The overlap between miscarriage and extreme preterm birth in a limited-resource setting on the Thailand-Myanmar border: a population cohort study.
ABSTRACT: Background : No universal demarcation of gestational age distinguishes miscarriage and stillbirth or extreme preterm birth (exPTB). This study provides a synopsis of outcome between 22 to <28 weeks gestation from a low resource setting. Methods : A retrospective record review of a population on the Thailand-Myanmar border was conducted. Outcomes were classified as miscarriage, late expulsion of products between 22 to < 28 weeks gestation with evidence of non-viability (mostly ultrasound absent fetal heart beat) prior to 22 weeks; or exPTB (stillbirth/live born) between 22 to < 28 weeks gestation when the fetus was viable at ?22 weeks. Termination of pregnancy and gestational trophoblastic disease were excluded. Results : From 1995-2015, 80.9% (50,046/ 61,829) of registered women had a known pregnancy outcome, of whom 99.8% (49,931) had a known gestational age. Delivery between 22 to <28 weeks gestation included 0.9% (472/49,931) of pregnancies after removing 18 cases (3.8%) who met an exclusion criteria. Most pregnancies had an ultrasound: 72.5% (n=329/454); 43.6% (n=197) were classified as miscarriage and 56.4% (n=257) exPTB. Individual record review of miscarriages estimated that fetal death had occurred at a median of 16 weeks, despite late expulsion between 22 to <28 weeks. With available data (n=252, 5 missing) the proportion of stillbirth was 47.6% (n=120), congenital abnormality 10.5% (24/228, 29 missing) and neonatal death was 98.5% (128/131, 1 missing). Introduction of ultrasound was associated with a 2-times higher odds of classification of outcome as exPTB rather than miscarriage. Conclusion : In this low resource setting few (<1%) pregnancy outcomes occurred in the 22 to <28 weeks gestational window; four in ten were miscarriage (late expulsion) and neonatal mortality approached 100%. In the scale-up to preventable newborns deaths (at least initially) greater benefits will be obtained by focusing on the viable newborns of ? 28 weeks gestation.
Project description:Few studies have examined fetal, infant and maternal mortality and morbidity among pregnant women at very early gestation with an open cervix and prolapsed membranes. We carried out a study describing the outcomes of women hospitalized with prolapsed membranes at 22-28 weeks' gestation.We prospectively recruited women with singleton pregnancies admitted at 22-28 weeks' gestation to tertiary hospitals of the Canadian Perinatal Network between 2005 and 2009. Time-to-delivery, perinatal death, neonatal intensive care unit (NICU) admission, severe neonatal morbidity and severe maternal morbidity were compared between women admitted at 22-25 vs. 26-28 weeks gestation. Logistic regression was used to estimate adjusted odds ratios (AOR) and 95% confidence intervals.129 women at 22-25 weeks gestation and 65 women at 26-28 weeks gestation were admitted to hospital and the median time-to-delivery was 4 days in both groups. Stillbirth rates were 12.4% vs 4.6% among women admitted at earlier vs later gestation (AOR 2.8, 95% CI 0.5-14.8), while perinatal death rates were 38.0% vs 6.1% (AOR 14.1, 95% CI 3.5-59.0), respectively. There were no significant differences in NICU admission and severe morbidity among live-born infants; 89.4% and 82.3% died or were admitted to NICU, (P value 0.18), and 53.9% vs 44.0% of NICU infants had severe neonatal morbidity (P value 0.28). Antibiotics, tocolysis and cerclage did not have a significant effect on perinatal death. Maternal death or severe maternal morbidity occurred in 8.5% and 6.2% of women admitted at 22-25 vs 26-28 weeks (AOR 1.2, 95% CI 0.4-4.2).Perinatal mortality among women with prolapsed membranes at very early gestation is high, although significantly lower among those admitted at a relatively later gestational age. Rates of adverse maternal outcomes are also high. This information can be used to counsel women with prolapsed membranes at 22 to 28 weeks gestation.
