Maternal and cord blood hormones in relation to birth size

Birth size has been associated with adult life diseases, but the endocrine factors that are likely involved are not established. We evaluated the associations of maternal and cord blood hormones with birth size in normal pregnancies, and examined possible effect modification by maternal height, on the basis of prior suggestive evidence. In a prospective study of normal singleton pregnancies in Boston, USA and Shanghai, China, maternal hormone levels at the 27th gestational week were available for 225 pregnancies in Boston and 281 in Shanghai and cord blood measurements for 92 pregnancies in Boston and 110 in Shanghai. Pearson partial correlation coefficients of log-transformed hormone levels with birth weight and length were calculated. Overall, positive correlations with birth weight were found for maternal estriol (r = 0.19; p < 0.001) and progesterone (r = 0.15; p < 0.001) and these associations were more evident among taller mothers. There was an inverse association of cord blood progesterone (r = ?0.16; p < 0.03) with birth weight. In Boston, cord blood IGF-1 was positively associated with birth weight (r = 0.22; p < 0.04) and length (r = 0.25; p < 0.02), particularly among taller mothers (r = 0.43 and 0.38, respectively; p < 0.02), whereas among taller mothers in Shanghai the associations of IGF-2 with birth size appeared to be at least as strong as those of IGF-1. In conclusion, maternal estriol and progesterone, and cord blood IGF-1 were positively correlated with birth size. All correlations tended to be more pronounced among offspring of taller mothers. Among taller mothers in Shanghai, IGF-2 appeared to be at least as strongly associated with birth size as IGF-1.     

#19 Associations of maternal and umbilical cord hormone concentrations with maternal,gestational and neonatal factors

PURPOSE: High birth weight has been associated with adult breast and prostate cancer risk in epidemiologic studies and is hypothesized to be mediated through higher in utero estrogen concentrations. This hypothesis is based on maternal estrogen concen- trations, while limited data exist on the fetal circulation.METHODS: Concentrations of androstenedione, testosterone, estradiol, estriol, estrone, dehydroepiandrosterone (DHEA) and DHEA-Sulfate (DHEAS) were measured in maternal and mixed umbilical cord sera from 86 normal, singleton pregnancies. Maternal samples were collected at admission for labor and delivery.RESULTS: In the maternal sera, only estriol was positively correlated with gestational age (Spearman r = 0.35 ) and birth size including, birth weight (r = 0.36), length (r = 0.30) and head circumference (r = 0.25). Cord DHEAS concentrations, but none of the other hormones, were positively correlated with gestational age (r = 0.32), birth weight (r = 0.34), birth length (r = 0.41) and head circumference (r = 0.24). In linear regression analyses, maternal estriol and cord DHEAS predicted birth weight after adjustment for gestational age. No other hormones were independently associated with birth weight. Inspection of mean hormone levels by strata of birth weight (<2500, 2500–3499, 3500+), however, revealed nonlinear relations with the lowest birth weight babies having the lowest maternal estriol and cord DHEAS and no consistent pattern in the upper two categories.CONCLUSION: These data show an association between hormone concentrations and birth weight, however, the hormones involved and their patterns of association differ between the fetal and maternal results. In addition, these data are not consistent with the hypothesis that higher estrogen concentrations in high birth weight babies mediate the positive association with breast cancer risk observed in epidemiologic studies.     

