Days Of Gestational Age Research Articles

To find the correlation between transverse cerebellar diameter measured by cranial ultrasound within 48 h of birth and gestational age as estimated by last menstrual period

Background: Gestational age (GA) may be assessed at any time during pregnancy, and several modes of assessment exist, each requiring better diagnostic techniques that may result in more precise estimates of GA, which could lead to quicker medical management of a pregnant patient. The largest diameter across both hemispheres, measured from outer to outer margin, is the transverse cerebellar diameter (TCD). Aims and Objectives: We aimed to predict the correlation between TCD measured by cranial ultrasound within 48 h of birth and GA as estimated by the last menstrual period. Materials and Methods: The present study was conducted in the Department of Pediatrics, Dr. S. N. Medical College, Jodhpur, Rajasthan. Ethical clearance was obtained from the Institutional Ethical Committee. It was a cross-sectional observational study and the duration of the study was 6 months. We split the population into three groups based on GA: (a) <32 weeks of GA, (b) 32–36+6 days of GA, and (c) 37–42 weeks of GA. We enrolled 25 neonates from each group. Results: A very strong positive correlation between TCD and GA in infants was <32 weeks of gestation age, in infants 32–36 weeks+6 days of gestation age, and in infants 37–42 weeks of gestation age. Regression analysis shows a very strongly significant relationship. Hence, the TCD is a better predictor of GA in the third trimester. Our study reported that there is a close relationship between TCD and GA, with TCD increasing linearly from <32 weeks to 42 weeks. GA can be predicted to be 1.43 weeks by assessing TCD on neonatal cranial ultrasonography images. Conclusion: The TCD is a better predictor of GA in the third trimester. Our study reported that there is a close relationship between TCD and GA, with TCD increasing linearly from <32 weeks to 42 weeks.

Assessment of extremely premature lambs supported by the Extrauterine Environment for Neonatal Development (EXTEND).

Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.

Timing of antenatal corticosteroids and survival without neurologic disabilities at 5½ years in children born before 35 weeks of gestation

The efficacy of antenatal corticosteroids for neonatal preterm complications wanes beyond 7 days after treatment. The neurodevelopmental effects of longer treatment-to-birth intervals have not been adequately evaluated. This study aimed to assess the impact of antenatal corticosteroid timing on survival without moderate or severe neurologic disabilities at 5½ years. This was a secondary analysis of the EPIPAGE-2 study, a national population-based cohort (France) that recruited neonates in 2011 and followed them up at 5½ years (results first reported in 2021). Participants were children born alive between 24+0 and 34+6 weeks, with a complete corticosteroid course, delivery >48 hours after the first injection, and neither limitation of care decided before birth nor severe congenital malformation. The study included 2613 children, 2427 of whom were alive at 5½ years; 71.9% (1739/2427) had a neurologic assessment at this age; 1537 had a clinical examination (complete for 1532), and 202 were assessed with a postal questionnaire. Exposure was defined as the interval between the first injection of the last antenatal corticosteroid course and delivery in days, studied in 2 categories (days 3-7 and after day 7), in 4 categories (days 3-7, 8-14, 15-21, and after day 21), and continuously in days. The main outcome was survival at 5½ years without moderate/severe neurologic disabilities, defined as moderate/severe cerebral palsy, or unilateral or bilateral blindness or deafness, or Full-Scale Intelligence Quotient 2 standard deviations below the mean. A multivariate analysis with a generalized estimated equation logistic regression model assessed the statistical association between the main outcomes and the interval from the first corticosteroid injection of the last course to birth. Multivariate analyses were adjusted for potential confounders, defined with a directed acyclic graph: gestational age in days, number of corticosteroid courses, multiple pregnancy, and cause of prematurity in 5 categories. Because neurologic follow-up was complete in only 63.2% of cases (1532/2427), the analyses used imputed data. Among 2613 children, 186 died between birth and 5½ years. Overall survival was 96.6% (95% confidence interval, 95.9-97.0), and survival without moderate or severe neurologic disabilities was 86.0% (95% confidence interval, 84.7-87.0). Survival without moderate or severe neurologic disabilities was lower after day 7 (85.0%) than during the interval from day 3 to day 7 (87.0%) (adjusted odds ratio, 0.70; 95% confidence interval, 0.54-0.89). The association of a >7-day interval between antenatal corticosteroid administration and birth with a lower rate of survival without moderate or severe neurologic disabilities among children aged 5½ years emphasizes the importance of better targeting women at risk of preterm delivery to optimize the timing and thus benefits of treatment.

