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Background: Fetal growth monitoring is important for twin pregnancies. However, there has been no clinically validated tool for monitoring fetal growth of twin pregnancies in China. This study aims to develop and validate a chorionicity-specific growth chart of ultrasound estimated fetal weight (EFW) for Chinese twin pregnancies., Methods: This retrospective cohort study included all twin pregnancies who delivered two live fetuses with gestational age ≥ 34 weeks without severe obstetric complications at a tertiary hospital from January 2007 to March 2021. The participants were divided into a development set (delivered in or before December 2017) and a validation set (delivered in or after January 2018). Chorionicity-specific growth charts were created using the generalized additive models for location, scale, and shape (GAMLSS) based on the development set. The fetuses from the validation set were classified into three groups based on the last EFW: small-for-gestational-age (SGA) indicated by both the newly established twin charts and the Hadlock singleton chart currently used for twin pregnancies in China, suspected SGA indicated by only the singleton chart, and no SGA indicated by either chart. The incidence of neonatal outcomes among the three groups was then compared accordingly, including intensive care unit (NICU) stay length, respiratory diseases, and neurological disorders., Results: The development set included 883 twin pregnancies and a total of 6374 EFW measurements between 16 and 38 weeks of gestation, and the validation set included 801 twin pregnancies and 7630 EFW measurements. In the development set, monochorionic diamniotic (MCDA) twins had a significantly lower EFW compared to dichorionic diamniotic (DCDA) twins beginning at 26 weeks, with the difference gradually increasing thereafter, supporting the establishment of chorionicity-specific growth charts. Of the 1,602 twin neonates in the validation set, 103 (6.4%) were classified into the SGA group, 164 (10.2%) into the suspected SGA group, and 1335 (83.3%) into the no SGA group. The incidence of respiratory diseases and neurological disorders was comparable between the suspected SGA group and the no SGA group, but apparently higher in the SGA group. Meanwhile, NICU stay lengths were consistently longer for twins in the SGA group compared to the no SGA group (difference: 0.57, 95% CI: 0.31-0.83), with no significant differences observed between the suspected SGA and no SGA groups., Conclusions: The fetal growth trajectories differed by chorionicity, with a lower EFW for MCDA twins beginning at 26 weeks. The establishment of chorionicity-specific growth chart could reduce overdiagnosis of SGA and improve fetal growth monitoring of twin pregnancies., (© 2024. The Author(s).)

Background: There is growing evidence of bidirectional associations between rheumatoid arthritis and adverse pregnancy outcomes (APOs) in observational studies, but little is known about the causal direction of these associations. Therefore, we explored the potential causal relationships between rheumatoid arthritis and APOs using a bidirectional two-sample Mendelian randomization (MR) in European and Asian populations., Methods: We conducted a bidirectional two-sample Mendelian randomization analysis using available summary statistics from released genome-wide association studies. Summary statistics for instrument-outcome associations were retrieved from two separate databases for rheumatoid arthritis and adverse pregnancy outcomes, respectively. The inverse-variance weighted method was used as the primary MR analysis, and cML-MA-BIC was used as the supplementary analysis. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran Q statistic method were implemented as sensitivity analyses approach to ensure the robustness of the results., Results: Our study showed that a higher risk of rheumatoid arthritis in the European population was associated with gestational hypertension (OR: 1.04, 95%CI: 1.02-1.06), pre-eclampsia (OR: 1.06, 95%CI: 1.01-1.11), fetal growth restriction (OR: 1.08, 95%CI: 1.04-1.12), preterm delivery (OR:1.04, 95%CI: 1.01-1.07). Furthermore, we found no evidence that APOs had causal effects on rheumatoid arthritis in the reverse MR analysis. No association between rheumatoid arthritis and APOs was found in East Asian population. There was no heterogeneity or horizontal pleiotropy., Conclusions: This MR analysis provides the positive causal association from rheumatoid arthritis to gestational hypertension, pre-eclampsia, fetal growth restriction and preterm delivery genetically. It highlights the importance of more intensive prenatal care and early intervention among pregnant women with rheumatoid arthritis to prevent potential adverse obstetric outcomes., (© 2024. The Author(s).)

Background: To assess pregnancy outcomes in women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection., Methods: This was a retrospective cohort study that included pregnant women who contracted coronavirus disease 2019 (COVID-19) once or twice during pregnancy and who gave birth between 1 October 2022 and 15 August 2023 in Shanghai First Maternity and Infant Hospital (Shanghai, China). We collected their clinical data and compared the frequency of adverse pregnancy outcomes between the reinfection group and the primary infection group, such as preterm birth, fetal growth restriction (FGR), hypertensive disorders of pregnancy (HDP), common pregnancy-related conditions, birth weight, and neonatal unit admission., Results: We observed a 7.7% reinfection rate among the 1,405 women who contracted COVID-19 during pregnancy. There were no significant differences in the frequency of preterm birth, FGR, HDP, other common pregnancy-related conditions, birth weight, or rate of neonatal unit admission between the reinfection and single infection groups. All our participants were unvaccinated, and all had mild symptoms., Conclusion: Our study showed no significant association between SARS-CoV-2 reinfection and adverse pregnancy outcomes., (© 2024. The Author(s).)

Background: Gestational weight gain (GWG) is an important indicator for monitoring maternal and fetal health., Objective: To evaluate the effect of GWG outside the recommendations of the Institute of Medicine (IOM) on fetal and neonatal outcomes., Study Design: A prospective cohort study with 1642 pregnant women selected from 2017 to 2023, with gestational age ≤ 18 weeks and followed until delivery in the city of Araraquara, Southeast Brazil. The relationship between IOM-recommended GWG and fetal outcomes (abdominal subcutaneous tissue thickness, arm and thigh subcutaneous tissue area and intrauterine growth restriction) and neonatal outcomes (percentage of fat mass, fat-free mass, birth weight and length, ponderal index, weight adequateness for gestational age by the Intergrowth curve, prematurity, and Apgar score) were investigated. Generalized Estimating Equations were used., Results: GWG below the IOM recommendations was associated with increased risks of intrauterine growth restriction (IUGR) (aOR 1.61; 95% CI: 1.14-2.27), low birth weight (aOR 2.44; 95% CI: 1.85-3.21), and prematurity (aOR 2.35; 95% CI: 1.81-3.05), and lower chance of being Large for Gestational Age (LGA) (aOR 0.38; 95% CI: 0.28-0.54), with smaller arm subcutaneous tissue area (AST) (-7.99 g; 95% CI: -8.97 to -7.02), birth length (-0.76 cm; 95% CI: -1.03 to -0.49), and neonatal fat mass percentage (-0.85%; 95% CI: -1.12 to -0.58). Conversely, exceeding GWG guidelines increased the likelihood of LGA (aOR 1.53; 95% CI: 1.20-1.96), with lower 5th-minute Apgar score (aOR 0.42; 95% CI: 0.20-0.87), and increased birth weight (90.14 g; 95% CI: 53.30 to 126.99)., Conclusion: Adherence to GWG recommendations is crucial, with deviations negatively impacting fetal health. Effective weight control strategies are imperative., (© 2024. The Author(s).)

Introduction: Restriction in the growth of the fetus is a leading cause of stillbirth, neonatal mortality, and short- and long-term morbidity. Documented existing scientific evidence have shown the effects of maternal drugs use, alcohol drinking, tobacco smoking, cocaine use and heroin use on fetal growth restriction. However, data is lacking on the effects of khat chewing during pregnancy on fetal growth status and newborn size at birth. Therefore, the aim of the present study was to measure the effect of chewing khat during pregnancy on fetal growth and size at birth in eastern Ethiopia., Method: A cohort study was conducted in selected health institutions in eastern Ethiopia. All pregnant women fulfilled the eligibility criteria in the selected health institutions was the source population. The calculated sample size of exposed and unexposed groups included in the study, in total, was 344. Data collection was performed prospectively by interviewers administered questionnaires, and anthropometric, clinical and ultrasound measurements. Data was analyzed using SPSS version 27 and STATA version 16 software. The survival analysis (cox proportional hazards model) and generalized linear model (GLM) for the binomial family analysis were performed to estimate the crude and adjusted relative risk and attributable risk (AR) with corresponding 95% CI of chewing khat on fetal growth restriction. The mediation effect has been examined through Generalized Structural Equation Modeling (GSEM) analysis using the Stata 'gsem' command. Statistically significant association was declared at p-value less than 5%., Results: In the present study, the incidence of fetal growth restriction (FGR) among the study cohorts was 95 (29.7%); of this, 81 (85.3%) were among khat chewer cohorts. The relative risk of fetal growth restriction among khat chewer cohort mothers was significantly higher (aRR = 4.32; 95%CI 2.62-7.12). Moreover, the incidence of small for gestational age at birth among the present study cohorts was 100 (31.3%); 84 (84%) were from khat chewer cohorts' deliveries. More importantly, in the present study, 98.95% of the ultrasound-identified fetuses with FGR were found to be SGA at birth. Hence, in the current study, FGR was highly associated with SGA at birth. In additional analysis, the regression coefficient of khat chewing during pregnancy on fetal growth restriction has been decreased in size from path o, β = 0.43, p < 0.001 to path o', β = 0.32, p < 0.001, after adjusting for gestational hypertension and maternal anemia., Conclusion: In sum, the present study showed khat chewing during pregnancy is not simply affected the mothers, but it also affected the unborn fetuses. Therefore, the health workers as well as the local community and religious leaders should give high emphasis on provision of health education regarding the damage of chewing khat by pregnant mothers, with especial focus of the effects on their fetuses., (© 2024. The Author(s).)

