Unsuccessful attempts to induce peroxisomes in two cases of Zellweger disease by treatment with clofibrate

The cerebro-hepato-renal syndrome of Zellweger is a fatal hereditary disease and most of the affected infants die before the age of 6 months. Most probably the fatal outcome of the disease is due to an apparent complete lack of peroxisomes in the liver, kidneys, and brain. Treatment with clofibrate is known to increase drastically the number of peroxisomes in mammalian liver. We therefore treated two infants with the Zellweger syndrome with clofibrate (30 and 45 mg/kg body weight, respectively) for 3-4 wk. No clinical effect of the treatment was observed in any of the two cases, and the pattern of abnormal bile acids in serum did not change. No peroxisomes could be detected by electron microscopy of liver biopsies taken immediately after the treatment. Our failure to induce peroxisomes in the two Zellweger patients is in accord with the hypothesis that the protein missing in this autosomal recessive disease is absolutely essential for the formation of peroxisomes.     

Maternal micronutrients and fetal outcome

Maternal micronutrient deficiency has been related to adverse fetal effects. It is believed that micronutrient supplementation during pregnancy may improve fetal and neonatal outcome. Despite biological plausibility, the evidence base for individual micronutrient benefit on neonatal morbidity, mortality, growth and development is patchy and often contradictory, except for the role of folic acid in prevention of neural tube defects. Single micronutrient supplementation interventions have not been shown to consistently affect size at birth or duration of gestation. Sound evidence is generally lacking that micronutrient supplementation can reduce infection-related adverse pregnancy outcomes. However, preliminary data suggests that antenatal zinc supplements may cause reduction in later diarrheal and infectious morbidity in infants. The evidence linking maternal micronutrient deficiency to children's cognitive and motor functioning also lacks a clear consensus except for iodine in endemic areas. There is a pressing need for good quality randomized controlled trials evaluating food based and multiple micronutrient interventions in pregnancy and preconceptually. Future studies should also evaluate the effect on body composition and metabolism along with the functional consequences.     

Maternal regulation of fetal growth

The birth weight of the mothers, sibs, maternal aunts and their children were compared with those of 400 full-term, appropriate-for-gestational age, 181 true premature, 200 small-for-gestational age, and 261 correlation was found between the weight of the newborns and their mothers and maternal relatives in each case. The findings support the Ounsted theory that the rate of fetal growth is influenced by a familial component with maternal transmission. This regulation does not operate in true prematurity where the effect of environmental and pathological factors seems to prevail over the familial and genetic features.     

Maternal to fetal transmission of cervical carcinoma

Reported cases of metastases to the placenta are uncommon, and maternal transmission of tumor to the fetus is even more infrequent. However, vertical transmission of tumor can occur and should be considered as a potential etiology of malignancy in newborns and infants born to mothers with a history of cancer during gestation. Here, we present the imaging findings and clinical course of an unusual case of maternal cervical neuroendocrine carcinoma presenting as bilateral petrous temporal bone lesions in an infant.     

Maternal serum alkaline phosphatase and fetal maturity

Total as well as heat stable alkaline phosphatase activity was determined in sera of 70 normal pregnant mothers. Rise in activity was observed with advancement of gestation and was due to increased concentration of heat stable fraction. Statistically significant differences in levels between various gestational age groups suggest the assay of this enzyme for assessment of fetal maturity. Total alkaline phosphatase activity of 15 K.A. units/dl or more, with more than 50% of it being heat stable fraction, indicated a mature fetus (37 weeks or more gestation).     

Maternal and fetal influences on blood pressure.

