Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort.

BACKGROUND: Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data from the HELMi birth cohort, we investigated them collectively, considering maternal and infant secretor status. METHODS: HMO composition in breastmilk collected 3 months postpartum (n = 350 mothers) was profiled using high-performance liquid chromatography. Infant gut microbiota taxonomic and functional development was studied at 3, 6, and 12 months (n = 823 stool samples) via shotgun metagenomic sequencing, focusing on HMO metabolism via glycoside hydrolase (GH) analysis. Maternal and infant secretor statuses were identified through phenotyping and genotyping, respectively. Child health, emphasizing allergies and antibiotics as proxies for infectious diseases, was recorded until 2 years. FINDINGS: Mother's parity, irritable bowel syndrome, gestational diabetes, and season of milk collection associated with HMO composition. Neither maternal nor infant secretor status associated with infant gut microbiota, except for a few taxa linked to individual HMOs. Analysis stratified for birth mode revealed distinct patterns between the infant gut microbiota and HMOs. Child health parameters were not associated to infant or maternal secretor status. INTERPRETATION: This comprehensive exploration unveils intricate links between secretor genotype, maternal factors, HMO composition, infant microbiota, and child health. Understanding these nuanced relationships is paramount for refining strategies to optimize early life nutrition and its enduring impact on long-term health. FUNDING: Sweet Crosstalk EU H2020 MSCA ITN, Academy of Finland, Mary and Georg C. Ehrnrooth Foundation, Päivikki and Sakari Sohlberg Foundation, and Tekes.

The Prevalence and Risk Analysis of Cerebral Palsy and Other Neuro-Psychological Comorbidities in Children with Low Birth Weight in Taiwan: A Nationwide Population-Based Cohort Study.

Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009-2013) and 151,810 controls were analyzed using Taiwan's National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants.

INVITED REVIEW: Impact of Maternal Health and Nutrition on the Microbiome and Immune Development of Neonatal Calves.

This comprehensive review highlights the intricate interplay between maternal factors and the co-development of the microbiome and immune system in neonatal calves. Based on human and mouse studies, multiple prenatal and postnatal factors influence this process by altering the host-associated microbiomes (gut, respiratory tract, skin), microbial colonization trajectories, and priming of the immune systems (mucosal and systemic). This review emphasizes the importance of early life exposure, highlighting postnatal factors that work in synergy with maternal factors in further finetuning the co-development of the neonatal microbiome and immunity. In cattle, there is a general lack of research to identify the maternal effect on the early colonization process of neonatal calves (gut, respiratory tract) and its impact on the priming of the immune system. Past studies have primarily investigated the maternal effects on the passive transfer of immunity at birth. The co-development process of the microbiome and immune system is vital for lifelong health and production in cattle. Therefore, comprehensive research beyond the traditional focus on passive immunity is an essential step in this endeavor. Calf microbiome research reports the colonization of diverse bacterial communities in newborns, which is affected by the colostrum feeding method immediately after birth. In contrast to human studies reporting a strong link between maternal and infant bacterial communities, there is a lack of evidence to clearly define cow-to-calf transmission in cattle. Maternal exposure has been shown to promote the colonization of beneficial bacteria in neonatal calves. Nonetheless, calf microbiome research lacks links to early development of the immune system. An in-depth understanding of the impact of maternal factors on microbiomes and immunity will improve the management of pregnant cows to raise immune-fit neonatal calves. It is essential to investigate the diverse effects of maternal health conditions and nutrition during pregnancy on the gut microbiome and immunity of neonatal calves through collaboration among researchers from diverse fields such as microbiology, immunology, nutrition, veterinary science, and epidemiology.

Prenatal maternal infections and early childhood developmental outcomes: analysis of linked administrative health data for Greater Glasgow & Clyde, Scotland.

