Congenital Malformations In Offspring Research Articles

Folic acid supplementation: too much of a good thing?

Morrow and colleagues1 report on the association of folate use and major malformations in women with epilepsy (see page 506) .1 The data, derived from their prospective study of pregnancy...

Maternal asthma, asthma medication use, and the risk of congenital heart defects

Asthma is a common problem that complicates pregnancy. Several drugs are considered acceptable for use during pregnancy, although none have been classified as safe. Few studies have assessed the health impact of maternal asthma/medication use on the fetus. A population-based case-control study was conducted in New York State to determine if cardiac congenital malformations in offspring were associated with maternal use of asthma medication and/or maternal asthma. Cases were cardiac anomalies in the New York State Congenital Malformations Registry. Controls were live births without any major birth defects randomly selected from birth certificates and frequency matched by year of birth. Data were collected through a 30 min telephone interview. Exposure was maternal asthma/medication use, maternal asthma/no medication use, no asthma/medication use, and no asthma/no medication use (reference). A total of 502 (59.4%) cases and 1,066 (53.8%) controls participated. A positive association was seen between any heart defect and women with asthma who used medication (OR 2.38; 95% CI: 1.18, 4.82). No significant associations were observed between heart defects and either women with asthma who did not use medication or women without asthma who used asthma medications. When considering types of medication used, offspring of women with asthma who used bronchodilators had an increased risk of any heart defect (OR 2.20; 95%CI: 1.05, 4.61). These results suggest that both maternal asthma status (controlled vs. uncontrolled; severe vs. mild) and asthma medication use, particularly bronchodilators, may play a role in cardiac malformations in offspring.

Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register

Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register

Radiotherapy for childhood cancer and risk for congenital malformations in offspring: a population‐based cohort study

Offspring of childhood cancer survivors may be at risk of genetic disease due to the mutagenic cancer treatments received by their parents. Congenital malformations were evaluated in a population-based cohort study of 1715 offspring of 3963 childhood cancer survivors and 6009 offspring of 5657 survivors' siblings. The Danish Central Population Register, Cancer Registry and Hospital Register were used to identify study subjects and congenital malformations. Gonadal and uterine radiation doses were characterized based on standard radiation-treatment regimens. The prevalence of congenital malformations at birth in offspring of survivors (44 cases, 2.6%) was slightly higher but not statistically different from that of offspring of siblings (140 cases, 2.3%) [prevalence proportion ratio (PPR), 1.1; 95% confidence interval, 0.8-1.5] or of the general population (observed-to-expected ratio, 1.2; 0.9-1.6). Including malformations diagnosed later in life did not change the ratios appreciably. The risk for malformations was slightly higher in the offspring of irradiated parents than in that of non-irradiated parents (PPR 1.2 vs 1.0) but was unrelated to gonadal dose. This study provides evidence that cancer therapy of children does not increase the risk for malformations in their offspring. Continued monitoring of genetic risks among their offspring, however, is warranted.

Treatment of asthma during pregnancy: more solid evidence needed

In this issue of Thorax , a paper by Tata and colleagues1 assesses the association between maternal asthma and gestational exposure and asthma medications with the risk of congenital malformation in offspring using The Health Improvement Network primary care database ( see page 981 ). Their findings showed that gestational exposure to commonly used asthma medications seems to be safe, although a moderate teratogenic risk of cromones cannot be excluded. This is important information for many doctors, mainly pulmonologists and allergologists involved in the treatment of asthma in pregnant women. It indicates that we can approach the pregnant patient with asthma in the traditional manner, without major concerns and using all the available treatment options with the exclusion of cromones which, in any case, currently represent an unusual therapeutic choice. The results of this study enable us to reassure our pregnant patients. We have all found that one of the most complicated aspects of the work of a chest physician is to convince a pregnant patient with asthma to adhere to prescribed therapy. Several surveys have shown that women decrease and/or stop asthma medications during early pregnancy, probably because they are concerned about the safety of asthma medications during pregnancy.2–4 Conversely, physicians appear to be reluctant to prescribe asthma medications for pregnant women. A multicentre study found that pregnant women with asthma were significantly less likely to be prescribed corticosteroids in the emergency department: only 44% of pregnant women were treated with corticosteroids compared with 66% of non-pregnant women.5 Those who were admitted to hospital were less likely to be treated with corticosteroids at discharge and were almost three times …

Folic acid use and major congenital malformations in offspring of women with epilepsy: a prospective study from the UK Epilepsy and Pregnancy Register

Objective: In the general population, folic acid supplementation during pregnancy has been demonstrated to reduce the frequency of neural tube defects (NTDs) and other major congenital malformations (MCMs). It is...

Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study

Background:Clinical advice to pregnant women with asthma is to maintain optimal therapeutic management; however, potential adverse effects of asthma treatments on fetal development remain uncertain. A study was undertaken to...

