Regional perinatal mortality differences in the Netherlands; care is the question

Background. Perinatal mortality is an important indicator of health. European comparisons of perinatal mortality show an unfavourable position for the Netherlands. Our objective was to study regional variation in perinatal mortality within the Netherlands and to identify possible explanatory factors for the found differences. Methods. Our study population comprised of all singleton births (904,003) derived from the Netherlands Perinatal Registry for the period 2000-2004. Perinatal mortality including stillbirth from 22+0weeks gestation and early neonatal death (0-6 days) was our main outcome measure. Differences in perinatal mortality were calculated between 4 distinct geographical regions North-East-South-West. We tried to explain regional differences by adjustment for the demographic factors maternal age, parity and ethnicity and by socio-economic status and urbanisation degree using logistic modelling. In addition, regional differences in mode of delivery and risk selection were analysed as health care factors. Finally, perinatal mortality was analysed among five distinct clinical risk groups based on the mediating risk factors gestational age and congenital anomalies. Results. Overall perinatal mortality was 10.1 per 1,000 total births over the period 2000-2004. Perinatal mortality was elevated in the northern region (11.2 per 1,000 total births). Perinatal mortality in the eastern, western and southern region was 10.2, 10.1 and 9.6 per 1,000 total births respectively. Adjustment for demographic factors increased the perinatal mortality risk in the northern region (odds ratio 1.20, 95% CI 1.12-1.28, compared to reference western region), subsequent adjustment for socio-economic status and urbanisation explained a small part of the elevated risk (odds ratio 1.11, 95% CI 1.03-1.20). Risk group analysis showed that regional differences were absent among very preterm births (22+0- 25+6weeks gestation) and most prominent among births from 32+0gestation weeks onwards and among children with severe congenital anomalies. Among term births (37+0weeks) regional mortality differences were largest for births in women transferred from low to high risk during delivery. Conclusion. Regional differences in perinatal mortality exist in the Netherlands. These differences could not be explained by demographic or socio-economic factors, however clinical risk group analysis showed indications for a role of health care factors

Determinants of birthweight and intrauterine growth in liveborn twins

We explored the relationship of umbilical cord insertion and fusion of placentas with birthweight in monozygotic monochorionic (MZ MC), monozygotic dichorionic (MZ DC), and dizygotic (DZ) twins. In addition, we evaluated some of the possible factors responsible for the restricted intrauterine growth of twins compared with singletons. The birthweight of 4529 liveborn twin pairs of the East Flanders Prospective Twin Survey was prospectively recorded, placentas were examined, and site of umbilical cord insertion was determined after delivery. Birthweight of 76 490 liveborn singletons was obtained from the Study Centre for Perinatal Epidemiology (SPE). Infants with a peripheral cord insertion weighed 150 g less (P < 0.001) than infants with a central cord insertion. DZ infants had a significantly (P < 0.001) higher incidence of central cord insertion than MZ DC and MZ MC infants. MZ DC infants with fused placentas and a peripheral cord insertion weighed on average 300 g less (P < 0.01) than infants with separate placentas and a central cord insertion. In DZ infants, fusion of the placentas did not affect birthweight. Twins gain less weight per week of gestation than singletons from 32 weeks onwards (twins: 128 g, 156 g, 75 g and singletons: 118 g, 251 g, 149 g, weeks 27-31,32-36, 37-42 respectively). From week 32 onwards, parity, birth rank, cord insertion and number of placentas also influenced birthweight of twins. We conclude that the difference between the birthweights of DZ, MZ DC, and MZ MC infants may originate from the least favourable antenatal situation, namely fused placentas with a peripheral cord insertion, which occurs most frequently in MZ twins. Gestation is the main determinant of birthweight. Other placental and maternal factors have a modest but significant influence on prenatal growth

Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview.

People who were small at birth have been shown to have an increased risk of CHD and chronic bronchitis in later life. These findings have led to the fetal origins hypothesis that proposes that the fetus adapts to a limited supply of nutrients, and in doing so it permanently alters its physiology and metabolism, which could increase its risk of disease in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. People who had been exposed to famine in late or mid gestation had reduced glucose tolerance. Whereas people exposed to famine in early gestation had a more atherogenic lipid profile, somewhat higher fibrinogen concentrations and reduced plasma concentrations of factor VII, a higher BMI and they appeared to have a higher risk of CHD. Though the latter was based on small numbers, as could be expected from the relatively young age of the cohort. Nevertheless, this is the first evidence in humans that maternal undernutrition during gestation is linked with the risk of CHD in later life. Our findings broadly support the hypothesis that chronic diseases originate through adaptations made by the fetus in response to undernutrition. The long-term effects of intrauterine undernutrition, however, depend upon its timing during gestation and on the tissues and systems undergoing critical periods of development at that time. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This gives the fetal origins hypothesis a new dimension. It may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences for health in later life. CHD may be viewed as the price paid for successful adaptations to an adverse intra-uterine environment. It also implies that the long-term consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. We need to know more about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations

Adult survival after prenatal exposure to the Dutch famine 1944--45.

Early life events may affect adult survival. We studied the effect of prenatal exposure to the Dutch famine 1944--45 on survival among 2254 people born in Amsterdam. Mortality up to age 50 was highest among those born before the famine (15.2%) and among those exposed to famine in late gestation (14.6%). It was lower among those exposed in mid- (11.2%) or early gestation (11.5%), and was lowest among those conceived after the famine (7.2%). These differences were caused by effects on mortality in the first year after birth and were mainly related to nutrition and infections. There was no effect of exposure to famine on mortality after the age of 18. The hazard ratio was 1.4 [0.8, 2.3] for those born before the famine, 1.1 [0.5, 2.3] for those exposed in late gestation, 0.8 [0.3, 1.8] for those exposed in mid-gestation and 1.1 [0.5, 2.5] in those exposed in early gestation compared with those conceived after the famine. We could not demonstrate effects of prenatal exposure to famine on cause-specific mortality after the age of 18. Because prenatal exposure to famine is linked to cardiovascular risk factors and disease, increased cardiovascular mortality in the future may be expected