Adverse live-born pregnancy outcomes among pregnant people with anorexia nervosa.

BACKGROUND: Previous findings related to the association of adverse pregnancy outcomes with anorexia nervosa are mixed. OBJECTIVE: This study aimed to investigate the association of adverse live-born pregnancy outcomes with anorexia nervosa using adjustment modeling accounting for confounding factors, and a mediation analysis addressing the contribution of underweight prepregnancy body mass index and gestational weight gain to those outcomes. STUDY DESIGN: The sample included California live-born singletons with births between 2007 and 2021. The administrative data set contained birth certificates linked to hospital discharge records. Anorexia nervosa diagnosis during pregnancy was obtained from International Classification of Diseases codes on hospital discharge records. Adverse pregnancy outcomes examined included gestational diabetes, gestational hypertension, preeclampsia, anemia, antepartum hemorrhage, premature rupture of membranes, premature labor, cesarean delivery, oligohydramnios, placenta previa, chorioamnionitis, placental abruption, severe maternal morbidity, small for gestational age, large for gestational age, low birthweight, and preterm birth (by timing and indication). Risk of each adverse outcome was calculated using Poisson regression models. Unadjusted risk of each adverse outcome was calculated, and then the risks were adjusted for demographic factors. The final adjusted model included demographic factors, anxiety, depression, substance use, and smoking. A mediation analysis was performed to estimate the excess risk of adverse outcomes mediated by underweight prepregnancy body mass index and gestational weight gain below the American College of Obstetricians and Gynecologists recommendation. RESULTS: The sample included 241 pregnant people with a diagnosis of anorexia nervosa and 6,418,236 pregnant people without an eating disorder diagnosis. An anorexia nervosa diagnosis during pregnancy was associated with many adverse pregnancy outcomes in unadjusted models (relative risks ranged from 1.65 [preeclampsia] to 3.56 [antepartum hemorrhage]) in comparison with people without an eating disorder diagnosis. In the final adjusted models, birthing people with an anorexia nervosa diagnosis were more likely to have anemia, preterm labor, oligohydramnios, severe maternal morbidity, a small for gestational age or low-birthweight infant, and preterm birth between 32 and 36 weeks with spontaneous preterm labor (adjusted relative risks ranged from 1.43 to 2.55). Underweight prepregnancy body mass index mediated 7.78% of the excess in preterm births and 18.00% of the excess in small for gestational age infants. Gestational weight gain below the recommendation mediated 38.89% of the excess in preterm births and 40.44% of the excess in low-birthweight infants. CONCLUSION: Anorexia nervosa diagnosis during pregnancy was associated with a number of clinically important adverse pregnancy outcomes in comparison with people without an eating disorder diagnosis. Adjusting for anxiety, depression, substance use, and smoking during pregnancy decreased this risk. A substantial percentage of the excess risk of adverse outcomes was mediated by an underweight prepregnancy body mass index, and an even larger proportion of excess risk was mediated by gestational weight gain below the recommendation. This information is important for clinicians to consider when caring for patients with anorexia nervosa. Considering and treating anorexia nervosa and comorbid conditions and counseling patients about mediating factors such as preconception weight and gestational weight gain may improve live-born pregnancy outcomes among people with anorexia nervosa.

The validity of hospital diagnostic and procedure codes reflecting morbidity in preterm neonates born <32 weeks gestation.

OBJECTIVE: To determine the validity of diagnostic hospital billing codes for complications of prematurity in neonates <32 weeks gestation. STUDY DESIGN: Retrospective cohort data from discharge summaries and clinical notes (n = 160) were reviewed by trained, blinded abstractors for the presence of intraventricular hemorrhage (IVH) grades 3 or 4, periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), stage 3 or higher, retinopathy of prematurity (ROP), and surgery for NEC or ROP. Data were compared to diagnostic billing codes from the neonatal electronic health record. RESULTS: IVH, PVL, ROP and ROP surgery had strong positive predictive values (PPV > 75%) and excellent negative predictive values (NPV > 95%). The PPVs for NEC (66.7%) and NEC surgery (37.1%) were low. CONCLUSION: Diagnostic hospital billing codes were observed to be a valid metric to evaluate preterm neonatal morbidities and surgeries except in the instance of more ambiguous diagnoses such as NEC and NEC surgery.

