Administration of vitamin K to newborn infants and childhood cancer.

OBJECTIVES--To investigate whether childhood cancer is associated with intramuscular administration of vitamin K to newborn infants. DESIGN--Routines for administration of vitamin K to infants born after normal deliveries during 1973-89 were obtained from maternity hospitals. Occurrence of cancer up to the end of 1991 was identified by comparing these records with the national cancer registry. Adherence to the routine method of administering vitamin K was checked with the medical records of a sample of 396 infants (196 who had developed childhood cancer and 200 controls). SETTING--All maternity hospitals in Sweden. SUBJECTS--1,384,424 full term infants born after non-instrumental deliveries, 1,085,654 of whom were born in units where vitamin K was routinely given by intramuscular injection and 272,080 of whom were born where it was given orally. MAIN OUTCOME MEASURES--Odds ratios for cancer after intramuscular administration of vitamin K versus oral administration after stratification for year of birth. RESULTS--Adherence to routine method of administering vitamin K was 92% in the 235 cases where individual information could be found. The risk of cancer after intramuscular administration of vitamin K was not elevated compared with that after oral administration: odds ratios of 1.01 (95% confidence interval 0.88 to 1.17) for all childhood cancers and 0.90 (0.70 to 1.16) for childhood leukaemia. CONCLUSIONS--The alleged association between intramuscular vitamin K prophylaxis to newborn infants and childhood cancer could not be verified in the present study of full term infants born after non-instrumental delivery.     

Neonatal vitamin K administration and childhood cancer in the north of England: retrospective case-control study.

OBJECTIVE: To explore the possible association between intramuscular vitamin K given to neonates and the subsequent development of childhood cancer. DESIGN: Retrospective case-control study on the basis of hospital records. SETTING: The former Northern Health region of England. SUBJECTS: 685 children who were born and lived in the region and who developed cancer before their 15th birthday, and 3442 controls also born between 1960 and 1991 and matched only for date and hospital of birth. The notes of a further 701 index cases were untraceable. MAIN EXPOSURE MEASURE: Administration of intramuscular vitamin K versus no exposure to vitamin K. RESULTS: There was no association between the administration of vitamin K and the development of all childhood cancers (unadjusted odds ratio 0.89; 95% confidence interval 0.69 to 1.15) or for all acute lymphoblastic leukaemia (1.20; 0.75 to 1.92), but there was a raised odds ratio for acute lymphoblastic leukaemia developing 1-6 years after birth (1.79; 1.02 to 3.15). No such association was seen in a separate cohort-based study not dependent on case note retrieval in which the rates of acute lymphoblastic leukaemia in children born in hospital units where all babies received vitamin K were compared with those born in units where less than a third received prophylaxis. CONCLUSIONS: It is not possible, on the basis of currently published evidence, to refute the suggestion that neonatal intramuscular vitamin K administration increases the risk of early childhood leukaemia. Any association may have been masked in earlier studies that did not use controls matched for time and locality by other unidentified factors affecting the spatiotemporal variations in incidence of leukaemia.     

Vitamin K and childhood cancer: a population based case-control study in Lower Saxony,Germany.

OBJECTIVE--To confirm or refute a possible association of parenteral vitamin K prophylaxis and childhood cancer. DESIGN--Population based case-control study. Comparison of vitamin K exposure in children with leukaemia or other common tumours with two control groups. SETTING--State of Lower Saxony (north western part of Germany); case recruitment from the German childhood cancer registry. SUBJECTS--272 children with leukaemia, nephroblastoma, neuroblastoma, rhabdomyosarcoma, and tumours of the central nervous system diagnosed between 1 July 1988 and 30 June 1993; children were aged between 30 days and 15 years at diagnosis. 334 population based controls without diagnoses of cancer matched to the leukaemia cases for age and sex. MAIN EXPOSURE MEASURES--Parenteral vitamin K prophylaxis (intramuscular and subcutaneous) versus oral and no vitamin K prophylaxis. RESULTS--An association between parenteral vitamin K exposure and childhood cancer (leukaemias and other tumours combined) could not be confirmed (odds ratio 1.04, 95% confidence interval 0.74 to 1.48). For leukaemias the observed odds ratio was only 0.98 (0.64 to 1.50) (comparison of leukaemia cases with local controls 1.24 (0.68 to 2.25); state controls 0.82 (0.50 to 1.36)). These odds ratios remained almost unchanged when several potential confounders were considered in the logistic regression model. CONCLUSIONS--This population based study adds substantial evidence that there is no association between parenteral vitamin K and childhood cancer.     