Neonatal mortality by gestational age in days in infants born at term: A cohort study in Sao Paulo city, Brazil.

Birth at term comprises a period with heterogeneous neonatal outcomes that tend to be worse for infants born earlier. However, few studies have analyzed this period, in which each day can make a difference. Therefore, we aim to assess neonatal mortality (NM) according to gestational age (GA) at birth measured in days in term liveborn infants born in 2012-2017 in São Paulo, the largest city in Latin America. This population-based cohort study assessed term liveborn infants followed until the end of the neonatal period. We analyzed 7 models for NM according to GA in days: crude NM adjusted for maternal and prenatal variables, NM additionally adjusted for type of birth and type of hospital, and adjusted NM stratified by type of birth (cesarean and vaginal) and by type of hospital (public and private). We included 440,119 live infants born at 259-293 days of gestation. The median GA at birth was 274 days. In all models, NM was higher for infants born early term, decreasing in infants born full term and rising again in infants born late term. In the unadjusted model, hazard ratios of NM changed daily, decreasing from 3.34 to 1.00 on day 278 and increasing again thereafter. In the stratified analysis according to type of hospital, being born in a public hospital was associated with a reduced risk of NM for infants born at 278-283 days of pregnancy. There was a decrease in GA related to obstetric interventions, especially cesarean sections, which increased NM. The loss of days of pregnancy was larger in private hospitals. Increasing the granularity of GA to days is feasible and has the potential to drive public policies. To the best of our knowledge, this is the first Brazilian study on GA in days using a national live births database.

Quantitative and Qualitative Analysis of Emergency Physician Performed Biparietal Diameter Estimate for Gestational Age.

An accurate estimation of fetal gestational age is essential for the management of pregnant patients who present to the emergency department (ED). Point-of-care-ultrasound (POCUS) is an integral part of emergency medicine training and includes measurement of fetal gestational age by the biparietal diameter (BPD) method. In this study we performed a quantitative assessment of emergency physician (EP)-performed BPD estimate of gestational age to identify the percentage of studies performed in our department that had an estimated gestational age within 14 days of an adjusted radiological or obstetrical estimation. We performed a chart review of our ED ultrasound database and electronic medical records for cases where a BPD measurement was performed by an EP. We recorded the ED gestational age estimate in days and the radiological or obstetrical estimate of gestational age in days. We then calculated the difference in days between the two examinations. We used a normal binomial approximation to calculate 95% confidence intervals. A secondary analysis looked at the quality of the images based on measurement placement and the view obtained. Seventy-four cases met eligibility criteria; of those, 67 (91%) had a gestational age estimation within 14 days of the adjusted radiological or obstetrical estimate (95% confidence interval 81-96%). This study shows that EP-performed BPD measurements for gestational age are quantitatively accurate, with 91% of estimates within 14 days of a standard radiological or obstetrical estimation.

Urinary glyphosate concentration in pregnant women in relation to length of gestation

Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort. Glyphosate and its primary degradation product [aminomethylphosphonic acid (AMPA)] were measured in urine samples collected during the second trimester from 163 pregnant women: 69 preterm births (<37 weeks) and 94 term births, the latter randomly selected as a subset of TIDES term births. We examined the relationship between exposure and length of gestation using multivariable logistic regression models (dichotomous outcome; term versus preterm) and with weighted time-to-event Cox proportional hazards models (gestational age in days). We conducted these analyses in the overall sample and secondarily, restricted to women with spontaneous deliveries (n = 90). Glyphosate and AMPA were detected in most urine samples (>94 %). A shortened gestational length was associated with maternal glyphosate (hazard ratio (HR): 1.31, 95 % confidence interval (CI) 1.00–1.71) and AMPA (HR: 1.32, 95%CI: 1.00–1.73) only among spontaneous deliveries using adjusted Cox proportional hazards models. In binary analysis, glyphosate and AMPA were not associated with preterm birth risk (<37 weeks). Our results indicate widespread exposure to glyphosate in the general population which may impact reproductive health by shortening length of gestation. Given the increasing exposure to GBHs and the public health burden of preterm delivery, larger confirmatory studies are needed, especially in vulnerable populations such as pregnant women and newborns.

