Human placental lactogen (human chorionic somatomammotropin) and oxytocin during pregnancy: Individual patterns and associations with maternal-fetal attachment, anxiety, and depression.

Previous studies support links among maternal-fetal attachment, psychological symptoms, and hormones during pregnancy and the post-partum period. Other studies connect maternal feelings and behaviors to oxytocin and suggest that an increase in oxytocin during pregnancy may prime maternal-fetal attachment. To date, researchers have not examined a possible association between maternal-fetal attachment with human placental lactogen although animal models are suggestive. In the current study, we sought to describe oxytocin and human placental lactogen levels as related to psychological constructs across pregnancy. Seventy women participated in the study. At each of three time-points (early, mid, and late pregnancy), the women had their blood drawn to assess oxytocin and human placental lactogen levels, and they completed psychological assessments measuring maternal-fetal attachment, anxiety, and depression. Our results indicate that oxytocin levels were statistically similar across pregnancy, but that human placental lactogen significantly increased across pregnancy. Results did not indicate significant associations of within-person (comparing individuals to themselves) oxytocin or human placental lactogen levels with maternal-fetal attachment. Additionally, results did not show between-person (comparing individuals to other individuals) oxytocin or human placental lactogen levels with maternal-fetal attachment. Oxytocin levels were not associated with anxiety; rather the stage of pregnancy moderated the effect of the within-person OT level on depression. Notably, increasing levels of human placental lactogen were significantly associated with increasing levels of both anxiety and depression in between subject analyses. The current study is important because it describes typical hormonal and maternal fetal attachment levels during each stage of pregnancy, and because it suggests an association between human placental lactogen and psychological symptoms during pregnancy. Future research should further elucidate these relationships.

Low serum placental lactogen at term is associated with postnatal symptoms of depression and anxiety in women delivering female infants.

BACKGROUND: Placental endocrine insufficiency may increase the risk of depression and anxiety during pregnancy and/or after birth. This study investigated the association between serum human placental lactogen (hPL) and measures of perinatal mental health, accounting for selective serotonin-reuptake inhibitor (SSRI) usage. METHOD: Caucasian women with singleton, term pregnancies recruited at their pre-surgical appointment prior to an elective caesarean section (ELCS) were studied. Serum hPL levels were measured by ELISA in maternal blood collected at the pre-surgical appointment. Depression and anxiety scores were derived from Edinburgh Postnatal Depression Scale (EPDS) and the trait subscale of the State-Trait Anxiety Inventory (STAI) questionnaires completed at recruitment and three postnatal time points. Data was analysed by unadjusted and adjusted multiple linear regression. RESULTS: In adjusted linear regressions, term maternal serum hPL levels were negatively associated with postnatal EPDS and STAI score ten weeks postnatal for mothers who had girls (B= -.367, p = .022, 95% CI -.679, -.056; and B= -.776, p = .030, 95% CI -1.475, -.077 respectively). Excluding women prescribed SSRIs strengthened the relationship at 10 weeks and uncovered an earlier association between hPL and mood scores within one week of delivery (EPDS B= -.357, p = .041, 95 % CI -.698, -.015; and STAI B= -.737, p = .027, 95 % CI -1.387, -.086). In mothers who had boys, there were no associations between hPL and mood scores at any time point. CONCLUSION: Low hPL at term associated with postnatal depression and anxiety symptoms exclusively in mothers of girls. Insufficiency in hPL may contribute to maternal mood symptoms.

Human placental lactogen mRNA in maternal plasma play a role in prenatal diagnosis of abnormally invasive placenta: yes or no?

Objective: To determine whether maternal plasma human placental lactogen (hPL) mRNA levels can predict abnormally invasive placenta. Study design: Sixty-eight singleton pregnant women with prior Cesarean deliveries were classified into three groups: 35 with normal placentation (control group); 21 with placenta previa alone (placenta previa group); 12 with placenta previa and placenta accreta (placenta accreta group). Maternal plasma hPL mRNA concentrations were measured by real-time reverse-transcription polymerase chain reaction Result: The multiple of the median (median, range) for hPL mRNA was significantly higher for the placenta accreta group (2.78, 1.09-4.56) than the control (1.00, 0.29-2.98) or placenta previa (1.12, 0.33-3.25) groups (Steel-Dwass test, p < .001 and p = .005, respectively), was not significantly different between the women with placenta accreta who underwent hysterectomies (2.96, 1.38-4.56) and the women whose deliveries did not result in hysterectomy (2.36, 1.09-3.25) in the placenta accreta group (Mann-Whitney U test, p = .372). Conclusion: hPL mRNA in maternal plasma may indicate abnormally invasive placenta but cannot predict whether abnormally invasive placenta will result in hysterectomy.