To study maternal and fetal influences on blood pressure in childhood 405 children aged 4 years who were born and still resident in the Salisbury health district were visited at home for blood pressure and growth measurements. Information on the pregnancy, delivery, and baby was abstracted from the routine obstetric notes. Similar to recent findings in adults, the child's systolic pressure was inversely related to birth weight and positively related to placental weight. Systolic pressure at 4 years increased by 1.2 mm Hg for every SD decrease in the ratio of head circumference to length at birth, and by 1.1 mm Hg for every SD decrease in ponderal index at birth. Mothers whose haemoglobin concentrations fell below 100g/l during pregnancy had children whose systolic pressures were on average 2.9 mm Hg higher than the children of mothers with higher haemoglobin concentrations. Patterns of placental weight, birth weight, head circumference, and length that are associated with high blood pressure in adults are also associated with higher blood pressure in 4 year old children. Identification of the intrauterine influences that lead to these patterns of fetal growth could lead to the primary prevention of hypertension.     

Maternal constraint of fetal growth and its consequences

The major non-genetic factor determining the size of the fetus at term is maternal constraint. This term refers to a set of poorly defined processes by which maternal and uteroplacental factors act to limit the growth of the fetus, presumably by limiting nutrient availability and/or the metabolic-hormonal drive to grow. Maternal constraint can be divided into supply-limited constraint (e.g. maternal size) and demand-driven constraint (e.g. twinning). Maternal constraint acts in all pregnancies, but is greater in some situations, particularly those involving young maternal age, small maternal size, nulliparous and multiple pregnancies. Maternal constraint is an important physiological cause of the variation in birth size, but is not without longer-term consequences. There is increasing evidence that maternal constraint is an important factor in determining the increased risk of adult diseases in those who have poor fetal growth due to pathophysiological factors. The evidence is reviewed and placed in the context of discussing the evolutionary significance of maternal constraint. The role of predictive adaptive responses as the basis of programming, and the effects of maternal constraint on these responses are discussed. Changing demography means that maternal constraint must increasingly be considered as a significant factor in determining the pattern of disease.     

Maternal physical activity mode and fetal heart outcome

Background

Maternal leisure-time physical activity (LTPA) improves cardiac autonomic function in the fetus. The specific physical activity attributes (e.g., mode) that produce this benefit are not well understood.

Aim

To determine if more time spent performing non-continuous LTPA during pregnancy is significantly associated with lower fetal heart rate (HR) and increased heart rate variability (HRV).

Study design

This paper presents a retrospective analysis of previously reported data. Fetal magnetocardiograms (MCG) were recorded from 40 pregnant women at 36-wk gestational age.

Outcome measures

Metrics of fetal HR and HRV, self-reported min of continuous and non-continuous LTPA performed during the 3-months preceding the 36-wk assessment point and covariates (maternal weight change pre to 36-wk, age, and resting HR and fetal activity state during MCG recordings.

Results

Positive correlations were significant (p < 0.05) between min of continuous LTPA, the time domain metrics that describe fetal overall HRV, short-term HRV and a frequency domain metric that reflects vagal activity. Time spent in non-continuous LTPA was positively correlated (p < 0.05) with two HRV metrics that reflect fetal overall HRV. In the multiple regression analyses, minutes of non-continuous LTPA remained associated with fetal vagal activity (p < 0.05) and the relationships between minutes of non-continuous LTPA and fetal overall HRV (p < 0.005) persisted.

Conclusion

These data suggest non-continuous physical activity provides unique benefits to the fetal autonomic nervous system that may give the fetus an adaptive advantage. Further studies are needed to understand the physiological mechanisms and long-term health effects of physical activity (both non-continuous and continuous) performed during pregnancy to both women and their offspring.     

Maternal fetal immunological relationship particularly mycobacterial immunity.

