Marginal maternal vitamin B12 status increases the risk of offspring with spina bifida

OBJECTIVE: The purpose of this study was to investigate B vitamins and homocysteine as risk factor for offspring with spina bifida. STUDY DESIGN: Blood samples from 45 mothers and their children with spina bifida and from 83 control mothers and their children were obtained to determine the levels of serum and red blood cell folate, serum vitamin B(12), whole blood vitamin B(6), and total plasma homocysteine. RESULTS: In the case mothers, the vitamin B(12) concentration was 21% lower (95% CI, 8%-33%) compared with control mothers. Unlike folate, vitamin B(6,) and homocysteine, a vitamin B(12) concentration of 相似文献   

Folate, vitamin B12, and homocysteine levels in South Asian women with growth-retarded fetuses

OBJECTIVE. To investigate whether intrauterine growth retardation (IUGR) and preterm delivery in a poor population of South Asia was associated with altered maternal and fetal levels of folate, vitamin B12, and homocysteine. SUBJECTS AND METHODS. Hundred and twenty-eight pregnant women from a low socio-economic strata in the city of Lahore, Pakistan were followed with ultrasound of fetal growth from the 12th week of pregnancy. Blood samples were drawn from the woman and the cord at delivery. Serum was analyzed by a chemiluminescent immunoassay for folate and vitamin B12 and by fluorescence polarization immunoassay for total homocysteine (tHcy). RESULTS. Fourty-six infants showed IUGR. In term, but not preterm, deliveries with IUGR, maternal and cord blood folate levels were half of those in deliveries of normal birth weight infants (P=0.004 and P=0.005). The risk of IUGR was reduced among women with folate levels in the highest quartile (OR 0.31, 95% CI 0.10--0.84). There was no association between vitamin B12 and IUGR. Total homocysteine levels were higher in women delivering IUGR infants (P=0.02). There was an inverse correlation between cord blood folate and tHcy levels (r=-0.26, P=0.006). We also found increased risks for hypertensive illness (OR 3.5, 95% CI 1.4--8.6) and premature delivery (OR 2.5, 95% CI 1.1--6.2) in women in the highest quartile of tHcy. CONCLUSIONS. The occurrence of IUGR increased with low maternal and cord concentrations of folate and high maternal levels of tHcy. Further studies on the effects of vitamin B supplementation through pregnancy are warranted.     

孕妇血清叶酸和维生素B12水平与子代神经管畸形发生的关系

目的 探讨我国神经管畸形(neural tube defects,NTD)高发地区孕妇血清叶酸、维生素B12(vitamin B12,VitB12)水平与子代NTD的关系.方法 采用病例对照研究设计,以NTD高发的山西省5个县作为研究现场.病例组为经B超诊断胎儿合并NTD并通过终止妊娠确诊的孕妇以及分娩NTD的孕妇,对照组为B超诊断胎儿发育正常的孕早、中和晚期孕妇.比较两组血清叶酸和VitB12水平(以几何均数及第5～95百分位数表示)的差异.分别以对照组血清叶酸和VitB12浓度的第10百分位作为界值,划分为2个水平组,分析低浓度水平组NTD的发病风险.结果 病例组和对照组血清VitB12浓度分别为83.8 pmol/L(30.5～209.1)pmol/L、102.6 pmol/L(51.9～269.7)pmol/L,差异具有统计学意义(P<0.05);两组孕妇血清叶酸浓度分别为10.5 pmol/L(4.4～24.5)nmol/L、12.9 pmol/L(6.3～32.7)nmol/L,差异具有统计学意义(P<0.05).子代合并脊柱裂的孕妇血清叶酸、VitB12浓度均低于对照组(P分别=0.017和0.001),子代合并无脑儿的孕妇仅血清叶酸浓度低于对照组(P=0.011),而子代合并脑膨出的孕妇血清叶酸、VitB12浓度与对照组相比差异均无统计学意义(P均>0.05).低VitB12水平孕妇发生NTD的校正危险度为正常水平者的2.58倍(95%CI:1.20～5.51),低叶酸水平孕妇发生NTD的校正危险度是正常叶酸水平孕妇的2.76倍(95%CI:1.30～5.87).结论 低水平血清叶酸和/或VitB12可能是本研究人群NTD发生的危险因素.     

