The lethal homozygous variant in the ATP1A2 gene is associated with FARIMPD syndrome phenotypes in newborns.

FARIMPD (Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, and dysmorphic facies) syndrome is a severe condition caused by ATP1A2 gene variants. The syndrome's novelty and rarity have limited its clinical and molecular knowledge. This research tries to provide new insight by investigating the cause of the early deaths due to FARIMPD syndrome in a particular family and reviewing previous studies. DNA and RNA were extracted from the blood samples of newborns and their parents, followed by whole exome sequencing and segregation analysis. A pathogenic homozygous nonsense variant (c.1234C > T: p.Arg412*) in the ATP1A2 gene was found in newborns. This variant is reported as homozygous for the first time. The migraine symptoms were the result of the heterozygous state of this particular variant, which supported the dominant inheritance pattern of this disease. Real-time PCR was used to analyze ATP1A2 gene expression in the newborns compared to parents and control subjects. The expression analysis also showed significant mRNA degradation in the newborns compared to heterozygous and healthy individuals, due to Nonsense-mediated mRNA Decay phenomena. Our study describes an ATP1A2 nonsense variant (c.1234C > T) that appears compatible with infant survival in the heterozygous and compound heterozygous states but is lethal in the homozygous state.

Incidence and causes of perinatal death in prenatally diagnosed vasa previa: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to estimate the perinatal mortality associated with prenatally diagnosed vasa previa and to determine what proportion of those perinatal deaths are directly attributable to vasa previa. DATA SOURCES: The following databases have been searched from January 1, 1987, to January 1, 2023: PubMed, Scopus, Web of Science, and Embase. STUDY ELIGIBILITY CRITERIA: Our study included all studies (cohort studies and case series or reports) that had patients in which a prenatal diagnosis of vasa previa was made. Case series or reports were excluded from the meta-analysis. All cases in which prenatal diagnosis was not made were excluded from the study. METHODS: The programming language software R (version 4.2.2) was used to conduct the meta-analysis. The data were logit transformed and pooled using the fixed effects model. The between-study heterogeneity was reported by I2. The publication bias was evaluated using a funnel plot and the Peters regression test. The Newcastle-Ottawa scale was used to assess the risk of bias. RESULTS: Overall, 113 studies with a cumulative sample size of 1297 pregnant individuals were included. This study included 25 cohort studies with 1167 pregnancies and 88 case series or reports with 130 pregnancies. Moreover, 13 perinatal deaths occurred among these pregnancies, consisting of 2 stillbirths and 11 neonatal deaths. Among the cohort studies, the overall perinatal mortality was 0.94% (95% confidence interval, 0.52-1.70; I2=0.0%). The pooled perinatal mortality attributed to vasa previa was 0.51% (95% confidence interval, 0.23-1.14; I2=0.0%). Stillbirth and neonatal death were reported in 0.20% (95% confidence interval, 0.05-0.80; I2=0.0%) and 0.77% (95% confidence interval, 0.40-1.48; I2=0.0%) of pregnancies, respectively. CONCLUSION: Perinatal death is uncommon after a prenatal diagnosis of vasa previa. Approximately half of the cases of perinatal mortality are not directly attributable to vasa previa. This information will help in guiding physicians in counseling and will provide reassurance to pregnant individuals with a prenatal diagnosis of vasa previa.

Population-level changes in perinatal death for pregnancies prior to and during the COVID-19 pandemic: A pregnancy cohort analysis.

BACKGROUND: Results of population-level studies examining the effect of the COVID-19 pandemic on the risks of perinatal death have varied considerably. OBJECTIVES: To explore trends in the risk of perinatal death among pregnancies beginning prior to and during the pandemic using a pregnancy cohort approach. METHODS: This secondary analysis included data from singleton pregnancies ≥20 weeks' gestation in Alberta, Canada, beginning between 5 March 2017 and 4 March 2021. Perinatal death (i.e. stillbirth or neonatal death) was the primary outcome considered. The risk of this outcome was calculated for pregnancies with varying gestational overlap with the pandemic (i.e. none, 0-20 weeks, entire pregnancy). Interrupted time series analysis was used to further determine temporal trends in the outcome by time period of interest. RESULTS: There were 190,853 pregnancies during the analysis period. Overall, the risk of perinatal death decreased with increasing levels of pandemic exposure; this outcome was experienced in 1.0% (95% confidence interval [CI] 0.9, 1.0), 0.9% (95% CI 0.8, 1.1) and 0.8% (95% CI 0.7, 0.9) of pregnancies with no overlap, partial overlap and complete pandemic overlap respectively. Pregnancies beginning during the pandemic that had high antepartum risk scores less frequently led to perinatal death compared to those beginning prior; 3.3% (95% CI 2.7, 3.9) versus 5.7% (95% CI 5.0, 6.5) respectively. Interrupted time-series analysis revealed a decreasing temporal trend in perinatal death for pregnancies beginning ≤40 weeks prior to the start of the COVID-19 pandemic (i.e. with pandemic exposure), with no trend for pregnancies beginning >40 weeks pre-pandemic (i.e. no pandemic exposure). CONCLUSION: We observed a decrease in perinatal death for pregnancies overlapping with the COVID-19 pandemic in Alberta, particularly among those at high risk of these outcomes. Specific pandemic control measures and government response programmes in our setting may have contributed to this finding.

