Prenatal cannabis use disorder and gastroschisis in California, 2007-19.

BACKGROUND: Gastroschisis is a congenital anomaly of the abdominal wall with an unknown aetiology. Recent trends in the prevalence of gastroschisis suggest that changing environmental or behavioural factors may contribute. We examined whether prenatal cannabis use disorder was associated with gastroschisis. METHODS: The Study of Outcomes of Mothers and Infants is a population-based cohort compiled of California birth records that have been linked to Department of Health Care Access and Information hospitalization, emergency department and ambulatory surgery records. We included 2007-19 singleton live births (n = 5 774 656). Cannabis use disorder was measured by diagnosis codes at any visit during pregnancy or at birth. Gastroschisis was measured by diagnosis or surgical repair procedure codes at birth or during the first year of life. RESULTS: The prevalence of cannabis use disorder was about 1%. The prevalence of gastroschisis was 0.14% and 0.06% among those with and without cannabis use disorder, respectively. There were positive associations between cannabis use disorder and gastroschisis when using a multivariable model [adjusted risk ratio (aRR) = 1.3, 95% confidence interval (CI) 1.0, 1.7) and a matched sample approach (aRR = 1.5, 95% CI 1.1, 2.1). The association varied by maternal age and was largest among people aged >34 years (aRR = 2.5, 95% CI 1.0, 5.8). CONCLUSIONS: We confirm findings of a positive association between cannabis exposure and gastroschisis and add that it is strongest when maternal age is greater than 34 years. More investigation into whether the association is causal, and why the association varies by maternal age, is encouraged.

Characteristics of sleep in children with heavy prenatal alcohol exposure.

BACKGROUND: Sleep plays an important role in neurodevelopment. However, the effects of prenatal alcohol exposure on sleep quality have been understudied, despite reports of sleep disturbance in infants prenatally exposed to alcohol and elevated levels of sleep problems reported by caregivers of children with fetal alcohol spectrum disorders. The current study characterizes sleep in children with prenatal alcohol exposure using both objective (actigraphy) and subjective (questionnaires, sleep diaries) methods. METHODS: Participants aged 6-10 years, with and without prenatal alcohol exposure, were included in the study (alcohol-exposed [AE]: n = 35; control [CON]: n = 39). Objective sleep was measured via 24-h actigraphy for 2 weeks. Parents completed sleep diaries and sleep questionnaires (Children's Sleep Habits Questionnaire, Pediatric Sleep Questionnaire). Multivariate analysis of variance was used to characterize the sleep profile (objective, subjective) and examine group differences. RESULTS: There were no group differences on actigraphy metrics averaged across 2 weeks. However, the AE group showed significantly greater intraindividual variability on most actigraphy measures, particularly total sleep time, percent sleep, wake after sleep onset, and number of wake bouts. Parents reported significantly more sleep problems in the AE group than in the CON group, primarily driven by night wakings, parasomnias (e.g., sleepwalking), snoring, and daytime sleepiness. These effects were more severe in children >8.5 years of age. CONCLUSIONS: Despite similar 2-week average sleep outcomes, children with prenatal alcohol exposure showed greater intraindividual sleep variability and parents reported more sleep problems related to sleep behavior and snoring. These difficulties with sleep may be related to other cognitive and behavioral outcomes. Importantly, sleep is a modifiable behavior, and interventions that focus on variability in sleep, particularly in sleep duration, can impact the quality of life in children with prenatal alcohol exposure and their families.

Consistency and Variability of the Human Milk Oligosaccharide Profile in Repeat Pregnancies.

