Homocysteine and methylmalonic acid levels in pregnant Nepali women. Should cobalamin supplementation be considered?

OBJECTIVE: The aim of this study was to investigate homocysteine and methylmalonic acid levels as markers of functional cobalamin and folate status in pregnant Nepali women. DESIGN: Cross-sectional study. SETTING: Patan Hospital, Kathmandu, Nepal. SUBJECTS: A sub-sample (n=382) of all pregnant women (n=2856) coming for their first antenatal visit in a 12 month period, 1994-1995. The selection of the sub-sample was based on maternal haematocrit values, categorised into three groups: severely, moderately and non-anaemic women. As serum levels of total homocysteine (s-tHcy) and methylmalonic acid (s-MMA) were similar in the three groups, pooled data are presented. Women who had already received micronutrient supplementation (n=54) were excluded. The remaining women (n=328) were included in the statistical analysis. RESULTS: Overall mean values (+/-s.d.) of s-tHcy and s-MMA were 9.5 (+/-4.2) micromol/l and 0.39 (+/-0.32) micromol/l, respectively. Elevated s-tHcy (>7.5 micromol/l) was found in 68% of the women, while 61% had elevated s-MMA (>0.26 micromol/l). Low s-cobalamin values (<150 pmol/l) were observed in 49% of the women, while only 7% had low s-folate values (< or =4.5 nmol/l). s-tHcy was significantly correlated with s-MMA (r=0.28, P<0.001), s-cobalamin (r=-0.30, P<0.001) and s-folate (r=-0.24, P<0.001). s-MMA was significantly associated with s-cobalamin (r=-0.40, P<0.001), but not with s-folate. CONCLUSIONS: Functional cobalamin deficiency was very common in the study population, while functional folate deficiency was rather uncommon. We suggest considering cobalamin supplementation to pregnant Nepali women. SPONSORSHIP: The Norwegian Research Council and the Norwegian Universities Committee for Development, Research and Education.

Maternal hematological status and risk of low birth weight and preterm delivery in Nepal.

BACKGROUND: Our aim was to investigate associations between maternal characteristics, with emphasis on hematological status, and risk of low birth weight and preterm delivery among pregnant Nepali women. METHODS: In a case-control study, 1400 pregnant women attending Patan Hospital, Kathmandu, Nepal for antenatal care and delivery in the period 1994 to 1996 were included. Women with twin pregnancies (n=15) and those delivering infants with congenital malformations (n=13) were excluded from the study. Maternal characteristics including hematocrit values were recorded at the first antenatal visit. Main outcome measures included birth weight, gestation at delivery, Apgar score, mode of delivery, and perinatal death. Linear and logistic regression models were used to analyze data. RESULTS: Severe anemia (hematocrit < or =24%) was associated with a significantly increased risk of low birth weight (<2500 g) and preterm delivery (<37 weeks gestation). High hematocrit values (> or =40%) did not increase the risk of low birth weight or preterm delivery. The risk of low Apgar score or operative deliveries was significantly increased in women with severe anemia in the first trimester. Teenagers, women with short height or low body mass index, and those belonging to the ethnic group Brahmins, had significantly higher risks of delivering low birth weight infants. CONCLUSIONS: Severe maternal anemia, particularly in the first trimester, was significantly associated with adverse pregnancy outcome. Low maternal age, height or body mass index also increased the risk of low birth weight. Improvements in the nutritional status of young Nepali women could contribute to improved health among their infants.

Infant death rates and animal-shed delivery in remote rural areas of Nepal.

This article outlines a community-based retrospective study in a remote area of Nepal and describes local birth practices and their impact on infant mortality. Data collection was carried out in two steps, a household survey from September to October 1996 and a qualitative research phase. Data collected include socio-economic background, reproductive history, birth practices and child survival. Among 3007 live-born children, 660 (22%) died before their first birthday. In keeping with local customs, approximately half of the children were delivered in an animal shed and the other half in the home. Children born in an animal shed were at significantly higher risk of dying than were those born in the home even after adjusting for socio-economic status and biological variables. The association was stronger in the neonatal period (OR = 2.8, 95% CI 1.9-4.1) than during the post-neonatal period (OR= 1.3, 95% CI 1.02-1.6). The preparation of the delivery place was inadequate and thereby facilitated infection of both the newborn and the mother. Traditional norms and animal-shed delivery practices are common in the Jumla community. The reasons addressed for giving birth in the animal shed included (1) Household Deity's anger if delivery takes place in the home and (2) easy to clean the shed following the birth.