Project description:OBJECTIVE:To estimate the risk of adverse perinatal outcomes among women with isolated fetal growth restriction from 17 to 22 weeks of gestation. METHODS:This was a retrospective cohort study of all singleton, nonanomalous pregnancies undergoing ultrasonography to assess fetal anatomy between 17 and 22 weeks of gestation at a single center from 2010 to 2014. After excluding patients with fetal structural malformations, chromosomal abnormalities, or identified infectious etiologies, we compared perinatal outcomes between pregnancies with and without fetal growth restriction, defined as estimated fetal weight less than the 10th percentile for gestational age. Our primary outcome was small for gestational age (SGA) at birth, defined as birth weight less than the 10th percentile. Secondary outcomes included preterm delivery at less than 37 and less than 28 weeks of gestation, preeclampsia, abruption, stillbirth, neonatal death, neonatal intensive care unit admission, intraventricular hemorrhage, need for respiratory support, and necrotizing enterocolitis. RESULTS:Of 12,783 eligible patients, 355 (2.8%) had early second-trimester fetal growth restriction. Risk factors for growth restriction were African American race and tobacco use. Early second-trimester growth restriction was associated with a more than fivefold increase in risk of SGA at birth (36.9% compared with 9.1%, adjusted odds ratio [OR] 5.5, 95% CI 4.3-7.0), stillbirth (2.5% compared with 0.4%, OR 6.2, 95% CI 2.7-12.8), and neonatal death (1.4% compared with 0.3%, OR 5.2, 95% CI 1.6-13.5). Rates of indicated preterm birth at less than 37 weeks of gestation (7.3% compared with 3.3%, OR 2.3, 95% CI 1.5-3.5) and less than 28 weeks of gestation (2.5% compared with 0.2%, OR 10.8, 95% CI 4.5-23.4), neonatal need for respiratory support (16.9% compared with 7.8%, adjusted OR 1.6, 95% CI 1.1-2.2), and necrotizing enterocolitis (1.4% compared with 0.2%, OR 7.7, 95% CI 2.3-20.9) were also significantly higher for those with growth restriction. Rates of preeclampsia, abruption, and other neonatal outcomes were not significantly different. CONCLUSION:Although fetal growth restriction in the early second trimester occurred in less than 3% of our cohort and most of those with isolated growth restriction did not have adverse outcomes, it is a strong risk factor for SGA, stillbirth, neonatal death, and indicated preterm birth.
Project description:BACKGROUND:The prevalence of early pregnancy loss through miscarriage and medically terminated pregnancy (MTP) is largely unknown due to lack of early registration of pregnancies in most regions, and especially in low- and middle-income countries. Understanding the rates of early pregnancy loss as well as the characteristics of pregnant women who experience miscarriage or MTP can assist in better planning of reproductive health needs of women. METHODS:A prospective, population-based study was conducted in Belagavi District, south India. Using an active surveillance system of women of childbearing age, all women were enrolled as soon as possible during pregnancy. We evaluated rates and risk factors of miscarriage and MTP between 6 and 20 weeks gestation as well as rates of stillbirth and neonatal death. A hypothetical cohort of 1000 women pregnant at 6 weeks was created to demonstrate the impact of miscarriage and MTP on pregnancy outcome. RESULTS:A total of 30,166 women enrolled from 2014 to 2017 were included in this analysis. The rate of miscarriage per 1000 ongoing pregnancies between 6 and 8 weeks was 115.3, between 8 and 12 weeks the miscarriage rate was 101.9 per 1000 ongoing pregnancies and between 12 and 20 weeks the miscarriage rate was 60.3 per 1000 ongoing pregnancies. For those periods, the MTP rate was 40.2, 45.4, and 48.3 per 1000 ongoing pregnancies respectively. The stillbirth rate was 26/1000 and the neonatal mortality rate was 24/1000. The majority of miscarriages (96.6%) were unattended and occurred at home. The majority of MTPs occurred in a hospital and with a physician in attendance (69.6%), while 20.7% of MTPs occurred outside a health facility. Women who experienced a miscarriage were older and had a higher level of education but were less likely to be anemic than those with an ongoing pregnancy at 20 weeks. Women with MTP were older, had a higher level of education, higher parity, and higher BMI, compared to those with an ongoing pregnancy, but these results were not consistent across gestational age periods. CONCLUSIONS:Of women with an ongoing pregnancy at 6 weeks, about 60% will have a living infant at 28 days of age. Two thirds of the losses will be spontaneous miscarriages and one third will be secondary to a MTP. High maternal age and education were the risk factors associated with miscarriage and MTP. TRIAL REGISTRATION:The trial is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475 .
