ADHD is one of the most common psychiatric disorders in children and adolescents. Altered functional connectivity has been associated with ADHD symptoms. This study aimed to investigate abnormal changes in the functional connectivity of resting-state brain networks (RSNs) among adolescent patients with different subtypes of ADHD.The data were obtained from the ADHD-200 Global Competition, including fMRI data from 88 ADHD patients  and 67 typically developing controls (TD-C). Group ICA was utilized to research aberrant brain functional connectivity within the different subtypes of ADHD.In comparison with the TD-C group, the ADHD-C group showed clusters of decreased functional connectivity in the left inferior occipital gyrus (p = 0.0041) and right superior occipital gyrus (p = 0.0011) of the dorsal attention network (DAN), supplementary motor area (p = 0.0036) of the executive control network (ECN), left supramarginal gyrus (p = 0.0081) of the salience network (SN), middle temporal gyrus (p = 0.0041), and superior medial frontal gyrus (p = 0.0055) of the default mode network (DMN), while the ADHD-I group showed decreased functional connectivity in the right superior parietal gyrus (p = 0.0017) of the DAN and left middle temporal gyrus (p = 0.0105) of the DMN. In comparison with the ADHD-I group, the ADHD-C group showed decreased functional connectivity in the superior temporal gyrus (p = 0.0062) of the AN, inferior temporal gyrus (p = 0.0016) of the DAN, and the dorsolateral superior frontal gyrus (p = 0.0082) of the DMN. All the clusters surviving at p < 0.05 (AlphaSim correction).The results suggested that decreased functional connectivity within the DMN and DAN was responsible, at least in part, for the symptom of inattention in ADHD-I patients. Similarly, we believed that the impaired functional connectivity within networks may contribute to the manifestations of ADHD-C patients, including inattention, hyperactivity/impulsivity, and unconscious movements. Attention-deficit/hyperactivity disorder (ADHD) has emerged as a common contributor to neuro developmental disorders as well as frequent psychological and behavioral problems among children . The gloIn previous studies, resting-state functional MRI (rs-fMRI) was widely used to examine the brain of ADHD patients , 10. In In the present study, group independent component analysis (ICA), a data-driven approach, was adopted to extract the components . ICA is http://fcon1000.projects.nitrc.org/indi/adhd200/index.html) and selected exclusively from the New York University (NYU) Child Study Center. In accordance with HIPAA guidelines and 1000 Functional Connectomes Project protocols, all datasets are anonymous, with no protected health information included. For both ADHD and TD subjects, the inclusion criteria were as follows: age of 7–17 years, no history of neurological disease, and no diagnosis of either schizophrenia or affective disorder, an image covering at least 95% of the brain, an IQ score > 80, and head movement less than 2.0. Subjects were enrolled if they were right-handed and their information was complete . Finally, fMRI data from a total of 155 volunteers aged between 7 and 17 years were collected, including 67 typically developing controls (TD-C), 56 ADHD-C patients, and 32 ADHD-I patients . IBM SPSS software  was used for statistical analysis. One-way analysis of variance was performed with age, ADHD index, verbal IQ, performance IQ, and Full IQ, and the Chi squared test was used to evaluate the differences in gender among the three groups. A p value of < 0.05 was considered statistically significant, as shown in Table Public fMRI data were downloaded from the ADHD-200 Global Competition  sequence with the following imaging parameters: repetition time (TR) = 2000 ms; echo time (TE) = 15 ms; flip angle (FA) = 90°; FOV reading = 240 mm; slice thickness = 4 mm; number of slices = 33; and voxel size = 3 × 3 × 4 mmhttp://rfmri.org/dpabi). The preprocessing steps were as follows: (1) remove the first 10 volumes to ensure that the BOLD signal was stable; (2) slice timing, correct the difference due to acquisition times between slices in the volume; (3) head motion correction; (4) normalization, register the data to the EPI standard template and resample it to 3.0 × 3.0 × 3.0 mm3; and (5) spatial smoothing with a 6-mm full width at half maximum (FWHM) Gaussian kernel [The original fMRI data were preprocessed using a public toolbox named DPABI  for all subjects, including ADHD patients and TD-C. This toolbox implements estimation of the independent components (ICs) on concatenated data of subject-specific spatial maps and time courses across subjects [We employed the ICA, a data-driven analysis technique , to idensubjects . First, subjects . The infThe RSN components were subsequently selected via an automated process that defines the components that most closely matched the RSNs for each individual subject, based on spatial correlation analyses with the RSNs templates. All templates represent regions that have repeatedly been implicated in the RSNs.https://www.nitrc.org/projects/wfu_pickatlas/) in the SPM toolbox based on centroid coordinates and radii. The component with the largest correlation coefficient was selected as the RSN we were interested in. A total of six components were identified. Figure There were six RSNs of interest, namely, the AN, DAN, DMN, ECN, SN, and SMN. All RSN templates were created with WFU_PickAtlas (http://restfmri.net/forum/RESTplusV1.2) was the toolbox of our choice for statistical analysis. In order to verify whether the six ICs differed among the three groups, analysis of variance (ANOVA) on ICs  was performed with the result of the one-sample t-test serving as an explicit mask, where age and gender were controlled as covariates. The differences between the groups of ICs were obtained by two-sample t-test  with the result of ANOVA serving as an explicit mask. Similarly, age and gender were eliminated as covariates. Finally, a Spearman correlation analysis was performed between the ADHD index and mean signals of ICs that we delineated as ROIs.On the basis of the number of original subjects, the selected ICs  were reclassified into three groups. The Resting-State fMRI Data Analysis Toolkit plus V1.2  of AN, inferior temporal gyrus (p = 0.0016) of DAN, as well as dorsolateral superior frontal gyrus (p = 0.0082) of DMN. However, an increase in the FC was found in the middle temporal gyrus (p = 0.0051) of DMN, as illustrated in Fig. 2 of AN, The above results have demonstrated a significant area of FC abnormalities in RSNs in ADHD patients. A Spearman correlation analysis was performed between ADHD index and the mean signals of ICs that we delineated as ROIs, in order to verify whether the ADHD indices of the two groups of ADHD patients were associated with FC abnormalities. All correlation analyses were performed in the ADHD-C and ADHD-I groups. An inverse relationship with the ADHD index was only found for the left supplementary motor area of ECN in the ADHD-C group . The results showed no significant difference (p > 0.05) after a multiple comparison correction.In this study, group ICA was performed and both subtypes of ADHD patients showed impaired FCs in major RSNs in comparison with TD-C. We found that the FCs of the DAN, ECN, SN, and DMN were significantly reduced in ADHD-C patients, including the right inferior occipital gyrus and the superior occipital gyrus of DAN, supplementary motor area of ECN, left supramarginal gyrus of SN, and middle temporal gyrus and superior medial frontal gyrus of DMN.Many previous studies have demonstrated abnormal functional connections within the DMN of ADHD patients, especially the temporal lobe , 28, 29.When comparing the ADHD-I to the TD-C group, we found a few regions showing enhanced FC, such as the supramarginal gyrus of AN and the precentral gyrus of SMN. Previous studies have shown that patients with ADHD were more sensitive to sound, which may be related to the enhanced FC in AN . Jean-ArDaniel von Rhein revealed that SN plays a role in supervision and decision when the brain processes external stimuli . The maiIn conclusion, group ICA allowed the use of interrelated analytical methods for evaluating FCs of ADHD in adolescents in this study. We found that these major RSNs in both subtypes of ADHD patients showed FC changes in comparison with the TD-C group, and FC differences were also observed between the two subtypes of ADHD patients. Our study elucidates the abnormal changes in the RSNs of different subtypes of adolescent ADHD patients, which may prove helpful for the management of adolescent ADHD patients. In the future, studies employing a multimodal imaging approach using techniques such as structural MRI, diffusion tensor imaging and fMRI, will be necessary to comprehensively investigate the brain changes in adolescents with ADHD. These further studies will contribute to the management and treatment of ADHD in adolescents.One of the limitations of our study was the absence of any psychological assessment of the cognitive parameters associated with ADHD. Moreover, the participant numbers in the three groups were substantially different, which was likely to have an impact on the results of statistical analysis. In addition, the six RSN templates were created by WFU_PickAtlas in the SPM toolbox directory based on centroid coordinates and radii. The differences between our templates and the actual anatomical RSNs would have also affected the accuracy of our results.