The prevalence of anemia in pregnant Nepali women--a study in Kathmandu.

BACKGROUND: Anemia in pregnancy is associated with maternal and perinatal morbidity and mortality. The World Health Organization has suggested that where up-to-date information is not available, prevalence studies should be undertaken. METHODS: The distribution of hematocrit in 2280 pregnant women attending Patan Hospital, Kathmandu, for their first antenatal visit in a twelve month period, 1994-95, was studied. Anemia was defined as a hematocrit value < or =34% in the first and third trimesters, or < or =33% in the second trimester. Severe anemia was defined as a hematocrit value < or =24%. The prevalence of anemia and severe anemia, and associations with socio-demographic (age, ethnic group, living area, maternal and paternal education and occupation) and biological (height, body mass index, parity, gestation) variables were investigated. RESULTS: The hematocrit values ranged from 11-49% with a mean value of 32.6% (s.d. 3.9). The prevalences of anemia and severe anemia were 62.2% and 3.6%, respectively. High prevalence of anemia was observed among teenagers, farmers, women of short height, the ethnic groups Lama/Sherpa/Tamang, and women married to industrial workers or illiterate men. Also, the risk of anemia increased with gestation. Work within the service professions, higher education and high body mass index, were associated with a lower risk of anemia. CONCLUSIONS: A high prevalence of anemia among pregnant women in Kathmandu was observed. The hematocrit values were related to socio-demographic and biological factors. In order to plan focused and effective intervention, studies on the etiology of anemia among pregnant women in rural and urban areas of Nepal need to be carried out.

Seasonal variation in risk of anemia among pregnant Nepali women.

OBJECTIVE: We aimed to investigate whether there is any seasonal variation in risk of anemia among pregnant Nepali women. METHODS: We studied the hematocrit values in pregnant women (n=5495) attending Patan Hospital, Kathmandu for the first antenatal visit in the 2-year period from January 1994 until December 1995. In a sub-sample of subjects (n=2706), additional information was obtained through interviews and clinical examinations. Logistic regression models were used to analyze data. RESULTS: Mean hematocrit values recorded in the monsoon period were significantly lower than hematocrit values recorded in the winter. The prevalence of moderate (hematocrit 25-33%) and severe (hematocrit<25%) anemia was highest in September. CONCLUSIONS: We found a clear seasonal variation in risk of anemia, which was associated with rainfall and temperature. The monsoon seems to be a period when interventions may give the most beneficial effects.

Anaemia in pregnancy: possible causes and risk factors in Nepali women.

OBJECTIVE: The aim of this study was to investigate the importance of nutritional deficiencies and infections in the development of anaemia in pregnant Nepali women. DESIGN: Case-control study. SETTING: Patan Hospital, Kathmandu, Nepal. SUBJECTS: A sub-sample (n=479) of all pregnant women (n=2856) coming for their first antenatal visit in a 12 month period, 1994-1995. Women who had already received any micronutrient supplementation (n=82), and those whose serum samples showed macroscopic haemolysis (n=7) were excluded. The remaining women (n=390) were included in the statistical analysis. They were divided into three groups; a non-anaemic control group, haematocrit (Hct)>33% (n=82), and two case-groups: moderately anaemic, Hct 25-33% (n=254), and severely anaemic, Hct<25% (n=54). RESULTS: We found high prevalences of nutritional deficiencies and intestinal infections, both among cases and controls. The prevalence of low s-ferritin was high, especially among the severely anaemic women (55.6%). In a multiple logistic regression model, the presence of low s-vitamin A, elevated s-C-reactive protein or hookworm infection was associated with a significantly increased risk of severe anaemia. The adjusted odds ratios (95% CI) were 8.38 (1.99, 35.30), 4.91 (1.22, 19.67) and 5.43 (1.20, 24.61), respectively. CONCLUSIONS: In addition to the present routine iron and folate supplementation to pregnant Nepali women, vitamin A supplementation needs to be considered. Prevention and treatment of infections should, together with dietary advice, be emphasized more strongly in the antenatal care. SPONSORSHIP: The Norwegian Research Council and the Norwegian Universities Committee for Development, Research and Education. European Journal of Clinical Nutrition (2000) 54, 3-8

