Maternal exposure to chemical and physical factors during pregnancy and cardiovascular malformations in the offspring

The possible effect of chemical and physical factors during pregnancy on the occurrence of cardiovascular malformations in the offspring was studied in 573 cases and 1,055 controls. The cases represented all verified cardiovascular malformations in Finland during 1982-1984. The controls were randomly selected from all babies born during the same period. Case and control mothers were interviewed by midwives approximately 3 months after delivery using a structured questionnaire. Maternal alcohol consumption during the first trimester of pregnancy was more common among the mothers of case infants (45.9%) than those of controls (39.6%). Exposure to organic solvents at work was slightly more prevalent among the ventricular septal defect group (12.1%) than the control mothers (7.8%). However, neither association was significant when adjusted for maternal age in logistic regression analysis. Moreover, one or both of these associations may be chance effects resulting from multiple comparisons. The risk of cardiovascular malformations was not associated with maternal smoking, or coffee, tea, or cola consumption, and was equal in urban and rural areas. Maternal exposures to anesthetic gases, pesticides, wood preservatives, microwave ovens, and video display terminals at work or home were not associated with the risk of cardiovascular malformations. It is concluded that some common environmental exposures during early pregnancy to physical and chemical factors should not necessarily be considered hazardous for the developing fetal heart. The causes of the majority of cardiovascular malformations remain unknown.     

Phenotypic modulation of fibroblastic cells in mice pubic symphysis during pregnancy,partum and postpartum

In many species, the cartilaginous pubic symphysis of the pregnant female is gradually replaced by a fibrous connective tissue, forming a flexible and elastic interpubic ligament. This newly formed ligament is responsible for the separation of the pubic bones, enabling safe delivery of the young. Following labor, the ligament undergoes rapid involution. To our knowledge, no previous work has focused on the phenotypic modulation that is responsible for the changes present at the interpubic ligament throughout the relaxation and closing of the symphysis. The purpose of this study was to investigate the ultrastructural features and immunophenotype of the peculiar cell type found in the pubic symphysis of cycling, pregnant and postpartum mice. In particular, immunohistochemistry studies were conducted on the expressions of the cytoskeletal proteins desmin, vimentin and -smooth muscle actin (-SMA). During pregnancy, the pubic symphysis cells always expressed -SMA, whereas the expression of vimentin and desmin was transient from early pregnancy to postpartum. Furthermore, the expression patterns of these three cytoskeletal proteins were distinct. Cells present in the medial region of the mouse symphysis in cycling and at D12 displayed ultrastructural features characteristic of a typical fibroblast. In contrast, during the last week of pregnancy and in postpartum these cells acquired ultrastructural features representative of a myofibroblast; for example, a fibronexus and a contractile apparatus were found to be present lying in close contact with the extracellular collagenous and elastic system fibrils. Taken together, these results strongly suggest a contractile function for these cells which might contribute to support of the varying mechanical stresses present during pubic bone movement.This work was supported by grants from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). This paper is part of a thesis submitted to the Department of Histology and Embryology of the Biology Institute State University of Campinas, in partial fulfillment of the requirements for the Masters degree.     

Urinary cadmium levels during pregnancy and postpartum

It is well established that pregnancy induces physiological, metabolical and hormonal changes. As a consequence, trace metal metabolism can be affected. The aim of the present study was to assess the urinary cadmium levels in women during gestation and postpartum. The survey was conducted in a group of nonoccupationally cadmium-exposed women from Southern Catalonia (NE, Spain). Urine samples were obtained before pregnancy, during the 6th, 10th, 26th, and 30th wk of gestation, as well as during the 5th and 24th wk after delivery. Urinary cadmium levels were determined by graphite furnace atomic absorption spectrophotometry. The concentrations of zinc and copper in plasma were also measured. Moreover, to assess the effect of the diet during pregnancy, dietary ingestions of zinc, iron, and calcium were also determined. A significant decrease of plasma zinc levels could be observed during the last two trimesters of pregnancy, while plasma copper concentrations significantly increased during the same period. Urinary cadmium concentrations ranged from 0.05 to 3.79 μg/g creatinine (geometric mean 0.49±2.26 μg/g creatinine). No significant changes in urinary cadmium concentrations during pregnancy and postpartum could be observed.     

