ADHD) symptoms. We probed the causal nature of this putative effect of birth weight on ADHD symptoms using the twin differences design, which accounts for genetic and shared environmental confounds.Available evidence points towards lower birth weight as a risk factor for the development of attention deficit/hyperactivity disorder (MZ) and 6,698 dizygotic (DZ) pairs – parents, teachers or twins rated the twins’ ADHD symptoms at nine assessment waves (2–16 years). We implemented the twin differences design, which completely accounts for shared environmental and genetic confounding in MZ twins. We tested whether: (a) the lighter‐born twins had elevated ADHD symptoms compared to the heavier‐born twins, by regressing within‐pair differences of ADHD symptoms on within‐pair differences of birth weight among MZ twins; (b) the effect of birth weight on ADHD was moderated by gender, gestational age and low birth weight; (c) this effect changed with age at ADHD assessment using adapted latent growth curve models; and (d) results differed for inattention and hyperactivity/impulsivity.In a large population‐based twin sample – 3,499 monozygotic (ADHD symptoms from early childhood to late adolescence. The lighter‐born twin had more ADHD symptoms than the heavier‐born cotwin among MZ twins across assessment waves and raters. No moderation effect was detected. The magnitude of the effect of birth weight decreased significantly across time for hyperactivity/impulsivity, but the decrease failed to reach significance for inattention. Estimates for inattention were significantly larger than for hyperactivity/impulsivity at each time point, implying stronger effect of birth weight on inattention symptoms.Birth weight significantly predicted ADHD symptoms. Effect of birth weight persists across a 14‐year period from childhood into late adolescence, in particular for inattention symptoms.Our findings provide stringent evidence for environmental effect of lower birth weight on the causal pathway to elevated  Birth weight is an index of foetal growth and a marker of the prenatal environment , a large longitudinal study of twins born in England and Wales between 1994 and 1996, which is representative of the UK population as shown in Table During first contact, parents reported each twin's birth weight in pounds or kilograms, which were then converted into grams for analyses. Twins’ median age was 1.6 years when birth weight data were collected.ADHD symptoms were assessed using age‐appropriate parent‐reported questionnaires, which are Behar's Preschool Behaviour Questionnaire . We did not include teacher and self‐reported scales available at only one data collection point. Prior to analysis for each ADHD scale, twins with missing ADHD data on that particular scale were excluded and all variables were standardized.Two types of estimates were obtained: (a) the unadjusted phenotypic estimates from the whole twin sample and (b) the estimates from twin differences in MZ twins (MZ estimates). To obtain unadjusted phenotypic estimates, nonindependence of data within twin pairs were accounted for by allowing within‐twin pair correlations  were obtained using bootstrapping  for all estimates. The moderating effects of gender, gestational age and low birth weight  on these estimates were tested ; andwhether this difference in means between ‘lighter’ and ‘heavier’ twins was significantly larger at age 8 compared to age 16 years (difference observed at age 8 years minus difference at age 16 years). Computed estimates for (i) and (ii) were bootstrapped 10,000 times to obtain 95% CI.To test whether the MZ estimates significantly differed depending on ADHD symptom dimensions, further analyses were carried out in MZ twins using the CPRS‐R, which has nine items for each symptom dimension. Two models were fitted for each of the symptom dimensions assessed at each age. In the first model, the MZ estimates for both symptom dimensions were constrained to be the same. The second model did not include equality constraints, thereby allowing both MZ estimates to be different. The difference in goodness of fit was then tested using the Satorra‐Bentler Chi‐square test. A significant difference would indicate that the effect of birth weight differs for the two dimensions.Descriptive sample statistics regarding mean birth weight, number of twins and gender proportion for each ADHD scale are shown in Table  = −.075, 95% CI: −.091, −.058), but became nonsignificant in adolescence . In contrast, despite being the most stringent type of estimates, all MZ estimates were significant from early childhood to adolescence with small effect sizes ranging from β = −.038  to β = −.237 . These effect sizes were not moderated by gender, gestational age and low birth weight , with a correlation of r = −.09 when considering population‐based studies only. This may reflect that the environmental architecture underlying ADHD is just as complex as their genetic architecture, which involves small effects of many genetic variants  in covariate‐adjusted analyses compared to unadjusted analyses . In addition, other prenatal unmeasured nonshared environmental factors associated with foetal growth, such as positioning in the womb, placentation, or differences in nutritional availability could also explain the findings .Table S7. Moderating effect of low birth weight .Table S8. Corresponding change in symptoms for change in 1 kg.Table S9. Phenotypic, DZ and MZ twin difference estimates after excluding twins with very low birth weight .Table S10. Descriptive statistics for parameters in latent growth curve modelling.Figure S1. Predicted inattention levels of monozygotic twins for Conners’ Parent Rating Scale‐Revised from age 8 to 16 years.Figure S2. Predicted hyperactivity/impulsivity levels of monozygotic twins for Conners’ Parent Rating Scale‐Revised from age 8 to 16 years.Click here for additional data file.


Magnetic nanosensors have become attractive instruments for the diagnosis and treatment of different diseases. They represent an efficient carrier system in drug delivery or in transporting contrast agents. For such purposes, magnetic nanosensors are used in vivo . To remove specific compounds from blood, magnetic nanosensors act as elimination system, which represents an extracorporeal approach. This review discusses principles, advantages and risks on recent advances in the field of magnetic nanosensors. First, synthesis methods for magnetic nanosensors and possibilities for enhancement of biocompatibility with different coating materials are addressed. Then, attention is devoted to clinical applications, in which nanosensors are or may be used as carrier- and elimination systems in the near future. Finally, risk considerations and possible effects of nanomaterials are discussed when working towards clinical applications with magnetic nanosensors. Functionalization of magnetic nanoparticles (MNPs) for biomedical and clinical applications as nanosensors has received considerable attention in the past. Particularly in cancer diagnosis and treatment, magnetic nanosensors are widely explored as potential alternatives, either to identify less invasive diagnostic tools such as collection of cancer cells or tissue material or to specifically deliver medications within the tumor.A magnetic nanosensor is a MNP functionalized with sensing moieties, which interact with proteins, DNA or cell surfaces. While many magnetic nanosensors are available, this review will exclusively focus on magnetic nanosensors designed to be used as diagnostic or therapeutic tools in medicine. Magnetic nanoparticles for general biomedical applications –5, or diFrom a clinical perspective, it is important to make a distinction between magnetic nanosensors applied in vivo  and magnetic nanosensors, which are used extracorporeally . The distinction is important since different requirements for materials, properties and handling are needed. Concerning in vivo applications, drugs are attached to MNPs and carried to a specific location, a process called drug delivery. In another in vivo system, magnetic nanosensors as contrast agents are available to convert a biochemical information (e.g. tumor tissue) through radiation into an analytic signal (imaging of the tumor) in magnetic resonance imaging (MRI). In extracorporeal approaches such as blood purification, magnetic nanosensors are used to bind and collect specific biochemical or cellular entities that on the top allow for detailed analysis or diagnosis after recovery of the sensors. Blood purification with magnetic nanosensors can be considered similar to a dialysis device, whereas no sensor particles are allowed to reach the body after the purified blood is redirected to the patient .When aiming towards magnetic nanosensors in clinical applications the material and synthesis are key for their functionality. Therefore, the following section will cover different synthesis pathways and functionalizations of MNPs. Subsequently, chances of applying nanosensors in different medical applications as well as risk considerations when using nanomaterials are discussed.There are a number of ways to synthesize MNPs, which are described in detail by Schüth et al. . As a br2O3 or Fe3O4. In comparison to other metal and metal-oxide nanoparticles, SPIONs have the advantage of being compatible in a biological environment [With the described surface modification and functionalization carbon-coated MNPs became as interesting as the already widely explored superparamagnetic iron oxide nanoparticles (SPIONs) . SPIONs ironment . Also, tironment . This haironment . Concernironment . These aThe main difference between carbon-coated MNPs and SPIONs, from a pure materials point of view, is the higher saturation magnetization of the former, which leads to a much faster separation of carbon-coated MNPs when applying a magnetic field. Additionally, SPIONs are superparamagnetic while carbon-coated MNPs are ferromagnetic . This me2O3). As a consequence, MNPs have become resistant to nonspecific adsorption of proteins [Physicochemical characteristics of the synthesized magnetic nanosensors determine biocompatibility. As a consequence, interactions with the biological milieu such as the blood have to be considered carefully. Blood is a complex liquid consisting of different molecular and cellular entities. Therefore, it is important to ensure that magnetic nanosensors do not interfere with blood in any other way than intended, nor should they induce any unwanted reactions such as inflammation. In general, a suitable coating with a polymer is sufficient to achieve biocompatibility before the sensing functionality is implemented Fig. . A widelproteins . Due to Magnetic nanosensors as carrier system, focusing on in vivo methods, and Magnetic nanosensors as elimination system for the extracorporeal removal of a molecular or cell entity from blood.The use of magnetic nanosensors in clinical applications will be discussed based on the two categories of intracorporeal (in vivo) and extracorporeal applications. This will be covered in the sections Magnetic nanoparticles are considered ideal candidates for drug delivery for several reasons. Their