Trends and adverse pregnancy and birth outcomes associated with stimulant-related disorder diagnosis.

BACKGROUND AND AIMS: Stimulant-related disorders (SRD), or the continued misuse of illicit or prescribed stimulants, during pregnancy can have adverse health effects for mothers and infants. This study aimed to measure prevalence and trends of SRD diagnosis in pregnancy, and associations between SRD diagnosis and adverse maternal and infant health outcomes, among pregnant individuals in California. DESIGN: Retrospective cohort study. SETTING: California, USA. PARTICIPANTS: Pregnant individuals from the Study of Outcomes in Mothers and Infants (SOMI) with singleton live births between 2012 and 2020 (n = 3 740 079). MEASUREMENTS: SRD diagnosis (excluding cocaine) and maternal (gestational diabetes, gestational hypertension [gHTN], severe maternal morbidity [SMM]) and infant (very preterm birth [gestational age <32 weeks], preterm birth [gestational age 32-37 weeks], neonatal intensive care unit [NICU] admission, small for gestational age [SGA]) outcomes were classified using International Classification of Disease (ICD) codes and vital statistics. Risk ratios were estimated with modified Poisson log linear regression that accounted for sibling pregnancies. Covariates included maternal sociodemographic characteristics, mental and physical health problems, nicotine use and co-occurrence of other diagnosed substance use disorders. Bias analyses were conducted to address unmeasured confounding and exposure misclassification. FINDINGS: SRD diagnosis among pregnant individuals increased from 2012 to 2020 (554 to 748 per 100 000 births). SRD diagnosis was associated with an increased risk of SMM (adjusted risk ratio [aRR] = 2.3; 95% confidence interval [CI] = 2.2-2.5), gHTN (aRR = 1.8; 95% CI = 1.7-1.9), very preterm birth (aRR = 2.2, 95% CI = 2.0-2.5), preterm birth (aRR = 2.1, 95% CI = 2.1-2.2) and NICU admission (aRR = 2.0, 95%CI = 1.9-2.0), and a decreased risk of gestational diabetes (aRR = 0.8; 95% CI = 0.8-0.9). SRD diagnosis was not associated with infants born SGA. Findings were generally robust to unmeasured confounding and misclassification of diagnosis. CONCLUSIONS: Stimulant-related disorder diagnosis during pregnancy appears to be associated with an increased risk for select adverse maternal and infant health outcomes including severe maternal morbidity, gestational hypertension, very preterm birth, preterm birth and neonatal intensive care unit admission.

Changes in the Treatment and Outcomes of Different Severities of Neonatal Hypoxic Ischemic Encephalopathy in California: A Retrospective Cohort Study.

Objective: Evaluate the changes in management and outcomes of Californian infants with hypoxic ischemic encephalopathy (HIE). Study Design: Infants with HIE were identified from a California administrative birth cohort using ICD codes and divided into two epochs, Epoch 1 (2010-2015) and Epoch 2 (2016-2019). Risk ratios (RR) for therapeutic hypothermia (TH) in each epoch and their outcomes were calculated using log-linear regression. Results: In this cohort, 4779 infants with HIE were identified. Incidence of HIE in California increased yearly from 0.5/1,000 California births to a peak of 1.5/1,000 births in 2018. The use of TH in infants with mild HIE increased in Epoch 2 compared to Epoch 1. There was no significant difference in outcomes between epochs for infants with mild HIE that received TH. Conclusion: Significantly more infants with mild HIE received TH since 2015 in California, but no difference in outcomes was found for these patients.

Birth defects among offspring of California firefighters, 2007-2019.

PURPOSE: Limited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects. METHODS: Data from California birth certificates (2007-2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories. RESULTS: Offspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings. CONCLUSIONS: Offspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure.

Cardiovascular Events During Pregnancy: Implications for Adverse Pregnancy Outcomes in Individuals With Autoimmune and Rheumatic Diseases.

