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.

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.

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.

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.

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.

Effect of delayed interval delivery of remaining fetus(es) in multiple pregnancies on survival: a systematic review and meta-analysis.

BACKGROUND: The management of the pregnancy after delivery of the first fetus during a second-trimester miscarriage or very early preterm birth has not been well defined. OBJECTIVE: The objective of the study was to evaluate whether delayed interval delivery of the remaining fetus(es) in twins/triplets is associated with improved survival, when compared with immediate delivery, after miscarriage or very preterm birth of the first fetus in multiple pregnancy. DATA SOURCES: PubMed, MEDLINE, and Cochrane Library were systematically searched through January 2019. STUDY ELIGIBILITY CRITERIA (STUDY DESIGN, POPULATIONS, AND INTERVENTIONS): The following eligibility criteria applied: full-text original article; included at least 5 cases of delayed interval delivery for remaining fetus(es); and reported the survival rate of the first-born and the remaining fetus(es). STUDY APPRAISAL AND SYNTHESIS METHODS: K.W.C. and W.W. searched, screened, and reviewed the articles. The quality of the studies was assessed according to the Strengthening the Reporting of Observational studies in Epidemiology checklist. If possible, data were stratified for assigned chorionicity. Effect sizes were pooled through a meta-analysis. RESULTS: A total of 2295 published article and abstracts were identified. Only 16 studies met inclusion criteria. Meta-analysis of 492 pregnancies (432 twins [88%], 56 triplets [11%], 3 quadruplets and 1 quintuplets) showed that delayed interval delivery significantly improved the perinatal survival of remaining fetus(es) compared with the first born (odds ratio, 5.22, 95% confidence interval, 2.95-9.25, I2 = 53%), before 20+0 weeks (odds ratio, 6.32, 95% confidence interval, 1.99-20.13, I2 = 0%), between 20+0 and 23+6 weeks (odds ratio, 3.31, 95% confidence interval, 1.95-5.63, I2 = 0%), and after 24+0 weeks (odds ratio, 1.92, 95% confidence interval, 1.21-3.05, I2 = 0%), in dichorionic twin pregnancy (odds ratio, 14.89, 95% confidence interval, 6.19-35.84, I2 = 0%), and unselected triplet pregnancy (odds ratio, 2.33, 95% confidence interval, 1.02-5.32, I2 = 0%. ). Among the survivors, there were no significant differences in the short-term and long-term neonatal morbidities between the first-born and the remaining fetus(es). Serious maternal morbidity was reported in 39% of pregnancy after delayed interval delivery (71 of 183). In addition, 2 cases were managed by postpartum hysterectomy and 1 reported postoperative uterovaginal fistula. There were no recorded cases of maternal mortality. CONCLUSION: Delayed interval delivery when a fetus has delivered in a multiple pregnancy is an effective management option to increase the survival rate of the remaining fetus(es). About 39% of women may experience morbidity following this management option.

Predictors of perinatal outcome in early-onset fetal growth restriction: A study from an emerging economy country.

OBJECTIVE: To identify antenatal predictors of adverse perinatal outcomes in a population of preterm fetuses with early placental insufficiency diagnosed by Doppler abnormalities. METHOD: In this cross-sectional study of a cohort of singleton pregnant women diagnosed with early placental insufficiency, relationships between perinatal variables (arterial and venous Doppler, gestational age, birth weight, oligohydramnios, estimated fetal weight, and fetal weight z-scores) and major neonatal complications were analyzed by logistic regression. RESULTS: Two hundred sixty-five women were delivered, between 24 and 33 weeks gestation. The overall frequency of intact survival was 57.9% (n = 154). Gestational age thresholds for best prediction of survival was 27 + 6 weeks and for intact survival was 29 + 0 weeks gestation. Fetal weight and absent/reversed ductus venosus a-wave were the main predictors of survival in the regression model. When fetal weight was substituted for fetal weight z-score, ductus venosus abnormal Doppler predicted mortality and absent or reversed umbilical artery diastolic velocities predicted intact survival. CONCLUSIONS: This study illustrates the impact of gestational age and fetal weight on perinatal outcomes in early placental insufficiency, with well-defined thresholds. Gestational age and fetal weight, or a combination of fetal weight z-scores and fetal Doppler parameters, were the best predictors of intact survival in our sample.