large surface-to volume ratio allows for a high loading with active substances. Moreover, these MNPs can be directed by a magnet and facilitate targeted delivery of drugs. Finally, stable dispersions and fast transportation in fluids can be realized due to the small size of the MNPs.A subcategory for drug delivery is the group of chemotherapeutics. Classically, therapy with a chemotherapeutic drug is non-specific and the drug is applied systemically. Therefore, non-specific targeting of cells leads to many unwanted and sometimes severe side effects. Magnetic particles are engineered with a chemotherapeutic agent and designed to be target specific, reaching the area of the tumor cell with the help of a magnet Fig. . FunctioSimilar to the loading of MNPs with chemotherapeutics, MNPs can be equipped with radioactive isotopes or radionuclides. The radionuclide-loaded MNPs are guided to the tumor cells and, upon internalization, kill then cancer cells through continuous irradiation –55. HalfGenetic disease treatment presents a further possible field of application for magnetic nanosensors. Classically, patients with a genetic disease, are treated with exogenous DNA to correct mutations, which are responsible for the disease. Also, antisense-RNA can be used to silence defective genes. However, with the current treatment methods different challenges are faced: (1) There is a clear lack of tissue specificity. (2) Transfection efficiency needs to be improved as introduction of the nucleic acids into cells is difficult using classical approaches . (3) TheAnother group of MNPs are magnetic nanosensors used as contrast agents in MRI to image specific organs. After injection, the magnetic nanosensors agglomerate in specific areas and—upon irradiation with radio waves—enhance the contrast and therefore increase image quality . Such coSimilar to the use of functionalized MNPs as contrast agents is the technique of hyperthermia. A rise in tumor temperature makes cancer cells more susceptible to chemotherapy or radiation, and can directly cause cellular death. Therefore, MNPs as energy-transducing particles may be used locally to overheat tumor cells. This would be an attractive method for treatment of deep tissue seated tumors , 61.Blood purification describes the second category where magnetic nanosensors may be applied clinically, focusing on removal of non-cellular and cellular compounds. The challenge for magnetic nanosensors in blood purification lies in the functionalization of the MNPs with a suitable linking agent such as a metal coordinative ligand, a peptide or an antibody to bind solely the specific target , 62.While current methods such as adsorption, filtration or dialysis clearly allow elimination of small molecules , harmful substances are often biomolecules of large size . To remove complex-structured compounds, plasma exchange is mandatory with the disadvantage of loss of plasma . As an aIron carbide nanoparticles have been functionalized in diverse ways to purify blood from metal ions, steroid drugs (i.e. digoxin known as an antiarrhythmic agent) as well as proteins . Successful elimination of lead, digoxin and IL-6 was achieved with an EDTA-like chelator as metal coordinating ligand, with an antibody such as digoxin-binding FAB fragments or with an anti-IL-6 antibody, respectively . With thWhen considering clinical scenarios, which would profit from blood purification using magnetic nanosensors, sepsis may be a main focus. Sepsis is a complex overwhelming response of the body to a systemic infection. It is potentially life-threatening as it often leads to organ failure and finally to death . On one Another area of interest in blood purification is the identification and/or removal of blood cells. This gives rise to the possibility of fast and efficient detection and treatment of diseases. A classical way of cell separation is based on cell size with the disadvantage, however, of not being able to separate cells of similar sizes. Also, when using the affinity cell separation technique, chemical or electrical properties may be similar in different cells. Magnetic separation based on the use of nanoparticles suffers from no such limitation as MNPs are coated with specific antibodies directed against a surface marker of the desired cells .Isolation of hematopoietic stem cells from bone marrow or peripheral blood from a healthy donor presents a realistic future application for MNPs. Such donor cells are used to reintroduce functional stem cells in a recipient after chemotherapy for leukemia or lymphoma with killing of not only neoplastic, but also of growing cells by the cytotoxic agents. Although due to the low abundance of stem cells in bone marrow aspirate or peripheral blood, it is challenging to separate them, the use of magnetic nanosensors may present a suitable approach .Another application for the removal of cells may be explored targeting circulating tumor cells (CTCs). These cells are thought to be a key factor in the process of metastasis . Their pImportant to note when targeting blood purification with magnetic nanosensors is the need for a suitable device, which allows for efficient injection, mixing and removal of the magnetic nanosensors –81 Fig..Among magnetic nanosensors certain characteristics are shared for in vivo as well as extracorporeal applications. First and foremost, the particles need to be biocompatible. Therefore, they should refrain from non-specific adsorption as well as from agglomeration (unless desired in the target tissue). Second, it is a prerequisite that the particles are non-toxic. Not only cytotoxicity, but also tissue inflammation should be avoided. These are key parameters for the safe use of nanosensors, which are discussed later in the risk assessment part. Even magnetic nanosensors are used in a similar way in vivo and extracorporeally, different requirements need to be met for each application. Generally, the particles used for in vivo applications are smaller to account for faster transport and tissue penetration inside the body in comparison to extracorporeal separation applications. Additionally, for in vivo applications the nanoparticles need to be either small enough to be filtered by kidneys or big enough to be eliminated by liver and spleen or they are biodegradable. All these characteristics decrease the risk for accumulation in the body.Specific requirements for the synthesis of magnetic nanosensors depending on the purpose of the application are summarized in Table When considering in vivo as well as extracorporeal MNP applications safety aspects are of utmost importance. In general, since the discovery of the nanoscale, nanoparticles opened up new fields of research and subsequently various applications of nanoparticles were found. Due to their small size, nanoparticles were initially believed to have little to no influence on living organisms. Only later, when researchers started broader investigations regarding possible risks of nanoparticles, adverse effects were discovered.In vitro assessment of nanoparticles concerning toxicity is undertaken in the same way as the assessment of chemical compounds in solution . This isVarious studies exist assessing possible toxic effects of MNPs in a living organism. Surface characteristics determine distribution within the body, whereas size, dose and entry point of nanoparticles are important as well. In general, inflammation may be triggered through stimulation of effector cells, producing proinflammatory mediators, whereas the proinflammatory effect seems to be surface-dependant . When MNNanoparticles, once present in the body, may target various systems. There are effects of nanoparticles found on the circulatory system, where nanoparticles indirectly influence for example blood pressure . ImportaA recent study mimicked the clinical scenario with ferromagnetic iron carbide nanoparticles used for blood purification methods, which theoretically escaped magnetic separation and entered the blood system of mice . These pThe reproductive system is another target of nanoparticles with possible detrimental effects. Upon in vivo applications, nanoparticles may accumulate in reproductive organs , 103, whAll these various possible effects that certain nanoparticles may or may not exhibit display the challenge in the risk assessment for nanoparticles in medical applications. Regulatory and toxicology studies have to address the fate of such nanosensors. Therefore, available magnetic nanomaterials for in vivo applications become limited. Up to now only SPIONs, due to the biodegradability of iron oxide, are clinically used. Non-biodegradable MNPs, even though they may be biocompatible, pose a challenge as accumulation and therefore unknown and detrimental effects in tissue are possible. Mechanisms are needed, which allow total excretion of such non-biodegradable MNPs. To the best of our knowledge, this is so far not achieved.In nanosensor systems where the particles eliminate compounds from the blood, ideally all MNPs are removed from the blood with a strong magnet before the blood is redirected into the body. Therefore, biodegradability and excretion is not a relevant aspect. This alters the question relevance for regulatory approval. Nevertheless, biocompatibility in blood, dispersability and the subsequent removal of the magnetic nanosensors are to be considered. Reintroduction of the blood has to be performed excluding even traces of nanosensors. Elsewise, they will be introduced into the bloodstream of the patient and this may have harmful consequences .Recently, a method for detection of trace amounts of MNPs in complex fluids was published . The autThe use of magnetic nanosensors in clinical applications has seen great advances over the last few years. Magnetic nanosensors for MRI are readily used as contrast agents in clinical applications , 59. Add®, a method to separate T-Cells from blood, a first FDA-approved clinical application for magnetic nanosensors has been established [In extracorporeal applications for magnetic nanosensors decent progress has been made. With CliniMACSablished .When looking towards the treatment of sepsis, a lot of research for the application of magnetic nanosensors is currently ongoing, academic and industrial wise . SeveralEven though the progress in possible clinical applications is visible, risk considerations may not be left out. A magnetic nanosensor needs to be safe for handling and treatment. There are still possible unclear variables towards the safety of magnetic nanosensors. Not to forget is the fact that long-term studies with magnetic nanosensors are not yet available to address and define possible long-term effects of such nanoparticles.To sum up, magnetic nanosensors towards medical applications, show great promise as novel medication-, diagnostic- and separation tools. The variety of already approved magnetic nanosensors as contrast agents in MRI boost the confidence that magnetic nanosensors may also be reliably applied in vivo for targeted drug delivery. For extracorporeal applications, the treatment of sepsis with magnetic nanosensors shows great promise should it become commercially available.