Duration of antidepressant use during pregnancy and risk of major congenital malformations

Antidepressant use during the gestational period is a controversial topic. To determine whether duration of antidepressant use during the first trimester increases the risk of major congenital malformations in offspring of women diagnosed with psychiatric disorders. A case-control study was performed among women who had been pregnant between January 1998 and December 2002. Data were obtained from a Medication and Pregnancy registry, built by linking three databases from the province of Quebec, and a self-administered questionnaire. Women eligible for this study had to be 15-45 years old at the beginning of pregnancy, have at least one diagnosis of psychiatric disorder before pregnancy, have used antidepressants for > or =30 days in the year prior to pregnancy and have a pregnancy ending with a delivery. Cases were defined as any major congenital malformation diagnosed in the offspring's first year of life. Odds ratios, adjusted for relevant confounders, were estimated using logistic regression. Among the 2329 women meeting the inclusion criteria, 189 (8.1%) infants were born with a major congenital malformation. Duration of antidepressant use during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations: 1-30 days v. 0 day, adjusted OR=1.23 (95% CI 0.77-1.98); 31-60 days v. 0 day, adjusted OR=1.03 (95% CI 0.63-1.69); > or =61 days v. 0 day, adjusted OR=0.92 (95% CI 0.50-1.69). These data do not support an association between duration of antidepressant use during the first trimester of pregnancy and major congenital malformations in the offspring of women with psychiatric disorders. These findings should help clinicians decide whether to continue antidepressant therapy during pregnancy.

Paternal age as a risk factor for congenital malformations

The role of advanced maternal age as a risk factor for congenital malformations in offspring is known. However, the influence of paternal age is not clear. To evaluate the association between advanced paternal age and the risk for congenital malformations. Analysis of maternal and paternal age of cases (malformed newborns) and controls from ECLAMC Database (Latin American Collaborative Study of Congenital Malformations) registered at the University of Chile Clinical Hospital during the decade from Jan 1 1997 to Dec 31 2006. Newborns and stillborns were grouped according to maternal age into 6 intervals. In each interval, paternal ages of cases and controls were compared. The inverse procedure was performed to assess maternal age effect. Other variables as gestational age and birth weight were analyzed for the intervals of maternal and paternal ages. No significant differences were observed in paternal age between cases and controls in any of the intervals of maternal age. However, mean maternal age was higher for cases than for controls (p =0,0149). Gestational age and birth weight depend more on being case or control than on the age of parents. No differences in paternal age were observed between cases and controls in this series of newborns.

Risk of Hypospadias in Offspring of Women Using Loratadine during Pregnancy

Loratadine, a second-generation antihistamine, is commonly used to treat seasonal allergies. Some studies have suggested that use of loratadine by pregnant women increases the risk of hypospadias in male offspring. This meta-analysis was designed to assess the strength of the association between loratadine and hypospadias. To locate pertinent articles published in any language from January 1989 until August 2007, we searched electronic databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS, CINAHL and others), conference proceedings and bibliographies. Studies were eligible for this analysis if they were cohort, case-control or case series studies that reported the incidence of hypospadias in the offspring of women who were or were not exposed to loratadine during pregnancy. Two authors independently extracted information on study design, participant characteristics, measures of outcome, control for potential confounding factors and risk estimates using a standardized data collection form. The Newcastle-Ottawa Scale was then used to assess the quality of each study. We used a random-effects meta-analysis model to combine the risk data. In 1402 potentially relevant titles, we found three case-control studies and seven cohort studies that reported the incidence of hypospadias or other congenital malformations in offspring of women who did or did not use loratadine during pregnancy. Together the studies in our meta-analysis provided information about 453 053 male births in Brazil, Canada, Denmark, Israel, Italy, Sweden, the UK and the US.Of 2694 male infants born to women using loratadine, 39 (1.4%) had hypospadias. Of 450 413 male infants born to women not using loratadine, 4231 (0.9%) had hypospadias. Women who used loratadine during pregnancy were not significantly more likely to have a son with hypospadias (unadjusted odds ratio [OR] 1.27, 95% CI 0.73, 2.23; adjusted OR 1.28, 95% CI 0.69, 2.39). The results of our systematic review and meta-analysis of controlled observational studies indicate that the use of loratadine during pregnancy does not significantly increase the risk of hypospadias in male offspring.

Adverse reproductive outcomes among male painters with occupational exposure to organic solvents

Objectives: To assess the risks of reproductive disorders and birth defects in offspring of male painters with exposure to organic solvents, and to determine the shape of the dose-response relationship....

