Nutrient intakes in women and congenital diaphragmatic hernia in their offspring

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a severe birth defect where there is an opening in the diaphragm through which a portion of the abdominal contents protrudes into the thoracic cavity. The etiologies of CDH remain unknown, although experimental animal data suggest dietary factors might play a role. This study examined whether maternal nutrient intakes were associated with delivering infants with CDH. METHODS: We analyzed infants with isolated CDH who were born from 1997 to 2003 and recruited into the National Birth Defects Prevention Study (NBDPS), a multisite, population‐based case‐control study. Exposure data were obtained from telephone interviews, which were completed within 24 months after delivery, and were available for 377 case mothers and 5,008 control mothers. A food frequency questionnaire was used to derive nutrient intakes during the year before pregnancy. RESULTS: A crude OR of 0.6 (95% CI: 0.3–1.0) was observed for higher intake of choline. Elevated ORs (1.4 to 1.7) were found for lower intakes of choline, cysteine, methionine, and protein. Among women who took vitamin supplements, higher intakes of B vitamins (i.e., folate, vitamin B1, B2, B6, and B12), minerals (i.e., calcium, iron, magnesium, and zinc), and vitamin E were inversely associated with CDH (ORs from 0.7–0.3). Moreover, among women who did not take vitamin supplements, lower intakes of calcium, retinol, selenium, vitamin B12, and vitamin E had positive associations with CDH (ORs from 1.4 to 2.1). CONCLUSIONS: Our observations contribute to a limited body of evidence suggesting a woman's periconceptional diet might be associated with CDH in her offspring. Birth Defects Research (Part A), 2008. © 2007 Wiley‐Liss, Inc.     

Descriptive epidemiology of anophthalmia and microphthalmia, Hawaii, 1986-2001

BACKGROUND: Population-based epidemiologic data on anophthalmia and microphthalmia in the United States are limited and have come mainly from only a few states. The intent of this study was to report on the epidemiology of these eye defects. METHODS: Cases were derived from a population-based birth defects registry in Hawaii and comprised all infants and fetuses with anophthalmia and microphthalmia who were delivered during 1986-2001. Anophthalmia and microphthalmia rates per 10,000 births were determined for selected factors, and comparisons were made by calculating the rate ratios and 95% confidence intervals (CIs). RESULTS: Ninety-six cases of anophthalmia and microphthalmia were identified, with a rate of 3.21 per 10,000 live births. The eye defects were isolated in 5 cases (5.2%), and 24 cases (25.0%) had confirmed chromosomal abnormalities. The risk of anophthalmia and microphthalmia varied over time and was significantly higher for live-born infants with low birth weights and gestational ages. The anophthalmia and microphthalmia rates also varied by maternal race/ethnicity, sex, and plurality, although these differences were not statistically significant. CONCLUSIONS: Anophthalmia and microphthalmia frequently occurred with other birth defects, and the rate was consistent with that found in the literature. The risk of defects differed significantly with time period, birth weight, and gestational age. The impact of many factors on anophthalmia and microphthalmia in Hawaii was frequently consistent with that reported elsewhere.     

Conserved genetic pathways associated with microphthalmia,anophthalmia, and coloboma

The human eye is a complex organ whose development requires extraordinary coordination of developmental processes. The conservation of ocular developmental steps in vertebrates suggests possible common genetic mechanisms. Genetic diseases involving the eye represent a leading cause of blindness in children and adults. During the last decades, there has been an exponential increase in genetic studies of ocular disorders. In this review, we summarize current success in identification of genes responsible for microphthalmia, anophthalmia, and coloboma (MAC) phenotypes, which are associated with early defects in embryonic eye development. Studies in animal models for the orthologous genes identified overlapping phenotypes for most factors, confirming the conservation of their function in vertebrate development. These animal models allow for further investigation of the mechanisms of MAC, integration of various identified genes into common developmental pathways and finally, provide an avenue for the development and testing of therapeutic interventions. Birth Defects Research (Part C) 105:96–113, 2015. © 2015 Wiley Periodicals, Inc.     

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.     

Periconceptional dietary intake of myo-inositol and neural tube defects in offspring

BACKGROUND: Periconceptional intake of nutrients in addition to folic acid may contribute to neural tube defect (NTD) etiologies; a likely candidate is myo-inositol. We investigated whether maternal periconceptional dietary intake of myo-inositol influenced NTD risk. METHODS: Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. Interviews were conducted with mothers of 454 NTD cases and with mothers of 462 nonmalformed controls. A standard 100-item food frequency questionnaire was used to assess nutrient intake. RESULTS: We observed small increases in risk, with increases slightly more evident for anencephaly, associated with intakes of myo-inositol less than the highest intake quartile, e.g., risk of anencephaly was 1.3 (0.7-2.4) among fetuses whose mothers consumed lowest versus highest intakes of myo-inositol. These small increases, however, were imprecise, and also did not indicate increasing risk with decreasing level of myo-inositol intake. Adjusted risk estimates did not differ considerably from their unadjusted counterparts. CONCLUSIONS: Our results do not indicate that myo-inositol intake, as measured in this study, is strongly associated with risk of human NTDs.     