ObjectiveTo investigate whether mechanical vibrational energy from using an electric toothbrush may cause an increase in the incidence of benign paroxysmal positional vertigo (BPPV) and prevent successful treatment of BPPV with canalith repositioning procedure.MethodsThis was a retrospective study conducted at an otolaryngology private practice. A survey of 111 patients who were diagnosed with BPPV in an otolaryngology practice between May 2012 and January 2017 was conducted using a questionnaire that included questions regarding demographics, inner ear pathology, treatment method, and use of an electric toothbrush. The results were recorded and compared using a chi-square test of analysis or Fisher’s exact test.ResultsOverall, 47 (42.3%) of the 111 BPPV patients used an electric toothbrush, whereas 64 of the 111 (57.6%) patients did not. Six (12.7%) of the 47 patients experienced dizziness with electric toothbrush use. Of the 47 patients using an electric toothbrush, 33 (70.2%) had a resolution of symptoms after Epley treatment, whereas 14 (23.4%) of 47 patients did not. Of the 64 patients who did not use an electric toothbrush, 15 (23.4%) did not have resolution after Epley treatment. Of the 47 patients using an electric toothbrush, 6 (12.8%) had a recurrence of BPPV diagnosed in the office, whereas 41 (82.2%) did not. Seven (10.9%) of those who did not use an electric toothbrush had a recurrence of BPPV, whereas 57 (89.1%) of the 64 patients did not. These results were not statistically significant (p = 0.77).ConclusionsThis study suggests that the mechanical vibrations from electric toothbrush use do not have an association with recurrent BPPV. The results align with some publications demonstrating that vibrations in the head and neck area from the use of an electric toothbrush can initiate dizziness; however, it does not appear that this modality of vibration is significant for inducing recurrent BPPV. Benign paroxysmal positional vertigo (BPPV) is the most common type of vestibular disorder, with a lifetime prevalence estimated at 2.4% in the general population . BPPV isResearchers have reported that vibratory stimuli of the head and neck could induce nystagmus in patients with vestibular disorders . LacknerThe aim of this study was to investigate if the mechanical vibrational energy from electric toothbrush use may cause otoconia to become dislodged, thus increasing the incidence of BPPV. Specifically, we were interested in whether the use of an electric toothbrush prevents successful treatment of BPPV, with the canalith repositioning procedure acting as a mechanism for recalcitrant BPPV. We hypothesized that there was a relationship between electric toothbrush use and recalcitrant BPPV.A chart review was conducted of all the patients diagnosed with BPPV in an otolaryngology private practice between May 2012 and January 2017. A positive diagnosis of BPPV was defined as the presence of nystagmus elicited in a Dix-Hallpike maneuver by a physician in the practice. We directly surveyed a total of 404 patients with BPPV from this group using a questionnaire that included questions regarding demographics, diagnosis of an inner ear disorder, diagnosis of BPPV, treatment method, improvement of BPPV, and use of an electric toothbrush. Of these patients, 111 responded to our survey. Patients who answered yes to the use of electric toothbrushes were asked the questions regarding the following: length of time using an electric toothbrush, frequency of electric toothbrush use, whether the patient experienced dizziness while using their electric toothbrush, and whether the patient used another vibration device . The inclusion criteria included any patient older than 18 years who was seen at the otolaryngology clinic. The exclusion criteria excluded patients under the age of 18 years. The patients were surveyed through phone calls or direct questionnaires. The Institutional Review Board at Beaumont Hospital, Farmington Hills, reviewed and approved all aspects of the study, including the content of the survey, in accordance with institutional, federal, and international guidelines.http://vassarstats.net/tab2x2.html) ) compared with the non-electric toothbrush user group (seven users [10.9%]), but this difference was not statistically significant (p = 0.77).Additionally, of the 47 study participants who use electric toothbrushes, 6 (12.8%) reported dizziness when using their electric toothbrushes. The data collected suggest that the vibrations produced during electric toothbrush use have a minimal effect on unresolved BPPV after an initial head positioning maneuver treatment, as well as recurrence of BPPV when comparing electric toothbrush users with non-electric toothbrush users. Multiple confounding factors such as medications, use of other vibratory devices, and associated inner ear disorders were similar across each group and do not seem to influence the results obtained when comparing the two groups.One limitation of the study is that the specific dates of initial BPPV diagnosis, initiation of electric toothbrush use, and the use of electric toothbrushes relative to the initial head positioning maneuver treatment were not established. More specific timelines included in a subsequent study may prove beneficial in determining a possible link between electric toothbrush use and recurrent BPPV. Another limitation to the study is the recall bias of the patients pertaining to their electric toothbrush use. It would have been important to ellicit if the patients experiencing symptomatic recurrence had been using electric toothbrushes prior to initial Epley treatment. Further investigations into the etiology of BPPV recurrence and the association with multiple factors, including patient compliance with post-Epley instructions, noise exposure after initial treatment, and blood pressure regulation following Epley, would be warranted.Clinically, the findings of this study suggest that electric toothbrush use does not increase the risk of persistent BPPV symptoms with appropriate therapy. The findings are limited to the population surveyed, and therefore physicians should be cognizant of geographic disparities that may have affected the data, although all participants were randomized and there were no statistically significant characteristic differences among the population surveyed. Of course, with the limitations of this study previously stated, it is imperative to discuss with the patient that the recurrence of BPPV symptoms may return in light of vibrational device use. Post-Epley instructions should always be given to the patient in order to increase the likelihood of symptom resolution, and with the data found in this study, patients may be informed that electric toothbrush use can safely be continued. Based on our data, this study suggests that the mechanical vibrations from electric toothbrushes do not have an association with recurrent BPPV. A small subset of BPPV patients in the study did experience dizziness with electric toothbrush use. The results align with some publications that demonstrate that dizziness can be initiated with vibrations in the head and neck area; however, this study suggests that an electric toothbrush’s vibration is not a significant risk factor for inducing recurrent BPPV.


Birth weight is continuously decreasing in Japan since food satiation has become a problem in recent years. The present study aimed to develop and examine the reliability and validity of a scale for the assessment of risk factors for low birth weight in infants born at term.A self-administered postal questionnaire survey comprising a low birth weight risk assessment scale was conducted on mothers with children of nursery school or kindergarten age. After item analysis , factor structure was confirmed by an exploratory factor analysis using the main factor method promax rotation. The reliability of this scale was confirmed by Cronbach’s α coefficient and Item–Total correlation. The validity was confirmed by known-groups validity and internal validity.The responses of 630 mothers  were analyzed. Factor analysis  obtained an optimal scale comprising 25 items in the following nine factors: “guidance at each checkup,” “adequate rest,” “support from husband,” “effects on the fetus,” “support from society,” “support from family,” “effects of minor troubles,” “good lifestyle habits,” and “fall risk and lifestyle changes.” The overall Cronbach’s α coefficient for the scale was 0.701. Known-groups validity examination revealed significant differences in scale scores of birth weight, birth history, and maternal smoking status.The scale demonstrated internal consistency, construct validity, and known-groups validity, indicating that it can be used as an indicator of low birth weight risk. In the future, this scale may be included in medical questionnaires as part of health guidance for pregnant women at a risk of delivering low birth weight children.The online version of this article (10.1186/s12913-019-3886-7) contains supplementary material, which is available to authorized users. Three elements form the background to this study. First, the mean birth weight in Japan is continuously decreasing , 2, withThe first step was to clarify the factors affecting birth weight. In a preliminary study, semi-structured interviews with 12 mothers of young children, including low birth weight infants, identified maternal lifestyle and psychological characteristics during pregnancy as potential causes of low birth weight . We consThe present study aimed to clarify the causal relationship between maternal daily lifestyle during pregnancy and low infant birth weight and to develop a scale for the assessment of maternity risk factors for low birth weight in infants born at term. A low birth weight risk assessment scale for use in prenatal checkups was developed, and its reliability and validity were examined.Subjects were mothers with the youngest child below school age (≤6 years).This was a questionnaire-based survey. A total of 3400 questionnaires were distributed to 42 nursery schools and kindergartens in A Prefecture (including those in remote islands) between February and March 2015. After requesting and obtaining consent from the heads of the Nursery School Association and Private Kindergarten Association Recommended Facilities in A Prefecture, the nursery schools and kindergartens distributed questionnaire packages  to parents and guardians. Postal return of the completed questionnaire to the researchers using the return envelope was considered as the final consent for participation.Questions regarding maternal characteristics included maternal age, height, pre-pregnancy weight, age at the time of delivery, weight gain during pregnancy, participation in classes for mothers, employment status, and the number of children in the family. Questions for pre-school children included age, sex, birth weight, and gestational age at birth. In addition, a draft scale prepared by the below mentioned method was included. Responses were scored from 1 to 4 points to attain a score for each item. The magnitude of the score demonstrated the degree of relevance to risk factors for low birth weight.p < 0.05.In order to assess subject characteristics, descriptive statistics were calculated for all variables, and characteristics were then selected for inclusion in the scale on the basis of the item analysis criteria. According to their employment status during pregnancy, women were classified as “non-working” if they continued as full-time homemakers during pregnancy or “working” if they were regular or non-regular employees or were self-employed during pregnancy. Statistical package SPSS 20.0 was used for the analysis with significance set at The scale was developed on the basis of item analysis, and scale reliability and validity were then examined. The inclusion of each item was determined as follows: (i) the presence of floor or ceiling effects was confirmed on the basis of mean values and standard deviations ; (ii) Good–Poor analysis  was performed; and (iii) inter-item correlation matrix was obtained.The reliability of the scale was determined on the basis of the Cronbach’s α coefficient and correlation analysis between the item and scale [Item–Total correlation] to investigate item inclusion. The validity of the scale was examined as