Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Stabilizing prevalence trends of eczema, asthma and rhinoconjunctivitis in Dutch schoolchildren (2001-2010).

In contrast to many countries, a decrease in childhood wheeze prevalence was previously reported for the Netherlands. In repeated cross-sectional surveys in 2001, 2005 and 2010, we investigated whether this trend continued, and additionally examined prevalence trends of eczema, asthma and rhinoconjunctivitis among 8- to 11-year-old schoolchildren eligible for a routine physical examination. Overall, ~90% participated (mean age: 8.8 years in 2001 and 10.5 years in 2005 and 2010). Eczema, wheeze and asthma prevalence did not change significantly between 2001 and 2010, but rhinoconjunctivitis prevalence increased from 8.4% in 2001 to 12.3% in both 2005 and 2010 (Ptrend < 0.01). In conclusion, after a decrease in wheeze prevalence among Dutch schoolchildren between 1989 and 2001, no further decrease was observed until 2010. Similarly, the prevalence of eczema and asthma remained stable, but rhinoconjunctivitis prevalence increased between 2001 and 2010. The latter may be an effect of older age and not a true increase over time.

The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study.

OBJECTIVE: To investigate whether the intestinal microbiota composition in early infancy is associated with subsequent weight development in children. METHODS: Analyses were conducted within the KOALA Birth Cohort Study (n = 2834). This cohort originates from two recruitments groups: pregnant women with a conventional lifestyle (no selection based on lifestyle) and pregnant women recruited through alternative channels (organic shops, anthroposophic clinicians/midwives, Steiner schools and relevant magazines). From 909 one-month-old infants, fecal samples were collected and analyzed by quantitative PCR targeting bifidobacteria, Bacteroides fragilis group, Clostridium difficile, Escherichia coli, Lactobacilli and total bacteria counts. Between the ages of 1 and 10 years, parent-reported weight and height was collected at 7 time points. Age- and gender-standardized body mass index (BMI) z-scores were calculated. Data were analyzed using generalized estimating equation. RESULTS: Colonization with B. fragilis group was borderline significantly associated with a higher BMI z-score of 0.15 (95% confidence interval (CI): -0.02 to 0.31), in the conventional subcohort. After stratification for fiber intake (P(forinteraction) = 0.003), colonization with B. fragilis group was associated with a 0.34 higher BMI z-score among children with a low-fiber intake in this subcohort (95% CI: 0.17-0.53). Higher counts among colonized children were positively associated with BMI z-score only in children within the conventional subcohort and a high-fiber diet (BMI z-score 0.08; 95% CI: 0.01-0.14), but inversely associated in children with a low-fiber diet (BMI z-score -0.05; 95% CI: -0.10 to 0.00), and in children recruited through alternative channels (BMI z-score -0.10; 95% CI: -0.17 to -0.03). The other bacteria were not associated with BMI z-scores, regardless of subcohort. CONCLUSION: Using a targeted approach, we conclude that the intestinal microbiota, particularly the B. fragilis group, is associated with childhood weight development. To identify the potential impact of additional bacterial taxa, further prospective studies applying an unconstrained in-depth characterization of the microbiota are needed.

Maternal smoking during pregnancy and childhood overweight and fat distribution: the KOALA Birth Cohort Study.

UNLABELLED: What is already known about this subject There is an association between maternal smoking during pregnancy and higher body mass index (BMI) and overweight in childhood. What this study adds The association between maternal smoking during pregnancy and childhood overweight develops with age, starting with a lower birth weight, followed by weight catch-up in the first year after birth, finally leading to overweight at school age. Children of mothers who had smoked during pregnancy had a higher risk of exceeding the 85th percentile of BMI, waist circumference and total skinfold thickness at school age. BACKGROUND: Maternal smoking during pregnancy is associated with childhood overweight, but the association with fat distribution is not clear. OBJECTIVE: To explore the longitudinal association between smoking during pregnancy and childhood overweight and fat distribution. METHODS: In the KOALA Birth Cohort Study, repeated questionnaires were administered to 2698 mother-child pairs, including questions on smoking at 14 and 34 weeks of pregnancy. Main outcomes were birth weight, weight gain in the first year, body mass index (BMI) z-scores and overweight (BMI ≥85th percentile) at 1, 2, 4-5 and 6-7 years (n = 1730) and waist circumference and four skinfold thicknesses measured at home visits at age 6-7 years in a subgroup (n = 418). We used multivariable linear and logistic regression, with generalized estimating equations (GEE) for repeated measurements. RESULTS: Maternal smoking was associated with lower birth weight, higher weight gain in the first year and increasing overweight after infancy (change with age P = 0.02 in the GEE). Maternal smoking vs. non-smoking during pregnancy was associated with a higher risk of the child exceeding the 85th percentile of BMI (adjusted odds ratio [aOR] 3.72; 95% CI 1.33-10.4), waist circumference (aOR 2.65; 95% CI 1.06-6.59) and sum of skinfold thicknesses (aOR 4.45; 95% CI 1.63-12.2) at the age of 6-7 years. CONCLUSIONS: Maternal smoking during pregnancy is associated with lower birth weight, weight catch-up and development of overweight into childhood.

