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Underreporting of maternal deaths on death certificates and the magnitude of the problem of maternal mortality.

OBJECTIVES: I studied the extent to which maternal deaths are underreported on death certificates. METHODS: We collected data on maternal deaths from death certificates, linkage of death certificates with birth and fetal death records, and review of medical examiner records. RESULTS: Thirty-eight percent of maternal deaths were unreported on death certificates. Half or more deaths were unreported for women who were undelivered at the time of death, experienced a fetal death or therapeutic abortion, died more than a week after delivery, or died as a result of a cardiovascular disorder. CONCLUSIONS: The number of maternal deaths is substantially underestimated when death certificates alone are used to identify deaths, and it is unlikely that the Healthy People 2010 objective of reducing the maternal mortality rate to no more than 3.3 deaths per 100000 live births by 2010 can be achieved. Increasing numbers of births to older women and multiple-gestation pregnancies are likely to complicate efforts to reduce maternal mortality.

Adolescent↗

Maternal mortality in a maternity hospital in Turkey.

BACKGROUND: To determine the leading causes of maternal mortality in a large maternity hospital and to define priorities regarding this subject throughout Turkey. METHODS: Retrospective, institutional study among 100,531 live births between 1983 and 1992. RESULTS: Seventeen maternal deaths took place in this institution. Thus, the overall maternal mortality ratio was 16.9 per 100,000. The leading causes of maternal mortality were hemorrhage in seven (41.2%) and pulmonary embolism in six (35.3%) patients. The majority of deaths were observed in the 25-29 and 30-34 age groups and in patients with parity more than two. CONCLUSION: The relatively low figure of 16.9/100,000 for maternal mortality may be seen as a promising health index. However, obstetric hemorrhage is still the leading cause of this series. Pregnant women less than 20 years old and greater than 35 years old, and grand multiparous women as well as women with hypertension and heart disease are at high mortality risk. The observation of such cases demands further efforts for improved obstetric care in the hospital and throughout Turkey.

Adolescent↗

Maternal health services and maternal mortality in Papua New Guinea.

Surveys of maternal mortality rates in rural areas of Papua New Guinea over the past thirty years report 2-18 deaths per 1000 live births. The national maternal mortality register commenced in 1970 and reports rates of 2-7/1000 deaths for urban areas and 7-20/1000 deaths for rural areas. However, less than a quarter of maternal deaths are believed to be reported to the register: most of the unreported deaths are unsupervised confinements. Nevertheless obstetrical causes now account for 20% of total admissions to hospital and health centres in Papua New Guinea, and are the commonest causes of admission. The great majority of obstetrical admissions come from urban and periurban areas. Most rural women continue to confine at home where only a small fraction of maternal deaths are reported. It is as yet unclear whether modern health services have made any impact on rural maternal mortality rates. A plea is made for more complete reporting of maternal deaths to the national register of both supervised and unsupervised confinements.

Female↗

Effects of preweaning exposure to novel maternal odors on maternal responsiveness and selectivity in adulthood.

We examined the effects of odor exposure in the nest on the offspring's subsequent adult responsivity to pups scented with the same odor or a different odor. It was hypothesized that animals receiving exposure to the odor in the nest would be more maternally responsive to pups scented with the (same) exposed odor than to unscented (water-scented) pups. In the first part of the study (Part A), Sprague-Dawley female rat pups (days 1-18 of age) either received exposure to an artificial lemon odor or to the natural (water) odor in the nest. In the second part of the study (Part B), rat pups were exposed daily to lemon or neutral odorants in an incubator at a distance from the mother and the nest. On day 21, animals received odor preference tests for lemon versus neutral pine bedding. On day 60, animals were mated and their pups were removed at 15-min intervals at the time of parturition. Animals were then tested for maternal behavior to foster pups on day 1 or 7 after parturition. Foster pups were scented either with the lemon odor or with water (unscented). Early exposure to lemon in the nest context enhanced animals' attraction to the lemon odor in juvenile tests. In adult maternal tests, exposure to odor on the mother and in the nest had two effects. It increased the latency for animals to express maternal behavior; however, once mothers expressed maternal behavior, they spent more time licking and crouching over pups scented with the same odorant to which they had been exposed earlier on their own mothers. Simple exposure to the lemon odorant out of context of the nest had no effect on adult maternal latencies or behavior.

Animals↗

Effect of maternal blood phenylalanine level on mouse maternal phenylketonuria offspring.