Incidence, predictors and immediate neonatal outcomes of birth asphyxia in Nigeria.

OBJECTIVE: To determine the incidence and sociodemographic and clinical risk factors associated with birth asphyxia and the immediate neonatal outcomes of birth asphyxia in Nigeria. DESIGN: Secondary analysis of data from the Maternal and Perinatal Database for Quality, Equity and Dignity Programme. SETTING: Fifty-four consenting referral-level hospitals (48 public and six private) across the six geopolitical zones of Nigeria. POPULATION: Women (and their babies) who were admitted for delivery in the facilities between 1 September 2019 and 31 August 2020. METHODS: Data were extracted and analysed on prevalence and sociodemographic and clinical factors associated with birth asphyxia and the immediate perinatal outcomes. Multilevel logistic regression modelling was used to ascertain the factors associated with birth asphyxia. MAIN OUTCOME MEASURES: Incidence, case fatality rate and factors associated with birth asphyxia. RESULTS: Of the available data, 65 383 (91.1%) women and 67 602 (90.9%) babies had complete data and were included in the analysis. The incidence of birth asphyxia was 3.0% (2027/67 602) and the case fatality rate was 16.8% (339/2022). The risk factors for birth asphyxia were uterine rupture, pre-eclampsia/eclampsia, abruptio placentae/placenta praevia, birth trauma, fetal distress and congenital anomaly. The following factors were independently associated with a risk of birth asphyxia: maternal age, woman's education level, husband's occupation, parity, antenatal care, referral status, cadre of health professional present at the birth, sex of the newborn, birthweight and mode of birth. Common adverse neonatal outcomes included: admission to a special care baby unit (SCBU), 88.4%; early neonatal death, 14.2%; neonatal sepsis, 4.5%; and respiratory distress, 4.4%. CONCLUSIONS: The incidence of reported birth asphyxia in the participating facilities was low, with around one in six or seven babies with birth asphyxia dying. Factors associated with birth asphyxia included sociodemographic and clinical considerations, underscoring a need for a comprehensive approach focused on the empowerment of women and ensuring access to quality antenatal, intrapartum and postnatal care.

Prevalence, perinatal outcomes and factors associated with neonatal sepsis in Nigeria.

OBJECTIVE: To examine the prevalence, perinatal outcomes and factors associated with neonatal sepsis in referral-level facilities across Nigeria. DESIGN: Secondary analysis of data from the Maternal and Perinatal Database for Quality, Equity and Dignity Programme in 54 referral-level hospitals across Nigeria. SETTING: Records covering the period from 1 September 2019 to 31 August 2020. POPULATION: Mothers admitted for birth during the study period, and their live newborns. METHODS: Analysis of prevalence and sociodemographic and clinical factors associated with neonatal sepsis and perinatal outcomes. Multilevel logistic regression modelling identified factors associated with neonatal sepsis. MAIN OUTCOME MEASURES: Neonatal sepsis and perinatal outcomes. RESULTS: The prevalence of neonatal sepsis was 16.3 (95% CI 15.3-17.2) per 1000 live births (1113/68 459) with a 10.3% (115/1113) case fatality rate. Limited education, unemployment or employment in sales/trading/manual jobs, nulliparity/grand multiparity, chronic medical disorder, lack of antenatal care (ANC) or ANC outside the birthing hospital and referral for birth increased the odds of neonatal sepsis. Birthweight of <2500 g, non-spontaneous vaginal birth, preterm birth, prolonged rupture of membranes, APGAR score of <7 at 5 min, birth asphyxia, birth trauma or jaundice were associated with neonatal sepsis. Neonates with sepsis were more frequently admitted to a neonatal intensive care unit (1037/1110, 93.4% vs 8237/67 346, 12.2%) and experienced a higher rate of death (115/1113, 10.3% vs 933/67 343, 1.4%). CONCLUSIONS: Neonatal sepsis remains a critical challenge in neonatal care, underscored by its high prevalence and mortality rate. The identification of maternal and neonatal risk factors underscores the importance of improved access to education and employment for women and targeted interventions in antenatal and intrapartum care.

