Fetal cerebellar growth and Sylvian fissure maturation: international standards from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. RESULTS: Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-diameter and Sylvian-fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation, with complete overlap of the mean gestational age and 95% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. CONCLUSION: We present, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Non-communicable diseases among adolescents: current status, determinants, interventions and policies.

BACKGROUND: Addressing non-communicable disease (NCDs) is a global priority in the Sustainable Development Goals, especially for adolescents. However, existing literature on NCD burden, risk factors and determinants, and effective interventions and policies for targeting these diseases in adolescents, is limited. This study develops an evidence-based conceptual framework, and highlights pathways between risk factors and interventions to NCD development during adolescence (ages 10-19 years) and continuing into adulthood. Additionally, the epidemiologic profile of key NCD risk factors and outcomes among adolescents and preventative NCD policies/laws/legislations are examined, and a multivariable analysis is conducted to explore the determinants of NCDs among adolescents and adults. METHODS: We reviewed literature to develop an adolescent-specific conceptual framework for NCDs. Global data repositories were searched from Jan-July 2018 for data on NCD-related risk factors, outcomes, and policy data for 194 countries from 1990 to 2016. Disability-Adjusted Life Years were used to assess disease burden. A hierarchical modeling approach and ordinary least squares regression was used to explore the basic and underlying causes of NCD burden. RESULTS: Mental health disorders are the most common NCDs found in adolescents. Adverse behaviours and lifestyle factors, specifically smoking, alcohol and drug use, poor diet and metabolic syndrome, are key risk factors for NCD development in adolescence. Across countries, laws and policies for preventing NCD-related risk factors exist, however those targeting contraceptive use, drug harm reduction, mental health and nutrition are generally limited. Many effective interventions for NCD prevention exist but must be implemented at scale through multisectoral action utilizing diverse delivery mechanisms. Multivariable analyses showed that structural/macro, community and household factors have significant associations with NCD burden among adolescents and adults. CONCLUSIONS: Multi-sectoral efforts are needed to target NCD risk factors among adolescents to mitigate disease burden and adverse outcomes in adulthood. Findings could guide policy and programming to reduce NCD burden in the sustainable development era.

Characterizing Agreement in the Level of Interarm Blood Pressure Readings of Adults in the Emergency Department (CALIBRATE Study).

Background: Increased interarm systolic blood pressure difference (IASBPD) is one of the major predictors of cardiovascular disease. An IASBPD of >10 mmHg is of clinical significance. However, studies have reported a high number of patients visiting the emergency department (ED) with high IASBPD and varying correlation of IASBPD to age, ethnic background, and comorbidities such as hypertension and diabetes. Objective: The CALIBRATE study aimed to measure the IABPDs in the multiethnic patient population presenting to the ED in Qatar and to assess the distribution of IASBPD in this population. Methods: In a sitting position, two consecutive blood pressure (BP) measurements were recorded from the right and left arms for each participant using a calibrated automated machine and appropriate cuff sizes. The data were recorded using predefined data fields, including patient demographics, past medical, and social and family history. The continuous variables were reported as mean or median based on the distribution of data. The data were analyzed using Stata MP 14.0. Results: A total of 1800 patients, with a mean age of 34 (10) years, were prospectively recruited from the ED. The median absolute systolic BP difference (ΔSBP) between the right and left arms was 6 (3-10) mmHg, and it was the same for the first (ΔSBP1) and the second readings (ΔSBP2). The absolute average of ΔSBP1 and ΔSBP2 was 7 (4-10) mmHg. The difference in systolic BP difference (SBP) of < 20 mmHg for interarm blood pressure was seen in the 95th percentile of the population. No meaningful association could be detected between the IABPD and the study variables such as age, demographics, regions of interest, and risk factors. Conclusion: In population presenting to the ED, the IASBPD of at least 20 mmHg reached at the 95th percentile, validating the known significant difference. The utility of SBP difference can be improved further by taking the average of two individual readings.

