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Cellular and molecular overview of gestational diabetes mellitus: Is it predictable and preventable?World Journal of Diabetes Nov 2023In contrast to overt diabetes mellitus (DM), gestational DM (GDM) is defined as impaired glucose tolerance induced by pregnancy, which may arise from exaggerated...
BACKGROUND
In contrast to overt diabetes mellitus (DM), gestational DM (GDM) is defined as impaired glucose tolerance induced by pregnancy, which may arise from exaggerated physiologic changes in glucose metabolism. GDM prevalence is reported to be as high as 20% among pregnancies depending on the screening method, gestational age, and the population studied. Maternal and fetal effects of uncontrolled GDM include stillbirth, macrosomia, neonatal diabetes, birth trauma, and subsequent postpartum hemorrhage. Therefore, it is essential to find the potential target population and associated predictive and preventive measures for future intensive peripartum care.
AIM
To review studies that explored the cellular and molecular mechanisms of GDM as well as predictive measures and prevention strategies.
METHODS
The search was performed in the Medline and PubMed databases using the terms "gestational diabetes mellitus," "overt diabetes mellitus," and "insulin resistance." In the literature, only full-text articles were considered for inclusion (237 articles). Furthermore, articles published before 1997 and duplicate articles were excluded. After a final review by two experts, all studies (1997-2023) included in the review met the search terms and search strategy (identification from the database, screening of the studies, selection of potential articles, and final inclusion).
RESULTS
Finally, a total of 79 articles were collected for review. Reported risk factors for GDM included maternal obesity or overweight, pre-existing DM, and polycystic ovary syndrome. The pathophysiology of GDM involves genetic variants responsible for insulin secretion and glycemic control, pancreatic β cell depletion or dysfunction, aggravated insulin resistance due to failure in the plasma membrane translocation of glucose transporter 4, and the effects of chronic, low-grade inflammation. Currently, many antepartum measurements including adipokines (leptin), body mass ratio (waist circumference and waist-to-hip ratio], and biomarkers (microRNA in extracellular vesicles) have been studied and confirmed to be useful markers for predicting GDM. For preventing GDM, physical activity and dietary approaches are effective interventions to control body weight, improve glycemic control, and reduce insulin resistance.
CONCLUSION
This review explored the possible factors that influence GDM and the underlying molecular and cellular mechanisms of GDM and provided predictive measures and prevention strategies based on results of clinical studies.
PubMed: 38077798
DOI: 10.4239/wjd.v14.i11.1693 -
International Journal of Infectious... Feb 2024Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants...
OBJECTIVES
Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied.
METHODS
Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV.
RESULTS
Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions.
CONCLUSION
In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.
Topics: Infant; Infant, Newborn; Humans; Female; Pregnancy; Chikungunya virus; Pregnant Women; Cohort Studies; Nigeria; Cleft Lip; Infectious Disease Transmission, Vertical; Cleft Palate; Chikungunya Fever; Zika Virus Infection; Zika Virus; Stillbirth; Immunoglobulin M; Dengue
PubMed: 38056689
DOI: 10.1016/j.ijid.2023.11.036 -
BMC Pregnancy and Childbirth Dec 2023Globally, more than 2.6 million stillbirths occur each year. The vast majority (98%) of stillbirths occur in low- and middle-income countries, and over fifty percent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, more than 2.6 million stillbirths occur each year. The vast majority (98%) of stillbirths occur in low- and middle-income countries, and over fifty percent (55%) of these happen in rural sub-Saharan Africa.
METHODS
This is a systematic review and meta-analysis developed using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. A literature search was performed using PubMed, the Cochrane Library, Google Scholar, EMBASE, Scopus, the Web of Sciences, and gray literature. Rayyan`s software was used for literature screening. A random effects meta-analysis was conducted with STATA version 17. Heterogeneity was checked by using Cochran's Q and I2 tests. Funnel plots and Egger's test were used to examine the risk of publication bias. The protocol of the study was registered in PROSPERO with a registration number of CRD42023391874.
RESULTS
Forty-one studies gathered from eight sub-Saharan countries with a total of 192,916 sample sizes were included. Nine variables were highly linked with stillbirth. These include advanced maternal age (aOR: 1.43, 95% CI: 1.16, 1.70), high educational attainment (aOR: 0.55, 95% CI: 0.47, 0.63), antenatal care (aOR: 0.45, 95% CI: 0.35, 0.55), antepartum hemorrhage (aOR: 2.70, 95% CI: 1.91, 3.50), low birth weight (aOR: 1.72, 95% CI: 1.56-1.87), admission by referral (aOR: 1.55, 95% CI: 1.41, 1.68), history of stillbirth (aOR: 2.43, 95% CI: 1.84, 3.03), anemia (aOR: 2.62, 95% CI: 1.93, 3.31), and hypertension (aOR: 2.22, 95% CI: 1.70, 2.75).
