Systematic review and meta-analysis: Evaluating the influence of intrahepatic cholestasis of pregnancy on obstetric and neonatal outcomes.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid, particularly glycine conjugate, may compromise blood flow and cause functional hypoxia-ischemia. AIMS: This meta-analysis aims to assess the association between ICP and key pregnancy outcomes including emergency caesarian sections (C-sections), preeclampsia, hemorrhage, preterm birth, small for gestational age, admission rate to neonatal intensive care union (NICU), gestational age, and stillbirth. MATERIALS AND METHODS: Literature search across five databases (PubMed, Embase, Web of Science) was done to detect relevant studies published up until June 2023. Meta-analysis of the identified studies was done using a random-effects model, and the results presented as Odds ratio (OR). RESULTS: A literature search identified 662 studies. Of them, 21 met the inclusion criteria. There was a significant association between ICP and odds of C-section (OR: 1.42, p <0.001), preeclampsia (OR: 2.64, p <0.001), NICU admission (OR: 2.1, p <0.001), and pre-term birth (OR: 2.64, p <0.001). ICP was not associated with postpartum hemmorhage (OR: 1.31, p = 0.13), small for gestational age (OR: 0.87, p = 0.07), stillbirth (OR: 1.49, p = 0.29). CONCLUSIONS: Our results confirm the adverse effects of ICP on co-existing pregnancy complications, obstetric and neonatal outcomes. ICP in associated with severe complications including increased rates of preeclampsia, emergency C-sections, preterm births, l gestational periods and higher rates of NICU admissions. These results may assist healthcare professionals in formulating comprehensive care guidelines for expectant mothers and newborns.

Adverse Pregnancy Outcomes and Subsequent First-Time Use of Psychiatric Treatment Among Fathers in Denmark.

Importance: Becoming a first-time parent is a major life-changing event and can be challenging regardless of the pregnancy outcome. However, little is known how different adverse pregnancy outcomes affect the father's risk of psychiatric treatment post partum. Objective: To examine the associations of adverse pregnancy outcomes with first-time psychiatric treatment in first-time fathers. Design, Setting, and Participants: This nationwide cohort study covered January 1, 2008, to December 31, 2017, with a 1-year follow-up completed December 31, 2018. Data were gathered from Danish, nationwide registers. Participants included first-time fathers with no history of psychiatric treatment. Data were analyzed from August 1, 2022, to February 20, 2024. Exposures: Adverse pregnancy outcomes including induced abortion, spontaneous abortion, stillbirth, small for gestational age (SGA) and not preterm, preterm with or without SGA, minor congenital malformation, major congenital malformation, and congenital malformation combined with SGA or preterm compared with a full-term healthy offspring. Main Outcomes and Measures: Prescription of psychotropic drugs, nonpharmacological psychiatric treatment, or having a psychiatric hospital contact up to 1 year after the end of the pregnancy. Results: Of the 192 455 fathers included (median age, 30.0 [IQR, 27.0-34.0] years), 31.1% experienced an adverse pregnancy outcome. Most of the fathers in the study had a vocational educational level (37.1%). Fathers experiencing a stillbirth had a significantly increased risk of initiating nonpharmacological psychiatric treatment (adjusted hazard ratio [AHR], 23.10 [95% CI, 18.30-29.20]) and treatment with hypnotics (AHR, 9.08 [95% CI, 5.52-14.90]). Moreover, fathers experiencing an early induced abortion (≤12 wk) had an increased risk of initiating treatment with hypnotics (AHR, 1.74 [95% CI, 1.33-2.29]) and anxiolytics (AHR, 1.79 [95% CI, 1.18-2.73]). Additionally, late induced abortion (>12 wk) (AHR, 4.46 [95% CI, 3.13-6.38]) and major congenital malformation (AHR, 1.36 [95% CI, 1.05-1.74]) were associated with increased risk of nonpharmacological treatment. In contrast, fathers having an offspring being born preterm, SGA, or with a minor congenital malformation did not have a significantly increased risk of any of the outcomes. Conclusions and Relevance: The findings of this Danish cohort study suggest that first-time fathers who experience stillbirths or induced abortions or having an offspring with major congenital malformation had an increased risk of initiating pharmacological or nonpharmacological psychiatric treatment. These findings further suggest a need for increased awareness around the psychological state of fathers following the experience of adverse pregnancy outcomes.

Sirenomelia or mermaid syndrome with a cleft lip in a Tanzanian newborn: a case report.

