Influenza and congenital anomalies: a systematic review and meta-analysis
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
STUDY QUESTION: Does first trimester maternal influenza infection increase the risk of non-chromosomal congenital anomalies (CA)? SUMMARY ANSWER: First trimester maternal influenza exposure is associated with raised risk of a number of non-chromosomal CA, including neural tube defects, hydrocephaly, congenital heart defects, cleft lip, digestive system defects and limb reduction defects. WHAT IS KNOWN ALREADY: Hyperthermia is a well-established risk factor for neural tube defects. Previous studies suggest influenza may be a risk factor not only for neural tube defects, but also other CA. No systematic review has previously been undertaken. STUDY DESIGN, SIZE, DURATION: Systematic review and meta-analysis. A search of EMBASE and PUBMED was performed for English and Dutch studies published up to July 2013. A total of 33 studies (15 case-control, 10 cohort and 8 ecological) were included in the systematic review of which 22 studies were included in the meta-analysis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: A total of 29 542 babies with congenital anomaly (1112 exposed) from case-control studies and 1608 exposed pregnancies resulting in 56 babies with congenital anomaly from cohort studies were included in the meta-analysis. Maternal influenza exposure was defined as any reported influenza, influenza-like illness or fever with flu, with or without serological or clinical confirmation during the first trimester of pregnancy. Data for 24 (sub)groups with congenital anomaly available from ≥3 studies were analysed using the DerSimonian-Laird random effects model. The hypothesis of publication bias was assessed using funnel plots and risk of bias of included studies was assessed using a slightly modified version of the Newcastle-Ottawa scale. MAIN RESULTS AND THE ROLE OF CHANCE: First trimester maternal influenza exposure was associated with an increased risk of any congenital anomaly [adjusted odds ratio (AOR) 2.00, 95% CI: 1.62-2.48], neural tube defects [odds ratio (OR) 3.33, 2.05-5.40], hydrocephaly (5.74, 1.10-30.00), congenital heart defects (1.56, 1.13-2.14), aortic valve atresia/stenosis (AOR 2.59, 1.21-5.54), ventricular septal defect (AOR 1.59, 1.24-2.14), cleft lip (3.12, 2.20-4.42), digestive system (1.72, 1.09-2.68) and limb reduction defects (2.03, 1.27-3.27). An increased risk for cleft lip (but not for cleft palate) was also reported by ecological studies not included in the meta-analysis. Study outcomes reported for 27 subgroups of congenital anomaly could not be included in the meta-analysis. Visual inspection of funnel plots did not suggest evidence for publication bias. LIMITATIONS, REASONS FOR CAUTION: This study enrolled observational studies that can be subject to limitations such as confounding, retrospective maternal exposure reports and non-response of intended participants. Influenza exposed pregnancies can also have been exposed to influenza related medication. WIDER IMPLICATIONS OF THE FINDINGS: Prevention of influenza in pregnant women may reduce congenital anomaly risk, and would be relevant to more than just neural tube defects. More research is needed to determine whether influenza and/or its related medication is teratogenic, to determine the role of hyperthermia in teratogenicity and the role of other environmental factors such as nutritional status in determining susceptibility.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.007 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it