Elevated plasma homocysteine in early pregnancy: a risk factor for the development of nonsevere preeclampsia

OBJECTIVE: We have recently demonstrated that an elevated plasma homocysteine in early pregnancy is associated with the development of severe preeclampsia. The aim of this study was to determine whether an elevated plasma homocysteine in early pregnancy is also associated with the development of nonsevere preeclampsia.STUDY DESIGN: Blood was obtained from patients attending for a first antenatal visit. Subjects were asymptomatic women who subsequently developed nonsevere preeclampsia. Controls were matched for parity, gestational age, and date of sample collection. Plasma homocysteine was measured using fluorescence polarization immunoassay.RESULTS: There were 71 cases of nonsevere preeclampsia sampled at a mean gestational age (±SD) of 15.9±3.6 weeks and 142 controls at 15.6±3.4 weeks. The preeclampsia cases had a mean (±SD) homocysteine level of 8.4±2.4 μmol/L, whereas controls had a mean homocysteine of 7.07±1.5 μmol/L (P≤.0001).CONCLUSION: Women who develop nonsevere preeclampsia have higher plasma homocysteine levels in early pregnancy compared with women who remain normotensive throughout pregnancy. An elevated plasma homocysteine value in early pregnancy may be associated with a 4-fold increased risk for development of nonsevere preeclampsia.     

Prenatal diagnostic rates and postnatal outcomes of fetal orofacial clefts in a Taiwanese population

Objective

To report the incidence, prenatal diagnostic rate, and postnatal outcomes of fetal orofacial cleft at a tertiary referral center in Taiwan.

Methods

The demographic data, maternal and fetal characteristics, and postnatal outcomes for fetuses with cleft lip and/or cleft palate (CL/P) born between January 1998 and December 2008 at Chang Gung Memorial Hospital, Taipei, were reviewed retrospectively, and diagnostic rates were evaluated according to cleft type.

Results

Among 26 499 deliveries, 84 were affected with CL/P. The mean maternal age and gestational age at detection of CL/P were 30.37 years (range 21-41 years) and 24.7 weeks (range 18-33 weeks), respectively. Thirty-one fetuses had associated structural anomalies, 5 of which involved chromosomal aberrations. CL/P was diagnosed prenatally for 74 (88%) fetuses. After consultations, 17 pregnancies (20%) were aborted. The postnatal survival rate was 95.5% (64/67 infants). The type of cleft had a significant influence on correct prenatal diagnosis (P < 0.001).

Conclusion

For fetuses diagnosed prenatally with an orofacial cleft, access to an experienced craniofacial team, well-planned delivery, and pediatric intensive care led to favorable postnatal outcomes after lethal malformations were excluded through detailed sonographic and chromosomal evaluations.     

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.     

Fetal and maternal plasma homocysteine levels during the second half of uncomplicated pregnancy

Objective: To measure fetal and maternal plasma homocysteine (Hcy) concentrations in uncomplicated pregnancies.

Methods: Paired maternal venous and fetal umbilical cord blood (n?=?81) samples were evaluated for plasma Hcy and vitamin B₁₂ levels, in addition to eight neonatal umbilical cord blood samples obtained immediately following delivery.

Results: Both fetal and maternal Hcy concentrations were positively correlated with advancing gestational age (ρ?=?0.44, p?<?0.0001; and ρ?=?0.27, p?<?0.05, respectively). Fetal plasma Hcy concentrations [2.2?µmol/l (IQR: 2.0–3.2)] were significantly lower than both neonatal umbilical vein [5.0?µmol/l (IQR: 4.4–6.5); p?<?0.001] and maternal plasma Hcy levels [4.4?μmo/l (IQR: 3.4–5.4); p?<?0.001]. In addition, Hcy values at term were higher in the umbilical vein compared with the umbilical artery [5.0?μmol/l (IQR: 3.4–5.4) versus 4.2?μmol/l (IQR: 3.7–5.5), respectively; p?=?0.016]. Significant correlation was noted and between fetal and maternal Hcy levels (ρ?=?0.50, p?<?0.0001), while fetal Hcy was negatively correlated with maternal B₁₂ concentrations (ρ?=??0.32, p?<?0.001).

Conclusions: Fetal Hcy levels were significantly lower than maternal and neonatal levels and correlated with gestational age across the second half of pregnancy.     

Increased homocysteine levels exist in women with preeclampsia from early pregnancy

Objective: The present prospective study examines the levels of maternal plasma folate, vitamin B₁₂ and homocysteine in normotensive control (NC) women and women with preeclampsia (PE) from early pregnancy till delivery.