International standards for fetal brain structures based on serial ultrasound measurements from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured using ultrasound, in healthy, well-nourished women at low risk of impaired fetal growth and poor perinatal outcome, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicenter, longitudinal study. The sample analyzed was selected randomly from the overall FGLS population, ensuring an equal distribution among the eight diverse participating sites and of three-dimensional (3D) ultrasound volumes across pregnancy (range: 15-36 weeks' gestation). We measured, in planes reconstructed from 3D ultrasound volumes of the fetal head at different timepoints in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle, atrium of the posterior horn of the lateral ventricle (PV) and cisterna magna (CM). Fractional polynomials were used to construct the standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were selected at random. After exclusions, 3D ultrasound volumes from 442 fetuses born without a congenital malformation were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures, except the PV, showed increasing size with gestational age, and the size of the POF, SF, PV and CM showed increasing variability. The 3rd , 5th , 50th , 95th and 97th smoothed centiles are presented. The 5th centiles for the POF and SF were 3.1 mm and 4.7 mm at 22 weeks' gestation and 4.6 mm and 9.9 mm at 32 weeks, respectively. The 95th centiles for the PV and CM were 8.5 mm and 7.5 mm at 22 weeks and 8.6 mm and 9.5 mm at 32 weeks, respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcome. We recommend these as international standards for the assessment of measurements obtained using ultrasound from fetal brain structures. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Core outcome sets for prevention and treatment of postpartum haemorrhage: an international Delphi consensus study.

OBJECTIVE: To develop core outcome sets (COS) for studies evaluating interventions for (1) prevention and (2) treatment of postpartum haemorrhage (PPH), and recommendations on how to report the COS. DESIGN: A two-round Delphi survey and face-to-face meeting. POPULATION: Healthcare professionals and women's representatives. METHODS: Outcomes were identified from systematic reviews of PPH studies and stakeholder consultation. Participants scored each outcome in the Delphi on a Likert scale between 1 (not important) and 9 (critically important). Results were discussed at the face-to-face meeting to agree the final COS. Consensus at the meeting was defined as ≥ 70% of participants scoring the outcome as critically important (7-9). Lectures, discussion and voting were used to agree how to report COS outcomes. MAIN OUTCOME MEASURES: Outcomes from systematic reviews and consultations. RESULTS: Both Delphi rounds were completed by 152/205 (74%) participants for prevention and 143/197 (73%) for treatment. For prevention of PPH, nine core outcomes were selected: blood loss, shock, maternal death, use of additional uterotonics, blood transfusion, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. For treatment of PPH, 12 core outcomes were selected: blood loss, shock, coagulopathy, hysterectomy, organ dysfunction, maternal death, blood transfusion, use of additional haemostatic intervention, transfer for higher level of care, women's sense of wellbeing, acceptability and satisfaction with the intervention, breastfeeding, and adverse effects. Recommendations were developed on how to report these outcomes where possible. CONCLUSIONS: These COS will help standardise outcome reporting in PPH trials. TWEETABLE ABSTRACT: Core outcome sets for PPH: nine core outcomes for PPH prevention and 12 core outcomes for PPH treatment.

Mass deworming for soil-transmitted helminths and schistosomiasis among pregnant women: A systematic review and individual participant data meta-analysis.

The objective of the review is to use individual participant data (IPD) meta-analysis to explore the effect of mass deworming during pregnancy. We developed a search strategy and searched the databases till March 2018. We included individually randomised controlled trials; cluster randomised controlled trials and quasi randomised studies providing preventive or therapeutic deworming drugs for soil transmitted helminthiases and schistosomiasis during pregnancy. All IPD were assessed for completeness, compared to published reports and entered into a common data spreadsheet. Out of the seven trials elgible for IPD, we received data from three trials; out of 8,515 potential IPD participants; data were captured for 5,957 participants. Findings from this IPD suggest that mass deworming during pregnancy reduces maternal anaemia by 23% (Risk ratio [RR]: 0.77, 95% confidence intreval [CI]: 0.73-0.81; three trials; 5,216 participants; moderate quality evidence). We did not find any evidence of an effect of mass deworming during pregnancy on any of the other outcomes. There was no evidence of effect modification; however these findings should be interpreted with caution due to small sample sizes. The quality of evidence was rated as moderate for our findings. Our analyses suggest that mass deworming during pregnancy is associated with reducing anaemia with no evidence of impact on any other maternal or pregnancy outcomes. Our analyses were limited by the availability of data for the impact by subgroups and effect modification. There is also a need to support and promote open data for future IPDs.

Seasonality and within-subject clustering of rotavirus infections in an eight-site birth cohort study.

Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.

The antepartum stillbirth syndrome: risk factors and pregnancy conditions identified from the INTERGROWTH-21st Project.