Background: Velamentous cord insertion (VCI) and marginal cord insertion (MCI) are well-known risk factors for adverse perinatal outcomes in singleton pregnancies. However, the potential links between VCI or MCI and perinatal outcomes in twin pregnancies have yet to be systematically evaluated. This study aimed to investigate the relationships between VCI or MCI and perinatal outcomes in twin pregnancies., Methods: This retrospective single-center cohort study included women with twin pregnancies who gave birth in a tertiary hospital in Southwest, China between January 2017 and December 2022. VCI and MCI were identified by abdominal ultrasound and confirmed after placental delivery. Logistic regression, multinomial logit regression and generalized estimation equation models were used to evaluate the association between VCI or MCI and perinatal outcomes., Results: A total of 3682 twin pregnancies were included, including 100 (2.7%) pregnancies with VCI and 149 (4.0%) pregnancies with MCI. Compared to pregnancies with normal cord insertion, both monochorionic and dichorionic pregnancies with VCI were associated with an increased risk of preterm delivery 32-34 weeks (aRRR 2.94, 95% CI 1.03-8.39; aRRR 2.55, 95% CI 1.19-5.46, respectively), while pregnancies with MCI were not associated with preterm delivery. VCI was associated with a higher incidence of placental previa (aOR 6.36, 95% CI 1.92-21.04) in monochorionic pregnancies and placental accreta (aOR 1.85, 95% CI 1.06-3.23) in dichorionic pregnancies. MCI was associated with an increased risk of preeclampsia (aOR 3.07, 95% CI 1.49-6.32), intertwin birthweight discordance ≥ 20% (aOR 2.40, 95% CI 1.08-5.60) and selective fetal growth restriction (aOR 2.46, 95% CI 1.08-5.60) in monochorionic pregnancies and small-for-gestational age neonates (aOR 1.97, 95% CI 1.24-3.14) in dichorionic pregnancies., Conclusions: VCI was associated with an increased risk of preterm delivery in twin pregnancies irrespective of chorionicity, whereas MCI was associated with an increased preeclampsia risk, significant intertwin birthweight discordance in monochorionic pregnancies and small-for-gestational age neonates in dichorionic pregnancies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The purpose of this study was to investigate the relationship between the size and duration of asymptomatic subchorionic hematoma and pregnancy outcomes in women with singleton pregnancies., Methods: This was a retrospective study that enrolled 701 singleton pregnant women who were diagnosed with asymptomatic subchorionic hematoma by ultrasound at 5-10 gestational weeks. The control group recruited 640 normal pregnant women without subchorionic hematoma who were matched with subchorionic hematoma group on baseline characteristics. The pregnancy outcomes were compared between the two groups, and the associations of the size and duration of subchorionic hematoma with pregnancy outcomes were analyzed by logistic regression model., Results: Compared with the normal pregnancy group, the incidence of, gestational diabetes mellitus, gestational thrombocytopenia, placenta adhesion, fetal growth restriction, macrosomia in subchorionic hematoma group were higher (all P < 0.05). After adjusting for confounding factors, the hematoma size was positively associated with the occurrence of gestational hypothyroidism (adjusted OR[95%CI]: 1.029[1.004-1.054]), intrahepatic cholestasis of pregnancy (adjusted OR[95%CI]: 1.095[1.047-1.146]), term premature rupture of membranes (adjusted OR[95%CI]: 1.044[1.005-1.085]), hypertensive disorders of pregnancy (adjusted OR[95%CI]: 1.030[1.0004-1.060]), gestational thrombocytopenia (adjusted OR[95%CI]: 1.078 [1.045-1.113]), placenta adhesion (adjusted OR[95%CI]: 1.054 [1.027-1.082]), and the duration of hematoma was positively associated with the incidence of term premature rupture of membranes (adjusted OR[95%CI]: 1.070[1.027-1.115]), gestational diabetes mellitus (adjusted OR[95%CI]: 1.938 [1.886-1.993]) and fetal growth restriction (adjusted OR[95%CI]: 1.194 [1.124-1.268])., Conclusions: The presence, size and duration of a first-trimester asymptomatic subchorionic hematoma may be associated with adverse pregnancy outcomes at later gestations such as term premature rupture of membranes and fetal growth restriction., (© 2023. The Author(s).)

Background: Little research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC)., Methods: We conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions., Results: In total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p < 0.0001). Furthermore, the level of diagnostic certainty declined slightly across all outcomes investigated from the pre-COVID-19 to the intra-COVID-19 period. Nonetheless, diagnostic certainty was especially low for certain outcomes (i.e., stillbirth and NBSI) regardless of period; still, other outcomes, such as preterm birth and LBW, had moderate to high levels of diagnostic certainty. Results were mostly consistent when the analysis was focused on the facilities designated for COVID-19 care., Conclusion: This study succeeded in providing prevalence estimates for key adverse birth outcomes using GAIA criteria during the COVID-19 pandemic in Kinshasa, DRC. Furthermore, our study adds crucial real-world data to the literature surrounding the impact of the COVID-19 pandemic on maternal and neonatal services and outcomes in Africa., (© 2023. The Author(s).)

Background: Small-for-gestational-age neonates (SGA) are at increased risk of neonatal morbidity. Nulliparity represents a risk factor for SGA; birthweight charts may perform differently for the detection of SGA among nulliparas. This study aimed at describing the prevalence of SGA in nulliparas according to different birthweight charts and evaluating the diagnostic performance of these charts to maternal and perinatal outcomes., Methods: This is a secondary analysis of a Brazilian cohort of nulliparas named Preterm SAMBA study. Birthweight centiles were calculated using the Intergrowth-21st, WHO-Fetal Growth Charts, Birth in Brazil population chart and GROW-customised chart. The risks of outcomes among SGA neonates and their mothers in comparison to neonates with birthweights between the 40 th -60 th centiles were calculated, according to each chart. ROC curves were used to detect neonatal morbidity in neonates with birth weights below different cutoff centiles for each chart., Results: A sample of 997 nulliparas was assessed. The rate of SGA infants varied between 7.0-11.6%. All charts showed a significantly lower risk of caesarean sections in women delivering SGA neonates compared to those delivering adequate-for-gestational-age neonates (OR 0.55-0.64, p < .05). The charts had poor performance (AUC 0.492 - 0.522) for the detection of neonatal morbidity related to SGA born at term., Conclusion: The populational and customised birthweight charts detected different prevalence of small-for-gestational-age neonates and showed similar and poor performance to identify related neonatal adverse outcomes in this population., (© 2022. The Author(s).)

Background: Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak., Methods: This study included singletons born after 24 gestational weeks in 2017-2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated., Results: Of 46,610 live births included, 154 (3.3, 95% CI 2.8-3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05-3.10) and primipara (OR 2.68, 95% CI 1.89-3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17-3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81-22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly., Conclusions: The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.

Background: Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction / fetal growth restriction (IUGR/FGR) in pregnant migrants., Method: Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany., Results: The Median age was 27 years, 49% of patients were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76% of patients, in 40% the delivery mode was caesarian section. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1% of pregnancies. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (< 2500 g) occurred in 6.1%. Birth weights below the 10th percentile of birth weight for gestational age were observed in 8.5% of the total cohort., Conclusions: Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR/FGR was found. We note that the rate of caesarian section births was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.

