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BMC Pregnancy and Childbirth Jul 2023There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product...
BACKGROUND
There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates.
METHODS
Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass.
RESULTS
The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development.
CONCLUSIONS
This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.
Topics: Infant, Newborn; Female; Humans; Premature Birth; Progesterone; Obstetric Labor, Premature; Fatty Acids, Omega-3
PubMed: 37464260
DOI: 10.1186/s12884-023-05842-9 -
Schizophrenia Research Dec 2023Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schizophrenia is a severe mental illness that affects a significant proportion of the global population, particularly those of childbearing age. Several studies have attempted to find an association between schizophrenia and obstetric complications, with varying results.
OBJECTIVE
The primary objective of this systematic review and meta-analyses was to summarize the relationship between maternal schizophrenia and perinatal pregnancy outcomes.
DATA SOURCES
PubMed, Web of Science and Ovid EMBASE were searched from January 2001 to September 2022 using keywords related to pregnancy, women, schizophrenia.
STUDY SELECTION
A total of 23 independent studies across 21,253 individuals with schizophrenia were identified and included in the analysis.
DATA EXTRACTION
The following data were extracted: author, year of publication, country/continent of data collection, study design, demographic characteristics, diagnoses criteria, related complications. Data were analyzed using random-effects pairwise meta-analysis and were reported as prevalence and odd ratios (OR). Statistical heterogeneity was quantified with the I statistic.
RESULTS
The prevalence of adverse perinatal pregnancy outcomes was represented in descending order: cesarean section (26.0 %); labor induction (24.0 %); small for gestational age (10.5 %); gestational diabetes mellitus (9.2 %); preterm birth (9.1 %); low birth weight (7.8 %); preterm rupture of membranes (6.1 %); 1-Minute Apgar Score < 7 (5.6 %); large for gestational age (5.5 %); birth defect (5.4 %); antepartum hemorrhage (4.4 %);preeclampsia/eclampsia (4.8 %); postpartum hemorrhage (3.9 %); 5-Minute Apgar Score < 7 (3.6 %); gestational hypertension (3.3 %); placental abruption (1.0 %); placenta previa (0.6 %); thromboembolic disease (0.4 %); neonatal mortality (0.3 %) (P ≤ 0.05). There was a higher risk of adverse outcomes including gestational diabetes mellitus, preeclampsia/eclampsia, placental abruption, thromboembolic disease, preterm birth, birth defect, 1-Minute Apgar score < 7, small for gestational age, low birth weight and neonatal mortality compared with non-schizophrenia population (P ≤ 0.05).
CONCLUSIONS
Women with schizophrenia are at higher risk of adverse perinatal pregnancy outcomes. It is imperative that research efforts continue to focus on the reproductive safety of women with schizophrenia during their childbearing years.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pregnancy Outcome; Premature Birth; Diabetes, Gestational; Abruptio Placentae; Cesarean Section; Pre-Eclampsia; Eclampsia; Schizophrenia; Placenta
PubMed: 37979419
DOI: 10.1016/j.schres.2023.11.001 -
Ultrasound in Obstetrics & Gynecology :... Oct 2023To review the evidence on the effect of mode of delivery on perinatal outcome of fetuses born before 32 weeks' gestation. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To review the evidence on the effect of mode of delivery on perinatal outcome of fetuses born before 32 weeks' gestation.
METHODS
MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), the ClinicalTrials.gov registry and gray literature sources were searched, starting from the year 2000 to reflect contemporary practice in perinatal care. Non-randomized or randomized studies that included singleton fetuses without chromosomal abnormality or major congenital defect delivered vaginally or via Cesarean section were eligible for inclusion in the analysis. Primary outcomes were neonatal death, defined as death in the first 28 days of age, and survival to discharge. Secondary outcomes were other adverse perinatal events. The ROBINS-I tool was used to assess the risk of bias. The overall quality of evidence for the outcomes was assessed according to GRADE. Summary odds ratios (ORs) with 95% CIs were calculated, and random-effects models were used for data synthesis. Subgroup analysis was performed for delivery before 28 weeks, delivery between 28 and 32 weeks and according to fetal presentation at delivery.