脐血瘦素、IGF—Ⅰ、脂联素与胎儿宫内发育迟缓的意义

目的探讨脐血瘦素、IGF—Ⅰ和脂联素与胎儿宫内生长迟缓的关系。方法选择2006年10月至2007年10月在我院新生儿47例,宫内生长迟缓（小于胎龄儿,SGA）组16例,适于胎龄儿（AGA）组31例为正常对照组。采用放射免疫分析法对新生儿脐血瘦素、IGF—Ⅰ及脂联素进行检测分析;测量新生儿体质量、身长、头围、足长及胎盘重量,计算体重指数（BMI）。结果（1）宫内生长迟缓组脐血瘦素、IGF-Ⅰ及脂联素水平水平明显低于正常对照组（P均〈0．01）。（2）脐血脂联素水平与出生体质量、胎盘重量、BMI水平均呈正相关（P均〈0．05）。（3）脐血瘦素及IGF-Ⅰ水平分别与新生儿出生体质量、身长、头围、足长、BMI及胎盘重量呈显著正相关（P〈0．01）。结论脐血瘦素、IGF—Ⅰ及脂联素水平与胎儿生长发育及营养状态密切相关,脐血瘦素素、IGF—Ⅰ或脂联素水平降低可能是胎儿宫内生长迟缓发生的原因之一。     

Altered Umbilical Cord Blood Nutrient Levels,Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI)

Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.     

Arsenic-associated oxidative stress, inflammation, and immune disruption in human placenta and cord blood

Background

Arsenic (As) exposure during pregnancy induces oxidative stress and increases the risk of fetal loss and low birth weight.

Objectives

In this study we aimed to elucidate the effects of As exposure on immune markers in the placenta and cord blood, and the involvement of oxidative stress.

Methods

Pregnant women were enrolled around gestational week (GW) 8 in our longitudinal, population-based, mother–child cohort in Matlab, an area in rural Bangladesh with large variations in As concentrations in well water. Women (n = 130) delivering at local clinics were included in the present study. We collected maternal urine twice during pregnancy (GW8 and GW30) for measurements of As, and placenta and cord blood at delivery for assessment of immune and inflammatory markers. Placental markers were measured by immunohistochemistry, and cord blood cytokines by multiplex cytokine assay.

Results

In multivariable adjusted models, maternal urinary As (U-As) exposure both at GW8 and at GW30 was significantly positively associated with placental markers of 8-oxoguanine (8-oxoG) and interleukin-1β (IL-1β); U-As at GW8, with tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ); and U-As at GW30, with leptin; U-As at GW8 was inversely associated with CD3⁺ T cells in the placenta. Cord blood cytokines (IL-1β, IL-8, IFNγ, TNFα) showed a U-shaped association with U-As at GW30. Placental 8-oxoG was significantly positively associated with placental proinflammatory cytokines. Multivariable adjusted analyses suggested that enhanced placental cytokine expression (TNFα and IFNγ) was primarily influenced by oxidative stress, whereas leptin expression appeared to be mostly mediated by As, and IL-1β appeared to be influenced by both oxidative stress and As.

Conclusion

As exposure during pregnancy appeared to enhance placental inflammatory responses (in part by increasing oxidative stress), reduce placental T cells, and alter cord blood cytokines. These findings suggest that effects of As on immune function may contribute to impaired fetal and infant health.     

微量元素锌、铜、硒对胎盘镉转运的影响

目的:评价微量元素锌、铜、硒对胎盘镉转运的影响。方法:于2002年11月至2003年1月选择湖北省大冶市的待产孕妇,进行问卷调查和体格检查,同时检测全血锌、铜、硒和镉水平。采集新生儿脐血和胎盘标本用于测定镉含量。分析孕妇锌、铜、硒的营养状况是否与胎盘镉转运存在显著关联。结果:47例20～34岁孕妇全血镉(μg/L)为0.8～25.2,新生儿脐血镉(μg/L)为0.020～1.48,孕妇血镉显著高于脐血镉(T=564P<0.01)。孕妇胎盘组织镉含量(μg/g干重)为0.082～3.97。多因素线性回归分析显示,低血铜孕妇与血铜水平正常者相比新生儿脐血镉显著增加,低血锌孕妇的胎盘镉显著高于血锌正常者,低血硒孕妇的胎盘镉显著低于血硒正常者。结论:微量元素铜、锌、硒可能影响胎盘镉转运。     

Relationship of Plasma Carotenoids,Retinol and Tocopherols in Mothers and Newborn Infants

Objective:We studied the relationship between maternal and cord plasma concentrations of carotenoids, retinol, and tocopherols in normal mother-baby pairs.