OBJECTIVE: This study examined maternal cardiovascular (CV) events relative to adverse pregnancy outcomes among individuals with autoimmune rheumatic diseases (ARDs), primary antiphospholipid syndrome (APS), and those with neither. METHODS: Using a California population-based birth cohort (2005-2020), we identified those with CV events (CVEs), ARDs, and APS through International Classification of Diseases, 9th and 10th revisions, Clinical Modification codes in maternal discharge records. Selected adverse pregnancy outcomes identified from birth certificates were preterm birth (PTB; < 37 weeks' gestation), small-for-gestational-age infants (SGA; birth weight < 10th percentile for age and sex), and a composite of either outcome. Adjusted risk ratios (aRRs) for adverse outcomes and their 95% CIs were calculated. RESULTS: CVEs occurred more frequently in individuals with ARDs (265 of 19,340 [1.4%]) and primary APS (428 of 7758 [5.5%]) than those without (17,130 of 7,004,334 [0.3%]). The presence vs absence of CVEs was associated with a greater incidence of adverse outcomes in ARD (53.2% vs 26.6%), APS (30.6% vs 20.7%), and non-ARD/APS pregnancies (28.2% vs 15.2%). CVEs were associated with increased risks of SGA in all groups (aRRs 1.2-1.5) and PTB in ARD (aRR 1.6, 95% CI 1.3-2.0) and non-ARD/APS (aRR 1.7, 95% CI 1.7-1.8) pregnancies. CONCLUSION: CVEs were associated with modestly increased risks (20-70%) for PTB, SGA, or both across the groups. Notably, > 50% of ARD pregnancies with CVEs experienced adverse pregnancy outcomes. Given that ARD and APS pregnancies have higher (although still low) rates of CVEs and have higher baseline risks of adverse pregnancy outcomes than the general population, the additional burden conferred by CVEs is clinically important.

Risk of Adverse Neonatal Outcomes After Combined Prenatal Cannabis and Nicotine Exposure.

Importance: The prevalence of cannabis use in pregnancy is rising and is associated with adverse perinatal outcomes. In parallel, combined prenatal use of cannabis and nicotine is also increasing, but little is known about the combined impact of both substances on pregnancy and offspring outcomes compared with each substance alone. Objective: To assess the perinatal outcomes associated with combined cannabis and nicotine exposure compared with each substance alone during pregnancy. Design, Setting, and Participants: This retrospective population-based cohort study included linked hospital discharge data (obtained from the California Department of Health Care Access and Information) and vital statistics (obtained from the California Department of Public Health) from January 1, 2012, through December 31, 2019. Pregnant individuals with singleton gestations and gestational ages of 23 to 42 weeks were included. Data were analyzed from October 14, 2023, to March 4, 2024. Exposures: Cannabis-related diagnosis and prenatal nicotine product use were captured using codes from International Classification of Diseases, Ninth Revision, Clinical Modification, and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification. Main Outcome and Measures: The main outcomes were infant and neonatal death, infants small for gestational age, and preterm delivery. Results were analyzed by multivariable Poisson regression models. Results: A total of 3 129 259 pregnant individuals were included (mean [SD] maternal age 29.3 [6.0] years), of whom 23 007 (0.7%) had a cannabis-related diagnosis, 56 811 (1.8%) had a nicotine-use diagnosis, and 10 312 (0.3%) had both in pregnancy. Compared with nonusers, those with cannabis or nicotine use diagnoses alone had increased rates of infant (0.7% for both) and neonatal (0.3% for both) death, small for gestational age (14.3% and 13.7%, respectively), and preterm delivery (<37 weeks) (12.2% and 12.0%, respectively). Moreover, risks in those with both cannabis and nicotine use were higher for infant death (1.2%; adjusted risk ratio [ARR], 2.18 [95% CI, 1.82-2.62]), neonatal death (0.6%; ARR, 1.76 [95% CI, 1.36-2.28]), small for gestational age (18.0%; ARR, 1.94 [95% CI, 1.86-2.02]), and preterm delivery (17.5%; ARR, 1.83 [95% CI, 1.75-1.91]). Conclusions and Relevance: These findings suggest that co-occurring maternal use of cannabis and nicotine products in pregnancy is associated with an increased risk of infant and neonatal death and maternal and neonatal morbidity compared with use of either substance alone. Given the increasing prevalence of combined cannabis and nicotine use in pregnancy, these findings can help guide health care practitioners with preconception and prenatal counseling, especially regarding the benefits of cessation.

