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Impact: Bronchopulmonary dysplasia has multiple definitions that are currently based on phenotypic characteristics. Using an unsupervised machine learning approach, we created BPD subclasses (e.g., endotypes) by clustering whole microarray data. T helper 17 cell differentiation was the most significant pathway differentiating the BPD endotypes. Introduction: Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Discovery of BPD endotypes in an unbiased format, derived from the peripheral blood transcriptome, may uncover patterns underpinning this complex lung disease. Methods: An unsupervised agglomerative hierarchical clustering approach applied to genome-wide expression of profiling from 62 children at day of life five was used to identify BPD endotypes. To identify which genes were differentially expressed across the BPD endotypes, we formulated a linear model based on least-squares minimization with empirical Bayes statistics. Results: Four BPD endotypes (A, B,C,D) were identified using 7,319 differentially expressed genes. Across BPD endotypes, 5,850 genes had a p value < 0.05 after multiple comparison testing. Endotype A consisted of neonates with a higher gestational age and birthweight. Endotypes B-D included neonates between 25 and 26 weeks and a birthweight range of 640 to 940 g. Endotype D appeared to have a protective role against BPD compared to Endotypes B and C (36% vs. 62% vs. 60%, respectively). The most significant pathway focused on T helper 17 cell differentiation. Conclusion: Bioinformatic analyses can help identify BPD endotypes that associate with clinical definitions of BPD. [ABSTRACT FROM AUTHOR]

Objective: Physiological blood pressure changes in pregnancy are insufficiently defined. This paper describes the blood pressure changes across healthy pregnancies in a Southern Chinese population to present gestational - age - specific blood pressure ranges with smoothed centiles (3rd, 10th, 50th, 90th, and 97th)., Methods: Antenatal blood pressure measurements [median (interquartile range) 9 (8 - 10) per woman] were repeated in 17, 776 women from a Southern China population. Multilevel cubic splines models were used to derive longitudinal reference ranges for systolic blood pressure (SBP) and diastolic blood pressure (DBP) from 6 to 42 weeks of gestation for the normal pregnancies (excluding chronic hypertension, preeclampsia, diabetic ones, and preterm birth et al.)., Results: Systolic and diastolic BP increased from 6 weeks of gestation: 50th centile (3rd - 97th centile) 106 (87 - 125); 61 (47 - 77) mm Hg to 12 weeks of gestation: 50th centile (3rd - 97th centile) 108 (88 - 129); 64 (49 - 81) mm Hg. Then, the lowest value of 107 (87 - 129); 62 (47 - 78) mm Hg was reached at 16 weeks and 20 weeks of gestation, respectively. Systolic and diastolic BP then rose to a maximum median (3rd - 97th centile) of 115 (96 - 135); 68 (53 - 85) mm Hg at 42 weeks of gestation. Additionally, the ascending tendency of SBP after 16 weeks of gestation was interrupted by two fluctuations that occurred at 24 weeks and 30 weeks of gestation., Conclusions: In summary, our study provides blood pressure reference values for Southern Chinese women with normal pregnancies. To identify gestational hypertension and hypotension, centiles for gestational - age - specific BP should be defined in healthy pregnancies. Understanding these changes in low risk pregnancies is essential to optimize maternal blood pressure management., Competing Interests: Declarations. Ethics approval and consent to participate: This study has ethical approval from the Longgang District Maternal & Child Healthcare Hospital Research Ethics Committee (No. LGFYYXLLL-2022-016). All participants have signed the written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Identifying high-risk neonates with abnormal fetal growth is crucial for health risk prediction and early intervention. Small for gestational age (SGA) and large for gestational age (LGA) classifications highlight neonates having a higher risk for postnatal diseases. Accurate diagnosis depends on precise anthropometric measurements and appropriate reference data. In 2010, specific neonatal charts for Italian singletons (INeS charts) were published, tracing separately for first- and later-born neonates due to a 3% birth weight difference. We present INeS charts for birth weight non-separated by first- and later-born babies useful when information on parity is unavailable or unreliable, or for better comparisons with other neonatal charts that are not separated by birth-order., Methods: INeS charts were traced using a parametric function. Starting with the parameters estimates published in a different paper, INeS charts not separated by birth order were traced for the gestational age range of 23 to 42 weeks. In a second step the charts were parametrized as Cole and Green Lambda Mu and Sigma (LMS) model, allowing computation of standard deviation scores., Results: The centiles of non-separated INeS charts follow between first- and later-born charts. Distances varied due to changing first-born proportions with gestational age, Max differences of about 100g with later born and 70g with first-born were observed at term. S and L functions have a similar shape for boys and girls. S function shows a pick at about 29 weeks, L function has positive values in all the range of gestational age with a pick at 39 weeks., Conclusions: The study presents non-separated Birth Weight INeS charts, bridging the gap when parity information is unavailable. Differences with separated charts were generally small, making them reliable for neonatal health assessment. Insights from L and S parameters contribute to standardized birth weight and adjust it by sex and Gestational Age, useful for defining SGA or LGA neonates. The paper enhances neonatal care tools, showcasing INeS chart flexibility in different clinical scenarios and supporting neonatology research., (© 2024. The Author(s).)

Background: Barriers exist for the provision of surgery for permanent contraception in the postpartum period. Prenatal counseling has been associated with increased rates of fulfillment of desired postpartum contraception in general, although it is unclear if there is impact on permanent contraception specifically. Thus, we aimed to investigate the association between initial timing for prenatal documentation of a contraceptive plan for permanent contraception and fulfillment of postpartum contraception for those receiving counseling. Methods: This is a planned secondary analysis of a multi-site cohort study of patients with documented desire for permanent contraception at the time of delivery at four hospitals located in Alabama, California, Illinois, and Ohio over a two-year study period. Our primary exposure was initial timing of documented plan for contraception (first, second, or third trimester, or during delivery hospitalization). We used univariate and multivariable logistic regression to analyze fulfillment of permanent contraception before hospital discharge, within 42 days of delivery, and within 365 days of delivery between patients with a documented plan for permanent contraception in the first or second trimester compared to the third trimester. Covariates included insurance status, age, parity, gestational age, mode of delivery, adequacy of prenatal care, race, ethnicity, marital status, and body mass index. Results: Of the 3103 patients with a documented expressed desire for permanent contraception at the time of delivery, 2083 (69.1%) had a documented plan for postpartum permanent contraception prenatally. After adjusting for covariates, patients with initial documented plan for permanent contraception in the first or second trimester had a higher odds of fulfillment by discharge (aOR 1.57, 95% C.I 1.24–2.00), 42 days (aOR 1.51, 95% C.I 1.20–1.91), and 365 days (aOR 1.40, 95% C.I 1.11–1.75), compared to patients who had their first documented plan in the third trimester. Conclusions: Patients who had a documented prenatal plan for permanent contraception in trimester one and two experienced higher likelihood of permanent contraception fulfillment compared to those with documentation in trimester three. Given the barriers to accessing permanent contraception, it is imperative that comprehensive, patient-centered counseling and documentation regarding future reproductive goals begin early prenatally. Plain language summary: Permanent contraception is a highly desired form of postpartum contraception in the United States, however there are several barriers to accessing it. In this paper, we investigate whether the timing of when a patient has a documented plan for postpartum contraception has an impact on if they achieve postpartum contraception. This is a cohort study from four hospitals in Illinois, Ohio, California, and Alabama for patients with a desire for postpartum permanent contraception documented in their medical record. We specifically investigated the trimester (first, second, or third) where a patient had a plan for permanent contraception first documented. We then used univariate and multivariate models to determine the relationship between the timing of a plan for permanent contraception and if a patient achieved the procedure at three time-points: hospital discharge, 42-days, and 365-days. Our findings showed that of the 3103 patients in our cohort, only 69.1% of them had a documented plan for postpartum contraception at any point before going to the hospital for their delivery admission. We additionally found that patients who had a documented plan for permanent contraception in the first or second trimester had a higher odds of receiving their postpartum contraception procedure compared to people who had their first documented plan in the third trimester. This showed us the importance of earlier counseling regarding contraception for pregnant patients. There are many barriers to accessing postpartum contraception, so having patient focused counseling about future goals around reproductive health early on in pregnancy is critical. [ABSTRACT FROM AUTHOR]