Background: Offspring of women with type 1 diabetes are at increased risk of fetal growth patterns which are associated with perinatal morbidity. Our aim was to compare rates of large- and small-for-gestational age (LGA; SGA) defined according to different criteria, using data from the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT)., Methods: This was a pre-specified analysis of CONCEPTT involving 225 pregnant women and liveborn infants from 31 international centres ( ClinicalTrials.gov NCT01788527; registered 11/2/2013). Infants were weighed immediately at birth and GROW, INTERGROWTH and WHO centiles were calculated. Relative risk ratios, sensitivity and specificity were used to assess the different growth standards with respect to perinatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, respiratory distress, neonatal intensive care unit (NICU) admission and a composite neonatal outcome., Results: Accelerated fetal growth was common, with mean birthweight percentiles of 82.1, 85.7 and 63.9 and LGA rates of 62, 67 and 30% using GROW, INTERGROWTH and WHO standards respectively. Corresponding rates of SGA were 2.2, 1.3 and 8.9% respectively. LGA defined according to GROW centiles showed stronger associations with preterm delivery, neonatal hypoglycaemia, hyperbilirubinaemia and NICU admission. Infants born > 97.7th centile were at highest risk of complications. SGA defined according to INTERGROWTH centiles showed slightly stronger associations with perinatal outcomes., Conclusions: GROW and INTERGROWTH standards performed similarly and identified similar numbers of neonates with LGA and SGA. GROW-defined LGA and INTERGROWTH-defined SGA had slightly stronger associations with neonatal complications. WHO standards underestimated size in preterm infants and are less applicable for use in type 1 diabetes., Trial Registration: This trial is registered with ClinicalTrials.gov . number NCT01788527 . Trial registered 11/2/2013.

Background: This study aims to investigate galectin-1 (Gal-1) expression in the serum and placenta of pregnant women with fetal growth restriction (FGR) and its significance., Methods: Thirty-one pregnant women with single-birth FGR but without comorbidities, eight pregnant women with FGR and preeclampsia (PE), and eight pregnant women with FGR and gestational diabetes mellitus (GDM) were enrolled as the study group, while 20 pregnant women with normal singleton pregnancy in the same period were enrolled as the control group. The serum Gal-1 level was detected using an enzyme-linked immunosorbent assay (ELISA), and Gal-1 expression in the placenta was detected by western blot., Results: The results revealed that, compared with the control group, the serum Gal-1 level decreased in the women with FGR without comorbidities, and the difference was statistically significant (P < 0.001). Compared with the control group, the difference in serum Gal-1 expression in the FGR-PE group was not statistically significant (P = 0.29). The peripheral serum Gal-1 level decreased in the FGR-GDM group compared with the control group, and the difference was statistically significant (P < 0.001). The serum Gal-1 level was positively correlated with birth weight (r 2  = 0.172, P < 0.01). Compared with the control group, the Gal-1 expression level decreased in the placenta of the pregnant women with FGR without comorbidities (P < 0.05)., Conclusions: Gal-1 exhibits low expression in the serum and placenta of pregnant women with FGR. In addition, Gal-1 may be involved in the pathogenesis of FGR and could represent a new diagnostic marker of the disease.

Background: To identify the relationship between quadruple test for aneuploidy screening (alpha-fetoprotein: AFP; free beta-human chorionic gonadotropin: b-hCG; unconjugated estriol: uE3 and inhibin-A: IHA) and fetal growth restriction and to construct predictive models for small-for-gestational-age (SGA) fetuses., Methods: Women who underwent quadruple test for aneuploidy were followed-up for final outcomes. The multiples of the median (MoMs) of the four biochemical markers for the SGA group and those of normal fetuses were compared. The models for predicting SGA by the individual biomarkers and their combination were constructed using binary logistic regression analysis, and their diagnostic performances in predicting SGA were determined., Results: Of 10,155 eligible pregnant women, 578 (5.7%) and 9577 (94.3%) had SGA and normal growth, respectively. High levels of AFP, b-hCG and IHA but low levels of uE3 significantly increased the risk of SGA. The constructed predictive equations had predictive performance for SGA, with areas under the receiver-operated characteristic curve of 0.724, 0.655, 0.597, 0.664 and 0.754 for AFP, b-hCG, uE3, IHA, and the combination, respectively., Conclusion: The quad test for aneuploidy screening could also be used as a predictor of SGA, without extra-effort and extra-cost.

Background: Factors associated with low birth weight at term (TLBW), a proxy for intrauterine growth restriction (IUGR), are not well-elucidated in socioeconomically vulnerable populations. This study aimed to identify the factors associated with TLBW in impoverished Brazilian women., Methods: Records in the 100 Million Brazilian Cohort database were linked to those in the National System of Information on Live Births (SINASC) to obtain obstetric, maternal, birth and socioeconomic data between 2001 and 2015. Multivariate logistic regression was performed to investigate associations between variables of exposure and TLBW., Results: Of 8,768,930 term live births analyzed, 3.7% presented TLBW. The highest odds of TLBW were associated with female newborns (OR: 1.49; 95% CI: 1.47-1.50), whose mothers were black (OR: 1.20; 95% CI: 1.18-1.22), had a low educational level (OR: 1.57; 95% CI: 1.53-1.62), were aged ≥35 years (OR: 1.44; 95% CI: 1.43-1.46), had a low number of prenatal care visits (OR: 2.48; 95% CI: 2.42-2.54) and were primiparous (OR: 1.62; 95% CI: 1.60-1.64). Lower odds of TLBW were found among infants whose mothers lived in the North, Northeast and Center-West regions of Brazil compared to those in the South., Conclusion: Multiple aspects were associated with TLBW, highlighting the need to comprehensively examine the mechanisms underlying these factors, especially in more vulnerable Brazilian populations, in order to contribute to the elaboration of health policies and promote better conditions of life for poor and extremely poor mothers and children.

Background: Twin growth discordance was demonstrated to be a risk factor for adverse perinatal outcomes, and prenatal ultrasonographic methods were utilized to predict twin growth discordance to improve outcomes. The results currently reported are not consistent due to the poor unified parameters and gestational durations., Methods: A total of 71 dichorionic twins with growth discordance and 346 dichorionic twins with normal growth were respectively included in the retrospective cohort study. The weight discordance of more than 25% was defined as a "growth discordant twin". The clinical baseline information, maternal outcomes, twin birth weights and fetal growth parameters (which were measured by ultrasound) were compared between the two groups from early gestation to late gestation. Multiple logistic regression and receiver operating characteristic curves were adopted to evaluate the predictive value of the growth parameters., Results: Compared with normal dichorionic twins, the clinical baseline conditions were similar in the twins those finally developed growth discordance. The fetal growth parameters and the deepest volume pocket of amniotic fluid in early and mid-pregnancy showed no obvious predictive values. The fetal growth parameters in late pregnancy showed predictive values, especially the discordance of estimated fetal weight (EFW) in the early third-trimester (P < 0.001, area under the curve, 0.822; the cut-off value, 20%; sensitivity, 66.67%; specificity, 91.30%; positive predictive value, 88.46%)., Conclusion: Two assessment approaches were suggested and adopted to predict twin growth discordance in the current study. Twin growth should be assessed longitudinally and dynamically. Normal twins may show growth imbalance in the early stage. The discordance of EFW in late pregnancy may be a useful indicator for a growth discordance of more than 25%, which is required further confirmation.

Background: Intrauterine fetal death (IUFD) is a tragic event and, despite efforts to reduce rates, its incidence remains difficult to reduce. The objective of the present study was to examine the etiological factors that contribute to the main causes and conditions associated with IUFD, over an 11-year period in a region of North-East Italy (Friuli Venezia Giulia) for which reliable data in available., Methods: Retrospective analysis of all 278 IUFD cases occurred between 2005 and 2015 in pregnancies with gestational age ≥ 23 weeks., Results: The incidence of IUFD was 2.8‰ live births. Of these, 30% were small for gestational age (SGA), with immigrant women being significantly over-represented. The share of SGA reached 35% in cases in which a maternal of fetal pathological condition was present, and dropped to 28% in the absence of associated pathology. In 78 pregnancies (28%) no pathology was recorded that could justify IUFD. Of all IUFDs, 11% occurred during labor, and 72% occurred at a gestational age above 30 weeks., Conclusion: The percentage of IUFD cases for which no possible cause can be identified is quite high. Only the adoption of evidence-based diagnostic protocols, with integrated immunologic, genetic and pathologic examinations, can help reduce this diagnostic gap, contributing to the prevention of future IUFDs.

Background: Studies comparing the outcome of spontaneous versus assisted reproductive technologies (ART) pregnancies report heterogeneous results. Despite the success of ART to overcome infertility, concern is growing regarding both its safety and its effect on maternal and child health. The objective of this study was to compare maternal and child-health outcomes after ART relative to natural conception., Methods: A population-based birth cohort study was carried out among pregnant women expected to deliver in 2015 in Pelotas, southern Brazil. Maternal outcomes included pregnancy complications and gestational weight gain. Gestational age, weight, intrauterine growth restriction, length and head circumference, and 1-min and 5-min Apgar, as well as health problems at birth and breastfeeding were defined as offspring outcomes. Statistical analyses were performed using linear and logistic regression. G-formula was used to perform mediation analysis., Results: The study included 4252 babies born by spontaneously pregnancies and 23 babies born after ART. Adjusted analyses showed that children conceived from ART presented lower means of gestational age (p = 0.001), birth weight (p = 0.002), length (p < 0.001), and head circumference at birth (p = 0.02). However, more than 90% of the effect of ART over these outcomes was mediated by multiple pregnancy., Conclusion: Our findings suggest that the possible negative effect on the child-health outcomes is due mainly to the higher incidence of multiple pregnancies and not because of ART. The reasons for the increase in adverse pregnancy outcomes associated with ART singleton pregnancies are still uncertain and warrants further research. Further large-population studies are needed to confirm these results.

