The aim of our study was to assess associations between smoking behavior before and during pregnancy and selected adverse birth outcomes. This study is based on the Murmansk County Birth Registry (MCBR). Our study includes women who delivered a singleton pregnancy after 37 weeks of gestation . Smoking information was self-reported and assessed at the first antenatal visit during pregnancy. We adjusted for potential confounders using logistic regression. The highest proportion of infants with low values of birth weight, birth length, head circumference, ponderal index and of the Apgar score at 5 min was observed for women who smoked both before and during pregnancy. We observed a dose-response relationship between the number of cigarettes smoked per day during pregnancy and the odds of the aforementioned adverse birth outcomes; neither were there significant differences in their occurrences among non-smokers and those who smoked before but not during pregnancy. Moreover, smoking reduction during pregnancy relative to its pre-gestation level did not influence the odds of the adverse birth outcomes. Our findings emphasize a continued need for action against tobacco smoking during pregnancy. Tobacco smoking is a public health problem. Even though this habit is less common among women than men in Russia, it appears to be on the increase among women aged ≥15 years , while iSmoking during pregnancy is known to impair placental development by reducing blood flow . It can Birth weight, length and head circumference at birth are major indices of fetal growth that maternal smoking appears to suppress . CompareThe ponderal index is a measure of birth weight in relation to crown-heel length . It is uThe Apgar score is widely used as a standardized index of the newborn health status in the immediate neonatal period . A low ABased on the evidence reviewed, enough uncertainty remains to warrant further examination of the impact of smoking on birth weight, length, head circumference, the ponderal index and Apgar score. We hereby do so by comparing their respective odds ratio for smokers, those who reduced the number of cigarettes smoked during pregnancy, and those who smoked before pregnancy but stopped doing so during the first trimester.The Murmansk County Birth Registry (MCBR) contains detailed information on more than 99% of all births in Murmansk County (Northwest Russia) during the period 2006–2011. The MCBR was a cooperative effort between the University of Tromsø (Norway), Murmansk County Health Department and all delivery departments in Murmansk County. Detailed information about its design and implementation has been provided previously .A total of 52,806 pregnancies were registered in the MCBR from 1 January 2006 to 31 December 2011. For the purpose of this study, we excluded women if they had delivered before 37 completed weeks of gestation or had a multiple pregnancy. Our study focused on three main tobacco-smoking issues related to pregnancy: (i) smoking status; (ii) number of cigarettes smoked daily; and (iii) smoking reduction compared to its pre-gestation frequency. Sampling details and missing data are summarized in Based on medical records and personal interviews with expecting mothers, the MCBR contains information on maternal characteristics including age, ethnicity, residence, educational level, marital status, parity, alcohol abuse as diagnosed by a doctor, self-reported smoking (number of cigarettes per day before and during pregnancy), and maternal weight and height measured at the first antenatal visit. Information in the MCBR on gestational diabetes, excessive weight gain during pregnancy, gestational age and year of delivery was derived from individual obstetric journals. Based on newborn delivery records, the MCBR also contains data about birth weight, length, head circumference and Apgar score at 5 min.Low birth weight, length and head circumference were defined according to the World Health Organization as mean values minus 2 standard deviations (M-2SD) for girls and boys separately . Respect3 (cm), and a low score below the 10th centile (<2.14) was taken as an estimate of disproportionate IGR. The Apgar score at 5 min is a combined score of five readily identifiable neonatal characteristics that includes skin color, heart rate, respiratory effort, muscle tone, and reflexes [We used the ponderal index in newborns to assess asymmetrical intrauterine growth retardation (IGR). This was defined as 100 × birth weight (g)/lengthreflexes . Scores smokers, those who did so before but not during pregnancy were defined as quitters, and as non-smokers when they neither smoked before or during pregnancy. Number of cigarettes smoked per day during pregnancy was taken as a categorical variable, specifically as 0, 1–5, 6–10, and ≥11. Smoking reduction during pregnancy relative to its pre-gestation level was dichotomized as “Yes” and “No”. The latter included women who increased the number of cigarettes smoked per day during pregnancy, as well as those who did not change their smoking pattern. Smoking status was assessed during the first antenatal visit.Smoking status during pregnancy included the variables: ‘Smoking before pregnancy’ and ‘Smoking during pregnancy’. Women who smoked before and during pregnancy were designated as Adjustments were made for maternal age, place of residence, ethnicity, maternal education, marital status, year of delivery, parity, body mass index at the first antenatal visit, gestational diabetes, excessive weight gain in pregnancy, gestational age and alcohol abuse.Categorical variables are presented as numbers or percentages and Pearson’s Chi-square tests were used to assess statistical significance of differences. By logistic regression, we examined the associations between several adverse birth outcomes and smoking status during pregnancy, the number of cigarettes smoked per day during pregnancy, as well as reduction in smoking while pregnant. Crude and adjusted odds ratios (OR) were calculated with 95% confidence intervals (CI). We tested for trends by entering ordinal variables as continuous in the regression analyses. All statistical analyses were conducted using SPSS version 23 .This study was approved by the Ethical Committees of the Northern State Medical University, Arkhangelsk (Russia) (identification code: No. 08/12-14 from 10.12.2014) and the Norwegian Regional Committee for Medical and Health Research Ethics (REC-North), Tromsø (Norway) (identification code: No. 2014/1660).p < 0.001), with ponderal index the exception. For the latter, the highest proportion of newborns with a low value was most common among women who smoked 1–5 cigarettes per day during pregnancy, while the lowest proportion occurred among those who smoked ≥11 cigarettes daily.The prevalence of neonatal indices with low values included: birth weight (1.1%), birth length (0.6%), head circumference (2.4%), ponderal index (11.0%), and Apgar score at 5 min (1.0%). These adverse birth outcomes were more prevalent in women who smoked during pregnancy  and theiAssociations between daily numbers of smoked cigarettes during pregnancy and selected adverse birth outcomes are presented in ≥11 cigarettes in 1–5 cigarettes of 1.57 with 95% CI: 1.38–1.80), while those who smoked ≥11 cigarettes per day during pregnancy were almost two-fold less likely to have such infant .A dose-response relationship is evident between the number of cigarettes smoked per day during pregnancy and the odds of low birth weight, low birth length, low head circumference, low ponderal index and low Apgar score at 5 min. Adjustment for potential confounders did not change these associations. Respectively, mothers who smoked ≥11 cigarettes per day while pregnant were 2.1, 5.4, 5.2 and 2.1 times more likely to deliver an infant with low values of birth weight, birth length, head circumference and Apgar score at 5 min compared to non-smokers  or due to restricted fetal growth . ConsequKato et al.  indicateSeveral reports identify reduced head circumference and biparietal diameter as parameters of total growth restriction in fetuses of smoking mothers ,18,32,33Our adjusted odds for asymmetrical infants was 15% higher among women who smoked both before and during pregnancy compared to non-smokers. Previous studies with the ponderal index as a continuous variable have demonstrated decreases in its mean with maternal smoking ,35, althThe absence of an association between maternal smoking and the odds of having infants with low Apgar score at 5 min might have been influenced by the fact that we focused on term births only. Walfisch et al.  also obsadjusted = 2.48 with 95% CI = 1.76–3.49). Ward et al. [The dose-response relationship we demonstrate between daily number of cigarettes smoked during pregnancy and adverse birth outcomes is supported by earlier reports. Our finding is comparable to that indicated by Ko et al. , namely d et al.  have invd et al.  and Wangd et al. . Even thd et al.  compriseThe number of studies examining dose-response relationships between daily cigarettes smoked during pregnancy and other anthropometric parameters of the newborn is limited. Jaddoe et al.  investigLindley et al.  also demWe did not find an association between low Apgar scores at 5 min and maternal smoking. However, a dose-response relationship between these variables was evident. Most of the studies estimating dose-responses were done more than 20 years ago and showed differential results. For example one study suggested a negative influence of maternal smoking on Apgar score at 5 min , while oWe observed that women who stop smoking after pregnancy recognition are at no greater risk of having a term baby with all selected adverse birth outcomes compared to non-smokers. Nijiati et al.  also shoThe lack of an effect of reduced smoking observed may have been limited by a number of factors, including the accuracy/completeness of our data on smoking, heterogeneity of mitigating factors and the relatively low number of cigarettes smoked daily by Russian women. However, in some studies a statistical association between reduction number of cigarettes smoked per day during pregnancy and birth weight has not been observed ,43,44.Our information on smoking behavior before and during pregnancy was based on self-reporting and assessed only in the first antenatal visit in the first trimester. Consequently, underreporting of maternal smoking across different smoking categories may have occurred and led to misclassification. Tobacco smoking in Russia during the study period was restricted for children, and its use during pregnancy was not discouraged. Meta-analyses of studies comparing self-reported smoking with biochemical assessments have concluded that self-reports of smoking are accurate in most studies and are sufficiently sensitive and specific .In our study, information about smoking reduction during pregnancy compared to before gestation was missing for 49.4% of all smokers. This nonresponse may have led to bias. Nevertheless, our observation of no association between a reduction in the daily number of cigarettes smoked during pregnancy and risk of infants with low birth weight is supported by previous studies ,43,44. SThe major strength of our study is that it is based on birth registry data, and thereby included both socio-demographic and clinical characteristics of the women. Even though the registry data were collected in clinics, it corresponds to 98.8% of the official number of births recorded by the Murmansk County Health Department . This alIn conclusion, women who stopped smoking during the first trimester were at no higher risk of having a baby with the selected adverse birth outcomes as compared to non-smokers. Of special interest is that a smoking reduction during pregnancy was not associated with a reduction in the adverse birth outcomes examined, although the limited statistical power for this aspect of our work cannot be precluded. Our study illustrates that smoking before and during pregnancy leads to infants with reduced birth weight, birth length, head circumference, and ponderal index. Moreover, dose-response relationships were observed between maternal smoking and these adverse birth outcomes. Our study findings reemphasize the need for continued action against tobacco smoking during pregnancy.