follows: (i) content validity of the scale was investigated; (ii) construct validity was investigated using exploratory factor analysis; and (iii) known-groups validity was investigated. Concurrent validity could not be investigated as no adequate scale exists for investigating criterion validity; therefore, known-groups validity was tested. The following three variables according to their known-groups validity were classified and subjected to comparative analysis of the mean scale total scores: (i) birth weights classified as “< 2500 g” or “≥2500 g” (t-test); (ii) birth histories classified as “primipara” or “multipara” (t-test); and (iii) maternal smoking status classified into the following five groups: “no history of smoking,” “stopped smoking before this pregnancy,” “permanently stopped smoking during this pregnancy,” “temporarily stopped smoking during this pregnancy,” and “continued smoking throughout this pregnancy” [one-way analysis of variance (ANOVA) and Tukey–Kramer honestly significant difference (HSD) test].The study aims and outline, subject rights , protection of privacy through questionnaire anonymity, use of ID numbers instead of names, protection of personal information, data confidentiality, restriction of data use to the present study, destruction of questionnaires immediately after finishing the present study, and the fact that returning a completed questionnaire would be considered as consent for participation were explained to all subjects.Out of the 3400 questionnaires distributed, responses were received from 671 mothers . The aim of this study was to construct a scale to assess pregnant women who may deliver a low birth weight baby because of their lifestyles, which may affect the development of the fetus lurking in their daily life. Responses from mothers of twins or sick babies, which are conditions that are considered to be associated with low birth weight, were excluded from the analysis. In total, the responses from 630 mothers of babies  and 916 mothers of pre-school children were analyzed.Maternal characteristics were as follows: mean age, 35.7 [standard deviation (SD)], 4.9; range, 23–51) years; mean number of children in the family, 2.2 ; mean age at time of delivery, 31.2  years; and employment status during pregnancy, 397 non-working (43.3%) and 519 working (56.7%). Child characteristics were as follows: mean age, 3.6  years; sex, 463 boys (53.3%) and 406 girls (46.7%)  . Therefore, the item “I consumed alcohol”, which had the greatest number of low coefficient values in the inter-item correlation matrix, was excluded, and factor analysis was repeated for the remaining 32 items. However, Cronbach’s α coefficient for the 11th factor remained low; therefore, the factor analysis process was repeated until Cronbach’s α coefficient increased and the results stabilized. The following items were eliminated from subsequent analyses: “I consumed alcohol,” “I often experienced abdominal bloating,” “I thought that the saying, ‘deliver them small and raise them big,’ held true for me and my child(ren),” and “I refrained from driving a car.” Factor analysis was conducted on the remaining 29 items, and the lowest Cronbach’s α coefficient increased to 0.460. At this point, nine factors were extracted. Factor analysis was conducted again excluding four items with a factor loading of under 0.35 . As a result, an optimal scale was obtained, which was interpreted without contradictions in the meanings of the items. The final scale comprised 25 items in 9 factors. The details and results of this analysis are shown in Fig. Kaiser–Meyer–Olkin test with the sampling adequacy of 0.640 and the screen plot with changes in factor eigenvalues indicated that 9 factors were appropriate. The cumulative contribution ratio of the sum of squared load amount after extraction was 57.0%. Therefore, items with factor loading ≥0.35 were included in the scale, and subsequent examinations of reliability and validity were conducted for 25 items in 9 factors. The factor pattern and factor correlation matrix are shown in Table The 9 factors were labeled to reflect the related content assessment as follows. (i) guidance at each checkup: maternal feelings at the time of guidance ; (ii) adequate rest: the state of maternal rest during pregnancy ; (iii) support from husband: support provided by the husband and related maternal satisfaction (two items); (iv) effects on the fetus: effects of alcohol consumption and tobacco on the fetus (two items); (v) support from society: social support other than that provided by the husband and family and related maternal satisfaction (two items); (vi) support from family: support provided by parents (including in-laws) and related maternal satisfaction (two items); (vii) effects of minor troubles: the extent of and related maternal feelings regarding minor troubles, such as morning sickness (three items); (viii) good lifestyle habits: good lifestyle habits during pregnancy (three items); and (ix) fall risk and lifestyle changes: concern regarding falling during pregnancy and associated lifestyle changes (two items).The strongest positive correlation in the factor correlation matrix was between “social support” and “family support” (0.417), followed by among “support from husband”, “support from society”, and “support from family,” between “adequate rest” and “good lifestyle habits” (0.336–0.395), and between “effects on the fetus” and “fall risk and lifestyle habits” (0.234).These findings show a structure comprising two groups, one related to daily lifestyle during pregnancy, including “adequate rest,” “good lifestyle habits,” “effects on the fetus,” “effects of minor trouble,” “guidance at each checkup,” and “fall risk and lifestyle changes” and one related to support including “support from husband,” “support from family,” and “support from society.”The mean scale total score was 68.5 , and the normal probability–probability plot showed a normal distribution. The scale score was 25–100 points. Regarding the overall reliability of the scale, Cronbach’s α coefficient for each item ranged from 0.09–0.585 and that for the overall scale was 0.701 . Regarding birth history, the mean total scores of primipara were significantly higher than those of multipara . One-way ANOVA revealed a significant difference in scores for maternal smoking status, whereas multiple comparison (Tukey–Kramer HSD test) demonstrated that the “no history of smoking” group had significantly higher mean total scores than the “continued smoking throughout this pregnancy” group (p < 0.00). The “stopped smoking before this pregnancy” group had significantly higher mean total scores than the “continued smoking throughout this pregnancy” group (p < 0.00), while the “permanently stopped smoking during this pregnancy” group also had significantly higher mean total scores than the “continued smoking throughout this pregnancy” group (p < 0.00)  for the 8th factor were low, they were within the acceptable range for the present study, which combined 25 items into one questionnaire. Thus, internal consistency was ensured, and reliability of the scale was confirmed.Content validity of the scale was ensured by repeated confirmation among the authors during the scale development. The results of exploratory factor analysis to investigate construct validity showed a nine-factor structure for the low birth weight risk assessment scale. These nine factors cover all of the important items capable of assessing risk factors for low birth weight, indicating construct validity of the present scale. The 1st factor is an indicator of the extent of self-monitoring during pregnancy related to indications and guidance received during prenatal checkups. Prenatal checkups have important implications not only for the identification and subsequent management of abnormal cases but also for the provision of guidance regarding maternal lifestyle improvements in uneventful pregnancies. Maternal build, such as being underweight or obese, affects fetal development . PrenataThe 2nd factor is an indicator of the degree of mental and physical rest obtained during pregnancy. Changes in hormonal balance together with the increasing size of the abdomen with the growth of the fetus exert a psychological effect, and the occurrence of minor troubles also affects daily life and employment during pregnancy. Therefore, adequate rest and good quality sleep enable recovery from pregnancy fatigue, minimize physical and mental effects, and are essential for promoting and maintaining self-care ability.The 3rd, 5th, and 6th factors are indicators of the degree of support from the husband, family, and society and maternal satisfaction with such support. The presence of support can relieve maternal anxiety or emotional changes experienced during pregnancy . HusbandThe 4th factor is an indicator of effects on the fetus. Alcohol consumption during any stage of pregnancy is believed to affect the fetus, potentially resulting in miscarriage, deformity, brain damage, intrauterine growth retardation, or low birth weight . MeanwhiThe 7th factor is an indicator of the extent of minor troubles. Morning sickness during the first trimester of pregnancy is a common cause of psychological conflict and, if severe, can cause difficulties while eating and, in some cases, severe dehydration or malnutrition. In addition to causing difficulties for the mother, this has effects on the fetus; therefore, related items are important in terms of effects on birth weight.The 8th factor is an indicator of the extent to which positive habits are incorporated into the daily lifestyle. Being underweight before pregnancy and insufficient weight gain during pregnancy lead to poor fetal nutritional status, which can cause low birth weight . TherefoFinally, the 9th factor is an indicator of maternal risk of falls. Falls during pregnancy are associated with the risk of miscarriage and premature birth; therefore, great care must be taken to avoid falling. Women in Japan tend to switch to lower heels during pregnancy .No existing scale could be found for investigating concurrent validity; therefore, known-groups validity was verified. A significant difference was observed in the mean total subscale scores on inter-group comparison regarding birth weight, birth history, and maternal smoking status. The present findings are consistent with those of previous studies showing that infant birth weight tends to be lower among primipara compared with that in multipara  and thatThese findings demonstrate the validity of this scale comprising 25 items in 9 factors as a scale capable of assessing maternity risk factors for low birth weight in infants born at term.The reliability and validity of this maternity low birth weight risk assessment scale were verified; thus, it can be used for the screening of high-risk pregnancies during health guidance. This scale would be particularly useful for identifying high-risk pregnancies during obtaining the history of mothers in prenatal checkups or during consultations with pregnant employees in the labor management section in their company regardless of the ability of the consultant.There are some limitations in the present study. This was a cohort study regarding the daily lifestyles of pregnant women. The survey method may have introduced recall bias as responses were obtained from women with children of nursery school or kindergarten age looking back at and recalling their pregnancy lifestyles. Ideally, the survey should have been conducted either during pregnancy or soon after birth. However, the present study used a systematic oral history method focusing on mothers with children of nursery school and kindergarten age who were able to reflect and recall their lifestyle and sense of values during pregnancy . The scaThe present study developed and examined the reliability and validity of a low birth weight risk assessment scale with items that reflect potential causes of low birth weight identified through a preliminary survey and previous research. The scale ultimately comprised the nine factors of “guidance at each checkup,” “adequate rest,” “support from husband,” “effects on fetus,” “support from society,” “support from family,” “effects of minor troubles,” “good lifestyle habits,” and “fall risk and lifestyle changes,” for which reliability  and construct validity  were confirmed.Additional file 1:For mothers with at least one preschool-aged child Survey on mothers’ living conditions during pregnancy. (DOCX 781 kb)


