Subsequent kidney transplant after pediatric heart transplant: Prevalence and risk factors.

Pediatric heart failure and transplantation carry associated risks for kidney failure and potential need for kidney transplant following pediatric heart transplantation (KT/pHT). This retrospective, United Network of Organ Sharing study of 10,030 pediatric heart transplants (pHTs) from 1987 to 2020 aimed to determine the incidence of waitlisting for and completion of KT/pHT, risk factors for KT/pHT, and risk factors for nonreceipt of a KT/pHT. Among pHT recipients, 3.4% were waitlisted for KT/pHT (median time of 14 years after pHT). Among those waitlisted, 70% received a KT/pHT, and 18% died on the waitlist at a median time of 0.8 years from KT/pHT waitlisting (median age of 20 years). Moderate-high sensitization at KT/pHT waitlisting (calculated panel reactive antibody, ≥ 20%) was associated with a lower likelihood of KT/pHT (adjusted hazard ratio, 0.67; 95% confidence interval, 0.47-0.95). Waitlisting for heart transplantation simultaneously with kidney transplant (adjusted hazard ratio, 3.73; 95% confidence interval, 2.01-6.92) was associated with increased risk of death on the KT/pHT waitlist. While the prevalence of KT/pHT is low, there is substantial mortality among those waitlisted for KT/pHT. These findings suggest a need to consider novel risk factors for nonreceipt of KT/pHT and death on the waitlist in prioritizing criteria/guidelines for simultaneous heart-kidney transplantation.

Latent class analysis to characterize neonatal risk for neurodevelopmental differences.

BACKGROUND: Neonatal risk factors, such as preterm birth and low birth weight, have been robustly linked to neurodevelopmental deficits, yet it is still unclear why some infants born preterm and/or low birth weight experience neurodevelopmental difficulties while others do not. The current study investigated this heterogeneity in neurodevelopmental abilities by examining additional neonatal morbidities as risk factors, utilizing latent class analysis to classify neonates into groups based on similar neonatal risk factors, and including neonates from the full spectrum of gestational age. METHODS: Neonates who received neonatal care at an academic public hospital during an almost 10-year period (n = 19,951) were included in the latent class analysis, and 21 neonatal indicators of health were used. Neonatal class, sex, and the interaction between neonatal class and sex were used to examine differences in neurodevelopment at 18 months of age in a typically developing population. RESULTS: The best fitting model included five infant classes: healthy, hypoxic, critically ill, minorly ill, and complicated delivery. Scores on the parent-rated neurodevelopmental measure differed by class such that infants in the critically ill, minorly ill, and complicated delivery classes had lower scores. There was no main effect of sex on the neurodevelopmental measure scores, but the interaction between sex and neonatal class was significant for three out of five neurodevelopmental domains. CONCLUSIONS: The current study extends the understanding of risk factors in neurodevelopment by including several neonatal medical conditions that are often overlooked and by using a person-centered, as opposed to variable-centered, approach. Future work should continue to examine risk factors, such as maternal health during pregnancy and medical interventions for newborns, in relation to neonatal risks and neurodevelopment by using a person-centered approach.

Bypassing of nearest labor & delivery unit is contingent on rurality, wealth, and race.

Patient decisions to bypass the closest labor & delivery (L&D) facility in favor of other birthing locations can have consequences for the provision of health care in rural and micropolitan areas as patient volumes decline and payer mixes change. Among 220 589 uncomplicated births in Iowa, we document characteristics of birth parents who bypass their closest birthing facility, show how this bypassing behavior results in changed travel times to delivery facilities across the rural/urban divide, and indicate the parts of the state where bypassing behavior is most prevalent. From 2013 to 2019, 55.2% of deliveries occurred in facilities that were further from birthing parents' residences than the closest L&D facility. Bypassing is associated with White, non-Hispanic race/ethnicity, and private insurance status. Although bypassing is least common among micropolitan birth parents, this group has the greatest travel burden to birthing facilities and exhibits increasing rates of bypassing over time. Perinatal quality improvement programs can target locations and populations where low-risk birthing parents can be encouraged to deliver close to home if medically appropriate, particularly in small towns and rural areas. This can potentially alleviate the risk of obstetric deserts by ensuring L&D units maintain patient volumes necessary to continue operations.

