Corrigendum: Perinatal autopsy in Ghana: healthcare workers knowledge and attitude.

[This corrects the article DOI: 10.3389/fgwh.2022.1021474.].

Exploring the shared decision making process of caesarean sections at a teaching hospital in Ghana: a mixed methods study.

BACKGROUND: Caesarean section (CS) rates are rising. Shared decision making (SDM) is a component of patient-centered communication which requires adequate information and awareness. Women in Ghana have varying perceptions about the procedure. We sought to explore mothers' knowledge. perceptions and SDM-influencing factors about CSs. METHODS: A transdisciplinary mixed-methods study was conducted at the maternity unit of Korle-Bu Teaching Hospital in Accra, Ghana from March to May, 2019. Data collection was done in four phases: in-depth interviews (n = 38), pretesting questionnaires (n = 15), three focus group discussions (n = 18) and 180 interviewer administered questionnaires about SDM preferences. Factors associated with SDM were analyzed using Pearson's Chi-square test and multiple logistic regression. RESULTS: Mothers depicted a high level of knowledge regarding medical indications for their CS but had low level of awareness of SDM. The perception of a CS varied from dangerous, unnatural and taking away their strength to a life-saving procedure. The mothers had poor knowledge about pain relief in labour and at Caesarean section. Health care professionals attributed the willingness of mothers to be involved in SDM to their level of education. Husbands and religious leaders are key stakeholders in SDM. Insufficient consultation time was a challenge to SDM according to health care professionals and post-partum mothers. Women with parity ≥ 5 have a reduced desire to be more involved in shared decision making for Caesarean section. AOR = 0.09, CI (0.02-0.46). CONCLUSION: There is a high knowledge about the indications for CS but low level of awareness of and barriers to SDM. The fewer antenatal care visits mothers had, the more likely they were to desire more involvement in decision making. Aligned to respectful maternity care principles, greater involvement of pregnant women and their partners in decision making process could contribute to a positive pregnancy experience. Education, including religious leaders and decision- making tools could contribute to the process of SDM.

Effect of intimate partner violence in pregnancy on maternal and perinatal outcomes at the Korle Bu teaching hospital, Ghana: An observational cross sectional study.

OBJECTIVE: To determine the association between intimate partner violence and pregnancy outcomes. METHODS: This was a descriptive study of sociodemographic characteristics of participants, their partners and intimate partner violence. Participants' delivery records were reviewed for additional medical and obstetric information and abused women and their neonates followed until discharge. χ2 and Student t test were used to assess associations, followed by logistic regression with odds ratio (OR) and 95% confidence intervals (CI). A value of P less than 0.05 was considered statistically significant. RESULTS: The study included 270 participants of whom 84 (31.1%) reported experiencing domestic violence during pregnancy. One hundred and fourteen (42%) had experienced domestic violence pre-pregnancy and 69 (60.5%) of these women experienced further domestic violence during pregnancy. Emotional violence was commonest 80/270 (29.6%) and no sexual violence was reported. Domestic violence declined from 42% (pre-pregnancy) to 31.1% (in-pregnancy) (P = 0.009). Risk factors during pregnancy were young age (15-24 years; OR 5.8, 95% CI1.65-20.38), nulliparity (OR 3.75, 95% CI 1.90-7.41), and partner's alcohol consumption (OR 5.04, 95% CI 2.50-10.13). Associated outcomes included late prenatal booking, gestational hypertension, and cephalopelvic disproportion. CONCLUSION: We found high prevalence of domestic violence during pregnancy, preponderance of emotional abuse, and decline of physical abuse. Nulliparity, younger age, and partner's alcohol consumption predicted abuse. Late-booking, gestational hypertension, cephalopelvic disproportion, and fetal distress were associated.

Testicular Sperm Extraction and Intracytoplasmic Sperm Injection in Management of Obstructive Azoospermia: A Two-Year Multicenter Review in Ghana.