Controversies surrounding the administration of vitamin K to newborns: a review.

OBJECTIVE: To determine (1) the most effective method of administering vitamin K to infants to prevent hemorrhagic disease of the newborn (HDNB) and (2) the safest method, in light of preliminary evidence suggesting that intramuscular administration of vitamin K is associated with childhood cancer. DATA SOURCES: A MEDLINE search of articles published between Jan. 1, 1991, and Apr. 30, 1994, with the use of MeSH terms "hemorrhagic disease of the newborn", articles were limited to those involving human subjects, from birth to adolescence, and to articles from journals indexed through Index Medicus and written in English. References of all articles found through the initial search, the earliest of which was published in 1967, were also reviewed. STUDY SELECTION: Six controlled trials met the selection criteria: a minimum 4-week follow-up period, a minimum of 60 subjects and a comparison of oral and intramuscular administration or of regimens of single and multiple doses taken orally. All retrospective case reviews were evaluated. Because of its thoroughness, the authors selected a meta-analysis of almost all cases involving patients more than 7 days old published from 1967 to 1992. Only five studies that concerned safety were found, and all of these were reviewed. DATA EXTRACTION: In controlled trials, the risk of HDNB caused by vitamin K deficiency among infants receiving different regimens of vitamin K; in case studies, method of vitamin K administration and incidence of hemorrhagic disease; and in studies concerning safety, odds ratios and relative risks of childhood cancer following intramuscular administration of vitamin K. DATA SYNTHESIS: Vitamin K (1 mg, administered intramuscularly) is currently the most effective method of preventing HDNB. The previously reported relation between intramuscular administration of vitamin K and childhood cancer has not been substantiated. An oral regimen (three doses of 1 to 2 mg, the first given at the first feeding, the second at 2 to 4 weeks and the third at 8 weeks) may be an acceptable alternative but needs further testing in large clinical trials. CONCLUSION: There is no compelling evidence to alter the current practice of administering vitamin K intramuscularly to newborns.     

Administration of Vitamin K to newborns: implications and recommendations.

The review by Drs. Brousson and Klein (see pages 307 to 315 of this issue) identifies controversies surrounding the administration of vitamin K to babies shortly after birth. Controlled studies comparing the effect of oral and intramuscular administration are unlikely to be conducted because of the large number of subjects needed. The evidence presented in the review should dispel concerns that intramuscular administration may be associated with childhood cancer. Oral administration of a single dose of vitamin K soon after is associated with significant biochemical vitamin K deficiency by 1 month of age, but the relation of biochemical abnormality to clinical manifestations of late hemorrhagic disease of the newborn is less clear. Epidemiologic studies indicate a small, but significant, increase in the incidence rate of hemorrhagic disease after oral administration of vitamin K (1.0 to 6.4 incidents per 1000 000 infants), compared with the incidence rate after intramuscular administration (0.25 incidents per 100 000 infants). Although repeated oral doses of vitamin K may be and effective alternative regimen, there is no approved oral vitamin K formulation, there are concerns about patient compliance, and there has been limited investigation of such regimen. Therefore, intramuscular administration of a single dose of 1.0 mg of vitamin K shortly after birth is recommended.     

The use of vitamin K in the perinatal period. Fetus and Newborn Committee,Canadian Paediatric Society.

