Maternal body weight trajectories across the life course and risk of preterm delivery.

We examined the association between life course body weight percentile trajectories and risk for preterm delivery (PTD). Data about women's weight at birth, age 18, and before pregnancy were obtained by retrospective self-report in a cohort of 1410 black women in metropolitan Detroit. Growth mixture models were used to categorize women with similar weight percentile trajectories across these time points. Log-Poisson models were used to examine the association between the trajectory groups and PTD. Four trajectory groups with different beginning and endpoints of their weight percentiles (high-high, high-low, low-high and low-low) best fit the data. The groups with the highest prevalence of PTD were those that started low (low-high, 21%; low-low, 18%). The low-high group had a higher prevalence of PTD than the high-high trajectory group in unadjusted models (prevalence ratio=1.49 [95% confidence interval (CI) 1.11, 2.00]). The association became not significant after adjusting for maternal age at delivery, income, diabetes and hypertension. When compared with the high-high trajectory group, the low-low trajectory seemed to also have a higher prevalence of PTD after adjusting for maternal age at delivery, income, diabetes and hypertension (prevalence ratio=1.35 [95% CI 1.00, 1.83]). Results suggest that a woman's risk for PTD is influenced by her body weight trajectory across the life course.

Polymorphisms in the promoter region of iNOS predispose to rheumatoid arthritis in south Indian Tamils.

Nitric oxide synthase (NOS) catalyses the production of nitric oxide (NO) from L-Arginine, which participates in diverse biological processes including inflammation and apoptosis. Macrophages, chondrocytes, osteoblasts and osteoclasts express inducible NOS (iNOS) at the site of synovial inflammation. NO produced at the inflamed joint may contribute to peri-articular bone loss, mediate apoptosis and regulate Th1/Th2 balance in rheumatoid arthritis (RA). Variations in the promoter region of NOS gene regulate the nitric oxide synthase expression and iNOS (NOS2) polymorphisms have been associated with susceptibility to autoimmune disorders. Hence, this study was conducted to identify the possible contributions of NOS2 -1659G/A, -1026C/A, -277A/G promoter polymorphisms towards development of RA in South Indian Tamils. A total of 242 (219 females, 23 males) patients with RA (mean age 41.2 ± 10.9 years, disease duration 8.5 ± 4.3 years) and 279 age- and sex-matched healthy individuals of South Indian Tamil ethnicity were genotyped for NOS2 -1659C/T, -1026G/T and -277A/G promoter polymorphisms by TaqMan chemistry. Nature of disease (erosive or nonerosive), the presence of extra-articular manifestations, seropositivity for rheumatoid factor and anticyclic citrullinated peptide, serum C-reactive protein (CRP) level and response to therapy were assessed for all patients. The three single nucleotide polymorphisms (SNPs) were in Hardy-Weinberg equilibrium. The frequency of GG genotype and G allele of NOS2-277 was higher in patients (pc = 5.7 × 10-9 , OR = 6.09, 95% CI = 3.09-12.8 and pc = 4 × 10-13 , OR = 2.37, 95% CI = 2.06-3.62, respectively) compared to controls. Similarly, the frequency of NOS2-1026 (rs2779249) GT genotype and the T allele was higher in patients with RA (pc = .01, OR = 1.61, 95% CI = 1.09-2.36, and pc = .04, OR = 1.40, 95% CI = 1.02-1.91, respectively). However, no significant difference in frequency of NOS2-1659C/T polymorphism was observed between patients and controls. None of the studied SNPs were associated with erosive disease, seropositivity or extra-articular manifestations. The -277A/G and -1026 G/T promoter polymorphisms in iNOS may confer susceptibility to RA in South Indian Tamils.

Association of NKG2D gene variants with susceptibility and severity of rheumatoid arthritis.

