Biomedical subjects

Martha M Werler

Publications and source records attributed to Martha M Werler.

At least 19 recordsLinked to original sources

PubMed2007

Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis.

BACKGROUND: There is equivocal evidence in the published literature that folic acid supplementation during pregnancy may protect against the common congenital anomalies cleft lip with or without cleft palate (CLP) and cleft palate alone (CP). We undertook this meta-analysis to test the hypothesis that nonsyndromic oral cleft birth prevalences are different for those whose mothers took folic acid-containing supplements and for those whose mothers did not. METHODS: Human studies published in English were identified through MEDLINE, bibliography reviews, and contacting experts in the field. Within strata of prospective and case-control studies, CLP, CP, and all clefts, respectively, were analyzed using either a fixed or random effects model, as appropriate. We assessed for publication bias using Begg and Mazumdar's rank correlation and Egger's regression-based tests. RESULTS: Five prospective studies were analyzed, yielding combined relative risks of 0.51 (95% CI: 0.32, 0.95) for CLP, 1.19 (95% CI: 0.43, 3.28) for CP, and 0.55 (95% CI: 0.32, 0.95) for all clefts. Twelve case-control studies were assessed, which resulted in combined relative risks of 0.77 (95% CI: 0.65, 0.90) for CLP, 0.80 (95% CI: 0.69, 0.93) for CP, and 0.78 (95% CI: 0.71, 0.85) for all clefts. CONCLUSIONS: In aggregate, our results support the hypothesis of a protective effect of folic acid-containing supplement intake during pregnancy on the risk for oral clefts, although this conclusion is tempered by the potential for bias and uncontrolled confounding.

Cleft Lip↗

PubMed2006

Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant mortality and morbidity. A previous cohort study suggested a possible association between maternal use of the selective serotonin-reuptake inhibitor (SSRI) fluoxetine late in the third trimester of pregnancy and the risk of PPHN in the infant. We performed a case-control study to assess whether PPHN is associated with exposure to SSRIs during late pregnancy. METHODS: Between 1998 and 2003, we enrolled 377 women whose infants had PPHN and 836 matched control women and their infants. Maternal interviews were conducted by nurses, who were blinded to the study hypothesis, regarding medication use in pregnancy and potential confounders, including demographic variables and health history. RESULTS: Fourteen infants with PPHN had been exposed to an SSRI after the completion of the 20th week of gestation, as compared with six control infants (adjusted odds ratio, 6.1; 95 percent confidence interval, 2.2 to 16.8). In contrast, neither the use of SSRIs before the 20th week of gestation nor the use of non-SSRI antidepressant drugs at any time during pregnancy was associated with an increased risk of PPHN. CONCLUSIONS: These data support an association between the maternal use of SSRIs in late pregnancy and PPHN in the offspring; further study of this association is warranted. These findings should be taken into account in decisions as to whether to continue the use of SSRIs during pregnancy.

Antidepressive Agents↗

PubMed2006

Fat intake and the risk of gastroschisis.

BACKGROUND: Young age has been associated with an increased risk of gastroschisis. It has been suggested that the pathogenesis of gastroschisis may be related to vascular disruption. Nutrients that may be associated with vasoconstriction include dietary fat and its subtypes. The objective of this study was to examine the association between dietary fats and gastroschisis and whether maternal age modified this association. METHODS: Data came from the National Birth Defects Prevention Study (NBDPS), which included 304 isolated gastroschisis cases and 3313 controls. Dietary intake in the year prior to conception was ascertained using a food frequency questionnaire, and included total, saturated, monosaturated, and polyunsaturated fat and cholesterol. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounders. Age and smoking were tested as effect modifiers. RESULTS: Higher mean intakes of total energy, total fat, and cholesterol as well as the subtypes of fats were found for gastroschisis cases compared to controls. Cases were more likely to be in the middle (adjusted OR [AOR], 1.3; 95% CI, 0.9-1.9) and highest (AOR, 1.2; 95% CI, 0.8-1.7) tertile of total fat intake compared to controls. This pattern was also true for saturated fat intake. No association was found for mono or polyunsaturated fat. Cases were less likely to be in the middle (AOR, 0.6; 95% CI, 0.4-0.9) and highest (AOR, 0.8; 95% CI, 0.6-1.2) tertiles for cholesterol. There was no evidence of effect modification. CONCLUSIONS: A possible weak effect of increased risk of gastroschisis associated with higher intakes of total fat or saturated fat was found in the NBDPS; however, this did not help to explain why younger aged women are at greater risk of having an infant with this type of birth defect.