BACKGROUND: Previous research has linked prenatal maternal infections to later childhood developmental outcomes and socioemotional difficulties. However, existing studies have relied on retrospectively self-reported survey data, or data on hospital-recorded infections only, resulting in gaps in data collection. METHODS: This study used a large linked administrative health dataset, bringing together data from birth records, hospital records, prescriptions and routine child health reviews for 55,856 children born in Greater Glasgow & Clyde, Scotland, 2011-2015, and their mothers. Logistic regression models examined associations between prenatal infections, measured as both hospital-diagnosed prenatal infections and receipt of infection-related prescription(s) during pregnancy, and childhood developmental concern(s) identified by health visitors during 6-8 week or 27-30 month health reviews. Secondary analyses examined whether results varied by (a) specific developmental outcome types (gross-motor-skills, hearing-communication, vision-social-awareness, personal-social, emotional-behavioural-attention and speech-language-communication) and (b) the trimester(s) in which infections occurred. RESULTS: After confounder/covariate adjustment, hospital-diagnosed infections were associated with increased odds of having at least one developmental concern (OR: 1.30; 95% CI: 1.19-1.42). This was broadly consistent across all developmental outcome types and appeared to be specifically linked to infections occurring in pregnancy trimesters 2 (OR: 1.34; 95% CI: 1.07-1.67) and 3 (OR: 1.33; 95% CI: 1.21-1.47), that is the trimesters in which foetal brain myelination occurs. Infection-related prescriptions were not associated with any clear increase in odds of having at least one developmental concern after confounder/covariate adjustment (OR: 1.03; 95% CI: 0.98-1.08), but were associated with slightly increased odds of concerns specifically related to personal-social (OR: 1.12; 95% CI: 1.03-1.22) and emotional-behavioural-attention (OR: 1.15; 95% CI: 1.08-1.22) development. CONCLUSIONS: Prenatal infections, particularly those which are hospital-diagnosed (and likely more severe), are associated with early childhood developmental outcomes. Prevention of prenatal infections, and monitoring of support needs of affected children, may improve childhood development, but causality remains to be established.

Maternal diet quality trajectories from pregnancy to 3.5 years postpartum and associated maternal factors.

PURPOSE: This study examined maternal diet quality trajectories from pregnancy to 3.5 years postpartum and associated maternal factors. METHODS: Data of 473 Australian women from the Healthy Beginnings Trial were used. A food frequency questionnaire collected dietary intake in pregnancy and 1, 2 and 3.5 years postpartum. Diet quality scores were calculated using the 2013 Dietary Guideline Index (DGI-2013) and RESIDential Environments Guideline Index (RDGI). Group-based trajectory modelling identified diet quality trajectories from pregnancy to 3.5 years postpartum. Multivariable logistic regression investigated factors associated with maternal diet quality trajectories. RESULTS: Two stable trajectories of low or high diet quality were identified for the DGI-2013 and RDGI. Women who smoked had higher odds of following the low versus the high DGI-2013 (OR 1.77; 95%CI 1.15, 2.75) and RDGI (OR 1.80; 95%CI 1.17, 2.78) trajectories, respectively. Women who attended university had lower odds of following the low versus the high DGI-2013 (OR 0.41; 95%CI 0.22, 0.76) and RDGI (OR 0.38; 95%CI 0.21, 0.70) trajectories, respectively. Women who were married had lower odds of following the low versus the high DGI-2013 trajectory (OR 0.39; 95%CI 0.17, 0.89), and women who were unemployed had higher odds of following the low versus the high RDGI trajectory (OR 1.78; 95%CI 1.13, 2.78). Maternal age, country of birth, household composition and pre-pregnancy body mass index were not associated with diet quality trajectories. CONCLUSION: Maternal diet quality trajectories remained stable from pregnancy to 3.5 years postpartum. Women who smoked, completed high school or less, were not married or were unemployed tended to follow low, stable diet quality trajectories.

A Conceptual Thematic Framework of Psychological Adjustment in Caregivers of Children with Craniofacial Microsomia.

