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The Cochrane Database of Systematic... Mar 2017Down's syndrome occurs when a person has three copies of chromosome 21 (or the specific area of chromosome 21 implicated in causing Down's syndrome) rather than two. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three copies of chromosome 21 (or the specific area of chromosome 21 implicated in causing Down's syndrome) rather than two. It is the commonest congenital cause of mental disability. Non-invasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal) and false negative screening tests (i.e. a fetus with Down's syndrome will be missed). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
To estimate and compare the accuracy of first and second trimester serum markers with and without first trimester ultrasound markers for the detection of Down's syndrome in the antenatal period, as combinations of markers.
SEARCH METHODS
We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), the Database of Abstracts of Reviews of Effectiveness (the Cochrane Library 25 August 2011), MEDION (25 August 2011), the Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), the National Research Register (Archived 2007), and Health Services Research Projects in Progress database (25 August 2011). We did not apply a diagnostic test search filter. We did forward citation searching in ISI citation indices, Google Scholar and PubMed 'related articles'. We also searched reference lists of retrieved articles SELECTION CRITERIA: Studies evaluating tests of combining first and second trimester maternal serum markers in women up to 24 weeks of gestation for Down's syndrome, with or without first trimester ultrasound markers, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
DATA COLLECTION AND ANALYSIS
Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
MAIN RESULTS
Twenty-two studies (reported in 25 publications) involving 228,615 pregnancies (including 1067 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high risk pregnancies. Ten studies made direct comparisons between tests. Thirty-two different test combinations were evaluated formed from combinations of eight different tests and maternal age; first trimester nuchal translucency (NT) and the serum markers AFP, uE3, total hCG, free βhCG, Inhibin A, PAPP-A and ADAM 12. We looked at tests combining first and second trimester markers with or without ultrasound as complete tests, and we also examined stepwise and contingent strategies.Meta-analysis of the six most frequently evaluated test combinations showed that a test strategy involving maternal age and a combination of first trimester NT and PAPP-A, and second trimester total hCG, uE3, AFP and Inhibin A significantly outperformed other test combinations that involved only one serum marker or NT in the first trimester, detecting about nine out of every 10 Down's syndrome pregnancies at a 5% false positive rate. However, the evidence was limited in terms of the number of studies evaluating this strategy, and we therefore cannot recommend one single screening strategy.
AUTHORS' CONCLUSIONS
Tests involving first trimester ultrasound with first and second trimester serum markers in combination with maternal age are significantly better than those without ultrasound, or those evaluating first trimester ultrasound in combination with second trimester serum markers, without first trimester serum markers. We cannot make recommendations about a specific strategy on the basis of the small number of studies available.
Topics: Biomarkers; Chorionic Gonadotropin; Down Syndrome; Estriol; False Positive Reactions; Female; Humans; Inhibins; Maternal Age; Nuchal Translucency Measurement; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy-Associated Plasma Protein-A; Sensitivity and Specificity; alpha-Fetoproteins
PubMed: 28295159
DOI: 10.1002/14651858.CD012599 -
ANZ Journal of Surgery Sep 2021Meckel's diverticulum (MD) is the most common congenital malformation in the gastrointestinal tract. Limited up-to-date evidence is available regarding MD in pregnancy....
INTRODUCTION
Meckel's diverticulum (MD) is the most common congenital malformation in the gastrointestinal tract. Limited up-to-date evidence is available regarding MD in pregnancy. We aim to review the available pertinent literature to help support clinical decision making and patient management in the future.
MATERIALS AND METHODS
The search term 'Meckel's diverticulum' was combined with 'pregnant' or 'pregnancy'. Database searches of EMBASE, Medline and PubMed were conducted. All papers published in English from 01/01/1990 to 01/01/2021 were included. Simple statistical analysis (t-test) was performed.
RESULTS
Twenty-seven cases were included. Average age = 26.9 years. Average gestation = 25.1 weeks. Occurrence: first trimester = 3.7%; second trimester = 48.1% and third trimester = 48.1%. Presenting symptoms: abdominal pain 88.9%; nausea/vomiting 59.3%; fever 18.5%; abdominal distension 18.5%; haematochezia 11.1%; constipation 11.1%; haematemesis 3.7%, diarrhoea 3.7% and asymptomatic 3.7%. Mean duration of preceding symptoms = 3.4 days. Diagnostic imaging modalities utilised: ultrasound = 40.7%; CT = 25.9%; MRI = 14.8%; abdominal X-ray = 11.1% and endoscopy = 7.4%. All cases required definite surgical management: laparotomy = 65.4%; laparoscopy = 15.4%; C-section = 19.2% and unreported = 3.8%. Main intra-operative findings: perforated MD = 40.7%; intussusception with MD as a lead point = 11.1%; bleeding MD = 11.1%, inflamed MD = 11.1%; small bowel obstruction = 11.1%; gangrenous MD = 3.7%; volvulus = 3.7% and unspecified = 7.4%. Mean length from ileocolic junction = 51.7 cm. Average length of stay was 7.1 days. T-test (p-value = 0.12) when comparing management strategy. Three maternal complications and two foetal mortalities.
