Maternal–fetal status of copper,iron, molybdenum,selenium and zinc in patients with gestational diabetes

Objective: The status of essential trace elements such as copper, iron, zinc, selenium and molybdenum was investigated in gestational diabetic pregnancies at term, and data were compared to control pregnancies. Fetal/maternal ratios of the elements and copper/zinc ratio were also computed in control and study populations.

Methods: Samples from maternal venous, umbilical artery and umbilical vein were collected from gestational diabetic and control pregnant women, at the time of spontaneous delivery or Cesarean section, and concentrations of various trace elements were determined by atomic absorption spectrophotometry.

Results: The concentrations of copper, iron, molybdenum, selenium and zinc averaged 2156.2?μg/l, 2020.1?μg/l, 13.1?μg/l, 102.3?μg/l and 656.2?μg/l, respectively, in maternal venous blood in control pregnant women at term (n?=?15) while in the corresponding gestational diabetic group (n?=?15), concentrations of the trace elements averaged 2345.8?μg/l, 2061.6?μg/l, 15.0?μg/l, 75.2?μg/l and 610.3?μg/l, respectively. Student's t test showed that the selenium concentration was significantly lower (p?<?0.05)in the diabetic group compared to controls. Values of other elements were not significantly different. Umbilical blood/maternal blood ratios of the trace elements showed varying differences. The Cu/Zn ratio was found to be significantly different between umbilical and maternal samples of control and study groups, indicating a possibility of compromised antioxidant function in diabetic pregnancies.

Conclusions: We speculate that altered maternal–fetal status of some essential trace elements in gestational diabetes patients could have deleterious influences on the health of the mother as well as the fetus and newborn.     

Maternal–fetal transport kinetics of manganese in perfused human placental lobule in vitro

Objective: There have been no detailed reports relating to maternal–fetal transport kinetics of manganese, an essential trace element in the human pregnancies, and hence we have attempted to study the transport kinetics of this trace element in the human placenta in vitro.

Methods: Human placentae from normal uncomplicated pregnancies were collected postpartum. Manganese chloride solution (GFS Chem Inc., Columbus, OH), 10 times the physiological concentrations, along with antipyrine (Sigma Chem Co., St. Louis, MO) as reference marker were then injected as a single bolus (100?µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples collected from maternal and fetal circulations over a period of five minutes. National Culture and Tissue Collection medium, diluted with Earle’s buffered salt solution was used as the perfusate and serial perfusate samples from fetal venous perfusate collected for a period of 30?min. Concentration of manganese in perfusate samples was assessed by atomic absorption spectrophotometry, while that of antipyrine was assessed by spectrophotometry. Transport kinetics of substances studied were computed using established permeation parameters.

Results: Differential transport rates of manganese and antipyrine in 12 perfusions differed significantly for 25.75, 90% efflux fractions (ANOVA test, p?<?0.05), while those of 10 and 50% efflux fractions were not significantly different between the study and reference substances. Transport fraction (TF) of manganese averaged 54.9% of bolus dose in 12 perfusions, whereas that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of manganese and antipyrine was statistically significant (Student’s t-test, p?<?0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, elimination rate of manganese compared to reference marker were significantly different (ANOVA test, p?<?0.05) between the study and reference substances.

Conclusions: Our studies show for the first time maternal–fetal transport kinetics of manganese in human placenta in vitro. Considering the restricted transfer of this essential trace element despite its small molecular weight, we hypothesize possibility of active transport of manganese across the human placental membrane. Further studies relating to manganese placental transport in “diabetic model” placental perfusions are in progress.     

Maternal–fetal transport kinetics of methotrexate in perfused human placenta: In vitro study

Objective. Folate antagonists are widely used in the treatment of diverse cancerous states. A paucity of data on transport characteristics of one such widely used drug, methotrexate, in the human placenta, prompted us to study its permeation characteristics in vitro.