NKG2D (KLRK1) is a C-type lectin receptor present on natural killer (NK) cells, γδ, CD8+ and CD4+ T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4+ T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with rheumatoid arthritis (RA). Eight different single nucleotide polymorphisms (SNP) in the NKG2 gene were genotyped in 236 patients with RA and 187 controls using Taqman 5' nuclease assays. NKG2D genotype/allele frequency did not differ between patients and controls. Subgroup analysis showed that the frequency of A allele of NKG2D9 and T allele of NKG2D10 was significantly higher in patients with deformities (a marker of severe disease) [11 versus 5%, Pc = 0·03, odds ratio (OR) = 2·44, 95% confidence interval (CI) = 1·09-5·98 and 10 versus 4%, Pc = 0·04, OR = 2·45, 95% CI = 1·05-6·39, respectively], while the frequency of alleles G of NKG2D9 and A of NKG2D10 was greater in patients without deformities (Pc = 0·03, OR = 0·41, 95% CI = 0·17-0·91 and Pc = 0·04, OR = 0·41, 95% CI = 0·16-0·96). Similar trends of association were observed with deforming phenotype of RA in female patients and deforming young onset RA subgroups. Haplotype analysis revealed that the frequency of haplotype G-C-A-G-A-T-C-C was higher in patients than in controls (12 versus 8%, P = 0·04, OR = 1·61, 95% CI = 1·01-2·55), suggesting that it may predispose to RA. Our study suggests that the NKG2D gene polymorphisms may modify the risk of development and severity of RA.

Toxic epidermal necrolysis due to therapy with cyclophosphamide and mesna. A case report of a patient with seronegative rheumatoid arthritis and rheumatoid vasculitis.

Rheumatoid vasculitis usually occurs on the background of seropositive rheumatoid arthritis, although in rare cases the patients can be seronegative. We report a woman with seronegative rheumatoid arthritis with rheumatoid vasculitis who developed toxic epidermal necrolysis involving most of her body surface area, while on therapy with intravenous cyclophosphamide and mesna. After withdrawal of suspected offending agents, administration of intravenous immunoglobulin, and supportive therapy, she had a favorable outcome. Such an occurrence is rare and serves to educate about a potentially life-threatening adverse event associated with a commonly used immunosuppressive agent.

Unusual co-existence of dural sinus thrombosis and aneurysmal subarachnoid hemorrhage in a patient with lupus.

Subarachnoid hemorrhage and dural sinus thrombosis are important manifestations of neuropsychiatric lupus erythematosus. We report the case of a woman with relapsed lupus nephritis, in partial remission, who presented with the unusual combination of dural sinus thrombosis (due to protein S functional deficiency) and aneurysmal subarachnoid hemorrhage. She had a fatal outcome, as has often been reported with subarachnoid hemorrhage in the context of active lupus. To our knowledge, this is the first report of such an unusual association in lupus, and highlights unique challenges in the management of intracranial hemorrhage in the context of dural sinus thrombosis.

Is the placental disk really an ellipse?

The mean surface shape of placenta is round and common abnormalities of shape are associated with vascular abnormalities and reduced placental functional efficiency. A long-standing approach is to describe shapes as elliptic, and to quantify them by "length" and "breadth". We test this description in two cohorts: National Collaborative Perinatal Project and Pregnancy, Infection and Nutrition Study. We conclude that quantifying placental shape as elliptic is ambiguous and problematic. The "breadth" of the placenta should be interpreted as a combination of two different measurements: placental size and irregularity of the placental surface. It has no intrinsic functional significance.

Placental measurements associated with intelligence quotient at age 7 years.

We hypothesized that placental villous branching that is measured by disk chorionic plate expansion and disk thickness is correlated with factors also involved in regulation of branching growth of other fetal viscera (e.g. lung, kidney) including neuronal dendrites, and thus may be associated with variation in childhood intelligence quotient (IQ). IQ at age 7 years was assessed using the Wechsler Intelligence Scale for Children. Placental measures [placental weight (g), thickness (mm), chorionic plate surface diameters (cm), area (cm2), shape, and cord length and cord eccentricity] were independent variables in regression analyses of age 7-year IQ in 12,926 singleton term live born infants with complete placental data. Analyses were stratified on gender with adjustment for socioeconomic status, race, parity, gestational age, exact age at testing and centered parental ages. After adjustment for covariates, placental measurements were independently associated with IQ at age 7 years but results varied by gender. Chorionic plate diameters were only associated with higher IQ in girls. Placental thickness was positively associated with higher IQ for boys and girls. We have previously shown that placental measures affect age 7-year body mass index and diastolic blood pressure. Here we demonstrate that specific measures, placental chorionic plate diameters in girls and disk thickness, independent of gender, are correlated with age 7-year IQ. Further exploration of the possible interaction of these factors on the placental villous arborization reflected by the chorionic plate expansion and placental thickness that correlate with age 7-year IQ, as well as other age 7 somatic features as previously addressed, is indicated.