RESULTS
A total of 27 retrospective studies (22 887 neonates) were included in the systematic review and meta-analysis, all of which reported on singleton pregnancies. Among cases born before 28 weeks, vaginal delivery significantly increased the risk of neonatal death of fetuses with any type of presentation (n = 1496) (OR 1.87 (95% CI, 1.05-3.35); I = 65%, very low quality of evidence) and of fetuses with breech presentation (n = 733) (OR 3.55 (95% CI, 2.42-5.21); I = 21%, moderate quality of evidence). The odds of survival to discharge were significantly decreased among fetuses with breech presentation delivered before 28 weeks (n = 646) (OR 0.36 (95% CI, 0.24-0.54); I = 21%, low quality of evidence). Among breech fetuses born between 28 and 32 weeks, vaginal delivery increased the odds of perinatal death (intrapartum and neonatal) (n = 1581) (OR 3.06 (95% CI, 1.47-6.35); I = 0%, high quality of evidence). In non-cephalic fetuses born between 24 and 32 weeks, vaginal delivery decreased the odds of survival to discharge (n = 1030) (OR 0.28 (95% CI, 0.19-0.40); I = 0%, moderate quality of evidence). No significant effect on mortality of mode of delivery was observed in cephalic fetuses at any gestational age.
CONCLUSIONS
This systematic review and meta-analysis suggests that vaginal delivery in severe preterm birth is associated with an increased risk of neonatal and perinatal death in breech fetuses, while no significant association was observed for cephalic fetuses. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Cesarean Section; Perinatal Death; Breech Presentation; Retrospective Studies
PubMed: 37128165
DOI: 10.1002/uog.26241 -
The Journal of Maternal-fetal &... Dec 2023Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract. (Observational Study)
Observational Study
BACKGROUND
Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract.
OBJECTIVES
To investigate whether HCA with a fetal inflammatory response (FIR) has a worse clinical outcome than HCA alone. Further, if FIR or a positive maternal microbiologic culture obtained prior to birth were related to adverse neonatal outcomes in a cohort of extremely preterm (EP) neonates.
METHODS
Prospective observational cohort study recruiting EP singleton pregnancies (gestational age at birth ≤28 weeks) with confirmed HCA. FIR was defined by fetal neutrophils in the chorionic vessels and/or umbilical vessels. Positive culture was defined as growth of potentially pathogenic bacteria in a sample from the cervicovaginal tract prior to birth, or if a cervicovaginal culture was lacking, a culture result from the placenta was used. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between FIR, a positive culture result and adverse outcomes, defined as bronchopulmonary dysplasia (BPD), brain pathology assessed by magnetic resonance imaging, retinopathy of prematurity, necrotizing enterocolitis, early-onset neonatal sepsis, and perinatal death. A composite outcome variable included one or more adverse outcomes.
RESULTS
We included 71 cases with HCA, of which 51 (72%) had FIR. Maternal age, rate of clinical chorioamnionitis (CCA), preterm pre-labor rupture of membranes (PPROM), the number of women receiving antenatal steroids and antibiotics, and the rate of positive maternal cultures of potentially pathogenic bacteria were all significantly higher in the HCA with FIR. Neonates in the FIR group had significantly higher levels of blood leukocytes compared to those without. FIR was associated with a longer interval from PPROM to delivery (log-rank test: = .022). Microbiological sampling had been performed in 63 (89%) cases, of which 60 (95%) were cervicovaginal samples. No associations were found between a positive culture and adverse neonatal outcomes, in contrast to FIR, that was significantly associated to BPD and brain pathology.
CONCLUSIONS
In a cohort of EP pregnancies with confirmed HCA, the presence of FIR was associated with advanced maternal age, CCA, PPROM, antenatal steroids and antibiotics, and a positive maternal culture of potentially pathogenic bacteria. However, the presence of FIR, and not a positive culture, was associated with adverse neonatal outcomes.