The incidence of hemorrhagic disease of the newborn (HDNB) can be expected to increase in Canada as breast-feeding becomes more popular. There are three clinical patterns of hemorrhagic disease: early HDNB (usually related to maternal drug ingestion), classic HDNB (related to breast-feeding) and late hemorrhagic disease of infancy (related to the combination of breast-feeding and diseases that cause fat malabsorption). Despite the knowledge that the disease can virtually be prevented by the administration of vitamin K, not all newborns are being routinely considered for such treatment. The Canadian Paediatric Society has made several recommendations: (a) women who take drugs that interfere with vitamin K1 metabolism should receive oral doses of vitamin K1 daily for a minimum of 2 weeks before expected delivery; (b) all healthy term infants should receive a single dose of vitamin K1, orally or intramuscularly, within 6 hours after birth; (c) all other newborns, including preterm, low-birthweight and sick infants, should receive a single intramuscular dose of vitamin K1 within 6 hours after birth; and (d) infants at high risk for secondary late-onset hemorrhagic disease due to fat malabsorption should receive vitamin K1 orally every day or intramuscularly once a month.     

Comparison of the antiemetics metoclopramide and promethazine in labour.

A double blind trial was conducted in 477 mothers in labour to compare the antiemetics metoclopramide 10 mg and promethazine 25 mg and placebo when added to the first dose of pethidine. Metoclopramide and promethazine were equally effective, and both better than placebo, in reducing the incidence of nausea and vomiting after the administration of pethidine. Seventy seven per cent of mothers were drowsy, and 8% slept in the hour after the pethidine injection, with no difference between the groups. The sedative effect was more persistent in the promethazine group, 66% of whom were still drowsy after delivery. One third of the mothers in each group needed further analgesia, with 77% of these ultimately requesting an epidural. The reduction in pain half an hour and one hour after pethidine, assessed by a visual analogue scale, were, respectively, 22% and 22% for placebo; 26% and 23% for metoclopramide; 13% and 9% for promethazine. Analgesia after metoclopramide was significantly better than that after promethazine in terms of pain score, duration of first injection, and need for Entonox. Metoclopramide is therefore to be preferred to promethazine as an antiemetic in labour.     

Vitamin D Deficiency in Early Pregnancy

Objective

Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.

Study Design

This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.

Results

Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years). Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL). Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057).

Conclusion

Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.     

Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour.

OBJECTIVE--To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. DESIGN--Double blind, randomised controlled trial. SETTING--Two metropolitan teaching hospitals in Perth, Western Australia. SUBJECTS--All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. MAIN OUTCOME MEASURES--Postpartum haemorrhage, nausea, vomiting, and increased blood pressure. RESULTS--3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure. CONCLUSIONS--There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose-response for oxytocin may be warranted.     

Assessment of the protective effect of vitamin E during development of experimental myocardial damage

It was shown that creatinphosphokinase activity of blood serum might be used as a criterion for evaluating the level of sparsely distributed damage in myocardium as a result of adrenaline administration. The protective effect of vitamin E under adrenaline-induced myocarditis was studied. The best effect was obtained after triple intramuscular injection of vitamin E before administration of pathological agent. Intravenous injection of the preparation has no benefits over that of intramuscular way of administration. Preventive action of vitamin E shows functioning itself in an increase of the quantity and activity of ubiquinone--the component of electron transport chain in mitochondria.     

Outcomes of Induction of Labour in Women with Previous Caesarean Delivery: A Retrospective Cohort Study Using a Population Database

Background

There is evidence that induction of labour (IOL) around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery). However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39–41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management.

Methods and Findings

We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981–2007 (n = 46,176). Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401) of women who underwent IOL 39–41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71–0.91]). There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08–1.55]). In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07–0.75]) and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90–1.07] at 40 weeks of 1.08 [0.94–1.23] and at 41 weeks of 0.77 [0.60–1.00]).