Project description:Objective?This study aims to evaluate pregnancy outcomes in patients with spontaneous and iatrogenic chorioamniotic separation diagnosed by ultrasound after 17 weeks. Methods?This is a retrospective cohort study of women with a singleton pregnancy who were diagnosed with chorioamniotic separation (n?=?106) after 17 weeks' gestation from January 2000 to January 2013. Patients with chorioamniotic separation were compared with a group of patients who had obstetric ultrasounds without a diagnosis of chorioamniotic separation. Those without chorioamniotic separation were matched (1:1) on gestational age on the date of the ultrasound (?±?2 weeks) (n?=?106). The primary outcome was preterm delivery (< 37 weeks). Secondary outcomes included intrauterine growth restriction, stillbirth, and neonatal morbidity. Results?The rate of preterm delivery was significantly higher for those with chorioamniotic separation than for those without (57.5 vs. 17.1%, p?<?0.0001). There were no significant differences in the rate of aneuploidy, intrauterine growth restriction, stillbirth, or neonatal demise. The rate of stillbirth was significantly higher among those with chorioamniotic separation diagnosed before 24 weeks as compared with those diagnosed after 24 weeks (9.7 vs. 0%, p?=?0.03). Conclusions?Chorioamniotic separation is associated with preterm delivery. If diagnosed before 24 weeks, the rate of stillbirth is significantly higher.
Project description:<h4>Background</h4>Fetal growth restriction (FGR) due to placental insufficiency is a major risk factor for stillbirth. While small-for-gestational-age (SGA; weight <?10th centile) is a commonly used proxy for FGR, detection of FGR among appropriate-for-gestational-age (AGA; weight ??10th centile) fetuses remains an unmet need in clinical care. We aimed to determine whether reduced antenatal growth velocity from the time of routine mid-trimester ultrasound is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency among term AGA infants.<h4>Methods</h4>Three hundred and five women had biometry measurements recorded from their routine mid-trimester (20-week) ultrasound, at 28 and 36?weeks' gestation, and delivered an AGA infant. Mid-trimester, 28- and 36-week estimated fetal weight (EFW) and abdominal circumference (AC) centiles were calculated. The EFW and AC growth velocities between 20 and 28?weeks, and 20-36?weeks, were examined as predictors of four clinical indicators of placental insufficiency: (i) low 36-week cerebroplacental ratio (CPR; CPR <?5th centile reflects cerebral redistribution-a fetal adaptation to hypoxia), (ii) neonatal acidosis (umbilical artery pH <?7.15) after the hypoxic challenge of labour, (iii) low neonatal body fat percentage (BF%) reflecting reduced nutritional reserve and (iv) placental weight?<?10th centile.<h4>Results</h4>Declining 20-36-week fetal growth velocity was associated with all indicators of placental insufficiency. Each one centile reduction in EFW between 20 and 36?weeks increased the odds of cerebral redistribution by 2.5% (odds ratio (OR)?=?1.025, P?=?0.001), the odds of neonatal acidosis by 2.7% (OR?=?1.027, P?=?0.002) and the odds of a <?10th centile placenta by 3.0% (OR?=?1.030, P?<?0.0001). Each one centile reduction in AC between 20 and 36?weeks increased the odds of neonatal acidosis by 3.1% (OR?=?1.031, P?=?0.0005), the odds of low neonatal BF% by 2.8% (OR?=?1.028, P?=?0.04) and the odds of placenta <?10th centile by 2.1% (OR?=?1.021, P?=?0.0004). Falls in EFW or AC of >?30 centiles between 20 and 36?weeks were associated with two-threefold increased relative risks of these indicators of placental insufficiency, while low 20-28-week growth velocities were not.<h4>Conclusions</h4>Reduced growth velocity between 20 and 36?weeks among AGA fetuses is associated with antenatal, intrapartum and postnatal indicators of placental insufficiency. These fetuses potentially represent an important, under-recognised cohort at increased risk of stillbirth. Encouragingly, this novel fetal assessment would require only one additional ultrasound to current routine care, and adds to the potential benefits of routine 36-week ultrasound.
