Offspring Outcomes Research Articles

In Utero Exposure to Maternal COVID-19 Vaccination and Offspring Neurodevelopment at 12 and 18 Months

Uptake of COVID-19 vaccines among pregnant individuals was hampered by safety concerns around potential risks to unborn children. Data clarifying early neurodevelopmental outcomes of offspring exposed to COVID-19 vaccination in utero are lacking. To determine whether in utero exposure to maternal COVID-19 vaccination was associated with differences in scores on the Ages and Stages Questionnaire, third edition (ASQ-3), at 12 and 18 months of age. This prospective cohort study, Assessing the Safety of Pregnancy During the Coronavirus Pandemic (ASPIRE), enrolled pregnant participants from May 2020 to August 2021; follow-up of children from these pregnancies is ongoing. Participants, which included pregnant individuals and their offspring from all 50 states, self-enrolled online. Study activities were performed remotely. In utero exposure of the fetus to maternal COVID-19 vaccination during pregnancy was compared with those unexposed. Neurodevelopmental scores on validated ASQ-3, completed by birth mothers at 12 and 18 months. A score below the established cutoff in any of 5 subdomains (communication, gross motor, fine motor, problem solving, social skills) constituted an abnormal screen for developmental delay. A total of 2487 pregnant individuals (mean [SD] age, 33.3 [4.2] years) enrolled at less than 10 weeks' gestation and completed research activities, yielding a total of 2261 and 1940 infants aged 12 and 18 months, respectively, with neurodevelopmental assessments. In crude analyses, 471 of 1541 exposed infants (30.6%) screened abnormally for developmental delay at 12 months vs 203 of 720 unexposed infants (28.2%; χ2 = 1.32; P = .25); the corresponding prevalences at 18 months were 262 of 1301 (20.1%) vs 148 of 639 (23.2%), respectively (χ2 = 2.35; P = .13). In multivariable mixed-effects logistic regression models adjusting for maternal age, race, ethnicity, education, income, maternal depression, and anxiety, no difference in risk for abnormal ASQ-3 screens was observed at either time point (12 months: adjusted risk ratio [aRR], 1.14; 95% CI, 0.97-1.33; 18 months: aRR, 0.88; 95% CI, 0.72-1.07). Further adjustment for preterm birth and infant sex did not affect results (12 months: aRR, 1.16; 95% CI, 0.98-1.36; 18 months: aRR, 0.87; 95% CI, 0.71-1.07). Results of this cohort study suggest that COVID-19 vaccination was safe during pregnancy from the perspective of infant neurodevelopment to 18 months of age. Additional longer-term research should be conducted to corroborate these findings and buttress clinical guidance with a strong evidence base.

Early Home Visits and Health Outcomes in Low-Income Mothers and Offspring

Individuals with low income may have heightened rates of obesity and hypertension. To determine whether prenatal and infancy home visitation by nurses reduces maternal and offspring obesity and hypertension. This randomized clinical trial of prenatal and infancy nurse home visitation in a public health care system in Memphis, Tennessee, enrolled 742 women with no previous live births and at least 2 sociodemographic risk factors (unmarried, <12 years of education, unemployed) from June 1, 1990, through August 31, 1991. At registration during pregnancy, 727 mothers (98%) were unmarried, and 631 (85%) lived below the federal poverty level. At offspring ages 12 and 18 years, maternal and offspring obesity and hypertension were assessed by staff masked to treatment. The data analysis was performed from July 1, 2021, to October 31, 2023. Women assigned to the control group received free transportation for prenatal care and child developmental screening and referral at child ages 6, 12, and 24 months. Women assigned to nurse visitation received transportation and screening plus prenatal and infant and toddler nurse home visits. Obesity and hypertension among mothers and their offspring at child ages 12 and 18 years, although not hypothesized in the original trial design, were analyzed using post-double selection lasso method. Of the 742 participants randomized (mean [SD] age, 18.1 [3.2] years), interviews were completed with 594 mothers and 578 offspring at child age 12 years and 618 mothers and 629 offspring at child age 18 years. Obesity was assessed for 576 offspring at age 12 years and 605 at age 18 years and for 563 and 598 mothers at child ages 12 and 18 years, respectively. Blood pressure was assessed for 568 offspring aged 12 years and 596 aged 18 years and 507 and 592 mothers at child ages 12 and 18 years, respectively. There were no overall treatment-control differences in offspring obesity or hypertension at ages 12 and 18 years combined, although nurse-visited female offspring, compared with controls, had a lower prevalence of obesity (adjusted relative risk [ARR], 0.449; 95% CI, 0.234-0.858; P = .003) and severe obesity (ARR, 0.185; 95% CI, 0.046-0.748; P < .001). There were reductions at ages 12 and 18 years combined for stage 1 and stage 2 hypertension for nurse-visited vs control group mothers, with differences limited to mothers of females (stage 1: ARR, 0.613 [95% CI, 0.440-0.855; P = .001]; stage 2: ARR, 0.217 [95% CI, 0.081-0.582; P < .001]). For both obesity and hypertension outcomes, there was no intervention effect among male offspring or the mothers of males. Self-reported maternal health aligned with program effects on hypertension. In this clinical trial follow-up at offspring ages 12 and 18, nurse-visited female offspring had lower rates of obesity and mothers of females had lower rates of hypertension than control-group counterparts. These findings suggest that risks for chronic disease among mothers of females and their female offspring who live in extreme poverty may be prevented with prenatal and infant and toddler home visitations by nurses. ClinicalTrials.gov Identifier: NCT00708695.