Conclusions

A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications.     

Severe Adverse Maternal Outcomes among Women in Midwife-Led versus Obstetrician-Led Care at the Onset of Labour in the Netherlands: A Nationwide Cohort Study

ObjectiveTo test the hypothesis that it is possible to select a group of low risk women who can start labour in midwife-led care without having increased rates of severe adverse maternal outcomes compared to women who start labour in secondary care.ResultsNulliparous and parous women who started labour in midwife-led care had lower rates of SAMM, postpartum haemorrhage and manual removal of placenta compared to women who started labour in secondary care. For SAMM the adjusted odds ratio’s and 95% confidence intervals were for nulliparous women: 0.57 (0.45 to 0.71) and for parous women 0.47 (0.36 to 0.62).ConclusionsOur results suggest that it is possible to identify a group of women at low risk of obstetric complications who may benefit from midwife-led care. Women can be reassured that we found no evidence that midwife-led care at the onset of labour is unsafe for women in a maternity care system with a well developed risk selection and referral system.     

Tea and coffee consumption and risk of oral cavity cancer: Results of a large population-based case-control study,the ICARE study

BackgroundResults on the relationship between coffee and tea drinking and the risk of oral cavity cancer are contrasted.The aim of this study was to evaluate the relation between coffee and tea drinking and the risk of oral cavity cancer in France, a high incidence area.Material and methodsWe conducted a population based case–control study with face-to-face interviews and standardized questionnaires (the ICARE study, Investigation of occupational and environmental causes of respiratory cancers). We used data from 689 cases of oral cavity squamous cell carcinoma and 3481 controls. Odds-ratios (ORs) and 95% confidence intervals (95% CI) associated with tea and coffee consumption (quantity, duration, cumulative consumption) were estimated by unconditional logistic regression with adjustment for age, gender, area of residence, education, body mass index, tobacco smoking and alcohol drinking.ResultsWe observed inverse associations between oral cavity cancer and tea or coffee consumption (odds ratio, 0.39; 95% CI 0.21–0.70, for the highest quartile of tea consumption, and 0.60, 95% CI 0.34–1.05, for the highest quartile of coffee consumption). Exclusive tea or coffee consumption was associated with a reduced risk of oral cavity cancer and their joint effect was multiplicative. No differences in risk between men and women or between consumers of tobacco and alcohol and non-consumers were observed. The odds ratios related to the subsites usually included in the oropharynx (soft palate and base of the tongue) did not differ significantly from that observed for the other subsites of the oral cavity.ConclusionsTea and coffee drinking may decrease the risk of oral cavity cancer through antioxidant components which play a role in the repair of cellular damages. These findings need further investigation in prospective studies and the underlying mechanisms in humans remain to be clarified.     

Iatrogenic hyponatraemia of the newborn due to maternal fluid overload: a prospective study.

Over five weeks 136 out of 246 deliveries were studied. Maternal plasma sodium concentrations were normal at admission. At delivery no significant difference was found between maternal and infant cord plasma sodium concentrations. Twenty-four of the 41 mothers who had received only oral fluids during labour had infants whose cord plasma sodium concentrations were normal. Of the 95 mothers who had been given intravenous fluids, however, only 14 infants with normal plasma sodium concentrations, 31 had a concentrations of 130 mmol (mEq)/1 or less and nine of these had a concentration of 125 mmol/1 or less. There was a highly significant inverse relation between cord plasma sodium concentration and rate of fluid administration, suggesting that hyponatraemia was due to intravenous treatment with predominantly sodium-free solutions. Endogenous antidiuretic activity probably increases during labour, and synthetic oxytocin in large doses has been shown to have an antidiuretic effect. The dose used in this study did not appear to have such an effect. Glucose solutions are often used as a vehicle for oxytocin; 83% of all fluid intake in this study was 5% or 10% glucose in water. Fluid balance in labour should be supervised closely, and oxytocin should be given in a more concentrated solution.     

