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

Importance: The 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. Objective: To 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 Participants: This 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 Measures: The 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. Results: The 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 Relevance: This 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.

Prenatal exposure to per- and polyfluoroalkyl substances, fetal thyroid function, and intelligence quotient at 7 years of age: Findings from the Sheyang Mini Birth Cohort Study.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. OBJECTIVES: This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. METHODS: The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. RESULTS: The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (ß = -6.21, 95 % confidence interval [CI]: -12.21, -0.21), with more pronounced associations observed among girls (ß = -9.57, 95 % CI: -18.33, -0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. CONCLUSIONS: Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

The associations between maternal and fetal exposure to endocrine-disrupting chemicals and asymmetric fetal growth restriction: a prospective cohort study.

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables (ß = 0.003, p < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 µg/g creatinine vs. 1.71 µg/g creatinine [p < 0.05]; cord blood BPA, 1.96 µg/L vs. -0.86 µg/L [p < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR.

Placental MFSD2A expression in fetal growth restriction and maternal and fetal DHA status.

INTRODUCTION: Fetal growth restriction (FGR) may affect placental transfer of key nutrients to the fetus, such as the fatty acid docosahexaenoic acid (DHA). Major facilitator superfamily domain containing 2A (MFSD2A) has been described as a specific DHA carrier in placenta, but its expression has not been studied in FGR. The aim of this study was to evaluate for the first time the placental MFSD2A levels in late-FGR pregnancies and the maternal and cord plasma DHA. METHODS: 87 pregnant women from a tertial reference center were classified into late-FGR (N = 18) or control (N = 69). Fatty acid profile was determined in maternal and cord venous plasma, as well as placental levels of MFSD2A and of insulin mediators like phospho-protein kinase B (phospho-AKT) and phospho-extracellular regulated kinase (phospho-ERK). RESULTS: Maternal fatty acid profile did not differ between groups. Nevertheless, late-FGR cord vein presented higher content of saturated fatty acids than control, producing a concomitant decrease in the percentage of some unsaturated fatty acids. In the late-FGR group, a lower DHA fetal/maternal ratio was observed when using percentages, but not with concentrations. No alterations were found in the expression of MFSD2A in late-FGR placentas, nor in phospho-AKT or phospho-ERK. DISCUSSION: MFSD2A protein expression was not altered in late-FGR placentas, in line with no differences in cord DHA concentration between groups. The increase in the saturated fatty acid content of late-FGR cord might be a compensatory mechanism to ensure fetal energy supply, decreasing other fatty acids percentage. Future studies are warranted to elucidate if altered saturated fatty acid profile in late-FGR fetuses might predispose them to postnatal catch-up and to long-term health consequences.

The influence of maternal prepregnancy weight and gestational weight gain on the umbilical cord blood metabolome: a case-control study.

BACKGROUND: Maternal overweight/obesity and excessive gestational weight gain (GWG) are frequently reported to be risk factors for obesity and other metabolic disorders in offspring. Cord blood metabolites provide information on fetal nutritional and metabolic health and could provide an early window of detection of potential health issues among newborns. The aim of the study was to explore the impact of maternal prepregnancy overweight/obesity and excessive GWG on cord blood metabolic profiles. METHODS: A case control study including 33 pairs of mothers with prepregnancy overweight/obesity and their neonates, 30 pairs of mothers with excessive GWG and their neonates, and 32 control mother-neonate pairs. Untargeted metabolomic profiling of umbilical cord blood samples were performed using UHPLC‒MS/MS. RESULTS: Forty-six metabolites exhibited a significant increase and 60 metabolites exhibited a significant reduction in umbilical cord blood from overweight and obese mothers compared with mothers with normal body weight. Steroid hormone biosynthesis and neuroactive ligand‒receptor interactions were the two top-ranking pathways enriched with these metabolites (P = 0.01 and 0.03, respectively). Compared with mothers with normal GWG, in mothers with excessive GWG, the levels of 63 metabolites were increased and those of 46 metabolites were decreased in umbilical cord blood. Biosynthesis of unsaturated fatty acids was the most altered pathway enriched with these metabolites (P < 0.01). CONCLUSIONS: Prepregnancy overweight and obesity affected the fetal steroid hormone biosynthesis pathway, while excessive GWG affected fetal fatty acid metabolism. This emphasizes the importance of preconception weight loss and maintaining an appropriate GWG, which are beneficial for the long-term metabolic health of offspring.