The genetic mouse model BTBR-Pah(enu2) was used to more thoroughly investigate the pathogenesis of maternal phenylketonuria (MPKU). More specifically, it was used to examine the effect of maternal blood phenylalanine (PHE) level on the pregnancy outcome of MPKU offspring as determined by certain key measures of development at birth (i.e., head circumference, weight, and crown-rump length of offspring). In this study, we clearly observed that elevated maternal blood PHE levels, whether they were caused by the maternal diet or the maternal genotype, were responsible for fetal abnormalities. As in human MPKU, significant reductions (P < 0.0001) in birth weight, crown-rump length, and head circumference were seen in offspring gestated under the condition of high maternal blood PHE levels. These findings strongly suggest that there are sufficient similarities between human MPKU and MPKU in this mouse model to establish it as a very promising model for future studies designed to characterize human MPKU more thoroughly.

Abortion, Spontaneous↗

Maternal-fetal distribution and transfer of dioxins in pregnant women in Japan, and attempts to reduce maternal transfer with Chlorella (Chlorella pyrenoidosa) supplements.

Dioxins can be transferred from mother to fetus via the placenta, or to nursing infants via breast milk, potentially causing developmental health problems in children. To assess pediatric health risks from dioxins, exposure of mothers and children to dioxins must be clarified. Methods of reducing maternal transfer of dioxins should also be investigated. Concentrations of 28 dioxin (polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and co-planar polychlorinated biphenyls) congeners in blood, adipose tissue, breast milk, cord blood and placenta collected from 44 pregnant Japanese women were measured. In addition, to investigate potential reductions in maternal transfer of dioxins, 23 pregnant women were instructed to take Chlorella pyrenoidosa supplements during pregnancy. Correlations were observed between dioxin total toxic equivalents (total TEQ) in blood and total TEQ in adipose tissue (r=0.913, P<0.0001), breast milk (r=0.695, P=0.0007), and cord blood (r=0.759, P<0.0001). Dioxin levels transferred to fetuses and nursing infants reflect cumulative maternal concentrations of dioxins. A linear regression equation was introduced to predict total TEQ in breast milk and cord blood from dioxin levels in maternal blood, which should prove useful in evaluating fetal and infant risk of dioxin exposure. Total TEQ in cord blood were approximately 26% lower than in maternal blood (P<0.0001). The results of this study suggest that transplacental transfer differs depending on the dioxin congener. Total TEQ in breast milk were approximately 30% lower in the Chlorella group than in controls (P=0.0113). This finding suggests that maternal transfer of dioxins can be reduced using dietary measures such as Chlorella supplements.

Adipose Tissue↗

Changes in maternal and fetal nicotine distribution after maternal administration of monoclonal nicotine-specific antibody to rats.

Vaccination against nicotine to elicit the production of nicotine-specific antibodies is a potential treatment for tobacco addiction which reduces nicotine distribution from serum to brain. Vaccination of pregnant rats also reduces the distribution of maternally-administered nicotine to the fetal brain. Whether this is due to maternal antibody reducing the transfer of nicotine from mother to fetus, or to fetal antibody altering the distribution of nicotine within the fetus, is not clear. In the current study, passive immunization of rats with the murine monoclonal nicotine-specific antibody Nic311 was used as a surrogate for vaccination because antibody transfer to the fetus was anticipated to be lower than with vaccination. Pregnant rats received nicotine from gestational day (GD) 18-20 as frequent i.v. boluses to simulate nicotine exposure from smoking. Nic311 was administered at doses of 30, 80 or 240 mg/kg on GD 19. Fetal serum Nic311 levels on GD 20 were <3% of concurrent maternal levels, but concentrations of up to 20 ug/ml in fetal serum were obtained owing to the very high levels in maternal serum. Accumulation of the chronically administered nicotine, measured on GD 20, was not changed by Nic311 treatment in either maternal or fetal brain. The early distribution of nicotine to maternal brain, measured 5 min after a dose, was markedly reduced by Nic311, while the early distribution of nicotine to whole fetus and fetal brain was not substantially altered. These data suggest that the limited transfer of Nic311 to the fetus in turn limits the ability of Nic311 to reduce nicotine distribution to the fetal brain.

Animals↗

Fas ligand expression by maternal decidual cells is negatively correlated with the abundance of leukocytes present at the maternal-fetal interface.