Thirty-nine paired maternal and cord blood from normal full term deliveries were tested for lymphocyte function by proliferative response to mitogens-Phytohemagglutinin-P (PHA) and Poke week mitogens (PWM). Monocyte function was assessed by the ability of the monocytes to release hydrogen peroxide (H2O2) in response to standard stimulus (PMA). Mycobacterial immunity was assessed by lymphocyte proliferative response to purified proteins derivative (PPD) and IgM and IgG antibody response to H37Rv and 5 atypical mycobacteria. Lymphocyte functions were significantly lower in cord blood (PHA 20.6, PWM 21.2) as compared with maternal blood (PHA 65.8, PWM 37.8). The capacity of fetal monocytes to release H2O2 was comparable to maternal monocytes. The mean proliferative response of fetal lymphocytes to tubercular protein (PPD) was 0.67 as compared (P less than 0.01) to maternal lymphocytes (3.79). Nearly 86% of the cord blood did not show any response to PPD. None of the cord blood showed IgM antibody response to H37Rv nor to any of the range of 5 atypical mycobacteria though maternal IgM and IgG response was present. There was only passive transfer of IgG antibody from mother to fetus. Hence, though this is a highly endemic area for atypical mycobacteria and M. tuberculosis, there was apparently no transplacental transfer of antigen in normal sensitized mothers.     

Maternal administration of indomethacin and neonatal tricuspid insufficiency

The authors report the case of a neonate who presented since birth with refractory hypoxemia, peripheral edemas, ascites and pleural effusions. The mother had been given indomethacin for the 10 preceding days, in order to avoid premature labour. Echocardiography showed a tricuspid valve dysfunction with important regurgitation in the neonate. Under symptomatic treatment, clinical symptoms disappeared within 10 days. Echocardiography was normal by age 3 months. The responsibility of administration of indomethacin to the mother is discussed.     

Maternal anxiety in late pregnancy: effect on fetal movements and fetal heart rate

AIM: To determine whether maternal state and trait anxiety levels affect fetal movements or fetal heart rate (FHR) in the third trimester. SUBJECTS: Forty-one healthy pregnant nulliparous women not on medication and with a singleton pregnancy. STUDY DESIGN: Maternal anxiety was assessed using the Spielberger State- Trait Anxiety Inventory (Form Y) at 36 gestational weeks. The fetuses of the women were examined at 37-40 gestational weeks with ultrasound observation of fetal movements and cardiotocography (CTG). The results of the fetal examinations were compared between women with low and high anxiety scores (low scores being defined as scores below the median and high scores as scores equal to or above the median of the study population), and correlation analyses between anxiety scores and the outcome variables were performed. OUTCOME MEASURES: The presence and duration (expressed as a percentage of the total examination time) of FHR patterns A, B, C, and D, the percentage duration of fetal movements in each FHR pattern, baseline FHR and FHR variability in each FHR pattern. RESULTS: The presence of FHR patterns A, B, C, and D, the duration of FHR patterns A, B, and C, FHR variability in FHR patterns A, B, and C, baseline FHR and the percentage duration of fetal movements in each FHR pattern did not differ between women with low and high state and trait anxiety scores. In fetuses with FHR pattern D, the duration of FHR pattern D increased with increasing maternal trait anxiety scores, (rho=0.88; p=0.008), and FHR variability in FHR pattern D increased with maternal state and trait anxiety scores (r=0.86, p=0.01; r=0.96, p=0.001). CONCLUSION: Maternal anxiety does not seem to affect fetal movements or baseline FHR in late pregnancy, but there is a possible association between maternal anxiety and the duration of FHR pattern D and FHR variability in FHR pattern D.     

Maternal smoking and fetal growth of full term infants

Results of investigation into the effects of maternal smoking and other selected independent variables on fetal growth indicated that smoking by gravida was assoicated with reductions in birth weights and crown-heel lengths, but not with ponderal indices of newborn infants. Mothers of single infants were interviewed following delivery and before discharge about the amount of smoking during pregnancy. Infants were weighed and measured at birth, and step-wise multiple regression analyses were used to interpret the data for 4 groups of infants: males born to primiparas, males born to multiparas, females born to primiparas, and females born to multiparas. Results indicate that maternal smoking during pregnancy was associated with reductions in birth weights and crown-heel lengths, but not in ponderal indices of these groups of full-term infants. The effects of smoking on fetal growth did not appear to be related to poor maternal nutrition, and mean weight gains during the last 2 trimesters of pregnancy were not significantly different in smoking and nonsmoking mothers. Conflicting opinions exist concerning whether the reduction in crown-heel lengths are transitory or not; thus further study is recommended.