Perinatal outcomes of infants with congenital limb malformations: an observational study from a tertiary referral center in Central Europe.

BACKGROUND: Congenital limb malformations are rare, and their perinatal outcomes are not well described. This study analyzed the perinatal outcomes of infants with congenital limb malformations. METHODS: All infants with congenital limb malformations who underwent prenatal assessment and delivery at our tertiary referral center from 2004 through 2017 were retrospectively identified. Neonatal outcome parameters were assessed, and the predictors of worse perinatal outcomes were determined. RESULTS: One hundred twenty-four cases of congenital limb malformations were identified, of which 104 (83.9%) were analyzed. The upper limb was affected in 15 patients (14.4%), the lower limb in 49 (47.1%), and both limbs in 40 (38.5%) patients. A fetal syndrome was identified in 66 patients (63.5%); clubfoot and longitudinal reduction defects were the most frequent malformations. In total, 38 patients (36.5%) underwent termination, seven (6.7%) had stillbirth, and 59 (56.7%) had live-born delivery. Rates of preterm delivery and transfer to the Neonatal Intensive Care Unit were 42.4 and 25.4%, respectively. Localization of the malformation was a determinant of perinatal outcome (P = .006) and preterm delivery (P = .046). CONCLUSIONS: Congenital limb malformations frequently occur bilaterally and are associated with poor perinatal outcomes, including high rates of stillbirth and preterm delivery. Multidisciplinary care and referral to a perinatal center are warranted.

Cause and predictors of neonatal mortality among neonates admitted to neonatal intensive care units of public hospitals in eastern Ethiopia: a facility-based prospective follow-up study.

BACKGROUND: The first month is the most crucial period for child survival. Neonatal mortality continues to remain high with little improvement over the years in Sub-Saharan Africa, including Ethiopia. This region shows the least progress in reducing neonatal mortality and continues to be a significant public health issue. In this study setting, the causes and predictors of neonatal death in the neonatal intensive care units are not well documented. Hence, this study aimed to determine the causes and predictors of neonatal mortality among infants admitted to neonatal intensive care units in eastern Ethiopia. METHODS: A facility-based in prospective follow-up study was conducted among neonates admitted to neonatal intensive care units of public hospitals of eastern Ethiopia from November 1 to December 30, 2018. Data were collected using a pre-tested structured questionnaire and a follow-up checklist. The main outcomes and causes of death were set by pediatricians and medical residents. EpiData 3.1 and Statistical Package for Social Sciences Version 25 software were used for data entry and analysis, respectively. Multivariable logistic regression was used to identify the predictors of facility-based neonatal mortality. RESULTS: The proportion of facility-based neonatal mortality was 20% (95% CI:16.7-23.8%). The causes of death were complications of preterm birth (28.58%), birth asphyxia (22.45%), neonatal infection (18.36%), meconium aspiration syndrome (9.18%), respiratory distress syndrome (7.14%), and congenital malformation (4.08%). Low birth weight, preterm births, length of stay of the neonatal intensive care unit, low 5 min APGAR score, hyperthermia, and initiation of feeding were predictors of neonatal death among infants admitted to the neonatal intensive care units of public hospitals in eastern Ethiopia. CONCLUSIONS: The proportion of facility-based neonatal deaths was unacceptably high. The main causes of death were preventable and treatable. Hence, improving the timing and quality of antenatal care is essential for early detection, anticipating high-risk newborns, and timely interventions. Furthermore, early initiation of feeding and better referral linkage to tertiary health facilities could lead to a reduction in neonatal death in this setting.