Background: The primary aim of the study is to test the null hypothesis that there are no statistically significant differences in intracranial volumes between male and female fetuses. Furthermore, we have studied the symmetry of the cerebral hemispheres in the cohort of low-risk fetuses. Methods: 200 normal fetuses between 18 and 37 gestational weeks (gw) were included in the cohort and all had in utero MR, consisting of routine and 3D-volume imaging. The surfaces of the cerebral ventricles, brain and internal table of the skull were outlined manually and volume measurements were obtained of ventricles (VV), brain parenchyma (BPV), extraaxial CSF spaces (EAV) and the total intracranial volume (TICV). The changes in those values were studied over the gestational range, along with potential gender differences and asymmetries of the cerebral hemispheres. Results: BPV and VV increased steadily from 18 to 37 gestational weeks, and as a result TICV also increased steadily over that period. TICV and BPV increased at a statistically significantly greater rate in male relative to female fetuses after 24gw. The greater VV in male fetuses was apparent earlier, but the rate of increase was similar for male and female fetuses. There was no difference between the genders in the left and right hemispherical volumes, and they remained symmetrical over the age range measured. Conclusions: We have described the growth of the major intracranial compartments in fetuses between 18 and 37gw. We have shown a number of statistically different features between male and female fetuses, but we have not detected any asymmetry in volumes of the fetal cerebral hemispheres. Highlights: In utero magnetic resonance imaging can be used to calculate intracranial volumes in fetuses. In this paper, we present volume data of the major intracranial compartments (cerebral ventricular system (VV), brain parenchymal volume (BPV), extraaxial CSF volume (EAV) and total intracranial volume (TICV) in normal male and female fetuses over a wide gestational age. We have shown that BPV and TICV increase at a statistically significant greater rate in male fetuses when compared with female fetuses. As a result, male fetuses have statistically significant larger BPV and TICV than female fetuses after 24 gestational weeks. There was no statistical evidence for asymmetry of hemispheric volumes in neither male nor female fetuses at any gestational age studied. [ABSTRACT FROM AUTHOR]

Background: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America. Methods: This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to 'deep phenotyping' (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the placental disorders of pregnancy (pregnancy hypertension, fetal growth restriction and stillbirth). Our clinical sites are in The Gambia (Farafenni), Kenya (Kilifi County), and Mozambique (Maputo Province). In each country, 50 non-pregnant women of reproductive age will be recruited each month for 1 year, to provide a final national sample size of 600; these women will provide culturally-, ethnically-, seasonally- and spatially-relevant control data with which to compare women with normal and complicated pregnancies. Between the three countries we will recruit ≈10,000 unselected pregnant women over 2 years. An estimated 1500 women will experience one/more placental complications over the same epoch. Importantly, as we will have accurate gestational age dating using the TraCer device, we will be able to discriminate between fetal growth restriction and preterm birth. Recruitment and follow-up will be primarily facility-based and will include women booking for antenatal care, subsequent visits in the third trimester, at time-of-disease, when relevant, during/immediately after birth and 6 weeks after birth. Conclusions: To accelerate progress towards the women's and children's health-relevant Sustainable Development Goals, we need to understand how a variety of social, chronic disease, biomarker and pregnancy-specific determinants health interact to result in either a resilient or a compromised pregnancy for either mother or fetus/newborn, or both. This protocol has been designed to create such a depth of understanding. We are seeking funding to maintain the cohort to better understand the implications of pregnancy complications for both maternal and child health. [ABSTRACT FROM AUTHOR]

Background: Neonatal sepsis is an invasive infection, usually bacterial, and often occurring during the neonatal period (0-28 days). Neonatal sepsis causes a high burden of morbidity and mortality in developing countries like Ethiopia. There are fragmented, inconsistency, and no review has been conducted to report the magnitude and associated factors of neonatal sepsis in Ethiopia. Thus, this study aimed to assess the pooled prevalence of neonatal sepsis and its association with birth weight and gestational age among admitted neonates in Ethiopia.Methods: Electronic media searches like PubMed, CINHAL, EMBASE, Google Scholar, Web of Science, Cochrane library databases and African health science library were used. All original peer-reviewed papers which reported the prevalence of neonatal sepsis in Ethiopia were included in this study. Two reviewers independently extracted the data using a standardized data extraction format for eligibility and appraised their quality. Data were analyzed using Stata version 14 software. The pooled prevalence of neonatal sepsis was estimated with the random-effect model. Heterogeneity between studies was assessed by I 2 statistics test. Subgroup and meta-regression analyses were done to assess the source of variation between the studies. Egger's test followed by trim and fill analysis were used to determine publication bias. A sensitivity analysis was carried out.Result: A total of 952 research papers reviewed, of which, eight studies were finally included in this systematic review and meta-analysis. The random effect pooled prevalence of neonatal sepsis in Ethiopia was 49.98% (CI: 36.06, 63.90). In subgroup analysis, the pooled estimated neonatal sepsis among cross-sectional studies was 53.15% while the cohort was 40.56%. Newborns with a birth weight of less than 2.5 kg were 1.42 times more likely to develop neonatal sepsis infection compared to normal babies. The odds ratios of preterm babies were 3.36 to develop neonatal sepsis compared to term infants.Conclusion: The pooled prevalence of neonatal sepsis in Ethiopia was high. Thus, health care providers should adhere to aseptic precautions while performing procedures, especially in preterm and low birth weight infants were recommended. [ABSTRACT FROM AUTHOR]

Background: Conducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet approaching parents at this difficult time raises challenges for the obtaining of valid informed consent to such research. This study asked: what light does the empirical literature cast on an ethically defensible approach to the obtaining of informed consent in perinatal clinical trials?Methods: A systematic search identified 49 studies. Analysis began by applying philosophical frameworks which were then refined in light of the concepts emerging from empirical studies to present a coherent picture of a broad literature.Results: Between them, studies addressed the attitudes of both parents and clinicians concerning consent in neonatal trials; the validity of the consent process in the neonatal research context; and different possible methods of obtaining consent.Conclusions: Despite a variety of opinions among parents and clinicians there is a strongly and widely held view that it is important that parents do give or decline consent for neonatal participation in trials. However, none of the range of existing consent processes reviewed by the research is satisfactory. A significant gap is evaluation of the widespread practice of emergency 'assent', in which parents assent or refuse their baby's participation as best they can during the emergency and later give full consent to ongoing participation and follow-up. Emergency assent has not been evaluated for its acceptability, how such a process would deal with bad outcomes such as neonatal death between assent and consent, or the extent to which late parental refusal might bias results. This review of a large number of empirical papers, while not making fundamental changes, has refined and developed the conceptual framework from philosophy for examining informed consent in this context. [ABSTRACT FROM AUTHOR]

