Is socioeconomic deprivation at the neighborhood level, measured by an Area Deprivation Index, an independent risk factor for neonatal intensive care unit (NICU) mortality and morbidity among extremely premature infants?In a cohort study of 2765 extremely premature infants  admitted to 4 level IV NICUs in different US regions, national Area Deprivation Index percentile was associated with the risk of NICU mortality and morbidities after adjusting for multiple covariates.These findings have implications for public health measures, which should target areas of neighborhood deprivation to improve prenatal care with the aim of improving NICU outcomes. This cohort study investigates the association of the Area Deprivation Index with in-hospital mortality of extremely premature infants and 3 key morbidities, including late-onset sepsis, necrotizing enterocolitis, and severe intraventricular hemorrhage. Socioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality.To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants.This retrospective cohort study was performed at 4 level IV NICUs in the US Northeast, Mid-Atlantic, Midwest, and South regions. Non-Hispanic White and Black infants with gestational age of less than 29 weeks and born between January 1, 2012, and December 31, 2020, were included in the analysis. Addresses were converted to census blocks, identified by Federal Information Processing Series codes, to link residences to national ADI percentiles.ADI, race, birth weight, sex, and outborn status.In the primary outcome, the association between ADI and NICU mortality was analyzed using bayesian logistic regression adjusted for race, birth weight, outborn status, and sex. Risk factors were considered significant if the 95% credible intervals excluded zero. In the secondary outcome, the association between ADI and NICU morbidities, including late-onset sepsis, necrotizing enterocolitis (NEC), and severe intraventricular hemorrhage (IVH), were also analyzed.P < .001), those who died before NICU discharge vs survived , those with late-onset sepsis or NEC vs those without , and those with severe IVH vs those without . In a multivariable bayesian logistic regression model, lower birth weight, higher ADI, and male sex were risk factors for mortality , while Black race and outborn status were not. The ADI was also identified as a risk factor for sepsis or NEC and severe IVH.A total of 2765 infants with a mean (SD) gestational age of 25.6 (1.7) weeks and mean (SD) birth weight of 805 (241) g were included in the analysis. Of these, 1391 (50.3%) were boys, 1325 (47.9%) reported Black maternal race, 498 (18.0%) died before NICU discharge, 692 (25.0%) developed sepsis or NEC, and 353 (12.8%) had severe IVH. In univariate analysis, higher median ADI was found among Black compared with White infants (77  vs 57 ; The findings of this cohort study of extremely preterm infants admitted to 4 NICUs in different US geographic regions suggest that ADI was a risk factor for mortality and morbidity after adjusting for multiple covariates. Racial disparities confound the effects of socioeconomic status, with families of racial minority groups bearing a higher burden of adverse health outcomes and lower quality of health care,11 even among those with higher socioeconomic status and educational levels.14 In addition, due in part to a history of housing discrimination and structural racism in the US, members of racial minority groups more often live in socioeconomically disadvantaged communities.15 These complex interactions between race and socioeconomic status necessitate consideration when evaluating maternal and infant outcomes.Socioeconomic disadvantage impacts maternal health and access to care, affecting the preterm delivery rate16 first described this metric in relation to disparities in life expectancy that correlated with area deprivation. Kind et al17 adapted, updated, and validated the ADI at the neighborhood level using block groups, the smallest geographical unit used by the US Census Bureau. In the most recent iteration, ADI has been normalized at the national level to generate percentiles that can be easily compared, with higher values indicating greater disadvantage. National ADI percentiles and state ADI deciles using 2018 US Census Bureau data are published online in an interactive map.19The Area Deprivation Index (ADI) is a metric that measures area disadvantage, determined by 17 census variables, including measures of poverty, educational level, housing, and employment status. Singh and Soahpush20 cardiovascular disease,21 and in-hospital COVID-19 mortality.22 The ADI has also been used to investigate disparity in neonatal health outcomes, such as the rates of exclusive breastfeeding,23 neurobehavioral differences and brain structure in term infants,25 respiratory morbidity after NICU discharge in infants with bronchopulmonary dysplasia,26 and length of stay in infants with neonatal opioid withdrawal syndrome.27Associations between ADI and health outcomes have been investigated in many populations, including adult patients with Alzheimer disease,In this project, we investigated the association of the ADI, a granular, comprehensive, geospatially linked measure of deprivation, and demographic characteristics with in-hospital mortality of extremely premature infants and 3 key morbidities . We hypothesized that maternal residence in areas with greater deprivation is associated with increased NICU mortality and morbidity risk. Our study includes 8 years of data from 4 regional referral NICUs located in 4 US regions: Midwest, Northeast, Mid-Atlantic, and South.STROBE) reporting guideline. Maternal self-reported race was used to determine the infants’ race. Hispanic infants were excluded because this ethnicity category was not specified in the earlier years of the study, and they accounted for relatively few patients (5%-10%) at all but 1 NICU, at Columbia University. We also excluded Asian infants and other  race categories with very few patients. We excluded infants with missing outcomes data from the analysis. Each institution’s institutional review board reviewed and approved the