Background: The objective of this study was to evaluate treatment outcomes and assess predictors of clinical pregnancy in obstructive azoospermia cases treated with testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in Ghana. Methods: This study was a retrospective study conducted on 67 men seeking treatment for obstructive azoospermia at two study sites in Ghana from January 2018 to December 2019. First, archived data were reviewed and treatment outcomes of cases of obstructive azoospermia from the hospital records were evaluated. Infertile men who met the inclusion criteria were recruited. Descriptive data were expressed in the form of frequencies and percentages. The dependent and independent variables were analyzed using multiple logistic regression and reported as odds ratios (ORs). The confidence interval (CI) was set at 95% and a p-value <0.05 was considered significant. Results: The mean age of male participants was 42.43±9.11 years (mean±SD) while the mean age of their partners was 32.89±5.73 years (mean±SD). The average duration of infertility before intervention was 5.01±3.60 years (mean±SD). Successful pregnancy was observed in 52.2% (35/67) of the participants. After adjusting for confounders, the rate of a successful clinical pregnancy was 0.07 lower for every additional year increase in the male's age [AOR=0.93 (95%CI=0.87-0.99), p=0.02]. Conclusion: Overall the rate of clinical pregnancy following TESE/ICSI from our study was 52.2%. A man's age was a strong predictor of successful clinical pregnancy among couples treated with TESE-ICSI for obstructive azoospermia in Ghana.

Factors Associated with Ruptured Ectopic Pregnancy: A 10-Year Review at a District Hospital in Ghana.

Background: Approximately 1-2% of all pregnancies are ectopic. Despite a decline in ectopic pregnancy-related mortality, there is still a paucity of information on the factors associated with clinical presentation and outcomes in Sub-Saharan Africa which is essential in determining the most appropriate treatment modalities. Methods: We performed a ten-year retrospective chart review of cases of ectopic pregnancies managed at the Lekma hospital and assessed them for peculiar risk factors, clinical presentation, and outcomes. Associations between patients' sociodemographic characteristics, clinical presentation, and treatment outcome were evaluated using multiple logistic regression and reported as adjusted odds ratios (AOR). The confidence interval (CI) was set at 95%, and a p value <0.05 were considered significant. Results: Over the ten-year period, there were 115 ectopic pregnancies and 14,450 deliveries (7.9/1,000). The mean age ± standard deviation of the 115 patients was 27.61 ± 5.56. More than half of the patients were single (59/115, 51.3%). The majority (71.3%) of the patients presented with a ruptured ectopic pregnancy. After adjusting for covariates, the odds of an ectopic pregnancy presenting as ruptured among single patients was 2.63 times higher than that of married patients (AOR = 3.63, 95% CI: 1.33-9.93, p=0.01). Ectopic pregnancies located in the isthmic region of the tube had a 77% lower odds of presenting as ruptured than those located in the ampullary region (AOR = 0.23, 95% CI: 0.07-0.74, p=0.01). The odds of rupturing were 1.69 times increased for every additional week after the missed period (AOR = 2.69, 95% CI: 1.56-4.64, p < 0.01). No mortalities were reported as a result of an ectopic pregnancy. Conclusion: Most of the cases of ectopic pregnancy presented ruptured. Marital status and period of amenorrhoea were significantly associated with rupture.

Perinatal autopsy in Ghana: Healthcare workers knowledge and attitude.

Background: Perinatal mortality refers to stillbirths and early neonatal deaths. Stillbirth, the death of a foetus from 28 weeks or with a birth weight below 1,000 g, and early neonatal deaths, the death of a new-born within 24 h of delivery, are among the most distressing global health problems, with approximately 2 million stillbirths occurring annually. Although a post-mortem examination of the stillborn baby is essential for understanding and learning the cause of stillbirth, many couples decline the procedure. Sub-Saharan Africa has one of the highest stillbirth rates in the world, yet there is a dearth of studies on post-mortem uptake from the region. Aim: To explore healthcare professionals' views and perceptions of perinatal autopsy in Ghana. Methods: Mixed-method approach consisted of semi-structured interviews and an electronic cross-sectional survey to evaluate the views and perceptions of healthcare professionals at Korle-Bu Teaching Hospital on autopsy for stillbirths and early neonatal deaths. Descriptive quantitative data were summarised in frequencies and percentages, and statistical results and descriptions were tabulated and coded in terms of types of barriers. For the qualitative aspect, the audio-taped interviews were transcribed, themes generated, and direct quotes and descriptions were coded for all knowledge, beliefs, attitudes and practices concerning the barriers and facilitators for post-mortem. Results: Ninety-nine healthcare professionals participated. No participant had formal training regarding counselling for perinatal autopsy and 40% had " no idea " who is responsible for counselling and obtaining consent for a perinatal autopsy. Forty-four percent (44%) of the participants knew of only the "Conventional/ Full" autopsy and <4% were aware of less invasive methods of performing an autopsy. Qualitative data showed healthcare worker influence, religious and financial considerations impede the implementation of perinatal autopsies. Despite the low uptake of perinatal autopsies, interviews from healthcare workers suggest acceptance rates would improve if parents knew about different options, especially less invasive procedures. Conclusion: At Ghana's largest referral centre, perinatal autopsy counselling and uptake are at extremely low levels. Most healthcare professionals have little knowledge, skills, and capacity to advise parents regarding perinatal autopsies. Training is needed to update the workforce on recommended perinatal autopsy practices.