The metabolism of retinyl methyl ether in the rat in vivo

1. Retinyl methyl ether was converted into vitamin A in vitamin A-deficient rats regardless of whether administered by oral, intraperitoneal, intramuscular or subcutaneous route; intramuscular administration seemed to be the best for conversion as well as storage. 2. Significantly, unchanged retinyl methyl ether was also found in the liver after oral administration but not after administration by other routes. 3. Oral administration of 1mg of retinyl methyl ether led to a progressive increase in liver vitamin A with time reaching a value of 16% of administered dose after 24h. No retinyl methyl ether was detectable in liver at any time-interval in this experiment. 4. Conversely, oral administration of 4mg of retinyl methyl ether/day for 4 days led to the accumulation of 25% of the dose as unchanged retinyl methyl ether in the liver 1 day after the last dose; however, it was gradually but completely converted into vitamin A over a period of 18 days. 5. The significance of these findings with special reference to the fundamental metabolism of vitamin A, the site of conversion of retinyl methyl ether into vitamin A, the relative efficiency of various routes of administration and its biological activity are discussed.     

Leptin −2548 G/A polymorphisms are associated to clinical progression of oral cancer and sensitive to oral tumorization in nonsmoking population

Oral cancer is causally associated with environmental carcinogens, and the susceptibility to carcinogen-mediated tumorigenesis is proposed to be genotype-dependent. Leptin (LEP) and leptin receptor (LEPR) both play a crucial role in the mediation of physiological reactions and carcinogenesis and may serve as a candidate biomarker of oral cancer. The current case-control study aimed to examine the effects of LEP −2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) single-nucleotide polymorphisms (SNPs) with or without interacting to environmental carcinogens on the risk for oral squamous cell carcinoma. The SNPs of three genetic allele, from 567 patients with oral cancer and 560 healthy controls in Taiwan were analyzed. The results shown that the patients with polymorphic allele of LEP −2548 have a significant low risk for the development of clinical stage (A/G: adjusted odds ratio [AOR] = 0.670, 95% confidence interval [CI] = 0.454-0.988, P < 0.05; A/G + G/G: AOR = 0.676, 95% CI = 0.467-0.978, P < 0.05) compared to patients with ancestral homozygous A/A genotype. In addition, an interesting result was found that the impact of LEP −2548 G/A SNP on oral carcinogenesis in subjects without tobacco consumption is higher than subjects with tobacco consumption. These results suggest that the genetic polymorphism of LEP −2548 G/A (rs7799039), LEPR K109R (rs1137100), and LEPR Q223R (rs1137101) were not associated to the susceptibility of oral cancer; SNP in LEP −2548 G/A showed a poor clinicopathological development of oral cancer; population without tobacco consumption and with polymorphic LEP −2548 G/A gene may significantly increase the risk to have oral cancer.     

Mortality among oral contraceptive users: 20 year follow up of women in a cohort study.