The dependences of the SHG intensity on the polarization of the incoming light is revealed and interpreted in terms of electric polarization induced in the plane of the film. As the THz pulse pumps the medium in the range of phononic excitations, the induced polarization is explained as a dynamical change of the ferrolectric order parameter. It is estimated that under action of the THz pulse the ferroelectric order parameter acquires an in-plane component up to 6% of the net polarization.Second Harmonic Generation induced by the electric field of a strong nearly single-cycle terahertz pulse with the peak amplitude of 300 kV/cm is studied in a classical inorganic ferroelectric thin film of (Ba Fundamentally, these are counterintuitive phenomena in which subtle excitations of atoms or spins are able to lead to dramatic changes in crystallographic, electric, or magnetic properties of media. In ferroics, ultrafast control of the order parameter (electric polarization or magnetization) is a particularly important problem, understanding of which might be essential for future progress in information processing technology. In the last decades a substantial progress has been achieved in ultrafast optical control of spins in magnetically ordered materials and all-optical magnetic recording. It has been shown that exciting magnets on a timescale much faster than characteristic times of atomic, orbital and spin motion can steer magnetization dynamics along yet unexplored non-thermodynamic routes3. Ultrafast coherent control of the magnetic phase transitions via active optical pumping of the soft mode5 and magnetization reversal via a strongly non-equilibrium state6 have been demonstrated. Thermodynamically, critical behaviors of the electric polarization and the magnetization are very similar7. Nevertheless, the possibility of switching of the electric polarization by ultrashort laser pulses has not been reported until now. Naturally it raises interests to the problem of ultrafast optical control of electric polarization in ferroelectric materials.Photoinduced nonequilibrium phase transitions triggered by femtosecond or picosecond laser pulses is a subject of intense and multidisciplinary research16. Obviously, measurement techniques based on electric contacts are not able to provide the required temporal resolution. An elegant solution for a detection of the order parameter in ferroelectrics can be based on time-resolved X-ray diffraction. However, this technique is very challenging and, as a matter of fact, it is available in very few places in the world19. Nonlinear optical technique of the Second Harmonic Generation (SHG) is known to be very sensitive to the order parameter in ferroelectrics22 and it is by far less challenging than the studies in the X-ray spectral range25. However, despite this fact practically nothing is known about ultrafast nonlinear optical response of ferroelectrics26. Consequently, this lack of knowledge considerably hampers optimization and interpretation of experiments in which ultrafast dynamics in ferroics is probed with the help of second harmonic generation and visible light.Despite the enormous amount of experiments reporting on optical control of spins, there are very few studies of ultrafast dynamics of the electric polarization0.8Sr0.2)TiO3 (BST) to the electric field of nearly single-cycle THz pulses picosecond pulses. For this we employ a pump-probe method. Freely propagating nearly single-cycle THz pulses with the amplitude up to 300 kV/cm excites ferroelectric ((Ba0.8Sr0.2)TiO3) film. Femtosecond pulses in the near-infrared spectral range probe the response of the system by SHG. Analysis of the time-resolved non-linear optical response reveals that the experimental results can be explained assuming that under action of the THz pulse the ferroelectric order parameter acquires an in-plane component up to 6% of the net polarization.Here we report about experimental study of ultrafast nonlinear optical response of ferroelectric  of the near-infrared probe pulse could be rotated with respect to the XL axis by angle φ or set in the P-state (φ = 0). The polarization of the second harmonic light was chosen either in the P- or S-states of incidence .In the second experiment, we fixed the polarization of the near-infrared probe pulse in the P-state and rotated the electric field of the THz pulse changing τd between the THz-pump and near-infrared probe pulses. Figure Hence the data show that the THz electric field clearly affects the process of the second harmonic generation. To reveal ultrafast dynamics of these electric field induced changes, we performed pump-probe measurements of the SHG signal. In particular, the signal was measured as a function of the delay 3 (STO) and Si are shown in Fig. For comparison, we also measured temporal evolution of the SHG signals from centrosymmetric crystals excited by the intense THz pulse. The SHG transients for SrTiOThe spectra obtained as Fourier transforms of the time-traces for BST and STO as well as for THz pulse are plotted in Fig. 27. We also compared the data with loops obtained by measuring the SHG signal in an electric field which varies with the frequency of 100 Hz. To deduce the loops we employed the procedure of reconstruction of the electric polarization as described previously28. It is based on the dependence of SHG intensity on ferroelectric polarization:Ω) is the ferroelectric (switchable) polarization, which depends on the electric field of the THz pulse; P0 is remanent polarization i.e. unswitchable polarization; α is the proportionality coefficient, which is determined by the Fresnel factors and the nonlinear optical susceptibility.Finally, from the measured SHG traces we deduced how the induced electric polarization changes upon a change of the electric field of the THz pulse. These dependencies were compared with the hysteresis loops measured with the help of the Soyer-Tower technique , one has to subtract from the SHG intensity the background signal 0 + P(EΩ). The result of such a data processing is shown in Fig. In order to deduce the field dependence of the electric polarization P, in the electric-dipole approximation, it is possible to generate second harmonic signal by applying an external electric field, which breaks the inversion symmetry. This is so-called electric field induced second harmonic (EFISH). For electric field oscillating at THz frequency we will call it TEFISH. Taking into account that Ω ≪ ω and Ω + ω + ω ≅ 2ω, TEFISH polarization can be described as 29.In centrosymmetric crystals : electronic, ionic and piezoelectric. As the employed THz pulses pump the medium in the range of phononic excitations, it is natural to assume that the THz electric field induces ferroelectric polarization due to the ionic contribution.For ferroelectric material electric field dependent nonlinear optical polarization has several contributions , a polarization is induced along the same axis and the intensity acquires an additional contribution:When the in-plane electric field is applied along the [100] axis  and γ = 0.06  first increases  dependence for the Sout state of the SHG electric field changes only in intensity. For the Pout state, the two-fold Iω2(φ) dependence changes passing through four-fold dependence. Cross-sections of the 3D plots along the planes O3 domain nucleation time under electric field of 200 kV/cm was about 0.47 ps34. The strength of the electric field required for the switching and nucleation time are very close to the amplitude and the period of the THz electric field used in our experiments. Thus, it seems that in our experiment a switching of the 90-degrees ferroelectric domains, as schematically shown in Fig. The question arises: can we really switch out-of-plane domains by an in-plane electric field? Very recently it was shown that in classical ferroelectric PbTiO3 (BST) thin film (thickness 500 nm) was deposited on MgO (001) substrate by RF-sputtering of stoichiometric polycrystalline target. Transparent and mirror-smooth film was realized by means of layer-by-layer growth (Frank-van der Merwe mechanism). Details of the growth conditions have been previously reported in ref. 0.8Sr0.2)TiO3 solid solutions belong to ferroelectric perovskites. In the paraelectric phase, they have a cubic unit cell (space group Pm3m). In the ferroelectric phase below the Curie temperature . At room temperature, the soft mode is overdamped with the following parameters: Ω = 46 cm−1 (2.40 THz), ΔΩ = 50 cm−1 (1.5 THz)37. The as-grown film consists of 180-degrees domains which are not compensated due to an interfacial strain and show built-in polarization in the [001] crystallographic direction38. The size of domains is about 500 nm.Heteroepitaxial . The SHG signal was detected by a Photo-Multiplier Tube in the current regime.The THz pulses were generated by optical rectification of the femtosecond laser pulses, generated by high-energy 10 Hz Cr:Forsterite chirped-pulse amplification laser at the central wavelength of 1240 nm with 100 fs pulse duration and 20 mJ output energy, in the nonlinear organic crystal OH1Supplementary information


Low birth weight (LBW) infants constitute a vulnerable subset of infants with impaired immunity in early life. In India, there is scarcity of studies that focus on immunization practices in such infants. This analysis aimed to examine immunization practices in LBW infants with the intention to identify areas requiring intervention.Data on immunization status of LBW infants enrolled in an individually randomized, double–masked, placebo–controlled trial of neonatal vitamin A supplementation were analysed. Study outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3. Multivariable logistic regression was performed to identify factors associated with the outcome(s).Out of 10 644 LBW infants enrolled in trial, immunization data were available for 10 517 (98.8%). Less than one–third (29.7%) were fully immunized by one year of age. Lowest wealth quintile (adjusted odds ratio (AOR) 0.39, 95% confidence interval (CI) 0.32–0.47), Muslim religion  and age of mother <20 years  were associated with decreased odds of full immunization. Proportion of infants with delayed vaccination for DPT1 and DPT3 were 52% and 81% respectively. Lowest wealth quintiles , Muslim religion , mother aged <20 years  and birth weight <2000 g  were associated with higher odds of delayed vaccination for DPT–1. Maternal education (≥12 years of schooling) was associated with high odds of full immunization  and low odds of delayed vaccination for both DPT–1  and DPT–3 In this population, LBW infants are at a risk of delayed and incomplete immunization and therefore need attention. The risks are even higher in identified subgroups that should specifically be targeted Approximately 15% of infants born in low and middle income countries (LMIC) have a low birth weight <2500 g) [500 g [2]Low birth weight (LBW) infants have a lower passive immunity prior to vaccination and also their immune defences are functionally impaired in early life ,7,8. FurPrevious studies, largely from high income countries, suggest that LBW infants are less likely to receive vaccines on time and be fully immunized –14. The Recently, few studies have been conducted that document immunization practices in LBW infants from rural Ghana ,22. HoweThe present analysis utilizes data on the immunization status of low birth weight infants enrolled in a large individually randomized, double–masked, placebo–controlled trial of neonatal vitamin A supplementation within 72 hours of birth. This study was conducted in Faridabad and Palwal districts in the state of Haryana, North India from June 2010 to July 2012 . The triThe trial was approved by the ethics review committees of the Society for Applied Studies, World Health