Exposure to bilingual or monolingual maternal speech during pregnancy affects the neurophysiological encoding of speech sounds in neonates differently.

Introduction: Exposure to maternal speech during the prenatal period shapes speech perception and linguistic preferences, allowing neonates to recognize stories heard frequently in utero and demonstrating an enhanced preference for their mother's voice and native language. Yet, with a high prevalence of bilingualism worldwide, it remains an open question whether monolingual or bilingual maternal speech during pregnancy influence differently the fetus' neural mechanisms underlying speech sound encoding. Methods: In the present study, the frequency-following response (FFR), an auditory evoked potential that reflects the complex spectrotemporal dynamics of speech sounds, was recorded to a two-vowel /oa/ stimulus in a sample of 129 healthy term neonates within 1 to 3 days after birth. Newborns were divided into two groups according to maternal language usage during the last trimester of gestation (monolingual; bilingual). Spectral amplitudes and spectral signal-to-noise ratios (SNR) at the stimulus fundamental (F0) and first formant (F1) frequencies of each vowel were, respectively, taken as measures of pitch and formant structure neural encoding. Results: Our results reveal that while spectral amplitudes at F0 did not differ between groups, neonates from bilingual mothers exhibited a lower spectral SNR. Additionally, monolingually exposed neonates exhibited a higher spectral amplitude and SNR at F1 frequencies. Discussion: We interpret our results under the consideration that bilingual maternal speech, as compared to monolingual, is characterized by a greater complexity in the speech sound signal, rendering newborns from bilingual mothers more sensitive to a wider range of speech frequencies without generating a particularly strong response at any of them. Our results contribute to an expanding body of research indicating the influence of prenatal experiences on language acquisition and underscore the necessity of including prenatal language exposure in developmental studies on language acquisition, a variable often overlooked yet capable of influencing research outcomes.

The frequency-following response in late preterm neonates: a pilot study.

Introduction: Infants born very early preterm are at high risk of language delays. However, less is known about the consequences of late prematurity. Hence, the aim of the present study is to characterize the neural encoding of speech sounds in late preterm neonates in comparison with those born at term. Methods: The speech-evoked frequency-following response (FFR) was recorded to a consonant-vowel stimulus /da/ in 36 neonates in three different groups: 12 preterm neonates [mean gestational age (GA) 36.05 weeks], 12 "early term neonates" (mean GA 38.3 weeks), and "late term neonates" (mean GA 41.01 weeks). Results: From the FFR recordings, a delayed neural response and a weaker stimulus F0 encoding in premature neonates compared to neonates born at term was observed. No differences in the response time onset nor in stimulus F0 encoding were observed between the two groups of neonates born at term. No differences between the three groups were observed in the neural encoding of the stimulus temporal fine structure. Discussion: These results highlight alterations in the neural encoding of speech sounds related to prematurity, which were present for the stimulus F0 but not for its temporal fine structure.

Placental MFSD2A expression in fetal growth restriction and maternal and fetal DHA status.

INTRODUCTION: Fetal growth restriction (FGR) may affect placental transfer of key nutrients to the fetus, such as the fatty acid docosahexaenoic acid (DHA). Major facilitator superfamily domain containing 2A (MFSD2A) has been described as a specific DHA carrier in placenta, but its expression has not been studied in FGR. The aim of this study was to evaluate for the first time the placental MFSD2A levels in late-FGR pregnancies and the maternal and cord plasma DHA. METHODS: 87 pregnant women from a tertial reference center were classified into late-FGR (N = 18) or control (N = 69). Fatty acid profile was determined in maternal and cord venous plasma, as well as placental levels of MFSD2A and of insulin mediators like phospho-protein kinase B (phospho-AKT) and phospho-extracellular regulated kinase (phospho-ERK). RESULTS: Maternal fatty acid profile did not differ between groups. Nevertheless, late-FGR cord vein presented higher content of saturated fatty acids than control, producing a concomitant decrease in the percentage of some unsaturated fatty acids. In the late-FGR group, a lower DHA fetal/maternal ratio was observed when using percentages, but not with concentrations. No alterations were found in the expression of MFSD2A in late-FGR placentas, nor in phospho-AKT or phospho-ERK. DISCUSSION: MFSD2A protein expression was not altered in late-FGR placentas, in line with no differences in cord DHA concentration between groups. The increase in the saturated fatty acid content of late-FGR cord might be a compensatory mechanism to ensure fetal energy supply, decreasing other fatty acids percentage. Future studies are warranted to elucidate if altered saturated fatty acid profile in late-FGR fetuses might predispose them to postnatal catch-up and to long-term health consequences.

