[Determination of seven perfluoroalkyl and polyfluoroalkyl substances in serum of pregnant women and evaluation of neonatal neurobehavior based on high performance liquid chromatography-tandem mass spectrometry].

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively used as synthetic fluorine-containing compounds in various consumer products, including surfactants, cookware, lubricants, clothing, and food packaging, since the 1950s. Evidence has shown that PFASs cross the placental barrier and interfere with fetal thyroid hormone homeostasis, which is crucial for fetal growth and neurobehavioral development in children aged 2-9 years. However, no epidemiological data on the association between prenatal PFAS exposure and neonatal neurobehavioral development are available. In this study, we explored the association between prenatal PFAS exposure and neonatal neurobehavioral development based on the Ezhou cohort study. Blood samples (10 mL) were collected during the third trimester of pregnancy (28-36 weeks) at the Ezhou maternal and child health hospital. The blood specimens were centrifuged at 4000 r/min for 15 min immediately after collection, separated, stored at -80 ℃. The samples were analyzed for seven PFASs, namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonamide (PFOSA). The PFASs were separated using a C18 column (100 mm×2.1 mm, 1.7 µm) at an oven temperature of 40 ℃, injection volume of 10 µL, and flow rate of 0.4 mL/min via gradient elution with methanol and ammonium acetate aqueous solution. The instrument was operated in negative electrospray ionization mode with multiple reaction monitoring. The correlation coefficients (r2), limits of detection (LODs) and quantification (LOQs), and spiked recoveries of the seven PFASs were 0.993-0.999, 0.006-0.020 ng/mL, 0.020-0.066 ng/mL, and 84.6%-116.8%, respectively. Neonatal behavioral neurological assessment (NBNA) was used to evaluate newborn cognitive development 72 h after birth; this tool consisted of five clusters, including behavior (six items), passive muscle tone (four items), active muscle tone (four items), primitive reflexes (three items), and general assessment (three items). Each item was rated on a three-point scale (0, 1, or 2), with the 20 items having a maximum score of 40. A total of 379 mother-newborn pairs were included in the analysis. The PFASs with the highest exposure levels was PFOA, with median levels of 19.4 ng/mL. Linear regression models were used to test the effects of ln-converted PFAS levels in newborns. After adjusting for confounding factors, the linear regression model showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(ß(95% CI): 0.36(-0.64, 0.08)) and general assessment(ß(95% CI): 0.34(-0.61, 0.07)) in all newborns. Furthermore, PFNA exposure was associated with decreased passive muscle tone(ß(95% CI): 0.38(-0.74, 0.01)) and total NBNA(ß(95% CI): 0.37(-0.68, 0.06)). PFDA exposure was associated with decreased behavior(ß(95% CI): 0.28(-0.54, 0.01)), while PFHxS exposure was associated with elevated total NBNA(ß(95% CI): 0.27(0.05-0.48)). Gender stratification analysis showed that PFOS exposure during pregnancy was associated with decreased active muscle tone(ß(95% CI): 0.54(-0.73, 0.35)) and general assessment(ß(95% CI): 0.50(-0.88, 0.13)), PFNA exposure during pregnancy was associated with decreased passive muscle tone(ß(95% CI): 0.67(-1.2, 0.14)) and total NBNA(ß(95% CI): 0.45(-0.91, 0.01)), PFDA exposure during pregnancy was associated with decreased behavior(ß(95% CI): 0.44(-0.71, 0.17)), PFHxS exposure was associated with elevated total NBNA(ß(95% CI): 0.41(0.02-0.80)) in male newborns, and PFOA exposure was associated with decreased general assessment(ß(95% CI): -0.27(-0.51, 0.02)), and PFDA exposure was associated with elevated behavior(ß(95% CI): 0.46(0.40-0.52)) in female newborns. The proposed method separates and detects various PFASs without the need for cumbersome pretreatment processes, and has the advantages of low LODs, satisfactory recoveries, and accurate precision. Thus, it allows for the simultaneous analysis of trace PFASs in microserum samples from pregnant women. Our results also showed that prenatal PFAS exposure can lead to neurobehavioral disorders in offspring, with male newborns showing greater sensitivity than female newborns.

[Therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation on respiratory failure in preterm infants with a gestational age of 28-34 weeks: a prospective randomized controlled study]. / 容量保证的高频振荡通气模式对胎龄28~34å‘¨æ—©äº§å„¿å‘¼å¸è¡°ç«­ç–—æ•ˆçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure. METHODS: A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups. RESULTS: After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05). CONCLUSIONS: Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.

Parental folic acid deficiency delays neurobehavioral development in rat offspring by inhibiting the differentiation of neural stem cells into neurons.

Maternal folate status during pregnancy is associated with the neurodevelopment of offspring; however, study results on the association between paternal folate status and offspring neurodevelopment are inconsistent. This study aimed to explore whether parental folic acid deficiency affects the neurobehavioral development of offspring by affecting the differentiation of neural stem cells (NSCs) into neurons. In the present study, the offspring were divided into four groups: parental folic acid deficient group (D-D), maternal folic acid deficient and paternal folic acid normal group (D-N), maternal folic acid normal and paternal folic acid deficient group (N-D), and parental folic acid normal group (N-N). For in vivo study, neurobehavioral indexes, and neuron-specific nuclear protein (NeuN) and glial fibrillary acidic protein (GFAP) expression in the brain hippocampus and cerebral cortex of offspring were measured at different time points. For in vitro study, NSCs were cultured from the hippocampus and striatum, and neuronal and astrocytic differentiation were measured. The results demonstrated that parental folic acid deficiency decreased the brain folate level in offspring, delayed early sensory-motor reflex development, impaired spatial learning and memory ability in adolescence and adulthood, decreased differentiation of NSCs into neurons and increased differentiation of NSCs into astrocytes in vivo and in vitro. These impacts on the neurodevelopment of offspring were most pronounced in D-D group, followed by D-N group and N-D group. In conclusion, parental folic acid deficiency inhibits the neurobehavioral development of offspring, possibly by inhibiting the differentiation of NSCs into neurons.

Fetal heart rate variability and infant self-regulation: the impact of mother's prenatal depressive symptoms.

BACKGROUND: Foetal heart rate (FHR) variability is considered a marker of foetal neurobehavioral development associated with infant self-regulation and thus may be an early precursor of the adverse impact of mother's prenatal depressive symptoms on infant self-regulation. OBJECTIVE: This study analysed the mediator role of FHR variability in the association between mother's prenatal depressive symptoms and infant self-regulation at three months. METHODS: The sample comprised 86 first-born infants and their mothers. Mothers reported on depressive symptoms at the first trimester of pregnancy and on depressive symptoms and infant self-regulation at three months postpartum. FHR variability was recorded during routine cardiotocography at the third trimester of pregnancy. A mediation model was tested, adjusting for mother's postnatal depressive symptoms. RESULTS: Higher levels of mother's prenatal depressive symptoms were associated with both lower FHR variability and lower infant self-regulation at three months. FHR variability was associated with infant self-regulation and mediated the association between mother's prenatal depressive symptoms and infant self-regulation at three months. CONCLUSION: Findings suggested FHR variability as an early precursor of infant self-regulation that underlies the association between mother's prenatal depressive symptoms and infant self-regulation. Infants of mothers with higher levels of prenatal depressive symptoms could be at risk of self-regulation problems, partially due to their lower FHR variability.

Prenatal exposures to isoflavones and neurobehavioral development in children at 2 and 4 years of age: A birth cohort study.