Organization (WHO) and by the state government of Haryana. It is registered with ClinicalTrials.gov, number NCT01138449. Permission was taken from all the concerned investigators of the primary trial for this secondary data analysisStudy teams identified pregnant women through household surveillance at intervals of 3 months in areas allocated to them. The pregnancies identified were followed up until delivery and birth outcomes were reported to the co–ordinators who then informed the enrolment workers immediately . For eacAt enrolment, information was collected primarily on household characteristics , infant characteristics , maternal characteristics  and father’s education. Each enrolled infant was allocated a home visit worker for further follow up until 12 months of age. All infants were contacted when aged 29 days and at 3, 6 and 12 months and at each such visit, information was collected on vital status and immunization.At each visit, the study team member looked for written documentation of vaccines administered to the infant. The documents reviewed were maternal and child health card, immunization card of the infant or any slip(s) issued by the facility where vaccination was done. The study team made several attempts to obtain written documented evidence of vaccination. This included a wait time, to ensure the mother ample time to search for the missing record, telephoning the father for any relevant information, and also postponing the visit to a later date. If the immunization card was still not available the team helped mother to report accurate dates by referring to important events or festivals. Also, the mother was asked to recall which vaccines were given, at what body site and the mode of vaccination . An infant was categorised as “not vaccinated” when the mother reported infant had never been vaccinated.The primary outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3 in LBW infants. In concordance with the guidelines of the National Immunization Program in India, an infant was considered “fully immunized” if he/she had received BCG, 3 doses of DPT, OPV each and measles by one year of age . HepatitOperationally, “delayed vaccination” was defined as having received the vaccine after 4 weeks of recommended/due time ,29,30. IAdditionally, sensitivity analysis was done to assess whether delayed DPT3 vaccination reflected delayed DPT1 vaccination. Starting with follow–up at receipt of DPT1 vaccination, an infant was labelled as having a “delayed receipt” of DPT–3 when it was given >12 weeks after DPT–1 .For the analyses, infants with known vaccination status, dates of vaccination and with complete data on covariates were included. Infants who were lost to follow–up or died before the vaccination due date, were excluded. This principle was followed for all the time points of analysis. Data analysis was performed using STATA version 11 . Proportions were calculated for all categorical variables used in the analysis. Median  was calculated for delay in vaccination (in days), from the recommended time, for each of the vaccine that was considered in the analysis. Chi–square test was done to compare proportions and Wilcoxon–Mann–Whitney 2– sample rank sum test to compare medians across the two birth weight categories.P–value of <0.20 were then included in the final multivariable logistic regression model   had increased odds of full immunization. Mother’s age was also an important determinant. Compared to mother’s aged 20–25 years, those aged 26–30 years  and >30 years  had higher odds of getting their child fully immunized. Also, delivery at a government health facility  increased the odds (OnlineSupplementary Document). Lower wealth quintile, belonging to a Muslim family, mother’s age <20 years, delivered by unskilled attendant, ≥4 living children for the woman and female sex of the infant were associated with decreased odds. Unlike in the combined analysis wherein father’s education was associated with increased odds of the child for being full immunized, in the sensitivity analysis, father’s education did not emerge as a statistically significant determinant. However, mother’s education and delivery at the government health facility were associated with increased odds.In the sensitivity analysis, using data documented through immunization cards, 15.2% of LBW infants were fully immunized by 12 months of age. The determinants of full immunization in these infants were essentially similar to those obtained when combined data obtained through immunization cards and reliable histories were analysed , mother aged <20 years  and birth weight <2000 g  were associated with higher odds of delayed vaccination with first–dose of DPT (DPT–1) vaccine (Online Supplementary Document(Online Supplementary Document)). On the other hand, higher maternal education  and delivery in a government facility  were associated with lower odds of delay for DPT–1. For DPT–3, higher maternal education was associated with reduced odds of delayed vaccination .In the sensitivity analysis, using data obtained through immunization cards, 46.6% and 79.2% of the LBW infants had delay in vaccination for DPT–1 and DPT–3 respectively. Lower wealth quintiles, Muslim religion, mother aged <20 years and birth weight <2000 g were associated with higher odds of delayed vaccination with first–dose of DPT (DPT–1) vaccine . Low birth weight was associated with increased odds of delayed vaccination for DPT–1  and DPT–3  in male infants but there was no such significant association in female infants. After adjusting for the late vaccination with DPT–1, birth weight had no significant association with delay in DPT–3 vaccine  (Online Supplementary Document(Online Supplementary Document).As part of the exploratory analysis, determinants of full immunization and delayed vaccination were also documented for normal birth weight infants. Lower wealth quintiles, belonging to Muslim community, mother’s age <20 years and female sex were associated with low odds to full immunization, largely similar to that observed in low birth weight infant. Higher maternal education and delivery at a government facility were associated with increased odds of full immunization and decreased odds of delayed vaccination. They are presented in Table S3 and S4 in The present secondary data analysis aimed to understand immunization practices in low birth weight babies and elucidate their determinants. Only a third of LBW infants were fully immunized and majority had delayed vaccination for DPT–1 and DPT–3. The findings pertain to study districts where overall immunization performance is lower compared to other districts of the state. These study districts are recognized as “low performing” by the government of Haryana, based on the indicators for uptake of immunization services ,35. HoweThe strength of this study is the robust population– based surveillance system and low loss to follow up. All babies were recruited within 72 hours of birth and weight measured by trained study team, thereby reducing chances of misclassification of infants by birth weight. To achieve adequate quality of data on vaccination status, the study team members were rigorously trained and underwent periodic inter and intra observer standardization exercises .A limitation that must be considered while interpreting the findings is that the main trial excluded sick babies or those that were unable to feed. Such babies would include a certain proportion of LBW infants  and in them, the delay and incompleteness in vaccination may be possibly of greater magnitude. Excluding them, therefore, may underestimate the actual delay and incompleteness in immunization. Also, in this setting, we recognize that a small proportion of pregnant women, especially those having the first baby, tend to go to their parents home for delivery and these were therefore not available for enrolment. The immunization practices of these primigravida mothers could be different from those who would have had children previously and this might have possibly affected the findings observed. There was no reliable data on gestational age and so through the current analysis, it would be difficult to interpret whether the immunization practices were influenced by prematurity or not. In around one–fifth of the infants, data on immunization was obtained through reliable history instead of documented evidence in form of immunization card. Thus, the possibility of reporting inaccurate vaccination dates cannot be ruled out. Other factors that could affect immunization uptake such as maternal illness and distance from the health facility were not considered as data was unavailable for these variables. Delayed immunization and low rates of full immunization could also be due to factors affecting supply ie, shortage of vaccines and skilled manpower and other logistic issues but these have not been considered in the current analysis.After adjustment for potential confounders, being born with low birth weight emerged as a significant determinant of full immunization, and in male infants, also for delayed vaccination with DPT–1 and DPT–3. Interestingly, it was not associated with delay for either DPT–1 or DPT–3 vaccination in females. It could possibly mean that family members/caregivers might hesitate vaccinating their LBW infant, early in life, as they are considered fragile and this fear may be more for male babies, as they are valued more in a patriarchal society like that of Haryana. Lower wealth quintiles, Muslim religion and young maternal age (<20 years) were found to be associated with lower odds of full immunization and higher odds of delayed vaccination for DPT–1 in the final multivariable model. This is in concordance with findings from earlier studies ,36–38. BIn the final regression model; female sex of the infant, delivery by an unskilled attendant and increasing number of children a woman had were also associated with low odds of full immunization. Social constructs in traditional Indian society subject females towards unequal treatment, notably in the state of Haryana. Studies have reported a household level gender– based differential in terms of allocation of food, care seeking and education, usually with the female child being neglected –42. DeliSimilar to previous studies, in this study as well, high maternal education was found to be strongly associated with improved vaccination status of the infant ,45. IncrTo the best of our knowledge, it is one of the few data presented from LMIC, particularly in India, to understand the immunization practices in LBW infants and their determinants. The findings show that immunization uptake in these infants was inadequate. Strengthening of essential newborn care practices early in life, with a focus on timely initiation of vaccination and ensuring full immunization should form the linchpin of the low birth weight infant care package. In the current study, poor immunization uptake was observed in the economically weaker sections of the society. This calls for due emphasis on ensuring equity in terms of utilization of immunization services and improving coverage.Data surveillance and monitoring should routinely focus on identifying groups that are underserved by vaccination. Mobilization activities need to focus on infants from the marginalized sections of the society. Interventions aimed at delaying the age at child birth, addressing female bias, providing targeted education on the importance of immunization to mothers of child bearing age and to women of certain religious communities could prove beneficial. Promoting institutional births and emphasizing on immunization as an integral part of the discharge counselling package would be warranted. Interventions that target the determinants should necessarily be accompanied by efforts to improve the health system.