BACKGROUND: Sirenomelia or sirenomelia sequence, also known as mermaid syndrome, is a rare congenital anomaly involving the caudal region of the body. The syndrome is characterized by partial or complete fusion of lower extremities, renal agenesis, absent urinary tract, ambiguous external genitalia, imperforate anus, and single umbilical artery. Sirenomelia is often associated with several visceral congenital malformations, rendering it invariably incompatible with extrauterine life. CASE PRESENTATION: We present the case of 22-year-old Black African woman who delivered a term newborn by caesarean section at a gestation age of 37 weeks due to obstructed labor with fetal distress. The newborn was a fresh stillbirth weighing 2100 g and had fusion of the lower extremities, a single upper limb, ambiguous genitalia, imperforate anus, and a cleft lip. The mother had made only two prenatal visits, at which she was found to be normotensive and normoglycemic. She was not screened for routine fetomaternal infections and missed supplementation for folic acid during the critical first trimester. She did not undergo any obstetric ultrasonography. The parents of the newborn were not close relatives and there was no family history of consanguinity. Further genetic testing was not performed due to lack of laboratory capacity, and post mortem examination was not permitted due to cultural taboo and restrictions relating to handling of deceased newborns. CONCLUSION: Sirenomelia is a rare congenital malformation with very poor prognosis. Specific interventions during pre-conception and early prenatal care are critical in the prevention of specific congenital anomalies. Early obstetric ultrasonography is invaluable for diagnosis of sirenomelia as well as counseling for possible termination of pregnancy.

[Factors influencing inflammatory diseases in the bitch and the survival of her offsprings]. / Einflussfaktoren auf entzündliche Erkrankungen der Mutterhündin und das Überleben ihrer Nachkommen.

INTRODUCTION: Feeding raw meat is becoming increasingly common among dog owners. This feeding practice can pose a hygienic risk and can lead to health risks for dogs and their owners. Hygienically sound food rations, that are balanced in terms of all nutrients and energy, must be feed to breeding dogs. The aim of this study was to record the influence of raw feeding on the occurrence of mastitis, metritis and the survival of puppies. An online questionnaire was sent to kennel club registered dog breeders in Germany and Switzerland. A total of 531 litters were recorded and evaluated. Mastitis and/or metritis were present in 9,2 % and 2,8 % (n = 49 and n = 15, respectively) of the breeding bitches. 29 % (n = 154) of the breeders reported loss of puppies in the litter. The most common cause were stillbirths (n = 105 litters with 187 stillborn puppies), and/or early mortality (n = 50 litters with 73 puppies that died in the first 48 hours). The occurrence of puppy losses in the litter and/or a higher proportion of puppy losses in the litter was favored by increased body weight of the bitch in larger dog breeds, existing previous illnesses, previously reported gestation or postpartum problems, increasing length of the parturition phase and/or a cesarean section. A higher total number of surviving puppies was associated with increased weight and anamnestic reported health of the bitch and the use of milk powder instead of other milk substitutes. A relationship between raw feeding and the occurrence of mastitis, metritis, the total number of surviving puppies and/or the occurrence or proportion of pup losses in the litter and was not found in this study. However very few breeders in this cohort fed their bitches raw, which in turn was due to the random selection of breeders. Many years of breeding experience and the increasing parity of the bitch had a clearly positive influence on the health of the bitch.

INTRODUCTION: L'alimentation à base de viande crue est de plus en plus répandue parmi les propriétaires de chiens. Cette pratique alimentaire peut présenter un risque hygiénique et entraîner des dangers pour la santé des chiens et de leurs propriétaires. Des rations alimentaires hygiéniques et équilibrées en termes de nutriments et d'énergie doivent en particulier être données aux chiens reproducteurs. L'objectif de cette étude était d'enregistrer l'influence de l'alimentation crue sur l'apparition de mammites, de métrites et sur la survie des chiots. Un questionnaire en ligne a été envoyé aux éleveurs de chiens enregistrés auprès d'un club d'élevage en Allemagne et en Suisse. Au total, 531 portées ont été enregistrées et évaluées. Une mammite et/ou une métrite étaient présentes chez 9,2 % et 2,8 % (n = 49 et n = 15, respectivement) des chiennes reproductrices. 29 % (n = 154) des éleveurs ont signalé la perte de chiots dans la portée. La cause la plus fréquente était la mortinatalité (n = 105 portées avec 187 chiots mort-nés) et/ou la mortalité précoce (n = 50 portées avec 73 chiots morts dans les 48 premières heures). Les pertes de chiots dans la portée et/ou une proportion plus élevée de pertes de chiots dans la portée était favorisée par un poids corporel plus élevé de la chienne dans les grandes races de chiens, des maladies antérieures existantes, des problèmes de gestation ou de post-partum déjà signalés, une durée plus longue de la phase de parturition et/ou une césarienne. Un nombre total plus élevé de chiots survivants a été associé à un poids plus élevé et à un état de santé anamnestique de la chienne, ainsi qu'à l'utilisation de lait en poudre plutôt que d'autres substituts du lait. Cette étude n'a pas mis en évidence de lien entre l'alimentation crue et l'apparition de mammites, de métrites, le nombre total de chiots survivants et/ou l'apparition ou la proportion de pertes de chiots dans la portée. Cependant, très peu d'éleveurs de cette cohorte ont nourri leurs chiennes avec des aliments crus, ce qui est dû à la sélection aléatoire des éleveurs. Une longue expérience de l'élevage et l'augmentation de la parité de la chienne ont eu une influence clairement positive sur la santé de la chienne.