Selective fetal growth restriction in dichorionic diamniotic twin pregnancy: systematic review and meta-analysis of pregnancy and perinatal outcomes.

OBJECTIVE: Most of the published literature on selective fetal growth restriction (sFGR) has focused on monochorionic twin pregnancies. The aim of this systematic review was to report on the outcome of dichorionic diamniotic (DCDA) twin pregnancies complicated by sFGR. METHODS: MEDLINE, EMBASE and The Cochrane Library databases were searched. The inclusion criteria were DCDA twin pregnancies complicated by sFGR. The outcomes explored were intrauterine death (IUD), neonatal death and perinatal death (PND), survival of at least one and both twins, preterm birth (PTB) (either spontaneous or iatrogenic) prior to 37, 34, 32 and 28 weeks' gestation, pre-eclampsia (PE) or gestational hypertension, neurological, respiratory and infectious morbidity, Apgar score < 7 at 5 min, necrotizing enterocolitis, retinopathy of prematurity and admission to the neonatal intensive care unit (NICU). A composite outcome of neonatal morbidity, defined as the occurrence of respiratory, neurological or infectious morbidity, was also evaluated. Random-effects meta-analysis was used to analyze the data, and results are reported as pooled proportion or odds ratio (OR) with 95% CI. RESULTS: Thirteen studies reporting on 1339 pregnancies with sFGR and 6316 pregnancies without sFGR were included. IUD occurred in 2.6% (95% CI, 1.1-4.7%) of fetuses from DCDA pregnancies with sFGR and 0.6% (95% CI, 0.3-9.7%) of those from DCDA pregnancies without sFGR, while the respective values for PND were 5.2% (95% CI, 3.5-7.3%) and 1.7% (95% CI, 0.1-5.7%). Spontaneous or iatrogenic PTB before 37 weeks complicated 84.1% (95% CI, 55.6-99.2%) of pregnancies with sFGR and 69.1% (95% CI, 45.4-88.4%) of those without sFGR. The respective values for PTB before 34, 32 and 28 weeks were 18.4% (95% CI, 4.4-38.9%), 13.0% (95% CI, 9.5-17.1%) and 1.5% (95% CI, 0.6-2.3%) in pregnancies with sFGR and 10.2% (95% CI, 3.1-20.7%), 7.8% (95% CI, 6.8-9.0%) and 1.8% (95% CI, 1.3-2.4%) in those without sFGR. PE or gestational hypertension complicated 19.9% (95% CI, 12.4-28.6%) of pregnancies with sFGR and 12.8% (95% CI, 10.4-15.4%) of those without sFGR. Composite morbidity occurred in 28.2% (95% CI, 7.8-55.1%) of fetuses from pregnancies with sFGR and 13.9% (95% CI, 6.5-23.5%) of those from pregnancies without sFGR. When stratified according to the sFGR status within a twin pair, composite morbidity occurred in 39.0% (95% CI, 11.1-71.5%) of growth-restricted fetuses and 29.9% (95% CI, 3.5-65.0%) of appropriately grown fetuses (OR, 1.9 (95% CI, 1.7-3.1)), while the respective values for PND were 3.0% (95% CI, 1.8-4.5%) and 1.6% (95% CI, 0.9-2.6%) (OR, 2.1 (95% CI, 1.0-4.1)). On risk analysis, DCDA pregnancies complicated by sFGR had a significantly higher risk of IUD (OR, 5.2 (95% CI, 3.2-8.6)) and composite morbidity or admission to the NICU (OR, 3.2 (95% CI, 1.9-5.6)) compared to those without sFGR, while there was no difference in the risk of PTB before 34 weeks (P = 0.220) or PE/gestational hypertension (P = 0.210). CONCLUSIONS: DCDA twin pregnancies complicated by sFGR are at high risk of perinatal morbidity and mortality. The findings of this systematic review are relevant for counseling and management of complicated DCDA twin pregnancies, in which twin-specific, rather than singleton, outcome data should be used. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal and Neonatal Autopsy in the Molecular Age: Exploring Tissue Selection for Testing Success.