Gestational hormone trajectories and early pregnancy failure: a reassessment.

BACKGROUND: Studies have commonly assessed the endocrinolgical status of women once miscarriage is threatened or suspected; few studies have explored the antecedent hormonal environment or used a longitudinal strategy. Using refined statistical techniques, we sought to re-evaluate whether gestational hormone trajectories in early pregnancy can identify future miscarriage in asymptomatic pregnancies. METHODS: This prospective cohort study followed 105 women over-conception; 72 had normal term pregnancy outcomes while 33 experienced early pregnancy failure between 35 and 115 days of gestation. Participants attended a pre-conception and antenatal clinic at Newcastle University, United Kingdom (UK). Evaluation methods included ultrasound, clinical assessments of pregnancy progress and serial measurements of gestational hormones by radioimmunoassays. Linear mixed-effects regression analysis examined hormone relationships with pregnancy outcomes. RESULTS: Detailed longitudinal illustration of gestational hormones, antecedent to miscarriage indications, revealed early pathophysiological trends. In particular, oestradiol showed as marked a deviation from normal as progesterone before miscarriage was evident, reflecting a deficiency in the ovarian response to rising human chorionic gonadotrophin (hCG) levels. Regression analysis provided equations for gestational hormone slopes that significantly differentiated asymptomatic women with subsequent early pregnancy failure, compared to women with normal term pregnancies. Both progesterone and oestradiol displayed negative mean slopes in pregnancies destined for failure; in this group, both human placental lactogen (hPL) and hCG revealed mean positive trajectories that imitated normal pregnancies but at slower rates of increase. CONCLUSIONS: Oestradiol, progesterone and hCG trajectories, from 50 days of gestation, have good potential for revealing pathophysiology and for identifying which asymptomatic pregnancies are destined for subsequent failure. In asymptomatic patients where there is concern about viability and ultrasound diagnosis is ambiguous, a combined hormonal profile could contribute to guiding patient care decisions.

Chorionic somatomammotropin impacts early fetal growth and placental gene expression.

Several developmental windows, including placentation, must be negotiated to establish and maintain pregnancy. Impaired placental function can lead to preeclampsia and/or intrauterine growth restriction (IUGR), resulting in increased infant mortality and morbidity. It has been hypothesized that chorionic somatomammotropin (CSH) plays a significant role in fetal development, potentially by modifying maternal and fetal metabolism. Recently, using lentiviral-mediated in vivo RNA interference in sheep, we demonstrated significant reductions in near-term (135 days of gestation; dGA) fetal and placental size, and altered fetal liver gene expression, resulting from CSH deficiency. We sought to examine the impact of CSH deficiency on fetal and placental size earlier in gestation (50 dGA), and to examine placental gene expression at 50 and 135 dGA. At 50 dGA, CSH-deficient pregnancies exhibited a 41% reduction (P ≤ 0.05) in uterine vein concentrations of CSH, and significant (P ≤ 0.05) reductions (≈21%) in both fetal body and liver weights. Placentae harvested at 50 and 135 dGA exhibited reductions in IGF1 and IGF2 mRNA concentrations, along with reductions in SLC2A1 and SLC2A3 mRNA. By contrast, mRNA concentrations for various members of the System A, System L and System y+ amino acid transporter families were not significantly impacted. The IUGR observed at the end of the first-third of gestation indicates that the near-term IUGR reported previously, began early in gestation, and may have in part resulted from deficits in the paracrine action of CSH within the placenta. These results provide further compelling evidence for the importance of CSH in the progression and outcome of pregnancy.

A proteomic clock of human pregnancy.