Parent mental health and child behavior during the COVID-19 pandemic.

Objective: Child behavior, which encompasses both internalizing and externalizing behaviors, is associated with many outcomes, including concurrent and future mental health, academic success, and social well-being. Thus, understanding sources of variability in child behavior is crucial for developing strategies aimed at equipping children with necessary resources. Parental mental health (PMH) difficulties and preterm birth may be risk factors for child behavior (CB) problems. Moreover, not only are PMH difficulties more common among parents of preterm children, but preterm children might also be more sensitive than full-term children to environmental stressors. In this study, we examined how PMH and CB changed during the COVID-19 pandemic, how change in PMH related to change in CB, and whether preterm children were more susceptible than full-term children to change in PMH. Methods: Parents that participated in a study prior to the pandemic were invited to complete follow-up questionnaires during the pandemic about PMH and CB. Forty-eight parents completed follow-up questionnaires. Results: Our results suggested that parental depression symptoms, children's internalizing symptoms, and children's externalizing symptoms significantly increased, and parental well-being significantly decreased during the pandemic. Change in parental depression symptoms, but not change in parental anxiety symptoms or parental well-being, was associated with change in children's internalizing and externalizing symptoms. Prematurity did not moderate change in PMH, change in CB, or the effect of change in PMH on change in CB. Conclusion: Our findings have the potential to inform efforts aimed at equipping children with behavioral resources.

Risk of early birth by body mass index in a propensity score-matched sample: A retrospective cohort study.

OBJECTIVE: Evaluate the risk of preterm (<37 weeks) or early term birth (37 or 38 weeks) by body mass index (BMI) in a propensity score-matched sample. DESIGN: Retrospective cohort analysis. SETTING: California, USA. POPULATION: Singleton live births from 2011-2017. METHODS: Propensity scores were calculated for BMI groups using maternal factors. A referent sample of women with a BMI between 18.5 and <25.0 kg/m2 was selected using exact propensity score matching. Risk ratios for preterm and early term birth were calculated. MAIN OUTCOME MEASURES: Early birth. RESULTS: Women with a BMI <18.5 kg/m2 were at elevated risk of birth of 28-31 weeks (relative risk [RR] 1.2, 95% CI 1.1-1.4), 32-36 weeks (RR 1.3, 95% CI 1.2-1.3), and 37 or 38 weeks (RR 1.1, 95% CI 1.1-1.1). Women with BMI ≥25.0 kg/m2 were at 1.2-1.4-times higher risk of a birth <28 weeks and were at reduced risk of a birth between 32 and 36 weeks (RR 0.8-0.9) and birth during the 37th or 38th week (RR 0.9). CONCLUSION: Women with a BMI <18.5 kg/m2 were at elevated risk of a preterm or early term birth. Women with BMI ≥25.0 kg/m2 were at elevated risk of a birth <28 weeks. Propensity score-matched women with BMI ≥30.0 kg/m2 were at decreased risk of a spontaneous preterm birth with intact membranes between 32 and 36 weeks, supporting the complexity of BMI as a risk factor for preterm birth. TWEETABLE ABSTRACT: Propensity score-matched women with BMI ≥30 kg/m2 were at decreased risk of a late spontaneous preterm birth.

Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity.

