Manuel Porto

The association between prenatal stress and infant birth weight and gestational age at birth: A prospective investigation

OBJECTIVE The aim was to test a model of the influence of maternal prenatal psychosocial stress on birth outcomes after controlling for biomedical risk. STUDY DESIGN In a prospective study a sociodemographically homogeneous sample of 90 women was assessed during the third trimester with standard, reliable questionnaires that measured episodic and chronic stress, strain (response to stress), and pregnancy-related anxiety. Birth outcomes included infant birth weight, gestational age at birth, and intrapartum complications. Parity and biomedical (antepartum) risk was also coded. Bivariate and multivariate analyses were performed after controlling for the effects of biomedical risk factors. RESULTS Independent of biomedical risk, each unit increase of prenatal life event stress (from a possible sample range of 14.7 units) was associated with a 55.03 gm decrease in infant birth weight and with a significant increase in the likelihood of low birth weight (odds ratio 1.32), and each unit increase of prenatal pregnancy anxiety (from a possible sample range of 5 units) was associated with a 3-day decrease in gestational age at birth. CONCLUSION Independent of biomedical risk, maternal prenatal stress factors are significantly associated with infant birth weight and with gestational age at birth.

Prenatal psychosocial factors and the neuroendocrine axis in human pregnancy.

Objective Physiological processes including neuroendocrine function have been proposed as mediators of the relationship between prenatal psychological state and pregnancy outcome; however, there are virtually no human studies that have systematically assessed such mechanisms. Neuroendocrine processes are significantly altered during pregnancy, and are characterized by the evolution of a transient neuroendocrine system, the placenta, and modifications in endocrine control mechanisms. Because these alterations have implications for neuroendocrine responsivity to exogenous conditions, the aim of the present study was to examine the cross-sectional association between prenatal psychosocial factors and stress-related neuroendocrine parameters during human pregnancy. Method Fifty-four adult women with a singleton, intrauterine pregnancy were recruited before 28 weeks of gestation. Maternal antecubital venous blood samples were withdrawn at 28 weeks of gestation for bioassays of adrenocorticotropin hormone (ACTH), beta-endorphin (betaE), and cortisol. Measures of prenatal stress, social support, and personality were collected using a two-part, self-report questionnaire administered at 28 and 30 weeks of gestation. Biomedical data were obtained from the medical record. Factors known to influence neuropeptide and hormone levels during pregnancy were controlled, including gestational age, circadian variation, and obstetric risk. Results In the present sample, prenatal psychosocial stress, social support, and personality variables were associated with neuroendocrine parameters in two primary ways. First, certain psychosocial factors were significantly associated with plasma levels of ACTH, betaE, and cortisol, and second, psychosocial factors were associated with a measure of disregulation of the normal relationship between two pro-opiomelanocortin (POMC) derivatives, ACTH and betaE. Furthermore, a combination of the maternal psychosocial and sociodemographic factors during pregnancy accounted for 36% of the variance in ACTH, 22% of the variance in the ACTH-betaE disregulation index, 13% of the variance in cortisol, and 3% of the variance in betaE. Conclusions The present findings are consistent with the premise that maternal-placental-fetal neuroendocrine parameters are significantly associated, both in magnitude and specificity, with features of maternal psychosocial functioning in pregnancy despite the systemic alterations associated with the endocrinology of pregnancy. These findings provide a basis for further investigations of the role of the neuroendocrine system as a putative mediating pathway between prenatal psychosocial factors and birth outcome, and possibly also as a mechanism linking features of the maternal psychosocial environment to fetal/infant brain development.

Perinatal outcome in pregnancy complicated by massive obesity

OBJECTIVE: Our objective was to determine the impact of massive obesity during pregnancy, defined as maternal weight >300 pounds, on perinatal outcome. STUDY DESIGN: A case-controlled study was conducted. Between Jan. 1, 1986, and Dec. 31, 1990, 111 pregnant women weighing >300 pounds who were delivered at Long Beach Memorial Womens Hospital were identified with a perinatal data base search. A control group matched for maternal age and parity was selected, and perinatal variables were compared between groups. To control for potential confounding medical complications, massively obese patients with diabetes and/or chronic hypertension antedating the index pregnancy were excluded from the obese group, and the data were reanalyzed. The Student t test x2, and Fishers exact statistical analysis were used where appropriate. RESULTS: Massively obese pregnant women are significantly more likely to have a multitude of adverse perinatal outcomes, including primary cesarean section (32.4% vs 14.3%, p = 0.002), macrosomia (30.2% vs 11.6%, pp = 0.0001), intrauterine growth retardation (8.1% vs 0.9%, p = 0.03), and neonatal admission to the intensive care unit (15.6% vs 4.5%, p = 0.01). They also are significantly more likely to have chronic hypertension (27.0% vs 0.9%, p < 0.0001) and insulin-dependent diabetes mellitus (19.8% vs 2.7%, p = 0.0001). However, when those massively obese pregnant women with diabetes and/or hypertension antedating pregnancy are excluded from analysis, no statistically significant differences in perinatal outcome persisted. CONCLUSION: Massively obese pregnant women are at high risk for adverse perinatal outcome; however, this risk appears to be related to medical complications of obesity. (Am J Obstet Gynecol 1992;167:958–62.)

