Opioid Detoxification in Pregnancy: Systematic Review and Meta-Analysis of Perinatal Outcomes

Objective We sought to compare the efficacy and safety of detoxification from opioids compared with opioid replacement therapy (ORT) during pregnancy. Study Design We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to June 2017 for English-language randomized-controlled trials or cohort studies that compared detoxification with ORT. We sought studies with outcomes data on maternal abstinence at the time of delivery, neonatal abstinence syndrome (NAS), stillbirth, and preterm birth (PTB). We calculated pooled relative risks (RRs) with a random-effects model, assessed heterogeneity using the chi-square test for heterogeneity, and quantified heterogeneity using the I 2 test. We assessed publication bias using funnel plots and the Harbord test. Results Three cohort studies met the inclusion criteria; eligible studies included 235 women with opioid use disorder in pregnancy. Maternal detoxification was associated with increased risk of relapse (RR = 1.91; 95% confidence interval [CI] = 1.14–3.21); however, no treatment differences were observed for the rates of NAS (RR = 0.99; 95% CI = 0.38–2.53) or PTB (RR = 0.39; 95% CI = 0.10–1.60). Conclusion Our findings suggest an increased risk of relapse with detoxification treatment compared with ORT; however, detoxification does not alter the risk of PTB or NAS. Further studies should confirm our findings and explore mechanisms to fight the current opioid epidemic.

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Pregnancy and Delivery Outcomes Following Benzodiazepine Exposure: A Systematic Review and Meta-analysis

The Canadian Journal of Psychiatry ◽

10.1177/0706743720904860 ◽

2020 ◽

Vol 65 (12) ◽

pp. 821-834

Author(s):

Sophie Grigoriadis ◽

Lisa Graves ◽

Miki Peer ◽

Lana Mamisashvili ◽

Myuri Ruthirakuhan ◽

...

Keyword(s):

Birth Weight ◽

Gestational Age ◽

English Language ◽

Meta Analysis ◽

Perinatal Outcomes ◽

Cochrane Library ◽

Significant Heterogeneity ◽

Delivery Outcomes ◽

Increased Risk ◽

Nicu Admission

Objective: Understanding the effects of benzodiazepines (BZDs) on maternal/fetal health remains incomplete despite their frequent use. This article quantifies the effects of antenatal BZD exposure on delivery outcomes. Methods Data Sources: Medline, PsycINFO, CINAHL, Embase, and the Cochrane Library were searched till June 30, 2018. Study Selection: English-language cohort studies comparing antenatal BZD exposure to an unexposed group on any delivery outcome were eligible. In all, 23,909 records were screened, 56 studies were assessed, and 14 studies were included. Data Extraction: Two reviewers independently assessed quality and extracted data. Estimates were pooled using random effects meta-analysis. Sub-analyses examined several potential moderators including timing of exposure. Results: There were 9 outcomes with sufficient data for meta-analysis. Antenatal BZD exposure was significantly associated with increased risk of 6 outcomes initially: spontaneous abortion (pooled odds ratio = 1.86; 95% confidence interval [CI], 1.43 to 2.42), preterm birth (1.96; 95% CI, 1.25 to 3.08), low birth weight (2.24; 95% CI, 1.41 to 3.88), low Apgar score (2.19; 95% CI, 1.94 to 2.47), Neonatal Intensive Care Unit (NICU) admission (2.61; 95% CI, 1.64 to 4.14), and induced abortion (2.04; 95% CI, 1.23 to 3.40). There was significant heterogeneity between studies for most outcomes without consistent moderators. Birth weight (mean difference [MD]: −151.35 g; 95% CI, −329.73 to 27.03), gestational age (−0.49 weeks; 95% CI, −1.18 to 0.19), and small for gestational age (SGA; 1.42; 95% CI, 1.00 to 2.01) did not show significant associations although after adjusting for publication bias, gestational age, and SGA became significant, totaling 8 significant outcomes. Conclusions: Antenatal BZD exposure appears to be statistically associated with increased risk of several adverse perinatal outcomes. Although confounds cannot be ruled out, NICU admission does appear clinically relevant and consistent with the antidepressant literature.