BACKGROUND: Identifying preterm infants at risk for mortality or major morbidity traditionally relies on gestational age, birth weight, and other clinical characteristics that offer underwhelming utility. We sought to determine whether a newborn metabolic vulnerability profile at birth can be used to evaluate risk for neonatal mortality and major morbidity in preterm infants. METHODS: This was a population-based retrospective cohort study of preterm infants born between 2005 and 2011 in California. We created a newborn metabolic vulnerability profile wherein maternal/infant characteristics along with routine newborn screening metabolites were evaluated for their association with neonatal mortality or major morbidity. RESULTS: Nine thousand six hundred and thirty-nine (9.2%) preterm infants experienced mortality or at least one complication. Six characteristics and 19 metabolites were included in the final metabolic vulnerability model. The model demonstrated exceptional performance for the composite outcome of mortality or any major morbidity (AUC 0.923 (95% CI: 0.917-0.929). Performance was maintained across mortality and morbidity subgroups (AUCs 0.893-0.979). CONCLUSIONS: Metabolites measured as part of routine newborn screening can be used to create a metabolic vulnerability profile. These findings lay the foundation for targeted clinical monitoring and further investigation of biological pathways that may increase the risk of neonatal death or major complications in infants born preterm. IMPACT: We built a newborn metabolic vulnerability profile that could identify preterm infants at risk for major morbidity and mortality. Identifying high-risk infants by this method is novel to the field and outperforms models currently in use that rely primarily on infant characteristics. Utilizing the newborn metabolic vulnerability profile for precision clinical monitoring and targeted investigation of etiologic pathways could lead to reductions in the incidence and severity of major morbidities associated with preterm birth.

Machine learning guided postnatal gestational age assessment using new-born screening metabolomic data in South Asia and sub-Saharan Africa.

BACKGROUND: Babies born early and/or small for gestational age in Low and Middle-income countries (LMICs) contribute substantially to global neonatal and infant mortality. Tracking this metric is critical at a population level for informed policy, advocacy, resources allocation and program evaluation and at an individual level for targeted care. Early prenatal ultrasound examination is not available in these settings, gestational age (GA) is estimated using new-born assessment, last menstrual period (LMP) recalls and birth weight, which are unreliable. Algorithms in developed settings, using metabolic screen data, provided GA estimates within 1-2 weeks of ultrasonography-based GA. We sought to leverage machine learning algorithms to improve accuracy and applicability of this approach to LMICs settings. METHODS: This study uses data from AMANHI-ACT, a prospective pregnancy cohorts in Asia and Africa where early pregnancy ultrasonography estimated GA and birth weight are available and metabolite screening data in a subset of 1318 new-borns were also available. We utilized this opportunity to develop machine learning (ML) algorithms. Random Forest Regressor was used where data was randomly split into model-building and model-testing dataset. Mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate performance. Bootstrap procedures were used to estimate confidence intervals (CI) for RMSE and MAE. For pre-term birth identification ROC analysis with bootstrap and exact estimation of CI for area under curve (AUC) were performed. RESULTS: Overall model estimated GA had MAE of 5.2 days (95% CI 4.6-6.8), which was similar to performance in SGA, MAE 5.3 days (95% CI 4.6-6.2). GA was correctly estimated to within 1 week for 85.21% (95% CI 72.31-94.65). For preterm birth classification, AUC in ROC analysis was 98.1% (95% CI 96.0-99.0; p < 0.001). This model performed better than Iowa regression, AUC Difference 14.4% (95% CI 5-23.7; p = 0.002). CONCLUSIONS: Machine learning algorithms and models applied to metabolomic gestational age dating offer a ladder of opportunity for providing accurate population-level gestational age estimates in LMICs settings. These findings also point to an opportunity for investigation of region-specific models, more focused feasible analyte models, and broad untargeted metabolome investigation.

Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.

Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, possibly damaging, nucleotide variants in mothers from families with recurrent spontaneous preterm births (SPTB). DNA samples from 17 Finnish mothers who delivered at least one infant preterm were subjected to whole exome sequencing. All mothers were of northern Finnish origin and were from seven multiplex families. Additional replication samples of European origin consisted of 93 Danish sister pairs (and two sister triads), all with a history of a preterm delivery. Rare exonic variants (frequency <1%) were analyzed to identify genes and pathways likely to affect SPTB susceptibility. We identified rare, possibly damaging, variants in genes that were common to multiple affected individuals. The glucocorticoid receptor signaling pathway was the most significant (p<1.7e-8) with genes containing these variants in a subgroup of ten Finnish mothers, each having had 2-4 SPTBs. This pathway was replicated among the Danish sister pairs. A gene in this pathway, heat shock protein family A (Hsp70) member 1 like (HSPA1L), contains two likely damaging missense alleles that were found in four different Finnish families. One of the variants (rs34620296) had a higher frequency in cases compared to controls (0.0025 vs. 0.0010, p = 0.002) in a large preterm birth genome-wide association study (GWAS) consisting of mothers of general European ancestry. Sister pairs in replication samples also shared rare, likely damaging HSPA1L variants. Furthermore, in silico analysis predicted an additional phosphorylation site generated by rs34620296 that could potentially affect chaperone activity or HSPA1L protein stability. Finally, in vitro functional experiment showed a link between HSPA1L activity and decidualization. In conclusion, rare, likely damaging, variants in HSPA1L were observed in multiple families with recurrent SPTB.

Correction: Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth.

[This corrects the article DOI: 10.1371/journal.pgen.1007394.].

Maternal cigarette smoking before and during pregnancy and the risk of preterm birth: A dose-response analysis of 25 million mother-infant pairs.

BACKGROUND: Most of the women who smoke before pregnancy continue smoking during pregnancy, and some start to quit smoking after being pregnant, although existing guidelines for pregnancy recommend that women who smoke should quit smoking before pregnancy. Findings about the timing and intensity of maternal smoking, especially low-intensity smoking (1-9 cigarettes per day), and preterm birth are still inconsistent and ambiguous. This study aimed to examine the association of the timing of smoking and doses of smoking before pregnancy and during the first or second trimester of pregnancy with preterm birth in a large-scale population-based retrospective cohort study. METHODS AND FINDINGS: We used nationwide birth certificate data from singleton mother-infant pairs in the United States National Vital Statistics System, 2011-2018. All adult women with live singleton births, without preexisting hypertension or diabetes, and with complete data on smoking and gestational age at delivery were included. Participants reported their smoking status (yes or no) and daily number of cigarettes consumed before and during each trimester of pregnancy. The outcome of interest was preterm birth, defined as a birth before 37 weeks of gestation. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence intervals (CIs) of preterm birth associated with smoking status and the number of cigarettes consumed, adjusting for maternal age, race/ethnicity, parity, education levels, prepregnancy BMI, previous history of preterm birth, marital status, infant sex, and initiation of prenatal care. This study included 25,623,479 women, with a mean age of 29 years (range 20-50 years); 13,742,486 (53.6%) participants were of non-Hispanic white ancestry, 5,971,598 (23.3%) of Hispanic ancestry, and 3,417,456 (13.34%) of non-Hispanic black ancestry. The prevalence of preterm birth was 9.3% (n = 2,378,398). We found that maternal smoking during pregnancy, even at a very low level of intensity, was associated with an increased risk of preterm delivery. The adjusted ORs (95% CI) of preterm birth for mothers who smoked 1-2, 3-5, 6-9, 10-19, and ≥20 cigarettes per day during the first trimester compared with mothers who did not smoke were 1.31 (1.29-1.33), 1.31 (1.30-1.32), 1.33 (1.31-1.35), 1.44 (1.43-1.45), and 1.53 (1.52-1.55), respectively (all P values < 0.001), whereas for those who smoked during the second trimester, the corresponding ORs were 1.37 (1.35-1.39), 1.36 (1.35-1.38), 1.36 (1.34-1.38), 1.48 (1.47-1.49), and 1.59 (1.58-1.61), respectively (all P values < 0.001). Furthermore, smokers who quit before pregnancy, regardless of smoking intensity, had a comparable risk of preterm birth with nonsmokers, although this was not the case when cessation occurred in the first or second trimester of pregnancy. The major limitation of this study is the self-reported information about smoking, which may be subject to information bias. In addition, we cannot rule out the possibility of residual confounding caused by unmeasured factors in an observational research design. CONCLUSIONS: In this study, we observed that low-intensity cigarette consumption during either the first or second trimester of pregnancy, even as low as 1-2 cigarettes per day, was associated with an increased risk of preterm birth. These findings suggest that there is no safe level or safe trimester for maternal smoking during pregnancy. Women of reproductive age who smoke should be strongly encouraged and supported to quit smoking before pregnancy.