Evaluation of an obstetric and neonatal care upskilling program for community health workers in Papua New Guinea.

BACKGROUND: 60% of women in Papua New Guinea (PNG) give birth unsupervised and outside of a health facility, contributing to high national maternal and perinatal mortality rates. We evaluated a practical, hospital-based on-the-job training program implemented by local health authorities in PNG between 2013 and 2019 aimed at addressing this challenge by upskilling community health workers (CHWs) to provide quality maternal and newborn care in rural health facilities. METHODS: Two provinces, the Eastern Highlands and Simbu Provinces, were included in the study. In the Eastern Highlands Province, a baseline and end point skills assessment and post-training interviews 12 months after completion of the 2018 training were used to evaluate impacts on CHW knowledge, skills, and self-reported satisfaction with training. Quality and timeliness of referrals was assessed through data from the Eastern Highlands Province referral hospital registers. In Simbu Province, impacts of training on facility births, stillbirths and referrals were evaluated pre- and post-training retrospectively using routine health facility reporting data from 2012 to 2019, and negative binomial regression analysis adjusted for potential confounders and correlation of outcomes within facilities. RESULTS: The average knowledge score increased significantly, from 69.8% (95% CI:66.3-73.2%) at baseline, to 87.8% (95% CI:82.9-92.6%) following training for the 8 CHWs participating in Eastern Highlands Province training. CHWs reported increased confidence in their skills and ability to use referral networks. There were significant increases in referrals to the Eastern Highlands provincial hospital arriving in the second stage of labour but no significant difference in the 5 min Apgar score for children, pre and post training. Data on 11,345 births in participating facilities in Simbu Province showed that the number of births in participating rural health facilities more than doubled compared to prior to training, with the impact increasing over time after training (0-12 months after training: IRR 1.59, 95% CI: 1.04-2.44, p-value 0.033, > 12 months after training: IRR 2.46, 95% CI:1.37-4.41, p-value 0.003). There was no significant change in stillbirth or referral rates. CONCLUSIONS: Our findings showed positive impacts of the upskilling program on CHW knowledge and practice of participants, facility births rates, and appropriateness of referrals, demonstrating its promise as a feasible intervention to improve uptake of maternal and newborn care services in rural and remote, low-resource settings within the resourcing available to local authorities. Larger-scale evaluations of a size adequately powered to ascertain impact of the intervention on stillbirth rates are warranted.

Chromosome analysis of 303 pregnancy losses in Mexico.

BACKGROUND: Chromosomal abnormalities are present in 50 to 60% of miscarriages and in 6 to 19% of stillbirths. Although microarrays are preferred for studying chromosomal abnormalities, many hospitals cannot offer this methodology. OBJECTIVE: To present the results of the cytogenetic analysis of 303 products of conception (POC), which included 184 miscarriages, 49 stillbirths and 17 cases of undefined age. MATERIAL AND METHODS: Karyotyping, fluorescence in situ hybridization, short tandem repeats and microarrays were used, depending on the type of loss and available sample. RESULTS: In 29 POCs we found maternal tissue and were eliminated from the analyses. Informative results were obtained in 250 (91.2 %)/274 cases; the karyotyping success rate was 80.7%; that of single nucleotide polymorphism microarrays, 94.5%; and that of fluorescence in situ hybridization and short tandem repeat, 100%. Cytogenetic abnormalities were observed in 57.6% of miscarriages and in 24.5% of stillbirths; 94% of total anomalies were numerical and 6% were submicroscopic. CONCLUSIONS: Karyotyping with simultaneous short tandem repeat study to rule out contamination of maternal cells is effective for studying miscarriages; in stillbirths, microarrays are recommended.

ANTECEDENTES: Las alteraciones cromosómicas están presentes en 50 a 60 % de los abortos espontáneos y en 6 a 19 % de los mortinatos. Aunque se prefieren los microarreglos para estudiarlos, numerosos hospitales no pueden ofrecerlos. OBJETIVO: Presentar los resultados del estudio citogenético de 303 productos de la concepción (POC), 184 se obtuvieron de abortos espontáneos, 49 fueron mortinatos y en 17 no se identificó la de edad gestacional. MATERIAL Y MÉTODOS: Se empleó cariotipo, hibridación in situ con fluorescencia, secuencias cortas repetidas en tándem y microarreglos, según el tipo de pérdida y la muestra disponible. RESULTADOS: En 29 POC se encontró tejido materno, por lo que fueron eliminados de los análisis. En 250 (91.2 %)/274 casos se obtuvieron resultados informativos; la tasa de éxito del cariotipo fue de 80.7 %; la de los microarreglos de SNP, de 94.5 %; y la de la hibridación fluorescente in situ y la repetición corta en tándem, de 100 %. Se observaron anomalías citogenéticas en 57.6 % de los abortos espontáneos y en 24.5 % de los mortinatos; 94 % de las anomalías fueron numéricas y 6 %, submicroscópicas. CONCLUSIONES: El cariotipo en conjunto con el estudio de secuencias cortas repetidas en tándem para descartar contaminación de células maternas es efectivo para estudiar abortos espontáneos; los microarreglos se recomiendan en los mortinatos.

