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Rigorous perinatal epidemiologic research depends on population-based parental and neonatal sociodemographic and clinical data. Here we describe the creation of linked birth cohort files (LBCF), an enriched data source that combines information from vital records with maternal delivery and infant hospital encounter records.Probabilistic linkage techniques were used to link vital records (i.e., birth and fetal death certificates) from the California Department of Public Health with hospital inpatient, ambulatory surgery and emergency department encounter data for mothers and infants from the California Department of Health Care Access and Information.From 2012 to 2018, 95% of live birth records were successfully linked to maternal and newborn hospital records while 85% of fetal death records were linked to a maternal delivery record. Overall, 93% of postnatal hospital encounters of infants (i.e.,1 year old) were matched to a linked record.The LBCF is a rich resource opening many possibilities for understanding perinatal health outcomes and opportunities for linkage to longitudinal, social determinant, and environmental data. To optimally use this file for research, analysts should evaluate possible shortcomings or biases of the data sources being linked.

There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on "CHD-lymphoma" associations.From3 million live births (1988-2004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD-lymphoma through the California BioBank. We performed case-control epigenome-wide association analyses (EWAS) using two comparison groups with reciprocal discovery and validation to identify differential methylation associated with CHD-lymphoma.After correction for multiple testing at the discovery and validation stages, individuals with CHD-lymphoma had differential newborn methylation at six sites relative to two comparison groups. Our top finding was significant in both EWAS and indicates PPFIA1 cg25574765 was hypomethylated among individuals with CHD-lymphoma (mean beta = 0.04) relative to both unaffected individuals (mean beta = 0.93, p = 1.5 × 10We identified associations between molecular changes present in the genome at birth and risk of childhood lymphoma among those with CHD. Our findings also highlight novel perinatal exposures that may underlie methylation changes in CHD predisposing to lymphoma.

Vitamin D deficiency is associated with adverse pregnancy events. However, its role in the etiology of congenital anomalies remains unclear. We examined the association between vitamin D status, measured through prepregnancy diet, UV exposure, season of conception, and congenital anomalies.We used data from the National Birth Defects Prevention Study, a U.S. population-based case-control study (1997-2011). Prepregnancy dietary vitamin D was calculated from food frequency questionnaires and evaluated using tertiles, based on the distribution in controls. We used the National Oceanic and Atmospheric Administration Weather Service to assign UV indices based on location and estimated date of conception, then dichotomized UV exposure (low vs. high). Seasons of conception was categorized as fall/winter spring/summer. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI).Lower prepregnancy dietary vitamin D intake (65.21 IU/d vs.107.55 IU/d) was associated with increased odds of anencephaly (aOR = 1.28, 95% CI 1.01, 1.63), hypospadias (aOR = 1.21, 95% CI 1.04, 1.40), septal defects (aOR = 1.16, 95% CI 1.05, 1.30), diaphragmatic hernia (aOR = 1.42, 95% CI 1.13, 1.79), and gastroschisis (aOR = 1.27, 95% CI 1.07, 1.52). Findings were consistent when we stratified by UV exposure and season of conception.Our findings suggest lower dietary intake of vitamin D may be associated with increased risk of select congenital anomalies. Further investigations are warranted to evaluate the effects of other nutrients and appropriate thresholds and sources of vitamin D using serum.

To investigate the association of infertility with atherosclerotic cardiovascular disease (ASCVD) among postmenopausal participants in the Women's Health Initiative (WHI). We hypothesized that nulliparity and pregnancy loss may reveal more extreme phenotypes of infertility, enabling further understanding of the association of infertility with ASCVD.Prospective cohort study.Forty clinical centers in the United States.A total of 158,787 postmenopausal participants in the Women's Health Initiative cohort.Infertility, parity, and pregnancy loss.The primary outcome was risk of ASCVD among women with and without a history of infertility, stratified by history of live birth and pregnancy loss. Cox proportional-hazards models were adjusted for demographics and risk factors for ASCVD.Among 158,787 women, 25,933 (16.3%) reported a history of infertility; 20,427 (80%) had at least 1 live birth; and 9,062 (35%) had at least 1 pregnancy loss. There was a moderate overall association between infertility and ASCVD (adjusted hazard ratio, 1.02; 95% confidence interval [CI], 0.99-1.06) over 19 years of follow-up. Among nulliparous women, infertility was associated with a 13% higher risk of ASCVD (95% CI, 1.04-1.23). Among nulliparous women who had a pregnancy loss, infertility was associated with a 36% higher risk of ASCVD (95% CI, 1.09-1.71).Women with a history of infertility overall had a moderately higher risk of ASCVD compared with women without a history of infertility. Atherosclerotic cardiovascular disease risk was much higher among nulliparous infertile women and among nulliparous infertile women who also had a pregnancy loss, suggesting that in these more extreme phenotypes, infertility may be associated with ASCVD risk.