Genetic Associations with Gestational Duration and Spontaneous Preterm Birth.

BACKGROUND: Despite evidence that genetic factors contribute to the duration of gestation and the risk of preterm birth, robust associations with genetic variants have not been identified. We used large data sets that included the gestational duration to determine possible genetic associations. METHODS: We performed a genomewide association study in a discovery set of samples obtained from 43,568 women of European ancestry using gestational duration as a continuous trait and term or preterm (<37 weeks) birth as a dichotomous outcome. We used samples from three Nordic data sets (involving a total of 8643 women) to test for replication of genomic loci that had significant genomewide association (P<5.0×10-8) or an association with suggestive significance (P<1.0×10-6) in the discovery set. RESULTS: In the discovery and replication data sets, four loci (EBF1, EEFSEC, AGTR2, and WNT4) were significantly associated with gestational duration. Functional analysis showed that an implicated variant in WNT4 alters the binding of the estrogen receptor. The association between variants in ADCY5 and RAP2C and gestational duration had suggestive significance in the discovery set and significant evidence of association in the replication sets; these variants also showed genomewide significance in a joint analysis. Common variants in EBF1, EEFSEC, and AGTR2 showed association with preterm birth with genomewide significance. An analysis of mother-infant dyads suggested that these variants act at the level of the maternal genome. CONCLUSIONS: In this genomewide association study, we found that variants at the EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C loci were associated with gestational duration and variants at the EBF1, EEFSEC, and AGTR2 loci with preterm birth. Previously established roles of these genes in uterine development, maternal nutrition, and vascular control support their mechanistic involvement. (Funded by the March of Dimes and others.).

Cohort study of respiratory hospital admissions, air quality and sociodemographic factors in preterm infants born in California.

BACKGROUND: Preterm infants suffer from respiratory morbidity especially during the first year of life. OBJECTIVE: To investigate the association of air quality and sociodemographic indicators on hospital admission rates for respiratory causes. METHODS: This is a retrospective cohort study. We identified all live-born preterm infants in California from 2007 to 2012 in a population-based administrative data set and linked them to a data set measuring several air quality and sociodemographic indicators at the census tract level. All sociodemographic and air quality predictors were divided into quartiles (first quartile most favourable to the fourth quartile least favourable). Mixed effect logistic models to account for clustering at the census tract level were used to investigate associations between chronic air quality and sociodemographic indicators respiratory hospital admission during the first year of life. RESULTS: Of 205 178 preterm infants, 5.9% (n = 12 033) were admitted to the hospital for respiratory causes during the first year. In the univariate analysis, comparing the first to the fourth quartile of chronic ozone (risk ratio [RR] 1.29, 95% confidence interval [CI] 1.21, 1.37), diesel (RR 1.10, 95% CI 1.02, 1.17) and particulate matter 2.5 (RR 1.07, 95% CI 1.01, 1.14) exposure were associated with hospital admission during the first year. Following adjustment for confounders, the risk ratios for hospital admission during the first year were 1.53 (95% CI 1.37, 1.72) in relation to educational attainment (per cent of the population over age 25 with less than a high school education) and 1.23 (95% CI 1.09, 1.38) for poverty (per cent of the population living below two times the federal poverty level). CONCLUSIONS: Among preterm infants, respiratory hospital admissions in the first year in California are associated with socioeconomic characteristics of the neighbourhood an individual is living in.