328 Chorionic villi angiogenic protein expression in normal human pregnancy

Our goal was to examine the changes in chorionic villi (CV) expression of angiogenic proteins VEGF165, VEGF165b and MMP-9 throughout gestation in normal human pregnancy. Placentas were obtained from normal pregnant women who underwent elective abortion in the first and second trimesters of pregnancy, and from women who delivered at term. CV protein expressions were analyzed by ELISA using monoclonal antibodies to human VEGF165, VEGF165b and MMP-9 proteins (R&D Systems, Minneapolis, MN). Non-parametric test considered p<0.05 as significant. Our study highlights gestational age-specific alterations in all three CV proteins. VEGF165b protein peaked in the 2nd trimester while VEGF165 protein peaked in the third. MMP-9 protein progressively increased with increase in gestational age. Spearman's correlation showed that VEGF165, VEGF165b and MMP-9 proteins were significantly correlated with gestational age in days (r2=+0.236, p=0.001; r2= +0.158, p=0.028; r2=+0.475, p=0.0001, respectively). In the 3rd trimester, a significant positive correlation was seen between VEGF165 and VEGF165b (r2=+0.368, p=0.001); and a significant negative correlation was seen between VEGF165 and MMP-9 proteins (r2= -0.306, p=0.003). Of the three proteins selected, VEGF165 is the dominant angiogenic protein and its overexpression can result in tumorigenesis. VEGF165b is down-regulated in tumors. MMP-9 degrades ECM and promotes endothelial cell migration and is considered angiogenic. The 3rd trimester of human pregnancy is a unique phase when maximum angiogenesis needs to occur, yet as pregnancy approaches parturition the angiogenic process needs to be terminated. The correlation seen between the two isoforms of VEGF in the 3rd trimester suggest that when fetal demand is at its peak the two VEGF isoforms work synergistically to maximize angiogenesis. And, the ample presence of VEGF165b in the 3rd trimester and the inverse correlation seen between MMP-9 and VEGF165 could be mechanisms at place to restrict overexpression of VEGF165 and placental angiogenesis as pregnancy approaches parturition.

Association between maternal diabetes and cardiac left ventricular structure and function in the neonate: a study from the Copenhagen Baby Heart Study

Abstract Background Prenatal exposure to maternal diabetes has been associated with increased risk of congenital heart defects. Purpose To evaluate whether maternal diabetes is associated with more subtle morphological and functional cardiac changes in neonates without congenital heart defects. Methods We included 17,869 newborns sampled from the Copenhagen Baby Heart Study, all of whom underwent transthoracic echocardiography within 30 days of delivery. We investigated the association between exposure to maternal diabetes (pre-existing diabetes [type 1 or type 2 diabetes] or gestational diabetes [GDM]) and the neonates' echocardiographic indices of left ventricular structure (left posterior wall thickness in end-diastole [LVPWd], interventricular septum thickness in end-diastole [IVSd], left ventricular internal diameter in end-systole [LVIDs] and end-diastole [LVIDd]), systolic function (fractional shortening [FS], stroke volume [SV]) and diastolic function (mitral valve peak early and atrial filling velocities, deceleration time of early filling, and E/A-ratio), using linear and logistic regression. Models were adjusted for maternal age, infant sex, infant birth weight for gestational age and gestational age in days. In additional analyses, we evaluated the relationship between HbA1C levels in first and third trimester and left ventricular structure and function. Results We found that infants exposed to pre-existing maternal diabetes (n=x) had, on average, a thicker LVPWd (mean difference 0.12 mm [95% CI: 0.06–0.19]), a smaller LVIDs (−0.27 mm [95% CI: −0.46, −0.07]) and LVIDd (−0.43 mm [95% CI: −0.66, −0.19]), and decreased SV (−0.50 ml [95% CI: −0.77, −0.23]). We found no significant differences in IVSd, FS, and measures of diastolic function for infants exposed to pre-existing maternal diabetes compared with infants not exposed to diabetes. Infants exposed to GDM (n=) also had thicker LVPWd (0.06 mm [95% CI: −0.28, −0.01]) and smaller LVIDs (−0.15 mm [95% CI: −0.28, −0.01]); however, on average, IVSd, LVIDd, and measures of systolic and diastolic function did not differ for infants born to mothers with and without GDM. We observed no consistent association between HbA1C levels measured early and late in pregnancy in mothers with diabetes and indices of left ventricular structure and function. Conclusion In conclusion, we found that exposure to maternal pre-existing diabetes, and to a lesser degree GDM, was associated with changes in neonatal left ventricular structure and function, including a thicker left ventricular posterior wall, smaller left ventricular internal diameters, and lower stroke volumes. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Rigsbospitalet Research Foundation