Hypertensive disorders of pregnancy among women with a history of leukemia or lymphoma.

OBJECTIVE: Hypertension during pregnancy can adversely affect maternal and fetal health. This study assessed whether diagnosis of leukemia or lymphoma prior to pregnancy is associated with hypertensive disorders of pregnancy including gestational hypertension, preeclampsia and eclampsia. STUDY DESIGN: A cross-sectional study used two statewide population-based datasets that linked birth certificates with sources of maternal medical history: hospital discharges in California and Surveillance, Epidemiology, and End Results (SEER) cancer registry data in Iowa. Birth years included 2007-2012 in California and 1989-2018 in Iowa. MAIN OUTCOME MEASURES: Primary outcome measure was hypertension in pregnancy measured from combined birth certificate and hospital diagnoses in California (for gestational hypertension, preeclampsia, or eclampsia) and birth certificate information (gestational hypertension or eclampsia) in Iowa. RESULTS: After adjusting for maternal age, race, education, smoking, and plurality, those with a history of leukemia/lymphoma were at increased risk of hypertensive disorders of pregnancy in Iowa (odds ratio (OR) = 1.86; 95% CI 1.07-3.23), but not in California (OR = 1.12; 95% CI 0.87-1.43). In sensitivity analysis restricting to more severe forms of hypertension in pregnancy (preeclampsia and eclampsia) in the California cohort, the effect estimate increased (OR = 1.29; 95% CI 0.96-1.74). CONCLUSION: In a population-based linked cancer registry-birth certificate study, an increased risk of hypertensive disorders of pregnancy was observed among leukemia or lymphoma survivors. Findings were consistent but non-significant in a second, more ethnically diverse study population with less precise cancer history data. Improved monitoring and surveillance may be warranted for leukemia or lymphoma survivors throughout their pregnancies.

The risk of preterm birth among women with a history of leukemia or lymphoma.

OBJECTIVE: Leukemia and lymphoma are top cancers affecting children, adolescents and young adults with high five-year survival rates. Late effects of these cancers are a concern in reproductive-age patients, including pregnancy outcomes such as preterm birth. Our study aimed to evaluate whether diagnosis of leukemia or lymphoma prior to pregnancy was associated with preterm birth (<37 weeks gestation). METHODS: We conducted a cross-sectional study using a population-based dataset from California with linked birth certificates to hospital discharge records and an Iowa-based sample that linked birth certificates to Surveillance, Epidemiology, and End Results (SEER) cancer registry data. Preterm birth was defined using birth certificates. We ascertained history of leukemia and lymphoma using discharge diagnosis data in California and SEER registry in Iowa. RESULTS: Prevalence of preterm birth in California and Iowa was 14.6% and 12.0%, respectively, in women with a history of leukemia/lymphoma compared to 7.8% and 8.2%, respectively, in women without a cancer history. After adjusting for maternal age, race, education, smoking, and plurality, Women with history of leukemia/lymphoma were at an increased risk of having a preterm birth in California (odds ratio (OR) 1.89; 95% confidence interval (CI) 1.56-2.28) and Iowa (OR 1.61; 95% CI 1.10-2.37) compared to those with no cancer history. CONCLUSION: In both California and Iowa, women with a history of leukemia or lymphoma were at increased risk for preterm birth. This suggests the importance of counseling with a history of leukemia/lymphoma prior to pregnancy and increased monitoring of women during pregnancy.

Metabolic differences among newborns born to mothers with a history of leukemia or lymphoma.