Methods: The present study includes 126 NC and 62 PE women. Maternal blood was collected at 3 time points during pregnancy (T1?=?16th–20th weeks, T2?=?26th–30th weeks and T3?=?at delivery). Levels of folate, vitamin B₁₂ and homocysteine were estimated by the chemiluminescent microparticle immunoassay technology.

Results: Maternal plasma folate levels were similar between NC and PE women at all the time points across gestation. Maternal plasma vitamin B₁₂ levels were significantly higher in PE (p?<?0.05) as compared with NC at T2. Maternal plasma homocysteine levels were higher in PE as compared with NC at all the time points, i.e. T1, T2 (p?<?0.05 for both) and T3 (p?<?0.01).

Conclusion: Our results indicate that higher homocysteine levels exist in women with PE from early pregnancy and continue till delivery.     

Low maternal vitamin B12 is a risk factor for neural tube defects: a meta-analysis

Abstract

Objective.?The objective of this study was to assess whether low level of maternal vitamin B₁₂ is associated with an increased risk of fetal neural tube defects (NTDs), in order to contribute to research on further reduction of NTDs under a background of mandatory folic acid (FA) fortification.

Methods.?A meta-analysis was conducted. We retrieved and evaluated the studies published on the risk of low level of maternal vitamin B₁₂ for NTDs. The homogeneity of the studies was examined using the forest graph. Meta-analysis was applied to calculate the odds ratio (OR) of fetal NTDs in relation to low maternal B₁₂ and its 95% confidence interval (CI).

Results.?We identified nine published articles including 567cases and 1566 controls in the meta-analysis. All the studies selected were homogeneous according to the forest graph (χ²?=?15.05, P?<?0.1). The estimated OR value of fetal NTDs in relation to low maternal B₁₂ was 2.41 (95% CI: 1.90–3.06).

Conclusion.?Low maternal B₁₂ status could be an important risk factor for the development of fetal NTDs. The addition of synthetic B₁₂ to current recommendations for periconceptional FA tablet supplements or FA-fortified foods should be considered.     

Plasma homocysteine,vitamin B<Subscript>12</Subscript> and folate levels in hydatidiform moles and histopathological subtypes

Objective  To investigate the association of mole hydatidiform with plasma homocysteine, vitamin B₁₂, and folate levels. Methods  Sixty-eight patients diagnosed with mole hydatidiform at our clinic between February and October 2007 were assessed in a case-control study. Plasma homocysteine, vitamin B₁₂, and folate levels, taken before evacuation of patients with hydatidiform mole, were compared with the results of 100 healthy normal pregnants of first trimester; and also plasma homocysteine, vitamin B₁₂, and folate levels were compared according to histopathological types of mole hydatidiforms. SPSS 14.0 package program was used to analyze the data. Logarithmic transformation was applied for variables. Parameters were expressed as mean ± standard deviation. Results  The mean of plasma homocysteine levels was higher in molar group (0.8 ± 0.13) than in normal pregnant group (0.7 ± 0.13) and the difference was statistically significant (P < 0.001). The mean of plasma vitamin B₁₂ levels was found to be similar both in normal pregnant women (2.4 ± 0.17) and in the molars (2.4 ± 0.15) (P = 0.272). The mean of plasma folate levels was lower in molar group (1.0 ± 0.15) than in normal pregnant women (1.2 ± 0.17) and the difference was statistically significant (P < 0.001). The hydatidiform moles of 68 patients were divided into two groups according to histopathological examination: 36 patients were partial moles and the others were complete. The difference of plasma mean homocysteine, vitamin B₁₂, and folate levels in these two groups was not statistically significant. There were statistically significant differences of plasma mean homocysteine and folate levels one by one in complete and in partial moles when compared with the normal pregnants. The mean of plasma folate levels were lower (1.0 ± 0.17 for partials, 1.0 ± 0.13 for completes) and the homocysteine levels were higher (0.9 ± 0.14 for partials, 0.8 ± 0.12 for completes) than the levels of normal group. Conclusion  This study suggests that there may be an association between plasma folate and homocysteine levels with hydatidiform moles. Folate may play a protective role in preventing molar pregnancy. Further controlled prospective studies are needed to investigate the possible effect of homocysteine, vitamin B₁₂, and folate in molar pregnancies.     

Can serum ferritin,vitamin B12 and folic acid levels affect serum screening tests during pregnancy?