Maternal Stress, Anxiety, Well-Being, and Sleep Quality in Pregnant Women throughout Gestation.

BACKGROUND: Maternal stress, anxiety, well-being, and sleep quality during pregnancy have been described as influencing factors during pregnancy. AIM: We aimed to describe maternal stress, anxiety, well-being, and sleep quality in pregnant women throughout gestation and their related factors. METHODS: A prospective study including pregnant women attending BCNatal, in Barcelona, Spain (n = 630). Maternal stress and anxiety were assessed by the Perceived Stress Scale (PSS) and State-Trait Anxiety Inventory (STAI)-validated questionnaires. Maternal well-being was assessed using the World Health Organization Well-Being Index Questionnaire (WHO-5), and sleep quality was assessed using the Pittsburgh Sleep Quality Index Questionnaire (PSQI). All questionnaires were obtained twice during the second and third trimester of pregnancy. A multivariate analysis was conducted to assess factors related to higher maternal stress and anxiety and worse well-being and sleep quality. RESULTS: High levels of maternal stress were reported in 23.1% of participants at the end of pregnancy, with maternal age <40 years (OR 2.02; 95% CI 1.08-3.81, p = 0.03), non-white ethnicity (OR 2.09; 95% CI 1.19-4.02, p = 0.01), and non-university studies (OR 1.86; 95% CI 1.08-3.19, p = 0.02) being the parameters mostly associated with it. A total of 20.7% of women had high levels of anxiety in the third trimester and the presence of psychiatric disorders (OR 3.62; 95% CI 1.34-9.78, p = 0.01) and non-university studies (OR 1.70; 95% CI 1.11-2.59, p = 0.01) provided a significant contribution to high anxiety at multivariate analysis. Poor maternal well-being was observed in 26.5% of women and a significant contribution was provided by the presence of psychiatric disorders (OR 2.96; 95% CI 1.07-8.25, p = 0.04) and non-university studies (OR 1.74; 95% CI 1.10-2.74, p = 0.02). Finally, less sleep quality was observed at the end of pregnancy (p < 0.001), with 81.1% of women reporting poor sleep quality. CONCLUSION: Maternal stress and anxiety, compromised maternal well-being, and sleep quality disturbances are prevalent throughout pregnancy. Anxiety and compromised sleep quality may increase over gestation. The screening of these conditions at different stages of pregnancy and awareness of the associated risk factors can help to identify women at potential risk.

Developmental Trajectory of the Frequency-Following Response During the First 6 Months of Life.

PURPOSE: The aim of the present study is to characterize the maturational changes during the first 6 months of life in the neural encoding of two speech sound features relevant for early language acquisition: the stimulus fundamental frequency (fo), related to stimulus pitch, and the vowel formant composition, particularly F1. The frequency-following response (FFR) was used as a snapshot into the neural encoding of these two stimulus attributes. METHOD: FFRs to a consonant-vowel stimulus /da/ were retrieved from electroencephalographic recordings in a sample of 80 healthy infants (45 at birth and 35 at the age of 1 month). Thirty-two infants (16 recorded at birth and 16 recorded at 1 month) returned for a second recording at 6 months of age. RESULTS: Stimulus fo and F1 encoding showed improvements from birth to 6 months of age. Most remarkably, a significant improvement in the F1 neural encoding was observed during the first month of life. CONCLUSION: Our results highlight the rapid and sustained maturation of the basic neural machinery necessary for the phoneme discrimination ability during the first 6 months of age.

Effects of a Mediterranean Diet Intervention on Maternal Stress, Well-Being, and Sleep Quality throughout Gestation-The IMPACT-BCN Trial.