Maternal investment during pregnancy in wild meerkats

Maternal investment in offspring development is a major determinant of the survival and future reproductive success of both the mother and her young. Mothers might therefore be expected to adjust their investment according to ecological conditions in order to maximise their lifetime fitness. In cooperatively breeding species, where helpers assist breeders with offspring care, the size of the group may also influence maternal investment strategies because the costs of reproduction are shared between breeders and helpers. Here, we use longitudinal records of body mass and life history traits from a wild population of meerkats (Suricata suricatta) to explore the pattern of growth in pregnant females and investigate how the rate of growth varies with characteristics of the litter, environmental conditions, maternal traits and group size. Gestational growth was slight during the first half of pregnancy but was marked and linear from the midpoint of gestation until birth. The rate of gestational growth in the second half of pregnancy increased with litter size, maternal age and body mass, and was higher for litters conceived during the peak of the breeding season when it is hot and wet. Gestational growth rate was lower in larger groups, especially when litter size was small. These results suggest that there are ecological and physiological constraints on gestational growth in meerkats, and that females may also be able to strategically adjust their prenatal investment in offspring according to the likely fitness costs and benefits of a particular breeding attempt. Mothers in larger groups may benefit from reducing their investment because having more helpers might allow them to lower reproductive costs without decreasing breeding success.     

Maternal stress during pregnancy and early childhood development

We estimate the impact of prenatal stress on early childhood development outcomes known as “middle years” or intermediate outcomes, which has not been studied previously. Using a unique measure of actual maternal stress induced by a large earthquake, we find that relative to children that were not exposed, in utero maternal stress reduces children’s cognitive skills and socio-emotional problems by age 3, and that the effects are heterogeneous. The negative impacts on cognitive skills occur during the first trimester of pregnancy and are found among both low and high-income children, and boys and girls. The harmful effects on socio-emotional behaviors occur when stress is experienced in the last trimester of pregnancy.     

Maternal caffeine intake during pregnancy and orofacial clefts

BACKGROUND: Moderate caffeine intake during pregnancy is common, but little is known about its potential association with birth defects. METHODS: The National Birth Defects Prevention Study is a population‐based, case‐control study of major birth defects, excluding infants with single‐gene disorders and chromosomal abnormalities. This analysis includes infants with cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft was secondary to holoprosencephaly or amniotic band sequence. Mothers reported dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before pregnancy and reported intake of medications containing caffeine during pregnancy. We assessed the association between dietary caffeine intake, frequency of consuming each type of caffeinated beverage, medications containing caffeine, and CL/P or CPO among infants born from October 1997 through December 2004. RESULTS: This analysis included 1531 infants with CL/P, 813 infants with CPO, and 5711 infants with no major birth defects (controls). Examining dietary sources among control mothers, 11% reported consuming at least 300 mg of caffeine per day and 17% reported consuming less than 10 mg of caffeine per day; high consumption (≥3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas); medications containing at least 100 mg caffeine/dose were reported by less than 1%. Although some effect estimates were elevated for moderate caffeine intake from all beverages, estimates were closer to the null for high caffeine levels. Isolated CL/P was associated with use of medications containing at least 100 mg of caffeine per dose. CONCLUSIONS: Our data do not suggest an association between maternal dietary caffeine intake and orofacial clefts, but caffeine‐containing medications merit further study. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Maternal urinary cadmium concentrations in early pregnancy in relation to prenatal and postpartum size of offspring

