{"product_id":"flu-shot-in-early-pregnancy-and-birth-defect-risk-what-a-major-review-of-1-2-million-pregnancies-shows","title":"Flu Shot in Early Pregnancy and Birth Defect Risk: What a Major Review of 1.2 Million Pregnancies Shows","description":"\u003cp\u003eIn this updated systematic review and meta-analysis, researchers pooled 31 observational studies covering 1,223,024 pregnant people to examine whether influenza vaccination in the first trimester increases the risk of birth defects. The pooled adjusted results showed no increased risk of total birth defects among people vaccinated in the first trimester (adjusted odds ratio 1.03, 95% CI 0.98–1.07). The pooled adjusted results showed no increased risk of major birth defects among people vaccinated in the first trimester (adjusted odds ratio 1.03, 95% CI 0.98–1.09). The findings were consistent across vaccine types, adjuvant use, how birth defects were assessed, and control group type, and they held up in all sensitivity analyses.\u003c\/p\u003e\n\n\u003ch1\u003eFlu Shot in Early Pregnancy and Birth Defect Risk: What a Major Review of 1.2 Million Pregnancies Shows\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Question Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#methods\"\u003eHow the Researchers Conducted the Study\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#studies\"\u003eWhat Studies Were Included\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#findings\"\u003eKey Findings: Birth Defect Risks\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#organ\"\u003eFindings for Specific Organ Systems\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#subgroups\"\u003eSubgroup and Sensitivity Analyses\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Study\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations for Pregnant People\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a pooled analysis of 31 observational studies and 1,223,024 pregnant people, first-trimester influenza vaccination was not associated with increased total birth defects (adjusted odds ratio 1.03, 95% CI 0.98–1.07).\u003c\/li\u003e\n\u003cli\u003eMajor birth defects also showed no increased risk with first-trimester vaccination (adjusted odds ratio 1.03, 95% CI 0.98–1.09); both confidence intervals include 1.0, so results are consistent with no difference.\u003c\/li\u003e\n\u003cli\u003eFindings were consistent across vaccine types, adjuvant use, birth defect assessment methods, and control group types, and held in all sensitivity analyses.\u003c\/li\u003e\n\u003cli\u003eAll included studies were observational, so they show associations rather than cause and effect; adjusted estimates came from fewer studies (10 for total, 6 for major birth defects).\u003c\/li\u003e\n\u003cli\u003eThe CDC and ACOG recommend influenza vaccination at any stage of pregnancy, and vaccination also protects infants under six months through antibodies passed across the placenta.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Question Matters\u003c\/h2\u003e\n\u003cp\u003eInfluenza (flu) virus infection places a heavy burden on health worldwide. The virus causes 3 to 5 million cases of severe illness each year. Pregnant people are more susceptible to influenza infection than the general population. This higher susceptibility comes from physiologic changes and immunosuppression (a weakened immune response) during pregnancy. Influenza infection during pregnancy can increase the risk of several adverse pregnancy outcomes, including miscarriage and preterm birth.\u003c\/p\u003e\n\n\u003cp\u003eBecause of these risks, the Centers for Disease Control and Prevention (CDC) and the American College of Obstetricians and Gynecologists (ACOG) recommend that all pregnant people receive the influenza vaccine. The CDC and ACOG recommend the influenza vaccine at any stage of pregnancy. Despite these recommendations, vaccination rates among pregnant people remain persistently low. Surveys report uptake of 61.2% in the United States and between 1.7% and 40.6% in the European Union. In China, only 11.4% of pregnant people expressed willingness to receive an influenza vaccine during pregnancy.\u003c\/p\u003e\n\n\u003cp\u003eOne major reason for low uptake is concern about potential adverse events after maternal influenza vaccination. These concerns include stillbirth, preterm birth, low birth weight, and birth defects (BDs).\u003c\/p\u003e\n\n\u003cp\u003eThe first trimester is a crucial stage of embryonic development. During this period, the organs of the embryo form. This stage is particularly vulnerable to external factors that may cause birth defects, such as drugs and infection. Vaccination during pregnancy has been consistently shown to effectively prevent influenza in expectant mothers. Vaccination also protects infants under six months of age through the transmission of protective antibodies across the placenta.