Can exhaled inflammatory markers predict a steroid response in wheezing preschool children?

BACKGROUND: The efficacy of inhaled corticosteroids (ICS) varies among wheezing preschool children. Currently, it is not possible to predict which fraction of wheezing children will benefit from an ICS treatment. OBJECTIVE: We explored whether fractional exhaled nitric oxide (FeNO) and inflammatory markers in exhaled breath condensate (EBC) can predict an ICS response in preschool wheezers. METHODS: An 8-week ICS study (registered at Clinicaltrial.gov: NCT 00422747; 200 µg; beclomethasone extra-fine daily) was performed in 93 wheezing children (age range 2.0-4.4 years). At baseline, FeNO was determined off-line. EBC was collected using a closed glass-condenser. The acidity of EBC was determined and other EBC markers [interleukin (IL)-1α, IL-2, IL-4, IL-5, IL-10, soluble intercellular adhesion molecule, interferon-γ, eotaxin] were measured using a multiplex immunoassay. The change in airway resistance (Rint) and symptom score following ICS treatment was related to atopy (positive Phadiatop Infant test), FeNO and EBC markers. RESULTS: Airway resistance and symptoms mildly improved after ICS treatment [median (IQR): 1.4 (1.2-1.7) to 1.3 (1.1-1.5) kPa s/L, symptom score: 26 (23-28) to 28 (24-29), P < 0.01, respectively]. Only IL-10 and atopy had limited predictive value regarding a change in symptoms [ß (SE) =-0.13 (0.07), P = 0.08, ß (SE) = 2.05 (1.17), P = 0.08, respectively]. CONCLUSIONS AND CLINICAL RELEVANCE: We did not find convincing evidence that FeNO and EBC markers could predict an ICS response in preschool wheezers. Recommendations for future studies on this topic are given.

Maternal fatty acid status in pregnancy and childhood atopic manifestations: KOALA Birth Cohort Study.

BACKGROUND: Prevalence of atopic disorders has increased rapidly, but aetiological factors responsible for this increase are still largely unknown. Prenatal exposure to a pro-inflammatory fatty acid status is hypothesized although little research has been carried out. OBJECTIVE: To investigate whether prenatal fatty acid exposures are associated with atopy in childhood. METHODS: In the KOALA Birth Cohort Study, maternal blood samples (n=1275) at 34-36 weeks of pregnancy were assayed for n-6 and n-3 long-chain polyunsaturated fatty acids (LCPs). The full spectrum of offspring atopic manifestations (wheeze, asthma, allergic rhinoconjunctivitis, eczema, atopic dermatitis, allergic sensitization, and high total IgE) until the age of 6-7 years was assessed by repeated parental questionnaires and measurements of total and specific IgE. Associations of maternal fatty acid status with child atopic outcomes were analysed using multivariable logistic regression and generalized estimating equations for repeated measurements. RESULTS: High ratio of maternal n-6 vs. n-3 LCPs was associated with a lower risk of eczema in the child (P for trend 0.012). More specifically, we found a decreased risk of eczema in the first 7 months of life with increasing arachidonic acid levels (P for trend 0.013). No associations were found between maternal fatty acids and offspring airway-related atopic manifestations, sensitization, or high total IgE. CONCLUSION AND CLINICAL RELEVANCE: The development of atopic disorders in early childhood is associated with prenatal exposure to n-6 vs. n-3 fatty acids, but with inconsistencies between different manifestations. Further exploration of associations with maternal diet and genetic variants in genes regulating fatty acid metabolism are required. This study shows that the influence of prenatal exposure to fatty acids on the risk of eczema in the child is limited to the first year of life.

Early-life rotavirus and norovirus infections in relation to development of atopic manifestation in infants.

