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ObjectivesThere is a need for effective and safe treatment during pregnancy in women with chronic inflammatory diseases. This study evaluated placental transfer of certolizumab pegol (CZP), an Fc-free anti-tumour necrosis factor drug, from CZP-treated pregnant women to their infants.MethodsCRIB was a pharmacokinetic (PK) study of women ≥30 weeks pregnant receiving commercial CZP for a locally approved indication (last dose ≤35 days prior to delivery). Blood samples were collected from mothers, umbilical cords and infants at delivery, and infants again at weeks 4 and 8 post-delivery. CZP plasma concentrations were measured with a highly sensitive and CZP-specific electrochemiluminescence immunoassay (lower limit of quantification 0.032 μg/mL).ResultsSixteen women entered and completed the study. Maternal CZP plasma levels at delivery were within the expected therapeutic range (median [range] 24.4 [5.0–49.4] μg/mL). Of the 16 infants, 2 were excluded from the per-protocol set: 1 due to missing data at birth and 1 due to implausible PK data. Of the remaining 14 infants, 13 had no quantifiable CZP levels at birth (<0.032 μg/mL), and 1 had a minimal CZP level of 0.042 μg/mL (infant/mother plasma ratio 0.0009); no infants had quantifiable CZP levels at weeks 4 and 8. Of 16 umbilical cord samples, 1 was excluded due to missing data; 3/15 had quantifiable CZP levels (maximum 0.048 μg/mL).ConclusionsThere was no to minimal placental transfer of CZP from mothers to infants, suggesting lack of in utero foetal exposure during the third trimester. These results support continuation of CZP treatment during pregnancy, when considered necessary.Trial registration number NCT02019602; Results.

PurposeSertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants.MethodPregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed.ResultsNine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants.ConclusionPlacental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment.Trial registrationThe trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.

To determine the threshold of umbilical cord blood procalcitonin for early-onset neonatal infection diagnosis. This prospective study was conducted on 126 neonates in the neonatal care unit of Hue University of Medicine and Pharmacy Hospital, Vietnam, from June 01, 2023 to August 31, 2024. All neonates showed signs at birth or risk factors for early-onset infection (EOI) and were divided into two groups: EOI group and non-EOI group. Umbilical cord blood samples were collected for procalcitonin analysis immediately after birth. The median procalcitonin (PCT) levels in umbilical cord blood were significantly higher in the EOI group (0.154 ng/ml [0.092-0.197]) compared to the non-EOI group (0.097 ng/ml [0.082-0.134]; p < 0.001). Receiver operating characteristic (ROC) curve determined the optimal threshold value of PCT of 0.142 ng/ml with an AUC 0.751 (95% CI: 0.661-0.841, p<0.001) in the total population. At this cut-off, the Se, Sp, PPV, and NPV were 68.2%, 76.8%, 61.2%, and 81.8%, respectively. The optimal cut-off value for preterm neonates was 0.122 ng/ml (AUC: 0.785, 95% CI: 0.658-0.911, p<0.001) corresponding a Se of 79.2%, Sp of 74.1%, PPV of 73.1%, and NPV of 80.0%. In term group, the optimal cut-off value was 0.150 ng/ml (AUC: 0.726, 95% CI: 0.583-0.860, p<0.01), with a Se of 60.0%, Sp of 80.4%, PPV of 52.2%, and NPV of 84.9%. Umbilical cord blood PCT concentration were elevated in neonates with EOI. PCT could be a valuable marker for the early diagnosis of EOI.