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Psychological interventions as an alternative and add-on to antidepressant medication to prevent depressive relapse: systematic review and meta-analysis

The British Journal of Psychiatry ◽

10.1192/bjp.2020.198 ◽

2020 ◽

pp. 1-8

Author(s):

Josefien Johanna Froukje Breedvelt ◽

Maria Elisabeth Brouwer ◽

Mathias Harrer ◽

Maria Semkovska ◽

David Daniel Ebert ◽

...

Keyword(s):

Psychological Intervention ◽

Meta Analysis ◽

Antidepressant Medication ◽

Cochrane Library ◽

Psychological Interventions ◽

Relapse Risk ◽

Increased Risk ◽

Antidepressant Use ◽

Randomised Controlled ◽

Risk Of Relapse

Background After remission, antidepressants are often taken long term to prevent depressive relapse or recurrence. Whether psychological interventions can be a viable alternative or addition to antidepressants remains unclear. Aims To compare the effectiveness of psychological interventions as an alternative (including delivered when tapering antidepressants) or addition to antidepressants alone for preventing depressive relapse. Method Embase, PubMed, the Cochrane Library and PsycINFO were searched from inception until 13 October 2019. Randomised controlled trials (RCTs) with previously depressed patients in (partial) remission where preventive psychological interventions with or without antidepressants (including tapering) were compared with antidepressant control were included. Data were extracted independently from published trials. A random-effects meta-analysis on time to relapse (hazard ratio, HR) and risk of relapse (risk ratio, RR) at the last point of follow-up was conducted. PROSPERO ID: CRD42017055301. Results Among 11 included trials (n = 1559), we did not observe an increased risk of relapse for participants receiving a psychological intervention while tapering antidepressants versus antidepressants alone (RR = 1.02, 95% CI 0.84–1.25; P = 0.85). Psychological interventions added to antidepressants significantly reduced the risk of relapse (RR = 0.85, 95% CI 0.74–0.97; P = 0.01) compared with antidepressants alone. Conclusions This study found no evidence to suggest that adding a psychological intervention to tapering increases the risk of relapse when compared with antidepressants alone. Adding a psychological intervention to antidepressant use reduces relapse risk significantly versus antidepressants alone. As neither strategy is routinely implemented these findings are relevant for patients, clinicians and guideline developers.

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Maternal and neonatal characteristics of a Canadian urban cohort receiving treatment for opioid use disorder during pregnancy

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174418000478 ◽

2018 ◽

Vol 10 (1) ◽

pp. 132-137 ◽

Cited By ~ 1

Author(s):

C. Miller ◽

D. Grynspan ◽

L. Gaudet ◽

E. Ferretti ◽

S. Lawrence ◽

...

Keyword(s):

Replacement Therapy ◽

Retrospective Chart Review ◽

Opioid Use Disorder ◽

Prescription Opioid ◽

Opioid Use ◽

Maternal Characteristics ◽

Ottawa Hospital ◽

Increased Risk ◽

Opioid Replacement Therapy ◽

In Pregnancy

AbstractThe epidemic of prescription and non-prescription opioid misuse is of particular importance in pregnancy. The Society of Obstetricians and Gynaecologists of Canada currently recommends opioid replacement therapy with methadone or buprenorphine for opioid-dependent women during pregnancy. This vulnerable segment of the population has been shown to be at increased risk of blood-borne infectious diseases, nutritional insecurity and stress. The objective of this study was to describe an urban cohort of pregnant women on opioid replacement therapy and to evaluate potential effects on the fetus. A retrospective chart review of all women on opioid replacement therapy and their infants who delivered at The Ottawa Hospital General and Civic campuses between January 1, 2013 and March 24, 2017 was conducted. Data were collected on maternal characteristics, pregnancy outcomes, neonatal outcomes and corresponding placental pathology. Maternal comorbidities identified included high rates of infection, tobacco use and illicit substance use, as well as increased rates of placental abruption compared with national averages. Compared with national baseline averages, the mean neonatal birth weight was low, and the incidence of small for gestational age infants and congenital anomalies was high. The incidence of NAS was comparable with estimates from other studies of similar cohorts. Findings support existing literature that calls for a comprehensive interdisciplinary risk reduction approach including dietary, social, domestic, psychological and other supports to care for opioid-dependent women in pregnancy.

