Cord blood fatty acid‐binding protein‐4 levels are upregulated at both ends of the birthweight spectrum

Papathanasiou, Aimilia Eirini; Briana, Despina D.; Gavrili, Stavroula; Georgantzi, Sophia; Papathoma, E; Marmarinos, Antonios; Christou, Christos; Voulgaris, Konstantinos; Gourgiotis, Dimitrios; Malamitsi‐Puchner, Ariadne

doi:10.1111/apa.14826

Cited by 9 publications

(4 citation statements)

References 30 publications

(39 reference statements)

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“…Maternal and cord blood FABP4 concentrations were not correlated, suggesting fetal tissues might be the main source of FABP4 in cord blood ( 7 ). Consistent with our data, birth weight z score was positively correlated with cord blood FABP4 levels, while gestational age was negatively correlated with cord blood FABP4 levels in previous studies ( 37 , 38 ). Fetal FABP4 may be expressed at higher levels in earlier gestational ages.…”

Section: Discussionsupporting

confidence: 92%

Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol

Liu

Zheng

et al. 2021

Front. Endocrinol.

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Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.

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Section: Discussionsupporting

confidence: 92%

Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol

Liu

Zheng

et al. 2021

Front. Endocrinol.

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“…Although FGR is a multifactorial condition caused by fetal, placental, and maternal factors, the underlying mechanism frequently includes impaired oxygen and nutrition supply to the developing fetus. 19 Placental fatty acid transport is a crucial factor for determining fetal fat deposition. PUFAs should be transported from the maternal circulation across the syncytiotrophoblast and the fetal capillary endothelium.…”

Section: Discussionmentioning

confidence: 99%

Maternal serum fatty acid binding protein‐4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns

Bolluk,

Oğlak,

Kayaoğlu Yıldırım

et al. 2023

J of Obstet and Gynaecol

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PurposeThis study aimed to determine fatty acid binding protein‐4 (FABP‐4) concentrations in maternal serum of fetal growth restriction (FGR) pregnancies and controls of normal pregnancies. Furthermore, we hypothesized that the alterations in FABP‐4 levels might correlate with FGR severity.MethodsWe performed this prospective case–control study with 83 pregnant women. The study groups included 26 FGR pregnancies without abnormal fetal Doppler flow patterns and 25 pregnancies complicated with FGR accompanied by abnormal fetal Doppler flow patterns.ResultsThe median serum FABP‐4 concentrations were significantly higher in the FGR cases with abnormal Doppler flow pattern group (2.09 ng/mL) than in the FGR cases without abnormal Doppler flow pattern group (1.62 ng/mL) and the control group (1.20 ng/mL, p < 0.001). A significant negative correlation was observed between maternal serum FABP‐4 levels and time to birth from blood sample collection (r = −0.356 and p = 0.001), gestational week at birth (r = −0.386 and p < 0.001), and birth weight (r = −0.394 and p < 0.001). A 1.35 ng/mL cut‐off value of serum FABP‐4 level could be used to discriminate FGR cases with a 78.4% sensitivity and 60.6% specificity. The optimal cut‐off value of FABP‐4 levels as an indicator for the diagnosis of FGR with abnormal Doppler flow pattern was estimated to be 1.76 ng/mL, which yielded a sensitivity of 84.0% and a specificity of 75.8%.ConclusionFABP‐4 is a crucial biomarker in the diagnosis and determining the severity of pregnancies with restricted fetal growth. We consider that FABP‐4 is a powerful, reliable, and unique biomarker to diagnose FGR pregnancies.

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“…For example, Suski et al studied the difference in plasma proteome between preterm newborns stratified by their gestational age and found significant differences in proteins belonging to the inflammatory, immunomodulatory, and coagulation domains. In addition, various cord blood proteins have been reported as associated with birth weight in single-protein studies . Nevertheless, the long-term outcomes associated with the cord blood proteome remain understudied.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, various cord blood proteins have been reported as associated with birth weight in single-protein studies. 25 , 26 Nevertheless, the long-term outcomes associated with the cord blood proteome remain understudied. Cord blood contains proteins secreted from almost all tissues of both mother and fetus and is associated with the physiological and pathological state of the fetus.…”