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.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.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]).The hospital rate of active treatment for infants born at 22-23 weeks was not associated with improved survival for 24-27 week infants.

Objectives: To assess the associations between genitourinary and wound infections during the birth hospitalization and early postpartum hospital encounters, and to evaluate clinical risk factors for early postpartum hospital encounters among patients with a genitourinary or wound infection during the birth hospitalization. Study Design: We conducted a population-based cohort study of births in California during 2016-2018 and postpartum hospital encounters. We identified genitourinary and wound infections using diagnosis codes. Our main outcome was early postpartum hospital encounter, defined as a readmission or ED visit within 3 days after discharge from the birth hospitalization. We evaluated the association of genitourinary and wound infections (overall and subtypes) with early postpartum hospital encounter using logistic regression, adjusting for sociodemographic factors and comorbidities and stratified by mode of birth. We then evaluated factors associated with early postpartum hospital encounter among patients with genitourinary and wound infections. Results: Among 1,217,803 birth hospitalizations, 5.5% were complicated by genitourinary and wound infections and 1.8% resulted in an early postpartum hospital encounter. Genitourinary or wound infection was associated with an early postpartum hospital encounter among patients with both vaginal births (aRR 1.26, 95% CI 1.17, 1.36) and cesarean births (aRR 1.23, 95% CI 1.15, 1.32). Major puerperal infection, followed by wound infection, among patients with a cesarean birth conferred the highest risk of an early postpartum hospital encounter (6.4% and 4.3%, respectively). Among patients with genitourinary and wound infections at birth hospitalization, factors associated with an early postpartum hospital encounter included severe maternal morbidity, major mental health condition, prolonged postpartum hospital stay, and, among cesarean births, postpartum hemorrhage (P-value < 0.05). Conclusions: Genitourinary and wound infections during hospitalization for birth may increase risk of a readmission or ED visit within the first few days after discharge, particularly among patients who have a major puerperal infection or wound infection.

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.

Objective The objective of our study was to examine factors associated with distance to care for first surgical repair among infants with myelomeningocele in California. Study Design A total of 677 eligible cases with complete geocoded data were identified for birth years 2006 to 2012 using data from the California Perinatal Quality Care Collaborative linked to hospital and vital records. The median distance from home to birth hospital among eligible infants was 9 miles, and from birth hospital to repair hospital was 15 miles. We limited our analysis to infants who lived close to the birth hospital, creating two study groups to examine transfer distance patterns: “lived close and had a short transfer” (i.e., lived Results We found that low birth weight (aRR = 1.44; 95% CI = 1.04, 1.99) and preterm birth (aRR = 1.41; 95% CI = 1.01, 1.97) were positively associated, whereas initiating prenatal care early in the first trimester was inversely associated (aRR = 0.64; 95% CI = 0.46, 0.89) with transferring a longer distance (≥15 miles) from birth hospital to repair hospital. No significant associations were noted by maternal race-ethnicity, socioeconomic indicators, or the level of hospital care at the birth hospital. Conclusion Our study identified selected infant factors associated with the distance to access surgical care for infants with myelomeningocele who had to transfer from birth hospital to repair hospital. Distance-based barriers to care should be identified and optimized when planning deliveries of at-risk infants in other populations. Key Points

Most studies of severe maternal morbidity (SMM) include only cases that occur during birth hospitalizations. We examined the increase in cases when including SMM during antenatal and postpartum (within 42 days of discharge) hospitalizations, using longitudinally linked data from 1,010,250 births in California from September 1, 2016, to December 31, 2018. For total SMM, expanding the definition resulted in 22.8% more cases; for nontransfusion SMM, 45.1% more cases were added. Sepsis accounted for 55.5% of the additional cases. The increase varied for specific indicators, for example, less than 2% for amniotic fluid embolism, 7.0% for transfusion, 112.9% for sepsis, and 155.6% for acute myocardial infarction. These findings reiterate the importance of considering SMM beyond just the birth hospitalization and facilitating access to longitudinally linked data to facilitate a more complete understanding of SMM.