Background: In developed countries, prenatal maternal stress has been associated with poor fetal growth, however this has not been evaluated in rural sub-Saharan Africa. We evaluated the effect of prenatal maternal stress on fetal growth and birth outcomes in rural Ghana., Methods: Leveraging a prospective, rural Ghanaian birth cohort, we ascertained prenatal maternal negative life events, categorized scores as 0-2 (low stress; referent), 3-5 (moderate), and > 5 (high) among 353 pregnant women in the Kintampo North Municipality and Kintampo South District located within the middle belt of Ghana. We employed linear regression to determine associations between prenatal maternal stress and infant birth weight, head circumference, and length. We additionally examined associations between prenatal maternal stress and adverse birth outcome, including low birth weight, small for gestational age, or stillbirth. Effect modification by infant sex was examined., Results: In all children, high prenatal maternal stress was associated with reduced birth length (β = - 0.91, p = 0.04; p-value for trend = 0.04). Among girls, moderate and high prenatal maternal stress was associated with reduced birth weight (β = - 0.16, p = 0.02; β = - 0.18, p = 0.04 respectively; p-value for trend = 0.04) and head circumference (β = - 0.66, p = 0.05; β = - 1.02, p = 0.01 respectively; p-value for trend = 0.01). In girls, high prenatal stress increased odds of any adverse birth outcome (OR 2.41, 95% CI 1.01-5.75; p for interaction = 0.04). Sex-specific analyses did not demonstrate significant effects in boys., Conclusions: All infants, but especially girls, were vulnerable to effects of prenatal maternal stress on birth outcomes. Understanding risk factors for impaired fetal growth may help develop preventative public health strategies., Trial Registration: NCT01335490 (prospective registration). Date of Registration: April 14, 2011. Status of Registration: Completed.

Background: High Body Mass Index (BMI) and gestational weight gain (GWG) affect an increasing number of pregnancies. The Institute of Medicine (IOM) has issued recommendations on the optimal GWG for women according to their pre-pregnancy BMI (healthy, overweight or obese). It has been shown that pregnant women rarely met the recommendations; however, it is unclear by how much. Previous studies also adjusted the analyses for various women's characteristics making their comparison challenging., Methods: We analysed individual participant data (IPD) of healthy women with a singleton pregnancy and a BMI of 18.5 kg/m 2 or more from the control arms of 36 randomised trials (16 countries). Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were used to describe the association between GWG outside (above or below) the IOM recommendations (2009) and risks of caesarean section, preterm birth, and large or small for gestational age (LGA or SGA) infants. The association was examined overall, within the BMI categories and by quartile of GWG departure from the IOM recommendations. We obtained aOR using mixed-effects logistic regression, accounting for the within-study clustering and a priori identified characteristics., Results: Out of 4429 women (from 33 trials) meeting the inclusion criteria, two thirds gained weight outside the IOM recommendations (1646 above; 1291 below). The median GWG outside the IOM recommendations was 3.1 kg above and 2.7 kg below. In comparison to GWG within the IOM recommendations, GWG above was associated with increased odds of caesarean section (aOR 1.50; 95%CI 1.25, 1.80), LGA (2.00; 1.58, 2.54), and reduced odds of SGA (0.66; 0.50, 0.87); no significant effect on preterm birth was detected. The relationship between GWG below the IOM recommendation and caesarean section or LGA was inconclusive; however, the odds of preterm birth (1.94; 1.31, 2.28) and SGA (1.52; 1.18, 1.96) were increased., Conclusions: Consistently with previous findings, adherence to the IOM recommendations seem to help achieve better pregnancy outcomes. Nevertheless, even in the context of clinical trials, women find it difficult to adhere to them. Further research should focus on identifying ways of achieving a healthier GWG as defined by the IOM recommendations.

Background: To compare the prevalence of preterm birth, post term birth, intra-uterine growth restriction and distribution of Apgar scores in offspring of foreign-born women in Western Australia with that of their Australian-born non-Indigenous and Indigenous counterparts., Methods: A population-based linked data study, involving 767,623 singleton births in Western Australia between 1980 and 2010 was undertaken. Neonatal outcomes included preterm birth, post term births, intra-uterine growth restriction (assessed using the proportion of optimal birth weight) and low Apgar scores. These were compared amongst foreign-born women from low, lower-middle, upper middle and high income countries and Australian-born non-Indigenous and Indigenous women over two different time periods using multinomial logistic regression adjusted for covariates., Results: Compared with Australian born non-Indigenous women, foreign-born women from low income countries were at some increased risk of extreme preterm (aRRR 1.59, 95% CI 0.87, 2.89) and very early preterm (aRRR 1.63, 95% CI 0.92, 2.89) births during the period from 1980 to 1996. During the period from 1997 to 2010 they were also at some risk of extreme preterm (aRRR 1.42, 95% CI 0.98, 2.04) very early preterm (aRRR 1.34, 95% CI 1.11, 1.62) and post term birth (aRRR 1.93, 95% CI 0.99, 3.78). During this second time period, other adverse outcomes for children of foreign-born women from low income and middle income countries included increases in severe (aRRR 1.69, 95% CI 1.30, 2.20; aRRR 1.72, 95% CI 1.53, 1.93), moderate (aRRR 1.54, 95% CI 1.32, 1.81; aRRR 1.59, 95% CI 1.48, 1.70) and mild (aRRR 1.28, 95% CI 1.14, 1.43; aRRR 1.31, 95% CI 1.25, 1.38) IUGR compared to children of Australian-born non-Indigenous mothers. Uniformly higher risks of adverse outcomes were also demonstrated for infants of Indigenous mothers., Conclusions: Our findings illustrate the vulnerabilities of children born to foreign women from low and middle-income countries. The need for exploratory research examining mechanisms contributing to poorer birth outcomes following resettlement in a developed nation is highlighted. There is also a need to develop targeted interventions to improve outcomes for these women and their families.

Background: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes., Methods: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained., Discussion: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure., Trial Registration: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

Background: Fetal growth is dependent upon utero-placental vascular supply of oxygen and nutrients from the mother and has been proposed to be compromised by vigorous intensity exercise in the third trimester. The aim of this systematic review was to investigate the effects of vigorous intensity exercise performed throughout pregnancy, on infant and maternal outcomes., Methods: Electronic searching of the PubMed, Medline, EMBASE, Cochrane Library, Web of Science and CINAHL databases was used to conduct the search up to November 2018. Study designs included in the systematic review were randomised control trials, quasi-experimental studies, cohort studies and case-control studies. The studies were required to include an intervention or report of pregnant women performing vigorous exercise during gestation, with a comparator group of either lower intensity exercise or standard care., Results: Ten cohort studies (n = 32,080) and five randomized control trials (n = 623) were included in the systematic review (n = 15), with 13 studies included in the meta-analysis. No significant difference existed in birthweight for infants of mothers who engaged in vigorous physical activity and those who lacked this exposure (mean difference = 8.06 g, n = 8006). Moreover, no significant increase existed in risk of small for gestational age (risk ratio = 0.15, n = 4504), risk of low birth weight (< 2500 g) (risk ratio = 0.44, n = 2454) or maternal weight gain (mean difference = - 0.46 kg, n = 1834). Women who engaged in vigorous physical activity had a small but significant increase in length of gestational age before delivery (mean difference = 0.21 weeks, n = 4281) and a small but significantly reduced risk of prematurity (risk ratio = - 0.20, n = 3025)., Conclusions: Findings from this meta-analysis indicate that vigorous intensity exercise completed into the third trimester appears to be safe for most healthy pregnancies. Further research is needed on the effects of vigorous intensity exercise in the first and second trimester, and of exercise intensity exceeding 90% of maximum heart rate., Trial Registration: PROSPERO trial registration CRD42018102109 .