Maternal and fetal/neonatal outcomes in pregnancy, delivery and postpartum following bariatric surgery and comparison with pregnant women with obesity: a study protocol for a prospective cohort

BackgroundBeing obese can lead to various complications during pregnancy, such as Gestational Diabetes Mellitus (GDM), pregnancy induced hypertension (PIH), Pre-Eclampsia (PE), and Large Gestational Age (LGA). Although bariatric surgery is an effective way to treat obesity, it can also result in complications and may be linked to having small for gestational age (SGA) babies. This cohort study protocol aims to compare the maternal and fetal/neonatal outcomes of two groups of Iranian pregnant women: those who have undergone bariatric surgery and those who are obese but have not had bariatric surgery.MethodsIn this study Pregnant women (< 14 weeks’ gestation) (n = 38 per group) are recruited either from one of the obesity clinic (exposure group = with a history of bariatric surgery) or primary healthcare clinics in Tehran city (comparison group = pregnant women with obesity and and no history of bariatric surgery). Dietary intake and nutrient status are assessed at < 14, 28, and 36 weeks. Maternal and fetal/neonatal outcomes are compared between the two groups, including gestational diabetes, preeclampsia, preterm labor, intrauterine growth restriction, severe nausea and vomiting, abortion, placenta previa and abruption, venous thrombosis, vaginal bleeding, cesarean delivery, meconium aspiration, and respiratory distress. Maternal serum levels of ferritin, albumin, zinc, calcium, magnesium, selenium, copper, vitamins A, B9, B12, and 25-hydroxy Vit D are checked during 24th to 28th weeks. Maternal and neonatal outcomes, including height, weight, head circumference, fetal abnormality, infection, small or large fetus, low birth weight, macrosomia, NICU admission, and total weight gain during pregnancy, are measured at birth. Maternal and offspring outcomes, including weight, height, head circumference, total weight gain during pregnancy, newborn diseases, postpartum bleeding, breastfeeding, and related problems, are assessed 6 weeks after delivery. Child's weight, height, and head circumference are followed at 2, 4, 6, 8, 10, and 12 months after birth. Maternal stress, anxiety, and depression are assessed with the DASS-21 questionnaire, and physical activity is evaluated using the PPAQ questionnaire in the first and third trimesters.DiscussionBy assessing the levels of micronutrients in the blood of pregnant women along with the evaluation of pregnancy outcomes, it is feasible to gain a more accurate understanding of how bariatric surgery affects the health and potential complications for both the mother and the fetus/newborn. This information can help specialists and patients make more informed decisions about the surgery. Additionally, by examining issues such as stress, anxiety, and depression in women undergoing surgery, this study can contribute to recognizing these problems, which can also affect pregnancy outcomes.

Association of Mild Iodine Insufficiency during Pregnancy with Child Neurodevelopment in Patients with Subclinical Hypothyroidism or Hypothyroxinemia.

Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years. This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 μg/L were considered iodine sufficient, and concentrations of 150 μg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years. A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 μg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], Padj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status (p > 0.05). Maternal urinary iodine concentrations ≤150 μg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia. · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ..

Gestational Weight Gain, Pregnancy Related Complications and the Short-Term Risks for the Offspring.

Maternal obesity influences pregnancy course in several different manners, and imbalanced nutrition during pregnancy may lead to various adverse pregnancy outcomes. Additionally, nutritional status during pregnancy may have implications for the health of the offspring and may possibly influence early motor development in children. The aim of this study was to assess the impact of excessive gestational weight gain (EGWG) on pregnancy outcomes and infant's motor development within the first twelve months of life. The study included 200 participants divided in two groups based on their gestational weight gain. Maternal, perinatal, and neonatal factors were analyzed, and early motor development was assessed using the Alberta infant motor scale (AIMS). EGWG was significantly associated with: pre-pregnancy BMI (p < 0.001), family history for cardiovascular diseases (p = 0.013) and diabetes mellitus (p = 0.045), hypertensive disorder of pregnancy (p = 0.003), gestational diabetes mellitus (p < 0.001), gestational anemia (p = 0.001), vitamin D deficiency (p = 0.001), metformin use (p = 0.045), pre-labor premature rupture of membranes (p = 0.031), amniotic fluid index (p = 0.047), and APGAR score in the first five min of life (p = 0.007). Scored by AIMS, EGWG was significantly associated with parameters of early motor development at the age of three AIMS total (p < 0.001), six AIMS total (p < 0.001), nine AIMS total (p < 0.001), and twelve AIMS total (p < 0.001) months of infant's life. The link between EGWG and adverse neurodevelopmental outcomes in offspring is a complex and multifaceted issue. Our results imply significant alterations in early motor development in the group of infants born from mothers who gained weight excessively during pregnancy. Further studies are needed to unravel the intricacies of this relationship and inform strategies for preventive interventions and supportive care during pregnancy and infancy.

Effect of Maternal Adverse Childhood Experiences (ACEs) and Maternal Resiliency on Early Childhood Outcomes on Vaccination Adherence and Emergency Department Visits

Introduction: Adverse Childhood Experiences (ACEs) are traumatic events that occurred to an individual during ages 0-17 years. The 1998 Adverse Childhood Experiences (ACE) suggested higher ACE scores contributed to negative future health outcomes. The tool is now used to screen at-risk populations for the development of chronic health conditions. Protective factors, such as resilience, were later studied and found to offset the negative health impacts of traumatic childhood events. The 7Cs questionnaire was a tool developed to measure resilience in adolescents and demonstrated better health outcomes despite the presence of higher ACE scores. This pilot study evaluated whether higher maternal ACEs would result in more frequent pediatric ED visits and less vaccination adherence and whether higher 7Cs would be protective. Methods: This IRB approved study recruited pregnant women and new mothers in a tertiary NJ urban hospital, between their second trimester and their child’s one month well visit at the pediatric clinic. All subjects completed the Adverse Childhood Events (ACEs) survey, 7Cs resilience tool, and a Maternal Health questionnaire at the time of recruitment. A review of children’s electronic medical records was conducted at 2-, 4-, 6-, and 12-months to evaluate pediatric outcomes, adherence to AAP recommended vaccine schedule and emergency department visits. Results: Total of 34 women were enrolled, their and their children’s medical and demographic data collected. There was no difference in higher ACE scores and number of ED visits for the babies (OR 0.9645 [CI 0.7643 - 1.2172]), with no effect seen with higher resilience scores and number of ED visits (OR 0.8477 [0.6192 – 1.1604]). Increase in ACE scores resulted in reduction in vaccination adherence (OR 0.3555 [CI 0.1417 – 0.8923]). Increase in resilience scores decreased vaccination adherence by 44% (OR 0.5578 [CI 0.4164 - 0.7471]). Conclusion: There was no significant relationship between ACE or resilience scores and pediatric ED visits. A higher ACE score and lower levels of resilience were associated with decreased child vaccine adherence rate. ACE scores relate to higher traumatic childhoods, suggest poorer outcomes in offspring. Women with higher ACE scores could benefit from closer interventions and resources from obstetricians, and closer follow up of their children by the pediatricians.

