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Interventions during pregnancy to prevent preterm birth: an overview of Cochrane systematic reviews.
Medley, N, Vogel, JP, Care, A, Alfirevic, Z
The Cochrane database of systematic reviews. 2018;(11):CD012505
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Abstract
BACKGROUND Preterm birth (PTB) is a major factor contributing to global rates of neonatal death and to longer-term health problems for surviving infants. Both the World Health Organization and the United Nations consider prevention of PTB as central to improving health care for pregnant women and newborn babies. Current preventative clinical strategies show varied efficacy in different populations of pregnant women, frustrating women and health providers alike, while researchers call for better understanding of the underlying mechanisms that lead to PTB. OBJECTIVES We aimed to summarise all evidence for interventions relevant to the prevention of PTB as reported in Cochrane systematic reviews (SRs). We intended to highlight promising interventions and to identify SRs in need of an update. METHODS We searched the Cochrane Database of Systematic Reviews (2 November 2017) with key words to capture any Cochrane SR that prespecified or reported a PTB outcome. Inclusion criteria focused on pregnant women without signs of preterm labour or ruptured amniotic membranes. We included reviews of interventions for pregnant women irrespective of their risk status. We followed standard Cochrane methods.We applied GRADE criteria to evaluate the quality of SR evidence. We assigned graphic icons to classify the effectiveness of interventions as: clear evidence of benefit; clear evidence of harm; clear evidence of no effect or equivalence; possible benefit; possible harm; or unknown benefit or harm. We defined clear evidence of benefit and clear evidence of harm to be GRADE moderate- or high-quality evidence with a confidence interval (CI) that does not cross the line of no effect. Clear evidence of no effect or equivalence is GRADE moderate- or high-quality evidence with a narrow CI crossing the line of no effect. Possible benefit and possible harm refer to GRADE low-quality evidence with a clear effect (CI does not cross the line of no effect) or GRADE moderate- or high-quality evidence with a wide CI. Unknown harm or benefit refers to GRADE low- or very low-quality evidence with a wide CI. MAIN RESULTS We included 83 SRs; 70 had outcome data. Below we highlight key results from a subset of 36 SRs of interventions intended to prevent PTB. OUTCOME preterm birthClear evidence of benefitFour SRs reported clear evidence of benefit to prevent specific populations of pregnant women from giving birth early, including midwife-led continuity models of care versus other models of care for all women; screening for lower genital tract infections for pregnant women less than 37 weeks' gestation and without signs of labour, bleeding or infection; and zinc supplementation for pregnant women without systemic illness. Cervical cerclage showed clear benefit for women with singleton pregnancy and high risk of PTB only.Clear evidence of harmNo included SR reported clear evidence of harm.No effect or equivalenceFor pregnant women at high risk of PTB, bedrest for women with singleton pregnancy and antibiotic prophylaxis during the second and third trimester were of no effect or equivalent to a comparator.Possible benefitFour SRs found possible benefit in: group antenatal care for all pregnant women; antibiotics for pregnant women with asymptomatic bacteriuria; pharmacological interventions for smoking cessation for pregnant women who smoke; and vitamin D supplements alone for women without pre-existing conditions such as diabetes.Possible harmOne SR reported possible harm (increased risk of PTB) with intramuscular progesterone, but this finding is only relevant to women with multiple pregnancy and high risk of PTB. Another review found possible harm with vitamin D, calcium and other minerals for pregnant women without pre-existing conditions. OUTCOME perinatal deathClear evidence of benefitTwo SRs reported clear evidence of benefit to reduce pregnant women's risk of perinatal death: midwife-led continuity models of care for all pregnant women; and fetal and umbilical Doppler for high-risk pregnant women.Clear