Childbirth outcomes and ethnic disparities in Suriname: a nationwide registry-based study in a middle-income country.

BACKGROUND: Our study aims to evaluate the current perinatal registry, analyze national childbirth outcomes and study ethnic disparities in middle-income country Suriname, South America. METHODS: A nationwide birth registry study was conducted in Suriname. Data were collected for 2016 and 2017 from the childbirth books of all five hospital maternity wards, covering 86% of all births in the country. Multinomial regression analyses were used to assess ethnic disparities in outcomes of maternal deaths, stillbirths, teenage pregnancy, cesarean delivery, low birth weight and preterm birth with Hindustani women as reference group. RESULTS: 18.290 women gave birth to 18.118 (98%) live born children in the five hospitals. Hospital-based maternal mortality ratio was 112 per 100.000 live births. Hospital-based late stillbirth rate was 16 per 1000 births. Stillbirth rate was highest among Maroon (African-descendent) women (25 per 1000 births, aOR 2.0 (95%CI 1.3-2.8) and lowest among Javanese women (6 stillbirths per 1000 births, aOR 0.5, 95%CI 0.2-1.2). Preterm birth and low birthweight occurred in 14 and 15% of all births. Teenage pregnancy accounted for 14% of all births and was higher in Maroon women (18%) compared to Hindustani women (10%, aOR 2.1, 95%CI 1.8-2.4). The national cesarean section rate was 24% and was lower in Maroon (17%) than in Hindustani (32%) women (aOR 0.5 (95%CI 0.5-0.6)). Cesarean section rates varied between the hospitals from 17 to 36%. CONCLUSION: This is the first nationwide comprehensive overview of maternal and perinatal health in a middle income country. Disaggregated perinatal health data in Suriname shows substantial inequities in outcomes by ethnicity which need to be targetted by health professionals, researchers and policy makers.

Mortality Rate and Major Causes of Death by Gestational Age in Korean Children under 5 Years of Age.

BACKGROUND: Preterm birth is associated with increased infant mortality. However, it is not clear whether prematurity is associated with mortality after 1 year of age. There is a lack of research on mortality rate and causes of death after infancy in preterm babies in Korea. We aimed to analyze the mortality rates and causes of deaths up to 5 years of age in Korea. METHODS: Using the Microdata Integrated Service of Statistics Korea database, this retrospective cohort study screened infants born between 2010 and 2012. After applying the exclusion criteria, 1,422,913 live births were classified into the following groups by gestational age: those born at < 32 weeks' gestation (n = 10,411), those born between 32 and 36 weeks' gestation (n = 75,657), and those born at ≥ 37 weeks' gestation (n = 1,336,845). The association of gestational age with mortality in infancy (< 1 year of age) and childhood (1-5 years of age) was analyzed, with and without covariates. The major causes of death in infancy and childhood were analyzed by gestational age. RESULTS: Overall, 4,930 (0.3%) children died between birth and 5 years of age, with 19.1% of these deaths occurring after infancy. Adjusted hazard ratios (HRs) for infant death were 78.79 (95% confidence interval [CI], 71.33-87.04) and 4.62 (95% CI, 4.07-5.24) for the < 32 and 32-36 weeks groups, respectively, compared to the full-term group; the adjusted HRs for deaths occurring at ages 1-5 years were 9.25 (95% CI, 6.85-12.50) and 2.42 (95% CI, 1.95-3.01), respectively. In infancy, conditions originating in the perinatal period were the most common cause of deaths in the < 32 and 32-36 weeks groups (88.7% and 41.9%, respectively). Contrarily, in the ≥ 37 weeks group, conditions originating in the perinatal period explained 22.7% of infant deaths, with congenital malformations primarily accounting for 29.6% of these deaths. The most common cause of death in children (after infancy) in the < 32 weeks group was perinatal causes (25.0%); in the 32-36 weeks group, congenital malformation and nervous system disease were the common causes (21.7% and 19.1%, respectively). In the ≥ 37 weeks group, injury, poisoning, and other consequences of external causes explained 26.6% of childhood deaths, followed by neoplasms and nervous system disease (15.7% and 14.7%, respectively). CONCLUSION: Low gestational age is associated with not only infant mortality but also child mortality. The major causes of death differed by gestational age in infancy and childhood. For the care of preterm infants, especially those born at < 32 weeks' gestation, particular attention and continuous monitoring are needed in consideration of the major causes of deaths until 5 years of age.