Maternal hyperhomocysteinaemia is a risk factor for congenital heart disease

OBJECTIVE: To investigate the inter-relation between mother and infant homocysteine, folate and vitamin B12 status and the risk of a child with congenital heart disease (CHD). DESIGN: Case-control study. SETTING: Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. POPULATION: Participants were 149 case-mothers and their children with CHD (n = 151) and 183 control-mothers with their children (n = 175). METHODS: Approximately 17 months after the index-pregnancy maternal fasting, children's random venous blood samples were drawn to measure plasma total homocysteine, serum and red blood cell (RBC) folate, and serum vitamin B12 concentrations. Data were compared between cases and controls using the Mann-Whitney U test. The biochemical parameters were dichotomised according to the cutoff value of the 10th percentile of vitamin concentrations and the 90th percentile of homocysteine concentrations based on control data. Risk estimates for the association between CHD and the biochemical parameters were estimated in a logistic regression model. MAIN OUTCOME MEASURES: Medians (minimum-maximum) and odds ratios (OR) (95% confidence intervals [CI]). RESULTS: The OR (95% CI) of having a child with CHD was 2.9 (1.4-6.0) for maternal hyperhomocysteinaemia (>14.3 micromol/l). This finding is substantiated by a significant concentration-dependent risk (Ptrend = 0.004). Hyperhomocysteinaemic case-mothers showed significantly lower serum folate and vitamin B12 concentrations than normohomocysteinaemic case-mothers. Serum and RBC folate concentrations were significantly higher in case-children than that in control-children. CONCLUSIONS: Maternal hyperhomocysteinaemia is associated with an increased risk of CHD, partially due to low folate and vitamin B12 status. The folate status of children warrants further investigation.     

The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring

Objective  The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.
Design  Case–control study.
Setting  Eight clinic sites in the Netherlands, 1999–2001.
Sample  A total of 50 mothers of children with SB and 81 control mothers.
Methods  Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns.
Main outcome measures  Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference.
Results  A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated ( r = 0.51, P < 0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2–6.1) and OR 3.5 (95% CI 1.5–7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.
Conclusion  The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.     

Folate and vitamin B12 levels in abnormal pap smears: a case control study

OBJECTIVE: This study aimed to explore the risk of abnormal cervical cytology in relation to serum folate and vitamin B12 levels, and demographic characteristics. PATIENTS AND METHODS: A case-control study was carried out among women attending the gynecology clinic for cervical cytology screening. At the follow-up clinic visit, fasting blood samples were collected from 103 cases with abnormal cervical cytology of the cervix and 175 controls with cytological normal smears and serum folate and vitamin B12 levels were measured. Data from cases and controls were compared. Logistic regression analysis was used to estimate the relative odds of abnormal cytology with increasing vitamin B12 levels. RESULTS: There were no significant differences between cases and controls in demographic characteristics and mean folate levels (p > 0.05). The mean vitamin B12 level of cases was significantly lower than that of controls (p < 0.001). Dichotomized logistic regression analyses of vitamin B12 levels were significantly different (p < 0.001). The predicted percentages at a cut-off value of 0.5 were as follows: sensitivity 70.0%, specificity 74.6%, positive predictive value 71.8% and negative predictive value 72.6%. The logistic regression analysis of the 1st and the 4th quartiles of vitamin B12 levels showed a significant difference p < 0.001, OR: 1.525 (CI, 1.175-1.875). CONCLUSION: The results of this study suggest that lower vitamin B12 levels are associated with abnormal cervical cytology. It is recommended that women should consume not only folate-rich foods such as fruits and vegetables but also vitamin B12-rich foods such as meat, fish, milk products and eggs in a balanced way.     