OBJECTIVES: To identify risk factors for antepartum stillbirth, including fetal growth restriction, among women with well-dated pregnancies and access to antenatal care. DESIGN: Population-based, prospective, observational study. SETTING: Eight international urban populations. POPULATION: Pregnant women and their babies enrolled in the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. METHODS: Cox proportional hazard models were used to compare risks among antepartum stillborn and liveborn babies. MAIN OUTCOME MEASURES: Antepartum stillbirth was defined as any fetal death after 16 weeks' gestation before the onset of labour. RESULTS: Of 60 121 babies, 553 were stillborn (9.2 per 1000 births), of which 445 were antepartum deaths (7.4 per 1000 births). After adjustment for site, risk factors were low socio-economic status, hazard ratio (HR): 1.6 (95% CI, 1.2-2.1); single marital status, HR 2.0 (95% CI, 1.4-2.8); age ≥40 years, HR 2.2 (95% CI, 1.4-3.7); essential hypertension, HR 4.0 (95% CI, 2.7-5.9); HIV/AIDS, HR 4.3 (95% CI, 2.0-9.1); pre-eclampsia, HR 1.6 (95% CI, 1.1-3.8); multiple pregnancy, HR 3.3 (95% CI, 2.0-5.6); and antepartum haemorrhage, HR 3.3 (95% CI, 2.5-4.5). Birth weight <3rd centile was associated with antepartum stillbirth [HR, 4.6 (95% CI, 3.4-6.2)]. The greatest risk was seen in babies not suspected to have been growth restricted antenatally, with an HR of 5.0 (95% CI, 3.6-7.0). The population-attributable risk of antepartum death associated with small-for-gestational-age neonates diagnosed at birth was 11%. CONCLUSIONS: Antepartum stillbirth is a complex syndrome associated with several risk factors. Although small babies are at higher risk, current growth restriction detection strategies only modestly reduced the rate of stillbirth. TWEETABLE ABSTRACT: International stillbirth study finds individual risks poor predictors of death but combinations promising.

Converging on child mental health - toward shared global action for child development.

We are a group of researchers and clinicians with collective experience in child survival, nutrition, cognitive and social development, and treatment of common mental conditions. We join together to welcome an expanded definition of child development to guide global approaches to child health and overall social development. We call for resolve to integrate maternal and child mental health with child health, nutrition, and development services and policies, and see this as fundamental to the health and sustainable development of societies. We suggest specific steps toward achieving this objective, with associated global organizational and resource commitments. In particular, we call for a Global Planning Summit to establish a much needed Global Alliance for Child Development and Mental Health in all Policies.

International estimated fetal weight standards of the INTERGROWTH-21st Project.

OBJECTIVE: Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH-21st Fetal Growth Standards that are available for use worldwide. METHODS: Women with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study (FGLS) and INTERBIO-21st Fetal Study (FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9-14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference (HC), biparietal diameter, occipitofrontal diameter, abdominal circumference (AC) and femur length (FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models. RESULTS: Of the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0-14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log(EFW) = 5.084820 - 54.06633 × (AC/100)3 - 95.80076 × (AC/100)3 × log(AC/100) + 3.136370 × (HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis-fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data (n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at < 37 weeks' gestation, the EFW centiles were, as expected, higher than those of babies born preterm. Comparing EFW cross-sectional values with the INTERGROWTH-21st Preterm Postnatal Growth Standards confirmed that preterm postnatal growth is a different biological process from intrauterine growth. CONCLUSIONS: We provide an assessment of EFW, as an adjunct to routine ultrasound biometry, from 22 to 40 weeks' gestation. However, we strongly encourage clinicians to evaluate fetal growth using separate biometric measures such as HC and AC, as well as EFW, to avoid the minimalist approach of focusing on a single value. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound-based gestational-age estimation in late pregnancy.