BACKGROUND: Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable because it will enable targeted interventions ahead of clinical manifestations. The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging. An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome. OBJECTIVE: The recent availability of a highly multiplexed platform affording the simultaneous measurement of 1310 plasma proteins opens the door for a more explorative approach. The major aim of this study was to examine whether analysis of plasma collected during gestation of term pregnancy would allow identifying a set of proteins that tightly track gestational age. Establishing precisely timed plasma proteomic changes during term pregnancy is a critical step in identifying deviations from regular patterns caused by fetal and maternal maladaptations. A second aim was to gain insight into functional attributes of identified proteins and link such attributes to relevant immunological changes. STUDY DESIGN: Pregnant women participated in this longitudinal study. In 2 subsequent sets of 21 (training cohort) and 10 (validation cohort) women, specific blood specimens were collected during the first (7-14 weeks), second (15-20 weeks), and third (24-32 weeks) trimesters and 6 weeks postpartum for analysis with a highly multiplexed aptamer-based platform. An elastic net algorithm was applied to infer a proteomic model predicting gestational age. A bootstrapping procedure and piecewise regression analysis was used to extract the minimum number of proteins required for predicting gestational age without compromising predictive power. Gene ontology analysis was applied to infer enrichment of molecular functions among proteins included in the proteomic model. Changes in abundance of proteins with such functions were linked to immune features predictive of gestational age at the time of sampling in pregnancies delivering at term. RESULTS: An independently validated model consisting of 74 proteins strongly predicted gestational age (P = 3.8 × 10-14, R = 0.97). The model could be reduced to 8 proteins without losing its predictive power (P = 1.7 × 10-3, R = 0.91). The 3 top ranked proteins were glypican 3, chorionic somatomammotropin hormone, and granulins. Proteins activating the Janus kinase and signal transducer and activator of transcription pathway were enriched in the proteomic model, chorionic somatomammotropin hormone being the top-ranked protein. Abundance of chorionic somatomammotropin hormone strongly correlated with signal transducer and activator of transcription-5 signaling activity in CD4 T cells, the endogenous cell-signaling event most predictive of gestational age. CONCLUSION: Results indicate that precisely timed changes in the plasma proteome during term pregnancy mirror a proteomic clock. Importantly, the combined use of several plasma proteins was required for accurate prediction. The exciting promise of such a clock is that deviations from its regular chronological profile may assist in the early diagnoses of pregnancy-related pathologies, and point to underlying pathophysiology. Functional analysis of the proteomic model generated the novel hypothesis that chrionic somatomammotropin hormone may critically regulate T-cell function during pregnancy.

Maternal Serum Prolactin and Prediction of Postpartum ß-Cell Function and Risk of Prediabetes/Diabetes.

OBJECTIVE: The insulin resistance of mid- to late pregnancy poses a physiologic stress test for the pancreatic ß-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of ß-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of ß-cell function in pregnancy. Given their respective roles in the ß-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman's underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODS: Three hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and ß-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTS: The postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (ß = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35-0.72, P = 0.0002). CONCLUSIONS: Serum prolactin in pregnancy predicts postpartum ß-cell function and risk of prediabetes/diabetes.

Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements.

BACKGROUND: Maternal perception of reduced fetal movements (RFM) is associated with increased risk of fetal growth restriction (FGR) and stillbirth, mediated by placental insufficiency. The maternally expressed imprinted gene PHLDA2 controls fetal growth, placental development and placental lactogen production in a mouse model. A number of studies have also demonstrated abnormally elevated placental PHLDA2 expression in human growth restricted pregnancies. This study examined whether PHLDA2 was aberrantly expressed in placentas of RFM pregnancies resulting in delivery of an FGR infant and explored a possible relationship between PHLDA2 expression and placental lactogen release from the human placenta. METHODS: Villous trophoblast samples were obtained from a cohort of women reporting RFM (N = 109) and PHLDA2 gene expression analysed. hPL levels were assayed in the maternal serum (N = 74). RESULTS: Placental PHLDA2 expression was significantly 2.3 fold higher in RFM pregnancies resulting in delivery of an infant with FGR (p < 0.01), with highest levels of PHLDA2 expression in the most severe cases. Placental PHLDA2 expression was associated with maternal serum hPL levels (r = -0.30, p = 0.008, n = 74) although this failed to reach statistical significance in multiple linear regression analysis controlling for birth weight (p = 0.07). CONCLUSIONS: These results further highlight a role for placental PHLDA2 in poor perinatal outcomes, specifically FGR associated with RFM. Furthermore, this study suggests a potential relationship between placental PHLDA2 expression and hPL production by the placenta, an association that requires further investigation in a larger cohort.