We examined the longitudinal predictors of electrophysiological and behavioral markers of inhibitory control in adolescence. Participants were 63 adolescent boys who have been followed since birth as part of a prospective longitudinal study on the developmental pathways to attention-deficit hyperactivity disorder (ADHD). At 17 years of age, they completed the stop-signal task (SST) while electroencephalography (EEG) was continuously recorded. Inhibitory control was evaluated by the stop-signal reaction time (SSRT) as well as by the amplitude of the event-related potential (ERP) component of N2 during successful inhibition. We found that higher inattention symptoms throughout childhood predicted reduced amplitude  of the N2 in adolescence. Furthermore, the N2 amplitude was longitudinally predicted by the early precursors of child familial risk for ADHD and early childhood temperament. Specifically, father’s inattention symptoms (measured in the child’s early infancy) and child’s effortful control at 36 months of age directly predicted the N2 amplitude in adolescence, even beyond the consistency of inattention symptoms throughout development. The SSRT was predicted by ADHD symptoms throughout childhood but not by the early precursors. Our findings emphasize the relevance of early familial and temperamental risk for ADHD to the prediction of a later dysfunction in inhibitory control. Attention-deficit hyperactivity disorder (ADHD) is early-onset and a chronic neurodevelopmental disorder , with anThe heterogeneity of ADHD is reflected in both its behavioral symptoms  and its Among the executive functions, one of the most consistent deficits associated with ADHD is in inhibitory control ,13. InhiAt the behavioral level, one of the most widely used measures of inhibitory control is the stop-signal task (SST), which is based on the theoretical horse-race model . The SSTThe association between behavioral performance in the SST and ADHD has been well established ,26,27 inAt the neurophysiological level, inhibitory control can be studied with a high degree of temporal resolution by recording event-related potentials (ERPs). This technique enables the identification of the precise timing of brain processes during cognitive tasks; this is especially beneficial in the case of inhibitory control, considering the absence of a behavioral response. The inhibitory control process in the SST has been mainly linked to the ERP component N2 , which iAlthough ADHD is considered a developmental disorder, its developmental course is not fully known, and, specifically, the developmental pathways leading to its core deficit of inhibitory control in adolescence are relatively uninvestigated. Adolescence is a period of rapid changes in brain maturation, accompanied by extensive behavioral and cognitive changes ,46, whicEvidence exists to support a relation between a familial risk for ADHD and child inhibitory control deficits ,55. An iFurthermore, in our longitudinal study, 24-month-old toddlers at high familial risk, based on their fathers’ ADHD symptoms, were rated by their parents as lower on temperamental effortful control  compared to a matched control group . Indeed,A few studies have examined the association between child temperamental effortful control and the N2 amplitude on inhibition trials in the Go/NoGo task ,68,69,70Familial risk for ADHD, reflected by parental ADHD symptoms ,55, and This study is part of a prospective longitudinal high-risk study on the developmental course of ADHD and its core neurocognitive deficits. We focused on the behavioral and electrophysiological aspects of inhibitory control in adolescence from a developmental perspective. Our first goal was to corroborate previous findings regarding the specificity of inattention symptoms to behavioral aspects of inhibitory control and to test whether these symptoms, measured several times throughout development, would also show specificity to the electrophysiological aspect of inhibitory control in adolescence. Secondly, we aimed to examine the contribution of familial and temperamental risk for ADHD  as early predictors of inhibitory control in adolescence. Based on the literature and previous results from our longitudinal study , we hypoM = 17.37 years, SD = 0.41, range 16.52–18.48) who took part in the Ben-Gurion Infant Developmental Study (BIDS) from birth. Recruitment to the prospective longitudinal study was conducted at the maternity ward of the Soroka Medical Center in Be’er Sheva, Israel. Families were recruited based on several inclusion criteria. First, because of the higher prevalence of ADHD among males, compared to females [M = 3296.07 g, SD = 419.75) and gestational age . The study included two-parent families; parents were either native-born or immigrants who studied in the country and spoke the local language. At the entrance to the longitudinal study, the mean age of parents was 29.95 years (SD = 4.90) for mothers and 33.65 years (SD = 5.44) for fathers. The mean number of years of education was 12.80 (SD = 1.72) for mothers and 12.32 (SD = 1.77) for fathers. Another inclusion criterion was based on paternal ADHD symptoms; at the hospital, fathers completed a yes/no format questionnaire that included 18 ADHD items from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DMS-IV) [Ns = 50–114, including participants who discontinued participation or who could not be reached) in any of the study variables ; all ts < |1.66|, ps > 0.09.Our sample consisted of 63 male adolescents  . In the (DMS-IV) . These cV = 0.40, p < 0.05.According to mothers’ reports, 20 (32%) participants were diagnosed with ADHD, at an average age of 8.76 years, by qualified medical professionals. A diagnostic process was not conducted as part of the study, and, therefore, we did not have accurate information regarding the specific presentation of symptoms ; furthermore, we did not have information regarding the updated status of diagnosis in adolescence. According to the Conners’ Rating Scales-Revised  reportedThe Conners’ Adult ADHD Rating Scale (CAARS)  was usedChild effortful control was measured at 36 months of age using the Children’s Behavior Questionnaire (CBQ) . We usedThe ADHD Rating Scale-IV  was usedThe Conners’ Rating Scales-Revised  for each symptom domain .ADHD symptom domains at 54 months and 7 years were significantly correlated; During a lab visit at 17 years of age, participants completed a computerized SST  while elA shortened version of the Raven’s Standard Progressive Matrices  was usedSD = 4.83, range = 23–49) for successful stop and 144.05  for successful go.EEG data during the SST were recorded from 128 scalp sites using EGI HydrocCel Geodesic Sensor Net (HCGSN) and system . The eleIn stop-signal locked ERP, there is some overlap with ERP activity arising from the previous go stimulus; although this activity may be suppressed, it is not entirely eliminated by the averaging process. One approach that can solve this problem is to calculate difference waves in which the go stimulus ERP is subtracted from the stop-signal ERP ,83. AccoThe first aim of the study was to examine the concurrent and longitudinal relation between inhibitory control and ADHD symptoms. This was examined with a series of regression models that were constructed hierarchically to examine the specificity of child ADHD symptoms domains to the electrophysiological and behavioral measures of inhibitory control in adolescence. The control variable of mother’s education was entered in step 1. As recommended by Brocki and colleagues  and WåhlAll procedures performed in studies involving human participants were in accordance with the ethical standards of the Ben-Gurion University of the Negev research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol of the study was approved by the Human Subjects Research Committee (1407-1).Informed consent was obtained from all individual participants included in the study.missing completely at random (MCAR), as indicated by a non-significant Little’s MCAR test, χ2(35) = 44.94, p = 0.12. Multiple imputations were conducted to handle the missing data for early childhood measures; 20 imputations were used to avoid a decrease in statistical power and to achieve an accurate estimation [Among the 57 participants with ERP data, two (3%) did not have data for father’s symptoms, and six (10%) did not have the CBQ data. The missing pattern was timation .rs < 0.20, ps > 0.15, except for mother’s years of education, which had a marginally significant correlation with adolescents’ N2 amplitude at age 17 years, r = −0.25, p = 0.06; therefore, it was controlled in further analyses. There were no outliers beyond the range of 3.5 SD above or below the average of each variable. Descriptive statistics of SST measures are presented in Parental background variables  and adolescent background variables  did not correlate with any of the dependent variables, The intercorrelations among study variables are presented in F = 2.96, MSE = 3.65, p < 0.05, η2p = 0.14, in the inattention domain. Participants in the lower quartile of inattention symptoms showed larger negative amplitudes than those in the other three quartiles together, F = 7.94, MSE = 3.65, p < 0.01, η2p = 0.13; no significant differences were found between the top three quartiles. No significant effects were found for the quartiles of hyperactivity-impulsivity symptoms. The quartiles that were used to produce relatively equal-sized groups were: T scores for the lower quartile , which were 40–47 for inattention (n = 14) and 43–49 for hyperactivity-impulsivity symptoms (n = 14); T scores for the upper quartile  were 59-77 for inattention (n = 12) and 68-87 for hyperactivity-impulsivity symptoms (n = 18). It should be mentioned that these analyses were conducted using ANCOVAs, controlling for mothers’ education. See Although the linear correlation between the N2 mean amplitude and concurrent symptoms was not significant, when dividing each symptoms domain into quartiles, there was a main effect for group, p < 0.05). The models were significant, and adjusted R2 was 11%, F = 3.24, p < 0.05, for the prediction of the N2 amplitude and 10%, F = 2.81, p < 0.05, for the prediction of the SSRT.To examine the longitudinal predictions of childhood symptoms domains  to the behavioral and electrophysiological markers of inhibitory control at 17 years of age, we computed hierarchical regressions models for the prediction of the SSRT and the N2 mean amplitude measures. The results are presented in β = −0.06, z = −0.86, p = 0.40 and β = 0.03, z = 0.82, p = 0.41 for childhood effortful control and paternal inattention, respectively. The entire path model explained 27% of the variance of inattention symptoms throughout childhood and 29% of the variance of the N2 amplitude; it showed a good fit to the data with a comparative fit index (CFI) of 1, a goodness-of-fit (GFI) of 0.99, a root mean squared error of approximation (RMSEA) lower than 0.01, and a standardized root mean squared residual indices (SRMR) of 0.02. ERP waveforms and topographic maps illustrating the N2 for adolescents with high and low levels of childhood effortful control and paternal inattention symptoms are shown in β = −0.33, z = −2.71, p < 0.01 and β = 0.35, z = 2.94, p < 0.01, respectively. The early precursors did not predict the SSRT in adolescence.A path analysis was constructed to examine the direct paths of early precursors of ADHD  and their indirect paths through childhood inattention symptoms to the mean N2 amplitude in adolescence. As seen in β = −0.29, z = 2.22, p < 0.05. The subscales of inhibition, low-intensity pleasure, and perceptual sensitivity did not predict the N2 amplitude in adolescence.To examine which aspects of child temperamental effortful control predicted the N2 amplitude, we conducted similar path analyses, as presented in Using a prospective longitudinal design, we examined the utility of early childhood familial and temperamental risk factors of ADHD as predictors of behavioral and electrophysiological markers of inhibitory control in adolescence. First, we found that a reduced amplitude of the N2 component during successful