Dear Editor, We read with interest Dingermann et al.'s recent paper I Low gestational age is associated with less anastomotic complications after open primary repair of esophageal atresia with tracheoesophageal fistula i . The data presented in the paper do not support the conclusion that low gestational age is associated with less anastomotic complications after open primary repair of esophageal atresia. Response to: Low gestational age is associated with less anastomotic complications after open primary repair of esophageal atresia with tracheoesophgeal fistula. [Extracted from the article]

Background: Conducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet, approaching the parents of these infants at such a difficult time raises challenges to obtaining valid informed consent for such research. In this study, we asked, What light does the analytical literature cast on an ethically defensible approach to obtaining informed consent in perinatal clinical trials?Methods: In a systematic search, we identified 30 studies. We began our analysis by applying philosophical frameworks, which were then refined as concepts emerged from the analytical studies, to present a coherent picture of a broad literature.Results: Between them, the studies addressed four themes. The first three were the ethical basis for parental informed consent for neonatal and/or perinatal research, the validity of parental consent in this context, and the range of possible options in methods for gaining consent. The last was the issue of risk and the possibility of a double-standard or asymmetry in the current approaches to the requirement for consent for research and consent for clinical treatment.Conclusions: In addressing these issues, the analysed studies showed that, whilst there are a variety of possible defences for seeking parental 'consent' to neonatal and/or perinatal clinical trials, these are all consistent with the strongly and widely held view that it is important that parents do give (or decline) consent for such research. So far as the method of obtaining consent is concerned, none of the existing consent processes reviewed by the research is satisfactory, and there are philosophical reasons for supposing that at least some parents will fail to give valid consent in a neonatal context. Furthermore, in giving parental 'consent' in a perinatal context, parents are authorising infant participation, not giving 'proxy consent'. Finally, there are reasons for giving weight to both parental 'consent' and the infant's best interests in both research and clinical treatment. However, there are also reasons to treat these factors differently in the two contexts, and this may be partly due to the differing relevance of risk in each case. A significant gap is the lack of any detailed discussion of a process of emergency and/or urgent 'assent', in which parents assent or refuse their baby's participation as best they can during the emergency and later give full consent to continuing participation and follow-up. [ABSTRACT FROM AUTHOR]

Background: Improved access to quality antenatal care (ANC) promotes healthy behaviors and early complication management, enhancing maternal and newborn outcomes. The Enhancing Nutrition and Antenatal Infection Treatment for Maternal and Child Health (ENAT) intervention in Ethiopia aimed to increase newborn birth weight by improving ANC utilization and quality. ENAT task shared and decentralized ANC services to facilitate early contact and point of care (POC) testing and management of maternal infections and anemia. This study assessed if task sharing and decentralization improved utilization and quality of ANC services at primary health care facilities. Methods: The study assessed changes in ANC coverage and quality before and after the ENAT intervention, in 65 health centers and 303 health posts across Amhara and Oromia regions of Ethiopia. The intervention task shared ANC services at health centers (Augst 2018-January 2021) and then decentralized services to health posts (February 2021-February 2022). Using descriptive analyses, this study assessed, between baseline and endline, changes in coverage in the proportion of women who: enrolled early into ANC; had at least one ANC contact; and had four or more ANC contacts. Similarly, the study separately assessed each quality indicator through changes in the proportion of iron and folic acid supplementation, and deworming tablets, and POC testing and treatment for anemia, syphilis, and asymptomatic bacteriuria at baseline, phase I and phase II. Results: ANC utilization and quality improved in the 368 sites. Between baseline and endline the proportion of women having an ANC contact before 16 weeks of gestational age increased from 6 to 37%, while those receiving at least one ANC contact and four or more ANC contacts increased from 74 to 91% and 45–57%, respectively. Iron and folic acid supplementation and deworming increased from 44 to 97% and from 44 to 79%, respectively. In the final 12 months of the intervention, 87%, 80%, and 87% of pregnant women attending ANC received POC testing for anemia, syphilis, and asymptomatic bacteriuria, respectively. Conclusions: Our findings suggest that bringing ANC services closer to communities can increase early ANC contact and enhance the coverage and quality of services, leading to better maternal and newborn health outcomes. [ABSTRACT FROM AUTHOR]

Background: The World Health Organisation states that newborns should receive colostrum as soon as possible after birth. However, among newborns needing neonatal intensive care, initiation of lactation and access to colostrum might be delayed. At the centre of this study, a tertiary care hospital in Sweden (10,000 deliveries/year), few admitted infants received colostrum within the day of birth, warranting a quality improvement. In order to reduce the time from birth to first colostrum received by infants admitted to the Neonatal Intensive Care Unit (NICU), a new clinical routine including a colostrum-kit, was implemented as standard care in June 2018. The colostrum-kit contained information about hand expression of breastmilk as well as material for collecting, labelling and transporting the colostrum. The kit should be handed to all birthing parents with infants admitted to the NICU. Methods: Data on time in minutes from birth to first colostrum administered to the infant (oral mouth care, oral feeding or gavage feeding) was retrieved for all infants born between 1 September 2016 and 31 October 2023, admitted to the NICU within 1h from birth. Infants were divided into four time-cohorts, compared with nonparametric ANOVA. Results: The study included 3618 infants born at 22 + 0 – 43 + 0 weeks gestational age, of whom 2814 (78%) had available data on time to colostrum. Median (IQR) time in hours was 35 (20–36) pre-implementations, followed by 18 (7–38), 11 (4–26) and 8 (3–22) in the subsequent follow-up cohorts, p < 0.001. Subgroups of mode of delivery had median (IQR) pre-implementation of 30 (19–54) for vaginal and 47 (23–72) for caesarean section that reached 7 (2–18) and 9 (3–26) in the last follow-up. Subgroups of gestational age (< 28, 28–31, 32–36, > 36 weeks) had a pre-implementation time of 48 (26–80), 46 (23–73), 33 (20–60) and 32 (19–57), that in the last follow-up was reduced to 4 (2–20), 7 (2–29), 9 (2–33) and 9 (4–19). Conclusions: Implementing a colostrum-kit for infants admitted to the NICU significantly reduced the time to first colostrum administered to the infant in all gestational ages. The difference between subgroups of gestational age or mode of delivery was reduced. The effect persisted over time. [ABSTRACT FROM AUTHOR]