evidence of harmNo included SR reported clear evidence of harm.No effect or equivalenceFor pregnant women at high risk of PTB, antibiotic prophylaxis during the second and third trimester was of no effect or equivalent to a comparator.Possible benefitOne SR reported possible benefit with cervical cerclage for women with singleton pregnancy and high risk of PTB.Possible harmOne SR reported possible harm associated with a reduced schedule of antenatal visits for pregnant women at low risk of pregnancy complications; importantly, these women already received antenatal care in settings with limited resources. OUTCOMES preterm birth and perinatal deathUnknown benefit or harmFor pregnant women at high risk of PTB for any reason including multiple pregnancy, home uterine monitoring was of unknown benefit or harm. For pregnant women at high risk due to multiple pregnancy: bedrest, prophylactic oral betamimetics, vaginal progesterone and cervical cerclage were all of unknown benefit or harm. AUTHORS' CONCLUSIONS Implications for practiceThe overview serves as a map and guide to all current evidence relevant to PTB prevention published in the Cochrane Library. Of 70 SRs with outcome data, we identified 36 reviews of interventions with the aim of preventing PTB. Just four of these SRs had evidence of clear benefit to women, with an additional four SRs reporting possible benefit. No SR reported clear harm, which is an important finding for women and health providers alike.The overview summarises no evidence for the clinically important interventions of cervical pessary, cervical length assessment and vaginal progesterone because these Cochrane Reviews were not current. These are active areas for PTB research.The graphic icons we assigned to SR effect estimates do not constitute clinical guidance or an endorsement of specific interventions for pregnant women. It remains critical for pregnant women and their healthcare providers to carefully consider whether specific strategies to prevent PTB will be of benefit for individual women, or for specific populations of women.Implications for researchFormal consensus work is needed to establish standard language for overviews of reviews and to define the limits of their interpretation.Clinicians, researchers and funders must address the lack of evidence for interventions relevant to women at high risk of PTB due to multiple pregnancy.
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Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone in prevention of preterm birth in women with a short cervix.
Pustotina, O
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(14):1830-1838
Abstract
OBJECTIVE To compare the efficacy of dydrogesterone, 17-OH progesterone (17OHP) and oral or vaginal micronized progesterone with cerclage for the prevention of preterm birth in women with a short cervix. METHODS The study included 95 women with singleton gestation and cervical length (CL) ≤ 25 mm. Among these, 35 women were asymptomatic at 15-24 weeks and 60 had symptoms of threatened late miscarriage (LM) or preterm delivery (PD) at 15-32 weeks. Patients were randomized to receive dydrogesterone, 17OHP or oral/vaginal micronized progesterone; after one week of therapy 15 women underwent cerclage. RESULTS Efficacy of vaginal progesterone (VP) for the prevention of preterm birth reached 94.1%. In asymptomatic women pregnancy outcomes were comparable to cerclage. In women with threatened LM/PD, combination therapy with VP, indomethacin and treatment of bacterial vaginosis (BV) with the subsequent use VP until 36 weeks together with CL monitoring significantly decreased the rate of preterm birth (RR 0.01; 0.0001-0.24) and low birth weight (LBW) (RR 0.04; 0.01-0.96). CL increase during the first week of treatment with a subsequent plateau phase indicated treatment efficacy. Dydrogesterone, 17OHP, and micronized oral progesterone (OP) were associated with PD in 91.7% of women. CONCLUSIONS Combination management strategy including VP significantly benefits pregnancy outcomes in women with a short cervix compared with cerclage. Dydrogesterone, 17OHP, and OP were not found to be efficacious.
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Yogurt consumption during pregnancy and preterm delivery in Mexican women: A prospective analysis of interaction with maternal overweight status.