\u003c\/p\u003e\n\n\u003cp\u003eInfluenza vaccination during pregnancy is generally considered safe. However, some studies have explored potential concerns about first-trimester vaccination. For example, Pasternak and colleagues reported a slight increase in the risk of birth defects in the H1N1-vaccinated population during the first trimester. This finding came from unadjusted analyses (unadjusted odds ratio 2.26, 95% CI 1.40–3.66). This association was no longer statistically significant after adjustment for confounders (other factors that could explain the link). Chambers and colleagues found no significant association between influenza vaccination and birth defects (adjusted odds ratio 0.79, 95% CI 0.26–2.42). However, the wide confidence interval in that study reflects limited precision.\u003c\/p\u003e\n\n\u003cp\u003eSeveral meta-analyses have explored the association between influenza vaccination and birth defects. However, few studies have specifically focused on people vaccinated during the first trimester, and the sample sizes in these studies are relatively small. These earlier analyses also did not scrutinize potential associations between birth defects and other pivotal variables related to influenza vaccination. One such variable is the difference between pandemic monovalent vaccines (vaccines targeting a single pandemic strain) and seasonal multivalent vaccines (vaccines targeting several strains). The impact of influenza vaccination during early pregnancy on the occurrence of birth defects therefore remained uncertain. The researchers conducted this updated systematic review and meta-analysis to address this issue and to provide further evidence in reproductive health.\u003c\/p\u003e\n\n\u003ch2 id=\"methods\"\u003eHow the Researchers Conducted the Study\u003c\/h2\u003e\n\u003cp\u003eThe researchers followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement when conducting and reporting this study. They registered the review protocol in advance in PROSPERO (registration number CRD42023450641).\u003c\/p\u003e\n\n\u003cp\u003eThe team included cohort studies and case-control studies if the studies met three criteria. First, the study evaluated the association between influenza vaccination during pregnancy and adverse pregnancy outcomes. Second, the study included at least one exposure group that received influenza vaccine during the first trimester. Third, the study included total birth defects, major birth defects, or organ system specific birth defects as outcomes among live-born infants. Major birth defects are major structural anomalies with serious health or developmental consequences.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers excluded studies for two main reasons. First, they excluded conference abstracts, recommendations, and reviews. Second, they excluded studies that did not report the original number of events and total participants in the vaccination and control groups. They also excluded studies that did not report an adjusted effect size with 95% confidence intervals (CIs).\u003c\/p\u003e\n\n\u003cp\u003eThe team searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. The search covered the earliest available date (1981) to 28 April 2023. The researchers used a pre-designed search strategy that combined MeSH terms (standardized medical subject headings) and free-text words. Search terms included, but were not limited to, pregnancy, maternal, gestation, pregnant, influenza vaccine, flu vaccine, influenza virus vaccine, flu vaccination, influenza vaccination, and influenza virus vaccination. The team also manually checked the reference lists of included articles and relevant systematic reviews for additional literature.\u003c\/p\u003e\n\n\u003cp\u003eTwo reviewers independently screened titles and abstracts, then checked full texts for eligibility. A third reviewer resolved any disagreements. The reviewers extracted data using standardized forms that had been pilot-tested. The forms captured general study information, vaccination information, birth defect information, and adjusted effect estimates with 95% confidence intervals.\u003c\/p\u003e\n\n\u003cp\u003eTwo reviewers independently assessed the risk of bias in the included studies using the Newcastle-Ottawa Scale (NOS). This scale scores studies on three categories: selection of subjects, comparability of study groups, and assessment of exposure. The maximum score is 9 points. Studies with a quality score of 7 or higher were considered high quality.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers defined first-trimester vaccination (the exposed group) as receiving influenza vaccine during 0 to 13 weeks plus 6 days of gestation. They classified people who received the influenza vaccine during the second or third trimester, or who did not receive the vaccine during pregnancy, as the control group.