Background: Some observational studies have shown improved birth outcomes for women of low socioeconomic position (SEP) receiving antenatal midwifery versus physician care. To understand for whom and under what circumstances midwifery care is associated with better birth outcomes we examined whether psychosocial risk including substance use, mental illness, social assistance, residence in a neighbourhood of low/moderate SEP, and teen maternal age modified the association between model of care (midwifery versus physician) and small-for-gestational-age (SGA) or preterm birth (PTB) for women of low SEP., Methods: For this retrospective cohort study, maternity data from the British Columbia Perinatal Data Registry were linked with Medical Services Plan billing data. We report adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for SGA birth (< the 10th percentile) and PTB (< 37 weeks' completed gestation). For tests of interaction between antenatal models of care and psychosocial risk, p-values < 0.10 were considered statistically significant. Women were eligible for inclusion if they were residents of British Columbia, Canada, carried a singleton fetus, had low to moderate medical/obstetric risk, birthed between April 1, 2008 and Dec. 31, 2012, and received a health insurance subsidy (n = 33,937)., Results: Midwifery versus obstetrician patients had lower odds of PTB. The difference was 31% larger among substance users (aOR 0.24, 95% CI: 0.11-0.54) compared to non-substance users (aOR 0.55, 95% CI: 0.45-0.68). Additionally, there was a 34% statistically significant absolute difference in odds of PTB for midwifery versus obstetrician patients with both mental illness and substance use (aOR 0.18, 95% CI: 0.06-0.55) compared to women with neither mental illness nor substance use (aOR 0.52, 95% CI: 0.41-.66). Results demonstrated a consistent association between midwifery versus physician care and lower odds of SGA, yet effects were not statistically significantly different for women with higher or lower psychosocial risk., Conclusion: Among low SEP women in British Columbia, Canada, antenatal midwifery compared to obstetrician care was associated with reduced odds of PTB. Odds were lower among women with substance use, and mental illness and substance use, than among women without these risk factors.

Background: Implementation of high-quality national audits for perinatal mortality are needed to improve the registration of all perinatal deaths and the identification of the causes of death. This study aims to evaluate the implementation of a Regional Audit System for Stillbirth in Emilia-Romagna Region, Italy., Methods: For each stillbirth (≥ 22 weeks of gestation, ≥ 500 g) occurred between January 1, 2014 to December 1, 2016 (n = 332), the same diagnostic workup was performed and a clinical record with data about mother and stillborn was completed. Every case was discussed in a multidisciplinary local audit to assess both the cause of death (ReCoDe classification) and the quality of care. Data were reviewed by the Regional Audit Group. Stillbirth rates, causes of death and the quality of care were established for each case., Results: Total stillbirth rate was 3.09 per 1000 births (332/107,528). Late stillbirth rate was 2.3 per 1000 (251/107,087). Sixteen stillbirths were not registered by the Regional Birth Register. The most prevalent cause of death was placental disorder (33.3%), followed by fetal (17.6%), cord (14.2%) and maternal disorders (7.6%). Unexplained cases were 14%. Compared to local audits, the regional group attributed different causes of death in 17% of cases. At multivariate analysis, infections were associated with early stillbirths (OR 3.38, CI95% 1.62-7.03) and intrapartum cases (OR 6.64, CI95% 2.61-17.02). Placental disorders were related to growth restriction (OR 1.89, CI95% 1.06-3.36) and were more frequent before term (OR 1.86, CI95% 1.11-3.15). Stillbirths judged possibly/probably preventable with a different management (10.9%) occurred more frequently in non-Italian women and were mainly related to maternal disorders (OR 6.64, CI95% 2.61-17.02)., Conclusions: Regional Audit System for Stillbirth improves the registration of stillbirth and allows to define the causes of death. Moreover, sub-optimal care was recognized, allowing to identify populations which could benefit from preventive measures.

Background: Fetal growth has been known to be associated with particulate matter (PM) air pollution during gestation. Given that regular working may deviate outdoor air pollution exposure, the association between air pollution and fetal growth restriction can be different across maternal working status. This study was to assess possible effect modification by maternal employment in the association between exposure to PM during pregnancy and fetal growth restriction., Methods: Using hourly PM less than or equal to 10 and 2.5 μm in diameter (PM 10 and PM 2.5 ) regulatory monitoring data for 2001-2012 and 2008-2012, respectively, and birth certificate data for 2002-2012, we computed maternal exposures with district-level averages of PM 10 and PM 2.5 during one year before birth, entire pregnancy, and the 1st, 2nd and 3rd trimesters. The outcomes of fetal growth restriction were assessed by small for gestational age (SGA, weighted <10th percentile in the same gestational age) as well as low birth weight (LBW, < 2.5 kg) at term. We performed logistic regression to examine the association between PM and each of fetal growth restriction outcomes adjusting for individual risk factors. For effect modification by maternal employment, we estimated adjusted odds ratio (OR) of SGA or LBW for interquartile (IQR) increases in PM 10 or PM 2.5 stratified by employed and non-employed mothers. We also computed relative excess risk due to interaction (RERI) to investigate additive interaction., Results: Among 824,011 singleton term births, 34.0% (279,856) were employed and 66.0% (544,155) were non-employed mothers. Proportions of LBW were 1.5% in employed and 1.6% in non-employed (P < 0.001). SGA occurred in 12.7% of employed and 12.8% of non- employed (P = 0.124) mothers. For non-employed mothers, we observed increased odds of SGA per IQR increase in PM 10 for one year before birth (OR = 1.02, 95% confidence intervals (CI): 1.00-1.04, P = 0.028). ORs of SGA for full pregnancy period and the 3rd trimester were also positive but did not reach statistical significance. We did not observe positive association for PM 2.5 . RERI was not significant both for PM 10 and PM 2.5 ., Conclusions: We did not observe evidence of effect modification by maternal employment in the association between ambient PM and fetal growth restriction. Future studies using more refined exposure measures should confirm this finding.

Background: To compare the rates of adverse pregnancy outcomes between women with normal and abnormal inhibin-A levels., Methods: Based on a prospective database of Down syndrome screening program, the consecutive records were comprehensively reviewed. Pregnancies were classified into three groups: normal, high (> 2 MoM) and low (< 0.5 MoM) inhibin-A levels. The pregnancies with medical diseases, chromosome abnormalities and fetal anomalies were excluded. The primary outcomes were the rates of preterm birth, preeclampsia, and fetal growth restriction (FGR)., Results: Of 6679 recruited pregnancies, 5080 met the inclusion criteria, including 4600, 205 and 275 pregnancies in the group of normal, high, and low inhibin-A levels respectively. The rates of preterm birth, preeclampsia and FGR were significantly higher in the group of high levels; (RR, 1.51, 95%CI: 1.01-2.26; 3.47, 95% CI: 2.13-5.65; 3.04, 95% CI: 1.99-4.65 respectively), whereas the rates of other adverse outcomes were comparable. However, the rate of spontaneous preterm birth among women with high inhibin-A was not significantly increased. Based on multivariate analysis, the preterm birth rate was not significantly associated with inhibin-A levels, but it was rather a consequence of preeclampsia and FGR. Low levels of serum inhibin-A were not significantly associated with any adverse outcomes., Conclusions: High levels of maternal serum inhibin-A in the second trimester are significantly associated with abnormal placentation, which increases the risk of preeclampsia and FGR with a consequence of indicated preterm birth but not a risk of spontaneous preterm birth. In contrast, low inhibin-A levels were not associated with any common adverse pregnancy outcomes.

Background: Growing evidence indicates that the risk of obstetric and perinatal outcomes is higher in women with assisted reproductive technology (ART). However, there is little known about pregnancy related complications and co-morbidity in gestational diabetes mellitus (GDM) following singleton pregnancies achieved by ART in comparison with spontaneous conception (SC)., Methods: Two hundred sixty singleton pregnant women conceived by ART and 314 pregnant women conceived by spontaneous conception (SC) were participated in this prospective cohort study. All participants were enrolled after GDM screening through one-step oral glucose tolerance test (OGTT) and then grouped into GDM and non-GDM groups. Women were followed for pregnancy outcomes including pregnancy-induced hypertension (PIH), preeclampsia, antepartum hemorrhage (APH), cesarean section (CS), preterm birth (PTB), intrauterine growth restriction (IUGR), being small or large for gestational age (SGA or LGA), macrosomia, low birth weight (LBW), respiratory distress, neonatal hypoglycemia, NICU admission and perinatal mortality from antenatal visits to delivery. Confounding factors were adjusted in logistic regression model in order to estimate adjusted odds ratios (aORs)., Results: Among 260 ART and 314 SC, 135 and 152 women were GDM women, respectively. Higher maternal age and pre-gravid BMI, shorter duration of gestation and lower gestational weight gain were observed in GDM groups (ART-GDM and SC-GDM) compared to those of the SC group. ART-GDM group had a higher risk (95% confidence interval) of obstetric complications including PIH [aOR:7.04 (2.24-22.15)], preeclampsia [aOR:7.78 (1.62-37.47)], APH [aOR:3.46 (1.28-9.33)], emergency CS [aOR:2.64 (1.43-4.88)], and perinatal outcomes such as PTB [aOR:3.89 (1.51-10.10)], LBW [aOR:3.11 (1.04-9.30)] and NICU admission [aOR:4.36 (1.82-10.45)], as well as neonatal hypoglycemia [aOR: 4.91 (1.50-16.07)], compared to SC group. SC-GDM group showed a higher risk of PIH [aOR: 4.12 (1.31-12.89)], emergency CS [aOR: 2.01 (1.09-3.73] and LGA [aOR: 5.20 (1.07-25.20)], compared to SC group. Additionally, ART group had a higher risk of PIH [aOR: 3.46(1.02-11.68), preeclampsia 5.29 (1.03-27.09), and NICU admission [aOR: 2.53 (1.05-6.09)] compared to SC. Insulin requirement (41.8% vs. 25.7%) was significantly higher in ART-GDM group compared to SC-GDM group., Conclusion: The findings of this study suggest that GDM occurring after ART conception increases the risk of adverse obstetric and perinatal outcomes.