Limiting adverse birth outcomes in resource-limited settings (LABOR): protocol of a prospective intrapartum cohort study.

Background: Each year, nearly 300,000 women and 5 million fetuses or neonates die during childbirth or shortly thereafter, a burden concentrated disproportionately in low- and middle-income countries. Identifying women and their fetuses at risk for intrapartum-related morbidity and death could facilitate early intervention. Methods: The Limiting Adverse Birth Outcomes in Resource-Limited Settings (LABOR) Study is a multi-country, prospective, observational cohort designed to exhaustively document the course and outcomes of labor, delivery, and the immediate postpartum period in settings where adverse outcomes are frequent. The study is conducted at four hospitals across three countries in Ghana, India, and Zambia. We will enroll approximately 12,000 women at presentation to the hospital for delivery and follow them and their fetuses/newborns throughout their labor and delivery course, postpartum hospitalization, and up to 42 days thereafter. The co-primary outcomes are composites of maternal (death, hemorrhage, hypertensive disorders, infection) and fetal/neonatal adverse events (death, encephalopathy, sepsis) that may be attributed to the intrapartum period. The study collects extensive physiologic data through the use of physiologic sensors and employs medical scribes to document examination findings, diagnoses, medications, and other interventions in real time. Discussion: The goal of this research is to produce a large, sharable dataset that can be used to build statistical algorithms to prospectively stratify parturients according to their risk of adverse outcomes. We anticipate this research will inform the development of new tools to reduce peripartum morbidity and mortality in low-resource settings.

Associations between malaria in pregnancy and neonatal neurological outcomes.

OBJECTIVE: To compare neurological functioning of neonates born to mothers with and without malaria in pregnancy. METHODS: Pregnant women presenting at Korle Bu Teaching Hospital, Ghana were recruited into this prospective observational study. Malaria exposure was determined by clinically documented antenatal malaria infection; parasitemia in maternal, placental, or umbilical cord blood; or placental histology. Neurological functioning was assessed using the Hammersmith Neonatal Neurological Examination within 48 hours of birth. Performance was classified as "optimal" or "suboptimal" by subdomain and overall. RESULTS: Between November 21, 2018 and February 10, 2019, a total of 211 term-born neonates, of whom 27 (13%) were exposed to malaria in pregnancy, were included. In the reflexes subdomain, exposed neonates tended to score lower (adjusted mean difference -0.34, 95% confidence interval -0.70 to 0.03), with an increased risk (adjusted risk ratio 1.63, 95% confidence interval 1.09 to 2.44) of suboptimal performance compared with unexposed neonates. There were no significant between-group differences in scores or optimality classification for the remaining subdomains and overall. CONCLUSIONS: Malaria-exposed neonates had similar neurological functioning relative to unexposed neonates, with differences confined to the reflexes subdomain, suggesting potential underlying neurological immaturity or injury. Further studies are needed to confirm these findings and determine the significance of malaria in pregnancy on long-term neurological outcomes.

Gestational Age-Specific Distribution of the Hammersmith Neonatal Neurological Examination Scores Among Low-Risk Neonates in Ghana.

