Associations between periconceptional alcohol consumption and craniosynostosis, omphalocele, and gastroschisis

BACKGROUND: Alcohol consumption during pregnancy is known to be associated with certain birth defects, but the risk of other birth defects is less certain. The authors examined associations between maternal alcohol consumption during pregnancy and craniosynostosis, omphalocele, and gastroschisis among participants in the National Birth Defects Prevention Study, a large, multicenter case–control study. METHODS: A total of 6622 control infants and 1768 infants with birth defects delivered from 1997–2005 were included in the present analysis. Maternal alcohol consumption was assessed as any periconceptional consumption (1 month prepregnancy through the third pregnancy month), and by quantity‐frequency, duration, and beverage type. Alcohol consumption throughout pregnancy was explored for craniosynostosis since the period of development may extend beyond the first trimester. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression analysis. OR were adjusted for age, race/ethnicity, and state of residence at time of infant's birth. Gastroschisis OR were also adjusted for periconceptional smoking. RESULTS: Periconceptional alcohol consumption and craniosynostosis showed little evidence of an association (OR = 0.92; CI: 0.78–1.08), but alcohol consumption in the second (OR = 0.65; CI: 0.47–0.92) and third trimesters (OR = 0.68; CI: 0.49–0.95) was inversely associated with craniosynostosis. Periconceptional alcohol consumption was associated with omphalocele (OR = 1.50; CI: 1.15–1.96) and gastroschisis (OR = 1.40; CI: 1.17–1.67). CONCLUSIONS: Results suggest that maternal periconceptional alcohol consumption is associated with omphalocele and gastroschisis, and second and third trimester alcohol consumption are inversely associated with craniosynostosis. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

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.     

Nutrient intakes in women and risks of anophthalmia and microphthalmia in their offspring

BACKGROUND: There is a paucity of information about risk factors for the human eye anomalies anophthalmia and microphthalmia. In this population-based case-control study we investigated whether periconceptional intakes of supplemental folic acid, dietary folate, vitamin A, and several other nutrients were associated with these eye defects. METHODS: This study included data on deliveries that had estimated due dates from 1997-2002 and were part of the National Birth Defects Prevention Study (the National Birth Defects Prevention Study is a population-based case-control study of a wide spectrum of birth defects, incorporating data from 10 birth defects surveillance systems in the United States [Arkansas, California, Georgia/Centers for Disease Control and Prevention, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah]). Cases were those infants or fetuses born with either anophthalmia or microphthalmia. Liveborn infants without major malformations were eligible as controls. Maternal interviews were conducted, primarily by telephone, in English or Spanish. Participation in the interview was 71% among case mothers and 68% among control mothers. Interviews were completed with 89 case mothers and 4,143 control mothers. A shortened version of the food frequency questionnaire from the Nurse's Health Study was used to assess frequency of intake of 58 food items during the year before pregnancy. RESULTS: Our results did not indicate reduced risks for these eye malformations associated with maternal intake of vitamin supplements containing folic acid. The data did not show an association between malformation risk and higher or lower intakes of vitamin A. We also did not observe strong evidence that an abundance or a lack of dietary intake of any other nutrient was associated with increased risk of the studied eye malformations. CONCLUSIONS: Our observations contribute to a limited body of findings on these rare eye defects.     

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.     

Interaction between maternal smoking and malnutrition in infant risk of gastroschisis

BACKGROUND: Gastroschisis is a severe birth defect characterized by a tear in the infant's abdominal wall. Young mothers have the highest risk of having an infant with gastroschisis. In an animal model, the defect resulted from exposure of pregnant mice to carbon monoxide (CO) in combination with a low protein and low zinc diet. METHODS: We evaluated this model in a study of 55 infants with gastroschisis and 94 age-matched controls that included maternal interview with a food frequency questionnaire. Smoking cigarettes (> or = 1 pack/day) or marijuana (more than once) 3 months prior to pregnancy indicated CO exposure. Low protein or zinc intake and a low body mass index (BMI) indicated maternal malnutrition. RESULTS: When assessed separately, high CO, low protein, low zinc, and low BMI were each significantly associated with an increased risk of gastroschisis. Although we observed significant CO-BMI and CO-zinc interactions after adjusting for income, only a combination of high CO exposure and low BMI yielded a synergistic adverse effect. Compared to the low risk of having an infant with gastroschisis for mothers who did not have low BMI and did not smoke, the risk of having an infant with gastroschisis was 16.3 times (95% CI, 2.49-113.4) higher for mothers who did not have low BMI but smoked, and 19.7 times (95% CI, 4.33-89.6) higher for mothers who did not smoke but had low BMI. However, the risk was 26.5 times (95% CI, 7.85-89.4) higher for mothers who had low BMI and smoked. CONCLUSIONS: Our results suggest that young mothers are at increased risk of having an infant with gastroschisis if they smoke and are also malnourished.     