Risk factors and maternal outcomes following preterm premature rupture of membrane in the second trimester of gestation.

PURPOSE: To characterize the population of women who underwent mid-trimester preterm premature rupture of membrane (PPROM) in a country where mid-trimester abortions are legal and available. METHODS: A retrospective cross-sectional cohort study was conducted at a tertiary referral hospital, during 2013-2016. Mid-trimester defined as gestational age 13 + 0 to 23 + 6 weeks. Rupture of membrane was defined by documentation of fluid passing through the cervix on sterile speculum examination, and a positive Nitrazine (Bristol-Myers Squibb, Princeton, NJ) or erning test. All records were evaluated for medical history, laboratory data, postnatal examination, and autopsy findings, and a database was constructed. RESULTS: A total of 61 women were hospitalized for mid-trimester PPROM during the study period. Mean maternal age was 32 ± 5.98, range 20-45 years old. The majority (50, 82%) of patients decided to terminate their pregnancy before reaching the limit of viability at 24 weeks gestation. The overall prognosis of pregnancies reaching term was better than expected, with six (9.8%) patients delivering live babies and four of them born at term (36 ± 5 to 40 ± 6 weeks gestation), all after PPROM following amniocentesis or selective fetal reduction. A total of 60% of women with hypothyroidism had unbalanced TSH levels above 4.0 mIU/L prior to their pregnancy. A notable number of women (15, 24.6%) had PPROM following a pregnancy achieved by assisted reproductive technology (ART). CONCLUSIONS: Most women with diagnosed mid-trimester PPROM opted for pregnancy termination before the limit of viability when granted the choice. Possible risk factors for early PPROM are unbalanced hypothyroidism and ART. PPROM following amniocentesis can in some cases reseal and reach term, suggesting conservative treatment is a reasonable management for those cases.

Prevalence and Outcome of Preterm Births in the National Referral Hospital in Bhutan: An Observational Study.

INTRODUCTION: Preterm birth-related complications are the leading cause of under-5 mortality globally. Bhutan does not have a reliable preterm birth rate or data regarding outcome of preterm babies. AIM: To determine the preterm birth rate at the Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Thimphu, Bhutan, and assess their outcomes. METHODS: All live preterm births at JDWNRH from 1 January 2017 to 31 December 2017 were followed from birth till hospital discharge. Maternal demographic data, pregnancy details and delivery details were collected. Morbidity and mortality information as well as discharge outcome were collected on babies admitted to neonatal intensive care unit (NICU). RESULTS: Preterm birth rate among live births was 6.4%. Most mothers were younger than 30 years, housewives and had secondary education. Pregnancy registration rate and adequacy of antenatal visits were high. Most preterm births were singleton and the predominant mode of delivery was cesarean section. More than half of the births were initiated spontaneously, and the male:female ratio was 1.2:1. Most babies were late preterm and low birth weight. Half of them required NICU admission. Overall mortality rate was 11% and 21.6% for admitted preterm neonates. Preterm small-for-gestational-age neonates, and those born after provider-initiated preterm birth had significantly increased risk of mortality. Most preterm neonates were discharged without complications. The rate of extrauterine growth restriction was high. CONCLUSION: This is the first study on the prevalence of preterm births and their outcomes in the largest tertiary-care hospital in Bhutan.

Perinatal care provided for babies born at 23 and 24 weeks of gestation.