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.

Machine learning approaches to the identification of children affected by prenatal alcohol exposure: A narrative review.

Fetal alcohol spectrum disorders (FASDs) affect at least 0.8% of the population globally. The diagnosis of FASD is uniquely complex, with a heterogeneous physical and neurobehavioral presentation that requires multidisciplinary expertise for diagnosis. Many researchers have begun to incorporate machine learning approaches into FASD research to identify children who are affected by prenatal alcohol exposure, including those with FASD. This narrative review highlights these efforts. Following an introduction to machine learning, we summarize examples from the literature of neurobehavioral screening tools and physiologic markers of exposure. We discuss individual efforts, including models that classify FASD based on parent-reported neurocognitive or behavioral questionnaires, 3D facial imaging, brain imaging, DNA methylation patterns, microRNA profiles, cardiac orienting response, and dysmorphic facial features. We highlight model performance and discuss the limitations of these approaches. We conclude by considering the scalability of these approaches and how these machine learning models, largely developed from clinical samples or highly exposed birth cohorts, may perform in the general population.

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.

Childhood Aggressive Behavior and Adolescent Substance Use Initiation.

BACKGROUND: Drug and alcohol use before the age of 14 is associated with adverse outcomes over the life course. While previous studies have identified numerous sociodemographic characteristics associated with youth substance use initiation, few have examined the relationship between behavioral characteristics, such as childhood aggression, and substance use initiation in adolescence. METHODS: This longitudinal study consisted of 2985 children from the Future of Families and Child Wellbeing Study. Aggression was measured using primary caregiver report when the children were about the age of 9 and cigarette, alcohol, and marijuana use was measured using the child report when the children were age 9 and age 15. Separate multivariable Poisson regression models were fitted for each substance use initiation outcome. RESULTS: Childhood aggression was positively associated with the initiation of cigarette and marijuana use in adolescence (aRR = 2.3 [95% CI = 1.5,3.4] and aRR = 1.3 [95% CI = 1.1,1.6], respectively). Childhood aggression was not associated with adolescent alcohol use initiation (aRR = 1.2 [95% CI = 0.9,1.5]). CONCLUSIONS: The presence of aggressive behavior in childhood was associated with the initiation of cigarette and marijuana use in adolescence. These results may be used to identify children at higher risk of cigarette and marijuana use, who may benefit from additional monitoring for substance use initiation.

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.

Disparities in the impact of heat wave definitions on emergency department visits during the first year of life among preterm and full-term infants in California.