Isoflavones (ISOs) are plant-derived estrogen-like compounds, which were already proved with cognition benefits on elderly people. However, studies assessing the associations between prenatal ISOs exposure and children's neurodevelopment are scarce. This study aimed to examine the associations between maternal urinary ISOs concentrations, including genistein (GEN), daidzein (DAD), glycitein (GLY), and metabolite equol (EQU), and children's neurodevelopment, based on a Chinese cohort study. Participants in this study were pregnant women recruited at 12-16 weeks of gestation, and they provided a single spot urine sample for the ISOs assay. Neurodevelopment was measured using the Child Behavior Checklist (CBCL) at 2 and 4 years of age. Negative binomial regression analysis and Generalized Estimating Equation (GEE) were performed to examine the associations between maternal urinary ISOs concentrations and CBCL scores. Associations were observed between moderate levels of prenatal ISOs exposure and decreased risks of childhood neurobehavioral problems, while the highest level of prenatal ISOs exposure was associated with increased risks of neurobehavioral problems among children. The neuroprotective effects were consistently between moderate DAD exposure and specific neurobehavioral problems, across different ages and sexes. For example, compared with the lowest exposure level, the third quartile group was associated with less Anxious/Depressed problems in boys at 2 years of age (RR=0.72 (95%CI: 0.52, 0.99)), girls at 2 years of age (RR=0.70 (95%CI: 0.46, 1.06)), boys at 4 years of age (RR=0.73 (95%CI: 0.55, 0.96)), and girls at 4 years of age (RR=0.95 (95%CI: 0.68, 1.31)).

Zika Virus affects neurobehavioral development, and causes oxidative stress associated to blood-brain barrier disruption in a rat model of congenital infection.

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with several neurodevelopmental outcomes after in utero infection. Here, we studied a congenital ZIKV infection model with immunocompetent Wistar rats, able to predict disabilities and that could pave the way for proposing new effective therapies. We identified neurodevelopmental milestones disabilities in congenital ZIKV animals. Also, on 22nd postnatal day (PND), blood-brain barrier (BBB) proteins disturbances were detected in the hippocampus with immunocontent reduction of ß_Catenin, Occludin and Conexin-43. Besides, oxidative stress imbalance on hippocampus and cortex were identified, without neuronal reduction in these structures. In conclusion, even without pups' microcephaly-like phenotype, congenital ZIKV infection resulted in neurobehavioral dysfunction associated with BBB and oxidative stress disturbances in young rats. Therefore, our findings highlighted the multiple impact of the congenital ZIKV infection on the neurodevelopment, which reinforces the continuity of studies to understand the spectrum of this impairment and to provide support to future treatment development for patients affected by congenital ZIKV.

Effect of omega-6 linoleic acid on neurobehavioral development in Caenorhabditis elegans.

Linoleic acid (LA, omega-6), an essential polyunsaturated fatty acid, is supplied by vegetable oils such as corn, sunflower and soybean. Supplementary LA in infants and children is required for normal growth and brain development, but has also been reported to induce brain inflammation and neurodegenerative diseases. This controversial role of LA development requires further investigation. Our study utilized Caenorhabditis elegans (C. elegans) as a model to clarify the role of LA in regulating neurobehavioral development. A mere supplementary quantity of LA in C. elegans larval stage affected the worm's locomotive ability, intracellular ROS accumulation and lifespan. We found that more serotonergic neurons were activated by supplementing LA above 10 µM thereby promoting locomotive ability with upregulation of serotonin-related genes. Supplementation with LA above 10 µM also inhibited the expression of mtl-1, mtl-2 and ctl-3 to accelerate oxidative stress and attenuate lifespan in nematodes; however, enhancement of stress-related genes such as sod-1, sod-3, mtl-1, mtl-2 and cyp-35A2 by supplementary LA under 1 µM decreased oxidative stress and increased the worm's lifespan. In conclusion, our study reveals that supplementary LA possesses both pros and cons in worm physiology and provides new suggestions for LA intake administration in childhood.

The Impact of Early Life Experiences and Gut Microbiota on Neurobehavioral Development in Preterm Infants: A Longitudinal Cohort Study.