Antiepileptic Drug Use of Women With Epilepsy and Congenital Malformations in Offspring

Antiepileptic Drug Use of Women With Epilepsy and Congenital Malformations in Offspring

Maternal analgesic use and cardiovascular malformations

Certain drugs used during pregnancy have been associated with an increased risk of congenital malformations in offspring. Whether maternal use of analgesics increases the risk of cardiovascular malformations (CVM) is unclear. We used data from the Baltimore-Washington Infant Study, a population-based case-control investigation of environmental factors and CVM, to examine CVM and maternal analgesic use during the periconceptional period (3 months before and 3 months after conception). During the period 1981–1989, 2,842 infants with CVM (case infants) and 3,516 nonmalformed infants (control infants) were ascertained with information on maternal drug use elicited from home interviews. We compared case and control infants on frequency of maternal use of analgesics during the periconceptional period using odds ratios (ORs) and 95% confidence intervals (CIs) for ORs. Fisher's Exact CIs for ORs were estimated when one or more cell counts fell below 5. Periconconceptional use of any analgesic among control mothers was 20.0%, with the more commonly used analgesics being medications containing aspirin (10.2%), nonsteroidal anti-inflammatory drugs (NSAIDs) (5.9%), and opioids (5.4%). Analyses type of analgesic and CVM diagnosis identified associations of: ibuprofen with transposition of the great arteries (TGA) (OR = 2.1, CI = 1.3, 3.4); atrioventricular septal defects (OR = 1.8, CI = 1.1, 2.8); and membranous ventricular septal defects (OR = 1.5, CI = 1.1, 2.1). Medications containing codeine were also associated with TGA (OR = 1.9, CI = 1.1, 3.2). Maternal use of ibuprofen or codeine containing analgesics during the periconceptional period might be associated with an increased risk of certain cardiovascular malformations in infants. Further investigation into these findings is needed to examine potential confounding by indication.

Antiepileptic drug use of women with epilepsy and congenital malformations in offspring

To compare the risk for congenital malformations in offspring between women with epilepsy being treated with antiepileptic drugs (AEDs) during pregnancy and those who discontinued their antiepileptic medication before pregnancy in a population-based cohort of female patients with epilepsy. All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the first time during 1985 to 1994 were identified from the Social Insurance Institution of Finland. Information on births during 1991 to 2000 was obtained from the National Medical Birth Registry. Information on AED use during pregnancy and on pregnancy outcomes was abstracted from medical records. Congenital malformations were more common among offspring of women on antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially higher in the offspring of patients using valproate as monotherapy (OR = 4.18; 95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11) than of untreated patients. Polytherapy without valproate was not associated with increased risk of malformations. Excess risk was confined to patients using valproate during pregnancy. The risk for malformations was not elevated in offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as monotherapy or polytherapy without valproate).

Antiepileptic Drugs Are Not All Equally Teratogenic

These researchers aimed to clarify the risk for congenital malformations in offspring of women with epilepsy treated with antiepileptic drugs (AEDs). Using a large, population-based database in Finland that records pharmaceutical reimbursements, available to all citizens, the researchers identified all women with epilepsy who were eligible to receive full reimbursement for AEDs over a 9-year period. The researchers retrospectively identified 2450 children born to this cohort and reviewed their records for evidence of any congenital malformation. They compared risks associated with (1) use during the …

Congenital malformations in offspring of Hispanic and African-American women in California, 1989-1997.

Little is known about risks of most specific birth defects among infants born to U.S.-born and foreign-born Hispanic or African-American women. Using data from a large population-based registry, we explored risks of selected congenital malformation phenotypes in offspring of U.S.-born and foreign-born Hispanic and African-American women, relative to non-Hispanic white women, in California. Approximately 2.2 million live births and stillbirths occurred during the ascertainment period, 1989-1997. Information on maternal racial-ethnic background and other covariates was obtained from birth certificate and fetal death files. Adjusted relative risks (ARRs) for the 20 groupings of malformations designated by three-digit British Pediatric Association (BPA) codes ranged from 0.6 (genital organ malformations, among infants born to foreign-born Hispanics) to 1.7 (anencephaly, also among infants born to foreign-born Hispanics). Grouping by four-digit BPA codes revealed that among infants born to U.S.-born Hispanics, 46 of the ARRs were < or = 0.8 and 12 were > or = 1.3; among infants born to foreign-born Hispanics, 75 of the ARRs were < or = 0.8 and 15 were > or = 1.3; and among infants born to African-American women, 45 ARRs were < or = 0.8 and 25 were > or = 1.3. For each racial-ethnic group of women, the observed variability in risks covered most organ systems. Although the results suggested that (in comparison with non-Hispanic whites) each racial-ethnic group was more likely to have reduced risk for specific defects (rather than elevated risk), in general, the range of the relative risks was comparatively narrow.

Congenital malformations in births with orofacial clefts among 3.6 million California births, 1983-1997.