In recent years, significant improvements in survival and survival-free of major morbidity in babies born at 23+0 to 24+6  weeks of gestation have led to a more pro-active approach to resuscitation at these peri-viable gestations. Antenatal counselling and interventions, intrapartum care and postnatal advice should be part of the package of care provided to optimise outcomes for these babies and their families. This observational study assesses the perinatal care provided to mothers and their babies who were born at 23 and 24 weeks of gestations over a two-year period at a tertiary maternity hospital in New Zealand.

Bilirubin in the Vitreous Body of the Eye of Human Fetuses.

The bilirubin content in the vitreous body of the eye of human fetuses of gestation week 17-31 was measured. During gestation weeks 17-19, the mean bilirubin concentration was 8.67 µmol/liter; then, decreased to 1.37 µmol/liter (gestation weeks 20 to 31). Bilirubin, being an endogenous antioxidant, is probably involved in protection of the retina and lens from LPO processes that intensively develop in retinal neurons and lens fibers.

Mediating roles of preterm birth and restricted fetal growth in the relationship between maternal education and infant mortality: A Danish population-based cohort study.

BACKGROUND: Socioeconomic disparities in infant mortality have persisted for decades in high-income countries and may have become stronger in some populations. Therefore, new understandings of the mechanisms that underlie socioeconomic differences in infant deaths are essential for creating and implementing health initiatives to reduce these deaths. We aimed to explore whether and the extent to which preterm birth (PTB) and small for gestational age (SGA) at birth mediate the association between maternal education and infant mortality. METHODS AND FINDINGS: We developed a population-based cohort study to include all 1,994,618 live singletons born in Denmark in 1981-2015. Infants were followed from birth until death, emigration, or the day before the first birthday, whichever came first. Maternal education at childbirth was categorized as low, medium, or high. An inverse probability weighting of marginal structural models was used to estimate the controlled direct effect (CDE) of maternal education on offspring infant mortality, further split into neonatal (0-27 days) and postneonatal (28-364 days) deaths, and portion eliminated (PE) by eliminating mediation by PTB and SGA. The proportion eliminated by eliminating mediation by PTB and SGA was reported if the mortality rate ratios (MRRs) of CDE and PE were in the same direction. The MRRs between maternal education and infant mortality were 1.63 (95% CI 1.48-1.80, P < 0.001) and 1.19 (95% CI 1.08-1.31, P < 0.001) for low and medium versus high education, respectively. The estimated proportions of these total associations eliminated by reducing PTB and SGA together were 55% (MRRPE = 1.27, 95% CI 1.15-1.40, P < 0.001) for low and 60% (MRRPE = 1.11, 95% CI 1.01-1.22, P = 0.037) for medium versus high education. The proportions eliminated by eliminating PTB and SGA separately were, respectively, 46% and 11% for low education (versus high education) and 48% and 13% for medium education (versus high education). PTB and SGA together contributed more to the association of maternal educational disparities with neonatal mortality (proportion eliminated: 75%-81%) than with postneonatal mortality (proportion eliminated: 21%-23%). Limitations of the study include the untestable assumption of no unmeasured confounders for the causal mediation analysis, and the limited generalizability of the findings to other countries with varying disparities in access and quality of perinatal healthcare. CONCLUSIONS: PTB and SGA may play substantial roles in the relationship between low maternal education and infant mortality, especially for neonatal mortality. The mediating role of PTB appeared to be much stronger than that of SGA. Public health strategies aimed at reducing neonatal mortality in high-income countries may need to address socially related prenatal risk factors of PTB and impaired fetal growth. The substantial association of maternal education with postneonatal mortality not accounted for by PTB or SGA could reflect unaddressed educational disparities in infant care or other factors.

Distinct mortality patterns at 0-2 days versus the remaining neonatal period: results from population-based assessment in the Indian state of Bihar.

