Antihypertensive Medication Use before and during Pregnancy and the Risk of Severe Maternal Morbidity in Individuals with Prepregnancy Hypertension.

OBJECTIVE: Our objective is to examine severe maternal morbidity (SMM) and patterns of antihypertensive medication use before and during pregnancy among individuals with chronic hypertension. STUDY DESIGN: We examined 11,759 pregnancies resulting in a live birth or stillbirth to individuals with chronic hypertension and one or more antihypertensive prescription 6 months before pregnancy (Optum, 2007-17). We examined whether study outcomes were associated with the use of medication as compared to no use during pregnancy. In addition, patterns of medication use based on the Food and Drug Administration guidance and literature were evaluated. Medication use was divided into prepregnancy and during pregnancy use and classified as pregnancy recommended (PR) or not pregnancy recommended (nPR) or no medication use. SMM was defined per the Centers for Disease Control and Prevention definition of 21 indicators. Risk ratios (RR) reflecting the association of SMM with the use of antihypertensive medications were computed using modified Poisson regression with robust standard errors and adjusted for maternal age, education, and birth year. RESULTS: Overall, 83% of individuals filled an antihypertensive prescription during pregnancy and 6.3% experienced SMM. The majority of individuals with a prescription prior to pregnancy had a prescription for the same medication in pregnancy. Individuals with any versus no medication use in pregnancy had increased adjusted RR (aRR) of SMM (1.18, 95% confidence interval [CI]: 0.96-1.44). Compared to the use of PR medications before and during pregnancy, aRRs were 1.42 (95% CI: 1.18-1.69, 12.4% of sample) for nPR use before and during pregnancy, 1.52 (1.23-1.86; 12.4%) for nPR (before) and PR (during) use, and 2.67 (1.73-4.15) for PR and nPR use. Patterns with no medication use during pregnancy were not statistically significant. CONCLUSION: Pattern of antihypertensive medication use before and during pregnancy may be associated with an elevated risk of SMM. Further research is required to elucidate whether this association is related to the severity of hypertension, medication effectiveness, or suboptimal quality of care. KEY POINTS: · Individuals with any medication use compared to no medication use in pregnancy had an increased risk of SMM.. · Specific medication use patterns were associated with an elevated risk of SMM.. · Pattern of antihypertensive medication use before and during pregnancy may be associated with an increased risk of SMM..

Risk factors and pregnancy outcomes vary among Asian American, Native Hawaiian, and Pacific Islander individuals giving birth in California.

OBJECTIVE: To compare frequencies of risk factors and pregnancy outcomes in ethnic groups versus the combined total of Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations. METHODS: Using linked birth and fetal death certificate and maternal hospital discharge data (California 2007-2018), we estimated frequencies of 15 clinical and sociodemographic exposures and 11 pregnancy outcomes. Variability across 15 AANHPI groups was compared using a heat map and compared to frequencies for the total group (n = 904,232). RESULTS: AANHPI groups varied significantly from each other and the combined total regarding indicators of social disadvantage (e.g., range for high school-level educational or less: 6.4% Korean-55.8% Samoan) and sociodemographic factors (e.g., maternal age <20 years: 0.2% Chinese-8.8% Guamanian) that are related to adverse pregnancy outcomes. Perinatal outcomes varied significantly (e.g., severe maternal morbidity: 1.2% Korean-1.9% Filipino). No single group consistently had risk factors or outcome prevalence at the extremes, i.e., no group was consistently better or worse off across examined factors. CONCLUSIONS: Substantial variability in perinatal risk factors and outcomes exists across AANHPI groups. Aggregation into "AANHPI" is not appropriate for outcome reporting.

Does active treatment in infants born at 22-23 weeks correlate with outcomes of more mature infants at the same hospital? An analysis of California NICU data, 2015-2019.

