Reference ranges and determinants of total hCG levels during pregnancy: the Generation R Study.

Human chorionic gonadotropin (hCG) is a pregnancy hormone secreted by the placental synctiotrophoblast cell layer that has been linked to fetal growth and various placental, uterine and fetal functions. In order to investigate the effects of hCG on clinical endpoints, knowledge on reference range (RR) methodology and determinants of gestational hCG levels is crucial. Moreover, a better understanding of gestational hCG physiology can improve current screening programs and future clinical management. Serum total hCG levels were determined in 8195 women participating in the Generation R Study. Gestational age specific RRs using 'ultrasound derived gestational age' (US RRs) were calculated and compared with 'last menstrual period derived gestational age' (LMP RRs) and a model-based RR. We also investigated which pregnancy characteristics were associated with hCG levels. Compared to the US RRs, the LMP RRs were lower, most notably for the median and lower limit levels. No considerable differences were found between RRs calculated in the general population or in uncomplicated pregnancies only. Maternal smoking, BMI, parity, ethnicity, fetal gender, placental weight and hyperemesis gravidarum symptoms were associated with total hCG. We provide gestational RRs for total hCG and show that total hCG values and RR cut-offs during pregnancy vary depending on pregnancy dating methodology. This is likely due to the influence of hCG on embryonic growth, suggesting that ultrasound based pregnancy dating might be less reliable in women with high/low hCG levels. Furthermore, we identify different pregnancy characteristics that influence total hCG levels considerably and should therefore be accounted for in clinical studies.

Individual accumulation of heterogeneous risks explains perinatal inequalities within deprived neighbourhoods.

Dutch' figures on perinatal mortality and morbidity are poor compared to EU-standards. Considerable within-country differences have been reported too, with decreased perinatal health in deprived urban areas. We investigated associations between perinatal risk factors and adverse perinatal outcomes in 7,359 pregnant women participating in population-based prospective cohort study, to establish the independent role, if any, for living within a deprived urban neighbourhood. Main outcome measures included perinatal death, intrauterine growth restriction (IUGR), prematurity, congenital malformations, Apgar at 5 min < 7, and pre-eclampsia. Information regarding individual risk factors was obtained from questionnaires, physical examinations, ultrasounds, biological samples, and medical records. The dichotomous Dutch deprivation indicator was additionally used to test for unexplained deprived urban area effects. Pregnancies from a deprived neighbourhood had an increased risk for perinatal death (RR 1.8, 95% CI [1.1; 3.1]). IUGR, prematurity, Apgar at 5 min < 7, and pre-eclampsia also showed higher prevalences (P < 0.05). Residing within a deprived neighbourhood was associated with increased prevalence of all measured risk factors. Regression analysis showed that the observed neighbourhood related differences in perinatal outcomes could be attributed to the increased risk factor prevalence only, without a separated role for living within a deprived neighbourhood. Women from a deprived neighbourhood had significantly more 'possibly avoidable' risk factors. To conclude, women from a socioeconomically deprived neighbourhood are at an increased risk for adverse pregnancy outcomes. Differences regarding possibly avoidable risk factors imply that preventive strategies may prove effective.

Determinants of folic acid use in early pregnancy in a multi-ethnic urban population in The Netherlands: the Generation R study.

OBJECTIVE: Recommendations on folic acid use to prevent neural tube defects have been launched in several countries. Adequate folic acid use seems to be low. This study assesses the prevalence of folic acid use and identifies its determinants. METHODS: The study was embedded in the Generation R Study Rotterdam, the Netherlands, a population-based prospective cohort study between 2002 and 2006. Complete information of 6940 women was available. Information on folic acid use and potential determinants was obtained by questionnaires and physical examination. RESULTS: Of all women 37% adequately used folic acid during the preconception period. Most important risk factors for inadequate use were unplanned pregnancy (OR 9.5, CI 7.2-12.4, p<0.001), low educational level (OR 2.5, CI 1.8-3.6, p<0.001) and non-western ethnicity, (OR 3.5, CI 2.9-4.3, p<0.001). After stratification for ethnicity, unplanned pregnancy remained the most important risk factor for inadequate use. Other risk factors for inadequate use were younger age, single marital status, smoking, multiparity (all p<0.001) and alcohol use (p<0.05). In contrast, previous spontaneous abortion decreased the risk of inadequate folic acid use (p<0.001). CONCLUSION: Adequate preconception folic acid supplementation is still too low. Implementation of preconception programs and other public health strategies are strongly needed.