Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Prenatal Intravenous Magnesium at 30-34 Weeks' Gestation and Neurodevelopmental Outcomes in Offspring: The MAGENTA Randomized Clinical Trial.

Importance: Intravenous magnesium sulfate administered to pregnant individuals before birth at less than 30 weeks' gestation reduces the risk of death and cerebral palsy in their children. The effects at later gestational ages are unclear. Objective: To determine whether administration of magnesium sulfate at 30 to 34 weeks' gestation reduces death or cerebral palsy at 2 years. Design, Setting, and Participants: This randomized clinical trial enrolled pregnant individuals expected to deliver at 30 to 34 weeks' gestation and was conducted at 24 Australian and New Zealand hospitals between January 2012 and April 2018. Intervention: Intravenous magnesium sulfate (4 g) was compared with placebo. Main Outcomes and Measures: The primary outcome was death (stillbirth, death of a live-born infant before hospital discharge, or death after hospital discharge before 2 years' corrected age) or cerebral palsy (loss of motor function and abnormalities of muscle tone and power assessed by a pediatrician) at 2 years' corrected age. There were 36 secondary outcomes that assessed the health of the pregnant individual, infant, and child. Results: Of the 1433 pregnant individuals enrolled (mean age, 30.6 [SD, 6.6] years; 46 [3.2%] self-identified as Aboriginal or Torres Strait Islander, 237 [16.5%] as Asian, 82 [5.7%] as Maori, 61 [4.3%] as Pacific, and 966 [67.4%] as White) and their 1679 infants, 1365 (81%) offspring (691 in the magnesium group and 674 in the placebo group) were included in the primary outcome analysis. Death or cerebral palsy at 2 years' corrected age was not significantly different between the magnesium and placebo groups (3.3% [23 of 691 children] vs 2.7% [18 of 674 children], respectively; risk difference, 0.61% [95% CI, -1.27% to 2.50%]; adjusted relative risk [RR], 1.19 [95% CI, 0.65 to 2.18]). Components of the primary outcome did not differ between groups. Neonates in the magnesium group were less likely to have respiratory distress syndrome vs the placebo group (34% [294 of 858] vs 41% [334 of 821], respectively; adjusted RR, 0.85 [95% CI, 0.76 to 0.95]) and chronic lung disease (5.6% [48 of 858] vs 8.2% [67 of 821]; adjusted RR, 0.69 [95% CI, 0.48 to 0.99]) during the birth hospitalization. No serious adverse events occurred; however, adverse events were more likely in pregnant individuals who received magnesium vs placebo (77% [531 of 690] vs 20% [136 of 667], respectively; adjusted RR, 3.76 [95% CI, 3.22 to 4.39]). Fewer pregnant individuals in the magnesium group had a cesarean delivery vs the placebo group (56% [406 of 729] vs 61% [427 of 704], respectively; adjusted RR, 0.91 [95% CI, 0.84 to 0.99]), although more in the magnesium group had a major postpartum hemorrhage (3.4% [25 of 729] vs 1.7% [12 of 704] in the placebo group; adjusted RR, 1.98 [95% CI, 1.01 to 3.91]). Conclusions and Relevance: Administration of intravenous magnesium sulfate prior to preterm birth at 30 to 34 weeks' gestation did not improve child survival free of cerebral palsy at 2 years, although the study had limited power to detect small between-group differences. Trial Registration: anzctr.org.au Identifier: ACTRN12611000491965.

Intraventricular Hemorrhage in Very Preterm Children: Mortality and Neurodevelopment at Age 5.

OBJECTIVES: The objectives were to describe mortality and causes of death in children with intraventricular hemorrhage (IVH) and to study neurodevelopmental outcomes. METHODS: The study was a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. Children were recruited in 2011. A standardized assessment was conducted at age 5. Children born before 32 weeks' gestation and admitted to a NICU were eligible. Exposure was IVH defined by the Papile classification. Main outcomes were mortality, causes of death, and neurodevelopmental outcomes at age 5. RESULTS: Among the 3468 children included, 578 (16.7%) had grade 1 IVH, 424 (12.2%) grade 2 IVH, and 114 (3.3%) grade 3 IVH; 144 (4.1%) had intraparenchymal hemorrhage (IPH). Mortality was 29.7% (36 of 114) for children with grade 3 IVH and 74.4% (109 of 144) for those with IPH; 67.6% (21 of 31) and 88.7% (86 of 97) of deaths, respectively, were because of withholding and withdrawing of life-sustaining treatment. As compared with no IVH, low-grade IVH was not associated with measured neurodevelopmental disabilities at age 5. High-grade IVH was associated with moderate and severe neurodevelopmental disabilities, reduced full-scale IQ, and cerebral palsy. CONCLUSIONS: Rates of neurodevelopmental disabilities at age 5 did not differ between children without IVH and those with low-grade IVH. For high-grade IVH, mortality rate was high, mostly because of withholding and withdrawal of life-sustaining treatment, and we found a strong association with overall neurodevelopmental disabilities in survivors.

