Decision-making in the referral process of sonographers in primary care screening centers.

OBJECTIVES: To explore the decision-making process (whether or not to refer) of sonographers performing the 20 weeks standard anomaly scan (SAS) in the screening setting. METHODS: A survey was sent to SAS-sonographers; it assessed experience, training, volume, type of practice, perceived difficulty per organ system, feelings after missing anomalies and reasons for uncertainty and doubt concerning referral. RESULTS: The response rate was 50%. Sonographers tend to seek reasons for uncertainty in patient factors and not in their skills or difficulty of the scan. Most mentioned reasons to refer in case of doubt were repeated visualization of a possible abnormality (98%). We hypothesize that the need of repeated imaging of an abnormality might partly explain why some fetal anomalies are still being missed. Sonographers with limited experience and low volume SAS more often revised, referred and asked colleagues for help than experienced sonographers with high volume SAS. In cases of a missed diagnosis, sonographers frequently blamed internal factors (personal failure 71%). CONCLUSION: Level of experience and volume of SAS influence revision and referral rates. Personal factors seem to play a role in the decision-making process of screening sonographers. Future research should focus on these personal factors, to optimize screening ultrasound programs. © 2016 John Wiley & Sons, Ltd.

Maternal occupation during pregnancy, birth weight, and length of gestation: combined analysis of 13 European birth cohorts.

OBJECTIVES: We assessed whether maternal employment during pregnancy - overall and in selected occupational sectors - is associated with birth weight, small for gestational age (SGA), term low birth weight (LBW), length of gestation, and preterm delivery in a population-based birth cohort design. METHODS: We used data from >200 000 mother-child pairs enrolled in 13 European birth cohorts and compared employed versus non-employed women. Among employees, we defined groups of occupations representing the main sectors of employment for women where potential reproductive hazards are considered to be present. The comparison group comprised all other employed women not included in the occupational sector being assessed. We performed meta-analyses of cohort-specific estimates and explored heterogeneity. RESULTS: Employees had a lower risk of preterm delivery than non-employees [adjusted odds ratio (OR adj) 0.86, 95% confidence interval (95% CI) 0.81-0.91]. Working in most of the occupational sectors studied was not associated with adverse birth outcomes. Being employed as a nurse was associated with lower risk SGA infants (OR adj0.91, 95% CI 0.84-0.99) whereas food industry workers had an increased risk of preterm delivery (OR adj1.50, 95% CI 1.12-2.02). There was little evidence for heterogeneity between cohorts. CONCLUSIONS: This study suggests that, overall, employment during pregnancy is associated with a reduction in the risk of preterm birth and that work in certain occupations may affect pregnancy outcomes. This exploratory study provides an important platform on which to base further prospective studies focused on the potential consequences of maternal occupational exposures during pregnancy on child development.

Reproducibility of urinary bisphenol A concentrations measured during pregnancy in the Generation R Study.

The potential human health effects of bisphenol A (BPA) exposure are a public health concern. In order to design adequately powered epidemiological studies to address potential health effects, data on the reproducibility of BPA concentration in serial urine specimens taken during pregnancy are needed. To provide additional data on the reproducibility of maternal urine specimens, 80 women in the Generation R Study (Rotterdam, The Netherlands) contributed a spot urine specimen at <18, 18-25, and >25 weeks of pregnancy. Reproducibility, estimated by the intraclass correlation coefficient (ICC), was 0.32 (95% confidence interval: 0.18-0.46), and, on a creatinine basis, 0.31 (95% confidence interval: 0.16-0.47). Although the ICC observed in the Generation R Study is slightly higher than previous reproducibility studies of BPA, it nevertheless indicates a high degree of within-person variability that presents challenges for designing well-powered epidemiologic studies.

Fetal growth and prenatal exposure to bisphenol A: the generation R study.

BACKGROUND: Prenatal exposure to bisphenol A (BPA) has been associated with adverse birth outcomes, but findings of previous studies have been inconsistent. OBJECTIVE: We investigated the relation of prenatal BPA exposure with intrauterine growth and evaluated the effect of the number of measurements per subject on observed associations. METHODS: This study was embedded in a Dutch population-based prospective cohort study, with urine samples collected during early, mid-, and late pregnancy. The study comprised 219 women, of whom 99 had one measurement, 40 had two measurements, and 80 had three measurements of urinary BPA. Fetal growth characteristics were repeatedly measured by ultrasound during pregnancy and combined with measurements at birth. Linear regression models for repeated measurements of both BPA and fetal growth were used to estimate associations between urinary concentrations of creatinine-based BPA (BPACB) and intrauterine growth. RESULTS: The relationship between BPACB and fetal growth was sensitive to the number of BPA measurements per woman. Among 80 women with three BPA measurements, women with BPACB > 4.22 µg/g crea (creatinine) had lower growth rates for fetal weight and head circumference than did women with BPACB < 1.54 µg/g crea, with estimated differences in mean values at birth of -683 g (20.3% of mean) and -3.9 cm (11.5% of mean), respectively. When fewer measurements were available per woman, the exposure-response relationship became progressively attenuated and statistically nonsignificant. CONCLUSION: Our findings suggest that maternal urinary BPA may impair fetal growth. Because previous studies have shown contradictory findings, further evidence is needed to corroborate these findings in the general population.