BackgroundThe impacts of environmental cadmium (Cd) exposure on birth size parameters including weight, length and head circumference (HC) have been reported in multiple studies. However, little remains known of the impacts of maternal Cd exposure during pregnancy on size during in utero development and during early childhood. The aim of this study was to comprehensively investigate impacts of maternal Cd exposure during pregnancy on the size of offspring in utero (from 24 weeks pregnancy) until six months of age.MethodsPregnant mothers were recruited as part of an ongoing prospective birth cohort study based in Guangdong, China. Maternal urine samples were collected in the first and third trimesters of pregnancy, in which Cd concentrations were measured by inductively couple plasma mass spectrometry (ICPMS). In utero size indicators at 24 and 32 week of gestation, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and HC were derived from ultrasound examinations. Anthropometric measures of weight, height and HC at birth and one, three and six months of age were also collected. Associations of size measures at the various time points with maternal urinary Cd concentrations were assessed using linear regression models.ResultsThe median urinary Cd concentration was 1.00 and 0.98 μg/g creatinine in the first and third trimesters respectively. In univariate analysis, increased maternal Cd levels in the first trimester were associated with decreased HC (-0.17 cm/ug/g urinary Cd) at birth, and the association was particularly pronounced among males (-0.30 cm/ug/g urinary Cd). First trimester Cd exposure was also found to be significantly associated with decreased infant weight at three and six months of age among girls (−101 g/ug/g and −97 g/ug/g urinary Cd, respectively). Associations of similar magnitude were observed after adjustment for various maternal factors. No significant associations were observed with infant size measures or with measures of Cd in the third trimester.ConclusionsOur detailed study suggests that the first trimester is particularly critical window of susceptibility to sex-specific effects of Cd on size parameters at birth, with some effects persisting to six months of age. These compelling sex-dependent effects on HC and body weight warrant future studies examining longer-term health effects of pregnancy-related Cd exposures.     

Cell-mediated immunity in human pregnancy: Changes in lymphocyte reactivity during pregnancy and postpartum.

The function of thymus-dependent lymphocytes (T lymphocytes) was studied in women during pregnancy and labor and postpartum by evaluating the blastogenesis of peripheral lymphocytes, which were stimulated with phytohemagglutin-P (PHA-P) in both whole-blood semimicroculture and purifed lymphocyte culture. Data from 353 random samples (203 women) and 50 serial specimens from 10 women revealed that PHA-P induced-lymphocyte blastogenesis was significantly (p less than 0.005) reduced during pregnancy and labor but rapidly returned to normal several days after artificial termination in the early stage of pregnancy as well as after full-term delivery. These results indicate that the T-lymphocyte function in maternal peripheral blood is depressed by causes related to pregnancy. It seems very likely that depressed T-lymphocyte function during pregnancy is caused by inhibitory factors in the blood plasma derived from the feto-placental unit. Questions relating to the inhibitory factors in maternal plasma are discussed.     

Hemostatic profile during late pregnancy and early postpartum period in mares

Hemostasis is a physiological process that prevents excessive blood loss and represents a protective mechanism at the time of delivery. Peripartum hemorrhage is a recurring hazardous condition to mare's health; therefore, we aimed to study mares' hemostatic profile to investigate whether physiological adjustments occur during late pregnancy and early postpartum. Fifteen pregnant mares have been monitored from the 34th week of pregnancy until the third week after foaling. Fifteen nonpregnant mares were used as control group. Jugular blood samples were analyzed for platelet count (Plt), prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen (Fb). Platelet count showed significant changes at foaling (P < 0.05) and a negative correlation (r = −0.968; P = 0.032) with postpartum. Prothrombin time changed (P < 0.05) showing a significant correlation (r = 0.675; P = 0.016) with late pregnancy. Fibrinogen concentrations changed throughout the experimental period (P < 0.0001). The linear regression model revealed a positive correlation (r = 0.9210; P < 0.0001) between Fb and late pregnancy and a negative correlation (r = −0.9583; P = 0.042) between Fb and early postpartum. The shortening in PT recorded in the imminence of parturition along with the increase in Plt and Fb at foaling might reflect a physiological hypercoagulable state that constrains excessive bleeding, enhancing mares' odds of surviving. Our research improves the knowledge about blood coagulation in periparturient mares providing specific information on routine coagulation tests that may support in monitoring mare's hemostatic profile during late pregnancy and early postpartum.     