Methods: Healthy pregnant women (n=10) were recruited at a Montréal hospital. Venous blood samples were collected from the mothers at delivery and cord blood was obtained immediately post partum from the umbilical vein after clamping of the cord. All deliveries were full term deliveries and all babies had normal birth weights. Maternal and umbilical cord blood samples were handled identically. Plasma was digested with lipase and plasma carotenoids were extracted and measured using HPLC.

Results: Cord plasma concentration of carotenoids were significantly lower than that of maternal plasma (p<0.001). There was a high correlation of lutein (r=0.889, p=0.006) and cryptoxanthin (r=0.912, p=0.0002) between maternal plasma concentrations and cord plasma concentrations. The concentrations of the hydrocarbon carotenoids, α-carotene and β-carotene, were also correlated (r=0.779, p=0.0133, & r=0.782, p=0.0076, respectively) between maternal plasma and cord plasma. Whereas the plasma concentration of the acyclic carotenoid, lycopene, showed no correlation between the two groups, after adjustment for plasma triglycerides, the lycopene correlation between maternal and cord plasma was the highest (r=0.975, p=0.0001) of all the carotenoids tested. Cord plasma retinol concentration, which was 50% of that of maternal plasma, was also found to have no correlation with that of maternal plasma. Plasma concentration of α-tocopherol showed no correlation between two groups, whereas there was high correlation between cord and maternal γ-tocopherol concentrations (r=0.808, p=0.0047).

Conclusion: The nutritional status of mothers affects the nutritional status of their babies for certain fat soluble nutrients.     

Association of maternal blood lead level during pregnancy with child blood lead level and pregnancy outcome in Kuwait

High blood lead levels (BLL) in pregnancy are associated with poor pregnancy outcome and neuro-behavioral deficits in infants. We investigated the prevalence of high BLL in pregnant women and its impact on pregnancy outcome in Kuwait. Blood from 194 mother-infant pairs were analyzed for lead by Atomic Absorption Spectrophotometry. Data were collected on birth weight, crown-heel length, head circumference, APGAR score, gestational age, and placental weight. Results revealed that 28% of pregnant women and 58% of infants had BLL >10 g/dL. Cord BLL was significantly higher than maternal BLL (10.92 vs. 5.77 g/dL, p < .001). Maternal BLL was not significantly associated with any of the outcome variables tested, whereas, cord BLL was a significant negative predictor of APGAR score only in boys. A significant proportion of pregnant women and their children in Kuwait have lead levels well above the safety limit, which is a matter of public health concern.     

Seroprevalance of pertussis antibodies in maternal and cord blood of preterm and term infants

Background

The resurgence of pertussis has resulted in an increased morbidity and mortality, especially among young infants. The aim of our study was to determine the antibody concentrations against pertussis antigens in cord and maternal blood in both preterm and term infant–mother pairs and to evaluate the efficacy of transplacental antibody transfer.

Methods

Antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in maternal and cord blood samples were measured by in-house enzyme linked immunosorbent assay (ELISA) in 100 preterm infant–mother and 100 term infant–mother pairs. Geometric mean concentrations (GMCs) of pertussis antibodies and cord:maternal GMC ratios were calculated.

Results

Cord GMCs for anti-PT and anti-FHA in the preterm group were 13.15 and 14.55 ELISA U/ml (EU/ml), respectively. Cord GMCs for anti-PT and anti-FHA in the term group were 19.46 and 19.18 EU/ml, respectively. Cord anti-PT GMC was significanlty lower in the preterm group (p = 0.037). There were no differences between the groups with regard to maternal anti-PT and anti-FHA GMC. Placental transfer ratios for anti-PT and anti-FHA in preterms were 68% and 72%, respectively. The same ratios in terms were 107% and 120%, respectively and were significantly higher than those of preterms (p < 0.001). Placental transfer ratios were even lower in preterms <32 weeks when compared to preterms ≥32 weeks and terms. There was a strong correlation between maternal and cord anti-pertussis antibody levels both in preterm and term infants.