Relationship of hepatic and renal dysfunction with haemorrheological parameters in Plasmodium falciparum malaria.

OBJECTIVES: The present study was designed to assess hepatic and renal dysfunction in Plasmodium falciparum malaria, and evaluate if such abnormalities had any bearing with the hemorrheological dysfunction. METHODS: Sixty consecutive patients of Plasmodium falciparum malaria with hepatic and renal dysfunction (Group A) and twenty consecutive cases of uncomplicated falciparum malaria (Group B) were studied. Patients with past history of alcoholism, jaundice, chronic renal failure, bleeding diathesis or coagulopathy were excluded from the study. Laboratory investigations done were liver and renal function tests, complete blood count and coagulation profile. The data collected was analysed to inter - correlate parameters of hepatic, renal and hemorrheological dysfunction. RESULTS: In Group A, all had rigor and chill, icterus while 57% had oliguria and hepatomegaly, 37% splenomegaly, with less than 2% having overt bleeding diathesis. On evaluation, in Group A, 57% had acute renal failure, mean value of bilirubin was 13.91 (+/- 12.53) mg/dL, ALT 76.92 (+/- 37.48) IU/ml, AST 135.32 (+/- 97.33) IU/ml, mean PT was 13.03 (+/- 2.22) seconds, mean aPTT was 31.69 +/- 6.76 seconds, FDP by D-dimer was raised in 53% and LDH was raised in 78% respectively. In Group B mean PT was 11.93 (+/- 1.51) seconds, mean APTT was 29.39 +/- 2.89 seconds and FDP by D-dimer was raised in 30% respectively. Thrombocytopenia was seen in 26% cases in Group A and 15% cases in Group B. On analysis, in Group B, there was statistically significant negative correlation of total platelet count with serum AST (p = .010) and serum ALT (p = .036), serum ALP with BT (p = .036), but positively with CT (p = .006) and aPTT (p = .036). In Group A, serum bilirubin was found to have significant negative correlation with haemoglobin (p = .019),positive correlation with aPTT (p = .037), urea (p = .000) and serum creatinine (p = .000), serum ALP Positively with serum urea (p = .025) and serum creatinine (p = .037), serum urea negatively with haemoglobin(p = .015), so also did serum creatinine (p = .025),prothrombin time positively with serum urea(p = 0.037) and serum creatinine (p = 0.013), serum FDP positively with serum urea (p = 0.038) and serum creatinine (p = 0.022), bleeding time positively with serum AST(p = .002). CONCLUSION: Despite less than 2% of patients in Group A having clinically overt bleeding diathesis, raised FDP (53%), prolonged aPTT (67%), low total platelet count (26%) and anemia (87%) were found in a significant number of patients, suggesting subclinical DIC. Therefore patients with Plasmodium falciparum malaria have high incidence of subclinical haemorrheological disorders which do not amount to overt DIC but adversely affect renal function contributing to acute renal failure.

Variable placental thickness affects placental functional efficiency independent of other placental shape abnormalities.

Our previous work suggests that stressors that impact placental vascular growth result in a deformed chorionic surface shape, which reflects an abnormal placental three-dimensional shape. We propose to use variability of placental disk thickness as a reflector of deviations in placental vascular growth at the finer level of the fetal stems. We hypothesize that increased variability of thickness is associated with abnormal chorionic surface shape, but will be a predictor of reduced placental functional efficiency (smaller baby for a given placental weight) independent of shape. These measures may shed light on the mechanisms linking placental growth to risk of adult disease. The sample was drawn from the Pregnancy, Infection and Nutrition Study. In all, 94.6% of the cohort consented to placental examination. Of the 1023 delivered at term, those previously sectioned by the Pathology Department were excluded, leaving 587 (57%) cases with intact placentas that were sliced and photographed. The chorionic surface shape and the shape of a central randomly oriented placental slice were analyzed and measures were compared using correlation. Lower mean placental disk thickness and more variable disk thickness were each strongly and significantly correlated with deformed chorionic plate shapes. More variable disk thickness was strongly correlated with reduced placental efficiency independent of abnormal chorionic surface shape. Variability of placental disk thickness, simple to measure in a single randomly oriented central slice, may be an easily acquired measure that is an independent indicator of lowered placental efficiency, which may in turn program the infant and result in increased risk for development of adult diseases.

