Trends in use of hydroxychloroquine during pregnancy in systemic lupus erythematosus patients from 2001 to 2015.

BACKGROUND: Evidence suggests that continuing hydroxychloroquine (HCQ) during pregnancy in women with systemic lupus erythematosus (SLE) improves outcomes. We sought to describe time trends in the continuation, initiation, and duration of HCQ in a large population-based cohort of pregnant SLE women. METHODS: A cohort of pregnant women with SLE enrolled continuously in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2003-2015) health insurance between three months prior to conception and one month after delivery was identified. We assessed the proportion of women initiating or continuing HCQ and the duration of therapy during each calendar year in the study. RESULTS: A total of 5300 women with SLE were included. Of these, 852 (16.1%) were on HCQ treatment in the three-month period prior to their pregnancy. During pregnancy, the overall proportion of women with SLE taking HCQ increased from 12.4% in 2001 to 37.7% in 2015. Initiation of HCQ therapy during pregnancy increased from 2.7% in 2001 to 7.5% in 2010 ( p = 0.0002) (Medicaid) and from 4.9% in 2003 to 13.6% in 2015 ( p = 0.0001) (Clinformatics). Continuation of HCQ during pregnancy did not change significantly over time in either data set. The average cumulative day-supply of HCQ prescriptions during pregnancy increased from 37 days in 2001 to 77 days in 2010 ( p = 0.05) among HCQ initiators and from 79 days in 2001 to 125 days in 2010 ( p = 0.0009) among HCQ continuers in Medicaid. Among privately insured women, the average cumulative day-supply of HCQ prescriptions among HCQ continuers increased from 84 in 2004 to 163 in 2015 ( p = 0.0006) but did not change significantly among HCQ initiators. CONCLUSION: The proportion of women initiating HCQ during pregnancy and the average cumulative day-supply of HCQ increased from 2001 to 2015. While these findings are encouraging, overall HCQ use during pregnancy remains low.

Exposure to acid-suppressing drugs during pregnancy and the risk of asthma in childhood: an observational cohort study.

BACKGROUND: Some research has suggested a potential link between prenatal exposure to proton pump inhibitors (PPIs) or H2 -receptor antagonists (H2 RAs) and the development of childhood asthma. AIM: To quantify the relative risk of asthma in children who experienced pre-natal exposure to PPIs and/or H2 RAs, adjusting for potential confounders. METHODS: In this observational cohort study (NCT01787435), women aged 18-45 years with completed pregnancies between January 1996 and December 2010 were identified from The Health Improvement Network in the United Kingdom, and were linked to infants. Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS: Our analysis identified 2371 prenatally exposed and 7745 unexposed infants. The incidence of asthma (per 1000 person-years) was 19.52 in the unexposed cohort, 23.88 in the PPI cohort and 32.16 in the H2 RA cohort. After adjusting for maternal healthcare utilisation during the year before pregnancy, the HR for asthma in infants whose mothers received prescriptions at any time during pregnancy was 1.12 (95% confidence interval: 0.88-1.44) for PPIs and 1.43 (1.20-1.70) for H2 RAs, when compared with unexposed infants. With further adjustment for maternal comorbidities and other medications, the HR for asthma was 1.03 (0.76-1.40) for PPIs and 1.32 (1.05-1.64) for H2 RAs. CONCLUSIONS: Our analysis showed no association between prenatal exposure to PPIs and asthma in childhood after adjusting for confounders. The association found for H2 RAs may be explained largely by underlying environmental or genetic factors, as suggested by reductions in hazard ratio estimates following adjustment for maternal comorbidities.

Motor development in children prenatally exposed to selective serotonin reuptake inhibitors: a large population-based pregnancy cohort study.

