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1. Glucocorticoid receptor sensitivity in early pregnancy in an African American cohort

   https://doi.org/10.1111/aji.13252  

   Clarke, Lasha S. ; Corwin, Elizabeth J. ; Dunlop, Anne L. ; Hankus, Allison ; Bradner, Joshua M. ; Paul, Sudeshna ; Jiao, Yunshen ; Smith, Alicia K. ; Patrushev, Nikolay ; Mulle, Jennifer G. ; et al ( May 2020 , American Journal of Reproductive Immunology)

   Disruption in homeostatic feedback loops between inflammatory mediators and the hypothalamic‐pituitary‐adrenal (HPA) axis is a key mechanism linking chronic stress to inflammation and adverse health outcomes, including those occurring during pregnancy. In particular, alterations in glucocorticoid sensitivity may occur as a result of chronic stress, including that due to racial discrimination, and may be implicated in the persistent adverse maternal and infant health outcomes experienced by African Americans. While there are a few large‐scale studies in human pregnancy that measure both cytokines and HPA axis hormones, to our knowledge, none directly measure glucocorticoid sensitivity at the cellular level, especially in an African American population.

   We measured the full range of the dexamethasone (DEX) dose‐response suppression of TNF‐α in first‐trimester blood samples from 408 African American women and estimated leukocyte cell type contribution to the production of TNF‐α.

   The mean (SD) DEX level needed to inhibit TNF‐α production by 50% (ie, DEX IC₅₀) was 9.8 (5.8) nmol/L. Monocytes appeared to be the main driver of Uninhibited TNF‐α production, but monocyte counts explained only 14% of the variation. Monocyte counts were only weakly correlated with the DEX IC₅₀(r = −.11,P < .05). Moreover, there was no statistically significant correlation between the DEX IC₅₀and circulating pro‐inflammatory (CRP, IL‐6, IFN‐γ) or anti‐inflammatory (IL‐10) mediators (P > .05).

   These findings challenge some prior assumptions and position this comprehensive study of glucocorticoid sensitivity as an important anchor point in the growing recognition of interindividual variation in maternal HPA axis regulation and inflammatory responses.

    

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2. Risk factors for placental malaria, sulfadoxine-pyrimethamine doses, and birth outcomes in a rural to urban prospective cohort study on the Bandiagara Escarpment and Bamako, Mali

   https://doi.org/10.1186/s12936-022-04125-6  

   Vincenz, Claudius ; Dolo, Zachary ; Saye, Serou ; Lovett, Jennie L. ; Strassmann, Beverly I. ( March 2022 , Malaria Journal)

   Malaria in Mali remains a primary cause of morbidity and mortality, with women at high risk during pregnancy for placental malaria (PM). Risk for PM and its association with birth outcomes was evaluated in a rural to urban longitudinal cohort on the Bandiagara Escarpment and the District of Bamako.

   Placental samples (N = 317) were collected from 249 mothers who were participants in a prospective cohort study directed by BIS in the years 2011 to 2019. A placental pathologist and research assistant evaluated the samples by histology in blinded fashion to assess PM infection stage and parasite density. Generalized estimating equations (GEE) were used to model the odds of PM infection.

   In a multivariable model, pregnancies in Bamako, beyond secondary education, births in the rainy season (instead of the hot dry season), and births to women who had ≥ 3 doses of sulfadoxine-pyrimethamine (SP) instead of no doses were associated with reduced odds of experiencing PM (active and past infections combined). Births in later years of the study were strongly associated with reduced odds of PM. Maternal age, which was positively associated with offspring year of birth, was significant as a predictor of PM only if offspring year of birth was omitted from the model. Gravidity was positively associated with both maternal age and offspring year of birth such that if either variable was included in the model, then gravidity was no longer significant. However, if maternal age or year of offspring birth were not adjusted for, then the odds of PM were nearly two-fold higher in primigravida compared to multigravida. Birth outcomes improved (+ 285 g birth weight, + 2 cm birth length, + 75 g placental weight) for women who had ≥ 3 doses of SP compared to no doses, but no difference was detected in birth weight or length for women who had 2 instead of ≥ 3 SP doses. However, at 2 instead of ≥ 3 doses placentas were 36 g lighter and the odds of low birth weight (< 2500 g) were 14% higher. Severe parasite densities (> 10% erythrocytes infected) were significantly associated with decreases in birth weight, birth length, and placental weight, as were chronic PM infections. The women who received no SP during pregnancy (7% of the study total) were younger and lacked primary school education. The women who received ≥ 3 doses of SP came from more affluent families.

   Women who received no doses of SP during pregnancy experienced the most disadvantageous birth outcomes in both Bamako and on the Bandiagara Escarpment. Such women tended to be younger and to have had no primary school education. Targeting such women for antenatal care, which is the setting in which SP is most commonly administered in Mali, will have a more positive impact on public health than focusing on the increment from two to three doses of SP, although that increment is also desirable.

    

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3. Evidence that highly canalized fetal traits are sensitive to intergenerational effects of maternal developmental nutrition

   https://doi.org/10.1002/ajpa.24883  

   Ragsdale, Haley B. ; Lee, Nanette R. ; Kuzawa, Christopher W. ( November 2023 , American Journal of Biological Anthropology)

   Maternal experiences before pregnancy predict birth outcomes, a key indicator of health trajectories, but the timing and pathways for these effects are poorly understood. Here we test the hypothesis that maternal pre‐adult growth patterns predict pregnancy glucose and offspring fetal growth in Cebu, Philippines.