INTRODUCTION: Heat waves will be aggravated due to climate change, making this a critical public health threat. However, heat wave definitions to activate alert systems can be ambiguous, highlighting the need to assess a range of definitions to identify those that contribute to the most adverse health outcomes. Additionally, children are highly susceptible to the impacts of heat waves, especially infants, despite the lack of focus on this subpopulation. We aimed to assess the relationship between 30 heat wave definitions and the first all-cause emergency department (ED) visits for California infants. We also examined modification of this relationship by preterm birth status and demographic characteristics to identify possible health disparities. METHODS: Live-born, singleton deliveries from the Study of Outcomes in Mothers and Infants born in 2014-2018 were included. Thirty heat wave definitions were assessed based on temperature metrics (minimum/maximum temperatures), thresholds (90th; 92.5th; 95th; 97.5th; 99th percentiles), and duration (1-; 2-; 3-days). A time-stratified case-crossover design assessed heat wave impacts on ED visits using infants with a warm season ED visit (May-October) within the first year of life (n = 228,250). Effect modification by preterm birth status, age, sex, race/ethnicity, education, and delivery payment type was also investigated. RESULTS: Infants demonstrated increased risk of an ED visit with exposure to all heat definitions. The 3-day minimum temperature 99th percentile definition had the highest adjusted odds ratio (AOR: 1.14; 95% CI: 1.05-1.23) for the total population. Term infants were more affected by some heat waves than preterm infants. Effect modification was additionally identified, such as by maternal education. DISCUSSION: This study provides insight on the heat wave definitions that lead to adverse health outcomes and the identification of the most susceptible infants to these impacts, which has implications on heat-related interventions.

The association between depression and alcohol use among pregnant adults in the USA.

BACKGROUND: The prevalence of alcohol use among pregnant women aged 18-44 years old increased in recent years. The influence of mental health issues on an individual's likelihood to use alcohol during pregnancy has not been thoroughly investigated. This study will examine the association between experiencing a major depressive episode (MDE) in the past year and past-month alcohol use among pregnant women using the 2011-2020 National Survey on Drug Use and Health (NSDUH). METHODS: Pregnant women between the ages of 18 and 44 years old were included in the study for analysis. Multivariable logistic regression analysis was used to examine the association between past-year MDE and past-month alcohol use adjusting for age, race/ethnicity, marital status, and employment status. Additional logistic regression analysis was performed to investigate whether this relationship differed by trimester of pregnancy. RESULTS: A total of 6745 participants were included in the analytic sample. The prevalence of past-year MDE and past-month alcohol use was 7.67% and 9.15% respectively. Logistic regression analysis showed past-year MDE was significantly associated with past-month alcohol use in pregnant women adjusting for age, race/ethnicity, marital status, and employment status (aOR = 1.96; 95% CI, 1.34-2.87). This relationship became stronger in second and third trimesters of pregnancy. CONCLUSIONS: This study showed a positive association between MDE and past-month alcohol use among pregnant women, with strongest effect estimates in the third trimester. These findings may inform approaches for improved screening guidelines and health education for individuals who may be at higher risk of prenatal alcohol use.

Funding for Refugee Health Research From the National Institutes of Health Between 2000 and 2020.

Importance: The US has historically resettled more refugees than any other country, with over 3.5 million refugees since 1980. The National Institutes of Health (NIH) is the largest public funder of biomedical research and development, but its role in mitigating many health disparities refugees experience through its funded research remains unknown. Objective: To examine the NIH's research funding patterns on refugee health research over the last 2 decades. Design, Setting, and Participants: Secondary analysis of NIH-funded grants between 2000 and 2020 using a cross-sectional study design. The NIH Research Portfolio Online Reporting Tools database was used to find relevant grants. Data were analyzed from November 2021 to September 2022. Main Outcomes and Measures: NIH grants awarded by year, state, grant type, research area, funding institute, grant duration, and amount funded. Results: Of 1.7 million NIH grants funded over the 20-year study period, only 78 addressed refugee health. Funded grants were mostly training grants (23 grants [29%]), followed by hypothesis-driven research (R01 grants; 22 grants [28%]), pilot or preliminary investigation proposals (13 grants [17%]), and other types of grants (20 grants [26%]). The most studied research domain was mental health (36 grants [46%]), followed by refugee family dynamics and women's and children's health (14 grants [18%]). A total of 26 grants (33%) were funded by the National Institute of Mental Health and 15 (19%) were funded by the National Institute of Child Health and Human Development. Most grants were US-based (60 grants [76%]) and the state of Massachusetts received the greatest amount of funding ($14 825 852 [18%]). In 2020, the NIH allocated about $2.3 million to refugee health research, or less than 0.01% of its $42 billion budget that year. The number of grants funded in each time period did not always reflect changes in the number of refugees resettled in the US over the years. Conclusions and Relevance: This cross-sectional study found that there remain significant gaps in the understanding of and interventions in the health research needs of refugees locally and along the migratory route. To close these gaps, the NIH should increase its investments in comprehensive studies assessing the physical, mental, and social well-being of this expanding population. This can be achieved by ensuring that all NIH institutes allocate budgets specifically for refugee health research and extend support for the training of refugee researchers.