Methods. Placentas from normal pregnancies were collected post-partum. Methotrexate, along with antipyrine as reference marker were injected as a single bolus (100 μL) into the maternal arterial circulation of isolated perfused placental lobules; perfusate samples were collected from both maternal and fetal circulations over a study period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. The concentration of methotrexate in various samples was determined by high performance liquid chromatography, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using standard parameters.

Results. Differential transport rate of methotrexate for 10, 25, 50, 75 and 90% efflux fractions in fetal venous effluent averaged 0.52, 1.30, 2.37, 3.57 and 4.43 minutes in 12 perfusions, representing 1.01 + 0.08, 1.03 + 0.06, 0.95 + 0.03, 0.93 + 0.03, 0.93 + 0.03 respectively times antipyrine reference value. Student's t-test showed varying differences between the control and study group data. Transport Fraction (TF) of methotrexate, expressed as fraction of the drug appearing in fetal vein, during study period of 5 minutes averaged 24.00 + 2.50% of bolus dose while antipyrine TF averaged 68.73 + 2.01% of injected bolus dose, representing 24.00 percent of reference marker value. Student's t-test showed methotrexate and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, absorption and elimination rates of study and reference substances showed varying differences.

Conclusions. We report for the first time that the transport of methotrexate from maternal to fetal circulation is not negligible in human placenta at term. It is reasonable to assume that a direct risk for the fetus from methotrexate use in pregnancy cannot be excluded, and caution is warranted when it is used in emergency clinical situations.     

Maternal–fetal transport kinetics of carboplatin in the perfused human placental lobule: In vitro study

Objective. Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal–fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro.

Methods. Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters.

Results. The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 ± 0.10, 1.06 ± 0.06, 1.00 ± 0.02, 0.98 ± 0.01, and 0.99 ± 0.01, respectively, times the antipyrine reference value. Student's t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 ± 0.52% of bolus dose, while antipyrine TF averaged 68.60 ± 2.01% of injected bolus dose, representing 13.1% of reference marker value. Student's t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences.

Conclusions. We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.     

Maternal–fetal effects of magnesium sulfate on serum osmolality in pre-eclampsia

Objective: To determine the effects of magnesium sulfate therapy on maternal and fetal osmolality in pre-eclampsia. Methods: A total of 34 pre-eclamptic women and 22 normal pregnant women participated in the study. Venous blood was drawn upon admission to the labor and delivery unit. Pre-eclamptic patients received standard magnesium sulfate therapy and had a second sample of venous blood drawn 4 h following the beginning of therapy. Fetal umbilical vein blood was obtained immediately following delivery in both groups. Osmolality was measured using a vapor pressure osmometer. Electrolyte levels were measured with a NOVA 8 biomedical analyzer. Data were analyzed via Student's t test, linear regression and correlation with significance established at p < 0.05. Results:We found no significant difference between the maternal osmolalities of the control and pre-eclamptic groups. Interestingly, fetal cord blood osmolality was significantly lower than maternal osmolality in the normal pregnant women. Sodium levels were also lower, while potassium and ionized calcium levels were higher in the fetal blood. In women with pre-eclampsia treated with magnesium sulfate, there was no difference between the osmolality of the maternal and fetal blood, while potassium and ionized calcium levels were still higher in the fetal blood. Finally, we found no correlation between maternal osmolality and blood pressure. Conclusions: High blood pressure in pre-eclampsia is not associated with altered osmolality. An absence of the normal decrease in fetal osmolality is observed in pre-eclamptic women treated with magnesium sulfate.     

Comparison of maternal–and paternal–fetal attachment in Turkish couples

Objective

to compare maternal–fetal attachment (MFA) and paternal–fetal attachment (PFA) in terms of selected variables.

Design

cross-sectional study.

Setting

three training hospitals in Ankara, Turkey. The study was performed between December 2005 and March 2006.

Participants

a total of 144 pregnant women and 144 partners participated in the study; the response rate was 98%.

Findings

there was a statistically significant difference between MFA and PFA scores (p<0.001). A comparison of MFA and PFA scores according to the selected variables (education, employment status, planning of pregnancy, pregnancy risk status) revealed that the MFA scores for pregnant women were significantly higher than the PFA scores of their partners, except for unemployed partners. The MFA (ρ=−0.24, p<0.004) and PFA (ρ=−0.32, p<0.001) scores decreased with increasing age of both pregnant women and their partners.