Abstract Context Large, longitudinal studies on androgen levels in pregnant women with polycystic ovary syndrome (PCOS) are lacking. While metformin has a mild androgen-lowering effect in non-pregnant women with PCOS, its effects on maternal androgen levels in pregnancy are less well understood. Objective To describe androgen patterns in pregnant women with PCOS and in healthy control women, and to explore the potential effects of metformin on maternal androgen levels in PCOS. Design and Setting A post hoc analysis from a randomized, placebo-controlled, multicenter study carried out at 11 secondary care centers and a longitudinal single-center study on healthy pregnant women in Norway. Participants A total of 262 women with PCOS and 119 controls. Intervention The participants with PCOS were randomly assigned to metformin (2 g daily) or placebo, from first trimester to delivery. Main Outcome Measures Androstenedione (A4), testosterone (T), sex-hormone binding globulin (SHBG), and free testosterone index (FTI) at 4 time points in pregnancy. Results Women with PCOS versus healthy controls had higher A4, T, and FTI, and lower SHBG at all measured time points in pregnancy. In the overall cohort of women with PCOS, metformin had no effect on A4, T, SHBG, and FTI. In subgroup analyses, metformin reduced A4 (P = 0.019) in nonobese women. Metformin also reduced A4 (P = 0.036), T (P = 0.023), and SHBG (P = 0.010) levels through pregnancy in mothers with a male fetus. Conclusion Metformin had no effect on maternal androgens in PCOS pregnancies. In subgroup analyses, a modest androgen-lowering effect was observed in nonobese women with PCOS. In PCOS women carrying a male fetus, metformin exhibited an androgen-lowering effect.

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system. Control of mosquito populations using pesticides is important for malaria elimination, but effects of pesticides on humans aren’t well understood. Here, Prahl et al. show in a cohort of pregnant Ugandan women and their infants that household spraying with bendiocarb affects the fetal immune system and response to vaccination in infancy.

Objective To evaluate the effect of preoperative intake of oral carbohydrates versus standard preoperative fasting prior to elective cesarean delivery on plasma purine levels (hypoxanthine, xanthine, and uric acid) and beta-hydroxybutyrate (β-HB) in mother’s blood plasma and umbilical cord blood plasma. Methods Prospective randomized clinical trial, performed according to the Declaration of Helsinki, IRB approval (KB-0012/113/19, 13.05.2019). Patients with at term gestation with singleton uncomplicated pregnancies, scheduled for cesarean delivery under spinal anaesthesia were randomized in a 1:1 ratio to Group I (oral carbohydrate drinks (CHO Group, oral carbohydrate drink − 200 mL − 12.5% dextrose in water) 2 h prior to surgery in addition to standard solid fasting (6 h) or Group II which underwent only standard fasting (6 h - solids, 2 h for – liquids, SF Group). Blood samples were collected at 2 h after carbohydrate consumption (maternal) and at umbilical cord clamping (umbilical cord). The primary outcomes - plasma concentrations of hypoxanthine, xanthine, uric acid, in maternal blood and umbilical cord blood were measured using high-performance liquid chromatography. The secondary outcomes were blood pH, and lactate, and butyrate concentration. Results The study was conducted between August 2019, and March 2020 with 148 patients enrolled (75 CHO group; 73 SF group). Lower concentrations of hypoxanthine (3.87 (3.13–5.18) vs. 4.85 (3.88–6.53)µmol/l, p  = 0.00050) and xanthine (0.79 (0.68–0.95) vs. 1.00 (0.88–1.22) µmol/l, < 0.00001) were observed in the maternal blood plasma and umbilical cord blood plasma (10.6 (8.00-16.5) vs. 13.9 (8.53–24.8) µmol/l, p  = 0.035 and 1.05 (0.82–1.58) vs. 1.45 (0.94–3.17) µmol/l, p  = 0.0035) in patients supplemented with carbohydrates. No difference in β-hydroxybutyrate concentration was noted. Conclusions Oral carbohydrate loading prior to cesarean delivery was associated with lower plasma purine levels in maternal and umbilical cord blood. Further work to understand the role of the purinergic pathway and ATP metabolism in maternal and neonatal health may guide interventions such as carbohydrate loading to optimize outcomes. Trial registration ClinicalTrials.gov identifier NCT04069806 (20190823).