OBJECTIVE: Children with craniofacial microsomia (CFM) have complex healthcare needs, resulting in evaluations and interventions from infancy onward. Yet, little is understood about families' treatment experiences or the impact of CFM on caregivers' well-being. To address this gap, the NIH-funded 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program sought to develop a conceptual thematic framework of caregiver adjustment to CFM. DESIGN: Caregivers reported on their child's medical and surgical history. Narrative interviews were conducted with US caregivers (n = 62) of children aged 3-17 years with CFM. Transcripts were inductively coded and final themes and subthemes were identified. RESULTS: Components of the framework included: 1) Diagnostic Experiences, including pregnancy and birth, initial emotional responses, communication about the diagnosis by healthcare providers, and information-seeking behaviors; 2) Child Health and Healthcare Experiences, including feeding, the child's physical health, burden of care, medical decision-making, surgical experiences, and the perceived quality of care; 3) Child Development, including cognition and behavior, educational provision, social experiences, and emotional well-being; and 4) Family Functioning, including parental well-being, relationships, coping strategies, and personal growth. Participants also identified a series of "high" and "low" points throughout their journey and shared their priorities for future research. CONCLUSIONS: Narrative interviews provided rich insight into caregivers' experiences of having a child with CFM and enabled the development of a conceptual thematic framework to guide clinical care and future research. Information gathered from this study demonstrates the need to incorporate evidence-based psychological support for families into the CFM pathway from birth onward.

The maternal factors associated with infant low birth weight: an umbrella review.

BACKGROUND: In this umbrella review, we systematically evaluated the evidence from meta-analyses and systematic reviews of maternal factors associated with low birth weight. METHODS: PubMed, Scopus, and Web of Science were searched to identify all relevant published studies up to August 2023. We included all meta-analysis studies (based on cohort, case-control, cross-sectional studies) that examined the association between maternal factors (15 risk factors) and risk of LBW, regardless of publication date. A random-effects meta-analysis was conducted to estimate the summary effect size along with the 95% confidence interval (CI), 95% prediction interval, and heterogeneity (I2) in all meta-analyses. Hedges' g was used as the effect size metric. The effects of small studies and excess significance biases were assessed using funnel plots and the Egger's test, respectively. The methodological quality of the included studies was assessed using the AMSTAR 2 tool. RESULTS: We included 13 systematic Review with 15 meta-analysis studies in our study based on the inclusion criteria. The following 13 maternal factors were identified as risk factors for low birth weight: crack/cocaine (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.26-3.52), infertility (OR 1.34, 95% CI 1.2-1.48), smoking (OR 2.00, 95% CI 1.76-2.28), periodontal disease (OR 2.41, 95% CI 1.67-3.47), depression (OR 1.84, 95% CI 1.34-2.53), anemia (OR 1.32, 95% CI 1.13-1.55), caffeine/coffee (OR 1.34, 95% CI 1.14-1.57), heavy physical workload (OR 1.87, 95% CI 1.00-3.47), lifting ≥ 11 kg (OR 1.59, 95% CI 1.02-2.48), underweight (OR 1.79, 95% CI 1.20-2.67), alcohol (OR 1.23, 95% CI 1.04-1.46), hypertension (OR 3.90, 95% CI 2.73-5.58), and hypothyroidism (OR 1.40, 95% CI 1.01-1.94). A significant negative association was also reported between antenatal care and low birth weight. CONCLUSIONS: This umbrella review identified drug use (such as crack/cocaine), infertility, smoking, periodontal disease, depression, caffeine and anemia as risk factors for low birth weight in pregnant women. These findings suggest that pregnant women can reduce the risk of low birth weight by maintaining good oral health, eating a healthy diet, managing stress and mental health, and avoiding smoking and drug use.

The Concentration of Lactoferrin in Breast Milk Correlates with Maternal Body Mass Index and Parity.