Maternal corticotropin-releasing hormone levels during pregnancy and offspring adiposity

Objective: Animal models suggest that fetal exposure to glucocorticoids can program adiposity, especially central adiposity, later in life. We examined associations of maternal corticotropin‐releasing hormone (CRH) levels in the late 2nd trimester of pregnancy, a marker of fetal glucocorticoid exposure, with child adiposity at age 3 years. Research Methods and Procedures: We analyzed data from 199 participants in Project Viva, a prospective cohort study of pregnant women and their children, At age 3 years, the main outcomes were age‐sex‐specific BMI z score and the sum of subscapular (SS) and triceps (TR) skinfold thicknesses to represent overall adiposity, and ratio of SS to TR (SS:TR) to represent central adiposity. Results: Mean (standard deviation) maternal 2nd trimester log CRH was 4.94 (0.56) pg/mL. At age 3, mean (standard deviation) for BMI z score was 0.52 (1.02); for SS + TR, 16.51 (3.94) mm; and for SS:TR, 0.67 (0.17). Log CRH was mildly inversely correlated with birth weight (r = ?0.08), chiefly because of its association with length of gestation (r = ?0.21) rather than fetal growth (r = ?0.004). After adjustment for sociodemographic factors, maternal smoking, BMI, and gestational weight gain, fetal growth, length of gestation, breastfeeding duration, and (for SS:TR only) child's 3‐year BMI, each increment of 1 unit of log CRH was associated with a reduction in BMI z score [?0.43; 95% confidence interval (CI), ?0.73, ?0.14; p = 0.004] and possible reduction in SS + TR (?1.10; 95% CI, ?2.33, 0.14; p = 0.08). In contrast, log CRH was associated with higher SS:TR (0.07; 95% CI, 0.02, 0.13; p = 0.007). Discussion: Fetal exposure to glucocorticoids, although associated with an overall decrease in body size, may cause an increase in central adiposity.     

Long-term changes in medication during pregnancy

The Finnish Register of Congenital Malformations, established in 1963, rendered possible the study of changes in medication during pregnancy. The study consisted of 659 control mothers who had delivered a healthy child during the years 1964-1984. The data of this long-term follow-up study were collected by interviews at Maternal Health Care Centers after delivery and were completed by filed antenatal data. The results show a continuous decreasing trend in the usage of analgesics and tranquilizers but not in the usage of antiemetics, antibiotics, and vitamins. We believe that in Finland the publicity aimed at unnecessary medication during pregnancy has affected both the mothers and the health personnel.     

Adult respiratory distress syndrome during pregnancy and immediately postpartum.

From 1976 to 1983, the adult respiratory distress syndrome occurred in 14 patients during pregnancy or within a month postpartum. There were 8 survivors, giving a 43% mortality. All but 2 patients had obstetric-related precipitating events--labor problems, infections, eclampsia-toxemia, and obstetric hemorrhages. During emergency cesarean sections, 3 patients had respiratory problems that may have caused their respiratory distress syndrome. The average duration of mechanical ventilatory support was 16 days. Six patients had barotrauma with 1 patient sustaining an irreversible anoxic central nervous system injury. Infections were documented in 8 patients, 6 of whom had obstetric foci. There is a lack of information regarding the adult respiratory distress syndrome in this patient group. Though uncommon, it can cause substantial mortality and morbidity.     

Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife

Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites (CpGs) in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959–1964 and measured DNA methylation in blood (granulocytes) collected in 2001–2007 (mean age: 43 years). Seventeen CpGs were differentially methylated by MSP, with multiple CpGs mapping to CYP1A1, MYO1G, AHRR, and GFI1. These associations were consistent in direction with prior studies (e.g., MSP associated with more and less methylation in AHRR and CYP1A1, respectively) and, with the exception of AHRR CpGs, were not substantially altered by adjustment for active smoking. These preliminary results confirm prior prospective reports that MSP influences the offspring DNA methylation, and extends the timeframe to midlife, and suggest that these effects may persist into adulthood, independently of active smoking.