Prolactin receptors and placental lactogen drive male mouse pancreatic islets to pregnancy-related mRNA changes.

Pregnancy requires a higher functional beta cell mass and this is associated with profound changes in the gene expression profile of pancreatic islets. Taking Tph1 as a sensitive marker for pregnancy-related islet mRNA expression in female mice, we previously identified prolactin receptors and placental lactogen as key signalling molecules. Since beta cells from male mice also express prolactin receptors, the question arose whether male and female islets have the same phenotypic resilience at the mRNA level during pregnancy. We addressed this question in vitro, by stimulating cultured islets with placental lactogen and in vivo, by transplanting male or female islets into female acceptor mice. Additionally, the islet mRNA expression pattern of pregnant prolactin receptor deficient mice was compared with that of their pregnant wild-type littermates. When cultured with placental lactogen, or when transplanted in female recipients that became pregnant (day 12.5), male islets induced the 'islet pregnancy gene signature', which we defined as the 12 highest induced genes in non-transplanted female islets at day 12.5 of pregnancy. In addition, serotonin immunoreactivity and beta cell proliferation was also induced in these male transplanted islets at day 12.5 of pregnancy. In order to further investigate the importance of prolactin receptors in these mRNA changes we used a prolactin receptor deficient mouse model. For the 12 genes of the signature, which are highly induced in control pregnant mice, no significant induction of mRNA transcripts was found at day 9.5 of pregnancy. Together, our results support the key role of placental lactogen as a circulating factor that can trigger the pregnancy mRNA profile in both male and female beta cells.

Duration of maternal undernutrition differentially alters fetal growth and hormone concentrations.

To investigate the impact of duration of maternal undernutrition in twin sheep pregnancies, ewes were either fed 100% (C) or 50% of their nutrient requirements from 28 to 78 d gestational age (dGA) and readjusted to 100% beginning at 79 dGA (LC) or continuously restricted from 28 to 135 dGA (LL). Weights of the fetus, empty carcass, brain, and liver were greater in the LC than LL fetuses at 135 dGA (P ≤ 0.05). Although umbilical vein (UmV) glucose concentrations did not differ, the UmV:umbilical artery (UmA) glucose gradient was smaller (0.26 ± 0.03 vs 0.38 ± 0.03 and 0.39 ± 0.04 mmol L(-1); P ≤ 0.05) in LL than C and LC fetuses, respectively. Umbilical vein concentrations of IGF-1 were less (46.7 ± 5.62 vs 74.3 ± 6.71 ng/mL; P ≤ 0.05) in LL than LC fetuses. Additionally, LL fetuses tended (P ≤ 0.10) to have lower UmA concentrations of insulin (0.24 ± 0.13 vs 0.70 ± 0.15 ng/mL) and IGF-1 (66.6 ± 7.51 vs 91.4 ± 8.97 ng/mL) than LC fetuses. Although most of the observed differences occurred between LC and LL pregnancies, LC fetuses tended (P ≤ 0.10) to have greater UmV and UmA pCO2 than C fetuses. Furthermore, the UmV:UmA O2 content gradient tended to be greater (5.02 ± 0.43 vs 3.41 ± 0.47; P ≤ 0.10) in C than LL fetuses. UmA placental lactogen also tended to be greater (46.6 ± 4.40 vs 31.1 ± 4.69 ng/mL; P ≤ 0.10) in LL than C fetuses. These data suggest that in twin pregnancies, maternal undernutrition followed by realimentation induces a different fetal outcome compared with continuous nutrient restriction, and both may differ physiologically from control fed pregnancies.

Endocrine disruption in human placenta: expression of the dioxin-inducible enzyme, CYP1A1, is correlated with that of thyroid hormone-regulated genes.