Background: Lactoferrin (LF) is a multifunctional glycoprotein found in human milk and body fluids, which has been shown to play a vital role in regulating the immunity and supporting the intestinal health of infants. Aim: This study evaluated the association between maternal/parturient factors and LF concentration in the breast milk of Chinese mothers. Methods: 207 breast milk samples were collected from healthy mothers with in the first year of lactation. Maternal and parturient information was collected for these participants through questionnaires. The content of lactoferrin in breast milk was detected by liquid chromatography, and macronutrient concentration in breast milk was measured by human milk analyzer in only 109 samples. Results: Our findings demonstrated that the LF content was much higher within the first month of lactation than it was after that period (p < 0.05). When compared with normal and lean mothers, the LF content of obese mothers was considerably higher (p < 0.05). The parity and LF content showed a favorable correlation. The proportion of LF to total protein tended to decrease as lactation progressed. Protein, fat, dry matter, and energy content were significantly positively correlated with LF content (p < 0.001). Conclusion: Early breast milk tends to have a higher level of LF, and the change of LF concentration in breast milk is associated with the parity and body mass index of the mother.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

OBJECTIVE: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems. METHOD: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years. RESULTS: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047). CONCLUSION: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems.

Association between gestational weight gain and behavioral problems of the offspring aged 6-7 years: A population-based study in Japan.

OBJECTIVE: To identify the optimal gestational weight gain (GWG) thresholds for behavioral problems and prosocial behavior in 6- to 7-year-old children. METHODS: A retrospective cohort study was conducted using data from the Adachi Child Health Impact of Living Difficulty study, including all first-graders in public schools in Adachi, Tokyo, in 2017, 2019, and 2021 (n = 11 048, response rate = 80.1%). GWG was based on clinical records in the Mother and Child Health Handbook. Total difficulties and prosocial behavior were assessed using the Strength and Difficulties Questionnaire. Logistic regression models with restricted cubic splines, and quintile categories were employed to examine the association of GWG with the clinical range of total difficulties and prosocial behavior, controlling for covariates. RESULTS: The association between GWG and total difficulties exhibited a reverse J-shaped pattern, with low GWG, but not high GWG, increasing the risk (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.42, P = 0.039 for GWG < 7 kg; OR 1.03, 95% CI 0.85-1.24, P = 0.786 for GWG > 14 kg), referencing the median (10 kg). High GWG was associated with a lower risk of problems in prosocial behavior (OR = 0.77, 95% CI 0.62-0.95, P = 0.017 for GWG > 14 kg; OR 1.06, 95% CI 0.88-1.27, P = 0.532 for GWG <7 kg). CONCLUSION: GWG less than 7 kg may increase the risk of total difficulties, whereas GWG over 14 kg may serve as a protective factor for prosocial behavior in 6- to 7-year-old children.

Impact of Environmental Exposures on Human Breast Milk Lipidome in Future Immune-Mediated Diseases.

The composition of human breast milk (HBM) exhibits significant variability both between individuals and within the same individual. While environmental factors are believed to play a role in this variation, their influence on breast milk composition remains inadequately understood. Herein, we investigate the impact of environmental factors on HBM lipid composition in a general population cohort. The study included mothers (All Babies In Southeast Sweden study) whose children later progressed to one or more immune-mediated diseases later in life: type 1 diabetes (n = 9), celiac disease (n = 24), juvenile idiopathic arthritis (n = 9), inflammatory bowel disease (n = 7), hypothyroidism (n = 6), and matched controls (n = 173). Lipidome of HBM was characterized by liquid chromatography combined with high-resolution mass spectrometry. We observed that maternal age, body mass index, diet, and exposure to perfluorinated alkyl substances (PFASs) had a marked impact on breast milk lipidome, with larger changes observed in the milk of those mothers whose children later developed autoimmune diseases. We also observed differences in breast milk lipid composition in those mothers whose offspring later developed autoimmune diseases. Our study suggests that breast milk lipid composition is modified by a complex interaction between genetic and environmental factors, and, importantly, this impact was significantly more pronounced in those mothers whose offspring later developed autoimmune/inflammatory diseases. Our findings also suggest that merely assessing PFAS concentration may not capture the full extent of the impact of chemical exposures; thus, the more comprehensive exposome approach is essential for accurately assessing the impact of PFAS exposure on HBM and, consequently, on the health outcomes of the offspring.

The Effect of Maternal Diet and Physical Activity on the Epigenome of the Offspring.