Kriss, JL, Ramakrishnan, U, Beauregard, JL, Phadke, VK, Stein, AD, Rivera, JA, Omer, SB
Maternal & child nutrition. 2018;(2):e12522
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Abstract
Preterm delivery is an important cause of perinatal morbidity and mortality, often precipitated by maternal infection or inflammation. Probiotic-containing foods, such as yogurt, may reduce systemic inflammatory responses. We sought to evaluate whether yogurt consumption during pregnancy is associated with decreased preterm delivery. We studied 965 women enrolled at midpregnancy into a clinical trial of prenatal docosahexaenoic acid supplementation in Mexico. Yogurt consumption during the previous 3 months was categorized as ≥5, 2-4, or <2 cups per week. Preterm delivery was defined as delivery of a live infant before 37 weeks gestation. We used logistic regression to evaluate the association between prenatal yogurt consumption and preterm delivery and examined interaction with maternal overweight status. In this population, 25.4%, 34.2%, and 40.4% of women reported consuming ≥5, 2-4, and <2 cups of yogurt per week, respectively. The prevalence of preterm delivery was 8.9%. Differences in preterm delivery were non-significant across maternal yogurt consumption groups; compared with women reporting <2 cups of yogurt per week, those reporting 2-4 cups of yogurt per week had adjusted odds ratio (aOR) for preterm delivery of 0.81 (95% confidence interval, CI [.46, 1.41]), and those reporting ≥5 cups of yogurt per week had aOR of 0.94 (95% CI [.51, 1.72]). The association between maternal yogurt consumption and preterm delivery differed significantly for nonoverweight women compared with overweight women (p for interaction = .01). Compared with nonoverweight women who consumed <2 cups of yogurt per week, nonoverweight women who consumed ≥5 cups of yogurt per week had aOR for preterm delivery of 0.24 (95% CI [.07, .89]). Among overweight women, there was no significant association. In this population, there was no overall association between prenatal yogurt consumption and preterm delivery. However, there was significant interaction with maternal overweight status; among nonoverweight women, higher prenatal yogurt consumption was associated with reduced preterm delivery.
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Adverse Maternal and Neonatal Outcomes in Indicated Compared with Spontaneous Preterm Birth in Healthy Nulliparas: A Secondary Analysis of a Randomized Trial.
Tita, AT, Doherty, L, Roberts, JM, Myatt, L, Leveno, KJ, Varner, MW, Wapner, RJ, Thorp, JM, Mercer, BM, Peaceman, A, et al
American journal of perinatology. 2018;(7):624-631
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OBJECTIVE To compare the risks of adverse maternal and neonatal outcomes associated with spontaneous (SPTB) versus indicated preterm births (IPTB). METHODS A secondary analysis of a multicenter trial of vitamin C and E supplementation in healthy low-risk nulliparous women. Outcomes were compared between women with SPTB (due to spontaneous membrane rupture or labor) and those with IPTB (due to medical or obstetric complications). A primary maternal composite outcome included: death, pulmonary edema, blood transfusion, adult respiratory distress syndrome (RDS), cerebrovascular accident, acute tubular necrosis, disseminated intravascular coagulopathy, or liver rupture. A neonatal composite outcome included: neonatal death, RDS, grades III or IV intraventricular hemorrhage (IVH), sepsis, necrotizing enterocolitis (NEC), or retinopathy of prematurity. RESULTS Of 9,867 women, 10.4% (N = 1,038) were PTBs; 32.7% (n = 340) IPTBs and 67.3% (n = 698) SPTBs. Compared with SPTB, the composite maternal outcome was more frequent in IPTB-4.4% versus 0.9% (adjusted odds ratio [aOR], 4.0; 95% confidence interval [CI], 1.4-11.8), as were blood transfusion and prolonged hospital stay (3.2 and 3.7 times, respectively). The frequency of composite neonatal outcome was higher in IPTBs (aOR, 1.8; 95% CI, 1.1-3.0), as were RDS (1.7 times), small for gestational age (SGA) < 5th percentile (7.9 times), and neonatal intensive care unit (NICU) admission (1.8 times). CONCLUSION Adverse maternal and neonatal outcomes were significantly more likely with IPTB than with SPTB.
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Comparison of Interfaces for the Delivery of Noninvasive Respiratory Support to Low Birthweight Infants.