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Abstract P107: Are Sleep Disturbances Associated with the Development of Gestational Diabetes? A Systematic Review and Meta-analysis.

Circulation ◽

10.1161/circ.129.suppl_1.p107 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Michelle A Miller ◽

Ponnusamy Saravanan ◽

Manu Vatish ◽

Francesco P Cappuccio

Keyword(s):

Gestational Diabetes ◽

Publication Bias ◽

Sleep Disturbances ◽

Sleep Disordered Breathing ◽

Meta Analysis ◽

Cochrane Library ◽

Short Sleep ◽

Increased Risk ◽

In Pregnancy ◽

Disordered Breathing

Introduction and objectives: Physiological and hormonal changes occurring in pregnancy increase the risk of sleep disordered breathing (SDB), which, along with short sleep (SS) duration, may be associated with an increased risk of gestational diabetes mellitus (GDM). Exposure to GDM in the mother increases her lifetime risk of type-2 diabetes (T2D) as well as the risk of obesity, metabolic syndrome and, in later life, T2D of her children. The aim of this study was to systematically review the collective published evidence of associations between snoring/sleep-disordered breathing or sleep duration and increased risk of GDM. Hypothesis: We assessed the hypotheses that sleep disturbances, and/or short sleep during pregnancy may be associated with an increased risk of GDM. Materials and Methods: We performed systematic searches using MEDLINE, EMBASE, the Cochrane library and PsycINFO to assess the effect of snoring/sleep disordered breathing (SDB) or short sleep (SS) on the development of gestational diabetes (GDM) and impaired glucose tolerance in pregnancy. Prospective studies with measures of sleep disturbances at baseline and outcome measures of GDM or levels of glucose 1hr post GCT were included in a meta-analysis. We extracted odds ratios (OR) or relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model. Results: Overall, 7 studies met the inclusion criteria. They included 4,292 participants with 311 cases of GDM. In the pooled analysis, snoring/SDB and SS were both associated with a greater risk of GDM (RR: 2·27; 95% CI 1·65 to 3·12; P < 0· 00001) and (3·19 [1·56 to 6·54]; P < 0·002), respectively. There was no evidence of heterogeneity but there was evidence of publication bias and not all studies adjusted for obesity. Sensitivity analyses did not influence the pooled risk estimates. Conclusions: In conclusion, sleep disturbances may represent a risk factor for the development of GDM. Further studies are required to address the issues of publication bias and potential confounding, and to extend these observations to high-risk groups like women of ethnic minority groups whose risk of GDM is the greatest. Prevention, detection and treatment strategies need to be explored.

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Processed and Unprocessed Red Meat Consumption and Risk for Type 2 Diabetes Mellitus: An Updated Meta-Analysis of Cohort Studies

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph182010788 ◽

2021 ◽

Vol 18 (20) ◽

pp. 10788

Author(s):

Rui Zhang ◽

Jialin Fu ◽

Justin B. Moore ◽

Lee Stoner ◽

Rui Li

Keyword(s):

Diabetes Mellitus ◽

Cohort Studies ◽

Fixed Effects ◽

English Language ◽

Meta Analysis ◽

Meat Consumption ◽

Type Ii Diabetes Mellitus ◽

Red Meat ◽

The Body ◽

Cochrane Library

Type II diabetes mellitus (T2DM) is a metabolic disorder that occurs in the body because of decreased insulin activity and/or insulin secretion. The incidence of T2DM has rapidly increased over recent decades. The relation between consumption of different types of red meats and risk of T2DM remains uncertain. This meta-analysis was conducted to quantitatively assess the associations of processed red meat (PRM) and unprocessed red meat (URM) consumption with T2DM. We searched PubMed, Embase, Web of Science and The Cochrane Library for English-language cohort studies published before January 2021. Summary relative risks (RR) with 95% confidence interval (CI) were estimated using fixed effects and random effects. Additionally, dose–response relationships were explored using meta-regression. Fifteen studies (N = 682,963 participants, cases = 50,675) were identified. Compared with the lowest intake group, high consumption of PRM and URM increased T2DM risk by 27% (95% CI 1.15–1.40) and 15% (95% CI 1.08–1.23), respectively. These relationships were consistently strongest for U.S-based studies, though the effects of sex are inconclusive. In conclusion, PRM and URM are both positively associated with T2DM incidence, and these relationships are strongest in the U.S. reduction of red meat consumption should be explored as a target for T2DM prevention initiatives.

