Low Serum Vitamin B-12 Concentrations Are Prevalent in a Cohort of Pregnant Canadian Women.

BACKGROUND: Among Canadian women of reproductive age, 5% and 20% have serum vitamin B-12 concentrations indicative of deficiency (<148 pmol/L) and marginal status (148-220 pmol/L), respectively. Given the association between suboptimal vitamin B-12 and adverse pregnancy outcomes, an understanding of vitamin B-12 status during pregnancy, and factors that influence it, is required. OBJECTIVE: This prospective analysis from the PREFORM (PREnatal FOlic acid exposuRe on DNA Methylation in the newborn infant) study investigated 1) vitamin B-12 status in a cohort of Canadian pregnant women and their newborns, 2) the association of maternal dietary vitamin B-12 intake with maternal and cord blood concentrations of vitamin B-12 and its biomarkers, and 3) the association of fetal genetic polymorphisms with cord blood concentrations of vitamin B-12 and its biomarkers. METHODS: In pregnant Canadian women (n = 368; mean ± SD age: 32 ± 5 y), vitamin B-12 intakes were assessed in early (0-16 wk) and mid- to late (23-37 wk) pregnancy. Serum vitamin B-12 and plasma total homocysteine (tHcy) and methylmalonic acid (MMA) in maternal blood at 12-16 wk of pregnancy and at delivery (28-42 wk) and in cord blood were measured and compared by using regression analyses. The associations of 28 fetal genetic variants in vitamin B-12 metabolism and cord blood vitamin B-12, tHcy, and MMA concentrations were assessed by using regression analysis, with adjustment for multiple testing. RESULTS: A total of 17% and 38% of women had deficient and 35% and 43% had marginal serum vitamin B-12 concentrations at 12-16 wk of pregnancy and at delivery, respectively. Only 1.9-5.3% had elevated MMA (>271 nmol/L), and no women had elevated tHcy (>13 µmol/L). Maternal dietary vitamin B-12 intake during pregnancy was either weakly associated or not associated with maternal and cord blood vitamin B-12 (r(2) = 0.17-0.24, P < 0.0008), tHcy (P = NS) and MMA (r(2) = 0.05-0.11, P < 0.001). Fetal genetic polymorphisms were not associated with cord blood concentrations of vitamin B-12 and its biomarkers. CONCLUSIONS: Deficient and marginal serum vitamin B-12 concentrations are prevalent in Canadian pregnant women with the use of traditional cutoffs, despite supplement use. Given the growing interest among women to adhere to a vegetarian diet that may be lower in vitamin B-12, and vitamin B-12's importance in pregnancy, the functional ramifications of these observations need to be elucidated. This trial was registered at clinicaltrials.gov as NCT02244684.

High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood.

BACKGROUND: Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. OBJECTIVES: In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. DESIGN: Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. RESULTS: Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. CONCLUSIONS: Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684.

Pregnant Canadian Women Achieve Recommended Intakes of One-Carbon Nutrients through Prenatal Supplementation but the Supplement Composition, Including Choline, Requires Reconsideration.

BACKGROUND: Folate, vitamin B-6, vitamin B-12, and choline are involved in one-carbon metabolism and play critical roles in pregnancy including prevention of birth defects and promotion of neurodevelopment. However, excessive intakes may adversely affect disease susceptibility in offspring. Intakes of these nutrients during pregnancy are not well characterized. OBJECTIVE: Our aim was to determine dietary and supplemental intakes and major dietary sources of one-carbon nutrients during pregnancy. METHODS: In pregnant women (n = 368) at ≤16 wk postconception, supplement use >30 d before pregnancy was assessed by maternal recall and supplement and dietary intakes in early (0-16 wk) and late pregnancy (23-37 wk) were assessed by food-frequency questionnaire. RESULTS: Preconception, 60.1% (95% CI: 55.8, 64.3) of women used B vitamin-containing supplements. This increased to 92.8% (95% CI: 89.6, 95.2) in early and 89.0% (95% CI: 85.0, 92.3) in late pregnancy. Median supplemental folic acid, vitamin B-12, and vitamin B-6 were 1000 µg/d, 2.6 µg/d, and 1.9 mg/d, respectively. Forty-one percent and 50% of women had dietary intakes of folate and vitamin B-6 less than the estimated average requirement (520 mg/d dietary folate equivalents and 1.6 mg/d, respectively). Eight-seven percent of women had choline intakes less than the Adequate Intake (450 mg/d). Dietary intakes did not change appreciably during pregnancy. Fruits and vegetables and fortified foods contributed ∼57% to total dietary folate intake. Fruits and vegetables contributed ∼32% to total dietary vitamin B-6 intake and dairy and egg products contributed ∼37% to total dietary vitamin B-12 intake. CONCLUSIONS: Vitamin supplements were an important source of one-carbon nutrients during pregnancy in our sample. Without supplements, many women would not have consumed quantities of folate and vitamin B-6 consistent with recommendations. Given the importance of choline in pregnancy, further research to consider inclusion in prenatal supplements is warranted. This trial was registered at clinicaltrials.gov as NCT02244684.