Adolescent↗

PubMed2006

Teratogen update: pseudoephedrine.

Pseudoephedrine is contained in decongestants such as the Sudafed line of products. It is an alpha-adrenergic receptor agonist, which causes blood vessel constriction, including the therapeutic effect of reducing airflow resistance in the nasal cavity. Pseudoephedrine is one of the most commonly used medications in pregnancy, with an estimated 25% of women exposed. It has been demonstrated that alpha-adrenergic receptor agonists slow uterine blood flow, but their effects have not been studied in relation to most reproductive outcomes in animals or humans. Two analyses of health maintenance organization pharmacy data identified 9 malformed infants among 902 first-trimester pseudoephedrine exposures, suggesting no association with birth defects overall; however, studies of such data sets often lack sufficient power to identify risks for specific birth defects. The related compounds, epinephrine, ephedrine, and phenylephrine, have been associated with hemorrhages and cardiovascular and limb malformations in animal models. Risk of ventricular septal defects was associated with decongestant use in pregnant women in 1 recent study. The vasoconstrictive effects of these drugs raise the hypothesis that their use in early pregnancy might increase the risk of vascular disruption defects. Case-control studies, which often do have power to identify risks related to specific birth defects, have explored this hypothesis. Decongestant use in the first trimester has been associated with small increases in risks of 3 defects thought to arise, at least in some instances, from vascular disruption-gastroschisis, small intestinal atresia, and hemifacial microsomia. These findings are somewhat consistent in terms of magnitude of effect and suggest that risks are even greater among women also exposed to the vasoconstrictive effects of cigarette smoking. There are, however, limitations to these studies, including the possibilities of inaccurate recall of exposures and confounding by indication. In addition, the majority of decongestant use is in oral form and the question of whether intranasal formulations carry risk has not been adequately addressed.

Abnormalities, Drug-Induced↗

PubMed2006

Can folic acid protect against congenital heart defects in Down syndrome?

BACKGROUND: Several studies have suggested a protective effect of folic acid (FA) on congenital heart anomalies. Down syndrome (DS) infants are known to have a high frequency of heart anomalies. Not all children with DS suffer from heart anomalies, which raises the question whether maternal factors might affect the risk of these anomalies. Our objectives were to investigate whether first-trimester FA use protects against heart anomalies among DS children. METHODS: Women with liveborn DS children participating in the Slone Epidemiology Center Birth Defects Study between 1976 and 1997 were included. We performed case-control analyses using DS, with heart anomalies as cases and DS, without heart anomalies as controls. Subanalyses were performed for defects that have been associated with FA in non-DS populations (conotruncal, ventricular septal [VSD]) and for those that are associated with DS (ostium secundum type atrial septal defects [ASD] and endocardial cushion defects [ECD]). Exposure was defined as the use of any FA-containing product for an average of at least 4 days per week during the first 12 weeks of pregnancy, whereas no exposure was defined as no use of FA in these 12 weeks. RESULTS: Of the 223 cases, 110 (49%) were exposed versus 84 (46%) of the 184 controls. After adjustment for possible confounders, no protective effect of FA was found on heart anomalies overall (OR 0.95, 95% CI: 0.61-1.47) nor separately for conotruncal defects, VSDs, ASDs, or ECDs. CONCLUSIONS: Our study does not show a protective effect of FA on heart anomalies among infants with DS.