OBJECTIVES: The objective of this study is to investigate the impact of early life experiences and gut microbiota on neurobehavioral development in preterm infants during neonatal intensive care unit (NICU) hospitalization. METHODS: Preterm infants were followed from NICU admission until their 28th postnatal day or until discharge. Daily stool samples, painful/stressful experiences, feeding patterns, and other clinical and demographic data were collected. Gut microbiota was profiled using 16S rRNA sequencing, and operational taxonomic units (OTUs) were selected to predict the neurobehaviors. The neurobehavioral development was assessed by the Neonatal Neurobehavioral Scale (NNNS) at 36 to 38 weeks of post-menstrual age (PMA). Fifty-five infants who had NNNS measurements were included in the sparse log-contrast regression analysis. RESULTS: Preterm infants who experienced a high level of pain/stress during the NICU hospitalization had higher NNNS stress/abstinence scores. Eight operational taxonomic units (OTUs) were identified to be associated with NNNS subscales after controlling demographic and clinical features, feeding patterns, and painful/stressful experiences. These OTUs and taxa belonging to seven genera, i.e., Enterobacteriaceae_unclassified, Escherichia-Shigella, Incertae_Sedis, Veillonella, Enterococcus, Clostridium_sensu_stricto_1, and Streptococcus with five belonging to Firmicutes and two belonging to Proteobacteria phylum. The enriched abundance of Enterobacteriaceae_unclassified (OTU17) and Streptococcus (OTU28) were consistently associated with less optimal neurobehavioral outcomes. The other six OTUs were also associated with infant neurobehavioral responses depending on days at NICU stay. CONCLUSIONS: This study explored the dynamic impact of specific OTUs on neurobehavioral development in preterm infants after controlling for early life experiences, i.e., acute and chronic pain/stress and feeding in the NICU. The gut microbiota and acute pain/stressful experiences dynamically impact the neurobehavioral development in preterm infants during their NICU hospitalization.

7,10,13,16-Docosatetraenoic acid impairs neurobehavioral development by increasing reactive oxidative species production in Caenorhabditis elegans.

AIMS: To investigate human breast milk (HBM) lipids that may adversely affect infant neurodevelopment. MAIN METHODS: We performed multivariate analyses that combined lipidomics and psychologic Bayley-III scales to identify which HBM lipids are involved in regulating infant neurodevelopment. We observed a significant moderate negative correlation between 7,10,13,16-docosatetraenoic acid (omega-6, C22H36O2, the common name adrenic acid, AdA) and adaptive behavioral development. We further studied the effects of AdA on neurodevelopment by using Caenorhabditis elegans (C. elegans) as a model. Worms from larval stages L1 to L4 were supplemented with AdA at 5 nominal concentrations (0 µM [control], 0.1 µM, 1 µM, 10 µM, and 100 µM) and subjected to behavioral and mechanistic analyses. KEY FINDINGS: Supplementation with AdA from larval stages L1 to L4 impaired neurobehavioral development, such as locomotive behaviors, foraging ability, chemotaxis behavior, and aggregation behavior. Furthermore, AdA upregulated the production of intracellular reactive oxygen species. AdA-induced oxidative stress blocked serotonin synthesis and serotoninergic neuron activity and inhibited expression of daf-16 and the daf-16-regulated genes mtl-1, mtl-2, sod-1, and sod-3, resulting in attenuation of the lifespan in C. elegans. SIGNIFICANCE: Our study reveals that AdA is a harmful HBM lipid that may have adverse effects on infant adaptive behavioral development. We believe this information may be critical for AdA administration guidance in children's health care.

Therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation on respiratory failure in preterm infants with a gestational age of 28-34 weeks: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the therapeutic efficacy of volume-guaranteed high frequency oscillation ventilation (HFOV-VG) versus conventional mechanical ventilation (CMV) in the treatment of preterm infants with respiratory failure.@*METHODS@#A prospective study was conducted on 112 preterm infants with respiratory failure (a gestational age of 28-34 weeks) who were admitted to the Department of Neonatology, Jiangyin Hospital Affiliated to Medical School of Southeast University, from October 2018 to December 2022. The infants were randomly divided into an HFOV-VG group (44 infants) and a CMV group (68 infants) using the coin tossing method based on the mode of mechanical ventilation. The therapeutic efficacy was compared between the two groups.@*RESULTS@#After 24 hours of treatment, both the HFOV-VG and CMV groups showed significant improvements in arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, and partial pressure of oxygen/fractional concentration of inspired oxygen ratio (P<0.05), and the HFOV-VG group had better improvements than the CMV group (P<0.05). There were no significant differences between the two groups in the incidence rate of complications, 28-day mortality rate, and length of hospital stay (P>0.05), but the HFOV-VG group had a significantly shorter duration of invasive mechanical ventilation than the CMV group (P<0.05). The follow-up at the corrected age of 6 months showed that there were no significant differences between the two groups in the scores of developmental quotient, gross motor function, fine motor function, adaptive ability, language, and social behavior in the Pediatric Neuropsychological Development Scale (P>0.05).@*CONCLUSIONS@#Compared with CMV mode, HFOV-VG mode improves partial pressure of oxygen and promotes carbon dioxide elimination, thereby enhancing oxygenation and shortening the duration of mechanical ventilation in preterm infants with respiratory failure, while it has no significant impact on short-term neurobehavioral development in these infants.

Iron Supplementation Is Associated with Improvement of Motor Development, Hemoglobin Level, and Weight in Preterm Infants during the First Year of Life in China.

Iron supplementation is recommended for preterm infants due to impaired iron endowment. However, the health outcomes of this recommendation remain controversial. Thus, this study aimed to determine the association of iron supplementation with neurobehavioral development, hemoglobin (Hb), and anthropometric characteristics in preterm infants. A retrospective cohort design was applied to collect data from 1568 preterm infants at 0-3 months of corrected age (mo CA) from a hospital in South China. Infants were categorized into a 3-month iron supplementation group (IG, n = 697) or a control group (CG, n = 871) according to medical records, and then followed through to 12 mo CA. Data on neurobehavioral development, anthropometry, Hb level, history of diseases, and nutrition were collected at 3, 6, and 12 mo CA. The results showed that, compared with the CG, iron supplementation was positively related to improved gross motor skills and weight at 6 mo CA (ß = 1.894, ß = 5.322) and 12 mo CA (ß = 4.019, ß = 6.830) and fine motor skills at 12 mo CA (ß = 1.980), after adjustment for confounding factors including illness, nutritional supplements, and diet. Iron supplementation was also related to elevated Hb levels and its increase at 3 mo CA (ß = 2.196, ß = 3.920) and 6 mo CA (ß = 3.011, ß = 7.259). In conclusion, iron supplementation for 3 months in Chinese preterm infants is positively associated with improved motor development, elevated Hb levels, and higher body weight during the first year of life.

Early Life Stage Folic Acid Deficiency Delays the Neurobehavioral Development and Cognitive Function of Rat Offspring by Hindering De Novo Telomere Synthesis.

Early life stage folate status may influence neurodevelopment in offspring. The developmental origin of health and disease highlights the importance of the period of the first 1000 days (from conception to 2 years) of life. This study aimed to evaluate the effect of early life stage folic acid deficiency on de novo telomere synthesis, neurobehavioral development, and the cognitive function of offspring rats. The rats were divided into three diet treatment groups: folate-deficient, folate-normal, and folate-supplemented. They were fed the corresponding diet from 5 weeks of age to the end of the lactation period. After weaning, the offspring rats were still fed with the corresponding diet for up to 100 days. Neurobehavioral tests, folic acid and homocysteine (Hcy) levels, relative telomere length in brain tissue, and uracil incorporation in telomere in offspring were measured at different time points. The results showed that folic acid deficiency decreased the level of folic acid, increased the level of Hcy of brain tissue in offspring, increased the wrong incorporation of uracil into telomeres, and hindered de novo telomere synthesis. However, folic acid supplementation increased the level of folic acid, reduced the level of Hcy of brain tissue in offspring, reduced the wrong incorporation of uracil into telomeres, and protected de novo telomere synthesis of offspring, which was beneficial to the development of early sensory-motor function, spatial learning, and memory in adolescence and adulthood. In conclusion, early life stage folic acid deficiency had long-term inhibiting effects on neurodevelopment and cognitive function in offspring.