The aim of this review was to examine the current literature regarding the effect of maternal lifestyle interventions (i.e., diet and physical activity) on the epigenome of the offspring. PubMed, Scopus and Cochrane-CENTRAL were screened until 8 July 2023. Only randomized controlled trials (RCTs) where a lifestyle intervention was compared to no intervention (standard care) were included. Outcome variables included DNA methylation, miRNA expression, and histone modifications. A qualitative approach was used for the consideration of the studies' results. Seven studies and 1765 mother-child pairs were assessed. The most common types of intervention were dietary advice, physical activity, and following a specific diet (olive oil). The included studies correlated the lifestyle and physical activity intervention in pregnancy to genome-wide or gene-specific differential methylation and miRNA expression in the cord blood or the placenta. An intervention of diet and physical activity in pregnancy was found to be associated with slight changes in the epigenome (DNA methylation and miRNA expression) in fetal tissues. The regions involved were related to adiposity, metabolic processes, type 2 diabetes, birth weight, or growth. However, not all studies showed significant differences in DNA methylation. Further studies with similar parameters are needed to have robust and comparable results and determine the biological role of such modifications.

Burden of mental, behavioral, and neurodevelopmental disorders in the Finnish most preterm children: a national register study.

Etiologies and the whole picture in childhood mental, behavioral, and neurodevelopmental disorders related to gestational age are unclear. This study included all Finnish children (N = 341,632) born between January 1, 2001, and December 31, 2006, whose data including their mothers (N = 241,284) were collected from national registers. Children with unclear gestational age (GA) (N = 1245), severe congenital malformations (N = 11,746), and moderate/severe/undefined cognitive impairment (N = 1140), and those who died during the perinatal period (N = 599) were excluded. The main outcome was the prevalence of mental and behavioral disorders (International Classification of Disorders) at 0 - 12 years of age in association with GA, adjusted for gender and prenatal variables. Out of all included (N = 326,902) children 16.6% (N = 54,270) were diagnosed to have any mental health disorder at 0 - 12 years. Adjusted Odd Ratio (OR) were for any disorder in preterm (< 37 weeks) 1.37 [1.28 - 1.46] and 4.03 [3.08 - 5.26] in extreme preterm (≤ 28 weeks) versus term born children, p < 0.05. The lower the GA at birth, the higher the risk for multiple disorders and earlier onset of disorder, p < 0.05. Adjusted ORs were for male/female 1.94 [1.90 - 1.99], maternal mental health disorder (yes/not) 1.99 [1.92 - 2.07], and smoking during pregnancy (yes/not) 1.58 [1.54 - 1.62], and these risks were more common in preterm versus term born children (p < 0.05). Extreme early birth was a strong risk factor per se for any or multiple and early shown mental health disorders. Other risk factors for mental health accumulated to preterm children.

The Impact of Maternal and Perinatal Factors on the Neonatal Electrocardiogram.

INTRODUCTION: Myocardial development is still transitioning by the time of birth making the cardiomyocyte vulnerable to maternal and perinatal factors. We aimed at investigating the impact of maternal and perinatal factors on the neonatal electrocardiogram. METHODS: In a prospective cohort study, neonates underwent cardiac evaluation with electrocardiograms and echocardiograms (age 0-30 days). Associations between medical and demographic data, pregnancy, and birth-related factors, and electrocardiographic parameters were assessed. RESULTS: A total of 15,928 singletons with normal echocardiograms were included (52% boys). Neonates were divided into groups by accumulated number of maternal/perinatal factors: 0, 1, 2, 3, 4, and ≥5, and between-group differences in electrocardiographic parameters were analysed. We observed an additive effect with a leftward shift of the QRS axis and QT prolongation (all p < 0.01). Comparing extreme groups (0 vs. ≥5 maternal/perinatal factors), we found a 4.3% more left-shifted QRS axis (117 vs. 112°, p < 0.001) and a 0.8% prolonged QTcFridericia (QTcF; 363 vs. 366 ms, p < 0.001); the effect on QTcF was most pronounced in neonates examined in the first week of life (360 vs. 368 ms, p < 0.0001). CONCLUSION: We observed a cumulative effect of maternal and perinatal factors on neonatal electrocardiographic parameters, including a more left-shifted QRS axis and increased QT duration, although the variation was within normal reference ranges. Our findings add to the knowledge on the neonatal cardiac transition and the cardiac effect of maternal/perinatal factors.