OBJECTIVE: Accurate gestational-age (GA) estimation, preferably by ultrasound measurement of fetal crown-rump length before 14 weeks' gestation, is an important component of high-quality antenatal care. The objective of this study was to determine how GA can best be estimated by fetal ultrasound for women who present for the first time late in pregnancy with uncertain or unknown menstrual dates. METHODS: INTERGROWTH-21st was a large, prospective, multicenter, population-based project performed in eight geographically defined urban populations. One of its principal components, the Fetal Growth Longitudinal Study, aimed to develop international fetal growth standards. Each participant had their certain menstrual dates confirmed by first-trimester ultrasound examination. Fetal head circumference (HC), biparietal diameter (BPD), occipitofrontal diameter (OFD), abdominal circumference (AC) and femur length (FL) were measured every 5 weeks from 14 weeks' gestation until delivery. For each participant, a single, randomly selected ultrasound examination was used to explore all candidate biometric variables and permutations to build models to predict GA. Regression equations were ranked based upon minimization of the mean prediction error, goodness of fit and model complexity. An automated machine learning algorithm, the Genetic Algorithm, was adapted to evaluate > 64 000 potential polynomial equations as predictors. RESULTS: Of the 4607 eligible women, 4321 (94%) had a pregnancy without major complications and delivered a live singleton without congenital malformations. After other exclusions (missing measurements in GA window and outliers), the final sample comprised 4229 women. Two skeletal measures, HC and FL, produced the best GA prediction, given by the equation loge (GA) = 0.03243 × (loge (HC))2 + 0.001644 × FL × loge (HC) + 3.813. When FL was not available, the best equation based on HC alone was loge (GA) = 0.05970 × (loge (HC))2 + 0.000000006409 × (HC)3 + 3.3258. The estimated uncertainty of GA prediction (half width 95% interval) was 6-7 days at 14 weeks' gestation, 12-14 days at 26 weeks' gestation and > 14 days in the third trimester. The addition of FL to the HC model led to improved prediction intervals compared with using HC alone, but no further improvement in prediction was afforded by adding AC, BPD or OFD. Equations that included other measurements (BPD, OFD and AC) did not perform better. CONCLUSIONS: Among women initiating antenatal care late in pregnancy, a single set of ultrasound measurements combining HC and FL in the second trimester can be used to estimate GA with reasonable accuracy. We recommend this tool for underserved populations but considerable efforts should be implemented to improve early initiation of antenatal care worldwide. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The development and evaluation of a community-based clinical diagnosis tool and treatment regimen for postpartum sepsis in Bangladesh and Pakistan.

BACKGROUND: Postpartum sepsis accounts for most maternal deaths between three and seven days postpartum, when most mothers, even those who deliver in facilities, are at home. Case fatality rates for untreated women are very high. Newborns of ill women have substantially higher infection risk. METHODS/DESIGN: The objectives of this study are to: (1) create, field-test and validate a tool for community health workers to improve diagnostic accuracy of suspected puerperal sepsis; (2) measure incidence and identify associated risk factors and; (3) describe etiologic agents responsible and antibacterial susceptibility patterns. This prospective cohort study builds on the Aetiology of Neonatal Infection in South Asia study in three sites: Sylhet, Bangladesh and Karachi and Matiari, Pakistan. Formative research determined local knowledge of symptoms and signs of postpartum sepsis, and a systematic literature review was conducted to design a diagnostic tool for community health workers to use during ten postpartum home visits. Suspected postpartum sepsis cases were referred to study physicians for independent assessment, which permitted validation of the tool. Clinical specimens, including urine, blood, and endometrial material, were collected for etiologic assessment and antibiotic sensitivity. All women with puerperal sepsis were given appropriate antibiotics. DISCUSSION: This is the first large population-based study to expand community-based surveillance for diagnoses, referral and treatment of newborn sepsis to include maternal postpartum sepsis. Study activities will lead to development and validation of a diagnostic tool for use by community health workers in resource-poor countries. Understanding the epidemiology and microbiology of postpartum sepsis will inform prevention and treatment strategies and improve understanding of linkages between maternal and neonatal infections.

Urban and rural comparison of vitamin D status in Pakistani pregnant women and neonates.

We undertook a cross-sectional study in rural Jehlum and urban Karachi to evaluate the prevalence of vitamin D deficiency in Pakistani pregnant women and neonates and to assess any association of serum 25(OH) vitamin D [25(OH)D] concentration with vitamin D binding protein (Gc) genotypes. Altogether, 390 women and 266 neonates were recruited from urban and rural sites, respectively. Serum 25(OH)D was measured by an immunoassay, while Gc genotypes were identified using polymerase chain reaction followed by restriction fragment length polymorphism or PCR-RFLP. One-way analysis of variance or ANOVA and linear regression were used for statistical analysis. In urban Karachi, 99.5% of women and 97.3% of neonates were vitamin D deficient (< 50 nmol/L), while 89% of women and 82% of neonates were deficient in rural Jehlum. Gc genotypes were not associated with serum 25(OH)D concentrations in both women and their neonates. We conclude that vitamin D deficiency is highly prevalent in Pakistani women and their neonates, and Gc genotypes are not associated with serum 25(OH)D concentrations.