CONCLUSION
A significant association was found between stillbirth and maternal age, educational status, antenatal care, antepartum hemorrhage, birth weight, mode of arrival, history of previous stillbirth, anemia, and hypertension. Integrating maternal health and obstetric factors will help identify the risk factors as early as possible and provide early interventions.
Topics: Pregnancy; Female; Humans; Stillbirth; Hypertension; Africa South of the Sahara; Anemia; Hemorrhage; Prevalence
PubMed: 38049743
DOI: 10.1186/s12884-023-06148-6 -
Pregnancy Hypertension Mar 2024To observe the incidence of eclampsia before and after implementing Maternal Early Warning Trigger (MEWT) tool. (Observational Study)
Observational Study
OBJECTIVES
To observe the incidence of eclampsia before and after implementing Maternal Early Warning Trigger (MEWT) tool.
STUDY DESIGN
A retrospective observational study to evaluate the effect of introduction of MEWT tool in a tertiary referral center with 10,000 annual births. Two epochs of five years duration were compared before and after implementing MEWT tool. MEWT tool has triggers for early identification of clinical deterioration and pathways for four most important maternal morbidity causes including hypertension. Hypertension pathway has emphasis on rapid control of severe acute hypertension, lab tests and magnesium sulfate prophylaxis. All pregnant women who registered and delivered at the study institute were included.
MAIN OUTCOMES MEASURES
Primary outcome was effect of MEWT tool on the incidence of eclampsia. A subset analysis was done to study the effect of MEWT tool on maternal and perinatal outcomes in women with hypertensive disease. Maternal ICU admissions, HELLP, pulmonary oedema, intracranial bleed and maternal deaths, and perinatal mean birthweight and gestational age, NICU admissions, prematurity, stillbirths, and neonatal deaths were compared.
RESULTS
The study period had 37,043 and 45,637 women in pre- and post-MEWT periods. The incidence of eclampsia reduced by 45.4 % from 1.1 to 0.6 per 1000 women (p 0.001). The most significant reduction was seen with antepartum eclampsia (0.8 to 0.3 per 1000, p = 0.02). There was significant reduction in all maternal and perinatal outcomes in women with hypertensive disorders (3,506 and 6,016 in pre- and post- MEWT periods) after introduction of MEWT tool.
CONCLUSION
Integrating the MEWT tool into the obstetric practice helps in reducing the incidence of eclampsia and improving maternal and fetal outcomes.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Eclampsia; Pre-Eclampsia; Hypertension; HELLP Syndrome; Stillbirth
PubMed: 38043190
DOI: 10.1016/j.preghy.2023.11.007 -
Acta Obstetricia Et Gynecologica... Mar 2024Women with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Women with a prior stillbirth or a history of recurrent first trimester miscarriages are at increased risk of adverse pregnancy outcomes. However, little is known about the impact of a second trimester pregnancy loss on subsequent pregnancy outcome. This review investigated if second trimester miscarriage or termination for medical reason or fetal anomaly (TFMR/TOPFA) is associated with future adverse pregnancy outcomes.
MATERIAL AND METHODS
A systematic review of observational studies was conducted. Eligible studies included women with a history of a second trimester miscarriage or termination for medical reasons and their pregnancy outcomes in the subsequent pregnancy. Where comparative studies were identified, studies which compared subsequent pregnancy outcomes for women with and without a history of second trimester loss or TFMR/TOPFA were included. The primary outcome was livebirth, and secondary outcomes included: miscarriage (first and second trimester), termination of pregnancy, fetal growth restriction, cesarean section, preterm birth, pre-eclampsia, antepartum hemorrhage, stillbirth and neonatal death. Studies were excluded if exposure was nonmedical termination or if related to twins or higher multiple pregnancies. Electronic searches were conducted using the online databases (MEDLINE, Embase, PubMed and The Cochrane Library) and searches were last updated on June 16, 2023. Risk of bias was assessed using the Newcastle-Ottawa scale. Where possible, meta-analysis was undertaken. PROSPERO registration: CRD42023375033.
