Eva Pressman

Maternal Stress and Affect Influence Fetal Neurobehavioral Development.

The authors investigated the association between maternal psychological and fetal neurobehavioral functioning. Data were provided by 52 maternal-fetal pairs at 24, 30, and 36 weeks gestation. The relations between maternal measures and fetal heart rate, variability, and motor activity were statistically modeled. Fetuses of women who were more affectively intense, appraised their lives as more stressful, and reported more frequent pregnancy-specific hassles were more active across gestation. Fetuses of women who perceived their pregnancy to be more intensely and frequently uplifting and had positive emotional valence toward pregnancy were less active. Associations with fetal heart-rate measures were detected at 36 weeks gestation. These data provide evidence for proximal effects of maternal psychological functioning on fetal neurobehavior.

Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans

The in utero availability of methyl donors, such as choline, may modify fetal epigenetic marks and lead to sustainable functional alterations throughout the life course. The hypothalamic‐pituitaryadrenal (HPA) axis regulates cortisol production and is sensitive to perinatal epigenetic programming. As an extension of a 12‐wk dose‐response choline feeding study conducted in third‐trimester pregnant women, we investigated the effect of maternal choline intake (930 vs. 480 mg/d) on the epigenetic state of cortisolregulating genes, and their expression, in placenta and cord venous blood. The higher maternal choline intake yielded higher placental promoter methylation of the cortisol‐regulating genes, corticotropin releasing hormone (CRH; P=0.05) and glucocorticoid receptor (NR3C1; P=0.002); lower placental CRH transcript abundance (P=0.04); lower cord blood leukocyte promoter methylation of CRH (P=0.05) and NR3C1 (P=0.04); and 33% lower (P=0.07) cord plasma cortisol. In addition, placental global DNA methylation and dimethylated histone H3 at lysine 9 (H3K9me2) were higher (P=0.02) in the 930 mg choline/d group, as was the expression of select placental methyltransferases. These data collectively suggest that maternal choline intake in humans modulates the epigenetic state of genes that regulate fetal HPA axis reactivity as well as the epigenomic status of fetal derived tissues.—Jiang, X., Yan, J., West, A. A., Perry, C. A., Malysheva, O. V., Devapatla, S., Pressman, E., Vermeylen, F., Caudill, M. A. Maternal choline intake alters the epigenetic state of fetal cortisol‐regulating genes in humans. FASEB J. 26, 3563–3574 (2012). www.fasebj.org

Vertical skin incisions and wound complications in the obese parturient

OBJECTIVE To examine the relationship between the type of skin incision and postoperative wound complications in an obese population. METHODS A hospital-based perinatal database was used to identify women with a body mass index (BMI) of greater than 35 undergoing their first cesarean delivery. Hospital and outpatient medical records were reviewed for the following variables: age, insurance status, BMI, gestational age at delivery, birth weight, smoking history, prior abdominal surgery, existing comorbidities, preoperative hematocrit, chorioamnionitis, duration of labor and membrane rupture, dilation at time of cesarean delivery, type of skin and uterine incision, estimated blood loss, operative time, antibiotic prophylaxis, use of subcutaneous drains or sutures, endometritis, and length of stay. The primary outcome variable was any wound complication requiring opening the incision. Multiple logistic regression analysis was completed to determine which of these factors contributed to the incidence of wound complications. RESULTS From 1994 to 2000, 239 women with a BMI greater than 35 undergoing a primary cesarean delivery were identified. The overall incidence of wound complications in this group of severely obese patients was 12.1%. Factors associated with wound complications included vertical skin incisions (odds ratio [OR] 12.4, P < .001) and endometritis (OR 3.4, P = .03). A high preoperative hematocrit was protective (OR .87, P = .03). No other factors were found to impact wound complications. CONCLUSION Primary cesarean delivery in the severely obese parturient has a high incidence of wound complications. Our data indicate that a vertical skin incision is associated with a higher rate of wound complications than a transverse incision.

Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans

BACKGROUND In 1998 choline Adequate Intakes of 425 and 450 mg/d were established for nonpregnant and pregnant women, respectively. However, to our knowledge, no dose-response studies have been conducted to evaluate the effects of pregnancy or maternal choline intake on biomarkers of choline metabolism. OBJECTIVE We sought to quantify the effects of pregnancy and maternal choline intake on maternal and fetal indicators of choline metabolism. DESIGN Healthy pregnant (n = 26; 27 wk gestation) and nonpregnant (n = 21) women were randomly assigned to receive 480 or 930 mg choline/d for 12 wk. Fasting blood samples and placental tissue and umbilical cord venous blood were collected and analyzed for choline and its metabolites. RESULTS Regardless of the choline intake, pregnant women had higher circulating concentrations of choline (30%; P < 0.001) but lower concentrations of betaine, dimethylglycine, sarcosine, and methionine (13-55%; P < 0.001). Obligatory losses of urinary choline and betaine in pregnant women were ∼2-4 times as high (P ≤ 0.02) as those in nonpregnant women. A higher choline intake yielded higher concentrations of choline, betaine, dimethylglycine, and sarcosine (12-46%; P ≤ 0.08) in both pregnant and nonpregnant women without affecting urinary choline excretion. The higher maternal choline intake also led to a doubling of dimethylglycine in cord plasma (P = 0.002). CONCLUSION These data suggest that an increment of 25 mg choline/d to meet the demands of pregnancy is insufficient and show that a higher maternal choline intake increases the use of choline as a methyl donor in both maternal and fetal compartments. This trial was registered at clinicaltrials.gov as NCT01127022.

Fetal neurobehavioral development: Associations with socioeconomic class and fetal sex

This longitudinal study investigated neurobehavioral development in the human fetus from 24 to 36 weeks gestation. Subject (N=103) were stratified by socioeconomic class. Fetal data were collected for 50 min at three intervals, and included measures of heart rate, movement, and biobehavioral patterns. Repeated measures analysis of variance by fetal sex and maternal socioeconomic status was used to detect maturation effects and group differences. With advancing gestation, fetuses exhibited reduced heart rate, increased heart rate variability and coupling between movement and heart rate, increased movement vigor, and more biobehavioral concordance. Male fetuses displayed higher heart rate variability throughout gestation and somewhat earlier emergence of biobehavioral organization than females. Fetuses of women of lower socioeconomic status had reduced heart rate variability, moved less often and with less vigor, showed less coupling between movement and heart rate, and had fewer episodes of synchronous quiescence/activity. Results are discussed in terms of development of the central nervous system.

Human red cell Aquaporin CHIP. II. Expression during normal fetal development and in a novel form of congenital dyserythropoietic anemia.

Channel-forming integral protein (CHIP) is the archetypal member of the Aquaporin family of water channels. Delayed CHIP expression was shown recently in perinatal rat (Smith, B. L., R. Baumgarten, S. Nielsen, D. Raben, M. L. Zeidel, and P. Agre. 1993. J. Clin. Invest. 92:2035-2041); here we delineate the human patterns. Compared with adult, second and third trimester human fetal red cells had lower CHIP/spectrin ratios (0.72 +/- 0.12, 0.94 +/- 0.22 vs 1.18 +/- 0.11) and reduced osmotic water permeability (0.029, 0.026 vs 0.037 cm/s); CHIP was already present in human renal tubules by the second trimester. A patient with a novel form of congenital dyserythropoietic anemia (CDA) with persistent embryonic and fetal globins and absent red cell CD44 protein was studied because of reduced CHIP-associated Colton antigens. Novel CDA red cells contained < 10% of the normal level of CHIP and had remarkably low osmotic water permeability (< 0.01 cm/s), but no mutation was identified in Aquaporin-1, the gene encoding CHIP. These studies demonstrate: (a) unlike rat, human CHIP expression occurs early in fetal development; (b) red cell water channels are greatly reduced in a rare phenotype; and (c) disrupted expression of red cell CHIP and CD44 suggests an approach to the molecular defect in a novel form of CDA.