Dietary Supplements↗

PubMed2006

Alcohol consumption and time to recognition of pregnancy.

OBJECTIVES: Despite warnings to abstain from alcohol, American women who are or could become pregnant still drink. This study evaluates whether women who consume alcohol are at an increased risk of recognizing pregnancy later than women who do not, adjusting for confounding factors that have been associated with alcohol consumption during pregnancy. METHODS: The sample included 863 control women from a multisite case-control study conducted from 1996 to 2002 in the United States and Canada. Telephone interviews were conducted with mothers by trained nurse interviewers who administered standardized questionnaires on demographic and reproductive factors, and pregnancy exposures. RESULTS: Alcohol consumption was classified as none (42.0%), occasional (31.9%), regular (15.6%), and heavy (10.5%). Time to recognition of pregnancy was calculated as the date pregnancy was suspected minus the last menstrual period date (median: 31 days; range: 7-227 days). Unadjusted Cox proportional hazard models found that regular drinkers, but not heavy drinkers, had a significantly higher risk of recognizing pregnancy later than non-drinkers. However, this association went away after adjustment for demographic factors. Among women with unplanned pregnancies, heavy alcohol intake was associated with a 45% increased hazard ratio, compared to 0.80 for women with planned pregnancies; however, this finding was not statistically significant. CONCLUSIONS: While time to pregnancy recognition did not vary among drinkers and non-drinkers, results from this study reiterate previous findings that pregnant women consume alcohol, and that drinkers share social and demographic characteristics that could be used to target public health interventions.

Adult↗

PubMed2006

Nausea and vomiting in pregnancy: maternal characteristics and risk factors.

Nausea with or without vomiting (NVP) is probably the most frequently reported medical complaint of pregnancy, but few studies have considered risk factors for its development. We used data from an ongoing epidemiological study of pregnancies in four regional centres. Mothers of infants with congenital malformations (n = 17,158) and a sample of normal infants (n = 5,329) were interviewed within 6 months of delivery by trained nurse-interviewers using a standardised questionnaire. For all risk factors investigated, odds ratios and 95% confidence intervals were calculated using multiple logistic regression, controlling for potential confounders. The cumulative incidence (risk) of NVP was 67%. The risk of NVP and its timing during pregnancy were similar for mothers of malformed and normal infants, so data were combined. No changes in the NVP risk were observed over the 20-year study period. The risk decreased with increasing age, but increased with increasing gravidity. The risk also increased with increasing number of prior miscarriages. Further, within each gravidity category, the risk was higher for twin births than for singletons. Women who reported onset of NVP after the first trimester differed demographically from women whose NVP began earlier: they were less-well educated, had lower incomes, and were more likely to be black. The finding that the number of prior pregnancies, both complete and incomplete, and number of fetuses independently appear to increase the risk of NVP suggests a fetal 'dose' effect. Together with selected demographic characteristics that differentiate early- vs. late-onset NVP, these findings warrant further investigation.

Abortion, Spontaneous↗

PubMed2005

Gulf War veterans and hemifacial microsomia.

BACKGROUND: Concerns have been raised that more infants with Goldenhar syndrome were born to U.S. Gulf War veterans than expected. Goldenhar syndrome is considered a variant of the malformation hemifacial microsomia (HFM). We used data collected from a case-control study of HFM to estimate risk in relation to parental military service and, in particular, Gulf War service. METHODS: Cases with HFM who were three years old or younger were identified at craniofacial clinics in 24 U.S. cities and matched to controls by age and pediatrician. The mothers of 232 cases and 832 controls were interviewed between April 1996 and November 2002 about pregnancy events and exposures, including military service before the child was born and Gulf War deployment five to 11 years before the child was born. Odds ratios were adjusted for family income, race, and body mass index in early pregnancy. RESULTS: Four (1.7%) case mothers and 10 (1.2%) control mothers served in the military. Among fathers, 30 (12.9%) cases and 100 (12.0%) controls served in the military. The parents of four (1.7%) cases and 23 (2.8%) controls served in the Gulf War (multivariate adjusted odds ratio [MVOR], 0.8; 95% confidence interval [CI], 0.3-2.3). All four case parents with Gulf War service were in the Army compared to 9 of 23 control parents. The MVOR for parental Gulf War service in the Army was 2.8 (95% CI, 0.8-9.6). The corresponding MVOR for any parental service in the Army was 2.4 (95% CI, 1.4-4.2), based on 22 cases and 45 controls. CONCLUSIONS: The risk of HFM in offspring was not associated with parental service in the Gulf War five to 11 years before birth. The odds ratio for service in the Army was independent of Gulf War service and was associated with a modest increase in risk. Our findings for service in the Army may be confounded by unmeasured lifestyle factors.