Lifestyle and sociodemographic risk factors for stillbirth by region of residence in South Australia: a retrospective cohort study.

BACKGROUND: Stillbirth rates remain a global priority and in Australia, progress has been slow. Risk factors of stillbirth are unique in Australia due to large areas of remoteness, and limited resource availability affecting the ability to identify areas of need and prevalence of factors associated with stillbirth. This retrospective cohort study describes lifestyle and sociodemographic factors associated with stillbirth in South Australia (SA), between 1998 and 2016. METHODS: All restigered births in SA between 1998 ad 2016 are included. The primary outcome was stillbirth (birth with no signs of life ≥ 20 weeks gestation or ≥ 400 g if gestational age was not reported). Associations between stillbirth and lifestyle and sociodemographic factors were evaluated using multivariable logistic regression and described using adjusted odds ratios (aORs). RESULTS: A total of 363,959 births (including 1767 stillbirths) were included. Inadequate antenatal care access (assessed against the Australian Pregnancy Care Guidelines) was associated with the highest odds of stillbirth (aOR 3.93, 95% confidence interval (CI) 3.41-4.52). Other factors with important associations with stillbirth were plant/machine operation (aOR, 1.99; 95% CI, 1.16-2.45), birthing person age ≥ 40 years (aOR, 1.92; 95% CI, 1.50-2.45), partner reported as a pensioner (aOR, 1.83; 95% CI, 1.12-2.99), Asian country of birth (aOR, 1.58; 95% CI, 1.19-2.10) and Aboriginal/Torres Strait Islander status (aOR, 1.50; 95% CI, 1.20-1.88). The odds of stillbirth were increased in regional/remote areas in association with inadequate antenatal care (aOR, 4.64; 95% CI, 2.98-7.23), birthing age 35-40 years (aOR, 1.92; 95% CI, 1.02-3.64), Aboriginal and/or Torres Strait Islander status (aOR, 1.90; 95% CI, 1.12-3.21), paternal occupations: tradesperson (aOR, 1.69; 95% CI, 1.17-6.16) and unemployment (aOR, 4.06; 95% CI, 1.41-11.73). CONCLUSION: Factors identified as independently associated with stillbirth odds include factors that could be addressed through timely access to adequate antenatal care and are likely relevant throughout Australia. The identified factors should be the target of stillbirth prevention strategies/efforts. SThe stillbirth rate in Australia is a national concern. Reducing preventable stillbirths remains a global priority.

Laboratory investigation of causes of bovine abortion and stillbirth in the Republic of Korea, 2014-2020.