BACKGROUND: The increase in incidence of atopic diseases (ADs) in the developed world over the past decades has been associated with reduced exposure of childhood infections. OBJECTIVE: To investigate the relation between early intestinal viral infections in relation to the development of atopic symptoms (eczema, wheeze and atopic sensitization) in the first and second year(s) of life. METHODS: In the KOALA Birth Cohort Study, we assessed IgG seropositivity for rota- and norovirus (GGI.1 and GGII.4) at 1 year of age. This was related to allergic sensitization [specific immunoglobulin E (IgE)] at 1 and 2 years, and parent reported eczema and wheeze in the first 2 years, using logistic regression analysis adjusted for confounders. RESULTS: Rotavirus seropositivity (39%) was associated with an unexpected higher risk of recurrent wheeze in the first and second year of life [adjusted odds ratio (OR) 3.1 and 95% confidence intervals (CI) 1.1-9.1] and persistent and new recurrent wheeze (adjusted OR 2.7 and 95% CI 1.1-6.2). No further associations were found between intestinal viral seropositivity and atopic manifestations. CONCLUSION: Our data did not show a clear protection by enteric viral infections in young children on development of IgE response to allergens, but rotavirus infection in the first year was a risk factor for wheeze. However, this needs to be followed up to older ages in order to establish the true importance of intestinal viral infections and especially cumulative effects in AD aetiology. Exposure to rotavirus may offer a new and interesting focus on infant wheeze and later asthma development.

Meta-analysis of determinants for pet ownership in 12 European birth cohorts on asthma and allergies: a GA2LEN initiative.

BACKGROUND: Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors. AIM: The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies. METHODS: Within the EU-funded network of excellence GA(2)LEN, we performed meta-analyses with data from 12 ongoing European birth cohort studies on asthma and allergy. Each of the birth cohort studies enrolled between 485 and 4089 children. Pet ownership, allergic status (asthma, allergic rhinitis, eczema) of parents and siblings, parental education, access to ground floor, and number of people living at home were assessed by questionnaires. RESULTS: Among the 25 056 families from seven European countries cats (14.9%) were more common than dogs (12.0%). Allergic family history significantly reduced the odds to own a cat (adjusted combined random-effect OR 0.91; 95% CI 0.85-0.99), or dog (0.90; 0.86-0.94). A higher parental educational level had even more pronounced effects on cat (0.84; 0.71-0.98), and dog ownership (0.61; 0.54-0.70). Elder siblings reduced the odds to own cats, but not dogs. Convenient ground access significantly increased the odds, whereas crowding at home was not associated with cat or dog ownership. CONCLUSIONS: The chances to own a cat or dog were significantly reduced in allergic families, in parents with a higher educational level, and in homes without convenient ground access. In addition to parental allergies, social and housing factors should be considered as potential confounders in studies on pet exposure and allergic diseases.

Specific IgG4 response directed against the 45-kDa glycoprotein in trichinellosis: a re-evaluation of patients 15 years after infection.

The aim of this study was to evaluate the humoral immune response in late human trichinellosis with particular attention to the presence of IgG4 antibodies directed against the Trichinella-45-kDa glycoprotein (gp). This study re-evaluates subjects 15 years after they were involved in a trichinellosis outbreak that occurred in Central Italy following the consumption of raw boar meat infected with Trichinella britovi. The results show that ELISA tests using the E/S antigen identified five IgM- and eight IgG-positive patients and no IgA-positive patients. Tests using immunoblot (IB) with E/S antigens identified three IgM-, five IgA-, seven- IgG1- and three IgG4-positive sera. When the purified 45-kDa gp was used as an antigen, the IB revealed that six of the ten sera tested were positive for IgG4. Sera were also evaluated with a commercial kit, revealing that 11 of 12 patients had a highly sensitive reactivity against Trichinella proteins (64 and 44-43 kDa). In conclusion, humoral immune response against Trichinella is still present in these patients 15 years after the initial infection, including an IgG4 response directed to the 45-kDa gp.

Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on Diet and Cancer.

Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer was implemented by annual record linkage with the Netherlands Cancer Registry and a nationwide pathology registry. After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer cases and 2216 subcohort members were available for analysis. No association was seen between consumption of milk, yoghurt, cheese or fermented dairy products and ovarian cancer risk. The multivariable adjusted relative risk of epithelial ovarian cancer for women in the highest compared to the lowest quintile of intake of lactose or dairy fat was 0.93 (95% confidence interval (CI)=0.60-1.45; P(trend)=0.32) and 1.53 (95% CI=1.00-2.36; P(trend)=0.11), respectively. Lactose or dairy fat intakes were not associated with serous ovarian cancer risk. Our results do not support an association between consumption of dairy products or lactose intake and ovarian cancer.