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Diabetes in Pregnancy and Risk of Antepartum Depression: A Systematic Review and Meta-Analysis of Cohort Studies

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17113767 ◽

2020 ◽

Vol 17 (11) ◽

pp. 3767 ◽

Cited By ~ 1

Author(s):

Kai Wei Lee ◽

Siew Mooi Ching ◽

Navin Kumar Devaraj ◽

Seng Choi Chong ◽

Sook Yee Lim ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Cohort Studies ◽

Pregnant Women ◽

Meta Analysis ◽

Diabetes In Pregnancy ◽

Antepartum Depression ◽

Increased Risk ◽

In Pregnancy

Previous literature has reported that patients with diabetes in pregnancy (DIP) are at risk of developing antepartum depression but the results have been inconsistent in cohort studies. We conducted a systematic review and performed a meta-analysis to quantify the association between DIP and risk of antepartum depression in cohort studies. Medline, Cinahl, and PubMed databases were searched for studies investigating DIP involving pregnant women with pre-existing diabetes and gestational diabetes mellitus and their risk of antepartum depression that were published in journals from inception to 27 December 2019. We derived the summary estimates using a random-effects model and reported the findings as pooled relative risks (RR) and confidence interval (CI). Publication bias was assessed using a funnel plot and was quantified by Egger and Begg’s tests. Ten studies, involving 71,036 pregnant women were included in this meta-analysis. The pooled RR to develop antepartum depression was (RR = 1.430, 95% CI: 1.251–1.636) among women with gestational diabetes mellitus. Combining pregnant women with pre-existing diabetes mellitus and gestational diabetes mellitus, they had a significant increased risk of developing antepartum depression (RR = 1.431, 95% CI: 1.205–1.699) compared with those without it. In comparison, we found no association between pre-existing diabetes mellitus in pregnancy (RR = 1.300, 95% CI: 0.736–2.297) and the risk of developing antepartum depression. This study has a few limitations: first, different questionnaire and cut-off points were used in evaluation of depression across the studies. Second, there was a lack of data on history of depression prior to pregnancy, which lead to confounding bias that could not be solved by this meta-analysis. Third, data were dominated by studies in Western countries; this is due to the studies from Eastern countries failing to meet our inclusion criteria for statistical analysis. Women with gestational diabetes mellitus have an increased risk of developing antepartum depression compared to those without the disease. Therefore, more attention on the mental health status should be given on pregnant women diagnosed with pre-existing diabetes mellitus and gestational diabetes mellitus.

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Epidural-Related Fever and Maternal and Neonatal Morbidity: A Systematic Review and Meta-Analysis

Neonatology ◽

10.1159/000504805 ◽

2020 ◽

Vol 117 (3) ◽

pp. 259-270 ◽

Cited By ~ 3

Author(s):

Sophie Jansen ◽

Enrico Lopriore ◽

Christiana Naaktgeboren ◽

Marieke Sueters ◽

Jacqueline Limpens ◽

...

Keyword(s):