\u003c\/p\u003e\n\n\u003cp\u003eThe primary outcome was total birth defects. The secondary outcomes were major birth defects and 10 organ system specific birth defects. Major birth defects are structural congenital anomalies present at birth that have significant medical, social, cosmetic, or functional consequences. These anomalies typically require medical or surgical intervention. The organ system specific birth defects covered the nervous system, eye, ear, face and neck, and the circulatory system. The organ system specific birth defects also covered the respiratory system, cleft lip and cleft palate, the digestive system, genital organs and the urinary system. The remaining categories were the musculoskeletal system, other congenital malformations, and chromosome abnormalities.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers pooled all unadjusted and adjusted data separately. They measured between-study statistical heterogeneity (variation in results across studies) with Cochran's Chi-squared test and the I² statistic. They defined substantial statistical heterogeneity as I² of 50% or higher. They calculated odds ratios (ORs) with 95% confidence intervals using the Mantel-Haenszel random-effects model. Because the incidence of the outcome in this study is usually less than 5%, the researchers treated several effect measures as the same. The researchers treated odds ratio, hazard ratio (HR), prevalence risk (PR), and relative risk (RR) as the same effect measures.\u003c\/p\u003e\n\n\u003cp\u003eWhen pooling risk estimates, the researchers prioritized the unvaccinated group during pregnancy as the control group. When this group was not available, they chose people vaccinated during the second trimester, third trimester, or any combination of them as the control group.\u003c\/p\u003e\n\n\u003cp\u003eThe team performed subgroup analyses based on several factors:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eVaccine type (pandemic monovalent versus seasonal multivalent)\u003c\/li\u003e\n  \u003cli\u003eUse of adjuvants (nonadjuvanted versus adjuvanted versus nonadjuvanted\/adjuvanted)\u003c\/li\u003e\n  \u003cli\u003eStudy design (cohort study versus case-control study)\u003c\/li\u003e\n  \u003cli\u003eAssessment of birth defects (medical records versus self-reported versus medical records\/self-reported)\u003c\/li\u003e\n  \u003cli\u003eControl type (unvaccinated control versus second trimester control versus third trimester control versus second or third trimester control)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe researchers tested statistical differences among subgroups with an interaction test. They also used meta-regression analysis to evaluate heterogeneity.\u003c\/p\u003e\n\n\u003cp\u003eThe team conducted sensitivity analyses using four approaches. First, they added 1 birth defect to both the exposed and control groups in studies that reported no birth defect observed in all participants. Second, they deleted studies with a low quality score (NOS score less than 7). Third, they sequentially excluded one study at a time and recalculated the pooled estimate. This step assessed whether any single study disproportionately influenced the results. Fourth, they used the trim and fill method to impute potentially missing studies and adjust the pooled estimate for potential publication bias. To assess publication bias, the researchers conducted Egger's and Begg's tests and generated a funnel plot. They performed all statistical analyses using Stata version 17.0.\u003c\/p\u003e\n\n\u003ch2 id=\"studies\"\u003eWhat Studies Were Included\u003c\/h2\u003e\n\u003cp\u003eThe researchers initially identified 14,339 relevant studies from the literature search. They ultimately included 31 eligible studies involving 1,223,024 participants.\u003c\/p\u003e\n\n\u003cp\u003eThe included studies comprised 17 prospective studies, 10 retrospective studies, and 4 case-control studies. Of the 31 studies, 28 reported total birth defects, 16 reported major birth defects, and 12 reported organ system specific birth defects.\u003c\/p\u003e\n\n\u003cp\u003eAll vaccines mentioned in the included studies were inactivated influenza vaccines (vaccines made from killed virus). Fourteen studies used pandemic monovalent vaccination, and 13 studies used seasonal trivalent or quadrivalent influenza vaccines. Two studies used any of the aforementioned types, and 2 studies did not report the vaccine type.\u003c\/p\u003e\n\n\u003cp\u003eTwenty-three studies reported birth defects based on medical records, while 3 studies relied on self-reporting. Four studies used a combination of medical records and self-reported data, and 1 study did not mention the method.\u003c\/p\u003e\n\n\u003cp\u003eThe included studies exhibited a low risk of bias. Twenty-six studies (83.87%) achieved a Newcastle-Ottawa Scale score of 7 or higher.\u003c\/p\u003e\n\n\u003ch2 id=\"findings\"\u003eKey Findings: Birth Defect Risks\u003c\/h2\u003e\n\u003cp\u003eThe pooled analysis found no increased risk of total birth defects among people vaccinated during the first trimester. This finding came from 28 studies involving 1,213,781 pregnant people. The pooled unadjusted result was an odds ratio of 1.15 (95% CI 0.97–1.36), with substantial heterogeneity between studies (I² = 81.7%).