Background: The majority of infants who die in the neonatal period are born with a low birth weight (LBW, <2500 grams), or prematurely (before 37 weeks). Most deaths among these infants could be prevented with simple, low-cost interventions like kangaroo mother care (KMC) or prevention and early identification of infection. It is difficult, however, to determine birth weight and gestational age in community settings, and therefore necessary to find an appropriate alternative screening tool that can identify LBW and preterm infants. Methods: This cross-sectional study was conducted at a tertiary hospital in Nepal to compare the validity of using three different foot length measurement methods (plastic ruler, measuring tape, and paper footprint) as screening tools for identifying babies with birth weights <2000 grams or infants born preterm (<37 weeks). LBW was defined as less than 2000 grams because of the implication for use of KMC for these infants. Non-parametric receiver operating characteristics (ROC) analysis was completed to determine which measurement method best predicted LBW and preterm birth. For the method that was the best predictor for each outcome (i.e. highest area under the curve), further analyses were completed to determine sensitivity, specificity, likelihood ratios and predictive values of an operational screening cutoff to predict LBW or preterm birth in this setting. Results: Of the 811 infants included in this study, 30 infants had LBW and 54 were born preterm. The plastic ruler was the measurement method with the highest area under the curve, and thus predictive score for estimating both outcomes, so operational cutoffs were identified based on this method. An operational cutoff of 7.2 cm was identified to screen for infants weighing <2000 grams at birth (sensitivity: 75.9%, specificity: 90.3%), and 7.8 cm was determined as the operational cutoff to identify preterm infants (sensitivity: 76.9%, specificity: 53.9%). Conclusions: In Nepal, at least in community settings, foot length measurement with a hard ruler may be a valid proxy to identify at-risk infants when birth weight or gestational age is unavailable. Further studies and piloting should be conducted to identify exact cutoffs that can be used within community settings. [ABSTRACT FROM AUTHOR]

Background: Preterm delivery refers to childbirth that occurs before 37 full weeks' gestation. Globally, around 13.4 million babies are born preterm annually, a million died due to its complications. Identifying its determinants is mandatory to decrease preterm birth and thereby neonatal deaths. Therefore, this study aimed to identify the determinants of preterm delivery among mothers who gave birth in hospitals in the Wolaita zone, southern Ethiopia. Methods: A hospital-based unmatched case-control study design was conducted from March 29 to May 20, 2023, in the Wolaita zone, southern Ethiopia. Cases were women who gave birth after 28 weeks and before 37 completed weeks, and controls were women who gave birth at and after 37 and before 42 weeks of gestation from the first day of the last normal menstrual period. A consecutive sampling method was used. Data were collected by a structured interviewer-administered questionnaire. Data were coded and entered into Epi data 3.1 and analyzed by using SPSS version 25. Variables that had a P-value < 0.25 in the bivariate logistic regression analysis were entered into a multivariable logistic regression model. Finally, p-value < 0.05 was used to claim statistical significance. Result: From a total of 405 eligible participants, 399 respondents (133 cases and 266 controls) participated in this study with a response rate of 98.52%. The result of the multivariable analysis shows that mothers who resided in rural areas [AOR = 2.78:95% CI (1.51–5.12)], not receiving support from their partner [AOR = 2.37:95% CI (1.24–4.51)], less than four antenatal care visits [AOR = 4.52:95%CI (2.38–8.57)], developed pregnancy-induced hypertension [AOR = 5.25:95%CI (2.27–12.14)] and exposed for intimate partner violence [AOR = 2.95:95%CI (1.105–7.85)], had statistically significant association with experiencing preterm delivery. Conclusion and recommendation: Most of the determinants for preterm delivery have been proven modifiable. Thus, designing new strategies, providing comprehensive mobile clinic services to address hard-to-reach areas and Health care providers should give due attention to mothers with pregnancy-induced hypertension and exposure to intimate partner violence and increase the awareness of antenatal care follow-up and benefit of support during pregnancy to reduce preterm delivery. [ABSTRACT FROM AUTHOR]

Background: The neonatal outcomes across different percentiles of birth weight for gestational age are still unclear. Methods: This retrospective cohort study was conducted within 57 tertiary hospitals participating in the Chinese Neonatal Network (CHNN) from 25 provinces throughout China. Infants with gestational age (GA) 24+0-31+6 weeks who were admitted within 7 days after birth were included. The composite outcome was defined as mortality or any one of neonatal major morbidities, including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (cPVL), severe retinopathy of prematurity (ROP), and sepsis. Multivariable logistic regressions using generalized estimating equation approach were conducted. Results: A total of 8380 infants were included with a mean GA of 30 (28–31) weeks. Of these, 1373 (16.5%) were born at less than 28 weeks, while 6997 (83.5%) had a GA between 28 and 32 weeks. Our analysis indicated that the risk of composite outcomes was negatively associated with birth weight for gestational age, and compared to the reference group, the multiple-adjusted ORs (95%CI) of composite outcomes were 4.89 (3.51–6.81) and 2.16 (1.77–2.63) for infants with birth weight for gestational less than 10th percentile and 10th -30th percentile, respectively. The ORs (95%CI) of mortality, NEC, BPD, severe ROP, and sepsis in infants with birth weight for gestational age at 10th-30th percentile were 1.94 (1.56–2.41), 1.08 (0.79–1.47), 2.48 (2.03–3.04), 2.35 (1.63–3.39), and 1.39 (1.10–1.77), respectively. Conclusion: Our study suggested that the risk of adverse neonatal outcomes increased significantly when the birth weight for gestational age was below the 30th percentile. Regular monitoring and early intervention are crucial for these high-risk infants. [ABSTRACT FROM AUTHOR]

Background: Sepsis is the 3rd leading cause of neonatal mortality in Ethiopia contributing to 16% of neonatal death. In a hospital study, neonatal sepsis was the leading diagnosis at admission and the second leading cause of neonatal death at the neonatal intensive care unit. Among other factors repeated vaginal examination during labor is known to contribute to sepsis in low-income settings. However, there is limited evidence in the Ethiopian setting. Objective: The objective of this study was to examine the association between early-onset neonatal sepsis and repeated vaginal examinations. Methods: The study was conducted at Gandhi Memorial Hospital, a public maternity and newborn care hospital. We followed 672 mother-newborn pairs by phone until 7 days of age to detect clinical sepsis. Data were analyzed using SPSS version 20 software. Adjusted odds ratio risk (AOR) with a corresponding 95% confidence interval (CI) was used to show the strength of associations and variables with p-value < 0.05 were considered to be statistically significant. Results: The incidence of early-onset neonatal sepsis was found to be 20.83% (95% CI 17.60, 24.00). Having a frequent vaginal examination (four or more times) during labor and delivery, prolonged rupture of membranes, induced labor and gestational age < 37 weeks were strongly associated with the development of early-onset neonatal sepsis, (AOR 2. 69;95 CI: 1.08, 6.70) AOR 5.12(95% CI 1.31, 20.00), AOR of 5.24 (95% CI 1.72, AOR4.34 (95% CI 1.20, 15.68), 16.00), respectively. Conclusion: Frequent digital vaginal examination prolonged rupture of membranes, induced labor and gestational age < 37 weeks significantly increases the risk of early onset neonatal sepsis. We also recommend further study using neonatal blood culture to better diagnose early onset neonatal sepsis objectively. [ABSTRACT FROM AUTHOR]

Objective: This Study aims to investigate the risk factors of hypoglycemia in neonates through meta-analysis. Method: PubMed, Embase, Cochrane library, and Web of science databases were searched for case-control studies on risk factors for neonatal hypoglycemia. The search was done up to 1st October 2023 and Stata 15.0 was used for data analysis. Results: A total of 12 published studies were included, including 991 neonates in the hypoglycemic group and 4388 neonates in the non-hypoglycemic group. Meta-analysis results suggested caesarean section [OR = 1.90 95%CI (1.23, 2.92)], small gestational age[OR = 2.88, 95%CI (1.59, 5.20)], gestational diabetes [OR = 1.65, 95%CI (1.11, 2.46)], gestational hypertension[OR = 2,79, 95%CI (1.78, 4.35)] and respiratory distress syndrome[OR = 5.33, 95%CI (2.22, 12.84)] were risk factors for neonatal hypoglycemia. Conclusion: Based on the current study, we found that caesarean section, small gestational age, gestational diabetes, gestational hypertension, respiratory distress syndrome are risk factors for neonatal hypoglycemia. PROSPERO registration number: CRD42023472974. [ABSTRACT FROM AUTHOR]