Retinol and α-tocopherol concentrations in whole fish commonly fed in zoos and aquariums

Retinol (n = 17 spp.) and α-tocopherol (n = 9 spp.) concentrations in whole fish utilized for captive animal feeding programs were determined by high-performance liquid chromatography (HPLC) following routine storage and preparation after commercial purchase by two zoological institutions. Vitamin A activity was calculated from retinol values and ranged from 55 IU/100 g (immature herring) to >2,000 IU/100 g (salmon) on an as-fed basis. α-Tocopherol values, a measure of vitamin E activity, ranged from 0.9 IU/100 g (butterfish) to 12.3 IU/100 g (tilapia) on a wet basis. Vitamin levels in whole fish were intermediate to values previously quantified for muscle or liver tissues alone. Vitamin concentrations in fish livers were quantified separately in seven of these species; liver contributed 35–63% of total retinol measured and 8–34% of total α-tocopherol. Based on these analyses, whole fish commonly fed in zoos, aquariums, and marine zoological parks would appear to meet vitamin A requirements established for most species without additional supplementation, whereas levels of vitamin E quantified indicate a need for supplementation of diets for piscivores.     

Maternal influenza during pregnancy and risk of congenital abnormalities in offspring

BACKGROUND: The teratogenic effect of influenza viruses is currently being debated, and we examined the large population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) to study the possible association between maternal influenza and various congenital abnormalities (CAs). METHODS: The 1980-1996 HCCSCA includes 22,843 newborns or fetuses with CAs, and 38,151 matched controls (newborn infants without any abnormalities). RESULTS: In the case group, 1328 (5.8%) mothers had influenza at some time during their pregnancies compared to 1838 (4.8%) mothers in the control group (adjusted prevalence odds ratios [PORs], 1.3; 95% confidence interval [CI], 1.2-1.4). In the calculation of the adjusted PORs, the use of antifever drugs and maternal employment status were considered. When cases and their matched controls were compared, there was a higher prevalence of maternal influenza during the second and/or third month of pregnancy for the group of newborns with cleft lip +/- palate (adjusted POR, 3.2; 95% CI, 2.0-5.3), neural-tube defects (adjusted POR, 1.9; 95% CI, 1.1-3.3), and cardiovascular malformations (adjusted POR, 1.7; 95% CI, 1.3-2.3). However, a direct teratogenic effect from influenza viruses appears to be unlikely, and we suggest that the higher prevalence of the CAs indicated above can be explained mainly by fever, because this risk was reduced by the use of antifever drugs. Periconceptional folic acid supplementation also showed some preventive effect for these CAs. CONCLUSIONS: The indirect teratogenic effect of maternal influenza during pregnancy may be restricted by appropriate medical treatment (e.g., antifever drugs) and periconceptional folic acid supplementation.     

Telomere length status of somatic cell sheep clones and their offspring

This study was carried out to determine the telomere length status of sheep clones and their offspring, and to examine telomere dynamics and chromosomal abnormalities in culture propagated donor cells. Skin samples were collected from somatic cell nuclear transfer-derived sheep clones, and three of their progeny generated by natural mating. Samples were collected from control animals (n = 35), spanning in age from 1 month to 36 months of age. Genomic DNA was extracted from cell/tissue samples and their telomere lengths were assessed by terminal restriction fragment (TRF) analysis. Results revealed: that (a) sheep clones derived from cultured somatic cells have shortened telomere lengths compared to age-matched controls; (b) the offspring derived from natural mating between clones had normal telomere lengths compared to their age-matched counterparts; and donor cell cultures beyond 20 population doublings had significantly (P < 0.05) shortened telomeres and exhibited a higher numerical and structural chromosomal abnormalities.     

Early pregnancy agricultural pesticide exposures and risk of gastroschisis among offspring in the San Joaquin Valley of California

Background: Prevalence of gastroschisis has inexplicably been increasing over the past few decades. Our intent was to explore whether early gestational exposures to pesticides were associated with risk of gastroschisis. Methods: We used population‐based data, accompanied by detailed information from maternal interviews as well as information on residential proximity to a large number of commercial pesticide applications during early pregnancy. The study population derived from the San Joaquin Valley of California ( ). Cases were 156 infants/fetuses with gastroschisis and controls were 785 infants without birth defects. Results: Among 22 chemical pesticide groups analyzed, none had an elevated odds ratio with an associated confidence interval that excluded 1.0, although exposure to the triazine group showed borderline significance. Among 36 specific pesticide chemicals analyzed, only exposure to petroleum distillates was associated with an elevated risk, odds ratio = 2.5 (1.1–5.6). In general, a substantially different inference was not derived when analyses were stratified by maternal age or when risk estimation included adjustment for race/ethnicity, body mass index, folic acid supplement use, and smoking. Conclusion: Our study rigorously adds to the scant literature on this topic. Our a priori expectation was that we would observe certain pesticide compounds to be particularly associated with young age owing to the disproportionate risk observed for young women to have offspring with gastroschisis. We did not observe an exposure profile unique to young women. Birth Defects Research (Part A), 100:686–694, 2014. © 2014 Wiley Periodicals, Inc.     