Few population-based epidemiologic data are available on malformation phenotypes that co-occur with orofacial clefts. We explored the occurrence of structural congenital malformations in offspring with cleft palate (CP) and in offspring with cleft lip with or without CP (CLP), using data from a population-based active surveillance system. Ascertainment was performed among 3548991 liveborn and 23239 stillborn offspring of California women who delivered in nonmilitary hospitals during the period, 1983-1997. Structural congenital malformations were found in 91888 births. Among them, 2343 had CP and 4072 had CLP. Malformations were grouped according to 3- and 4-digit codes of the British Pediatric Association (BPA). Prevalences of each malformation grouping, defined by these codes, were calculated among: (1). all births with CP; (2). all births with CLP; (3). all births without CP or CLP but with another structural malformation; and (4). all births in the population at risk. These various prevalence measures were the basis of estimating relative risks. Observed relative risks indicated that some phenotypes were more likely and some were less likely to co-occur with either CP or CLP, with relative risks ranging from 0.5 to 2.4. For both CP and CLP, estimated relative risks were highest for malformations involving the respiratory system and lowest for spina bifida. The exclusion of all births (n = 10702) with chromosomal anomalies from comparisons did not materially alter observed relative risk estimates. Computations extended to 4-digit level BPA codes revealed elevated risks for a number of more specific diagnoses seen within the larger (3-digit level) groupings defined as eye, ear, respiratory, upper alimentary tract, and other musculoskeletal anomalies. In this large population-based cohort of infants and fetuses with CLP or CP, we observed several noncleft malformation groupings to be more common and others to be less common in their co-occurrence with orofacial clefts relative to their co-occurrence with any other malformation. These observed patterns tended to be similar for CP and for CLP.

Congenital malformations in offspring of diabetic mothers--animal and human studies.

Congenital malformations in offspring of diabetic mothers--animal and human studies.

Aspirin consumption during the first trimester of pregnancy and congenital anomalies: A meta-analysis

Objective: The purpose of this study was to determine, on the basis of published reports, whether aspirin use during the first trimester of pregnancy is associated with an increased risk of congenital malformations. Study design: We reviewed the literature for published studies that reported exposure to aspirin during the first trimester of pregnancy and congenital malformations. Two reviewers independently determined whether a study should be included in the final analysis and extracted the data. We calculated the pooled odds ratio and 95% CI. Results: Twenty-two studies met the inclusion criteria. In the eight studies that reported an overall risk, the risk of congenital malformations in offspring of women who were exposed to aspirin was not significantly higher than that in control subjects (odds ratio, 1.33; 95% CI, 0.94-1.89). However, a significantly increased risk of gastroschisis (odds ratio, 2.37; 95% CI, 1.44-3.88) was found. Conclusion: We found no evidence of an overall increase in the risk of congenital malformations that could be associated with aspirin. Aspirin exposure during the first trimester may be associated with an increased risk of gastroschisis. (Am J Obstet Gynecol 2002;187:·1623-30.)

Congenital malformations in offspring of Vietnamese women in California, 1985-97.

Little is known about reproductive outcome risks for Vietnamese women delivering infants and fetuses in the U.S. Using data from a large population-based registry, we explored risks of selected congenital malformation phenotypes in offspring of Vietnamese women in California. Data were derived from the California Birth Defects Monitoring Program, a population-based active surveillance system for collecting information on infants and fetuses with congenital malformations using multiple source ascertainment. Approximately 3.4 million births (liveborn and stillborn) occurred during the ascertainment period, 1985-97. Information on maternal race/ethnic background was obtained from California birth certificate and fetal death files. Vietnamese women delivered 45,453 births and 1,257,853 births were delivered to non-Hispanic white women. The overall prevalence of structural congenital malformations was 1.92 among Vietnamese and 2.63 among non-Hispanic whites per 100 births and fetal deaths. Grouping by 20 3-digit malformation codes of the International Classification of Diseases-Ninth Revision revealed relative risks of 0.8 or less for spina bifida, eye, upper alimentary, genital, urinary, musculoskeletal, "other" limb, and "other" musculoskeletal anomalies, and relative risks of 1.3 or more for anencephaly and chromosomal anomalies. Grouping by the more specific 4-digit malformation codes revealed 50, among 178, malformation groupings with associated relative risks of >or=1.3 or <or=0.8. Seventeen relative risk estimates suggested elevated risks for Vietnamese births, and 33 estimates suggested lowered risks for Vietnamese, relative to non-Hispanic white births. Simultaneous adjustment for maternal age, plurality, and child sex, did not substantially alter observed risks. These data contribute to a relatively sparse literature about an important subgroup of the U.S. population, but can not elucidate whether increased or decreased risks among Vietnamese are related to potential underlying genetic susceptibilities, to cultural, social, or political differences that could modify exposures, or to the many potential combinations between susceptibilities and exposures.