Objective: To examine the relation of serum folate, vitamin B₁₂ and ferritin levels to 1st and 2nd trimester serum screening markers. Methods: Fetal crown-rump length (CRL), nuchal translucency (NT), and first and second trimester serum screening tests of 228 pregnant women were obtained. In all cases, serum vitamin B₁₂, folic acid and ferritin levels were analyzed during the 11–14 week period. Levels below <15 µg/L, 3 ng/mL and 211 pg/mL were accepted as nutrient deficiency for serum ferritin, folic acid and vitamin B₁₂, respectively. Results of serum screening markers of women below and above these values were compared with each other. Results: Comparison of groups with ferritin levels <15 and >15 µg/L for 1st and 2nd trimester serum screening parameters revealed significant differences between groups in terms of pregnancy associated plasma protein-A (PAPP-A), free β-human chorionic gonadotropin (fb-hCG), AFP and hCG. Comparison of women with low versus normal B₁₂ levels revealed significant differences in terms of NT, PAPP-A and fb-hCG. Conclusion: Although sufficient, number of cases is limited in this study so results cannot be generalized to all population. It could be advised that in addition to folic acid supplementation, deficiencies of ferritin and B₁₂ must be corrected in patients considering pregnancy or early 1st trimester pregnant women to obtain more accurate serum screening results.     

Maternal high fat diet deficient in vitamin B12 influences long chain polyunsaturated fatty acid composition in rats

Objective: In India, there is a rise in non-communicable diseases due to diets deficient in vitamin B₁₂, low in docosahexaenoic acid (DHA) and increased consumption of westernized diet. The present study aims to examine the effect of maternal high fat diet (HFD) in absence of vitamin B₁₂ on pregnancy outcome and tissue fatty acid composition in dams.

Methods: Pregnant Wistar rats were assigned to following diets: Control (C), HFD, High fat diet supplemented with omega-3 fatty acids (HFDO), 4) High fat diet deficient in vitamin B₁₂ (HFBD), High fat deficient in vitamin B₁₂ supplemented with omega-3 fatty acids (HFBDO).

Results: There was no effect on pregnancy outcome as a consequence of different dietary treatments. The levels of DHA in HFBD group were lower (p?Conclusion: This data suggests that maternal HFD (using dairy fat) did not adversely affect pregnancy outcome. However, maternal HFBD reduced levels of placental DHA. This may have implications for reduced fetal brain growth and development.     

Vitamin C intake and the risk of preterm delivery

OBJECTIVE: Ascorbic acid deficiency may lead to premature rupture of the membranes. STUDY DESIGN: The study included a prospective cohort of pregnant women, aged >/=16 years, with singleton gestations who received care at one of four prenatal clinics in central North Carolina from 1995 through 1998. Vitamin C intake preconceptionally and during the second trimester was examined for its association with preterm delivery and subsets of preterm labor, premature rupture of the membranes, and medical induction in 2064 women. RESULTS: Women who had total vitamin C intakes of <10th percentile preconceptionally had twice the risk of preterm delivery because of premature rupture of the membranes (relative risk, 2.2; 95% CI, 1.1, 4.5). This risk was attenuated slightly for second-trimester intake (relative risk, 1.7; 95% CI, 0.8, 3.5). The elevated risk of preterm premature rupture of the membranes was greatest for women with a low vitamin C intake during both time periods. CONCLUSION: Because diet and supplement use are modifiable behaviors, corroboration of these findings would suggest a possible intervention strategy.     

Maternal vitamin D levels and the risk of perinatal death

Objective: To determine the association between maternal vitamin D levels and perinatal death.

Methods: A retrospective cross-sectional study of all non-anomalous, singleton births (≥24 weeks) with perinatal death compared to a matched control group. Only pregnancies with a recorded vitamin D level at booking (8–19 weeks gestation) were included for analysis. Maternal vitamin D levels were categorized into normal, deficient and insufficient cohorts and variables compared between the three groups.

Results: There were 31 perinatal deaths which were compared to 111 controls. Median vitamin D levels were lower in the perinatal death cohort compared to the control group (55?nmol/L versus 64?nmol/L, p?=?0.43). There was no significant increase in deaths between the normal and deficient (p?=?0.33) or insufficient (p?=?0.09) groups.

Conclusions: Low maternal vitamin D levels at booking were not associated with an increased risk of perinatal demise.     