OBJECTIVE To evaluate severe maternal morbidity (SMM) among patients with epilepsy and patients without epilepsy. METHODS We retrospectively examined SMM using linked birth certificate and maternal hospital discharge records in California between 2007 and 2012. Epilepsy present at delivery admission was the exposure and was subtyped into generalized, focal and other less specified, or unspecified. The outcomes were SMM and nontransfusion SMM from delivery up to 42 days' postpartum, identified using Centers for Disease Control and Prevention indicators. Multivariable logistic regression models were used to adjust for confounders, which were selected a priori. We also estimated the association between epilepsy and SMM independent of comorbidities by using a validated obstetric comorbidity score. Severe maternal morbidity indicators were then compared using the same multivariable logistic regression models. RESULTS Of 2,668,442 births, 8,145 (0.3%) were to patients with epilepsy; 637 (7.8%) had generalized, 6,250 (76.7%) had focal or other less specified, and 1,258 (15.4%) had unspecified subtypes. Compared with patients without epilepsy, patients with epilepsy had greater odds of SMM (4.3% vs 1.4%, adjusted odds ratio [aOR] 2.91, 95% CI 2.61-3.24) and nontransfusion SMM (2.9% vs 0.7%, aOR 4.16, 95% CI 3.65-4.75). Epilepsy remained significantly associated with increased SMM and nontransfusion SMM after additional adjustment for the obstetric comorbidity score, though the effects were attenuated. When grouped by organ system, all SMM indicators were significantly more common among patients with epilepsy-most notably those related to hemorrhage and transfusion. CONCLUSION Severe maternal morbidity was significantly increased in patients with epilepsy, and SMM indicators across all organ systems contributed to this.

Historical mortgage redlining, a racially discriminatory policy designed to uphold structural racism, may have played a role in producing the persistently elevated rate of severe maternal morbidity (SMM) among racialised birthing people.This study examined associations between Home-Owner Loan Corporation (HOLC) redlining grades and SMM in a racially and ethnically diverse birth cohort in California.We leveraged a population-based cohort of all live hospital births at ≥20 weeks of gestation between 1997 and 2017 in California. SMM was defined as having one of 21 procedures and diagnoses, per an index developed by Centers for Disease Control and Prevention. We characterised census tract-level redlining using HOLC's security maps for eight California cities. We assessed bivariate associations between HOLC grades and participant characteristics. Race and ethnicity-stratified mixed effects logistic regression models assessed the risk of SMM associated with HOLC grades within non-Hispanic Black, Asian/Pacific Islander, American Indian/Alaskan Native and Hispanic groups, adjusting for sociodemographic information, pregnancy-related factors, co-morbidities and neighbourhood deprivation index.The study sample included 2,020,194 births, with 24,579 cases of SMM (1.2%). Living in a census tract that was graded as "Hazardous," compared to census tracts graded "Best" and "Still Desirable," was associated with 1.15 (95% confidence interval [CI] 1.03, 1.29) and 1.17 (95% CI 1.09, 1.25) times the risk of SMM among Black and Hispanic birthing people, respectively, independent of sociodemographic factors. These associations persisted after adjusting for pregnancy-related factors and neighbourhood deprivation index.Historical redlining, a tool of structural racism that influenced the trajectory of neighbourhood social and material conditions, is associated with increased risk of experiencing SMM among Black and Hispanic birthing people in California. These findings demonstrate that addressing the enduring impact of macro-level and systemic mechanisms that uphold structural racism is a vital step in achieving racial and ethnic equity in birthing people's health.

Our objective is to examine severe maternal morbidity (SMM) and patterns of antihypertensive medication use before and during pregnancy among individuals with chronic hypertension. 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. 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. 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.· 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..

Residential proximity to greenspace is associated with various health outcomes.We estimated associations between maternal residential proximity to greenspace (based on an index of vegetation) and selected structural birth defects, including effect modification by neighborhood-level factors.Data were from the National Birth Defects Prevention Study (1997-2011) and included 19,065 infants with at least one eligible birth defect (cases) and 8925 without birth defects (controls) from eight Centers throughout the United States. Maternal participants reported their addresses throughout pregnancy. Each address was systematically geocoded and residences around conception were linked to greenspace, US Census, and US Department of Agriculture data. Greenspace was estimated using the normalized difference vegetation index (NDVI); average maximum NDVI was estimated within 100 m and 500 m concentric buffers surrounding geocoded addresses to estimate residential NDVI. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals comparing those in the highest and lowest quartiles of residential NDVI and stratifying by rural/urban residence and neighborhood median income.After multivariable adjustment, for the 500 m buffer, inverse associations were observed for tetralogy of Fallot, secundum atrial septal defects, anencephaly, anotia/microtia, cleft lip ± cleft palate, transverse limb deficiency, and omphalocele, (aORs: 0.54-0.86). Results were similar for 100 m buffer analyses and similar patterns were observed for other defects, though results were not significant. Significant heterogeneity was observed after stratification by rural/urban for hypoplastic left heart, coarctation of the aorta, and cleft palate, with inverse associations only among participants residing in rural areas. Stratification by median income showed heterogeneity for atrioventricular and secundum atrial septal defects, anencephaly, and anorectal atresia, with inverse associations only among participants residing in a high-income neighborhood (aORs: 0.45-0.81).Our results suggest that perinatal residential proximity to more greenspace may contribute to a reduced risk of certain birth defects, especially among those living in rural or high-income neighborhoods.