BACKGROUND: Leukemia and lymphoma are cancers affecting children, adolescents, and young adults and may affect reproductive outcomes and maternal metabolism. We evaluated for metabolic changes in newborns of mothers with a history of these cancers. METHODS: A cross-sectional study was conducted on California births from 2007 to 2011 with linked maternal hospital discharge records, birth certificate, and newborn screening metabolites. History of leukemia or lymphoma was determined using ICD-9-CM codes from hospital discharge data and newborn metabolite data from the newborn screening program. RESULTS: A total of 2,068,038 women without cancer history and 906 with history of leukemia or lymphoma were included. After adjusting for differences in maternal age, infant sex, age at metabolite collection, gestational age, and birthweight, among newborns born to women with history of leukemia/lymphoma, several acylcarnitines were significantly (p < .001 - based on Bonferroni correction for multiple testing) higher compared to newborns of mothers without cancer history: C3-DC (mean difference (MD) = 0.006), C5-DC (MD = 0.009), C8:1 (MD = 0.008), C14 (MD = 0.010), and C16:1 (MD = 0.011), whereas citrulline levels were significantly lower (MD = -0.581) among newborns born to mothers with history of leukemia or lymphoma compared to newborns of mothers without a history of cancer. CONCLUSION: The varied metabolite levels suggest history of leukemia or lymphoma has metabolic impact on newborn offspring, which may have implications for future metabolic consequences such as necrotizing enterocolitis and urea cycle enzyme disorders in children born to mothers with a history of leukemia or lymphoma.

Mortality and Major Neonatal Morbidity in Preterm Infants with Serious Congenital Heart Disease.

OBJECTIVE: To investigate the trends of 1-year mortality and neonatal morbidities in preterm infants with serious congenital heart disease (CHD). STUDY DESIGN: This cohort study used a population-based administrative dataset of all liveborn infants of 26-36 weeks gestational age with serious CHD born in California between 2011 and 2017. We assessed 1-year mortality and major neonatal morbidities (ie, retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage grade >2, and periventricular leukomalacia) across the study period and compared these outcomes with those in infants without CHD. RESULTS: We identified 1921 preterm infants with serious CHD. The relative risk (RR) of death decreased by 10.6% for each year of the study period (RR, 0.89; 95% CI, 0.84-0.95), and the RR of major neonatal morbidity increased by 8.3% for each year (RR, 1.08; 95% CI, 1.02-1.15). Compared with preterm neonates without any CHD (n = 234 522), the adjusted risk difference (ARD) for mortality was highest at 32 weeks of gestational age (9.7%; 95% CI, 8.3%-11.2%), that for major neonatal morbidity was highest at 28 weeks (21.9%; 95% CI, 17.0%-26.9%), and that for the combined outcome was highest at 30 weeks (26.7%; 95% CI, 23.3%-30.1%). CONCLUSIONS: Mortality in preterm neonates with serious CHD decreased over the last decade, whereas major neonatal morbidities increased. Preterm infants with a gestational age of 28-32 weeks have the highest mortality or morbidity compared with their peers without CHD. These results support the need for specialized and focused medical neonatal care in preterm neonates with serious CHD.

The association between preterm birth and postpartum mental healthcare utilization among California birthing people.

BACKGROUND: While mental health conditions such as postpartum depression are common, little is known about how mental healthcare utilization varies after term versus preterm delivery. OBJECTIVE: This study aimed to determine whether preterm birth is associated with postpartum inpatient and emergency mental healthcare utilization. STUDY DESIGN: The study sample was obtained from a database of live-born neonates delivered in California between the years of 2011 and 2017. The sample included all people giving birth to singleton infants between the gestational age of 20 and 44 weeks. Preterm birth was defined as <37 weeks' gestation. Emergency department visits and hospitalizations with a mental health diagnosis within 1 year after birth were identified using International Classification of Diseases codes. Logistic regression was used to compare relative risks of healthcare utilization among people giving birth to preterm infants vs term infants, adjusting for the following covariates: age, race or ethnicity, parity, previous preterm birth, body mass index, tobacco use, alcohol or drug use, hypertension, diabetes mellitus, adequacy of prenatal care, education, insurance payer, and the presence of a mental health diagnosis before birth. Results were then stratified by mental health diagnosis before birth to determine whether associations varied based on mental health history. RESULTS: Of our sample of 3,067,069 births, 6.7% were preterm. In fully adjusted models, compared with people giving birth to term infants, people giving birth to preterm infants had a 1.5 times (relative risk; 95% confidence interval, 1.4-1.7) and 1.3 times (relative risk; 95% confidence interval, 1.2-1.4) increased risk of being hospitalized with a mental health diagnosis within 3 months and 1 year after delivery, respectively. People giving birth to preterm infants also had 1.4 times (95% confidence interval, 1.3-1.5) and 1.3 times (95% confidence interval, 1.2-1.4) increased risk of visiting the emergency department for a mental health diagnosis within 3 months and 1 year after birth, respectively. Stratifying by preexisting mental health diagnosis, preterm birth was associated with an elevated risk of mental healthcare utilization for people with and without a previous mental health diagnosis. CONCLUSION: We found that preterm birth is an independent risk factor for postpartum mental healthcare utilization. Our findings suggest that screening for and providing mental health resources to birthing people after delivery are crucial, particularly among people giving birth to preterm infants, regardless of mental health history.

