Celeste Krewson

Maternal depression during pregnancy may be associated with offspring brain age through young adulthood, according to a recent study.

Maternal stress, anxiety, and depression have been associated with offspring development, increasing the risk of behavioral and emotional problems in children, and anxiety and depression in adulthood. Brain structure changes throughout different stages of life, making it possible to use age-dependent changes in brain structure to estimate brain age in an individual.

The difference between structural and chronological brain age is the brain age gap estimate (BrainAGE), with a more significant positive BrainAGE indicating neurodevelopmental or aging trajectories. This has been associated with age-related health problems, neuropsychiatric disease, dementia risk, and cognitive impairment risk.

Evidence has indicated a strong impact on brain age from early life events. Therefore, early adversity may put children at a greater risk of accelerated brain aging. This logic is used in the diathesis-stress model, which states that early-life predisposition can lead to psychological disorders. However, this model has not been applied to brain age.

To analyze how prenatal exposure to maternal depression and more recent stress affects brain age, investigators conducted a second neuroimaging follow-up of the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort.

Data was available for a subset of patients, indicating maternal depression during pregnancy. Neuroimaging data was also gathered during the first neuroimaging follow-up.

An Edinburgh Postnatal Depression Scale questionnaire was filled out by mothers of participants in the early 1990s, answering questions related to mental health and emotional well-being. Mothers answered these questionnaires during the twentieth week of pregnancy, 2 weeks after birth, 6 months after birth, and 18 months after birth.

A subset of young adult offspring underwent structural magnetic resonance imaging (MRI) in 2015, with another, overlapping sample of young adults undergoing MRI from 2020 to 2022. The first neuroimaging follow-up was completed by 131 participants aged 23 and 24 years, and the second neuroimaging follow-up was completed by 260 participants aged 28 to 30 years.

The 260 participants also completed a Social Readjustment Rating Scale, which included 43 questions on stressful life events in the previous year. MRI data between ages 28 and 30 years and data on maternal depression were available for 199 participants, 51% of which were males.

Investigators also measured brain age in participants. The difference between brain age based on cortical thickness and the chronological age of participants was used to calculate BrainAGE.

The mean age of participants was 29.5 years. The brain age of participants participating in the second neuroimaging follow-up ranged from 18.5 to 43.3 years. As their chronologic age was 28 to 30 years the BrainAGE of participants ranged from about 11 to 14 years. 

A high correlation was found between the BrainAGE of participants in their early 20s and late 20s. Some participants experienced accelerated brain age pacing, while others experienced decelerated pacing. Participants with a greater positive BrainAGE in their early 20s more often had a slower aging pace in the following 5 years.

While women in their late 20s had a more positive average BrainAGE than their male counterparts, no other significant sex differences were found. There was also no association found between recent stress and BrainAGE for participants in their late 20s, but greater age pacing was associated with greater recent stress in young adulthood.

Antenatal depression based on the Edinburgh Postnatal Depression Scale was found in 33% of mothers. A correlation was found between maternal depression during pregnancy and BrainAGE, with greater maternal depression associated with greater positive BrainAGE in participants in their late 20s. This association was independent of sex and recent stress.

Maternal depression was associated with brain age, while recent stress was associated with the pace of aging. This indicates that preventing and treating depression in pregnant mothers may impact long-term brain development in offspring.

Mareckova K, Mareček R, Jani M, Zackova L, Andryskova L, Brazdil M, et al. Association of maternal depression during pregnancy and recent stress with brain age among adult offspring. 

. 2023;6(1):e2254581. doi:10.1001/jamanetworkopen.2022.54581

Articles

In a recent study, maternal depression during pregnancy was associated with offspring brain age, while recent stress in offspring was associated with a greater aging pace. 

Maternal depression associated with offspring brain age

Vaginal metabolites may be early predictors of spontaneous preterm birth (sPTB), according to a recent study.