Bovine abortion is a critical problem in the cattle industry. Identifying causes of abortion is key to establishing appropriate herd management and prevention strategies. We used pathology examinations, detection of etiologic agents, and serology to determine the cause of bovine abortions in Korea. We analyzed 360 abortion and stillbirth cases submitted to the Animal and Plant Quarantine Agency from December 2014 to January 2020. The putative cause of abortion was identified in 140 of 360 (38.9%) cases; 124 of the 140 (88.6%) cases were attributed to infections. The most common etiologic agents detected were bovine viral diarrhea virus (65 of 360; 18.1%), Coxiella burnetii (19 of 360; 5.3%), Leptospira spp. (13 of 360; 3.6%), Listeria monocytogenes (9 of 360; 2.5%), and Neospora caninum (8 of 360; 2.2%). Minor abortifacient pathogens included Brucella abortus (2 of 360; 0.6%), bovine alphaherpesvirus 1 (2 of 360; 0.6%), Akabane virus (2 of 360, 0.6%), and bovine ephemeral fever virus (1 of 360; 0.3%). Non-infectious conditions included congenital anomalies (7 of 360; 1.9%), goiter (7 of 360; 1.9%), and vitamin A deficiency (2 of 360; 0.6%). Our diagnostic rate in cases with placenta submitted (42 of 86; 48.8%) was significantly higher than in cases without placenta (98 of 274; 35.8%), which highlights the value of submitting placentas. Our results confirm the status of the large variety of causative agents associated with abortions in cattle in Korea.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great interest, as it could have a substantial impact on infant RSV disease burden. In recent years, the clinical development of maternal RSV vaccines has advanced rapidly. OBJECTIVES: To assess the efficacy and safety of maternal respiratory syncytial virus (RSV) vaccination for preventing RSV disease in infants. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register and two other trials registries on 21 October 2022. We updated the search on 27 July 2023, when we searched MEDLINE, Embase, CENTRAL, CINAHL, and two trials registries. Additionally, we searched the reference lists of retrieved studies and conference proceedings. There were no language restrictions on our searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing maternal RSV vaccination with placebo or no intervention in pregnant women of any age. The primary outcomes were hospitalisation with clinically confirmed or laboratory-confirmed RSV disease in infants. The secondary outcomes covered adverse pregnancy outcomes (intrauterine growth restriction, stillbirth, and maternal death) and adverse infant outcomes (preterm birth, congenital abnormalities, and infant death). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (25 study reports) involving 17,991 pregnant women. The intervention was an RSV pre-F protein vaccine in four studies, and an RSV F protein nanoparticle vaccine in two studies. In all studies, the comparator was a placebo (saline, formulation buffer, or sterile water). We judged four studies at overall low risk of bias and two studies at overall high risk (mainly due to selection bias). All studies were funded by pharmaceutical companies. Maternal RSV vaccination compared with placebo reduces infant hospitalisation with laboratory-confirmed RSV disease (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.31 to 0.82; 4 RCTs, 12,216 infants; high-certainty evidence). Based on an absolute risk with placebo of 22 hospitalisations per 1000 infants, our results represent 11 fewer hospitalisations per 1000 infants from vaccinated pregnant women (15 fewer to 4 fewer). No studies reported infant hospitalisation with clinically confirmed RSV disease. Maternal RSV vaccination compared with placebo has little or no effect on the risk of congenital abnormalities (RR 0.96, 95% CI 0.88 to 1.04; 140 per 1000 with placebo, 5 fewer per 1000 with RSV vaccination (17 fewer to 6 more); 4 RCTs, 12,304 infants; high-certainty evidence). Maternal RSV vaccination likely has little or no effect on the risk of intrauterine growth restriction (RR 1.32, 95% CI 0.75 to 2.33; 3 per 1000 with placebo, 1 more per 1000 with RSV vaccination (1 fewer to 4 more); 4 RCTs, 12,545 pregnant women; moderate-certainty evidence). Maternal RSV vaccination may have little or no effect on the risk of stillbirth (RR 0.81, 95% CI 0.38 to 1.72; 3 per 1000 with placebo, no difference with RSV vaccination (2 fewer to 3 more); 5 RCTs, 12,652 pregnant women). There may be a safety signal warranting further investigation related to preterm birth. This outcome may be more likely with maternal RSV vaccination, although the 95% CI includes no effect, and the evidence is very uncertain (RR 1.16, 95% CI 0.99 to 1.36; 6 RCTs, 17,560 infants; very low-certainty evidence). Based on an absolute risk of 51 preterm births per 1000 infants from pregnant women who received placebo, there may be 8 more per 1000 infants from pregnant women with RSV vaccination (1 fewer to 18 more). There was one maternal death in the RSV vaccination group and none in the placebo group. Our meta-analysis suggests that RSV vaccination compared with placebo may have little or no effect on the risk of maternal death (RR 3.00, 95% CI 0.12 to 73.50; 3 RCTs, 7977 pregnant women; low-certainty evidence). The effect of maternal RSV vaccination on the risk of infant death is very uncertain (RR 0.81, 95% CI 0.36 to 1.81; 6 RCTs, 17,589 infants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.

Syncytiotrophoblast Markers Are Downregulated in Placentas from Idiopathic Stillbirths.

The trophoblast cells are responsible for the transfer of nutrients between the mother and the foetus and play a major role in placental endocrine function by producing and releasing large amounts of hormones and growth factors. Syncytiotrophoblast cells (STB), formed by the fusion of mononuclear cytotrophoblasts (CTB), constitute the interface between the foetus and the mother and are essential for all of these functions. We performed transcriptome analysis of human placental samples from two control groups-live births (LB), and stillbirths (SB) with a clinically recognised cause-and from our study group, idiopathic stillbirths (iSB). We identified 1172 DEGs in iSB, when comparing with the LB group; however, when we compared iSB with the SB group, only 15 and 12 genes were down- and upregulated in iSB, respectively. An assessment of these DEGs identified 15 commonly downregulated genes in iSB. Among these, several syncytiotrophoblast markers, like genes from the PSG and CSH families, as well as ALPP, KISS1, and CRH, were significantly downregulated in placental samples from iSB. The transcriptome analysis revealed underlying differences at a molecular level involving the syncytiotrophoblast. This suggests that defects in the syncytial layer may underlie unexplained stillbirths, therefore offering insights to improve clinical obstetrics practice.

Le morti in utero: risultati di un progetto pilota di sorveglianza della mortalità perinatale in Italia (SPItOSS).