Actuarial Survival Based on Gestational Age in Days at Birth for Infants Born at

To provide comprehensive, contemporary information on the actuarial survival of infants born at 22-25weeks of gestation in Canada. In a retrospective cohort study, we included data from preterm infants of 22-25weeks of gestation admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 2010 and 2017. Infants with major congenital anomalies were excluded. We calculated gestational age using invitro fertilization date, antenatal ultrasound dating, last menstrual period, obstetrical estimate, or neonatal estimate (in that order). Infants were followed until either discharge or death. Each day of gestational age was considered a category except for births at 22weeks, where the first 4days were grouped into one category and the last 3days were grouped intoanother category. For each day of life, an actuarial survival rate was obtained by calculating how many infants survived to discharge out of those who had survived up to that day. Of 4335 included infants, 85, 679, 1504, and 2067 were born at 22, 23, 24, and 25weeks of gestation, respectively. Survival increased from 32% at 22weeks to 83% at 254-6/7weeks. Graphs of actuarial survival developed for the first 6weeks after birth in male and female children indicated a steep increase in survival during the first 7-10days postnatally. Survival increased steadily with postnatal survival and was dependent on gestational age in days and sex of the child.

Associations of Trimester-Specific Exposure to Bisphenols with Size at Birth: A Chinese Prenatal Cohort Study.

Background:Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown.Objectives:Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth.Methods:The present study included 845 pregnant women from Wuhan, China (2013–2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile.Results:Medians (25th–75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19–3.85), 0.65 (0.34–1.39), and 0.38 (0.13–1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p-values () across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome.Conclusions:Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664

Prolonged early antenatal indomethacin exposure is safe for fetus and neonate

Objective: To evaluate fetal and neonatal safety of early-onset long-term antenatal indomethacin treatment (LIT) for short cervix.Methods: In this cohort study, women started LIT for short cervix (<25 mm) before completing 25 weeks. They followed a standardized regiment of oral indomethacin: 100 mg loading, 50 mg qid for 48 h, 25 mg qid until delivery or at 32 weeks gestational age (GA), whichever comes first. Weekly monitoring for oligohydramnios and ductus arteriosus (DA) constriction included confirmation of compliance with treatment/dose. This approach is established in our clinical practice. To identify LIT complications separate from prematurity, each neonate exposed to LIT were matched to two unexposed neonatal controls within ±3 days of GA of delivery and birth weight of ±10%. Odds ratios for neonatal variables included pulmonary hemorrhage, patent DA (PDA) requiring medical or surgical correction, necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), intraventricular hemorrhage (IVH) grade III–IV, other intracranial hemorrhage (ICH), neonatal mortality, calculated individually, and for total composite morbidity. Statistical determinants of neonatal morbidity were assessed using binary logistic regression. Exposure to LIT, maternal age, parity, BMI, GA at delivery, birth-weight (BW), neonatal gender, cord artery pH, and 5-min Apgar score were independent variables.Results: 166 LIT cases were matched with 332 controls. LIT median duration was 49 (3–108) days. Mean delivery GA was 34 weeks. LIT was stopped for 5 patients (2.9%) with oligohydramnios and 1 (0.6%) with DA constriction, without consequent morbidity. 71 cases (43%) completed LIT, stopping at 32 weeks. 95 stopped early for preterm premature ruptures of membranes (PPROM) (20%), active labor (11%) or patient choice (22%). Odds of any individual complication did not differ between treated cases and controls. LIT was not a statistical determinant of composite morbidity or any individual neonatal problem.Conclusion: Continuous early-onset indomethacin exposure, up to 15 weeks antenatally, did not increase fetal or neonatal complications. This level of safety is permissive to a randomized trial of indomethacin for the treatment of short cervix.