Despite sPTB being a leading cause of maternal and neonatal morbidity, there are few options for early risk identification and prevention. While the vaginal microbiome has been associated with sPTB, the relationship between these 2 factors remains unclear.

Metabolites have been observed to cause local and systemic effects, having associations with the microbiome, inflammation, and preterm birth. Investigators conducted a study to further understand the role of metabolites on sPTB.

The second-trimester vaginal metabolome was measured in 232 pregnant women. Of these, 80 pregnancies ended preterm. There were 635 metabolites identified, 549 of which were seen in over half of the study population, and 108 of which were seen in the entire population. 

Associations were found between the metabolome and microbiome, but community state types (CSTs) were not well separated. Microbiomes however were well separated. This indicated a strong but imperfect correlation between the vaginal microbiome and metabolome.

Six metabolite clusters (MC) were found, without as significant of separation as that between the vaginal microbiome and CSTs. Polyamine metabolism was the most enriched metabolite sub-pathway within each MC. Also, investigators found various enrichments of CSTs in MCs.

There was a significant difference between the metabolome of Black and White women, but only mild differences when looking at the correlation to MCs. Several MCs were significantly associated with sPTB in Black women but not White women. This indicated prematurity in Black women rather than with the microbiome structure.

Four metabolites were significantly associated with sPTB, 3 of which were of exogenous source. These 3 were ethyl β-glucopyranoside, tartrate, and diethanolamine. Investigators found these metabolites in over 95% of the study population.

Choline, an essential nutrient, was found to have lower levels in women with subsequent sPTB. Low levels of choline have also been linked to low betaine levels. As diethanolamine has been associated with disrupted choline metabolism, investigators hypothesized higher diethanolamine levels in sPTB may lower choline and betaine levels.

There were 13 vaginal metabolites associated with earlier sPTB. This included sugar or sugar alcohol metabolites found to be higher in early preterm birth. Interactions were found with both race and sPTB timing, with an additional sPTB-associated xenobiotic found as well.

These results showed enriched metabolite signatures among Black women with sPTB. Exogenous metabolites were also strongly associated with sPTB, indicating important risk factors.

Kindschuh WF, Baldini F, Liu MC, Liao J, Meydan Y, Lee HH, et al. Preterm birth is associated with xenobiotics and predicted by the vaginal metabolome. Nat Microbiol. 2023. doi:10.1038/s41564-022-01293-8

In a recent study, an association was found between vaginal metabolites and spontaneous preterm birth.

Vaginal metabolites may be early predictors of spontaneous preterm birth 

Artificial neural network (ANN) may be an efficient tool for predicting neonatal metabolic bone disease (MBD) during prenatal and postnatal periods, according to a recent study.

MBD is often seen in infants born preterm and lacking fetal mineral accumulation. Hypophosphatemia, hyperphosphatemia, and skeletal demineralization are all characteristics of MBD. Osteopenia, osteoporosis, rickets, and pathologic fractures can also all occur in MBD, increasing bone fragility and potentially impacting short- and long-term bone growth.

While infants at risk of MBD receive screening, there is a wide variety of diagnostic methods, and early recognition can be difficult because of the late onset of clinical symptoms and a lack of specific biochemical markers. This has led to a need for predictive tools for MBD.

A flexible and accurate machine learning algorithm, the ANN, has been able to predict multiple diseases. Investigators developed serial ANN models for the risk of MBD to determine the most efficient and accurate model for prediction.

Pregnant Chinese women gave written consent to participate in a diagnostic study, conducted from January 1, 2012, to December 31, 2021. Recruitment occurred early in pregnancy, and follow-up continued until 1 month after parturition.

To be included, participants needed to have a singleton pregnancy, complete clinical data during the antenatal, delivery, and postpartum periods, and surviving infants with detailed values of alkaline phosphatase. A peak serum alkaline phosphatase level above 500 U/L 72 hours after birth was used to determine MBD.

Data on maternal and neonatal characteristics were gathered from electronic health records. These characteristics included demographic data and prior pregnancy history, nutritional conditions during pregnancy, complications and comorbidities, medication use during pregnancy, birth outcomes, and neonatal disorders.