Systematic Review ◽

Cohort Studies ◽

Antibiotic Treatment ◽

Assessment Tool ◽

Meta Analysis ◽

Cochrane Library ◽

Increased Risk ◽

Observational Cohort ◽

Meta Analyses ◽

The Impact

Background: While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. Objectives: The aim of this systematic review was to investigate the effect of epidural-related intrapartum fever on maternal and neonatal outcomes. Methods: OVID MEDLINE, OVID Embase, the Cochrane Library, Cochrane Controlled Register of Trials, and clinical trial registries were searched for randomized controlled trials (RCT) and observational cohort studies from inception to November 2018. A total of 761 studies were identified with 100 eligible for full-text review. Only articles investigating the relationship between EA and maternal fever during labor were eligible for inclusion. Study quality was assessed using the Cochrane’s Risk of Bias tool and National Institute of Health Quality Assessment Tool. Two meta-analyses – one each for the RCT and observational cohort groups – were performed using the random-effects model of Mantel-Haenszel to produce summary risk ratios (RR) with 95% CI. Results: Twelve RCTs and 16 observational cohort studies involving 579,157 parturients were included. RRs for maternal fever for the RCT and cohort analyses were 3.54 (95% CI 2.61–4.81) and 5.60 (95% CI 4.50–6.97), respectively. Meta-analyses of RR for maternal infection in both groups were infeasible given few occurrences. Meta-analysis of data from observational studies showed an increased risk for maternal antibiotic treatment in the epidural group (RR 2.60; 95% CI 1.31–5.17). For both analyses, neonates born to women with an epidural were not evaluated more often for suspected sepsis. Neither analysis reported an increased rate of neonatal bacteremia or neonatal antibiotic treatment after EA, although data precluded conclusiveness. Conclusion: EA increases the risk of intrapartum fever and maternal antibiotic treatment. However, a definite conclusion on whether EA increases the risk for a proven maternal and/or neonatal bacteremia cannot be drawn due to the low quality of data. Further research on whether epidural-related intrapartum fever is of infectious origin or not is therefore needed.

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Neonatal outcomes after neuraminidase inhibitor use during pregnancy: a meta-analysis of cohort studies

10.22541/au.162180775.52826228/v1 ◽

2021 ◽

Author(s):

Jiangshan Lian ◽

Munire Adilijiang ◽

Caihua Chang ◽

Hai-yin Jiang ◽

Yongping Zhang

Keyword(s):

Cohort Studies ◽

Influenza Infection ◽

Meta Analysis ◽

Antiviral Treatment ◽

Neuraminidase Inhibitor ◽

Neonatal Outcomes ◽

Cochrane Library ◽

Increased Risk ◽

Adverse Neonatal Outcomes ◽

Antiviral Medications

AIM: Influenza infection poses a severe threat to pregnant mothers, and antiviral treatment is recommended. However, the safety of neuraminidase-inhibitor antiviral medications during pregnancy has not been well described. METHODS: A systematic review and meta-analysis were performed to evaluate the adverse neonatal outcomes associated with exposure to neuraminidase inhibitors during pregnancy. The PubMed, Embase, and Cochrane Library databases were searched to identify potential studies for inclusion. RESULTS: Nine cohort studies that estimated adverse neonatal outcomes associated with exposure to neuraminidase-inhibitor medication during pregnancy were included. Exposure to a neuraminidase inhibitor during pregnancy was not associated with an increased risk of congenital malformation (odds ratio [OR] 0.9, 95% confidence interval [CI] 0.72–1.12, P = 0.341), low Apgar score (OR 0.96, 95% CI 0.77–1.2, P = 0.733), or preterm birth (OR 0.99, 95% CI 0.89–1.09, P = 0.771) compared with no exposure. However, exposure to a neuraminidase inhibitor was associated with a reduced risk of low birth weight (OR 0.79, 95% CI 0.68–0.92, P = 0.002) and giving birth to a small-for-gestational-age infant (OR 0.78, 95% CI 0.69–0.88, P < 0.001). Further analyses limited to oseltamivir exposure were consistent with the overall results. CONCLUSION: Exposure to neuraminidase-inhibitor medication during pregnancy does not appear to be associated with adverse neonatal outcomes. We recommend further studies to investigate this association, which will help clinicians determine whether to prescribe a neuraminidase inhibitor during pregnancy.

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Risk of stroke in cancer survivors

Neurology ◽

10.1212/wnl.0000000000011264 ◽

2020 ◽

pp. 10.1212/WNL.0000000000011264

Author(s):

Fangfang Zhang ◽

Kuanhong Wang ◽

Peixin Du ◽

Wei Yang ◽

Yazhou He ◽

...