Influence of birth-related maternal and neonatal factors on the levels of energy metabolism mediators in infants born at 32 or fewer weeks of gestation.

BACKGROUND: Energy metabolism mediators, which include the adipokines (leptin, adiponectin, ghrelin) and insulin-like growth factor 1 [IGF-1], are hormone-like proteins, produced and expressed in the placenta and fetal membranes, with properties featuring metabolic adaptation and inflammatory processes. Due to the complexity of the metabolic adaptation of preterm neonates during the transition to extrauterine life, it becomes essential to recognize the factors that influence the alteration of the adipokines and IGF-1 levels in the early postpartum stage.This study assessed the significance of maternal-fetal-neonatal factors in predicting the levels of leptin, adiponectin, ghrelin, and IGF-1 in preterm infants born at 32 or fewer weeks of gestation, during the early stage of postnatal adaptation. METHODS: Energy metabolism mediator levels were measured in urine samples obtained from extremely (less than 28 weeks) and very (28-32 weeks) preterm infants, within 48 h after their birth, and before the initiation of enteral nutrition. The urine samples were analyzed using enzyme-linked immunosorbent assay (ELISA) kits. The collected data included all birth-related maternal and neonatal factors such as maternal age, race/ethnicity, hypertensive disorders of pregnancy, diabetes, gravidity, parity, type of pregnancy, mode of delivery, and antenatal use of corticosteroids, antibiotics, magnesium sulfate, Apgar scores at 1 and 5 min, gestational age, and birth weight. We investigated the correlation between the levels of the tested mediators, the significance of the differences in their average levels based on the dichotomized maternal and neonatal factors, and the effect of the selected factors, in multiple regression models. Data from the regression models constructed for leptin, adiponectin, ghrelin, and IGF-1 are presented as regression coefficient ß with Standard Error (SE) of ß, coefficient of determination (R2), and adjusted R2. Before including the factor in regression models, we tested for the multicollinearity effect. Two-sided P values <0.05 were considered statistically significant. RESULTS: Among the 70 studied infants, 47.1% were male, 40.6% were white, 28.6% were extremely preterm, and 18.6% were born with a weight <750 grams. Except for a mild interplay between the adiponectin and IGF-1 levels, there was no correlation between the levels of the other studied mediators. Up to 20% variation in the tested energy metabolism mediator levels was dependent on some of the birth-related maternal and neonatal characteristics. For instance, leptin levels were reduced in association with male gender (-0.493 [0.190], p < 0.02) and increased in infants born to primigravids (0.562 [0.215], p < 0.02). Adiponectin levels were increased in infants born to nulliparous as compared to multiparous women (0.400 [0.171], p < 0.03). Ghrelin levels were reduced in males (-0.057 [0.026], p < 0.04). IGF-1 levels were increased in the urine of extremely preterm neonates (0.357 [0.111], p < 0.01) and preterm infants born with an Apgar less than three at 1 min (0. 340 [p < 0.153], p < 0.04). CONCLUSIONS: Nearly one-fifth of the variation in the urinary levels of the adipokines (leptin, adiponectin, ghrelin) and IGF-1 during the early postnatal stage in infants born at 32 or fewer weeks of gestation was predicated on one or more of the maternal and neonatal factors such as the infant's sex, extreme preterm gestation, a low Apgar score at 1 min, or birth to nulliparous women or primigravida mothers. Further studies will be required to explain the role of energy metabolism mediators in the postnatal adaptation of preterm-born infants.

Impact of maternal age and body mass index on the structure and function of the heart in newborns: a Copenhagen Baby Heart Study.