Background: The nutritional status of the mother prior to and during pregnancy plays a vital role in fetal growth and development, and maternal undernourishment may lead to adverse perinatal outcomes including intrauterine growth restriction (IUGR). Several macronutrient interventions had been proposed for adequate protein and energy supplementation during pregnancy. The objective of this paper was to review the effect of balanced protein energy supplementation during pregnancy on birth outcomes. This paper is a part of a series of reviews undertaken for getting estimates of effectiveness of an intervention for input to Lives Saved Tool (LiST) model. Methods: A literature search was conducted on PubMed, Cochrane Library and WHO regional data bases to identify randomized trials (RCTs) and quasi RCTs that evaluated the impact of balanced protein energy supplementation in pregnancy. Balanced protein energy supplementation was defined as nutritional supplementation during pregnancy in which proteins provided less than 25% of the total energy content. Those studies were excluded in which the main intervention was dietary advice to pregnant women for increase in protein energy intake, high protein supplementation (i.e. supplementation in which protein provides at least 25% of total energy content), isocaloric protein supplementation (where protein replaces an equal quantity of nonprotein energy content), or low energy diet to pregnant women who are either overweight or who exhibit high weight gain earlier in gestation. The primary outcomes were incidence of small for gestational age (SGA) birth, mean birth weight and neonatal mortality. Quality of evidence was evaluated according to the Child Health Epidemiology Reference group (CHERG) adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Results: The final number of studies included in our review was eleven comprising of both RCTs and quasi-RCTs. Our meta-analysis indicates that providing pregnant females with balanced protein energy supplementation resulted in a significant reduction of 31 % in the risk of giving birth to small for gestational age infants (Relative risk (RR) =0.69, 95% Confidence interval (CI) 0.56 to 0.85). This estimate had been recommended for LiST as a proxy for reduction in IUGR. Pooled results for mean birth weight showed that balanced protein supplemented group gained more weight compared to control [Mean difference 59.89 g, 95 % CI 33.09-86.68]. This effect was more pronounced in malnourished women compared to adequately nourished women. There was no statistically significant effect of balanced protein energy supplementation on neonatal mortality (RR= 0.63, 95% CI 0.37 to 1.06). Conclusion: Providing pregnant females with balanced protein energy supplementation leads to reduction in risk of small for gestational age infants, especially among undernourished pregnant women. Given these findings, we can recommend balanced protein energy supplementation as an intervention among undernourished women for inclusion in the LiST model with a point estimate of 31% [95% CI 15% to 44%] reduction in IUGR. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is a state of increased requirement of macro- and micronutrients, and malnourishment or inadequate dietary intake before and during pregnancy, can lead to adverse perinatal outcomes including stillbirths. Many nutritional interventions have been proposed during pregnancy according to the nutritional status of the mother and baseline risk factors for different gestational disorders. In this paper, we have reviewed three nutritional interventions including peri-conceptional folic acid supplementation, balanced protein energy supplementation and multiple micronutrients supplementation during pregnancy. This paper is a part of a series to estimate the effect of interventions on stillbirths for input to Live Saved Tool (LiST) model. Methods: We systematically reviewed all published literature to identify studies evaluating effectiveness of periconceptional folic acid supplementation in reducing neural tube defects (NTD), related stillbirths and balanced protein energy and multiple micronutrients supplementation during pregnancy in reducing all-cause stillbirths. The primary outcome was stillbirths. Meta-analyses were generated where data were available from more than one study. Recommendations were made for the Lives Saved Tool (LiST) model based on rules developed by the Child Health Epidemiology Reference Group (CHERG). Results: There were 18 studies that addressed peri-conceptional folic acid supplementation for prevention of neural tube defects (NTDs). Out of these, 7 studies addressed folic acid supplementation while 11 studies evaluated effect of folic acid fortification. Pooled results from 11 fortification studies showed that it reduces primary incidence of NTDs by 41 % [Relative risk (RR) 0.59; 95 % confidence interval (CI) 0.52-0.68]. This estimate has been recommended for inclusion in the LiST as proxy for reduction in stillbirths. Pooled results from three studies considered to be of low quality and suggest that balanced protein energy supplementation during pregnancy could lead to a reduction of 45% in stillbirths [RR 0.55, 95 % CI 0.31-0.97]. While promising, the intervention needs more effectiveness studies before inclusion in any programs. Pooled results from 13 studies evaluating role of multiple micronutrients supplementation during pregnancy showed no significant effect in reducing stillbirths [RR = 0.98; 95% CI: 0.88 - 1.10] or perinatal mortality [RR = 1.07; 95% CI: 0.92 - 1.25; random model]. No recommendations have been made for this intervention for inclusion in the LiST model. Conclusions: Peri-conceptional folic acid supplementation reduces stillbirths due to NTDs by approximately 41%, a point estimate recommended for inclusion in LiST. [ABSTRACT FROM AUTHOR]

Background: The Cord Pilot Trial aimed to assess the feasibility of conducting a large UK randomised trial to compare the effects of alternative polices for timing of cord clamping (immediate within 20 seconds or deferred after at least 2 minutes) for very preterm birth before 32 weeks gestation. Initial recruitment was from March 2013 to February 2014, phase 2 was from March 2014 to February 2015. This paper updates the pilot trial protocol (Trials 15(1):258, 2014) and presents the changes for phase 2.Methods: An electronic randomisation system was introduced at three of the eight pilot sites. For follow-up of children, the Parent Report of Children's Abilities--Revised (PARCA-R) will not be used. For children recruited to the trial during phase 2, follow-up at age 2 years (corrected for gestation at birth) will be by parent completed Ages and Stages Questionnaire (Squire J, Ages and Stages Questionnaires (ASQ), 2009) alone unless funds can be secured for the additional Bayley Scales of Infant Development III (Bayley N, Bayley Scales of Infant and Toddler Development, Third Edition. (Bayley-III), 2005) assessments. To assess accuracy of the cranial ultrasound diagnosis of intraventricular haemorrhage: (i) quality of the scans will be assessed using the British Society of Paediatric Radiology recommendations, and (ii) scan results will be confirmed by independent adjudication. Within and between adjudicator reliability will be assessed. In addition to the analyses planned to assess feasibility of the full trial based on data from the first year of recruitment, data on compliance and outcomes will be presented by allocated group for all women and babies recruited.Trial Registration: ISRCTN21456601, registered on 28 February 2013. [ABSTRACT FROM AUTHOR]

Background: As obesity has increased worldwide, so have levels of obesity during pregnancy and excess gestational weight gain (GWG). The aim of this paper was to describe GWG among American Samoan women and examine the association between GWG and four adverse pregnancy and infant outcomes: cesarean delivery, small- and large-for-gestational age (SGA/LGA), and infant overweight/obesity., Methods: Data were extracted from prenatal care records of 632 Samoan women. Mixed-effects growth models were used to produce individual weight-for-gestational week curves from which second and third trimester weight gain was estimated. Binary logistic regression was used to examine associations between GWG and the outcomes of interest., Results: Most women were overweight/obese in early pregnancy (86%) and 78% exceeded the Institute of Medicine GWG guidelines. Greater GWG in the second trimester and early pregnancy weight were independently associated with increased odds of a c-section (OR 1.40 [95% CI: 1.08, 1.83]) and OR 1.51 [95% CI: 1.17, 1.95], respectively). Risk of delivering a LGA infant increased with greater third trimester weight gain and higher early pregnancy weight, while second trimester weight gain was negatively associated with SGA. Risk of infant overweight/obesity at 12 months increased with early pregnancy weight (OR: 1.23 [95% CI: 1.01, 1.51]) and infant birthweight., Conclusions: The high levels of pregnancy obesity and excessive GWG in American Samoa suggest that it is important for physicians to encourage women into prenatal care early and begin education about appropriate GWG and the potential risks of excess weight gain for both the mother and baby.