17-hydroxyprogesterone caproate for twin pregnancy: a double-blind, randomized clinical trial.

OBJECTIVE We sought to determine whether prophylactic treatment with 17-alpha-hydroxyprogesterone caproate (17Pc) in twin pregnancy will reduce neonatal morbidity (primary outcome) by prolonging pregnancy (secondary outcome). STUDY DESIGN This was a double-blind, randomized clinical trial. Mothers carrying dichorionic-diamniotic twins were randomly assigned (in a 2:1 ratio) to weekly injections of 250 mg of 17Pc or placebo, starting at 16-24 weeks and continued until 34 weeks. RESULTS In all, 160 women were randomized to 17Pc and 80 to placebo. Composite neonatal morbidity occurred with similar frequency in the 17Pc and placebo groups (14% vs 12%, respectively, P = .62). Mean gestational age at delivery was not affected by 17Pc (35.3 vs 35.9 weeks, P = .10), but a 3-day difference in median gestational age favored placebo (P = .02). There were no perinatal deaths with 17Pc and 3 with placebo. CONCLUSION In twin pregnancy, prophylactic treatment with 17Pc did not prolong gestation or reduce neonatal morbidity.

Maternal corticotropin-releasing hormone and habituation in the human fetus.

Elevated concentrations of maternal corticotrophin-releasing hormone (CRH) during the 2nd and early 3rd trimester of human pregnancy are associated with spontaneous preterm birth, but the effects of maternal CRH on the fetus are unknown. Maternal plasma was collected for analysis of CRH concentration, m = 156.24 +/- 130.91 pg/ml, from 33 pregnant women during Weeks 31-33 of gestation. Immediately after collection of plasma, fetal heart rate (FHR) measures were obtained in response to a challenge with a series of vibroacoustic stimuli. Fetuses of mothers with highly elevated CRH did not respond significantly to the presence of a novel stimulus in a repeated series, p = 0.016. These effects on the FHR response were not related to parity, fetal gender, medical (antepartum) risk, or eventual birth outcomes. Impaired dishabituation in these fetuses of mothers with high concentrations of CRH suggests that neurological systems rich with CRH receptors that support learning and memory, such as parahippocampal regions, may be targets for maternal/placental CRH, with implications for fetal neurological development.

Behavioral perinatology: biobehavioral processes in human fetal development.

Behavioral perinatology is as an interdisciplinary area of research that involves conceptualization of theoretical models and conduct of empirical studies of the dynamic time-, place-, and context-dependent interplay between biological and behavioral processes in fetal, neonatal, and infant life using an epigenetic framework of development. The biobehavioral processes of particular interest to our research group relate to the effects of maternal pre- and perinatal stress and maternal-placental-fetal stress physiology. We propose that behavioral perinatology research may have important implications for a better understanding of the processes that underlie or contribute to the risk of three sets of outcomes: prematurity, adverse neurodevelopment, and chronic degenerative diseases in adulthood. Based on our understanding of the ontogeny of human fetal development and the physiology of pregnancy and fetal development, we have articulated a neurobiological model of pre- and perinatal stress. Our model proposes that chronic maternal stress may exert a significant influence on fetal developmental outcomes. Maternal stress may act via one or more of three major physiological pathways: neuroendocrine, immune/inflammatory, and vascular. We further suggest that placental corticotropin-releasing hormone (CRH) may play a central role in coordinating the effects of endocrine, immune/inflammatory, and vascular processes on fetal developmental outcomes. Finally, we hypothesize that the effects of maternal stress are modulated by the nature, duration, and timing of occurrence of stress during gestation. In this paper, we elaborate on the conceptual and empirical basis for this model, highlight some relevant issues and questions, and make recommendations for future research in this area.