Case-Control Studies↗

PubMed2005

Trends and predictors of folic acid awareness and periconceptional use in pregnant women.

OBJECTIVE: The purpose of this study was to describe recent trends in folic acid awareness and use in the periconceptional period among pregnant women in relation to maternal sociodemographic and other relevant factors. STUDY DESIGN: From 1988 to 2002, 16,555 women from the Slone Epidemiology Center Birth Defects Study were interviewed about medication use before and during pregnancy (which included multivitamins and folic acid), about whether they were aware of any vitamins that might decrease the risk of birth defects, and about sociodemographic and medical factors. RESULTS: Awareness of folic acid benefits increased from 0 in 1988 to 50% in 1996 and thereafter. The use of folic acid in the periconceptional period increased from 15% in 1988 to 40% in the last few years. Maternal education was a strong independent predictor of both awareness and use as were ethnicity, whether the pregnancy was wanted, family income, and whether a health care provider was consulted before planning. CONCLUSION: Promoting the use of folic acid supplements, particularly among these disadvantaged groups, is essential to further decrease the prevalence of neural tube defects.

Adult↗

PubMed2005

Use of over-the-counter medications during pregnancy.

OBJECTIVE: The most common medications used in pregnancy are nonprescription or over-the-counter medications, although there has been little research on their risks or safety. We describe the patterns of over-the-counter medication use among pregnant women. STUDY DESIGN: Data were collected in 2 case-control studies of birth defects: the Slone Epidemiology Center Birth Defects Study (BDS) and the National Birth Defects Prevention Study (NBDPS). RESULTS: Among 7563 mothers of malformed and nonmalformed offspring in the Slone Epidemiology Center Birth Defects Study and 2970 mothers of nonmalformed offspring in the National Birth Defects Prevention Study, acetaminophen, ibuprofen, and pseudoephedrine were used by at least 65%, 18%, and 15%, respectively. Among women in the Slone Epidemiology Center Birth Defects Study, the use in pregnancy of aspirin and chlorpheniramine decreased from 1976 to 2004 and of ibuprofen, pseudoephedrine, diphenhydramine, dextromethorphan, and guaifenesin increased. Among women in the National Birth Defects Prevention Study, the use of acetaminophen, pseudoephedrine, diphenhydramine, and guaifenesin was higher during pregnancy than before pregnancy. CONCLUSION: Findings show that over-the-counter medications are used by most pregnant women. Studies that examine specific over-the-counter medications in relation to specific birth defects are necessary to better inform pregnant women about risks and safety.

Acetaminophen↗

PubMed2005

Maternal obesity, gestational diabetes, and central nervous system birth defects.