RESULTS
Ten studies were included, reporting on 12 004 subsequent pregnancies after a second trimester pregnancy miscarriage. No studies were found on outcomes after second trimester TFMR/TOPFA. Overall, available data were of "very low quality" using GRADE assessment. Meta-analysis of cohort studies generated estimated outcome frequencies for women with a previous second trimester loss as follows: live birth 81% (95% CI: 64-94), miscarriage 15% (95% CI: 4-30, preterm birth 13% [95% CI: 6-23]).The pooled odds ratio for preterm birth in subsequent pregnancy after second trimester loss in case-control studies was OR 4.52 (95% CI: 3.03-6.74).
CONCLUSIONS
Very low certainty evidence suggests there may be an increased risk of preterm birth in a subsequent pregnancy after a late miscarriage. However, evidence is limited. Larger, higher quality cohort studies are needed to investigate this potential association.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pregnancy Outcome; Abortion, Spontaneous; Pregnancy Trimester, Second; Stillbirth; Premature Birth; Cesarean Section; Abortion, Habitual
PubMed: 38037500
DOI: 10.1111/aogs.14731 -
Obstetrics and Gynecology Feb 2024To evaluate efficacy in achieving vaginal delivery with a standardized vaginal compared with oral misoprostol regimen for labor induction at term. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate efficacy in achieving vaginal delivery with a standardized vaginal compared with oral misoprostol regimen for labor induction at term.
METHODS
In this single-center, cluster randomized trial, we randomized induction method by week among individuals with gestational age of 37 weeks or more, cervical dilation of 2 cm or less, intact membranes, and indication for delivery to either oral (100 micrograms every 4 hours for up to two doses), or vaginal (25 micrograms every 3 hours for up to five doses) misoprostol regimens, followed by a standardized oxytocin protocol. Individuals with an antepartum stillbirth, major fetal anomalies, malpresentation, ruptured membranes, nonreassuring fetal status, or contraindication to prostaglandin were excluded. The primary outcome was vaginal delivery at first induction attempt. Secondary outcomes included time to delivery, need for oxytocin, chorioamnionitis, and adverse maternal and neonatal outcomes. Outcomes were recorded at the individual level and adjusted for clustering, with analysis by intention to treat.
RESULTS
Between May 24, 2021, to September 19, 2022, 1,322 women were randomized to vaginal misoprostol in 33 clusters and 1,224 to oral misoprostol in 37 clusters. Demographic characteristics or initial cervical dilation did not differ between groups. The primary outcome did not differ between induction regimens and occurred in 1,032 (78.1%) of the vaginal misoprostol arm and 945 (77.2%) of the oral misoprostol arm (adjusted relative risk [RR] 1.01, 95% CI, 0.97-1.05). Tachysystole with fetal heart rate changes occurred less frequently with vaginal compared with oral misoprostol (3.5% vs 5.9%, adjusted RR 0.59, 95% CI, 0.40-0.87). Time to delivery did not differ between groups. Oxytocin was less frequently required before delivery in the vaginal misoprostol group (68.8% vs 78.4%, adjusted RR 0.88, 95% CI, 0.84-0.92).
CONCLUSION
Induction of labor with vaginal compared with oral misoprostol protocols did not increase the frequency of vaginal delivery at term but did reduce the need for oxytocin use before delivery.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT04755218.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Infant; Misoprostol; Oxytocics; Oxytocin; Labor, Induced; Cervical Ripening; Administration, Intravaginal; Administration, Oral
PubMed: 37989142
DOI: 10.1097/AOG.0000000000005464 -
The Journal of Physiology Dec 2023Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However,...
Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O ) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow-up MRI was performed 6-months postpartum (n = 16/20). MRI techniques included phase-contrast and T1/T2 relaxometry for blood flow and oximetry imaging, respectively. O transport was measured in the following vessels (bilateral where appropriate): maternal abdominal descending aorta (DAo ), IVC, ovarian, paraspinal veins (PSV), uterine artery (UtA) and external iliacs, and umbilical. Maternal cardiac output was measured by summing DAo and superior vena cava flows. Supine mothers (n = 6) had lower cardiac output and O delivery in the DAo , UtA and external iliac arteries, and higher PSV flow than those in either the left (n = 8) or right (n = 6) lateral positions during MRI. However, O consumption in the gravid uterus, fetus, placenta and lower limbs was unaffected by maternal positioning. The ratio of IVC/PSV flow decreased in supine mothers while ovarian venous flow and O saturation were unaltered, suggesting a major route of pelvic venous return unaffected by maternal position. Placental-fetal O transport and consumption were similar between left and right lateral maternal positions. In comparison to non-pregnant findings, DAo and UtA O delivery and pelvic O consumption increased, while lower-limb consumption remained constant , despite reduced external iliac artery O delivery in late gestation. KEY POINTS: Though sleeping supine during the third trimester is associated with an increased risk of antepartum stillbirth, the underlying biological mechanisms are not fully understood. Maternal cardiac output and uteroplacental flow are reduced in supine mothers due to inferior vena caval compression from the weight of the gravid uterus. This MRI study provides a comprehensive circulatory assessment, demonstrating reduced maternal cardiac output and O delivery (uteroplacental, lower body) in supine compared to lateral positioning; however, O consumption (gravid uterus, fetus, placenta, lower limbs) was preserved. Unlike other mammalian species, the ovarian veins conduct substantial venous return from the human pregnant uterus that is unaffected by maternal positioning. Lumbar paraspinal venous flow increased in supine mothers. These observations may have important considerations during major pelvic surgery in pregnancy (i.e. placenta percreta). Future studies should address the importance of maternal positioning as a potential tool to deliver improved perinatal outcomes in pregnancies with compromised uteroplacental O delivery.