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.

Assessment of substance exposures in nail clipping samples: A systematic review.

BACKGROUND: Studies of prenatal substance exposure often rely on self-report, urine drug screens, and/or analyses of blood or meconium biomarkers. Accuracy of these measures is limited when assessing exposure over many weeks or months of gestation. Nails are increasingly being considered as a matrix from which to assess substance exposure. This systematic review synthesizes data on the validity of detecting alcohol, nicotine, cannabis, and opioid from nail clippings, with an emphasis on prenatal exposure assessment. METHODS: The systematic review was conducted using PRISMA 2020 guidelines. Seven databases were searched with keywords relevant to the four substances of interest. Results were summarized grouping manuscripts by the exposure of interest with focus on accuracy and feasibility. RESULTS: Of 2384 papers initially identified, 35 manuscripts were included in our qualitative synthesis. Only a few studies specifically looked at pregnant individuals or mother-child dyads. Across the four substances, many studies demonstrated a dose-response relationship between exposure and concentration of analytes in nails. Nail assays appear to detect lower level of exposure compared to hair; however, sample insufficiency, especially for multi-substance assays, remains a limitation. CONCLUSIONS: Based on the reviewed studies, nail clippings are an acceptable and potentially preferable matrix for the evaluation of these four prenatal substances when sampling frequency and/or study design necessitates assessment of past exposures over an extended period. Nails have the advantage of infrequent sampling and minimal invasiveness to assess a broad exposure period. Future studies should examine validity of analytes in toenail versus fingernail clippings.

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.

Pregnancy characteristics and outcomes among birthing individuals with a diagnosis of fetal alcohol syndrome.

BACKGROUND: Fetal alcohol syndrome (FAS) can have adverse effects on health outcomes throughout the life course. Adults with FAS have an increased risk of chronic and infectious diseases. Although these conditions can affect reproductive health, few have described perinatal outcomes among individuals with an FAS diagnosis. METHODS: We analyzed data from the Study of Mothers and Infants, an administrative birth cohort derived from California birth certificates linked with a hospital discharge database. The cohort consisted of 7.3 million singleton, live births between 2005 and 2021. FAS was identified by International Classification of Diseases (ICD) codes in maternal hospital discharge records. Pregnancy and birth outcomes were captured via ICD codes in maternal or infant records. We performed descriptive analyses for pregnancy and birth outcomes by maternal FAS diagnosis. RESULTS: There were 35 babies born to 30 individuals with an FAS diagnosis between 2005 and 2021 (0.5/100,000 live births). The prevalence of births to individuals with an FAS diagnosis increased over the period. Individuals with an FAS diagnosis were more likely to identify as non-Hispanic White, or "other/multiple" race, and less likely to be Hispanic than those without FAS. They were also more likely to be publicly insured and less than 18 years old. Birthing individuals with FAS were also more likely to use nicotine during pregnancy and to have diagnoses of mental health disorders, epilepsy, substance use disorders, preexisting or gestational hypertension, and sexually transmitted infections or other infections complicating pregnancy. Infants of individuals with FAS were more likely to be born prematurely or small for gestational age and be admitted to the neonatal intensive care unit. CONCLUSIONS: These findings highlight the need for improved recognition of FAS among birthing people. The results suggest that individuals with FAS would benefit from early and sustained medical care prior to pregnancy to optimize perinatal outcomes.