Placental surface shape, function, and effects of maternal and fetal vascular pathology.

GOAL: In clinical practice, variability of placental surface shape is common. We measure the average placental shape in a birth cohort and the effect deviations from the average have on placental functional efficiency. We test whether altered placental shape improves the specificity of histopathology diagnoses of maternal uteroplacental and fetoplacental vascular pathology for clinical outcomes. MATERIALS AND METHODS: 1225 Placentas from a prospective cohort had chorionic plate digital photographs with perimeters marked at 1-2 cm intervals. After exclusions of pre-term (n = 202) and velamentous cord insertion (n = 44), 979 (95.7%) placentas were analyzed. Median shape and mean perimeter were estimated. The relationship of fetal and placental weight was used as an index of placental efficiency termed "ß". The principal placental histopathology diagnoses of maternal uteroplacental and fetoplacental vascular pathologies were coded by review of individual lesion scores. Acute fetal inflammation was scored as a "negative control" pathology not expected to affect shape. ANOVA with Bonferroni tests for subgroup comparisons were used. RESULTS: The mean placental chorionic shape at term was round with a radius estimated at 9.1 cm. Increased variability of the placental shape was associated with lower placental functional efficiency. After stratifying on placental shape, the presence of either maternal uteroplacental or fetoplacental vascular pathology was significantly associated with lower placental efficiency only when shape was abnormal. CONCLUSIONS: Quantifying abnormality of placental shape is a meaningful clinical tool. Abnormal shapes are associated with reduced placental efficiency. We hypothesize that such shapes reflect deformations of placental vascular architecture, and that an abnormal placental shape serves as a marker of maternal uteroplacental and/or fetoplacental vascular pathology of sufficiently long standing to impact placental (and by extension, potentially fetal) development.

Birth weights smaller or larger than the placenta predict BMI and blood pressure at age 7 years.

We hypothesized that the altered placental proportions that influence birth weight affect childhood body proportions, and that these effects would be independent of birth weight. We also hypothesized that altered placental proportions might affect the fetal cardiovascular system, and may be reflected in variation in childhood blood pressure. By using linear regression with birth weight as the dependent variable, placental variables were entered as predictors. The predicted birth weights based on placental factors were then obtained. The ratio of the actual birth weight to that predicted by placental parameters (observed/expected ratio, OER) was used as the independent variable in analyses of age 7 year body mass index (BMI) and diastolic blood pressure (DBP) in the 15,902 singleton liveborns delivered between 34 and 43 weeks. The standardized residual birth weight was also used as a variable to examine the effects of birth weight that is not consistent with placental parameters. For each unit increase in the OER, BMI at 7 years increased 1 kg/m2 (P < 0.0001). The OER also had a significant effect on DBP (ß = 4.52, P < 0.001) at 7 years of age but only among African-American children. Results for the standardized residual birth weight variable were consistent with the OER. All results were adjusted for gestational age, sex, socioeconomic status, African-American race and maternal pre-pregnancy BMI. Being larger or smaller than predicted by one's placenta affects childhood body composition and blood pressure. The placental measurements provide insight into pathophysiological mechanisms of the developmental origins of adult disease.

Non-linear and gender-specific relationships among placental growth measures and the fetoplacental weight ratio.

