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Reports on Confidential Enquiries into Maternal Deaths: management strategies based on trends in maternal cardiac deaths over 30 years.

In the latest Report of the Confidential Enquiries into Maternal and Child Health (CEMACH; formerly Confidential Enquiries into Maternal Deaths (CEMD)), cardiac disease was the second commonest cause of maternal mortality. Currently there is much emphasis on appropriate referral and multidisciplinary planning for women with known cardiac disease. However, examining all maternal cardiac deaths in the CEMACH/CEMD reports over the last 30 years, to see whether the condition was known before pregnancy or developed during pregnancy, suggests that while reported maternal mortality due to cardiac disease overall has approximately doubled, the number due to known disease has changed little. Thus significant and increasing numbers of deaths occur in women without known disease, either in those with risk factors or in those who develop conditions in the absence of risk factors. Therefore, while there is a continuing need to counsel, refer and appropriately manage women with known pre-existing cardiac disease, attention must also be paid to screening women before pregnancy for evidence of cardiac disease or risk factors, and also to cardiac disease that develops de novo during pregnancy, since early screening and referral strategies alone will not prevent units from encountering such cases. All units therefore require processes for monitoring and managing women for the development of cardiac disease throughout their pregnancies.

Cause of Death↗

Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat.

Maternal infection during pregnancy is associated with increased risk for neurodevelopmental disorders. Polyriboinosinic-polyribocytidilic acid (poly I:C) or saline was administered to rats to model maternal infection; levels of TNFalpha, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were determined by ELISA. TNFalpha was significantly increased in maternal plasma, placenta, and amniotic fluid, while it was significantly decreased in fetal liver/spleen and neonatal brain. NGF and BDNF were significantly decreased in the placenta and fetal liver/spleen. There was no change in BDNF or NGF in the fetal or neonatal brain. Changes in TNFalpha, BDNF, and NGF after maternal exposure to poly I:C represent a potential mechanism through which maternal infection increases risk for neurodevelopmental disorders.

Amniotic Fluid↗

Maternal activity in relation to birth size in rural India. The Pune Maternal Nutrition Study.

OBJECTIVE: To describe the relationship of the mother's physical activity to the birth size of her baby in a rural Indian population. DESIGN: : Prospective observational study. SETTING: Six villages near Pune, Maharashtra, India. SUBJECTS: : A total of 797 women were studied after excluding abortions and termination of pregnancies (112), foetal anomalies (8), multiple pregnancies (3), incomplete pre-pregnancy anthropometry (14) and pregnancies detected later than 21 weeks of gestation (168). METHOD: An activity questionnaire was developed after focus group discussions and incorporated community-specific activities. It was validated against an observer-maintained diary. Activity scores were derived using published data on energy costs to weight the contributions of various activities. It was then administered to assess physical activity at 18 (+/-2) and 28 (+/-2) weeks of gestation. OUTCOME MEASURES: Birth outcome, maternal weight gain and neonatal anthropometry. RESULTS: The activity questionnaire was used to classify women into light, moderate and heavy activity categories. Maternal activity did not influence the incidence of prematurity or stillbirth, or the duration of gestation. It was inversely related to maternal weight gain up to 28 weeks of gestation (P=0.002). Higher maternal activity in early, as well as mid gestation, was associated with lower mean birth weight (P=0.05 and 0.02, respectively ), and smaller neonatal head circumference (P=0.005 and 0.009) and mid-arm circumference (P=0.03 and 0.01) after adjusting for the effect of major confounding factors. CONCLUSIONS: The Findings suggest that excessive maternal activity during pregnancy is associated with smaller foetal size in rural India, The approach described for developing an activity questionnaire has potential for adoption in other settings.

Birth Weight↗

Maternal serum alpha-fetoprotein screening and fetal chromosome anomalies: is lowering maternal age for amniocentesis preferable?

We have compared the cytogenetic abnormalities diagnosed prenatally in 1,098 patients referred for amniocentesis because of low maternal serum alpha-fetoprotein (MSAFP) to those of 445 patients whose indication was elevated MSAFP and those of 361 patients who had amniocentesis for "maternal anxiety." Autosomal trisomies, sex chromosome aberrations, and various structural rearrangements were detected in all 3 groups and actually exceeded the age-related incidence estimates. The frequency of chromosome anomalies in cases studied because of "maternal anxiety" with no prior screening was similar to that in the group referred for low MSAFP (1.38 and 1.27%, respectively). A relatively higher frequency (2.02%) was detected in the group whose indication was elevated MSAFP. Maternal serum screening is designed primarily to recalculate risk figures for Down syndrome, but not for other major chromosome abnormalities. The concept of prenatal screening for chromosome aberrations must therefore be reevaluated. We think that efforts should be directed at making amniocenteses more accessible to patients who request it. "Lowering" maternal age limits to 30 would encompass a greater proportion of pregnancies at risk and would be a step toward more effective prenatal diagnosis for chromosome abnormalities.