Human milk oligosaccharides (HMOs) are a set of complex carbohydrates and the third largest solid component of human milk, after lactose and lipids. To date, over 150 HMOs have been identified and the diversity of structures produced by lactating women is influenced by maternal genetics as well as other maternal, infant, and environmental factors. While the concentrations of individual HMOs have been shown to vary between individuals and throughout the course of lactation, the variability of HMO concentration profiles following different pregnancies occurring in the same woman is presently unknown. As such, the objective of this study was to compare HMO concentrations in human milk samples provided by the same women (n = 34) following repeat pregnancies. We leveraged existing human milk samples and metadata from the UC San Diego Human Milk Research Biorepository (HMB) and measured the concentrations of the 19 most abundant HMOs using high-performance liquid chromatography with fluorescence detection (HPLC-FL). By assessing dissimilarities in HMO concentration profiles, as well as concentration trends in individual structures between pregnancies of each participant, we discovered that HMO profiles largely follow a highly personalized and predictable trajectory following different pregnancies irrespective of non-genetic influences. In conclusion, this is the first study to assess the interactions between parity and time following delivery on variations in HMO compositions.

Concentrations of remdesivir and GS-441524 in human milk from lactating individuals diagnosed with COVID-19.

IMPACT: Findings from this study provide further reassuring evidence that infant exposure through human milk received from lactating individuals who require treatment with remdesivir is negligible.

T Cell Responses in Pregnant Women Who Received mRNA-Based Vaccination to Prevent COVID-19 Revealed Unknown Exposure to the Natural Infection and Numerous SARS-CoV-2-Specific CD4- CD8- Double Negative T Cells and Regulatory T Cells.

We studied T-cell responses to SARS-CoV-2 in 19 pregnant subjects at different gestational weeks who received three doses of mRNA-based vaccination to prevent COVID-19. SARS-CoV-2 peptide pools were used for T-cell recognition studies: peptides were 15 amino acids long and had previously been defined in COVID-19-convalescent subjects. T-cell activation was evaluated with the AIM assay. Most subjects showed coordinated, spike-specific CD4+ and CD8+ T-cell responses and the development of T cell memory. Non-spike-specific T cells in subjects who were not aware of previous COVID-19 infection suggested a prior undetected, asymptomatic infection. CD4- CD8- double negative (DN) T cells were numerous, of which a percentage was specific for SARS-CoV-2 spike peptides. Regulatory T cells (Treg), both spike- and non-spike-specific, were also greatly expanded. Two Treg populations were defined: a population differentiated from naïve T cells, and pTreg, reverting from pro-inflammatory T cells. The Treg cells expressed CCR6, suggesting homing to the endometrium and vaginal epithelial cells. The pregnant women responded to SARS-CoV-2 vaccination. Asymptomatic COVID-19 was revealed by the T cell response to the non-spike peptides. The numerous DN T cells and Treg pointed our attention to new aspects of the adaptive immune response in vaccine recipients.

Racial and Ethnic Inequities in Therapeutic Hypothermia and Neonatal Hypoxic-Ischemic Encephalopathy: A Retrospective Cohort Study.

OBJECTIVE: To investigate racial inequities in the use of therapeutic hypothermia (TH) and outcomes in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We queried an administrative birth cohort of mother-baby pairs in California from 2010 through 2019 using International Classification of Diseases codes to evaluate the association between race and ethnicity and the application of TH in infants with HIE. We identified 4779 infants with HIE. Log-linear regression was used to calculate risk ratios (RR) for TH, adjusting for hospital transfer, rural location, gestational age between 35 and 37 weeks, and HIE severity. Risk of adverse infant outcome was calculated by race and ethnicity and stratified by TH. RESULTS: From our identified cohort, 1338 (28.0%) neonates underwent TH. White infants were used as the reference sample, and 410 (28.4%) received TH. Black infants were significantly less likely to receive TH with 74 (20.0%) with an adjusted risk ratio (aRR) of 0.7 (95% CI 0.5-0.9). Black infants with any HIE who did not receive TH were more likely to have a hospital readmission (aRR 1.36, 95% CI 1.10-1.68) and a tracheostomy (aRR 3.07, 95% CI 1.19-7.97). Black infants with moderate/severe HIE who did not receive TH were more likely to have cerebral palsy (aRR 2.72, 95% CI 1.07-6.91). CONCLUSIONS: In this study cohort, Black infants with HIE were significantly less likely to receive TH. Black infants also had significantly increased risk of some adverse outcomes of HIE. Possible reasons for this inequity include systemic barriers to care and systemic bias.