Key conclusions and implications for practice

although partners have lower fetal attachment scores than pregnant women, it is important to recognise factors influencing the attachment of the mother and father towards their fetus. Prenatal midwives and nurses are in a unique position to assess attachment and to intervene to promote attachment behaviours.     

Maternal and fetal HLA-G 14 bp gene polymorphism in pregnancy-induced hypertension,preeclampsia, intrauterine growth restricted and normal pregnancies

Objective: Trophoblast expression of Human Leukocyte Antigene-G (HLA-G) is essential for feto-maternal immune tolerance and successful placentation. There is contradicting evidence on the relationship between HLA-G polymorphisms and preeclampsia (PE), intrauterine growth restriction (IUGR) and pregnancy-induced hypertension (PIH). Here, we investigate the association between both maternal and fetal HLA-G 14?bp insertion/deletion polymorphism and obstetrical complications.

Methods: Clinical and genetic data of 282 women/fetuses (31 severe PE, 8 mild PE, 46 IUGR, 42 PIH and 155 controls) were analyzed both individually and jointly under a codominant, a dominant and a recessive model.

Results: HLA-G 14?bp polymorphism was not associated with obstetrical complications, considering the mother and fetus genotypes both jointly and individually.

Conclusions: With this study we filled several gaps occurring in previous studies: we analyzed a very well-defined population of PE, PIH and IUGR pregnancies, considering both fetal and maternal HLA-G 14?bp polymorphism, individually and jointly. Our findings showed that fetal and maternal HLA-G 14?bp genotypes are not associated with increased risk for the development of obstetrical complications, suggesting that this polymorphism has no immuno-modulatory role in the development of PE, PIH or IUGR.     

Computer analysis of maternal–fetal heart rate recordings during labor in relation with maternal–fetal attachment and prediction of newborn acidemia

Objective: To assess combined maternal (MHR) and fetal heart rate (FHR) recordings during labor, in relation with maternal–fetal attachment and prediction of newborn acidemia.

Study design: Fifty-nine simultaneous MHR and FHR recordings were acquired in the final minutes of labor. Computer analysis followed the FIGO guidelines with estimation of MHR and FHR baselines, accelerations, decelerations, short- (STV) and long-term variabilities. MHR and FHR characteristics, their differences and correlations were assessed in relation to labor progression and to newborn umbilical artery blood (UAB) pH lower than 7.15 and 7.20. To assess prediction of acidemia, areas under ROC curves (auROC) were calculated.

Results: Progression of labor was associated with a significant increase in MHR accelerations and FHR decelerations both in the non-acidemic and acidemic fetuses (p?<?0.01). At the same time there was an increase in MHR–FHR correlations and differences in accelerations and decelerations in acidemic fetuses. The auROC ranged between 0.50 for FHR accelerations and 0.77 for MHR baseline plus FHR STV.

Conclusions: MHR and FHR respond differently during labor with signs of increased maternal–fetal attachment during labor progression in acidemic fetuses. Combined MHR–FHR analysis may help to improve prediction of newborn acidemia compared with FHR analysis alone.     

Maternal obesity induced by a ‘cafeteria’ diet in the rat does not increase inflammation in maternal,placental or fetal tissues in late gestation

IntroductionObesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation.MethodsMaternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation.ResultsDespite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver.ConclusionsMaternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation.     

Amniotic fluid levels of phospholipase A2 in fetal rats with retinoic acid induced myelomeningocele: the potential “second hit” in neurologic damage

Objectives: There is growing evidence of ongoing, in utero neurological damage in fetuses with myelomeningocele (MMC). Phospholipase A₂ (PLA₂) has known neurotoxic properties and is predominantly present in its secretory isoform (sPLA₂) in meconium, the passage of which is increased in MMC fetuses. The objective of this study was to determine if amniotic fluid (AF) levels of PLA₂ are elevated in a rat model of MMC.