Adult↗

Umbilical amino acid uptake at increasing maternal amino acid concentrations: effect of a maternal amino acid infusate.

OBJECTIVE: Our purpose was to establish whether, in normal human pregnancies, the maternal intravenous infusion of amino acids can increase fetal amino acid uptake and amino acid concentrations. STUDY DESIGN: Twenty-six normal pregnancies were studied at the time of cesarean delivery (38-40 weeks' gestation). In 10 cases an amino acid formulation (Freamine 8.5% III, Baxter) was infused into a maternal vein before cesarean delivery. Maternal blood samples were obtained during the course of the study. Umbilical venous and arterial samples were obtained from the clamped segment of the cord. There were no differences between the 2 groups for fetal and placental weights and for fetal oxygenation and acid-base balance. RESULTS: Maternal amino acid concentrations increased significantly in the group receiving infusions. Significant increases in umbilical venous concentrations were observed for most amino acids, except for histidine and threonine. The amino acid umbilical arteriovenous differences per mole of oxygen (AA/O(2) ratio) increased significantly for leucine, isoleucine, valine, methionine, phenylalanine, arginine, glycine, serine, alanine, and proline. There were no significant increases for lysine, histidine, and threonine. CONCLUSION: An increase in maternal concentrations leads to an increase in the delivery of most amino acids to the fetus.

Adult↗

Inherited long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and a fetal-maternal interaction cause maternal liver disease and other pregnancy complications.

Fetal-maternal interactions are critical determinants of maternal health during pregnancy and perinatal outcome. This review explores the causative relationship of a fetal disorder of mitochondrial fatty acid oxidation, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and the serious maternal liver diseases of pregnancy-preeclampsia, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts), and acute fatty liver of pregnancy. Features of the metabolic adaptation necessitated during the fetal-neonatal transition; common phenotypes of pediatric fatty acid oxidation disorders, including neonatal hypoketotic, hypoglycemia and hepatic crisis; and clinical abnormalities of HELLP and acute fatty liver of pregnancy are presented. Evidence that a common mutation in the alpha-subunit (LCHAD) of trifunctional protein, E474Q, is always one of the mutant alleles in fetal isolated LCHAD deficiency associated with these disorders of pregnancy that cause high maternal, fetal, and newborn morbidity and mortality is reviewed. Recommendations for molecular testing for LCHAD deficiency in families with life-threatening maternal liver disease are given.

3-Hydroxyacyl CoA Dehydrogenases↗

Maternal infection regulates BDNF and NGF expression in fetal and neonatal brain and maternal-fetal unit of the rat.

Maternal infection during pregnancy is associated with increased risk for neurodevelopmental disorders. Lipopolysaccharide (LPS) or saline was administered to rats to model maternal infection, and levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in maternal plasma, placenta, amniotic fluid, fetal liver/spleen, fetal brain, and cerebral cortex after birth were determined by ELISA or semiquantitative Western blot analysis. BDNF expression was significantly increased in the fetal brain (p=0.039); NGF expression was significantly increased in neonatal cortex (p=0.0009). Neurotrophic factor expression was also altered in other tissues of the maternal-fetal unit. Abnormal expression of neurotrophic factors represents a potential mechanism through which maternal infection increases risk for neurodevelopmental disorders.

Animals↗

Pneumococcal conjugate vaccines as maternal and infant immunogens: challenges of maternal recruitment.