Plasma vitamin A in mothers of children with orofacial clefts

OBJECTIVES: The contribution and exact role of exogenous factors, such as medications and drugs during pregnancy, maternal nutrition, in the etiology of orofacial clefts is not established. Vitamin A is essential for embryogenesis, both the lack and excess of retinol result in congenital malformations. DESIGN: This study was aimed to establish vitamin A status in Polish mothers of children with isolated orofacial clefts. MATERIAL AND METHODS: 34 mothers of children with isolated cleft lip (CL), 83 mothers of children with cleft lip and palate (CLP), 42 mothers of children with isolated cleft palate (CP) were studied. The control group consisted of 67 women who gave birth to healthy children. All participants were healthy women without symptoms of malabsorption. Plasma retinol levels were determined by high-performance liquid chromatography. RESULTS: There were no differences in mean plasma vitamin A levels between CL--2.09 +/- 0.61 mumol/l, CLP--2.21 +/- 0.52 mumol/l, CP--2.15 +/- 0.62 mumol/l and control--2.08 +/- 0.52 mumol/l. None of participants had vitamin A deficiency (concentration of retinol < 0.8 mumol/l). Among women, who were not supplemented with retinol containing vitamins during 3 months prior the study, 10.6% of mothers of children with orofacial clefts (n = 132) and only 5.8% of controls (n = 52) had levels of retinol above upper norm for women of childbearing age (N < 2.8 mumol/l). CONCLUSION: Periconceptional multivitamin supplementation has been reported to decrease the risk of orofacial clefts in offspring, but high intake of preformed vitamin A (retinol) might be undesirable.     

Myo-inositol, glucose and zinc status as risk factors for non-syndromic cleft lip with or without cleft palate in offspring: a case-control study

OBJECTIVE: To investigate myo-inositol, glucose and zinc status in mothers and their infants on cleft lip with or without cleft palate risk (CLP). DESIGN: Case-control study. SETTING: University Medical Centre Nijmegen, the Netherlands. POPULATION: Eighty-four mothers and their CLP child and 102 mothers and their healthy child. METHODS: Venous blood samples were obtained to determine serum myo-inositol and glucose and red blood cell zinc concentrations in mothers and children. Geometric means were calculated and compared between the groups. The blood parameters were dichotomised with cutoff points based on control values, P90 for glucose concentrations. MAIN OUTCOME MEASURES: Geometric means (P5-P95) and odds ratios (95% confidence intervals). RESULTS: The CLP children (P= 0.003) and their mothers (P= 0.02) had significantly lower red blood cell zinc concentrations than controls. A low maternal serum myo-inositol concentration (<13.5 micromol/L) and a low red blood cell zinc concentration (<189 micromol/L) increased CLP risk [odds ratio 3.0 (95% CI 1.2-7.4) and 2.0 (95% CI 0.8-4.8), respectively]. Children with low myo-inositol (<21.5 micromol/L ) or low red blood cell zinc concentrations (<118 micromol/L) were more likely to have CLP [odds ratio 3.4 (95% CI 1.3-8.6) and 3.3 (95% CI 1.3-8.0), respectively]. Glucose was not a risk factor for CLP in mothers and children. Maternal and child myo-inositol as well as zinc concentrations were slightly, albeit significantly correlated, r(Pearson)= 0.33 (P= 0.0006) and r(Pearson)= 0.23 (P= 0.01), respectively. CONCLUSION: This study demonstrates for the first time that zinc and myo-inositol are important in the aetiology of CLP.     