Preterm neonatal mortality in China during 2009-2018: A retrospective study.

In this retrospective analysis, we aimed to analyze the epidemic characteristics of neonatal mortality due to preterm birth at 28-36 weeks gestation in different regions from 2009 to 2018. Data were obtained from China's Under-5 Child Mortality Surveillance System (U5CMSS). The χ2 trend test, Poisson regression and the Cochran-Mantel-Haenszel method were used in this study. We found that 51.3%, 42.0% and 44.5% of neonate deaths were preterm infants, and immaturity was mainly attributed to 60.1%, 64.1% and 69.5% of these deaths, in the eastern, central and western regions, respectively. The preterm neonatal mortality rate due to immaturity dropped from 149.2, 216.5 and 339.5 in 2009 to 47.4, 83.8 and 170.1 per 100 000 live births in 2018, giving an average annual decline rate of 12.1%, 11.6% and 6.3% in the eastern, central and western regions, respectively, during the studying period. The relative risk of preterm neonatal mortality due to immaturity were 1.3 and 2.3 for the central regions and western regions in 2009-2010, ascending to 2.2 and 3.9 in 2017-2018. The proportion of preterm neonatal deaths with a gestational age <32 weeks was highest among the eastern region. There were significantly more preterm neonatal infants who were not delivered at medical institutions in the western region than in the eastern and central regions. The preterm infant, especially with gestational age <32 weeks, should receive the most attention through enhanced policies and programs to improve child survival. Priority interventions should be region-specific, depending on the availability of economic and healthcare resources.

Incidence and predictors of mortality among neonates referred to comprehensive and specialized hospitals in Amhara regional state, North Ethiopia: a prospective follow-up study.

BACKGROUND: Neonatal mortality is a major global public health problem. Ethiopia is among seven countries that comprise 50 % of global neonatal mortality. Evidence on neonatal mortality in referred neonates is essential for intervention however, there is no enough information in the study area. Neonates who required referral frequently became unstable and were at a high risk of death. Therefore, this study aimed to assess the incidence and predictors of mortality among referred neonates. METHOD: A prospective follow-up study was conducted among 436 referred neonates at comprehensive specialized hospitals in the Amhara regional state, North Ethiopia 2020. All neonates admitted to the selected hospitals that fulfilled the inclusion criteria were included. Face-to-face interviews, observations, and document reviews were used to collect data using a semi-structured questionnaire and checklists. Epi-data™ version 4.2 software for data entry and STATA™ 14 version for data cleaning and analysis were used. Variables with a p-value < 0.25 in the bi-variable logistic regression model were selected for multivariable analysis. Multivariable analyses with a 95% confidence level were performed. Variables with P < 0.05 were considered statistically significant. RESULT: Over all incidence of death in this study was 30.6% with 95% confidence interval of (26.34-35.16) per 2 months observation. About 23 (17.83%) deaths were due to sepsis, 32 (24.80%) premature, 40 (31%) perinatal asphyxia, 3(2.33%) congenital malformation and 31(24.03%) deaths were due to other causes. Home delivery [AOR = 2.5, 95% CI (1.63-4.1)], admission weight < 1500 g [AOR =3.2, 95% CI (1.68-6.09)], travel distance ≥120 min [AOR = 3.8, 95% CI (1.65-9.14)], hypothermia [AOR = 2.7, 95% CI (1.44-5.13)], hypoglycemia [AOR = 1.8, 95% CI (1.11-3.00)], oxygen saturation < 90% [AOR = 1.9, 95% (1.34-3.53)] at admission time and neonate age ≤ 1 day at admission [AOR = 3.4, 95% CI (1.23-9.84) were predictors of neonatal death. CONCLUSION: The incidence of death was high in this study. The acute complications arising during the transfer of referral neonates lead to an increased risk of deterioration of the newborn's health and outcome. Preventing and managing complications during the transportation process is recommended to increase the survival of neonates.