Drescher, GS, Hughes, CW
Respiratory care. 2018;(10):1197-1206
Abstract
BACKGROUND Bench and clinical data indicate that techniques for applying noninvasive respiratory support may vary in terms of effectiveness, application, and tolerability. We implemented a new nasal interface and flow-generation system for the delivery of noninvasive respiratory support (NRS) to replace previously used systems. Our goal was to determine whether there were significant differences in clinically relevant outcomes between our new method and conventional systems. METHODS We conducted a prospective observational study of preterm infants requiring noninvasive respiratory support during our initial implementation of a new nasal interface (RAM), and compared these data with a historic control group. Demographic, baseline, and clinical outcome data were collected. Clinical outcomes and comorbid conditions were compared by using the chi-square test for categorical information and the Student t test or Wilcoxon rank-sum test for quantitative data, depending on normality testing when using the Shapiro-Wilk test. Uni- and multivariate logistic regression were conducted to determine predictive factors for the development of bronchopulmonary dysplasia. RESULTS There were no significant group differences in important comorbid conditions, invasive mechanical ventilation days (P = .16), or NRS failure within the first 7 d after birth (P = .10). Although there were no significant differences in the use of CPAP or noninvasive ventilation, settings with were significantly higher (P < .001) in the RAM group. There were more incidences of retinopathy of prematurity (P = .02) post RAM implementation, and the time to first reintubation was significantly shorter in the RAM group (P = .044). However, there were significant reductions post RAM in total days on any respiratory support (P = .009), total NRS days (P = .02), and supplemental O2 duration (P = .02). There was a trend toward reductions in bronchopulmonary dysplasia rates (P = .053), and the incidence of device-related tissue breakdown was significantly reduced (P < .001) post RAM. Multivariate logistic regression results showed the type of system (odds ratio [OR] 0.19, 95% CI 0.04-0.87; P = .032) and total invasive ventilation time (OR 0.94, 95% CI 0.89-0.99; P = .02) were predictors for the development of bronchopulmonary dysplasia. CONCLUSIONS The ability to apply continuous distending pressure through consistent application of NRS with the RAM cannula attached to a ventilator may improve clinical outcomes, including the duration of respiratory support and pressure-ulcer rates. The influence of this system on the development of bronchopulmonary dysplasia and the significantly increased retinopathy of prematurity requires further study.
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Allostatic load, a measure of chronic physiological stress, is associated with pregnancy outcomes, but not fertility, among women with unexplained infertility.
Barrett, ES, Vitek, W, Mbowe, O, Thurston, SW, Legro, RS, Alvero, R, Baker, V, Bates, GW, Casson, P, Coutifaris, C, et al
Human reproduction (Oxford, England). 2018;(9):1757-1766
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Abstract
STUDY QUESTION Among infertile women undergoing ovarian stimulation, is allostatic load (AL), a measure of chronic physiological stress, associated with subsequent fertility and pregnancy outcomes? SUMMARY ANSWER AL at baseline was not associated with conception, spontaneous abortion or live birth, however, it was significantly associated with increased odds of pre-eclampsia and preterm birth among women who had a live birth in the study. WHAT IS KNOWN ALREADY Several studies have linked AL during pregnancy to adverse outcomes including preterm birth and pre-eclampsia, hypothesizing that it may contribute to well-documented disparities in pregnancy and birth outcomes. However, AL biomarkers change over the course of pregnancy, raising questions as to whether gestational AL assessment is a valid measure of cumulative physiologic stress starting long before pregnancy. To better understand how AL may impact reproductive outcomes, AL measurement in the non-pregnant state (i.e. prior to conception) is needed. STUDY DESIGN, SIZE, DURATION A secondary data analysis based on data from 836 women who participated in Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS), a multi-center, randomized clinical trial of ovarian stimulation conducted from 2011 to 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovulatory women with unexplained infertility (ages 18-40) were enrolled and at baseline, biological and anthropometric measures were collected. AL scores were calculated as a composite