Antenatal Origins of Individual Differences in Heart Rate

This study examines prenatal-to-postnatal stability in heart rate and variability from mid-gestation through the first year of life. Fetal heart rate data were collected from 52 healthy fetuses at 24, 30, and 36 weeks gestation, and again at 2 weeks and 12 months of age. Fetal heart rate measures were stable during gestation and positively associated with neonatal and infant measures. Maternal pulse rate and oxygen saturation were moderately associated with fetal heart rate. Together, fetal cardiac (heart rate and variability) and maternal physiologic measures (blood pressure and oxygen saturation) explained 40 and 48% of the variance in heart rate and variability, respectively, at 1 year of age. These common measures of individual differences in autonomic function are enduring characteristics that originate during fetal development.

Prenatal Maternal Anxiety Predicts Reduced Adaptive Immunity in Infants

Prenatal anxiety has been linked with altered immune function in offspring in animal studies, but the relevance for human health is unknown. We examined prenatal maternal anxiety as a predictor of adaptive immunity in infants at 2 and 6 months of age as part of a prospective longitudinal study. The humoral immune response to hepatitis B vaccine was assessed at 2 months (n=80) and 6 months (n=76) of age. Prenatal anxiety predicted lower hepatitis B antibody titers at 6 months of age independent of obstetric and socio-demographic covariates; the effects were limited to those infants who had not completed the 3-dose vaccine series (for transformed titer values, r=-.36, p<.05). Cell-mediated immune responses at 2 (n=56) and 6 (n=54) months of age were examined by ELISpot assays for interferon(IFN)-γ, interleukin(IL)-2, and IL-4 responder cell frequencies to three antigens: hepatitis B surface antigen, tetanus toxoid, and phytohaemagglutinin (PHA). Prenatal maternal anxiety was associated with reduced IFN-γ and increased IL-4 responder cell frequencies at 6 months of age, independent of obstetric and socio-demographic covariates. No effect of prenatal anxiety was found on adaptive immunity at 2 months of age. The findings provide the first demonstration in humans that prenatal anxiety alters adaptive immunity in the infant.

PRETERM PREMATURE RUPTURE OF THE MEMBRANES AND ANTIOXIDANTS: THE FREE RADICAL CONNECTION

Abstract Aim: To discuss the role of oxidant stress in preterm, premature rupture of the membranes (PPROM). Results: There is evidence to suggest that preterm, premature rupture of the membranes occurs secondary to focal collagen damage in the fetal membranes. Conclusion: Oxidant stress caused by increased ROS formation and/or antioxidant depletion may disrupt collagen and cause premature membrane rupture. We propose that supplementation with vitamins C and E may synergistically protect the fetal membranes, and decrease the risks of PPROM.

Fetal movement detection: Comparison of the toitu actograph with ultrasound from 20 weeks gestation

OBJECTIVE This study evaluates the validity of Doppler-detected fetal movement by a commercially available monitor and investigates whether characteristics of maternal body habitus and the intrauterine environment affect its performance. METHODS Fetal movement was evaluated in normal pregnancies using both ultrasound visualization and a fetal actocardiograph (Toitu MT320; Tofa Medical Inc., Malvern, PA). Data were collected for 32 min on 34 fetuses stratified by gestational age (20-25 weeks; 28-32 weeks; 35-39 weeks). Fetal and maternal characteristics were recorded. Comparisons between ultrasound-detected trunk and limb movements and actograph records were conducted based both on 10-s time intervals and on detection of individual movements. RESULTS Time-based comparisons indicated agreement between ultrasound and actograph 94.7% of the time; this association rose to 98% when movements of less than 1 s duration were excluded. Individual movements observed on ultrasound were detected by the actograph 91% of the time, and 97% of the time when brief, isolated movements were excluded. The overall kappa value for agreement was 0.88. The actograph was reliable in detecting periods of quiescence as well as activity. These findings did not vary by gestational age. The number of movements detected by the actograph, but not the single-transducer ultrasound, significantly increased over gestation. Maternal age, parity, weight, height, or body mass index were not consistently associated with actograph validity. Characteristics of the uterine environment, including placenta location, fetal presentation, and amniotic fluid volume also did not affect results. CONCLUSIONS The Toitu actograph accurately detects fetal movement and quiescence from as early as 20 weeks gestation and has utility in both clinical and research settings. Actographs are most useful for providing objective and quantifiable measures of fetal activity level, including number and duration of movements, while visualization through ultrasound is necessary for studies of movement quality, source, or mechanics.