The preterm birth (PTB) rate for singletons born in the tropical Caribbean island Puerto Rico increased from 11.3% in 1994, which was comparable to rates in the U.S., to as high as 18.3% in 2006 before decreasing to 15.5% in 2012. A few studies have reported that weather extremes are associated with higher risk of preterm birth, however, the effects of ambient temperature and precipitation has not been well examined in Puerto Rico. We compiled child birth data from the National Center for Health Statistics and weather data from the National Oceanic and Atmospheric Administration from 1994 to 2012. We explored the association between the weather factors and PTB rates with a distributed lag non-linear model (DLNM). We did not find direct association of lagged effect of temperature on birth outcome over monthly timescales. Both high intensity and frequency of precipitation and high frequency of storm and flood events are associated with increased risk of PTB rates. While the weather factors do not explain the marked increase and decrease in PTB rate, we emphasize the negative effects on PTB from weather extremes particularly precipitation in Puerto Rico. Despite its enormous social and economic cost, currently no model can precisely or roughly predict the occurrence of PTB.Preterm birth (PTB), defined as birth before 37 weeks of completed gestation, is the leading cause of neonatal morbidity in the U.S., and is also associated with a number of chronic health conditions and developmental disabilities that cause lifelong consequences7. Many of the epigenetic factors are interactive and connected and are collectively reflected as the socioeconomic status of the individual, where individuals of disadvantaged socioeconomic status are linked with poorer medical conditions and infertility treatment, and more intense mental health problems. Despite consideration of socioeconomic variabilities, the ethnic disparities of PTB rates between white (~11%) and black (~16%) infants in the U.S. remains a puzzle given current knowledge9. In addition, many researchers have explored the effects of environmental contaminant exposure, and have identified several pollutants contributing to PTB, including air pollutants such as particulate matter and sulfur dioxide11, drinking water pollutants such as atrazine and nitrate12, and other man-made pollutants such as bisphenol13, phthalate14, and pesticides15. Studies that explore the effects of weather conditions on PTB rates generally conclude that higher temperatures increase the odds of PTB23; however, other studies have found a protective effect of higher temperature on PTB selected regions24 or no conclusive effect25. High temperature has both negative biological and psychological effect and hence is plausible to be associated with the increase in PTB rates17. On the other hand, no study has quantified the effect of precipitation on PTB, though heavy precipitation has been noticed to exacerbate the negative maternal and pregnancy outcomes26 and also storm and flood events are considered to be stresses during pregnancy27.In addition to changes in obstetric practices, multidimensional factors are found to contribute to PTB including personal characteristics such as genetics, behavioral and psychological factors, medical conditions, infertility treatment and biology, and environmental influences such as contaminant exposures and climate disturbances23. Here we use comprehensive datasets of child natality and weather information for Puerto Rico to assess the integrative weather effects on PTB  and extreme hot (10% for 99th percentile of 31.9 °C) temperatures and PTB rates in Guangzhou, China. Comparatively several studies report protective effects of temperature on PTB rates, where high temperature is a protective factor31. Liang et al.24 reports that low temperatures (the 1st percentile temperature of 9 °C) have a RR on PTB rates of 1.54, while high temperatures have a RR of 0.62 (99th percentile) for 30 days before delivery in Shenzhen, China.We observed mixed effects of temperature on PTB rates for different regions, though generally temperature appears to be a protective factor or has no direct effect on preterm birth for this tropical island. In comparison, Cox 32, dehydration33, pre-eclampsia34, and other negative effects on maternal health and birth outcome. The effect of temperature on birth outcome is based on acute temporal association on the day/week of birth. The biological mechanisms of thermoregulation that are happening acutely during heat stress induce contractions and could lead to preterm labor and ultimately preterm birth34. This acute heat stress effect of temperature on PTB might explain that in this study temperature somewhat exhibits as a protective effect on PTB because there is only mild variation of temperature in Puerto Rico.Our approach to analyzing the association between temperature and PTB rate is different from the literature, as we use both the frequency of high temperature days in a month and the actual temperature values, due to the temperature patterns in Puerto Rico. There is no considerable variation of temperature from year to year in Puerto Rico  have little effect on PTB rates. This phenomenon points out that rather than the actual values of precipitation or temperature, it is the extreme climate events that have more impact on PTB, which is consistent with findings from literature36. Our findings highlight the concern for increased risk of adverse birth outcomes under the global warming scenario, which likely trigger more intense and frequent precipitation as suggested by both simulation and observation results38.We studied the association between precipitation and PTB rates, which is largely overlooked by literature. Lee 39. Maternal care might be disrupted during the storm events in addition to stress. However, on the other hand the pregnant women may be more careful about their health and be better taken care of by their family members. Hence the overall effect from storm events on PTB are subtle and sensitive to specification of the pregnant women’s socio-economic status27. Several studies, including the present study, highlight the trends over time in PTB rates climbing through the 1990s up until the mid-2000s, then gradually decreasing. This overall pattern in the U.S. has been previously attributed to several factors unrelated to weather, including obstetrics/gynecology standards practices around cesarean section delivery2  sites in the U.S.52. In a synoptic survey study, Cantonwine et al.53 found widespread exposure to phthalates among pregnant women living in this karst area particularly for those groups using private wells as drinking water, which strongly indicates the association of exposure to environmental chemicals and incidences of PTB in Puerto Rico. The increase and decrease trend of PTB rates that roughly coincide with the historical contaminants accumulation and recent reduction due to remediation procedures is a further evidence to support this link.The mechanism of how precipitation affects birth is unknown, though several studies point out that high precipitation is negatively related to human health. There are many intermediate factors associated with precipitation that impact PTB, such as environmental contamination and disease transmission that are not directly explored in this study. Although no study has quantitatively explored the association between precipitation and PTB, a comparative study on human health found that precipitation extremes are associated with changes to air moisture content55. Heat waves are typically defined by extreme temperatures (e.g. 95th percentile for summer time daily average temperatures or maximum temperatures) for at least 2 days. This relationship is likely due to increased risk of premature labor and/or premature rupture of membranes following heat stress and/or dehydration7. We used month as the lowest time scale for the following reasons: (1) only monthly level child birth natality data is publicly available from CDC; (2) Puerto Rico has general stable warm temperatures and monthly average temperature can capture the temperature variance sufficiently; and (3) the etiology threshold window for temperature effect on preterm birth is still debating and 1-monthly exposure before delivery is plausible to explore the short term effect of temperature exposure56. Nevertheless, this study might underestimate the near-birth association between temperature and PTB, as most prior studies examined their association at a daily level. Moreover, the effects of meteorological factors on health might be modified at different time lags in the short-term scale, for example, a study found that relative humidity showed negative effect at lag 1 day and positive effect at lag 5–7 days on adolescent hand, foot, and mouth disease57. Moreover, there are many more important factors such as gene, environmental pollution, social-economy status and health care affect PTB rates, whereas the effects of extreme weather conditions exhibit more as a “trigger” to negative birth outcomes58. In recent decades, the total number of child births dropped significantly but the drop in PTB rate has not followed the same decreasing rate. Reasons for the changes to PTB rates in Puerto Rico may not be clearly understood, and maybe influenced by the change in obstetric practices, recent economic downslide and population migration trend59, but the contributions of weather-intensified virus epidemics as well as exposure to environmental contaminants cannot be neglected.Our analysis should be considered in light of limitations. Numerous studies using daily data have found significant positive associations between heat waves, with 0 to 7- day lags, and PTB in the last month of gestation60. This natality data set includes information on mother’s residence, mother’s characteristics, birth characteristics, and maternal risk factors. The lowest level of geographic information is identified as areas with more than 100,000 people, and in Puerto Rico we have Bayamón, Caguas, Carolina, Mayagüez, Ponce, San Juan, nonmetropolitan areas, and combined areas with population less than 10,000. For representative spatial analysis, data completeness and geographic match of weather stations, in this study we chose three regions including San Juan, Mayagüez, and Ponce which represents 44% of the total child birth records  in the study period  of child birth certificates data from the National Center for Health Statistics in Centers for Disease Control and Prevention (NCHS CDC) representing the most comprehensive knowledge of maternal and child birth information in Puerto Rico61. The three weather stations are: Luis Muñoz Marín International Airport in San Juan , Mayagüez City Station , and Ponce 4 E station   in the same period at three selected stations where the majority of the population reside to represent weather conditions in the corresponding locationsThe temporal patterns of the weather factors in the three regions can be found in Appendix Figs 24. We used the distributed lag non-linear model (DLNM) to capture and explore the delayed effects of weather factors on PTB rates. The essence of the DLNM model is to apply a generalized linear model by fitting a cross-basis (cb) function of the independent variable62. The cross-basis function pictures both the shape and the distributed lagged effects of the variable (more details are available in literature)63. The general form of the DLNM model is:1 is the weather factor and month is from 1 to 12 in every year. We used Poisson distribution in our model. Our data showed that there is little variation in RMSE and AIC values for the changes of degrees for the polynomial fitting and the number of lags, though there are small variations in the shape of the model outputs. Our final model selection choice was to assign 1-month lag and 3-degrees of polynomial to all the weather factors. The effect of each weather factor on PTB was examined separately; therefore, x1 in the equation only refers to one of the factors exclusively, including precipitation intensity and frequency (DP10), temperature and warm temperature frequency (DX90), and frequencies of storm and flood events. The month variable is used to smooth the seasonal impact. We evaluated the lagged effects with relative risk (RR), which is calculated as the effect of a level of a weather factor on PTB against the effect from the mean value of that factor.We first performed a general exploration of the data, including descriptive statistics, Pearson correlation, time series examination, and ANOVA for group means comparison. We then performed a logistic regression analysis and panel linear model (plm) to examine the modeling ability by using the weather factors to predict the occurrence of PTB. Based on both the logistic regression and plm analyses, we did not obtain any convincing results to build a strong association between weather factors and PTB rate (Appendix 1). This lack of direct relationship has been noted by previous studies and indicates that the relationship is non-linearSupplementary File