Physically demanding work, fetal growth and the risk of adverse birth outcomes. The Generation R Study.

OBJECTIVES: Work-related risk factors, such as long work hours, and physically demanding work have been suggested to adversely influence pregnancy outcome. The authors aimed to examine associations between various aspects of physically demanding work with fetal growth in different trimesters during pregnancy and the risks of adverse birth outcomes. METHODS: Associations between physically demanding work and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in The Netherlands (2002-2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment) were included if they conducted paid employment and had a spontaneously conceived singleton live born pregnancy. Questions on physical workload were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on lifting, long periods of standing or walking, night shifts and working hours. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. RESULTS: There were no consistent significant associations between physically demanding work nor working hours in relation to small for gestational age, low birth weight or preterm delivery. Women exposed to long periods of standing had lower growth rates for fetal head circumference (HC), resulting in a reduction of approximately 1 cm (3%) of the average HC at birth. Compared with women working <25 h/week, women working 25-39 h/week and >40 h/week had lower growth rates for both fetal weight and HC, resulting in a difference of approximately 1 cm in HC at birth and a difference of 148-198 g in birth weight. CONCLUSION: Long periods of standing and long working hours per week during pregnancy seem to negatively influence intrauterine growth.

Work-related maternal risk factors and the risk of pregnancy induced hypertension and preeclampsia during pregnancy. The Generation R Study.

OBJECTIVE: To study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study. METHODS: Associations between occupational characteristics and hypertensive disorders during pregnancy were studied in 4465 pregnant woman participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002-2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment), were included if they conducted paid employment, had a spontaneously conceived singleton live born pregnancy, and did not suffer from pre-existing hypertension (n = 4465). Questions on physical demanding work were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on manually handling loads of 25 kg or more, long periods of standing or walking, night shifts, and working hours. To assess occupational exposure to chemicals, job titles and task descriptions were linked to a job-exposure-matrix (JEM), an expert judgment on exposure to chemicals at the workplace. Information on hypertensive disorders during pregnancy was obtained from medical records. RESULTS: We observed no consistent associations between any of the work related risk factors, such as long periods of standing or walking, heavy lifting, night shifts, and working hours, nor exposure to chemicals with hypertensive disorders during pregnancy. CONCLUSION: This prospective birth cohort study suggests that there is no association of hypertensive disorders during pregnancy with physically demanding work or exposure to chemicals. However, the low prevalence of PIH and PE, combined with the low prevalence of occupational risk factors limit the power for inference and larger studies are needed to corroborate or refute these findings.

Occupational exposure to chemical substances and time to pregnancy: a systematic review.

BACKGROUND: Fertility problems are an important health issue, as 10-15% of couples have difficulties conceiving. Reproductive function is thought to be compromised by lifestyle behaviours, but environmental contaminants and work-related factors are also thought to play a role. The objective of this review was to systematically summarize the available evidence concerning the influence of occupational exposure to chemicals on time to pregnancy (TTP). METHODS: A structured search on occupational exposure to chemicals and TTP was carried out in PubMed and Embase. Studies were included if TTP was used as outcome measure and exposure to chemicals at the job level was described. In total, 49 studies were included in this review. RESULTS: Studies varied widely in characterization of exposure, hampering a meta-analytic approach across all studies. For lead, strong indications for adverse effects on TTP were present, supporting the mandatory provisions for pregnant women being exposed to lead in many countries. These indications were also found for pesticide exposure, and one could argue that couples working in agriculture or horticultural trades must be informed about the risks of pesticide exposure. Epidemiologic evidence on other chemicals, such as organic solvents, and other metals remains equivocal, hampering clear counselling of couples who are trying to become pregnant. CONCLUSIONS: Despite some uncertainties in the evidence base, it may still be prudent to advise against lead and pesticide exposure at the workplace for couples trying to conceive. This review also identifies several priorities for future studies in the field of occupational epidemiology.

Congenital heart defects and parental occupational exposure to chemicals.