inhibition  was predicted by higher levels of inattention symptoms throughout childhood and not by hyperactivity-impulsivity symptoms. Childhood ADHD symptoms predicted the SSRT, but the effect was not specific to inattention or hyperactivity-impulsivity symptoms. Second, we found that paternal inattention symptoms, measured a few months after the child’s birth, and child temperamental effortful control, measured at 36 months of age, directly predicted individual differences in the N2 amplitude of adolescents. Direct pathways of predictions were found above and beyond the indirect pathway via the development of inattention symptoms. Adolescents’ SSRT was not predicted by the early precursors. These findings and their interpretations are discussed in detail.As a first stage, we tested the basic association between the behavioral and electrophysiological markers of inhibitory control and ADHD symptom domains; this was tested separately for concurrent and childhood symptoms. We found that higher levels of inattention symptoms throughout childhood were associated with reduced N2 amplitude during successful inhibition in adolescence. Such a linear correlation was not found with concurrent symptoms; however, the adolescents with the lowest level of inattention symptoms displayed larger N2 amplitudes compared to the rest. Our results were consistent with previous findings on the N2 in the SST, demonstrating a reduced amplitude among children diagnosed with ADHD compared to controls ,32,33,34First-order correlations between the N2 amplitude and the SSRT were found with both ADHD symptom domains in childhood. However, after accounting for the high overlap between the two domains, only inattention symptoms were predictive of the N2 amplitude, and neither of them was predictive of the SSRT (indicating the lack of specificity to either of the symptom domains). This emphasized the need to subtract the effect of this overlap when examining the specificity of ADHD symptom domains . TheInterestingly, this specificity was also found for paternal symptoms; paternal inattention symptoms predicted adolescent N2 amplitude, measured almost 17 years later. Our results suggested a plausible parent-of-origin effect in relation to adolescent inhibitory control because it was found that only paternal inattention symptoms, but not maternal symptoms, contributed to the prediction of adolescent N2 amplitude. Such an effect was also found in an earlier assessment in our study because only paternal inattention symptoms were predictive of child SSRT at 5 years of age . ConsistWe also found that temperamental effortful control at 36 months of age was predictive of the N2 amplitude at 17 years of age because lower levels of effortful control were related to a reduced N2 amplitude on successful inhibition. Child effortful control had a direct effect on the prediction of the N2 amplitude; this was above and beyond inattention symptoms (throughout childhood and in adolescence) and child familial risk of ADHD. This means that even after accounting for the part that ADHD  explains in the variance of the N2 amplitude, child effortful control still explained a unique part in this variance. This indicated that this relation was not derived from the overlap between effortful control and N2 amplitude with ADHD symptomatology throughout development. Such a longitudinal relation reflected the consistency of deficits in aspects of self-regulation throughout development. This was in accordance with previous cross-sectional studies on typically developing children, which showed concurrent associations between aspects of temperamental effortful control and the N2 amplitude in response to inhibition, using the Go/NoGo task , or a coThe path analysis demonstrated that both paternal inattention and child effortful control contributed to the prediction of inattention symptoms throughout childhood; however, the contribution of inattention symptoms to the prediction of the N2 amplitude was no longer significant. Inattention symptoms did not explain a unique additional part of the variance, above and beyond the part that was already explained by the early precursors. It should be considered that when we tested the contribution of ADHD symptoms in the more basic model before we added the early precursors, we found a significant modest effect of inattention symptoms throughout childhood. Still, a large part of the N2 variance was not explained by child symptomatology because individuals who exhibit deficits in inhibitory control at the brain activity level do not necessarily exhibit symptoms of ADHD. It seems that the early precursors were able to directly explain the part of the N2 variance that was explained by inattention symptoms, as well as some of the variance that was not explained by these symptoms. It is possible that the genetic and environmental risk, inherent in paternal symptomatology and child temperament, was able to predict inhibitory control difficulties of those who were at some level of risk for ADHD but did not exhibit a high level of inattention symptoms throughout development. This was consistent with evidence suggesting poor inhibitory control among non-affected family members of individuals with ADHD as compared to controls ,58. ThisIn a broader sense, deficits in self-regulatory skills in childhood and adolescence, including inhibitory control, are associated with a wide range of negative outcomes during development ,93,94,95The main aim of the study was to test the contribution of early familial and temperamental risk for ADHD to the prediction of inhibitory control in adolescence. Because of the overlap between early precursors, ADHD symptoms, and inhibitory control, it was necessary to examine whether the early precursors were directly related to inhibitory control or whether the relation actually derived from the overlap between inhibitory control and ADHD symptomatology. We found that the contributions of the early precursors to the electrophysiological aspect of inhibitory control were direct. Despite the statistical model that was tested and presented in Although SSRT was found to be related to N2 amplitude and ADHD symptoms in childhood, in contrast with previous behavioral studies ,27, we dOur study has some limitations that should be considered. First, our sample was limited to males. The decision to use a male-only sample was made when the study began, about 20 years ago, based on the higher prevalence of ADHD among males compared to females , and to The uniqueness of the study is its prospective longitudinal design, which enabled us to test how early childhood risk factors of ADHD contributed to the development of the electrophysiological signature of inhibitory control in adolescence. Our results highlight the close association between the brain activity of adolescents during inhibition and the development of attentional capacities on several levels. First, higher levels of inattention symptoms throughout childhood were found to predict a dysfunction in the brain mechanism involved in inhibition, as reflected by a reduced N2 amplitude in adolescence. Beyond that, paternal inattention as well as early childhood effortful control, particularly attentional focusing, predicted this electrophysiological response during inhibition, measured more than a decade later. These factors were also involved in the development of child inattention symptoms, but their predictions of adolescent brain activity were direct. These risk factors may represent an enduring biological risk, which could be related to the brain mechanism involved in inhibition. Our findings emphasize that an early deficit in self-regulatory skills may persist throughout development; early detection of children at risk for inhibitory control deficits could contribute to early intervention programs designed to mitigate future negative outcomes from such a deficit.


Is exposure to endocrine-disrupting chemicals during adolescence a risk factor for behaviors associated with attention-deficit/hyperactivity disorder (ADHD)?In this cross-sectional analysis of data from 205 adolescents participating in a prospective birth cohort study, exposure to select phthalates was associated with an increased risk of ADHD-related behaviors. Associations were strongest for phthalates with antiandrogenic activity.These findings support the potential importance of exposures to endocrine-disrupting chemicals, especially phthalates, during adolescence as correlates of ADHD-related behaviors. Attention-deficit/hyperactivity disorder (ADHD) is the most common childhood neurobehavioral disorder. Studies suggest that prenatal and early childhood exposure to endocrine-disrupting chemicals may be associated with ADHD, but the association during adolescence has not been studied to date.To evaluate the association between exposure to select endocrine-disrupting chemicals during adolescence and ADHD-related behaviors.For this cross-sectional analysis, data were collected from 205 adolescents in the New Bedford Cohort, an ongoing prospective birth cohort, between June 18, 2011, and June 10, 2014. The adolescents provided spot urine samples and underwent neurodevelopmental testing. Statistical analyses performed from January 15 to December 31, 2019, used a repeated-measures analysis with multivariate modified Poisson models to estimate the adjusted relative risk of ADHD-related behaviors associated with exposure to endocrine-disrupting chemicals.Urinary biomarker concentrations of endocrine-disrupting chemicals or their metabolites, including phthalates, parabens, phenols, and triclocarban, were quantified. Summary exposure measures were created, combining biomarker concentrations of chemicals with a shared mechanism of action, exposure pathway, or chemical class.Behaviors related to ADHD were assessed with up to 14 indices from self-, parent-, and teacher-completed behavioral checklists using validated and standardized instruments; specifically, the Conners Attention Deficit Scale and the Behavior Assessment System for Children, Second Edition. Scores on each index were dichotomized to identify those with evidence of a significant behavioral problem, defined by each scale’s interpretive guidelines.Among the 205 participants, the mean (SD) age at assessment was 15.3 (0.7) years, with 112 girls (55%) and 124 non-Hispanic White participants (61%). The median urine concentrations were 0.45 μmol/L of Σantiandrogenic phthalates, 0.13 μmol/L of ΣDEHP metabolites, 0.49 μmol/L of Σpersonal care product phthalates, 0.35 μmol/L of Σparabens, 0.02 μmol/L of Σbisphenols, and 0.02 μmol/L of Σdichlorophenols. A total of 82 (40%) had scores consistent with a significant behavioral problem, whereas 39 (19%) had an ADHD diagnosis. Each 2-fold increase in the sum of antiandrogenic phthalate concentrations was associated with a 1.34  increase in the risk of significant ADHD-related behavior problems, whereas a 2-fold increase in the sum of dichlorophenols was associated with a 1.15  increased risk. These associations tended to be stronger in male participants, but comparisons of sex-specific differences were imprecise.Endocrine-disrupting chemicals are used in a wide variety of consumer products resulting in ubiquitous exposure. The study findings suggest that exposure to some of these chemicals, particularly certain phthalates, during adolescence may be associated with behaviors characteristic of ADHD. This cross-sectional analysis evaluates the association between exposure to select endocrine-disrupting chemicals during adolescence and attention-deficit/hyperactivity (ADHD)–related behaviors. Similar to the prenatal period, adolescence is a critical time for brain development, characterized by structural and functional changes in the brain as well as the onset of behavioral problems, some of which may be due to hormonal changes.14 As such, exposure to EDCs during adolescence may be particularly detrimental.There is growing evidence that exposure to endocrine-disrupting chemicals (EDCs), such as phthalates and phenols, may be associated with ADHD.The objective of this study is to examine the association of adolescent