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.

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.

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.

Quality control of ultrasound for fetal biometry: results from the INTERGROWTH-21st Project.

OBJECTIVE: To assess a comprehensive package of ultrasound quality control in the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project, a large multicenter study of fetal growth. METHODS: Quality control (QC) measures were performed for 20 313 ultrasound scan images obtained prospectively from 4321 fetuses at 14-41 weeks' gestation in eight geographical locations. At the time of each ultrasound examination, three fetal biometric variables (head circumference (HC), abdominal circumference (AC) and femur length (FL)) were measured in triplicate on separately generated images. All measurements were taken in a blinded fashion. QC had two elements: (1) qualitative QC: visual assessment by sonographers at each study site of their images based on specific criteria, with 10% of images being re-assessed at the Oxford-based Ultrasound Quality Unit (compared using an adjusted kappa statistic); and (2) quantitative QC: assessment of measurement data by comparing the first, second and third measurements (intraobserver variability), remeasurement of caliper replacement in 10% (interobserver variability), both by Bland-Altman plots and plotting frequency histograms of the SD of triplicate measurements and assessing how many were above or below 2 SD of the expected distribution. The system allowed the sonographers' performances to be monitored regularly. RESULTS: A high level of agreement between self- and external scoring was demonstrated for all measurements (κ = 0.99 (95% CI, 0.98-0.99) for HC, 0.98 (95% CI, 0.97-0.99) for AC and 0.96 (95% CI, 0.95-0.98) for FL). Intraobserver 95% limits of agreement (LoA) of ultrasound measures for HC, AC and FL were ± 3.3%, ± 5.6% and ± 6.2%, respectively; the corresponding values for interobserver LoA were ± 4.4%, ± 6.0% and ± 5.6%. The SD distribution of triplicate measurements for all biometric variables showed excessive variability for three of 31 sonographers, allowing prompt identification and retraining. CONCLUSIONS: Qualitative and quantitative QC monitoring was feasible and highly reproducible in a large multicenter research study, which facilitated the production of high-quality ultrasound images. We recommend that the QC system we developed is implemented in future research studies and clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

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.

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.

Implementation of the INTERGROWTH-21st Project in India.

The South Asian site in the INTERGROWTH-21(st) Project was the city of Nagpur, in Maharashtra State, India, with approximately 4500 births per year among the target population with middle to high socio-economic status. These deliveries are mainly concentrated in 20 small private hospitals, most of which are in the city centre. The sample for the Newborn Cross-Sectional Study (NCSS) was drawn from ten of these hospitals, covering 76% of the target low-risk pregnant population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from the largest of these institutions, Ketkar Hospital, as well as several ancillary antenatal care clinics. Special activities to encourage participation and raise awareness of the study at this site included translating patient information leaflets into local languages and securing local media interest. Among the unique challenges of the Indian site was the coordination of the large number of hospitals involved in NCSS, a task that required careful planning and organisation by the field teams.

The objectives, design and implementation of the INTERGROWTH-21st Project.

INTERGROWTH-21(st) is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care.

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.

Influence of drying of biosludge on organochlorine compounds from pulp and paper industry.

Pulp and paper industry is one of the major sources of man-made generation of organochlorine compounds. During biological treatment of wastewater, part of organochlorine compounds is discharged with treated effluent and part is retained on biomass and disposed of as waste activated sludge. Due to presence of these compounds, the disposal of biosludge from pulp and paper industry has become an issue. The estimation of adsorbable organic halogen (AOX) compounds after drying and grinding resulted in 49% lower concentration of AOX due to stripping of purgeable compounds. These purgeable compounds are not released at 60 degrees C in aqueous medium during estimation of purgeable organic halogen (POX) compounds. Dispersion of sludge by sonication overcomes the loss of POX compounds and results in higher concentration ofAOX compounds. The drying of biosludge samples at 45, 100 degrees C and in presence of sun light resulted in 20.1, 49.0 and 29.6% removal of purgeable AOX compounds, respectively. The lab scale sorption study using dichloromethane (as volatile organochlorine compound) reveal that biosludge from pulp and paper industry is a good adsorbent of volatile organochlorine compounds and results in poor release of these compounds during estimation of POX compounds.

World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries.