CONTEXT: Thyroid hormone (TH) is essential for normal development; therefore, disruption of TH action by a number of industrial chemicals is critical to identify. Several chemicals including polychlorinated biphenyls are metabolized by the dioxin-inducible enzyme CYP1A1; some of their metabolites can interact with the TH receptor. In animals, this mechanism is reflected by a strong correlation between the expression of CYP1A1 mRNA and TH-regulated mRNAs. If this mechanism occurs in humans, we expect that CYP1A1 expression will be positively correlated with the expression of genes regulated by TH. OBJECTIVE: The objective of the study was to test the hypothesis that CYP1A1 mRNA expression is correlated with TH-regulated mRNAs in human placenta. METHODS: One hundred sixty-four placental samples from pregnancies with no thyroid disease were obtained from the GESTE study (Sherbrooke, Québec, Canada). Maternal and cord blood TH levels were measured at birth. The mRNA levels of CYP1A1 and placental TH receptor targets [placental lactogen (PL) and GH-V] were quantitated by quantitative PCR. RESULTS: CYP1A1 mRNA abundance varied 5-fold across 132 placental samples that had detectable CYP1A1 mRNA. CYP1A1 mRNA was positively correlated with PL (r = 0.64; P < .0001) and GH-V (P < .0001, r = 0.62) mRNA. PL and GH-V mRNA were correlated with each other (r = 0.95; P < .0001), suggesting a common activator. The mRNAs not regulated by TH were not correlated with CYP1A1 expression. CONCLUSIONS: CYP1A1 mRNA expression is strongly associated with the expression of TH-regulated target gene mRNAs in human placenta, consistent with the endocrine-disrupting action of metabolites produced by CYP1A1.

Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy.

OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors. SAMPLES: Serum samples from nonpregnant and pregnant women. METHODS: The effect of serum from pregnant women on the proliferation of rat beta cells was studied using [3H]thymidine incorporation and 5-ethynyl-2'-deoxyuridine proliferation assays. In addition, serum from pregnant and nonpregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for mitogenic activity in INS-1E cells. Proteins and peptides in mitogenic active serum fractions were identified by amino acid sequencing and mass spectrometry. MAIN OUTCOME MEASURES: Presence of circulating beta cell proliferating factors. RESULTS: Late gestational pregnancy serum significantly increased proliferation of rat beta cells compared with early pregnancy and nonpregnancy. The mitogenic active serum fractions contained proteins and peptides derived from kininogen-1, fibrinogen-α, α1-antitrypsin, apolipoprotein-A1, placental lactogen, angiotensinogen and serum albumin. CONCLUSION: Pregnancy serum is able to stimulate proliferation of rat beta cells. We have identified several circulating factors that may contribute to beta cell adaptation to pregnancy. Further studies are needed to elucidate their possible role in glucose homeostasis in the mother and her offspring.

Increased levels of cell-free human placental lactogen mRNA at 28-32 gestational weeks in plasma of pregnant women with placenta previa and invasive placenta.

We compared the levels of cell-free human placental lactogen (hPL) messenger RNA (mRNA) in maternal plasma at 28 to 32 weeks of gestation between women with diagnosis of placenta previa or invasive placenta and women with an uneventful pregnancy. Sensitivity and specificity of hPL mRNA for the prediction of invasive placenta were further explored. Plasma hPL mRNA were quantified by real-time reverse-transcriptase polymerase chain reaction in women with placenta previa (n = 13), invasive placenta (n = 5), and normal pregnancies (n = 92). Median (range) hPL mRNA was significantly higher in women with placenta previa, 782 (10-2301) copies/mL of plasma, and in those with invasive placenta, 615 (522-2102) copies/mL of plasma, when compared to normal pregnancies, 90 (4-4407) copies/mL of plasma, P < .01 and P < .05, respectively. We found a sensitivity of 100% and a specificity of 61.5% for the prediction of invasive placenta among women with placenta previa. In conclusion, expression of hPL mRNA is increased in plasma of women with placenta previa and invasive placenta at 28 to 32 weeks of gestation.

A randomised controlled trial comparing standard or intensive management of reduced fetal movements after 36 weeks gestation--a feasibility study.