While conventional autopsy is the gold-standard for determining cause of demise in the fetal and neonatal population, molecular analysis is increasingly used as an ancillary tool. Testing methods and tissue selection should be optimized to provide informative genetic results. This institutional review compares testing modalities and postmortem tissue type in 53 demises occurring between 20 weeks of gestation and 28 days of life. Testing success, defined as completion of analysis, varies by technique and may require viable cells for culture or extractable nucleic acid. Success was achieved by microarray in 29/30 tests (96.7%), karyotype in 40/54 tests (74.1%), fluorescent in situ hybridization in 5/9 tests (55.6%), and focused gene panels in 2/2 tests (100%). With respect to tissue type, postmortem prepartum amniotic fluid was analyzed to completion in 100% of tests performed; compared to 84.0%, 54.5%, and 80.8% of tests using placenta, fetal only, and mixed fetal-placental tissue collection, respectively. Sampling skin (83.3%, in cases with minimal maceration) and kidney (75.0%) were often successful, compared to lower efficacy of umbilical cord (57.1%) and liver (25.0%). Addition of genetic testing into cases with anomalous clinical and gross findings can increase the utility of the final report for family counseling and future pregnancy planning.

Prevalence of fetal anomalies, stillbirth, neonatal morbidity, or mortality in pregnancies complicated by placenta accreta spectrum disorders.

INTRODUCTION: Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases. MATERIAL AND METHODS: This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies. RESULTS: There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations. CONCLUSIONS: Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS.

Perinatal care and its association with perinatal death among women attending care in three district hospitals of western Uganda.

BACKGROUND: Provision of effective care to all women and newborns during the perinatal period is a viable strategy for achieving the Sustainable Development Goal 3 targets on reducing maternal and neonatal mortality. This study examined perinatal care (antenatal, intrapartum, postpartum) and its association with perinatal deaths at three district hospitals in Bunyoro region, Uganda. METHODS: A cross-sectional study was conducted in which a questionnaire was administered consecutively to 872 postpartum women before discharge who had attended antenatal care and given birth in the study hospitals. Data on care received during antenatal, labour, delivery, and postpartum period, and perinatal outcome were extracted from medical records of the enrolled postnatal women using a pre-tested structured tool. The care received from antenatal to 24 h postpartum period was assessed against the standard protocol of care established by World Health Organization (WHO). Poisson regression was used to assess the association between care received and perinatal death. RESULTS: The mean age of the women was 25 years (standard deviation [SD] 5.95). Few women had their blood tested for hemoglobin levels, HIV, and Syphilis (n = 53, 6.1%); had their urine tested for glucose and proteins (n = 27, 3.1%); undertook an ultrasound scan (n = 262, 30%); and had their maternal status assessed (n = 122, 14%) during antenatal care as well as had their uterus assessed for contraction and bleeding during postpartum care (n = 63, 7.2%). There were 19 perinatal deaths, giving a perinatal mortality rate of 22/1,000 births (95% Confidence interval [CI] 8.1-35.5). Of these 9 (47.4%) were stillbirths while the remaining 10 (52.6%) were early neonatal deaths. In the antenatal phase, only fetal examination was significantly associated with perinatal death (adjusted prevalence ratio [aPR] = 0.22, 95% CI 0.1-0.6). No significant association was found between perinatal deaths and care during labour, delivery, and the early postpartum period. CONCLUSION: Women did not receive all the required perinatal care during the perinatal period. Perinatal mortality rate in Bunyoro region remains high, although it's lower than the national average. The study shows a reduction in the proportion of perinatal deaths for pregnancies where the mother received fetal monitoring. Strategies focused on strengthened fetal status monitoring such as fetal movement counting methods and fetal heart rate monitoring devices during pregnancy need to be devised to reduce the incidence of perinatal deaths. Findings from the study provide valuable information that would support the strengthening of perinatal care services for improved perinatal outcomes.

Evaluation of an online education program for healthcare professionals on best practice management of perinatal deaths: IMPROVE eLearning.