Comparison of the effect of oral and transdermal hormone therapy on fasting and postmethionine homocysteine levels

OBJECTIVE: To compare the modifications on basal and post-methionine homocysteine (Hcy) levels induced by transdermal vs. oral continuous combined hormone therapy (HT). DESIGN: Prospective randomized study. SETTING: Outpatient service at university hospital. PATIENT(S): Twenty-four healthy postmenopausal women. INTERVENTION(S): Six-month administration of transdermal (50 microg/d of E(2) and 140-170 microg/d of norethisterone [NET] acetate; n = 12) or oral (2 mg of E(2) and 1 mg of NET acetate; n = 12) HT. MAIN OUTCOME MEASURE(S): Fasting levels of Hcy, cysteine (Cys), folate, and vitamin B12. Post-methionine Hcy concentrations. RESULT(S): During HT, a slight decrease of fasting Hcy (8.9 [6.7; 15.2] micromol/L vs. 8.3 [4.9; 12.0] micromol/L) and fasting Hcy/Cys, a possible index of Hcy trans-sulfuration (0.061 [0.039; 0.107] micromol/L vs. 0.048 [0.032; 0.093] micromol/L) was observed. Modifications were similar in the transdermal and oral group. Net decreases of Hcy and Hcy/Cys observed during HT were related linearly to pretreatment values (r = 0.821 and r = 0.775, respectively), and were significant for Hcy above, but not below, 9 micromol/L. Transdermal (33.5 [27.5; 75.9] micromol/L vs. 28.4 [17.4; 48.9] micromol/L) or oral HT (36.1 [17.7; 74.8] micromol/L vs. 29.9 [17.5; 50.3] micromol/L), decreased, similarly, post-methionine Hcy levels. CONCLUSION(S): Similarly to oral, transdermal HT reduces post-methionine Hcy and fasting Hcy when it is elevated.     

Investigation of multiple factors which may contribute to vitamin D levels of bedridden pregnant women and their preterm neonates

Objective: 25-Hydroxyvitamin D (25-OH-D) is the marker, which indicates vitamin D levels. The aim of this study was to investigate the possible factors, which contribute to serum 25-OH-D levels in bedridden mothers and their preterm neonates.

Methods: Twenty-six preterm neonates born during the period of 24–33 weeks of gestational age and 20 mothers (who experienced pregnancy complications) were recruited to the study.

Results: Five major results were obtained. (i) The 25-OH-D serum levels for preterm neonates and their mothers were found to possess strong correlation (ii) and both differed significantly in comparison with the optimal levels. (iii) An increase of mothers’ 25-OH-D serum levels was associated with an increased possibility that the neonates would be measured to have normal 25-OH-D levels. (iv) Sex was not a key factor to neonates’ 25-OH-D levels. (v) No correlation was found between mothers’ 25-OH-D levels and their vitamin D₃ supplement (400?IU/d during pregnancy).

Conclusions: Due to insufficient exposure to sunlight and a diet not enriched with vitamin D, bedridden pregnant women suffer from vitamin D deficiency and pregnancy complications lead often to birth of preterm neonates with the same deficiency. Mothers should increase the total amount of vitamin D intake (food and supplement).     

Ganirelix acetate use in normal- and poor-prognosis patients and the impact of estradiol patterns

OBJECTIVE: To evaluate cycle outcomes in patients with either poor or normal prognosis undergoing IVF treatment with a GnRH antagonist (ganirelix acetate) for LH suppression. DESIGN: Nonrandomized, noncontrolled, retrospective review. PATIENT(S): 204 patients, aged 23-41 years, undergoing IVF. INTERVENTION(S): Patients completed 225 consecutive cycles of IVF with a GnRH antagonist (Antagon; Organon, Roseland, NJ) for LH surge prevention. Sixty cycles were conducted in patients with a known poor prognosis, whereas 165 were conducted in patients with a normal IVF prognosis. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), for the series as a whole and according to prognosis, and serum E2 patterns. RESULT(S): The PR per initiated cycle for the series as a whole was 33.3%. The pregnancy rate was 42.1% per ET for the entire series, with a cycle cancellation rate of 21%. When evaluated by prognosis, the poor-prognosis patients had PRs of 8.3% per attempt and 15% per transfer, whereas the normal-prognosis patients had PRs of 40% per attempt and 45% per transfer. Pregnancy rate did not vary by E2 pattern (drop, plateau, or rise). Oral contraceptive pretreatment was noted to be associated with high cancellation rates in the group of known poor responders, whereas for the group as a whole, cycle outcome was unaffected by the use of oral contraceptives. CONCLUSION(S): Use of GnRH antagonists in patients with an a priori poor IVF prognosis results in predictably poor outcomes. Patients without factors predicting poor outcome have acceptable PRs. The pattern of E2 rise immediately after initiation of GnRH antagonists does not predict cycle outcome. Oral contraceptives can be successfully used to schedule antagonist-based IVF cycles but might increase the risk of cycle cancellation in some patient populations.     