Five predictive models were built using an ANN, with a receiver operating characteristic curve used to evaluate the model performance.

There were 10,801 Chinese women participating in the study, 65.8% of which were local residents, 98.1% of Han ethnicity, and 9.3% had uterine scanning. Of the infants, 55.1% were male and 44.9% female. MBD presented in 138 infants, only 6 of which were term infants. In comparison, 75.9% of control infants were term infants.

In putative predictive factors, offspring of women with inadequate folic acid during pregnancy were 2.31 times more likely to develop MBD, compared to 3.26 times higher when born to women taking calcium supplementation and 0.38 times lower when born to women taking iron supplements.

MBD risk factors included magnesium sulfate use in pregnancy and infants with low birth weight, anemia, septicemia, or respiratory distress syndrome.

The area under the receiver operating characteristic curve (AUC) was calculated for ANN models. Model 1 showed the highest AUC, followed by model 5, model 4, model 3, and model 2. As model 1 had a net reclassification improvement of 0.205 compared to model 5, it showed an improved discriminative ability.

Results also indicated improved identification of neonates at high risk of MBD with fewer instances of misclassification in model 1. Overall, model 1 showed the best performance for significant prenatal and postnatal factors and model 5 for postnatal factors, making them viable for use in clinical practice.

Jiang H, Guo J, Li J, Li C, Du W, Canavese F, et al. Artificial neural network modeling to predict neonatal metabolic bone disease in the prenatal and postnatal periods. 

 2023;6(1):e2251849. doi:10.1001/jamanetworkopen.2022.51849

Artificial neural network models have been developed which are able to accurately and efficiently predict neonatal metabolic bone disease.

Artificial neural network promising for predicting neonatal metabolic bone disease

The rate of active postnatal care has a direct association with the survival rate of periviable infants, according to a recent study.

Multiple factors impact the decision on whether periviable infants born at 22 to 25 weeks’ gestation should be given active care, such as individual bias, fear of adverse outcomes, medical ethics, local and national policies, and communication between parents and caregivers. An individualized approach is recommended by professional societies in the United States.

There is little evidence on why infant mortality rates differ based on geographic variation, but data from Sweden has associated lower infant mortality rates among periviable infants in areas with higher rates of active perinatal care. Therefore, regional differences in mortality may be impacted by regional differences in rates of active perinatal care.

Investigators conducted a cohort study to determine the association between active perinatal care and infant mortality for periviable infants. Data on live births and infant deaths was gathered from a US Centers for Disease Control and Prevention database.

Infants were divided into subgroups based on gestational age. Subgroups included 22 weeks’ 23 weeks’ 24 weeks’, and 25 weeks’ gestation. The birth weight of included infants was 400 to 999 g.

Ten United States regions were included in the study. Active postnatal care involved using assisted ventilation, neonatal intensive care unit (NICU), surfactant replacement therapy, antibiotics for suspected neonatal sepsis, or seizures. Aside from seizures, these conditions indicated active postnatal care had been administered.

Race characteristics, insurance status, early prenatal care, and higher-risk pregnancy data were also collected. There were 41,707 periviable infants included in the study, 78% of which were of singleton birth and 46.7% of which were female.

The gestational age of 13.7% of infants was 22 weeks, 23 weeks for 23.1%, 24 weeks for 30.5%, and 25 weeks for 32.7%. About 19% of infants were Hispanic, and about 30% were non-Hispanic black. Established prenatal care by 3 months was seen from 69.5% of mothers, and 15.4% of pregnancies were considered higher risk. Medicaid covered about 42% of births.

There was evidence of active postnatal care in 83.9% of infants, with rates varying by region and gestational age. Infants born at 25 weeks’ gestational age were given active postnatal care more often than those born at 22 weeks’ gestational age, 93.5% and 41.5% receiving care respectively.