Conclusions

Anti-pertussis antibody levels were generally low in infant–mother pairs and would not be adequate to confer protection until the onset of primary immunization series. Transplacental anti-pertussis antibody transfers and antibody levels were lower in the cord blood of preterm infants, especially in those <32 weeks. These findings support the rationale for maternal immunization, which in combination with cocooning, could be a better option for preterm infants.     

Associations between Maternal Dietary Patterns,Biomarkers and Delivery Outcomes in Healthy Singleton Pregnancies: Multicenter Italian GIFt Study

Background: Maternal nutrition represents a critical risk factor for adverse health outcomes in both mother and offspring. We aimed to investigate associations between maternal nutritional habits, biomarker status, and pregnancy outcome among Italian healthy normal-weight pregnancies. Methods: Multicenter prospective cohort study recruiting Italian healthy normal-weight women with singleton spontaneous pregnancies at 20 ± 2 weeks (T1) in Milan and Naples. All patients underwent nutritional evaluations by our collecting a 7-day weighed dietary record at 25 ± 1 weeks (T2) and a Food Frequency Questionnaire at 29 ± 2 weeks (T3). Maternal venous blood samples were collected at T3 to assess nutritional, inflammatory and oxidative biomarker concentrations (RBCs folate, vitamin D, hepcidin, total antioxidant capacity). Pregnancy outcomes were collected at delivery (T4). General linear models adjusted for confounding factors were estimated to investigate associations between maternal dietary pattern adherence, nutrient intakes, biomarker concentrations and delivery outcomes. Results: 219 healthy normal-weight pregnant women were enrolled. Vitamin D and RBCs folate concentrations, as well as micronutrient intakes, were consistently below the recommended range. In a multi-adjusted model, maternal adherence to the most prevalent ‘high meat, animal fats, grains’ dietary pattern was positively associated with hepcidin concentrations and negatively associated with gestational age at delivery in pregnancies carrying female fetuses. Hepcidin plasma levels were further negatively associated to placental weight, whereas vitamin D concentrations were positively associated to neonatal weight. Conclusions: A high adherence to an unbalanced ‘high meat, animal fats, grains’ pattern was detected among Italian normal-weight low-risk pregnancies, further associated with maternal pro-inflammatory status and gestational age at delivery. This evidence underlines the need for a dedicated nutritional counseling even among low-risk pregnancies.     

Interaction between cadmium (Cd), selenium (Se) and oxidative stress biomarkers in healthy mothers and its impact on birth anthropometric measures