OBJECTIVE: To investigate whether hospital rates of active treatment for infants born at 22-23 weeks is associated with survival of infants born at 24-27 weeks. STUDY DESIGN: We included all liveborn infants 22-27 weeks of gestation delivered at California Perinatal Quality Care Collaborative hospitals from 2015 to 2019. We assessed (1) the correlation of active treatment (e.g., endotracheal intubation, epinephrine) in 22-23 week infants and survival until discharge for 24-27 week infants and (2) the association of active treatment with survival using multilevel models. RESULT: The 22-23 week active treatment rate was associated with infant outcomes at 22-23 weeks but not 24-27 weeks. A 10% increase in active treatment did not relate to 24-25 week (adjusted OR: 1.00 [95% CI: 0.95-1.05]), or 26-27 week survival (aOR: 1.02 [0.95-1.09]). CONCLUSION: The hospital rate of active treatment for infants born at 22-23 weeks was not associated with improved survival for 24-27 week infants.

Subsequent risk of stillbirth, preterm birth, and small for gestational age: A cross-outcome analysis of adverse birth outcomes.

BACKGROUND: Stillbirth, preterm birth, and small for gestational age (SGA) birth have an increased recurrence risk. The occurrence of one of these biologically related outcomes could also increase the risk for another one of these outcomes in a subsequent pregnancy. OBJECTIVES: We assessed cross-outcome risks for subsequent stillbirth, preterm birth, and SGA. METHODS: We used live birth and fetal death records to identify singleton, sequential birth pairs in California (1997-2017). Stillbirth was defined as delivery at ≥20 weeks of gestation of a foetus that died in utero; preterm birth as live birth at 20-36 weeks; and small for gestational age as sex-specific birthweight <10th percentile for gestational age. Risk ratios (RR) were computed using modified Poisson regression and adjusted for potential confounders. Sensitivity analyses included analysing a cohort restricted to primiparous index births and using inverse-probability censoring weights. RESULTS: Of 3,108,532 birth pairs, 16,668 (0.5%), 260,596 (8.4%) and 331,109 (10.7%) of index births were stillborn, preterm and SGA, respectively. Among individuals with an index stillbirth, the adjusted RRs were 1.90 (95% confidence interval [CI] 1.83, 1.98) for subsequent preterm and 1.35 (95% CI 1.28, 1.41) for subsequent SGA. Among those with index preterm birth, the adjusted RRs were 2.02 (95% CI 1.92, 2.13) for stillbirth and 1.42 (95% CI 1.41, 1.44) for SGA. Among those with index SGA, the adjusted RRs were 1.54 (95% CI 1.46, 1.63) for stillbirth and 1.45 (95% CI 1.44, 1.47) for preterm birth. Similar results were reported for sensitivity analyses. CONCLUSIONS: Individuals experiencing stillbirth, preterm birth, or SGA in one pregnancy had an increased risk of one of these biologically related outcomes in a subsequent pregnancy. These findings could encourage enhanced surveillance for individuals who experience stillbirth, preterm birth, or SGA and desire a subsequent pregnancy.

The impact of Severe Maternal Morbidity on probability of subsequent birth in a population-based study of women in California from 1997-2017.

IMPORTANCE: Complications during pregnancy and birth can impact whether an individual has more children. Individuals experiencing SMM are at a higher risk of general and reproductive health issues after pregnancy, which could reduce the probability of a subsequent birth. OBJECTIVE: To examine whether experiencing SMM during an individual's first birth affects their probability of having an additional birth, and whether this effect varies by maternal factors. METHODS: This retrospective cohort study US linked vital records and maternal discharges from 1997 to 2017 to identify all California births. The exposure, Severe Maternal Morbidity (SMM) was identified using a Centers for Disease Control and Prevention index. Individuals whose first birth was a singleton live birth were followed until their second birth or December 31, 2017, whichever came first. Hazard ratios for having a subsequent birth were estimated using Cox proportional hazard regression models. This association was assessed overall and stratified by maternal factors of a priori interest: age, race/ethnicity, and payer. RESULTS: Of the 3,916,413 individuals in our study, 51,872 (1.3%) experienced SMM at first birth. Compared to those who do not experience SMM, individuals who had SMM had a lower hazard, or instantaneous rate, of subsequent birth (adjusted HR 0.83, 95% CI: 0.82, 0.84); this association was observed in all levels of stratification (for example, adjusted HR range for known race/ethnicity: 0.78, 95% CI: 0.76, 0.80 for non-Hispanic White to 0.90, 95% CI: 0.88, 0.92 for Hispanic) and all indicators of SMM (0.24, 95% CI: 0.17, 0.35 for cardiac arrest/ventricular fibrillation to 0.84, 95% CI: 0.80, 0.87 for eclampsia). CONCLUSION AND RELEVANCE: Our findings suggest that individuals who experience SMM at the time of their first birth are less likely to have a subsequent birth as compared to those who do not experience SMM at the time of their first birth. While the reasons for these findings are unclear, they could inform reproductive life planning discussions for individuals experiencing SMM. Future directions include studies exploring the reasons for not having a subsequent birth.

