Classification of Diseases Ninth (ICD-9) and Tenth Revision (ICD-10) coding. We applied the modified Centers for Disease Control and Prevention algorithm for SMM used by the Alliance for Innovation on Maternal Health to hospitalizations across the antenatal period through 42 days postpartum. Morbidity was examined both with and without blood transfusion. RESULTS: Overall, 594,056 deliveries were included in the analysis, and 3,947 deliveries met criteria for SMM at delivery without transfusion and 9,593 with transfusion for aggregate rates of 150.1 (95% CI 146.7-153.5) using ICD-9 codes and 196.6 (95% CI 189.5-203.7) using ICD-10 codes per 10,000 deliveries. Severe maternal morbidity at birth increased steadily across both ICD-9 and ICD-10 from 129.4 in 2009 (95% CI 126.2-132.6) using ICD-9 to 214.3 per 10,000 (95% CI 206.9-221.8) in 2018 using ICD-10. Adding prenatal and postpartum hospitalizations increased cases by 21.9% under both ICD-9 and ICD-10, resulting in a 2018 rate of 258.7 per 10,000 (95% CI 250.5-266.9). The largest increase in detected morbidity in the prenatal or postpartum time period was attributed to sepsis cases. CONCLUSION: Inclusion of prenatal and postpartum hospitalizations in the identification of SMM resulted in increased ascertainment of morbid events. These results suggest a need to ensure surveillance of care quality activities beyond the birth event.

Assisted reproductive technology treatment increases obstetric and neonatal risks over that of the underlying infertility diagnosis.

OBJECTIVE: To determine whether assisted reproductive technology (ART) treatment adds obstetric and neonatal risks over and above that of underlying infertility-related diagnoses. DESIGN: Retrospective study of linked ART, birth certificate, hospital discharge data, and outpatient insurance claims data in Massachusetts (2013-2017). SETTING: Database. PATIENT(S): Singleton deliveries in women with and without diagnoses of tubal disease, polycystic ovarian syndrome (PCOS), other ovulatory conditions, or endometriosis, identified from the insurance claims and ART data. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ART and non-ART pregnancy and delivery outcomes were compared with each other and with women with no history of infertility or usage of fertility treatment (fertile group). Generalizing estimating equations with Poisson distribution and exchangeable correlation structure were used to obtain adjusted relative risk ratios (aRRs) and 95% confidence intervals (CIs). RESULT(S): Infertility-related diagnoses significantly increased the risks of pregnancy hypertension (PCOS: aRR, 1.13, 95% CI 1.00-1.27), preeclampsia/eclampsia (tubal: aRR 1.28, 95% CI 1.02-1.61; PCOS: aRR 1.23, 95% CI 1.06-1.43; other ovulatory: aRR 1.11, 95% CI 1.02-1.20), gestational diabetes (tubal: aRR 1.28, 95% CI 1.08-1.50; PCOS: aRR 1.58, 95% CI 1.42-1.75; other ovulatory: aRR 1.19, 95% CI 1.12-1.26), and placental problems (tubal aRR 1.47, 95% CI 1.11-1.94), as well as low birthweight and prematurity, compared with deliveries from the fertile group. Within each diagnosis, the use of ART consistently increased the risk of placental problems (aRR 1.49-2.86) but varied for other conditions. CONCLUSION(S): Our study demonstrated that compared with the fertile group, risk was elevated in pregnancies and deliveries from women with tubal, PCOS, other ovulatory, and endometriosis diagnoses who did/did not undergo ART treatment. Placental abnormalities were particularly elevated in ART compared to non-ART deliveries having the same diagnosis.

Trends and inequities in severe maternal morbidity in Massachusetts: A closer look at the last two decades.

It is estimated that 50,000-60,000 pregnant people in the United States (US) experience severe maternal morbidity (SMM). SMM includes life-threatening conditions, such as acute myocardial infarction, acute renal failure, amniotic fluid embolism, disseminated intravascular coagulation, or sepsis. Prior research has identified both rising rates through 2014 and wide racial disparities in SMM. While reducing maternal death and SMM has been a global goal for the past several decades, limited progress has been made in the US in achieving this goal. Our objectives were to examine SMM trends from 1998-2018 to identify factors contributing to the persistent and rising rates of SMM by race/ethnicity and describe the Black non-Hispanic/White non-Hispanic rate ratio for each SMM condition. We used a population-based data system that links delivery records to their corresponding hospital discharge records to identify SMM rates (excluding transfusion) per 10, 000 deliveries and examined the trends by race/ethnicity. We then conducted stratified analyses separately for Black and White birthing people. While the rates of SMM during the same periods steadily increased for all racial/ethnic groups, Black birthing people experienced the greatest absolute increase compared to any other race/ethnic group going from 69.4 in 1998-2000 to 173.7 per 10,000 deliveries in 2016-2018. In addition, we found that Black birthing people had higher rates for every individual condition compared to White birthing people, with rate ratios ranging from a low of 1.11 for heart failure during surgery to a high of 102.4 for sickle cell anemia. Obesity was not significantly associated with SMM among Black birthing people but was associated with SMM among White birthing people [aRR 1.18 (95% CI: 1.02, 1.36)]. An unbiased understanding of how SMM has affected different race/ethnicity groups is key to improving maternal health and preventing SMM and mortality among Black birthing people. SMM needs to be addressed as both a medical and public health challenge.