OBJECTIVES: to describe the results of a pilot population-based perinatal mortality surveillance system, with regards to stillbirths; to study maternal, obstetric, and foetal characteristics, evaluating risk factors and understanding causes. DESIGN: a cross-sectional study was conducted on incident cases of stillbirths collected by the surveillance system from July 2017 to June 2019 in three Italian Regions (Lombardy, Tuscany, and Sicily). SETTING AND PARTICIPANTS: data on stillbirths, resulting from the in-hospital multidisciplinary audits, organised using the Significant Event Audit methodology, were analysed. According to the World Health Organization (WHO) definitions, the project identified stillbirths as foetuses born dead >=28 weeks of gestation. The WHO International Classification of Diseases-Perinatal Mortality was used to categorise the causes of foetal death. MAIN OUTCOMES MEASURES: maternal characteristics, obstetric and foetal findings were investigated. Unadjusted relative risks and 95% confidence intervals were computed with respect to the background population. Finally, causes of death and contributing maternal conditions have been considered. RESULTS: the maternity and neonatal units of the three participating Regions notified 520 stillbirths, of which 435 cases underwent to the multidisciplinary audit (83.7%); 40.0% of cases occurred in the gestational age range between 36 and 39 weeks. The risk of stillbirth was significantly increased in mothers with foreign citizenship (RR: 1.39; 95%CI: 1.13-1.71), multiple pregnancies (RR: 1.59; 95%CI 1.05-2.42), and pregnancies conceived with assisted reproductive technologies (RR: 2.15; 95%CI 1.45-3.19). The rate of congenital malformations was 6.0%. A diagnosis of foetal growth restriction was reported in 10.3% of cases, although the percentage of dead foetuses weighting <10° centile was at least twice in almost all gestational age periods. Post-mortem and placental histological examinations were carried out in more than 70% and more than 90% of cases, respectively. CONCLUSIONS: the implementation of a population-based surveillance system with high participation rate of maternity units and the use of universally accepted definitions could improve the identification of stillbirth avoidable risk factors and potentially modifiable predisposing maternal conditions, highlighting issues of perinatal assistance in need of improvement.

Looking after bubba for all our mob: Aboriginal and Torres Strait Islander community experiences and perceptions of stillbirth.

The stillbirth rate among Aboriginal and Torres Strait Islander women and communities in Australia is around double that of non-Indigenous women. While the development of effective prevention strategies during pregnancy and improving care following stillbirth for women and families in communities has become a national priority, there has been limited progress in stillbirth disparities. With community permission, this study aimed to gain a better understanding of community experiences, perceptions, and priorities around stillbirth. We undertook an Indigenous researcher-led, qualitative study, with community consultations guided by a cultural protection protocol and within an unstructured research framework. A total of 18 communities were consulted face-to-face through yarning interviews, focus groups and workshops. This included 54 community member and 159 health professional participants across remote, regional, and urban areas of Queensland, Western Australia, Victoria, South Australia, and Northern Territory. Thematic analysis of consultation data identified common themes across five focus/priority areas to address stillbirth: Stillbirth or Sorry Business Baby care needs to be family-centered; using Indigenous "ways of knowing, being, and doing" to ensure cultural safety; application of Birthing on Country principles to maternal and perinatal care; and yarning approaches to improve communication and learning or education. The results underscore the critical need to co-design evidence-based, culturally appropriate, and community-acceptable resources to help reduce existing disparities in stillbirth rates.

Impact of the COVID-19 pandemic on perinatal care and outcomes: A retrospective study in a tertiary hospital in Northern Ghana.

BACKGROUND: Perinatal mortality remains a global challenge. This challenge may be worsened by the negative effects of the COVID-19 pandemic on maternal and child health. OBJECTIVES: Examine the impact of the COVID-19 pandemic on perinatal care and outcomes in the Tamale Teaching Hospital in northern Ghana. METHODS: A hospital-based retrospective study was conducted in the Tamale Teaching Hospital. We compared antenatal care attendance, total deliveries, cesarean sections, and perinatal mortality before the COVID-19 pandemic (March 1, 2019 to February 28, 2020) and during the COVID-19 pandemic (March 1, 2020 to February 28, 2021). Interrupted time series analyses was performed to evaluate the impact of the COVID-19 pandemic on perinatal care and outcomes at TTH. RESULTS: A total number of 35,350 antenatal visits and 16,786 deliveries were registered at TTH from March 2019 to February 2021. Antenatal care, early neonatal death, and emergency cesarean section showed a rapid decline after the onset of the pandemic, with a progressive recovery over the following months. The total number of deliveries and fresh stillbirths showed a step change with a marked decrease during the pandemic, while the macerated stillbirths showed a pulse change, a temporary marked decrease with a quick recovery over time. CONCLUSION: The COVID-19 pandemic had a negative impact on perinatal care and outcomes in our facility. Pregnancy monitoring through antenatal care should be encouraged and continued even as countries tackle the pandemic.

Causes of stillbirths at Kgapane hospital, Limpopo province.