The abundance of leukocytes at the maternal-fetal interface could influence the fate and invasion of extravillous trophoblasts. However, the mechanism(s) involved in determining the number of leukocytes present at the maternal-fetal interface as well as the nature of the interactions between invading fetal trophoblasts, maternal leukocytes and decidual cells are not well understood. In the present studies, we examined Fas ligand (FasL)/Fas expression at the maternal-fetal interface in human placental tissues of early pregnancy by immunohistochemistry. The types of cells and their localization were also characterized by specific cell markers (cytokeratin, vimentin and CD45 for trophoblast, decidual cells and leukocytes, respectively). The cells undergoing apoptosis and specific apoptotic trophoblasts were detected by TUNEL assay and M30 cytoDEATH immunostaining, respectively. Using single or double immunostaining, we found that FasL expression in decidual cells was negatively correlated with the number of Fas-expressing leukocytes in the same region. Furthermore, the density of leukocytes had an inverse relationship with the number of interstitial trophoblasts present in the same area. We observed also that extravillous trophoblasts are viable despite expressing Fas and being in close proximity to decidual cell-derived FasL. These data support our hypothesis that maternal decidual cell-derived FasL may be involved in preventing the recruitment of Fas-bearing leukocytes at the maternal-fetal interface through apoptosis induction by Fas/FasL interaction, thereby promoting trophoblast invasion.

Decidua↗

The changing maternal "self" hypothesis: a mechanism for maternal tolerance of the fetus.

Recent advances in placental biology and immunology lead us to propose a novel hypothesis for maternal tolerance of the semi-allogeneic fetus and amelioration of rheumatoid arthritis (RA) during pregnancy. The initial event in this hypothesis is extrusion of placental apoptotic syncytiotrophoblast debris recently identified to contain intracellular fetal HLA Class II molecules, into maternal blood. The second event is uptake of apoptotic syncytiotrophoblast by immature maternal dendritic cells and presentation of fetal HLA class II peptides. In addition to presenting foreign antigens, HLA molecules also present HLA self-peptides. In the setting of the non-inflammatory environment of pregnancy, this process is expected to induce peripheral tolerance of fetal antigens through T cell death, anergy or induction of regulatory T cells in the lymph nodes. This hypothesis suggests a mechanism by which the simultaneous presentation of fetal and self (RA-associated) HLA peptides by tolerogenic dendritic cells during pregnancy may explain the observed amelioration of RA as a secondary benefit of fetal tolerance. After delivery, apoptotic syncytiotrophoblast debris disappears from maternal blood, autoimmunity returns and RA recurs. Thus, during pregnancy maternal immunologic "self" includes fetal HLA Class II as a result of apoptotic syncytiotrophoblast uptake by maternal tolerogenic dendritic cells.

Arthritis, Rheumatoid↗

How does maternal smoking affect birth weight and maternal weight gain? Evidence from the Ontario Perinatal Mortality Study.

A large data set was used to examine the possibility that maternal smoking during pregnancy causes low birth weights by reducing maternal appetite, eating, and weight gain. As always, birth weight distributions shifted downward as maternal smoking level increased. Maternal weight gain distributions, on the other hand, were the same for smokers and nonsmokers. Within each level of maternal weight gain, from less than five pounds to over 40 pounds, the more the mothers smoked the greater was the percentage of neonates weighing less than 2,500 grams. This evidence supports a direct effect of maternal smoking on birth weight, possibly due to the hypoxic effects of carbon monoxide, rather than one mediated through eating. Efforts to prevent or reduce smoking should have greater benefits for mother and child than would efforts to increase food intake among pregnant women who smoke.

Birth Weight↗

Dopamine antagonists during parturition disrupt maternal care and the retention of maternal behavior in rats.

Brief contact with pups at parturition enables the female rat to establish and retain the full repertoire of maternal behaviors, allowing her to respond rapidly to pups in the future. To determine whether the dopamine system is involved in the retention of maternal behavior, females were continuously infused with dopamine antagonists during the periparturitional period and then allowed either a brief interaction period with pups (3 h) or no interaction with pups (pups removed as they were born). Females were exposed to either the D1-like antagonist SCH 23390 (0.1 or 1.0 mg/kg/day) or the D2-like antagonist clebopride (0.5 or 1.0 mg/kg/day). The high dose of either DA antagonist resulted in significant attenuation of maternal care immediately postpartum. When tested for the retention of maternal behavior 7 days later, however, only the females exposed to the D2 antagonist displayed a delayed response to shown full maternal behavior (FMB) towards donor pups. Thus, while both dopamine receptor subtypes appear necessary for the full and rapid expression of maternal behavior during the early postpartum period, only the D2 receptor subtype appears to be involved in the retention of this behavior.

Animals↗

Length of maternal hospital stay for uncomplicated deliveries, 1988-1995: the impact of maternal and hospital characteristics.