Project description:OBJECTIVE:To report maternal sleep practices in women who experienced a stillbirth compared with controls with ongoing live pregnancies at similar gestation. DESIGN:Prospective case-control study. SETTING:Forty-one maternity units in the United Kingdom. POPULATION:Women who had a stillbirth after ? 28 weeks' gestation (n = 291) and women with an ongoing pregnancy at the time of interview (n = 733). METHODS:Data were collected using an interviewer-administered questionnaire that included questions on maternal sleep practices before pregnancy, in the four weeks prior to, and on the night before the interview/stillbirth. MAIN OUTCOME MEASURES:Maternal sleep practices during pregnancy. RESULTS:In multivariable analysis, supine going-to-sleep position the night before stillbirth had a 2.3-fold increased risk of late stillbirth [adjusted Odds Ratio (aOR) 2.31, 95% CI 1.04-5.11] compared with the left side. In addition, women who had a stillbirth were more likely to report sleep duration less than 5.5 hours on the night before stillbirth (aOR 1.83, 95% CI 1.24-2.68), getting up to the toilet once or less (aOR 2.81, 95% CI 1.85-4.26), and a daytime nap every day (aOR 2.22, 95% CI 1.26-3.94). No interaction was detected between supine going-to-sleep position and a small-for-gestational-age infant, maternal body mass index, or gestational age. The population-attributable risk for supine going-to-sleep position was 3.7% (95% CI 0.5-9.2). CONCLUSIONS:This study confirms that supine going-to-sleep position is associated with late stillbirth. Further work is required to determine whether intervention(s) can decrease the frequency of supine going-to-sleep position and the incidence of late stillbirth. TWEETABLE ABSTRACT:Supine going-to-sleep position is associated with 2.3× increased risk of stillbirth after 28 weeks' gestation. PLAIN LANGUAGE SUMMARY:Stillbirth, the death of a baby before birth, is a tragedy for mothers and families. One approach to reduce stillbirths is to identify factors that are associated with stillbirth. There are few risk factors for stillbirth that can be easily changed, but this study is looking at identifying how mothers may be able to reduce their risk. In this study, we interviewed 291 women who had a stillbirth and 733 women who had a live-born baby from 41 maternity units throughout the UK. The mothers who had a stillbirth were interviewed as soon as practical after their baby died. Mothers who had a live birth were interviewed during their pregnancies at the same times in pregnancy as when the stillbirths occurred. We did not interview mothers who had twins or who had a baby with a major abnormality. Mothers who went to sleep on their back had at least twice the risk of stillbirth compared with mothers who went to sleep on their left-hand side. This study suggests that 3.7% of stillbirths after 28 weeks of pregnancy were linked with going to sleep lying on the back. This study also shows that the link between going-to-sleep position and late stillbirth was not affected by the duration of pregnancy after 28 weeks, the size of the baby, or the mother's weight. Women who got up to the toilet once or more at night had a reduced risk of stillbirth. This is the largest of four similar studies that have all shown the same link between the position in which a mother goes to sleep and stillbirth after 28 weeks of pregnancy. Further studies are needed to see whether women can easily change their sleep position in late pregnancy and whether changing the position a mother goes to sleep in reduces stillbirth.