BACKGROUND: Maternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn. METHODS: Infants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m2) < 18.5; 18.5-24.9 (reference); 25-29.9; 30-34.9 and ≥ 35 and maternal age (years) < 25; 25-29; 30-34 (reference); 35-39 and ≥ 40. Outcomes were LV parameters ascertained by 2D-echocardiography. Associations between each maternal factor and infant LV parameters were analysed with either a linear model adjusted for the child's weight and length at birth, gestational age, sex, age at TTE, and maternal smoking, or a linear mixed model, further adjusted for random effects of analyst and month of analysis. Analyses investigating impact of maternal BMI were adjusted for maternal age, and vice versa. RESULTS: The study cohort included 24,294 infants. Compared with infants in the BMI reference group, infants born to women with a BMI ≥ 25 kg/m2 generally had smaller measures of LV internal diameters in end-diastole, reaching statistical significance for BMI 30-34.9 kg/m2 [-0.11 ± 0.04 mm, p = 0.01]. All groups of infants born to women with a BMI ≥ 25 kg/m2 had significantly smaller LV internal diameters in end-systole: BMI 25-29.9 kg/m2 [-0.04 ± 0.02 mm, p = 0.04], BMI 30-34.9 kg/m2 [-0.12 ± 0.03 mm, p = 0.001] and BMI ≥ 35 kg/m2 [-0.11 ± 0.05 mm, p = 0.03]. Compared with infants in the age reference group, infants born to women ≥ 40 years had significantly smaller LV internal diameters in end-diastole [-0.15 ± 0.04 mm, p = 0.001] and end-systole [-0.09 ± 0.04 mm, p = 0.009]. CONCLUSIONS: Systematic population-based echocardiography of infants showed that a maternal prepregnancy BMI ≥ 25 kg/m2 and maternal age ≥ 40 years were associated with smaller systolic and diastolic LV diameters. The long-term effects are unknown. CLINICAL TRIAL REGISTRATION: April 2016, Copenhagen Baby Heart, NCT02753348 .

Nutrition, stress, and healthcare use during pregnancy are associated with low birth weight: evidence from a case-control study in West Ethiopia.

Background: Low Birth Weight (LBW) remains a major public health concern globally, especially in lower and middle-income countries. In Ethiopia in general and in the study area in particular there is limited evidence regarding maternal factors associated with low birth weight. This study aimed to identify the maternal factors associated with low birth weight among neonates born in public health facilities in the west Wollega zone, West Ethiopia. Methods: We used a case-control study design and selected participant mothers with a newborn using the delivery database from three public hospitals and five health centers, between March 2022 and April 2022. Cases were identified using a newborn birth weight of <2,500 grams. Controls were identified using a newborn birth weight of ≥2,500 grams. An interviewer-administered structured questionnaire and chart review were used for data collection. Model fitness was assessed by Hosmer and Lemenshow goodness-of-fit test, including multi-collinearity checks. Candidate predictor variables were selected (using a value of p <0.25 in bivariable logistic regression models) for multivariable logistic regression to quantify the association between independent variables and LBW, expressed using Odds Ratios (OR) with a 95% Confidence Interval (CI). Mean and Standard Deviation (SD), all such values. Results: A total of 324 mothers with their newborns (81 cases and 243 controls) were eligible for inclusion. The mean age of participants was 27.9 years (SD 6.4) in cases and 25 years (SD 3.9) in controls. Mean birth weight was 2,128 grams (SD 1,697) in cases and 2,988 grams (SD 378) in controls. In multivariable logistic regression analysis, lack of nutritional counseling (OR = 2.4; 95%CI: 1.24-4.72), maternal middle upper arm circumference of <23 cm (OR = 3.1; 95%CI: 1.64-5.91), maternal stress during pregnancy (OR = 2.8; 95% CI:1.23-6.36), and antenatal follow up less than four visits (OR = 2.8; 95% CI: 1.12-6.82) were independently associated with LBW. Conclusion: In this study, lack of nutritional counseling, maternal undernutrition, maternal stress during pregnancy, and antenatal follow-up visits less than recommended were associated with LBW. Special attention should be given to promoting antenatal care and counseling mothers on nutrition and relaxation to prevent stress during pregnancy.

Maternal factors in the origin of cleft lip/cleft palate: A population-based case-control study.