Background: The relation between grand multiparity (GMP) and the possible adverse pregnancy outcomes is not well identified. GMP (parity ≥5 births) frequently occurs in the Arab nations; therefore, this study aimed to identify the correlation between GMP and the different adverse maternal and neonatal outcomes in the Saudi population., Method: This cohort study was conducted on a total of 3327 women from the labour ward in King Khaled University Hospital, Riyadh, Saudi Arabia. Primiparous, multiparous and grand multiparous females were included. Socio-demographic data and pregnancy complications like gestational diabetes or hypertension, preeclampsia and intrauterine growth restriction were retrieved from the participants' files. In addition, the labour ward records were used to extract information about delivery events (e.g. spontaneous preterm delivery, caesarean section [CS]) and neonatal outcomes including anthropometric measurements, APGAR score and neonatal admission to the intensive care., Results: Primiparas responses were more frequent in comparison to multiparas and GMP (56.8% and 33%, and 10.2% respectively). In general, history of miscarriage was elevated (27.2%), and was significantly higher in GMP (58.3%, p < 0.01). Caesarean delivery was also elevated (19.5%) and was significantly high in the GMP subgroup (p < 0.01). However, after adjustment for age, GMP were less likely to deliver by CS (odds ratio: 0.6, 95% CI: 0.4-0.8; p < 0.01). The two most frequent pregnancy-associated complications were gestational diabetes and spontaneous preterm delivery (12.6% and 9.1%, respectively). The former was significantly more frequent in the GMP (p < 0.01). The main neonatal complication was low birth weight (10.7%); nevertheless, neonatal admission to ICU was significantly higher in GMP (p = 0.04), and low birth weight was more common in primiparas (p < 0.01). Furthermore, logistic regression analysis revealed an insignificant increase in the maternal or neonatal risks in GMP compared to multiparas after adjustment for age., Conclusion: Grand multiparous Saudi females have similar risks of maternal and neonatal complications compared to the other parity groups. Advanced age might play a major role on pregnancy outcomes in GMP. Nevertheless, grand multiparty might not be discouraged as long as women are provided with good perinatal care.

Background: Fetal growth restriction (FGR) is a serious obstetric condition for which there is currently no treatment. The EVERREST Prospective Study has been designed to characterise the natural history of pregnancies affected by severe early onset FGR and establish a well phenotyped bio-bank. The findings will provide up-to-date information for clinicians and patients and inform the design and conduct of the EVERREST Clinical Trial: a phase I/IIa trial to assess the safety and efficacy of maternal vascular endothelial growth factor (VEGF) gene therapy in severe early onset FGR. Data and samples from the EVERREST Prospective Study will be used to identify ultrasound and/or biochemical markers of prognosis in pregnancies with an estimated fetal weight (EFW) <3rd centile between 20+0 and 26+6 weeks of gestation., Methods: This is a 6 year European multicentre prospective cohort study, recruiting women with a singleton pregnancy where the EFW is <3rd centile for gestational age and <600 g at 20+0 to 26+6 weeks of gestation. Detailed data are collected on: maternal history; antenatal, peripartum, and postnatal maternal complications; health economic impact; psychological impact; neonatal condition, progress and complications; and infant growth and neurodevelopment to 2 years of corrected age in surviving infants. Standardised longitudinal ultrasound measurements are performed, including: fetal biometry; uterine artery, umbilical artery, middle cerebral artery, and ductus venosus Doppler velocimetry; and uterine artery and umbilical vein volume blood flow. Samples of maternal blood and urine, amniotic fluid (if amniocentesis performed), placenta, umbilical cord blood, and placental bed (if caesarean delivery performed) are collected for bio-banking. An initial analysis of maternal blood samples at enrolment is planned to identify biochemical markers that are predictors for fetal or neonatal death., Discussion: The findings of the EVERREST Prospective Study will support the development of a novel therapy for severe early onset FGR by describing in detail the natural history of the disease and by identifying women whose pregnancies have the poorest outcomes, in whom a therapy might be most advantageous. The findings will also enable better counselling of couples with affected pregnancies, and provide a valuable resource for future research into the causes of FGR., Trial Registration: NCT02097667 registered 31 st October 2013.

Background: The burden of pregnancy complications associated with well defined, already established systemic rheumatic diseases preexisting pregnancy such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma is well known. Systemic rheumatic diseases are characterized by a long natural history with few symptoms, an undifferentiated picture or a remitting course making difficult a timely diagnosis. It has been suggested that screening measures for these diseases could be useful but the impact of unrecognized systemic rheumatic disorders on pregnancy outcome is unknown. The objective of the study was to evaluate the impact of previously unrecognized systemic autoimmune rheumatic on the incidence of preeclampsia and fetal growth restriction (FGR)., Methods: A longitudinal cohort-study with enrolment during the first trimester of pregnancy of women attending routine antenatal care using a two-step approach with a self-reported questionnaire, autoantibody detection and clinical evaluation of antibody-positive subjects. The incidence of FGR and preeclampsia in subjects with newly diagnosed rheumatic diseases was compared to that of selected negative controls adjusting for potential confounders by logistic regression analysis., Results: The prevalence of previously unrecognized systemic rheumatic diseases was 0.4 % for rheumatoid arthritis (19/5232), 0.25 % (13/5232) for systemic lupus erythematosus, 0.31 % (16/5232) for Sjögren's syndrome, 0.3 % for primary antiphospholipid syndrome (14/5232) and 0.11 % (6/5232) for other miscellaneous diseases. Undifferentiated connective tissue disease was diagnosed in an additional 131 subjects (2.5 %). The incidence of either FGR or preeclampsia was 6.1 % (36/594) among controls and 25.3 % (50/198) in subjects with unrecognized rheumatic diseases (excess incidence = 3.9 % (95 % CI = 2.6-9.6) or 34 % (95 % CI = 22-44) of all cases of FGR/preeclampsia). The incidence of small for gestational age infant (SGA) was higher among subjects with unrecognized rheumatic diseases (41/198 as compared to 46/594; adjOdds Ratio = 3.1, 95 % CI =1.96-4.95) than in controls. The excess incidence associated with unrecognized rheumatic diseases was 2.7 % (95 % CI = 1.5-4) or 25 % (95 % CI = 12.8-34.8) of all SGA cases., Conclusions: Unrecognized autoimmune systemic rheumatic disorders are associated with a significant proportion of preeclampsia and fetal growth failure, suggesting that their role in the etiology of adverse pregnancy outcome is probably undervalued.

Background: Fetal growth restriction (FGR) is associated with increased infant mortality rates and ill-health in adulthood. Evaluation of fetal growth requires ultrasound. As a result, ultrasound-assisted evaluations of causes of FGR in malaria-endemic developing countries are rare. We aimed to determine factors associated with indicators of abnormal fetal growth in rural lowland Papua New Guinea (PNG)., Methods: Weights and growth of 671 ultrasound-dated singleton pregnancies (<25 gestational weeks) were prospectively monitored using estimated fetal weights and birthweights. Maternal nutritional status and haemoglobin levels were assessed at enrolment, and participants were screened for malaria on several occasions. FGR was suspected upon detection of an estimated fetal weight or birthweight <10(th) centile (small-for-gestational age) and/or low fetal weight gain, defined as a change in weight z-score in the first quartile. Factors associated with fetal weight and fetal weight gain were additionally assessed by evaluating differences in weight z-scores and change in weight z-scores. Log-binomial and linear mixed effect models were used to determine factors associated with indicators of FGR., Results: SGA and low weight gain were detected in 48.3% and 37.0% of pregnancies, respectively. Of participants, 13.8%, 21.2%, and 22.8% had a low mid-upper arm circumference (MUAC, <22 cms), short stature (<150 cms) and anaemia (haemoglobin <90 g/L) at first antenatal visit. 24.0% (161/671) of women had at least one malaria infection detected in peripheral blood. A low MUAC (adjusted risk ratio [aRR] 1.51, 95% CI 1.29, 1.76, P < 0.001), short stature (aRR 1.27, 95% CI 1.04, 1.55, P = 0.009), and anaemia (aRR 1.27, 95% CI 1.06, 1.51, P = 0.009) were associated with SGA, and a low body mass index was associated with low fetal weight gain (aRR 2.10, 95% CI 1.62, 2.71, P < 0.001). Additionally, recent receipt of intermittent preventive treatment in pregnancy was associated with increased weight z-scores, and anaemia with reduced change in weight z-scores. Malaria infection was associated with SGA on crude but not adjusted analyses (aRR 1.13, 95% CI 0.95, 1.34, P = 0.172)., Conclusion: Macronutrient undernutrition and anaemia increased the risk of FGR. Antenatal nutritional interventions and malaria prevention could improve fetal growth in PNG.