Maternal red blood cell folate concentration at 10–12 weeks gestation and pregnancy outcome

Objective: To determine if maternal circulating red blood cell (RBC) folate concentration in early pregnancy is associated with late gestation pregnancy complications including small for gestational age (SGA) infants, preeclampsia and preterm birth (PTB) in a socioeconomically disadvantaged population. Method: This was a retrospective case control study, conducted at Lyell McEwin Health Service, South Australia, including 400 primiparous women. RBC folate and demographic data were collected at 10–12 weeks gestation. Pregnancy outcome data were obtained from patient case notes. Results: Patients who were folate deficient were more likely to develop pregnancy complications, specifically SGA (OR 6.9, 95% CI 2–24.3) and PTB (OR 5.4 95% CI 1.4–21.2). Those who were folate insufficient were also at increased risk of SGA (OR 3.0, 95% CI 1.3–7.7). No association between folate and preeclampsia was found. Women who were supplementing with folic acid delivered infants who were 179?g heavier (5.5% increased birth weight, P?=?0.003) and 4.5 days later, compared to those who did not supplement. Furthermore, low RBC folate was associated with cigarette smoking (P?<?0.001). Conclusions: Maternal RBC folate concentration in early pregnancy is associated with SGA and PTB, but not with preeclampsia.     

Protective effect of hyperemesis gravidarum for nonsyndromic oral clefts

OBJECTIVE: To evaluate whether hyperemesis gravidarum is associated with a decreased risk for nonsyndromic oral clefts and to examine the relationship between hyperemesis gravidarum, birth weight, and gestational age. METHODS: This was a population-based, matched case-control study of 1950 subjects with oral clefts (1368 with cleft lip with or without cleft palate; 582 with cleft palate) collected from the Hungarian Congenital Abnormality Registry and 1955 controls identified from the National Birth Registry. RESULTS: Fewer mothers of newborns with oral clefts had early-onset hyperemesis gravidarum than did mothers of controls (cleft lip with or without cleft palate: 83 cases and 121 controls, odds ratio [OR] = 0.67, 95% confidence interval [CI] 0.50, 0.89; cleft palate: 42 cases and 64 controls, OR = 0.63, 95% CI 0.42, 0.94). The use of dimenhydrinate was more common among mothers of subjects with cleft palate (OR = 2.47, 95% CI 1.11, 5.49), whereas iron seemed to have a protective effect against this condition (OR = 0.26, 95% CI 0.09, 0.80). Gestational age and birth weight were not significantly associated with hyperemesis gravidarum. CONCLUSION: This study suggests that hyperemesis gravidarum provides a protective effect against risk to oral clefts in newborns.     

Maternal serum ferritin and fetal growth

OBJECTIVE: To determine the relationship between maternal serum ferritin and concentrations and specific types of fetal growth restriction (FGR). METHODS: Serum ferritin concentrations were measured at approximately 25 and 36 weeks' gestation in 480 multiparas with singleton fetuses who participated in a study of risk factors for repeated FGR. Asymmetric FGR was defined by low birth weight for gestational age criteria and a ponderal index less than 2.32, and symmetric FGR was defined by the same birth weight for gestational age criteria and a ponderal index of at least 2.32. RESULTS: Among 480 infants, 370 were appropriate for gestational age (AGA), 58 had asymmetric FGR, and 52 had symmetric FGR. Higher ferritin concentrations were associated with black race, maternal age 25 years or older, and smoking. Mothers of asymmetric-FGR infants had higher mean ferritin levels than mothers of AGA infants at 25 weeks' (38.0 versus 20.2 microg/L, P < .01) and 36 weeks' gestation (21.0 versus 13.3 microg/L, P < .01), whereas mothers of symmetric-FGR infants had significantly lower ferritin levels at 36 weeks (8.3 microg/L). For mothers with serum ferritin levels of at least 26 microg/L (highest quartile at 25 weeks), the adjusted odds ratio (OR) for asymmetric-FGR infants was 3.4, 95% confidence interval (CI) 1.6, 7.2. There was a similar association between the highest quartile of serum ferritin at 36 weeks (at least 20 microg/L) and asymmetric FGR (adjusted OR 2.7, 95% CI 1.3, 5.8). Women with serum ferritin levels less than 3 microg/L (lowest quartile at 36 weeks) had an adjusted OR for symmetric-FGR infants of 2.2, 95% CI 1.01, 4.6. CONCLUSION: High maternal serum ferritin levels are associated with asymmetric FGR, whereas low serum ferritin levels are associated with symmetric FGR.     