OBJECTIVES: To estimate the association between prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) and motor development in children considering the effect of maternal symptoms of anxiety and depression before, during and after pregnancy. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort study (MoBa) (1999-2008). POPULATION: A total of 51 404 singleton pregnancies. METHODS: Self-reported use of SSRIs was collected for the 6 months before pregnancy and prospectively during pregnancy. We used ordinal logistic regression as the statistical analysis. MAIN OUTCOME MEASURES: Motor development was assessed by maternal reports of fine and gross motor development at child age 3 years by items from the Ages and Stages Questionnaire (ASQ). The maternal ASQ scores were compared with data from a MoBa sub-study where clinicians assessed motor development with the Gross and Fine Motor Mullen scales of early learning. RESULTS: In all 381 women (0.7%) reported use of SSRIs during pregnancy, of these 159 reported on at least two questionnaires (prolonged use). Prolonged SSRI exposure was associated with a delay in fine motor development, odds ratio 1.42 (95% CI 1.07-1.87) compared with no SSRI exposure, after adjusting for symptoms of anxiety and depression before and during pregnancy. Severity of maternal depression seemed to explain the association only partially. Stratifying on depression after pregnancy had no impact on the estimated effect of SSRIs. CONCLUSIONS: Prolonged prenatal exposure to SSRIs was weakly associated with a delayed motor development at age 3 years, but not to the extent that the delay was of clinical importance. TWEETABLE ABSTRACT: Long-term prenatal SSRI exposure is weakly associated with delayed motor development independent of depression.

Prenatal exposure to antidepressants and language competence at age three: results from a large population-based pregnancy cohort in Norway.

OBJECTIVE: To examine the association between maternal use of selective serotonin reuptake inhibitors (SSRI) in pregnancy and language competence in their children at age three taking into account maternal symptoms of anxiety and depression. DESIGN: Population-based prospective pregnancy cohort study. SETTING: The Norwegian Mother and Child Cohort Study; recruited pregnant women from 1999 through 2008. POPULATION: 45,266 women with 51,748 singleton pregnancies. METHODS: The association between short- or long-term use of SSRI during pregnancy and language competence in the child was investigated using multinomial logistic regression with three outcome categories: long, complicated sentences, fairly complete sentences and language delay. MAIN OUTCOME MEASURES: Children's language competence at age three measured by maternal report on a validated language grammar scale. RESULTS: Women reported use of SSRI in 386 (0.7%) pregnancies. Of these, 161 (42%) reported long-term use. Compared with children whose mothers took no SSRI, using the best language category as the reference, adjusted relative risk ratios (RRR) of having fairly complete sentences were 1.21 (95% CI 0.85-1.72) and 2.28 (1.54-3.38) for short- and long-term SSRI use, respectively. The adjusted RRRs of language delay were 0.86 (0.42-1.76) and 2.30 (1.21-4.37). Symptoms of anxiety and depression in pregnancy were independently related to language delay, adjusted RRR 1.25 (1.03-1.50) and 1.83 (1.40-2.40) for short- and long-term symptoms, respectively. CONCLUSIONS: Prolonged use of SSRI during pregnancy was associated with lower language competence in children by age three independently of depression. Having symptoms of depression throughout pregnancy had an independent effect.

Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study.

OBJECTIVE: To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH). DESIGN: Cohort study. SETTING: United States of America. POPULATION OR SAMPLE: Medicaid beneficiaries. METHODS: We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding. MAIN OUTCOME MEASURES: The occurrence of PPH during the delivery hospitalisation. RESULTS: There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses. CONCLUSIONS: The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

BACKGROUND: Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). AIM: To identify whether and in whom either of these strategies should be preferred in daily practice. METHODS: A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (≥80% GPA adherence) and coxib users (without GPA use) aged ≥50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ≥65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders. RESULTS: Within the NSAID cohort (n = 617,220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (≥80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (≥80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50). CONCLUSIONS: The risk of UGI events was similar in nsNSAID+GPA (≥80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred.

Comparative safety of antiepileptic drugs during pregnancy.