Abstract Context Vitamin D (VD) deficiency in pregnancy and the neonatal period has impacts on childhood outcomes. Maternal VD sufficiency is crucial for sufficiency in the neonate, though the effect of early versus late pregnancy 25-hydroxy-vitamin D (25(OH)D) levels on neonatal levels is unknown. Furthermore, chemiluminescence immunoassays (CLIAs) are widely used, though their validity in measuring 25(OH)D specifically in cord blood specimens has not been established. Objective To assess the validity of a CLIA in the measurement of cord blood 25(OH)D and to evaluate maternal determinants of neonatal 25(OH)D, including early versus late pregnancy 25(OH)D levels. Design This is an ancillary analysis from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), a randomized, double-blinded, placebo-controlled study. Participants and Intervention A total of 881 pregnant women at high risk of having offspring asthma were randomized to receive VD supplementation or placebo. Serum samples were collected from mothers in early and late pregnancy and from offspring cord blood at birth. 25(OH)D levels were assayed by CLIA in all maternal and offspring samples and by LC-MS/MS in all offspring samples and a subset of 200 maternal third trimester samples. Results Cord blood 25(OH)D levels were higher as measured by CLIA (mean 37.13 ng/mL [SD 18.30]) than by LC-MS/MS (mean 23.54 ng/mL [SD 11.99]), with a mean positive bias of 13.54 ng/mL (SD 12.92) by Bland-Altman analysis. This positive bias in measurement by CLIA was not observed in maternal samples. Third trimester 25(OH)D was a positive determinant of neonatal 25(OH)D levels. Conclusion Chemiluminescence immunoassays overestimate 25(OH)D levels in human cord blood samples, an effect not observed in maternal blood samples. The quantification of 25(OH)D by CLIA should therefore not be considered valid when assayed in cord blood samples. Third trimester, but not first trimester, maternal 25(OH)D is one of several determinants of neonatal 25(OH)D status.

Abstract Context The relationship of maternal and infant 25-hydroxyvitamin D concentration [25(OH)D] with infant growth is unclear. Objective Our objective was to explore whether 25(OH)D in pregnancy, umbilical cord blood (UCB), or in infancy was associated with infant growth. Design This study involved 798 healthy infants and their mothers in Finland. We assessed 25(OH)D during pregnancy, from UCB at birth, and from the infant at the age of 12 months. Main Outcome Measures Infant length, weight, length-adjusted weight, and head circumference at 6 and 12 months and midupper-arm circumference at 12 months. Results Of the mothers and infants, 96% and 99% were vitamin D sufficient [25(OH)D ≥50 nmol/L], respectively. Mothers with pregnancy 25(OH)D >125 nmol/L had the shortest, lightest (in weight), and thinnest (in length-adjusted weight) infants at 6 months (P for all < 0.05). For each 10 nmol/L higher UCB 25(OH)D, the infants were 0.03 SD score (SDS) shorter at 6 months (95% CI −0.05 to −0.01), adjusted for birth size, infant 25(OH)D, and parental height. Higher UCB 25(OH)D associated with smaller head circumference at 6 and 12 months (P for all <0.05) but attenuated after adjustments. Mothers with pregnancy 25(OH)D >125 nmol/L had the thinnest infants at 12 months (P = 0.021). For each 10 nmol/L higher infant 25(OH)D, the infants were 0.03 SDS lighter (−0.05 to −0.01) and 0.03 SDS thinner (−0.05 to 0.00) at 12 months. Conclusions Our results suggest that high pregnancy, cord blood, and infant vitamin D concentration may have disadvantageous effects on infant growth. We investigated the effect of 25-hydroxyvitamin D concentration in pregnancy, cord blood, and infancy on postnatal growth and found that higher vitamin D status predicts slower infant growth.