Association between Z-score for birth weight and postoperative outcomes in neonates and infants with congenital heart disease.

OBJECTIVE: We hypothesized that infants with fetal growth restrictions have increased mortality and morbidity after congenital heart disease surgery. METHODS: The study included patients in The Society of Thoracic Surgeons Congenital Heart Surgery Database (2010-2016) who underwent cardiac surgery at a corrected gestational age of ≤44 weeks. Patients were classified as severely (birth weight Z-score -4 to -2), moderately (Z-score -2 to -1), and mildly growth restricted (Z-score -1.0 to -0.5) and compared with a reference population (Z-score 0-0.5). Multivariable logistic regression clustering on center was used to evaluate the association of birth weight Z-score with operative mortality and postoperative complications and its interaction with gestational age was assessed. RESULTS: In 25,244 patients, operative mortality was 8.6% and major complications occurred in 19.4%. Compared with the reference group, the adjusted odds ratio (AOR) of mortality was increased in infants with severe (AOR, 2.4; 95% confidence interval [CI], 2.0-3.0), moderate (AOR, 1.7; 95% CI, 1.4-2.0), and mild growth restriction (AOR, 1.4; 95% CI, 1.2-1.6). The AOR for major postoperative complications was increased for severe (AOR, 1.4; 95% CI, 1.2-1.7) and moderate growth restriction (AOR, 1.2; 95% CI, 1.1-1.4). There was significant interaction between birth weight Z-score and gestational age (P = .007). CONCLUSIONS: Even birth weight Z-scores slightly below average are independent risk factors for mortality and morbidity in infants who undergo cardiac surgery. The strongest association between poor fetal growth and operative mortality exists in early-term infants. These novel findings might account for some of the previously unexplained variation in cardiac surgical outcomes.

Pregnancy after bariatric surgery in women with rheumatic diseases and association with adverse birth outcomes.

BACKGROUND: Autoimmune rheumatic diseases (ARDs) and bariatric surgery are each risk factors for adverse birth outcomes. To date, no study has investigated their combined impact on birth outcomes. OBJECTIVES: The objective of this study was to evaluate the impact of bariatric surgery on pregnancy outcomes in women with an ARD. As a secondary comparison, we assessed the risk of bariatric surgery on the same outcomes in women without an ARD. SETTING: Records maintained by the California Office of Statewide Health Planning and Development. METHODS: This cohort study included infants born between 20-44 weeks of gestation in California between 2011-2018. Risks of adverse pregnancy outcomes were evaluated for women with a history of bariatric surgery as compared to women without a history of bariatric surgery, stratified by ARD, using log-linear regression with a Poisson distribution. RESULTS: The study included 3,574,165 infants, of whom 10,823 (0.3%) were born to women who had an ARD and 13,529 (0.38%) to women with a history of bariatric surgery. There were 155 infants born to women (0.0043%) with both an ARD and a history of bariatric surgery. In women with an ARD and without bariatric surgery, the prevalence of preterm births was 18%, compared to 17.4% in women with both ARD and bariatric surgery; in women without ARD but with prior bariatric surgery, the prevalence of preterm births was 13.7%, compared to 8.2% in women without bariatric surgery. Except for neonatal intensive care unit (NICU) admissions, women with an ARD and history of bariatric surgery were not at a statistically increased risk of having other adverse pregnancy outcomes as compared to women with an ARD and no history of bariatric surgery. CONCLUSION: Our study shows that women with ARD already have a high occurrence of several adverse birth outcomes, and this was not further increased by a history of bariatric surgery. The infants born to women with a history of ARD and bariatric surgery were admitted to the NICU significantly more than the infants born to women with an ARD and no history of bariatric surgery.