Background Hydroxychloroquine is a treatment for rheumatic disease and considered safe during pregnancy. Interest in hydroxychloroquine has increased as it is being examined as a potential treatment and prophylaxis for coronavirus disease 2019. Data on the risks of specific birth defects associated with hydroxychloroquine use are sparse. Methods Using data from two case–control studies (National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study), we described women who reported hydroxychloroquine use in pregnancy and the presence of specific major birth defects in their offspring. Cases had at least one major birth defect and controls were live‐born healthy infants. Women self‐reported medication use information in the few months before pregnancy through delivery. Results In total, 0.06% (19/31,468) of case and 0.04% (5/11,614) of control mothers in National Birth Defects Prevention Study, and 0.04% (11/29,838) of case and 0.05% (7/12,868) of control mothers in Birth Defects Study reported hydroxychloroquine use. Hydroxychloroquine users had complicated medical histories and frequent medication use for a variety of conditions. The observed birth defects among women taking hydroxychloroquine were varied and included nine oral cleft cases; the elevated observed:expected ratios for specific oral cleft phenotypes and for oral clefts overall had 95% confidence intervals that included 1.0. Conclusion While teratogens typically produce a specific pattern of birth defects, the observed birth defects among the hydroxychloroquine‐exposed women did not present a clear pattern, suggesting no meaningful evidence for the risk of specific birth defects. The number of exposed cases is small; results should be interpreted cautiously.

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.

Interpregnancy interval (IPI) is associated with adverse perinatal outcomes, but its contribution to severe maternal morbidity (SMM) remains unclear. We examined the association between IPI and SMM, using data linked across sequential pregnancies to women in California during 1997–2012. Adjusting for confounders measured in the index pregnancy (i.e., the first in a pair of consecutive pregnancies), we estimated adjusted risk ratios for SMM related to the subsequent pregnancy. We further conducted within-mother comparisons and analyses stratified by parity and maternal age at the index pregnancy. Compared with an IPI of 18–23 months, an IPI of

Maternal race/ethnicity is associated with mortality in neonates with hypoplastic left heart syndrome (HLHS). We investigated whether maternal race/ethnicity and other sociodemographic factors affect timing of transfer after birth and whether timing of transfer impacts mortality in infants with HLHS. We linked two statewide databases, the California Perinatal Quality Care Collaborative and records from the Office of Statewide Health Planning and Development, to identify cases of HLHS born between 1/1/06 and 12/31/11. Cases were divided into three groups: birth at destination hospital, transfer on day of life 0–1 (“early transfer”), or transfer on day of life ≥ 2 (“late transfer”). We used log-binomial regression models to estimate relative risks (RR) for timing of transfer and Cox proportional hazard models to estimate hazard ratios (HR) for mortality. We excluded infants who died within 60 days of life without intervention from the main analyses of timing of transfer, since intervention may not have been planned in these infants. Of 556 cases, 107 died without intervention (19%) and another 52 (9%) died within 28 days. Of the 449 included in analyses of timing of transfer, 28% were born at the destination hospital, 49% were transferred early, and 23% were transferred late. Late transfer was more likely for infants of low birthweight (RR 1.74) and infants born to US-born Hispanic (RR 1.69) and black (RR 2.45) mothers. Low birthweight (HR 1.50), low 5-min Apgar score (HR 4.69), and the presence of other major congenital anomalies (HR 3.41), but not timing of transfer, predicted neonatal mortality. Late transfer was more likely in neonates born to US-born Hispanic and black mothers but was not associated with higher mortality. Supplementary Information The online version of this article (10.1007/s00246-021-02561-w) contains supplementary material, which is available to authorized users.

Objective To determine the rates of high-risk infant follow-up (HRIF) attendance and the characteristics associated with follow-up among infants with hypoxic-ischemic encephalopathy (HIE) in California. Study design Using population-based datasets, 1314 infants with HIE born in 2010-2016 were evaluated. The characteristics associated with follow-up were identified through multivariable logistic regression. Results 73.9% of infants attended HRIF by age 1. Follow-up rates increased and variation in follow-up by clinic decreased over time. Female infants; those born to African-American, single, less than college-educated, or publicly insured caregivers; and those referred to high-volume or regional programs had lower follow-up rates. In multivariable analysis, Asian and Pacific Islander race/ethnicity had lower odds of follow-up; infants with college- or graduate school-educated caregivers or referred to mid-volume HRIF programs had greater odds. Conclusion Sociodemographic and program-level characteristics were associated with lack of follow-up among HIE infants. Understanding these characteristics may improve the post-discharge care of HIE infants.