CONCLUSION
MD and associated pathology are difficult to diagnose in the pregnant cohort. Current imaging demonstrates low diagnostic accuracy and a deviation away from recognised nuclear medicine investigations. Surgery appears the definitive management with both open and laparoscopic approaches utilised. Significant maternal morbidity and foetal mortality are associated with this condition.
Topics: Adult; Female; Humans; Intestinal Perforation; Intussusception; Laparoscopy; Laparotomy; Meckel Diverticulum; Pregnancy
PubMed: 34152674
DOI: 10.1111/ans.17014 -
Obstetrics and Gynecology Jul 2015To estimate the effectiveness of physical examination-indicated cerclage in the setting of second-trimester cervical dilatation by systematic review and meta-analysis of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the effectiveness of physical examination-indicated cerclage in the setting of second-trimester cervical dilatation by systematic review and meta-analysis of published studies.
DATA SOURCES
We searched MEDLINE, EMBASE, Scopus, ClinicalTrials.gov, Web of Science, and the Cochrane Library for studies published between 1966 and 2014 that evaluated cervical cerclage for the treatment of cervical insufficiency.
METHODS OF STUDY SELECTION
The search yielded 6,314 citations. We included cohort studies and randomized controlled trials comparing cerclage placement with expectant management of women with cervical dilatation between 14 and 27 weeks of gestation. Two investigators independently reviewed each citation for inclusion or exclusion and discordant decisions were arbitrated by a third reviewer. Summary estimates were reported as the mean difference and 95% confidence interval (CI) for continuous variables or relative risk and with 95% CI for dichotomous outcomes. Fixed- and random-effects meta-analysis was used, depending on heterogeneity.
TABULATION, INTEGRATION, AND RESULTS
Ten studies met inclusion criteria and were included in the final analysis. One was a randomized controlled trial, two were prospective cohort studies, and the remaining seven were retrospective cohort studies. Of the 757 women, 485 (64%) underwent physical examination-indicated cerclage placement and 272 (36%) were expectantly managed. Cerclage was associated with increased neonatal survival (71% compared with 43%; relative risk 1.65, 95% CI 1.19-2.28) and prolongation of pregnancy (mean difference 33.98 days, 95% CI 17.88-50.08).
CONCLUSION
Physical examination-indicated cerclage is associated with a significant increase in neonatal survival and prolongation of pregnancy of approximately 1 month when compared with no such cerclage. The strength of this conclusion is limited by the potential for bias in the included studies.
Topics: Abortion, Spontaneous; Cerclage, Cervical; Female; Humans; Physical Examination; Pregnancy; Pregnancy Trimester, Second; Premature Birth; Uterine Cervical Incompetence
PubMed: 26241265
DOI: 10.1097/AOG.0000000000000850 -
Acta Obstetricia Et Gynecologica... Jul 2023According to a precautionary principle, it is recommended that pregnant women and women trying to conceive abstain from alcohol consumption. In this dose-response... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
According to a precautionary principle, it is recommended that pregnant women and women trying to conceive abstain from alcohol consumption. In this dose-response meta-analysis, we aimed to examine the association between alcohol consumption and binge drinking and the risk of miscarriage in the first and second trimesters.
MATERIAL AND METHODS
The literature search was conducted in MEDLINE, Embase and the Cochrane Library in May 2022, without any language, geographic or time limitations. Cohort or case-control studies reporting dose-specific effects adjusting for maternal age and using separate risk assessments for first- and second-trimester miscarriages were included. Study quality was assessed using the Newcastle-Ottawa Scale. This study is registered with PROSPERO, registration number CRD42020221070.
RESULTS
A total of 2124 articles were identified. Five articles met the inclusion criteria. Adjusted data from 153 619 women were included in the first-trimester analysis and data from 458 154 women in the second-trimester analysis. In the first and second trimesters, the risk of miscarriage increased by 7% (odds ratio [OR] 1.07, 95% confidence interval [CI] 0.96-1.20) and 3% (OR 1.03, 95% CI 0.99-1.08) for each additional drink per week, respectively, but not to a statistically significant degree. One article regarding binge drinking and the risk of miscarriage was found, which revealed no association between the variables in either the first or second trimester (OR 0.84 [95% CI 0.62-1.14] and OR 1.04 [95% CI 0.78-1.38]).