exposure to EDCs, specifically phthalates, phenols, and triclocarban, with ADHD-related behaviors. We hypothesize that exposure to certain EDCs during adolescence is particularly detrimental to adolescent behavior given the rapid brain development that occurs during this time.15 The original aim of the study was to examine the association of prenatal organochlorine and metal exposures with subsequent neurodevelopment among children living near the New Bedford Harbor Superfund site. Eligibility requirements included newborns who were vaginally delivered to mothers who were at least 18 years of age and who were available for neonatal examination. In-person neurodevelopmental testing was performed when participants were approximately 15 years of age between 2008 and 2014. Of the 788 newborns enrolled in the New Bedford Cohort, 660 (84%) met eligibility criteria  for these assessments and, of those newborns, 528 (80%) completed assessments. Midway through the 15-year follow-up, the study added assessment of exposure to EDCs. We invited the 252 participants who were evaluated in this last half of the study to provide spot urine samples at 2 points: during neurodevelopmental assessments and approximately 1 week later   reporting guideline. The study research protocol was reviewed and approved by the human participants committee of the Brigham and Women’s Hospital . Written informed parental consent and child assent were obtained from participants. The analysis of deidentified specimens at the Centers for Disease Control and Prevention (CDC) laboratory  was determined not to constitute engagement in human participants research.We analyzed data from the New Bedford Cohort, a prospective birth cohort of mother-infant pairs recruited after delivery at a New Bedford, Massachusetts, hospital between 1993 and 1998.16 In brief, of the 252 adolescents invited to provide urine samples, 205 (81%) provided at least 1 sample. Urine samples were collected in sterile polypropylene cups and frozen until processing and analysis.16 It was not possible to analyze all urine specimens, owing to resource limitations; of the 144 adolescents (57%) who provided 2 samples, 60 had each sample analyzed separately, and the mean concentration was used in analyses. For the remaining 84, equal volumes of the 2 samples were pooled for analysis.16 Specific gravity was measured using a digital refractometer .Urine sample collection and analysis have been described elsewhere.20 Batch 1 included 11 phthalate metabolites and 8 phenols. Five additional biomarkers of phthalates or the phthalate substitute cyclohexane-1,2-dicarboxylic acid, monohydroxy isononyl ester (MHINCH), 3 additional phenols, and triclocarban were measured in batch 2 (Urine concentrations of 28 biomarkers were quantified at the CDC in 2 batches (2012 and 2016), based on the timing of collection. batch 2 .16Because batch 1 analyses did not include all biomarkers, urinary concentrations of all analytes were available for 178 participants (87%), with the remaining 27 participants missing concentrations of MHINCH, monohydroxyisobutyl phthalate (MHiBP), monoisononyl phthalate (MNP), monohydroxybutyl phthalate (MHBP), bisphenol F (BPF), bisphenol S (BPS), ethylparaben, and triclocarban. The limits of detection for the target analytes ranged from 0.2 to 2.3 μg/L; for concentrations less than the limit of detection, instrument readings were used in data analyses. The study-specific urine quality assurance and quality control samples for both between-batch and within-batch analyses demonstrated the excellent reproducibility of the analytic chemistry methods used.16 the molar sum (Σ) of 11 phthalate metabolites derived from antiandrogenic parent compounds was created to estimate Σantiandrogenic phthalates (in units of micromoles per liter): mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethylhexyl phthalate (MEHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-n-butyl phthalate (MBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), MHiBP, monocarboxyoctyl phthalate (MCOP), MNP, and MHBP.23 Summary measures for phthalates found in personal care products  was the molar sum of monoethyl phthalate (MEP), MBP, MHBP, MiBP, and MHiBP; the sum of di(2-ethylhexyl) phthalate (DEHP) metabolites  was the molar sum of MECPP, MEHHP, MEOHP, and MEHP; total parabens  was the molar sum of butyl, ethyl, methyl, and propyl paraben; total bisphenols  was the molar sum of bisphenol A (BPA) and its replacements BPF and BPS; and total dichlorophenols  was the molar sum of 2,4-dichlorophenol and 2,5-dichlorophenol.Because people are routinely exposed to multiple EDCs, we created summary exposure measures by combining biomarker concentrations for chemicals with a shared mechanism of action, exposure pathway, or chemical class. As described elsewhere,25 Both instruments have excellent internal reliability, with coefficient α values of 0.85 to 0.96 for the CADS and 0.74 to 0.95 for the BASC-2 , depending on the reporter. The BASC-2 scales are moderately correlated (r ∼ 0.5-0.6) with the Conners ADHD index, which, in turn, has excellent discriminant validity for ADHD diagnosis.25 Parents and adolescents completed these checklists at the study visit and first urine sample collection, while teachers completed them a median (SD) of 2.5 (6.6) months after the first urine sample collection. The BASC-2 consists of 139 to 176 questions, and the CADS consists of 14 to 15 questions, depending on the reporter. For each question, the frequency of adverse behavior is ranked using a 4-point Likert scale. Responses generate composite behavioral indices expressed as age- and sex-adjusted T-scores standardized to a mean (SD) of 50 (10), where a higher score indicates more adverse behavior. These measures generate 14 ADHD-related behavior indices. From the BASC-2, we included indices of inattention , hyperactivity , and executive function (teacher- and parent-reported). From the CADS parent and teacher reports, we included indices for inattention and hyperactivity based on Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic criteria and a CADS index of overall ADHD behaviors. All 205 adolescents with exposure data had at least 1 outcome measure, 204 (99.5%) had parent- and self-completed checklists, and 173 (84%) had teacher-completed checklists.Attention-deficit/hyperactivity disorder–related behaviors were assessed using validated behavioral checklists from the Behavior Assessment System for Children, Second Edition  and Conners Attention Deficit Scale .Data on parental demographic charateristics , health history, and tobacco use during pregnancy were collected in a questionnaire administered to mothers approximately 2 weeks after delivery. When the child was 15 years of age, the data on demographic characteristics, smoking habits, and child medical history  were updated via medical record reviews and questionnaires. Self-reported adolescent tobacco, alcohol, and marijuana use was ascertained with the CDC Youth Risk Behavior Survey. Umbilical cord serum levels of polychlorinated biphenyls and dichlorodiphenyldichloroethylene were used as biomarkers of prenatal organochlorine exposures. Childhood blood lead levels were abstracted from medical records of lead exposure screening; the maximum concentration between 12 and 36 months of age was calculated.z scores were calculated using CDC US reference data.26Using a structured diary, adolescents recorded food consumption and personal care product use for the 24 hours prior to urine sample collection. Diary data were used to estimate exposure risk factors during that 24-hour period, including the number of personal care products used and caffeinated beverages consumed, as well as the amount of fast food or canned food consumed. Height and weight were measured at the time of urine sample collection, and body mass index 2 transformation of urinary biomarker concentrations. We dichotomized outcomes at the 98th percentile, which BASC-2 and CADS guidelines define as indicative of significant behavioral problems. To leverage the multiple indices of ADHD-related behavior, maximize power, and avoid multiple comparisons, we used a repeated-measures analysis design, considering each of the 14 binary indices as a repeated measure reflecting a single underlying outcome.28 We used multivariate modified Poisson models with robust error variance and an independent working correlation that can accommodate missing behavioral scores, so participants with at least 1 behavioral measure were included. Analyses were performed using SAS, version 9.4 (SAS Institute Inc).Statistical analyses were performed from January 15 to December 31, 2019. Regression diagnostics supported logWe examined whether a child’s sex modified the association between urinary biomarker concentrations and ADHD-related behavior. In secondary analyses, we dichotomized outcomes at the 85th percentile, indicating a possible significant behavior problem. We also considered individual chemicals not included in summary exposure measures , as well as the individual chemicals that comprised the summary measures.29All models included the child’s sex and mean age at completion of BASC-2 and CADS to adjust for fundamental determinants of behavior, urine-specific gravity to account for urine dilution, and an indicator for ADHD measure. We then used prior literature to inform a directed acyclic graph to select other covariates, including the child’s race/ethnicity (non-Hispanic White vs other) and the following maternal characteristics at the time of delivery: age (as a continuous variable), marital status (married vs unmarried), educational level (<high school vs ≥high school), annual household income (<$20 000 vs ≥$20 000), and smoking during pregnancy (yes or no).30Because not all biomarkers were measured in the first batch of urine samples, some biomarker measures were missing for 27 participants, and some covariate information was missing for 14 participants; thus, our complete case analyses had a sample size of 164 to 190 depending on the urine biomarker measure. In a sensitivity analysis, we imputed missing values  based on 20 imputations using models with all covariates, behavioral outcomes, and biomarker concentrations in this analysis.We performed additional sensitivity analyses, including adjusting for umbilical cord serum polychlorinated biphenyls and dichlorodiphenyldichloroethylene, and adjusting for 12-month to 36-month maximum blood lead levels, because exposure to these chemicals hase been associated with ADHD-related behaviors in the New Bedford Cohort. We adjusted for whether adolescents had smoked cigarettes in the past 30 days or ever tried alcohol or marijuana (n = 60). We also conducted an unadjusted analysis and analyses separately examining measures reflecting attention vs hyperactivity and impulsivity problems, adjusting for factors associated with increased EDC exposure risk, adjusting for body mass index, adjusting for a family history (parent or sibling) of mental illness (n = 86), adjusting for diagnosis of behavioral problems other than ADHD (n = 74), removing those with a diagnosis of ADHD (n = 39), removing those taking prescription medication for behavioral problems (n = 22), and removing siblings (n = 14). We removed individual BASC-2 behavior measures (12 indices) with instrument validity indicators that suggested a negative or positive bias or lack of internal consistency.The mean (SD) age of the 205 participants at assessment was 15.3 (0.7) years, with 112 girls (55%) and 124 non-Hispanic White participants (61%). A substantial proportion of study adolescents were born to mothers who, at the time of delivery, were unmarried (87 [42%]), had less than a high school education (30 [15%]), or had annual household incomes less than $20 000 (66 [32%]) . Compare31The median urine concentrations were 0.45 μmol/L of Σantiandrogenic phthalates, 0.13 μmol/L of ΣDEHP metabolites, 0.49 μmol/L of Σpersonal care product phthalates, 0.35 μmol/L of Σparabens, 0.02 μmol/L of Σbisphenols, and 0.02 μmol/L of Σdichlorophenols . Individ1Of the 205 adolescents in this analysis, 82 (40%) had scores consistent with