Section: Introductionmentioning

confidence: 99%

Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories

Van Pee,

Martens,

Alfano

et al. 2024

JAMA Netw Open

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ImportanceThe cord blood proteome, a repository of proteins derived from both mother and fetus, might offer valuable insights into the physiological and pathological state of the fetus. However, its association with birth weight and growth trajectories early in life remains unexplored.ObjectiveTo identify cord blood proteins associated with birth weight and the birth weight ratio (BWR) and to evaluate the associations of these cord blood proteins with early growth trajectories.Design, Setting, and ParticipantsThis cohort study included 288 mother-child pairs from the ongoing prospective Environmental Influence on Early Aging birth cohort study. Newborns were recruited from East-Limburg Hospital in Genk, Belgium, between February 2010 and November 2017 and followed up until ages 4 to 6 years. Data were analyzed from February 2022 to September 2023.Main Outcomes and MeasuresThe outcome of interest was the associations of 368 inflammatory-related cord blood proteins with birth weight or BWR and with early life growth trajectories (ie, rapid growth at age 12 months and weight, body mass index [BMI] z score, waist circumference, and overweight at age 4-6 years) using multiple linear regression models. The BWR was calculated by dividing the birth weight by the median birth weight of the population-specific reference growth curve, considering parity, sex, and gestational age. Results are presented as estimates or odds ratios (ORs) for each doubling in proteins.ResultsThe sample included 288 infants (125 [43.4%] male; mean [SD] gestation age, 277.2 [11.6] days). The mean (SD) age of the child at the follow-up examination was 4.6 (0.4) years old. After multiple testing correction, there were significant associations of birth weight and BWR with 7 proteins: 2 positive associations: afamin (birth weight: coefficient, 341.16 [95% CI, 192.76 to 489.50]) and secreted frizzled-related protein 4 (SFRP4; birth weight: coefficient, 242.60 [95% CI, 142.77 to 342.43]; BWR: coefficient, 0.07 [95% CI, 0.04 to 0.10]) and 5 negative associations: cadherin EGF LAG 7-pass G-type receptor 2 (CELSR2; birth weight: coefficient, −237.52 [95% CI, −343.15 to −131.89]), ephrin type-A receptor 4 (EPHA4; birth weight: coefficient, −342.78 [95% CI, −463.10 to −222.47]; BWR: coefficient, −0.11 [95% CI, −0.14 to −0.07]), SLIT and NTRK-like protein 1 (SLITRK1; birth weight: coefficient, −366.32 [95% CI, −476.66 to −255.97]; BWR: coefficient, −0.11 [95% CI, −0.15 to −0.08]), transcobalamin-1 (TCN1; birth weight: coefficient, −208.75 [95% CI, −305.23 to −112.26]), and unc-5 netrin receptor D (UNC5D; birth weight: coefficient, −209.27 [95% CI, −295.14 to −123.40]; BWR: coefficient, −0.07 [95% CI, −0.09 to −0.04]). Further evaluation showed that 2 proteins were still associated with rapid growth at age 12 months (afamin: OR, 0.32 [95% CI, 0.11-0.88]; TCN1: OR, 2.44 [95% CI, 1.26-4.80]). At age 4 to 6 years, CELSR2, EPHA4, SLITRK1, and UNC5D were negatively associated with weight (coefficients, −1.33 to −0.68 kg) and body mass index z score (coefficients, −0.41 to −0.23), and EPHA4, SLITRK1, and UNC5D were negatively associated with waist circumference (coefficients, −1.98 to −0.87 cm). At ages 4 to 6 years, afamin (OR, 0.19 [95% CI, 0.05-0.70]) and SLITRK1 (OR, 0.32 [95% CI, 0.10-0.99]) were associated with lower odds for overweight.Conclusions and RelevanceThis cohort study found 7 cord blood proteins associated with birth weight and growth trajectories early in life. Overall, these findings suggest that stressors that could affect the cord blood proteome during pregnancy might have long-lasting associations with weight and body anthropometrics.

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Cord blood fatty acid‐binding protein‐4 levels are upregulated at both ends of the birthweight spectrum

Cited by 9 publications

References 30 publications

Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol

Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol

Maternal serum fatty acid binding protein‐4 level is upregulated in fetal growth restriction with abnormal Doppler flow patterns

Cord Blood Proteomic Profiles, Birth Weight, and Early Life Growth Trajectories

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