Correlation between maternal and umbilical cord 25-hydroxy-vitamin D levels over a range of values. A prospective observational study from the United Arab Emirates.

Worldwide vitamin D insufficiency is remarkably prevalent in both children and adults, including pregnant women. The total amount of the vitamin is best measured by 25-hydroxy-vitamin D (25(OH)D), which is a measurement of total serum cholecalciferol 25(OH)D3 and ergocalciferol 25(OH)D2. There is a known correlation between maternal and umbilical cord blood (UCB) 25(OH)D; however, whether specific maternal demographics or comorbidities influence the correlation remains uncertain. This prospective observational study was designed to study if maternal 25(OH)D levels, maternal age and BMI, amount of supplementation, mode of delivery, diabetes, hypertension/preeclampsia, or sunlight exposure had an impact on the correlation. Women were enrolled in the study at admission to the labor ward. If they agreed to participate, venous blood was directly collected and analyzed for 25(OH)D. The UCB was sampled after delivery from the unclamped cord and immediately analyzed for 25(OH)D. ANOVA, Fisher's exact test, Pearson's correlation, and test of the differences between correlations using Fisher's z-transformation with Bonferroni correction were used accordingly. Of the 298 women enrolled, blood from both the mother and umbilical cord was analyzed successfully for 25(OH)D in 235 cases. The crude correlation between maternal and UCB 25(OH)D was very strong over all values of 25(OH)D (r = 0.905, R2 = 0.821, p <0,001) and remained strong independently of maternal demographics or co-morbidities (r ≥ 0.803, R2 ≥ 0.644, p <0.001). For women who delivered by caesarean section in second stage the correlation was strong (r ≥ 0.633, R2 ≥ 0.4, p <0.037). Test of differences between correlations showed significant stronger correlation in women with unknown 25(OH)D3 supplementation compared to women receiving 10.000 IU/week (p = 0.02) and 20.000IU/week (p = 0.01) and that the correlation was significantly stronger for women with a BMI of 25-29.9 compared to women with a BMI of <24.9 (p = 0.004) and 30-34.9 (p = 0.002). 213 (91%) women had lower 25(OH)D compared to the neonate, with a mean difference of -13.7nmol/L (SD = 15.6). In summary, the correlation between maternal and UCB 25(OH)D is very strong throughout low to high maternal levels of 25(OH)D with lower levels in maternal blood. Typical maternal demographics and comorbidities did not affect the transition.

Evaluation of preadipocyte factor-1 (Pref-1) level in cord blood of newborns born by mothers with gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic complication, which leads to short and long-term consequences in both mother and fetus exposed to hyperglycemia. The aetiology of this condition is proposed to be based on the dysfunction of the adipose tissue, which is characterised by the aberrant generation of adipokines. One of them is preadipocyte factor-1 (Pref-1), which could mediate controlling the adaptation of the maternal metabolism to pregnancy. AIMS: The study aims to examine the level of Pref-1 in the cord blood of healthy pregnant women's neonates and fetuses born to mothers with GDM. MATERIALS AND METHODS: Cord blood samples were collected from 30 newborns of mothers with GDM and 40 newborns of healthy pregnant women. Pref-1 concentrations were measured with an ELISA kit. RESULTS: Fetal Pref-1 concentrations were significantly lower in newborns of mothers with GDM compared to the normal pregnancy group children (5.32 ± 0.29 vs. 7.38 ± 0.53; p < 0.001). Mothers with GDM had a significantly higher index of BMI before pregnancy, maternal gestational weight gain, and maternal fasting glucose. In-depth analysis through multiple variant linear regression revealed a significant association between fetal serum Pref-1 levels, exposure to GDM, and gestational age. CONCLUSION: These findings contribute valuable insights into maternal-fetal health and pave the way for more targeted and effective clinical interventions.