BACKGROUND: The objectives of this study were to understand the differences in mortality rate, risk factors for mortality, and cause of death distribution in three neonatal age sub-groups (0-2, 3-7, and 8-27 days) and assess the change in mortality rate with previous assessments to inform programmatic decision-making in the Indian state of Bihar, a large state with a high burden of newborn deaths. METHODS: Detailed interviews were conducted in a representative sample of 23,602 live births between January and December 2016 (96.2% participation) in Bihar state. We estimated the neonatal mortality rate (NMR) for the three age sub-groups and explored the association of these deaths with a variety of risk factors using a hierarchical logistic regression model approach. Verbal autopsies were conducted using the PHMRC questionnaire and the cause of death assigned using the SmartVA automated algorithm. Change in NMR from 2011 to 2016 was estimated by comparing it with a previous assessment. RESULTS: The NMR 0-2-day, 3-7-day, and 8-27-day mortality estimates in 2016 were 24.7 (95% CI 21.8-28.0), 13.2 (11.1 to 15.7), 5.8 (4.4 to 7.5), and 5.8 (4.5 to 7.5) per 1000 live births, respectively. A statistically significant reduction of 23.3% (95% CI 9.2% to 37.3) was seen in NMR from 2011 to 2016, driven by a reduction of 35.3% (95% CI 18.4% to 52.2) in 0-2-day mortality. In the final regression model, the highest odds for mortality in 0-2 days were related to the gestation period of ≤ 8 months (OR 16.5, 95% CI 11.9-22.9) followed by obstetric complications, no antiseptic cord care, and delivery at a private health facility or home. The 3-7- and 8-27-day mortality was driven by illness in the neonatal period (OR 10.33, 95% CI 6.31-16.90, and OR 4.88, 95% CI 3.13-7.61, respectively) and pregnancy with multiple foetuses (OR 5.15, 95% CI 2.39-11.10, and OR 11.77, 95% CI 6.43-21.53, respectively). Birth asphyxia (61.1%) and preterm delivery (22.1%) accounted for most of 0-2-day deaths; pneumonia (34.5%), preterm delivery (33.7%), and meningitis/sepsis (20.1%) accounted for the majority of 3-7-day deaths; meningitis/sepsis (30.6%), pneumonia (29.1%), and preterm delivery (26.2%) were the leading causes of death at 8-27 days. CONCLUSIONS: To our knowledge, this is the first study to report a detailed neonatal epidemiology by age sub-groups for a major Indian state, which has highlighted the distinctly different mortality rate, risk factors, and causes of death at 0-2 days versus the rest of the neonatal period. Monitoring mortality at 0-2 and 3-7 days separately in the traditional early neonatal period of 0-7 days would enable more effective programming to reduce neonatal mortality.

Neonatal Intensive Care Variation in Medicaid-Insured Newborns: A Population-Based Study.

OBJECTIVE: To assess the contribution of maternal and newborn characteristics to variation in neonatal intensive care use across regions and hospitals. STUDY DESIGN: This was a retrospective population-based live birth cohort of newborn infants insured by Texas Medicaid in 2010-2014 with 2 subcohorts: very low birth weight (VLBW) singletons and late preterm singletons. Crude and risk-adjusted neonatal intensive care unit (NICU) admission rates, intensive and intermediate special care days, and imaging procedures were calculated across Neonatal Intensive Care Regions (n = 21) and hospitals (n = 100). Total Medicaid payments were calculated. RESULTS: Overall, 11.5% of live born, 91.7% of VLBW, and 37.6% of infants born late preterm were admitted to a NICU, receiving an average of 2 days, 58 days, and 5 days of special care with payments per newborn inpatient episode of $5231, $128 075, and $10 837, respectively. There was little variation across regions and hospitals in VLBW NICU admissions but marked variation for NICU admissions in late preterm newborn infants and for special care days and imaging rates in all cohorts. The variation decreased slightly after health risk adjustment. There was moderate substitution of intermediate for intensive care days across hospitals (Pearson r VLBW -0.63 P < .001; late preterm newborn -0.53 P < .001). CONCLUSIONS: Across all risk groups, the variation in NICU use was poorly explained by differences in newborn illness levels and is likely to indicate varying practice styles. Although the "right" rates are uncertain, it is unlikely that all of these use patterns represent effective and efficient care.