The BetterBirth Program relied on carefully structured coaching that was multilevel, collaborative, and provider-centered to motivate birth attendants to use the WHO Safe Childbirth Checklist and improve adherence to essential birth practices. It was scaled to 60 sites as part of a randomized controlled trial in Uttar Pradesh, India. The BetterBirth Program relied on carefully structured coaching that was multilevel, collaborative, and provider-centered to motivate birth attendants to use the WHO Safe Childbirth Checklist and improve adherence to essential birth practices. It was scaled to 60 sites as part of a randomized controlled trial in Uttar Pradesh, India. 10.1056/NEJMoa1701075]. The results showed that the intervention had no significant effect on maternal or perinatal mortality or maternal morbidity, despite having positive effects on essential birth practices.)Shifting childbirth into facilities has not improved health outcomes for mothers and newborns as significantly as hoped. Improving the quality and safety of care provided during facility-based childbirth requires helping providers to adhere to essential birth practices—evidence-based behaviors that reduce harm to and save lives of mothers and newborns. To achieve this goal, we developed the BetterBirth Program, which we tested in a matched-pair, cluster-randomized controlled trial in Uttar Pradesh, India. The goal of this intervention was to improve adoption and sustained use of the World Health Organization Safe Childbirth Checklist (SCC), an organized collection of 28 essential birth practices that are known to improve the quality of facility-based childbirth care. Here, we describe the BetterBirth Program in detail, including its 4 main features: implementation tools, an implementation strategy of coaching, an implementation pathway (Engage-Launch-Support), and a sustainability plan. This coaching-based implementation of the SCC motivates and empowers care providers to identify, understand, and resolve the barriers they face in using the SCC with the resources already available. We describe important lessons learned from our experience with the BetterBirth Program as it was tested in the BetterBirth Trial. For example, the emphasis on relationship building and respect led to trust between coaches and birth attendants and helped influence change. In addition, the cloud-based data collection and feedback system proved a valuable asset in the coaching process. More research on coaching-based interventions is required to refine our understanding of what works best to improve quality and safety of care in various settings. (After publication of this article, the impact results of the BetterBirth intervention were published in the New England Journal of Medicine [volume 377, pages 2313-2324, doi:  Marx Delaney.See related article by ,The reduction of preventable maternal and neonatal morbidity and mortality associated with childbirth remains a critical challenge in global health.One important component of high-quality health care is the provision of care according to evidence-based guidelines. In facility-based childbirth care, one of the main causes of preventable harm is the failure to deliver essential birth practices to all mothers and newborns at the appropriate time during childbirth. Essential birth practices are provider behaviors for which evidence exists to prove that they increase the quality and safety of care during childbirth; these practices, when performed consistently and correctly, can save the lives of mothers and newborns. The failure to perform these practices is often called a “know-do” gap and has been identified in many areas of health care.One of the main causes of preventable harm in facility-based childbirth care is the failure to deliver essential birth practices.,,In specific health care settings, well-implemented checklists have successfully bridged the know-do gap, changing provider behavior by increasing adherence to evidence-based guidelines.–Experience with the WHO Surgical Safety Checklist and with similar quality-improvement and patient-safety interventions has established that simply introducing a checklist to a facility or provider without a plan for engagement and sustained reinforcement does not lead to improvement in health care practices.While checklists have successfully bridged the know-do gap, experience has shown that a plan for engagement and sustained reinforcement is also needed to improve health care practices.With the BetterBirth Program, we aimed to develop a systematic approach that would enable health care workers to adopt and use the WHO Safe Childbirth Checklist during their provision of childbirth care. As such, we sought to empower birth attendants and other facility and district personnel to identify, understand, and ultimately resolve barriers they might face in using the SCC to deliver quality maternal and newborn care, with coaching as the main strategy to engage with health care workers. The BetterBirth Trial, a matched-pair, cluster-randomized controlled trial, was implemented in 120 facilities  across 24 districts in the state of Uttar Pradesh, India.,–Opportunity: “external” and systems-level barriers concerning the circumstances under which the provider must practice the new behavior Ability: barriers concerning the provider's knowledge, skills, and competence related to the new behavior Motivation: “internal” barriers concerning the provider's willingness to change his or her behavior Supplies: a subset of Opportunity, specifically referring to the availability of necessary medications, equipment, and other consumable materialsBehavior change interventions and adoption of evidence-based practices are enhanced by application of a theoretical framework to organize strategies of behavior change.Global Health: Science and Practice presents results on the effect of the intervention on birth practices.Here, we describe the design of the BetterBirth Program in detail. We include specific, concrete examples to illustrate the various aspects of our intervention: quotes that the implementation team gathered in focus group discussions with coaches and other examples drawn from the Coach Support Tools . We have described the methodology of the BetterBirth Trial,The BetterBirth Program incorporated 4 key components: implementation tools, an implementation strategy, an implementation pathway, and a sustainability plan.Supplement). These pause points allow birth attendants to make their “checks” both at critical times when they can protect the mother and newborn against dangerous complications and when it is convenient for them to take the time to perform the checks.By reminding birth attendants to perform essential birth practices at the appropriate time, the SCC is intended to improve the safety and quality of care received by mothers and newborns. The SCC is organized into 4 pause points, or critical moments, in facility-based childbirth care, when birth attendants should “check” that they have completed essential birth practices: (1) on admission, (2) just before pushing (or before cesarean delivery), (3) soon after birth (within 1 hour), and (4) at discharge , called CommCare, allowed coaches to record their observations and put those observations to use in further coaching. For example, a coach would record whether a birth attendant performed specific practices (such as skin-to-skin warming and breastfeeding), and if not, diagnose and record the underlying barrier according to the OAMS framework. Coaches and coach team leaders were able to access a summary report of that birth attendant's practices or an aggregate report of the facility's practices. These summary data were generally displayed in a visual heat map .The success of the U.S. agricultural extension service resulted from how it pursued its goals: extension agents went out “into the field” to work with local farmers on integrating new developments in technology and farming techniques into the farmers' work. Moreover, each extension agent was guided by certain principles, which led to more successful relationships with the farmers:In the program, nurse coaches worked closely with birth attendants, who were also typically nurses, to provide the support that the birth attendants needed in order to use the SCC to improve care. Simultaneously, coach team leaders, who were either physicians or public health professionals, supported facility and district leaders as they strengthened the health care systems' facilitation of the use of the SCC. To ensure a local facility-level champion, coaches and facility leaders collaboratively chose and provided support to a childbirth quality coordinator (CQC) , who conducted many of the coaching tasks in the absence of the BetterBirth coach. The CQC was identified during the first 2 months of the program. Please see the To prepare coaches, each coach attended a 5-day interactive training that focused on core coaching skills, such as effective communication, respectful relationship building, and barrier and solution identification, as well as on the OAMS behavior-change framework. Throughout the trial, coaches and coach team leaders also received 2–3 day refresher trainings, which offered similar skills training and opportunities for peer learning and troubleshooting. Coach team leaders also provided supportive supervision to coaches during facility visits, in which both coaches and coach team leaders were present.increase birth attendants' motivation to use the SCC. If a birth attendant did not perform a specific essential birth practice, a coach might explain the significance of that practice by using the SCC as a visual aid or by telling a story about a childbirth in which the practice was performed. Coaches had to identify what motivated each birth attendant—competition among peers or other facilities, facts and data, or emotional stories—and tailor their approach accordingly. Coaches would keenly observe the birth attendant and the contextual environment, as well as probe with open-ended questions, to understand the root cause of the barrier. When describing how coaches overcame resistance to using the SCC, one coach noted:Coaches pursued 3 main types of activities during their facility visits. First, based on local circumstances and dynamics, coaches worked to We have to empathize with the birth attendant and explain the importance of conducting each item on the SCC. As humans, it's not always possible for us to remember each item—especially when we are busy.Similarly, coaches celebrated success, both with the birth attendant and among the birth attendant's peers within the facility.Coaches pursued 3 main types of activities: motivated birth attendants to use the checklist; observed, recorded, and fed back information about use of the checklist; and guided birth attendants to solve problems.observed, recorded, and fed back information about SCC use, the status of the facility's