Topics: Female; Humans; Pregnancy; Feasibility Studies; Fetus; Magnetic Resonance Imaging; Oxygen; Oxygen Consumption; Placenta; Vena Cava, Superior
PubMed: 37906114
DOI: 10.1113/JP285097 -
Cureus Sep 2023Background One of the leading causes contributing to morbidity and mortality globally is attributed to eclampsia. Hence, it is vital to comprehensively review each...
Background One of the leading causes contributing to morbidity and mortality globally is attributed to eclampsia. Hence, it is vital to comprehensively review each female having eclampsia and to evaluate the factors that govern the outcomes in females with eclampsia. Aim To decode the fetal and maternal outcomes in subjects having eclampsia and to evaluate various factors that govern the outcomes. Methods This retrospective cohort and epidemiological study commenced at the Department of Obstetrics and Gynaecology, Netaji Subhash Chandra Bose Medical College, Jabalpur, Madhya Pradesh, in January 2016 till April 2017, and included females that either developed eclampsia in hospital stay duration or presented with pre-existing eclampsia. In included females, various fetal and maternal parameters were assessed along with the outcome of pregnancy. The institutional data records and the database were also used to determine the prevalence and incidence of eclampsia. Baseline maternal parameters were recorded from the already-existing institute data. These included the gestational age (in years), socioeconomic status, educational attainment, parity, gravidity, and the number of weeks of gestation present at the time of delivery. Antenatal care data assessed were blood pressure recordings, any proteinuria documented in the data, and the number of antenatal visits by the subjects. Statistical analysis was performed to assess both parameters. Results In the current investigation, there were 0.34% eclampsia cases among females visiting the institution for deliveries. Incidences of stillbirth were seen in 19.04% and 8% of study participants, respectively. We found 9.52% (n=4) of female infants to have perished from eclampsia. Preterm births, a delayed start to the treatment, and insufficient care were all linked to poor foetal and mother outcomes. The longer the period between the beginning of a fit and delivery, the greater the likelihood of unfavourable results. Seizure onset before or after birth, parity, or subject age had no impact on mother or foetal health. The p-value for statistical significance was kept at 0.05. Conclusion Most of the research participant women, had intrapartum eclampsia, postpartum eclampsia, and antepartum eclampsia, based on the time of the convulsions in relation to the labor. It was highlighted that there was no conclusive evidence linking the date of the fit's beginning to unfavourable results or an elevated risk of complications. Neonatal mortality and stillbirth were observed with vaginal delivery in eclampsia cases. Outcomes in eclampsia can be improved by early treatment initiation, timely and appropriate referral, early disease recognition, and appropriate antenatal care.
PubMed: 37900531
DOI: 10.7759/cureus.45971 -
Reproductive Health Oct 2023In Cambodia, stillbirths and their underlying factors have not been systematically studied. This study aimed to assess the proportion and trends in stillbirths between...
Stillbirth rates and their determinants in a national maternity hospital in Phnom Penh, Cambodia in 2017-2020: a cross-sectional assessment with a nested case-control study.
BACKGROUND
In Cambodia, stillbirths and their underlying factors have not been systematically studied. This study aimed to assess the proportion and trends in stillbirths between 2017 and 2020 in a large maternity referral hospital in the country and identify their key determinants to inform future prevention efforts.
METHODS
This was a retrospective cross-sectional analysis with a nested case-control study of women giving birth at the National Maternal and Child Health Centre (NMCHC) in Phnom Penh, 2017-2020. We calculated percentages of singleton births at ≥ 22 weeks' gestation resulting in stillbirth and annual stillbirth rates by timing: intrapartum (fresh) or antepartum (macerated). Multivariable logistic regression was used to explore factors associated with stillbirth, where cases were all women who gave birth to a singleton stillborn baby in the 4-year period. One singleton live birth immediately following each case served as an unmatched control. Multiple imputation was used to handle missing data for gestational age.