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.

Associations between unstable housing, obstetric outcomes, and perinatal health care utilization.

BACKGROUND: While there is a growing interest in addressing social determinants of health in clinical settings, there are limited data on the relationship between unstable housing and both obstetric outcomes and health care utilization. OBJECTIVE: The objective of the study was to investigate the relationship between unstable housing, obstetric outcomes, and health care utilization after birth. STUDY DESIGN: This was a retrospective cohort study. Data were drawn from a database of liveborn neonates linked to their mothers' hospital discharge records (2007-2012) maintained by the California Office of Statewide Health Planning and Development. The analytic sample included singleton pregnancies with both maternal and infant data available, restricted to births between the gestational age of 20 and 44 weeks, who presented at a hospital that documented at least 1 woman as having unstable housing using the International Classification of Diseases, ninth edition, codes (n = 2,898,035). Infants with chromosomal abnormalities and major birth defects were excluded. Women with unstable housing (lack of housing or inadequate housing) were identified using International Classification of Diseases, ninth edition, codes from clinical records. Outcomes of interest included preterm birth (<37 weeks' gestational age), early term birth (37-38 weeks gestational age), preterm labor, preeclampsia, chorioamnionitis, small for gestational age, long birth hospitalization length of stay after delivery (vaginal birth, >2 days; cesarean delivery, >4 days), emergency department visit within 3 months and 1 year after delivery, and readmission within 3 months and 1 year after delivery. We used exact propensity score matching without replacement to select a reference population to compare with the sample of women with unstable housing using a one-to-one ratio, matching for maternal age, race/ethnicity, parity, prior preterm birth, body mass index, tobacco use during pregnancy, drug/alcohol abuse during pregnancy, hypertension, diabetes, mental health condition during pregnancy, adequacy of prenatal care, education, and type of hospital. Odds of an adverse obstetric outcome were estimated using logistic regression. RESULTS: Of 2794 women with unstable housing identified, 83.0% (n = 2318) had an exact propensity score-matched control. Women with an unstable housing code had higher odds of preterm birth (odds ratio, 1.2, 95% confidence interval, 1.0-1.4, P < .05), preterm labor (odds ratio, 1.4, 95% confidence interval, 1.2-1.6, P < .001), long length of stay (odds ratio, 1.6, 95% confidence interval, 1.4-1.8, P < .001), emergency department visits within 3 months (odds ratio, 2.4, 95% confidence interval, 2.1-2.8, P < .001) and 1 year after birth (odds ratio, 2.7, 95% confidence interval, 2.4-3.0, P < .001), and readmission within 3 months (odds ratio, 2.7, 95% confidence interval, 2.2-3.4, P < .0014) and 1 year after birth (odds ratio, 2.6, 95% confidence interval, 2.2-3.0, P < .001). CONCLUSION: Unstable housing documentation is associated with adverse obstetric outcomes and high health care utilization. Housing and supplemental income for pregnant women should be explored as a potential intervention to prevent preterm birth and prevent increased health care utilization.

Patterns of Preterm Birth among Women of Native Hawaiian and Pacific Islander Descent.

OBJECTIVE: To describe the characteristics and risk factors for preterm birth in Hawaiian and Pacific Islander women. STUDY DESIGN: Retrospective cohort study of 10,470 women of Hawaiian or Pacific Islander descent drawn from a population-based birth cohort dataset in California. Variables were examined across preterm birth subtype (spontaneous, provider initiated) and by gestational age grouping (early preterm birth and late preterm birth) and all preterm births. RESULTS: Hawaiian/Pacific Islander women were at higher risk for preterm birth when they had fewer than three prenatal visits; were underweight, reported tobacco, alcohol, or illicit drugs use in pregnancy; had a diagnosis of anemia, gestational diabetes, preexisting diabetes, or hypertension with or without pre-eclampsia; or had a history of previous preterm birth. Obesity was found to be protective for preterm birth. CONCLUSION: Women of Hawaiian and Pacific Islander descent demonstrate a similar yet unique constellation of risk and protective factors for preterm birth as compared with other groups at high risk for preterm birth. Interventions aimed to prevent preterm birth need to support the specific needs of this population.