\u003c\/p\u003e\n\n\u003cp\u003eThe pooled adjusted data also showed no association between first-trimester influenza vaccination and total birth defects. This analysis included 10 studies. The adjusted odds ratio was 1.03 (95% CI 0.98–1.07), with no heterogeneity between studies (I² = 0.0%).\u003c\/p\u003e\n\n\u003cp\u003eAn odds ratio of 1.03 means the odds of a birth defect were about 3% higher in the vaccinated group than in the control group. However, the 95% confidence interval ranged from 0.98 to 1.07. Because this range includes 1.0, the result is not statistically significant. In plain terms, the data are consistent with no difference between the groups.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers also found no increased risk for major birth defects. The pooled unadjusted data from 16 studies showed an odds ratio of 1.11 (95% CI 0.97–1.25), with moderate heterogeneity (I² = 44.7%). The pooled adjusted data from 6 studies showed an odds ratio of 1.03 (95% CI 0.98–1.09), with no heterogeneity (I² = 0.0%).\u003c\/p\u003e\n\n\u003cp\u003eThese results mean that first-trimester influenza vaccination was not linked to a higher risk of birth defects overall or of major birth defects. The adjusted analyses, which account for other factors that could influence the results, showed estimates very close to 1.0.\u003c\/p\u003e\n\n\u003ch2 id=\"organ\"\u003eFindings for Specific Organ Systems\u003c\/h2\u003e\n\u003cp\u003eBased on unadjusted data, the researchers found no increased risk for birth defects in 9 of the 10 organ system specific categories. The one exception was the urogenital system.\u003c\/p\u003e\n\n\u003cp\u003eFor circulatory system birth defects, the adjusted data showed no increased risk. This finding came from 5 studies, with an adjusted odds ratio of 0.98 (95% CI 0.89–1.07) and no heterogeneity (I² = 0.0%).\u003c\/p\u003e\n\n\u003cp\u003eThe organ system categories examined were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eCongenital malformations of the nervous system\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of the eye\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of the ear, face, and neck\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of the circulatory system\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of the respiratory system\u003c\/li\u003e\n  \u003cli\u003eCleft lip and cleft palate\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of the digestive system\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of genital organs and the urinary system\u003c\/li\u003e\n  \u003cli\u003eCongenital malformations of the musculoskeletal system\u003c\/li\u003e\n  \u003cli\u003eOther congenital malformations and chromosome abnormalities\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"subgroups\"\u003eSubgroup and Sensitivity Analyses\u003c\/h2\u003e\n\u003cp\u003eThe subgroup analyses examined different vaccine types, different adjuvants, different methods of assessing birth defects, and different control types. The results of all these subgroup analyses were consistent with the primary results.\u003c\/p\u003e\n\n\u003cp\u003eOne finding stood out in the subgroup analysis by study design. The pooled unadjusted data of cohort studies showed a slight increased risk of birth defects. However, the pooled adjusted data for cohort studies showed a non-significant association.\u003c\/p\u003e\n\n\u003cp\u003eMeta-regression included variables such as vaccine type, use of adjuvants, study design, and assessment of birth defects. This analysis revealed no significant differences in heterogeneity between subgroups.\u003c\/p\u003e\n\n\u003cp\u003eThe researchers also performed four types of sensitivity analyses, and the results were consistent across all of them for the primary results. These analyses tested whether the findings depended on studies with zero events, low-quality studies, any single study, or potentially missing studies due to publication bias.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\u003cp\u003eThis study provides updated evidence that influenza vaccination in early pregnancy does not increase the risk for birth defects. The finding is based on a very large body of evidence: 31 studies and more than 1.2 million pregnant people.\u003c\/p\u003e\n\n\u003cp\u003eThe adjusted analyses are especially reassuring. Adjusted analyses account for other factors that could influence birth defect risk, such as maternal age, smoking, and other health conditions. In these adjusted analyses, the odds ratios were 1.03 for both total birth defects and major birth defects. Both confidence intervals included 1.0, meaning the results are statistically consistent with no increased risk.\u003c\/p\u003e\n\n\u003cp\u003eThe consistency of the findings across subgroups adds further reassurance. The results did not change based on vaccine type, adjuvant use, how birth defects were assessed, or which control group was used. The results also held up across all sensitivity analyses.