Corrigendum: Impact of SARS-CoV-2 Infection During Pregnancy on Infant Neurobehavioral Development: A Case-Control Study.

[This corrects the article DOI: 10.3389/fped.2021.762684.].

Does inflammation mediate behavioural alterations in anaesthesia-induced developmental neurotoxicity?

Anaesthesia exposure early in life potentially impairs neurobehavioural development. A recent study in the Journal investigated the possibility that progesterone mitigates anaesthesia-induced developmental neurotoxicity in neonatal rats exposed to sevoflurane. The novel findings show that the steroid hormone progesterone protects against development of behavioural alterations caused by sevoflurane. The protective mechanism is proposed to relate to anti-inflammatory properties of progesterone, which brings up important questions regarding the role of inflammation in mediating the neurobehavioural alterations in anaesthesia-induced developmental neurotoxicity. We discuss this mechanism and encourage new research that may clarify the underlying mechanisms of progesterone-induced protection and extend these findings into a translational model.

Neuropsychological effects in children exposed to anticonvulsant monotherapy during gestation: Phenobarbital, carbamazepine, and phenytoin.

OBJECTIVE: Usage during pregnancy of the antiseizure medication (ASM), phenobarbital (PB), carbamazepine (CBZ), and phenytoin (PHT), has been associated with adverse pregnancy outcomes. While morphological effects on offspring are well-documented, inconsistent findings have been reported on neuropsychological development, possibly due to differences in attention to maternal demographics, and other design characteristics. Herein, we report the results of a carefully designed protocol used to examine the effects of gestational monotherapy with PB, CBZ, or PHT upon children's general mental abilities, when compared to age- and gender- matched children born to unexposed women of similar age, education, and socioeconomic status. METHODS: For each ASM, we selected qualifying cases from children born to PB, CBZ, or PHT monotherapy-exposed and unexposed women. Following the application of inclusion, exclusion, and matching criteria, our sample included 34 PB-exposed, 40 PHT-exposed, and 41 CBZ-exposed children along with matched unexposed children for each drug group. Criteria were applied through examination of maternal medical and educational histories, parental socioeconomic characteristics, and child's age and gender. Each child's physical and neuropsychological characteristics were examined, using standardized protocols. We report on the cognitive performance of the children as assessed by the Wechsler Intelligence Scale for Children - III (WISC-III), the leading measure of mental ability in the U.S. RESULTS: An overall mixed model ANOVA of the adjusted performance of the children across all groups controlling for maternal IQ revealed significant effects on verbal IQ, but not full-scale IQ or performance IQ. In the individual drug and unexposed group comparisons, only reduced verbal and full-scale IQ scores in PB-exposed versus matched unexposed children were found. Comparisons between drug groups revealed a significant reduction in verbal IQ and full-scale IQ in PB-exposed versus PHT-exposed children, but not in other drug-drug comparisons. SIGNIFICANCE: These results demonstrate effects on children's mental ability due to prenatal PB exposure, such that analyses adjusted for maternal IQ scores, revealed reduced verbal mental abilities and reduced full-scale IQ scores when scores in exposed children were compared to scores from children of the same age and sex born to demographically similar, healthy unexposed women. When comparisons were made between drug groups, children exposed prenatally to PB performed significantly worse than prenatally PHT-exposed children, but CBZ-exposed children's scores were not significantly different from those of PB or PHT-exposed groups. In light of shared effects on structural teratogenicity, these findings suggest that use of PB monotherapy for the management of seizures during pregnancy may be associated with increased risk in comparison to PHT when neurobehavioral functioning is considered, and that only PB-exposed children have reduced performance compared to matched controls. Attention to these effects is critical in the developing world where use of these older medications remains predominant, and prudent choices can be made to reduce impact on cognitive development.