Background: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. Methods: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). Results: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. Conclusion: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation. [ABSTRACT FROM AUTHOR]

The Global Network's Antenatal Corticosteroids Trial (ACT), was a multi-country, cluster-randomized trial to improve appropriate use of antenatal corticosteroids (ACS) in low-resource settings in low-middle income countries (LMIC). ACT substantially increased ACS use in the intervention clusters, but the intervention failed to show benefit in the targeted < 5th percentile birth weight infants and was associated with increased neonatal mortality and stillbirth in the overall population. In this issue are six papers which are secondary analyses related to ACT that explore potential reasons for the increase in adverse outcomes overall, as well as site differences in outcomes. The African sites appeared to have increased neonatal mortality in the intervention clusters while the Guatemalan site had a significant reduction in neonatal mortality, perhaps related to a combination of ACS and improving obstetric care in the intervention clusters. Maternal and neonatal infections were increased in the intervention clusters across all sites and increased infections are a possible partial explanation for the increase in neonatal mortality and stillbirth in the intervention clusters, especially in the African sites. The analyses presented here provide guidance for future ACS trials in LMIC. These include having accurate gestational age dating of study subjects and having care givers who can diagnose conditions leading to preterm birth and predict which women likely will deliver in the next 7 days. All study subjects should be followed through delivery and the neonatal period, regardless of when they deliver. Clearly defined measures of maternal and neonatal infection should be utilized. Trials in low income country facilities including clinics and those without newborn intensive care seem to be of the highest priority. [ABSTRACT FROM AUTHOR]

Background: A major unresolved safety concern for malaria case management is the use of artemisinin combination therapies (ACTs) in the first trimester of pregnancy. There is a need for human data to inform policy makers and treatment guidelines on the safety of artemisinin combination therapies (ACT) when used during early pregnancy. Methods: The overall goal of this paper is to describe the methods and implementation of a study aimed at developing surveillance systems for identifying exposures to antimalarials during early pregnancy and for monitoring pregnancy outcomes using health and demographic surveillance platforms. This was a multi-center prospective observational cohort study involving women at health and demographic surveillance sites in three countries in Africa: Burkina Faso, Kenya and Mozambique [(ClinicalTrials.gov Identifier: NCT01232530)]. The study was designed to identify pregnant women with artemisinin exposure in the first trimester and compare them to: 1) pregnant women without malaria, 2) pregnant women treated for malaria, but exposed to other antimalarials, and 3) pregnant women with malaria and treated with artemisinins in the 2nd or 3rd trimesters from the same settings. Pregnant women were recruited through community-based surveys and attendance at health facilities, including antenatal care clinics and followed until delivery. Data from the three sites will be pooled for analysis at the end of the study. Results are forthcoming. Discussion: Despite few limitations, the methods described here are relevant to the development of sustainable pharmacovigilance systems for drugs used by pregnant women in the tropics using health and demographic surveillance sites to prospectively ascertain drug safety in early pregnancy. Trial registration: NCT01232530 [ABSTRACT FROM AUTHOR]

An introduction is presented in which the authors discuss various reports published within the issue on topics related to pregnancy outcome and neonatal health.

Background: Placenta accreta spectrum disorders (PASDs) increase the mortality rate for mothers and newborns over a decade. Thus, the purpose of the study is to evaluate the neonatal outcomes in emergency cesarean section (CS) and planned surgery as well as in Cesarean hysterectomy and the modified one-step conservative uterine surgery (MOSCUS). The secondary aim is to reveal the factors relating to poor neonatal outcomes. Methods: This was a single-center retrospective study conducted between 2019 and 2020 at Tu Du Hospital, in the southern region of Vietnam. A total of 497 pregnant women involved in PASDs beyond 28 weeks of gestation were enrolled. The clinical outcomes concerning gestational age, birth weight, APGAR score, neonatal intervention, neonatal intensive care unit (NICU) admission, and NICU length of stay (LOS) were compared between emergency and planned surgery, between the Cesarean hysterectomy and the MOSCUS. The univariate and multivariable logistic regression were used to assess the adverse neonatal outcomes. Results: Among 468 intraoperatively diagnosed PASD cases who underwent CS under general anesthesia, neonatal outcomes in the emergency CS (n = 65) were significantly poorer than in planned delivery (n = 403). Emergency CS increased the odds ratio (OR) for earlier gestational age, lower birthweight, lower APGAR score at 5 min, higher rate of neonatal intervention, NICU admission, and longer NICU LOS ≥ 7 days with OR, 95% confidence interval (CI) were 10.743 (5.675–20.338), 3.823 (2.197–6.651), 5.215 (2.277–11.942), 2.256 (1.318–3.861), 2.177 (1.262–3.756), 3.613 (2.052–6.363), and 2.298 (1.140–4.630), respectively, p < 0.05. Conversely, there was no statistically significant difference between the neonatal outcomes in Cesarean hysterectomy (n = 79) and the MOSCUS method (n = 217). Using the multivariable logistic regression, factors independently associated with the 5-min-APGAR score of less than 7 points were time duration from the skin incision to fetal delivery (min) and gestational age (week). One minute-decreased time duration from skin incision to fetal delivery contributed to reduce the risk of adverse neonatal outcome by 2.2% with adjusted OR, 95% CI: 0.978 (0.962–0.993), p = 0.006. Meanwhile, one week-decreased gestational age increased approximately two fold odds of the adverse neonatal outcome with adjusted OR, 95% CI: 1.983 (1.600–2.456), p < 0.0001. Conclusions: Among pregnancies with PASDs, the neonatal outcomes are worse in the emergency group compared to planned group of cesarean section. Additionally, the neonatal comorbidities in the conservative surgery using the MOSCUS method are similar to Cesarean hysterectomy. Time duration from the skin incision to fetal delivery and gestational age may be considered in PASD surgery. Further data is required to strengthen these findings. Highlights: - The increased rate of poor neonatal outcomes in PASDs is mainly related to emergency cesarean section. - The MOSCUS method and Cesarean hysterectomy are likely similar to the risk of adverse neonatal outcomes. - Time duration from the skin incision to fetal delivery and gestational age are potential predictors in the surgery of PASDs. [ABSTRACT FROM AUTHOR]

Aim: To evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome. Methods: This prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis. Results: Late-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA. Conclusions: HCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention. [ABSTRACT FROM AUTHOR]