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.     

Selected gene polymorphisms and their interaction with maternal smoking, as risk factors for gastroschisis

BACKGROUND: Gastroschisis is a severe birth defect in which the infant is born with a portion of the intestines extruding through a small tear in the abdominal wall, usually to the right of the umbilical cord. Its etiology is unknown, but the prevailing hypothesis is that it results from a vascular accident at the time of involution of the right umbilical vein or of the development of the superior mesenteric artery. METHODS: In a case-control study of 57 cases of gastroschisis and 506 controls, we tested DNA for polymorphisms of 32 genes representing enzymes involved in angiogenesis, blood vessel integrity, inflammation, wound repair, and dermal or epidermal strength. RESULTS: In logistic regression, controlling for maternal ethnicity, and using the homozygote wild-type as referent, the following gene polymorphisms were associated with an increased risk for a gastroschisis for heterozygotes: ICAM1 gly241arg (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1 -3.4); NOS3 glu298asp (OR, 1.9; 95% CI, 1.1-3.4); NPPA 2238T > C (OR, 1.9; 95% CI, 1.0-3.4); and ADD1 gly460trp (OR, 1.5; 95% CI, 0.8-2.8). Additionally, for the NPPA and ADD1 single-nucleotide polymorphisms (SNPs), the homozygote variants had a significantly higher risk than the heterozygotes (OR, 7.5; 95% CI, 1.7-33.5 and OR, 4.9; 95% CI, 1.9-12.9, respectively). Three SNPs showed a strong interaction with maternal smoking. The risk for smokers with 1 or 2 variant alleles compared to nonsmokers with the wild-type allele were: NOS3 (OR, 5.2; 95% CI, 2.4-11.4); ICAM1 (OR, 5.2; 95% CI, 2.1-12.7); and NPPA (OR, 6.4; 95% CI, 2.8-14.6). CONCLUSIONS: These results support the hypothesis of a vascular compromise as part of a multifactorial etiology of gastroschisis involving both genes and environmental factors.     

Seven-week embryo with gastroschisis, multiple anomalies, and physiologic hernia suggests early onset of gastroschisis

Gastroschisis is an increasingly common birth defect involving the development of the ventral body wall. Extrusion of the bowel is usually paraumbilical, usually right sided, and associated anomalies are less common than in omphalocele. Recently, hypotheses regarding the timing of the typical gastroschisis defect have come into question. Unlike previous theories, Feldkamp et al. (2007) has postulated that gastroschisis occurs much earlier in development, before abdominal wall closure, which is completed by about 35 days postconception. We present a case of a spontaneously aborted dysmorphic embryo which exhibits features of the normal physiologic herniation of the midgut as well as gastrochisis. The co-existence of the abdominal wall defect in this abnormal embryo with the physiologic hernia supports the early development of this defect and also illustrates the causal heterogeneity of gastroschisis.     

RETRACTED ARTICLE: High Fat Feeding of Lactating Mice Causing a Drastic Reduction in Fat and Energy Content in Milk without Affecting the Apparent Growth of Their Pups and the Production of Major Milk Fat Globule Membrane Components MFG-E8 and Butyrophilin

Lactating mice were fed either a low fat or a high fat diet. Milk samples were collected and the composition was examined. Triglyceride and free fatty acid contents were greatly reduced in the milks of high fat diet group, while protein and lactose contents were almost the same between both diet groups. Although the energy content of each component was also lower in milk of high fat diet group, there was apparently no significant difference in the growth of the pups raised by either diet group. This discrepancy might be in part explained by a hypothesis that the pups might monitor calorie content in milk and keep suckling until the energy intake reaches their satisfaction. Moreover, nearly the same amounts of major milk fat globule membrane proteins MFG-E8 and butyrophilin were shown to be present in the milks from both diet groups and gene expression of both proteins in the mammary glands were also indistinguishable, suggesting that production of major MFGM components is not simply related to fat production and secretion.     