Air pollution in the week prior to delivery and preterm birth in 24 Canadian cities: a time to event analysis

BackgroundNumerous studies have examined the association between air pollution and preterm birth (< 37 weeks gestation) but findings have been inconsistent. These associations may be more difficult to detect than associations with other adverse birth outcomes because of the different duration of exposure in preterm vs. term births, and the existence of seasonal cycles in incidence of preterm birth.MethodsWe analyzed data pertaining to 1,001,700 singleton births occurring between 1999 and 2008 in 24 Canadian cities where daily air pollution data were available from government monitoring sites. In the first stage, data were analyzed in each city employing Cox proportional hazards models using gestational age in days as the time scale, obtaining city-specific hazard ratios (HRs) with their 95% confidence intervals (CIs) expressed per interquartile range (IQR) of each air pollutant. Effects were examined using distributed lag functions for lags of 0–6 days prior to delivery, as well as cumulative lags from two to six days. We accounted for the potential nonlinear effect of daily mean ambient temperature using a cubic B-spline with three internal knots. In the second stage, we pooled the estimated city-specific hazard ratios using a random effects model.ResultsPooled estimates across 24 cities indicated that an IQR increase in ozone (O3, 13.3 ppb) 0–3 days prior to delivery was associated with a hazard ratio of 1.036 (95% CI 1.005, 1.067) for preterm birth, adjusting for infant sex, maternal age, marital status and country of birth, neighbourhood socioeconomic status (SES) and visible minority, temperature, year and season of birth, and a natural spline function of day of year. There was some evidence of effect modification by gestational age and season. Associations with carbon monoxide, nitrogen dioxide, particulate matter, and sulphur dioxide were inconsistent.ConclusionsWe observed associations between daily O3 in the week before delivery and preterm birth in an analysis of approximately 1 million births in 24 Canadian cities between 1999 and 2008. Our analysis is one of a limited number which have examined these short term associations employing Cox proportional hazards models to account for the different exposure durations of preterm vs. term births.

Three-dimensional power Doppler ultrasound evaluation of placental blood flow in normal monochorionic diamniotic twin pregnancies

BackgroundMonochorionic diamniotic (MCDA) twin pregnancies are at higher risk of adverse outcomes and complications, which are attributed to the influence of placental morphology in MCDA twins. Monitoring of placental function is an important index for clinical decisions. The aim of our study was to evaluate the placental blood flow estimated using three-dimensional power Doppler (3D-PD) ultrasound and the vascular indices distribution with gestational age (GA) in normal MCDA twin pregnancies.MethodsOne hundred four MCDA twin pregnancies and 106 singleton pregnancies (GA range, 14–32 weeks) were included in this prospective study. 3D-PD volume data of each fetus was obtained separately from the placenta at the site of umbilical cord insertion. We analyzed the volume data using sonobiopsy technique. The placental vascularization index (VI), flow index (FI) and vascularizationflow index (VFI), were auto-calculated. The means and standard deviation values of three vascular indices per fetus were calculated and regression analysis of the vascular indices as a function of GA was performed in twin pregnancies. The vascular indices of twin and singleton pregnancies were compared using independent t-test.ResultsThere were no significant differences in VI, FI or VFI among the fetuses of twins (p > 0.05). These vascular indices increased over the course of pregnancy (p < 0.05). We obtained the regression equations for the indices as a function of GA in days: VI = exp. (4.369–28.533/GA) (R2 = 0.699, p < 0.05), FI = exp. (3.916–13.003/GA) (R2 = 0.511, p < 0.05), and VFI = exp. (3.577–37.468/GA) (R2 = 0.675, p < 0.05). There were no significant differences in three vascular indices between MCDA twin and singleton groups (p > 0.05).Conclusions3D-PD placental data using sonobiopsy technique could reflect the placental blood flow of each twin, which could be applied to the study of placental perfusion in MCDA twin pregnancies. This study also presented the vascular indices distribution with GA in normal twin pregnancies, which might be useful for early detection of MCDA complications.

Correlation Between Placental Matrix Metalloproteinase 9 and Tumor Necrosis Factor-α Protein Expression Throughout Gestation in Normal Human Pregnancy.