Methods: Timed pregnant Sprague–Dawley rats were gavage fed 60?mg/kg/bodyweight retinoic acid (RA) in olive oil at embryonic day 10 (E10). Amniocentesis was performed at multiple gestational time points on MMC fetuses, RA-exposed fetuses without MMC and control fetuses. AF PLA₂ levels were analyzed by a fluorescent enzyme activity assay. PLA₂ isoforms were determined by measuring activity in the presence of specific inhibitors.

Results: There was no difference in AF PLA₂ activity between groups on E15. PLA₂ activity was significantly increased in MMC fetuses on E17, E19 and E21 (p?<?0.001). Secretory PLA₂ primarily accounted for the overall greater activity.

Conclusions: PLA₂ levels are elevated in the AF of fetal rats with MMC and may contribute to ongoing neural injury. This pathway may be a useful drug target to limit ongoing damage and better preserve neurologic function.     

Trends and characteristics of fetal and neonatal mortality due to congenital anomalies,Colombia 1999–2008

Objective: To describe fetal and neonatal mortality due to congenital anomalies in Colombia.

Methods: We analyzed all fetal and neonatal deaths due to a congenital anomaly registered with the Colombian vital statistics system during 1999–2008.

Results: The registry included 213,293 fetal deaths and 7,216,727 live births. Of the live births, 77,738 (1.08%) resulted in neonatal deaths. Congenital anomalies were responsible for 7321 fetal deaths (3.4% of all fetal deaths) and 15,040 neonatal deaths (19.3% of all neonatal deaths). The fetal mortality rate due to congenital anomalies was 9.9 per 10,000 live births and fetal deaths; the neonatal mortality rate due to congenital anomalies was 20.8 per 10,000 live births. Mortality rates due to congenital anomalies remained relatively stable during the study period. The most frequent fatal congenital anomalies were congenital heart defects (32.0%), central nervous system anomalies (15.8%), and chromosomal anomalies (8.0%). Risk factors for fetal and neonatal death included: male or undetermined sex, living in villages or rural areas, mother’s age >35 years, low and very low birthweight, and <28 weeks gestation at birth.

Conclusions: Congenital anomalies are an important cause of fetal and neonatal deaths in Colombia, but many of the anomalies may be preventable or treatable.     

Effects of 17β-estradiol and trimegestone alone,and in combination,on the bone and uterus of ovariectomized rats

Trimegestone is a novel norpregnane progestin ,which is being developed ,in combination with 17β-estradiol ,for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis. A model of osteoporosis in the ovariectomized rat has been used to evaluate the effects of 17β-estradiol and trimegestone ,alone and in combination ,on bone and uterus in these animals. Two treatment protocols were investigated ,preventive with treatment starting immediately after ovariectomy and curative with treatment starting 1 or 6 months after ovariectomy. 17β-Estradiol was administered subcutaneously at a dose of 10 μg/kg/day with trimegestone or norethisterone being administered orally at a dose of 1 mg/kg/day; treatment was given 5 days per week. Treatment on both protocols was for 6 months. Given alone ,17β-estradiol maintained bone mass ,either partially or completely ,when given on the preventive protocol ,or on the curative protocol with treatment starting 1 month after ovariectomy; it did not restore bone mass when given on the curative protocol with 6 months lapsing between ovariectomy and start of treatment. Trimegestone did not block the beneficial effects of 17β-estradiol on bone. 17β-Estradiol induced uterine hypertrophy on all these protocols and this was blocked completely by trimegestone. Trimegestone administered alone had no effect on bone or uterus but ,when given in combination with 17β-estradiol ,it did not inhibit the effect of 17β-estradiol in maintaining bone mass but completely blocked its uterotropic effect. Norethisterone at a similar dose did not inhibit the effects of 17β-estradiol on bone but also did not block its uterotropic effect.     

The relationship of maternal–fetal attachment and depression with social support in pregnant women referring to health centers of Tabriz–Iran, 2016

Purpose: The objective of this study was to determine the relationship of maternal–fetal attachment and depression during pregnancy with social support.