RESULTS
Between 2017 and 2020, 3.2% of singleton births ended in stillbirth (938/29,742). The stillbirth rate increased from 24.8 per 1000 births in 2017 to 38.1 per 1000 births in 2020, largely due to an increase in intrapartum stillbirth rates which rose from 18.8 to 27.4 per 1000 births in the same period. The case-control study included 938 cases (stillbirth) and 938 controls (livebirths). Factors independently associated with stillbirth were maternal age ≥ 35 years compared to < 20 years (aOR: 1.82, 95%CI: 1.39, 2.38), extreme (aOR: 3.29, 95%CI: 2.37, 4.55) or moderate (aOR: 2.45, 95%CI: 1.74, 3.46) prematurity compared with full term, and small-for-gestational age (SGA) (aOR: 2.32, 1.71, 3.14) compared to average size-for-age. Breech/transverse births had nearly four times greater odds of stillbirth (aOR: 3.84, 95%CI: 2.78, 5.29), while caesarean section reduced the odds by half compared with vaginal birth (aOR: 0.50, 95%CI: 0.39, 0.64). A history of abnormal vaginal discharge increased odds of stillbirth (aOR: 1.42, 95%CI: 1.11, 1.81) as did a history of stillbirth (aOR: 3.08, 95%CI: 1.5, 6.5).
CONCLUSIONS
Stillbirth prevention in this maternity referral hospital in Cambodia requires strengthening preterm birth detection and management of SGA, intrapartum care, monitoring women with stillbirth history, management of breech births, and further investigation of high-risk referral cases.
Topics: Child; Pregnancy; Female; Infant, Newborn; Humans; Adult; Stillbirth; Case-Control Studies; Cross-Sectional Studies; Retrospective Studies; Cesarean Section; Cambodia; Hospitals, Maternity; Premature Birth; Fetal Growth Retardation
PubMed: 37865789
DOI: 10.1186/s12978-023-01703-y -
BMC Pregnancy and Childbirth Oct 2023Preterm birth is the leading cause of neonatal and under-five mortality worldwide. It is a complex syndrome characterized by numerous etiologic pathways shaped by both... (Observational Study)
Observational Study
BACKGROUND
Preterm birth is the leading cause of neonatal and under-five mortality worldwide. It is a complex syndrome characterized by numerous etiologic pathways shaped by both maternal and fetal factors. To better understand preterm birth trends, the Global Alliance to Prevent Prematurity and Stillbirth published the preterm birth phenotyping framework in 2012 followed by an application of the model to a global dataset in 2015 by Barros, et al. Our objective was to adapt the preterm birth phenotyping framework to retrospective data from a low-resource, rural setting and then apply the adapted framework to a cohort of women from Migori, Kenya.
METHODS
This was a single centre, observational, retrospective chart review of eligible births from November 2015 - March 2017 at Migori County Referral Hospital. Adaptations were made to accommodate limited diagnostic capabilities and data accuracy concerns. Prevalence of the phenotyping conditions were calculated as well as odds of adverse outcomes.
RESULTS
Three hundred eighty-seven eligible births were included in our study. The largest phenotype group was none (no phenotype could be identified; 41.1%), followed by extrauterine infection (25.1%), and antepartum stillbirth (16.7%). Extrauterine infections included HIV (75.3%), urinary tract infections (24.7%), malaria (4.1%), syphilis (3.1%), and general infection (3.1%). Severe maternal condition was ranked fourth (15.6%) and included anaemia (69.5%), chronic respiratory distress (22.0%), chronic hypertension prior to pregnancy (5.1%), diabetes (3.4%), epilepsy (3.4%), and sickle cell disease (1.7%). Fetal anaemia cases were the most likely to transfer to the newborn unit (OR 5.1, 95% CI 0.8, 30.9) and fetal anomaly cases were the most likely to result in a pre-discharge mortality (OR 3.9, 95% CI 0.8, 19.2).
CONCLUSIONS
Using routine data sources allowed for a retrospective analysis of an existing dataset, requiring less time and fewer resources than a prospective study and demonstrating a feasible approach to preterm phenotyping for use in low-resource settings to inform local prevention strategies.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Anemia; Kenya; Premature Birth; Prospective Studies; Retrospective Studies; Stillbirth
PubMed: 37845611
DOI: 10.1186/s12884-023-06012-7