Changes in metabolic acidosis following birth in intensive care unit neonates.

BACKGROUND: Little is known about how and why metabolic acidosis changes within the first six hours of life in intensive care unit neonates. OBJECTIVE: To determine changes in pH and base excess between paired umbilical cord arterial and neonatal arterial blood samples during the first 6 h of life, to identify factors associated with the direction and magnitude of change, and to examine morbidity and mortality in newborns with acidosis at birth or as neonates. STUDY DESIGN: Retrospective cohort study of all deliveries from a single institution between 2016-2020 with paired umbilical cord arterial and neonatal arterial samples obtained within 6 h of life meeting rigorous criteria to ensure sample integrity. The primary outcomes were the direction and magnitude of change of pH and base excess. Multiple factors were assessed for possible correlation with pH and base excess change. The secondary outcome was the association between a composite outcome of death or cerebral palsy and pathologic acidosis (pH ≤ 7.1) at birth or as a neonate. RESULTS: 102 patients met inclusion criteria. Newborn arterial gasses were obtained at a median of 1.5 h (74 % < 2 h). pH improved in 71 % of cases and worsened in 29 %, and base excess improved in 52 % and worsened in 48 %, with wide observed ranges in both parameters. The paired pH and base excess values were moderately (r = 0.38) and strongly (r = 0.63) positively correlated, respectively, but were not correlated with time since birth (r = 0.14). Low birth weight, prematurity or respiratory failure were associated with worsening or less improvement, while worse initial acidosis was associated with greater improvement. Death or survival with cerebral palsy was more common with pathologic acidosis in either cord or newborn sample as compared with those without acidosis (27.3 % vs 3.7 %, p = 0.003), and was more common in those with isolated neonatal acidosis as compared to those without acidosis (50 % vs 3.7 %, p = 0.016). CONCLUSIONS: Changes in pH and base excess occurred over a wide range between delivery and the first newborn blood gas in the first 6 h of life, and we identified several factors associated with direction of change. Metabolic acidosis at birth cannot reliably be inferred from neonatal arterial values. Neonatal acidosis, including acidosis following a normal pH and base excess at birth, was associated with morbidity and mortality.

How does maternal anemia affect the levels of umbilical cord brain-derived neurotrophic factor?

OBJECTIVE: In this study, we aimed to evaluate the effect of maternal iron deficiency anemia on the umbilical cord level of brain-derived neurotrophic factor (BDNF), which plays a very important role in the central nervous system. METHODS: Our research was planned as a quantitative, prospective, and analytical type of study. A total of 90 volunteers, term, singleton pregnant hospitalized in the Health Sciences University Ümraniye Training and Research Hospital Gynecology and Obstetrics Clinic between September 2021 and August 2022 were included in this study. While 45 of these pregnants were pregnant women with iron deficiency anemia (hemoglobin ≤ 110 g/L and serum ferritin level ≤ 12 µg/L), 45 cases were in the control group without iron deficiency anemia (hemoglobin > 110 g/L, serum ferritin > 12 µg/L). When pregnant were admitted to the hospital, blood samples were taken to analyze hemoglobin, mean cell volume (MCV), iron, unsaturated iron binding capacity, total iron binding capacity, serum ferritin, transferrin, and CRP levels. Also, we noted the maternal age, gravida, parity, birth weight, head circumference, type of birth, 1. minute Apgar score, and 5. minute Apgar score. During the delivery; after the umbilical cord had been clamped and cut, we took 5 cc of umbilical cord blood. Then, we put it in the serum-separating laboratory tubes. After we centrifuged these blood samples, we put the serum parts in the Eppendorf tubes to be stored at -80 degrees Celsius. At the end of the study, we calculated the level of BDNF using special human brain-derived neurotrophic factor ELISA kits. The umbilical cord BDNF levels of the maternal iron deficiency anemia group and the control group were compared statistically. RESULTS: When we evaluated the fetal umbilical cord BDNF values of 90 participants, the median value BDNF in the babies of 45 anemic mothers was 3.16 (IQR 0.73), and the median BDNF value of the babies of 45 healthy mothers was 5.37 (IQR 1.02). We found a statistical difference between BDNF and hemoglobin, hematocrit, MCV, and iron values between these two groups. CONCLUSION: In conclusion, the BDNF value of the babies of healthy individuals is higher than that of anemic individuals. Our study showed that the amount of BDNF in the umbilical cord blood was significantly affected by maternal iron deficiency anemia.