Vedolizumab Does Not Affect Antibody Secreting Cell Recruitment to the Lactating Mammary Gland of Mothers With Inflammatory Bowel Disease.

Despite a known role for α4ß7 and MAdCAM-1 for the recruitment of antibody secreting cells to the lactating mammary gland, vedolizumab which targets integrin α4ß7 did not lower breastmilk IgA in lactating mothers with IBD receiving the drug. It is likely that antibody secreting cells alternatively employ α4ß1 to arrest on VCAM-1 also expressed by the lactating mammary gland.

Adverse neonatal outcomes in pregnant women with asthma: An updated systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma. OBJECTIVE: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes. SEARCH STRATEGY: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma. DATA COLLECTION AND ANALYSIS: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined. MAIN RESULTS: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance. CONCLUSIONS: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma.

Predicting fetal alcohol spectrum disorders in preschool-aged children from early life factors.

BACKGROUND: Early life factors, including parental sociodemographic characteristics, pregnancy exposures, and physical and neurodevelopmental features measured in infancy are associated with fetal alcohol spectrum disorders (FASD). The objective of this study was to evaluate the performance of a classifier model for diagnosing FASD in preschool-aged children from pregnancy and infancy-related characteristics. METHODS: We analyzed a prospective pregnancy cohort in Western Ukraine enrolled between 2008 and 2014. Maternal and paternal sociodemographic factors, maternal prenatal alcohol use and smoking behaviors, reproductive characteristics, birth outcomes, infant alcohol-related dysmorphic and physical features, and infant neurodevelopmental outcomes were used to predict FASD. Data were split into separate training (80%: n = 245) and test (20%: n = 58; 11 FASD, 47 no FASD) datasets. Training data were balanced using data augmentation through a synthetic minority oversampling technique. Four classifier models (random forest, extreme gradient boosting [XGBoost], logistic regression [full model] and backward stepwise logistic regression) were evaluated for accuracy, sensitivity, and specificity in the hold-out sample. RESULTS: Of 306 children evaluated for FASD, 61 had a diagnosis. Random forest models had the highest sensitivity (0.54), with accuracy of 0.86 (95% CI: 0.74, 0.94) in hold-out data. Boosted gradient models performed similarly, however, sensitivity was less than 50%. The full logistic regression model performed poorly (sensitivity = 0.18 and accuracy = 0.65), while stepwise logistic regression performed similarly to the boosted gradient model but with lower specificity. In a hold-out sample, the best performing algorithm correctly classified six of 11 children with FASD, and 44 of 47 children without FASD. CONCLUSIONS: As early identification and treatment optimize outcomes of children with FASD, classifier models from early life characteristics show promise in predicting FASD. Models may be improved through the inclusion of physiologic markers of prenatal alcohol exposure and should be tested in different samples.

The Association of Gestational Age and Size with Management Strategies and Outcomes in Symptomatic Neonatal Tetralogy of Fallot.

 In neonatal, symptomatic tetralogy of Fallot (sTOF), data are lacking on whether high-risk groups would benefit from staged (SR) or complete repair (CR). We studied the association of gestational age (GA) at birth and z-score for birth weight (BWz), with management strategy and outcomes in sTOF. California population-based cohort study (2011-2017) of infants with sTOF (defined as catheter or surgical intervention prior to 44 weeks corrected GA) was performed, comparing management strategy and timing by GA and BWz categories. Multivariable models evaluated composite outcomes and days alive and out of hospital (DAOOH) in the first year of life. Among 345 patients (SR = 194; CR = 151), management strategy did not differ by GA or BWz with complete repair defined as prior to 44 weeks corrected gestational age; however, did differ by GA with regard to complete/timely repair (defined as complete repair within first 30 days of life). Full-term and early-term neonates underwent CR 20 (95%CI: - 27.1, - 14.1; p < 0.001) and 15 days (95%CI: - 22.1, - 8.2; p < 0.001) sooner than preterm neonates. Prematurity and major anomaly were associated with mortality or non-cardiac morbidity, while only major anomaly was associated with mortality or cardiac morbidity (OR = 3.5, 95%CI: 1.8,6.7, p < .0001). Full-term infants had greater DAOOH compared to preterm infants (35.2 days, 95%CI: 4.0, 66.5, p = 0.03). LGA infants and those with major anomaly had significantly lower DAOOH. In sTOF, patient specific risk factors such as prematurity and major anomaly were more associated with outcomes than management strategy.