OBJECTIVE: To describe gestational age-specific distribution of scores for the Hammersmith Neonatal Neurological Examination (HNNE) up to 48 h after birth in a low-risk, term-born, single-center sample in Ghana. STUDY DESIGN: This is a nested substudy of a larger prospective study (IMPRINT: Impact of Malaria in Pregnancy on Infant Neurodevelopment) comprising 140 low-risk, term-born neonates at Korle Bu Teaching Hospital in Accra, Ghana, between November 2018 and February 2019. The sample was stratified into three gestational age groups: early-term (37 + 0-38 + 6, weeks + days; n = 61), full-term (39 + 0-40 + 6, weeks + days; n = 52), and late/post-term (41 + 0-42 + 6, weeks + days; n = 27). Neonates were administered the 34-item HNNE by trained physicians. As per the original British scoring system, raw scores for the Ghanaian sample were plotted and scores > 10th centile were assigned a score of 1, 5th-10th centile 0.5, and < 5th centile 0. RESULTS: The range of raw scores for 16/34 HNNE items varied with gestational age. Specifically, 100% (7/7), 50% (5/10), 33% (1/3), 33% (1/3), 20% (1/5), and 14% (1/7) of items within the orientation and behavior, tone, abnormal signs/patterns, movements, tone patterns, and reflexes subdomain, respectively showed a different distribution of scores above the 10th centile across the three gestational age groups. CONCLUSION: Differences in gestational age-specific results within our sample in comparison to the original British sample could be, albeit unlikely, due to misclassification of gestational age, unmeasured maternal or fetal morbidity, or perhaps more likely, variation in testing or test conditions, or some combination of these. Genetic variation in neurological development is also a possibility. Further research is warranted to determine the reasons for differences. Our findings highlight the need to determine the accuracy and reliability of standardized neurologic assessments in predicting neurodevelopmental risk for infants in low- and middle-income countries.

Venous thromboembolism risk and prophylaxis in hospitalized obstetric patients at a tertiary hospital in Accra, Ghana: A comparative cross-sectional study.

OBJECTIVE: To determine the prevalence of venous thromboembolism risk and thromboprophylaxis among obstetric inpatients, comparing prenatal and postnatal women. METHODS: We assessed 546 obstetric inpatients at the Korle-Bu Teaching Hospital for the prevalence study. Out of this number, 223 were recruited, comprising 111 prenatal and 112 postnatal mothers. A structured interviewer-administered questionnaire was used to obtain data on participants' venous thromboembolism risk, which was categorized into high, intermediate, and low using the Royal College of Obstetricians and Gynaecologists guidelines. Data on thromboprophylaxis were also obtained and analyzed. Values were considered statistically significant at p < 0.05. RESULTS: Overall venous thromboembolism risk among the study population was 82/223 (36.8%). All patients at high risk were prenatal, 59/112 (52.7%) of postnatal mothers were at intermediate risk, compared with 20/111 (18.0%) of prenatal women (p < 0.001). Prevalence of thromboprophylaxis was 5/82 (6.1%). All prenatal high-risk patients received thromboprophylaxis, whereas only 2/20 (10.0%) of women with intermediate risk received thromboprophylaxis. The incidence of venous thromboembolism was 3/546 (0.6%) in the obstetric inpatients. CONCLUSION: Our study found a high prevalence of venous thromboembolism risk among obstetric inpatients at the Korle-Bu Teaching Hospital. However, thromboprophylaxis was low. Further research is needed to audit recent practice of thromboprophylaxis and perinatal outcome.

Neonatal neurological examination in a resource-limited setting: What defines normal?