Hyperglycemia and retinopathy of prematurity in very low birth weight infants.

OBJECTIVE: Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP. METHODS: A retrospective case-control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000 g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO(2)), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure. RESULTS: In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10 mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO(2) (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10 mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16-0.86). CONCLUSION: In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.     

Vitamin B12 and folate statuses are associated with diet in pregnant women,but not with anthropometric measurements in term newborns

Objective: To investigate the frequencies of vitamin B12 and folate deficiencies in pregnant women in low socioeconomic group, the relation between the animal-source foods consumption and maternal vitamin B12-folate statuses, and their impacts on anthropometric measurements of the infants. Methods: A total of 208 pregnant women in the last trimester were included in the study. A questionnaire about socio-demographic status, consumption of meat, egg, milk-dairy products, multivitamin supplementation was used. Vitamin B₁₂ and folate concentrations were studied by chemiluminescence method. The babies of Vitamin B₁₂ deficient mothers were evaluated after birth. Results: The rate of vitamin B₁₂ deficiency was 47.6% and folate deficiency was 17.3% of pregnant women. Animal food consumption was inadequate about half of pregnant women and vitamin B₁₂ levels in these women were significantly low. There were no statistically significant relationships between the birth weight, birth length and head circumference measurements, and maternal vitamin B₁₂ and folate concentrations. Conclusion: The rate of vitamin B12 deficiency in pregnant women in low socioeconomic population is high. Although there were no significant effects of the vitamin B12 and folate deficiencies on birth size, additional studies are required to elucidate the subsequent effects.     

Pregnancy-induced hypertension is associated with lower infant mortality in preterm singletons

OBJECTIVE: To assess the association between pregnancy-induced hypertension (PIH) and infant mortality. DESIGN: Retrospective cohort study. SETTING: Birth and infant death registration dataset of the USA. POPULATION: A total of 17,432,987 eligible, liveborn singleton births in 1995-2000. METHODS: Multivariate logistic regression was applied to evaluate the association between PIH and infant mortality, with adjustment of potential confounders. MAIN OUTCOME MEASURES: Infant death (0-364 days) and its three components: early neonatal death (0-6 days), late neonatal death (7-27 days), and postneonatal death (28-364 days). RESULTS: There was a significant reduction in infant mortality associated with PIH in early preterm infants (OR = 0.59, 95% CI: 0.56-0.63) and in late preterm infants (OR = 0.80, 95% CI: 0.73-0.87), but a significant increase in term infants (OR = 1.08, 95% CI: 1.02-1.14). Both in early preterm and late preterm births, early neonatal mortality (OR = 0.38, 95% CI: 0.34-0.42; OR = 0.68, 95% CI: 0.61-0.77) and late neonatal mortality (OR = 0.59, 95% CI: 0.50-0.70; OR = 0.76, 95% CI: 0.61-0.96) were decreased in infants born to mothers with PIH compared with those born to mothers with normal blood pressure. The PIH-associated reduction in neonatal mortality among preterm singletons was stronger in small-for-gestational-age infants than in normal growth infants and stronger in infants born to nulliparous women than in those born to multiparous women. CONCLUSIONS: PIH is associated with lower risk of infant death in preterm births but higher risk in term births.     