Stress and anxiety are frequent occurrences among pregnant women. We aimed to evaluate the effects of a Mediterranean diet intervention during pregnancy on maternal stress, well-being, and sleep quality throughout gestation. In a randomized clinical trial, 1221 high-risk pregnant women were randomly allocated into three groups at 19-23 weeks' gestation: a Mediterranean diet intervention, a Mindfulness-Based Stress Reduction program, or usual care. All women who provided self-reported life-style questionnaires to measure their anxiety (State Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS)), well-being (WHO Five Well Being Index (WHO-5)), and sleep quality (Pittsburgh sleep quality index (PSQI)) at enrollment and at the end of the intervention (34-36 weeks) were included. In a random subgroup of 106 women, the levels of cortisol and related metabolites were also measured. At the end of the intervention (34-36 weeks), participants in the Mediterranean diet group had significantly lower perceived stress and anxiety scores (PSS mean (SE) 15.9 (0.4) vs. 17.0 (0.4), p = 0.035; STAI-anxiety mean (SE) 13.6 (0.4) vs. 15.8 (0.5), p = 0.004) and better sleep quality (PSQI mean 7.0 ± 0.2 SE vs. 7.9 ± 0.2 SE, p = 0.001) compared to usual care. As compared to usual care, women in the Mediterranean diet group also had a more significant increase in their 24 h urinary cortisone/cortisol ratio during gestation (mean 1.7 ± SE 0.1 vs. 1.3 ± SE 0.1, p < 0.001). A Mediterranean diet intervention during pregnancy is associated with a significant reduction in maternal anxiety and stress, and improvements in sleep quality throughout gestation.

Speech-Encoding Deficits in Neonates Born Large-for-Gestational Age as Revealed With the Envelope Frequency-Following Response.

OBJECTIVES: The present envelope frequency-following response (FFR ENV ) study aimed at characterizing the neural encoding of the fundamental frequency of speech sounds in neonates born at the higher end of the birth weight continuum (>90th percentile), known as large-for-gestational age (LGA). DESIGN: Twenty-five LGA newborns were recruited from the maternity unit of Sant Joan de Déu Barcelona Children's Hospital and paired by age and sex with 25 babies born adequate-for-gestational age (AGA), all from healthy mothers and normal pregnancies. FFR ENV s were elicited to the/da/ syllable and recorded while the baby was sleeping in its cradle after a successful universal hearing screening. Neural encoding of the stimulus' envelope of the fundamental frequency (F 0ENV ) was characterized through the FFR ENV spectral amplitude. Relationships between electrophysiological parameters and maternal/neonatal variables that may condition neonatal neurodevelopment were assessed, including pregestational body mass index (BMI), maternal gestational weight gain and neonatal BMI. RESULTS: LGA newborns showed smaller spectral amplitudes at the F 0ENV compared to the AGA group. Significant negative correlations were found between neonatal BMI and the spectral amplitude at the F 0ENV . CONCLUSIONS: Our results indicate that in spite of having a healthy pregnancy, LGA neonates' central auditory system is impaired in encoding a fundamental aspect of the speech sounds, namely their fundamental frequency. The negative correlation between the neonates' BMI and FFR ENV indicates that this impaired encoding is independent of the pregnant woman BMI and weight gain during pregnancy, supporting the role of the neonatal BMI. We suggest that the higher adipose tissue observed in the LGA group may impair, via proinflammatory products, the fine-grained central auditory system microstructure required for the neural encoding of the fundamental frequency of speech sounds.

Death and severe morbidity in isolated periviable small-for-gestational-age fetuses.