To our knowledge, this study may be the first to examine the antagonistic role of selenium (Se) on oxidative stress induced by cadmium (Cd) and its impact on birth measures. Cd and Se levels were measured in umbilical-cord blood and the placentas of a subsample of 250 healthy mothers who participated between 2005 and 2006 in the project “Prenatal Exposure to Pollutants”. The median Cd levels in cord and maternal blood and placental tissue were 0.78 μg/l, 0.976 μg/l and 0.037 μg/g dry wt., respectively. The median levels of Se in cord serum and placental tissue were 65.68 μg/l and 1.052 μg/g dry wt., respectively. Se was more than 100-fold in molar excess over Cd in both cord serum and placental tissue. The median molar Cd/Se ratios in cord serum and placental tissue were 0.008 and 0.024, respectively, which were much lower than unity. This study suggests that both Cd and Se play a role in the mechanism of oxidative stress, but, the process underlying this mechanism remains unclear. Nevertheless, three biomarkers of oxidative stress had inconsistent relationships with Cd and/or Se in various matrices, perhaps due to potential untested confounders. Our results generally support an association between low in utero exposure to Cd and the anthropometric development of the fetus. Adjusted regression models indicated a negative association of cord blood Cd levels ≥0.78 μg/l with Apgar 5-min scores and birth height. Maternal Cd levels ≥0.976 μg/l were associated with a 5.94-fold increased risk of small-for-gestational-age births, which increased to 7.48-fold after excluding preterm births. Placenta weight decreased with increasing placental Cd levels ≥0.037 μg/g dry wt. (p = 0.045), an association that became stronger after excluding preterm births or adjusting for birth weight. Cord Se levels ≥65.68 μg/l were positively associated with placenta weight (p = 0.041) and thickness (p = 0.031), an association that remained unchanged after excluding preterm births. Cord Se levels, however, were negatively associated with cephalization index, but only after excluding preterm births (p = 0.017). Each birth measure was again modeled as a function of the Cd/Se ratios in cord blood and placenta tissue. Interestingly cord ratios ≥0.008 were negatively associated with Apgar-5 min score (p = 0.047), birth weight (p = 0.034) and placenta thickness (p = 0.022). After excluding preterm births, only the association with placenta thickness remained significant (p = 0.021), while birth weight (p = 0.053) was marginally significant. In contrast, cephalization index increased with Cd/Se ratios ≥0.008 (p = 0.033), an association that became marginally significant after excluding preterm births (p = 0.058). For placental Cd/Se ratios ≥0.024, only placenta weight was reduced with (p = 0.037) and without (p = 0.009) the inclusion of preterm births. These findings do not support an antagonistic mechanism between Cd and Se. The role of oxidative mechanisms either induced by Cd exposure or alleviated by Se on these birth anthropometric measures was examined by principal component analysis. Se did not have a clear protective role against Cd-induced adverse effects despite its substantial excess over Cd, and its role in alleviating oxidative stress by reducing malondialdehyde levels. The results may suggest that the extent of the Se beneficial effects is not governed only by its concentration but also by the chemical forms of Se that interact with various proteins. Consequently, the speciation of Se in such studies is essential for understanding and predicting Se availability for absorption.     

Plasma or red blood cell phospholipids can be used to assess docosahexaenoic acid status in women during pregnancy

The suitability of using plasma phopholipids (PLs) to assess docosahexaenoic acid (DHA) status during pregnancy is well accepted. Recent discussions have centered around whether red blood cells (RBCs) can be used to indicate DHA status. We tested the hypothesis that in pregnant women participating in an intervention study when fed a functional food containing DHA, maternal plasma PL DHA would be positively associated with maternal RBC PL and umbilical cord blood RBC PL DHA. Maternal and umbilical cord blood samples were obtained at delivery from women whose mean dietary intake was 187 mg/d (including the amount consumed from the DHA-functional food). Maternal plasma and RBCs and cord blood RBC lipids were extracted and PLs separated by thin-layer chromatography. Phopholipid lipids were methylated, and fatty acids were identified using gas chromatography. Fifty-nine maternal samples and 30 cord blood samples were analyzed. There were moderate to strong correlations between DHA in all compartments (maternal plasma vs maternal RBC PL DHA weight percent [wt%], r = 0.633, P ≤ .001; maternal plasma vs cord blood RBC PL DHA wt%, r = 0.458, P ≤ .01; maternal RBCs vs cord blood RBC PL DHA wt%, r = 0.376, P ≤ .01). These results support the practice of using either plasma PLs or RBC PLs to assess maternal and infant DHA status.     

Placental expression of the heme transporter, feline leukemia virus subgroup C receptor, is related to maternal iron status in pregnant adolescents

Little is known about the expression of heme transporters in human placenta and possible associations between these transporters and maternal or neonatal iron status. To address this area of research, relative protein expression of 2 heme transporters, Feline Leukemia Virus, Subgroup C, Receptor 1 (FLVCR1) and Breast Cancer Resistance Protein (BCRP), was assessed using Western-blot analysis in human placental tissue in relation to maternal/neonatal iron status and placental iron concentration. Placental FLVCR1 (n = 71) and BCRP (n = 83) expression were assessed at term (36.6-41.7 wk gestation) in a cohort of pregnant adolescents (13-18 y of age) at high-risk of iron deficiency. Both FLVCR1 and BCRP were detected in all placental samples assayed. Placental FLVCR1 expression was positively related to placental BCRP expression (n = 69; R(2) = 0.104; P < 0.05). Adolescents that were anemic at delivery had lower placental FLVCR1 expression (n = 49; P < 0.05). Placental FLVCR1 expression was positively associated with placental iron concentration at delivery (n = 61; R(2) = 0.064; P < 0.05). In contrast, placental BCRP expression was not significantly associated with maternal iron status or placental iron content. Both FLVCR1 and BCRP are highly expressed in human placental tissue, but only FLVCR1 was significantly inversely associated with maternal iron status and placental iron concentration. Further analysis is needed to explore potential functional roles of FLVCR1 in human placental iron transport.     

