Maternal caffeine intake during pregnancy and orofacial clefts

BACKGROUND: Moderate caffeine intake during pregnancy is common, but little is known about its potential association with birth defects. METHODS: The National Birth Defects Prevention Study is a population‐based, case‐control study of major birth defects, excluding infants with single‐gene disorders and chromosomal abnormalities. This analysis includes infants with cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), excluding infants whose cleft was secondary to holoprosencephaly or amniotic band sequence. Mothers reported dietary caffeine intake from coffee, tea, sodas, and chocolate in the year before pregnancy and reported intake of medications containing caffeine during pregnancy. We assessed the association between dietary caffeine intake, frequency of consuming each type of caffeinated beverage, medications containing caffeine, and CL/P or CPO among infants born from October 1997 through December 2004. RESULTS: This analysis included 1531 infants with CL/P, 813 infants with CPO, and 5711 infants with no major birth defects (controls). Examining dietary sources among control mothers, 11% reported consuming at least 300 mg of caffeine per day and 17% reported consuming less than 10 mg of caffeine per day; high consumption (≥3 servings per day) was reported by 8% (coffee), 4% (tea), and 15% (sodas); medications containing at least 100 mg caffeine/dose were reported by less than 1%. Although some effect estimates were elevated for moderate caffeine intake from all beverages, estimates were closer to the null for high caffeine levels. Isolated CL/P was associated with use of medications containing at least 100 mg of caffeine per dose. CONCLUSIONS: Our data do not suggest an association between maternal dietary caffeine intake and orofacial clefts, but caffeine‐containing medications merit further study. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Influence of Echinacea purpurea intake during pregnancy on fetal growth and tissue angiogenic activity

The process of angiogenesis and control of blood vessels sprouting are fundamental to human health, as they play key roles in many physiological and pathological conditions. Intake of different pharmaceuticals with antiangiogenic activity by pregnant women may lead to severe developmental disturbances as it was described in case of thalidomide. It may also cause immunomodulatory effects as it was shown for antibiotics, theobromine, caffeic acid or catechins on the pregnant mice model. At present, Echinacea purpurea-based phytoceuticals are among the most popular herbals in the marketplace. Many compounds of Echinacea extracts (polysaccharides, alkamides, polyphenols, glycoproteins) exert immunomodulatory, anti-oxidative and anti-inflammatory activity. Echinacea is one of the most powerful and effective remedies against many kinds of bacterial and viral infections. In previous studies we shown significant inhibitory effect of the Echinacea purpurea based remedy on tumour angiogenic activity using cutaneous angiogenesis test, and an inhibitory effect on L-1 sarcoma growth was observed . The aim of the present study was to establish whether pharmaceuticals containing alcoholic extracts of Echinacea purpurea given to pregnant mice influence angiogenic activity and tissue VEGF and bFGF production of their fetuses. We showed that angiogenic activity of tissue homogenates was increased in Esberitox group and diminished in case of Immunal forte as compared to standard diet group. In case of Echinapur group we did not find significant differences in angiogenic activity. VEGF and bFGF concentration were lower in all groups compared to the control. In the case of Echinapur and Esberitox number of fetuses in one litter were slightly lower as compared to control group, but the difference is on the border of statistical significance. In conclusion, there is some possibility that pharmaceuticals containing Echinacea purpurea might influence fetal development in human also, because they may interfere with embrional angiogenesis , and should not be recommended for pregnant women.     

A prospective study of maternal and fetal outcome in acute Lassa fever infection during pregnancy.

Several viral infections have been reported to result in more severe disease in pregnant than non-pregnant women, but the relative risks have not been well characterised. This has now been done for Lassa fever in a prospective study of 68 pregnant and 79 non-pregnant women who were admitted to hospital in Sierra Leone with confirmed Lassa fever. Lassa fever was the main cause of maternal mortality in the hospital, accounting for 25% of maternal deaths. Twelve of 40 patients in the third trimester died, compared with two of 28 in the first two trimesters and 10 of 79 non-pregnant women. The odds ratio for death in the third trimester compared with the first two trimesters was 5.57 (95% confidence intervals 1.02 to 30.26). The condition of the mother improved rapidly after evacuation of the uterus, whether by spontaneous abortion, evacuation of retained products of conception, or normal delivery; 10 of 26 women without uterine evacuation died, but only four of 39 women with evacuation died (p = 0.0016). The odds ratio for death with pregnancy intact was 5.47 (95% confidence interval 1.35 to 22.16). Fetal and neonatal loss was 87%. The risk of death from Lassa fever in the third trimester is significantly higher than that in the first two trimesters and higher than that for non-pregnant women, but evacuation of the uterus can significantly improve the mother''s chance of survival.     