BACKGROUND: Maternal obesity and diabetes are both associated with increased risk of congenital central nervous system (CNS) malformations in the offspring and may share a common underlying mechanism. Our objective was to evaluate whether gestational diabetes influenced the association of prepregnancy maternal obesity and risks for CNS birth defects. METHODS: This Texas population-based case-control study evaluated births occurring January 1997 through June 2001. Data came from structured telephone interviews. Cases (n=477) were mothers of offspring with anencephaly (n=120), spina bifida (n=184), holoprosencephaly (n=49), or isolated hydrocephaly (n=124). Controls (n=497) were mothers of live infants without abnormalities randomly selected from the same hospitals as cases. Response rates were approximately 60% for both cases and controls. We evaluated maternal obesity (body mass index > or =30.0 kg/m) and risks for CNS birth defects, as well as whether gestational diabetes influenced the risks. RESULTS: After adjusting for maternal ethnicity, age, education, smoking, alcohol use, and periconceptional vitamin use, obese women had substantially increased risks of delivering offspring with anencephaly (odds ratio=2.3; 95% confidence interval=1.2-4.3), spina bifida (2.8; 1.7-4.5), or isolated hydrocephaly (2.7; 1.5-5.0), but not holoprosencephaly (1.4; 0.5-3.8). Odds ratios were higher for the joint effects of maternal obesity and gestational diabetes, with evidence for interaction on a multiplicative scale. CONCLUSIONS: Maternal obesity and gestational diabetes may increase the risk of CNS birth defects through shared causal mechanisms.

Central Nervous System Diseases↗

PubMed2005

Methylenetetrahydrofolate reductase polymorphisms and the risk of gestational hypertension.

BACKGROUND: Evidence on the association of 5,10 methylentetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in women with gestational hypertension is inconsistent. It is also unknown whether the fetal genotype is relevant, or whether folic acid supplementation modifies this association. METHODS: The study population was composed of U.S. and Canadian white women with nonmalformed infants participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery regarding multivitamin use in pregnancy and the occurrence of gestational hypertension, among other factors. DNA was extracted from cheek swabs and gene alleles determined by restriction fragment length polymorphism analysis. We compared the prevalence of the 677TT/CT and 1298CC/AC genotypes between cases with gestational hypertension (54 mothers and their 51 offspring) and controls (100 mothers and their 99 offspring). We also estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression to control for geographic region and calendar year. RESULTS: The T allele was present in 69% of women with gestational hypertension versus 57% of control women (compared with 677CC, OR = 1.9; 95% CI = 0.9-4.0). The offspring of case and control women had a 677TT/CT genotype prevalence of 68% and 47%, respectively (2.4; 1.1-5.0). Among women supplemented with folic acid during the first 5 months of pregnancy, the ORs for maternal and fetal 677TT/CT genotypes were 0.9 (0.3-2.5) and 2.1 (0.7-6.0), respectively. Neither maternal nor fetal 1298CC/AC genotypes were associated with an increased risk of gestational hypertension. CONCLUSION: Maternal and fetal MTHFR C677T polymorphism may be associated with a moderately increased risk of gestational hypertension, and there is a suggestion that this association may be diminished among women receiving folate supplementation during pregnancy.

Adult↗

PubMed2004

Maternal use of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), and muscular ventricular septal defects.

BACKGROUND: Muscular ventricular septal defects (mVSDs) are the most common congenital heart defects. Previous studies have suggested maternal use of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), and/or fever as risk factors. We evaluated the association between mVSDs and maternal use of acetaminophen or NSAIDs adjusting for fever. METHODS: Infants with nonsyndromic mVSDs (cases) and without birth defects (controls), with gestational age > or =37 weeks and their mothers were enrolled in the National Birth Defects Prevention Study. Two exposure periods were defined: the first trimester of pregnancy, and one month before pregnancy through delivery. Mothers reporting fever or medication use at least once during either period were considered exposed. Adjusted odds ratios and 95% confidence intervals were estimated independently for each exposure period. RESULTS: The analysis included 168 cases and 692 controls. Two case groups were evaluated: all mVSD infants (n = 168) (including those with associated minor cardiac defects or noncardiac defects), and infants with isolated mVSDs (n = 133). Mothers of cases were less likely to be African-American than Caucasian (OR, 0.36; 95% CI, 0.18, 0.73). Approximately equal numbers of case mothers and control mothers (10.4 versus 9.7%, respectively) reported at least one febrile episode during the first trimester. Neither acetaminophen nor NSAID exposure was significantly associated with mVSDs. This was true for both case groups and both exposure periods. CONCLUSIONS: Significant associations were not detected between the occurrence of mVSDs and maternal use of NSAIDs or acetaminophen adjusting for maternal fever, nor were they detected between maternal fever and mVSDs.