Thymidylate synthase polymorphisms and risks of human orofacial clefts

OBJECTIVE: Underlying mechanisms are unknown by which folic acid use in early pregnancy may reduce risks of orofacial clefts. Thymidylate synthase (TYMS) is a folate‐dependent enzyme that catalyzes reductive methylation of deoxyuridylate to thymidylate, thereby playing a central role in DNA synthesis and repair. We investigated two TYMS functional variants (a 28‐bp tandem repeat in the promoter enhancer region of the 5′‐UTR; and TYMS 1494del6 (rs16430): a 6‐bp deletion in the 3′‐UTR) for their risk of cleft palate (CP) and of cleft lip with/without CP (CLP). We investigated effect measure modification between these variants and maternal folate intake for cleft risk. DESIGN: This case‐control study included deliveries from July 1999 to June 2003 from select areas of California. Case groups included CLP or CP alone. Nonmalformed, liveborn controls were randomly selected. Maternal interviews provided information on vitamin use and dietary folate intake. DNA was derived from newborn bloodspots. RESULTS: Data were available for 304 CLP cases, 123 CP cases, and 581 controls. 1496del6 variants did not appear to influence risk of CP or CLP. Homozygosity for the 28‐bp VNTR variant influenced CP risk (odds ratios, OR = 1.8, 95% confidence interval, 1.1–3.1), particularly among Hispanic infants, OR 2.1 (1.0–4.6). Effect measure modification was observed between the 28‐bp VNTR and combined folate intake for CP with an OR of 10.0 (1.6–60.9). CONCLUSION: Although these findings are consistent with biological mechanisms, they were based on relatively small sample sizes and may represent false‐positive discoveries. Replication is warranted in other populations. Birth Defects Research (Part A) 97:95–100, 2013. © 2013 Wiley Periodicals, Inc.     

Dietary vitamin A intake below the recommended daily intake during pregnancy and the risk of congenital diaphragmatic hernia in the offspring

BACKGROUND

Vitamin A has been related to the etiology of congenital diaphragmatic hernia (CDH). We performed a case‐control study to investigate whether maternal dietary vitamin A intake is related to CDH in the offspring.

METHODS

Thirty‐one pregnancies diagnosed with CDH and 46 control pregnancies were included during the study. After CDH diagnosis and inclusion of controls by risk set sampling, maternal vitamin A intake was investigated with a food frequency questionnaire. Serum retinol and retinol‐binding protein were determined. Univariable and multivariable logistic regression models were used to calculate risk estimates with adjustment for potential confounders.

RESULTS

We found no significant differences in the overall nutrient and vitamin A intake between case and control mothers. After stratification in body mass index (BMI) categories, case mothers with normal weight showed a lower energy adjusted vitamin A intake (685 vs. 843 μg retinol activity equivalents [RAEs] / day; p = 0.04) and a slightly lower serum retinol (1.58 vs. 1.67 μmol/L; p = 0.08) than control mothers. Vitamin A intake <800 μg retinol activity equivalents (recommended daily intake) in normal weight mothers was associated with a significantly increased CDH risk (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.5–34.4; p = 0.01). Associations were not significantly different in underweight and overweight mothers.

CONCLUSIONS

In normal‐weight mothers, dietary vitamin A intake during pregnancy below the recommended daily intake is significantly associated with an increased risk of a child with CDH. This finding supports the retinoid hypothesis in human CDH, but warrants further investigation in larger study populations. Birth Defects Research (Part A), 2013. © 2013 Wiley Periodicals, Inc.     

Ontologies of developmental anatomy: their current and future roles

A central problem in current biology is elucidating the molecular networks that drive developmental change and physiological function. Such knowledge is needed partly to understand these networks, partly to be able to manipulate them, and partly to understand and help treat those human congenital abnormalities that arise as a result of mutation. Thus far, bioinformatics technology has been of limited use in this enterprise, mainly because its core focus has been on sequence technology and data archiving. For bioinformatics to be of use in this next tier of investigations, genetic and protein data need to be both archived and searchable by tissue since this is the level at which these networks operate. The resulting databases in turn require ontologies of developmental anatomy that can provide the formal infrastructure for handling gene expression, microarray and other tissue-based data. Here, the progress in making such ontologies, particularly for the developing mouse, is reported and the uses to which they are and will be put, together with the resources and tools currently available for investigating molecular networks and the genetic basis of congenital abnormalities, are considered.     

Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene

Congenital microphthalmia (CMIC) is a common developmental ocular disorder characterized by a small, and sometimes malformed, eye. Posterior microphthalmia (PM) and nanophthalmia are two rare subtypes of isolated CMIC characterized by extreme hyperopia due to short axial length and elevated lens/eye volume ratio. While nanophthalmia is associated with a reduced size in both anterior and posterior segments, PM involves a normal-size anterior chamber but a small posterior segment.