Relation of fetal and infant growth to plasma fibrinogen and factor VII concentrations in adult life.

OBJECTIVE--To determine whether reduced fetal and infant growth are associated with higher plasma fibrinogen and factor VII concentrations in adult life. DESIGN--Follow up study of men born during 1920-30 whose weights at birth and at 1 year had been recorded by health visitors, and men born during 1935-43 whose size at birth had been measured in detail. SETTING--Hertfordshire and Preston, England. SUBJECTS--591 men born in east Hertfordshire who still lived there and 148 men born in Preston who still lived in or close to the city. MAIN OUTCOME MEASURES--Plasma fibrinogen and factor VII concentrations. RESULTS--Among men in Hertfordshire mean plasma fibrinogen and factor VII concentrations fell with increasing weight at 1 year (from 3.21 g/l in men of less than or equal to 18 lb to 2.93 g/l in men greater than or equal to 27 lb and from 122% of standard to 103%; p less than 0.001, p less than 0.005 respectively). The trends were independent of cigarette smoking, alcohol consumption, body mass index, and social class. Neither plasma fibrinogen nor factor VII concentration was related to birth weight. In men in Preston, however, fibrinogen concentration fell progressively as the ratio of placental weight to birth weight decreased (p = 0.01). CONCLUSIONS--Reduced growth in fetal life and infancy is strongly related to high plasma concentrations of the haemostatic factors fibrinogen and factor VII. This may be a persisting response to impaired liver development during a critical early period.     

Exposure to non-steroidal anti-inflammatory drugs during pregnancy and risk of miscarriage: population based cohort study

Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage.Design Population based cohort study. Prenatal use of NSAIDs, aspirin, and paracetamol (acetaminophen) ascertained by in-person interview.Setting Kaiser Permanente Medical Care Program, a healthcare delivery system, in the San Francisco area of the United States.Participants 1055 pregnant women recruited and interviewed immediately after their positive pregnancy test. Median gestational age at entry to the study was 40 days.Main outcome measures Pregnancy outcomes up to 20 weeks of gestation.Results 53 women (5%) reported prenatal NSAID use around conception or during pregnancy. After adjustment for potential confounders, prenatal NSAID use was associated with an 80% increased risk of miscarriage (adjusted hazard ratio 1.8 (95% confidence interval 1.0 to 3.2)). The association was stronger if the initial NSAID use was around the time of conception or if NSAID use lasted more than a week. Prenatal aspirin use was similarly associated with an increased risk of miscarriage. However, prenatal use of paracetamol, pharmacologically different from NSAIDs and aspirin, was not associated with increased risk of miscarriage regardless of timing and duration of use.Conclusion Prenatal use of NSAIDs and aspirin increased the risk of miscarriage. These findings need confirmation in studies designed specifically to examine the apparent association.     

Widespread body pain and mortality: prospective population based study

ObjectiveTo determine whether there is excess mortality in groups of people who report widespread body pain, and if so to establish the nature and extent of any excess.DesignProspective follow up study over eight years. Mortality rate ratios were adjusted for age group, sex, and study location.SettingNorth west England.Participants6569 people who took part in two pain surveys during 1991-2.Results1005 (15%) participants had widespread pain, 3176 (48%) had regional pain, and 2388 (36%) had no pain. During follow up mortality was higher in people with regional pain (mortality rate ratio 1.21, 95% confidence interval 1.01 to 1.44) and widespread pain (1.31, 1.05 to 1.65) than in those who reported no pain. The excess mortality among people with regional and widespread pain was almost entirely related to deaths from cancer (1.55 (1.09 to 2.19) for regional pain and 2.07 (1.37 to 3.13) for widespread pain). The excess cancer mortality remained after exclusion of people in whom cancer had been diagnosed before the original survey and after adjustment for potential confounding factors. There were also more deaths from causes other than disease (for example, accidents, suicide, violence) among people with widespread pain (5.21, 0.94 to 28.78).ConclusionThere is an intriguing association between the report of widespread pain and subsequent death from cancer in the medium and long term. This may have implications for the long term follow up of patients with “unexplained” widespread pain symptoms, such as those with fibromyalgia.

What is already known on this topic

Widespread body pain, the cardinal symptom of fibromyalgia, is commonAn organic basis for symptoms is found in only a small proportion of peopleTreatment is difficult, and studies with short term follow up have shown that symptoms commonly persist

What this study adds

This was the first study with long term follow up of people with widespread pain in the communityThese people experience an increased mortality and the excess is principally related to deaths from cancer     

Chronic intake of caffeine during gestation down regulates metabotropic glutamate receptors in maternal and fetal rat heart

Summary. Caffeine is the most widely consumed substance in the world which antagonizes adenosine effects. Adenosine acting through A₁ receptors inhibits glutamate release which binds to metabotropic glutamate receptors (mGluRs). Recently, we have shown that maternal caffeine intake during gestation causes down-regulation of A₁ and metabotropic glutamate receptors in the brain of both rat mothers and fetuses. In the present work we provide evidence that caffeine also affects receptors in hearts, causing a decrease in mGluRs from both maternal and fetal hearts. A decrease in G_q/11 and PLC β₁ proteins level was also observed in both tissues. However, phospholipase C activity was only affected in fetal heart, being significantly decreased. These results suggest an in vivo cross-talk mechanism between adenosine and glutamate receptors in peripheral tissues. Therefore, special attention should be paid to caffeine ingestion during gestation.     

Peripheral blood concentrations of progesterone and oestradiol during human pregnancy and delivery

To evaluate the significance of progesterone and estradiol in human uterine activity during pregnancy and delivery the blood concentrations of these hormones were monitored weekly during the last trimester of pregnancy and at the onset of labour in 15 women, and before and 3 hours after the induction of term delivery in 83 parturients. Neither plasma concentrations of progesterone or estradiol nor the ratio of progesterone to estradiol changed significantly during the last trimester of pregnancy or at the onset of delivery. After the induction of delivery parturients with initial progesterone dominance (ratio of progesterone to estradiol higher than 5 before induction) demonstrated a significant fall in serum concentration of progesterone and in the ratio of progesterone to estradiol while estradiol concentration rose significantly. In estrogen dominant women (progesterone to estradiol ratio equal to or lower than 5) the serum concentration of progesterone and the ratio of progesterone to estradiol rose significantly during the 3 hours after the induction of delivery. Our results suggest that the peripheral blood levels of progesterone and estradiol do not correlate with the tissue biochemical changes which prepare the uterine cervix and myometrium for delivery. The observation that the ratio of progesterone to estradiol decreased in progesterone-dominant and increased in estrogen-dominant women stresses the importance of a well balanced equilibrium of these hormones for prostaglandin metabolism during human delivery.     

Relation of nicotine yield of cigarettes to blood nicotine concentrations in smokers.

Blood nicotine and carboxyhaemoglobin (COHb) concentrations were studied in 330 smokers (206 women and 124 men). Blood nicotine concentrations in individual smokers varied from 25 to 444 nmol/l (4 to 72 ng/ml). The average concentration, 203 nmol/l (33 ng/ml), was the same in the men and the women, although cigarette consumption was higher in the men. Despite large differences in nicotine yield, there was no relation between blood nicotine concentration and the type of cigarette smoked: smokers of plain, untipped cigarettes (1.9 mg nicotine), cigarettes with unventilated filters (1.3 mg nicotine), and cigarettes with ventilated filters (0.8 mg nicotine) had similar blood nicotine concentrations. Cigarette consumption was also similar in these three groups. The correlation between blood nicotine concentration and nicotine yield of cigarette, though significant, was low (0.21, p < 0.001), showing that the nicotine yield of the cigarettes accounted for only 4.4% of the variation in blood nicotine concentrations. Similarly, the low correlation of 0.30 between COHb concentration and cigarette consumption suggests that cigarette consumption accounted for only 9% of the variation in the amount of smoke taken into the smokers'' lungs. These results suggest that the assumed health advantage of switching to lower-tar and lower-nicotine cigarettes may be largely offset by the tendency of smokers to compensate by increasing inhalation. The findings of epidemiological studies showing lower risks with filter-tipped cigarettes may be attributable to other factors such as biases in the samples and changes in the quality and carcinogenicity of tobacco tar, rather than to reduced tar intake.     

Sex-specific differences in fetal and infant growth patterns: a prospective population-based cohort study

Background

The objective of this study was to assess whether sex-specific differences in fetal and infant growth exist.

Methods

This study was embedded in the Generation R Study, a population-based prospective birth cohort. In total, 8556 live singleton births were included. Fetal growth was assessed by ultrasound. During the first trimester, crown-rump-length (CRL) was measured. In the second and third trimester of pregnancy head circumference (HC), abdominal circumference (AC) and femur length (FL) were assessed. Information on infant growth during the first 2 years of life was obtained from Community Health Centers and included HC, body weight and length.