Timing of administration of antenatal magnesium sulphate and correlation with umbilical cord blood magnesium levels in preterm babies.

BACKGROUND: The effectiveness of MgSO4 for foetal neuroprotection is acknowledged, but the best time to provide it in relation to birth is a conundrum, and dose schedule is yet unknown. Understanding the determinants of the magnesium levels in cord blood aids in determining the appropriate timing and length of administration. AIM AND OBJECTIVE: To assess the cord blood magnesium concentration in relation to the timing of MgSO4 and delivery. To achieve ROC in relation to optimum level of cord blood magnesium concentration in relation to neonatal outcome variables. STUDY DESIGN: A prospective observational study conducted in a tertiary care hospital over 2 years in women having preterm delivery from 26 weeks to 33 + 6 weeks, who received Neuroprophylaxis. Cord blood was collected for magnesium level estimation. Baby followed 24 h after delivery. ROC analysis performed for predicting an optimal cut-off for a continuous predictor predicting binary outcome. RESULTS: 85 recruited cases divided into bolus group, bolus + infusion group. The mean cord blood magnesium (n = 85) was 3.8 mg/dl. The AUROC for Gestational Age at Administration predicting Baby Outcome: 0.699, It was statistically significant (p = 0.034). The AUROC for Cord Blood Mg predicting Baby Outcome: 0.606, It was not statistically significant (p = 0.262). CONCLUSION: Mean cord blood magnesium levels served as a tool to determine the timing and duration of Neuroprophylaxis. Mean cord blood magnesium of 3.8 mg/dl should be achieved to serve the purpose of Neuroprotection. To achieve this, Bolus followed by Infusion should be administered for at-least 6 h prior to delivery.

Association of free maternal and fetal ropivacaine after epidural analgesia for intrapartum caesarean delivery: a prospective observational trial.

BACKGROUND: Ropivacaine is present in plasma in both protein-bound and free forms. The free form is responsible for the occurrence of toxic side effects. During obstetric epidural analgesia, free ropivacaine enters the fetal circulation depending on various factors. The aim of this study was to analyse a potential association between ropivacaine concentrations in maternal and fetal plasma and hence the extent of fetal exposure to ropivacaine. METHODS: In this prospective monocentre study, parturients who met the following criteria were included in the study: 1. epidural administration as part of obstetric anaesthesia, and 2. subsequent intrapartum caesarean delivery, which 3. was performed after an epidural bolus administration of ropivacaine within the existing epidural analgesia. Total and free ropivacaine concentrations were analysed in maternal blood at baseline, prior to epidural bolus administration for caesarean delivery, and in maternal and fetal (umbilical venous, oxygenated) blood at delivery. The results are presented as mean ±â€¯SD or median (25/75th percentile). RESULTS: We screened 128 parturients who went into labour at term and requested epidural analgesia, of whom 39 were ultimately included in the study. An intrapartum caesarean delivery was performed after the epidural application of 207 (166/276) mg ropivacaine during an epidural treatment period of 577 (360/1010) min. Total and free ropivacaine concentrations were 1402 ±â€¯357 ng/ml and 53 ±â€¯46 ng/ml, respectively, in maternal venous blood and 457 ±â€¯243 ng/ml and 43 ±â€¯27 ng/ml, respectively, in fetal blood. The maternal total and free ropivacaine concentrations were significantly correlated (r = 0.873; P < 0.0001). CONCLUSION: The results of the present study suggest that determining the concentration of free ropivacaine in maternal blood may be a feasible option for estimating neonatal exposure to ropivacaine.