GOALS: Fetal growth depends on placental growth; the fetoplacental weight ratio (FPR) is a common proxy for the balance between fetal and placental growth. Male and female infants are known to have differing vulnerabilities in fetal life, during parturition and in infancy. We hypothesized that these differences may be paralleled by differences in how birth weight (BW) and the fetoplacental weight ratio (FPR) are affected by changes in placental proportions. MATERIALS AND METHODS: Placental proportion measures (disk shape, larger and smaller chorionic diameters, chorionic plate area calculated as the area of an ellipse with the 2 given diameters, disk thickness, cord eccentricity and cord length) were available for 24,601 participants in the Collaborative Perinatal Project delivered between >34 and <43 completed weeks. The variables were standardized and entered into multiple automated regression splines (MARS 2.0, Salford Systems, Vista CA) to identify nonlinearities in the relationships of placental growth measures to BW and FPR with results compared for male and female infants. RESULTS: Changes in chorionic plate growth in female compared to male infants resulted in a greater change in BW and FPR. The positive effects of umbilical cord length on BW reversed at the mean umbilical cord length in females and at +0.08 SD in male infants. CONCLUSIONS: Female infants' BW and FPR are each more responsive to changes in placental chorionic plate growth dimensions than males; this may account for greater female resilience (and greater male vulnerability) to gestational stressors. The effect of umbilical cord length on FPR may be due to longer cords carrying greater fetal vascular resistance. Again male fetuses show a higher "threshold" to the negative effects of longer cords on FPR.

Allometric metabolic scaling and fetal and placental weight.

BACKGROUND: We tested the hypothesis that the fetal-placental relationship scales allometrically and identified modifying factors of that relationship. MATERIALS AND METHODS: Among women delivering after 34 weeks but prior to 43 weeks' gestation, 24,601 participants in the Collaborative Perinatal Project (CPP) had complete data for placental gross proportion measures, specifically, placental weight (PW), disk shape, larger and smaller disk diameters and thickness, and umbilical cord length. The allometric metabolic equation was solved for alpha and beta by rewriting PW = alpha(BW)beta as ln(PW) = ln alpha + beta[ln(BW)]. alpha(iota) was then the dependent variable in regressions with p < 0.05 significant. RESULTS: Mean beta was 0.78 + 0.02 (range 0.66, 0.89), which is consistent with the scaling exponent 0.75 predicted by Kleiber's Law. Gestational age, maternal age, maternal BMI, parity, smoking, socioeconomic status, infant sex, and changes in placental proportions each had independent and significant effects on alpha. CONCLUSIONS: We find an allometric scaling relation between the placental weight and the birthweight in the CPP cohort with an exponent approximately equal to 0.75, as predicted by Kleiber's Law. This implies that: (1) placental weight is a justifiable proxy for fetal metabolic rate when other measures of fetal metabolic rate are not available; and (2) the allometric relationship between placental and birthweight is consistent with the hypothesis that the fetal-placental unit functions as a fractal supply limited system. Furthermore, our data suggest that the maternal and fetal variables we examined have at least part of their effects on the normal balance between placental weight and birth weight via effects on gross placental growth dimensions.

Rates of preterm delivery among Black women and White women in the United States over two decades: an age-period-cohort analysis.

The authors assessed the influence of age, period, and cohort effects on rates of preterm delivery in the United States. Rates of preterm delivery for singleton births (<37 weeks) in seven age groups (15-19, 20-24,., 45-49 years), five periods (1975, 1980, 1985, 1990, 1995), and 11 maternal birth cohorts (1926-1930, 1931-1935,., 1976-1980) were examined. Over the 20-year study interval, preterm delivery increased by 3.6% among Blacks (from 15.5% in 1975 to 16.0% in 1995) and by 22.3% among Whites (from 6.9% to 8.4%). Among Black primigravid women, rates of preterm delivery increased from 1975 to 1990 and began to decline thereafter; among Whites, the rates increased between 1975 and 1995. In Blacks, women aged 25-29 years had the lowest rates for the first and second births, and women aged 30-34 years had the lowest rate for subsequent births. In Whites, the age groups with the lowest preterm delivery rates were 20-24 years for first births and 25-29 years for subsequent births. Cohort-specific rates of preterm delivery remained fairly constant across age strata and periods for Whites, but a small trend was apparent for Blacks aged 30-44 years. The consistency of the observed age effects across periods and cohorts suggests that the age effect is partly due to biologic factors. The presence of period effects might be linked to the increased survival of premature infants or to increased viability among births occurring at lower lengths of gestation.

Testing a sociomedical model for preterm delivery.