OBJECTIVE: This study aims to predict perinatal death or severe sequelae in isolated small-for-gestational-age fetuses, diagnosed at a periviable gestational age, based on ultrasound and Doppler parameters at diagnosis. DESIGN: Observational study. SETTING: A tertiary perinatal centre. POPULATION: A cohort of singleton non-malformed fetuses suspected to be small for gestational age (estimated fetal weight, EFW, <10th centile) diagnosed at 22.0-25.6 weeks of gestation. The following parameters were recorded at diagnosis: severe smallness (<3rd centile); absent or reversed end-diastolic velocity in umbilical artery; abnormal middle cerebral artery Doppler; abnormal cerebroplacental ratio; abnormal uterine artery Doppler; and absent or reversed end-diastolic velocity in the ductus venosus. METHODS: Logistic regression analysis. MAIN OUTCOME MEASURES: Predictive performance of EFW and Doppler parameters for short-term adverse outcome of perinatal morbimortality and composite serious adverse outcomes (death, neurological impairment or severe bronchopulmonary dysplasia). RESULTS: A total of 155 pregnancies were included. There were 13 (8.4%) intrauterine and 11 (7.7%) neonatal deaths. A short-term adverse perinatal outcome occurred in 40 (25.8%) pregnancies. There were 31 (20%) cases of serious adverse outcomes. For the prediction of serious adverse outcomes, the combination of absent or reversed end-diastolic velocity in the umbilical artery and impaired middle cerebral artery detected by Doppler evaluation achieved a detection rate of 87%, with a false-positive rate of 14% (accuracy 86%). CONCLUSION: In periviable isolated small-for-gestational-age fetuses, a Doppler evaluation of the umbilical and fetal brain circulation can accurately predict short-term adverse perinatal complications and serious adverse outcomes.

Prenatal daily musical exposure is associated with enhanced neural representation of speech fundamental frequency: Evidence from neonatal frequency-following responses.

Fetal hearing experiences shape the linguistic and musical preferences of neonates. From the very first moment after birth, newborns prefer their native language, recognize their mother's voice, and show a greater responsiveness to lullabies presented during pregnancy. Yet, the neural underpinnings of this experience inducing plasticity have remained elusive. Here we recorded the frequency-following response (FFR), an auditory evoked potential elicited to periodic complex sounds, to show that prenatal music exposure is associated to enhanced neural encoding of speech stimuli periodicity, which relates to the perceptual experience of pitch. FFRs were recorded in a sample of 60 healthy neonates born at term and aged 12-72 hours. The sample was divided into two groups according to their prenatal musical exposure (29 daily musically exposed; 31 not-daily musically exposed). Prenatal exposure was assessed retrospectively by a questionnaire in which mothers reported how often they sang or listened to music through loudspeakers during the last trimester of pregnancy. The FFR was recorded to either a /da/ or an /oa/ speech-syllable stimulus. Analyses were centered on stimuli sections of identical duration (113 ms) and fundamental frequency (F0  = 113 Hz). Neural encoding of stimuli periodicity was quantified as the FFR spectral amplitude at the stimulus F0 . Data revealed that newborns exposed daily to music exhibit larger spectral amplitudes at F0 as compared to not-daily musically-exposed newborns, regardless of the eliciting stimulus. Our results suggest that prenatal music exposure facilitates the tuning to human speech fundamental frequency, which may support early language processing and acquisition. RESEARCH HIGHLIGHTS: Frequency-following responses to speech were collected from a sample of neonates prenatally exposed to music daily and compared to neonates not-daily exposed to music. Neonates who experienced daily prenatal music exposure exhibit enhanced frequency-following responses to the periodicity of speech sounds. Prenatal music exposure is associated with a fine-tuned encoding of human speech fundamental frequency, which may facilitate early language processing and acquisition.

Maternal and neonatal immune response to SARS-CoV-2, IgG transplacental transfer and cytokine profile.