Project description:BACKGROUND:We aimed to evaluate and improve the accuracy of the ultrasound scan in estimating gestational age in late pregnancy (ie, after 24 weeks' gestation) in low-income and middle-income countries (LMICs), where access to ultrasound in the first half of pregnancy is rare and where intrauterine growth restriction is prevalent. METHODS:This prospective, population-based, cohort study was done in three LMICs (Bangladesh, Pakistan, and Tanzania) participating in the WHO Alliance for Maternal and Newborn Health Improvement study. Women carrying a live singleton fetus dated by crown-rump length (CRL) measurements between 8+0-14+6 weeks of gestation, who were willing to return for two additional ultrasound scans, and who planned on delivering in the study area were enrolled in the study. Participants underwent ultrasonography at 24+0-29+6 weeks and at 30+0-36+6 weeks' gestation. Birthweights were measured within 72 h of birth, and the proportions of infants who had a small-for-gestational-age birthweight (ie, a birthweight <10% of the standard birthweight for the infant's gestational age and sex according to the INTERGROWTH-21st project newborn baby reference standards) and appropriate-for-gestational-age birthweights were ascertained. Estimation of gestational age by standard fetal biometry measurements in addition to transcerebellar diameter (TCD) measurements was compared with gold-standard CRL measurements by use of Bland-Altman plots to calculate the mean difference and 95% limits of agreement. Statistical modelling was done to develop new gestational age prediction formulas for third trimester ultrasonography in LMICs. FINDINGS:Between Feb 7, 2015, and Jan 9, 2017, 1947 women were enrolled in the study. 1387 pregnant women had an ultrasound scan at 24+0-29+6 weeks of gestation and 1403 had an ultrasound scan between 30+0-36+6 weeks of gestation. Of the 1379 unique infants whose birthweights were available, 981 (71·1%) infants were born with an appropriate-for-gestational-age birthweight and 398 (28·9%) infants were born with a small-for-gestational-age birthweight. The accuracy of late pregnancy ultrasound biometry using existing formulas to estimate gestational age in LMICs was similar to that in high-income settings. With standard dating formulas, late pregnancy ultrasound at 24+0-29+6 weeks' gestation was accurate to within approximately plus or minus 2 weeks of the gold-standard CRL measurement of gestational age, and late pregnancy ultrasound was accurate to within ±3 weeks of the CRL measurement at 30+0-36+6 weeks' gestation. In infants who were ultimately born small for gestational age, individual parameters systematically underestimated gestational age, apart from TCD, which showed minimal bias. By use of a novel parsimonious model formula that combined TCD with femur length, gestational age at the 24+0 -29+6-week ultrasound scan was estimated to within ±10·5 days of the CRL measurement and estimated to within ±15·1 days of the CRL measurement at the 30+0-36+6-week ultrasound scan. Similar results were observed in infants who were small-for-gestational-age. INTERPRETATION:Incorporation of TCD and the use of new formulas in late pregnancy ultrasound scans could improve the accuracy of gestational age estimation in both appropriate-for-gestational-age and small-for-gestational-age infants in LMICs. Given the high rates of small-for-gestational-age infants in LMICs, these results might be especially relevant. Validation of this new formula in other LMIC populations is needed to establish whether the accuracy of the late pregnancy ultrasound can be narrowed to within approximately 2 weeks. FUNDING:Bill & Melinda Gates Foundation.
Project description:OBJECTIVE:To examine the relationship between prospectively assessed maternal sleep position and subsequent adverse pregnancy outcomes. METHODS:This was a secondary analysis of a prospective observational multicenter cohort study of nulliparous women with singleton gestations who were enrolled between October 2010 and May 2014. Participants had three study visits that were not part of clinical care. They prospectively completed in-depth sleep questionnaires between 6 0/7 and 13 6/7 weeks of gestation and 22 0/7 and 29 6/7 weeks of gestation, the first and third study visits. A subset of women also underwent level 3 home sleep tests using the Embletta Gold device. The primary outcome was a composite of adverse pregnancy outcomes such as stillbirth, a small-for-gestational-age newborn, and gestational hypertensive disorders. RESULTS:A total of 8,706 (of 10,038) women had data from at least one sleep questionnaire and for pregnancy outcomes, and they comprised the population for this analysis. The primary outcome occurred in 1,903 pregnancies (22%). There was no association between reported non-left lateral or supine sleep during the last week of the first visit (adjusted odds ratio [aOR] 1.00 [95% CI 0.89-1.14]) or third visit (aOR 0.99 [95% CI 0.89-1.11] and the composite or any individual outcome, except for an apparent protective effect for stillbirth at the third visit (aOR 0.27 (95% CI 0.09-0.75). Women with objectively measured supine sleep position for at least 50% of the time were no more likely than those in the supine position 50% or less of the time to have the composite adverse outcome. CONCLUSIONS:Going to sleep in the supine or right lateral position, as self-reported before the development of pregnancy outcome and objectively assessed through 30 weeks of gestation, was not associated with an increased risk of stillbirth, a small-for-gestational-age newborn, or gestational hypertensive disorders.