The placenta is a complex organ that influences prenatal growth and development, and through fetal programming impacts postnatal health and well-being lifelong. Little information exists on placental pathology in the presence of congenital heart disease (CHD). Our objective is to characterize the placenta in CHD and investigate for distinctions based on type of malformation present. Placental pathology from singleton neonates prenatally diagnosed and delivered at > 37 weeks gestation was analyzed. Placental findings of absolute weight, placental weight-to-newborn birth weight ratio, chorangiosis, villus maturity, thrombosis, and infarction were recorded and analyzed based on four physiological categories of CHD: (1) single ventricle-aortic obstruction, (2) single ventricle-pulmonic obstruction, (3) two-ventricle anomalies, and (4) transposition of the great arteries (TGA). Associations between fetal Doppler assessments of middle cerebral/umbilical arterial flow and placental findings were investigated. A total of 120 cases of complex CHD were analyzed. Overall placental-to-birth weight ratios were < 10th percentile for 77% and < 3rd percentile for 49% with abnormalities of chorangiosis (18%), hypomature villi (15%), thrombosis (41%), and infarction (17%) common. There was no association between fetal Doppler flow measures and placental abnormalities. Newborns with TGA had the greatest degree of placental abnormality. Placentas of newborns with CHD are smaller than expected and manifest a number of vascular abnormalities, with TGA most prominent. Fetal Doppler does not correlate with these abnormalities. Studies investigating the relationship between placental abnormalities and postnatal outcomes may offer insight into the fetal origins of outcome variability in CHD. The placenta is one of the least understood of human organs and arguably one of the most important, not only for the health of a woman and her fetus during pregnancy, but also for the lifelong health of both , 2. The The role the placenta plays in congenital heart disease, the most common birth defect in the human, is poorly understood. Placentation and early fetal cardiovascular development may be linked in a number of ways and it is reasonable to suspect that abnormalities in one process may be associated with the other. In mothers carrying a fetus with congenital heart disease (CHD), an imbalance in pro-angiogenic and anti-angiogenic factors in both maternal blood and fetal cord blood is reported . MaternaPlacental structure and function may influence outcomes in the fetus with CHD and is thus worthy of exploration. Investigational focus on the placenta might offer clues that can prognosticate for outcomes, as well as identify potentially modifiable variables that may prove to be candidates for prenatal therapy. In order to better understand the relationship between the placenta and CHD, the objectives of this study are to (1) investigate characteristics of the placenta at birth in CHD, (2) explore for differences in these characteristics based on type of heart malformation present, and (3) determine the possible relationship between placental characteristics and fetal echocardiographic Doppler parameters of blood flow in a variety of forms of CHD.This is a single center cohort study. Fetuses with CHD prenatally diagnosed and managed at the Fetal Heart Program at the Children’s Hospital of Philadelphia (CHOP) and delivered in our Special Delivery Unit at CHOP were enrolled. Subjects include (1) singleton fetuses with hemodynamically important congenital heart disease, defined as anomalies requiring surgical or catheter-based intervention within the first 6 months of life, and (2) fetuses delivered ≥ 37 weeks gestation and for whom an intact placenta was available for pathology examination. In order to reduce bias and diminish influence from confounding factors, subjects are excluded if there was any known identifiable genetic, chromosomal, or syndromic diagnosis before or after birth, any major additional anomaly , or prematurity < 37 weeks gestation. Institutional Review Board permission was obtained for the study.Placenta pathology reports were reviewed with tabulation of predetermined anatomical and pathological characteristics. Placental examinations were performed per standardized institutional protocol with initial review by any one of the three perinatal pathologists. Finalized reports and placental images were retrospectively reviewed by one pathologist (EM) for the following variables: placental weight, villous maturity, villous chorangiosis, villous infarction, and thrombosis. The diagnosis of chorangiosis is based on the previously defined histologic criteria of ≥ 10 villi containing ≥ 10 capillaries in ≥ 10 microscopic fields . Villus z score for gestational age at birth [http://peditools.org/fenton2013/index.php] [Records were reviewed for birth weight and then converted to dex.php]  and (2) dex.php] .Subjects underwent fetal echocardiography per our laboratory clinical protocol  includinz scores, placental weight or weight ratios, and fetal Doppler flow indices are examined by one-way ANOVA. Differences between groups in the proportion of subjects with placental weight–birth weight ratios < 10%, or < 3% or with placental findings of thrombosis, infarction, chorangiosis, or hypomature villi are examined by Chi-square contingency table analysis. Associations between placental weight measures, thrombosis, infarction, villus maturity, and fetal Doppler blood flow indices are examined by regression analysis. p value of < 0.05 is considered significant.Data are reported for the entire cohort and comparisons made between subsets based on categories of CHD. In order to detect for possible differences in placental characteristics specific to type of congenital heart disease, subjects were divided into categories based on type of cardiovascular physiology as follows: (1) single ventricle with aortic obstruction (group 1), (2) single ventricle with pulmonic obstruction (group 2), (3) two-ventricle anatomy (group 3), and (4) transposition of the great arteries with no, or hemodynamically insignificant small, ventricular septal defect (group 4). Differences between groups for numerical values of birth weight, birth weight One hundred and twenty subjects are included in the study. The distribution of anatomical type of CHD among the groups of physiological categories is listed in Table z score is normal (− 0.02 ± 0.91); however, the placentas are smaller than expected. Overall, placental weight as characterized by birth weight-to-placental weight ratio is a mean of 7.42 ± 1.3, in comparison to expected for normal at a mean of 39 weeks gestational age of 7.1 as per Baergen   . FurtherOur findings support the value of further investigation of the placenta in CHD, in particular in patients with TGA. Prospective investigation looking at details of maternal factors influencing placental health  will be important to incorporate into future study analysis. Knowledge gained may identify modifiable variables during pregnancy leading to treatment such as maternal supplemental oxygenation, or maternal anti-thrombotic therapy in select pregnant women, thus ushering in an era of fetal therapy that may improve outcomes for patients with CHD.


Severe iodine deficiency in mothers is known to impair foetal development. Pregnant women in the UK may be iodine insufficient, but recent assessments of iodine status are limited. This study assessed maternal urinary iodine concentrations (UIC) and birth outcomes in three UK cities. Spot urines were collected from 541 women in London, Manchester and Leeds from 2004–2008 as part of the Screening for Pregnancy End points (SCOPE) study. UIC at 15 and 20 weeks’ gestation was estimated using inductively coupled plasma-mass spectrometry (ICP-MS). Associations were estimated between iodine status (UIC and iodine-to-creatinine ratio) and birth weight, birth weight centile (primary outcome), small for gestational age (SGA) and spontaneous preterm birth. Median UIC was highest in Manchester : 126, 158) and London  and lowest in Leeds , but the proportion with UIC <50 µg/L was <20% in all three cities. No evidence of an association was observed between UIC and birth weight centile , nor with odds of spontaneous preterm birth . Given the finding of iodine concentrations being insufficient according to World Health Organization (WHO) guidelines amongst pregnant women across all three cities, further studies may be needed to explore implications for maternal thyroid function and longer-term child health outcomes. Iodine is essential for the synthesis of the thyroid hormones triiodothyronine T3) and thyroxine (T4) which regulate growth and metabolism . Materna and thyrThe introduction of iodine into livestock feed and the widespread adoption of iodophors in the dairy industry after the 1930s resulted in the reduction of overt signs of iodine deficiency in the United Kingdom (UK) population by the 1960s ,5,6. To Although the UK adult population is considered iodine sufficient , recent We therefore aimed to assess iodine status in the three UK sites of the Screening for Pregnancy Endpoints (SCOPE) international birth cohort, and assess associations between maternal iodine status and birth outcomes, including birth weight, birth centile, small for gestational age (SGA) and spontaneous preterm birth.clinicaltrials.gov NCT02357667.We analysed samples from three English centres from the Screening for Pregnancy Endpoints (SCOPE) birth cohort. The SCOPE study was previously reported in detail elsewhere . In brieParticipants were interviewed during antenatal clinic visits at 15 (± 1) and 20 (± 1) weeks’ gestation. Participant characteristics were recorded including age, ethnicity, diet, body mass index (BMI), smoking, marital status, employment and socioeconomic status. Participant socioeconomic index was scored using the New Zealand Socio-economic Index 1996. Spot urines were collected for 643 women at the three UK cities; 619 samples were collected at 15 weeks and 585 at 20 weeks, with 547 providing samples at both time points.Urinary iodine concentration (UIC) was measured in all samples taken at 15 and 20 weeks of gestation. Assessment of individual iodine status typically requires a series of 24 hour urine collections, however spot urines are considered an acceptable tool for assessing iodine status on a population basis . It is a127iodine concentration was measured at the University of Leeds using inductively coupled plasma-mass spectrometry (ICP-MS) , accredited by the Centers for Disease Control and Prevention (CDC) Ensuring the Quality of Urinary Iodine Procedures (EQUIP) standardisation programme. Test samples, calibration standards, and quality control samples were diluted 1:10 prior to analysis. Individual samples consisted of 500 μL of participant urine, 4000 μL of diluent (1% tetramethylammonium hydroxide (Sigma Aldrich), 0.01% Triton X-100 (Sigma Aldrich)) and 500 µL high purity H2O (>18.2 MΩ.cm). Tellurium (10 μg/L) (Sigma Aldrich) was included as an internal standard for the ICP-MS analysis. Sample concentration was determined against a urine matrix matched calibration curve spiked with 0, 5, 10, 40, 70, 100, 400 and 800 μg/L iodide (Sigma Aldrich). The accuracy of the results was further validated through the inclusion of internal quality control urines: A , B  and