BACKGROUND: Women presenting with reduced fetal movements (RFM) in the third trimester are at increased risk of stillbirth or fetal growth restriction. These outcomes after RFM are related to smaller fetal size on ultrasound scan, oligohydramnios and lower human placental lactogen (hPL) in maternal serum. We performed this study to address whether a randomised controlled trial (RCT) of the management of RFM was feasible with regard to: i) maternal recruitment and retention ii) patient acceptability, iii) adherence to protocol. Additionally, we aimed to confirm the prevalence of poor perinatal outcomes defined as: stillbirth, birthweight <10th centile, umbilical arterial pH <7.1 or unexpected admission to the neonatal intensive care unit. METHODS: Women with RFM ≥36 weeks gestation were invited to participate in a RCT comparing standard management (ultrasound scan if indicated, induction of labour (IOL) based on consultant decision) with intensive management (ultrasound scan, maternal serum hPL, IOL if either result was abnormal). Anxiety was assessed by state-trait anxiety index (STAI) before and after investigations for RFM. Rates of protocol compliance and IOL for RFM were calculated. Participant views were assessed by questionnaires. RESULTS: 137 women were approached, 120 (88%) participated, 60 in each group, 2 women in the standard group did not complete the study. 20% of participants had a poor perinatal outcome. All women in the intensive group had ultrasound assessment of fetal size and liquor volume vs. 97% in the standard group. 50% of the intensive group had IOL for abnormal scan or low hPL after RFM vs. 26% of controls (p < 0.01). STAI reduced for all women after investigations, but this reduction was greater in the standard group (p = 0.02). Participants had positive views about their involvement in the study. CONCLUSION: An RCT of management of RFM is feasible with a low rate of attrition. Investigations decrease maternal anxiety. Participants in the intensive group were more likely to have IOL for RFM. Further work is required to determine the likely level of intervention in the standard care arm in multiple centres, to develop additional placental biomarkers and to confirm that the composite outcome is valid. TRIAL REGISTRATION: ISRCTN07944306.

Growth restricting effects of a single course of antenatal betamethasone treatment and the role of human placental lactogen.

UNLABELLED: Betamethasone (BET) is a widely used treatment for women who are at high risk of preterm delivery. In sheep, BET-induced growth restriction was found to be associated with reduced placenta lactogen (PL), a key regulator of fetal growth. We therefore hypothesized that also in humans a single course of BET administration is associated with a reduction of PL, associated with a deceleration in fetal growth. OBJECTIVE: To investigate effects of a single course of antenatal BET in humans on birth weight and PL. METHODS: Women exposed to BET (2 × 12 mg; n = 44) with normally grown fetuses between 23 + 5 and 34 + 0 wks (weeks + days of gestation) who delivered between 23 + 5 to 42 + 0 wks were compared to gestational age-matched controls (n = 49). Maternal gestational blood samples were obtained before, during and after BET treatment and at the time of birth. MAIN OUTCOME MEASURES: BET effects on fetal anthropometrics, placental morphometry and placental PL-protein and maternal plasma levels. RESULTS: The mean duration of days between BET administration and birth was 52 days. BET treatment was associated with decreased birth weight (-18.2%), head circumference (-8.6%), body length (-6.0%), and placental width (-5.5%), as compared to controls. These changes were irrespective of possible maternal confounders (gestational age at birth, maternal age, maternal BMI gain during pregnancy, smoking etc.). However, neither PL-plasma levels within 48 h after BET treatment nor placental PL-protein levels and maternal plasma levels at birth were changed after BET treatment. In central regions of the placenta, BET treatment increased the circumference of syncytiotrophoblast nuclei by +4.7% and nucleus surface area by +9.4% compared to controls, but these changes were not related to placental PL-protein or maternal PL-plasma levels at birth. CONCLUSION: A single course of BET treatment was accompanied with reduced fetal growth, but this growth restricting effect was not associated with altered placental or maternal plasma PL levels. Altered expression of PL appears not to be causal for BET-induced fetal growth restriction in the human.

[Congenital heart diseases in pregnant women--a risk factor for fetal distress].