BACKGROUND: Congenital heart defects (CHDs) are the most common major malformations in newborns. In this study we examined the associations between the occurrence of CHDs in children and periconceptional occupational parental exposures to chemicals. METHODS: In an age-matched case-control study with standardized data collection at c. 15 months after birth, 424 mothers and 421 fathers of a child with CHD and 480 mothers and 477 fathers of a non-malformed child, filled out questionnaires on periconceptional general and job characteristics. A job exposure matrix, which links the information on job title and a description of work tasks to an expert judgement on exposure to chemicals in the workplace, was used. RESULTS: The overall prevalence of occupational exposure to chemicals was 5.0 in cases and 6.2% in controls for mothers [odds ratio (OR) adjusted = 0.92; 95% confidence interval (CI): 0.26-3.25], while 22.3 and 15.9% for fathers, respectively (OR adjusted = 1.23; 95% CI: 0.39-3.91). No association of maternal occupational exposure to chemicals with risk of CHDs was found. Paternal exposure to phthalates was associated with a higher incidence of CHDs in general (OR adjusted = 2.08; 95% CI: 1.27-3.40). Paternal exposure to phthalates was associated with perimembranous ventricular septal defect (OR adjusted = 2.84; 95% CI: 1.37-5.92), to polychlorinated compounds with atrioventricular septal defect (OR adjusted = 4.22; 95% CI: 1.23-14.42) and to alkylphenolic compounds with coarctation of the aorta (OR adjusted = 3.85; 95% CI: 1.17-12.67). CONCLUSIONS: Periconceptional paternal (but not maternal) occupational exposure to certain chemicals is associated with an increased risk of CHDs in children. The results, however, must be interpreted cautiously as exposure probabilities are a crude measure of exposure.

Intrauterine exposure to mild analgesics during pregnancy and the occurrence of cryptorchidism and hypospadia in the offspring: the Generation R Study.

BACKGROUND: Recently, over-the-counter mild analgesic use during pregnancy has been suggested to influence the risk of reproductive disorders in the offspring. We examined the influence of maternal exposure to mild analgesics during pregnancy on the occurrence of cryptorchidism and hypospadia in their offspring. METHODS: Associations between maternal exposure to mild analgesics during pregnancy and cryptorchidism or hypospadia in the offspring were studied in 3184 women participating in a large population-based prospective birth cohort study from early pregnancy onwards in the Netherlands (2002-2006), the Generation R Study. Cryptorchidism and hypospadia were identified during routine screening assessments performed in child health care centres by trained physicians. The use of mild analgesics was assessed in three prenatal questionnaires in pregnancy, resulting in four periods of use, namely, periconception period, first 14 weeks of gestation, 14-22 weeks of gestation and 20-32 weeks of gestation. Logistic regression analyses were used to study the associations between maternal exposure to mild analgesics and cryptorchidism and hypospadia. RESULTS: The cumulative prevalence over 30 months of follow up was 2.1% for cryptorchidism and 0.7% for hypospadia. Use of mild analgesics in the second period of pregnancy (14-22 weeks) increased the risk of congenital cryptorchidism [adjusted odds ratio (OR) 2.12; 95% confidence interval (CI) 1.17-3.83], primarily due to the use of acetaminophen (paracetamol) (adjusted OR 1.89; 95% CI 1.01-3.51). Among mothers of cryptorchid sons, 33.8% reported (23 of 68) the use of mild analgesics during pregnancy, compared with 31.8% (7 of 22) of mothers with a boy with hypospadia and 29.9% (926 of 3094) of mothers with healthy boys. CONCLUSIONS: Our results suggest that intrauterine exposure to mild analgesics, primarily paracetamol, during the period in pregnancy when male sexual differentiation takes place, increases the risk of cryptorchidism.

Thrombophylaxis and bleeding complications after cesarean section.

OBJECTIVE: To evaluate the safety of different regimes of thromboprophylaxis with low molecular weight heparins (LMWHs) in women undergoing cesarean section. DESIGN: Retrospective single-center cross-sectional study. SETTING: University Medical Center, The Netherlands. POPULATION: All women that delivered by cesarean section in the Erasmus Medical Center, Rotterdam, between January 2004 and December 2007 received thromboprophylaxis. We included women who received thromboprophylaxis according to the routine administration schedule at that time. METHODS: Three different consecutive regimes of thromboprophylaxis were used. In the first period, women received dalteparin 5000IU pre- and postoperatively (group A), in the second period, nadroparin 5700IU was administered pre- and postoperatively (group B), and in the third period, nadroparin 2850IU was administered not earlier than 6-12 hours postoperatively (group C). Detailed information on individual characteristics, cesarean section and postpartum period were extracted from patient files. MAIN OUTCOME MEASURES: Postoperative bleeding complications. RESULTS: A total of 1527 women were eligible and included. In group B, significantly more women experienced bleeding complications (necessitating either conservative treatment or re-laparotomy) compared with the other two groups (19/574 women in group B vs. 9/647 in group A and 1/306 in group C). After adjusting for potential confounders (maternal age, body mass index, and occurrence of preeclampsia/hemolysis, elevated liver enzymes and low platelet count) these effects remained significant (p=0.005). The incidence of thromboembolism was not different in the three groups. CONCLUSIONS: Different regimes of thromboprophylaxis in women with cesarean section influenced the occurrence of bleeding complications.