The study purpose was to contribute to the development of a model for preterm birth that brings together social, psychosocial and biomedical factors. The three research questions were: (a) Which social and psychosocial factors influence the risk of preterm delivery? (b) Are the effects of social and psychosocial factors independent? (c) Do the biomedical factors identified and measured here explain the effect of social and psychosocial factors? The sample comprised 739 low-income black non-Hispanic women. Interviews were conducted after delivery, and medical records were abstracted. Nearly a quarter of the women delivered preterm (23.5%). Two social factors strongly predicted risk of preterm delivery: inadequacy of time and money for non-essentials. The effect of both was stronger than expected from each alone and was partially mediated by psychosocial factors. Several psychosocial factors also predicted preterm delivery risk but only stress and locus of control were independent predictors. With the inclusion of biomedical factors, stress (OR = 1.86, P = 0.005) and locus of control (OR = 1.75, P = 0.007) continued to be strongly associated with preterm delivery. The effect of inadequate resources for non-essentials was no longer significant, suggesting mediation. These strong effects of social and psychosocial factors should be examined in future studies.

An intersection of women's and perinatal health: the role of chronic conditions.

This paper has three objectives: 1) to review data on the prevalence of chronic disease among women of reproductive age; 2) to establish that chronic diseases are an important influence on perinatal health; and 3) to emphasize opportunities where women's health and perinatal health can intersect. This involves broadening strategies aimed at improving perinatal health to emphasize a woman's overall health, regardless of childbearing status or plans, and using perinatal health care as a bridge to ongoing care for women. These issues are discussed in the context of a continuum often used to organize perinatal health interventions.

Environmental tobacco smoke and low birth weight: a hazard in the workplace?

Low birth weight (LBW) increases infant morbidity and mortality worldwide. One well-established risk factor is maternal smoking. Environmental tobacco smoke (ETS) exposure has recently been focused on as another potential risk factor. In this article, we review epidemiologic literature on the effects of ETS on LBW and intrauterine growth retardation (IUGR), the cause of LBW related to maternal smoking. As we consider the feasibility of modifying women's exposure, we focus our discussion on workplace exposure to ETS. The workplace is particularly important to consider because women of child-bearing age are present in the workplace in greater numbers now than ever before. In addition, certain subgroups of working women may be particularly at risk from the effects of ETS on pregnancy because they work in environments with higher exposure or they are more susceptible to its effects. We conclude that there is consistent evidence to relate maternal ETS exposure to an increased risk of adverse pregnancy outcomes and that this association may be generalized to the work environment. In studies with positive findings, infants exposed to ETS antenatally were 1.5-4 times more likely to be born with LBW, but few studies examined LBW. Most studies looked at measures of IUGR. ETS was associated with reductions in birth weight (adjusted for gestational age) ranging from 25 to 90 g. Infants born to women exposed to ETS were generally 2-4 times more likely to be born small-for-gestational age. ETS exposure in the workplace can and should be minimized to protect pregnant women from its adverse effects.

Risk factor profiles of placental abruption in first and second pregnancies: heterogeneous etiologies.

The objective of this study was to identify risk factors for placental abruption in first and second pregnancies and to compare the risk-factor profiles for evidence of etiologic heterogeneity. A prospective cohort design was used. The study took place at university-based medical centers that participated in the U.S. Collaborative Perinatal Project (1959-1965). A total of 10,774 first pregnancies only and 6529 first and second pregnancies of women were enrolled in the study. Participation rate was 96%. All pregnancies were selected at some centers, whereas other centers used either random or systematic sampling. The main outcome measure was placental abruptions in first and second pregnancies. The placental abruption rate was 1.7% (n = 182) for first and 2.2% (n = 143) for second pregnancies. Prior abruption increased risk in second pregnancies significantly (odds ratio [OR] = 3.2, 95% confidence interval [CI]: 1.7-5.8) after adjusting for other risk factors. Placental infarcts and smoking duration were associated with an increased risk for abruption in second but not first pregnancies. Effect of placental infarcts was modified by gestational age with strongest risk for abruption at shortest gestations. For each year of smoking prior to pregnancy, risk of abruption increased 40% (OR = 1.4, 95% CI 1.0-1.8). Etiologies of placental abruption for first and second pregnancies were different, indicating heterogeneity in their risk-factor profiles. Future research would best consider abruption as a heterogeneous complication to further knowledge of its etiology.