Incidence and determinants of neonatal mortality in the first three days of delivery in northwestern Ethiopia: a prospective cohort study.

BACKGROUND: Addressing sustainable development goals to reduce neonatal mortality remains a global challenge, and it is a concern in Ethiopia. As a result, the goal of this study was to assess the incidence and determinants of neonatal mortality in the first 3 days among babies delivered in the referral hospitals of the Amhara National Regional State. METHODS: A hospital-based prospective cohort study was conducted among 810 neonates in the first 3 days of delivery between March 1 and August 30, 2018. The neonates were followed up from the time of admission to 72 h. Interviewer-administered questionnaires and medical record reviews were conducted for data collection. Data were entered into Epi-data manager version 4.4 and analysed using STATA™ version 16.0. The neonate's survival time was calculated using the Cox-Proportional hazards model. RESULTS: The overall incidence of neonatal mortality in this study was 151/1000 births. Neonatal mortality was significantly higher among neonates whose mothers came between 17 and 28 weeks of gestation for the first visit; among those whose mothers labour was not monitored with a partograph, mothers experienced postpartum haemorrhage and developed a fistula first 24 h, and experienced obstructed labour. However, 39% were less risky among neonates whose mothers were directly admitted and whose mothers had visited health facilities in less than 1-h, both. CONCLUSIONS: This study revealed that approximately 1 in 7 neonates died within the first 3 days of life. The determinants were the timing of the first antenatal visit, quality of labour monitoring, maternal complications, and delay in seeking care. Thus, scaling up evidence-based interventions and harmonising efforts to improve antenatal care quality, promote institutional deliveries, provide optimal essential and emergency obstetric care, and ensure immediate postnatal care may improve neonatal survival.

Association between antenatal corticosteroid use and perinatal mortality among preterm births in hospitals in Tanzania.

OBJECTIVES: The primary aims of this study were to investigate if exposure to antenatal corticosteroids (ACS) was associated with lower rates of perinatal mortality (primary outcome) and other adverse perinatal outcomes (i.e., stillbirth, early neonatal mortality, APGAR score of < 7 at 5 mins, neonatal sepsis and respiratory distress syndrome) in preterm infants in hospitals in Tanzania. We also examine factors associated with administration of ACS among women at risk of preterm delivery. METHODS: A hospital-based prospective chart review study was undertaken in four hospitals located in Nyamagana and Sengerema districts, Tanzania. The study population included all stillborn and live born preterm infants delivered between 24 to 34 weeks of gestation between July 2019 to February 2020. A total 1125 preterm infants were delivered by 1008 women (895 singletons, 230 multiple). Sociodemographic and medical data were recorded from participants' medical records. RESULTS: Three hundred and fifty-six (35.3%) women were administered at least one dose of ACS between 24 to 34 weeks' gestation and 385 (34.2%) infants were exposed to ACS. Infants exposed to ACS had a lower rate of perinatal mortality (13.77%) compared to those who were not exposed (28.38%). Multivariate analysis indicated that infants exposed to ACS were less likely to die during perinatal period, aRR 0.34 (95%CI 0.26-0.44). Only one-third of the sample was provided with ACS. Administration of ACS was associated with maternal education, attending antenatal care more than 3 times, method used to assess gestational age, maternal infection, exposure to maternal antibiotics, delivery mode and level of health facility. CONCLUSION: ACS significantly reduced the risk in perinatal mortality among infants born preterm in a limited resource setting. However, only about one-third of eligible women were provided with ACS, indicating low usage of ACS. Numerous factors were associated with low usage of ACS in this setting.

Incidence, associated risk factors, and the ideal mode of delivery following preterm labour between 24 to 28 weeks of gestation in a low resource setting.