BACKGROUND:  Stillbirths are a global public health challenge, predominantly affecting low- and middle-income countries. The causes of most stillbirths are preventable. OBJECTIVES:  this study reviewed perinatal clinical audit data from Kgapane Hospital over a 4-year period with a special focus on the factors associated with stillbirths. METHODS:  File audits were done for all stillbirths occurring at Kgapane Hospital and its catchment area from 2018 to 2021. The data from these audits were analysed to identify factors associated with stillbirths. RESULTS:  A total of 392 stillbirths occurred during the study period at Kgapane Hospital and its surrounding clinics, resulting in a stillborn rate of 19.06/1000 births. Of the 392 stillbirths recorded, audits were conducted on 354 of the maternal case records. The five most common causes of stillbirths identified were: hypertensive disorders in pregnancy (HDP) (29.7%), intrauterine growth restriction without HDP (11.6%), birth asphyxia (7.1%), premature labour ( 1000 g) (6.5%) and maternal infections (5.9%) including HIV with unsuppressed VL, intrauterine infection, coronavirus disease (COVID) and syphilis. Modifiable factors that can form the basis of improvement strategies should include training, timeous referral, plus improved resources and staffing. CONCLUSION:  Understanding the causes of stillbirths can guide improvement strategies to reduce this heart-breaking complication of pregnancy.Contribution: Family physicians working in rural hospitals are also responsible for perinatal care. Understanding the factors associated with stillbirths will guide them to develop improvement strategies to reduce these preventable deaths.

Obstetric and neonatal outcomes, antiseizure medication profile, and seizure types in pregnant women in a vulnerability state from Brazil.

This retrospective cohort study described the obstetric and neonatal outcomes, antiseizure medication (ASM) use, and types of seizures in pregnant women with epilepsy (PWWE). Data collected from the medical records of 224 PWWE aged < 40 years with controlled or refractory seizures and 492 pregnant women without epilepsy (PWNE) control group from high-risk maternity hospitals in Alagoas between 2008 and 2021 were included in this study. The obstetric and neonatal outcomes observed in PWWE were pregnancy-related hypertension (PrH) (18.4%), oligohydramnios (10.3%), stillbirth (6.4%), vaginal bleeding (6%), preeclampsia (4.7%), and polyhydramnios (3%). There was a greater likelihood of PrH in PWWE with generalized tonic-clonic seizures (GTCS) and that of maternal intensive care unit (ICU) admissions in those with GTCS and status epilepticus, and phenytoin and lamotrigine use. PWWE with GTCS had a higher risk of stillbirth and premature delivery. PWWE with status epilepticus were treated with lamotrigine. Phenobarbital (PB) with diazepam were commonly used in GTCS and status epilepticus. Total 14% patients did not use ASM, while 50.2% used monotherapy and 35.8% used polytherapy. Total 60.9% of patients used PB and 25.2% used carbamazepine. This study described the association between the adverse obstetric and neonatal outcomes and severe seizure types in PWWE.

Trends and geospatial distribution of stillbirths in Uganda, 2014-2020.

INTRODUCTION: Uganda with 17.8 stillbirths per 1,000 deliveries in 2021, is among the countries with a high burden of stillbirths globally. In 2014, Uganda adopted the World Health Organization Every New-born Action Plan (ENAP), which targets < 10 stillbirths per 1,000 deliveries by 2035. Little is known about the trends of stillbirth burden since ENAP was introduced. We assessed the temporal, and spatial distribution of stillbirths, in Uganda, 2014-2020, to inform programming for safe pregnancies and deliveries. METHODS: We obtained and analysed stillbirth surveillance data from the District Health Information System, 2014-2020. A stillbirth was defined as the death of a foetus > 28 weeks of pregnancy or weighing > 1000 g before or during birth and reported to a health facility. We calculated annual incidence rates of stillbirths per 1,000 deliveries at district, regional, and national levels. We used logistic regression to determine the significance of trends. RESULTS: The overall national annual incidence of stillbirths decreased from 24/1,000 deliveries in 2014 to 17/1,000 deliveries in 2020. During the same period, reporting rates declined from 71% in 2014 to 46% in 2020. The central region continuously had the highest incidence rate for the past 5 years despite the largest decline (OR = 0.79; CI = 0.77-0.83, P < 0.001) while the eastern region had the smallest decline (OR = 0.59; CI = 0.57-0.61, P < 0.001). Districts with persistently high annual incidence rates of stillbirths (> 30/1000) included Mubende, Kalangala, Hoima, and Nebbi. There was no difference in the reporting rates of the most- vs. least-affected districts. CONCLUSION: Even with suboptimal reporting, the incidence of stillbirths remained above the national target. Specific areas in the country appear to have particularly high stillbirth rates. We recommend continuous capacity building in managing pregnant women with an emphasis on the most affected districts, and investigation into the reasons for low reporting.

Anti-tumor necrosis factor-α therapy may not be safe during pregnancy in women with inflammatory bowel disease: an updated meta-analysis and systematic review.