OBJECTIVE: To describe the results of the Hammersmith Neonatal Neurological Examination (HNNE) in a low-risk, term-born, contemporary sample in Ghana. Of particular interest was to compare these findings with the original British study that validated the HNNE, and published data from other low- and middle-income countries. STUDY DESIGN: In a nested substudy of a larger prospective study (IMPRINT: Impact of Malaria in Pregnancy on Infant Neurodevelopment), 140 low-risk, term-born neonates (39.3 ± 1.4 weeks gestation) at Korle Bu Teaching Hospital in Accra, Ghana were administered the 34-item HNNE from birth to 48 h of age by trained physicians. Neonates' performance was compared with previously published normative data from the United Kingdom (1998), and published data from Thailand, Myanmar, Vietnam, and Uganda. RESULTS: Ghanaian neonates demonstrated lower scores on 29/34 HNNE items relative to normative data from the United Kingdom (P < .05), with only 5% of Ghanaian neonates in our sample classified as neurologically optimal. There were significant differences in the proportion of neonates scoring optimally per HNNE item between our Ghanaian sample, compared with published data from other settings (Thai [13/16 items], Burmese [14/16 items], Vietnamese [7/9 items], and Ugandan [22/34 items] neonates). Raw scores were markedly different between Ghanaian and British neonates, with Ghanaian neonates demonstrating lower median and wider range of scores. These differences were less prominent between Ghanaian and Ugandan neonates. CONCLUSION: Our findings raise questions as to whether or not the thresholds for optimality for the HNNE based on data from the United Kingdom are applicable to Ghanaian newborns. Our study could not fully resolve whether the differences in scores were due to genetic differences in developmental pathways, the implementation of the assessment, or the characteristics of our sample. Low proportions of neonates scoring optimally from other low- and middle-income countries suggest the need for further research to determine the clinical utility of the HNNE in resource-limited settings, including the predictive value for neurodevelopment later in infancy.

Risk factors for ectopic pregnancy among pregnant women attending a tertiary healthcare facility in Accra, Ghana.

OBJECTIVE: To investigate risk factors for ectopic pregnancy among pregnant women attending the Korle-Bu Teaching Hospital, Accra, Ghana. METHODS: In an unmatched case-control study from September to November 2015, 104 women with ectopic pregnancy (cases) were compared with 208 women with intrauterine pregnancy (controls). Data were collected by interviewer-administered questionnaire and record review. Bivariable analysis was used to compare characteristics. Multivariate logistic regression was used to assess associations between risk factors and ectopic pregnancy. Adjusted odds ratios (aORs) and 95% confidence interval (CIs) were reported. RESULTS: Risk factors for ectopic pregnancy were being single (aOR, 5.5; 95% CI, 2.15-14.65), sexual debut at younger than 15 years (aOR, 36.4; 95% CI, 2.49-532.49), multiple sexual partners (aOR, 4.8; 95% CI, 1.76-13.36), previous instrumental evacuation of uterus (aOR, 5.8; 95% CI, 1.20-27.99); previous diagnosis of infertility (aOR, 6.1; 95% CI, 1.36-27.28), being uninsured (aOR, 11.8; 95% CI, 4.23-32.74), and condom use (aOR, 6.1; 95% CI, 1.36-27.28). CONCLUSION: Women who were single with early sexual intercourse, multiple partners, instrumental evacuation of the uterus, and diagnosis of infertility were at risk of ectopic pregnancy. Identification of these factors should facilitate early diagnosis and treatment of ectopic pregnancy.

The Impact of Plasmodium Infection on Placental Histomorphology: A Stereological Preliminary Study.

Background: Malaria during pregnancy may threaten the mother's health and cause serious structural damage to the internal architecture of the placenta, which subsequently affects the pregnancy outcome. A better understanding of the impact of malaria parasites on the placenta morphology is crucial for better management of pregnant women and their babies. Aim: To assess by stereology the histomorphology of selected placental structures in placenta malaria compared with normal placentae at term. Method: A total of 10 placentae comprising 5 controls and 5 cases were selected from 50 placentae that were collected at term (38 weeks ± 2 weeks) from the maternal delivery suit of Korle-Bu Teaching Hospital in Accra, Ghana. Blood from the placentae was collected for both rapid diagnostic test and microscopic examinations. Samples collected were examined for Plasmodium parasites, after which they were classified as study group (Plasmodium positive) or control (Plasmodium negative). Stereological quantification using systematic uniform random sampling technique with test point and intersection counting of photomicrographs were employed to estimate the mean volume densities of syncytial knots, syncytial necrosis, foetal capillaries, and intervillous spaces of the placentae on a total of 1,600 photomicrographs. Results: Out of the fifty placental samples from the maternal side tested for Plasmodium, six representing 12% were found to be infected with the parasite by both rapid diagnostic test and microscopy. On stereological assessment, the mean volume density of syncytial knots was significantly higher in the placental malaria group compared with the control placentae at term (P = 0.0080), but foetal capillaries (P = 0.7813), intervillous spaces (P = 0.8078), and syncytial necrosis (P = 0.8249) were not significantly different. Conclusion: This preliminary result indicates that placental malaria may cause significant increase in the syncytial knots but not foetal capillaries, intervillous spaces, or syncytial necrosis. This finding signifies early maturation of the placenta and may be crucial in understanding perinatal outcomes.