Background: The effect of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus in the neonatal period on developing brain is still unknown. This study aims to investigate the long-term neurodevelopmental outcomes of newborns exposed to SARS-CoV-2 & Delta variant. Methods: At a tertiary referral center, a prospective observational cohort research was carried out. All babies who were equal to or more than 34 gestational weeks gestation and were admitted to the NICU between January 2021 and January 2022 due to SARS-CoV-2 infection (Delta - or Delta +) were included in the study. Infants who were hospitalized for non-SARS-CoV-2 reasons at similar dates and who had no history of invasive mechanical ventilation were incorporated as a control group using a 2:1 gender and gestational age match. Thirty infants were assigned to the study group and sixty newborns to the control group based on the sample size calculation. These toddlers' neurodevelopment was evaluated between the ages of 18 and 24 months using the Bayley-II scale. Results: We enrolled 90 infants. SARS-CoV-2-positive infants had poorer psychomotor development index (PDI) scores and significantly greater mildly delayed performances (MDPs) at 18–24 months (PDI p = 0.05, MDPs p = 0.03, respectively). Delta variant showed statistically significant lower MDI and PDI scores (MDI p=0.03, PDI p=0.03, respectively). A smaller head circumference of SARS-CoV-2-positive toddlers was detected in the first year (p < 0.001), which improved at the second age. Conclusion: SARS-CoV-2-positive neonates revealed lower PDI scores and greater MDPs at 18th-24th months. The effect is most noticeable in Delta variant. Longer-term examination of neurodevelopmental outcomes and reevaluation of these children between the ages of 5 and 12 are critical. [ABSTRACT FROM AUTHOR]

Background: Repeated cryopreservation of embryos should occasionally be considered when embryos were not suitable for transfer. The effect of re-cryopreservation on embryos remains contentious. Methods: This retrospective cohort study aimed to evaluate the pregnancy and neonatal outcomes of twice vitrificated blastocyst derived from once vitrified embryos. Total 410 vitrified-warmed blastocyst transfer cycles were divided into two groups according to the times of embryo vitrification: (1) vitrified blastocysts derived from fresh blastocysts (control group, n = 337); (2) twice vitrified blastocysts derived from once vitrified embryos (n = 73). The primary outcome was live birth rate. Multivariable logistic or linear regression analysis model was performed to describe the association between embryo cryopreservation times and clinical outcomes. Results: No difference was observed in female age at retrieval and transfer, infertility period, body mass index (BMI), infertility type, endometrial thickness, and embryo transfer numbers between the two groups. The pregnancy outcomes of embryos in repeated cryopreservation group were comparable to those of embryos in control group, including implantation rate, clinical pregnancy rate, and live birth rate. In multivariate logistic regression analysis, the cryopreservation times did not affect the outcomes of biochemical pregnancy, clinical pregnancy, and live birth. Moreover, there was no difference in gestational age, birthweight and sex ratio of singleton newborns between groups. After correcting several possible confounding variables, no significant association was observed between cryopreservation times and neonatal birthweight. Conclusion: In conclusion, pregnancy and neonatal outcomes achieved with twice vitrified blastocyst transfer were comparable to those achieved with vitrified blastocyst transfer in control group. [ABSTRACT FROM AUTHOR]

Background: We previously conducted a primary survey of pregnant women with hereditary thrombophilia based on national surveillance in Japan, but did not examine their thrombosis-related characteristics. Antithrombin (AT) deficiency, protein C (PC) deficiency and protein S (PS) deficiency are the major types of hereditary thrombophilia in Japan. Methods: We examined their detailed information related to thrombosis, and evaluated peripartum outcomes in comparison with control data obtained from the Japan Society of Obstetrics and Gynecology. Results: Definite or probable AT deficiency, PC deficiency and PS deficiency were observed in 80, 50, and 317 pregnancies, respectively, from 2014 to 2018 in Japan, with prevalence rates among total deliveries of 0.011%, 0.007%, 0.044%. The number of pregnancies with AT, PC and PS deficiency might have been as many as 27, 17 and 108 every year if complete answers had been provided. In the peripartum period of current pregnancies, 27.5% of women with AT deficiency, 28.0% with PC deficiency and 13.2% with PS deficiency developed thrombosis (p < 0.001 vs. control). Pregnant women with AT and PC deficiency were more susceptible to thrombosis than those with PS deficiency (P < 0.01). Of the thromboses, 92.3% occurred during pregnancy, 62.8% at less than 15 gestational weeks. The earliest onset of thrombosis was 5 gestational weeks. Prophylactic anticoagulation significantly prevented the onset of both antepartum and postpartum thrombosis (p < 0.0001). The rate of recurrent pregnancy loss in women with low PC or PS activities was significantly higher than in controls (p < 0.0001); however, it is unknown whether recurrent pregnancy loss is related to hereditary PS deficiency. There seem to have been few serious maternal or fetal/neonatal complications due to placental insufficiency related to a hypercoagulable state other than growth restriction. Conclusions: This survey revealed the thrombosis-related characteristics of pregnant women with hereditary thrombophilia in Japan. We suggest prophylactic anticoagulation to prevent maternal or fetal/neonatal complications. [ABSTRACT FROM AUTHOR]

Background Approximately 1 in 5 pregnant women in the United Kingdom are obese. In addition to being associated generally with poor health, obesity is known to be a contributing factor to pregnancy and birth complications and the retention of gestational weight can lead to long term obesity. This paper describes the protocol for a cluster randomised trial to evaluate whether a weight management intervention for obese pregnant women is effective in reducing women's Body Mass Index at 12 months following birth. Methods/design The study is a cluster randomised controlled trial involving 20 maternity units across England and Wales. The units will be randomised, 10 to the intervention group and 10 to the control group. 570 pregnant women aged 18 years or over, with a Body Mass Index of +/=30 (kg/m2) and between 12 and 20 weeks gestation will be recruited. Women allocated to the control group will receive usual care and two leaflets giving advice on diet and physical activity. In addition to their usual care and the leaflets, women allocated to the intervention group will be offered to attend a weekly 1.5 hour weight management group, which combines expertise from Slimming World with clinical advice and supervision from National Health Service midwives, until 6 weeks postpartum. Participants will be followed up at 36 weeks gestation and at 6 weeks, 6 months and 12 months postpartum. Body Mass Index at 12 months postpartum is the primary outcome. Secondary outcomes include pregnancy weight gain, quality of life, mental health, waist-hip ratio, child weight centile, admission to neonatal unit, diet, physical activity levels, pregnancy and birth complications, social support, self-regulation and self-efficacy. A cost effectiveness analysis and process evaluation will also be conducted. Discussion This study will evaluate the effectiveness of a theory-based intervention developed for obese pregnant women. If successful the intervention will equip women with the necessary knowledge and skills to enable them to make healthier choices for themselves and their unborn child.` [ABSTRACT FROM AUTHOR]

Background Both air pollution exposure and socioeconomic status (SES) are important indicators of children's health. Using highly resolved modeled predictive surfaces, we examine the joint effects of air pollution exposure and measures of SES in a population level analysis of pregnancy outcomes in North Carolina (NC). Methods Daily measurements of particulate matter <2.5 μm in aerodynamic diameter (PM2.5) and ozone (O3) were calculated through a spatial hierarchical Bayesian model which produces census-tract level point predictions. Using multilevel models and NC birth data from 2002- 2006, we examine the association between pregnancy averaged PM2.5 and O3, individual and area-based SES indicators, and birth outcomes. Results Maternal race and education, and neighborhood household income were associated with adverse birth outcomes. Predicted concentrations of PM2.5 and O3 were also associated with an additional effect on reductions in birth weight and increased risks of being born low birth weight and small for gestational age. Conclusions This paper builds on and complements previous work on the relationship between pregnancy outcomes and air pollution exposure by using 1) highly resolved air pollution exposure data; 2) a five-year population level sample of pregnancies; and 3) including personal and areal level measures of social determinants of pregnancy outcomes. Results show a stable and negative association between air pollution exposure and adverse birth outcomes. Additionally, the more socially disadvantaged populations are at a greater risk; controlling for both SES and environmental stressors provides a better understanding of the contributing factors to poor children's health outcomes. [ABSTRACT FROM AUTHOR]