Maternal pneumococcal immunization may be a strategy for the prevention of pneumococcal disease during the first months of life before infant-administered pneumococcal conjugate vaccine (PCV) becomes protective. Preparatory to a Phase III efficacy trial to investigate this strategy for preventing early infant otitis media (OM), we are conducting a Phase I-II randomized, double-masked trial to determine if maternal 9-valent PCV immunization alters active antibody production in infants who are immunized with PCV-7 and to compare local and systemic adverse events among women immunized with PCV-9 or placebo. A pilot study was conducted in 1997 in a Minneapolis-St. Paul health maintenance organization, HealthPartners (HP), to estimate enrollment rate for the proposed Phase III trial. A total of 154 pregnant women were selected of whom 122 appeared to be eligible from ICD codes in the HP claims database; 76 responded, and 46 of these were eligible for participation. Four of the 46 reported that they would be very likely and 21 somewhat likely to participate; an estimated 20% (25/122) participation rate. The records of 4,289 women in their second trimester have been reviewed to date for the Phase I/II trial; 2,589 (60%) were found not to be eligible; and an additional 1,015 (24%) could not be contacted. Of the 685 remaining, 558 (81%) were not interested in participating when interviewed, and 127 (19%) have consented. Most (46%) of those who declined participation have cited concern about the safety of vaccination during pregnancy. While the overall participation rate of second trimester women is only 3% (127/4,289), maternal attrition (2.8%) and infant attrition from the study before age 7 months (3.9%) are lower than projected (25%). Differences in study design could explain the difference in participation rates estimated in the pilot study and experienced in the Phase I/II study. Reports of safety from large-scale studies of maternal PCV immunization in industrialized countries are needed before women are receptive to maternal immunization to protect their infants against pneumococcal disease.

Adult↗

Mononuclear cell subpopulations in preterm and full-term neonates: independent effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy, and mode of delivery.

Blood samples from 29 preterm (24-32 weeks of gestation) and 21 full-term (37-42 weeks of gestation) neonates were analysed for surface markers of lymphocyte subtypes and macrophages, and the effects of gestational age, neonatal infection, maternal pre-eclampsia, maternal betamethason therapy and mode of delivery were assessed with multiple regression analysis. Gestational age alone had few independent effects (increase in CD3+, CD8+CD45RA+, and CD11alpha+ cells, and decrease in CD14+, HLA-DR- cells) during the third trimester on the proportions of the immune cell subtypes studied. Neonatal infection and mother's pre-eclampsia had the broadest and very opposite kinds of effects on the profile of immune cells in the blood. Infection of the neonate increased the proportions of several 'immature' cells (CD11alpha-CD20+, CD40+CD19-, and CD14+HLA-DR-), whereas mother's pre-eclampsia decreased the proportions of naive cell types (CD4+CD8+, CD5+CD19+). In addition, neonatal infection increased the proportion of T cells (CD3+, CD3+CD25+, and CD4+/CD8+ ratio, and CD45RA+ cells), while maternal pre-eclampsia had a decreasing effect on the proportion of CD4+ cells, CD4+/CD8+ ratio, and proportions of CD11alpha+, CD14+ and CD14+HLA-DR+ cells. Maternal betamethason therapy increased the proportion of T cells (CD3+) and macrophages (CD14+, CD14+HLA-DR+), but decreased the proportion of natural killer (NK) cells. Caesarean section was associated with a decrease in the proportion of CD14+ cells. We conclude that the 'normal range' of proportions of different mononuclear cells is wide during the last trimester; further, the effect of gestational age on these proportions is more limited than the effects of other neonatal and even maternal factors.

Antigens, CD↗

Maternal cell traffic bounds for immune modulation: tracking maternal H-2 alleles in spleens of baby mice by DNA fingerprinting.

We have previously reported that the immunization of pregnant mice with T-dependent antigens successfully induced suppression of the antigen-specific plaque-forming cell (PFC) response to the relevant antigens in the offspring. This suppression was not caused by the administered antigens, the antibodies produced by the pregnant mother, or lactational transfer, but was dependent on the presence of the intact maternal T cells. It was major histocompatibility complex (MHC)-restricted manner tolerance, which continued for at least one-sixth of the murine life. Traditionally, the placenta acts as a natural barrier, not allowing the cells to pass through. However, the results presented strongly suggested that maternal T cells pass through the placenta and subsequently induce tolerance. In this present study, we attempted to substantiate the presence of maternal cells in the fetal circulation through the use of molecular techniques. We found that a highly polymorphic microsatellite sequence within the class II Eb gene of the H-2 complex is useful for the molecular detection of various H-2 alleles. DNA polymorphic analysis was used for tracking maternal H-2 alleles in the spleens of baby mice. The main procedure involved polymerase chain reaction amplification and restriction fragment length polymorphism analysis of the DNA sequence encompassing the H-2-specific microsatellite from the genomic DNA of baby mice. The results indicated that maternal T cells of immunized pregnant mice cross the placenta into the fetus, eventually inducing antigen-specific immunological tolerance in the offspring.

Alleles↗

Maternal characteristics and maternal limit-setting styles.