Prepregnancy body mass index and gestational weight gain affect the offspring neurobehavioral development at one year of age.

OBJECTIVE: Recent data show that maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) are associated with offspring neurobehavior in childhood. However, little is known about the effect on infants that less than 20 months of age, and whether this association has sex differences. METHODS: In this birth cohort study, a total of 661 mother-infant pairs were enrolled in Shanghai, China, between February 2017 and April 2019. Maternal prepregnancy BMI was categorized according to the Chinese classification and GWG according to the 2009 Institute of Medicine (IOM). Neurobehavioral development for infants of 12 months of age was assessed by Gesell Developmental Scale (GDS), which contained five subscales of gross motor, fine motor, adaptive behavior, language, and social behavior. RESULTS: Abnormal maternal prepregnancy BMI and excessive GWG were associated with infant birth weight and/or birth length (p < .05), while no influence was found on yearling weight or length. Women who were overweight/obese prior to pregnancy or excessive GWG during pregnancy had infants who were more deficient in neurobehavioral developmental including language (p < .01) and/or social behavior (p < .05). Specifically, excessive GWG was associated with lower language ability in girls but not boys (p < .05). CONCLUSIONS: Aberrant prepregnancy BMI and excessive GWG not only affect the body size of newborn infants, but also impair their neurobehavioral development, suggesting that general guidance to the women should be advised to attain optimal prepregnancy BMI and GWG.

Impact of SARS-CoV-2 Infection During Pregnancy on Infant Neurobehavioral Development: A Case-Control Study.

Background: Previous studies on the pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the general population and pregnant women, while little is known about the effects of SARS-CoV-2 on retardation during and after pregnancy. The purpose of this study was to evaluate the potential influence of SARS-CoV-2 on infant neurobehavioral development. Methods: A case-control study was conducted in Wuhan Maternal and Child Health Hospital, China. Nine pregnant women with SARS-CoV-2 infection and 9 controls matched by maternal age, parity, and status of chronic disease were included. Infantile neurobehavioral development was assessed through the Ages and Stages Questionnaires Edition 3 (ASQ-3). Results: The majority of pregnant women with SARS-CoV-2 experienced cesarean section (7 of 9), which was higher than the control group (5 of 9). The throat swabs of all newborn were negative. We found that compared with the control group, neonates of mothers with SARS-CoV-2 infection during pregnancy had lower scores in communication, gross movement, fine movement, problem solving, and personal-social domains; but only fine movement domain yielded statistical significance (P = 0.031). Conclusion: Infection with SARS-CoV-2 during pregnancy may have a certain impact on infant neurobehavioral development. Further studies with larger sample size are warranted for validation.

Association of Iron-Deficiency Anemia and Non-Iron-Deficiency Anemia with Neurobehavioral Development in Children Aged 6-24 Months.