Success of community approach to HPV vaccination in school-based and non-school-based settings in Haiti.

OBJECTIVES: To assess the success of a human papillomavirus (HPV) vaccination program among adolescent girls aged 9-14 years in Haiti and to understand predictors of completion of a two-dose HPV vaccination series. METHODS: Data collection was conducted during HPV vaccination campaigns in Port-au-Prince between August 2016 and April 2017. Descriptive statistics and logistic regression models were used to examine characteristics associated with vaccination series completion of school based and non-school based vaccination delivery modalities. RESULTS: Of the 2,445 adolescent girls who participated in the awareness program, 1,994 participants (1,307 in non-school program, 687 in school program) received the first dose of the vaccine; 1,199 (92%) in the non-school program and 673 (98%) in the school program also received the second dose. Menarche (OR: 1.87; 95% CI, 1.11-3.14), if the participant was a prior patient at the GHESKIO clinics (OR: 2.17; 95% CI, 1.32-3.58), and participating in the school-based program (OR: 4.17; 95% CI, 2.14-8.12) were significantly associated with vaccination completion. CONCLUSIONS: Vaccination in school- and non-school-based settings was successful, suggesting that a nationwide HPV vaccination campaign using either approach would be successful using either approach.

Recurrence of severe maternal morbidity: A population-based cohort analysis of California women.

BACKGROUND: Severe maternal morbidity (SMM) has increased in the United States by 45% in the last decade. While the recurrence of several adverse pregnancy outcomes from one pregnancy to the next has been established, the recurrence risk of SMM is unknown. OBJECTIVE: To determine whether women who have SMM in a first pregnancy are at increased risk of SMM in their second pregnancy, compared to women who did not have SMM in their first pregnancy. METHODS: This is a population-based study using linked vital statistics and hospital discharge records from the Office of Statewide Health Planning and Development in California from 1997 to 2012. The study population had their first two singleton births (live births or stillbirths) in California between 1997 and 2012 (n = 1 180 357). The primary exposure was SMM during the hospitalisation at first birth, and the primary outcome was SMM during the hospitalisation at second birth. Prevalence and risk ratios of SMM at second birth were computed for women who did and did not have SMM at first birth, as well as for certain specific indicators of SMM. RESULTS: Of the 1 180 357 women included in this analysis, 9088 (77 per 10 000 births) experienced SMM at first birth. Among these women, the prevalence of SMM at second birth was 470 per 10 000 births, compared to 68 per 10 000 births among women without SMM at first birth. This corresponded to an unadjusted risk ratio of 6.87 (95% CI 6.23, 7.57), which did not differ substantially when adjusted for factors known to be associated with SMM (6.42, 95% CI 5.86, 7.13). CONCLUSION: Women experiencing SMM in their first pregnancy were at an approximately sixfold increased risk of experiencing SMM in their second pregnancy.

Severe maternal morbidity among U.S.- and foreign-born Asian and Pacific Islander women in California.