BACKGROUND: Preterm labour, between 24 to 28 weeks of gestation, remains prevalent in low resource settings. There is evidence of improved survival after 24 weeks though the ideal mode of delivery remains unclear. There are no clear management protocols to guide patient management. We sought to determine the incidence of preterm labour occurring between 24 to 28 weeks, its associated risk factors and the preferred mode of delivery in a low resource setting with the aim of streamlining patient care. METHODS: Between February 2020 and September 2020, we prospectively followed 392 women with preterm labour between 24 to 28 weeks of gestation and their newborns from admission to discharge at Kawempe National Referral hospital in Kampala, Uganda. The primary outcome was perinatal mortality associated with the different modes of delivery. Secondary outcomes included neonatal and maternal infections, admission to the Neonatal Special Care Unit (SCU), need for neonatal resuscitation, preterm birth and maternal death. Chi-square test was used to assess the association between perinatal mortality and categorical variables such as parity, mode of delivery, employment status, age, antepartum hemorrhage, digital vaginal examination, and admission to Special Care unit. Multivariate logistic regression was used to assess the association between comparative outcomes of the different modes of delivery and maternal and neonatal risk factors. RESULTS: The incidence of preterm labour among women who delivered preterm babies between 24 to 28 weeks was 68.9% 95% CI 64.2-73.4). Preterm deliveries between 24 to 28 weeks contributed 20% of the all preterm deliveries and 2.5% of the total hospital deliveries. Preterm labour was independently associated with gravidity (p-value = 0.038), whether labour was medically induced (p-value <0.001), number of digital examinations (p-value <0.001), history of vaginal bleeding prior to onset of labour (p-value < 0.001), whether tocolytics were given (p-value < 0.001), whether an obstetric ultrasound scan was done (p-value <0.001 and number of babies carried (p-value < 0.001). At multivariate analysis; multiple pregnancy OR 15.45 (2.00-119.53), p-value < 0.001, presence of fever prior to admission OR 4.03 (95% CI .23-13.23), p-value = 0.002 and duration of drainage of liquor OR 0.16 (0.03-0.87), p-value = 0.034 were independently associated with preterm labour. The perinatal mortality rate in our study was 778 per 1000 live births. Of the 392 participants, 359 (91.5%), had vaginal delivery, 29 (7.3%) underwent Caesarean delivery and 4 (1%) had assisted vaginal delivery. Caesarean delivery was protective against perinatal mortality compared to vaginal delivery OR = 0.36, 95% CI 0.14-0.82, p-value = 0.017). The other protective factors included receiving antenatal corticosteroids OR = 0.57, 95% CI 0.33-0.98, p-value = 0.040, Doing 3-4 digital exams per day, OR = 0.41, 95% 0.18-0.91, p-value = 0.028) and hospital stay of > 7 days, p value = 0.001. Vaginal delivery was associated with maternal infections, postpartum hemorrhage, and admission to the Special Care Unit. CONCLUSION: Caesarean delivery is the preferred mode of delivery for preterm deliveries between 24 to 28 weeks of gestation especially when labour is not established in low resource settings. It is associated with lesser adverse pregnancy outcomes when compared to vaginal delivery for remote gestation ages.

Bias in comparisons of mortality among very preterm births: A cohort study.

BACKGROUND: Several studies of prenatal determinants and neonatal morbidity and mortality among very preterm births have resulted in unexpected and paradoxical findings. We aimed to compare perinatal death rates among cohorts of very preterm births (24-31 weeks) with rates among all births in these groups (≥24 weeks), using births-based and fetuses-at-risk formulations. METHODS: We conducted a cohort study of singleton live births and stillbirths ≥24 weeks' gestation using population-based data from the United States and Canada (2006-2015). We contrasted rates of perinatal death between women with or without hypertensive disorders, between maternal races, and between births in Canada vs the United States. RESULTS: Births-based perinatal death rates at 24-31 weeks were lower among hypertensive than among non-hypertensive women (rate ratio [RR] 0.67, 95% CI 0.65-0.68), among Black mothers compared with White mothers (RR 0.94, 95%CI 0.92-0.95) and among births in the United States compared with Canada (RR 0.74, 95%CI 0.71-0.75). However, overall (≥24 weeks) perinatal death rates were higher among births to hypertensive vs non-hypertensive women (RR 2.14, 95%CI 2.10-2.17), Black vs White mothers (RR 1.86, 95%CI 184-1.88;) and births in the United States vs Canada (RR 1.08, 95%CI 1.05-1.10), as were perinatal death rates based on fetuses-at-risk at 24-31 weeks (RR for hypertensive disorders: 2.58, 95%CI 2.53-2.63; RR for Black vs White ethnicity: 2.29, 95%CI 2.25-2.32; RR for United States vs Canada: 1.27, 95%CI 1.22-1.30). CONCLUSION: Studies of prenatal risk factors and between-centre or between-country comparisons of perinatal mortality bias causal inferences when restricted to truncated cohorts of very preterm births.