High-risk childbirth practices in remote Nepal and their determinants.

This study describes birth-related practices and their determinants among women in the Jumla district of Nepal. Data were derived from a household survey in 1996. Of 939 married women of reproductive age, 657 who had given birth to their last child during the previous five years were included in the analysis. Qualitative information was further obtained from traditional birth attendants (TBAs), mothers-in-law, community leaders and pregnant women. High-risk practices were common and related to local custom and lack of knowledge on the importance of cleanliness. Husband's level of education greater than fifth grade significantly reduced the high-risk practices in all stages of childbirth, independent of other socio-economic, biological and village variables.

The effect of male occupational exposure in infertile couples in Norway.

The objective of the study was to assess whether reduced semen quality in infertile couples is associated with occupational exposures known to be hazardous to fertility. Results of the first semen analysis were linked to occupational exposure data from a self-administered questionnaire. Reduced semen quality was found in men exposed to electromagnetic fields (odds ratio, 3.22; confidence interval, 1.46 to 7.09). A tendency toward reduced semen quality was seen in commuters (OR, 1.52; CI, 0.89 to 2.59), shift workers (OR, 1.46; CI, 0.89 to 2.40), and men exposed to heavy metals (OR, 1.47; CI, 0.76 to 2.87). In general, the impact of occupational exposure on semen quality in infertile couples in Norway seemed to be minor. However, occupational exposure mapping is still important in individual infertility investigations.

Secular trends in sperm variables for groups of men in fertile and infertile couples.

OBJECTIVE: To assess possible secular trends in sperm variables in men according to previous or subsequent paternity. DESIGN: A comparison of secular trends in sperm variables 1975-1994 in men under investigation for infertility in groups according to previous and subsequent paternity, based on data from the Medical Birth Registry of Norway. SETTING: University hospital, Sperm laboratory and the Medical Birth Registry of Norway. MATERIAL: Samples were obtained from: 1108 men who had fathered at least one child before the analysis. 1786 men who had at least one child after the analysis, and 2286 men with no children registered. MAIN OUTCOME MEASURES: Sperm concentration, seminal fluid volume, total number of spermatozoa per ejaculate. RESULTS: Analyzed by year of evaluation, men with no child registered had a significant secular decrease of sperm concentration, total number of sperms per ejaculate and seminal volume. The group with subsequent children had significant secular decrease of sperm concentration and total sperm count per ejaculate, while no significant changes were found for the group with previous children. Analyzed by year of birth, a significant decrease of sperm concentration and total sperm count was found for the group without and for the group with subsequent children. CONCLUSION: The results are compatible with a cohort effect, exhibiting a trend of deteriorating sperm variables in consecutive birth cohorts.

[The P-pill for men--when will it be available?]. / Den mannlige p-pillen--når kommer den?

Although the development of a hormonal contraceptive for men has proved to be more of a challenge than oral contraception for women, several experimental prototypes already satisfy many of the criteria that must be met. Steroid regimes are more effective in Asians than in men of other ethnic backgrounds. They are inexpensive, and the effect is reversible.GnRH analogues are promising, but further research is needed and is being carried out. Androgens must be used as a supplement to all hormonal strategies in order to maintain normal sexual function. The impact of androgens on lipid metabolism and prostate physiology must be clarified. Lack of funding is the greatest barrier to further research and the development of a hormonal contraceptive for men.

Follow-up after torsion of the spermatic cord.