OBJECTIVES: To determine the independent association of selected maternal and hospital characteristics with length of maternal hospital stay for uncomplicated vaginal deliveries. METHOD: Linear regression analysis using National Hospital Discharge Survey data from 1988 to 1995. Independent variables were year, maternal age and race, method of payment, and hospital ownership, size, and geographic location. The outcome measure was length of maternal hospital stay for uncomplicated vaginal deliveries. RESULTS: Length of stay was independently associated with year, geographic region, payment method, and hospital size. From 1988 to 1995, the mean length of stay fell from 2.1 to 1.5 days. The rate of decrease was similar for all regions, methods of payment, and hospital size. Women in the West had a shorter mean length of stay (1.5 days) than women in the Northeast (2.2 days). The difference by method of payment was smaller. Length of stay was shortest for women without insurance (1.8 days) and longest for women covered by Blue Cross (2.1 days). Maternal age and race and type of hospital ownership were not independently associated with the length of stay. CONCLUSIONS: Significant variations existed in the length of time women are hospitalized for normal childbirth. These variations are primarily associated with where a woman lives and whether she is insured. Given the current public debate on the impact of shortened hospital stays, these variations need to be explored and their effects on maternal and infant well-being clarified.

Adolescent↗

Effect of skim milk supplementation of the maternal diet on lactational amenorrhea, maternal prolactin, and lactational behavior.

Effect of skim milk supplementation of the maternal diet on lactational amenorrhea was studied in 30 pairs of healthy lactating women matched for parity, body mass index, and previous experience of lactational amenorrhea. Supplementation of the maternal diet had no significant effect on the time of resumption of regular menstruation or ovulation, maternal prolactin concentrations, breast-feeding pattern, maternal body mass index, or infant weight. However, the supplemented group breast-fed nearly exclusively (supplemental feeds were introduced but did not exceed 20% of total feeds) for a significantly longer duration (P < 0.05) than did the control group. Previous experience of lactational amenorrhea was significantly positively correlated with the time of resumption of menstruation in the supplemented (P < 0.01) and control (P < 0.05) groups when frequency of breast-feeding, maternal body mass index, and supplementary feeds to the infant were controlled for. Thus, maternal nutritional supplementation does not appear to affect the contraceptive benefit of lactation when the frequency of breast-feeding is not compromised but apparently lengthens the duration of nearly full breast-feeding.

Adult↗

Rates of Down's syndrome at the upper extreme of maternal age--absence of a "leveling" effect and evidence for artifacts resulting from analyses of rates by five-year maternal age intervals.

A "leveling" in the first order exponential increase of the rate of Down's syndrome with maternal age over 40 years of age has been suggested by others in review of data reported by five-year maternal age interval. In contrast, data reviewed here analyzed by one-year interval reveal no evidence for such an effect when the observed rates (O) at each maternal age in the 40--49-year age range and in the 45--49-year age range are compared with those predicted (P) from first order exponential equations derived from data in the 33--44-year age range. The sign of O -- P is not predominantly negative as would be expected if there were a "leveling" effect. Part of the evidence for leveling in previous studies may derive from the fact that rates have been plotted at the midpoints of the intervals rather than at the true mean maternal ages of mothers having births in these five-year intervals. It is shown that in the three data sources considered here, the difference between the quin-quennial mean maternal age and the interval midpoint is greater at older ages than at younger ages. Thus, plotting rates at the midpoint of five-year intervals results in significant graphic underestimate of the rates, and may result in a slight leveling effect. It is suggested that selective underascertainment of births to those in the older maternal ages in previous studies may also have contributed to the leveling effect observed earlier.

Adult↗

The mediating effect of maternal nutrition knowledge on the association between maternal schooling and child nutritional status in Lesotho.

The present study tested whether maternal nutrition knowledge was a mediating factor in the association between maternal schooling and child nutritional status, and whether the mechanism involved differed according to socioeconomic status. The data were collected in Lesotho on 921 mother-child pairs and included scores from a nutrition knowledge test, socioeconomic and demographic information, and the child's anthropometric data. A wealth factor derived from a factor analysis was used to stratify the sample into two socioeconomic groups. Two-stage least-squares estimation was used to test the mediating role of nutrition knowledge between maternal schooling and child weight-for-age. Results showed that both the importance of maternal schooling and the mechanism by which it affects the child's weight-for-age are contingent upon the family's socioeconomic status. While maternal schooling was positively associated with weight-for-age for both wealthier and poorer households, the size of the effect was much larger for the latter group. The effect of maternal schooling on weight-for-age was mediated by the mother's nutrition knowledge only among wealthier households. These results imply that, in Lesotho, nutrition education for mothers could contribute to improving children's growth, but only in households that have access to a minimum level of resources. For poorer households, nutrition education would not be sufficient.

Adult↗

Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis.