systems (such as supply availability), and any barriers the birth attendant, facility, and/or district faced in using the SCC. By making birth attendants and facility leaders aware of the performance (and nonperformance) of essential birth practices within the facility, the coaches helped to identify areas for improvement. The importance of this task draws from the lessons learned with the Standards-Based Management and Recognition (SBM-R) model.Second, using the Pulse app, coaches Similarly, Coach team leaders collected information on and offered feedback about the state of a facility's systems and practices to facility leaders. When coaches were not able to directly observe any of the pause points during the facility visit, they still found opportunities to discuss past cases, current supply gaps, and skilled birth attendant national guidelines. Coaches and coach team leaders also completed structured diaries for each facility visit and district engagement that captured qualitative information about each of their interactions, drawing not only from direct observations but also from discussions related to practices and processes even in the absence of direct observations. The coach team leader qualitative tool specifically captured information on team-based coaching discussions and data feedback meetings, particularly around supply availability as well as facility-level practice and processes changes.problem solving, coaches guided birth attendants through a problem-solving process based on the results of the second task . When the coach identified an essential birth practice that the birth attendant did not perform even after prompting from the coach, the coach collaborated with the birth attendant to identify what barrier blocked her from performing the practice and to categorize that barrier according to the OAMS framework. Finally, the coach and the birth attendant agreed upon a strategy for resolving the identified barrier and worked together as a team toward realizing that strategy. The coach team leader helped by facilitating the escalation of the problem to higher levels of facility and district leadership if needed, where the coach team leader also facilitated the problem-solving process. When there was turnover of staff and shift changes, coaches and coach team leaders would make every effort to arrange their visits such that they could work individually with as many birth attendants at the facility.In the third task, Coaches did not typically have problems finding time with birth attendants to discuss cases and review feedback and thus were generally able to build a strong relationship and rapport with each birth attendant. When coaches observed that birth attendants were routinely not performing the tasks associated with the fourth pause point (at discharge), they engaged the birth attendants in discussions to determine what barriers were preventing the adherence to these essential birth practices. The birth attendants pointed out that, for cultural and logistical reasons , mothers often left the facility—against medical advice—much earlier than the expected 24 hours postpartum recommended by the SCC. Their early departures left no time for the birth attendants to perform the fourth pause point. Together, birth attendants and coaches agreed to administer the discharge practices (pause point 4) regardless of how soon the mother left the facility. They also decided together to approach the female community health workers  who accompanied women to the facility for childbirth in order to educate them on the need for women to remain in the facility for 24 hours after giving birth. The birth attendants shared with the ASHAs the potential dangers of leaving the facility early and warning signs to watch for once a mother had returned home. As a result, the ASHAs began to encourage mothers to remain at the facility longer post-delivery.What coaches focused on was only one part of the intervention. Equally, if not more, important was how the coaches pursued their tasks. First, coaching in the BetterBirth Program was multilevel. While coaches worked with birth attendants, coach team leaders similarly worked with facility and district leaders to strengthen the systems necessary to facilitate sustained use of the SCC. For example, coaches noticed birth attendants refusing to administer the bacille Calmette-Guérin (BCG) vaccine to only 1 or 2 babies at a time, instead asking the mothers to return to the facility at a later time for the vaccine. Discussions with birth attendants revealed that they believed they were required to use all 10 doses of vaccine in each vial immediately upon opening it; thus, to avoid waste, they would only vaccinate if many babies were present in the facility at once. To resolve the misunderstanding, coaches and coach team leaders worked with facility- and district-level health care leaders to clarify the policy around the supply of BCG vaccine. In addition, at a district-level meeting, leaders explained to the birth attendants the ready availability of plenty of vaccine as well as the procedures for acquiring more for their facility, in order to motivate them to vaccinate each baby—to open a vial even when only 1 baby was present. To be successful, this effort required collaboration not only between the peer-to-peer pairings of coaches and birth attendants, coach team leaders, and health care leadership but also between the 2 pairs as well.Coaching was multilevel, collaborative, and provider-centered.collaborative. Coaches worked with birth attendants, and coach team leaders worked with facility and district leaders, in a supportive, constructive, respectful peer-to-peer manner. The coaches were also nurses  with similar backgrounds and training as the birth attendants they coached; the coach team leaders who worked with facility and district leaders—both clinical and administrative—were physicians or experienced public health professionals. Coaches and coach team leaders used strong communication skills and a nonjudgmental attitude to build a relationship of trust and understanding with the individual(s) they coached. One birth attendant remarked:Second, coaching in the BetterBirth Program was At first I didn't think that this young BetterBirth Coach could help me very much. But she was very polite and pleasant to work with. The coach helps me to remember and learn to do each practice in a systematic and consistent way for every patient. I bring the skills, she brings the process.Another noted:It wasn't like talking to someone who was trying to find mistakes. It was like talking to a friend.Birth attendants and facility and district leaders thus were invited to be active, equal participants in the process of improvement.provider-centered. Similar to the Client-Oriented, Provider-Efficient services model (COPE), coaching focused on enabling providers to identify problems and develop their own solutions using local resources.Third, coaching was The BetterBirth implementation pathway incorporated 3 stages: Engage, Launch, and Support . Each stEngage stage of the BetterBirth implementation pathway was collaborating with key leaders at multiple levels of the health care system to introduce them to the SCC and gather support for the BetterBirth Program, identify local needs, and engage in problem solving to begin addressing those needs.The core of the During the Engage stage of the BetterBirth Trial in Uttar Pradesh, India, implementers worked closely with state health care officials to adapt the SCC to fit the Government of India maternal and child health guidelines. Coach team leaders from the BetterBirth Program also met with facility and district leaders in order to secure their commitment to the BetterBirth Program and to identify their priority areas for improvement.Launch stage aimed for collaboration between BetterBirth Coaches and those individuals who would be adopting and using the SCC (and those who would be directly supporting them). This stage involved introducing the key stakeholders to the SCC and gathering support for the BetterBirth Program's goals and methods, beginning to identify local barriers to adopting essential birth practices, and engaging in problem solving to begin resolving those barriers. BetterBirth Coaches led a “launch event” with facility personnel, seeking both to strengthen the sense of responsibility and motivation for ensuring high-quality care in childbirth services and to create an atmosphere of excitement and inspiration that would build confidence in the idea of behavior and system change.The –During the Launch stage in the BetterBirth Trial, coaches used a flipbook illustrated with diagrams of SCC essential birth practices and motivational multimedia presentations to engage participants in a discussion about why each practice on the SCC is critical for a safe childbirth.Support stage was to bolster the adoption and ongoing use of the SCC within facilities and to reinforce birth attendants' adherence to essential birth practices. To this end, coaches and coach team leaders visited facilities and worked directly with birth attendants and facility leaders (as well as with other facility personnel) to increase motivation, collect data, provide feedback, and problem solve around barriers to behavior change.The central goal of the The Support stage of the BetterBirth Trial in Uttar Pradesh involved coaches visiting each intervention facility 43 times over 8 months. During the first 4 months, coaches visited each facility twice per week, then the frequency of their visits tapered until they visited each facility only once in the eighth month. Coach team leaders followed a similar but less intensive schedule, visiting each facility 23 times. Each coach was responsible for 2–4 facilities at a time; each coach team leader managed 4–5 facilities at a time.Coaches visited each intervention facility 43 times over an 8-month period.empower health facility leadership and staff. Coaching helped birth attendants and facility and district leaders to recognize the barriers they faced in using the SCC, and helped them develop the strategies to resolve those barriers by using the resources already available within the facility and the district—and, when possible, by strengthening the facility and district systems to support the use of the SCC. By empowering the birth attendants and facility and district leaders through coaching, the BetterBirth Program sought to create culture and capacity change that would last beyond the coaches' visits. As one birth attendant commented:BetterBirth Coaches and Coach Team Leaders provided neither monetary nor other material benefits to the individuals or facilities they coached, nor did they offer those individuals direct skills training. Instead, a coach's central goal was to My coach helps to show me the path to where the solution exists. Now I feel confident to bring up issues to the MOIC [Medical Officer In