The effects of metallothionein 2A polymorphism on lead metabolism: are pregnant women with a heterozygote genotype for metallothionein 2A polymorphism and their newborns at risk of having higher blood lead levels?

Objectives

Numerous studies indicate that certain genetic polymorphisms modify lead toxicokinetics. Metallothioneins are protective against the toxicity of many metals, including lead. The aim of this study was to determine whether the maternal metallothionein 2A (MT2A) -5 A/G single-nucleotide polymorphism is related to the lead levels in maternal blood, placental tissue and cord blood in 91 pregnant women and their newborns.

Methods

Venous blood from the mother was collected to investigate lead levels and MT2A polymorphism. Cord blood and placenta were collected for lead levels. Analyses were made using an Atomic Absorption Graphite Furnace Spectrophotometer. Standard PCR–RFLP technique was used to determine MT2A polymorphism.

Results

Blood lead levels of heterozygote genotype (AG) mothers were statistically higher than those of homozygote genotype (AA) (P?P?Conclusion This study suggests that pregnant women with AG genotype for MT2A polymorphism might have high blood lead levels and their newborns may be at risk of low-level cord blood lead variation.     

Effect of Maternal Nutritional Status and Mode of Delivery on Zinc and Iron Stores at Birth

Zinc and iron deficiencies among infants aged under 6 months may be related with nutrient store at birth. This study aimed to investigate the association between zinc and iron stores at birth with maternal nutritional status and intakes during pregnancy. 117 pregnant women were enrolled at the end of second trimester and followed until delivery. Clinical data during pregnancy, including pre-pregnancy body mass index (BMI) and at parturition were collected from medical record. Zinc and iron intakes were estimated from a food frequency questionnaire. Serum zinc and ferritin were determined in maternal blood at enrollment and cord blood. Mean cord blood zinc and ferritin were 10.8 ± 2.6 µmol/L and 176 ± 75.6 µg/L, respectively. Cord blood zinc was associated with pre-pregnancy BMI (adj. ß 0.150; p = 0.023) and serum zinc (adj. ß 0.115; p = 0.023). Cord blood ferritin was associated with pre-pregnancy BMI (adj. ß −5.231; p = 0.009). Cord blood zinc and ferritin were significantly higher among those having vaginal delivery compared to cesarean delivery (adj. ß 1.376; p = 0.007 and 32.959; p = 0.028, respectively). Maternal nutritional status and mode of delivery were significantly associated with zinc and iron stores at birth. Nutrition during preconception and pregnancy should be ensured to build adequate stores of nutrients for infants.     

血清睾酮与妊高征发病相关性研究

目的:测定妊高征患者血清睾酮水平并探讨其临床意义。方法:采用放射免疫分析法测定妊高征患者30例、正常孕妇20例血清及其新生儿脐血睾酮水平。结果:妊高征患者血清睾酮水平(0.153±0.078nmol/L)明显高于正常孕妇组(0.023±0.015nmol/L),有显著性差异(P<0.001)。妊高征组脐血睾酮水平(0.052±0.041nmol/L)低于正常孕妇组(0.119±0.059nmol/L),有显著性差异(P<0.05),两组睾酮水平与新生儿性别无关(P>0.05)。结论:孕妇血清睾酮在妊高征的病理生理中起调节或加强作用。     

Cord Serum Calcitriol Inversely Correlates with Maternal Blood Pressure in Urinary Tract Infection-Affected Pregnancies: Sex-Dependent Immune Implications