Preconception folate and vitamin B(6) status and clinical spontaneous abortion in Chinese women

OBJECTIVE: To assess the association between preconception homocysteine and B vitamin status and risk of clinical spontaneous abortion in women from Anqing, China. METHODS: All women were aged 21-34 years, had never smoked, and were primigravid. Patients (n = 49) were women with a clinically recognized pregnancy who experienced a fetal death before 100 days' gestation. Controls (n = 409) were women who maintained a pregnancy that ended in a live birth. Homocysteine, folate, and vitamins B(6) and B(12) concentrations were measured in plasma obtained before conception. RESULTS: Mean vitamin B(6) concentration was lower in patients than in controls (34.0 versus 37.9 nmol/L, P =.04). In addition, the risk of spontaneous abortion tended to increase with decreasing plasma vitamin B(6) and folate concentration (P for trend =.06 and.07, respectively), although the significance of these trends was further reduced in logistic models that included age, body mass index, and both vitamins. The risk of spontaneous abortion was four-fold higher among women with suboptimal plasma concentrations of both folate and vitamin B(6) (folate less than or equal to 8.4 nmol/L and vitamin B(6) less than or equal to 49 nmol/L) than in those with higher plasma concentrations of both vitamins (odds ratio 4.1, 95% confidence interval 1.2, 14.4). Homocysteine and vitamin B(12) status were not associated with spontaneous abortion risk. CONCLUSION: Suboptimal preconception folate and vitamin B(6) status, especially when they occur together, may increase the risk of clinical spontaneous abortion. Additional prospective studies are needed to confirm these findings and to determine whether antenatal B vitamin supplementation reduces spontaneous abortion risk.     

Folate and vitamin B12 concentrations in maternal and fetal blood, and amniotic fluid in second trimester pregnancies complicated by neural tube defects.

OBJECTIVE: To investigate maternal and fetal folate and vitamin B12 concentrations in pregnancies affected by neural tube defects (NTD). DESIGN: Measurement of folate and vitamin B12 concentrations in amniotic fluid, fetal blood and maternal blood samples in midgestation. SUBJECTS: 32 women undergoing termination of pregnancy at 14-21 weeks gestation for social reasons (n = 24) or for fetuses with neural tube defects (n = 8). INTERVENTIONS: Fetoscopy before intra-amniotic injection of prostaglandins. RESULTS: In normal pregnancies there was a positive correlation between maternal and fetal serum folate, and the fetal serum and red blood cell folate concentrations were higher than the maternal. There were no differences in amniotic fluid, maternal blood or fetal blood folate concentrations between pregnancies with NTD and normal pregnancies. Although amniotic fluid vitamin B12 was lower in pregnancies with NTD, maternal serum vitamin B12 concentration was not reduced. CONCLUSION: In this small group of pregnancies with NTD at mid-gestation there is no evidence to suggest folate or vitamin B12 deficiency.     

Congenital malformations after the use of inhaled budesonide in early pregnancy

OBJECTIVE: To study possible teratogenic risks with the use of an inhaled glucocorticoid, budesonide, in early pregnancy. METHODS: Using the Swedish Medical Birth Registry, congenital malformations were studied in 2014 infants whose mothers had used inhaled budesonide for asthma in early pregnancy. The presence of congenital malformations was checked further with auxiliary registries. RESULTS: No increase in the general rate of congenital malformations was observed: 3.8% (95% confidence interval [CI] 2.9, 4.6) of the infants had a congenital malformation diagnosed, which is similar to the population rate (3.5%). After exposure to budesonide, four infants were born with orofacial clefts; this also is similar to the expected number (3.3). CONCLUSION: Even though a specific teratogenic effect of use of budesonide in early pregnancy cannot be ruled out, it is unlikely that a clinically significant teratogenic risk exists.     