Background: Reviews of perinatal deaths are mostly facility based. Given the number of women who, globally, deliver outside of facilities, this data may be biased against total population data. We aimed to analyse population based perinatal mortality data from a LMIC setting (Mpumalanga, South Africa) to determine the causes of perinatal death and the rate of maternal complications in the setting of a perinatal death., Methods: A secondary analysis of the South African Perinatal Problems Identification Program (PPIP) database for the Province of Mpumalanga was undertaken for the period October 2013 to January 2014, inclusive. Data on each individual late perinatal death was reviewed. We examined the frequencies of maternal and fetal or neonatal characteristics in late fetal deaths and analysed the relationships between maternal condition and fetal and/or neonatal outcomes. IBM SPSS Statistics 22.0 was used for data analysis., Results: There were 23503 births and 687 late perinatal deaths (stillbirths of ≥ 1000gr or ≥ 28 weeks gestation and early neonatal deaths up to day 7 of neonatal life) in the study period. The rate of maternal complication in macerated stillbirths, fresh stillbirths and early neonatal deaths was 50.4%, 50.7% and 25.8% respectively. Mothers in the other late perinatal deaths were healthy. Maternal hypertension and obstetric haemorrhage were more likely in stillbirths (p = <0.01 for both conditions), whereas ENNDs were more likely to have a healthy mother (p < 0.01). The main causes of neonatal death were related to immaturity (48.7%) and hypoxia (40.6%). 173 (25.2%) of all late perinatal deaths had a birth weight less than the 10(th) centile for gestational age., Conclusion: A significant proportion of women have no recognisable obstetric or medical condition at the time of a late perinatal death; we may be limited in our ability to predict poor perinatal outcome if emphasis is put on detecting maternal complications prior to a perinatal death. Intrapartum care and hypertensive disease remain high priority areas for addressing perinatal mortality. Consideration needs to be given to novel ways of detecting growth restriction in a LMIC setting.

Background: The birth weight and gestational age at birth are two important variables that define neonatal morbidity and mortality. In developed countries, chronic maternal diseases like hypertension, diabetes mellitus, renal disease or collagen vascular disease is the most common cause of intrauterine growth restriction (IUGR). Maternal nutrition, pregnancy induced hypertension, chronic maternal infections, and other infections such as cytomegalovirus, parvovirus, rubella and malaria are the other causes of IUGR. The present study examines the secular trend of Small for Gestational Age (SGA) over 15 years and risk factors for SGA from a referral hospital in India., Methods: Data from 1996 to 2010 was obtained from the labour room register. A rotational sampling scheme was used i.e. 12 months of the year were divided into 4 quarters. Taking into consideration all deliveries that met the inclusion criteria, babies whose birth weights were less than 10(th) percentile of the cut off values specific for gestational ages, were categorized as SGA. Only deliveries of live births that occurred between 22 and 42 weeks of pregnancy were considered in this study. Besides bivariate analyses, multivariable logistic regression analysis was done. Nagelkerke R(2) statistics and Hosmer and Lemeshow chi-square statistics were used as goodness of fit statistics., Results: Based on the data from 36,674 deliveries, the incidence of SGA was 11.4% in 1996 and 8.4% in 2010. Women who had multiple pregnancies had the higher odds of having SGA babies, 2.8 (2.3-3.3) times. The women with hypertensive disease had 1.8 (1.5-1.9) times higher odds of having SGA. Underweight women had 1.7 (1.3 - 2.1) times and anaemic mothers had 1.29 (1.01 - 1.6) times higher odds. The mothers who had cardiac disease were 1.4 (1.01 - 2.0) times at higher odds for SGA. In teenage pregnancies, the odds of SGA was 1.3 (1.1 - 1.5) times higher than mothers in the age group 20 to 35 years., Conclusions: There is a significant reduction in the incidence of SGA by 26% over 15 years. The women with the above modifiable risk factors need to be identified early and provided with health education on optimal birth weight.

Background: The association between fetal gender and pregnancy outcomes has been thoroughly demonstrated in western populations. However, this association has not been thoroughly documented in China. The primary objective of the present study is to determine whether the association of adverse pregnancy and labour outcomes with male fetuses applies to the Chinese population., Methods: This cross-sectional hospital-based retrospective survey collected data from thirty-nine hospitals in 2011 in mainland China. A total of 109,722 women with singleton pregnancy who delivered after 28 weeks of gestation were included., Results: Of these pregnancies, the male-to-female sex ratio was 1.2. The rates of preterm birth (7.3% for males, 6.5% for females) and fetal macrosomia (8.3% for males, 5.1% for females) were higher for male newborns, whereas fetal growth restriction (8.0% for females, 5.4% for males) and malpresentation (4.3% for females, 3.6% for males) were more frequent among female-bearing mothers. A male fetus was associated with an increased incidence of operative vaginal delivery (1.3% for males, 1.1% for females), caesarean delivery (55.0% for males, 52.9% for females), and cephalopelvic disproportion/failure to progress (10.0% for males, 9.2% for female). Male gender was also significantly associated with lower Apgar scores (<7 at 5 min, adjusted odds ratio 1.3, 95% CI 1.0-1.6), as well as a neonatal intensive care unit admission and neonatal death, even after adjustments for confounders (adjusted odds ratio 1.3, 95% CI 1.1-1.5, adjusted odds ratio 1.4, 95% CI 1.1-1.8)., Conclusion: We confirm the existence of obvious neonatal gender bias and adverse outcomes for male fetuses during pregnancy and labour in our population. Further research is required to understand the mechanisms and clinical implications of this phenomenon.

Background: Limited information is available concerning investigating the separate effect of teenage childbirth on medical issues in the antenatal and perinatal periods. Therefore, this study aimed to assess medical problems in antenatal and perinatal periods among early youth, adolescent and young adult mothers in Taiwan., Methods: This retrospective population-based cohort study was conducted by using data from Taiwan's National Health Insurance Research Database. A total of 335,590 mothers aged less than 25 years who had singleton births were identified between 2002 and 2011. Univariate and multivariate logistic regression analyses were conducted to estimate unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) of each medical problem category in the antenatal and perinatal periods., Results: Compared with mothers aged 20-24 years, adolescents (16-19 years) and early youth mothers (≤ 15 years), particularly those aged 10-15, had a significantly higher risk of intrauterine growth retardation (IUGR, OR = 1.37, 95% CI: 1.00-1.89) and preterm delivery (OR = 2.98, 95% CI: 2.48-3.58) after adjusting for demographic characteristics and clinical factors. Additionally, adolescents mothers were at an increased risk of anemia (OR = 1.32, 95% CI: 1.24-1.40), oligohydramnios (OR = 1.21, 95% CI: 1.12-1.32), failed labor induction (OR = 1.33, 95% CI: 1.24-1.43), and fetal distress (OR = 1.20, 95% CI: 1.14-1.26) after adjustment., Conclusions: Not all young mothers in our study experienced the same magnitude of increased medical problems in the antenatal and perinatal periods. However, a sufficiently higher probability of having IUGR and preterm delivery was observed among early youth and adolescent mothers.

Background: To analyze trends in LBW (low birth weight) rate using birth registry data and identify factors associated with LBW in São Luís comparing two birth cohorts separated by a 12-year interval., Methods: 2,426 births were included in 1997/98 and 5,040 in 2010. The dependent variable was LBW (<2,500 g). Multiple logistic regression was performed to determine the association of independent variables with LBW. Data were also obtained from SINASC (Brazilian National Birth Registry) to analyze stillbirth and LBW rates trends from 1996 to 2010, using 3-year moving averages., Results: LBW, intrauterine growth restriction (IUGR) and preterm birth rates did not differ between the two cohorts. Despite this, birth registry data showed increasing LBW rate up to 2001, coinciding with decreasing stillbirth rate. Both stillbirth and LBW rates decreased thereafter. A significant reduction was observed in the percentage of teenage mothers, mothers with up to 4 years of education, family income up to one minimum wage and mothers who did not attend prenatal care. There was an increase in maternal age ≥35 years and schooling ≥12 years. The variables associated with LBW in 1997/98 were young maternal age (<18 years), maternal smoking during pregnancy and primiparity. Variables that remained in the adjusted model in 2010 were female gender, income <3 minimum wages, lack of prenatal care, maternal smoking during pregnancy and primiparity., Conclusions: Although LBW rate did not differ between the two cohorts, this apparent stability masked an increase up to 2001 and a decrease thereafter. The rise in LBW rate paralleled reduction in the stillbirth rate, suggesting improvement in obstetrical and newborn care. Maternal, socioeconomic and demographic factors associated with LBW differed between the two cohorts, except for smoking during pregnancy and parity that were significantly associated with LBW in both cohorts.

