Definitions, terminology and standards for reporting of births and deaths in the perinatal period: International Classification of Diseases (ICD-11).

Despite efforts to reduce stillbirths and neonatal deaths, inconsistent definitions and reporting practices continue to hamper global progress. Existing data frequently being limited in terms of quality and comparability across countries. This paper addresses this critical issue by outlining the new International Classification of Disease (ICD-11) recommendations for standardized recording and reporting of perinatal deaths to improve data accuracy and international comparison. Key advancements in ICD-11 include using gestational age as the primary threshold to for reporting, clearer guidance on measurement and recording of gestational age, and reporting mortality rates by gestational age subgroups to enable country comparisons to include similar populations (e.g., all births from 154 days [22+0 weeks] or from 196 days [28+0 weeks]). Furthermore, the revised ICD-11 guidance provides further clarification around the exclusion of terminations of pregnancy (induced abortions) from perinatal mortality statistics. Implementing standardized recording and reporting methods laid out in ICD-11 will be crucial for accurate global data on stillbirths and perinatal deaths. Such high-quality data would both allow appropriate regional and international comparisons to be made and serve as a resource to improve clinical practice and epidemiological and health surveillance, enabling focusing of limited programmatic and research funds towards ending preventable deaths and improving outcomes for every woman and every baby, everywhere.

Whole Exome Sequencing Revealing a Novel PBX1 Gene Variant in a Chinese Family Causing Recurrent Neonatal Death.

BACKGROUND: Causative mutations of PBX1 are associated with congenital abnormalities of the kidney and urinary tract (CAKUT), often accompanied by hearing loss, abnormal ear morphology, or developmental delay. The aim of the present investigation was to introduce a novel variant in the PBX1 gene identified in a Chinese family, leading to recurrent neonatal mortality. METHODS: A pregnant woman (gravida 5, para 0), who had experienced recurrent neonatal deaths, sought genetic etiology diagnosis. Whole exome sequencing (WES) was conducted to identify sequence variants and copy number variants in the fetus presenting with posterior nuchal cystic hygroma and fetal hydrops. RESULTS: A novel NM_002585.4:c.694G>C(p.D232H) in PBX1 was identified in the fetus through trio whole exome sequencing (WES), revealing a paternal mosaic PBX1 variant in blood at 11.54% (6/52 variants reads). Subsequent parental Sanger sequencing confirmed the variant detected by WES. Ultimately, the variant was classified as likely pathogenic, leading the family to elect pregnancy termination at 17 weeks gestation. CONCLUSION: The novel variant in the PBX1 gene appears to be a significant factor contributing to recurrent neonatal deaths in the Chinese family. Such findings expand the spectrum of PBX1 gene variants and provide valuable perinatal guidance for diagnosing fetuses with PBX1 mutations.

Seroprevalence of canid alphaherpesvirus-1 and associated risk factors in domestic dogs in North Queensland, Australia.

Canid alphaherpesvirus-1 (CaHV-1) may cause a highly fatal haemorrhagic disease in neonatal pups and is associated with reproductive, respiratory and ocular disease in older dogs. Although assumed to have a world-wide distribution, there have been few reports of CaHV-1 in Australia. The aim of this study was to investigate the seroprevalence of CaHV-1 in household dogs in a residential suburb in Townsville, as well as in dogs attending two dog shows in the region. Study participants were recruited through door-to-door non-probability sampling (Douglas dogs, n = 185) or invited to participate (Show dogs; n = 76). Dog owners completed a questionnaire that investigated possible risk factors for recent exposure to CaHV-1. A serum sample from each dog was assayed for anti-CaHV-1 antibodies using a commercially available ELISA. Associations between seropositive dogs and owner-reported risk factors were analysed using univariable analysis and multivariable logistic regression models. The seroprevalence of CaHV-1 was 11.4 % (95 % CI 6.8-15.9 %) and 17.1 % (95 % CI 5.5-28.8) for the Douglas and Show dogs, respectively, with a pooled seroprevalence of 13 % (95 % CI 8.3-17.7 %). Dogs that had suffered from conjunctivitis within the previous 3 months or were involved in breeding were more likely to be seropositive to CaHV-1. No other significant risk factors were identified. In conclusion, CaHV-1 is circulating in dogs in North Queensland and may be contributing to foetal and neonatal losses in this region.