Methods: This cross-sectional study was done on 287 primipara women. The data collection tools used included a demographic characteristics questionnaire, Maternal–Fetal Attachment Scale, the Edinburgh Postnatal Depression Scale and the Social Support Scale. Pearson’s correlation test and general linear model were used for data analysis.

Results: The mean maternal–fetal attachment score was 90.0 (SD: 10.3). The highest score was obtained in the “role taking” domain and the lowest in the “interaction with the fetus” domain. The mean depression score was 8.5 (SD: 4.0). The score of perceived social support was 135.5 (SD: 15.6). Pearson’s correlation test showed a significant positive correlation between social support and maternal–fetal attachment (r?=?0.36, p?r= ?0.14, p?=?.018).

Conclusion: The present study found a significant relationship between maternal–fetal attachment, depression and social support. It is recommended to devise plans for increasing the support given to women and to improve the society’s and families’ awareness about these issues in the attempt to have healthy mothers and thereby healthy families and communities.     

Sildenafil citrate improves fetal outcomes in pregnant, l-NAME treated,Sprague–Dawley rats

Objectives

This study aimed to investigate the effects of sildenafil citrate on various fetal and physiological parameters, including fetal mortality, number of pups, placental weights and micro-albuminuria in pregnant, l-NAME treated Sprague–Dawley rats.

Study design

Twenty-four pregnant female Sprague–Dawley rats were divided into 3 groups (n = 8). In the l-NAME treated group (PRE), l-NAME (0.3 g/l, drinking water) was used to induce pre-eclampsia-like symptoms on day 1 of the experiment. The experimental group (SCT) also received l-NAME (0.3 g/l, drinking water) on day 1 of the experiment. However, sildenafil citrate (10 mg/kg, s.c., daily) was administered as the test compound from day 7 until day 19. The experimental control (CON) did not receive either l-NAME or sildenafil citrate. l-NAME administration was discontinued in both the PRE and the SCT groups on day 19 of the experiment and the animals were given access to normal drinking water ad libitum. All the animals were sacrificed on day 20, at which time a laparotomy was performed and the various fetal parameters measured. On day 0 and day 20, blood pressure measurements were recorded non-invasively and protein estimations in 24 h urine samples were conducted.

Results

Sildenafil citrate decreased fetal mortality and protein excretion and further demonstrated a trend toward increasing birth and placental weights in pregnant, l-NAME treated, Sprague–Dawley rats. In addition, sildenafil citrate administration ameliorated the amplification of the l-NAME induced hypertension in the SCT group.

Conclusion

We speculate that sildenafil citrate by potentiating the effects of nitric oxide in vivo improves uterine artery blood flow resulting in improved fetal outcomes in pregnant, l-NAME treated, Sprague–Dawley rats.     

Recent trends in placenta accreta in the United States and its impact on maternal–fetal morbidity and healthcare-associated costs, 1998–2011

Objective: To describe the prevalence, trends, adverse maternal-fetal morbidities and healthcare costs associated with placenta accreta (PA) in the United States (US) between 1998 and 2011.

Methods: A retrospective, cross-sectional analysis of inpatient hospital discharges was conducted using the National Inpatient Sample (NIS). We used International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify both cases of PA and of selected comorbidities. Survey logistic regression was used to assess the association between PA and various maternal–fetal outcomes. Joinpoint regression modeling was used to estimate annual percent changes (APCs) in PA prevalence during the study period.

Results: The prevalence of PA from 1998 to 2011 was 3.7 per 1000 delivery-related discharges. After adjusting for known or suspected confounders, PA conferred between a 20% to over a 19-fold increased odds of experiencing an adverse outcome. This resulted in a higher mean, per-hospitalization, cost of inpatient care after adjustment for inflation ($5561 versus $4989), translating into over $115 million dollars in additional inpatient expenditures relative to non-PA affected deliveries from 2001 to 2011.

Conclusions: This study updates recent trends in the prevalence of PA, which is valuable to clinicians and policymakers as they formulate targeted strategies to address factors related to PA.