(1) Background: Anemia has comprehensive adverse effects on the growth and development of children. In this study, we analyzed the potential effects of different types of anemia on early-life neurobehavioral development. (2) Methods: A total of 2601 children aged 6-24 months, whose parents agreed to participate in this study, underwent routine blood tests and neurobehavioral development assessment. The children's parents or other primary caregivers were interviewed with a face-to-face questionnaire at the time of enrollment in the study. Anemia was determined by hemoglobin < 110 g/L and classified into iron-deficiency and non-iron-deficiency anemia according to the levels of serum ferritin, C-reactive protein, and alpha-1-acid glycoprotein. Neurobehavioral development was assessed by the China Developmental Scale for Children and divided into five domains: gross motor, fine movement, adaptability, language, and social behavior. The development quotient (DQ) was used to measure the level of total neurobehavioral development and each domain of neurobehavioral development. (3) Results: The prevalence of anemia in children aged 6-24 months was 26.45%, of which iron-deficiency anemia only accounted for 27.33%. Compared with children without anemia, those with iron-deficiency anemia had a significantly lower developmental quotient (DQ) for total neurobehavioral development and gross motor and adaptability development. The partial regression coefficients were -1.33 (95% CI -2.36, -0.29; p = 0.012), -1.88 (95% CI -3.74, -0.03; p = 0.047), and 1.48 (95% CI -2.92, -0.05; p = 0.042), respectively. Children with non-iron-deficiency anemia had significantly lower DQ for total neurobehavioral development and gross motor and fine movement development than those without anemia. The partial regression coefficients were -0.94 (95% CI -1.64, -0.25; p = 0.008), -1.25 (95% CI -2.48, -0.03; p = 0.044), and -1.18 (95% CI -2.15, -0.21; p = 0.017), respectively. There were no statistically significant differences in total neurobehavioral development and the five domains of neurobehavioral development between children with non-iron-deficiency and iron-deficiency anemia. The partial ß values were 0.40 (95% CI -1.53, 2.33; p = 0.684), 0.21 (95% CI -1.39, 1.81; p = 0.795), 0.63 (95% CI -1.03, 2.28; p = 0.457), 0.16 (95% CI -1.78, 2.10; p = 0.871), 0.35 (95% CI -1.32, 2.01; p = 0.684), and 0.34 (95% CI -0.77, 1.46; p = 0.545), respectively. (4) Conclusions: Both iron-deficiency anemia and non-iron-deficiency anemia were negatively correlated with the neurobehavioral development of children. Negative correlations were found between iron-deficiency anemia and gross motor and adaptability development and between non-iron-deficiency anemia and gross motor and fine movement development.

Effects of Early Vocal Contact in the Neonatal Intensive Care Unit: Study Protocol for a Multi-Centre, Randomised Clinical Trial.

Preterm infants are at risk for developing altered trajectories of cognitive, social, and linguistic competences compared to a term population. This is mainly due to medical and environmental factors, as they are exposed to an atypical auditory environment and simultaneously, long periods of early separation from their parents. The short-term effects of early vocal contact (EVC) on an infant's early stability have been investigated. However, there is limited evidence of its impact on the infant's autonomic nervous system maturation, as indexed by heart rate variability, and its long-term impact on infant neurodevelopment. Our multi-centric study aims to investigate the effects of EVC on a preterm infant's physiology, neurobehaviour, and development. Eighty stable preterm infants, born at 25-32 weeks and 6 days gestational age, without specific abnormalities, will be enrolled and randomised to either an intervention or control group. The intervention group will receive EVC, where mothers will talk and sing to their infants for 10 min three times per week for 2 weeks. Mothers in the control group will be encouraged to spend the same amount of time next to the incubator and observe the infant's behaviour through a standard cluster of indicators. Infants will be assessed at baseline; the end of the intervention; term equivalent age; and 3, 6, 12, and 24 months corrected age, with a battery of physiological, neurobehavioral, and developmental measures. Early interventions in the neonatal intensive care unit have demonstrated effects on the neurodevelopment of preterm infants, thereby lowering the negative long-term effects of an atypical auditory and interactional environment. Our proposed study will provide new insight into mother-infant early contact as a protective intervention against the sequelae of prematurity during this sensitive period of development. Early intervention, such as EVC, is intuitive and easy to implement in the daily care of preterm infants. However, its long-term effects on infant neurodevelopment and maternal sensitivity and stress are still unclear. Trial Registration: NCT04759573, retrospectively registered, 17 February 2021.

Effects of exposure to urban particulate matter SRM 1648a during pregnancy on the neurobehavioral development of offspring mice.

The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5-21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group. Our data showed that prenatal PM exposure caused the offspring mice's anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.