Matrix metalloproteinases (MMPs), specifically MMP-9 plays a role in human placentation. The enzyme confers an invasive ability to cytotrophoblasts and degrades the endometrial matrix as the cells infiltrate the decidua to keep up with placental growth. Since tumor necrosis factor-α (TNF-α) can induce the synthesis of MMP-9, we investigated the patterns of changes in and correlation between placental villous MMP-9 and TNF-α expressions throughout normal human gestation. Placentas were obtained from 179 normal pregnant women who underwent elective abortion or term delivery. Chorionic villi isolated from placental samples were grouped as first, second, and third trimester (70/7-130/7, 131/7-236/7, and 370/7-424/7 weeks, respectively). Chorionic villous TNF-α and MMP-9 proteins were assayed using enzyme immunoassay kits. There were significant differences in MMP-9 and TNF-α protein expressions among the trimester groups ( P = .001). The MMP-9 protein increased progressively with an increase in gestational age (GA), but TNF-α peaked in the second trimester. Within each trimester group, we searched for the effects of variation of GA in days on the 2 variables. A significant positive correlation between MMP-9 and GA was noted in the first trimester ( r = 0.364, P = .005). No other comparisons were significant. When GA was controlled for, partial correlation revealed a significant positive correlation between TNF-α and MMP-9 only in the second trimester ( r = 0.300, P = .018). We hypothesize that the TNF-α peak and the positive correlation between TNF-α and MMP-9 in the second trimester of normal human gestation could contribute toward a successful pregnancy outcome.

A reference range of fetal abdominal circumference growth velocity between 20 and 36weeks' gestation.

To create a single equation and reference range for abdominal circumference growth velocity (ACGV) between 20 and 36weeks in singleton pregnancies. Observational study of pregnant women having routine scans for abdominal circumference (AC) at 20 and 36weeks' gestation. Exclusion criteria were multiple pregnancy, abnormal karyotype, major fetal abnormalities, and absent data on first-trimester dating. Scan image quality and AC measurement reliability were assessed according to INTERGROWTH-21st criteria. Regression models for the AC mean and standard deviation were fitted separately at 20 and 36weeks, and z scores were calculated. Abdominal circumference growth velocity was defined as the z score difference between 20 and 36weeks divided by the interval in days and multiplied by 100. The study population included 3334 fetuses. The equation for ACGV is (((AC36 -53.090-1.081*GA36 )/(0.057638*GA36 +0.622741))-((AC20 +68.349-1.571*GA20 )/(0.06265*GA20 -2.55361)))*100/(GA36 -GA20 ), where AC is expressed in millimeters and GA is gestational age in days. The 3rd, 5th, 10th, 50th, 90th, 95th, and 97th centiles are -1.8997, -1.6785, -1.3091, -0.0069, 1.3255, 1.7279, 1.9973, respectively. We have defined ACGV between 20 and 36weeks, and we have established its reference range. Further studies are needed to evaluate the clinical significance of growth patterns in the tail ends of this distribution.

Ventricular myocardium development and the role of connexins in the human fetal heart

The developmental timeline of the human heart remains elusive. The heart takes on its characteristic four chambered appearance by ~56 days gestational age (DGA). However, owing to the complexities (both technical and logistical) of exploring development in utero, we understand little of how the ventricular walls develop. To address this, we employed diffusion tensor magnetic resonance imaging to explore the architecture and tissue organization of the developing heart aged 95–143 DGA. We show that fractional anisotropy increases (from ~0.1 to ~0.5), diffusion coefficients decrease (from ~1 × 10−3mm2/sec to ~0.4 × 10−3mm2/sec), and fiber paths, extracted by tractography, increase linearly with gestation, indicative of the increasing organization of the ventricular myocytes. By 143 DGA, the developing heart has the classical helical organization observed in mature mammalian tissue. This was accompanied by an increase in connexin 43 and connexin 40 expression levels, suggesting their role in the development of the ventricular conduction system and that electrical propagation across the heart is facilitated in later gestation. Our findings highlight a key developmental window for the structural organization of the fetal heart.

Survival of very preterm infants admitted to neonatal care in England 2008–2014: time trends and regional variation

ObjectiveTo analyse survival trends and regional variation for very preterm infants admitted to neonatal care.SettingAll neonatal units in England.PatientsInfants born at 22+0–31+6 weeks+daysgestational age (GA) over 2008–2014 and admitted to...

Development of a birthweight standard and comparison with currently used standards. What is a 10th centile?