C . External validation of our results was provided by inclusion of the certified reference material Seronorm Trace Metal Urine Level 1 , and through participation in the CDC EQUIP programme. Observed values were 63.3 μg/L (n = 99), 98.6 μg/L (n = 99) and 157.9 μg/L (n = 99) for quality control urines A, B and C respectively. The observed value for certified reference material was 102.7 μg/L (n = 33). Assessment of intra-run precision gave coefficients of variation (CV) of 1.42% at 60 μg/L, 1.67% at 98 μg/L and 2.34% at 159 μg/L. Inter-run precision gave a CV of 2.4% at 60 μg/L, 4.7% at 98 μg/L and 6.0% at 159 μg/L. The method limit of quantification was 1.46 μg/L.Urinary Urinary creatinine concentrations were assessed through a standard microplate assay utilising the Jaffe reaction. Assessment of creatinine intra-assay precision gave a CV of 2% at 10 mg/L, 1% at 70 mg/L and 1.1% at 120 mg/L. Assessment of inter-assay precision gave a CV of 14.5% at 10 mg/L, 9.7% at 70 mg/L and 5.5% at 120 mg/L.The primary and a priori outcome for the analysis was birth weight centile. Secondary outcomes were birth weight, SGA, and spontaneous preterm birth. SGA was defined as a birth weight centile <10th on a customised centile chart that accounts for maternal height, weight, parity, ethnicity, neonatal gestation at delivery and sex . This dePrior to analysis, a set of exclusion parameters were applied. Analysis was limited to participants with urine samples at both time points, using the mean UIC per participant . ExploraLinear regression was used to quantify associations between UIC and I:Cr for continuous birth outcomes (birth weight and birth weight centile) and logistic regression was used for binary outcomes (SGA and spontaneous preterm birth < 37 weeks). Estimates (with 95% CI) are presented based on the arithmetic mean across the two time points for both UIC and I:Cr for mothers providing both samples  and stratified by time point . All results are presented as unadjusted and adjusted for known confounders. Directed acyclic graphs were used to inform which variables should be included as covariates, and to prevent over-adjustment . EthniciEthical approval was gained from local research ethics committees for each SCOPE recruitment site . All participants provided written informed consent.Geometric mean UIC varied by marital status, geographical location, neonatal gestational age at delivery and gestational time point . UIC alsEstimates for birth weight and spontaneous preterm birth outcomes were not substantially changed on adjustment for maternal BMI (data not shown).World Health Organization (WHO) guidelines are commonly applied for assessing iodine deficiency disorders . These gDespite the presence of iodine insufficiency in the cohort, there was no evidence of any association between UIC or I:Cr and birth outcomes. Only a small number of studies have assessed potential links between UIC in pregnancy and neonatal outcomes ,21,22,23Charoenratana et al.  found thWhilst London and Manchester participants had higher UIC values, they also had smaller proportions of participants in the lowest category of socioeconomic status, with London having the smallest. In contrast, Leeds had the highest proportion. As our study found that lower socioeconomic status was associated with lower UIC, our results may suggest that regions of the UK with a greater proportion of citizens with a lower socioeconomic index may be at greater risk of iodine insufficiency. Additionally, participants in the 25–29 age category generally had lower UIC values than participants in other age categories, whilst active smokers generally had lower mean UIC values than non-smokers. Whilst the proportion of participants in each cohort with UIC values <50 µg/L was adequate under WHO guidelines for the general population , our observed proportions still constitute a large number of pregnant women who may be at risk for inadequate iodine intakes, if these samples are representative of the UK population as a whole .This study also found that UIC decreased on average between the two time points. A number of changes occur in foetal physiology during the second trimester of pregnancy, with the most notable being the activation of the foetal thyroid between weeks 16–18 of pregnancy . An incrOur study was limited by a number of factors. Sample collection was restricted to the second trimester of pregnancy, and used spot rather than 24 h urine samples, which are limited in their applicability for assessing iodine status to the population level, rather than providing information on individual chronic iodine intakes. In addition, recruitment was restricted to a small number of UK cities and as a result, the study may have been limited in its assessment of iodine status in surrounding suburban and rural areas. Our study also has a number of strengths. These include the large number of participants available for each of our three geographical sites compared with many prior UK iodine studies, the collection of demographic details through face-to-face interviews with participants, the use of robust analytical procedures for assessing biomarkers of iodine status, and controlling for a number of potentially confounding variables in the statistical modelling. To the best of our knowledge, this is the first study to compare iodine status between geographically separate UK populations. In conclusion, we have demonstrated that the iodine status of pregnant women in our study cohort is generally insufficient by WHO guidelines, with variations in iodine concentrations occurring across different cities in the UK. This finding broadly supports conclusions made by prior UK studies that pregnant women in the UK are insufficient in dietary iodine ,14,15,16


Background: Although the benefits of immediate, continuous, uninterrupted skin-to-skin contact (SSC) and early breastfeeding have been widely researched and confirmed, the challenge remains to improve the consistency of this practice. Fewer than half of newborns worldwide are breastfed in the first hour.Design: Cross-sectional descriptive study utilizing iterative review and analysis of video ethnography as well as data extracted from patient records.Sample and Setting: Eighty-four medically uncomplicated mothers and full-term newborns were observed during the first hour after birth at a Baby-Friendly designated hospital in the United States.Findings: Process mapping using an algorithm which included Robson criteria indicated that although included mothers were expected to give birth vaginally and had no medical concerns that would preclude eligibility for SSC in the first hour after birth, 31 of 84 newborns (37%) did not receive immediate SSC after vaginal birth as planned and only 23 (27.4%) self-attached and suckled.Conclusion: Process mapping of optimal skin-to-skin practice in the first hour after birth using the algorithm, HCP-S2S-IA, produced an accurate and useful measurement, illuminating how work is conducted and providing patterns for analysis and opportunities for improvement with targeted interventions. According to UNICEF,The purpose of this study was to analyze the process of uninterrupted SSC between healthy newborns and their mothers immediately after planned vaginal birth in a hospital that had implemented this practice change for both vaginal and cesarean births.This research design was a cross-sectional descriptive study utilizing video ethnographic iterative review and analysis as well as data extracted from patient records.® in 2009, and redesignated in 2014, and is located in California, a state with one of the highest breastfeeding rates in the United States.24The study was conducted at Loma Linda University Medical Center (LLUMC), a large teaching hospital with ∼2,500 births per year. The hospital was designated Baby-Friendly15 This observational study, approved by the hospital's Institutional Review Board, included mothers who were planning a vaginal birth. The protocol included video recording stable babies and mothers in SSC during the first hour after birth and documenting the medications mothers had received during labor.Hospitals designated “Baby-Friendly” by the U.S. authority, Baby-Friendly USA, are expected to implement the routine practice of helping new mothers breastfeed within the first hour after birth. This is interpreted as immediate, continuous, uninterrupted SSC for all healthy newborns for at least 1 hour after both vaginal and cesarean births whether or not the mother plans to breastfeed. If the mother plans to breastfeed, SSC should continue until the completion of the first breastfeed. The staff at the study hospital had received a 5-day in-service training on the importance of, and application of, skin-to-skin using the PRECESS method.Over the course of 4 weeks, 1 week each in May, July, August, and December 2013, informed consent was obtained from clinically uncomplicated nulliparas and multiparas planning a vaginal delivery. Mothers were approached upon arrival to the labor and delivery ward. Informed consent materials were available in English and Spanish, with translation services available for Spanish-speaking participants. The study's inclusion criteria included women who were ≥18 years of age, low risk (as determined by the admitting doctor), English or Spanish speaking as their primary language, and who were estimated to be between 37 and 42 weeks gestation. Infants were eligible if they were full-term gestation, stable, and had no known abnormalities. To safeguard protected health information, names and identifying information were removed from data collection material, which were assigned a linked code. This unique code was also recorded on the video of the baby taken during the first hour after birth.Ninety-six mothers consented to participate in the study. Five had been scheduled for repeat cesareans, and therefore did not meet the inclusion criteria and were considered mistakenly consented. Other participants removed from study analysis included one mother with a previously undisclosed physical condition that would preclude breastfeeding and one who was recategorized as at less than 37 weeks gestation after being consented. One mother was removed after the baby was born with an unexpected cleft. Of these 88, 4 did not include para status in the medical record, resulting in 84 dyads in the final group who could be categorized by Robson criteria. Standard procedures were followed for all study participants, with the exception of the addition of the video recording of the baby for the first hour after birth while skin-to-skin with the mother.Immediately after the birth, video recording of the mother and baby commenced. Hospital protocol stated that the baby would remain in SSC with the semireclined mother for at least the first hour after birth unless there was a medical reason to discontinue. The baby was allowed to move, uninterrupted, through Widström's 9 Stages . The stu25 a well-established method of monitoring and auditing, is used worldwide to standardize comparison methods between hospitals, systems, and countries. Births are categorized as 1 of 10 groups based on five parameters: obstetric history (parity and previous cesarean section), onset of labor , fetal presentation or lie , number of neonates, and gestational age (preterm or term). Appropriate data were accessed from the patient record for each mother to determine the Robson criteria and allow for analysis of the variance in experience of nulliparas and multiparas, of induced mothers, or of mothers who had a vaginal birth after cesarean (VBAC).Robson criteria,Healthy Children Project Skin-to-Skin Implementation Algorithm, (HCP-S2S-IA) was used to categorize the prebirth Robson criteria as well as operationalize the collection of specific measurable elements of the SSC practice. The tool has been shown to be relevant and has been applied in hospital settings for both vaginal and cesarean births in Australia and Japan. Analysis of collected data has been shown to provide insight into where dyads remain on, or leave, the pathway of best practice.26The process measurement tool, the 27 that defined and illustrated each stage and then attending a 2-hour workshop about Widström's 9 Stages. The two reviewers separately and independently coded all of the video recordings using MAXQDA 11.0.2, 2013 