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Maternal Consumption of Coffee and Caffeine-containing Beverages and Oral Clefts: A Population-based Case-Control Study in Norway |
Anne Marte W Johansen, Allen J Wilcox, Rolv T Lie, Lene F Andersen, Christian A Drevon |
Abstract |
A large, population-based case-control study of facial clefts was carried out in Norway between 1996 and 2001. The study included 573 cases—377 with cleft lip with or without cleft palate and 196 with cleft palate only—and 763 randomly selected controls. Maternal consumption of coffee and other caffeine-containing beve... |
Keywords: caffeine, cleft lip, cleft palate, coffee, pregnancy |
Orofacial clefts are among the most common birth defects, and the prevalence in Norway (2.2 per 1,000 livebirths) is particularly high. The etiology of clefts is complex and largely unknown. The high risk of recurrence of clefts among first-degree relatives (as much as 56 times the background prevalence) suggests a str... |
Coffee consumption is relatively high in Norway. In the latest nationwide study, average coffee intake was half a liter a day, with peak intake among those aged 40–60 years (8). Data from animal studies suggest that large single doses of caffeine may cause palatal clefts as well as other birth defects (9), although stu... |
Coffee is a commonly consumed beverage among pregnant women, and even a small increase in malformation risk could be a matter of concern. We used data from a population-based case-control study to evaluate the association of maternal consumption of coffee and caffeinated beverages in early pregnancy with the risk of de... |
MATERIALS AND METHODS |
All infants born with facial clefts in Norway are treated at government expense in surgical centers at university hospitals located in Oslo and Bergen. In collaboration with these 2 centers, we identified all babies born from 1996 to 2001 who were referred for treatment for either cleft lip with or without cleft palate... |
Our present study was approved by the regional ethics review board, the Norwegian Data Inspectorate, and the US National Institute of Environmental Health Sciences Review Board. All participating mothers provided informed consent. |
Participants |
There were 676 women in Norway who delivered infants requiring surgery for orofacial clefts during 1996–2001. We excluded 24 mothers who did not speak Norwegian or whose infant died after birth, leaving 652 eligible mothers. Of these, 88% (n = 573) agreed to participate. We randomly selected 1,022 control mothers of li... |
Data collection |
Mothers completed a 32-page questionnaire covering demographic characteristics, reproductive history, and exposures during pregnancy (including smoking, alcohol consumption, coffee intake, medication use, and occupational and household exposures). Median time from delivery to completion of the questionnaire was 14 week... |
Statistical methods |
The risk of delivering offspring with an orofacial cleft was estimated by odds ratios with 95% confidence intervals in unconditional logistic regression models. All beverages were summarized and were analyzed in the same way, as follows. “Cups per day” was computed from reported number of cups consumed per day, per wee... |
An estimate of caffeine from all sources was computed from the data on coffee, tea, and caffeinated soft drinks. Caffeine content was estimated as 100 mg per cup of coffee, 40 mg per cup of tea, and 20 mg per cup of caffeinated soft drink based on values from the Norwegian Health Authorities Web page (http://www.matpor... |
Adjustments were made for potential confounders (factors associated with clefts in other studies, most of which were also associated in our study), namely, dietary vitamin A (quartiles), dietary folate (quartiles), folic acid supplement (400 μg/day, yes or no), vitamin supplement use (yes or no), consumption of alcohol... |
RESULTS |
Women who gave birth to infants with CLP were taller, less educated, and less likely to work during the first trimester compared with mothers who gave birth to healthy controls (Table 1). Compared with mothers of controls, fewer mothers of CLP cases used a folic acid supplement, and they were more often coffee consumer... |
Maternal coffee consumption was associated with an increased risk of CLP. In the adjusted analyses, the odds ratio of CLP increased by 7% per-cup increase in daily coffee intake (adjusted odds ratio = 1.07, 95% confidence interval (CI): 1.00, 1.16). Compared with those for women with zero coffee consumption, the adjust... |
Consumption of caffeine-containing tea was associated with a decrease in the odds ratio of both CLP and CPO (Table 2). Compared with no tea intake, daily tea intake of 3 or more cups gave adjusted odds ratios of 0.55 (95% CI: 0.32, 0.95) for CLP and 0.58 (95% CI: 0.31, 1.07) for CPO. Soft drinks that contain caffeine w... |
Table 3 shows maternal intake of caffeine from all beverages in relation to cleft risk. Although there was a positive association in the crude analysis, the association was reduced after adjustment. We also considered mothers who reported drinking coffee during the year before pregnancy but not during the first trimest... |
DISCUSSION |
Maternal intake of coffee during the first 3 months of the pregnancy was associated in a dose-response manner with risk of delivering an infant with CLP. In contrast, we found no evidence of an association between coffee intake and risk of CPO. The association between coffee and CLP was only slightly decreased by adjus... |