Secondary physical features in children with FASD.

OBJECTIVE: The diagnoses included within the umbrella term fetal alcohol spectrum disorders (FASD), are based on the documentation of prenatal alcohol exposure (PAE), growth deficits and a pattern of dysmorphic physical features and neurobehavioral impairments. Although 3 key facial features (short palpebral fissures, a smooth philtrum and a thin vermilion of the upper lip) are the only dysmorphic features taken into account for the diagnosis of Fetal Alcohol Syndrome (FAS) or partial FAS (pFAS), several other features are commonly seen in individuals with these diagnoses. The goals of our study were to determine if some of these secondary physical features also occur more frequently in children with alcohol-related neurodevelopmental disorder (ARND) relative to controls, and if a cluster of these features combined in a dysmorphology score could be used to identify those negatively impacted by PAE but who do not have the cardinal physical features that led to a diagnosis of FAS or pFAS. METHODS: Among 2681 children recruited for the Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (CoFASP) study, 1726 had an FASD or sufficient evidence of PAE having occurred or not in their pregnancy. Children were then categorized into groups using the modified Hoyme diagnostic criteria (FAS (n = 24), pFAS (n = 99) and ARND (n = 87), and No FASD (n = 1516), including those with No FASD and a history of PAE (No FASD/PAE, n = 498) and those with No FASD and no history of PAE (No FASD/No PAE, n = 1018). The frequencies of 26 secondary dysmorphic features were compared among these groups, both individually and combined in non-weighted and weighted dysmorphic scores. Correlations of the total dysmorphic scores with an index of overall cognitive ability were also compared by group status. RESULTS: Several of these features were significantly more frequent in children with FAS than in those with No FASD diagnosis with or without PAE but not in comparison to those with ARND. The number of features was also significantly higher in the FAS group as compared to all other groups for both weighted and unweighted dysmorphology scores but were not higher in the group with ARND when compared to the groups with No FASD either in the presence or absence of PAE. Although not diagnostic, higher total dysmorphology scores were predictive of lower general cognitive abilities in the group with ARND, suggesting severity of alcohol-related dysmorphology is predictive of severity of alcohol-related neurobehavioral impairment. CONCLUSION: Secondary physical features were not more frequent in children with ARND compared to children without an FASD diagnosis but were a marker for lower cognitive function. The use of secondary physical features to support a diagnosis of ARND was not supported in this sample.

Breastfeeding and neurodevelopment in infants with prenatal alcohol exposure.

BACKGROUND: Few studies have evaluated the differential benefits of breastfeeding on infant neurodevelopment at varying levels of prenatal alcohol exposure (PAE). This study examined whether the association between breastfeeding and neurodevelopment is modified by prenatal drinking pattern. METHODS: The study included 385 infants from Ukraine born to women prospectively enrolled in a cohort study during pregnancy. Neurodevelopment was assessed at six and 12 months using the Bayley Scales of Infant Development II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Linear regression modeling with interaction terms and stratification by PAE group was used to determine the relationship between breastfeeding, PAE, and neurodevelopment. RESULTS: A significant interaction between PAE and breastfeeding was observed for the MDI and PDI at six and 12 months. Infants with high PAE who were breastfed at least four months had BSID-II scores 14 or more points higher compared to those never breastfed. Counterintuitively, those with moderate PAE had poorer performance on the BSID-II at 12 months when breastfed longer. CONCLUSION: There was a significant joint effect of PAE and breastfeeding on infant neurodevelopment at six and 12 months. Breastfeeding may provide distinct benefits to infants exposed to high levels of PAE. IMPACT: We found a positive effect of breastfeeding on infant neurodevelopment among infants with prenatal alcohol exposure (PAE), particularly those exposed to higher levels during gestation. This study is one of the first to evaluate whether breastfeeding mitigates harm caused by PAE. Breastfeeding may provide distinct benefits to infants with higher levels of PAE.