Prevalence of adhesions and associated postoperative complications after cesarean section in Ghana: a prospective cohort study.

BACKGROUND: The global increase in Cesarean section rate is associated with short- and long-term complications, including adhesions with potential serious maternal and fetal consequences. This study investigated the prevalence of adhesions and association between adhesions and postoperative complications in a tertiary referral hospital in Accra, Ghana. METHODS: In this prospective cohort study, 335 women scheduled for cesarean section at Korle-Bu Teaching Hospital in Accra, Ghana were included from June to December 2015. Presence or absence of adhesions was recorded and the severity of the adhesions was scored using a classification system. Associations between presence and severity of adhesions, postoperative complications, and maternal and infant outcomes at discharge and 6 weeks postpartum were assessed using multivariate logistic and linear regression analysis. RESULTS: Of the participating women, 128 (38%) had adhesions and 207 (62%) did not. Prevalence of adhesions increased with history of caesarean section; 2.8% with no CS but may have had an abdominal surgery, 51% with one previous CS, 62% with >1 CS). Adhesions significantly increased operation time (mean 39.2 (±15.1) minutes, absolute adjusted difference with presence of adhesions 9.6 min, 95%CI 6.4-12.8), infant delivery time (mean 5.4 (±4.8) minutes, adjusted difference 2.4 min, 95%CI 1.3-3.4), and blood loss for women with severe adhesions (mean blood loss 418.8 ml (±140.6), adjusted difference 57.6 ml (95%CI 12.1-103.0). No differences for other outcomes were observed. CONCLUSION: With cesarean section rates rising globally, intra-abdominal adhesions occur more frequently. Risks of adhesions and associated complications should be considered in counseling patients for cesarean section.

The relationship between maternal plasma leptin levels and fetal growth restriction.

Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and Delta SD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and Delta SD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.

Significant increase in maternal plasma leptin concentration in induced delivery: a possible contribution of pro-inflammatory cytokines to placental leptin secretion.

Maternal plasma leptin concentration is significantly increased during pregnancy. However, its roles in pregnancy, especially in labor, have not been fully clarified. We measured plasma leptin concentrations in pregnant women during the course of induced labor, just after spontaneous vaginal delivery and Cesarean section at term. We also studied the regulation of leptin secretion from term placental tissue and BeWo cells, a trophoblastic cell-line. Plasma leptin concentrations increased significantly during labor (58.9 +/- 9.2 ng/ml) compared to those before labor induction (37.5 +/- 5.8 ng/ml, P<0.05), then decreased 3-6 days postpartum (14 +/- 3 ng/ml, n = 6, P<0.0001) to the levels of normal nonpregnant women. Leptin concentrations within an hour and 24 hours after spontaneous vaginal delivery were significantly higher than those after Cesarean section (P<0.05 for both comparisons). Similarly, leptin mRNA expression in placental tissues obtained after spontaneous vaginal delivery was significantly greater than that in those obtained after Cesarean section without labor (P<0.05). IL-1alpha and TNF-alpha treatment significantly stimulated leptin secretion and leptin mRNA expression in explant culture of human term placental tissue and in BeWo cells as compared with those in vehicle controls (P<0.05, for all comparisons). By contrast, oxytocin and prostaglandin F(2alpha) treatment had no effects on leptin secretion from explant culture of human term placental tissue or from BeWo cells. These data indicate that pro-inflammatory cytokines might stimulate placental leptin secretion, thus finally contributing to the increase in plasma leptin concentration during labor.

Free-to-total leptin ratio in maternal plasma is constant throughout human pregnancy.