Rheumatic heart disease in pregnancy and neonatal outcomes: A systematic review and meta-analysis.

PURPOSE: Associations between rheumatic heart disease (RHD) in pregnancy and fetal outcomes are relatively unknown. This study aimed to review rates and predictors of major adverse fetal outcomes of RHD in pregnancy. METHODS: Medline (Ovid), Pubmed, EMcare, Scopus, CINAHL, Informit, and WHOICTRP databases were searched for studies that reported rates of adverse perinatal events in women with RHD during pregnancy. Outcomes included preterm birth, intra-uterine growth restriction (IUGR), low-birth weight (LBW), perinatal death and percutaneous balloon mitral valvuloplasty intervention. Meta-analysis of fetal events by the New-York Heart Association (NYHA) heart failure classification, and the Mitral-valve Area (MVA) severity score was performed with unadjusted random effects models and heterogeneity of risk ratios (RR) was assessed with the I2 statistic. Quality of evidence was evaluated using the GRADE approach. The study was registered in PROSPERO (CRD42020161529). FINDINGS: The search identified 5949 non-duplicate records of which 136 full-text articles were assessed for eligibility and 22 studies included, 11 studies were eligible for meta-analyses. In 3928 pregnancies, high rates of preterm birth (9.35%-42.97%), LBW (12.98%-39.70%), IUGR (6.76%-22.40%) and perinatal death (0.00%-9.41%) were reported. NYHA III/IV pre-pregnancy was associated with higher rates of preterm birth (5 studies, RR 2.86, 95%CI 1.54-5.33), and perinatal death (6 studies, RR 3.23, 1.92-5.44). Moderate /severe mitral stenosis (MS) was associated with higher rates of preterm birth (3 studies, RR 2.05, 95%CI 1.02-4.11) and IUGR (3 studies, RR 2.46, 95%CI 1.02-5.95). INTERPRETATION: RHD during pregnancy is associated with adverse fetal outcomes. Maternal NYHA III/IV and moderate/severe MS in particular may predict poor prognosis.

Does Birth Interval Matter in Under-Five Mortality? Evidence from Demographic and Health Surveys from Eight Countries in West Africa.

In sub-Saharan Africa (SSA), every 1 in 12 children under five dies every year compared with 1 in 147 children in the high-income regions. Studies have shown an association between birth intervals and pregnancy outcomes such as low birth weight, preterm birth, and intrauterine growth restriction. In this study, we examined the association between birth interval and under-five mortality in eight countries in West Africa. A secondary analysis of the Demographic and Health Survey (DHS) data from eight West African countries was carried out. The sample size for this study comprised 52,877 childbearing women (15-49 years). A bivariate logistic regression analysis was carried out and the results were presented as crude odds ratio (cOR) and adjusted odds ratios (aOR) at 95% confidence interval (CI). Birth interval had a statistically significant independent association with under-five mortality, with children born to mothers who had >2 years birth interval less likely to die before their fifth birthday compared to mothers with ≤2 years birth interval [cOR = 0.56; CI = 0.51 - 0.62], and this persisted after controlling for the covariates [aOR = 0.55; CI = 0.50 - 0.61]. The country-specific results showed that children born to mothers who had >2 years birth interval were less likely to die before the age of five compared to mothers with ≤2 years birth interval in all the eight countries. In terms of the covariates, wealth quintile, mother's age, mother's age at first birth, partner's age, employment status, current pregnancy intention, sex of child, size of child at birth, birth order, type of birth, and contraceptive use also had associations with under-five mortality. We conclude that shorter birth intervals are associated with higher under-five mortality. Other maternal and child characteristics also have associations with under-five mortality. Reproductive health interventions aimed at reducing under-five mortality should focus on lengthening birth intervals. Such interventions should be implemented, taking into consideration the characteristics of women and their children.

Prevalence of common symptoms of neonatal illness in Northwest Ethiopia: A repeated measure cross-sectional study.