Maternal Mental Health Diagnoses and Infant Emergency Department Use, Hospitalizations, and Death.

BACKGROUND: The period surrounding childbirth is a uniquely vulnerable time for women and their mental health. We sought to describe the association between maternal mental health diagnoses in the year prior and after birth and infant Emergency Department (ED) utilization, hospitalization, and death. METHODS: We studied mothers who gave singleton live birth in California (2011-2017) and their infants using linked infant birth and death certificates and maternal and infant discharge records. Maternal mental health diagnoses in the year before and after birth were identified using International Classification of Diseases (ICD) codes. We abstracted infant ED visits, hospitalizations, discharge diagnoses, deaths, and causes of death. Log-linear regression was used to compare relative risks of infant outcomes between mothers with and without mental health diagnoses, adjusting for maternal variables. RESULTS: Of the 3,067,069 mother-infant pairs, 85,047 (2.8%) mothers had at least one mental health diagnosis in the year before and after birth. Infants of mothers with mental health diagnoses were more likely to visit the ED (aRR 1.2, CI:1.1-1.2), have three or more ED visits (aRR 1.4, CI:1.3-1.4), be hospitalized (aRR 1.1, CI:1.04-1.1), and die (aRR 1.7, CI:1.6-1.8) in the first year of life. These infants were also more likely to be diagnosed with accidental injuries, nonaccidental trauma, and non-specific descriptive diagnosis (fussiness/fatigue/brief resolved unexplained event). CONCLUSION: This large administrative cohort study showed associations between maternal mental health diagnoses and infant acute ED visits, hospitalization, and death. This study underscores the urgent need to understand what is driving these findings and how to mitigate this risk.

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. METHODS: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. RESULTS: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs). CONCLUSIONS: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible.

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.

Maternal circulating miRNAs contribute to negative pregnancy outcomes by altering placental transcriptome and fetal vascular dynamics.

Circulating miRNAs the in blood are promising biomarkers for predicting pregnancy complications and adverse birth outcomes. Previous work identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following prenatal alcohol exposure and regulated epithelial-mesenchymal transition in the placenta. Here we show that a single intravascular administration of pooled murine-conserved HEamiRNAs to pregnant mice on gestational day 10 (GD10) attenuates umbilical cord blood flow during gestation, explaining the observed intrauterine growth restriction (IUGR), specifically decreased fetal weight, and morphometric indices of cranial growth. Moreover, RNAseq of the fetal portion of the placenta demonstrated that this single exposure has lasting transcriptomic changes, including upregulation of members of the Notch pathway (Dll4, Rfng, Hey1), which is a pathway important for trophoblast migration and differentiation. Weighted gene co-expression network analysis also identified chemokine signaling, which is responsible for regulating immune cell-mediated angiogenesis in the placenta, as an important predictor of fetal growth and head size. Our data suggest that HEamiRNAs perturb the expression of placental genes relevant for angiogenesis, resulting in impaired umbilical cord blood flow and subsequently, IUGR.

What drives outcomes in infants of mothers with congenital heart disease? A mediation analysis.

OBJECTIVE: Infants of mothers with adult congenital heart disease (ACHD) are at increased risk for adverse pregnancy and neonatal outcomes. We aim to identify mediators in the relationship between ACHD and pregnancy and infant outcomes. STUDY DESIGN: Case-control study using linked maternal and infant hospital records. Structural equation modeling was performed to assess for potential mediators of pregnancy and infant outcomes. RESULT: We showed an increased risk of multiple adverse infant and pregnancy outcomes among infants born to mothers with ACHD. Maternal placental syndrome and congestive heart failure were mediators of prematurity. Prematurity and critical congenital heart disease in the infant were mediators of infant outcomes. However, the direct effect of ACHD on outcomes beyond that explained by these mediators remained significant. CONCLUSION: While significant mediators of infant and pregnancy outcomes were identified, there was a large direct effect of maternal ACHD. Further studies should aim to identify more factors that explain these infants' vulnerability.