Objectives The aim of this study was to understand the associations between hypertensive disorders of pregnancy (HDP) and postpartum complications throughout the newly defined 12-week postpartum transition. Study design We conducted a retrospective cohort study of the associations of HDP (any/subtype) with postpartum complications among 2.5 million California births, 2008-2012. We identified complications from discharge diagnoses from maternal hospital encounters (emergency department visits and readmissions) in the 12 weeks after giving birth. We compared rates of complications, overall and by diagnostic category, between groups defined by HDP. In survival analyses, we calculated the adjusted hazard ratios of postpartum complications associated with HDP. We adjusted for maternal age, race/ethnicity, prepregnancy obesity, chronic diabetes, gestational diabetes, insurance, delivery mode, gestational age and birth outcome (term and size). Results Among women with and without HDP, 12.8 and 7.7%, respectively, had a hospital encounter within 12 weeks of giving birth [adjusted hazard ratio 1.5, 95% confidence interval (95% CI): 1.5-1.5]. HDP was associated with increased risk across all major categories of complications: hypertension-related, adjusted hazard ratio 11.8 (95% CI: 11.2-12.3); childbirth-related, 1.4 (1.3-1.4); and other, 1.4 (1.4-1.4). Risk of any complication differed by hypertensive subtype: chronic hypertension with super-imposed preeclampsia, adjusted hazard ratio 1.8 (95% CI: 1.7-1.8); chronic hypertension, 1.6 (1.6-1.7); preeclampsia/eclampsia, 1.3 (1.3-1.4); and gestational hypertension, 1.2 (1.2-1.3). Over a quarter (28.9%) of maternal hospital encounters occurred more than 6 weeks after giving birth; this did not differ substantially by HDP status. Conclusion Women with HDP are at an increased risk for virtually all postpartum complications, including those not related to hypertension, and may benefit from enhanced and comprehensive postpartum care.

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.

OBJECTIVE: To evaluate outpatient opioid dispensing and the incidence of persistent opioid use after ectopic pregnancy. METHODS: This cohort study used US employer-based claims data to identify opioid-naïve individuals experiencing ectopic pregnancy from November 1, 2008 to September 30, 2015. Treatment was categorized as surgical, medical (using methotrexate), or unknown. New opioid prescriptions were defined as prescriptions filled from one week before to one week after an ectopic pregnancy treatment. For those who filled a new opioid prescription, we calculated the incidence and risk factors for persistent opioid use. Persistent opioid use was defined as having filled at least one opioid prescription both from 8 to 90 days after treatment and from 91 to 365 days after treatment. RESULTS: Of the 15,338 individuals who had an ectopic pregnancy and were opioid naïve, 7,047 (45.9%, 95% Confidence Interval (CI) 45.2%, 46.7%) filled an opioid prescription at the time of treatment, of whom 4.1% (95% CI 3.6%, 4.6%) developed persistent opioid use. The risk of persistent opioid use was lower among those who had surgical versus medical treatment (3.7% and 6.8%, respectively; Relative Risk (RR) = 0.54, 95% CI 0.38, 0.77). Variables most strongly associated with persistent opioid use were a history of benzodiazepine use (RR = 1.99; 95% CI 1.43, 2.78; adjusted RR (aRR) = 1.57, 95% CI 1.11, 2.22), antidepressant use (RR = 1.91, 95% CI = 1.45, 2.53; aRR = 1.53, 95% CI 1.08, 2.18), and a pre-existing pain disorder (RR = 1.58, 95% CI 1.26, 1.99; aRR = 1.47, 95% CI = 1.16, 1.85) in the year before treatment. CONCLUSION: New opioid use is common following an ectopic pregnancy, with approximately 4% of those with new opioid use developing persistent opioid use. New pain management guidelines need to be developed to prevent persistent opioid use after ectopic pregnancy.

STUDY QUESTION Are women who fill a benzodiazepine prescription before conception at increased risk of ectopic pregnancy? SUMMARY ANSWER Risk of ectopic pregnancy is 50% higher among women who fill a benzodiazepine prescription before conception. WHAT IS KNOWN ALREADY Benzodiazepine use in pregnancy increases the risk of miscarriage, adverse birth outcomes and adverse child development outcomes. STUDY DESIGN, SIZE, DURATION Using data from US commercial insurance claims, we performed a cohort study of 1 691 366 pregnancies between 1 November 2008 and 30 September 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS We identified ectopic pregnancies using diagnosis and procedure codes and used unadjusted and inverse probability of treatment (IPT)-weighted log-binomial models to calculate relative risks (RR) of ectopic pregnancy for pregnant women who did and did not fill any prescriptions for benzodiazepines in the 90 days before conception. Two sub-groups of women with specific indications for benzodiazepine use were also examined—women who had a least one diagnosis for anxiety disorder and women who had at least one diagnosis of insomnia in the year before conception. MAIN RESULTS AND THE ROLE OF CHANCE Of the 1 691 366 pregnancies, 1.06% filled at least two benzodiazepine prescriptions totaling at least 10 days supply in the 90 days before conception. Among women with a benzodiazepine prescription, there was an excess of 80 ectopic pregnancies per 10 000 pregnancies, and their IPT-weighted risk of ectopic pregnancies was 1.47 (95% CI 1.32 to 1.63) times greater relative to women without benzodiazepine prescriptions before conception. The IPT-weighted RR between ectopic pregnancy and benzodiazepine use was 1.34 (95% CI 1.18 to 1.53) among women with anxiety disorder diagnoses and 1.28 (95% CI 0.99 to 1.68) among women with an insomnia diagnosis. LIMITATIONS, REASONS FOR CAUTION We relied on outpatient prescription data to identify benzodiazepine use before conception, which could result in over- or under-estimation of actual benzodiazepine consumption. We relied on medical claim codes to identify pregnancies and conception date, which may result in misclassification of pregnancy outcomes and gestational length. WIDER IMPLICATIONS OF THE FINDINGS This study found that women who have a benzodiazepine prescription before conception are at an increased risk of ectopic pregnancy. This information can help women, and their healthcare providers make more fully informed decisions about benzodiazepine use in their reproductive years. STUDY FUNDING/COMPETING INTEREST(S) Funding for this project was provided by a Banting Postdoctoral Fellowship and a Stanford Maternal and Child Health Research Institute Postdoctoral Award. Data access for this project was provided by the Stanford Center for Population Health Sciences Data Core. The PHS Data Core is supported by a National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085) and internal Stanford funding. The authors have no competing interest. TRIAL REGISTRATION NUMBER N/A.