Background: In Western countries, active maternal smoking during pregnancy is recognized as the most important preventable risk factor for adverse birth outcomes. However, the effect of passive maternal smoking is less clear and has not been extensively studied. In Japan, there has been only one epidemiological study which examined the effects of active smoking during early pregnancy on birth outcomes although the effects of passive smoking were not assessed., Methods: Study subjects were 1565 mothers with singleton pregnancies and the babies born from these pregnancies. Data on active maternal smoking status in the first, second, and third trimesters and maternal environmental tobacco smoke (ETS) exposure at home and work were collected with self-administered questionnaires., Results: Compared with children born to mothers who had never smoked during pregnancy, children born to mothers who had smoked throughout their pregnancy had a significantly increased risk of small-for-gestational-age (SGA) (adjusted odd ratio [OR] = 2.87; 95% confidence interval: 1.11 - 6.56). However, active maternal smoking only in the first trimester and active maternal smoking in the second and/or third trimesters but not throughout pregnancy were not significantly associated with SGA. With regard to the risk of preterm birth, the adjusted ORs for the above-mentioned three categories were not significant; however, the positive linear trend was significant (P for trend = 0.048). No significant association was found between active maternal smoking during pregnancy and the risk of low birth weight. There was a significant inverse relationship between active maternal smoking during pregnancy and birth weight; newborns of mothers who had smoked throughout pregnancy had an adjusted mean birth weight reduction of 169.6 g. When classifying babies by gender, a significant positive association between active maternal smoking throughout pregnancy and the risk of SGA was found only in male newborns, however, the interaction was not significant. Maternal ETS exposure at home or work was not significantly associated with any birth outcomes., Conclusions: This is the first study in Japan to show that active maternal smoking throughout pregnancy, but not during the first trimester, is significantly associated with an increased risk of SGA and a decrease in birth weight. Thus, women who smoke should quit smoking as soon as possible after conception.

Background: Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers., Methods: From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit., Results: In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054)., Conclusions: Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.

Background: Interpretation of previous associations between water intake and adverse birth outcomes is challenging given that amount and type of water consumed can be non-specific markers of exposure or underlying behavioural characteristics. We examined the relationship between water intake measures and adverse birth outcomes in participants from three study sites in the United States., Methods: Using a prospective cohort study, we examined daily intake of bottled, cold tap, total tap, and total water in relation to birth weight and risk of small-for-gestational-age (SGA) among term births and risk of preterm delivery., Results: Based on water consumption data collected between 20-24 weeks of gestation, the adjusted mean birth weight was 27 (95% confidence interval [CI]: -34, 87), 39 (95% CI: -22, 99), and 50 (95% CI: -11, 110) grams higher for the upper three total water intake quartiles (> 51-78, > 78-114, and > 114 ounces/day) compared to the lowest quartile (≤ 51 ounces/day). Adjusted birth weight results were similar for bottled water, cold tap water, and total tap water intake. An exposure-response gradient was not detected for either preterm delivery or SGA with increasing total water intake and total tap water intake, but adjusted relative risks for all three upper quartiles were below 1.0 (range: 0.6-0.9) for SGA., Conclusion: These data suggest that high water intake may be associated with higher mean birth weight following adjustment for confounding.

Background: Activated Protein C Resistance (APCR), a poor anticoagulant response of APC in haemostasis, is the commonest heritable thrombophilia. Adverse outcomes during pregnancy have been linked to APCR. This study determined the frequency of APCR, factor V gene known and novel SNPs and adverse outcomes in a group of pregnant women., Methods: Blood samples collected from 907 pregnant women were tested using the Coatest Classic and Modified functional haematological tests to establish the frequency of APCR. PCR-Restriction Enzyme Analysis (PCR-REA), PCR-DNA probe hybridisation analysis and DNA sequencing were used for molecular screening of known mutations in the factor V gene in subjects determined to have APCR based on the Coatest Classic and/or Modified functional haematological tests. Glycosylase Mediated Polymorphism Detection (GMPD), a SNP screening technique and DNA sequencing, were used to identify SNPs in the factor V gene of 5 APCR subjects., Results: Sixteen percent of the study group had an APCR phenotype. Factor V Leiden (FVL), FV Cambridge, and haplotype (H) R2 alleles were identified in this group. Thirty-three SNPs; 9 silent SNPs and 24 missense SNPs, of which 20 SNPs were novel, were identified in the 5 APCR subjects. Adverse pregnancy outcomes were found at a frequency of 35% in the group with APCR based on Classic Coatest test only and at 45% in the group with APCR based on the Modified Coatest test. Forty-eight percent of subjects with FVL had adverse outcomes while in the group of subjects with no FVL, adverse outcomes occurred at a frequency of 37%., Conclusions: Known mutations and novel SNPs in the factor V gene were identified in the study cohort determined to have APCR in pregnancy. Further studies are required to investigate the contribution of these novel SNPs to the APCR phenotype. Adverse outcomes including early pregnancy loss (EPL), preeclampsia (PET) and intrauterine growth restriction (IGUR) were not significantly more frequent in subjects with APCR compared to normal pregnant women however Pregnancy induced hypertension (PIH) was found to be associated with FVL in our study group.

Background: The consequences of in utero growth restriction have been attracting scholarly attention for the past two decades. Nevertheless, the diagnosis of growth-restricted neonates is as yet an unresolved issue. Aim of this study is the evaluation of the performance of simple, common indicators of nutritional status, which are used in the identification of growth-restricted neonates., Methods: In a cohort of 418 consecutively born term and near term neonates, four widely used anthropometric indices of body proportionality and subcutaneous fat accretion were applied, singly and in combination, as diagnostic markers for the detection of growth-restricted babies. The concordance of the indices was assessed in terms of positive and negative percent agreement and of Cohen's kappa., Results: The agreement between the anthropometric indices was overall poor with a highest positive percent agreement of 62.5% and a lowest of 27.9% and the kappa ranging between 0.19 and 0.58. Moreover, 6% to 32% of babies having abnormal values in just one index were apparently well-grown and the median birth weight centile of babies having abnormal values of either of two indices was found to be as high as the 46th centile for gestational age (95%CI 35.5 to 60.4 and 29.8 to 63.9, respectively). On the contrary, the combination of anthropometric indices appeared to have better distinguishing properties among apparently and not apparently well-grown babies. The median birth weight centile of babies having abnormal values in two (or more) indices was the 11th centile for gestational age (95%CI 6.3 to 16.3)., Conclusions: Clinical assessment and anthropometric indices in combination can define a reference standard with better performance compared to the same indices used in isolation. This approach offers an easy-to-use tool for bedside diagnosis of in utero growth restriction.

Background: Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined., Methods: We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies., Results: We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed., Conclusion: Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs.

Background: It is unclear whether the high rates of low birth weight in South Asia are due to poor fetal growth or short pregnancy duration. Also, it is not known whether the traditional focus on preventing low birth weight has been successful. We addressed these and related issues by studying births in Kaniyambadi, South India, with births from Nova Scotia, Canada serving as a reference., Methods: Population-based data for 1986 to 2005 were obtained from the birth database of the Community Health and Development program in Kaniyambadi and from the Nova Scotia Atlee Perinatal Database. Menstrual dates were used to obtain comparable information on gestational age. Small-for-gestational age (SGA) live births were identified using both a recent Canadian and an older Indian fetal growth standard., Results: The low birth weight and preterm birth rates were 17.0% versus 5.5% and 12.3% versus 6.9% in Kaniyambadi and Nova Scotia, respectively. SGA rates were 46.9% in Kaniyambadi and 7.5% in Nova Scotia when the Canadian fetal growth standard was used to define SGA and 6.7% in Kaniyambadi and < 1% in Nova Scotia when the Indian standard was used. In Kaniyambadi, low birth weight, preterm birth and perinatal mortality rates did not decrease between 1990 and 2005. SGA rates in Kaniyambadi declined significantly when SGA was based on the Indian standard but not when it was based on the Canadian standard. Maternal mortality rates fell by 85% (95% confidence interval 57% to 95%) in Kaniyambadi between 1986-90 and 2001-05. Perinatal mortality rates were 11.7 and 2.6 per 1,000 total births and cesarean delivery rates were 6.0% and 20.9% among live births >or= 2,500 g in Kaniyambadi and Nova Scotia, respectively., Conclusion: High rates of fetal growth restriction and relatively high rates of preterm birth are responsible for the high rates of low birth weight in South Asia. Increased emphasis is required on health services that address the morbidity and mortality in all birth weight categories.

Background: Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term., Methods/design: The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm., Discussion: This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term., Trial Registration: Dutch Trial Register and ISRCTN-Register: ISRCTN10363217.