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations.

BACKGROUND: Choline deficiency during pregnancy can lead to adverse birth outcomes, including impaired neurodevelopment and birth defects. Genetic variants of choline and one-carbon metabolism may also influence birth outcomes by altering plasma choline concentrations. The effects of maternal ad libitum choline intake during pregnancy and fetal genetic variants on maternal and cord concentrations of choline and its metabolites are unknown. OBJECTIVES: This prospective study sought to assess the effect of 1) maternal dietary choline intake on maternal and cord plasma concentrations of choline and its metabolites, and 2) fetal genetic polymorphisms on cord plasma concentrations. METHODS: The dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16 wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire. Plasma concentrations of free choline and its metabolites were measured in maternal samples at recruitment and delivery, and in the cord blood. Ten fetal genetic variants in choline and one-carbon metabolism were assessed for their association with cord plasma concentrations of free choline and its metabolites. RESULTS: Mean maternal plasma free choline, dimethylglycine, and trimethylamine N-oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%, respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P < 0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at delivery, respectively (all P < 0.005). Maternal plasma concentrations of betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery were moderately strong, whereas maternal concentrations of free choline were not significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of these metabolites. Neither maternal dietary intake nor fetal genetic variants predicted maternal or cord plasma concentrations of choline and its metabolites. CONCLUSION: These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684.

Outcomes of pregnancy in women with hereditary hemorrhagic telangiectasia.

OBJECTIVE: To describe pregnancy outcomes in women with hereditary hemorrhagic telangiectasia (HHT). METHODS: This was a retrospective descriptive study of women with HHT (18-55 years of age) from the Toronto HHT Database using a telephone questionnaire regarding pregnancy, delivery, and neonatal outcomes. RESULTS: A total of 244 pregnancies were reported in 87 women with HHT. Miscarriages occurred in 20%. Hereditary hemorrhagic telangiectasia-related complications included minor hemoptysis during two pregnancies (1.1%) and hemothorax during four pregnancies (2.1%). One patient presenting with a hemothorax had presented during a previous pregnancy with a transient ischemic attack, most likely resulting from paradoxical emboli. One patient presented with an intracranial hemorrhage, and one patient presented with heart failure. These complications occurred in women previously unscreened and untreated for arteriovenous malformations. Other complications not clearly related to HHT were deep vein thrombosis (n=1), pulmonary embolism (n=1), myocardial infarction (n=1), and myocardial ischemia (n=1). Women noticed an increased frequency of epistaxis and development of new telangiectases during pregnancy. Epidural or spinal anesthesia was performed in 92 of 185 deliveries (50%) without complications. None of these women had undergone screening for spinal arteriovenous malformation before anesthesia. CONCLUSION: Women with HHT who have not been screened for arteriovenous malformations are at risk for serious pregnancy complications.

Abdominal visceral adiposity in the first trimester predicts glucose intolerance in later pregnancy.

