Prenatal famine, birthweight, reproductive performance and age at menopause: the Dutch hunger winter families study.

STUDY QUESTION: Is there an association between acute prenatal famine exposure or birthweight and subsequent reproductive performance and age at menopause? SUMMARY ANSWER: No association was found between intrauterine famine exposure and reproductive performance, but survival analysis showed that women exposed in utero were 24% more likely to experience menopause at any age. WHAT IS KNOWN ALREADY: Associations between prenatal famine and subsequent reproductive performance have been examined previously with inconsistent results. Evidence for the effects of famine exposure on age at natural menopause is limited to one study of post-natal exposure. STUDY DESIGN, SIZE, DURATION: This cohort study included men and women born around the time of the Dutch famine of 1944-1945. The study participants (n = 1070) underwent standardized interviews on reproductive parameters at a mean age of 59 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were grouped as men and women with prenatal famine exposure (n = 407), their same-sex siblings (family controls, n = 319) or other men and women born before or after the famine period (time controls, n = 344). Associations of famine exposure with reproductive performance and menopause were analysed using logistic regression and survival analysis with competing risk, after controlling for family clustering. MAIN RESULTS AND THE ROLE OF CHANCE: Gestational famine exposure was not associated with nulliparity, age at birth of first child, difficulties conceiving or pregnancy outcome (all P> 0.05) in men or women. At any given age, women were more likely to experience menopause after gestational exposure to famine (hazard ratio 1.24; 95% CI 1.03, 1.51). The association was not attenuated with an additional control for a woman's birthweight. In this study, there was no association between birthweight and age at menopause after adjustment for gestational famine exposure. LIMITATIONS, REASON FOR CAUTION: Age at menopause was self-reported and assessed retrospectively. The study power to examine associations with specific gestational periods of famine exposure and reproductive function was limited. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support previous results that prenatal famine exposure is not related to reproductive performance in adult life. However, natural menopause occurs earlier after prenatal famine exposure, suggesting that early life events can affect organ function even at the ovarian level. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the NHLBI/NIH (R01 HL-067914). TRIAL REGISTRATION NUMBER: Not applicable.

The effect of folinic acid supplementation on homocysteine concentrations in newborns.

OBJECTIVE: The incidence of cerebrovascular accidents (CVA) occurring perinatally is relatively high and aspects of the multifactorial pathophysiology remain unclear. Elevated homocysteine concentrations have been shown to be associated with an increased risk for CVA in children and even in newborns. We studied the possible homocysteine lowering effect of folinic acid in newborns. METHOD: We included 37 newborns in our prospective randomized folinic acid (given as 5-formyltetrahydrofolate) intervention study from patients admitted to our neonatal intensive care unit (18 controls, 19 intervention group). We measured total homocysteine (tHcy) and plasma folate concentrations at three time points (baseline, 1 and 2 weeks after intervention). The intervention group was treated with folinic acid (70 µg/kg/day) for 2 weeks. We calculated median concentrations (25th and 75th percentiles). RESULTS: Median tHcy concentrations at the three time points did not differ from each other in the control group nor in the intervention group. We also could not observe different tHcy concentrations between both groups. Plasma folate concentrations increased in the intervention group (mean increase 167% (95% confidence interval (CI) -291, 625)) compared with control group (mean increase -12% (95% CI -132, 108)), P for treatment effect: 0.03. CONCLUSION: We could not demonstrate a homocysteine lowering effect of folinic acid administration in newborns. This indicates that one carbon metabolism in newborns differs form adults. Cobalamin might be a better strategy to lower tHcy concentrations in newborns.

Rationale and design of the prevention of respiratory infections and management in children (PRIMAKid) study: a randomized controlled trial on the effectiveness and costs of combined influenza and pneumococcal vaccination in pre-school children with recurrent respiratory tract infections.

Health and economic burden of recurrent respiratory tract infections (RTIs) in early childhood is considerable. A systematic review of licensed influenza and pneumococcal vaccines showed substantial efficacy in children, but the health-economic impact of such vaccines among pre-school children with recurrent RTIs is unknown. We therefore, designed a double-blind randomized controlled trial to determine the effectiveness and costs of a combined influenza and pneumococcal vaccination program among a primary care based cohort of children with recurrent episodes of RTI aged between 18 and 72 months. We will enroll 690 children over three consecutive years (2003--2005) who will be randomly allocated to receive vaccinations against influenza and pneumococcal disease, influenza alone or hepatitis B in a similar schedule. Follow up by parental diaries, tympanic temperature measurements, questionnaires and interviews is planned until May 2006. Primary outcome is number of febrile RTIs. Other outcomes include duration and severity of RTI episodes, medical consumption, safety and costs.

Negative attitude of highly educated parents and health care workers towards future vaccinations in the Dutch childhood vaccination program.

BACKGROUND: It is unknown whether further expansion of the Dutch childhood vaccination program with other vaccines will be accepted and whom should be targeted in educational strategies. AIM: To determine attitudes of parents towards possible future vaccinations for their children and the behavioural determinants associated with a negative attitude. DESIGN: Questionnaire study. METHODS: Parents of children aged between 3 months and 5 years of day-care centres were asked to fill out a questionnaire. Determinants of a negative attitude to comply with possible future vaccinations against example diseases such as pneumonia or influenza, hepatitis B, TBC, smallpox and SARS were assessed using polytomous logistic regression analysis. RESULTS: Of the 283 respondents, 123 (43%) reported a positive attitude towards all vaccinations, 129 (46%) reported to have a positive attitude to have their child vaccinated against some diseases and 31 (11%) had no intention to comply with any new vaccination. Determinants of a fully negative attitude were a high education of the parent (odds ratio [OR] 3.3, 95% confidence interval [95% CI]: 1.3-8.6), being a health care worker (OR 4.2, 95% CI: 1.4-12.6), absence of religion (OR 2.6, 95% CI: 1.0-6.7), perception of vaccine ineffectiveness (OR 6.9, 95% CI: 2.5-18.9) and the perception that vaccinations cause asthma or allergies (OR 82.4, 95% CI: 8.9-766.8). CONCLUSION: Modifiable determinants for a negative attitude to comply with new vaccinations are mainly based on lack of specific knowledge. These barriers to vaccinations might be overcome by improving health education in the vaccination program, especially when targeted at educated parents and health care workers.

[Multiple pregnancies: epidemiology and management]. / Meerlingzwangerschappen; epidemiologie en beleid.

Since the 1980s, the percentage of multiple pregnancies in the Netherlands has increased. Nowadays, the percentage of triplets is decreasing but there is still an increase in the percentage of twin pregnancies. A major cause is that Dutch women tend to delay starting a family until an advanced age. This increases their chances of a spontaneous multiple pregnancy. Moreover, they are prone to subfertility and consequently have a greater chance of undergoing treatments involving assisted-reproduction techniques such as intra-uterine insemination (IUI) and in-vitro fertilisation. In the Netherlands, the majority of higher order multiple pregnancies result from mild ovarian hyperstimulation in combination with IUI. In case of in-vitro fertilisation, since the practice of transferring a maximum of two embryos still results in 20-25% twin pregnancies, single-embryo transfer should be advocated more often.