\u003c\/p\u003e\n\n\u003cp\u003eFor patients, the authors say this study may help alleviate concerns about vaccination safety during pregnancy and support informed decision-making. They also rate the level of evidence for birth defects as very low certainty, and they say causal inferences cannot be made. The first trimester is a vulnerable period of organ formation, and this study directly addresses that vulnerable window. The evidence supports the current recommendations from the CDC and ACOG that all pregnant people receive the influenza vaccine at any stage of pregnancy.\u003c\/p\u003e\n\n\u003cp\u003eInfluenza infection itself carries real risks during pregnancy. Pregnant people are more susceptible to infection and face a higher risk of adverse outcomes such as miscarriage and preterm birth. Vaccination protects the pregnant person and also protects infants under six months of age through antibodies passed across the placenta.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Study\u003c\/h2\u003e\n\u003cp\u003eThe study has several limitations that patients should understand. First, all included studies were observational. Observational studies can show associations but cannot prove cause and effect in the same way that randomized controlled trials can.\u003c\/p\u003e\n\n\u003cp\u003eSecond, the unadjusted analyses showed substantial heterogeneity for total birth defects (I² = 81.7%). This means the unadjusted results varied considerably between studies. The adjusted analyses, however, showed no heterogeneity (I² = 0.0%), which strengthens confidence in those findings.\u003c\/p\u003e\n\n\u003cp\u003eThird, the number of studies contributing adjusted data was smaller than the number contributing unadjusted data. Ten studies provided adjusted data for total birth defects, and 6 studies provided adjusted data for major birth defects. The adjusted estimates are therefore based on fewer studies, although the total participant numbers remain large.\u003c\/p\u003e\n\n\u003cp\u003eFourth, the researchers noted that earlier studies on this topic had relatively small sample sizes. Earlier studies also did not examine key variables such as the difference between pandemic monovalent and seasonal multivalent vaccines. This updated review addressed those gaps, but the underlying evidence still comes from observational studies.\u003c\/p\u003e\n\n\u003cp\u003eFifth, the methods used to assess birth defects varied across studies. Most studies used medical records, but some relied on self-reporting or a combination of sources. The researchers accounted for this variation in subgroup analyses, and the results remained consistent.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations for Pregnant People\u003c\/h2\u003e\n\u003cp\u003eBased on this study and current guidelines, pregnant people can be reassured that first-trimester influenza vaccination was not associated with an increased risk of birth defects. This reassurance rests on a body of evidence covering more than 1.2 million pregnancies.\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003eDiscuss influenza vaccination with your healthcare provider. The CDC and ACOG recommend vaccination at any stage of pregnancy, including the first trimester.\u003c\/li\u003e\n  \u003cli\u003eThis study directly examined first-trimester vaccination and found no increased risk of total or major birth defects.\u003c\/li\u003e\n  \u003cli\u003eUnderstand that influenza infection itself poses risks during pregnancy, including miscarriage and preterm birth. The authors note that, although causal inferences cannot be made, vaccination during pregnancy has the potential to contribute to the prevention of influenza-related complications.\u003c\/li\u003e\n  \u003cli\u003eRemember that vaccination during pregnancy also protects your baby during the first six months of life, before the baby is old enough to be vaccinated. Protective antibodies pass from mother to baby across the placenta.\u003c\/li\u003e\n  \u003cli\u003eAsk your provider about which vaccine type is appropriate for you. The vaccines in the included studies were all inactivated influenza vaccines.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eIf you have specific health conditions or previous pregnancy complications, talk with your healthcare provider about your individual situation. This study reports population-level findings, and your provider can help apply them to your personal health circumstances.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eDoes getting a flu shot in the first trimester raise the risk of birth defects?\u003c\/h3\u003e\n\u003cp\u003eIn a pooled analysis of 31 observational studies covering 1,223,024 pregnant people, first-trimester influenza vaccination was not linked to a higher risk of total birth defects (adjusted odds ratio 1.03, 95% CI 0.98–1.07) or major birth defects (adjusted odds ratio 1.03, 95% CI 0.98–1.09). Because both confidence intervals include 1.0, the results are consistent with no difference.