OBJECTIVE: To determine if vitamin C and E supplementation in high-risk pregnant women with low nutritional status reduces pre-eclampsia. DESIGN: Multicentred, randomised, controlled, double-blinded trial. SETTING: Antenatal care clinics and Hospitals in four countries. POPULATION: Pregnant women between 14 and 22 weeks' gestation. METHOD: Randomised women received 1000 mg vitamin C and 400 iu of vitamin E or placebo daily until delivery. MAIN OUTCOME MEASURES: Pre-eclampsia, low birthweight, small for gestational age and perinatal death. RESULTS: Six hundred and eighty-seven women were randomised to the vitamin group and 678 to the placebo group. Groups had similar gestational ages (18.1; SD 2.4 weeks), socio-economic, clinical and demographical characteristics and blood pressure at trial entry. Risk factors for eligibility were similar, except for multiple pregnancies: placebo group (14.7%), vitamins group (11.8%). Previous pre-eclampsia, or its complications, was the most common risk factor at entry (vitamins 41.6%, placebo 41.3%). Treatment compliance was 87% in the two groups and loss to follow-up was low (vitamins 2.0%, placebo 1.3%). Supplementation was not associated with a reduction of pre-eclampsia (RR: 1.0; 95% CI: 0.9-1.3), eclampsia (RR: 1.5; 95% CI: 0.3-8.9), gestational hypertension (RR: 1.2; 95% CI: 0.9-1.7), nor any other maternal outcome. Low birthweight (RR: 0.9; 95% CI: 0.8-1.1), small for gestational age (RR: 0.9; 95% CI: 0.8-1.1) and perinatal deaths (RR: 0.8; 95% CI: 0.6-1.2) were also unaffected. CONCLUSION: Vitamins C and E at the doses used did not prevent pre-eclampsia in these high-risk women.

An international survey of practice variation in the use of antibiotic prophylaxis in cesarean section.

OBJECTIVE: To examine the use of antibiotic prophylaxis in cesarean section in different countries and in relation to a reference regimen. METHOD: Fifty consecutive cesarean sections performed in eight centers in five countries were surveyed. Data from each center were compared to a regimen recommended by the Cochrane Collaboration (one dose of ampicillin or cefazolin administered to all women shortly before the procedure or immediately after cord clamping) using logistic regression with adjustment for procedure type. RESULT: Prophylaxis was used widely, but only four centers administered prophylaxis to all women. Ampicillin and cefazolin were the principal antibiotics used, but broad-spectrum agents and multidrug regimens were also used commonly. Only two centers reliably administered the antibiotic at the appropriate time. The majority of women received only one dose of antibiotic in only three centers. CONCLUSION: The use of antibiotic prophylaxis in cesarean section was variable and often at odds with published recommendations.

Birthweight-specific neonatal mortality in developing countries and obstetric practices.

OBJECTIVES: To evaluate birthweight-specific neonatal mortality and perinatal interventions in major medical centers in developed and developing countries. METHODS: A survey was developed and electronically mailed to 13 medical centers participating in the Global Network for Perinatal and Reproductive Health (GNPRH). The ability of a center to provide requested data was assessed. The mortality rates and use of specific perinatal interventions in centers in developing countries were compared with developed countries. RESULTS: Nine centers in developing countries responded to the survey, and three centers in developed countries were used for comparison. Data collection was highly variable. Most developing country centers were able to provide data by birthweight but not by gestational age. The differences in mortality rates between developing and developed countries were more pronounced at lower gestational ages and birthweights. A difference was found in perinatal interventions between developing and developed countries. In the former, viability was generally considered 28 weeks, and the gestational age at which cesarean sections were usually performed for the sake of the fetus at preterm gestations varied from 26 to 37 weeks. Most centers did not routinely induce for pPROM; only five out of nine centers used antibiotics to prolong latency. Most centers used tocolysis beginning at 26-28 weeks through 32-37 weeks, and a variety of tocolytic agents were used. Most centers routinely used corticosteroids for preterm infants, and all centers employed repeat weekly steroid dosing if undelivered. CONCLUSIONS: Despite the fact that the GNPRH centers included in this study represent some of the best health care available in these countries, they lag far behind centers in developed countries in neonatal mortality rates and their use of various obstetric practices. Furthermore, incomplete and inconsistent data collection complicates the evaluation of the factors contributing to high neonatal mortality rates.

Serum lipids in cases of oral contraceptives.