BACKGROUND: The neonatal period is the most vulnerable stage of life. In Ethiopia, neonatal illness is common and the reduction in neonatal mortality is not as significant as for under-five mortality. OBJECTIVES: To determine the prevalence and factors associated with neonatal illness symptoms reported by mothers delivering in health facilities in Northwest Ethiopia. METHODS: A repeated measure cross-sectional study design was employed to collect data from 358 randomly selected deliveries in 11 health facilities from November 2018 to March 2019. A pretested and interviewer-administered structured questionnaire adapted from the literature was employed to record neonatal outcomes (illnesses and/or deaths) at birth, 24 hours, 7th, 14th and 28th day from birth. Cleaned data was exported to STATA version 14 software for analysis. Multilevel analysis was used to identify individual and facility-level characteristics associated with neonatal illness symptoms. RESULTS: The prevalence of neonatal illness symptoms was 27.8% (95% CI; 23.2, 32.8) of the 338 babies born alive and the neonatal mortality rate was 41/1000 live births (14/338). The most common symptoms or conditions of neonatal illness reported by mothers' in the study area were possible serious bacterial infections (95.8%, 90/94), localized bacterial infections (43.6%, 41/94), low birth weight (23.4%, 22/94), diarrhea (18.1%, 17/94), prematurity (14.9%, 14/94), and jaundice (7.5%, 7/94). Among the babies who died, neonates who had possible serious bacterial infections, low birth weight, localized bacterial infections, and prematurity took the highest proportions with 100% (14/14), 64.3% (9/14), 50% (7/14), and 42.9% (6/14), respectively. Having a maximum of 3 children (AOR = 1.96; 95% CI = 1.1-3.6), having twins or triplets during pregnancy (AOR = 2.43; 95% CI = 1.1-6.1), and lack of antenatal counseling (AOR = 1.83; 95% CI = 1.1-3.3) were among the maternal factors associated with neonatal illness. Having low birth length (AOR = 7.93; 95% CI = 3.6-17.3), and having a poor breastfeeding quality (AOR = 2.37; 95% CI = 1.4-4.0) were found to be the neonatal factors associated with neonatal illness. CONCLUSIONS: This study indicated a high prevalence of neonatal illness symptoms in Northwest Ethiopia. Therefore, early detection, referral and better management of symptoms or conditions with a high mortality, like sepsis and low birth weight are compulsory to save the lives of many neonates. Strengthening the health extension programme to improve antenatal care service utilization and breastfeeding quality of neonates among postpartum women is crucial.

Factors associated with neonatal mortality in a tertiary hospital in Phnom Penh, Cambodia.

This study aimed to identify hospital neonatal mortality rate (NMR) and the causes of neonatal deaths, and to understand risk factors associated with neonatal mortality in a national tertiary hospital in Cambodia. The study included all newborn infants, aged 0-28 days old, hospitalized in the Pediatrics department of Khmer-Soviet Friendship Hospital between January 2016 and December 2017. In total, 925 infants were included in the study. The mean gestational age was 35.9 weeks (range, 24-42 weeks). Preterm infants and low birth weight accounted for 47.5% and 56.7%, respectively. With respect to payment methods, the government (53.5%) and non-governmental organizations (NGO) (13.7%) paid the fees as the families were not in a financial position to do so. The hospital NMR at the Pediatrics department was 9.3%. Respiratory distress syndrome (37.2%) was the main cause of deaths followed by hypoxic-ischemic encephalopathy (31.4%) and neonatal infection (21.0%). Factors associated with neonatal mortality were Apgar score at 5th minute <7 (adjusted odds ratio (AOR) = 3.57), payment by the government or NGO (AOR = 11.32), admission due to respiratory distress (AOR = 11.94), and hypothermia on admission (AOR = 9.41). The hospital NMR in the Pediatrics department was 9.3% (95% confidence interval 7.50-11.35) at Khmer-Soviet Friendship Hospital; prematurity and respiratory distress syndrome were the major causes of neonatal mortality. Introducing continuous positive airway pressure machine for respiratory distress syndrome and creating neonatal resuscitation guidelines and preventing hypothermia in delivery rooms are required to reduce the high NMR.

Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations.