\u003c\/p\u003e\n\u003ch3\u003eWhat does an adjusted odds ratio of 1.03 with a confidence interval of 0.98 to 1.07 mean?\u003c\/h3\u003e\n\u003cp\u003eAn odds ratio of 1.03 means the odds of a birth defect were about 3% higher in vaccinated people than in controls. The 95% confidence interval, 0.98 to 1.07, is the range of values compatible with the data. Because that range includes 1.0, the result is not statistically significant, meaning the data are consistent with no difference between groups.\u003c\/p\u003e\n\u003ch3\u003eWhich pregnant people were counted as vaccinated in the first trimester?\u003c\/h3\u003e\n\u003cp\u003eFirst-trimester vaccination meant receiving influenza vaccine from 0 to 13 weeks plus 6 days of gestation. People vaccinated in the second or third trimester, or not vaccinated during pregnancy, formed the control group. All vaccines in the included studies were inactivated influenza vaccines, and the studies covered both pandemic monovalent and seasonal trivalent or quadrivalent vaccines.\u003c\/p\u003e\n\u003ch3\u003eWere certain vaccine types or adjuvants linked to birth defects?\u003c\/h3\u003e\n\u003cp\u003eNo. Results were consistent across vaccine types (pandemic monovalent versus seasonal multivalent), across adjuvanted versus nonadjuvanted vaccines, across how birth defects were assessed, and across control group types. The findings also held in all four sensitivity analyses, including after removing lower-quality studies and after checking whether any single study drove the results.\u003c\/p\u003e\n\u003ch3\u003eDoes the flu vaccine protect the baby as well as the pregnant person?\u003c\/h3\u003e\n\u003cp\u003eVaccination during pregnancy effectively prevents influenza in expectant mothers. It also protects infants under six months of age, before they are old enough to be vaccinated, through protective antibodies passed across the placenta. Influenza infection itself carries real risks in pregnancy, including miscarriage and preterm birth, and pregnant people are more susceptible to infection than the general population.\u003c\/p\u003e\n\u003ch3\u003eWhat are the limitations of the evidence on first-trimester flu vaccination?\u003c\/h3\u003e\n\u003cp\u003eAll 31 included studies were observational, so they can show associations but cannot prove cause and effect the way randomized trials can. Unadjusted results for total birth defects varied considerably between studies, though adjusted results did not. Adjusted estimates came from fewer studies: 10 for total birth defects and 6 for major birth defects, though participant numbers remained large.\u003c\/p\u003e\n\u003ch3\u003eShould I delay flu vaccination because I am worried about birth defects?\u003c\/h3\u003e\n\u003cp\u003eThe CDC and ACOG recommend influenza vaccination at any stage of pregnancy, including the first trimester. The authors say these findings may help alleviate concerns about vaccination safety during pregnancy, but they rate the level of evidence for birth defects as very low certainty. Discuss timing and which vaccine type is appropriate with your healthcare provider, especially if you have specific health conditions or previous pregnancy complications, since these findings are population-level.\u003c\/p\u003e\n\u003ch3\u003eI'm pregnant and worried the flu shot in my first trimester could cause birth defects — when should I get a second opinion before deciding?\u003c\/h3\u003e\n\u003cp\u003eA second opinion is reasonable if you are weighing first-trimester influenza vaccination against birth-defect concerns, especially if you have a specific health condition or previous pregnancy complications. Pooled adjusted data from 31 studies and more than 1.2 million pregnant people show no increased risk of total birth defects (adjusted odds ratio 1.03, 95% CI 0.98–1.07) or major birth defects (1.03, 95% CI 0.98–1.09), with consistent results across vaccine types, adjuvants, assessment methods and control groups. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Maternal influenza vaccination during the first trimester of pregnancy and risk for birth defects: an updated systematic review and meta-analysis.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Wu Y, Liu C, Qian X, Zhou Y, Xiong Y.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e BMC Pregnancy and Childbirth (2026) 26:713. DOI: 10.1186\/s12884-026-09238-3\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor affiliations:\u003c\/strong\u003e School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; and Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Chinese Evidence-based Medicine Center, Sichuan University, Chengdu, Sichuan, China\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eReview registration:\u003c\/strong\u003e PROSPERO CRD42023450641\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding and access:\u003c\/strong\u003e This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research. 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