Inverse associations of cord blood mitochondrial DNA copy number with childhood adiposity.

OBJECTIVE: The objective of this study was to examine associations between umbilical cord mitochondrial DNA copy number (mtDNAcn) and adiposity across childhood. METHODS: In a prospective birth cohort of Dominican and African American children from New York City, New York (1998-2006), mtDNAcn was measured in cord blood. Children (N = 336) were evaluated for their height, weight, and bioimpedance at age 5, 7, 9, and 11 years. We used linear mixed-effects models to assess associations of mtDNAcn tertiles in cord blood with child BMI, BMI z scores, fat mass index, and body fat percentage. Latent class growth models and interactions between mtDNAcn and child age or child age2 were used to assess associations between age and adiposity trajectories. RESULTS: BMI was, on average, 1.5 kg/m2 higher (95% CI: 0.58, 2.5) in individuals with mtDNAcn in the low- compared with the middle-mtDNAcn tertile. Results were similar for BMI z score, fat mass index, and body fat percentage. Moreover, children in the low-mtDNAcn group had increased odds of being in an "increasing" or "high-stable" adiposity class. CONCLUSIONS: Lower mtDNAcn at birth may predict greater childhood adiposity, highlighting the potential key role of perinatal mitochondrial function in adiposity during development.

Trends in Apgar scores and umbilical artery pH: a population-based cohort study on 10,696,831 live births in Germany, 2008-2022.

Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682).          Conclusion: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022.

Correlation of fetal heart rate dynamics to inflammatory markers and brain-derived neurotrophic factor during pregnancy.

OBJECTIVES: This study aims to show the relation between biomarkers in maternal and cord-blood samples and fetal heart rate variability (fHRV) metrics through a non-invasive fetal magnetocardiography (fMCG) technique. METHODS: Twenty-three women were enrolled for collection of maternal serum and fMCG tracings immediately prior to their scheduled cesarean delivery. The umbilical cord blood was collected for measurement of biomarker levels. The fMCG metrics were then correlated to the biomarker levels from the maternal serum and cord blood. RESULTS: Brain-derived neurotrophic factor (BDNF) had a moderate correlation with fetal parasympathetic activity (0.416) and fetal sympathovagal ratios (-0.309; -0.356). Interleukin (IL)-6 also had moderate-sized correlations but with an inverse relationship as compared to BDNF. These correlations were primarily in cord-blood samples and not in the maternal blood. CONCLUSIONS: In this small sample-sized exploratory study, we observed a moderate correlation between fHRV and cord-blood BDNF and IL-6 immediately preceding scheduled cesarean delivery at term. These findings need to be validated in a larger population.

The Impact of Prenatal Alcohol Exposure on Longitudinal Growth, Nutritional Status, and Insulin-Like Growth Factor 1 in Early Childhood in Leyte, the Philippines.

OBJECTIVE: To assess the impact and potential mechanistic pathways of prenatal alcohol exposure (PAE) on longitudinal growth and nutritional status in early childhood. STUDY DESIGN: A cohort of 296 mother-infant dyads (32% with PAE vs 68% unexposed) were recruited in Leyte, the Philippines, and followed from early gestation through 24 months of age. PAE was assessed using serum phosphatidylethanol (PEth) captured twice prenatally and in cord blood and supplemented with self-reported alcohol consumption. Linear mixed models were used to examine longitudinal effects of PAE on growth from birth through 2 years including key potential mediating factors (placental histopathology, and infant serum leptin and Insulin-like Growth Factor 1 [IGF-1]). RESULTS: After adjusting for potential confounders, we found that PAE was significantly associated with a delayed blunting of linear growth trajectories (height-for-age z-score, body length) and weight (weight-for-age z-score, body weight) that manifested between 4 and 6 months and continued through 12-24 months. PAE was also associated with a decreased rate of mid-upper-arm circumference growth from birth to 12 months, and a lower mean IGF-1 levels at birth and 6 months. CONCLUSION: This study demonstrates a delayed impact of PAE on growth that manifested around 6 months of age, underscoring the importance of routine clinical monitoring in early childhood. Furthermore, the findings supported prior animal model findings that suggest a mechanistic role for IGF-1 in PAE-induced growth delay.