a significant behavioral problem as defined by at least 1 BASC-2 or CADS ADHD-related measure , whereasIn covariate-adjusted models, summary measures of phthalates were consistently associated with an increased risk of significant ADHD-related behavior problems ; Table 4P = .002 for interaction), in which a 2-fold increase corresponded to a 1.62  increased risk of significant ADHD-related behavior problems in male adolescents compared with a 1.06  increased risk in female adolescents  . HoweverWhen considering the more inclusive threshold for those with possible significant behavioral problems (>85th percentile), we observed similar, albeit slightly attenuated, findings. For example, each 2-fold increase in Σantiandrogenic phthalates was associated with a 1.21  increased risk of possible significant (vs 1.34 for clearly significant) ADHD-related behavior problems , and thiAssociations were similar, but more precise, in models imputing missing data .32 Experimental animal studies also support the potential for EDC exposures to be associated with adverse behavior in adolescence, including behaviors consistent with ADHD.36 Furthermore, there is well-established evidence demonstrating the unique association that neurotoxicant exposures  during adolescence have with adverse behavior.38Previous studies have reported associations of prenatal and early postnatal exposure to phthalates and BPA with an increase in ADHD-related behaviors. However, to our knowledge, no other published studies have analyzed associations between adolescent EDC biomarker concentrations and ADHD-related behaviors. Adolescence is a critical period for brain development and may be another time of heightened vulnerability to EDC exposure. Several cross-sectional studies  have reported associations between increased urinary phthalate and BPA concentrations and ADHD-related behaviors.This analysis focused on ADHD-related behaviors as opposed to clinical ADHD diagnosis. By relying on multiple indices of ADHD-related behavior (from the BASC-2 and CADS) from multiple observers , we were able to leverage a uniquely comprehensive characterization of adolescent behavior, including behaviors that can vary over time  and thus may be susceptible to variations in exposure risk factors. In particular, combining information from these multiple measures increased the power of our analysis, resulting in more stable estimates of association than would have been possible by examining each behavioral measure individually. In addition, by expressing multiple measures as a single outcome, we did not induce the statistical issues associated with multiple comparisons.42 However, adjustments for these factors did not affect associations, suggesting that reverse causation from these habits was unlikely. Furthermore, excluding adolescents with a diagnosis of ADHD enhanced the existing associations (eTable 4 in the 44 In addition, participants were from a small geographical region, which may potentially affect the generalizability of our findings.This study has some limitations. The assessed EDCs have short elimination half-lives, as well as short-term variability in exposure, resulting in the potential for nondifferential exposure misclassification, which could bias results toward the null. However, our study collected urine samples at 2 different times from most participants, allowing us to better characterize each participant’s mean or usual exposure. Given the cross-sectional design of this analysis, another challenge is the potential for reverse causation, such that existing behavioral problems may alter habits that enhance EDC exposure via changes in, for instance, diet, substance use, and/or personal care product use.45 The identification of modifiable risk factors for ADHD is of great public health importance. These findings contribute new insights into the potential detrimental neurobehavioral outcomes of EDC exposure during adolescence.Our results support the importance of adolescent exposure to EDCs, particularly phthalates, as a potential risk factor for significant ADHD-related behavior problems. Attention-deficit/hyperactivity disorder is a common and costly neurobehavioral disorder; US health care and education expenditures associated with ADHD in children and adolescents are estimated to be $38 billion to $72 billion annually, while costs associated with ADHD in adults, including lost wages, are much higher, ranging from $143 billion to $266 billion annually.


Releasing that component from its polymer efficiently and economically is a serious challenge, but a currently low‐availability yet potentially valuable pharmaceutical, nutraceutical, and agricultural‐chemical product is suddenly recognized as being accessible in huge quantities.Tricin's discovery in monocot lignins also added to the long‐appreciated realization that grasses, and commelinid monocots in general, are special in the plant kingdom. For evolutionary reasons about which we can only superficially speculate, grasses have at least four notable plant cell wall traits, none of which is unique but their combination is striking. 1) Commelinids have ferulates  Gra Commelinn Ralph, . p‐Couma(Medicago sativa) and its related M. truncatula, are rare dicots in possessing tricin in their lignins. The research groups involved have built upon substantial work on tricin in grasses, well covered in the paper by ortho to the B‐ring phenol  of the parent flavonoid naringenin to produce tricin as the ultimate product (Fig. et al., It is with this background that we come back to the presence of tricin in dicots. As the paper in question notes, alfalfa uct Fig. . The autThe ‘new’ hydroxylase genes/enzymes revealed in


Background: A policy to extend funding of maternal pregnancy influenza and pertussis vaccinations to community pharmacies could address low pregnancy vaccine uptake. The policy has been implemented in one region in New Zealand. This study explored the views and experiences of women eligible for the vaccines and health care professionals regarding funded maternal vaccinations in pharmacy. Methods: Women in late pregnancy or with an infant, and midwives, pharmacists, and general practice staff were selected purposively and interviewed regarding maternal vaccinations and the new policy, including their awareness and views of the funded vaccinations in pharmacies, and how this policy worked in practice. Enablers and barriers to vaccination by pharmacists were explored. Interviews were transcribed and analysed using a framework approach. Results: Fifty-three interviews were conducted. Most women and health care professionals viewed funded maternal vaccinations in pharmacies positively with respect to increasing awareness and providing delivery options. Many women received messages from pharmacies. Most pharmacies used posters, leaflets and/or verbal explanation to pregnant women to raise awareness of the vaccinations. Not all pharmacies provided these vaccinations, and frontline staff could help to raise awareness. Conclusion: Funded maternal vaccinations in pharmacies are generally well accepted and provide an opportunity to increase uptake and prevent disease.  Immunisation during pregnancy is a more recent addition to national immunisation schedules that aims to reduce mortality and morbidity from vaccine-preventable diseases during pregnancy and early infancy. Pertussis (whooping cough) causes hospitalisations and deaths, particularly of infants who are too young to have completed their primary series of pertussis vaccination ,2,3. In Influenza infection during pregnancy is associated with adverse fetal outcomes, and with an increased risk of influenza-associated mortality and morbidity for pregnant women compared with the general population . InfluenTherefore, maternal vaccinations during pregnancy are recommended in many developed countries ,18,19. HIt has been proposed that pharmacy recommendations or funded administration in pharmacy of vaccinations during pregnancy could increase awareness and uptake ,22,30. IAlthough pharmacy administration of vaccines is associated with increased uptake ,33, pharThe aim of this study was to explore the effect of funding maternal Tdap and influenza vaccinations through community pharmacies on accessibility and uptake, the awareness and views of health professionals and women of this service, the experience of women in using this service, and barriers and enablers to uptake. This paper presents the qualitative findings related to funded maternal vaccinations during pregnancy in pharmacy. This qualitative study sought a range of views on vaccination during pregnancy, including the funding of these through pharmacy, from users, potential users, and health care providers. The study was conducted in New Zealand with ethical approval granted by the NZ Ministry of Health Northern B Health and Disability Ethics Committee (18/NTB/43). The NZ birth cohort is approximately 60,000 births per year. Uptake of pertussis vaccine during pregnancy has been low in NZ , approxiIn NZ, most women are enrolled with a general practice for primary health care, which includes a free antenatal visit. Women who are not enrolled with a general practice can still attend a general practice (unless the practice is full up) but pay more. However, pregnant women then usually choose a lead maternity carer (LMC) for their pregnancy and birth care and for infant care up to age six weeks, when the first dose of infant vaccinations are due. The LMC is usually a midwife working independently or (less frequently) a hospital midwife, available without charge, and based at a public hospital in one of the 20 District Health Board (DHB) regions in NZ . Women rIn NZ, maternal doses of pertussis and influenza vaccine during pregnancy have been government funded (completely free for the patient) through general practice and hospitals nationwide since 2010 (influenza)  and 2013The vaccine administration fee paid by the government to general practice is NZ$21.37 exclusive of goods and services tax (US$13.52), and to pharmacy  is NZ$19.57 exclusive of tax (US$12.39). The influenza vaccine cost is NZ$9 excluding tax (US$5.70) and the pertussis vaccine price paid by the government is confidential. General practice and pharmacy purchase the influenza vaccine and are reimbursed. General practice is provided with government-paid pertussis vaccine, but for the Waikato project pharmacy is reimbursed. Typically, an appointment would be required at the general practice to have the vaccination administered, and general practices are usually only open on weekdays. Pharmacies usually require no appointment for vaccinations, and many pharmacies are open six days a week, with some pharmacies open until late at night, and on Sundays. There is no administration fee charged to the recipient for the vaccination at any venue.To provide vaccinations in New Zealand, a pharmacist must have successfully completed an approved vaccinator course, been assessed administering two vaccinations, hold a current annual practising certificate, and have a current cardio-pulmonary resuscitation certificate . They muTraining and promotion were used to support the delivery of these maternal vaccinations at pharmacies. An educational evening was held for pharmacists in Waikato in October 2016. Each pharmacy (whether vaccinating or not) received two telephone calls with messages about maternal vaccinations, posters promoting free maternal vaccinations in pharmacy and general practice, and a key facts card on vaccinations during pregnancy for staff and could receive t-shirts promoting vaccination during pregnancy. Local consumer media wrote about the initiative. Social media messages were released aimed at female consumers and promoting maternal vaccinations and informing women that free vaccinations during pregnancy were available from pharmacies and general practices. Pharmacies with social media pages were emailed links that they could use to help the campaign. Waikato members of the NZ College of Midwives received two email messages regarding the availability of vaccinations for pregnant women in community pharmacies, including a list