BACKGROUND: Hypertension and coronary heart disease are programmed by maternal undernutrition in utero. The feeding of low-protein diets to rats during their pregnancy results in higher blood pressure in the offspring from the age of weaning. OBJECTIVE: To determine whether a low-protein diet increases foetal exposure to glucocorticoids of maternal origin, resulting in altered hypothalamic-pituitary-adrenal axis function and hypertension. DESIGN: Rats were fed an 18% casein diet (control) or a 9% casein diet (low protein) during pregnancy. Low-protein-fed dams were injected with metyrapone to inhibit corticosterone synthesis or with metyrapone plus a replacement dose of corticosterone. The offspring of these pregnancies had their blood pressure determined when they were aged 7 weeks. METHODS: The systolic blood pressure was determined using an indirect tail-cuff method. Glucocorticoid action in the hypothalamus was measured using glycerol-3 phosphate dehydrogenase as a reference enzyme. RESULTS: Blood pressures of rats exposed to maternal low-protein diets in utero were elevated significantly relative to those of control rats. The animals that had been exposed to a maternal low-protein diet also exhibited increased glycerol-3 phosphate dehydrogenase (GPDH) activity in the hypothalamus, whereas their pyruvate kinase activity was not changed. The offspring of rats injected with metyrapone did not have raised blood pressure or GPDH activities. Replacement of corticosterone during pregnancy had no effect upon the blood pressures and GPDH activities of male offspring, but it reversed the effects of metyrapone in female offspring. CONCLUSIONS: Exposure to a maternal low-protein diet in utero programmes hypertension in the rat. The data are consistent with the hypothesis that corticosteroids of maternal origin play a role in this programming effect.

Animals↗

A 50-year audit of maternal mortality in the Peninsula Maternal and Neonatal Service, Cape Town (1953-2002).

OBJECTIVE: To audit trends in maternal mortality in the Peninsula Maternal and Neonatal Service (PMNS) over a 50-year period, with respect to rates and patterns of causation. DESIGN: Retrospective and prospective audit. SETTING: The PMNS, an integrated perinatal service composed of primary, secondary and tertiary facilities in Cape Town. Population All women giving birth in the area of the Cape Peninsula served by the PMNS over the 50-year period. METHODS: Data on maternal deaths were collected for 1953-2002 inclusive, from annual obstetric and gynaecological reports. Three triennia (1954-1956, 1981-1983 and 1999-2001) were selected for a detailed comparison of trends in rates and causes of death. MAIN OUTCOME MEASURES: Maternal mortality rates (MMRs). Causes of maternal deaths. RESULTS: Total deliveries increased from 7315 in 1953 to 27,575 in 2002. The MMR declined from 301 deaths per 100,000 deliveries in 1953 to 31.2 in the triennium, 1987-1989. From 1999, the MMR increased, reaching 112 in 2002. Comparing 1954-1956 (MMR of 253.9) with 1981-1983 (MMR of 43.8), there was a marked decline in the MMR related to hypertension (80.4 to 11.3), haemorrhage (50.8 to 4.2), abortion (55 to 4.2), suspected pulmonary embolism (25.4 to 2.8), pregnancy-related sepsis (8.5 to 4.2) and cardiac disease (21.2 to 2.8). Comparing 1981-1983 (MMR of 43.8) with 1999-2001 (MMR of 59.4), there was a decline in the MMR associated with abortion (4.2 to 0). The MMR for haemorrhage, suspected pulmonary embolism and cardiac disease remained the same. There was a slight increase in the MMR attributed to hypertension (11.3 to 14.5) and pregnancy-related sepsis (4.2 to 7.3). There was a marked increase in the MMR associated with non-pregnancy-related infections/AIDS (4.2 to 18.2). CONCLUSIONS: The MMR for all causes of maternal death declined significantly from 1953 to 1981 as a result of several interventions. From 1999, there has been a non-significant increase in MMR, predominantly due to the burden of HIV/AIDS-related mortality.

Cause of Death↗

The relationship of maternal age, quickening, and physical symptoms of pregnancy to the development of maternal-fetal attachment.

In a study of maternal-fetal attachment we explored three variables that could influence such attachment: maternal age, the experience of quickening, and the physical symptoms of pregnancy. A convenience sample of 80 pregnant women filled out the Cranley maternal-fetal attachment scale and the pregnancy symptoms checklist. Maternal age and physical symptoms were not found to be significantly correlated to maternal-fetal attachment, but quickening, as well as the degree and frequency of fetal movement, were correlated, at the P less than or equal to 0.0001 level. Income, ultrasound, and planning of pregnancy were also found to be significantly related to maternal-fetal attachment.

Adolescent↗