Utilizing Repetitive Serial Placental Ultrasounds for Diagnosing a Massive Subchorionic Thrombohematoma: Insights Into Soluble FMS-Like Tyrosine Kinase-1/Placental Growth Factor (sFlt-1/PlGF) Trends.

The patient, a 34-year-old primigravida with no prior medical history, presented at 23 + 0 weeks with gestational hypertension and fetal growth restriction (FGR). Ultrasound examination showed a placental mass, and subsequent repeated ultrasound scans revealed changes in the mass' echogenicity, raising suspicion of a massive subchorionic thrombohematoma (MST). While the blood pressure was mildly elevated without proteinuria and organ dysfunctions, serum soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratios showed significantly elevated values. A cesarean section was performed at 29 + 2 weeks due to the nonreassuring fetal status. The female infant, with Apgar scores of 1/1 at one/five minutes and an umbilical artery pH of 7.16, remained unresponsive and died seven hours postdelivery. Pathology examination revealed a massive hematoma in the subchorionic space, measuring 22 mm thick, directly beneath the umbilical cord attachment. This case underscores the importance of repetitive placental ultrasound in MST diagnosis and suggests the potential utility of sFlt-1/PlGF ratios in predicting adverse outcomes.

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.

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.

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.

Co-Twin Prognosis After Single Intrauterine Fetal Death at a Tertiary Care Hospital in India: A Retrospective Observational Study.

INTRODUCTION: Twin pregnancy is associated with an increased risk of perinatal morbidity. Besides, if intrauterine death of a single twin occurs, it increases the morbidity of the surviving co-twin perinatally and postnatally. AIM:  The objective of this study was to determine the incidence of single intrauterine fetal death (SIUFD) in a twin pregnancy and fetal outcome defined in dimensions according to the complications in the surviving co-twin. MATERIAL AND METHODS: Data on twin pregnancies were collected retrospectively for a period of five years (from 2015 to 2019) from the labour room records of the Central Records Department (CRD) at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Cases with SIUFD were studied individually and neonatal follow-up was taken post delivery for up to three to eight years. Inclusion criteria were SIUFD in twin pregnancies after 14 weeks gestation, chorionicity pre-defined by early trimester ultrasonography. Exclusion criteria were higher-order pregnancy and monoamniotic twins. RESULTS: A total of 1246 (4.273%) twin deliveries were conducted in the study period. Of these, 107 (8.587%) pregnancies had SIUFD with co-twin surviving in utero. Among these, 77 (72%) were dichorionic diamniotic (DCDA) twin pregnancies and 30 (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The incidence of SIUFD was 8.5%. Preterm birth was the most common complication observed in our study and was found in 53.5% and 58.3% of participants in DCDA and MCDA twins, respectively. Early neonatal death (within 24 hours of life) of the surviving twin was found in 29.2% monochorionic twins with SIUFD. SIUFD at < 28 weeks gestation led to a greater number of early neonatal deaths of surviving twins. The incidence of neurodevelopmental disorders (cerebral palsy, developmental delay, epilepsy) in our population after birth was 7.5% (n=93). CONCLUSION: Twin pregnancies with SIUFD have an increased incidence of preterm labour, increased neonatal death of the surviving twin, and neurodevelopmental disorders (cerebral palsy, developmental delay, epilepsy). Monochorionicity and SIUFD at <28 weeks gestation are associated with increased neonatal deaths in co-twin. The Incidence of neurodevelopmental disorders is not directly associated with chorionicity, but developmental delay is more profoundly seen in the monochorionic group.

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.

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.

Care, connection, and social distancing: The challenges of baby loss during the COVID-19 pandemic in Aotearoa New Zealand.