Placental transcriptomic signatures of prenatal and preconceptional maternal stress

Prenatal exposure to maternal psychological stress is associated with increased risk for adverse birth and child health outcomes. Accumulating evidence suggests that preconceptional maternal stress may also be transmitted intergenerationally to negatively impact offspring. However, understanding of mechanisms linking these exposures to offspring outcomes, particularly those related to placenta, is limited. Using RNA sequencing, we identified placental transcriptomic signatures associated with maternal prenatal stressful life events (SLEs) and childhood traumatic events (CTEs) in 1 029 mother-child pairs in two birth cohorts from Washington state and Memphis, Tennessee. We evaluated individual gene-SLE/CTE associations and performed an ensemble of gene set enrichment analyses combing across 11 popular enrichment methods. Higher number of prenatal SLEs was significantly (FDR < 0.05) associated with increased expression of ADGRG6, a placental tissue-specific gene critical in placental remodeling, and decreased expression of RAB11FIP3, an endocytosis and endocytic recycling gene, and SMYD5, a histone methyltransferase. Prenatal SLEs and maternal CTEs were associated with gene sets related to several biological pathways, including upregulation of protein processing in the endoplasmic reticulum, protein secretion, and ubiquitin mediated proteolysis, and down regulation of ribosome, epithelial mesenchymal transition, DNA repair, MYC targets, and amino acid-related pathways. The directional associations in these pathways corroborate prior non-transcriptomic mechanistic studies of psychological stress and mental health disorders, and have previously been implicated in pregnancy complications and adverse birth outcomes. Accordingly, our findings suggest that maternal exposure to psychosocial stressors during pregnancy as well as the mother’s childhood may disrupt placental function, which may ultimately contribute to adverse pregnancy, birth, and child health outcomes.

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

BackgroundSerotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database.ResultsNone of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites.ConclusionsMethylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.

Cohort change in the educational gradient in women’s employment around childbirth in Japan

In contrast to many high-income countries, there is no clear positive relationship between maternal education and employment in Japan. However, recent policy, normative, and labor market changes are expected to have encouraged highly educated women to continue working, especially in regular employment, resulting in an increasing positive educational gradient. Despite this expectation, little is known about the changes in the educational gradient in recent cohorts. This paper examines the changes in the educational gradient in women’s employment around their first and second births using nationally representative panel survey data of women born in the 1960–1989 cohorts in Japan. The results show a significant increase in the positive educational gradient in employment rates around the first and second births in the 1980s cohort. Highly educated women are more likely to be in regular employment and less likely to leave employment, which contributes to their higher employment continuity. Conversely, the employment rates of women with lower levels of education have not increased to the same extent across the cohorts, and they have become more likely to be in nonstandard employment. These findings suggest that the weak relationship between maternal education and employment is changing in Japan, which may contribute to greater inequality in the labor market, household, and offspring outcomes in the future.

Divergent planes of nutrition in mature rams influences body composition, hormone and metabolite concentrations, and offspring birth measurements, but not semen characteristics or offspring growth.