The association of in-utero exposure to air pollution and atherogenic index of plasma in newborns.

BACKGROUND: Prenatal exposure to particulate matter (PM) and traffic was associated with the programming of cardiovascular diseases (CVDs) in early life. However, the exact underlying mechanisms are not fully understood. Therefore, we aimed to evaluate the association between in-utero exposure to PMs and traffic indicators with the atherogenic index of plasma (AIP) in newborns, which is a precise index reflecting an enhancement of lipid risk factors for CVDs. METHODS: In this cross-sectional study, a total of 300 mother-newborn pairs were enrolled in Sabzevar, Iran. Spatiotemporal land-use regression models were used to estimate the level of PM1, PM2.5 and PM10 at the mother's residential address. The total length of streets in different buffers (100,300 and 500m) and proximity to major roads were calculated as indicators of traffic. The AIP of cord blood samples was calculated using an AIP calculator. Multiple linear regression models were used to examine the association of PM concentrations as well as traffic indicators with AIP controlled for relevant covariates. RESULTS: PM2.5 exposure was significantly associated with higher levels of AIP in newborns. Each interquartile range (IQR) increment of PM2.5 concentration at the mothers' residential addresses was associated with a 5.3% (95% confidence interval (CI): 0.0, 10.6%, P = 0.04) increase in the AIP. Associations between PM1, PM10 and traffic indicators with cord blood level of AIP were positive but not statistically significant. CONCLUSION: Our findings showed that in utero exposure to PM2.5 may be associated with CVDs programming through the increase of atherogenic lipids.

Eucapnic pH coupled with arterial cord pH improves hypoxic-ischemic encephalopathy prediction.

OBJECTIVE: To consider the classical use of "pH < 7.0 and/or a base deficiency ≥12 mmol/L" as markers of the risk of neonatal hypoxic-ischemic encephalopathy (HIE), recalling various criticisms of the use of these markers in favor of that of neonatal eucapnic pH, which appears to be a better marker of this risk. METHODS: Fifty-five cases of acidemia with pH < 7.00 were collected from a cohort from the Nice University Hospital with eight cases of HIE. We compared the receiver operating characteristics curves established from the positive likelihood ratio (+LR) for each case of: umbilical cord artery pH (pHa), neonatal eucapnic pH (pH euc-n) in isolation (not matched to pHa), and matched pHa to its own pH euc-n. RESULTS: The areas under the curve (AUC) are identical for pHa and pH euc-n, but AUC for the matched pair pHa-pH euc-n appears superior but non-significant because of the small number in our cohort. However, using the bootstrap method, the partial AUC for a sensitivity greater than 75% indicates the significant superiority (P < 0.01) of the matched pair pHa-pH euc-n approach. CONCLUSION: The originality of this study lies in the use of two methodologic approaches: (1) standardized partial analysis of the AUCs of the pHa curve and that of pHa matched to its own pH euc-n, and (2) bootstrap statistical technique, that allowed us to conclude (P < 0.01) that the combined use of pH measured at the cord coupled with its eucapnic correction is better for diagnosing metabolic acidosis and best predicting the risk of HIE.

The Correlation Between the Total Decelerations and Accelerations Areas and Cord Blood pH in Women with Low-Risk Pregnancies.