Objective The aim of this study is to examine factors associated with early neonatal (death within first 7 days of birth) and infant (death during the first year of life) mortality among infants born with myelomeningocele. Study design We examined linked data from the California Perinatal Quality Care Collaborative, vital records, and hospital discharge records for infants born with myelomeningocele from 2006 to 2011. Survival probability was calculated using Kaplan-Meier Product Limit method and 95% confidence intervals (CI) using Greenwood's method; Cox proportional hazard models were used to estimate unadjusted and adjusted hazard ratios (HR) and 95% CI. Results Early neonatal and first-year survival probabilities among infants born with myelomeningocele were 96.0% (95% CI: 94.1-97.3%) and 94.5% (95% CI: 92.4-96.1%), respectively. Low birthweight and having multiple co-occurring birth defects were associated with increased HRs ranging between 5 and 20, while having congenital hydrocephalus and receiving hospital transfer from the birth hospital to another hospital for myelomeningocele surgery were associated with HRs indicating a protective association with early neonatal and infant mortality. Conclusion Maternal race/ethnicity and social disadvantage did not predict early neonatal and infant mortality among infants with myelomeningocele; presence of congenital hydrocephalus and the role of hospital transfer for myelomeningocele repair should be further examined. Key points · Mortality in myelomeningocele is a concern. · Social disadvantage was not associated with death. · Hospital-based factors should be further examined.

Objective The aim of this study is to assess whether the risk of postpartum readmission within 6 weeks of giving birth differs for women who had stillbirths compared with live births. Study design Using data from the Office of Statewide Health Planning and Development in California, we performed a population-based cohort study of 7,398,640 births between 1999 and 2011. We identified diagnoses and procedures associated with the first postpartum hospital readmission that occurred within 6 weeks after giving birth. We used log-binomial models to estimate relative risk (RR) of postpartum readmission for women who had stillbirth compared with live birth deliveries, adjusting for maternal demographic, prepregnancy, pregnancy, and delivery characteristics. Results The rate of postpartum readmission was higher among women who had stillbirths compared with women who had live births (206 and 96 per 10,000 births, respectively). After adjusting for maternal demographic and medical characteristics, the risk of postpartum readmission for women who had stillbirths was nearly 1.5 times greater (adjusted RR = 1.47, 95% confidence interval: 1.35-1.60) compared with live births. Among women with stillbirths, the most common indications at readmission were uterine infection or pelvic inflammatory disease, psychiatric conditions, hypertensive disorder, and urinary tract infection. Conclusion Based on our findings, women who have stillbirths are at higher risk of postpartum readmissions within 6 weeks of giving birth than women who have live births. Women who have stillbirths may benefit from additional monitoring and counseling after hospital discharge for potential postpartum medical and psychiatric complications. Key points · Women who have stillbirths are at nearly 1.5 times greater risk of postpartum readmission than women who have live births.. · Uterine infections and pelvic inflammatory disease, and psychiatric conditions are the most common reasons for readmission among women who had a stillbirth.. · Women who have stillbirths may benefit from additional monitoring and counseling after hospital discharge for potential postpartum medical and psychiatric complications..