The condition of fetoplacental system in pregnant women with congenital heart diseases was studied by means of ultrasound, dopplerometry, cardiotocography, by determination of estradiol, progesterone and placental lactogen in the blood of pregnant women and in the umbilical cord and by means of pathomorphologic study of the placenta. It is shown that congenital heart diseases complicated by heart failure in pregnant women--a important risk factor for fetal distress bouth in the preclinical stage of placental insufficiency (violation of the utero-placental blood flow, changes of fetoplacental hormones levels) and in conjunction with clinical signs of fetal suffering (distress and growth retardation).

Predictors of poor perinatal outcome following maternal perception of reduced fetal movements--a prospective cohort study.

BACKGROUND: Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). RFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. OBJECTIVE: To identify predictors of poor perinatal outcome after maternal perception of reduced fetal movements (RFM). DESIGN: Prospective cohort study. METHODS: 305 women presenting with RFM after 28 weeks of gestation were recruited. Demographic factors and clinical history were recorded and ultrasound performed to assess fetal biometry, liquor volume and umbilical artery Doppler. A maternal serum sample was obtained for measurement of placentally-derived or modified proteins including: alpha fetoprotein (AFP), human chorionic gonadotrophin (hCG), human placental lactogen (hPL), ischaemia-modified albumin (IMA), pregnancy associated plasma protein A (PAPP-A) and progesterone. Factors related to poor perinatal outcome were determined by logistic regression. RESULTS: 22.1% of pregnancies ended in a poor perinatal outcome after RFM. The most common complication was small-for-gestational age infants. Pregnancy outcome after maternal perception of RFM was related to amount of fetal activity while being monitored, abnormal fetal heart rate trace, diastolic blood pressure, estimated fetal weight, liquor volume, serum hCG and hPL. Following multiple logistic regression abnormal fetal heart rate trace (Odds ratio 7.08, 95% Confidence Interval 1.31-38.18), (OR) diastolic blood pressure (OR 1.04 (95% CI 1.01-1.09), estimated fetal weight centile (OR 0.95, 95% CI 0.94-0.97) and log maternal serum hPL (OR 0.13, 95% CI 0.02-0.99) were independently related to pregnancy outcome. hPL was related to placental mass. CONCLUSION: Poor perinatal outcome after maternal perception of RFM is closely related to factors which are connected to placental dysfunction. Novel tests of placental function and associated fetal response may provide improved means to detect fetuses at greatest risk of poor perinatal outcome after RFM.

Serum biomarkers for detecting ectopic pregnancy.

Unless an ectopic pregnancy is visible by ultrasound, diagnosis can be a challenge. Differentiating ectopic pregnancies from intrauterine pregnancies can be impossible without intervention or follow-up. This poses a clinical dilemma to the practitioner given the inherent danger to the mother of tubal rupture of an ectopic pregnancy versus the fear of intervening in the case of a desired pregnancy without certainty of diagnosis. Early diagnostic modalities are clearly lacking, and serum biomarkers are currently being investigated as a solution to need for a rapid and accurate test for ectopic pregnancy.

Placental mRNA in maternal plasma as a predictor of ectopic pregnancy.

OBJECTIVE: To measure and compare placental mRNA expression in the maternal circulation among women with intrauterine and ectopic pregnancies. METHODS: Plasma was collected from patients in early pregnancy at risk of ectopic pregnancy. Clinical information was prospectively collected and entered into a dedicated database. mRNA was isolated from maternal plasma and quantitative RT-PCR was performed to measure mRNA for human gonadotropin (hCG) and human placental lactogen (hPL). GAPDH mRNA expression was used as an internal control. RESULTS: Twelve women with ectopic pregnancy and 13 women with intrauterine pregnancy were enrolled. Patients with ectopic pregnancy were 6 times more likely to have undetectable levels of hPL mRNA (relative risk [RR] 6.36; 95% confidence interval [CI], 1.70-23.20; P<0.01). They were also 8 times more likely to have undetectable levels of hCG mRNA (RR 8.64, 95% CI, 1.30-57.10; P<0.01). mRNA copy numbers for hPL and hCG (normalized by GAPDH) were significantly lower in the ectopic group than in the intrauterine group. CONCLUSION: Placental mRNA is present in the maternal circulation in significantly lower copies in cases of ectopic pregnancy compared with cases of intrauterine pregnancy. Measurement of placental mRNA in the maternal circulation may help to distinguish between intrauterine and ectopic pregnancies.