Fetal acidosis among low-risk pregnancies is not common; however, identifying those at risk for this complication antenatally is of great interest. We aimed to assess the correlation between the total decelerations area during the last 120 min of fetal monitoring prior to delivery and neonatal acidemia in low-risk pregnancies and whether the total acceleration area has a protective effect in the presence of decelerations. A retrospective cohort study was conducted among women with term low-risk pregnancies. A researcher blinded to fetal outcomes interpreted electronic fetal monitor patterns during the 120 min prior to delivery. The primary outcome was fetal acidemia, defined as umbilical artery pH below 7.10. The correlation between the total decelerations and accelerations areas and cord blood pH was tested using the Spearman correlation coefficient. A total of 109 women were included and of these, six (5.5%) delivered infants with cord blood pH < 7.10. A significant correlation was demonstrated between the total decelerations area and cord blood pH (p = 0.01). No correlation was found between the total accelerations area and cord blood pH. Among low-risk pregnancies, a correlation was found between the total decelerations area but not the total accelerations area during the final 120 min of labor and cord blood pH.

Increased Y Chromosome Microdeletions in Cord Blood of Male Newborns From Assisted Reproductive Technology Compared to Natural Conception.

OBJECTIVES: To investigate the incidence of Y chromosome microdeletions in male newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and natural conception (NC). METHODS: A total of 186 male newborns were recruited, including 35 conceived by ICSI, 37 conceived by IVF, and 114 conceived naturally. DNA was extracted from umbilical cord blood after birth. The Yq genetic status of the newborns was determined according to 18 Y-specific sequence tagging sites (STS) markers covering 3 azoospermia factor (AZF) sub-regions and internal control sequences. RESULTS: Partial AZF microdeletions were identified in 8 of 35 (22.9%) ICSI newborns, 4 of 37 (10.8%) IVF newborns, and 1 of 114 (0.9%) NC newborns. There was a statistically significant difference in the proportion of newborns with partial Y chromosome microdeletions between the ICSI, IVF, and NC groups. When analyzed individually, only the SY114 and SY152 STS markers showed a statistically significant difference in incidence between the 3 cohorts. CONCLUSIONS: Our study indicates that the population of male children conceived through assisted reproductive technologies (ART), particularly ICSI, is at an increased risk of genetic defect in the form of partial Y chromosome microdeletions. The growing population of ART-conceived children emphasizes the importance of studying the genetic repercussions of these procedures regarding the future fertility of males conceived in vitro.

Development of a new staining protocol for the Kleihauer-Betke test to facilitate the reading of difficult cases.

BACKGROUND: The Kleihauer-Betke (KB) test allows the detection of fetal red blood cells (containing fetal hemoglobin, HbF) in the maternal blood to identify and quantify potential fetal-maternal hemorrhages. In certain cases, detecting fetal red blood cells with conventional staining is difficult. False-positive results or overestimation of the quantity of fetal red blood cells may occur in cases of maternal hemoglobinopathy. In this study, we developed a new staining protocol to facilitate the reading of difficult smears and improve the precision of the quantification of fetal red blood cells; we also analyzed the performance of this new method. This study assessed blood samples with and without hemoglobin abnormalities, which present difficulties when interpreting the KB test. METHODS: The new staining formula is based on an improved elution technique and the use of a different stain instead of hematoxylin. To test this staining method, 16 samples from patients with abnormal hemoglobin electrophoresis and 14 samples from patients with normal hemoglobin electrophoresis were analyzed using the KB test with the classical staining method and the new staining method. In addition, a second series was prepared using the same samples spiked with fetal red blood cells from newborn blood, to compare the accuracy of the two methods in identifying fetal red blood cells. RESULTS: In the 60 slides analyzed with both staining methods, we found that the new technique improved the accuracy from 78 to 85%; lowered the coefficient of variation between the operators, which decreased from 20.7% to 12.7%; increased the specificity in our population from 56 to 70%; and decreased the number of false-positive cases by 30%. CONCLUSIONS: We successfully developed a new staining technique that facilitates the reading of difficult slides and improves the specificity of the detection of fetal red blood cells. This technique is recommended as a secondary method to use before sending the sample for additional exploration.