of pharmacies offering vaccines. Posters about funded maternal vaccinations in pharmacies and general practices were sent to hospitals and offered to midwives.Within the Waikato DHB region resides a population of approximately 420,000 people—23% of whom are Māori, 10% Asian, 3% Pacific peoples and 64% of other ethnicities, predominantly NZ European . There iSemi-structured interviews were conducted in the Waikato District Health Board area in November 2018 or late January until early May 2019. Eligible participants were from four groups: women who were pregnant or had a young infant (referred to as “women participants”); midwives; community pharmacists; and staff working in general practices. We planned to interview 18–20 women, intending for at least half to be of Māori ethnicity, and 10–12 participants from each of three groups: midwives, community pharmacists and general practice staff. Participants from each of the four groups were recruited with the intention to ensure that a wide range of experiences and perspectives and focus particularly on high-need areas and Māori. Half of the Māori women were recruited through the pharmacy the interviewer was working in, and the rest were recruited and interviewed on a Saturday at an extended hours city pharmacy with a large catchment. The other women were recruited through pharmacists and a midwife. We sought to enrol women with variation in age, geographical location, maternal vaccination status, place of vaccination and number of previous pregnancies. All participants needed sufficient English to be interviewed.Health care providers were selected for variation in their experience and geographical location, focusing most on rural and lower socioeconomic areas, and areas with proportionately larger Māori populations. We sought Māori health care providers, owner and non-owner GPs and pharmacists, and independent midwives and midwives with public hospital employment experience. The researcher worked with the College of Midwives regional coordinator to identify a range of midwives who were invited to participate.For general practice, as practice nurses do most vaccinations, more nurses  were invited into the study than GPs. Most pharmacists were deliberately selected as those who administered vaccinations, with two owners of rural pharmacies not offering vaccinations also approached. Following informed consent, interviews were conducted face-to-face at the participant’s workplace, in their home, in a pharmacy consultation room, or at a café, according to the participant’s preference, or by telephone. A token gift of a NZ$30 supermarket voucher was provided to each participant. The interview topics varied by group, i.e., woman eligible for a vaccination, midwife, pharmacist or general practice staff. For the findings reported in this manuscript, the key topic discussions used were: views and experiences of maternal vaccinations in pharmacy; awareness of maternal vaccinations during pregnancy; barriers and enablers for vaccine access relevant to pharmacy administration; the woman’s journey to having (or not having) a vaccination during pregnancy; barriers and enablers for pharmacy to provide vaccinations during pregnancy; and communication between pharmacy and other health care providers regarding vaccination during pregnancy or vaccination in general. Interviews were audio-recorded (with consent) or notes were taken.Recorded interviews were transcribed verbatim and checked against the recording. Transcripts and notes were read and reread by the first author, then coded using NVIVO Pro. The interviews were coded within four groups: women consumers (identified as Māori or non-Māori); midwives; pharmacists; and general practice staff. Within each group, coding nodes included specific topics discussed (deduction) and emerging themes (induction). For example, under the coding of women consumers were codes such as barriers to getting the vaccine, enablers to getting the vaccine, knowledge, views on pharmacists vaccinating, and the woman’s journey, and themes such as protect baby, empowered, safety, and trust. Analysis took place through a framework approach, by each of the four groups, systematically working through each coding node. Comparisons were made between and within groups for opinions, and experiences, and emerging themes were documented. Findings were shared and discussed between the researchers. Following a training session, the second author, a male Māori pharmacist, interviewed the Māori and Cook Island Māori women using the interview guide, receiving feedback following the first interviews. The first author, a female NZ European pharmacist and experienced interviewer, conducted all other interviews. The first author coded transcripts, conducted analyses and reported findings, with a review from the second author and OS on the Māori women findings before being finalised. Both interviewers hold positive views on vaccination but tried not to reveal that stance, rather seeking to understand and encouraging participants to share their views. While pharmacists were aware that their interviewer was also a pharmacist, other health care providers and most women were not. A minority of the Māori women had an existing relationship with the interviewer as their pharmacist. All authors had input into the study and reviewed the findings before being finalised. HPH is a female NZ European vaccination researcher, CCG is a male NZ European academic general paediatrician, OS is a male Māori general paediatrician practising in hospital, and FD is a public health physician. All authors are positive about vaccination. Nine Māori, one Cook Island Māori and eight non-Māori women participants, 12 pharmacists, 12 people working in general practice, and 11 midwives were interviewed . Characteristics of the interviewed women are summarised in All 12 pharmacists approached agreed to participate. Ten of the 12 midwives approached agreed to be interviewed, and one additional midwife was recruited through snow balling when the tenth midwife suggested she would provide further useful insight. All seven general practices approached provided a practice nurse, GP and/or practice manager.Forty-seven interviews were conducted face-to-face, and a further six interviews were by telephone. Most interviews took approximately 25–30 min (range 7–52 min). Two participants declined audio-recording and notes were taken instead. The coding of participants indicates their subset with P for pharmacists, M for midwives, N for practice nurse, D for doctor, W for women and MW for Māori or Cook Island Māori women.The qualitative data presented begin with the awareness and views of pharmacists providing funded maternal vaccinations across all of the groups interviewed. It then outlines the uptake of maternal vaccinations in pharmacy and enablers and barriers to pharmacy staff recommending and providing these maternal vaccinations. The results section ends with key themes which included opportunity, and its inter-related themes of convenience, accessibility and proactivity; trust and missed opportunity. Time, awareness and communication also arose often. Most women participants reported that they knew pharmacies provided maternal vaccinations, primarily from pharmacy staff or midwives informing them, and, in one case, by seeing posters in the pharmacy. Three women were unaware of this service in pharmacy, and one was not asked about her awareness of the pharmacy service. The vaccinating pharmacists were all aware of funded maternal vaccinations in pharmacy and the time restrictions for funding for Tdap. The non-vaccinating pharmacists were aware of vaccinations in pharmacy but had low awareness of maternal vaccinations. All but one midwife was aware of pharmacists offering maternal vaccinations. This awareness arose from a number of sources including information emailed to midwives; their clients or the pharmacy reporting vaccination in pharmacies to the midwife; an immunisation update course; or pharmacy signage. One midwife was informed when receiving her own influenza vaccination in a pharmacy, and two others were contacted by pharmacists telling them about the service being provided. A few midwives did not know which pharmacies provided maternal vaccinations, that this included pertussis vaccine, that there was no cost to the woman, or knew of the service but not that it had started. These midwives tended not to recommend pharmacy as an option for maternal vaccinations.General practice staff were aware of pharmacists vaccinating, but most were unaware of funded maternal vaccinations or any pertussis vaccine administration in pharmacy. The only report of a general practice staff member informing the participant that their pharmacy provided vaccinations was one nurse. Four general practice participants worked in areas where pharmacies did not provide vaccinations.“easier”, and/or noting that they regularly visited pharmacies. Some had qualifications, e.g., providing that they trusted the pharmacy. One participant prone to anxiety preferred a doctor’s office for more reassurance, and another said she did not go to pharmacies generally but would prefer a vaccine from pharmacy. Women participants were mostly very positive, considering a pharmacy was “I think if you trust your pharmacist it’s a great idea.”W10All 10 vaccinating pharmacists were very positive about pharmacy provision of vaccinations generally and of funded maternal vaccinations specifically. Mostly they saw convenience for users or opportunity to raise awareness. They also enjoyed the variety and/or patient contact vaccination provided.“I think it’s such a valuable service because you’ve got so many people coming in that it frees up medical centres, it frees up nurse and doctor time. So if we can do it and it’s within our scope then why not spread the workload out.”P4“very positive” discussions with doctors regarding pharmacy-provided vaccinations, noting the weekend access. One vaccinating pharmacist in a rural high-need area reported negativity from a medical practice about his pharmacy offering vaccinations, including managing adverse reactions and taking their funding, requesting they do not vaccinate patients from their medical practice. This discouraged him from raising vaccinations with consumers. Conversely, one city pharmacist reported While positive about vaccinations in pharmacy for access, the two non-vaccinating pharmacy owners outlined multiple barriers, including maintaining their medical practice relationship, and preferring to provide other advanced services rather than vaccination which they saw as a general practice role. “…I get the whole demarcation between roles as well, and I still see vaccination in a nursing role.”P12These two pharmacists lacked knowledge about maternal vaccinations, and one worried about safety. They had no pregnancy vaccination posters in their pharmacies, unlike most other pharmacists interviewed. While one reported little need in their rural area because of accessible medical services, the other participant would offer the service if a pharmacist keen on providing vaccinations joined their staff. This pharmacist’s other pharmacy offered vaccinations, but a nearby GP expressed concern about funded influenza vaccination in pharmacy, reportedly having arranged extra general practice staffing for influenza vaccinations and holding concerns about pharmacy management of anaphylaxis and incomplete national immunisation records. The pharmacist wanted to maintain a good relationship with the GP, but the pharmacy continued to offer vaccinations. “more options”. Some midwives wanted more pharmacies to offer vaccinations. Most midwives were very positive, given the opportunity and convenience specific to the nature of pharmacy versus general practice, and wanting “I think the more places that it’s free, you know.”M7One midwife who provided vaccinations herself worried about the local pharmacy being too busy to do vaccinations and where women would wait after vaccinations. “Just seems strange to go to a pharmacist for it… but everyone has their own choices so… it’s just somewhere else, but I’ve not heard of