In a longitudinal study of 126 mothers and toddlers during toddlerhood, maternal limit-setting styles were assessed at 12, 24, and 36 months in relation to selected maternal characteristics. Mothers using teaching-based limit-setting styles at 12 months reported more optimal relationship histories of care and overprotection/control in their own families of origin. The main contributor to a maternal teaching-based limit-setting style in this sample was years of formal education, followed by a more multicausal conceptualization of how children develop. Thus, while years of formal education appear to facilitate the use of a teaching-based limit-setting style, formal education is not the only way to develop these skills. Maternal conceptualization of development may be amenable to intervention through a number of alternative learning activities. Further research is needed to explore the effects of different types of educational and learning opportunities on current maternal behavior, with the goal of optimizing socialization skills related to the development of toddler self-regulation.

Adolescent↗

Effect of maternal cholestasis on bile acid transfer across the rat placenta-maternal liver tandem.

Cholestasis of pregnancy induces alterations in bile acid transport by human trophoblast plasma membrane (TPM) vesicles. We investigated whether maternal cholestasis affects the overall ability of the rat placenta to carry out vectorial bile acid transfer from the fetus to the mother. Complete obstructive cholestasis (OCP) was maintained during the last week of pregnancy and released at term (day 21), before experiments were performed. In situ single-pass perfusion of one placenta per rat with 250 nmol [(14)C]glycocholic acid (GC) revealed an impaired uptake in OCP rats (2.28 vs. 5.53 nmol in control rats). Approximately 100% of GC taken up by control placentas was secreted in maternal bile over 120 minutes (5.38 nmol), whereas this was only 61% (1.40 nmol) of the GC taken up by OCP placentas. When 5 nmol GC was administered through the jugular vein no significant difference between both groups in total GC bile output was found. The efficiency (V(max)/K(M)) of adenosine triphosphate (ATP)-dependent GC transport by vesicles from the maternal side of TPM was decreased (-41%) in OCP. Moreover, histological examination of the placentas suggested a reduction in the amount of functional trophoblast in the OCP group. This was consistent with a lower antipyrine diffusion across the placenta in these animals. In sum, our results indicate that maternal cholestasis affects the ability of the placenta to efficiently carry out bile acid transfer from fetal to maternal blood. Changes in both the structure and the functionality of the chorionic tissue may account for this impairment.

Animals↗

Acute cocaine alters oxytocin levels in the medial preoptic area and amygdala in lactating rat dams: implications for cocaine-induced changes in maternal behavior and maternal aggression.

Acute cocaine administration has been correlated with disruptions in the onset and maintenance of maternal behavior as well as decreases in maternal aggressive behavior in rat dams. A growing body of evidence suggests that cocaine may alter oxytocin levels leading to impairments in maternal behavior and aggression. The current study assessed whether acute cocaine injections alter oxytocin (OT) levels in the medial preoptic area (MPOA), ventral tegmental area (VTA), amygdala (AMY), and hippocampus (HIP) on postpartum day (PPD) 1 or PPD 6. On PPD 1, 30 mg/kg cocaine reduced OT levels by approximately 26.9% (picograms/milligram) in the MPOA (t (18) = 3.44, P<.01) compared to saline. On PPD 6, 30 mg/kg cocaine significantly increased OT levels by approximately 20.9% (picograms/brain area) in the AMY (F (2,25) = 3.44, P=.05) relative to saline. These findings suggest that acute cocaine may disrupt maternal behavior and maternal aggression at least in part through its action on the oxytocinergic system.

Aggression↗

Effects of maternal nutritional status and maternal energy supplementation on length of postpartum amenorrhea among Guatemalan women.

To investigate the extent to which better maternal nutrition leads to reduction in length of postpartum amenorrhea, multivariate-logistic and linear-regression analyses were applied to data on 339 mother-infant pairs from the longitudinal Guatemalan Four Village Study, 1969-1977. Maternal triceps skinfold thickness was negatively associated with length of amenorrhea when infant supplementation (a proxy for reduced suckling) was accounted for. However, its effect was small: amenorrhea was only 0.5 mo shorter among women at the 75th percentile than among those at the 25th, equivalent to less than even one additional child during the women's reproductive years. Maternal supplementation was not associated with length of amenorrhea when infant supplementation was controlled. This is in contrast to previous studies in which breast-feeding or infant supplementation was not controlled. These results suggest that infant, not maternal, supplementation influences length of postpartum amenorrhea, and that maternal nutritional status has minimal influence.

Amenorrhea↗

Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination.