Failure of 17-hydroxyprogesterone to reduce neonatal morbidity or prolong triplet pregnancy: a double-blind randomized clinical trial

OBJECTIVE To test whether 17 alpha-hydroxyprogesterone caproate (17P) will reduce neonatal morbidity by increasing gestational age at delivery in triplet pregnancies. STUDY DESIGN Double-blind, randomized clinical trial. Mothers carrying trichorionic-triamniotic triplets were randomly assigned (in a 2:1 ratio) to weekly injections of 250 mg of 17P or placebo, starting at 16-22 weeks and continued until 34 weeks. Primary outcome was composite neonatal morbidity. RESULTS Fifty-six women were randomized to 17P and 25 to placebo. Composite neonatal morbidity occurred with similar frequency in the 17P and placebo groups (38% vs 41%, respectively; P = .71). Mean gestational age at delivery was not affected by 17P (31.9 vs 31.8 weeks; P = .36). There were 13 midtrimester fetal losses with 17P vs none with placebo (P < .02). CONCLUSION In triplet pregnancy, prophylactic treatment with 17P did not reduce neonatal morbidity or prolong gestation but was associated with increased midtrimester fetal loss.

Maternal Hypothalamic-Pituitary-Adrenal Disregulation during the Third Trimester Influences Human Fetal Responses

Maternal peptides from the hypothalamic-pituitary-adrenal (HPA) axis rise during human pregnancy. The effects of circulating maternal adrenocorticotropin (ACTH) and β-endorphin (BE) on human fetal behavior was determined in 135 women during their 32nd week of gestation. Fetal behavior was measured by assessing heart rate habituation to a series of repeated vibroacoustic stimuli. Individual differences in habituation were determined by computing the number of consecutive responses above the standard deviation during a control period. There was no significant relation between levels of ACTH, BE and the rate of fetal heart rate habituation. However, an index of HPA disregulation (uncoupling of ACTH and BE) was related significantly to fetal behavior. Fetal exposure to high levels of maternal BE relative to ACTH was associated with significantly lower rates of habituation. Results indicate that maternal stress and stress-related peptides influence fetal response patterns. It is possible that this influence persists over the life span.

Corticotrophin-releasing Hormone and Fetal Responses in Human Pregnancy

Abstract: During human pregnancy, maternal and fetal compartments of the human placenta produce and release corticotrophic‐releasing hormone (CRH). Elevations of placental CRH are associated with decreased gestational length (including preterm delivery). The effects of elevated placental CRH on human fetal neurological development are not known. Pregnant women in the 31st and 32nd week of gestation consented to procedures for collection of blood and measurement of fetal heart rate (FHR) in response to a series of 40 vibroacoustic stimuli (VAS). Measures of habituation and dishabituation were calculated from the FHR. All subjects were followed to delivery. Fetuses (N= 33) of women with highly elevated CRH were least responsive (p < .03) to stimulation after presentation of a novel (dishabituating) stimulus with control for parity, fetal gender, medical (antepartum) risk, and gestational length at term. In a larger sample (N= 156) a polynomial model predicted the pattern of FHR reactivity for the first 15 trials. Placental CRH concentration significantly predicted FHR reactivity after controlling for the effects of trial number, baseline FHR, inter‐trial interval, and presence of uterine contractions. Increased maternal CRH levels were significantly related to the length of gestation after controlling for the effects of fetal gender, parity, and medical risk (p= .05). The relationship between length of gestation and FHR was not significant suggesting separate actions of CRH on these events. Elevated placental CRH appears to accelerate certain developmental events (gestational length) and may influence the fetal nervous system. The impaired fetal responses to novelty and increased arousal observed in this study suggest that neurological systems may be targets for placental CRH during sensitive developmental periods.

Quantitation of uterine activity preceding preterm, term, and postterm labor

To assess uterine activity before labor in patients delivering preterm, at term, and postterm, the maximum spontaneous contraction frequency per 10-minute window during the initial portion of antepartum fetal heart rate monitoring was analyzed. Patients with multiple gestation, third trimester bleeding, polyhydramnios, or premature rupture of membranes and those already diagnosed with preterm labor were eliminated from the study. Of the 2446 remaining patients (7247 antepartum fetal heart rate tests) who went into spontaneous labor, 237 did so before 37 completed weeks of gestation, 1077 entered labor at term (38 to 42 completed weeks), and 1132 did so after 42 weeks. There was a significant increase in maximum uterine activity per 10-minute window from 30 to 44 weeks of gestation (average 4.7% per week; r = 0.97, p less than 0.0001). When compared with patients delivering spontaneously at term, average maximum uterine activity per 10-minute window was greatest in the preterm labor group (p less than 0.05) and least in the postterm labor group (p less than 0.05). These differences were present for several weeks preceding the onset of spontaneous labor. All three groups showed a surge of uterine activity during the 3 days before the onset of spontaneous labor.