Topics: Infant, Newborn; Female; Infant; Pregnancy; Humans; Chorioamnionitis; Infant, Extremely Premature; Prospective Studies; Premature Birth; Fetal Membranes, Premature Rupture; Gestational Age; Infant, Newborn, Diseases; Bronchopulmonary Dysplasia
PubMed: 37031964
DOI: 10.1080/14767058.2023.2196599 -
Journal of Assisted Reproduction and... Mar 2024Since the world's first in vitro fertilization baby was born in 1978, there have been more than 8 million children conceived through assisted reproductive technologies... (Review)
Review
Since the world's first in vitro fertilization baby was born in 1978, there have been more than 8 million children conceived through assisted reproductive technologies (ART) worldwide, and a significant proportion of them have reached puberty or young adulthood. Many studies have found that ART increases the risk of adverse perinatal outcomes, including preterm birth, low birth weight, small size for gestational age, perinatal mortality, and congenital anomalies. However, data regarding the long-term outcomes of ART offspring are limited. According to the developmental origins of health and disease theory, adverse environments during early life stages may induce adaptive changes and subsequently result in an increased risk of diseases in later life. Increasing evidence also suggests that ART offspring are predisposed to an increased risk of non-communicable diseases, such as malignancies, asthma, obesity, metabolic syndrome, diabetes, cardiovascular diseases, and neurodevelopmental and psychiatric disorders. In this review, we summarize the risks for long-term health in ART offspring, discuss the underlying mechanisms, including underlying parental infertility, epigenetic alterations, non-physiological hormone levels, and placental dysfunction, and propose potential strategies to optimize the management of ART and health care of parents and children to eliminate the associated risks. Further ongoing follow-up and research are warranted to determine the effects of ART on the long-term health of ART offspring in later life.
Topics: Child; Pregnancy; Infant, Newborn; Female; Humans; Middle Aged; Young Adult; Adult; Pregnancy Outcome; Premature Birth; Pregnancy, Multiple; Placenta; Reproductive Techniques, Assisted
PubMed: 38146031
DOI: 10.1007/s10815-023-02988-5 -
Clinical Obstetrics and Gynecology Dec 2023Periviable delivery, or a pregnancy at risk of delivery between 20 0/7 and 25 6/7 weeks gestational, is an uncommon event with profound physical, psychological, and...
Periviable delivery, or a pregnancy at risk of delivery between 20 0/7 and 25 6/7 weeks gestational, is an uncommon event with profound physical, psychological, and financial impact. Neonatal outcomes can be hard to predict and with the changing legal landscape around abortion access, management options may be compromised. Dynamic maternal and fetal factors make a cohesive and supportive care team critical for optimal care. Management of threatened periviable delivery in a post-Roe United States may prioritize fetal outcomes regardless of threat to maternal health due to legal restrictions.
Topics: Pregnancy; Infant, Newborn; Female; United States; Humans; Premature Birth; Infant, Extremely Premature; Prenatal Care
PubMed: 37963343
DOI: 10.1097/GRF.0000000000000819 -
European Journal of Neurology Dec 2023Data on disease-modifying therapy (DMT) exposure throughout pregnancy in patients with multiple sclerosis are scarce. In this analysis, we assessed pregnancy and fetal...
BACKGROUND AND PURPOSE
Data on disease-modifying therapy (DMT) exposure throughout pregnancy in patients with multiple sclerosis are scarce. In this analysis, we assessed pregnancy and fetal outcomes following maternal glatiramer acetate (GA) exposure in all three trimesters among cases reported between 1997 and 2020.
METHODS
Pregnancy reports of maternal in utero exposure to 20 and 40 mg/mL GA in all three trimesters from 1997 to 2020 were eligible. Both prospective pregnancy data, reported prior to knowledge of pregnancy outcome, and retrospective data were included. The primary endpoint was major congenital malformations (MCMs) based on the European Surveillance of Congenital Anomalies and Twins (EUROCAT) classification. Additional endpoints included fetal death, preterm birth, and low birth weight. The MCM rate was compared to the EUROCAT background rate.
RESULTS
A total of 618 GA-exposed pregnancies in all three trimesters resulted in 634 fetuses, including 14 twin pregnancies. One fetal death was reported. All 414 fetuses with data reported prior to knowledge of pregnancy outcome (prospective data) were live births and no fetal death was reported. Preterm birth was reported in 23/213 (10.8%) pregnancies with known gestational age. Low birth weight was reported in 13/203 (6.4%) infants with known birth weight. The prevalence of MCM in prospective live births ranged from 2.2% to 2.4%, which was similar to background rates (2.1%-3.0%). The frequency of these pregnancy and infant outcomes was comparable across GA doses.
CONCLUSIONS
In utero exposure to 20 and 40 mg/mL GA in three trimesters of pregnancy does not appear to be related to adverse pregnancy or infant outcomes.