Indoor environment and respiratory symptoms in children living in the Dutch-German borderland.

OBJECTIVE: To investigate the relation between indoor environmental risk factors and respiratory symptoms in 7-8-year-old children living in the Dutch-German borderland. METHODS: A nested case-control study was conducted among children participating in a large longitudinal study on respiratory health. Parents of all 781 children with respiratory complaints and an equal number of randomly selected controls were asked to complete a questionnaire, including questions on indoor environment. RESULTS: The parents of 1191 children (76.2%) participated. Past exposure to environmental (OR = 2.73, 95% CI 1.14-6.67) as well as in utero exposure (OR = 2.28, 95% CI 1.15-4.53) to tobacco smoke, use of an unvented geyser for water heating (OR = 3.01, 95% CI 1.21-7.56), long-term exposure to dampness (OR = 2.98, 95% CI 1.10-8.28) or pets (OR = 2.18, 95% CI 1.39-3.42) increased the risk of asthmatic symptoms in 7-8-year-old children. A middle or low socio-economic status also increased the risk of asthmatic symptoms. An inverse association with asthmatic symptoms was seen for wall-to-wall carpeting (OR = 0.57, 95% CI 0.33-0.95) and insulation measures (OR = 0.46, 95% CI 0.25-0.83). Except for the presence of an unvented geyser, these environmental risk factors also presented a risk for coughing symptoms in children. CONCLUSION: This study showed an increased risk of respiratory symptoms in children exposed to several indoor environmental risk factors.

Trends in the prevalence of respiratory symptoms and treatment in Dutch children over a 12 year period: results of the fourth consecutive survey.

BACKGROUND: Although there is considerable evidence that the prevalence of childhood asthma has increased over the last decades, it is not clear if this trend is still ongoing. A study was undertaken to investigate whether previously observed trends in the prevalence of respiratory symptoms, physician visits, medication use, and absence from school in Dutch children aged 8-9 years persisted in 2001. METHODS: Parents of 1154 children aged 8-9 years eligible for a routine physical examination in 2001 were asked to complete a questionnaire on the respiratory health of their child. RESULTS: In 2001, 1102 children (95.5%) participated in the survey. Similarly high response rates were obtained in the surveys of 1989, 1993 and 1997, with 1794, 1526 and 1670 children aged 8-9 years participating in the respective surveys. The decreasing trend previously observed for recent wheeze between 1989 and 1997 persisted into 2001, particularly in boys. After increasing between 1989 and 1997, the prevalence of shortness of breath with wheeze decreased between 1997 and 2001. The proportion of wheezy children using medication increased between 1989 and 2001 in boys (42.9% v 64.8%; p = 0.003), but the increase was not statistically significant in girls (34.0% v 45.7%; p = 0.096). CONCLUSION: The prevalence of recent wheeze in Dutch school children has declined steadily since 1989. The rising prevalence of medication use in symptomatic children over time may reflect better asthma control and may partly explain the concurrently decreasing trend in the prevalence of asthma symptoms in our study population.

Differences in asthma diagnosis and medication use in children living in Germany and the Netherlands.

AIM: To compare diagnosis and treatment between German and Dutch children with asthmatic symptoms at the age of 5-6 and 7-8 years, and the use of anti-asthma medication at 7-8 years of age. METHODS: Parents of 4462 children participated in two surveys, in 1995 and 1997. All 465 children identified with current asthmatic symptoms at the age of 5-6 (May 1995) or at 7-8 years of age (May 1997) were sent a third more detailed questionnaire (October 1997). RESULTS: Asthma diagnosis was more prevalent in Dutch children with current asthmatic complaints (50-60%), whereas over 90% of the German children with current asthmatic complaints had been diagnosed with bronchitis. Inhaled beta(2)-agonists were more frequently used by Dutch children compared to German children (67.3% vs. 45.6% p < 0.01) as were inhaled steroids (38.9% vs. 7.0% p < 0.01). Instead, German children more often used sodium cromoglycate or nedocromil as anti-inflammatory medication as compared with Dutch children (42.1% vs. 11.5% p < 0.01). CONCLUSIONS: Differences in diagnosis rates for asthma and bronchitis between German and Dutch children most likely result from differential labelling of complaints, and probably lead to differences in treatment practice, indicating possible undertreatment of German children with inhaled steroids.

Infant immunization and the occurrence of atopic disease in Dutch and German children: a nested case-control study.