Fifty-two patients were examined 4-10 1/2 years after operation for torsion of the spermatic cord. The testicular salvage rate was 56%. Loss of testicular tissue was correlated to preoperative duration of symptoms. Serum testosterone concentration was found to be within the reference range. FSH was elevated in patients with the longest duration of symptoms (> 24 h), suggesting an impairment of testicular function in these patients. There were two our of 13 patients with a severe oligo-azoospermia, both had a previous orchiopexy for undescended contralateral testis.

Identification of the complement regulatory protein CD59 in human colostrum and milk.

PROBLEM: Complement lytic activity has been demonstrated, and a potential for its activation is present in human colostrum and milk. This necessitates the presence of regulatory mechanisms protecting epithelial cells in the oropharynx and the gastrointestinal tract of the infant, the milk cellular elements, and bacteria colonizing the oropharynx and the gastrointestinal tract. Lactoferrin and C1 inhibitor have been attributed such a role. However, it is likely that additional protection against the cytolytic activity of the membrane attack complex is required. This has lead us to investigate the presence of the complement regulatory protein CD59 in human colostrum and milk, and to further characterize the source of secretion. METHOD: Samples of human colostrum and milk were obtained from volunteers at different stages of lactation, and separated into fat, skim milk, and milk cellular elements by centrifugation. Normal human mammary gland tissues were obtained from patients undergoing biopsy for benign conditions. SDS-PAGE and Western blotting, and an immuno dot-blot assay were used to identify CD59 in human milk. Immunohistochemistry was performed on all tissue samples and cytospins of the milk cellular elements, using monoclonal antibodies to CD59. RESULTS: CD59 was present in cell-free colostrum and milk as a 19-25 kDa glycoprotein. No variation in CD59 levels was detected between colostrum and milk. CD59 was present in great amounts in the cytoplasm and was highly expressed on the surface membrane on mammary gland acinar and ductal epithelial cells, while the milk cellular elements contained CD59 mainly in their cytoplasm. CONCLUSION: The complement regulatory protein CD59 present in cell-free human colostrum and milk may exert its effects both in the mammary gland and in the oropharynx and gastrointestinal tract of the infant. The lobuloalveolar epithelial cells in the mammary gland are the likely source of secretion.

Evaluation of a rapid enzyme immunoassay for detection of genital colonization of group B streptococci in pregnant women: own experience and review.

We have compared an enzyme immunoassay (ICON Step B, Hybritech) with cultures for demonstration of genital carriage of group B streptococci (GBS) in pregnant women, and studied the relationship between vaginal and rectal carriage of this organism. Pertinent literature has also been reviewed. Two hundred pregnant women at gestational week 17 were included. Swabs from the uterine cervix were tested for GBS by ICON Strep B immunoassay and ordinary cultures on blood agar. Additional swabs from the rectum were tested by cultures. The percentage of women with GBS in cervical secretions was 13.5% (27/200) by cultures and 4% (8/200) by the ICON Strep B immunoassay. The overall sensitivity of the immunoassay was 7.4%, and the specificity 96.5%. In conclusion, the sensitivity of rapid enzyme immunoassays is too low for accurate screening of GBS in the genital tract of pregnant women.

Identification of the complement regulatory proteins CD46, CD55, and CD59 in human fallopian tube, endometrium, and cervical mucosa and secretion.

PROBLEM: Complement lytic activity has been demonstrated, and a potential for its activation is present in human cervical and tubal secretions and in the endometrium. This necessitates the presence of regulatory mechanisms for protection of the sperm and the implanting allogeneic conceptus in the female genital tract. Complement regulatory proteins demonstrated on sperm and in seminal fluid have been attributed such a role. It is however likely that additional protection is required for a successful conception and implantation to take place. This lead us to investigate the distribution of the complement regulatory factors in cervical mucus and mucosa, uterine endometrium, and fallopian tube. METHOD: Endometrium and cervical mucosa were obtained from patients undergoing hysterectomy for benign conditions, and specimens were selected from different stages of the menstrual cycle. Fallopian tubes were obtained from patients submitted for sterilization, while cervical mucus was aspirated from volunteers undergoing gynecological examination. Immunohistochemistry was performed on all tissue samples, using monoclonal antibodies to membrane cofactor protein (MCP), decay accelerating factor (DAF), CD59 and complement receptor 1 (CR1). Western blot analysis was performed on cervical mucus under nonreducing conditions. RESULTS: MCP, DAF, and CD59 were found to be expressed in human endometrium and fallopian tube. No variation in expression was detected throughout the menstrual cycle. CR1 was not expressed. Soluble forms of DAF and CD59 were found to be present in cervical mucus. CONCLUSION: The complement regulatory proteins MCP, DAF, and CD59 are expressed throughout the female genital tract, and may thus play an important role in protecting the traversing sperm and implanting blastocyst from complement mediated damage.