Primary congenital glaucoma (PCG) and anterior segment defects (ASDs) are rare ocular malformations diagnosed early in life which can cause blindness. Pathogenic variants in several genes have been linked to these conditions, but little is known about nongenetic risk factors. We investigated the association between maternal nutrition and PCG and ASDs in the National Birth Defects Prevention Study, a large population-based, multicenter case-control study of major birth defects in the United States. Mothers of cases (n = 152) and control infants without a birth defect (n = 9,178) completed an interview which included a food frequency questionnaire capturing usual dietary intake in the year before pregnancy. Maternal nutrition was assessed through individual nutrient intake, calculating a Diet Quality Index for Pregnancy (DQI-P) score for each mother, and using latent class analysis to empirically derive four dietary patterns. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CI) using logistic regression. The results for individual nutrients varied, with some having an inverse or U-shaped pattern of association with increasing intake. The DQI-P was not associated with risk of PCG and ASDs (aOR 0.91; CI 0.49-1.66, highest vs. lowest quartile). The dietary pattern analysis suggested lower odds among women with a Prudent and Mexican dietary pattern (aOR 0.82, 95% CI 0.52-1.29; aOR 0.80, 95% CI 0.36-1.78, respectively) compared to those with a Western dietary pattern. We found that higher intake of some nutrients and certain dietary patterns may be inversely associated with PCG and ASDs, though caution is urged due to imprecision of estimates.

BackgroundUsing ICD-9 codes underestimates the prevalence of obesity in adults; however, the validity of these codes in studies of pregnancy-related outcomes is not known.ObjectivesTo compare classification of maternal obesity based on ICD-9 codes in hospital discharge records versus data from birth certificates in the same women, examine predictors of agreement, and assess how associations between obesity and two birth outcomes differ by source of weight data.MethodsThis population-based study included 2329145 California births between 2007 and 2012. We compared data on obesity from childbirth hospital discharge records (ICD-9 codes for obesity) and birth certificates (pre-pregnancy body mass index (BMI) calculated from weight and height) and identified predictors of agreement between the two sources. Logistic regression models assessed whether the two definitions of obesity resulted in different estimates of the associations of obesity with caesarean birth and large-for-gestational age.ResultsOverall, 464754 women (20.0%) had obesity based on their pre-pregnancy BMI while only 100002 (4.3%) had an obesity-related ICD-9 code. The sensitivity of ICD-9-based obesity was low at 16.2%; however, obesity codes were highly specific at 98.7%, with a negative predictive value of 82.5% and a positive predictive value of 75.2%. Among women with obesity identified by the birth certificate, those with pre-pregnancy and pregnancy-related complications (eg diabetes and hypertension) were more likely to have an obesity-related diagnosis in their delivery hospital discharge record. Using ICD-9 codes overestimated the association of obesity with caesarean birth and newborn large-for-gestational age.ConclusionsICD-9 codes in childbirth discharge records captured only one in five women with pre-pregnancy obesity. Sensitivity varied by maternal characteristics and conditions. This misclassification resulted in bias when examining the association of obesity and pregnancy-related outcomes.

Objective Our objective was to incorporate social and built environment factors into a compendium of multilevel factors among a cohort of very low birth weight infants to understand their contributions to inequities in NICU quality of care and support providers and NICUs in addressing these inequities via development of a health equity dashboard. Study design We examined bivariate associations between NICU patient pool and NICU catchment area characteristics and NICU quality of care with data from a cohort of 15,901 infants from 119 NICUs in California, born 2008–2011. Result NICUs with higher proportion of minority racial/ethnic patients and lower SES patients had lower quality scores. NICUs with catchment areas of lower SES, higher composition of minority residents, and more household crowding had lower quality scores. Conclusion Multilevel social factors impact quality of care in the NICU. Their incorporation into a health equity dashboard can inform providers of their patients’ potential resource needs.

BACKGROUND Fatty acids are crucial in embryologic development, including cardiogenesis. The impact of maternal periconceptional dietary fat intake on the risk of congenital heart defects (CHDs) has not been clearly elucidated. We hypothesized that maternal dietary fat intake during pregnancy is associated with risk of CHDs in offspring. METHODS We analyzed CHD cases and nonmalformed controls from the National Birth Defects Prevention Study, a case-control, multicenter population-based study of birth defects. We used multivariable logistic regression to analyze the association between maternal periconceptional dietary fat intake and occurrence of CHDs. RESULTS We examined 11,393 infants with CHDs (cases) and 11,029 infants without birth defects (controls). Multivariable analysis of maternal dietary fat intake adjusted for maternal energy intake demonstrated modest change in risk for 2 of the 25 CHDs analyzed; otherwise there was no association. Maternal dietary fat intake unadjusted for total energy was associated with increased risk for several CHDs. CONCLUSIONS After adjusting for total energy intake, maternal periconceptional dietary fat intake has a modest association with risk of a few specific CHDs. If maternal dietary fat intake does impact CHD risk, the effect is minimal. IMPACT In this large, case-control study, after adjusting for total caloric intake, maternal periconceptional dietary fat intake was not associated with increased odds of congenital heart defects. This study investigates the hypothesis that women's periconceptional fat intake alters the risk of congenital heart defects in offspring. Our results raise questions about the role maternal fat intake may play in cardiogenesis and risk of congenital heart defects. Additionally, they raise the question about whether maternal lipid metabolism, as opposed to fat intake, may influence cardiac development.