Our goal was to assess the role of early childhood vaccination in the occurrence of respiratory symptoms and allergic sensitization in 7-8-year-old Dutch and German children. A nested case-control study was conducted among children participating in a large longitudinal study on respiratory health, to study the relationship between vaccination (bacille Calmette-Guérin (BCG), pertussis, measles/mumps, rubella, and Haemophilus influenza type b (Hib)) and respiratory symptoms and allergic sensitization. Parents of 510 7-8-year-old children with respiratory complaints and an equal number of randomly selected children without respiratory complaints were asked to complete a questionnaire. Blood samples were collected for specific serum IgE analysis. Vaccination status was assessed through the records of the participating Municipal Health Services. No association between vaccination against pertussis, measles, rubella, or Hib and respiratory symptoms or allergic sensitization was found. For sensitization against house dust mite, BCG vaccination resulted in an increased risk (OR, 2.28; 95% CI, 1.05-4.96). Birth order was inversely associated with allergic sensitization, but was not related to respiratory symptoms. We found an association between BCG vaccination and the subsequent risk for sensitization against house dust mite. No evidence was found for an association between vaccination and respiratory symptoms. Earlier reports of an association of birth order with atopic disease were supported by the results of the present study.

Imported human trichinellosis: sequential IgG4 antibody response to Trichinella spiralis.

Two out of five members of one household presented with clinical signs of trichinellosis after their return to the Netherlands. The family had consumed Trichinella-infected pork in Montenegro, formerly Yugoslavia. Serological tests were performed at 1, 2, 6, and 18 months after ingestion of the infected meat. Trichinella-specific IgM, IgG, and IgA antibodies measured in sera from symptomatic and asymptomatic patients remained positive up to 18 months after ingestion. The measured IgG4 antibody response directed to a 45 kDa Trichinella spiralis antigen also persisted 18 months after ingestion for three of the family members.

[Interreg II--European regional study of chronic respiratory tract diseases in children in the Germany-Netherlands border zone]. / Interreg II--Euregionale Untersuchungen zu chronischen Atemwegserkrankungen bei Kindern im deutsch-niederländischen Grenzraum.

AIM OF THE STUDY: In Westelijke Mijnstreek (WM), Midden-Limburg (ML), both The Netherlands, and Kreis Heinsberg (HS), Germany, the relationship between quality of the indoor environment and respiratory symptoms in children was studied, finally resulting in proposals for prevention of respiratory symptoms in the three regions. This paper presents the results of the first part of the study, investigating prevalences of respiratory complaints. METHODS AND RESULTS: A brief questionnaire was used to document prevalences of respiratory complaints, physicians diagnoses and treatment in about 7,000 children 5-6 resp. 7-8 years of age from HS, ML and WM, in 1995 and 1997. Prevalences of respiratory symptoms differed slightly between the regions, but there were differences in physician-diagnosed asthma and bronchitis and treatment of the children. PERSPECTIVES: The brief questionnaire is a useful instrument to get an overview on respiratory symptoms. Since 1995, it is used by several German Municipal Health Services for Public Health Reports.

The effect of age on phosphatidylinositol kinase, phosphatidylinositol phosphate kinase and diacylglycerol kinase activities in rat brain cortex.

A previous study, in which a lysed fraction was used with endogenous phospholipids as substrate, revealed age-related changes in PA and PIP2 formation but not in PIP formation (Bothmer et al., Neurochem. Int. 21, 223-228, 1992). To rule out the influence of substrate availability in the present study, the effect of age on PI kinase, PIP kinase and DAG kinase activities was studied with exogenous phospholipids as substrate in the cerebral cortex from 8-month-old, 14-month-old and 26-month-old Brown Norway rats. PI kinase activity was predominantly located in a tight membrane-bound protein fraction, DAG kinase activity in cytosolic and loosely membrane-bound protein fractions, and PIP kinase activity was present in all three protein preparations. The effects of age were limited to a small increase in kinase activity in the tight membrane-bound protein fraction in 14-month-old and 26-month-old rats compared to 8-month-old rats, and a 10% decrease in PIP kinase activity in the cytosolic protein fraction in 14-month-old and 26-month-old rats compared to 8-month-old rats. DAG kinase activity showed no age-related changes. In conclusion, one should take care in comparing rat aging with human aging as PI kinase activity shows an age-related decline in human brain cortex (Jolles et al., J. Neurochem. 58, 2326-2329, 1992). Furthermore, previously reported decreases in PA formation rates in rat brain are probably not due to changes in DAG kinase itself but to changes in DAG availability, although further experimental evidence is needed to confirm this conclusion.