many taking that up.”M1Another midwife was also concerned about the busy-ness of pharmacy, and their ability to handle adverse reactions. Noting a client reported feeling rushed and insufficiently informed about the pharmacy-provided vaccination, she recommended general practice to her clients, although she reported receiving a similar complaint from a client about a vaccination from a practice nurse. One midwife preferred using a pharmacy near a medical centre in case an adverse event occurred. Most practice nurses were very positive about pharmacists providing maternal vaccinations, although some had qualifications, such as notifying the general practice, pharmacists having appropriate training or having emergency equipment. One practice nurse worried about how an adverse reaction would be managed in a pharmacy, and a practice manager from a Māori general practice preferred Māori-delivered health care for Māori. “I think it’s great because it improves access, so long as they’re safe you know and they’re obviously educated to do it, I assume they have oxygen on hand…”N1“it’s good” mainly because they were largely lost from general practice in pregnancy (see opportunity below). Although one GP speculated the local pharmacy might not provide vaccinations to maintain their relationship with the medical centre, the two practice owners indicated little financial concern with pharmacists vaccinating:Three of the four GPs wanted pharmacy notifications on vaccinations provided, with one concerned about reaching targets. One GP in a high-need area noted unmet need with midwives not vaccinating, but worried about anaphylaxis, communication from pharmacy to general practice, the pharmacy being busy, and that the pharmacy was doing it for financial reasons. The other GPs were more positive, with one employee GP noting “I don’t really have an issue with them doing it…. Does it really matter who gives the vaccination? Not really.…. We’re not in the vaccination game for the money out of it because there is no money in vaccinations…. As long as I’ve got the information, and so that we’re not spending wasted time chasing up someone who’s already had a vaccination…”D3 GP and practice ownerNine women (three Māori/Cook Island Māori and six non-Māori) received one or more maternal vaccinations in pharmacy, sometimes suggested by the midwife or pharmacy, or having seen information in the pharmacy about funded vaccinations. One Māori woman and one Cook Island Māori woman , both living in the same small town, reported only knowing about and having vaccinations whilst pregnant because the pharmacist mentioned it, despite having previous pregnancies. One non-Māori woman only received vaccinations during pregnancy because of the pharmacy:“…my midwife hasn’t mentioned it all I don’t think. Then I went to the pharmacy for something else, and the pharmacist just popped her head over and she’s like oh are you pregnant? Just like reminded me that I needed to get the whooping cough the second time round [after a previous pregnancy], coz I actually didn’t know whether I needed to the second time.”W11Women getting maternal vaccinations in pharmacies were largely satisfied with the service, although one reported insufficient privacy waiting for the 20 min post-vaccination period in a public thoroughfare between the pharmacy and other clinics. Pharmacists generally reported providing small numbers of maternal vaccinations e.g., one or two per month. One pharmacist working in a low socioeconomic area with high numbers of Māori, Indian and Pacific patients reported informing women about maternal vaccinations but some, particularly non-European did not return for them:“… we do a huge amount of dispensing for iodine and folic acid, and, but nowhere near the proportionate amount of vaccines. Most of the vaccinations we do are not of the lower socioeconomic group, they’re of the higher group…”P5Two pharmacists reported relatively high maternal vaccination uptake, one reached nine in one month with a concerted effort from all staff and strong use of promotion (see Proactivity). Another reported providing 10–20 maternal vaccinations in the preceding month, with staff discussing maternal vaccinations and providing leaflets with folic acid and iodine prescriptions, and midwives referring women for the vaccines.Many enablers and challenges to recommending and providing maternal vaccinations in pharmacy were described , with thFunded pharmacist-administered maternal vaccinations were considered to provide an opportunity to raise awareness of or provide vaccinations in a convenient way, supplementing existing information and delivery pathways, and with benefits for uptake. Most women participants reported hearing about vaccinations during pregnancy from pharmacy staff and/or seeing posters at their pharmacy, even if vaccinated elsewhere.Many pharmacists reported low awareness amongst pregnant women, or subgroups , supporting the potential for increasing awareness, although some pharmacists thought women’s awareness of maternal vaccinations might be improving. One pharmacist in a lower socioeconomic city area with a high Māori population observed:“A lot of women to be honest don’t know about the vaccinations that are recommended in pregnancy…. [or] don’t really know about the timing…”P9Collecting prescriptions for pregnancy supplements from the pharmacy provided a key opportunity for discussing maternal vaccinations, with children’s prescriptions and other visits sometimes providing multiple reminder opportunities. One pharmacist said their staff approached visibly pregnant women regarding vaccination. Some pharmacists noted that mentioning maternal vaccinations allowed an opportunity to address women’s concerns about maternal vaccinations, e.g., needle phobia or safety concerns. Midwives were positive that pharmacy provided another opportunity for a woman to become vaccinated, for example, noting they may not go to general practice. “So having it at the pharmacy, there could be a much bigger uptake and they’re discussing it with them when they go in to pick up a prescription. So even if their midwife hasn’t discussed it with them and sent them in, they’ve got another opportunity as well.”M5General practice participants also recognised the opportunity for consumer awareness. “…if somebody’s in there getting something else and once again opportunistically they could be immunised. So that’s good for the patients, that’s more convenient.”N1“we just don’t see them”.Instances were mentioned of some women not engaging with general practice at all or during the pregnancy, or not having a single GP. In one small rural town, where the pharmacies did not deliver vaccines, a practice nurse was very positive about pharmacists delivering vaccinations, indicating she missed approximately 80% of vaccinations that could be given during pregnancy, Box 1Case Study 1—MW4This Cook Island Māori woman living in a high deprivation area first presented to the midwife for this pregnancy at 25 weeks’ gestation. Despite having had her childhood vaccines and reporting her children were vaccinated, she had no maternal vaccinations before, only becoming aware of such vaccinations when the pharmacist informed her about it at 30 weeks’ gestation.“I was keen for it because, yeah, anything to help my baby”.“just because it’s different ay, to come into a pharmacy and getting that stuff done”, she reported feeling very comfortable with the pharmacist administration. As “a walk in,” she found pharmacy “a lot easier” for the vaccination, presumably than general practice where vaccinations are usually provided, and free administration was an important enabler for her.She had the pertussis vaccine immediately in the pharmacy, but influenza vaccine was unavailable (for summer). While nervous about getting the vaccine, Convenience and accessibility both arose frequently. Many participants across all groups appreciated that pharmacies required no appointment, would be likely to have a shorter wait before the vaccination, and typically had longer opening hours than general practice. Women who used the pharmacy for the vaccination did so for convenience, noting two reasons: not requiring an appointment; and expecting less waiting time than in general practice. Several observed that having other children to look after or work commitments meant the pharmacy accessibility was helpful. “… through the GP it’s a bit of a pain to make an appointment and go in and with a pharmacy you basically just walk in. Which is quite easy.”W18“easier” than pharmacy because she was there for blood tests.Conversely, one woman contacted several pharmacies who did not provide vaccinations or had no vaccinating pharmacist available on a Saturday before finding one that suited her timing. One woman used her general practice, being One pharmacist reported doing most maternal vaccinations on Saturdays, but another reported insufficient staffing to offer vaccinations on Saturdays.Some midwives in high-need areas and with mainly Māori clients outlined challenges to women in accessing general practice including transport/money for petrol, difficulty booking appointments, and chaotic lives and appreciated pharmacy having no appointments. One Māori midwife highlighted the challenges some clients had with booking and keeping appointments:“So my typical clients … they’re not booking an appointment at the GP. A lot of people I need to make three appointments to see them once.”M5Linked with the opportunity theme, some pharmacists were particularly proactive in raising awareness of maternal vaccinations. The main proactivity in the pharmacies was in having posters displayed, giving out pamphlets or using dispensary labels to provide a brief message about maternal vaccinations (particularly with prescriptions for folic acid or iodine in pregnancy), or providing verbal messages about vaccinations. Some women participants had noticed posters in the pharmacy about maternal vaccinations, and these posters were obvious in some pharmacies when doing the interviews, e.g., on the door as the pharmacy was entered, in the pharmacy window, in the consultation room and on the wall or door outside the consultation room.Some pharmacists informed local midwives of their service and gave them leaflets for women or posters about maternal vaccinations. A few pharmacist participants involved their non-pharmacist staff in informing pregnant women. One pharmacist said that if a woman was not ready to have a vaccination after a discussion, she would diary a call back to remind her about the vaccine. Other pharmacists had no call back or text system but saw merits in using it for pertussis vaccine given many women were not yet in the 28–38-week window when the pharmacist discussed vaccination with them. However, pharmacists were concerned about possible miscarriage before the text, and so would seek the woman’s permission, limit contact, and word the text carefully.Box 2Case study 2—P7“passionate” about vaccinations, having been involved in a vaccination project at under-graduate level. Together with pharmacy staff, they made the most of the resources available, having posters in the pharmacy and consultation room, staff wearing maternal vaccination promoting t-shirts on certain days, distributing pamphlets about maternal vaccinations, and posting information and video clips on the pharmacy Facebook page. To increase staff knowledge on maternal vaccinations, they used the one-page information sheet sent from the researchers to all pharmacies, discussed them at staff meetings, and encouraged front-line staff to complete the two quizzes on maternal vaccination.One pharmacy with two keen vaccinating pharmacists was especially proactive. Participant P7 described herself as They informed their local midwives that they provided vaccinations and gave midwives leaflets for their pregnant women regarding vaccinations, resulting in midwives referring women to them for the service.On seeing prescriptions for folic acid, iodine or iron tablets, or pregnant women in the pharmacy for other reasons, a staff member would discuss vaccinations and provide a leaflet.Tdap