Urinary tract infections (UTI) during pregnancy are frequently associated with hypertensive disorders, increasing the risk of perinatal morbidity. Calcitriol, vitamin D₃’s most active metabolite, has been involved in blood pressure regulation and prevention of UTIs, partially through modulating vasoactive peptides and antimicrobial peptides, like cathelicidin. However, nothing is known regarding the interplay between placental calcitriol, cathelicidin, and maternal blood pressure in UTI-complicated pregnancies. Here, we analyzed the correlation between these parameters in pregnant women with UTI and with normal pregnancy (NP). Umbilical venous serum calcitriol and its precursor calcidiol were significantly elevated in UTI. Regardless of newborn’s sex, we found strong negative correlations between calcitriol and maternal systolic and diastolic blood pressure in the UTI cohort (p < 0.002). In NP, this relationship was observed only in female-carrying mothers. UTI-female placentas showed higher expression of cathelicidin and CYP27B1, the calcitriol activating-enzyme, compared to male and NP samples. Accordingly, cord-serum calcitriol from UTI-female neonates negatively correlated with maternal bacteriuria. Cathelicidin gene expression positively correlated with gestational age in UTI and with newborn anthropometric parameters. Our results suggest that vitamin D deficiency might predispose to maternal cardiovascular risk and perinatal infections especially in male-carrying pregnancies, probably due to lower placental CYP27B1 and cathelicidin expression.     

Leptin Levels of the Perinatal Period Shape Offspring’s Weight Trajectories through the First Year of Age

Background: Leptin is a hormone regulating lifetime energy homeostasis and metabolism and its concentration is important starting from prenatal life. We aimed to investigate the association of perinatal leptin concentrations with growth trajectories during the first year of life. Methods: Prospective, longitudinal study, measuring leptin concentration in maternal plasma before delivery, cord blood (CB), and mature breast milk and correlating their impact on neonate’s bodyweight from birth to 1 year of age, in 16 full-term (FT), 16 preterm (PT), and 13 intrauterine growth-restricted (IUGR) neonates. Results: Maternal leptin concentrations were highest in the PT group, followed by IUGR and FT, with no statistical differences among groups (p = 0.213). CB leptin concentrations were significantly higher in FT compared with PT and IUGR neonates (PT vs. FT; IUGR vs. FT: p < 0.001). Maternal milk leptin concentrations were low, with no difference among groups. Maternal leptin and milk concentrations were negatively associated with all the neonates’ weight changes (p = 0.017 and p = 0.006), while the association with CB leptin was not significant (p = 0.051). Considering each subgroup individually, statistical analysis confirmed the previous results in PT and IUGR infants, with the highest value in the PT subgroup. In addition, this group’s results negatively correlated with CB leptin (p = 0.026) and showed the largest % weight increase. Conclusions: Leptin might play a role in neonatal growth trajectories, characterized by an inverse correlation with maternal plasma and milk. PT infants showed the highest correlation with hormone levels, regardless of source, seeming the most affected group by leptin guidance. Low leptin levels appeared to contribute to critical neonates’ ability to recover a correct body weight at 1 year. An eventual non-physiological “catch-up growth” should be monitored, and leptin perinatal levels may be an indicative tool. Further investigations are needed to strengthen the results.     

Bulky DNA Adducts in Cord Blood,Maternal Fruit-and-Vegetable Consumption,and Birth Weight in a European Mother–Child Study (NewGeneris)