Charge] or LMO [Lady Medical Officer].During the Support stage, coaches also collaborated with the personnel in each facility in order to produce a local sustainability plan for continuing to pursue the goals, methods, and effects of the program after the coaches moved on to other facilities. The local sustainability plan offered facility personnel another tool with which they could continue to practice and advocate better safety and quality of facility-based childbirth care.As a second part of the sustainability plan, a CQC was collaboratively chosen early in the BetterBirth Program by coaches and facility leaders to be the “local champion” of the SCC. The choice of facility CQC was based on a staff member's motivation and interest in the BetterBirth Program, his or her ability to influence and coach others, and the level of respect she or he held among other facility- and district-level personnel, rather than on his or her title or role in the facility. With support from coaches and facility leaders, the CQC was responsible for the use of the SCC within the facility during and after the implementation of the BetterBirth Program, making certain that the facility practiced the principles embodied by the BetterBirth Coaches, even when those coaches were not present. According to one CQC:We gained energy to continue quality and infection control measures and keep on improving [the] BetterBirth Program.Once the CQC was identified during the first 2 months of coaching, coaches oriented and supported CQCs in basic coaching skills for approximately 6 months before the intervention period ended. Within the intervention period, a formal training session was also organized at the district level to train the facility and district CQCs in observation and data collection techniques, delivering feedback, and other coaching methods. Practically, the CQC oriented new staff to the SCC, and continually motivated all staff in its adoption and use, and monitored and aided staff members in collaboratively addressing facility- and district-level barriers to SCC adherence. Another CQC reported:… a very high motivation and self-confidence that safe birth practices can be very well implemented and continued even in the absence of BetterBirth. I can manage and check things and supplies very easily.The CQC received no extra incentives for playing this role within the facility or district.–,Although the BetterBirth Program revolved around using the WHO Safe Childbirth Checklist to improve essential birth practices, coaching was at the core of the program. Recognizing that checklists alone do not resolve all the barriers to behavior change, we adapted lessons from other behavior-change strategies, including the Improvement Collaborative Approach, COPE, and SBM-R,Checklists alone do not resolve all barriers to behavior change.At the same time, the implementation of the intervention across 60 study facilities and 24 districts (representing a population of approximately 60 million) in the state of Uttar Pradesh as part of the BetterBirth Trial suggests that with the same level of resources, the BetterBirth Program is replicable in a variety of facilities in Uttar Pradesh and in other similar contexts globally. We partially attribute the scale-up to 60 sites to the robust cloud-based data collection and feedback system, Pulse, which proved to be a unique and valuable asset in the process of coaching. However, lower-cost, lower-tech models may also prove to be equally effective in ensuring a robust monitoring and data-feedback loop to facilitate bringing the coaching-based intervention to scale.,,Because we implemented the BetterBirth Program in the context of a matched-pair, cluster-randomized controlled trial, we followed a strict trial protocol for the intensity and frequency of coaching. For each of the 60 facilities, the intervention closely adhered to the protocol and the outlined implementation pathway . However, outside of a trial context, a truly provider-centered (and therefore adaptive) coaching approach would involve adjusting the timing of coaching visits to match the needs of the facilities and the hours of birth attendants who had less exposure to coaching during daylight hours. Still, several organizations across India are currently testing coaching-centered interventions of various intensities, suggesting that a coaching-based model could be realistic for this context, albeit with fewer facility visits. Jhpiego's SCC implementation across the state of Rajasthan, India, includes facility-based coaching visits every 2 weeks for the first 2 months, followed by 4 once-per-month coaching visits,,,,The BetterBirth Program was centered around coaching in an effort to encourage the consistent, effective delivery of essential birth practices through adoption and use of the SCC, and to sustain this change through individual and facility- or team-level empowerment. The trial showed an improvement in performance of these practices after only 2 months of the intervention.


Place of birth is a known determinant of health care outcomes, interventions and costs. Many studies have examined the maternal and perinatal outcomes when women plan to give birth in hospitals compared with births in birth centres or at home. However, these studies vary substantially in rigour; assessing their quality is challenging. Existing research appraisal tools do not always capture important elements of study design that are critical when comparing outcomes by planned place of birth. To address this deficiency, we aimed to develop a reliable instrument to rate the quality of primary research on maternal and newborn outcomes by place of birth.The instrument development process involved five phases: 1) generation of items and a weighted scoring system; 2) content validation via a quantitative survey and a modified Delphi process with an international, multi-disciplinary panel of experts; 3) inter-rater consistency; 4) alignment with established research appraisal tools; and 5) pilot-testing of instrument usability.A Birth Place Research Quality Index (ResQu Index) was developed comprising 27 scored items that are summed to generate a weighted composite score out of 100 for studies comparing planned place of birth. Scale content validation indices were .89 for clarity, .94 for relevance and .90 for importance. The Index demonstrated substantial inter-rater consistency; pilot-testing confirmed feasibility and user-friendliness.The ResQu Index is a reliable instrument to evaluate the quality of design, methods and interpretation of reported outcomes from research about place of birth. Higher-scoring studies have greater potential to inform evidence-based selection of birth place by clinicians, policy makers, and women and their families. The Index can also guide the design of future research on place of birth. The selection of birth place has important implications for the health and wellbeing of women and newborns, as well as for health services planning and healthcare costs –3. DecisEvidence on the relative safety of different places of birth is complex and frequently controversial . SeveralPolicy makers and clinician leaders have responded to the research with similar discordance. Some clinical guidelines and policy statements in high-income countries support access to midwife-led care in birth centres and home births as cost-effective options for women with uncomplicated pregnancies –26. OtheInconsistency in the design and quality of research on place of birth underpins the difficulty of crafting universally acceptable recommendations for service provision across birth settings. Further, the interpretation and dissemination of research findings can be subject to publication and critical bias, and the influence of professional viewpoints and culture , 32.Accurate information about relative and absolute risk is vital to inform women and their families, clinicians and health administrators as they work together to select optimal birth places within the context of a person-centred care plan and regional resources. However, without a reliable means to assess the quality of the evidence, it is not possible to interpret the best available data and its implications for the safety of women and infants. This study was designed to address the need for a standardised system for evaluating research on the safety of birth place. It aimed to develop and pilot test a novel instrument for appraising the quality and rigour of research that examines the impact of place of birth on maternal and perinatal outcomes.While there are several valuable instruments for assessing the quality of randomised and non-randomised clinical studies –38, thesWhen comparing outcomes across birth settings, the use of consistent definitions and inclusion criteria across cohorts, and reliable outcome measures, is imperative. A significant error in some published research on birth place is amalgamating data from unplanned home births (without skilled birth attendants) with data from planned births at home or in birth centres within integrated systems.Following revelations of critical flaws in some published studies –46, reseDevelopment of the ResQu Index involved five distinct phases: 1) generating items and a weighted scoring system; 2) conducting expert content validation via a quantitative survey and a modified Delphi process; 3) testing inter-rater consistency; 4) assuring compatibility with established research quality checklists and 5) piloting the ResQu Index in a large systematic review to assess instrument usability and feasibility.We developed this instrument to conduct an extensive systematic review of the literature on outcomes related to place of birth, within a larger research project [blinded]. A protocol was lodged with PROSPERO (CRD42016042291). Ethics clearance was not required for the instrument development.Item generation was informed by a literature review and the principles proposed by Vedam , Hutton Some items in the Index relate to rigour common to all research studies, addressing issues such as clarity of key terms, definitions of the ‘intervention’ (i.e. place of birth), integrity of data, appropriateness of sample size and selection, transparency of methods and comparability of cohorts. Other items relate specifically to studies of birth place as outlined by Vedam  and NoveEach item incorporates a rubric that scores the level of quality of the study design and interpretation of findings. Item scores are summed to generate a total composite Index score for a study. Scoring options vary from a simple yes/no response to a range of potential criteria. The expert content validation process (Phase 2) evaluated both the wording of the scoring rubrics and their relative numerical value (weighting).The first draft version of the ResQu Index contained 25 items, relating to five domains addressing: quality of design, sample definition, measurement of outcomes, comparability