Background: Early developmental interventions to prevent the high rate of neurodevelopmental problems in very preterm children, including cognitive, motor and behavioral impairments, are urgently needed. These interventions should be multi-faceted and include modules for caregivers given their high rates of mental health problems., Methods/design: We have designed a randomized controlled trial to assess the effectiveness of a preventative care program delivered at home over the first 12 months of life for infants born very preterm (<30 weeks of gestational age) and their families, compared with standard medical follow-up. The aim of the program, delivered over nine sessions by a team comprising a physiotherapist and psychologist, is to improve infant development (cognitive, motor and language), behavioral regulation, caregiver-child interactions and caregiver mental health at 24 months' corrected age. The infants will be stratified by severity of brain white matter injury (assessed by magnetic resonance imaging) at term equivalent age, and then randomized. At 12 months' corrected age interim outcome measures will include motor development assessed using the Alberta Infant Motor Scale and the Neurological Sensory Motor Developmental Assessment. Caregivers will also complete a questionnaire at this time to obtain information on behavior, parenting, caregiver mental health, and social support. The primary outcomes are at 24 months' corrected age and include cognitive, motor and language development assessed with the Bayley Scales of Infant and Toddler Development (Bayley-III). Secondary outcomes at 24 months include caregiver-child interaction measured using an observational task, and infant behavior, parenting, caregiver mental health and social support measured via standardized parental questionnaires., Discussion: This paper presents the background, study design and protocol for a randomized controlled trial in very preterm infants utilizing a preventative care program in the first year after discharge home designed to improve cognitive, motor and behavioral outcomes of very preterm children and caregiver mental health at two-years' corrected age., Clinical Trial Registration Number: ACTRN12605000492651.

As part of a supplement entitled "Born Too Soon", this paper focuses on care of the preterm newborn. An estimated 15 million babies are born preterm, and the survival gap between those born in high and low income countries is widening, with one million deaths a year due to direct complications of preterm birth, and around one million more where preterm birth is a risk factor, especially amongst those who are also growth restricted. Most premature babies (>80%) are between 32 and 37 weeks of gestation, and many die needlessly for lack of simple care. We outline a series of packages of care that build on essential care for every newborn comprising support for immediate and exclusive breastfeeding, thermal care, and hygienic cord and skin care. For babies who do not breathe at birth, rapid neonatal resuscitation is crucial. Extra care for small babies, including Kangaroo Mother Care, and feeding support, can halve mortality in babies weighing <2000 g. Case management of newborns with signs of infection, safe oxygen management and supportive care for those with respiratory complications, and care for those with signifi cant jaundice are all critical, and are especially dependent on competent nursing care. Neonatal intensive care units in high income settings are de-intensifying care, for example increasing use of continuous positive airway pressure (CPAP) and this makes comprehensive preterm care more transferable. For health systems in low and middle income settings with increasing facility births, district hospitals are the key frontier for improving obstetric and neonatal care, and some large scale programmes now include specific newborn care strategies. However there are still around 50 million births outside facilities, hence home visits for mothers and newborns, as well as women's groups are crucial for reaching these families, often the poorest. A fundamental challenge is improving programmatic tracking data for coverage and quality, and measuring disability-free survival. The power of parent's voices has been important in highincome countries in bringing attention to preterm newborns, but is still missing from the most aff ected countries. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format. [ABSTRACT FROM AUTHOR]

Background: Because of the role of inflammation in preterm birth (PTB), polymorphisms in and near the interleukin-6 gene (IL6) have been association study targets. Several previous studies have assessed the association between PTB and a single nucleotide polymorphism (SNP), rs1800795, located in the IL6 gene promoter region. Their results have been inconsistent and SNP frequencies have varied strikingly among different populations. We therefore conducted a meta-analysis with subgroup analysis by population strata to: (1) reduce the confounding effect of population structure, (2) increase sample size and statistical power, and (3) elucidate the association between rs1800975 and PTB. Results: We reviewed all published papers for PTB phenotype and SNP rs1800795 genotype. Maternal genotype and fetal genotype were analyzed separately and the analyses were stratified by population. The PTB phenotype was defined as gestational age (GA) < 37 weeks, but results from earlier GA were selected when available. All studies were compared by genotype (CC versus CG+GG), based on functional studies. For the maternal genotype analysis, 1,165 PTBs and 3,830 term controls were evaluated. Populations were stratified into women of European descent (for whom the most data were available) and women of heterogeneous origin or admixed populations. All ancestry was self-reported. Women of European descent had a summary odds ratio (OR) of 0.68, (95% confidence interval (CI) 0.51 - 0.91), indicating that the CC genotype is protective against PTB. The result for non-European women was not statistically significant (OR 1.01, 95% CI 0.59 - 1.75). For the fetal genotype analysis, four studies were included; there was no significant association with PTB (OR 0.98, 95% CI 0.72 - 1.33). Sensitivity analysis showed that preterm premature rupture of membrane (PPROM) may be a confounding factor contributing to phenotype heterogeneity. Conclusions: IL6 SNP rs1800795 genotype CC is protective against PTB in women of European descent. It is not significant in other heterogeneous or admixed populations, or in fetal genotype analysis. Population structure is an important confounding factor that should be controlled for in studies of PTB. [ABSTRACT FROM AUTHOR]

Background: In 1990, David Barker proposed that prenatal nutrition is directly linked to adult cardiovascular disease. Since then, the relationship between adult cardiovascular risk, metabolic syndrome and birth weight has been widely documented. Here, we used the TruSeq Methyl Capture EPIC platform to compare the methylation patterns in cord blood from large for gestational age (LGA) vs adequate for gestational age (AGA) newborns from the LARGAN cohort. Results: We found 1672 differentially methylated CpGs (DMCs) with a nominal p < 0.05 and 48 differentially methylated regions (DMRs) with a corrected p < 0.05 between the LGA and AGA groups. A systems biology approach identified several biological processes significantly enriched with genes in association with DMCs with FDR < 0.05, including regulation of transcription, regulation of epinephrine secretion, norepinephrine biosynthesis, receptor transactivation, forebrain regionalization and several terms related to kidney and cardiovascular development. Gene ontology analysis of the genes in association with the 48 DMRs identified several significantly enriched biological processes related to kidney development, including mesonephric duct development and nephron tubule development. Furthermore, our dataset identified several DNA methylation markers enriched in gene networks involved in biological pathways and rare diseases of the cardiovascular system, kidneys, and metabolism. Conclusions: Our study identified several DMCs/DMRs in association with fetal overgrowth. The use of cord blood as a material for the identification of DNA methylation biomarkers gives us the possibility to perform follow-up studies on the same patients as they grow. These studies will not only help us understand how the methylome responds to continuum postnatal growth but also link early alterations of the DNA methylome with later clinical markers of growth and metabolic fitness. [ABSTRACT FROM AUTHOR]