Preterm birth and nativity among Black women with gestational diabetes in California, 2013-2017: a population-based retrospective cohort study.

BACKGROUND: Despite the disproportionate prevalence of gestational diabetes (GDM) and preterm birth (PTB) and their associated adverse perinatal outcomes among Black women, little is known about PTB among Black women with GDM. Specifically, the relationship between PTB by subtype (defined as indicated PTB and spontaneous PT labor) and severity, GDM, and nativity has not been well characterized. Here we examine the risk of PTB by severity (early < 34 weeks, late 34 to 36 weeks) and early term birth (37 to 38 weeks) by nativity among Black women with GDM in California. METHODS: This retrospective cohort study used linked birth certificate and hospital discharge data for 8609 of the 100,691 self-identifying non-Hispanic Black women with GDM who had a singleton live birth between 20 and 44 weeks gestation in California in 2013-2017. Adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were examine risks for PTB, by severity and subtype, and early term birth using multivariate regression modeling. RESULTS: Approximately, 83.9% of Black women with GDM were US-born and 16.1% were foreign-born. The overall prevalence of early PTB, late PTB, and early term birth was 3.8, 9.5, and 29.9%, respectively. Excluding history of prior PTB, preeclampsia was the greatest overall risk factor for early PTB (cOR = 6.7, 95%, CI 5.3 to 8.3), late PTB (cOR = 4.3, 95%, CI 3.8 to 5.0), and early term birth (cOR = 1.8, 95%, CI 1.6 to 2.0). There was no significant difference in the prevalence of PTB by subtypes and nativity (p = 0.5963). Overall, 14.2% of US- compared to 8.9% of foreign-born women had a PTB (early PTB: aOR = 0.56, 95%, CI 0.38 to 0.82; late PTB: aOR = 0.57, 95%, CI 0.45 to 0.73; early term birth: aOR = 0.67, 95%, CI 0.58 to 0.77). CONCLUSIONS: Foreign-born status remained protective of PTB, irrespective of severity and subtype. Preeclampsia, PTB, and GDM share pathophysiologic mechanisms suggesting a need to better understand differences in perinatal stress, chronic disease, and vascular dysfunction based on nativity in future epidemiologic studies and health services research.

Health Advantages and Disparities in Preterm Birth Among Immigrants Despite Disparate Sociodemographic, Behavioral, and Maternal Risk Factors in San Diego, California.

INTRODUCTION: Reproductive health advantages have been reported among selected immigrants, but few studies have included new immigrants and refugees, nor simultaneously adjusted for socioeconomic, behavioral, and medical disparities. METHODS: We examined the risk of preterm birth (PTB, < 37 weeks' gestation) among singleton live births in San Diego County from 2007 to 2012. Multivariable regression was used to compare PTB (1) by nativity within racial/ethnic groups and (2) among immigrants compared to United States (US) born Whites, while adjusting for sociodemographic, behavioral, reproductive and medical variables. RESULTS: Among 230,878 singleton live births, overall PTB prevalence was highest among parturient women who were US-born Blacks (10.9%), Philippine (10.8%) and US-born Filipinas (10.7%), and US-born Asians (8.6%) despite differences in socioeconomic and maternal risk factors, and lowest among Somali (5.5%) migrants. Blacks born in Somalia or outside of the US, had significantly lower overall PTB prevalence compared to US-born Blacks (5.5% vs 7.6% vs 10.9%). Compared to US-born Whites, spontaneous PTB risk was significantly lower among Somali migrants (4.8% vs 3.7%, adjusted relative risk, aRR 0.7 [95% Confidence Intervals 0.5-0.9]), but higher among Philippine migrants (4.8% vs 7.7%, aRR 1.4 [1.3-1.6]). The strongest risk factor for overall PTB among nulliparous US-born Blacks was preexisting diabetes (aRR 3.81 [2.05-7.08]), and preexisting hypertension among Filipinas (aRR: 3.27 [2.36-4.54] and US-born Asians (aRR: 3.64 [1.61-8.24]). CONCLUSION: Black migrants had lower PTB prevalence compared to US-born Blacks, but this immigrant advantage was not observed in other racial/ethnic groups. Compared to US-born Whites, Somali migrants had significantly lower risk of spontaneous PTB while Filipinas had elevated risk.