PURPOSE: The purpose of the study was to examine the risk of severe maternal morbidity (SMM)-a composite of serious, potentially life-threatening conditions related to childbirth-among subgroups of nulliparous women with Asian and Pacific Islander race/ethnicity. METHODS: This study used linked hospital discharge and vital record data California to identify nulliparous Asian and Pacific Islander women from 1997 to 2012 (n = 453,525). We examined the risk of SMM for 15 Asian and Pacific Islander subgroups and compared the risk between U.S.- and foreign-born women. RESULTS: The risk of SMM was higher among Pacific Islander women than that among Asian women (148 and 127 cases per 10,000 births, respectively). Among Asian women, the risk of SMM ranged from 94 (Korean) to 165 (Filipina) cases per 10,000 births, and among Pacific Islander women, the risk ranged from 125 (Hawaiian) to 162 (Other). With the exception of Korean and Filipina women, relative risks of SMM for U.S.- versus foreign-born Asian and Pacific Islander women were similar. CONCLUSIONS: Differences in the risk of SMM exist between subgroups of the Asian and Pacific Islander community. These differences should be considered when conducting research on racial and ethnic differences of SMM and when counseling Asian and Pacific Islander women regarding their risk of SMM.

Tumor Mutational Burden as a Predictive Biomarker for Response to Immune Checkpoint Inhibitors: A Review of Current Evidence.

Treatment with immune checkpoint inhibitors (ICPIs) extends survival in a proportion of patients across multiple cancers. Tumor mutational burden (TMB)-the number of somatic mutations per DNA megabase (Mb)-has emerged as a proxy for neoantigen burden that is an independent biomarker associated with ICPI outcomes. Based on findings from recent studies, TMB can be reliably estimated using validated algorithms from next-generation sequencing assays that interrogate a sufficiently large subset of the exome as an alternative to whole-exome sequencing. Biological processes contributing to elevated TMB can result from exposure to cigarette smoke and ultraviolet radiation, from deleterious mutations in mismatch repair leading to microsatellite instability, or from mutations in the DNA repair machinery. A variety of clinical studies have shown that patients with higher TMB experience longer survival and greater response rates following treatment with ICPIs compared with those who have lower TMB levels; this includes a prospective randomized clinical trial that found a TMB threshold of ≥10 mutations per Mb to be predictive of longer progression-free survival in patients with non-small cell lung cancer. Multiple trials are underway to validate the predictive values of TMB across cancer types and in patients treated with other immunotherapies. Here we review the rationale, algorithm development methodology, and existing clinical data supporting the use of TMB as a predictive biomarker for treatment with ICPIs. We discuss emerging roles for TMB and its potential future value for stratifying patients according to their likelihood of ICPI treatment response. IMPLICATIONS FOR PRACTICE: Tumor mutational burden (TMB) is a newly established independent predictor of immune checkpoint inhibitor (ICPI) treatment outcome across multiple tumor types. Certain next-generation sequencing-based techniques allow TMB to be reliably estimated from a subset of the exome without the use of whole-exome sequencing, thus facilitating the adoption of TMB assessment in community oncology settings. Analyses of multiple clinical trials across several cancer types have demonstrated that TMB stratifies patients who are receiving ICPIs by response rate and survival. TMB, alongside other genomic biomarkers, may provide complementary information in selecting patients for ICPI-based therapies.

Reentrainment Impairs Spatial Working Memory until Both Activity Onset and Offset Reentrain.

Compression of the active phase (α) during reentrainment to phase-shifted light-dark (LD) cycles is a common feature of circadian systems, but its functional consequences have not been investigated. This study tested whether α compression in Siberian hamsters (Phodopus sungorus) impaired their spatial working memory as assessed by spontaneous alternation (SA) behavior in a T-maze. Animals were exposed to a 1- or 3-h phase delay of the LD cycle (16 h light/8 h dark). SA behavior was tested at 4 multiday intervals after the phase shift, and α was quantified for those days. All animals failed at the SA task while α was decompressing but recovered spatial memory ability once α returned to baseline levels. A second experiment exposed hamsters to a 2-h light pulse either early or late at night to compress α without phase-shifting the LD cycle. SA behavior was impaired until α decompressed to baseline levels. In a third experiment, α was compressed by changing photoperiod (LD 16:8, 18:6, 20:4) to see if absolute differences in α were related to spatial memory ability. Animals performed the SA task successfully in all 3 photoperiods. These data show that the dynamic process of α compression and decompression impairs spatial working memory and suggests that α modulation is a potential biomarker for assessing the impact of transmeridian flight or shift work on memory.