of the following baseline variables determined a priori: BMI, waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, dehydroepiandrosterone sulfate, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, C-reactive protein and HOMA score. Participants received ovarian stimulation for up to four cycles and if they conceived, were followed throughout pregnancy. We fit multi-variable logistic regression models examining AL (one-tailed and two-tailed) in relation to the following reproductive outcomes: conception, spontaneous abortion, live birth, pre-eclampsia, preterm birth and low birthweight. MAIN RESULTS AND THE ROLE OF CHANCE Adjusting for covariates, a unit increase in two-tailed AL score was associated with 62% increased odds of pre-eclampsia (OR: 1.62, 95% CI: 1.14, 2.38) 44% increased odds of preterm birth (OR: 1.44, 95% CI: 1.02, 2.08), and 39% increased odds of low birthweight (OR: 1.39, 95% CI: 0.99, 1.97). The relationship between AL and preterm birth was mediated by pre-eclampsia (P = 0.0003). In one-tailed AL analyses, associations were similar, but slightly attenuated. AL was not associated with fertility outcomes (conception, spontaneous abortion, live birth). LIMITATIONS, REASONS FOR CAUTION Results may not be generalizable to fertile women who conceive naturally or women with other types of infertility. Comparisons to previous, related work are difficult because variables included in AL composite measures vary across studies. AL may be indicative of overall poor health, rather than being specific to chronic physiological stress. WIDER IMPLICATIONS OF THE FINDINGS Our results suggest that chronic physiological stress may not impact success of ovarian stimulation, however, they confirm and extend previous work suggesting that AL is associated with adverse pregnancy outcomes. Physiological dysregulation due to chronic stress has been proposed as a possible mechanism underlying disparities in birth outcomes, which are currently poorly understood. Assessing biomarkers of physiological dysregulation pre-conception or in early pregnancy, may help to identify women at risk of adverse pregnancy outcomes, particularly pre-eclampsia. STUDY FUNDING/COMPETING INTEREST(S): Support for AMIGOS was provided by: U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936 and U10HD055925. Support for the current analysis was provided by T32ES007271, R25HD075737, P30ES001247 and P30ES005022. This research was made possible by funding by American Recovery and Reinvestment Act. The content is solely the responsibility of the authors and does not necessarily represent the official views of NICHD, NIEHS or NIH. E.B., W.V., O.M., R.A., M.R., V.B., G.W.B., C.C., E.E., S.K., R.U., P.C, H.Z., N.S. and S.T. have nothing to disclose. R.L. reported serving as a consultant to Abbvie, Bayer, Kindex, Odega, Millendo and Fractyl and serving as a site investigator and receiving grants from Ferring. K.H. reported receiving grants from Roche Diagnostics and Ferring. R.R. reported a grant from AbbVie. M.D. reported being on the Board of Directors of and a stockholder in Advanced Reproductive Care. TRIAL REGISTRATION NUMBER Clinical Trials.gov number: NCT01044862.
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[DENTAL CARE DURING PREGNANCY].
Rabinerson, D, Krispin, E, Gabbay-Benziv, R
Harefuah. 2018;(5):330-334
Abstract
Pregnancy is a period, in which, and due to hormonal changes, the prevalence of periodontal diseases rises. The causing organisms for these diseases may migrate to the uterus and cause premature delivery. The diet during pregnancy may also have a deleterious effect on the oral and dental health of the parturient woman, as well as to the teeth of her child. Some unique dietary, as well as pathological conditions, which may appear in pregnant women are known. These are referred to as pica and epulis. Physicians involved in taking care of pregnant women, such as dentists, obstetricians and family physicians, are normally reluctant to refer, or to perform dental care on a pregnant patient. The present review of the current literature suggests that there is no basis for this avoidance. This is because dental care has been found safe for both mother and fetus during the whole period of pregnancy. Furthermore, dental care is even recommended, if not mandatory, because it has been shown that such treatment may prevent early delivery and possible future damage to the newborn's teeth. Considering the lack of knowledge among those who are responsible for the welfare of both the mother and the fetus during pregnancy, we suggest a publication of an official recommendations paper for dental care during pregnancy, which will be issued by the relevant professional medical societies in Israel.