OBJECTIVE: To assess whether abdominal adiposity in early pregnancy is associated with a higher risk of glucose intolerance at a later gestational stage. RESEARCH DESIGN AND METHODS: Subcutaneous and visceral fat was measured with ultrasonography at approximately 12 weeks' gestation. A 50-g glucose challenge test (GCT) was performed between 24 and 28 weeks' gestation. The risk of having a positive GCT (>or=7.8 mmol/l) was determined in association with subcutaneous and visceral adipose tissue depths above their respective upper-quartile values relative to their bottom three quartile values. RESULTS: Sixty-two women underwent GCTs. A visceral adipose tissue depth above the upper quartile value was significantly associated with a positive GCT in later pregnancy (adjusted odds ratio 16.9 [95% CI 1.5-194.6]). No associations were seen for subcutaneous adipose tissue. CONCLUSIONS: Measurement of visceral adipose tissue depth in early pregnancy may be associated with glucose intolerance later in pregnancy.

A rare etiology of delayed postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage, immediate or delayed, is a leading cause of maternal death. The most common etiologies are retained products of conception, infection, and subinvolution of the placental implantation site. CASE: A 31-year-old woman, gravida 1, para 0, had an uneventful pregnancy after infertility treatment. She was delivered by intrapartum Caesarean section because of arrest of descent. Twelve days after delivery she had profuse, intermittent vaginal bleeding, but physical examination and pelvic ultrasound failed to reveal the cause. Angiography was performed and showed a left uterine artery pseudoaneurysm that was successfully treated with arterial embolization. CONCLUSION: Use of uterine angiography and embolization at an early stage in the search for the etiology of postpartum hemorrhage helps to decrease morbidity and mortality.

Intrahepatic cholestasis of pregnancy in women with a multiple pregnancy: an analysis of risks and pregnancy outcomes.

OBJECTIVE: This study was conducted to assess the incidence and perinatal outcomes of multiple pregnancies complicated by intrahepatic cholestasis of pregnancy in an urban population. METHODS: We performed a retrospective chart review of all multiple gestation deliveries at our institution between January 2004 and December 2005. Antepartum and delivery data were collected for all patients. Symptoms and treatment were also abstracted for patients in whom intrahepatic cholestasis was diagnosed. We used the Student two-tail t test and Fisher exact test to examine the differences between multiple gestation pregnancies with and without cholestasis of pregnancy. RESULTS: Data were available for 263 multiple pregnancies. The incidence of cholestasis was 4.2% (11/263), with a mean onset at 29.4 weeks. There were no differences in mean gestational age at delivery, preterm delivery rate, meconium histiocytosis, incidence of preeclampsia, or incidence of postpartum hemorrhage between women with and those without cholestasis. There were no intrauterine fetal deaths in the cholestasis group. CONCLUSION: Women with multiple gestations complicated by cholestasis of pregnancy do not have increased adverse perinatal outcomes. The absence of unexplained fetal demise may be a result of routine delivery before 40 weeks' gestation in multiple pregnancies.

Gastroschisis: what is the average gestational age of spontaneous delivery?

BACKGROUND/PURPOSE: To consolidate what is known about pregnancies complicated by fetal gastroschisis through analysis of one of the largest series yet reported and to define the average gestational age of spontaneous delivery. METHODS: From 1980 to 2001, 159 pregnancies complicated by fetal gastroschisis were identified at a tertiary care center. Gestational age at delivery, birth weight, preterm delivery rate, and maternal age were compared to the 2001 general population statistics. Patients with pregnancies complicated by gastroschisis who went into spontaneous labor (n = 86) were subdivided into 2 groups based on gestational age (< 37 weeks and > or = 37 weeks). Operative delivery rates for nonreassuring fetal status and Apgar scores were assessed. RESULTS: Gastroschisis occurred more often in younger mothers (< 21 years) (42% vs 7.3%), was more frequently associated with preterm labor and delivery (28% vs 6%), and was associated with more low-birth-weight babies (36% vs 10%). The mean gestational age at spontaneous labor was 36.6 weeks. In those patients who labored spontaneously, there were no significant differences in the operative delivery rates for fetal distress; however, there was a trend to lower Apgar scores in babies born at 37 weeks or more. CONCLUSION: Our data provide a framework for further studies to determine the optimal timing and mode of delivery for fetuses with gastroschisis.