Strategies to avert preventable mortality among mothers and children in the Eastern Mediterranean Region: new initiatives, new hope.

We conducted an assessment of maternal, newborn and child health and progress towards achieving Millennium Development Goals (MDG) 4 and 5 in the Eastern Mediterranean Region (EMR). We provide recommendations for scaling up and sustaining gains post-2015. Data were obtained from global data repositories. We constructed time trends from 1990 to 2013 and evaluated inequities across the Region. Under-5, neonatal and maternal mortality rates decreased 46%, 35%, and 50% respectively from 1990 to 2013. Pneumonia and diarrhoea accounted for 50% of all post-neonatal deaths; pregnancy- and delivery-related complications were the leading causes of neonatal and maternal deaths. Coverage of maternal, newborn and child health interventions is suboptimal, and poverty, food insecurity and conflict are pervasive across the Region. The EMR has made progress but is unlikely to attain MDG 4 and 5 targets. To sustain and further accelerate gains, the Region must reduce inequities and scale up implementation of recommendations made by the independent Expert Review Group.

The effectiveness of regionalization of perinatal care services--a systematic review.

BACKGROUND: Several reports recommend the implementation of perinatal regionalization for improvements in maternal and neonatal outcomes, while research evidence on the effectiveness of perinatal regionalization has been limited. The interventional studies have been assessed for robust evidence on the effectiveness of perinatal regionalization on improving maternal and neonatal health outcomes. METHODS: Bibliographic databases of Medline, EMbase, EconLit, HMIC have been searched using sensitive search terms for interventional studies that reported important patient or process outcomes. At least two authors assessed eligibility for inclusion and the risk of biases and extracted data from the included studies. As meta-analysis was not possible, a narrative analysis as well as a 'vote-counting' analysis has been conducted for important outcomes. RESULTS: After initial screenings 53 full text papers were retrieved. Eight studies were included in the review from the USA, Canada and France. Studies varied in their designs, and in the specifications of the intervention and setting. Only three interrupted time series studies had a low risk of bias, of which only one study reported significant reductions in neonatal and infant mortality. Studies of higher risk of bias were more likely to report improvements in outcomes. CONCLUSIONS: Implementing perinatal regionalization programs is correlated with improvements in perinatal outcomes, but it is not possible to establish a causal link. Despite several high profile policy statements, evidence of effect is weak. It is necessary to assess the effectiveness of perinatal regionalization using robust research designs in a more diverse range of countries.

International standards for early fetal size and pregnancy dating based on ultrasound measurement of crown-rump length in the first trimester of pregnancy.

OBJECTIVES: There are no international standards for relating fetal crown-rump length (CRL) to gestational age (GA), and most existing charts have considerable methodological limitations. The INTERGROWTH-21(st) Project aimed to produce the first international standards for early fetal size and ultrasound dating of pregnancy based on CRL measurement. METHODS: Urban areas in eight geographically diverse countries that met strict eligibility criteria were selected for the prospective, population-based recruitment, between 9 + 0 and 13 + 6 weeks' gestation, of healthy well-nourished women with singleton pregnancies at low risk of fetal growth impairment. GA was calculated on the basis of a certain last menstrual period, regular menstrual cycle and lack of hormonal medication or breastfeeding in the preceding 2 months. CRL was measured using strict protocols and quality-control measures. All women were followed up throughout pregnancy until delivery and hospital discharge. Cases of neonatal and fetal death, severe pregnancy complications and congenital abnormalities were excluded from the study. RESULTS: A total of 4607 women were enrolled in the Fetal Growth Longitudinal Study, one of the three main components of the INTERGROWTH-21(st) Project, of whom 4321 had a live singleton birth in the absence of severe maternal conditions or congenital abnormalities detected by ultrasound or at birth. The CRL was measured in 56 women at < 9 + 0 weeks' gestation; these were excluded, resulting in 4265 women who contributed data to the final analysis. The mean CRL and SD increased with GA almost linearly, and their relationship to GA is given by the following two equations (in which GA is in days and CRL in mm): mean CRL = -50.6562 + (0.815118 × GA) + (0.00535302 × GA(2) ); and SD of CRL = -2.21626 + (0.0984894 × GA). GA estimation is carried out according to the two equations: GA = 40.9041 + (3.21585 × CRL(0.5) ) + (0.348956 × CRL); and SD of GA = 2.39102 + (0.0193474 × CRL). CONCLUSIONS: We have produced international prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the first trimester that can be used throughout the world.