SARS-CoV-2 infected pregnant women are at increased risk of severe COVID-19 than non-pregnant women and have a higher risk of adverse pregnancy outcomes like intrauterine/fetal distress and preterm birth. However, little is known about the impact of SARS-CoV-2 infection on maternal and neonatal immunological profiles. In this study, we investigated the inflammatory and humoral responses to SARS-CoV-2 in maternal and cord blood paired samples. Thirty-six pregnant women were recruited at delivery at Hospital Sant Joan de Déu, Barcelona, Spain, between April-August 2020, before having COVID-19 available vaccines. Maternal and pregnancy variables, as well as perinatal outcomes, were recorded in questionnaires. Nasopharyngeal swabs and maternal and cord blood samples were collected for SARS-CoV-2 detection by rRT-PCR and serology, respectively. We measured IgM, IgG and IgA levels to 6 SARS-CoV-2 antigens (spike [S], S1, S2, receptor-binding domain [RBD], nucleocapsid [N] full-length and C-terminus), IgG to N from 4 human coronaviruses (OC43, HKU1, 229E and NL63), and the concentrations of 30 cytokines, chemokines and growth factors by Luminex. Mothers were classified as infected or non-infected based on the rRT-PCR and serology results. Sixty-four % of pregnant women were infected with SARS-CoV-2 (positive by rRT-PCR during the third trimester and/or serology just after delivery). None of the newborns tested positive for rRT-PCR. SARS-CoV-2 infected mothers had increased levels of virus-specific antibodies and several cytokines. Those with symptoms had higher cytokine levels. IFN-α was increased in cord blood from infected mothers, and in cord blood of symptomatic mothers, EGF, FGF, IL-17 and IL-15 were increased, whereas RANTES was decreased. Maternal IgG and cytokine levels showed positive correlations with their counterparts in cord blood. rRT-PCR positive mothers showed lower transfer of SARS-CoV-2-specific IgGs, with a stronger effect when infection was closer to delivery. SARS-CoV-2 infected mothers carrying a male fetus had higher antibody levels and higher EGF, IL-15 and IL-7 concentrations. Our results show that SARS-CoV-2 infection during the third trimester of pregnancy induces a robust antibody and cytokine response at delivery and causes a significant reduction of the SARS-CoV-2-specific IgGs transplacental transfer, with a stronger negative effect when the infection is closer to delivery.

Nasopharyngeal microbiota profiling of pregnant women with SARS-CoV-2 infection.

We aimed to analyze the nasopharyngeal microbiota profiles in pregnant women with and without SARS-CoV-2 infection, considered a vulnerable population during COVID-19 pandemic. Pregnant women were enrolled from a multicenter prospective population-based cohort during the first SARS-CoV-2 wave in Spain (March-June 2020 in Barcelona, Spain) in which the status of SARS-CoV-2 infection was determined by nasopharyngeal RT-PCR and antibodies in peripheral blood. Women were randomly selected for this cross-sectional study on microbiota. DNA was extracted from nasopharyngeal swab samples, and the V3-V4 region of the 16S rRNA of bacteria was amplified using region-specific primers. The differential abundance of taxa was tested, and alpha/beta diversity was evaluated. Among 76 women, 38 were classified as positive and 38 as negative for SARS-CoV-2 infection. All positive women were diagnosed by SARS-CoV-2 IgG and IgM/IgA antibodies, and 14 (37%) also had a positive RT-PCR. The overall composition of the nasopharyngeal microbiota differ in pregnant women with SARS-CoV-2 infection (positive SARS-CoV-2 antibodies), compared to those without the infection (negative SARS-CoV-2 antibodies) (p = 0.001), with a higher relative abundance of the Tenericutes and Bacteroidetes phyla and a higher abundance of the Prevotellaceae family. Infected women presented a different pattern of microbiota profiling due to beta diversity and higher richness (observed ASV < 0.001) and evenness (Shannon index < 0.001) at alpha diversity. These changes were also present in women after acute infection, as revealed by negative RT-PCR but positive SARS-CoV-2 antibodies, suggesting a potential association between SARS-CoV-2 infection and long-lasting shift in the nasopharyngeal microbiota. No significant differences were reported in mild vs. severe cases. This is the first study on nasopharyngeal microbiota during pregnancy. Pregnant women with SARS-CoV-2 infection had a different nasopharyngeal microbiota profile compared to negative cases.

Maternal short-term exposure to NO2 during pregnancy and its relationship with Doppler markers of placental function.