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Outcome of extremely preterm infants after iatrogenic or spontaneous birth.
Fritz, T, Källén, K, Maršál, K, Jacobsson, B
Acta obstetricia et gynecologica Scandinavica. 2018;(11):1388-1395
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Abstract
INTRODUCTION The risks of preterm birth are known. We investigated the perinatal and infant mortality and morbidity after iatrogenic or spontaneous onset of extremely preterm birth. MATERIAL AND METHODS The present study used data from the population-based EXPRESS study comprising all infants delivered before 27+0 gestational weeks in Sweden between 2004 and 2007. All fetuses alive at admission and with known mode of onset of delivery were included (682 live-born infants; 65 intrapartum deaths). Four multivariate regression models were applied with adjustments for gestational age, fetal gender, multiple pregnancy, and birthweight. RESULTS After adjustment for gestational age, no significant differences were found between iatrogenic and spontaneous onsets of birth regarding intrapartum death, early neonatal death (0-6 d), or death within 364 days. In the group with iatrogenic onset of delivery, there was an increased risk for severe morbidity (odds ratio [OR] 1.86, 95% confidence interval [95% CI] 1.15-3.02), severe bronchopulmonary dysplasia (OR 1.90, 95% CI 1.10-3.26), and retinopathy of prematurity (OR 1.99, 95% CI 1.21-3.27) after adjustment for gestational age, fetal gender, and multiple pregnancy. After additional adjustment for weight z-scores at 36 gestational weeks, the associations were not significant. Within the group with spontaneous onset of delivery, fetuses with preterm prelabor rupture of membranes had increased mortality risk. CONCLUSIONS No evidence was found for mode of onset of delivery (iatrogenic vs spontaneous) having an impact on neonatal or infant mortality or morbidity in extremely preterm infants. Instead, gestational age and growth deviation at birth seem to be associated with the outcome.
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Impact of prematurity for pancreatic islet and beta-cell development.
Bloomfield, FH
The Journal of endocrinology. 2018;(3):R161-R171
Abstract
As increasing numbers of babies born preterm survive into adulthood, it is becoming clear that, in addition to the well-described risks of neurodevelopmental sequelae, there also are increased risks for non-communicable diseases, including diabetes. Epidemiological studies indicate that risks are increased even for birth at late preterm and early term gestations and for both type 1 and type 2 diabetes. Thus, factors related to preterm birth likely affect development of the fetal and neonatal beta-cell in addition to effects on peripheral insulin sensitivity. These factors could operate prior to preterm birth and be related to the underlying cause of preterm birth, to the event of being born preterm itself, to the postnatal care of the preterm neonate or to a combination of these exposures. Experimental evidence indicates that factors may be operating during all these critical periods to contribute to altered development of beta-cell mass in those born preterm. Greater understanding of how these factors impact upon development of the pancreas may lead to interventions or management approaches that mitigate the increased risk of later diabetes.
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The Late Preterm: A Population at Risk.
Williams, JE, Pugh, Y
Critical care nursing clinics of North America. 2018;(4):431-443
Abstract
Late preterm infants (LPIs) are born between 34 0/7 and 36 6/7 weeks' gestation and account for 72% of all preterm births in the United States. Born as much as 6 weeks early, the LPI misses the critical growth and development specific to the third trimester. The loss of this critical period leaves the LPI physiologically and metabolically immature and prone to various morbidities. Common morbidities include respiratory complications, feeding difficulty, hypoglycemia, temperature instability, hyperbilirubinemia, and neurodevelopmental delays.