Occupational exposure to chemicals and fetal growth: the Generation R Study.

BACKGROUND: Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25% of infant mortality and morbidity. Several studies have shown that exposure to chemicals during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight. METHODS: Associations between maternal occupational exposure to various chemicals and fetal growth were studied in 4680 pregnant women participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002-2006), the Generation R Study. Mothers who filled out a questionnaire during mid-pregnancy (response: 77% of enrolment) were included if they conducted paid employment during pregnancy and had a spontaneously conceived singleton live born pregnancy (n = 4680). A job exposure matrix was used, linking job titles to expert judgement on exposure to chemicals in the workplace. Fetal growth characteristics were repeatedly measured by ultrasound and were used in combination with measurements at birth. Placental weight was obtained from medical records and hospital registries. Linear regression models for repeated measurements were used to study the associations between maternal occupational exposure to chemicals and intrauterine growth. RESULTS: We observed that maternal occupational exposure to polycyclic aromatic hydrocarbons, phthalates, alkylphenolic compounds and pesticides adversely influenced several domains of fetal growth (fetal weight, fetal head circumference and fetal length). We found a significant association between pesticide and phthalate exposure with a decreased placental weight. CONCLUSIONS: Our results suggest that maternal occupational exposure to several chemicals is associated with impaired fetal growth during pregnancy and a decreased placental weight. Further studies are needed to confirm these findings and to assess post-natal consequences.

Occupational exposure to endocrine disruptors and time to pregnancy among couples in a large birth cohort study: the Generation R Study.

OBJECTIVE: To study the influence of occupational exposure to endocrine disruptors (EDs) on time to pregnancy (TTP). DESIGN: Cross-sectional analysis within a prospective, population-based cohort study. SETTING: Medical center. PATIENT(S): Mothers and fathers who filled out a questionnaire during mid-pregnancy (response 77% and 82% of enrollment, respectively) were selected if the pregnancy was planned and either parent performed paid employment. In total, 2,774 mothers and 2,728 partners were included in the statistical analyses. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Self-reported TTP (months). RESULT(S): There was no correlation between maternal and paternal exposure, because κ values for agreement for all exposure categories ranged from 0.03 to 0.13. Paternal occupational exposure to heavy metals (hazard ratio of pregnancy 0.83; 95% confidence interval 0.71-0.97) and overall exposure to EDs (hazard ratio 0.85; 95% confidence interval 0.75-0.96) was statistically significantly associated with an increased TTP. Maternal occupational exposure to all categories of EDs showed prolonged TTP, but the decreased hazard ratios were not statistically significant. CONCLUSION(S): This birth cohort study provides indications for adverse effects of parental occupational exposure to EDs on TTP.

Levels of circulating endothelial cells in normotensive and severe preeclamptic pregnancies.

BACKGROUND: Preeclampsia is a disease hypothesized to originate from widespread endothelial dysfunction or damage. This study investigated whether circulating endothelial cells (CEC) can serve as a surrogate marker for disease severity in patients with preeclampsia, and if their number correlates to serum endothelial biomarkers for activation, dysfunction, or damage of those cells. METHODS: Blood was drawn consecutively from 30 patients admitted with a diagnosis of severe preeclampsia. Thirty healthy, normotensive, patients matched for age, body mass index, and gestational age served as a control group. We determined the number of CEC and serum concentrations of biomarkers indicative of endothelial damage (thrombomodulin) and activation (E-selectin), and the antiangiogenic protein (endoglin), which reflects endothelial dysfunction. RESULTS: Median CEC counts did not differ significantly between preeclamptic patients and the control group (median 5.3 vs. 3.5 CEC/mL, respectively) and were mostly within the normal range (i.e., <20 CEC/mL). However, serum concentrations of thrombomodulin (median 3.6 vs. 5.2 ng/mL; P = 0.006), E-selectin (median 32.0 vs. 42.9 ng/mL; P = 0.02), and especially endoglin (median 5.0 vs. 76.2 ng/mL; P < 0.0001) were significantly increased in severe preeclamptic patients. CEC counts did not correlate with any of the clinical parameters or routinely determined laboratory indices. CONCLUSION: Preeclampsia is characterized by endothelial dysfunction and activation rather than actual endothelial damage as characterized by increased CEC counts.