OBJECTIVE: To assess the safety of the newer antiepileptic drugs (AEDs) during pregnancy. METHODS: The study population was pregnant women who enrolled in the North American AED Pregnancy Registry between 1997 and 2011. Data on AED use and maternal characteristics were collected through phone interviews at enrollment, at 7 months' gestation, and postpartum. Malformations were confirmed by medical records. The risk of major malformations was calculated among infants exposed to specific AEDs in monotherapy during the first trimester of pregnancy and among an unexposed group. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with logistic regression. RESULTS: The risk of major malformations was 9.3% (30 of 323) for valproate, 5.5% (11 of 199) for phenobarbital, 4.2% (15 of 359) for topiramate, 3.0% (31 of 1.033) for carbamazepine, 2.9% (12 of 416) for phenytoin, 2.4% (11 of 450) for levetiracetam, and 2.0% (31 of 1,562) for lamotrigine. Compared with lamotrigine, the RR was 5.1 (95% CI 3.0-8.5) for valproate, 2.9 (1.4-5.8) for phenobarbital, and 2.2 (1.2-4.0) for topiramate. The proportion of women with epilepsy who had seizures during pregnancy ranged from 23% for valproate to 31% for lamotrigine. Valproate was associated with a higher risk of neural tube defects, hypospadias, cardiac defects, and oral clefts and phenobarbital with a higher risk of cardiac defects and oral clefts; 5 infants exposed to topiramate (1.4%) had a cleft lip. CONCLUSIONS: AEDs such as valproate and phenobarbital were associated with a higher risk of major malformations than newer AEDs such as lamotrigine and levetiracetam. Topiramate was associated with an increased risk of cleft lip compared with that of a reference population.

Diabetes therapy and cancer risk: causal effects and other plausible explanations.

Four reports in Diabetologia presented data on the association between hypoglycaemic agents and the risk of cancer. One study showed a higher risk of cancer overall in subjects with diabetes receiving insulin or sulfonylureas than in those on metformin. In another study, the risk of cancer overall increased with dose for any type of insulin and, among high doses, insulin glargine (A21Gly,B31Arg,B32Arg human insulin)-only users had a higher risk than subjects on human insulin. In two studies, users of insulin glargine alone had a higher risk of breast cancer than those on other insulins, a third study found no association. Whether these associations are causal or at least partially explained by chance or biases such as confounding, reverse causation, selection or detection biases is arguable. Current epidemiological evidence is insufficient to confirm a carcinogenic effect of specific insulins on specific cancers. However, the potential dose effect of insulin overall, and insulin glargine in particular, on colon and breast cancer deserves further attention.

Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005.

BACKGROUND: Few studies have examined the incidence of uncomplicated peptic ulcer or the trends in factors affecting its incidence. AIM: To estimate the incidence rate of uncomplicated peptic ulcer in the UK from 1997 to 2005 and report temporal changes in the main known preventive and risk factors. METHODS: Population-based cohort study of 1 049 689 patients enrolled in The Health Improvement Network in the UK. We estimated the incidence rate of uncomplicated peptic ulcer and evaluated temporal trends in demographic characteristics and prescription patterns for various anti-inflammatory and gastroprotective agents. RESULTS: Overall uncomplicated peptic ulcer incidence was 0.75 cases per 1000 persons-years, declining from 1.1 to 0.52 cases per 1000 person-years between 1997 and 2005. Distributions of age, gender and alcohol habits were similar in 1997 and 2005. The proportion of documented Helicobacter pylori-negative cases increased from 5% to 12%. Monthly prevalence of subjects with prescriptions for traditional non-aspirin NSAIDs changed from 7.7% to 6.8%, Coxibs from 0% to 0.7%, and proton pump inhibitors (PPIs) from 2.4% to 7.4%. The proportion of subjects on prescription NSAIDs on PPIs increased continuously over time. CONCLUSION: A reduction in H. pylori-related peptic ulcers, changing patterns in NSAID use and increasing PPI use may have contributed to a decline in uncomplicated peptic ulcer incidence in the UK.

Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies.