Acetaminophen↗

PubMed2004

Vasoactive exposures, vascular events, and hemifacial microsomia.

BACKGROUND: Based on experimental evidence and clinical observations, hemifacial microsomia (HFM) is one of several structural anomalies that are postulated to result from vascular disruption. We collected data in a case-control study to identify whether vasoactive exposures or vascular events during early pregnancy affect the risk of HFM. METHODS: Cases with a diagnosis of HFM were identified at craniofacial centers in 26 cities across the United States and Canada, from 1996 to 2002. Controls were matched to cases by age and pediatrician practice. Mothers of 230 cases and 678 controls were interviewed about pregnancy events and exposures. Case and control mothers were compared for early pregnancy use of vasoactive medications, cigarettes, and alcohol; singleton or multiple gestation; and diabetes, hypertension, or vaginal bleeding in the first half of pregnancy. RESULTS: Odds ratios (ORs) were significantly increased for vasoactive mediation use (OR, 1.9 overall; OR, 4.2 among smokers), multiple gestations (OR, 10.5), and diabetes (OR, 6.0). Vaginal bleeding in the second trimester and heavy alcohol intake were associated with increased risks, but the estimates were based on small numbers and, therefore, are unstable. No associations were observed for cigarette smoking without vasoactive medication use, hypertension, and vaginal bleeding in the first trimester. CONCLUSIONS: The increased risks of HFM associated with vasoactive medication use, multiple gestations, diabetes, and second trimester vaginal bleeding appear collectively to support the hypothesis that vascular disruption is one etiology for HFM, because each of these factors is related to effects on blood vessels.

Alcohol Drinking↗

PubMed2004

Demographic and reproductive factors associated with hemifacial microsomia.

OBJECTIVE: To identify demographic and reproductive risk factors for hemifacial microsomia in offspring. DESIGN: In a case-control study, maternal interviews were conducted within 3 years after delivery. Cases with hemifacial microsomia were ascertained from craniofacial centers in 26 cities in the United States and Canada. Controls were patients of the cases' pediatricians. Two hundred thirty-nine cases were compared with 854 controls. Odds ratios for various infant and maternal factors were estimated. RESULTS: Cases had lower birth weights, were more often male or a twin, and had more relatives with craniofacial malformations or hearing loss than controls. Case mothers had lower family incomes, had a lower body mass index, had more vaginal bleeding in the second trimester, and were more likely to have had a spontaneous abortion in a previous pregnancy. CONCLUSIONS: Nonmodifiable factors (age and parity) were not associated with hemifacial microsomia risk. Factors that are related to poverty (low family income, late recognition of pregnancy, and low body mass index) are associated with an increase in risk. High risk estimates for multiple pregnancies and second-trimester vaginal bleeding suggest a vascular etiology.

Case-Control Studies↗

PubMed2003

Case-crossover and case-time-control designs in birth defects epidemiology.

The case-crossover and the case-time-control designs can be used to evaluate the effect of intermittent exposures on the risk of acute events. To explore how birth defects epidemiology could benefit from these approaches, the authors compared them with a traditional case-control study design that evaluated the association between use of folic acid antagonists during the second and third pregnancy months and the risk of cardiovascular defects. Among 3,870 cases and 8,387 control infants in the Slone Epidemiology Center Birth Defects Study (1976-1998), the odds ratio was 2.3 (95% confidence interval (CI): 1.4, 3.9). The case-crossover approach compared folic acid antagonist use between the 2-month embryologically sensitive period (case window) and the 2 months preceding the last menstrual period (control window) among mothers of case infants (odds ratio = 1.0, 95% CI: 0.5, 2.0). Although it controls between-person confounding and avoids issues of control selection, this design may be biased by time trends of exposure prevalence during pregnancy. The case-time-control design, which adjusts for exposure time trends under certain assumptions, yielded an odds ratio of 2.9 (95% CI: 1.2, 7.2), but it requires controls. In the presence of gestational time trends of exposure, the new designs do not offer clear advantages over the case-control design.