Morbidity of Persistent Pulmonary Hypertension of the Newborn in the First Year of Life.

OBJECTIVE: To assess postdischarge mortality and morbidity in infants diagnosed with different etiologies and severities of persistent pulmonary hypertension of the newborn (PPHN), and to identify risk factors for these adverse clinical outcomes. STUDY DESIGN: This was a population-based study using an administrative dataset linking birth and death certificates, hospital discharge and readmissions records from 2005 to 2012 in California. Cases were infants ≥34 weeks' gestational age with International Classification of Diseases,9th edition, codes consistent with PPHN. The primary outcome was defined as postdischarge mortality or hospital readmission during the first year of life. Crude and adjusted risk ratio (aRR) with 95% CIs were calculated to quantify the risk for the primary outcome and to identify risk factors. RESULTS: Infants with PPHN (n = 7847) had an aRR of 3.5 (95% CI, 3.3-3.7) for the primary outcome compared with infants without PPHN (n = 3 974 536), and infants with only mild PPHN (n = 2477) had an aRR of 2.2 (95% CI, 2.0-2.5). Infants with congenital diaphragmatic hernia as the etiology for PPHN had an aRR of 8.2 (95% CI, 6.7-10.2) and infants with meconium aspiration syndrome had an aRR of 4.2 (95% CI, 3.7-4.6) compared with infants without PPHN. Hispanic ethnicity, small for gestational age, severe PPHN, and etiology of PPHN were risk factors for the primary outcome. CONCLUSIONS: The postdischarge morbidity burden of infants with PPHN is large. These findings extend to infants with mild PPHN and etiologies with pulmonary vascular changes that are thought to be short term and recoverable. These data could inform counseling of parents.

An Evaluation of Sexually Transmitted Infection and Odds of Preterm or Early-Term Birth Using Propensity Score Matching.

BACKGROUND: Few studies have examined the relationship between sexually transmitted infections (STIs) and preterm birth (<37 weeks gestation) by subtype (<32 weeks, 32-36 weeks, spontaneous, provider-initiated). Here, we evaluate the odds of preterm (by subtype) and early-term (37 and 38 weeks gestation) birth in women with an STI compared with a propensity score-matched reference population. METHODS: The sample was selected from California births in 2007 to 2012. Sexually transmitted infection was defined as a maternal diagnosis of chlamydia, gonorrhea, or syphilis in the birth certificate or hospital discharge record. A reference sample of women without an STI was selected using exact propensity score matching on maternal factors. Odds of preterm and early-term birth were calculated. RESULTS: Sixteen thousand three hundred twelve women were identified as having an STI during pregnancy and an exact propensity score-matched control was identified for 97.2% (n = 15,860). Women with an indication of syphilis during pregnancy were at 1.6 times higher odds of having a preterm birth and, in particular, at elevated odds of a birth less than 32 weeks due to preterm premature rupture of the membranes or provider-initiated birth (odds ratios 4.0-4.2). Women with gonorrhea were at increased odds of a preterm birth, a birth less than 32 weeks, or an early-term birth (odds ratios 1.2-1.8). Chlamydia did not raise the odds of either a preterm or early-term birth. CONCLUSIONS: Gonorrhea and syphilis increased the odds of a preterm birth. Gonorrhea also increased the odds of an early-term birth. Chlamydia did not raise the odds of an early birth.