Background: Tobacco-smoke, airborne, and dietary exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with reduced prenatal growth. Evidence from biomarker-based studies of low-exposed populations is limited. Bulky DNA adducts in cord blood reflect the prenatal effective dose to several genotoxic agents including PAHs.Objectives: We estimated the association between bulky DNA adduct levels and birth weight in a multicenter study and examined modification of this association by maternal intake of fruits and vegetables during pregnancy.Methods: Pregnant women from Denmark, England, Greece, Norway, and Spain were recruited in 2006–2010. Adduct levels were measured by the ³²P-postlabeling technique in white blood cells from 229 mothers and 612 newborns. Maternal diet was examined through questionnaires.Results: Adduct levels in maternal and cord blood samples were similar and positively correlated (median, 12.1 vs. 11.4 adducts in 10⁸ nucleotides; Spearman rank correlation coefficient = 0.66, p < 0.001). Cord blood adduct levels were negatively associated with birth weight, with an estimated difference in mean birth weight of –129 g (95% CI: –233, –25 g) for infants in the highest versus lowest tertile of adducts. The negative association with birth weight was limited to births in Norway, Denmark, and England, the countries with the lowest adduct levels, and was more pronounced in births to mothers with low intake of fruits and vegetables (–248 g; 95% CI: –405, –92 g) compared with those with high intake (–58 g; 95% CI: –206, 90 g)Conclusions: Maternal exposure to genotoxic agents that induce the formation of bulky DNA adducts may affect intrauterine growth. Maternal fruit and vegetable consumption may be protective.Citation: Pedersen M, Schoket B, Godschalk RW, Wright J, von Stedingk H, Törnqvist M, Sunyer J, Nielsen JK, Merlo DF, Mendez MA, Meltzer HM, Lukács V, Landström A, Kyrtopoulos SA, Kovács K, Knudsen LE, Haugen M, Hardie LJ, Gützkow KB, Fleming S, Fthenou E, Farmer PB, Espinosa A, Chatzi L, Brunborg G, Brady NJ, Botsivali M, Arab K, Anna L, Alexander J, Agramunt S, Kleinjans JC, Segerbäck D, Kogevinas M. 2013. Bulky DNA adducts in cord blood, maternal fruit-and-vegetable consumption, and birth weight in a European mother–child study (NewGeneris). Environ Health Perspect 121:1200–1206; http://dx.doi.org/10.1289/ehp.1206333     

Birth outcome measures and maternal exposure to heavy metals (lead,cadmium and mercury) in Saudi Arabian population

This cross-sectional study was conducted to assess the association between exposure to heavy metals (lead, cadmium and mercury) during pregnancy and birth outcomes in 1578 women aged 16–50 years who delivered in Al-Kharj hospital, Saudi Arabia, in 2005 and 2006. The levels of lead, cadmium and mercury were measured in umbilical cord blood, maternal blood and the placenta. Outcome variables were anthropometric measures taken at birth, along with the risk of being small-for-gestational age (SGA). We selected the 10th percentile as the cutoff for dichotomizing measures of birth outcome. Cadmium, despite its partial passage through the placenta had the most prominent effect on several measures of birth outcome. After adjustment for potential confounders, logistic regression models revealed that crown-heel length (p = 0.034), the Apgar 5-minute score (p = 0.004), birth weight (p = 0.015) and SGA (p = 0.049) were influenced by cadmium in the umbilical cord blood. Significant decreases in crown-heel length (p = 0.007) and placental thickness (p = 0.022) were seen with higher levels of cadmium in maternal blood. As placental cadmium increased, cord length increased (p = 0.012) and placental thickness decreased (p = 0.032). Only lead levels in maternal blood influenced placental thickness (p = 0.011). Mercury in both umbilical cord and maternal blood was marginally associated with placental thickness and placental weight, respectively. Conversely, placental mercury levels significantly influenced head circumference (p = 0.017), the Apgar 5-minute score (p = 0.01) and cord length (p = 0.026). The predictions of these models were further assessed with the area under the curve (AUC) of the receiver operating curves (ROCs), which were modest (larger than 0.5 and smaller than 0.7). The independence of gestational age or preterm births on the observed effect of metals on some measures of birth outcome, suggested detrimental effects of exposure on fetal development. The magnitude of the estimated effects might not necessarily be of clinical significance for infants but may have a considerable public-health relevance given the high prevalence of exposure to heavy metals. Further research should be conducted to confirm these findings and to evaluate their long-term risks, if any.