Objectives of this experiment were to characterize the effects of ram plane of nutrition on body composition, concentrations of hormones and metabolites, sperm characteristics, and offspring outcomes. Mature Rambouillet rams (n = 24, BW = 82.9 ± 2.63kg) were individually housed and randomly assigned to either a positive (POS; n = 8), maintenance (MAINT; n = 8), or negative (NEG; n = 8) plane of nutrition for an 84-day feeding period. Rams were fed a common diet, with daily feed allocations adjusted weekly based on body weight (BW) to achieve the targeted weight gain or loss (approximately 12% of initial BW). On 0, 28, 56, and 84-d, body condition score (BCS) and scrotal circumference (SC) were recorded, and blood and semen were collected. Following the feeding period, rams were placed in pens with 10 ewes each for a 28-d breeding period. Ewes were managed similarly throughout gestation and body weight and measurements were recorded at birth and weaning. Data were analyzed as repeated measures in time where appropriate with the mixed procedure of SAS, and individual ram was the experimental unit for all analysis. Ram BW was influenced by a treatment × day interaction (P < 0.001), with POS (0.12 ± 0.01kg) having greater daily weight change than MAINT (0.1 ± 0.01kg), which was greater than NEG (-0.12 ± 0.01kg). Ram BCS and SC were influenced by treatment × day interactions (P ≤ 0.01), being similar on day 0 but POS being greater than NEG by day 56. Concentrations of triiodothyronine (T3) and T3:T4 ratio exhibited treatment × day interactions (P ≤ 0.02), as POS had greater values than NEG by day 84 (P ≤ 0.02). Concentration of insulin-like growth factor-1 was greater in POS than MAINT and NEG (P ≤ 0.02), and non-esterified fatty acids and thyroxine (T4) were influenced by a day effect (P ≤ 0.01), but testosterone was unaffected (P ≥ 0.09). Minimal differences in semen volume, sperm concentration, motility, or morphology were observed among treatments (P ≥ 0.31). A similar proportion of ewes bred by rams in the respective treatments lambed and weaned lambs (P ≥ 0.54). Birth weight, chest circumference, and shoulder-hip length were greater (P ≤ 0.05) in NEG lambs compared with POS and MAINT; however, no differences were detected in weaning weight and weaning body measurements (P ≥ 0.40). Findings suggest paternal nutrition during the period of sperm development may influence offspring outcomes, potentially as a result of in-utero programming of paternal origin.

Household Income and Offspring Education Explain Blacks' Diminished Returns of Parental Education.

High parental education promotes various aspects of offspring well-being including reducing their risk of depression/anxiety, criminal justice involvement, and welfare reliance. However, according to minorities' diminished returns, these benefits are not equal across racial groups, with Black families experiencing diminished returns of parental education compared to White families. This study explores the role of household income and offspring educational attainment as potential serial pathways that operate as mechanisms underlying diminished returns of parental education on offspring outcomes in Black families. Gender differences in these effects were also explored. Utilizing data from the Future of Families and Child Wellbeing Study (FFCWS) over a 22-year follow-up period (seven waves), we examined the serial mediation by household income and offspring educational attainment in explaining the relationship between parental education and offspring outcomes namely depression, anxiety, criminal justice involvement, and welfare reliance [Temporary Assistance for Needy Families (TANF) and Supplemental Nutrition Assistance Program (SNAP)]. We used structural equation modeling (SEM) with household income as the first mediator and young adult education as the second mediator. Multi-group models were used to explore gender differences in these paths. The study confirmed the role of our proposed serial mediators for Blacks' weaker effects of parental education on offspring outcomes. We observed weaker effects of first affects household income, with this effect being for Black families compared to White families, which then impacted educational attainment of the offspring. The findings indicate that household income plays a crucial mediating role, but its effect is weaker in Black families. Additionally, the educational attainment of offspring from highly educated Black parents is less effective in improving outcomes compared to their White peers, further contributing to diminished returns. Some gender differences were observed for the effects of educational attainment on economic and health outcomes of young adults. The study underscores the need to reconsider traditional assumptions about the comparability of family conditions and outcomes across racial groups with similar levels of parental education. The findings highlight the importance of targeted policies and interventions aimed at enhancing the economic stability and educational outcomes of Black families to address these disparities. Policies should focus on promoting the economic well-being of highly educated Black parents and improving the educational outcomes of their children.

A maternal low-protein diet results in sex-specific differences in synaptophysin expression and milk fatty acid profiles in neonatal rats.

The developmental origins of health and disease hypothesis have highlighted the link between early life environment and long-term health outcomes in offspring. For example, maternal protein restriction during pregnancy and lactation can result in adverse metabolic and cognitive outcomes in offspring postnatal. Hence, in the present study, we assess whether an isocaloric low-protein diet (ILPD) affects the fatty acid profile in breast milk, the hippocampal synaptophysin (Syn) ratio, and the oxidative stress markers in the neonatal stage of male and female offspring. The aim of this work was to assess the effect of an ILPD on the fatty acid profile in breast milk, quantified the hippocampal synaptophysin (Syn) ratio and oxidative stress markers in neonatal stage of male and female offspring. Female Wistar rats were fed with either a control diet or an ILPD during gestation to day 10 of lactation. Oxidative stress markers were assessed in serum and liver. All quantifications were done at postnatal day 10. The results showed: ILPD led to decreases of 38.5% and 17.4% in breast milk volume and polyunsaturated fatty acids content. Significant decreases of hippocampal Syn ratio in male offspring (decreases of 98% in hippocampal CA1 pyramidal and CA1 oriens, 83%, stratum pyramidal in CA3, 80%, stratum lucidum in CA3, and 81% stratum oriens in CA3). Male offspring showed an increase in pro-oxidant status in serum and liver. Thus, the data suggest that male offspring are more vulnerable than females to an ILPD during gestation and lactation.