Prevalence, antenatal management and perinatal outcome of monochorionic monoamniotic twin pregnancy: a collaborative multicenter study in England, 2000-2013.

OBJECTIVES: To determine the prevalence of monochorionic monoamniotic (MCMA) twin pregnancy and to describe perinatal outcome and clinical management of these pregnancies. METHODS: In this multicenter cohort study, the prevalence of MCMA twinning was estimated using population-based data on MCMA twin pregnancies, collected between 2000 and 2013 from 11 Northern Survey of Twin and Multiple Pregnancy (NorSTAMP) maternity units. Pregnancy outcome at < 24 weeks' gestation, antenatal parameters and perinatal outcome (from ≥ 24 weeks to the first 28 days of age) were analyzed using combined data on pregnancies confirmed to be MCMA from NorSTAMP and the Southwest Thames Region of London Obstetric Research Collaborative (STORK) multiple pregnancy cohort for 2000-2013. RESULTS: The estimated total prevalence of MCMA twin pregnancies in the North of England region was 8.2 per 1000 twin pregnancies (59/7170), and the birth prevalence was 0.08 per 1000 pregnancies overall (singleton and multiple). Using combined data from NorSTAMP and STORK, the rate of fetal death (at < 24 weeks' gestation), including terminations of pregnancy and selective feticide, was 31.8% (54/170); the overall perinatal mortality rate was 14.7% (17/116), ranging from 69.2% at < 30 weeks to 4.5% at ≥ 33 weeks' gestation. MCMA twins that survived in utero beyond 24 weeks were delivered, usually by Cesarean section, at a median of 33 (interquartile range, 32-34) weeks of gestation. CONCLUSIONS: In MCMA twins surviving beyond 24 weeks of gestation, there was a higher survival rate compared with in previous decades, presumably due to early diagnosis, close surveillance and elective birth around 32-34 weeks of gestation. High perinatal mortality at early gestations was attributed mainly to extreme prematurity due to preterm spontaneous labor. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Mortality Rate-Dependent Variations in the Timing and Causes of Death in Extremely Preterm Infants Born at 23-24 Weeks' Gestation.

OBJECTIVES: To determine mortality rate-dependent variations in the timing and causes of death, and to subsequently identify the clinical factors associated with decreased mortality in extremely preterm infants born at 23-24 weeks' gestation. DESIGN: A retrospective cohort study. SETTING: Korean Neonatal Network registry that includes all level greater than or equal to 3 neonatal ICUs in Korea. PATIENTS: Eligible, actively treated infants born at 23-24 weeks' gestation (n = 574) from January 2014 to December 2016 were arbitrarily categorized based on institutional mortality rates of less than or equal to 50% (group I, n = 381) and greater than 50% (group II, n = 193). The primary outcome was mortality before discharge and the timing and causes of death according to the mortality rate. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The overall mortality rate was significantly lower in group I (40.7%) than in group II (79.3%). Regarding causes of death, mortalities due to cardiorespiratory, infectious, and gastrointestinal causes were significantly lower in group I than in group II. Mortality rates were significantly lower in group I, including all the subgroups that were categorized according to the timing of death, than in group II. The multivariate analyses showed that antenatal corticosteroid use, absence of oligohydramnios, birth weight, and body temperature at admission to the neonatal ICU were significantly associated with reduced mortality. CONCLUSIONS: The reduced mortality rate among the infants born at 23-24 weeks' gestation was attributable to decreased mortality ascribed to cardiorespiratory, infectious, and gastrointestinal causes, and it was associated with antenatal steroid use and body temperature at admission to the neonatal ICU.