Importance: Adverse long-term outcomes in individuals born before full gestation are not confined to individuals born at extreme gestational ages. Little is known regarding mortality patterns among individuals born in the weeks close to ideal gestation, and the exact causes are not well understood; both of these are crucial for public health, with the potential for modification of risk. Objective: To examine the risk of all-cause and noncommunicable diseases (NCD) deaths among young adults born preterm and early term. Design, Setting, and Participants: This multinational population-based cohort study used nationwide birth cohorts from Norway, Sweden, Denmark, and Finland for individuals born between 1967 and 2002. Individuals identified at birth who had not died or emigrated were followed up for mortality from age 15 years to 2017. Analyses were performed from June 2019 to May 2020. Exposures: Categories of gestational age (ie, moderate preterm birth and earlier [23-33 weeks], late preterm [34-36 weeks], early term [37-38 weeks], full term [39-41 weeks] and post term [42-44 weeks]). Main Outcomes and Measures: All-cause mortality and cause-specific mortality from NCD, defined as cancer, diabetes, chronic lung disease, and cardiovascular disease (CVD). Results: A total of 6 263 286 individuals were followed up for mortality from age 15 years. Overall, 339 403 (5.4%) were born preterm, and 3 049 100 (48.7%) were women. Compared with full-term birth, the adjusted hazard ratios (aHRs) for all-cause mortality were 1.44 (95% CI, 1.34-1.55) for moderate preterm birth and earlier; 1.23 (95% CI, 1.18-1.29) for late preterm birth; and 1.12 (95% CI, 1.09-1.15) for early-term birth. The association between gestational age and all-cause mortality were stronger in women than in men (P for interaction = .03). Preterm birth was associated with 2-fold increased risks of death from CVD (aHR, 1.89; 95% CI, 1.45-2.47), diabetes (aHR, 1.98; 95% CI, 1.44-2.73), and chronic lung disease (aHR, 2.28; 95% CI, 1.36-3.82). The main associations were replicated across countries and could not be explained by familial or individual confounding factors. Conclusions and Relevance: The findings of this study strengthen the evidence of increased risk of death from NCDs in young adults born preterm. Importantly, the increased death risk was found across gestational ages up to the ideal term date and includes the much larger group with early-term birth. Excess mortality associated with shorter gestational age was most pronounced for CVDs, chronic lung disease, and diabetes.

Antenatal N-acetylcysteine to improve outcomes of premature infants with intra-amniotic infection and inflammation (Triple I): randomized clinical trial.

BACKGROUND: Intrauterine infection and/or inflammation (Triple I) is an important cause of preterm birth (PTB) and adverse newborn outcomes. N-acetylcysteine (NAC) is a Food and Drug Administration (FDA)-approved drug safely administered to pregnant women with acetaminophen toxicity. METHODS: We conducted a single-center, quadruple-blind, placebo-controlled trial of pregnant women with impending PTB due to confirmed Triple I. Participants (n = 67) were randomized to an intravenous infusion of NAC or placebo mimicking the FDA-approved regimen. Outcomes included clinical measures and mechanistic biomarkers. RESULTS: Newborns exposed to NAC (n = 33) had significantly improved status at birth and required less intensive resuscitation compared to placebo (n = 34). Fewer NAC-exposed newborns developed two or more prematurity-related severe morbidities [NAC: 21% vs. placebo: 47%, relative risk, 0.45; 95% confidence interval (CI) 0.21-0.95] with the strongest protection afforded against bronchopulmonary dysplasia (BPD, NAC: 3% vs. placebo: 32%, relative risk, 0.10; 95% CI: 0.01-0.73). These effects were independent of gestational age, birth weight, sex, or race. Umbilical cord plasma NAC concentration correlated directly with cysteine, but not with plasma or whole blood glutathione. NAC reduced the placental expression of histone deacetylase-2, suggesting that epigenetic mechanisms may be involved. CONCLUSIONS: These data provide support for larger studies of intrapartum NAC to reduce prematurity-related morbidity. IMPACT: In this randomized clinical trial of 65 women and their infants, maternal intravenous NAC employing the FDA-approved dosing protocol resulted in lower composite neonatal morbidity independent of gestational age, race, sex, and birthweight. Administration of NAC in amniocentesis-confirmed Triple I resulted in a remarkably lower incidence of BPD. As prior studies have not shown a benefit of postnatal NAC in ventilated infants, our trial highlights the critical antenatal timing of NAC administration. Repurposing of NAC for intrapartum administration should be explored in larger clinical trials as a strategy to improve prematurity-related outcomes and decrease the incidence of BPD.