BACKGROUND: The IMPROVE (IMproving Perinatal Mortality Review and Outcomes Via Education) eLearning, developed by the Stillbirth Centre of Research Excellence in partnership with the Perinatal Society of Australia and New Zealand was launched in December 2019. Based on the successful face-to-face program, the eLearning aims to increase availability and accessibility of high-quality online education to healthcare professionals providing care for families around the time of perinatal death, to improve the delivery of respectful and supportive clinical care and increase best practice investigation of perinatal deaths. AIMS: To evaluate participants' reported learning outcomes (change in knowledge and confidence) and overall acceptability of the program. METHODS: Pre- and post-eLearning in-built surveys were collected over two years (Dec. 2019-Nov. 2021), with a mix of Likert and polar questions. Pre- and post-eLearning differences in knowledge and confidence were assessed using McNemar's test. Subgroup analysis of overall acceptability by profession was assessed using Pearson's χ2 . RESULTS: One thousand, three hundred and thirty-nine participants were included. The majority were midwives (80.2%, n = 1074). A significant improvement in knowledge and confidence was shown across all chapters (P < 0.01). The chapter showing the greatest improvement was perinatal mortality audit and classification (21.5% pre- and 89.2% post-education). Over 90% of respondents agreed the online education was relevant, helpful, acceptable, engaging. Importantly, 80.7% of participants considered they were likely to change some aspect of their clinical practice after the eLearning. There was no difference in responses to relevance and acceptability of the eLearning program by profession. CONCLUSIONS: The IMPROVE eLearning is an acceptable and engaging method of delivery for clinical education, with the potential to improve care and management of perinatal deaths.

Government health expenditures and neonatal mortality in China: Implication for Sustainable Development Goal 3.

This study utilized comprehensive graphical, descriptive and econometric methods to provide empirical answers to the nexus between government health expenditures and neonatal mortality in China. Secondary data from 2000 to 2021 was extracted from the World Development Indicators, after which it was analyzed empirically with the following results; in the past two decades, the incidence of neonatal death has reduced by 85%. Meanwhile, domestic general government health expenditure per capita ranged between $326.2 and $9.4 during the period with a mean value of $138. Average neonatal mortality rate recorded an approximately 10 deaths per 1000 live births, while government health expenditures and neonatal mortality showed a significant negative relationship in China. Therefore, this study confirms that China has been able to meet the SDG 3 with evidence indicating that this may be due to increased government health expenditure.

Cette étude a utilisé des méthodes graphiques, descriptives et économétriques complètes pour fournir des réponses empiriques au lien entre les dépenses publiques de santé et la mortalité néonatale en Chine. Les données secondaires de 2000 à 2021 ont été extraites des indicateurs de développement dans le monde, après quoi elles ont été analysées empiriquement avec les résultats suivants : au cours des deux dernières décennies, l'incidence des décès néonatals a diminué de 85 %. Dans le même temps, les dépenses de santé des administrations publiques nationales par habitant ont varié entre 326,2 et 9,4 dollars au cours de la période, avec une valeur moyenne de 138 dollars. Le taux de mortalité néonatale moyen a enregistré environ 10 décès pour 1 000 naissances vivantes, tandis que les dépenses publiques de santé et la mortalité néonatale ont montré une relation négative significative en Chine. Par conséquent, cette étude confirme que la Chine a été en mesure d'atteindre l'ODD 3 avec des preuves indiquant que cela pourrait être dû à l'augmentation des dépenses publiques de santé.

Spanish adaptation of the perinatal grief intensity scale.

AIMS/BACKGROUND: Assessing the intensity of perinatal grief is very important for identifying the more complex cases in mothers and fathers. Despite this, there are few assessment tools available. The aim of this study was to analyse the psychometric properties (factorial structure, reliability, and validity) of the Spanish version of the Perinatal Grief Intensity Scale (PGIS). DESIGN/METHODS: An online survey was completed by 291 mothers and fathers who had suffered perinatal loss in the previous six years. RESULTS: The results showed adequate fit indexes for the three-factor model of the PGIS: reality, confront others, and congruence. Reliability values for the overall scale and subscales were adequate. Finally, with regard to validity, significant (p < .05) and positive relationships were found with levels of complicated grief, event centrality, guilt, anxiety, and depression. There were also differences depending on whether participants exhibited high or low levels of complicated grief, and on the number of weeks of pregnancy at the time of the loss. CONCLUSION: In conclusion, the Spanish adaptation of the PGIS has adequate reliability and validity scores and a factorial structure consistent with the original version.

Retrospective evaluation of neonates with fatal congenital lung malformation: A single center 15-year forensic autopsy experience.