Survival through infancy was seen in 62.6% of infants overall, 18.9% born at 22 weeks’ gestational age, 50.8% born at 23 weeks’ gestational age, 70.7% born at 24 weeks' gestational age, and 81.7% at 25 weeks' gestational age. Survival rates differed between various regions.

A moderate positive correlation was found between region rate of active postnatal care and survival rate at 22 weeks’ gestation. Rates of active care did not have a significant effect on survival rate at 23 weeks’, 24 weeks’, or 25 weeks’ gestation. A positive correlation was also found between regional NICU admission and survival rate at 22 weeks’ gestation. 

While assisted ventilation immediately after birth also had a positive correlation with survival at 22 weeks’ gestation, a negative correlation was found at 25 weeks’ gestation. Surfactant administration therapy also had a negative correlation with survival at 25 weeks’ gestation. Antibiotics for suspected sepsis had no correlation with survival rate.

For perinatal care, a positive correlation was found between regional cesarean delivery rates and survival at 23 weeks’ gestation, but not 22 weeks’, 24 weeks’, or 25 weeks’ gestation. The correlation between antenatal corticosteroid administration and survival was moderately positive at 22 weeks’ gestation and moderately negative at 24 weeks’ gestation.

Silva ER, Shukla VV, Tindal R, Carlo WA, Travers CP. Association of active postnatal care with infant survival among periviableinfants in the US. JAMA Netw Open. 2023;6(1):e2250593. doi:10.1001/jamanetworkopen.2022.50593

In a recent study, the infant survival rate among periviable infants varied based on the type of active postnatal care received at certain gestational ages. 

 

Active postnatal care associated with periviable infant survival rate

Exposure to poor prenatal diet may lead to worse adiposity outcomes in children when psychosocial stress is present during pregnancy, according to a recent study.

Childhood adiposity has been linked to insulin resistance during childhood and risk of metabolic syndrome in adulthood. Knowledge on early-life determinants of body composition may support strategies for improving cardiometabolic health outcomes.

Cardiometabolic health is often affected by prenatal factors, with exposure to a proinflammatory diet associated with higher child body mass index (BMI) and obesity risk. However, little data has been gathered on long-term adiposity outcomes.

The effects of poor nutrition in pregnancy have been shown to be exacerbated by psychosocial stress. However, few studies have evaluated the correlation between psychosocial stress and outcomes associated with poor diet.

To determine the effects psychosocial stress has on the association between poor prenatal diet and adiposity outcomes in children, investigators conducted a study with participants from Project Viva, a cohort study of influences on maternal and child health.

The association between dietary inflammation and adiposity outcomes was evaluated, with offspring adiposity indices being the primary outcome. Dietary Inflammatory Index (DII) scores were used to measure dietary inflammation.

Adiposity outcomes were calculated through measurements of weight, length or height, subscapular and triceps skinfold thickness, and waist circumference. These measurements were taken in early childhood, midchildhood, and early adolescence. Body composition was also measured at midchildhood and early adolescence.

Using the Edinburgh Postpartum Depression Scale (EPDS), mothers reported depressive symptoms they were experiencing. Mothers with an EPDS score of 13 or higher were indicated as positive for depression, though this was not a clinical diagnosis.

Social vulnerability index (SVI) was calculated using residential address data. The 4 themes of SVI include socioeconomic status, household composition and disability, racial and ethnic and language status, and housing and transportation type.

There were 1060 participants, with an average maternal age of 32.6 years and prepregnancy BMI of 24.4. Non-Hispanic White mothers made up 77% of the study population.

The average DII score among participants was -2.7 units, while mean SVI was 38th percentile. Depressive symptoms were recorded in 8% of mothers. Lower pregnancy BMI, college education, and non-Hispanic White status were factors more often seen in the lowest DII quartile compared to the highest.

BMI scores decreased at a slower rate from childhood to early adolescence in children born to mothers in the highest prenatal DII quartile compared to the lowest. Children in this group also saw faster adiposity gain over time.