IntroductionIntrauterine conditions and accelerating early growth are associated with childhood obesity. It is unknown, whether fetal programming affects the early growth and could alterations in the maternal-fetal metabolome be the mediating mechanism. Therefore, we aimed to assess the associations between maternal and cord blood metabolite profile and offspring early growth.MethodsThe RADIEL study recruited 724 women at high risk for gestational diabetes mellitus (GDM) BMI ≥ 30 kg/m2 and/or prior GDM) before or in early pregnancy. Blood samples were collected once in each trimester, and from cord. Metabolomics were analyzed by targeted nuclear magnetic resonance (NMR) technique. Following up on offsprings’ first 2 years growth, we discovered 3 distinct growth profiles (ascending n = 80, intermediate n = 346, and descending n = 146) by using latent class mixed models (lcmm).ResultsFrom the cohort of mother-child dyads with available growth profile data (n = 572), we have metabolomic data from 232 mothers from 1st trimester, 271 from 2nd trimester, 277 from 3rd trimester and 345 from cord blood. We have data on 220 metabolites in each trimester and 70 from cord blood. In each trimester of pregnancy, the mothers of the ascending group showed higher levels of VLDL and LDL particles, and lower levels of HDL particles (p < 0.05). When adjusted for gestational age, birth weight, sex, delivery mode, and maternal smoking, there was an association with ascending profile and 2nd trimester total cholesterol in HDL2, 3rd trimester total cholesterol in HDL2 and in HDL, VLDL size and ratio of triglycerides to phosphoglycerides (TG/PG ratio) in cord blood (p ≤ 0.002).ConclusionAscending early growth was associated with lower maternal total cholesterol in HDL in 2nd and 3rd trimester, and higher VLDL size and more adverse TG/PG ratio in cord blood.Clinical trial registrationClinicalTrials.gov, http://www.clinicaltrials.com, NCT01698385.

Objective To determine whether maternal allopurinol treatment during suspected fetal hypoxia would reduce the release of biomarkers associated with neonatal brain damage. Design A randomised double-blind placebo controlled multicentre trial. Patients We studied women in labour at term with clinical indices of fetal hypoxia, prompting immediate delivery. Setting Delivery rooms of 11 Dutch hospitals. Intervention When immediate delivery was foreseen based on suspected fetal hypoxia, women were allocated to receive allopurinol 500 mg intravenous (ALLO) or placebo intravenous (CONT). Main outcome measures Primary endpoint was the difference in cord S100ß, a tissue-specific biomarker for brain damage. Results 222 women were randomised to receive allopurinol (ALLO, n=111) or placebo (CONT, n=111). Cord S100ß was not significantly different between the two groups: 44.5 pg/mL (IQR 20.2–71.4) in the ALLO group versus 54.9 pg/mL (IQR 26.8–94.7) in the CONT group (difference in median −7.69 (95% CI −24.9 to 9.52)). Post hoc subgroup analysis showed a potential treatment effect of allopurinol on the proportion of infants with a cord S100ß value above the 75th percentile in girls (ALLO n=5 (12%) vs CONT n=10 (31%); risk ratio (RR) 0.37 (95% CI 0.14 to 0.99)) but not in boys (ALLO n=18 (32%) vs CONT n=15 (25%); RR 1.4 (95% CI 0.84 to 2.3)). Also, cord neuroketal levels were significantly lower in girls treated with allopurinol as compared with placebo treated girls: 18.0 pg/mL (95% CI 12.1 to 26.9) in the ALLO group versus 32.2 pg/mL (95% CI 22.7 to 45.7) in the CONT group (geometric mean difference −16.4 (95% CI −24.6 to −1.64)). Conclusions Maternal treatment with allopurinol during fetal hypoxia did not significantly lower neuronal damage markers in cord blood. Post hoc analysis revealed a potential beneficial treatment effect in girls. Trial registration number NCT00189007, Dutch Trial Register NTR1383.