PROBLEM: The COVID-19 pandemic hindered access to routine healthcare globally, prompting concerns about possible increases in pregnancy loss and perinatal death. BACKGROUND: PUDDLES is an international collaboration exploring the impact of the COVID-19 pandemic on parents who experience pregnancy loss and perinatal death in seven countries, including Aotearoa New Zealand. AIM: To explore parents' experiences of access to healthcare services and support following baby loss during the COVID-19 pandemic in Aotearoa New Zealand. METHODS: We conducted in-depth, semi-structured interviews with 26 bereaved parents, including 20 birthing mothers, and six non-birthing parents (one mother and five fathers). Types of loss included 15 stillbirths, four late miscarriages, and one neonatal death. Participant ethnicities were broadly representative of Aotearoa New Zealand's multi-ethnic society. Data were analysed using Template Analysis. FINDINGS: Analysis revealed five themes relating to pandemic impact on bereaved parent's experiences. These were: 'Distanced and Impersonal care'; 'Navigating Hospital Rules'; Exclusion of Non-birthing Parents; 'Hindered Access to Social Support'; and 'Continuity of Relational Care'. DISCUSSION: The COVID-19 pandemic exacerbated isolation of bereaved parents through perceived impersonal care by healthcare professionals and restrictions on movement hindered access to social and cultural support. Compassionate bending of the rules by healthcare professionals and community postnatal visits by continuity of care midwives following the bereavement appeared to be mitigating factors. CONCLUSION: Social isolation is an added challenge for parents experiencing baby loss during a pandemic, which may be mitigated by flexible and compassionate care from healthcare professionals, especially continuity of care midwives.

Maintaining Parental Roles During Neonatal End-of-Life Care: A Review of the Literature.

Parents who are experiencing neonatal death need support in promoting and maintaining their parental role. This includes parenting their infant during end-of-life. Bedside nurses should partner with parents to help them maintain the parent-infant relationship by establishing effective communication, building trust, and promoting the parental role. By doing so, parents will utilize these experiences to process their grief through meaning-making.

Implementing palliative care, based on family-centered care, in a highly complex neonatal unit

Abstract Objective: To describe the causes and circumstances of neonatal mortality and determine whether the implementation of a palliative care protocol has improved the quality of end-of-life care. Methods: A retrospective observational study including all patient mortalities between January 2009 and December 2019. Cause of death and characteristics of support during the dying process were collected. Two periods, before and after the implementation of a palliative care protocol, were compared. Results: There were 344 deaths. Congenital malformations were the most frequent cause of death (45.6 %). Most patients died after the transition to palliative care (74.4 %). The most frequently cited criteria for initiating transition of care was poor neurocognitive prognosis (47.2 %). Parents accompanied their children in the dying process in 72 % of cases. Twenty-three percent of patients died outside the Neonatal Intensive Care Unit after being transferred to a private room to enhance family intimacy. After the addition of the palliative care protocol, statistically significant differences were observed in the support and patient experience during the dying process. Conclusions: The most frequent causes of death were severe congenital malformations. Most patients died accompanied by their parents after the transition to palliative care. The implementation of a palliative care protocol helped to improve the family-centered end-of-life care.

The influence of birthweight on mortality and severe neonatal morbidity in late preterm and term infants: an Australian cohort study.

Background: The aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. Methods: This was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000 and 2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests. Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. Findings: The final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0.19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants <1st centile (perinatal mortality rate 13.2/1000 births, adjusted Relative Risk Ratio (aRRR) of 12.96 (95% CI 10.14, 16.57) for stillbirth and aRRR 7.55 (95% CI 3.78, 15.08) for neonatal death). Severe neurological morbidity occurred in 7311 infants (0.74%), with the highest rate (19.6/1000 live births) in <1st centile cohort. There were 75,243 cases of severe morbidity (7.59% livebirths), with the peak incidence occurring in the <1st centile category (12.3% livebirths). The majority of adverse outcomes occurred in infants with birthweights between 10 and 90th centile. Almost 2 in 3 stillbirths, and approximately 3 in 4 cases of neonatal death, severe neurological morbidity or other severe morbidity occurred within this birthweight range. Interpretation: Although the incidence and risk of perinatal mortality, severe neurological morbidity and severe morbidity increased at the extremes of birthweight centiles, the majority of these outcomes occurred in infants that were apparently "appropriately grown" (i.e., birthweight 10th-90th centile). Funding: National Health and Medical Research Council, Mater Foundation, Royal Australian College of Obstetricians and Gynaecologists Women's Health Foundation - Norman Beischer Clinical Research Scholarship, Cerebral Palsy Alliance, University of Queensland Research Scholarship.