High risk of spontaneous preterm birth among infants with gastroschisis.

We examined the association between gastroschisis and preterm birth (PTB, <37 weeks) by subtype. The sample was drawn from singleton live births in California from 2007 to 2012 contained in a birth cohort file maintained by the California Office of Statewide Health Planning and Development (n = 2,891,965; 1,421 with gastroschisis). Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for PTB by gestational age (<34, 34-36, and any <37 weeks) and by type (spontaneous labor with intact membranes, preterm premature rupture of the membranes [PPROM], provider initiated) and were adjusted for maternal characteristics. Over 44.5% of infants with gastroschisis were born preterm because of spontaneous etiologies; notably, 8.4% of infants with gastroschisis were born <34 weeks because of spontaneous etiologies (adjusted RRs 9.1-12.2). Overall, 53.7% of infants with gastroschisis were born preterm compared with only 6.9% of infants without gastroschisis (adjusted RR 15.2, 95% CI 13.6-19.5) and are at particularly high risk of spontaneous PTB. Nearly 9% of infants with gastroschisis delivered <34 weeks, regardless of preterm etiology, indicating that these infants are at great risk for PTB morbidities in addition to the complications from gastroschisis.

Previous Adverse Outcome of Term Pregnancy and Risk of Preterm Birth in Subsequent Pregnancy.

Objective Evaluate risk of preterm birth (PTB, < 37 completed weeks' gestation) among a population of women in their second pregnancy with previous full term birth but other adverse pregnancy outcome. Methods The sample included singleton live born infants between 2007 and 2012 in a birth cohort file maintained by the California Office of Statewide Health Planning and Development. The sample was restricted to women with two pregnancies resulting in live born infants and first birth between 39 and 42 weeks' gestation. Logistic regression was used to calculate the risk of PTB in the second birth for women with previous adverse pregnancy outcome including: small for gestational age (SGA) infant, preeclampsia, placental abruption, or neonatal death (≤ 28 days). Risks were adjusted for maternal factors recorded for second birth. Results The sample included 133,622 women. Of the women with any previous adverse outcome, 4.7% had a PTB while just 3.0% of the women without a previous adverse outcome delivered early (relative risk adjusted for maternal factors known at delivery 1.4, 95% CI 1.3-1.5). History of an SGA infant, placental abruption, or neonatal death increased the adjusted risk of PTB in their second birth by 1.5-3.7-fold. History of preeclampsia did not elevate the risk of a preterm birth in the subsequent birth. Conclusions for Practice The findings indicate that women with previous SGA infant, placental abruption, or neonatal death, despite a term delivery, may be at increased risk of PTB in the subsequent birth. These women may be appropriate participates for future interventions aimed at reduction in PTB.

A review of metabolomics approaches and their application in identifying causal pathways of childhood asthma.

Because asthma is a disease that results from host-environment interactions, an approach that allows assessment of the effect of the environment on the host is needed to understand the disease. Metabolomics has appealing potential as an application to study pathways to childhood asthma development. The objective of this review is to provide an overview of metabolomics methods and their application to understanding host-environment pathways in asthma development. We reviewed recent literature on advances in metabolomics and their application to study pathways to childhood asthma development. We highlight the (1) potential of metabolomics in understanding the pathogenesis of disease and the discovery of biomarkers; (2) choice of metabolomics techniques, biospecimen handling, and data analysis; (3) application to studying the role of the environment on asthma development; (4) review of metabolomics applied to the outcome of asthma; (5) recommendations for application of metabolomics-based -omics data integration in understanding disease pathogenesis; and (6) limitations. In conclusion, metabolomics allows use of biospecimens to identify useful biomarkers and pathways involved in disease development and subsequently to inform a greater understanding of disease pathogenesis and endotypes and prediction of the clinical course of childhood asthma phenotypes.

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies.