Otto P. Bleker

Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity

BACKGROUND It is generally accepted that breast feeding has a beneficial effect on the health of infants and young children. Recently, a few studies have shown that the method of infant feeding is also associated with cardiovascular disease and its risk factors in adult life. AIMS To examine the association between the method of infant feeding in the first weeks after birth and glucose tolerance, plasma lipid profile, blood pressure, and body mass in adults aged 48–53 years. METHODS Subjects born at term between 1 November 1943 and 28 February 1947 in the Wilhelmina Gasthuis in Amsterdam around the time of a severe period of famine (late November 1944 to early May 1945). For 625 subjects, information was available about infant feeding at the time of discharge from hospital (on average 10.4 days after birth), and at least one blood sample after an overnight fast. RESULTS Subjects who were bottle fed had a higher mean 120 minute plasma glucose concentration after a standard oral glucose tolerance test than those who were exclusively breast fed. They also had a higher plasma low density lipoprotein (LDL) cholesterol concentration, a lower high density lipoprotein (HDL) cholesterol concentration, and a higher LDL/HDL ratio. Systolic blood pressure and body mass index were not affected by the method of infant feeding. CONCLUSIONS Exclusive breast feeding seems to have a protective effect against some risk factors for cardiovascular disease in later life.

Nifedipine and ritodrine in the management of preterm labor: A randomized multicenter trial

Objective To compare the efficacy of nifedipine with ritodrine in the management of preterm labor. Methods One hundred eighty-five singleton pregnancies with preterm labor were assigned randomly to either ritodrine intravenously (n = 90) or nifedipine orally (n = 95). The principal outcome assessed was delay of delivery. Results Ritodrine was discontinued in 12 patients because of severe maternal side effects, and their results were excluded from further analysis. More women in the ritodrine group delivered within 24 hours (22 versus 11, P = .006), within 48 hours (29 versus 21, P = .03), within 1 week (45 versus 36, P = .009), and within 2 weeks (52 versus 43, P = .005) compared with those receiving nifedipine. There were significantly fewer maternal side effects in the nifedipine group. Apgar scores and umbilical artery and vein pHs were similar in both groups. The number of admissions to the neonatal intensive care unit (NICU) in the nifedipine group was significantly lower than in the ritodrine group (68.4 versus 82.1%, P = .04). Conclusion Nifedipine in comparison with ritodrine in the management of preterm labor is significantly associated with a longer postponement of delivery, fewer maternal side effects, and fewer admissions to the NICU.

Blood pressure in adults after prenatal exposure to famine.

BACKGROUND Many studies have shown that low birth weight is associated with high blood pressure. The composition of the diet of pregnant women has also been found to affect blood pressure in their children. We assessed the effect of prenatal exposure to the Dutch famine of 1944-1945, during which the caloric intake from protein, fat and carbohydrate was proportionally reduced, on blood pressures in adults now aged about 50 years. METHODS AND RESULTS We measured blood pressures at home and in the clinic among people born at term in one hospital in Amsterdam, The Netherlands, between November 1 1943 and February 28 1947, for whom we had detailed birth records. Blood pressures of people exposed to famine during late (n = 120), mid-(n = 109) or early gestation (n = 68) were compared with those of people born in the year before or conceived in the year after the famine (unexposed subjects, n = 442). No effect of prenatal exposure on systolic and diastolic blood pressure was observed. The mean systolic blood pressure taken in the clinic in those exposed in late gestation, and adjusted for sex and age, was 1.3 mmHg higher than in the unexposed group (95% confidence interval -1.9 to 4.4). The mean systolic blood pressure differed by -0.6 mmHg (95% confidence interval -3.9 to 2.7) for those exposed in mid-gestation and -1.7 mmHg (95% confidence interval -5.6 to 2.2) for those exposed in early gestation. People who were small at birth had higher blood pressures. A 1 kg increase in birth weight was associated with a decrease of 2.7 mmHg (95% confidence interval 0.3 to 5.1) in systolic blood pressure. Analyses of blood pressures measured at home gave similar results. CONCLUSION High blood pressure was not linked to prenatal exposure to a balanced reduction of macronutrients in the maternal diet. However, it was linked to reduced fetal growth. We postulate that it might be the composition rather than the quantity of a pregnant womans diet that affects her childs blood pressure in later life.

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

Chronic diseases are the main public health problem in Western countries. There are indications that these diseases originate in the womb. It is thought that undernutrition of the fetus during critical periods of development would lead to adaptations in the structure and physiology of the fetal body, and thereby increase the risk of diseases in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. This thesis describes the effects of prenatal exposure to the Dutch famine on health in later life. We found indications that undernutrition during gestation affects health in later life. The effects on undernutrition, however, depend upon its timing during gestation and the organs and systems developing during that critical time window. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. Little is known 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.

Caesarean section on request: a comparison of obstetricians' attitudes in eight European countries

Objective  To explore the attitudes of obstetricians to performe a caesarean section on maternal request in the absence of medical indication.

Microalbuminuria in Adults after Prenatal Exposure to the Dutch Famine

Maternal undernutrition during gestation is associated with an increase in cardiovascular risk factors in the offspring in adult life. The effect of famine exposure during different stages of gestation on adult microalbuminuria (MA) was studied. MA was measured in 724 people, aged 48 to 53, who were born as term singletons in a university hospital in Amsterdam, the Netherlands, around the time of the Dutch famine 1944 to 1945. Twelve percent of people who were exposed to famine in mid gestation had MA (defined as albumin/creatinine ratio >/=2.5) compared with 7% of those who were not prenatally exposed to famine (odds ratio 2.1; 95% confidence interval 1.0 to 4.3). Correcting for BP, diabetes, and other influences that affect MA did not attenuate this association (adjusted odds ratio 3.2; 95% confidence interval 1.4 to 7.7). The effect of famine was independent of size at birth. Midgestation is a period of rapid increase in nephron number, which is critical in determining nephron endowment at birth. Fetal undernutrition may lead to lower nephron endowment with consequent MA in adult life.

Maternal nutrition during gestation and blood pressure in later life.

Objective To assess the link between maternal diet during pregnancy and blood pressure of the offspring. Design Follow-up study. Setting A university hospital in Amsterdam, The Netherlands. Participants People born at term as singletons between November 1943 and February 1947. Main outcome measure Blood pressure at adult age. Results Adult blood pressure was not associated with protein, carbohydrate or fat intake during any period of gestation. We found, however, after adjustment for sex that the systolic blood pressure decreased by 0.6 mmHg (0.1–1.1) for every 1% increase in protein/carbohydrate ratio in the third trimester. This association was present both in people who had been exposed to the famine during gestation as well as in those who had not been exposed. The association between protein/carbohydrate ratio in the third trimester and adult blood pressure was furthermore independent of maternal weight gain and final weight, and birth weight [increase for every 1% increase in protein/carbohydrate ratio 0.6 mmHg (0.0–1.2)]. Adjustment for adult characteristics such as body mass index, smoking and socio-economic status did not affect the observed association appreciably [adjusted increase 0.5 mmHg (0.0–1.0)]. Conclusion Adult blood pressure seems to be affected by small variations in the balance of macro-nutrients in the maternal diet during gestation rather than by relatively large variations in the absolute amounts.

Impaired insulin secretion after prenatal exposure to the Dutch famine

OBJECTIVE—We previously reported that people prenatally exposed to famine during the Dutch Hunger Winter of 1944–1945 have higher 2-h glucose concentrations after an oral glucose tolerance test in later life. We aimed to determine whether this association is mediated through alterations in insulin secretion, insulin sensitivity, or a combination of both. RESEARCH DESIGN AND METHODS—We performed a 15-sample intravenous glucose tolerance test in a subsample of 94 normoglycemic men and women from the Dutch Famine Birth Cohort. We used the disposition index, derived as the product of insulin sensitivity and the first-phase insulin response to glucose as a measure of the activity of the β-cells adjusted for insulin resistance. In all analyses, we adjusted for sex and BMI. RESULTS—Glucose tolerance was impaired in people who had been prenatally exposed to famine compared with people unexposed to famine (difference in intravenous glucose tolerance test Kg value −21% [95% CI −41 to −4]). People exposed to famine during midgestation had a significantly lower disposition index (−53% [−126 to −3]) compared with people unexposed to famine. Prenatal exposure to famine during early gestation was also associated with a lower disposition index, but this difference did not reach statistical significance. CONCLUSIONS—Impaired glucose tolerance after exposure to famine during mid-gestation and early gestation seems to be mediated through an insulin secretion defect.

Extensive platelet activation in preeclampsia compared with normal pregnancy: Enhanced expression of cell adhesion molecules

OBJECTIVES Platelets play an important role in the pathophysiologic mechanisms of preeclampsia. Our purpose was to investigate by means of flow cytometry to what extent platelets circulate in an activated state during normal pregnancy and whether this activation is more extensive in preeclampsia. STUDY DESIGN Platelets in whole blood from 10 preeclamptic third-trimester pregnant women (highest diastolic blood pressure range 100 to 130 mm Hg, proteinuria range 0.59 to 11.5 gm/24 hr) and from 10 normotensive third-trimester pregnant controls were analyzed with the following activation markers: anti-P-selectin (alpha-granule secretion), anti-CD63 (lysosomal secretion), PAC-1 (monoclonal antibody against fibrinogen receptor conformation of the glycoprotein IIb/IIIa complex), anti-platelet endothelial cell adhesion molecule-1, and annexin-V (a placental protein that binds to negatively charged phospholipids, present on the outside of the platelet plasma membrane after activation). The differences in surface antigen exposure between the two groups were determined by double-label flow cytometry. Flow cytometric data were analyzed in two ways: first, the percentages of activated platelets above a certain threshold compared with a nonpregnant control sample were determined, indicative for activation of a subpopulation of cells, and, second, the mean fluorescence intensities were determined, indicative of the mean surface antigen expression of the total platelet population. RESULTS Analysis of the percentage of activated platelets proved most informative. With this analysis an enhanced platelet activation status was present in 4 of 10 normotensive patients and a more extensive platelet activation status in all 10 preeclamptic patients, as indicated by P-selectin (p = 0.008) and CD63 (p = 0.03) expression. Increased platelet endothelial cell adhesion molecule-1 (p = 0.005) expression was also observed in preeclampsia. CONCLUSIONS Flow cytometric analysis clearly indicated that platelets circulate in a more extensively activated state during preeclampsia than during normal pregnancy. The increased platelet endothelial cell adhesion molecule-1 expression in preeclamptic patients demonstrates that, besides alpha-granular and lysosomal release, other hitherto unknown mechanisms are involved. Platelet endothelial cell adhesion molecule-1 appears to be the best marker to distinguish preeclamptic patients from normotensive pregnant women. Only a subpopulation of the platelets appears to be activated.

Blood pressure response to psychological stressors in adults after prenatal exposure to the Dutch famine

Objective There is increasing evidence that restricted prenatal growth is associated with exaggerated blood pressure responses to stress. We investigated the effect of maternal undernutrition on the adult offsprings stress response. Design A historical cohort study. Methods We performed continuous blood pressure and heart rate measurements during a battery of three 5-min physiological stress tests (Stroop test, mirror-drawing test and a public speech task) in 721 men and women, aged 58 years, born as term singletons in Amsterdam at about the time of the Dutch 1944–1945 famine. Results During the stress tests, the systolic blood pressure (SBP) rose from baseline by 20 mmHg during the Stroop test, by 30 mmHg during the mirror-drawing test and by 47 mmHg during the public speech task. The SBP and diastolic blood pressure increase during stress was highest among individuals exposed to famine in early gestation compared with unexposed subjects (4 mmHg extra systolic increase, P = 0.04; 1 mmHg diastolic increase, P = 0.1, both adjusted for sex). Exposure during mid and late gestation was not associated with a stress-related increment of blood pressure (P adjusted for sex > 0.6). Correcting for confounders in a multivariable model did not attenuate the association between famine exposure in early gestation and the SBP increment. The heart rate increment was not related to famine exposure during any part of gestation. Conclusion We found a greater blood pressure increase during stress among individuals exposed to famine in early gestation. Increased stress responsiveness may underlie the known association between coronary heart disease and exposure to famine in early gestation.