   Using multiple regression and path analysis, gestational age‐adjusted birthweight and variables reflecting infancy, childhood, and post‐childhood/adolescent weight gain (conditional weights) were used to predict pregnancy HbA1c and offspring birth outcomes among participants in the Cebu Longitudinal Health and Nutrition Survey.

   Maternal early/mid‐childhood weight gain predicted birth weight, length, and head circumference in female offspring. Late‐childhood/adolescent weight gain predicted birth length, birth weight, skinfold thickness, and head circumference in female offspring, and head circumference in male offspring. Pregnancy HbA1c did not mediate relationships between maternal growth and birth size parameters.

   In Cebu, maternal growth patterns throughout infancy, childhood, and adolescence predict fetal growth via a pathway independent of circulating glucose, with stronger impacts on female than male offspring, consistent with a role of developmental nutrition on offspring fetal growth. Notably, the strength of relationships followed a pattern opposite to what occurs in response to acute pregnancy stress, with strongest effects on head circumference and birth length and weakest on skinfolds. We speculate that developmental sensitivities are reversed for stable, long‐term nutritional cues that reflect average local environments. These findings are relevant to public health and life‐history theory as further evidence of developmental influences on health and resource allocation across the life course.

    

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4. Birth mode and infectious morbidity risks in Qom children of Argentina

   https://doi.org/10.1002/ajhb.23200  

   Martin, Melanie A. ; Veile, Amanda J. ; Valeggia, Claudia R. ( December 2018 , American Journal of Human Biology)

   Cesarean delivery may increase childhood infectious morbidity risks via altered birth exposures and subsequent immune, microbial, and epigenetic development. Many Latin American indigenous populations experience dual burdens of infectious and chronic diseases, and are particularly vulnerable to rising rates of cesarean delivery and associated adverse outcomes. The Qom/Toba are an indigenous population in Argentina experiencing rapid lifestyle transitions. We hypothesized that cesarean delivery would be associated with increased risk of infectious symptoms in Qom children after adjusting for gestational and nutritional factors.

   We conducted a secondary analysis of birth records and monthly anthropometric and illness data collected previously from 90 Qom children (aged 1‐55 months). We tested for additive effects of birth mode on risk of gastrointestinal (GI) and respiratory illness (RI) in mixed‐effects logistic regression models adjusting for child weight‐for‐age (WAZ), weaning, and gestational and maternal age.

   Cesarean deliveries accounted for 46% of births and were associated with maternal age < 20 and ≥ 30 years, gestational age < 39 weeks, and prenatal complications. GI and RI risks were reduced in association with cesarean delivery, greater WAZ, weaning, maternal age ≥ 30 years, and gestational age < 39 weeks.

   The relationship between cesarean delivery and reduced infectious risks may reflect statistical confounding with relatively rapid postnatal growth and greater adiposity. Postnatal growth trajectories may be important mediators of long‐term morbidity risks associated with cesarean delivery. The frequency of cesarean deliveries among the Qom remains concerning given traditionally high rates of fertility and adolescent pregnancy.

    

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5. Astragaloside IV alleviates lipopolysaccharide‐induced preeclampsia‐like phenotypes via suppressing the inflammatory responses

   https://doi.org/10.1002/kjm2.12313  

   Tuerxun, Dilihuma ; Aierken, Remila ; Zhang, Yan‐Mei ; Huang, Ying ; Sui, Shuang ; Li, Xiao‐Ying ; Abulikemu, Zulifeiya ; Dilixiati, Nuerbiye ( October 2020 , The Kaohsiung Journal of Medical Sciences)

   Preeclampsia (PE) is a major cause of perinatal and maternal mortality and morbidity, which affects 2% to 8% of pregnancies in the world. The aberrant maternal inflammation and angiogenic imbalance have been demonstrated to contribute to the pathogenesis of PE. This research aimed to investigate the effect of Astragaloside IV (AsIV) in the treatment of PE and the underlying mechanisms. A rat PE‐like model was established by tail vein injection of lipopolysaccharide (LPS) and different doses of AsIV (40 and 80 mg/kg) were treated at the same time. Systolic blood pressure, total urine protein and urine volume were observed. Serum and placenta inflammatory cytokines were measured by ELISA kit. The mRNA and protein expression of relative genes were analyzed by qRT‐PCR and Western blotting. In PE‐like rats, there were obvious increases in systolic blood pressure, total urine protein and urine volume, which were obviously alleviated by treatment with AsIV. Serum levels of interleukin (IL)‐1β, tumor necrosis factor alpha (TNF‐α), IL‐6 and IL‐18, as well as IL‐4, IL‐10, PIGF, VEGF and sFlt‐1, were all reversed by treatment with AsIV. Meanwhile, AsIV treatment improved abnormal pregnancy outcomes, such as low litter size and low fetal weight. In addition, AsIV treatment downregulated the mRNA expression of inflammatory gene IL‐1β and IL‐6 in PE rats model, and AsIV treatment inhibited the activation of TLR‐4, NF‐κB, and sFlt‐1 in the placenta of PE rats. Our findings indicated the first evidence that AsIV alleviated PE‐like signs, and this improvement effect is possibly through inhibition of inflammation response via the TLR4/NF‐κB signaling pathway.

    

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