vaccine was kept in stock to ensure it was always available.This pharmacy set a target of administering 10 maternal vaccinations for one particular month , encouraging staff to remember to mention it to pregnant women and posting more on Facebook. They reached nine maternal vaccinations that month, largely driven by the staff raising awareness. This high rate was not sustained though, partly because women who seemed interested did not return for it.Although some pharmacies were proactive, missed opportunity also existed, particularly where individual pharmacies did not offer vaccinations. Two women participants received no influenza vaccine, reportedly told by pharmacists that it was the wrong time of the year. “definitely” would have had it. “You don’t have to think about it, you don’t have to go anywhere. It’s done.”One NZ European woman received no vaccinations despite being “pro-vaccination” and knowing about maternal vaccinations from verbal messaging and posters in the pharmacy and her midwife). This participant had personal and health struggles, and an older child and full-time work, giving her little capacity to consider vaccinations. Had she been offered vaccinations in the pharmacy while waiting for a prescription she The opportunity to offer or discuss maternal vaccinations was reduced when a pregnant woman did not collect prescriptions from the pharmacy. Midwife-sent prescriptions were often uncollected in one pharmacy in a high-needs area. When a third-party collected the prescription, pharmacists’ privacy concerns meant vaccination information was not given. One pharmacist only discussed vaccinations during pregnancy when patients were obviously pregnant, not raising it when first dispensing pregnancy supplements:“…because you don’t know whether they’re pleased to be pregnant, whether they’re in a relationship or etc. it’s a bit dodgy to say ‘Oh I see you’re pregnant, you need to make sure you get your flu vaccine and your free whooping cough vaccine’ because you don’t know what state of mind they’re in and that’s the dilemma I have at this stage.”P5This pharmacist also noted many women were not getting iodine prescriptions later in pregnancy (the first prescriptions lasts three months), also limiting the opportunity to discuss vaccinations. Some pharmacists, despite enjoying providing vaccinations, reported that being busy with prescriptions reduced the opportunities to mention vaccinations. One time-poor pharmacist in a high-need area put labels on dispensed pregnancy supplements informing about vaccinations in lieu of a conversation, but reported administering no vaccinations to pregnant women, indicating that this strategy was ineffective. A midwife in that community reported low literacy was common, potentially limiting the effect of a written label without discussion. One vaccinating pharmacist had not used pregnancy supplement prescriptions as a prompt to raise vaccinations, but thought it was a good idea. Most pharmacists reported that non-vaccinating pharmacy staff did not identify and refer pregnant women for a discussion about vaccinations, due to insufficient knowledge or vaccinations not being top of mind.Some pharmacists did not inform local midwives that they administered maternal vaccinations. Such contact would raise the awareness of this service in pharmacies, provide an opportunity to answer questions , and help midwives signpost to pharmacies offering the service. Some communities had no pharmacies providing vaccinations, including a remote area in which two midwives wanted the pharmacy to offer vaccinations to aid access given residents’ challenges travelling to larger centres or making appointments in general practice. One midwife appreciated that one pharmacy in her small town provided vaccinations, but worried that women attending non-vaccinating pharmacies for prescriptions in pregnancy would not receive messages about vaccinations.Time often arose throughout the interviews, with saving time as a benefit of pharmacy delivery of maternal vaccinations, and insufficient time limiting opportunistic discussions about vaccinations in pharmacy. Convenience and accessibility of pharmacies, including long opening hours, helped women with limited time . Some women and midwives expected a shorter pre-vaccine wait in pharmacy than general practice. Pharmacists reported usually managing time to provide vaccinations when requested, or help address concerns such as needle phobia, without needing to arrange appointments. However, a few pharmacists discussed time pressures, limiting their patient contact, and proactivity with vaccinations. Waiting for training courses frustrated a pharmacy owner, limiting the number of staff able to vaccinate.Trust, relationships and communication arose throughout the interviews. For women and some health professionals, having a relationship with a pharmacy and knowing pharmacists had appropriate training to provide vaccinations aided trust. “I wouldn’t just rock up to a random pharmacy, …. I’d want to feel like I trusted the place...”MW1Unfamiliarity with pharmacies providing vaccinations caused some hesitancy about receiving a vaccination from there  saw benefits in extending the current funding of maternal vaccinations to pharmacy, given challenges in the existing care model and an opportunity to raise awareness. Providing another government-funded delivery option outside of primary care with convenience and access, and particularly the mechanism of unbooked opportunistic immunisation, was considered likely to increase uptake. Some women only received a vaccination during pregnancy because of their pharmacist, having been unaware of it previously. Women receiving vaccinations in pharmacy largely had positive experiences, although one woman experienced difficulties finding a vaccinating pharmacist. Pertussis vaccination during pregnancy is already government-funded through general practice, with low uptake. Extending funding to pharmacy is likely to increase the awareness and uptake and should have a similar cost-benefit to the current programme, assuming the vaccine cost and administration costs remain the same. With approximately 60,000 births each year, the cost of this programme extension to pharmacy should not be excessive but would depend on uptake. As the government is committed to funding vaccine uptake in general practice, extending funding to pharmacy may be more cost-effective than the cost of trying to increase uptake in general practice. A minority of general practice staff and midwives worried about pharmacies busy-ness or ability to manage adverse effects. Pharmacists did not express such concerns for managing vaccine administration, possibly because they felt prepared with training and emergency equipment in the unlikely event of a serious adverse effect. In New Zealand, pharmacists have insurance and can be disciplined in case of an error, but medical misadventure is usually covered by the Accident Compensation Corporation regardless of health practitioner. General practice staff wanted notifications about vaccinations administered to their patients in pharmacy. Communication between pharmacy and midwives and general practice appeared to help raise their awareness of vaccinations in pharmacy, and some midwives suggested pharmacy-delivery for maternal vaccinations to their clients.Some missed opportunities appeared, e.g., pharmacies providing no vaccines or having no promotional material, pharmacies not offering vaccines at the weekend, or pharmacists being too busy to mention vaccinations to pregnant women. Providing leaflets or stickers about maternal vaccinations instead might be ignored by those with low health literacy and provides no opportunity to address any concerns. Pharmacists varied in their proactivity, with one pharmacy using all staff to increase their maternal vaccination uptake. Widening vaccination administration to pharmacy is associated with increased uptake ,33. A peResearch conducted in the United States in 2010, found vaccinating pharmacists less positive about giving influenza vaccination during pregnancy than to the general public, with vaccine safety concerns raised . While aVaccinator pharmacists and recipients of pharmacist-administered vaccines were generally positive about the service, similar to other research ,46,47 whThe support of funded maternal vaccinations in pharmacy by most general practice staff  differs from previous negativity reported from general practice in NZ regarding pharmacists vaccinating ,49, and This research suggests that funding maternal vaccinations in pharmacy is likely to overcome some barriers to uptake through addressing gaps in awareness and increasing availability. Two women in late pregnancy previously unaware of vaccinations who the pharmacist informed and vaccinated, were in a high-need area, and both were Māori, a group disproportionately affected by pertussis during infancy , suggestEducating pharmacy technicians and pharmacy assistants about vaccination could increase pharmacy proactivity. Increasing vaccinator staff should also help, using intern pharmacists (pre-registration), and pharmacy technicians would help raise awareness, help the pharmacy be more proactive about maternal vaccinations, and allow vaccinations throughout all opening hours. Educating pharmacy technicians about vaccinations helped them raise vaccinations with consumers in a US study , and phaThe applicability of this research to other countries may depend on the model of care and uptake. Gaps between providers and/or limited awareness and uptake of maternal vaccinations may occur elsewhere ,55,60, aFor this initiative to work optimally, funded provision from all pharmacies, particularly in high-need areas, including remote areas, would help. Barriers to pharmacies offering vaccinations include sufficient funding, the need for training, and staff time ,54,61,62Quantitative data are needed to ascertain how funding maternal vaccination administration in pharmacy helps overall uptake, work that our team is undertaking currently.We conducted 53 interviews that explored funded maternal vaccinations in pharmacy from the perspectives of 18 women and 12 pharmacists, 11 midwives and 12 general practice staff. Previously published maternal vaccination qualitative research has typically excluded pharmacists . Wilson Qualitative research exploring pharmacy-delivered vaccinations has typically been limited to consumers’ ,63,64,65We chose our sample purposively to ensure that a wide range of experiences and views were captured. As indigenous people are disproportionately affected by vaccine-preventable diseases , we partMost women were recruited in pharmacy, and so women not attending pharmacies were effectively excluded. Some early interviews with Māori women were informative but short, but later interviews provided more depth. We interviewed few young women, with only one under 20 years, an age group associated with low maternal vaccination uptake . We focuData saturation was not sought but rather breadth, with a range of health care providers and women interviewed. We deliberately focused much of the sample on high-need populations, and conducted a large number of interviews. However, quantitative research is needed to show exactly what effect funding of pregnancy vaccinations in pharmacy has on uptake across all pregnancies and especially those in high-need groups. A cost analysis could also be helpful. The acceptance of immunisations occurring outside primary care in pharmacies means this is a valid way to increase uptake and prevent disease. Government-funded maternal vaccinations in pharmacy appear to address some barriers to uptake by increasing awareness and providing a more accessible option for administration that needs no appointment. This service appears to be useful, including in high-need communities, and was generally well accepted by women, pharmacists, midwives, and general practice staff. Maximising the opportunity of pharmacy to raise awareness and uptake requires all pharmacies to provide vaccinations, more vaccinators in pharmacy, and greater awareness and proactivity in front-line staff.