Maternal factors influencing late entry into prenatal care: a stratified analysis by race or ethnicity and insurance status.

Objective: Examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. Methods: The study population was drawn from singleton live births in California from 2007 to 2012 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and mother and infant hospital discharge records. The sample was restricted to infants delivered between 20 and 44 weeks gestation. Logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) for factors influencing late entry into prenatal care. Maternal age, education, smoking, drug or alcohol abuse/dependence, mental illness, participation in the Women, Infants and Children's program and rural residence were evaluated for women entering prenatal care > sixth month of gestation compared with women entering < fourth month. Backwards stepwise logistic regression was used to create final multivariable models of risk and protective factors for late prenatal care entry for each race or ethnicity and insurance payer. Results: The sample included 2,963,888 women. The percent of women with late entry into prenatal care was consistently higher among women with public versus private insurance. Less than 1% of white non-Hispanic and Asian women with private insurance entered prenatal care late versus more than 4% of white non-Hispanic and black women with public insurance. After stratifying by race or ethnicity and insurance status, women less than 18 years of age were more likely to enter prenatal care late, with young Asian women with private insurance at the highest risk (15.6%; adjusted RR 7.4, 95%CI 5.3-10.5). Among all women with private insurance, > 12-year education or age >34 years at term reduced the likelihood of late prenatal care entry (adjusted RRs 0.5-0.7). Drugs and alcohol abuse/dependence and residing in a rural county were associated with increased risk of late prenatal care across all subgroups (adjusted RRs 1.3-3.8). Participation in the Women, Infants, and Children's program was associated with decreased risk of late prenatal care for women with public insurance (adjusted RRs 0.6-0.7), but increased risk for women with private insurance (adjusted RRs 1.4-2.1). Conclusions: The percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. Participation in the Women, Infants, and Children's program and maternal age >34 years at delivery increased the likelihood of late prenatal care for some subgroups of women and decreased the likelihood for others. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care. Rationale: Optimal prenatal care includes initiation before the 14th week of gestation. Beginning care in the first trimester provides an opportunity for sonographic pregnancy dating or confirmation with best accuracy, which can later prove critical for management of preterm labor, maternal or fetal complications, or prolonged pregnancy. In order to improve maternal and infant health by increasing the number of women seeking prenatal care in the first trimester, it is important to examine the drivers for late entry. Here, we examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. We found the percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care.

Altered metabolites in newborns with persistent pulmonary hypertension.

BACKGROUND: There is an emerging evidence that pulmonary hypertension is associated with amino acid, carnitine, and thyroid hormone aberrations. We aimed to characterize metabolic profiles measured by the newborn screen (NBS) in infants with persistent pulmonary hypertension of the newborn (PPHN) METHODS: Nested case-control study from population-based database. Cases were infants with ICD-9 code for PPHN receiving mechanical ventilation. Controls receiving mechanical ventilation were matched 2:1 for gestational age, sex, birth weight, parenteral nutrition administration, and age at NBS collection. Infants were divided into derivation and validation datasets. A multivariable logistic regression model was derived from candidate metabolites, and the area under the receiver operator characteristic curve (AUROC) was generated from the validation dataset. RESULTS: We identified 1076 cases and 2152 controls. Four metabolites remained in the final model. Ornithine (OR 0.32, CI 0.26-0.41), tyrosine (OR 0.48, CI 0.40-0.58), and TSH 0.50 (0.45-0.55) were associated with decreased odds of PPHN; phenylalanine was associated with increased odds of PPHN (OR 4.74, CI 3.25-6.90). The AUROC was 0.772 (CI 0.737-0.807). CONCLUSIONS: In a large, population-based dataset, infants with PPHN have distinct, early metabolic profiles. These data provide insight into the pathophysiology of PPHN, identifying potential therapeutic targets and novel biomarkers to assess the response.