There is no known mechanism by which coffee intake might increase the risk of CLP. Effects on homocysteine is one potential pathway. Evidence suggests that maternal hyperhomocysteinemia may be linked to increased risk of CLP (13). Coffee intake increases the plasma concentration of homocysteine (14–16), as does smoking... |
Consumption of caffeine-containing tea was strongly associated with a reduced risk of both CLP and CPO. Potential health benefits of tea have been linked to its high content of antioxidants (19). This is not a likely explanation for the reduced cleft risk, however, because coffee has an even higher total content of ant... |
The association of coffee with CLP appears to be independent of the role of caffeine. We found no association between total caffeine intake and risk of CLP (reflecting the combination of the positive association with coffee and the negative association with tea). Only 5 women drank decaffeinated coffee exclusively, too... |
By the same token, high-quantity coffee consumers (>3 cups/day) were older, less educated, smoked more, and drank more alcohol per sitting compared with nonconsumers. Even though we adjusted for possible confounding factors, we cannot rule out the possibility of residual confounding by known factors such as smoking or ... |
Another potential source of bias in this study comes from possible selective participation of controls. While participation was relatively high (88% for cases and 76% for controls), the lower participation of controls leaves room for differential participation by coffee drinking. However, it is unlikely that such selec... |
Women may reduce their coffee consumption as they develop pregnancy symptoms of nausea and vomiting. Given that closure of the lip and palate occurs relatively late in the first trimester (8–12 weeks after the last menstrual period) (1), it is possible that reported coffee intake is greater than actual consumption at t... |
Our study had the advantage of enrolling mothers soon (an average of 15 weeks) after delivery. In addition, questions on coffee and other caffeinated beverages constituted only a small part of the questionnaire, with no specific emphasis on these beverages that would be expected to bias reporting. Another strength of t... |
A meta-analysis of 3 studies on maternal coffee consumption and orofacial clefts found a slight increase in the risk of clefts (11). All 3 studies used 0 cups as the reference category. When high coffee intake was compared with low intake, the pooled odds ratio was 1.2 (95% CI: 0.9, 1.6). One of the studies provided re... |
A recent cohort study from Denmark found that coffee intake was associated with a reduced risk of CLP (23). The authors observed an odds ratio of 0.66 (95% CI: 0.27, 1.62) when comparing daily intake of more than 5 cups of coffee with no intake. The Danish study had the advantage of a prospective design, although one c... |
In summary, results from our study showed a dose-dependent association between coffee consumption during the first trimester and increased risk of CLP. This association was specific to CLP, with no association found between coffee consumption and risk of CPO. There was little or no evidence for an association between c... |
Assessment of Glenohumeral |
Subluxation in Poststroke Hemiplegia: |
Comparison Between Ultrasound and |
Fingerbreadth Palpation Methods |
Praveen Kumar, Marianne Mardon, Michael Bradley, Selena Cray, |
Annette Swinkels |
Background. Glenohumeral subluxation (GHS) is a common poststroke compli |
cation. Treatment of GHS is hampered by the lack of objective, real-time clinical |
measurements. |
Objective. The aims of this study were: (1) to compare an ultrasound method of |
GHS measurement with the fingerbreadth palpation method using a receiver oper |
ating characteristic curve (ROC) and (2) to report the sensitivity and specificity of this |
method. |
Design. A prospective study was conducted. |
S etting. The study was conducted in local hospitals and day centers in the |
southwest of England. |
Patients. One hundred five patients who had one-sided weakness following a |
first-time stroke (51 men, 54 women; mean age=71 years, SD=11) and who gave |
informed consent were enrolled in the study. |
Measurements. Ultrasound measurements of acromion-greater tuberosity |
(AGT) distance were used for the assessment of GHS. Measurements were under |
taken on both shoulders by a research physical therapist trained in shoulder ultra |
sound with the patient seated in a standardized position. Fingerbreadth palpation |
assessment of GHS was undertaken by a clinical physical therapist based at the |
hospital, who also visited the day centers. |
Results. The area under the ROC curve was 0.73 (95% confidence interval [95% |
Cl] =0.63, 0.83), suggesting that the ultrasound method has good agreement com |
pared with the fingerbreadth palpation method. A cutoff point of £0.2 cm AGT |
measurement difference between affected and unaffected shoulders generated a |
sensitivity of 68% (95% CI=51%, 75%), a specificity of 62% (95% CI=47%, 80%), a |
positive likelihood ratio of 1.79 (95% CI=1.1, 2.9), and a negative likelihood ratio of |
0.55 (95% CI=0.4, 0.8). |
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