Non-disjoined chromosomes 15 from 115 cases of uniparental disomy (ascertained through Prader-Willi syndrome) and 13 cases of trisomy of maternal origin were densely typed for microsatellite loci spanning chromosome 15q. Of these 128 cases a total of 97 meiosis I (MI) errors, 19 meiosis II (MII) errors and 12 mitotic errors were identified. The genetic length of a map created from the MI errors was 101 cM, as compared with a maternal length of 137 cM based on CEPH controls. No significant differences were detected in the distribution of recombination events along the chromosome arm and a reduction was seen for most of the chromosome 15 intervals examined. It was estimated that 21% of tetrads leading to MI non-disjunction were achiasmate, which may account for most or all of the reduction in recombination noted. The mean age of mothers of cases involving MI errors which showed no transitions from heterodisomy to isodisomy was significantly lower (32.7) than cases showing one or more observable transitions (36.3) (P < 0.003, t -test). However, even among chiasmate pairs the highest mean maternal age was seen for multiple exchange tetrads. Chromosome-specific differences in maternal age effects may be related to the normal distribution of exchanges (and their individual susceptibilities) for each chromosome. However, they may also reflect the presence of multiple factors which act to ensure normal segregation, each affected by maternal age in a different way and varying in importance for each chromosome.

Chromosomes, Human, Pair 15↗

Relationships among prenatal maternal attachment, presence of postnatal depressive symptoms, and maternal role attainment.

PURPOSE: To examine the relationships among a woman's attachment to her fetus, the presence of postpartum depressive symptoms, and subsequent perceptions of maternal role attainment three months after birth DESIGN: A longitudinal, panel design SETTING: Hospital-sponsored childbirth education classes PARTICIPANTS: Primiparous women (N = 136) at 24-40 weeks of pregnancy and 9-14 weeks after the birth MAIN OUTCOME MEASURES: Perceived Competence Scale, Myself as Mother Scale, and My Baby Scale RESULTS: Prenatal maternal attachments was positively related to maternal role attainment to maternal role attainment. CONCLUSIONS: These findings enhance maternal identity theory and provide a means to evaluate the transition to motherhood.

Adolescent↗

Effect of ursodeoxycholic acid on the impairment induced by maternal cholestasis in the rat placenta-maternal liver tandem excretory pathway.

We investigated the effects of ursodeoxycholic acid (UDCA; 60 microg/day/100 g b.wt.) on the impairment induced by maternal obstructive cholestasis during pregnancy (OCP) in the rat placenta-maternal liver tandem excretory pathway. A blunted catheter was implanted in the common bile duct on day 14 of pregnancy, and the tip was cut on day 21. [(14)C]Glycocholate (GC) was then administered through the umbilical artery of "in situ" perfused placenta (placental transfer test) or through the maternal jugular vein (biliary secretion test), and GC bile output was measured. OCP impaired both GC placental transfer and maternal biliary secretion. UDCA moderately improved the latter but had a more marked beneficial effect on GC placental transfer. Histological examination revealed trophoblast atrophy and structural alterations, e.g., loss of apical membrane microvilli in OCP placentas. Gene expression level was investigated by real-time quantitative reverse transcription-polymerase chain reaction and Western blot analysis. OCP reduced both placental lactogen II (a trophoblast-specific gene) mRNA and the functional amount of epithelial tissue, determined by transplacental diffusion of antipyrin. Using a rapid filtration technique, impairment in the ATP-dependent GC transport across trophoblast apical plasma membranes obtained from OCP placentas was found. UDCA partially prevented all these changes. The expression level of organic anion transporters Oatp1, Oatp2, and Oatp4, and multidrug resistance-associated proteins Mrp1, Mrp2, and Mrp3 in whole placenta were not affected or were moderately affected by OCP but greatly enhanced by UDCA. In summary, UDCA partially prevents deleterious effects of OCP on the rat placenta-maternal liver tandem excretory pathway, mainly by preserving trophoblast structure and function.

Animals↗

The effect of maternal depressive symptomatology on maternal behaviors associated with child health.

National prevalence rates for depression among women are twofold compared with those of men, with women of childbearing age at greatest risk. Maternal depression not only negatively affects the health of the mother but may also influence the health and development of her offspring. This study examined the relationship between maternal depression and its influence on certain maternal behaviors associated with child health. A nationally representative, longitudinal data set with information on demographic, behavioral, and health care variables obtained from women in 1988 and 1991 was used. The results from logistic regression modeling indicate that maternal depression is associated with maternal behaviors (i.e., an increased likelihood of engagement in smoking, in not administering vitamins to a child, and not restraining children in appropriate car seats). Moreover, race differentials were found among these relationships. The implications of these results suggest the need to screen for depression among mothers of young children.

Adolescent↗