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.

Amnioreduction for Polyhydramnios in a Consecutive Series at a Single Center: Indications, Risks and Perinatal Outcomes.

Pregnancies complicated by severe polyhydramnios are associated with a high rate of underlying fetal anomaly. Amnioreduction may be offered to alleviate maternal symptoms. This is a retrospective study of amnioreductions performed on singleton and twin gestations complicated by symptomatic polyhydramnios between 2010 and 2023 at our tertiary referral center. The indications, procedural techniques and pregnancy and neonatal outcomes were retrieved from an archive database and reviewed with the use of the maternal and child medical record chart, the hospital electronic clinical discharge report and telephone recalls. Our study comprised 86 pregnancies, 65 singletons and 21 twin pregnancies. Fetal anomalies were identified in 79% of cases, mainly gastrointestinal obstructive anomalies; 9.3% of cases were idiopathic. The median gestational age at first amnioreduction was 32.5 weeks, and peri-procedural complications were rare (1 case of placental abruption and 2 cases of preterm delivery). The median gestational age at delivery was 36.5 weeks, with a median prolongation of the pregnancy from the time of first drain until birth of 30 days. Preterm labor < 37 weeks occurred in 48.8% of procedures, with 26.7% of patients delivering before 34 weeks and pPROM < 36 weeks recorded in 23.2% of cases. In conclusion, amnioreduction offered to alleviate maternal symptoms is a reasonably safe procedure with a low complication rate. These pregnancies necessitate management in a tertiary referral center because of their need for a multidisciplinary approach both prenatally and postnatally.

Perinatal outcomes associated with pre-exposure prophylaxis for HIV prevention during pregnancy: a systematic review and meta-analysis.

Background: The World Health Organization (WHO) recommends tenofovir disoproxil fumarate (TDF)-based oral pre-exposure prophylaxis (PrEP), the dapivirine vaginal ring, and long-acting intramuscular injectable cabotegravir (CAB-LA) for HIV prevention in populations at substantial risk of HIV infection. Pregnancy is a period of elevated risk of maternal HIV infection and transmission to the infant. This systematic review and meta-analysis assessed the risk of adverse perinatal outcomes among HIV-negative pregnant women with exposure to any PrEP modality. Methods: We conducted a systematic review by searching Medline, EMBASE, CINAHL, Global Health, the Cochrane Library, WHO ICTR, ISRCTN, PACTR, and ClinicalTrials.gov for studies published between 1 January 2000 and 29 August 2023. We included studies reporting on the association of antenatal exposure to any PrEP modality with 13 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB, spontaneous very PTB, low birthweight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA, miscarriage, stillbirth, or neonatal death (NND). Quality assessments of included studies were performed. Fixed-effect meta-analyses were conducted to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). The protocol is registered with PROSPERO, CRD42022339825. Findings: Of 18,598 citations identified, 13 studies (eight randomised controlled trials (RCTs) and five cohort studies), assessing 8712 pregnant women in Africa, were included. Oral PrEP, compared to no PrEP, was not associated with PTB in meta-analyses of six RCTs (OR 0.73, 95% CI 0.43-1.26; I2 = 0.0%) or five unadjusted cohort studies (OR 0.84, 95% CI 0.69-1.03; I2 = 0.0%), but was associated with a reduced risk of PTB in three adjusted cohort studies (aOR 0.67; 95% CI 0.52-0.88, I2 = 0.0%). There was no association of oral PrEP with LBW, vLBW, SGA, or NND, compared to no PrEP. There was no association with PTB when oral TDF/emtricitabine (FTC) PrEP, oral TDF PrEP, and tenofovir vaginal gel were compared to each other. There was no association of the dapivirine vaginal ring with PTB or NND, compared to placebo or oral TDF/FTC PrEP. We found no data on CAB-LA. Interpretation: We found no evidence of adverse perinatal outcomes associated with PrEP exposure during pregnancy. Our findings support the WHO recommendation to provide oral PrEP to women of reproductive age and pregnant women. More data is needed to assess the safety of all PrEP modalities in pregnancy. Funding: None.