OBJECTIVES: Orofacial clefts are among the most common birth defects, with an estimated worldwide incidence of around 1.5-1.7 per 1000 live-born babies. The most frequent form of orofacial clefts is cleft lip with or without cleft palate (CL ± CP). The role of environmental factors in the development of clefts is unclear in most patients, thus the aim of this study was to estimate possible maternal risk factors in the origin of CL ± CP. MATERIALS AND METHODS: 1648 CL ± CP cases, 2654 matched controls and 57 231 population controls were evaluated from The Hungarian Case-Control Surveillance of Congenital Abnormalities. Maternal factors during the critical period in cases and controls were compared. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated in a multivariable conditional logistic regression model. RESULTS: Among socio-demographic data, we have found significant differences between maternal employment. The proportion of unskilled mothers (6.5%) were higher in the CL ± CP group than in controls (3.5%). Medically recorded maternal anaemia, excessive vomiting and threatened abortion were associated with a higher risk of CL ± CP. An elevated risk was also found in various acute illnesses such as influenza (OR: 2.4, 95% CI: 3.0-5.8), acute bronchitis (OR: 4.5, 95% CI: 1.6-12.6) and urinary tract infections (OR: 3.5, 95% CI: 2.0-6.0). Maternal migraine and essential hypertension occurred more frequently in the mothers of cases than in controls. CONCLUSION: The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of CL ± CP.

Evaluation and Mechanistic Study of Transgenerational Neurotoxicity in Zebrafish upon Life Cycle Exposure to Decabromodiphenyl Ethane (DBDPE).

The novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant in the environment, which may evoke imperceptible effects in humans or wild animals. Hence in this study, zebrafish embryos were exposed to DBDPE (0, 0.1, 1, and 10 nM) until sexual maturity (F0), and F1 and F2 generations were cultured without further exposure to study the multi- and transgenerational toxicity and underlying mechanism. The growth showed sex-different changing profiles across three generations, and the social behavior confirmed transgenerational neurotoxicity in adult zebrafish upon life cycle exposure to DBDPE. Furthermore, maternal transfer of DBDPE was not detected, whereas parental transfer of neurotransmitters to zygotes was specifically disturbed in F1 and F2 offspring. A lack of changes in the F1 generation and opposite changing trends in the F0 and F2 generations were observed in a series of indicators for DNA damage, DNA methylation, and gene transcription. Taken together, life cycle exposure to DBDPE at environmentally relevant concentrations could induce transgenerational neurotoxicity in zebrafish. Our findings also highlighted potential impacts on wild gregarious fish, which would face higher risks from predators.

Prediction of Preterm Birth among Infants with Orofacial Cleft Defects.

OBJECTIVE: To develop risk prediction models for preterm birth among infants with orofacial clefts. DESIGN: Data from the Texas Birth Defects Registry for infants with orofacial clefts born between 1999-2014 were used to develop preterm birth predictive models. Logistic regression was used to consider maternal and infant characteristics, and internal validation of the final model was performed using bootstrapping methods. The area under the curve (AUC) statistic was generated to assess model performance, and separate predictive models were built and validated for infants with cleft lip and cleft palate alone. Several secondary analyses were conducted among subgroups of interest. SETTING: State-wide, population-based Registry data. PATIENTS/PARTICIPANTS: 6774 infants with orofacial clefts born in Texas between 1999-2014. MAIN OUTCOME MEASURE(S): Preterm birth among infants with orofacial clefts. RESULTS: The final predictive model performed modestly, with an optimism-corrected AUC of 0.67 among all infants with orofacial clefts. The optimism-corrected models for cleft lip (with or without cleft palate) and cleft palate alone had similar predictive capability, with AUCs of 0.66 and 0.67, respectively. Secondary analyses had similar results, but the model among infants with delivery prior to 32 weeks demonstrated higher optimism-corrected predictive capability (AUC = 0.74). CONCLUSIONS: This study provides a first step towards predicting preterm birth risk among infants with orofacial clefts. Identifying pregnancies affected by orofacial clefts at the highest risk for preterm birth may lead to new avenues for improving outcomes among these infants.