Effect of leonurine hydrochloride on endothelin and the endothelin receptor-mediated signal pathway in medically-induced incomplete abortion in rats

Objective

Endothelin (ET) is involved in uterine contractions. Our previous study showed that leonurine hydrochloride (LH) inhibits abnormal bleeding caused by incomplete abortion through an increase in uterine contractions in rats. The present study was conducted to show that LH treatment regulates the ET-mediated signal pathway in abortion in rats.

Study design

Early pregnancies in rats had incomplete abortions induced using mifepristone in combination with misoprostol. After the abortions, the rats were treated with LH orally for 7 days and surgery was performed. The sinistro-uterus was dissected for measurement of ET and nitric oxide (NO); the dextro-uterus was stored at −80°C for ET receptor (ET_A and ET_B) analysis. Myometrial cells from the dextro-uterus were cultured for measurement of phospholipase C (PLC) activity, intra-cellular Ca²⁺ concentration ([Ca²⁺]_i), and protein kinase C (PKC) activity.

Results

In in vivo experiments, LH treatment elevated the ET level and ET/NO ratio in rats with induced abortions and up-regulated ET_A mRNA expression (P < 0.01 vs. the model group), but there was no change in ET_B mRNA. LH significantly increased the [Ca²⁺]_i, PLC activity, and relative production of PKC protein in myometrial cells.

Conclusion

LH increased uterine contractions in rats with incomplete abortions by modulating the ET receptor-mediated signal pathway.     

Seropositivity of influenza A H1NI in mothers and infants following maternal vaccination with trivalent seasonal influenza vaccine after the 2009 pandemic

Objective

To assess H1N1 antibody titers between vaccinated and nonvaccinated maternal and cord blood sera after the 2009 pandemic.

Follicle-stimulating hormone and estradiol levels independently predict the success of assisted reproductive technology treatment

OBJECTIVE: To evaluate the relationship between early follicular phase levels of FSH and E(2) and outcomes of therapy with assisted reproductive technologies (ART). DESIGN: Retrospective cohort study. SETTING: ART centers in the United States. PATIENT(S): Women receiving 19,682 ART procedures performed in 135 clinics. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rates of clinical pregnancy, live birth delivery, and high ovarian response (>/=10 oocytes retrieved after stimulation). RESULT(S): The ratio of each FSH or E(2) value to the respective upper limit of normal value for the clinic was computed. Within each age group, rates of pregnancy, live birth, and high ovarian response decreased linearly as FSH levels increased. For example, among women 35 years of age and younger, pregnancy rates (PR) ranged from 41.1% (FSH ratio 0-0.5) to 18.5% (FSH ratio >2.0). The three outcomes exhibited a similar downward trend as E(2) ratios increased. When both hormone ratios were elevated, outcomes were least favorable. These relationships remained statistically significant after we adjusted for diagnosis, number of embryos transferred, previous births, previous ART therapy, and use of GIFT, zygote intrafallopian transfer (ZIFT), intracytoplasmic sperm injection (ICSI), or assisted hatching. CONCLUSION(S): The FSH and E(2) ratios predict ART success independent of age and other clinical prognostic factors.     

Risk factors for Toxoplasma gondii infection in mothers of infants with congenital toxoplasmosis: Implications for prenatal management and screening

OBJECTIVE: The purpose of this study was to determine whether demographic characteristics, history of exposure to recognized transmission vehicles, or illness that was compatible with acute toxoplasmosis during gestation identified most mothers of infants with congenital toxoplasmosis. STUDY DESIGN: Mothers of 131 infants and children who were referred to a national study of treatment for congenital toxoplasmosis were characterized demographically and questioned concerning exposure to recognized risk factors or illness. RESULTS: No broad demographic features identified populations that were at risk. Only 48% of mothers recognized epidemiologic risk factors (direct or indirect exposure to raw/undercooked meat or to cat excrement) or gestational illnesses that were compatible with acute acquired toxoplasmosis during pregnancy. CONCLUSION: Maternal risk factors or compatible illnesses were recognized in retrospect by fewer than one half of North American mothers of infants with toxoplasmosis. Educational programs might have prevented acquisition of Toxoplasma gondii by those mothers who had clear exposure risks. However, only systematic serologic screening of all pregnant women at prenatal visits or of all newborn infants at birth would prevent or detect a higher proportion of these congenital infections.