Keyword(s):

Cohort Studies ◽

Cancer Survivors ◽

Cancer Survival ◽

Meta Analysis ◽

Critical Role ◽

Population Based ◽

Cochrane Library ◽

Survival Duration ◽

Published Data ◽

Increased Risk

ObjectiveAccumulating evidence suggests that cancer survivors may have a relatively higher risk of stroke. The hypothesis of this meta-analysis was to determine whether cancer survivors have a relatively higher risk of stroke than non-cancer populations based on the published data from population-based cohort studies.MethodsPubmed, Embase and Cochrane Library were searched from inception to February 8, 2020 for population-based cohort studies. Effect estimates with 95% CIs were pooled using the random-effects model. We conducted subgroup analyses and meta-regression to explore sources of heterogeneity and the stability of the results.ResultsTwenty population-based cohort studies involving 10,479,530 participants were identified. Overall, the RR for stroke in cancer survivors was 1.66 (95% CI, 1.35–2.04; p < 0.001) compared with that in non-cancer controls, among which survivors of head and neck, hematologic, lung, pancreas and stomach cancer (all p < 0.05) showed consistent significant results, whereas no significant increased risk was observed for other cancer types. The effects were more prominent in cancer survivors with female gender (RR 1.38, 1.18–1.61; p < 0.001), younger age at cancer diagnosis (<45 years) (RR 2.57, 95% CI, 1.27–5.19; p = 0.009) and shorter cancer survival duration (≥1–2 years) (RR 1.69, 95% CI, 1.18–2.42; p = 0.004). Moreover, cancer survivors had a significantly increased risk of ischemic stroke (RR 1.53, 95% CI, 1.28–1.84; p < 0.001) compared with hemorrhagic stroke.ConclusionsCancer plays a critical role in the etiologic of stroke. Due to the existence of substantial heterogeneity among the included studies, the results should be interpreted with caution. However, early prevention and effective intervention of stroke in cancer survivors requires attention from the health policy makers.

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Burden and Determinant of Inadequate Dietary Diversity among Pregnant Women in Ethiopia: A Systematic Review and Meta-Analysis

Journal of Nutrition and Metabolism ◽

10.1155/2020/1272393 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Hagos Degefa Hidru ◽

Meresa Berwo Mengesha ◽

Yared Hailesilassie ◽

Fissaha Tekulu Welay

Keyword(s):

Dietary Intake ◽

Pregnant Women ◽

English Language ◽

Dietary Diversity ◽

Meta Analysis ◽

National Level ◽

Perinatal Outcomes ◽

Cochrane Library ◽

Medical Subject Headings ◽

Mesh Terms

Background. Inadequate dietary diversity intake during pregnancy results in increased risks of negative maternal and perinatal outcomes. About one million neonates die on the first day of life due to inadequate dietary intake during pregnancy as a result of maternal complication and adverse birth outcomes. This review summarizes the burden of inadequate dietary diversity and its determinants among pregnant women at the national level of Ethiopia. Methods. Studies were retrieved from selected electronic databases, including PubMed, Cochrane Library, and Google Scholar. Random-effects model meta-analysis was used to estimate the pooled burden of inadequate dietary diversity and its determinants at a 95% confidence interval with its respective odds ratio (OR) using statistical R-software version 3.6.1. Moreover, quality appraisal of the included studies, publication bias, and level of heterogeneity were checked with subgroup analysis and sensitivity influential test. The searches were restricted to articles published in the English language only, and Medical Subject Headings (MeSH terms) was used to help expand the search in advanced PubMed search. Result. A total of 850 articles were identified through the initial search of which 21 studies were included in the final review yielding a total sample size of 9,230 pregnant women. The pooled prevalence of inadequate dietary diversity was 53% (95% CI: 44%, 62%). Food insecurity [AOR = 2.18, (95% CI: 1.02, 4.63)], family size of greater than four [AOR = 1.46, (95% CI: 1.10, 1.95)], rural residence [AOR = 4.52, (95% CI: 1.02, 20.09)], no formal educational status [AOR = 4.50, (95% CI: 1.02, 20.09)], and a lack of counseling about dietary diversity [AOR = 2.75, (95% CI: 2.17, 3.48)] were among the significantly associated factors for inadequate dietary diversity. Conclusion. In this review, there was a high prevalence of inadequate dietary diversity among pregnant women at the national level in Ethiopia. Therefore, strengthening early counseling and diagnosis of dietary intake and undernutrition during the antenatal care period is important.

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