AIMS: Because of the widespread use of aspirin for prevention of cardiovascular diseases, side-effects associated with thromboprophylactic doses are of interest. This study summarizes the relative risk (RR) for serious upper gastrointestinal complications (UGIC) associated with aspirin exposure in general and with specific aspirin doses and formulations in particular. METHODS: After a systematic review, 17 original epidemiologic studies published between 1990 and 2001 were selected according to predefined criteria. Heterogeneity of effects was explored. Pooled estimates were calculated according to different study characteristics and patterns of aspirin use. RESULTS: The overall relative risk of UGIC associated with aspirin use was 2.2 (95% confidence interval (CI): 2.1, 2.4) for cohort studies and nested case-control studies and 3.1 (95% CI: 2.8, 3.3) for non-nested case-control studies. Original studies found a dose-response relationship between UGIC and aspirin, although the risk was still elevated for doses lower or up to 300 mg day(-1). The summary RR was 2.6 (95% CI: 2.3, 2.9) for plain, 5.3 (95% CI: 3.0, 9.2) for buffered, and 2.4 (95% CI: 1.9, 2.9) for enteric-coated aspirin formulations. CONCLUSIONS: Aspirin was associated with UGIC even when used at low doses or in buffered or enteric-coated formulations. The latter findings may be partially explained by channeling of susceptible patients to these formulations.

Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with an increase in upper gastrointestinal complications. There is no agreement, however, on whether all conventional NSAIDs have a similar relative risk (RR), and epidemiologic data are limited on acetaminophen. We studied the association between these medications and the risk of upper gastrointestinal bleed/perforation in a population-based cohort of 958,397 persons in the United Kingdom between 1993 and 1998. Our nested case-control analysis included 2,105 cases and 11,500 controls. RR estimates were adjusted for several factors known to be associated with upper gastrointestinal bleed/perforation. Compared with non-users, users of acetaminophen at doses less than 2 gm did not have an increased risk of upper gastrointestinal complications. The adjusted RR for acetaminophen at doses greater than 2 gm was 3.6 [95% confidence interval (95% CI) = 2.6-5.1]. The corresponding RRs for low/medium and high doses of NSAIDs were 2.4 (95% CI = 1.9-3.1) and 4.9 (95% CI = 4.1-5.8). The RR was 3.1 (95% CI = 2.5, 3.8) for short plasma half-life, 4.5 (95% CI = 3.5-5.9) for long half-life, and 5.4 (95% CI = 4.0-7.1) for slow-release formulations of NSAIDs. After adjusting for daily dose, the differences in RR between individual NSAIDs tended to diminish except for apazone. Users of H2 receptor antagonists, omeprazole, and misoprostol had RRs of 1.4 (95% CI = 1.2-1.8), 0.6 (95% CI = 0.4-0.9), and 0.6 (95% CI = 0.4-1.0), respectively. Among NSAID users, use of nitrates was associated with an RR of 0.6 (95% CI = 0.4-1.0).

Neural tube defects in relation to use of folic acid antagonists during pregnancy.

Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTDs). To determine whether periconceptional exposure to folic acid antagonists (FAAs) might therefore increase the risk of NTDs, the authors examined data from an ongoing case-control study of birth defects (1979-1998) in the United States and Canada. They compared data on 1,242 infants with NTDs (spina bifida, anencephaly, and encephalocele) with data from a control group of 6,660 infants with malformations not related to vitamin supplementation. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors and about medication use. The adjusted odds ratios of NTDs related to exposure to FAAs (including carbamazepine, phenobarbital, phenytoin, primidone, sulfasalazine, triamterene, and trimethoprim) during the first or second months after the last menstrual period, compared with no use in either month, were 2.8 (95% confidence interval: 1.7, 4.6) for FAAs as a group, 4.8 (95% confidence interval: 1.5, 16.1) for trimethoprim (based on five exposed cases), and 6.9 (95% confidence interval: 1.9, 25.7) for carbamazepine (six exposed cases). These results are adjusted for region, interview year, periconceptional folic acid supplementation, maternal age, weight, education, and infections early in pregnancy. These findings suggest that a number of FAAs may increase NTD risk, and they provide estimates of risk for selected drugs.