PIP: In India, a study was undertaken on different serum lipids in women using oral contraceptive pills for more than three months. 40 women attending a family planning center who were of proven fertility, ages ranging from 15-40 years, parity 1-6 and had used oral contraceptive for at least 3 months were studied. The cases were divided into 3 groups according to duration of pill use which varies from 6 months-18 months. Estimation of total lipid and fractionate cholesterol, phospholipids and triglycerides were done by thin layer paper chromatogrpahy. There was an increase in serum triglyceride level of 32% which is in agreement with other work and the level increased gradually as the duration of therapy increased. A significant increase in total lipids above control values which were present during first 3 cycles of use increased further during subsequent use. Rise in total lipids and cholesterol is unexpected because if the pills used are strongly estrogenic then the cholesterol level should decrease. However it has been pointed out by several workers that when estrogen is combined with progestogen, the metabolic effects of estrogen are unpredictable. Mean serum cholesterol level showed no significant changes up to 6 cycles, but showed significant rise as compared to control levels from 6-12 cycles. The relationship of these changes to atherosclerosis is not yet established and such changes cannot be dismissed as harmless.^ieng

Drug utilization in indoor ANC patients of Govt Medical College Hospital, Nagpur.

Drug utilization in the indoor patients of ANC ward of Govt. Medical College Hospital, Nagpur was studied in 42 patients. The prescriptions of these patients were audited to find number of drugs per prescription; prescribing trends and category-wise drug consumption. In most of the prescriptions drugs were prescribed by generic names (68.53%), Dosage form was mentioned, Frequency given, but duration was not mentioned. Dose in recommended units was not mentioned in 69.93% of prescriptions. Even though prescription of drugs was found to be rational, prescription writing was far from desired. The enquiry reveals these findings.

Calcium supplementation and prevention of pregnancy induced hypertension.

In a randomized controlled trial 201 healthy nulliparous women were randomly allocated by means of a computer generated randomization list. From 20 weeks of gestation until delivery they received either 2 g of oral elemental calcium (n = 103) per day or an identical placebo (n = 98). Eleven women (5.47%) were lost to follow-up after randomization. The study groups were very similar at the time of randomization; with respect to several clinical and demographic variables. Treatment compliance was very similar in both groups as was determined by pill count. The rate of pregnancy induced hypertension was lower in the calcium group than in the placebo group 8.24%; vs 29.03%; (RR = 0.28; 95% CI 0.14-0.59). The incidence of gestational hypertension was 6.18% in the calcium group and 17.20% in the placebo group (RR = 0.28; 95% CI 0.08-0.80), and the incidence of preeclampsia was 2.06% in the calcium group and 11.82% in the placebo group (RR = 0.13; 95% CI 0.01-0.64). In conclusion calcium supplementation given in pregnancy to nulliparous women reduces the incidence of pregnancy induced hypertension.

Serum Zinc levels in pregnant women, under oral contraceptive therapy and in normal (ovulating) women.

PIP: Serum zinc levels were estimated by atomic absorption spectrophotometer in 15 women with normal menstrual cycles, in 15 women taking oral contraceptives (OCs), and in 25 women with normal pregnancies in the 3rd trimester. In normally menstruating women, a significant increase in serum zinc levels was observed at the time of ovulation; i.e., from 0.586 mcgm/ml-0.840 mcgm/ml. In women taking combined OCs (Orlest), zinc levels were lower and a midcycle peak was missing. The serum zinc levels were decreased during the 3rd trimester of pregnancy to 0.289 mcgm/ml.^ieng

Cervical dilatation for early abortion (new approach).

PIP: Cervical dilatation prior to suction evacuation was attempted in 230 women seeking medical termination of pregnancy from 8-14 weeks gestation. The Dilex-C was used for 170 women and laminaria tents were used in 60 cases. Only 1 tent of the same size was inserted and kept in the cervical canal for 16 (group A), 12 (group B), and 8 hours (group C). Mean dilatation achieved in the Dilex-C and laminaria tent factions in group A was 10.06 mm and 10.48 mm; in group B it was 10.44 mm and 11.05 mm; and in group C the figures were 10.01 mm and 10.00 mm. Clinical trials with the Dilex showed a high degree of patient acceptance without any obvious cervical injury. None of the patients evidenced any displacement, hour glass formation bending or breaking, or difficulty in removal. A follow-up study at the end of 1 month indicated that no cases evidenced any signs of pelvic, uterine, or cervical infection.^ieng