A cross sectional study of newborn care practices in Gilgit, Pakistan.

OBJECTIVE: The purpose of this article is to explore the traditional newborn-care beliefs and practices and to identify factors that affect newborn health, aiming to design an appropriate, culturally-sensitive and acceptable intervention to reduce neonatal morbidity and mortality. METHODS: A cross sectional study was conducted in the district of Gilgit in Pakistan. A structured questionnaire was administered to 708 mothers who gave birth to a live child in the past one year. Descriptive and inferential analysis was performed to identify socio-economic and health care factors associated with newborn care practices. RESULTS: Illiterate mothers were more likely to use harmful newborn care practices, while those seeking health care from private sector were less likely to use harmful newborn care practices. Ninety-four percent of the newborns were given a bath soon after birth, likelihood to be 2 times more amongst illiterate mothers. Cord application was a very common practice, mostly with matti (crashed apricot seed), and a majority of the mothers reported newborn massage generally with mustard oil. The administration of colostrum as the first feed was relatively common in the study area. Twenty-seven percent of mothers reported giving pre-lacteals; from which prominent feeds included salt water (44%) and cow's milk (26%). Initiation of breastfeeding within 1 hour after birth was (71%), while (29%) reported to breastfeed their newborn within 24 hours. Thirty-seven percent newborns were exclusively breastfed for six months. CONCLUSION: This study underscores the existence and predominance of risky practices in newborn care; that stresses the need for health education programs to ensure safety of the newborn.

A cross sectional survey of newborn care practices in rural Sindh, Pakistan: implications for research and policy.

INTRODUCTION: Of annual four million neonatal deaths, majority in the developing world, approximately three-quarters die within the first week of life. Pakistan has one of the highest newborn mortality rates. STUDY DESIGN: We conducted a cross sectional study to assess knowledge, attitudes and practices of women of reproductive age in rural Pakistan. RESULTS: Of 1490 mothers interviewed, prevalence of newborn care practices ranged between 32% (early bathing of newborn) and 69% (use of traditional cord applications). Uptake of antenatal care services was identified as a strong predictor of good newborn care after controlling for skilled birth attendance, socio-economic status, age of mother and sex of infant (OR = 1.26; 95% CI: 1.00-1.57). CONCLUSIONS: The association of uptake of antenatal care services with good newborn care highlights the necessity to improve coverage of services with the integration of counseling about newborn care in order to reduce the burden of neonatal morbidity and mortality.

A rapid questionnaire assessment of environmental exposures to pregnant women in the INTERGROWTH-21st Project.

Impaired fetal growth and preterm birth are the leading causes of neonatal and infant mortality worldwide and there is a growing scientific literature suggesting that environmental exposures during pregnancy may play a causal role in these outcomes. Our purpose was to assess the environmental exposure of the Fetal Growth Longitudinal Study (FGLS) participants in the multinational INTERGROWTH-21(st) Project. First, we developed a tool that could be used internationally to screen pregnant women for such exposures and administered it in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is a study of fetal growth among healthy pregnant women living in relatively affluent areas, at low risk of adverse pregnancy outcomes and environmental exposures. We confirmed that most women were not exposed to major environmental hazards that could affect pregnancy outcomes according to the protocol's entry criteria. However, the instrument was able to identify some women that reported various environmental concerns in their homes such as peeling paint, high residential density (>1 person per room), presence of rodents or cockroaches (hence the use of pesticides), noise pollution and safety concerns. This screening tool was therefore useful for the purposes of the project and can be used to ascertain environmental exposures in studies in which the primary aim is not focused on environmental exposures. The instrument can be used to identify subpopulations for more in-depth assessment, (e.g. environmental and biological laboratory markers) to pinpoint areas requiring education, intervention or policy change.