Temporal heterogeneity of placental segmental fetal vascular malperfusion: timing but not etiopathogenesis.

Clinicopathologic correlations of segmental villous avascularity and other histological lesions of segmental fetal vascular malperfusion (SFVM) were analyzed retrospectively to determine whether lesions of various durations reflect different etiopathogeneses. The frequencies of 25 independent clinical and 43 placental phenotypes were statistically compared by ANOVA or Chi-square among 3 groups containing a total of 378 placentas with SFVM: group 1 contained 44 cases of recent SFVM (endothelial fragmentation, villous hypovascularity by CD34 immunostain, and/or stromal vascular karyorrhexis); group 2 contained 264 cases of established SFVM (clusters of avascular villi); and group 3 contained 70 cases of remote SFVM (villous mineralization). Statistically significant differences among the three study groups (p Bonferroni < 0.002) were found in four clinical variables (gestational age, frequencies of macerated stillbirth, induction of labor, and cesarean section) and in five placental variables (frequencies of fetal vascular ectasia, stem vessel luminal vascular abnormalities, diffusely increased extracellular matrix in chorionic villi, chorionic disk extravillous trophoblast microcysts, and excessive extravillous trophoblasts in the chorionic disc). In summary, the absence of statistically significant differences between the study groups regarding the most common causes of SFVM (hypertensive conditions of pregnancy, diabetes mellitus, fetal anomalies, and clinical and pathological features of umbilical cord compromise) is evidence that the three types of SFVM reflect temporal heterogeneity rather than etiopathogenesis. This evidence can be used to date the onset of fetal vascular malperfusion before delivery or stillbirth. The coexistence of different SVFM lesions of various durations indicates ongoing or repeat occurrences of FVM rather than single episodes.

Short-term efficacy of umbilical cord milking in preterm infants: systematic review and meta-analysis.

BACKGROUND: To systematically evaluate short-term efficacy of UCM versus other interventions in preterm infants. METHODS: Six engines were searched until February 2020 for randomized controlled trials (RCTs) assessing UCM versus immediate cord clamping (ICC), delayed cord clamping (DCC), or no intervention. Primary outcomes were overall mortality, intraventricular hemorrhage (IVH), and patent ductus arteriosus (PDA); secondary outcomes were need for blood transfusion, mean blood pressure (MBP), serum hemoglobin (Hb), and ferritin levels. Random-effects meta-analyses were used. RESULTS: Fourteen RCTs (n = 1708) were included. In comparison to ICC, UCM did not decrease mortality (RR 0.5, 95% CI 0.2-1.1), IVH (RR 0.7, 95% CI 0.5-1.0), or PDA (RR 1.0, 95% CI 0.7-1.5). However, UCM reduced need of blood transfusion (RR 0.5, 95% CI 0.3-0.9) and increased MBP (MD 2.5 mm Hg, 95% CI 0.5-4.5), Hb (MD 1.2 g/dL, 95% CI 0.8-1.6), and ferritin (MD 151.4 ng/dL, 95% CI 59.5-243.3). In comparison to DCC, UCM did not reduce mortality, IVH, PDA, or need of blood transfusion but increased MBP (MD 3.7, 95% CI 0.6-6.9) and Hb (MD 0.3, 95% CI -0.2-0.8). Only two RCTs had high risk of bias. CONCLUSIONS: UCM did not decrease short-term clinical outcomes in comparison to ICC or DCC in preterm infants. Intermediate outcomes improved significantly with UCM. IMPACT: In 14 randomized controlled trials (RCTs), umbilical cord milking (UCM) did not reduce mortality, intraventricular hemorrhage, or patent ductus arteriosus compared to immediate (ICC) or delayed cord clamping (DCC). UCM improved mean blood pressure and hemoglobin levels compared to ICC or DCC. In comparison to ICC, UCM reduced the need for blood transfusion. We updated searches until February 2020, stratified by type of control, and performed subgroup analyses. There was low quality of evidence about clinical efficacy of UCM. Most of RCTs had low risk of bias. UCM cannot be recommended as standard of care for preterm infants.