of cohorts, and accuracy of interpretation and reporting . Their areas of expertise included: research on birth place (16 experts), planned home birth (13), research methodology/study design (11), midwifery practice (11), evidence-based practice (10), health services (10), appraisal of evidence (10), public health (9), hospital maternity care (7), birth centres (7), health systems (5), statistics (5), population-based services (4), patient-oriented outcomes (4), global health (3). Two experts indicated professional interest in ‘transfer’ and one each ‘law or policy’, ‘nursing practice’ and ‘medical practice’. Anonymous response was possible, but twelve of the 21 experts supplied their names. All supplied the country/region in which they were based, including North America (11), Australia (7), United Kingdom (2), and the Netherlands (1). Several indicated that they also worked in a range of other countries or regions.Panel members were contacted using publicly-available contact details, and participation was voluntary. We emailed the panel of 42 experts explaining the background and purpose of the Index, and inviting them to participate in the expert review process. We outlined the conceptual basis and scope of the Index  and explThe content validation took place during June 2016, online via Survey Gizmo. Experts considered each item on the first draft version for clarity, importance and relevance, rating each aspect on a four-point ordinal scale from ‘very clear/important/relevant’ (1) to ‘not clear/important/relevant’ (4). In addition to the quantitative rating process, they were invited to provide written feedback on the wording and scoring rubric for each item, to suggest non-essential items that might be omitted, and to comment on individual items and/or the overall purpose, utility and scope of the draft Index .Following expert review, several items were amended in line with the experts’ quantitative responses and qualitative feedback  was calculated for the three aspects  of each item, being the proportion of experts that gave it a positive response (1 or 2). Items that achieved a total score above .80 for relevance were retained (except for one which scored low in importance). Those items below .80 for clarity were rephrased or modified to reflect the expert comments  Tables orho coefficient to explore the consistency of our total scores for the articles because the scores were continuous but not necessarily normally distributed [consensus on the three-tier scale using Cohen’s kappa statistic [To test inter-rater reliability, two members of the research team (VS and CR) used the second draft version of the ResQu Index (revised but still 25 items) to independently rate 20 studies. Stemler  describetributed . Secondltatistic . We usedIn addition to investigating inter-rater consistency and consensus, this process enabled us to review each study’s total Index scores, with particular attention to where the two raters diverged. In conjunction with further comments from expert reviewers, this contributed to the final version of the Index .To ascertain comprehensiveness, the ResQu Index was compared to the taxonomy of domains developed by Deeks and colleagues  in theirAs a final stage of development, two authors (VS and CR) assessed usability and feasibility by using the ResQu Index in a systematic review on maternal and perinatal outcomes related to place of birth for women at low risk of obstetric complications in high-income countries. We used the updated ResQu Index to rate 68 articles, comparing and discussing their ratings when total scores diverged. This process was done iteratively, in conjunction with the search and screening stages of the review. Having identified studies that met the eligibility criteria for the systematic review, one or both authors applied the current version of the Index.The final ResQu Index contains 27 items across five domains, each rated on a numerical scale where higher values indicated higher quality with respect to the aspect of quality being measured. The items and the final scoring rubrics are shown in The experts’ quantitative responses about the clarity, importance and relevance of the items in the first draft version are summarised in In addition to responding to the online survey, several experts corresponded directly with the project team, providing comments on the draft Index or the validation process, or seeking clarification. This correspondence, together with the quantitative and qualitative survey responses contributed to further revision of the Index. Accordingly, the wording and/or the relative weighting of scoring rubrics was refined, specifically to enhance clarity: three items were removed as feedback indicated that they were not perceived as relevant as others , as described above. The average (mean) of the I-CVIs for the retained items was 0.89 for clarity, 0.94 for relevance and 0.90 for importance . These lIn relation to the proposed scoring rubric for the retained items, the average S-CVI was 0.85. Of the 22 retained items, seven received a positive rating of 80% or less. Of these, five were substantially reworded and or reweighted. The other two (items 7 and 8) were merged into one with a revised scoring rubric .The four experts who used the Index to beta-test its applicability in scoring the two sample articles reported positive experiences in terms of usability and acceptability. Following their comments, the wording and scoring in the final version were fine-tuned.rho = .868, p<0.001), indicating a high degree of consistency in ratings. Comparing the two raters’ scores on the three-tier scale  also demonstrated substantial levels of consensus on the relative strength of the articles  [p<0.001) , 58.The comparison of the ResQu Index with the domains identified by Deeks and colleagues  demonstrThree ResQu items  on the maternal and perinatal outcomes of different places of birth, for women with healthy, low-risk pregnancies in high-income countries. Two authors separately and jointly used the ResQu Index system to inform a rigorous process of inclusion and exclusion of identified studies. They also developed a user dictionary (available on request) to assist with using the Index to assess studies in practice. While several low-scoring studies were excluded by the parameters of our systematic review , we were able to utilise the Index to examine the quality of studies to inform inclusion in our meta-analysis of data.Place of birth research has been plagued with controversy over study design, variables to be measured, cohort definition and other factors specific to this context. A growing volume of academic literature and media attention has focused on research about birth place. The availability of a reliable method to assess quality of the evidence has the potential to create consensus about the quality of studies among clinicians and researchers who have been (often fiercely) divided on the issue , 62, 63.The ResQu Index could facilitate the development of clinical guidelines on provision of maternity services across places of birth. For example, following a review of the evidence, some professional clinical bulletins  have relThe development of a quality assessment instrument is a complex process, benefiting from the contributions of a multidisciplinary team. Despite careful measures to maximise content validity and consistency, it inevitably involves subjective judgements, both in the selection and weighting of items, and their application to appraise published studies of place of birth. Other researchers may debate its relative emphasis on some aspects of this literature at the expense of others.The results of pilot-testing confirm that the Index is, like other such scales, subject to some personal interpretation. However, comparison of the inter-rater consistency and consensus of scores from two raters, including one non-clinician researcher, with a large selection of studies showed considerable similarity. One of the strengths of the Index is its capacity to facilitate multi-disciplinary, collaborative evaluation of research outputs, by using commonly-defined terms.The ResQu Index was not designed to assess qualitative studies and would not, by virtue of its focus on specific aspects of methodology, rate them highly. We acknowledge that some important questions about quality and safety of birth place, or person-centred care, cannot be answered by quantitative methods alone.The Birth Place Research Quality Index is a reliable, pragmatic tool to systematically appraise the quality of research on place of birth. The composite scoring system highlights the unique nature of childbirth and the specific characteristics of study design and analysis that must be considered when evaluating reported findings. We used a detailed, formal process to design and content validate the Index in consultation with an international panel of multi-disciplinary experts in this field. Pilot testing demonstrated usability, feasibility, and inter-rater consistency. The Index was well suited to systematic review of research on birth place. It could also be used to inform clinical guidelines on maternity service provision across birth settings, to inform the design of studies, or to provide a framework for peer review for publication.