Calorie restriction during gestation impacts maternal and offspring fecal microbiome in mice.

Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood. FGR was induced by 30% maternal calorie restriction (CR) during the second half of gestation in C57BL/6 mice. Pup weights were obtained on day of life 0, 1, and 7 and ages 3, 4 and 16 weeks. Fecal pellets were collected from pregnant dams at gestational day 18.5 and from offspring at ages 3 and 4 weeks of age. Bacterial genomic DNA was used for amplification of the V4 variable region of the 16S rRNA gene. Multivariable associations between maternal CR and taxonomic abundance were assessed using the MaAsLin2 package. Associations between microbial taxa and offspring outcomes were performed using distance-based redundancy analysis and Pearson correlations. FGR pups weighed about 20% less than controls. Beta but not alpha diversity differed between control and CR dam microbiomes. CR dams had lower relative abundance of Turicibacter, Flexispira, and Rikenella, and increased relative abundance of Parabacteroides and Prevotella. Control and FGR offspring microbiota differed by beta diversity at ages 3 and 4 weeks. At 3 weeks, FGR offspring had decreased relative abundance of Akkermansia and Sutterella and increased relative abundance of Anaerostipes and Paraprevotella. At 4 weeks, FGR animals had decreased relative abundance of Allobaculum, Sutterella, Bifidobacterium, and Lactobacillus, among others, and increased relative abundance of Turcibacter, Dorea, and Roseburia. Maternal Helicobacter abundance was positively associated with offspring weight. Akkermansia abundance at age 3 and 4 weeks was negatively associated with adult weight. We demonstrate gut microbial dysbiosis in pregnant dams and offspring at two timepoints following maternal calorie restriction. Additional research is needed to test for functional roles of the microbiome in offspring growth outcomes.

Lipid-focused dietary education intervention in pregnant women: study protocol for an open-label, parallel, randomised, intervention study addressing adverse pregnancy outcomes in China

IntroductionThe incidence of infants who are large-for-gestational-age (LGA) is on the rise in China, and its detrimental effects on health have received increasing attention. Diet-based interventions have the potential to...

Identifying gestational diabetes mellitus and assessing risk factors in affected women: a comprehensive study.

Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication associated with adverse health outcomes for both mothers and offspring. This study aimed to identify risk factors for GDM, a condition with a rapidly increasing global prevalence. We conducted a study involving 474 pregnant women who attended the obstetrics outpatient clinic of Kafkas University Faculty of Medicine Hospital between January 2022 and June 2023. Risk factors for GDM were assessed based on criteria recommended by the American Diabetes Association and the Committee on Practice of the American College of Obstetricians and Gynecologists. Statistical analyses, including descriptive statistics, Chi-square tests, Mann-Whitney U tests, and multivariate logistic regression. Individuals with GDM (mean age: 31.26±6.09 years) were significantly older than those without GDM (mean age: 28.36±4.89 years; p<0.001). Obesity prevalence was higher in the GDM group (32.5%) compared to the non-GDM group (14.3%; p<0.001). Individuals with GDM had higher rates of pre-diabetes (3.3% vs. 0.3%; p=0.007), a history of gestational diabetes (25.2% vs. 5.7%; p<0.001), high blood sugar in previous pregnancies (13.8% vs. 1.4%; p<0.001), and diabetes mellitus in 1st-degree relatives (40.7% vs. 20.3%; p<0.001). GDM was associated with increased pregnancies (p<0.001), preterm births (p<0.001), macrosomic babies (p=0.026), congenital anomalies (p=0.011), high cholesterol (p=0.036), and polyhydramnios (p=0.001) in previous pregnancies, as well as polyhydramnios in the index pregnancy (p=0.008). Regular exercise in previous pregnancies differed significantly based on GDM presence (p=0.037). Recognizing modifiable risk factors is crucial for preventing GDM and reducing associated health risks. Healthcare providers should be vigilant, especially among those with a family history of GDM, previous GDM, advanced maternal age, and other risk factors. Early lifestyle interventions show promise. Further research is needed for accurate GDM prediction.