Cyclic variation in the expression of Fc gamma receptors in human endometrium.

Cyclic variations of Fc gamma receptors (FcR) in human endometrium were studied in specimens from the fundal part, the lower part of the uterine cavity and from the endocervix obtained in the proliferative, ovulatory and early and late secretory phase. The three classes of FcR were studied using monoclonal antibodies (mAb) and indirect immunohistochemistry with avidin-biotin-peroxidase complexes. FcRI, FcRII and FcRIII were expressed on stomal cells throughout the cycle. In the late secretory phase some of the stromal cells had morphology comparable to predecidual cells. These cells express FcRIII only. FcRIII only were expressed on the glandular epithelium in all phases of the cycle. The endothelium was negative in the midcycle and positive early and late in the cycle for FcRI and FcRIII, although weak for FcRIII late in the cycle. FcRII was not expressed on the endothelium. Apparently the FcR activity in the endometrium does not vary during the menstrual cycle, except for small variation in the expression on the endothelium and the presence of FcRIII on positive predecidual cells. No differences in FcR expression were found in specimens taken from different parts of the uterine cavity.

Systemic and mucosal antibody responses to group B streptococci following immunization of the colonic-rectal mucosa.

The cervico-vaginal mucosa is poorly designed for inducing a mucosal immune response, but it can effect such a response evoked at other mucosal sites. This study was undertaken to determine whether colonic-rectal immunization with group B streptococci (GBS) might induce a local cervico-vaginal immune response. Mice were immunized with either fragmented GBS rectally, whole GBS rectally, or whole GBS subcutaneously. Cholera toxin (CT) was used as an adjuvant for the rectal immunizations. Following colonic-rectal immunization with whole GBS, the mean anti-GBS IgA antibody level in vaginal secretions was 735 kU/ml, with individual values reaching 3480 kU/ml. Corresponding levels of IgA antibodies never exceeded 10 kU/ml in serum and intestinal secretions, or 90 kU/g in feces. In vaginal secretions IgA antibodies to GBS also constituted a much larger fraction of total IgA than in serum, intestinal secretions and feces. Immunizations with fragmented GBS produced much lower IgA responses. Anti-GBS IgA response at the inductive site in the colon-rectum was not significant, as opposed to a strong anti-CT IgA response. Except in serum, the anti-GBS IgG responses to colonic-rectal immunizations were generally low, or absent. The results may provide a basis for the development of mucosal vaccines against GBS-infection.

Demonstration of Fc gamma receptors in human endometrium.

Cryostat sections of human endometrium bound sheep erythrocytes (E) sensitized with rabbit IgG antibody (A), (EA). Unsensitized E were not bound. Native, heat-aggregated IgG and Fc fragments of IgG inhibited the binding of EA, whereas IgM, IgA and F(ab')2 fragments of IgG did not. The data indicate the presence of receptors for the Fc part of IgG (FcR). Using immune complexes of horseradish peroxidase (HRP) and rabbit IgG antibodies to HRP and monoclonal antibodies (mAbs), FcR were located to the glandular epithelial and endothelial cells, macrophages and predecidual cells of the stroma. These structures were also stained by mAbs against all three FcR classes and a 40-kD low affinity placental FcR. Preliminary results indicate that the expression of FcR varies during different stages of the menstrual cycle. FcR in the endometrium may play a rôle in local immunoregulation necessary for nidation and development of the blastocyst.