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Preterm birth is the leading cause of child mortality under 5 years of age. Temporal trends in preterm birth rates are highly heterogeneous among countries and little information exists for China. To address this data gap, we investigated annual changes in preterm birth incidence rate and explored potential determinants of these changes in Shenzhen, China.A total of 1.4 million live births, during 2003-2012, were included from the Shenzhen birth registry. Negative-binominal regression models were used to estimate the annual percent changes in incidence. To identify the potential determinants behind temporal trends, we estimated the contribution of each changing risk factor to changes in rate by calculating the difference in population-attributable risk fraction.Annual preterm birth incidence rates increased by 0.94%  overall, 3.60%  for medically induced, and 3.13%  for preterm premature rupture of membranes, but decreased by 2.34%  for spontaneous preterm labor. Higher maternal educational attainment (0.20 rate increase), lower proportion of inadequate prenatal care (0.15 rate reduction), more multipara (0.08 rate reduction), decreased proportion of preeclampsia or eclampsia (0.05 rate reduction), and larger proportion of young and older pregnant women (0.04 rate increase) were significant contributors to the overall change over time. Contributions of changing risk factors were different between preterm birth subtypes.Preterm birth rate in Shenzhen, China increased overall during 2003-2012, although trends varied across three preterm birth subtypes. The rising rates were associated with changes in maternal education and age.The online version of this article (10.1186/s12978-018-0477-8) contains supplementary material, which is available to authorized users. Complications from preterm birth (PTB) is the leading cause of neonatal and child mortality worldwide. Numerous studies have reported changes in PTB incidence over the past two decades. These finding showed that the temporal trends in PTB rates are highly heterogeneous among countries, but there is little information available for China.China has the second greatest number of PTBs worldwide, with large disparities in PTB rates across different regions of the country. To better understand the temporal trends in PTB rates in mainland China, this study investigated changes in PTB rates by clinical subtype and explore potential determinants of the changes in Shenzhen, China.Based on the data analysis, we found that preterm birth rate increased in Shenzhen between 2003 and 2012, yet with varied trends among three PTB clinical subtypes. In detail, incidence rates increased in late preterm and medically induced preterm birth, but decreased in preterm birth due to spontaneous preterm labor. Maternal education, parity and prenatal care visits played important roles in determining secular trends for PTB rates. In summary, the Shenzhen findings provided complementary evidence to confirm the increasing trends of PTB rates in mainland China. Moreover, this study also suggested that advanced and highly educated pregnant women should be the key target population groups for future clinical intervention and public health prevention strategies in developed area of China.Complications from preterm birth (PTB) is the leading cause of neonatal and child mortality worldwide . GloballThe investigation of temporal trends in PTB rates is essential to inform policy and to design interventions for reducing the burden of PTB. Numerous prior studies have reported changes in PTB incidence over the past two decades. These findings showed that the temporal trends in PTB rates are highly heterogeneous among countries , 5. A glExisting studies of PTB rates have mainly focused on populations in Europe and North America, yet there is little information available for China , 5. AfteIdentifying risk factors specific to PTB subtypes will assist clinicians and policymakers in designing interventions to prevent PTB. Hence, a good knowledge of temporal trends in the rates of PTB subtypes and the reasons behind changing rates may enhance PTB prevention , 11, 12.We conducted a retrospective cohort study of births in Shenzhen, which located in Guangdong Province in southern China. Shenzhen is the first Special Economic Zone in China, stemming from China’s economic reform in 1980s. It is a megacity with a total population of about 11.9 million. During the past 30 years, the population of Shenzhen has experienced significant socioeconomic and health changes, reflecting the typical development of mainland China. Thus, Shenzhen provides an excellent opportunity to explore the drivers behind health changes in mainland China.n = 1.42 million).This birth registry database covers all midwifery clinics and hospitals, allowing for accurate PTB rate calculation. Furthermore, this system connects to a city-wide maternal and children health information system, what also allowed for capture of medical record data, including demographic and clinical information for both mother and newborn. The high validity and reliability of data from the Shenzhen Birth Registry Database was previously described [We used the Shenzhen Birth Registry Database to capture data for all live births from January 1, 2003 to December 31, 2012  Missing gestational (0.02%) or maternal (0.01%) ages; (2) With maternal age < 13 years or > 50 years (1.87%); or, (3) With gestational age < 22 weeks or > 46 weeks according to the distribution of gestational ages (0.36%) . The flo Missing We collected all variables available from the electronic medical record, and selected the variables for inclusion as PTB risk factors based on the literature . We extrWe also extracted maternal sociodemographic characteristics and chronic maternal conditions data. We categorized maternal education as no high school, high school and college, bachelor, and postgraduate degree. Chronic maternal conditions included clinically diagnosed hypertension, hepatopathy, nephropathy, and heart disease.We defined PTB as live born infants at less than 37 completed weeks of gestation from the date of LMP, or corrected by first trimester ultrasound if discrepant by more than 7 days. We classified PTB into spontaneous preterm birth and medically induced preterm birth (MI-PTB) according to clinical presentation, and then categorized spontaneous preterm births as preterm premature rupture of membranes (PROM-PTB) and preterm labor (S-PTB). The classification criteria were as follows: (1) MI-PTB, defined as labor induction and/or elective cesarean section without PROM; (2) PROM-PTB, regardless of delivery mode or induction and status; and, (3) S-PTB, which included all non-PROM associated vaginal deliveries. Based on this classification scheme, remaining births that did not meet the criteria for PROM-PTB and MI-PTB were categorized as S-PTB .We expressed incidence rate as the number of PTB infants per 100 live births . We calcAFp) for each changing risk factor. The Born Too Soon Preterm Prevention Analysis Group used this method to analyze drivers for increasing PTB rates in the U.S. [i.Identify distributions of each risk factor for 2003-2007 and 2008-2012. We selected the year of 2007 as the cut-off year because Shenzhen PTB rates increased after 2007.ii.Identify the PTB for every category of each risk factor during 2008-2012, using ORs generated from logistic regression models.iii.AFp for each PTB risk factor, and compute specific AFp values for 2003-2007 and 2008-2012. We defined AFpi and AFp, where, AFpi is the population attributed risk fraction for exposure category j of the (j = 1….n) ith risk factor, PFj is the proportion of the total population in exposure category j for the ith risk factor, RRj is the risk ratio for the exposure category j of the ith risk factor, approximated using ORs, and AFp is the population attributable risk across all risk factors i [Calculate actors i . The forFinally, to analyze the contribution of changing risk factors to changes in PTB rate, we calculated the difference in population-attributable risk fraction . An alpha level of 0.05 indicated statistical significance for a two-tailed test.A total of 1.42 million births were recorded in the Shenzhen Birth Registry Database between 2003 and 2012. After excluding the 32,172 (2.25%) ineligible records and 2135 (0.15%) still births, we included 1.39 million (97.6%) live births in this study. There were 78,252 (5.7%) PTBs with PROM-PTB, S-PTB and MI-PTB accounting for 9.5%, 51.4% and 39.4% of overall PTBs, respectively. PTB rates among different maternal and infant groups are presented in Table Figure As described by Table Table The contributions of risk factor changes to differences in PTB rates are shown in Fig. APC) were 1.34% and 4.19%, respectively. In stratified analyses according to maternal demographic characteristics, PTB rates rapidly increased in mothers with advanced age and high educational attainment, while these decreased in younger and mothers with low education. In addition, we found that higher educational attainment, adjusted for maternal age, increased PTB rates (projected increase rate = 0.20%), especially in MI-PTB.This study highlighted the time trends of preterm birth incidence rate by subtype, and investigated the reasons behinds the changing rates in China. Our results demonstrated that PTB rates increased from 5.59% to 6.06% in Shenzhen, China, over the period 2003-2012, with high heterogeneity across three PTB subtypes. This increase predominantly took place in late preterm and MI-PTB, and the corresponding annual percent change , as reported by Chang et al. . The mulExcept for the drivers for PTB rates, we found improving prenatal care was an important contributor to decreased PTB, especially in S-PTB. The strong contribution of prenatal care visits to PTB rate declines indicated that many women would have benefited from improved coverage of recommended basic antenatal care services . In geneStill, as for PTB trends in China, several important research questions remain to be answered in the future. First, PTB incidence rates increased in both Shenzhen and Hubei, but whether there were differences in trends between these single centers and China as a whole remains unclear. Second, although we found that changes in maternal age and education drove PTB rates, the pathways for these effects are unclear. Third, the cause of temporal trends in PTB rates is likely to be multifactorial, a result of changing risk factor incidences, clinical practices, and public policies, while few studies have assessed the contribution of these potential drivers.Several previous studies, including a global estimation and two local investigations in China, have characterized recent trends in their rates of preterm birth overall , 9, 10. The results of our study were limited by use of routinely collected registry data. This may have resulted in misclassified outcomes for some women. However, the high validity and reliability of the Shenzhen Birth Registry has been previously described , and an In summary, the Shenzhen findings confirm the previous reports of an increasing trend for PTB rates in mainland China. Moreover, this study also suggested that older and more highly educated pregnant woman, should be key target population groups for clinical PTB interventions and public health PTB prevention strategies in developed areas of China. However, considering the wide variation of PTB rates among geographic areas, we suggest caution in generalizing the Shenzhen findings.Preterm birth rate increased in Shenzhen between 2003 and 2012, yet with varied trends among three PTB subtypes. Maternal age, education, parity and prenatal care visits played important roles in determining secular trends for PTB rates. These findings represent potential targets for interventions or policies designed to reduce PTB. More knowledge on how these factors are associated with PTB in China is needed for shaping future prevention strategies. Our findings also highlight the importance of adequate prenatal care for reducing PTB in China.Additional file 1:Figure S1. Flowchart of final study population. Table S1. Temporal Trends in Preterm Birth Incidence Rates and Proportion of Preterm Birth Subtypes in Shenzhen, China, 2003-2012. Table S2. Sensitivity Analysis for Temporal Trends for Overall Preterm Birth Incidence Rates in Shenzhen, China, during 2003-2012. Table S3. Analysis of Factors Contributing to Changing Preterm Birth Incidence Rates in Shenzhen, 2003-2012. (DOCX 51 kb)