OBJECTIVE--To see whether the use of oral contraceptives influences mortality. DESIGN--Non-randomised cohort study of 17,032 women followed up on an annual basis for an average of nearly 16 years. SETTING--17 Family planning clinics in England and Scotland. SUBJECTS--Women recruited during 1968-74. At the time of recruitment each woman was aged 25-39, married, a white British subject, willing to participate, and either a current user of oral contraceptives or a current user of a diaphragm or intrauterine device (without previous exposure to the pill). MAIN OUTCOME MEASURES--Overall mortality and cause specific mortality. RESULTS--238 Deaths occurred during the follow up period. The main analyses concerned women entering the study while using either oral contraceptives or a diaphragm or intrauterine device. The overall relative risk of death in the oral contraceptive users was 0.9 (95% confidence interval 0.7 to 1.2). Though the numbers of deaths were small in most individual disease categories, the trends observed were generally consistent with findings in other reports. Thus the relative risk of death in the oral contraceptive users was 4.9 (95% confidence interval 0.7 to 230) for cancer of the cervix, 3.3 (95% confidence interval 0.9 to 17.9) for ischaemic heart disease, and 0.4 (95% confidence interval 0.1 to 1.2) for ovarian cancer. There was a linear trend in the death rates from cervical cancer and ovarian cancer (in opposite directions) with total duration of oral contraceptive use. Death rates from breast cancer (relative risk 0.9; 95% confidence interval 0.5 to 1.4) and suicide and probable suicide (relative risk 1.1; 95% confidence interval 0.3 to 3.6) were much the same in the two contraceptive groups. In 1981 the relative risk of death in oral contraceptive users from circulatory diseases as a group was reported to be 4.2 (95% confidence interval 2.3 to 7.7) in the Royal College of General Practitioners oral contraception study. The corresponding relative risk in this study was only 1.5 (95% confidence interval 0.7 to 3.0). CONCLUSIONS--These findings contain no significant evidence of any overall effect of oral contraceptive use on mortality. None the less, only small numbers of deaths occurred during the study period and a significant adverse (or beneficial) overall effect might emerge in the future. Interestingly, the mortality from circulatory disease associated with oral contraceptive use was substantially less than that found in the Royal College of General Practitioners study.     

Vitamin D Status at Birth and Future Risk of Attention Deficit/Hyperactivity Disorder (ADHD)

Objective

To investigate whether children with Attention Deficit/Hyperactivity Disorder have lower levels of Vitamin D₃ at birth than matched controls.

Material

Umbilical cord blood samples collected at birth from 202 children later diagnosed with Attention Deficit/Hyperactivity Disorder were analysed for vitamin D content and compared with 202 matched controls. 25-OH vitamin D₃ was analysed by liquid chromatography tandem mass spectrometry.

Results

No differences in cord blood vitamin D concentration were found between children with Attention Deficit/Hyperactivity Disorder (median 13.0 ng/ml) and controls (median 13.5 ng/ml) (p = 0.43). In a logistic regression analysis, Attention Deficit/Hyperactivity Disorder showed a significant association with maternal age (odds ratio: 0.96, 95% confidence interval: 0.92–0.99) but not with vitamin D levels (odds ratio: 0.99, 95% confidence interval: 0.97–1.02).

Conclusion

We found no difference in intrauterine vitamin D levels between children later developing Attention Deficit/Hyperactivity Disorder and matched control children. However, the statistical power of the study was too weak to detect an eventual small to medium size association between vitamin D levels and Attention Deficit/Hyperactivity Disorder.     

Impact of postmenopausal hormone therapy on cardiovascular events and cancer: pooled data from clinical trials.

OBJECTIVE: To examine the incidence of cardiovascular diseases and cancer from published clinical trials that studied other outcomes of postmenopausal hormone therapy as some surveys have suggested that it may decrease the incidence of cardiovascular diseases and increase the incidence of hormone dependent cancers. DESIGN: Trials that compared hormone therapy with placebo, no therapy, or vitamins and minerals in comparable groups of postmenopausal women and reported cardiovascular or cancer outcomes were searched from the literature. SUBJECTS: 22 trials with 4124 women were identified. In each group, the numbers of women with cardiovascular and cancer events were summed and divided by the numbers of women originally allocated to the groups. RESULTS: Data on cardiovascular events and cancer were usually given incidentally, either as a reason for dropping out of a study or in a list of adverse effects. The calculated odds ratios for women taking hormones versus those not taking hormones was 1.39 (95% confidence interval 0.48 to 3.95) for cardiovascular events without pulmonary embolus and deep vein thrombosis and 1.64 (0.55 to 4.18) with them. It is unlikely that such results would have occurred if the true odds ratio were 0.7 or less. For cancers, the numbers of reported events were too low for a useful conclusion. CONCLUSIONS: The results of these pooled data do not support the notion that postmenopausal hormone therapy prevents cardiovascular events.