Congenital lung malformation (CLM) is a leading cause of infant mortality. Clinical methods for diagnosing CLM mainly rely on computed tomography, magnetic resonance imaging, ultrasonography, and Doppler. However, forensic identification of the cause of death in neonates is challenging. Unequivocal classification criteria for CLM are missing as its forensic identification is ambiguous. Therefore, we aimed to analyze neonatal death cases at our center to assist in identifying those with congenital lung malformation. This retrospective study identified and classified the causes of deaths of neonates autopsied between January 2008 and April 2023. All cases born alive and died within 28 days with a clear time of death were selected, and forensic experts reviewed their records. The manner, cause of death, and other characteristics were noted and discussed. This retrospective study reveals a steady increase in autopsy cases from 2008 to 2015, attributed to improved parental consent, heightened awareness of autopsy importance, and enhanced medical resources. However, a subsequent decline post-2015 is observed, potentially influenced by advancements in medical technology and prenatal examination protocols. The top causes of neonatal mortality include respiratory diseases, asphyxia, congenital dysplasia, and fetal distress. Congenital lung malformations, particularly bronchopulmonary malformations, constitute a significant portion of congenital anomalies. This study underscores the importance of standardized autopsies and histopathological examinations in diagnosing and understanding CLM. Future research should focus on expanding case collections and elucidating the genetic basis of CLM to improve forensic management and outcomes.

Pathogens Identified by Minimally Invasive Tissue Sampling in India and Pakistan From Preterm Neonatal Deaths: The PURPOSE Study.

BACKGROUND: We identified pathogens found in internal organs and placentas of deceased preterm infants cared for in hospitals in India and Pakistan. METHODS: Prospective, observational study conducted in delivery units and neonatal intensive care units. Tissue samples from deceased neonates obtained by minimally invasive tissue sampling and placentas were examined for 73 different pathogens using multiplex polymerase chain reaction (PCR). RESULTS: Tissue for pathogen PCR was obtained from liver, lung, brain, blood, cerebrospinal fluid, and placentas from 377 deceased preterm infants. Between 17.6% and 34.1% of each type of tissue had at least 1 organism identified. Organism detection was highest in blood (34.1%), followed by lung (31.1%), liver (23.3%), cerebrospinal fluid (22.3%), and brain (17.6%). A total of 49.7% of the deceased infants had at least 1 organism. Acinetobacter baumannii was in 28.4% of the neonates compared with 14.6% for Klebsiella pneumoniae, 11.9% for Escherichia coli/Shigella, and 11.1% for Haemophilus influenzae. Group B streptococcus was identified in only 1.3% of the neonatal deaths. A. baumannii was rarely found in the placenta and was found more commonly in the internal organs of neonates who died later in the neonatal period. The most common organism found in placentas was Ureaplasma urealyticum in 34% of the samples, with no other organism found in >4% of samples. CONCLUSIONS: In organ samples from deceased infants in India and Pakistan, evaluated with multiplex pathogen PCR, A. baumannii was the most commonly identified organism. Group B streptococcus was rarely found. A. baumannii was rarely found in the placentas of these deceased neonates.

Adverse perinatal outcomes associated with timing of initiation of antiretroviral therapy: Systematic review and meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends immediate initiation of lifelong antiretroviral therapy (ART) for all people living with HIV, including pregnant women. As a result, an increasing number of women living with HIV conceive while taking ART, the vast majority of whom reside in low- and middle-income countries (LMICs). We aimed to assess the association between timing of ART initiation and perinatal outcomes. METHODS: We conducted a systematic literature review by searching PubMed, CINAHL (EBSCOhost), Global Health (Ovid), EMBASE (Ovid), and the Cochrane Central Register of Controlled Trials and four clinical trial databases (WHO International Clinical Trials Registry Platform, the Pan African Clinical Trials Registry, the ClinicalTrials.gov database, and the ISRCTN Registry) from 1 January 1980 to 28 April 2018. We identified studies reporting specific perinatal outcomes among pregnant women living with HIV according to timing of ART initiation and extracted data. Perinatal outcomes assessed were preterm birth (<37 weeks), very preterm birth (<32 weeks), low birthweight (<2500 g), very low birthweight (<1500 g), small for gestational age (<10th centile), very small for gestational age (<3rd centile) and neonatal death (<29 days). Random-effects meta-analyses examined perinatal outcomes associated with preconception and antenatal ART initiation as well as according to trimesters of antenatal initiation. We performed quality assessments and subgroup and sensitivity analyses, and assessed the effect of adjustment for confounders. This systematic review and meta-analyses is registered with PROSPERO, number CRD42021248987. RESULTS: Of 51 874 unique citations, 25 studies (eight prospective and 17 retrospective cohort studies) were eligible for analysis, including 40 920 women living with HIV. Preconception ART initiation was associated with a significantly increased risk of preterm birth (relative risk 1.16; 95% confidence interval [CI] 1.03-1.31) compared with antenatal ART initiation. Preconception ART initiation was not significantly associated with very preterm birth, low birthweight, very low birthweight, small for gestational age, very small for gestational age, or neonatal death. First trimester exposure (i.e. preconception or first trimester initiation) was not significantly associated with any increased risk of adverse perinatal outcomes. No significant association between timing of ART initiation and adverse perinatal outcomes was found in the studies of higher quality and those conducted in LMICs. CONCLUSION: Preconception ART initiation is associated with preterm birth but no other adverse perinatal outcomes. In LMICs, where most pregnant women living with HIV reside, the timing of ART initiation was not associated with any adverse perinatal outcomes.