Risk factors and outcomes associated with a short umbilical cord

OBJECTIVE: To identify risk factors and outcomes associated with a short umbilical cord. METHODS: We conducted a population-based case-control study using linked Washington State birth certificate-hospital discharge data for singleton live births from 1987 to 1998 to assess the association between maternal, pregnancy, delivery, and infant characteristics and short umbilical cord. Cases (n = 3565) were infants diagnosed with a short umbilical cord. Controls (n = 14260) were randomly selected from among births without a diagnosis of short umbilical cord. RESULTS: Case mothers were less likely to be overweight (body mass index 25 or more, odds ratio [OR] 0.7; 95% confidence interval [CI] 0.6, 0.8) and more likely to be primiparous (OR 1.4; 95% CI 1.3, 1.6). Case infants were more likely to be female (OR 1.3; 95% CI 1.2, 1.4), have a congenital malformation (OR 1.6; 95% CI 1.4, 1.8), and be small for their gestational age (risk ratio [RR] 1.6; 95% CI 1.4, 1.9). A short cord was associated with increased risk for maternal labor and delivery complications, including retained placenta (RR 1.6; 95% CI 1.2, 2.3) and operative vaginal delivery (RR 1.4; 95% CI 1.3, 1.5). Adverse fetal and infant outcomes in cases included fetal distress (RR 1.8; 95% CI 1.6, 2.1) and death within the first year of life among term infants (RR 2.4; 95% CI 1.2, 4.6). CONCLUSION: Modifiable risk factors associated with the development of a short cord were not identified. Case mothers and infants are more likely to experience labor and delivery complications. Term case infants had a 2-fold increased risk of death, which suggests closer postpartum monitoring of these infants.     

A common mutation in the 5,10-methylenetetrahydrofolate reductase gene as a new risk factor for placental vasculopathy

OBJECTIVE: This study was undertaken to investigate whether the cytosine-to-thymine substitution at nucleotide 677 (C677T) in the 5, 10-methylenetetrahydrofolate reductase gene is a risk factor for placental vasculopathy (abruptio placentae or placental infarction with fetal growth restriction). STUDY DESIGN: This case-control study enrolled 165 women with placental vasculopathy and 139 matched control women with normal pregnancy outcomes. Measurements included fasting total plasma homocysteine concentration, serum and red blood cell folate concentrations, serum vitamin B(12) concentration, whole-blood vitamin B(6) concentration, and analysis of the 5, 10-methylenetetrahydrofolate reductase gene C677T mutation. RESULTS: The median total plasma homocysteine concentration was significantly higher in the study group than in the control group (P <.01; odds ratio >97.5th percentile, 4.66; 95% confidence interval, 1.55-14.0). Homozygous genotype for the mutated 5,10-methylenetetrahydrofolate reductase gene was found in 12% of the study group and 5% of the control group (odds ratio, 2.45; 95% confidence interval, 1.00-6.02). CONCLUSIONS: Mild hyperhomocysteinemia was confirmed among women with placental vasculopathy, for which homozygosity for a mutated 5, 10-methylenetetrahydrofolate reductase gene was found to be a new risk factor. The risk of placental vasculopathy probably increases in conditions of low serum folate concentration.     

Serum vitamin K1 concentration and vitamin K-dependent clotting factor activity in maternal and fetal cord blood

The serum concentration of phylloquinone (vitamin K1) was measured in 34 healthy mothers and in the arterial cord blood of their newborn infants. In addition, the activities of factor II and of factors VII plus X were determined simultaneously in 16 paired maternal and fetal bloods. The serum vitamin K1 concentration was similar to that of control subjects in 27 mothers: 9.03 +/- 4.9 micrograms/L (mean and SD), with a simultaneous concentration of 10.4 +/- 5.3 micrograms/L in cord blood. Six mothers exhibited high serum vitamin K1 concentrations from 40 to 240 micrograms/L (median, 82) and the concentration in cord blood ranged from 25 to 115 micrograms/L (median, 71). One mother had a normal concentration of vitamin K1: 9 micrograms/L while no vitamin K1 was detectable in the serum of her infant. The activity of factor II and factors VII plus X was 7% and 7%, respectively, in this infant and 100% in the mother. All other mothers showed normal factor II and factors VII plus X activity, while the median activity was 47% (28%-56%) for factor II and 65% (35%-100%) for factors VII plus X in cord blood. These data suggest that vitamin K1 can cross the placental barrier but not in every case. Therefore the systematic administration of vitamin K1 to the newborn infant seems to be required to prevent the occurrence of the hemorrhagic disease.