A positive EPDS screen was reported in 88 mothers. Offspring of these mothers had a stronger association between prenatal DII levels and adiposity outcomes. SVI status moderated associations between DII and direct adiposity measures, but not proxy measures.

These results indicate a direct impact from prenatal psychosocial stress on the association between prenatal diet and adiposity outcomes. Investigators recommended that interventions for preventing childhood adiposity examine both prenatal diet and psychosocial stress in women.

This article was originally published by our sister publication Contemporary Pediatrics.

Monthé-Drèze C, Aris IM, Rifas-Shiman SL, Shivappa N, Hebert JR, Oken E, et al. The role of prenatal psychosocial stress in the associations of a proinflammatory diet in pregnancy with child adiposity and growth trajectories. 

. 2023;6(1):e2251367. doi:10.1001/jamanetworkopen.2022.51367

In a recent study, the association between poor prenatal diet and adiposity outcomes in children was directly impacted by prenatal psychosocial stress.

Prenatal psychosocial stress impacts proinflammatory diet and child adiposity

Vitamin C supplementation for pregnant smokers significantly improves airway function and decreases wheeze in children aged 5 years, according to a recent study.

Prenatal exposure to smoke from maternal smoking has been associated with an increased risk of impaired lung development, leading to decreased airway function and increased risk of wheeze and asthma. Over 10% ofindividuals in the United States smoke during pregnancy, causing over 400,000 infants to be exposed to in utero smoke.

Lower airway function in childhood often leads to similarly poor function in adulthood, increasing the risk of respiratory morbidity and chronic obstructive pulmonary disease. Randomized control trials have shown improved airways in children when mothers took vitamin C supplementation during pregnancy, but results in these trials were mixed.

To determine if improved airway function can be achieved early in life and maintained through preschool age, researchers conducted a follow-up investigation to their Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function trial cohort, examining the forced expiratory flow (FEF) of patients aged 5 years.

Participants in the trial included pregnant women aged 15 years and older who had a confirmed single gestation aged 13 to 22 weeks. These individuals also spoke English, had smoked at least 1 in the past week, and were receiving care at clinics near the recruitment sites.

There were 2 groups which participants were randomized into: 1 where they received vitamin C supplementation and 1 where they received a placebo. Data was gathered on participants’ smoking histories and medical adherence, and participants were given brief counseling on smoking cessation.

In the follow-up, FEF measurements for offspring aged 5 years was collected.FEF between 25% and 75% expired volume (FEF25-75), FEF at 50% expired volume (FEF50), and FEF at 75% expired volume (FEF75) were all recorded. Parents and caregivers were also surveyed on the prevalence of wheeze in their children between the child’s fourth and sixth birthdays.

There were 213 children evaluated, with mean ages of 3.1 years in the vitamin C group and 3.2 years in the placebo group. Successful FEF measurements at age 5 were recorded in 90.1% of these children.

Significantly improved FEF25-75 measurements were found in children born to pregnant smokers in the vitamin C supplementation group compared to the placebo group, with a mean difference of 17.2%. Mean FEF50 and FEF75 measurements also improved significantly for children born to women in the vitamin C supplementation group.

The occurrence of wheeze was also significantly lower in children born to pregnant smokers treated with vitamin-C supplementation compared to placebo. Overall, vitamin-C supplementation administered during pregnancy was associated with improved airway function in children born to pregnant smokers.

This article originally appeared on Contemporary Pediatrics®.

McEvoy CT, Shorey-Kendrick LE, Milner K, Harris J, Vuylsteke B, Cunningham M, et al. Effect of vitamin C supplementation for pregnant smokers on offspring airway function and wheeze at age 5 years: follow-up of a randomized clinical trial. 

. 2023;177(1):16–24. doi:10.1001/jamapediatrics.2022.4401

A follow-up of a trial cohort showed that children aged 5 years born to pregnant smokers had improved airway function when vitamin C supplementation was administered during pregnancy compared to placebo.