Case-Control Studies↗

PubMed2003

Epidemiologic analysis of maternal factors and amniotic band defects.

BACKGROUND: The group of defects identified as amniotic bands includes amnion rupture sequence (ARS) and body wall complex (BWC). Little is known about risk factors for either ARS or BWC, except that maternal age has been shown to affect risk inversely. METHODS: The present analysis used data collected from 1976 to 1998 as part of an ongoing case control study of birth defects in the metropolitan areas of Boston, Philadelphia, and Toronto. There were 73 cases with ARS and 11 cases with BWC. ARS cases were further subdivided according to affected structures: there were 53 with only limbs affected (ARS-L) and 20 with nonlimb defects with or without limb defects (ARS-NL). The control group comprised 12,227 subjects with other major malformations. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors. RESULTS: Multivariate adjusted odds ratios for BWC were increased more than threefold for maternal age < 25 years and maternal education < 12 years, but neither estimate was statistically significant. Corresponding estimates for ARS-L and ARS-NL ranged from 13 to 1.5 and also were not statistically significant. Cases were less likely to be white non-Hispanic than controls and the odds ratio for ARS-NL excluded the null. The multivariate adjusted odds ratio (MVOR) for unplanned pregnancy and BWC was 1.9 (95% confidence interval, 0.5-6.7) compared to 1.2 and 1.0 for ARS-L and ARS-NL, respectively. Neither parity nor maternal smoking was associated with any case group. The MVORs for first trimester acetaminophen use in relation to ARS-L and ARS-NL risks were 2.1 (1.1-3.9) and 3.4 (1.1-10.3), respectively. Such use was less common among BWC cases (MVOR was 0.4; 0.1-1.4). CONCLUSIONS: Risk estimates tended to be similar for ARS-L and ARS-NL cases but different for BWC cases, suggesting different etiologies. These data suggest that young maternal age, low maternal education, unplanned pregnancy, and non-white/non-Hispanic race/ethnicity might increase the risk of BWC in offspring. Inceased risks for acetaminophen use should be interpreted with caution because they may be confounded by indication for use.

Acetaminophen↗

PubMed2003

Association between prepregnancy maternal body mass index and the risk of having an infant with a congenital diaphragmatic hernia.

BACKGROUND: A previous study observed that women who are underweight prior to conception were significantly more likely to have infants affected by congenital diaphragmatic hernia (CDH). The objective of the current study was to examine the association between maternal body mass index and the risk of a CDH-affected offspring based on a larger number of cases of CDH. METHODS: A case control study was conducted using data collected by the Boston University Slone Epidemiology Center Birth Defects Study, which identifies infants with major malformations who are born in the metropolitan area surrounding Boston, Massachusetts; Philadelphia, Pennsylvania; and Toronto, Ontario, Canada. Control infants were selected from infants without malformations who were born in the same areas. The study included 85 cases of CDH and 655 controls delivered between 1993 and 1997. RESULTS: After adjustment for maternal education and maternal age, we observed that women who were thin or underweight for their height (body mass index < or = 19.0 kg/m2) had an increased risk of having an infant with isolated CDH (OR = 1.9; 95% CI = 0.92-4.1), but no increase in the risk of having a CDH infant with multiple defects (OR = 0.86; 95% CI = 0.29-2.6) compared with all other women. CONCLUSIONS: Although our finding for isolated CDH was not statistically significant (P = 0.08), it suggests that the offspring of thin or underweight women may have an increased risk of isolated CDH. This finding requires confirmation. If it is confirmed, further research on factors associated with being underweight should be explored such as diet, exercise, and use of drugs.

Body Mass Index↗