BACKGROUND: Maternal exposure to air pollution has been associated with poor obstetric outcomes. However, the available evidence on the impact of maternal exposure to air pollution on placental function is still scarce and is based on estimated ambient levels of air pollutants. OBJECTIVE: To evaluate the association between short-term maternal exposure to NO2 based on the objective personal measure of NO2 exposure and Doppler markers of placental function. METHODS: This study was based on a prospective cohort of 101 pregnant women, recruited at Hospital Sant Joan de Déu, Barcelona (Spain), between January 2017 and April 2018. NO2 diffusion tubes were worn by pregnant women to measure personal exposure to NO2 between weeks 28 and 32 of their pregnancy. Placental function was evaluated at the 32nd week of gestation by Doppler evaluation of mean uterine arteries pulsatility index (PI), umbilical artery PI, middle cerebral artery PI, cerebroplacental ratio (CPR) and ductus venosus PI. Linear regression models were applied to estimate the association of personal NO2 exposure and Doppler markers of placental function (one at a time), controlled for relevant covariates. RESULTS: Higher personal exposure to NO2 was significantly associated with lower mean uterine artery PI. Each one-interquartile range (IQR) increase in the exposure to NO 2 was associated with -0.07 (95% confidence intervals (CIs): -0.12, -0.02) decrease in uterine arteries PI. We also observed some suggestions for an inverse association between this exposure and CPR. A one-IQR increase in NO2 was associated with -0.18 (95% CIs: -0.37, 0.01) decrease in CPR. The findings for the rest of Doppler markers were not conclusive. CONCLUSIONS: Maternal exposure to NO2 could interfere with Doppler markers of placental function, potentially indicating a certain degree of cerebral vasodilatation with a decrease of mean uterine arteries PI.

A study on exposure to greenspace during pregnancy and lipid profile in cord blood samples.

Although evidence reporting the beneficial associations of prenatal greenspace exposure with pregnancy outcomes is increasing, there is still a lack of evidence on the potential association of such exposure to greenspace on fetal lipid profile. We aimed to first-time investigate the associations between prenatal exposure to greenspace and lipid levels in the cord blood. The present study was based on data from 150 expectant mothers, residents of Sabzevar city in Iran (2018). For each participant, we identified exposure to greenspace in residential surroundings, residential accessibility to green space, use of green spaces, and the number of plant pots inside the home. Measures of levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and TC/HDL-C and TG/HDL-C ratios in samples of cord blood were applied to identify the lipid profile. We developed adjusted linear regression models to estimate the associations of each indicator of greenspace exposure with each cord blood lipid. We found increased greenspace in residential surroundings across a 100 m buffer, higher residential accessibility to green space, and more use of green spaces were associated with decreased cord blood lipid levels. The remainder findings regarding the greenspace in residential surroundings across 300 m and 500 m buffers and the number of plant pots were null. Some suggestions were observed for a potential mediatory role of air pollution. This study suggests that greenspace exposure during pregnancy may influence positively fetal lipid levels in the cord blood.

Impact of the COVID-19 Pandemic on Maternal Well-Being during Pregnancy.

The outbreak of a pandemic has negative psychological effects. We aimed to determine the impact of the SARS-CoV-2 pandemic during pregnancy and identify the risk factors for maternal well-being. A multicenter, prospective, population-based study was carried out that included women (n = 1320) who were pregnant during the SARS-CoV-2 pandemic in Barcelona (Spain) compared against a pre-pandemic cohort (n = 345). Maternal well-being was assessed using the validated World Health Organization Well-Being Index Questionnaire (WHO-5 Index). Pregnant women attended during the COVID-19 pandemic showed worst WHO-5 well-being scores (median (IQR) of 56 (36−72) for the pandemic cohort vs. 64 (52−76) for the pre-pandemic cohort p < 0.001), with 42.8% of women presenting a poor well-being score vs. 28% for the pre-pandemic cohort (p < 0.001). Presence of a previous psychiatric disorder (OR 7.1; 95% CI 2.6−19, p < 0.001), being in the third trimester of pregnancy (OR 1.7; 95% CI 1.5−2, p < 0.001), or requiring hospital admission for COVID-19 (OR 4.7; 95% CI 1.4−16.7, p = 0.014), significantly contributed to low maternal well-being during the COVID-19 pandemic (multivariate analysis). Being infected by SARS-CoV-2 was not associated with a lower well-being score. We conclude that, during the COVID-19 pandemic, there were higher rates of poor maternal well-being; the infection of SARS-CoV-2 itself did not worsen maternal well-being, but other factors as psychiatric disorders, being in the third trimester of pregnancy or hospital admission for COVID-19 disease did.

Brain Oxygen Perfusion and Oxidative Stress Biomarkers in Fetuses with Congenital Heart Disease-A Retrospective, Case-Control Pilot Study.