Racial and Ethnic Disparities in Preterm Infant Mortality and Severe Morbidity: A Population-Based Study.

BACKGROUND: Disparities exist in the rates of preterm birth and infant mortality across different racial/ethnic groups. However, only a few studies have examined the impact of race/ethnicity on the outcomes of premature infants. OBJECTIVE: To report the rates of mortality and severe neonatal morbidity among multiple gestational age (GA) groups stratified by race/ethnicity. METHODS: A retrospective cohort study utilizing linked birth certificate, hospital discharge, readmission, and death records up to 1 year of life. Live-born infants ≤36 weeks born in the period 2007-2012 were included. Maternal self-identified race/ethnicity, as recorded on the birth certificate, was used. ICD-9 diagnostic and procedure codes captured neonatal morbidities (intraventricular hemorrhage, retinopathy of prematurity, periventricular leukomalacia, bronchopulmonary dysplasia, and necrotizing enterocolitis). Multiple logistic regression was performed to evaluate the impact of race/ethnicity on mortality and morbidity, adjusting for GA, birth weight, sex, and multiple gestation. RESULTS: Our cohort totaled 245,242 preterm infants; 26% were white, 46% Hispanic, 8% black, and 12% Asian. At 22-25 weeks, black infants were less likely to die than white infants (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.62-0.94). However, black infants born at 32-34 weeks (OR 1.64; 95% CI 1.15-2.32) or 35-36 weeks (OR 1.57; 95% CI 1.00-2.24) were more likely to die. Hispanic infants born at 35-36 weeks were less likely to die than white infants (OR 0.66; 95% CI 0.50-0.87). Racial disparities at different GAs were also detected for severe morbidities. CONCLUSIONS: The impact of race/ethnicity on mortality and severe morbidity varied across GA categories in preterm infants. Disparities persisted even after adjusting for important potential confounders.

The association of maternal lymphatic markers and critical congenital heart defects in the fetus-A population based case-control study.

The objective ot this study was to investigate whether lymphatic markers measured in women during the second trimester are associated with critical congenital heart defects (CCHDs) in offspring. This is a retrospective cohort study of pregnant women who participated in the California Prenatal Screening Program. CCHD data in the offspring was captured by linking birth certificate data with hospital patient discharge records. Second trimester samples were assayed for vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) AA/BB, and PDGF AB. Logistic models were used to evaluate the association between lymphatic biomarkers and CCHD. Models were adjusted for other serum biomarkers and maternal characteristics. Results are presented in odds ratios (OR) with 95% confidence intervals (CI). We identified 93 cases with CCHDs and 194 controls without CCHDs. The crude and adjusted OR for log (ln) VEGF was 1.07 (95%CI 0.94-1.22) and 1.08 (95%CI 0.94-1.24), respectively; for ln PDGF AB/BB was 0.93 (95%CI 0.6-1.35) and 0.58 (95%CI 0.32-1.05), respectively. There was a significant association between ln PDFG AA and CCHDs (crude OR 1.83 (95%CI 1.05-3.2); adjusted OR 2.41 (95%CI 1.06-5.44)). Levels of circulating PDGF AA were highest in cases with hypoplastic left heart syndrome (HLHS) (mean 8.78 +/- 1.54 pg/ml). In this study, increased mid-pregnancy maternal serum levels of PDGF AA were associated with CCHDs in offspring. The highest PDGF AA levels were found in mothers of fetuses with HLHS. These findings may be useful in screening for CCHDs and offer insight into their association with nuchal translucency.

Persistent Pulmonary Hypertension of the Newborn in Late Preterm and Term Infants in California.