Relationships between birth weight discordance and maternal and perinatal risks among twin pregnancies conceived following frozen embryo transfer.

STUDY QUESTION: Is intertwin birth weight discordance associated with adverse maternal and perinatal outcomes following frozen embryo transfer (FET)? SUMMARY ANSWER: For twins conceived following FET, intertwin birth weight discordance is related to elevated risks of neonatal mortality irrespective of chorionicity, and the risk of hypertensive disorders of pregnancy (HDP) is elevated for the mothers of dichorionic twins affected by such birth weight discordance. WHAT IS KNOWN ALREADY: While the relationships between intertwin birth weight discordance and adverse maternal or fetal outcomes have been studied for naturally conceived twins, similarly comprehensive analyses for twins conceived using ART remain to be performed. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study of all twin births from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China that were conceived following FET (N = 6265). PARTICIPANTS/MATERIALS, SETTING, METHODS: Intertwin birth weight discordance was defined as a 20% difference in neonatal birth weights. The primary study outcome was the incidence of HDP and neonatal death while secondary outcomes included gestational diabetes, placenta previa, placental abruption, intrahepatic cholestasis of pregnancy, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, stillbirth, birth defect, neonatal jaundice, necrotizing enterocolitis, and pneumonia incidence. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for maternal and neonatal outcomes. Subgroup analyses were conducted, and Kaplan-Meier survival analysis was used to estimate the survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model, an inverse probability weighting model, a restricted cubic spline analysis, and logistic regression models using other percentage cutoffs for discordance. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6101 females that gave birth to dichorionic twins during the study interval, birth weight discordance was observed in 797 twin pairs (13.1%). In this cohort, intertwin birth weight discordance was related to an elevated risk of HDP (aOR 1.56; 95% CI 1.21-2.00), and this relationship was confirmed through sensitivity analyses. Hypertensive disease risk rose as the severity of this birth weight discordance increased. Discordant birth weight was also linked to increased odds of neonatal mortality (aOR 2.13; 95% CI 1.03-4.09) and this risk also increased with the severity of discordance. Of the 164 women with monochorionic twins, the discordant group exhibited an elevated risk of neonatal death compared to the concordant group (crude OR 9.00; 95% CI 1.02-79.3). LIMITATIONS, REASONS FOR CAUTION: The limitations of this study are its retrospective nature and the fact that the available data could not specify which twins were affected by adverse outcomes. There is a lack of an established reference birth weight for Chinese twins born at a gestational age of 24-41 weeks. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that twins exhibiting a birth weight discordance are related to an elevated risk of adverse maternal and perinatal outcomes, emphasizing a potential need for higher levels of antenatal surveillance in these at-risk pregnancies. STUDY FUNDING/COMPETING INTEREST(S): Authors declare no conflict of interest. This study was funded by the Clinical Research Program of Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYLJ202118) and the National Natural Science Foundation of China (Grant Nos 82271693 and 82273634). TRIAL REGISTRATION NUMBER: N/A.

First- or second-trimester SARS-CoV-2 infection and subsequent pregnancy outcomes.

BACKGROUND: SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy. OBJECTIVE: This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness. STUDY DESIGN: A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at <20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at <37 weeks of gestation and <34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of <5th or <10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at <37 weeks of gestation. RESULTS: Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at <37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at <37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at <34 weeks of gestation, any major congenital malformation, and size for gestational age of <5th or <10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features. CONCLUSION: There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

Risk of fetal or neonatal death or neonatal intensive care unit admission associated with gadolinium magnetic resonance imaging exposure during pregnancy.