Fetuses with congenital heart disease (CHD) have circulatory changes that may lead to predictable blood flow disturbances that may affect normal brain development. Hypoxemia and hypoperfusion may alter the redox balance leading to oxidative stress (OS), that can be assessed measuring stable end-products. OS biomarkers (OSB) were measured in amniotic fluid in fetuses with (n = 41) and without CHD (n = 44) and analyzed according to aortic flow, expected cyanosis after birth, and a CHD classification derived from this. Birth head circumference (HC) was used as a neurodevelopment biomarker. CHD fetuses had higher levels of ortho-Tyrosine (o-Tyr) than controls (p = 0.0003). There were no differences in o-Tyr levels considering aortic flow obstruction (p = 0.617). Fetuses with expected extreme cyanosis presented the highest levels of o-Tyr (p = 0.003). Among groups of CHD, fetuses without aortic obstruction and extreme cyanosis had the highest levels of o-Tyr (p = 0.005). CHD patients had lower HC than controls (p = 0.023), without correlation with OSB. Patients with HC < 10th percentile, presented high levels of o-Tyr (p = 0.024). Fetuses with CHD showed increased OSB and lower HC when compared to controls, especially those with expected extreme cyanosis. Our results suggest that increased levels of OSB are more influenced by the effect of low oxygenation than by aortic flow obstruction. Future studies with larger sample size are needed to further investigate the role of OSB as an early predictor of neurodevelopmental problems in CHD survivors.

Deficient neural encoding of speech sounds in term neonates born after fetal growth restriction.

Infants born after fetal growth restriction (FGR)-an obstetric condition defined as the failure to achieve the genetic growth potential-are prone to neurodevelopmental delays, with language being one of the major affected areas. Yet, while verbal comprehension and expressive language impairments have been observed in FGR infants, children and even adults, specific related impairments at birth, such as in the ability to encode the sounds of speech, necessary for language acquisition, remain to be disclosed. Here, we used the frequency-following response (FFR), a brain potential correlate of the neural phase locking to complex auditory stimuli, to explore the encoding of speech sounds in FGR neonates. Fifty-three neonates born with FGR and 48 controls born with weight adequate-for-gestational age (AGA) were recruited. The FFR was recorded to the consonant-vowel stimulus (/da/) during sleep and quantified as the spectral amplitude to the fundamental frequency of the syllable and its signal-to-noise ratio (SNR). The outcome was available in 45 AGA and 51 FGR neonates, yielding no differences for spectral amplitudes. However, SNR was strongly attenuated in the FGR group compared to the AGA group at the vowel region of the stimulus. These findings suggest that FGR population present a deficit in the neural pitch tracking of speech sounds already present at birth. Our results pave the way for future research on the potential clinical use of the FFR in this population, so that if confirmed, a disrupted FFR recorded at birth may help deriving FGR neonates at risk for postnatal follow-ups.

Advancing tools for human early lifecourse exposome research and translation (ATHLETE): Project overview.

Early life stages are vulnerable to environmental hazards and present important windows of opportunity for lifelong disease prevention. This makes early life a relevant starting point for exposome studies. The Advancing Tools for Human Early Lifecourse Exposome Research and Translation (ATHLETE) project aims to develop a toolbox of exposome tools and a Europe-wide exposome cohort that will be used to systematically quantify the effects of a wide range of community- and individual-level environmental risk factors on mental, cardiometabolic, and respiratory health outcomes and associated biological pathways, longitudinally from early pregnancy through to adolescence. Exposome tool and data development include as follows: (1) a findable, accessible, interoperable, reusable (FAIR) data infrastructure for early life exposome cohort data, including 16 prospective birth cohorts in 11 European countries; (2) targeted and nontargeted approaches to measure a wide range of environmental exposures (urban, chemical, physical, behavioral, social); (3) advanced statistical and toxicological strategies to analyze complex multidimensional exposome data; (4) estimation of associations between the exposome and early organ development, health trajectories, and biological (metagenomic, metabolomic, epigenetic, aging, and stress) pathways; (5) intervention strategies to improve early life urban and chemical exposomes, co-produced with local communities; and (6) child health impacts and associated costs related to the exposome. Data, tools, and results will be assembled in an openly accessible toolbox, which will provide great opportunities for researchers, policymakers, and other stakeholders, beyond the duration of the project. ATHLETE's results will help to better understand and prevent health damage from environmental exposures and their mixtures from the earliest parts of the life course onward.