CONCLUSIONS
This meta-analysis revealed no dose-dependent association between miscarriage risk and alcohol consumption, but further focused research is recommended. The research gap regarding miscarriage and binge drinking needs further investigation.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Pregnancy Trimester, Second; Binge Drinking; Alcohol Drinking; Maternal Age
PubMed: 37221907
DOI: 10.1111/aogs.14566 -
The Journal of Maternal-fetal &... Jul 2022Pre-eclampsia (PE) is a serious pregnancy status characterized by high blood pressure. Although visfatin is usually associated with PE. Observational studies evaluating... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Pre-eclampsia (PE) is a serious pregnancy status characterized by high blood pressure. Although visfatin is usually associated with PE. Observational studies evaluating the relationship between circulating visfatin and pre-eclampsia have reported inconsistent results. We conducted this systematic review and meta-analysis to summarize published data on the association between visfatin and pre-eclampsia.
METHODS
Electronic databases PubMed, ISI web of science, EMBASE, Scopus and the Cochrane library were comprehensively searched for selection of eligible studies until January 5, 2020. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. The assessment of study quality was performed using the e Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity. Random-effects meta-regression was conducted to assess the impact of potential confounders on the estimated effect sizes. The protocol for this study was registered in PROSPERO (No. CRD42018105861) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
RESULTS
Thirteen studies comprising a total of 536 subjects were included in this meta-analysis. We observed that the pre-eclampsia risk is associated with a statistically significant elevation of visfatin level [SMD (1.33 µg/l) (95% CI 0.37, 2.2) = .007]. No significant publication bias was observed in the meta-analysis. Subgroup and sensitivity analyses indicated that the pooled effects size were affected by systolic blood pressure [SMD (1.82 µg/l) 95% CI (0.94, 2.7), < .05], gestational age [SMD (2.01 µg/l) 95% CI (0.57, 3.4), = .006], body mass index [SMD (1.6 µg/l) 95% CI (0.37, 3), < .05] and pregnancy trimesters[SMD (2.3 µg/l) 95% CI (0.95, 3.7), = .001]. Random-effects meta-regression showed a significant association of visfatin level with potential confounders including systolic blood pressure, gestational age and birth weight at delivery of pre-eclampsia patients.
CONCLUSIONS
Collectively, our data revealed that the increase of visfatin level can be associated with the risk of pre-eclampsia. However, further studies on pre-eclampsia populations are warranted for corroboration of our findings.
Topics: Body Mass Index; Female; Humans; Nicotinamide Phosphoribosyltransferase; Pre-Eclampsia; Pregnancy; Pregnancy Trimesters
PubMed: 32635792
DOI: 10.1080/14767058.2020.1789581 -
Journal of Trace Elements in Medicine... Dec 2023Supplementation is an alternative with potential benefits for the prevention of iodine deficiency in pregnancy. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Supplementation is an alternative with potential benefits for the prevention of iodine deficiency in pregnancy.
OBJECTIVE
To evaluate the effects of iodine supplementation on maternal thyroid hormone concentrations and iodine status during and/or before pregnancy.
METHODS
The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The search was conducted in the databases: Cochrane, Embase, Pubmed/MEDLINE and Scopus. Studies involving pregnant women of all trimesters who received oral iodine supplementation were included. Study selection was performed in the Rayyan program. Risk of bias was assessed by the Joanna Briggs Institute tool. Meta-analysis was performed in R software version 4.0.4.
RESULTS
Eleven articles with low and moderate risk of bias were included. According to the results of the meta-analysis, supplementation of 200 μg/day of iodine was able to change urinary iodine concentration during pregnancy, thus contributing to adequate intake. When evaluating the period when the intervention started, the best time to start supplementation was prior to pregnancy or in early pregnancy.
CONCLUSION
Daily iodine supplementation had satisfactory effects on iodine status and maternal thyroid hormone concentrations. Although supplementation with 200 µg showed positive effects on iodine status in pregnancy, some studies showed no effect. Prospero Registration: CRD42021249307 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=249307).
Topics: Pregnancy; Female; Humans; Iodine; Thyroid Gland; Dietary Supplements; Thyroid Hormones; Pregnant Women
PubMed: 37562272
DOI: 10.1016/j.jtemb.2023.127275 -
Ultrasound in Obstetrics & Gynecology :... Feb 2018The primary aim of this systematic review was to ascertain whether ultrasound signs suggestive of abnormally invasive placenta (AIP) are present in the first trimester... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The primary aim of this systematic review was to ascertain whether ultrasound signs suggestive of abnormally invasive placenta (AIP) are present in the first trimester of pregnancy. Secondary aims were to ascertain the strength of association and the predictive accuracy of such signs in detecting AIP in the first trimester.