Prior studies report a lower risk of mortality among neonates with hypoplastic left heart syndrome (HLHS) who are born at a cardiac surgical center, but many neonates with HLHS are born elsewhere and transferred for repair. We investigated the associations between the distance from maternal home to birth hospital, the need for transfer after birth, sociodemographic factors, and mortality in infants with HLHS in California from 2006 to 2011.We used linked data from two statewide databases to identify neonates for this study. Three groups were included in the analysis: "lived close/not transferred," "lived close/transferred," and "lived far/not transferred." We defined "lived close" versus "lived far" as 11 miles, the median distance from maternal residence to birth hospital. Log-binomial regression models were used to identify the association between sociodemographic variables, distance to birth hospital and transfer. Cox proportional hazards models were used to identify the association between mortality and distance to birth hospital and transfer. Models were adjusted for sociodemographic variables.Infants in the lived close/not transferred and the lived close/transferred groups (vs. the lived far/not transferred group) were more likely to live in census tracts above the 75th percentile for poverty with relative risks 1.94 (95% confidence interval [CI] 1.41-2.68) and 1.21 (95% CI 1.05-1.40), respectively. Neonatal mortality was higher among the lived close/not transferred group compared with the lived far/not transferred group (hazard ratio 1.77, 95% CI 1.17-2.67).Infants born to mothers experiencing poverty were more likely to be born close to home. Infants with HLHS who were born close to home and not transferred to a cardiac center had a higher risk of neonatal mortality than infants who were delivered far from home and not transferred. Future studies should identify the barriers to delivery at a cardiac center for mothers experiencing poverty.

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.We assessed cross-outcome risks for subsequent stillbirth, preterm birth, and SGA.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 birthweight10th 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.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.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.

Objective To propose postpartum recovery domains. Design Concept elicitation study. Setting Semi-structured interviews. Population Ten writing committee members and 50 stakeholder interviews (23 postpartum women, nine general obstetricians, five maternal and fetal medicine specialists, eight nurses and five obstetric anaesthetists). Methods Alternating interviews and focus group meetings until concept saturation was achieved (no new themes discussed in three consecutive interviews). Interviews were digitally recorded and transcribed, and an iterative coding process was used to identify domains. Main outcome measures The primary outcome was to identify recovery domains. We also report key symptoms and concerns. Discussion frequency and importance scores (0-100; 0 = not important; 100 = vitally important to recovery) were used to rank domains. Discussion frequency was used to rank factors helping and hindering recovery, and to determine the greatest challenges experienced postpartum. Results Thirty-four interviews and two focus group meetings were performed. The 13 postpartum recovery domains identified, (ranked highest to lowest) were: psychosocial distress, surgical/medical factors, infant feeding and breast health, psychosocial support, pain, physical function, sleep, motherhood experience, infant health, fatigue, appearance, sexual function and cognition. The most frequently discussed factors facilitating postpartum recovery were: family support, lactation/breastfeeding support and partner support. The most frequently discussed factor hindering recovery was inadequate social support. The most frequent challenges reported were: breastfeeding (week 1), breastfeeding (week 3) and sleep (week 6). Conclusions We propose 13 domains that comprehensively describe recovery in women delivering in a single centre within the USA. This provides a novel framework to study the postpartum recovery process. Tweetable abstract We propose 13 postpartum recovery domains that provide a framework to study the recovery process following childbirth.

Postpartum readmissions (PPRs) represent a critical marker of maternal morbidity after hospital childbirth. Most severe maternal morbidity (SMM) events result in a hospital admission, but most PPRs do not have evidence of SMM. Little is known about PPR and SMM beyond the first 6 weeks postpartum. We examined the associations of maternal demographic and clinical factors with PPR within 12 months postpartum. We categorized PPR as being with or without evidence of SMM to assess whether risk factors and timing differed. Using the Oregon All Payer All Claims database, we analyzed hospital births from 2012–2017. We used log-binomial regression to estimate associations between maternal factors and PPR. Our final analytical sample included 158,653 births. Overall, 2.6% (n = 4,141) of births involved at least 1 readmission within 12 months postpartum (808 (19.5% of PPRs) with SMM). SMM at delivery was the strongest risk factor for PPR with SMM (risk ratio (RR) = 5.55, 95% confidence interval (CI): 4.14, 7.44). PPR without SMM had numerous risk factors, including any mental health diagnosis (RR = 2.10, 95% CI: 1.91, 2.30), chronic hypertension (RR = 2.17, 95% CI: 1.85, 2.55), and prepregnancy diabetes (RR = 2.85, 95% CI: 2.47, 3.30), all which were on par with SMM at delivery (RR = 1.89, 95% CI: 1.49, 2.40).