To clarify the mechanism of leptin resistance during pregnancy, we measured plasma leptin concentrations, free to total leptin ratio (percent free leptin) and soluble leptin receptor concentrations in pregnant women, and compared the results with those in non-pregnant women. We collected plasma samples from 23 non-pregnant and 31 pregnant women in the third trimester. Plasma samples from 5 pregnant women were collected longitudinally in each trimester. Plasma leptin concentrations in pregnant women in the second trimester (17.4 +/- 3.2 ng/ml) were higher than those in the first trimester of pregnancy (11.0 +/- 2.8 ng/ml, n = 5), as previously reported. However, percent free leptin did not change significantly throughout pregnancy. Percent free leptin correlated with total leptin concentrations (ng/ml) in non-pregnant women (r = 0.727, P < 0.0001), but not in women in the third trimester of pregnancy (r = 0.006). Constant percent free leptin during pregnancy despite increased leptin concentrations indicates increased leptin binding capacity in pregnant women, that might partly contribute to the establishment of leptin resistance. On the other hand, soluble leptin receptor concentrations showed significant negative correlation with BMI and plasma leptin concentrations in pregnant women (r = -0.470, P < 0.01 and r = -0.493, P < 0.01, respectively) but not in non-pregnant women. These data suggest the possibility that soluble leptin receptor is a minor component of leptin binding capacity in the plasma of pregnant women.

Expression of nitric oxide synthase isoforms in the human placenta is not altered by labor.

Nitric oxide has various biological activities including smooth muscle relaxation, anti-inflammatory activity, anti-coagulatory activity. As the human placenta is known to express nitric oxide synthases, this study investigated the possible effect of labor on the expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in human placental tissues at term. Both eNOS and iNOS mRNA expression in placental tissues in labor were significantly higher than those in the amnion, chorion laeve, decidua vera and myometrium. The eNOS mRNA and protein expressions in placental tissues in labor (n = 12) were 1.6023 +/- 0.1652 (eNOS/GAPDH, mean +/- SEM) and 12.8 +/- 1.3 arbitrary units (AU), respectively, which were similar to those not in labor (n = 10), 1.5806 +/- 0.2042 (eNOS/GAPDH) and 11.4 +/- 1.8 AU. The iNOS mRNA and protein expressions in the placental tissues in labor were 1.2831 +/- 0.2436 (iNOS/GAPDH) and 10.7 +/- 2.1 AU respectively, similar to those not in labor, 1.9254 +/- 0.8004 (iNOS/GAPDH) and 13.3 +/- 1.8 AU. The guanosine 3',5'-cyclic monophosphate (cGMP) concentration in the placental tissues in labor was 23.6 +/- 1.4 fmol/g wet tissue, similar to that not in labor, 26.1 +/- 2.0 fmol/g wet tissue. These findings suggest that nitric oxide production in the human placenta is maintained during labor.

Resistin is expressed in the human placenta.

The mechanism for decreased insulin sensitivity in pregnant women is not fully clarified. Resistin, a novel peptide hormone, is specifically expressed in the adipose tissue and decreases insulin sensitivity in rodents. In the present study, we demonstrate resistin gene expression in the human placental tissue, mainly in trophoblastic cells. The resistin gene expression in term placental tissue was more prominent than was seen in the first trimester chorionic tissue. In contrast resistin gene expression in adipose tissue was rather weak and remained unchanged by pregnancy. Thus, resistin is a newly isolated placental hormone in humans which may modulate insulin sensitivity during pregnancy.

Possible role of placental leptin in pregnancy: a review.

Leptin was initially identified as an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. Subsequent animal studies revealed various physiologic functions of leptin. Leptin plays an essential role in reproduction by regulating gonadotropin-releasing hormone secretion from the hypothalamus. It also modulates glucose metabolism by increasing insulin sensitivity and activates the sympathetic nervous system. In humans, leptin is also produced by placental trophoblasts and is secreted into both the maternal and fetal circulation. Leptin production in the placenta is increased in pregnancies complicated with several pathologic conditions. Leptin gene expression in the placenta is augmented in severe preeclampsia, and maternal plasma leptin levels in severe preeclampsia are significantly higher than those in normotensive pregnant women. Leptin production in the placenta is also increased in diabetic pregnancy with insulin treatment. Furthermore, leptin is proposed to play a functional role in implantation by virtue of its stimulatory effect on matrix metalloproteinase expression in cytotrophoblast. Dysregulation of leptin metabolism and/or function in the placenta may be implicated in the pathogenesis of various disorders during pregnancy, such as recurrent miscarriage, gestational diabetes, intrauterine growth retardation, and preeclampsia. In this review, possible roles of placental leptin are discussed.