METHODS
An electronic search of MEDLINE, EMBASE, CINAHL and Cochrane databases (2000-2016) was performed. Only studies reporting on first-trimester diagnosis of AIP that was subsequently confirmed in the third trimester either during operative delivery or by pathological examination were included. Meta-analysis of proportions, random-effects meta-analysis and hierarchical summary receiver-operating characteristics curve analysis were used to analyze the data.
RESULTS
Seven studies, involving 551 pregnancies at high risk of AIP, were included. At least one ultrasound sign suggestive of AIP was detected in 91.4% (95% CI, 85.8-95.7%) of cases with confirmed AIP. The most common ultrasound feature in the first trimester of pregnancy was low implantation of the gestational sac close to a previous uterine scar, which was observed in 82.4% (95% CI, 46.6-99.8%) of cases. Anechoic spaces within the placental mass (lacunae) were observed in 46.0% (95% CI, 10.9-83.7%) and a reduced myometrial thickness in 66.8% (95% CI, 45.2-85.2%) of cases affected by AIP. Pregnancies with a low implantation of the gestational sac had a significantly higher risk of AIP (odds ratio, 19.6 (95% CI, 6.7-57.3)), with a sensitivity and specificity of 44.4% (95% CI, 21.5-69.2%) and 93.4% (95% CI, 90.5-95.7%), respectively.
CONCLUSIONS
Ultrasound signs of AIP can be present during the first trimester of pregnancy, even before 11 weeks' gestation. Low anterior implantation of the placenta/gestational sac close to or within the scar was the most commonly seen early ultrasound sign suggestive of AIP, although its individual predictive accuracy was not high. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Female; Humans; Myometrium; Placenta; Placenta Accreta; Pregnancy; Pregnancy Trimester, First; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 28833750
DOI: 10.1002/uog.18840 -
Human Reproduction Update Mar 2024Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes.
OBJECTIVE AND RATIONALE
We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection.
SEARCH METHODS
Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2.
OUTCOMES
We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women).
WIDER IMPLICATIONS
Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; COVID-19; Premature Birth; Prevalence
PubMed: 38016805
DOI: 10.1093/humupd/dmad030 -
Archives of Gynecology and Obstetrics Jun 2019Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on...
PURPOSE
Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy.
METHODS
We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy.
RESULTS
We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1-3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none.
CONCLUSION
Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1-3 and post-partum.
Topics: Adolescent; Adult; Biomarkers; Cohort Studies; Female; Humans; Leukocyte L1 Antigen Complex; Middle Aged; Pregnancy; Pregnancy Complications; Prospective Studies; Young Adult
PubMed: 30953184
DOI: 10.1007/s00404-019-05134-8 -
Journal of Obstetrics and Gynaecology... Feb 2015Because of an increased resistance of urinary pathogens to penicillin derivatives, nitrofurantoin is commonly used as an alternative in treating urinary tract infection... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Because of an increased resistance of urinary pathogens to penicillin derivatives, nitrofurantoin is commonly used as an alternative in treating urinary tract infection because a wide range of both Gram negative and positive organisms are sensitive to it. The safety of the fetus after exposure to nitrofurantoin remains controversial.
METHODS
We conducted a systematic review and meta-analysis to evaluate the fetal safety of nitrofurantoin. We searched Medline, EMBASE, references from published reports, and meeting abstracts for relevant studies. Articles were included in the review if they were human studies, reported pregnancy outcomes, reported the use of nitrofurantoin in the first trimester of pregnancy, and included a comparator group of unexposed pregnancies. The primary outcome was the rate of major malformations; secondary outcomes were rates of craniosynostosis, cleft lip or palate defects, cardiovascular defects, and hypoplastic left heart syndrome.
RESULTS
Eight studies reporting on 91 115 exposed cases and 1 578 745 unexposed controls were included in the primary meta-analysis examining the risk of major malformation. Five cohort studies reported on 9275 exposed and 1 491 933 unexposed infants, resulting in an overall RR of 1.01 (95% CI 0.81 to 1.26); however, three case-control studies with a total of 39 268 cases of major malformations and 129 394 controls gave an overall OR of 1.22 (95% CI 1.02 to 1.45). No increased risk for cardiovascular malformations, oral cleft, or craniosynostosis was identified. For assessing risk of hypoplastic left heart syndrome, only three articles were eligible; these demonstrated an OR of 3.07 (95% CI 1.59 to 5.93).
CONCLUSION
While no association was found between fetal exposure to nitrofurantoin and major malformation in cohort studies, there was a slight but significant teratogenic risk in case-control studies, which are more sensitive to adverse effects.
Topics: Abnormalities, Drug-Induced; Anti-Infective Agents, Urinary; Female; Humans; Maternal Exposure; Nitrofurantoin; Pregnancy; Pregnancy Trimester, First
PubMed: 25767948
DOI: 10.1016/S1701-2163(15)30337-6