The impact of maternal congenital heart disease on pregnancy outcomes in Malta: a retrospective study

Background: Most female patients with congenital heart disease (CHD) are becoming pregnant. Maternal CHD can have a negative impact on mother and fetus. This is the first study investigating pregnancy outcomes in Maltese grown-up congenital heart disease (GUCH) patients and one of few to compare these with outcomes in women without heart disease. Methods: Known GUCH pregnancies for the period of 2007-2014 were extracted from our database (GUCH cohort) and cardiovascular outcomes retrieved from hospital notes. A control cohort of 540 pregnancies in women without cardiovascular disease was generated through twenty-fold random matching based on subject age from among all pregnancies in Maltese nationals for the same 8-year period. Obstetric and offspring outcomes were compared between the two cohorts. Results: The GUCH cohort consisted of 27 pregnancies in 24 women. Cardiovascular complications occurred in only 1/27 (3.7%) pregnancies. Elective Caesarean sections were commoner (29.6% vs. 15.4%) and unassisted vaginal deliveries less frequent (51.9% vs. 64.6%) in the GUCH cohort (p=0.02). Obstetric complication rates were similar. GUCH women had smaller babies (median 3030 g vs. 3230 g; p=0.045) and showed a trend towards more small-for-gestational age babies (18.5% vs. 8.4%; p=0.08) and congenital malformations (7.4% vs. 2.4%; p=0.06). Conclusions: Despite the potential adverse effects of maternal CHD on mother and fetus, most pregnancies are uncomplicated and outcomes comparable to those in women without heart disease, particularly if baseline clinical status is good. Based on our findings, it is being proposed that prospective mothers be counselled about the possibility of having smaller infants.

The impact of maternal congenital heart disease on pregnancy outcomes in Malta: a retrospective study

Background: Most female patients with congenital heart disease (CHD) are becoming pregnant. Maternal CHD can have a negative impact on mother and fetus. This is the first study investigating pregnancy outcomes in Maltese grown-up congenital heart disease (GUCH) patients and one of few to compare these with outcomes in women without heart disease. Methods: Known GUCH pregnancies for the period of 2007-2014 were extracted from our database (GUCH cohort) and cardiovascular outcomes retrieved from hospital notes. A control cohort of 540 pregnancies in women without cardiovascular disease was generated through twenty-fold random matching based on subject age from among all pregnancies in Maltese nationals for the same 8-year period. Obstetric and offspring outcomes were compared between the two cohorts. Results: The GUCH cohort consisted of 27 pregnancies in 24 women. Cardiovascular complications occurred in only 1/27 (3.7%) pregnancies. Elective Caesarean sections were commoner (29.6% vs. 15.4%) and unassisted vaginal deliveries less frequent (51.9% vs. 64.6%) in the GUCH cohort (p=0.02). Obstetric complication rates were similar. GUCH women had smaller babies (median 3030 g vs. 3230 g; p=0.045) and showed a trend towards more small-for-gestational age babies (18.5% vs. 8.4%; p=0.08) and congenital malformations (7.4% vs. 2.4%; p=0.06). Conclusions: Despite the potential adverse effects of maternal CHD on mother and fetus, most pregnancies are uncomplicated and outcomes comparable to those in women without heart disease, particularly if baseline clinical status is good. Based on our findings, it is being proposed that prospective mothers be counselled about the possibility of having smaller infants.