BACKGROUND: Concerns have been raised about prenatal exposure to magnetic resonance imaging with gadolinium-based contrast agents because of nonclinical findings of gadolinium retention in fetal tissue and 1 population-based study reporting an association with adverse pregnancy outcomes. OBJECTIVE: This study aimed to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death and neonatal intensive care unit admission. STUDY DESIGN: We constructed a retrospective cohort of >11 million Medicaid-covered pregnancies between 1999 and 2014 to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death (primary endpoint) and neonatal intensive care unit admissions (secondary endpoint). Medicaid claims data were linked to medical records, Florida birth and fetal death records, and the National Death Index to validate the outcomes and gestational age estimates. Pregnancies with multiples, concurrent cancer, teratogenic drug exposure, magnetic resonance imaging focused on fetal or pelvic evaluation, undetermined gadolinium-based contrast agent use, or those preceded by or contemporaneous with congenital anomaly diagnoses were excluded. We adjusted for potential confounders with standardized mortality ratio weighting using propensity scores. RESULTS: Among 5991 qualifying pregnancies, we found 11 fetal or neonatal deaths in the gadolinium-based contrast agent magnetic resonance imaging group (1.4%) and 73 in the non-gadolinium-based contrast agent magnetic resonance imaging group (1.4%) with an adjusted relative risk of 0.73 (95% confidence interval, 0.34-1.55); the neonatal intensive care unit admission adjusted relative risk was 1.03 (0.76-1.39). Sensitivity analyses investigating the timing of magnetic resonance imaging or repeat magnetic resonance imaging exposure during pregnancy and simulating the impact of exposure misclassification corroborated these results. CONCLUSION: This study addressed the safety concerns related to prenatal exposure to gadolinium-based contrast agents used in magnetic resonance imaging and the risk thereof on fetal and neonatal death or the need for neonatal intensive care unit admission. Although the results on fatal or severe acute effects are reassuring, the impact on subacute outcomes was not evaluated.

The Danish newborn standard and the International Fetal and Newborn Growth Consortium for the 21st Century newborn standard: a nationwide register-based cohort study.

BACKGROUND: It is a matter of debate whether 1 universal standard, such as the International Fetal and Newborn Growth Consortium for the 21st Century standard, can be applied to all populations. OBJECTIVE: The primary objective was to establish a Danish newborn standard based on the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard to compare the percentiles of these 2 standards. A secondary objective was to compare the prevalence and risk of fetal and neonatal deaths related to small for gestational age defined by the 2 standards when used in the Danish reference population. STUDY DESIGN: This was a register-based nationwide cohort study. The Danish reference population included 375,318 singletons born at 33 to 42 weeks of gestation in Denmark between January 1, 2008, and December 31, 2015. The Danish standard cohort included 37,811 newborns who fulfilled the criteria of the International Fetal and Newborn Growth Consortium for the 21st Century standard. Birthweight percentiles were estimated using smoothed quantiles for each gestational week. The outcomes included birthweight percentiles, small for gestational age (defined as a birthweight of 3rd percentile), and adverse outcomes (defined as either fetal or neonatal death). RESULTS: At all gestational ages, the Danish standard median birthweights at term were higher than the International Fetal and Newborn Growth Consortium for the 21st Century standard median birthweights: 295g for females and 320 g for males. Therefore, the estimates of the prevalence rate of small for gestational age within the entire population were different: 3.9% (n=14,698) using the Danish standard vs 0.7% (n=2640) using the International Fetal and Newborn Growth Consortium for the 21st Century standard. Accordingly, the relative risk of fetal and neonatal deaths among small-for-gestational-age fetuses differed by SGA status defined by the different standards (4.4 [Danish standard] vs 9.6 [International Fetal and Newborn Growth Consortium for the 21st Century standard]). CONCLUSION: Our finding did not support the hypothesis that 1 universal standard birthweight curve can be applied to all populations.

The PURPOSe cause of death study in stillbirths and neonatal deaths in India and Pakistan: A review.

The PURPOSe study was a prospective, observational study conducted in India and Pakistan to determine the cause of death for stillbirths and preterm neonatal deaths, using clinical data together with minimally invasive tissue sampling (MITS) and the histologic and polymerase chain reaction (PCR) evaluation of fetal/neonatal tissues and the placenta. After evaluating all available data, an independent panel chose a maternal, a placental and a fetal/neonatal cause of death. Here, we summarise the major results. Among the most important findings were that most stillbirths were caused by fetal asphyxia, often preceded by placental malperfusion, and clinically associated with pre-eclampsia, placental abruption and a small-for-gestational-age fetus. The preterm neonatal deaths were primarily caused by birth asphyxia, followed by various infections. An important finding was that many of the preterm neonatal deaths were caused by a nosocomial infection acquired after neonatal intensive care (NICU) admission; the most common organisms were Acinetobacter baumannii, followed by Klebsiella pneumoniae, Escherichia coli/Shigella and Haemophilus influenzae. Group B streptococcus was less commonly present in the placentas or internal organs of the neonatal deaths.