BACKGROUND AND OBJECTIVES: There are limited epidemiologic data on persistent pulmonary hypertension of the newborn (PPHN). We sought to describe the incidence and 1-year mortality of PPHN by its underlying cause, and to identify risk factors for PPHN in a contemporary population-based dataset. METHODS: The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharges, readmissions, and birth and death certificates from 1 year before to 1 year after birth. We searched the database (2007-2011) for cases of PPHN (identified by International Classification of Diseases, Ninth Revision codes), including infants ≥34 weeks' gestational age without congenital heart disease. Multivariate Poisson regression was used to identify risk factors associated with PPHN; results are presented as risk ratios, 95% confidence intervals. RESULTS: Incidence of PPHN was 0.18% (3277 cases/1 781 156 live births). Infection was the most common cause (30.0%). One-year mortality was 7.6%; infants with congenital anomalies of the respiratory tract had the highest mortality (32.0%). Risk factors independently associated with PPHN included gestational age <37 weeks, black race, large and small for gestational age, maternal preexisting and gestational diabetes, obesity, and advanced age. Female sex, Hispanic ethnicity, and multiple gestation were protective against PPHN. CONCLUSIONS: This risk factor profile will aid clinicians identifying infants at increased risk for PPHN, as they are at greater risk for rapid clinical deterioration.

Inflammatory biomarkers and spontaneous preterm birth among obese women.

OBJECTIVE: To identify associations between second-trimester serum inflammatory biomarkers and preterm birth among obese women. METHODS: In this nested case-control study, we compared 65 serum inflammatory biomarkers in obese women whose pregnancies resulted in early spontaneous preterm birth (<32 weeks gestation, n = 34) to obese women whose pregnancies resulted in term birth (n = 34). These women were selected from a larger population-based California cohort. Random forest and classification and regression tree techniques were employed to identify biomarkers of importance, and adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Random forest and classification and regression tree techniques found that soluble vascular endothelial growth factor receptor-3 (sVEGFR3), soluble interleukin-2 receptor alpha-chain (sIL-2RA) and soluble tumor necrosis factor receptor-1 (sTNFR1) were related to preterm birth. Using multivariable logistic regression to compare preterm cases and term controls, decreased serum levels of sVEGFR3 and increased serum levels of sIL-2RA and sTNFR1 were associated with increased risk of preterm birth among obese women, aOR = 3.2 (95% CI: 1.0-9.9), aOR = 2.8 (95% CI: 0.9-9.0), and aOR = 4.1 (95% CI: 1.2-14.1), respectively. CONCLUSIONS: In this pilot study, we identified three serum biomarkers indicative of inflammation to be associated with spontaneous preterm birth among obese women: sVEGFR3, sIL-2RA and sTNFR1.

Risk of selected structural abnormalities in infants after increased nuchal translucency measurement.

OBJECTIVE: We sought to examine the association between increased first-trimester fetal nuchal translucency (NT) measurement and major noncardiac structural birth defects in euploid infants. STUDY DESIGN: Included were 75,899 singleton infants without aneuploidy or critical congenital heart defects born in California in 2009 through 2010 with NT measured between 11-14 weeks of gestation. Logistic binomial regression was employed to estimate relative risks (RRs) and 95% confidence intervals (CIs) for occurrence of birth defects in infants with an increased NT measurement (by percentile at crown-rump length [CRL] and by ≥3.5 mm compared to those with measurements <90th percentile for CRL). RESULTS: When considered by CRL adjusted percentile and by measurement ≥3.5 mm, infants with a NT ≥95th percentile were at risk of having ≥1 major structural birth defects (any defect, RR, 1.6; 95% CI, 1.3-1.9; multiple defects, RR, 2.1; 95% CI, 1.3-3.4). Infants with a NT measurement ≥95th percentile were at particularly high risk for pulmonary, gastrointestinal, genitourinary, and musculoskeletal anomalies (RR, 1.6-2.7; 95% CI, 1.1-5.4). CONCLUSION: Our findings demonstrate that risks of major pulmonary, gastrointestinal, genitourinary, and musculoskeletal structural birth defects exist for NT measurements ≥95th percentile. The ≥3-fold risks were observed for congenital hydrocephalus; agenesis, hypoplasia, and dysplasia of the lung; atresia and stenosis of the small intestine; osteodystrophies; and diaphragm anomalies.