IntroductionFetal growth charts are often used in clinical practice. It is important to understand the usefulness and the pitfalls associated with these tools. Without validation, it is difficult to ascertain if the cutoffs we intend are the ones we actually select. We developed a national standard for birthweight (BW) and compared it with other published reference values. Study designMulticenter retrospective study. We collected data on live births, including first trimester ultrasound and pathology, from 23 to 42 weeks’ gestational age (GA). We used a variation of the lambda (λ), mu (μ), and sigma (σ) method (LMS) to construct and smooth predicted centiles. GA data was plotted and modeled in days from 24 to 42 weeks. Resulting centiles were validated and compared with other published and widely used reference values. Data from both BW and estimated fetal weight was used to validate the model. ResultsData on 661,338 births were collected from 22 institutions, including 71,515 cases with first trimester ultrasound. We excluded preterm cesarean section from analysis, because of a significant bias (up to 18%) on BW and used exclusively first trimester ultrasound dates from 34 to 42 weeks. The standard compares favorably with tables currently in use, both ultrasound and birthweight based. ConclusionThe use of first trimester ultrasound limits variability by minimizing some random error sources, such as data introduction and GA errors, while allowing better precision (GA in days). This results in a narrower range in the extreme centiles than other charts. Validation with estimates of fetal weight are sound in second and early third trimester fetuses, because that will be a “real world” usage of this standard. While there are similarities between our series and some international/foreign growth charts, other are unfit to characterize our population. This reinforces the need for validation of standards, and sound methodological practices when doing so.

Heated, Humidified High-Flow Nasal Cannula vs Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome of Prematurity: A Randomized Clinical Noninferiority Trial.

Heated, humidified high-flow nasal cannula (HHHFNC) has gained increasing popularity as respiratory support for newborn infants thanks to ease of use and improved patient comfort. However, its role as primary therapy for respiratory distress syndrome (RDS) of prematurity needs to be further elucidated by large, randomized clinical trials. To determine whether HHHFNC provides respiratory support noninferior to nasal continuous positive airway pressure (nCPAP) or bilevel nCPAP (BiPAP) as a primary approach to RDS in infants older than 28 weeks' gestational age (GA). An unblinded, monocentric, randomized clinical noninferiority trial at a tertiary neonatal intensive care unit. Inborn infants at 29 weeks 0 days to 36 weeks 6 days of GA were eligible if presenting with mild to moderate RDS requiring noninvasive respiratory support. Criteria for starting noninvasive respiratory support were a Silverman score of 5 or higher or a fraction of inspired oxygen higher than 0.3 for a target saturation of peripheral oxygen of 88% to 93%. Infants were ineligible if they had major congenital anomalies or severe RDS requiring early intubation. Infants were enrolled between January 5, 2012, and June 28, 2014. Randomization to either HHHFNC at 4 to 6 L/min or nCPAP/BiPAP at 4 to 6 cm H2O. Need for mechanical ventilation within 72 hours from the beginning of respiratory support. The absolute risk difference in the primary outcome and its 95% confidence interval were calculated to determine noninferiority (noninferiority margin, 10%). An intention-to-treat analysis was performed. A total of 316 infants were enrolled in the study: 158 in the HHHFNC group (mean [SD] GA, 33.1 [1.9] weeks; 52.5% female) and 158 in the nCPAP/BiPAP group (mean [SD] GA, 33.0 [2.1] weeks; 47.5% female). The use of HHHFNC was noninferior to nCPAP with regard to the primary outcome: failure occurred in 10.8% vs 9.5% of infants, respectively (95% CI of risk difference, -6.0% to 8.6% [within the noninferiority margin]; P = .71). Significant between-group differences in secondary outcomes were not found between the HHHFNC and nCPAP/BiPAP groups, including duration of respiratory support (median [interquartile range], 4.0 [2.0 to 6.0] vs 4.0 [2.0 to 7.0] days; 95% CI of difference in medians, -1.0 to 0.5; P = .45), need for surfactant (44.3% vs 46.2%; 95% CI of risk difference, -9.8 to 13.5; P = .73), air leaks (1.9% vs 2.5%; 95% CI of risk difference, -3.3 to 4.5; P = .70), and bronchopulmonary dysplasia (4.4% vs 5.1%; 95% CI of risk difference, -3.9 to 7.2; P = .79). In this study, HHHFNC showed efficacy and safety similar to those of nCPAP/BiPAP when applied as a primary approach to mild to moderate RDS in preterm infants older than 28 weeks' GA. clinicaltrials.gov Identifier: NCT02570217.

Gestational age and birthweight for risk assessment of neurodevelopmental impairment or death in extremely preterm infants

BackgroundThe risk of poor outcomes in preterm infants is primarily determined by birthweight (BW) and gestational age (GA). It is not known whether BW is a better outcome predictor than...