BACKGROUND: Inflammatory Bowel Disease (IBD) affects reproductive-aged women. Active disease can lead to decreased fertility. Although the vast majority of international guidelines recommend for the continuation of anti-TNF-α during pregnancy, recent studies have raised concerns about the safety of anti-tumor necrosis factor-α (TNF-α) therapy during pregnancy, both for patients and for physicians. METHODS: Studies that evaluate the safety of anti-TNF-α therapy in pregnant women with IBD were identified using bibliographical searches. An updated meta-analysis was performed for pregnancy outcomes, such as live birth, abortion, still birth, preterm birth, low birth weight, congenital abnormalities, and neonatal infection. Odds ratio (OR) with 95% confidence interval (CI) are reported. Data on disease activity, timing of anti-TNF-α therapy were collected for further analysis. RESULTS: Overall, 11 studies were screened from on-line databases and international meeting abstracts. An increased risk of abortion (OR, 1.33; 95% CI, 1.02-1.74; P = 0.04) and preterm birth (OR, 1.16; 95% CI, 1.05-1.28; P = 0.004), and a decreased risk of live birth (OR, 0.83; 95% CI, 0.74-0.94; P = 0.002]) were found in the anti-TNF-α therapy group compared with the control group (no use of anti-TNF-α therapy). The subgroup analyses based on the disease activity showed there is no significant association between the use of anti-TNF-α therapy during pregnancy on adverse pregnancy outcomes of abortion, preterm birth, and live birth. The rates of still birth, low birth weight, and congenital abnormalities in the anti-TNF-α therapy group were not significantly different from those in the control group. CONCLUSIONS: Anti-TNF-α therapy does not increase the risks of still birth, low birth weight, and congenital abnormalities; however it may be assicated with increased risks of abortion and preterm birth, which are accompanied by a lower rate of live birth. Although these findings may be confounding by potential disease activity, they offer some opposite viewpoints with biologic agent use. Therefore, more studies are required to further confirm the safety of anti-TNF-α therapy in pregnancy with IBD.

Comparison of safety and effectiveness of antiretroviral therapy regimens among pregnant women living with HIV at preconception or during pregnancy: a systematic review and network meta-analysis of randomized trials.

BACKGROUND: Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. RESULTS: We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). CONCLUSIONS: Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

Changes in stillbirths and child and youth mortality in 2020 and 2021 during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has been extensively studied for its impact on mortality, particularly in older age groups. However, the pandemic effects on stillbirths and mortality rates in neonates, infants, children and youth remain poorly understood. This study comprehensively analyses the pandemic influence on young mortality and stillbirths across 112 countries and territories in 2020 and 104 in 2021. METHODS: Using data from civil registers and vital statistics systems (CRVS) and the Health Management Information System (HMIS), we estimate expected mortality levels in a non-pandemic setting and relative mortality changes (p-scores) through generalized linear models. The analysis focuses on the distribution of country-specific mortality changes and the proportion of countries experiencing deficits, no changes and excess mortality in each age group. RESULTS: Results show that stillbirths and under-25 mortality were as expected in most countries during 2020 and 2021. However, among countries with changes, more experienced deficits than excess mortality, except for stillbirths, neonates and those aged 10-24 in 2021, where, despite the predominance of no changes, excess mortality prevailed. Notably, a fifth of examined countries saw increases in stillbirths and a quarter in young adult mortality (20-24) in 2021. Our findings are highly consistent between females and males and similar across income levels. CONCLUSION: Despite global disruptions to essential services, stillbirths and youth mortality were as expected in most observed countries, challenging initial hypotheses. However, the study suggests the possibility of delayed adverse effects that require more time to manifest at the population level. Understanding the lasting impacts of the COVID-19 pandemic requires ongoing, long-term monitoring of health and deaths among children and youth, particularly in low- and lower-middle-income countries.

Paternal and maternal exposures to adverse childhood experiences and spontaneous fetal loss: a nationwide cross-sectional analysis.

BACKGROUND: Adverse childhood experiences (ACEs) might be associated with maternal spontaneous fetal loss, while evidence among Chinese population is limited. This study aims to explore the associations of adverse childhood experiences (ACEs) among women and their spouses with the risk of spontaneous abortion and stillbirth. METHOD: Data were from the China Health and Retirement Longitudinal Study (CHARLS) 2014 survey. ACEs were categorized into intra-familial ACEs and extra-familial ACEs. The associations of maternal and paternal ACEs with women's history of spontaneous abortion and stillbirth were investigated by logistic regression. RESULTS: 7,742 women were included with 9.05% and 2.47% experiencing at least one spontaneous abortion or stillbirth, respectively. Women exposed to 2, 3, and ≥ 4 ACEs were at significantly higher odds of spontaneous abortion, with adjusted odds ratios (ORs) of 1.52 (95% [CI, Confidence Interval] 1.10-2.10), 1.50 (95% CI 1.07-2.09) and 1.68 (95% CI 1.21-2.32), respectively. A significant association between ≥ 4 maternal intra-familial ACEs and stillbirth (OR 2.23, 95% CI 1.12-4.42) was also revealed. Furthermore, paternal exposures to 3 and ≥ 4 overall ACEs were significantly associated with their wives' history of spontaneous abortion, with adjusted ORs of 1.81 (95% CI 1.01-3.26) and 1.83 (95% CI 1.03-3.25), respectively. CONCLUSION: Both maternal and paternal ACEs were associated with spontaneous abortion, and potential mediators might need to be considered to further explore impacts of maternal and paternal ACEs on maternal reproductive health.