Steroids and risk of upper gastrointestinal complications.

Most antiinflammatory drugs have been associated with an increase in upper gastrointestinal complications. However, the literature on steroids is more limited than that on nonsteroidal antiinflammatory drugs (NSAIDs). To estimate the risk of upper gastrointestinal complications associated with use of steroids alone and in combination, a nested case-control analysis was conducted on the General Practice Research Database from the United KINGDOM: The authors identified 2,105 cases of upper gastrointestinal complications and 11,500 controls between 1993 and 1998. The adjusted odds ratios associated with current use of oral steroids were 1.8 (95% confidence interval (CI): 1.3, 2.4) for upper gastrointestinal complications overall and 2.4 (95% CI: 1.7, 3.4) for gastric and 1.2 (95% CI: 0.8, 1.9) for duodenal damage. Steroids were similarly associated with bleeding (odds ratio (OR) = 1.8; 95% CI: 1.3, 2.4) and perforations (OR = 1.6; 95% CI: 0.9, 3.1). Simultaneous use of steroids with low-medium and high NSAID doses, respectively, produced odds ratios of 4.0 (95% CI: 1.3, 12.0) and 12.7 (95% CI: 6.2, 26.1), compared with users of none. Whenever possible, antiinflammatory drugs should be given in monotherapy and at the lowest effective dose in order to reduce the risk of upper gastrointestinal complications.

The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents.

Most anti-inflammatory drugs have been associated with an increased risk of serious upper gastrointestinal complications. Epidemiological studies have estimated the magnitude of the risk for specific anti-inflammatory drugs. The risk of upper gastrointestinal tract bleeding or perforation increases around twofold with use of oral steroids or low dose aspirin, and increases around fourfold with use of nonaspirin nonsteroidal anti-inflammatory drugs. Acetaminophen at daily doses of 2000 mg and higher has also been associated with an increased risk. Overall, the risk is dose dependent and is greater with more than one anti-inflammatory drug taken simultaneously. Hence, whenever possible, anti-inflammatory drugs should be given in monotherapy and at the lowest effective dose in order to reduce the risk of serious upper gastrointestinal complications.

Epidemiologic assessment of the safety of conventional nonsteroidal anti-inflammatory drugs.

The use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) has been associated with upper gastrointestinal bleeding and perforation (UGIB), acute liver injury, acute renal injury, heart failure, and adverse reproductive outcomes. This article summarizes the effects of various factors, such as NSAID dose, duration of treatment, patient age, and ulcer history, on the incidences of these adverse side effects. We used the UK General Practice Research Database to study further the principal safety concern related to NSAIDs, namely, UGIB.

Folic acid antagonists during pregnancy and the risk of birth defects.

BACKGROUND: Multivitamin supplementation in pregnant women may reduce the risks of cardiovascular defects, oral clefts, and urinary tract defects in their infants. We evaluated whether the folic acid component of multivitamins is responsible for the reduction in risk by examining the associations between maternal use of folic acid antagonists and these congenital malformations. METHODS: We compared data on exposure to folic acid antagonists that act as dihydrofolate reductase inhibitors and to certain antiepileptic drugs for 3870 infants with cardiovascular defects, 1962 infants with oral clefts, and 1100 infants with urinary tract defects with data for 8387 control infants with malformations the risk of which is not reduced after vitamin supplementation. Mothers were interviewed within six months after delivery about their medication use. RESULTS: The relative risks of cardiovascular defects and oral clefts in infants whose mothers were exposed to dihydrofolate reductase inhibitors during the second or third month after the last menstrual period, as compared with infants whose mothers had no such exposure, were 3.4 (95 percent confidence interval, 1.8 to 6.4) and 2.6 (95 percent confidence interval, 1.1 to 6.1), respectively. The relative risks of cardiovascular defects, oral clefts, and urinary tract defects after maternal exposure to antiepileptic drugs were 2.2 (95 percent confidence interval, 1.4 to 3.5), 2.5 (95 percent confidence interval, 1.5 to 4.2), and 2.5 (95 percent confidence interval, 1.2 to 5.0), respectively. Use of multivitamin supplements containing folic acid diminished the adverse effects of dihydrofolate reductase inhibitors, but not that of antiepileptic drugs. CONCLUSIONS: Folic acid antagonists, which include such common drugs as trimethoprim, triamterene, carbamazepine, phenytoin, phenobarbital, and primidone, may increase the risk not only of neural-tube defects, but also of cardiovascular defects, oral clefts, and urinary tract defects. The folic acid component of multivitamins may reduce the risks of these defects.

Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s.

BACKGROUND: In the last decades, studies have estimated the upper gastrointestinal tract bleeding/perforation (UGIB) risk associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have also included the effect of patterns of NSAID use, risk factors for UGIB, and modifiers of NSAID effect. METHODS: Systematic review of case-control and cohort studies on serious gastrointestinal tract complications and nonaspirin NSAIDs published between 1990 and 1999 using MEDLINE. Eighteen original studies were selected according to predefined criteria. Two researchers extracted the data independently. Pooled relative risk estimates were calculated according to subject and exposure characteristics. Heterogeneity of effects was tested and reasons for heterogeneity were considered. RESULTS: Advanced age, history of peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal anti-inflammatory drug users with advanced age or a history of peptic ulcer had the highest absolute risks. The pooled relative risk of UGIB after exposure to NSAIDs was 3.8 (95% confidence interval, 3.6-4.1). The increased risk was maintained during treatment and returned to baseline once treatment was stopped. A clear dose response was observed. There was some variation in risk between individual NSAIDs, though these differences were markedly attenuated when comparable daily doses were considered. CONCLUSIONS: The elderly and patients with a history of peptic ulcer could benefit the most from a reduction in NSAID gastrotoxicity. Whenever possible, physicians may wish to recommend lower doses to reduce the UGIB risk associated with all individual NSAIDs, especially in the subgroup of patients with the greatest background risk.

Association of maternal short stature with stunting in Mexican children: common genes vs common environment.

OBJECTIVE: To evaluate the association between stunting in children and maternal short stature, controlling for potential environmental confounders. DESIGN: 1988 Mexico National Nutrition Survey. SETTING: Mexico SUBJECTS: The final sample size was 4663 pairs of children (<5 y) and their mothers (12-49 y) from a total of 13 236 surveyed houses. MAIN OUTCOME MEASURES: Stunting (height-for-age Z-scores <-2). RESULTS: The prevalence of stunting in children was 19%, and 10% of the mothers exhibited short stature (<145 cm). In the crude analysis, mothers with short stature were significantly more likely to have stunted children (odds ratio (OR)=4.0; 95% confidence interval (CI)=3.2-4.8; P-value <0.001). In a multiple logistic regression model the OR for child stunting was reduced, but remained significant OR=2.0; 95% CI=1.6-2.6; P-value <0.001) after adjustment for region, urban/rural residence, socio-economic status, household size, child age and presence of infection in the past 14 d, and maternal age, body mass index (BMI), and educational level. Adjusted ORs varied between regions (Mexico City, OR=3.9; North Mexico, OR=3. 1; Central Mexico, OR=2.0; South Mexico, OR=1.6. Comparison of crude vs adjusted estimates pointed to regional differences in the proportion of association between maternal and child short statures explained by environmental determinants. CONCLUSIONS: Maternal stature, reflecting her potential height and early environment, appeared to contribute to child height independently of the shared risk factors that could affect stature. Nonetheless, we could explain much of the association between stunting in children and maternal short stature by environmental factors, and part of the residual variability may be due to unmeasured determinants. Regional differences pointed to a predominance of environmental factors in explaining child stunting in poorer regions.