Sudden death with cardiac involvement in a neonate with carnitine-acylcarnitine translocase deficiency.

A female neonate born with normal Apgar scores at 38+2 weeks of gestational age unexpectedly passed away within less than 30 hours after birth. The situation mirrored her brother's earlier demise within 24 hours post-delivery, suggesting a possible genetic disorder. Gross examination revealed widespread cyanosis and distinct yellowish changes on the cardiac ventricles. Histopathological examination disclosed lipid accumulation in the liver, heart, and kidneys. Tandem mass spectrometry detected elevated levels of 10 amino acids and 14 carnitines in cardiac blood. Trio-whole genome sequencing (Trio-WGS) identified the SLC25A20 c.199-10T>G mutation associated with carnitine-acylcarnitine translocase disease (CACTD), a type of fatty acid oxidation disorders (FAODs) with a potential for sudden death. Further validation of gene expression confirmed the functional deficiency of SLC25A20, ultimately diagnosing CACTD as the underlying cause of the neonate's demise. This case highlights the importance of prenatal metabolic and genetic screening for prospective parents and emphasizes the need for forensic doctors to integrate metabolomic and genomic investigations into autopsies for suspected inherited metabolic diseases.

Factors associated with perinatal and neonatal deaths in Sao Tome & Principe: a prospective cohort study.

Background: Neonatal mortality reduction is a global goal, but its factors are seldom studied in most resource-constrained settings. This is the first study conducted to identify the factors affecting perinatal and neonatal deaths in Sao Tome & Principe (STP), the smallest Central Africa country. Methods: Institution-based prospective cohort study conducted at Hospital Dr. Ayres Menezes. Maternal-neonate dyads enrolled were followed up after the 28th day of life (n = 194) for identification of neonatal death-outcome (n = 22) and alive-outcome groups (n = 172). Data were collected from pregnancy cards, hospital records and face-to-face interviews. After the 28th day of birth, a phone call was made to evaluate the newborn's health status. Crude odds ratios and corresponding 95% confidence intervals were obtained. A p value <0.05 was considered statistically significant. Results: The mean gestational age of the death-outcome and alive-outcome groups was 36 (SD = 4.8) and 39 (SD = 1.4) weeks, respectively. Death-outcome group (n = 22) included sixteen stillbirths, four early and two late neonatal deaths. High-risk pregnancy score [cOR 2.91, 95% CI: 1.18-7.22], meconium-stained fluid [cOR 4.38, 95% CI: 1.74-10.98], prolonged rupture of membranes [cOR 4.84, 95% CI: 1.47-15.93], transfer from another unit [cOR 6.08, 95% CI:1.95-18.90], and instrumental vaginal delivery [cOR 8.90, 95% CI: 1.68-47.21], were factors significantly associated with deaths. The odds of experiencing death were higher for newborns with infectious risk, IUGR, resuscitation maneuvers, fetal distress at birth, birth asphyxia, and unit care admission. Female newborn [cOR 0.37, 95% CI: 0.14-1.00] and birth weight of more than 2,500 g [cOR 0.017, 95% CI: 0.002-0.162] were found to be protective factors. Conclusion: Factors such as having a high-risk pregnancy score, meconium-stained amniotic fluid, prolonged rupture of membranes, being transferred from another unit, and an instrumental-assisted vaginal delivery increased 4- to 9-fold the risk of stillbirth and neonatal deaths. Thus, avoiding delays in prompt intrapartum care is a key strategy to implement in Sao Tome & Principe.