Different Effect of High Fat Diet and Physical Exercise in the Hippocampal Signaling

Obesity is an epidemic disease that may affect brain function. The present study examined the effect of high fat diet (HF) and physical exercise on peripheral tissue and hippocampal signaling. CF-1 mice (n = 4, per cage) were divided into groups receiving high fat (HF) or control (CD) diets for 5 months, with or without voluntary exercise. Serum triacylglycerol, total cholesterol, HDLc, liver triacylglycerol and glycogen concentrations were evaluated (n = 6). Also, the phosphorylation state of the AKT → ERK 1/2 → CREB pathway (AKT, pAKTser473, ERK 1/2, pERK 1/2, CREB and pCREB, n = 4–6) was analyzed in the hippocampus. HF diet caused an increase in AKT phosphorylation at ser473 (P < 0.05), while exercise increased the phosphorylation of ERK 1/2 (P < 0.05) and CREB (P < 0.05). As expected, exercise reversed some of the harmful effects of HF, i.e., increased liver deposition of fat (P < 0.05) and fat gain in the abdominal region (P < 0.05). In conclusion, the effects of exercise and HF diet on brain signaling appear to affect the hippocampal AKT → ERK 1/2 → CREB pathway in independent ways: HF intake caused increased phosphorylation of AKTser473, while exercise increased ERK 1/2 → CREB signaling. The physiological relevance of these findings in brain function remains to be elucidated.     

Epidemiology of gastroschisis in metropolitan Atlanta, 1968 through 2000

BACKGROUND: An increase in the rate of gastroschisis has been documented by birth defects surveillance systems in the United States and in other countries. This study sought to evaluate historical trends in the rate of gastroschisis in Atlanta, Georgia, and to describe the epidemiology of gastroschisis over 33 years. METHODS: Gastroschisis cases were identified through the Metropolitan Atlanta Congenital Defects Program (MACDP) from 1968 through 2000. Poisson regression techniques were used to evaluate trends over time. Data on covariates were compared for three maternal age groups (< or =19, 20-24, and > or =25 years). RESULTS: From 1968 through 1975, the rate of gastroschisis was stable at 0.8 per 10,000 births. After 1975, the rate of gastroschisis was 2.3 per 10,000 births with no significant increase observed from 1976 through 2000. The rate of gastroschisis was six times higher among teenage mothers compared with mothers > or =25 years of age. Affected infants born to teenage mothers were less likely to be born to Black mothers compared to White mothers (rate ratio [RR], 0.4; 95% confidence interval [CI], 0.2-0.6). This was also true for mothers 20-24 years of age (RR, 0.5; 95% CI, 0.3-0.8) but not for mothers 25 years of age or older (RR, 1.6; 95% CI, 0.9-2.7). CONCLUSIONS: An increase in the rate of gastroschisis was observed in the mid-1970s, but no temporal trend has been observed since that time. In light of recent reports of an increasing prevalence of gastroschisis in the United States, continued monitoring of this birth defect is warranted.     

葡激酶突变体对高脂喂养大鼠血液常规指标的影响

目的研究葡激酶突变体（SakM）对高脂喂养大鼠血液常规的影响。方法选取60只Wistar大鼠,随机分为高脂药物组、高脂生理盐水组、正常药物对照组、正常生理盐水对照组,静脉注射SakM到大鼠体内,剂量按照0．5mg／kg体重,2d注射一次,连续15次,观察SakM对血液常规的影响。结果SakM对正常动物血液常规指标没有影响,但是能够改善高脂喂养动物的血液常规指标结论SakM长期使用不会影响正常动物血液常规指标,具有使用安全性,同时还能用来调节高脂喂养动物的血液常规指标。     

高脂饮食对小鼠脂质代谢和leptin基因表达水平的影响

目的建立高脂饮食诱导小鼠肥胖模型,分析高脂饲料对小鼠脂质代谢和leptin基因表达水平的影响。方法用高脂饲料饲喂小鼠,每周定时称重和断尾采血一次,分别测定血清中血糖、胆固醇、甘油三酯、胰岛素和leptin的浓度;5周后,分离、称重小鼠体脂并提取腹部脂肪组织RNA,半定量RT-PCR分析leptin基因表达水平。结果从第2周开始,实验组小鼠体重明显高于对照组小鼠,4周后,体重差异显著（P〈0．05）;血清中血糖、胆固醇、甘油三酯、胰岛素和leptin的含量随体重增加明显增高,4周后,差异显著（P〈0．05）;实验组体脂含量明显高于对照组（P〈0．05）,半定量RT-PCR分析表明,肥胖小鼠脂肪组织leptin基因表达水平高于对照组（P〈0．05）。结论高脂饮食诱导可建立小鼠肥胖模型,并能够引起高胰岛素和高leptin血症,为进一步研究肥胖的发病机制奠定基础。