Project description:BACKGROUND: Idiopathic recurrent miscarriage is defined as 3 consecutive pregnancy losses with no contributing features found on investigations. At present there are no treatments of proven efficacy for idiopathic recurrent miscarriage. Uterine natural killer (uNK) cells, the most predominant leucocyte in the endometrium are adjacent to foetal trophoblast cells and thought to be involved in implantation. The exact mechanisms of how uNK cells affect implantation are not clear but are probably through the regulation of angiogenesis. Multiple studies have shown an association between high density of uterine natural killer cells and recurrent miscarriage. We have shown that prednisolone reduces the number of uNK cells in the endometrium. The question remains as to whether reducing the number of uNK cells improves pregnancy outcome. METHODS: We propose a randomised, double-blind, placebo controlled trial of prednisolone with a pilot phase to assess feasibility of recruitment, integrity of trial procedures, and to generate data to base future power calculations. The primary aim is to investigate whether prednisolone therapy during the first trimester of pregnancy is able to improve live birth rates in patients with idiopathic recurrent miscarriage and raised uNK cells in the endometrium. Secondary outcomes include conception rate, karyotype of miscarriage, miscarriages (first and second trimester), stillbirths, pregnancy complications, gestational age at delivery, congenital abnormality and side effects of steroids. The trial has 2 stages: i) screening of non-pregnant women and ii) randomisation of the pregnant cohort. All patients who fit the inclusion criteria (<40 years old, > or =3 consecutive miscarriages with no cause found and no contraindications to prednisolone therapy) will be asked to consent to an endometrial biopsy in the mid-luteal phase to assess their levels of uNK cells. Women with high levels of uNK cells (> or =5%), will be randomised to either prednisolone or placebo when a pregnancy is confirmed. Follow-up includes 2 weekly ultrasound scans in the first trimester, an anomaly scan at 20 weeks gestation, growth scans at 28 and 34 weeks gestation and a postnatal follow-up at 6 weeks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN28090716.
Project description:BACKGROUND:Despite advances in healthcare, stillbirth rates remain relatively unchanged. We conducted a systematic review to quantify the risks of stillbirth and neonatal death at term (from 37 weeks gestation) according to gestational age. METHODS AND FINDINGS:We searched the major electronic databases Medline, Embase, and Google Scholar (January 1990-October 2018) without language restrictions. We included cohort studies on term pregnancies that provided estimates of stillbirths or neonatal deaths by gestation week. We estimated the additional weekly risk of stillbirth in term pregnancies that continued versus delivered at various gestational ages. We compared week-specific neonatal mortality rates by gestational age at delivery. We used mixed-effects logistic regression models with random intercepts, and computed risk ratios (RRs), odds ratios (ORs), and 95% confidence intervals (CIs). Thirteen studies (15 million pregnancies, 17,830 stillbirths) were included. All studies were from high-income countries. Four studies provided the risks of stillbirth in mothers of White and Black race, 2 in mothers of White and Asian race, 5 in mothers of White race only, and 2 in mothers of Black race only. The prospective risk of stillbirth increased with gestational age from 0.11 per 1,000 pregnancies at 37 weeks (95% CI 0.07 to 0.15) to 3.18 per 1,000 at 42 weeks (95% CI 1.84 to 4.35). Neonatal mortality increased when pregnancies continued beyond 41 weeks; the risk increased significantly for deliveries at 42 versus 41 weeks gestation (RR 1.87, 95% CI 1.07 to 2.86, p = 0.012). One additional stillbirth occurred for every 1,449 (95% CI 1,237 to 1,747) pregnancies that advanced from 40 to 41 weeks. Limitations include variations in the definition of low-risk pregnancy, the wide time span of the studies, the use of registry-based data, and potential confounders affecting the outcome. CONCLUSIONS:Our findings suggest there is a significant additional risk of stillbirth, with no corresponding reduction in neonatal mortality, when term pregnancies continue to 41 weeks compared to delivery at 40 weeks. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42015013785.