Results

In the first trimester, male CRL was larger than female CRL (0.12 SD [95% CI 0.03,0.22]). From the second trimester onwards, HC and AC were larger in males than in females (0.30 SD [95% CI 0.26,0.34] and 0.09 SD [95% CI 0.05,0.014], respectively). However, FL in males was smaller compared to female fetuses (0.21 SD [95% CI 0.17,0.26]). Repeated measurement analyses showed a different prenatal as well as postnatal HC growth pattern between males and females. A different pattern in body weight was observed with a higher body weight in males until the age of 12 months where after females have a higher body weight.

Conclusions

Sex affects both fetal as well as infant growth. Besides body size, also body proportions differ between males and females with different growth patterns. This sexual dimorphism might arise from differences in fetal programming with sex specific health differences as a consequence in later life.

     

Nutrient intake and cataract extraction in women: a prospective study.

OBJECTIVE--To examine prospectively the association between dietary intake of vitamins C and E, carotene, and riboflavin and cataract extraction in women. DESIGN--Prospective cohort study beginning in 1980 with eight years of follow up. SETTING--11 states of the United States. PARTICIPANTS--Female registered nurses who were 45 to 67 years of age. 50,828 women were included in 1980 and others were added as they became 45 years of age. MAIN OUTCOME MEASURE--Incidence of extraction of senile cataracts. RESULTS--493 cataracts were extracted during 470,302 person years of follow up. Intake of carotene and vitamin A was inversely associated with cataract: in multivariate analyses, women in the highest fifth of total vitamin A intake (excluding supplements) had a 39% lower risk of cataract relative to women in the lowest fifth (relative risk 0.61; 95% confidence interval 0.45 to 0.81). Neither riboflavin nor dietary vitamins E or C were associated with cataract in a multivariate analysis. Among specific food items spinach (rather than carrots, the greatest source of beta carotene) was most consistently associated with a lower relative risk. The risk of cataract was 45% lower among women who used vitamin C supplements for 10 or more years(relative risk 0.55 (0.32 to 0.96)), but no association was noted for multivitamin intake. CONCLUSION--Dietary carotenoids, although not necessarily beta carotene, and long term vitamin C supplementation may decrease the risk of cataracts severe enough to require extraction.     

Saliva levels of oestradiol and progesterone in relation to non-protein-bound concentrations in blood during late pregnancy

Serum and saliva samples were obtained from 25 women in the last eight weeks of pregnancy. The concentrations of oestradiol and progesterone were measured by radioimmunoassay. The proportion of each hormone which was not bound to protein in serum was measured by centrifugal ultrafiltration: for progesterone the unbound fraction was 2.5% (2.13--2.78%) and for oestradiol 1.27% (1--1.83%). There was only a weak relationship between the free hormone concentrations estimated in blood and the levels measured in saliva. We conclude that, for the situation examined here, saliva does not provide a useful measure of unbound, biologically active steroid.     

Low blood pressure and depression in older men: a population based study.

OBJECTIVE--To determine if an association exists between low blood pressure and depressive symptoms in older men living in the community. DESIGN--Cross sectional, population based study. SETTING--Town of Rancho Bernardo, California, United States. SUBJECTS--846 men aged 60-89 years. Comparisons between hypotensive, normotensive, and hypertensive groups were limited to 594 men not taking drugs for hypertension. MAIN OUTCOME MEASURES--Mean scores on Beck depression inventory and prevalence of scores > or = 13. RESULTS--Men with diastolic blood pressure < 75 mm Hg had significantly higher depression scores (mean scores 6.35 v 4.96; P < 0.001) and more categorical depression (7.6% v 1.8% with scores > or = 13; P < 0.01) than men with diastolic blood pressure levels between 75 and 85 mm Hg. Men with diastolic blood pressure levels > 85 mm Hg had higher depression scores than men with intermediate blood pressure levels (mean scores 5.85 v 4.96; P < 0.05). Men with diastolic hypotension scored significantly higher on both affective and somatic item subscales of the Beck depression inventory and on individual measures of fatigue, pessimism, sadness, loss of appetite, weight loss, and preoccupation with health. Low diastolic blood pressure was a significant predictor of both mean depression score and prevalence of categorical depression, independent of age and change in weight since the baseline visit. The presence of several chronic diseases was associated with depressed mood and higher blood pressure but not with low blood pressure. CONCLUSION--The association of relatively low diastolic blood pressure with higher depressive symptom scores and rates of categorical depression was independent of age or weight loss. Since fatigue is a prominent symptom of depression, any association of low blood pressure with fatigue could reflect depressive disorders or clinically important depression.