for the nine stages. This required an iterative process of repeatedly watching the videos to fine tune the start and end time of each stage, and the elements of behavior of the newborn during that time. Disagreements were resolved through conversation with the trainer.Iterative analysis of the video recording of each dyad was performed by two research assistants who had been blinded to patient records. The assistants had been trained to identify each of Widström's 9 Stages of newborn behavior. The training involved viewing a professional videoThe data in the Algorithm extracted from the video and patient record are displayed in According to Robson criteria for this Algorithm , 23  of the dyads in this study due to emergent cesarean birth. Reasons for these emergent cesareans included fetal distress (three), nonreassuring fetal heart tracing (two), failed VBAC , and failed inductions . Twenty-one (25%) did not get immediate SSC due to emergent care required for either the mother or the newborn after vaginal birth. Reasons for this included respiratory failure (five newborns), chorioamnionitis (four dyads), and postpartum hemorrhage (four mothers). Two newborns had fetal heart murmurs, one of which also had a mother who hemorrhaged. One of the mothers who hemorrhaged also had a uterine rupture and her newborn had respiratory failure. One newborn who was “jittery” went to the NICU. Two mothers refused their babies after the birth, and three had meconium-stained amniotic fluid so were taken directly to the exam table after birth before being returned to mother for SSC. Twelve (14.2%) of the dyads who did not receive SSC immediately after vaginal birth because of initial medical concerns did begin SSC within 5 minutes of birth. Fifty-three dyads (63.1%) met the standard by receiving immediate SSC after planned vaginal birth (either immediately after birth or within 5 minutes) .Of the 23 nulliparas who began labor spontaneously (Robson criteria 1), 1 (4.3%) was not observed to have immediate SSC due to emergent cesarean birth, and 5 (21.7%) did not get immediate SSC because of the need for emergent care for the mother or baby after vaginal birth. Of the 16 induced nulliparas (Robson criteria 2A), 4 (25%) were not observed to have SSC due to emergent cesarean birth, and 4 (25%) did not get immediate SSC due to the need for emergent care. Three (8.8%) of the 34 multiparas (Robson criteria 3 and 4A) were not observed to have SSC due to emergent cesarean birth (1 spontaneous labor and 2 induced), and 7 (21.2%) did not get immediate SSC because they required emergent care immediately after birth . Of the 10 VBAC dyads (Robson criteria 5A and B), 2 (20%) had emergent cesarean birth (1 spontaneous labor and 1 induced) and 4 (40%) required emergent care (3 spontaneous labor and 1 induced). The one set of twins (Robson criteria 8) required emergent care and did not experience immediate SSC.The second criterion of optimal SSC practice is continuous SSC. The process map Algorithm illustrates that 5 (9.4%) of the 53 dyads who began SSC immediately after birth were removed (4 for emergent care and 1 for routine care) and 48 (90.6%) continued on the best practice pathway. Of the five removed dyads, four were nulliparas . One induced nullipara (Robson 2A) was removed for the routine care of weighing and measuring the newborn. The newborns removed for emergent care were two spontaneous nulliparas (Robson 1), one induced nullipara (Robson 2A) and one induced multipara (Robson 4A), and both spontaneous nullipara neonates were examined by the NICU team for more than 5 minutes. The other two were examined by the labor and delivery nurses and returned to SSC after more than 5 minutes apart.All 48 (57.1%) of the remaining dyads had uninterrupted SSC, not interrupted by either staff or family.Of the 48 dyads who received immediate and uninterrupted SSC, 23 (47.9%) achieved the standard of best practice by demonstrating the instinctive behaviors described in Widström's 9 Stages and suckling in the first hour (the eighth stage), and 25 (52.1%) did not. Of the 15 nulliparas with spontaneous labor (Robson 1), 7 (46.7%) of the dyads achieved the standard and 8 (53.3%) did not. Of the six nulliparas who were induced (Robson 2A), none achieved the standard. Of the 14 multiparas with spontaneous labor (Robson 3), 10 (71.4%) of the dyads achieved the standard and 4 (28.6%) did not. Of the nine multiparas who were induced (Robson 4A), five (55.6%) of the dyads achieved the standards and four (44.4%) did not. Four (40%) of the 10 VBAC mothers (Robson 5) reached the final stage of the algorithm (3 with spontaneous labor and 1 induced). Of these, only one of the spontaneous labor dyads (5A) achieved the standard of suckling in the first hour after birth. Two spontaneous labor dyads and the one remaining induced dyad (5B) did not meet the standard.Thirty-six (42.9%) dyads of the total number of participants in this study did not get either immediate or uninterrupted SSC after vaginal birth. Ten (11.9%) of these dyads required emergent cesarean section. Eleven (13.1%) required emergent care before beginning SSC and 10 (11.9%) received delayed SSC (these comprised the 31 dyads classified as “Emergent Care for Mother or Infant”). Five (6%) dyads were removed for care (emergent or routine) for more than 5 minutes during the hour .The study protocol dictated that filming be continued if less than 8 minutes of separation occurred between mother and infant. The Algorithm specified recategorization based on a separation of more than 5 minutes. As a result, there are a number of infants included in the analysis who were separated for more than 5 but less than 10 minutes.Ten newborns (11.9%) experienced a delay of more than 5 minutes before being placed skin to skin with their mother, but were reunited within 10 minutes after birth. Of those who were removed from the Algorithm pathway, only three eventually suckled (30%). Of the 12 infants who were delayed less than 5 minutes, 4 (33%) did suckle within the first hour. Of the five infants who did not have continuous SSC, the one removed for routine care did not suckle. Of the four removed for emergent concerns, one was later removed by NICU for more than 10 minutes (so filming stopped) and three were returned within 10 minutes (and filming continued). Of those three, one suckled within the hour and two did not.Neonates who were born after labor inductions were the least likely to follow the stages to achieve breastfeeding in the first hour after birth. Thirty-five (41.7%) of the 84 participants were inductions, 16 nulliparas, and 19 multiparas. Of these neonates, only 5 (14.7%) reached the suckling stage (Widström's eighth stage). Of the 50 (60%) mothers who began labor spontaneously (23 nulliparous and 27 multiparous), 18 (36%) reached the suckling stage.Review of the four dyads with para unknown reveals that two did not receive immediate SSC due to emergent care for mother or infant, one experienced immediate, continuous, uninterrupted SSC but did not suckle, and one experienced immediate, continuous, uninterrupted SSC and did suckle. They are included in 29 (p.2) beginning with generalizable scientific evidence, the selection of a particular context, and a realistic and efficient measurement of performance. In the case of SSC immediately after birth and early breastfeeding, the generalizable scientific evidence indicates that SSC improves maternal birth outcomes as well as decreases infant morbidity and mortality. The context for this study was a Baby-Friendly designated hospital with a standard of care that included immediate, uninterrupted SSC for all stable babies and mothers after both vaginal and cesarean births and staff education provided to support this standard. In this study, the performance measurement of SSC  utilized a process algorithm (HCP-S2S-IA), which included Robson criteria, acknowledging the richness and complexity of the system being analyzed. The process allows for detection of specific limitations in the practice, illuminating barriers to the achievement of the standard of practice and highlighting opportunities to support the standard.Lack of initiation and lack of consistency are barriers to the universal application of SSC. Improvement in the performance of a healthcare practice “requires measures that reflect the richness and complexity of the phenomenon under scrutiny”Although mothers could only be consented into the study if they were expected to give birth vaginally and had no medical concerns that would preclude eligibility for SSC in the first hour after birth, 31 of 84 newborns (36.9%) either did not achieve a vaginal birth due to emergent cesarean or were unable to receive SSC after a vaginal birth. The Algorithm highlights these numbers and provides an opportunity for further exploration. Why are so many mothers and babies that were categorized as “healthy” during labor unable to experience SSC immediately after the birth? Five neonates were removed during the first hour after birth. The Algorithm highlights an opportunity for additional training of staff. Could these examination and resuscitation procedures that took less than 5 minutes have taken place while the baby remained in SSC with mom? Only 23 (27.4%) of the 84 newborns self-attached and suckled after vaginal birth. The process map illuminated patterns for closer scrutiny, including a large percentage of neonates and mothers who entered labor with no medical concerns but who required emergent care, many of whom had delayed or no SSC.Another pattern noted is the divergent pathway of dyads who had their labor induced. When viewed through the lens of this Algorithm, induction clearly emerges as a negative influence in achieving the optimal goal of suckling in the first hour after birth. Of the 34 inductions, 21 (61.8%) were separated immediately after birth, while 22 (44%) of the noninductions were separated. Of newborns who reached the suckling stage, only 31.3% of the inductions  did suckle within the first hour after birth, whereas 68.8% did not suckle. With the spontaneous labor dyads, 56.6% did suckle and 43.8% did not suckle within the first hour after birth.30 showing that as the dose of fentanyl and synthetic oxytocin increased, the probability of reaching the eighth stage (suckling) of Widström's 9 Stages in the first hour after birth while in SSC with mother decreased.The study is limited by a single location and by sample size, which could limit generalizability. Analysis is limited by the use of only Robson criteria and the clinical pathway as correlation parameters. Augmentation of labor with synthetic oxytocin is not reflected in this analysis, since it is not an element of Robson criteria, nor is epidural medication. We have presented data in another analysis of this studyImmediate, continuous, and uninterrupted SSC has been shown to support newborns in reaching the goal of suckling in the first hour after birth, while induction of labor has been shown to reduce rates of suckling in the first hour. The Algorithm presented provides a tool to help determine areas where specific interventions would be most effective, that is, reducing delays or decreasing interruptions during SSC.Not suckling in the first hour after birth places newborns at higher risk for neonatal morbidities and mortality. Examining patterns and developing strategies for change optimizes patient outcomes. Making considered and iterative changes that will lead to better patient outcomes requires accurate and powerful measurement of what is actually happening, how work is conducted in the usual way, and pattern analysis as described in this article. This process can lead to opportunities for improvement with targeted interventions. The next steps are review, reflection, and the development of specific plans for change.


Norman JE, Marlow N, Messow C-M, et al, for the OPPTIMUM study group. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet 387: 2106–16—2016; In this Article, in table 2, the upper 95% CI of the unadjusted odds ratio for the primary outcome of neonatal morbidity or death should be 1·07; in table 3, the p value of the treatment effect in the neonatal outcome in women with history of spontaneous preterm birth should be 0·033. These corrections have been made to the online version as of April 18, 2019.