Topics: Infant; Female; Pregnancy; Infant, Newborn; Humans; Glatiramer Acetate; Premature Birth; Retrospective Studies; Maternal Exposure; Prospective Studies; Pregnancy Outcome; Fetus; Fetal Death
PubMed: 37565380
DOI: 10.1111/ene.16036 -
Current Opinion in Nephrology and... Jan 2024The consequences of climate change, including heat and extreme weather events impact kidney function in adults and children. The impacts of climate change on kidney... (Review)
Review
PURPOSE OF REVIEW
The consequences of climate change, including heat and extreme weather events impact kidney function in adults and children. The impacts of climate change on kidney development during gestation and thereby on kidney function later in life have been poorly described. Clinical evidence is summarized to highlight possible associations between climate change and nephron mass.
RECENT FINDINGS
Pregnant women are vulnerable to the effects of climate change, being less able to thermoregulate, more sensitive to the effects of dehydration, and more susceptible to infections. Exposure to heat, wildfire smoke, drought, floods and climate-related infections are associated with low birth weight, preterm birth and preeclampsia. These factors are associated with reduced nephron numbers, kidney dysfunction and higher blood pressures in offspring in later life. Exposure to air pollution is associated with higher blood pressures in children and has variable effects on estimated glomerular filtration rate.
SUMMARY
Climate change has important impacts on pregnant women and their unborn children. Being born too small or too soon is associated with life-time risk of kidney disease. Climate change may therefore have a dual effect of impacting fetal kidney development and contributing to cumulative postnatal kidney injury. The impact on population kidney health of future generations may be significant.
Topics: Adult; Humans; Infant, Newborn; Pregnancy; Female; Climate Change; Premature Birth; Hypertension; Pre-Eclampsia; Nephrons
PubMed: 37800660
DOI: 10.1097/MNH.0000000000000932 -
Journal of Obstetrics and Gynaecology :... Dec 2024Vaginal bleeding during pregnancy has been recognised as a significant risk factor for adverse pregnancy outcomes. This study aimed to investigate the association... (Meta-Analysis)
Meta-Analysis Review
Vaginal bleeding during pregnancy has been recognised as a significant risk factor for adverse pregnancy outcomes. This study aimed to investigate the association between vaginal bleeding during the first trimester of pregnancy and clinical adverse effects using a systematic review and meta-analysis. Databases of Scopus, Web of Science, PubMed (including Medline), Cochrane Library and Science Direct were searched until June of 2023. Data analysis using statistical test fixed- and random-effects models in the meta-analysis, Cochran and meta-regression. The quality of the eligible studies was assessed by using the Newcastle-Ottawa Scale checklist (NOS). A total of 46 relevant studies, with a sample size of 1,554,141 were entered into the meta-analysis. Vaginal bleeding during the first trimester of pregnancy increases the risk of preterm birth (OR: 1.8, CI 95%: 1.6-2.0), low birth weight (LBW; OR: 2.0, CI 95%: 1.5-2.6), premature rupture of membranes (PROMs; OR: 2.3, CI 95%: 1.8-3.0), abortion (OR: 4.3, CI 95%: 2.0-9.0), stillbirth (OR: 2.5, CI 95%: 1.2-5.0), placental abruption (OR: 2.2, CI 95%: 1.4-3.3) and placenta previa (OR: 1.9, CI 95%: 1.5-2.4). Vaginal bleeding in the first trimester of pregnancy is associated with preterm birth, LBW, PROMs, miscarriage, stillbirth, placental abruption and placenta previa. Therefore, physicians or midwives need to be aware of the possibility of these consequences and manage them when they occur.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Stillbirth; Premature Birth; Abruptio Placentae; Placenta Previa; Placenta; Pregnancy Outcome; Abortion, Spontaneous; Uterine Hemorrhage
PubMed: 38305047
DOI: 10.1080/01443615.2023.2288224 -
Scientific Reports Feb 2024During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory...
During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1β), leading to myometrial contraction. Although IL-1β is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1β was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1β in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1β was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cells, Cultured; Cytokines; Inflammasomes; Interleukin-1beta; Labor, Obstetric; Myometrium; Obstetric Labor, Premature
PubMed: 38378749
DOI: 10.1038/s41598-024-54507-w