The impact of maternal congenital heart disease on pregnancy outcomes in Malta: a retrospective study

Background: Most female patients with congenital heart disease (CHD) are becoming pregnant. Maternal CHD can have a negative impact on mother and fetus. This is the first study investigating pregnancy outcomes in Maltese grown-up congenital heart disease (GUCH) patients and one of few to compare these with outcomes in women without heart disease. Methods: Known GUCH pregnancies for the period of 2007-2014 were extracted from our database (GUCH cohort) and cardiovascular outcomes retrieved from hospital notes. A control cohort of 540 pregnancies in women without cardiovascular disease was generated through twenty-fold random matching based on subject age from among all pregnancies in Maltese nationals for the same 8-year period. Obstetric and offspring outcomes were compared between the two cohorts. Results: The GUCH cohort consisted of 27 pregnancies in 24 women. Cardiovascular complications occurred in only 1/27 (3.7%) pregnancies. Elective Caesarean sections were commoner (29.6% vs. 15.4%) and unassisted vaginal deliveries less frequent (51.9% vs. 64.6%) in the GUCH cohort (p=0.02). Obstetric complication rates were similar. GUCH women had smaller babies (median 3030 g vs. 3230 g; p=0.045) and showed a trend towards more small-for-gestational age babies (18.5% vs. 8.4%; p=0.08) and congenital malformations (7.4% vs. 2.4%; p=0.06). Conclusions: Despite the potential adverse effects of maternal CHD on mother and fetus, most pregnancies are uncomplicated and outcomes comparable to those in women without heart disease, particularly if baseline clinical status is good. Based on our findings, it is being proposed that prospective mothers be counselled about the possibility of having smaller infants.

Long-term health risk of offspring born from assisted reproductive technologies.

Since the world's first in vitro fertilization baby was born in 1978, there have been more than 8 million children conceived through assisted reproductive technologies (ART) worldwide, and a significant proportion of them have reached puberty or young adulthood. Many studies have found that ART increases the risk of adverse perinatal outcomes, including preterm birth, low birth weight, small size for gestational age, perinatal mortality, and congenital anomalies. However, data regarding the long-term outcomes of ART offspring are limited. According to the developmental origins of health and disease theory, adverse environments during early life stages may induce adaptive changes and subsequently result in an increased risk of diseases in later life. Increasing evidence also suggests that ART offspring are predisposed to an increased risk of non-communicable diseases, such as malignancies, asthma, obesity, metabolic syndrome, diabetes, cardiovascular diseases, and neurodevelopmental and psychiatric disorders. In this review, we summarize the risks for long-term health in ART offspring, discuss the underlying mechanisms, including underlying parental infertility, epigenetic alterations, non-physiological hormone levels, and placental dysfunction, and propose potential strategies to optimize the management of ART and health care of parents and children to eliminate the associated risks. Further ongoing follow-up and research are warranted to determine the effects of ART on the long-term health of ART offspring in later life.

A high fiber diet intervention during pregnancy: The SPROUT (Single goal in PRegnancy to optimize OUTcomes) protocol paper

BackgroundInterventions to prevent excessive gestational weight gain (GWG) have had a limited impact on maternal and infant outcomes. Dietary fiber is a nutrient with benefits that counters many of the metabolic and inflammatory changes that occur during pregnancy. We will determine if a high dietary fiber (HFib) intervention provides benefit to maternal and infant outcomes. Methods and designPregnant women will be enrolled in an 18-week intervention and randomized in groups of 6–10 women/group into the intervention or control group. Weekly lessons will include information on high-dietary fiber foods and behavior change strategies. Women in the intervention group will be given daily snacks high in dietary fiber (10–12 g/day) to facilitate increasing dietary fiber intake. The primary aim will assess between-group differences for the change in maternal weight, dietary fiber intake, dietary quality, and body composition during pregnancy and up to two months post-partum. The secondary aim will assess between-group differences for the change in maternal weight, dietary fiber intake, and dietary quality from two months to one year post-partum and infant body composition from birth to one-year-old. DiscussionEffective and simple intervention strategies to improve maternal and offspring outcomes are lacking. Changes during the perinatal period are related to the risk of disease development in the mother and offspring. However, it is unknown which changes can be successfully targeted to have a meaningful impact. We will test the effect of an intervention designed to counter many of the metabolic and inflammatory changes that occur during pregnancy. Ethics and disseminationThe University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00145397). The results of the trial will be disseminated at conferences and in peer reviewed publications. Trial registrationClinicalTrials.gov ID: NCT04868110