study under a waiver of informed consent.We conducted a multicenter, retrospective cohort study of non-Hispanic Black and White premature infants born at a gestational age of less than 29 weeks and admitted to 1 of 4 academic level IV NICUs—University of Virginia in Charlottesville; University of Alabama at Birmingham; Washington University in St Louis, St Louis, Missouri; and Columbia University, New York City, New York—between January 1, 2012, and December 31, 2020. We followed the Strengthening the Reporting of Observational Studies in Epidemiology  ; NEC, as radiographic evidence of pneumatosis, pneumoperitoneum, or portal venous gas plus clinical signs and symptoms of sepsis according to the modified Bell staging criteria for stage 2 or higher2 tests. We analyzed the multivariable association between ADI and NICU outcomes using bayesian logistic regression adjusted for race, birth weight, outborn status, and sex. For each variable included in the multivariable models, we also performed univariate bayesian logistic regression analysis with primary and secondary outcomes. For computational efficiency, quantitative variables were centered and scaled before analysis. Two-sided P < .05 indicated statistical significance.We performed univariate comparisons among ADI, demographic characteristics, and primary and secondary outcomes using Wilcoxon rank sum or χ31 more correctly quantify the uncertainty in model parameters,32 and are often able to estimate models that may otherwise fail.33 We used weakly informative priors for all parameters. We considered a risk factor significant if the posterior 95% credible intervals (CrI) did not include zero and took the posterior median as the summary of the posterior in all regression analyses. We compared models with interaction terms to the baseline model and considered an interaction significant if the information criterion value was lower than that of the baseline model.In contrast with frequentist models, bayesian models provide more information about parameters through posterior distributions,We analyzed ADI and clinical data from 2765 extremely premature infants admitted during the study period. The mean (SD) gestational age was 25.6 (1.7) weeks; birth weight, 805 (241) g. In terms of sex and race, 1391 infants (50.3%) were boys and 1374 (49.7%) were girls, and 1325 (47.9%) reported Black maternal race and 1440 (52.1%) reported White maternal race. A total of 498 infants (18.0%) died before NICU discharge, 692 (25.0%) were diagnosed with sepsis or NEC, and 353 (12.8%) developed severe IVH. Inborn status ranged from 261 of 405 infants (64.4%) at Washington University in St Louis to 396 of 504 (78.6%) at Columbia University. P < .001). Among the 1777 infants (64.0%) with ADI above the national median, mortality was 20.0% (n = 355) compared with 14.0% (n = 138) in the 988 infants with ADI at or below the national median (P < .001). Higher ADI was also associated with self-reported Black maternal race , inborn status , diagnosis with sepsis or NEC , and severe IVH  (P < .001)  and lower mean (SD) birth weight  than White infants. We found no correlation between birth weight and ADI (r = −0.05). Significant intercenter variation in ADI existed, as shown eFigure 2 in In pooled data across the 4 centers, the distribution of ADI was skewed, with 1770 infants (64.0%) born to families residing in areas of higher deprivation, or ADI above the fiftieth national percentile. Mortality was similarly skewed, with more deaths among the infants with higher ADI  and high 36-86]) . FamilieP < .001). While mortality was not significantly higher for male (159 of 1391 [18.6%]) than female infants (239 of 1374 [17.4%]) overall, White male infants had higher mortality than White female infants , while mortality among Black infants did not differ by sex (131 of 650 [20.2%] vs 134 of 675 [19.9%]).Comparing male and female infants, we found no statistically significant difference in ADI , race , or the proportion of outborn infants . As expected, the mean (SD) birth weight was slightly higher for male than female infants , and a higher proportion were White race . Infants transferred to the study NICU after delivery at an outside hospital also had a higher rate of severe IVH .While most patients (1981 [71.6%]) were admitted following delivery at the same hospital, outborn infants had lower ADI  and loweP < .001) and 124 (35.1%) of those with severe IVH (P < .001) died. Compared with mean (SD) birth weight of 805 (241) g in the overall cohort, those diagnosed with sepsis or NEC had lower mean (SD) birth weight  as did those with severe IVH . Sepsis and NEC and severe IVH rates did not differ among infants grouped by sex or race.Infants with sepsis or NEC, severe IVH, or both had higher ADI than those without . CompareIn addition to comparing variable distributions among binary subgroups, we performed univariate bayesian logistic regression to estimate the association between each variable used in multivariable modeling and the primary and secondary outcomes. 34 of the model.We examined the association between ADI and NICU mortality while adjusting for the covariates identified in univariate analyses: birth weight, sex, race, and outborn status. Based on posterior median estimates, birth weight was the strongest risk factor for mortality , but national ADI percentile  and male sex  were also associated with mortality . Neitherz scores, we report the effect of changing either variable by 1 SD, rather than by 1 percentile (ADI) or 1 g (birth weight). Therefore, in the model for mortality, we interpreted the effect of decreasing birth weight by 1 SD to be 9 times that of increasing ADI by 1 SD. In contrast, in the model for severe IVH, the effects of birth weight and ADI were similar and still less than the effect of outborn status. When modeling sepsis and NEC, the effect of decreasing birth weight was about 3 times that of increasing ADI, and male sex and outborn status had intermediate effects. Race did not significantly affect any of the three outcomes modeled.Birth weight and ADI were also associated with NICU morbidity in multivariable models . Because35 While in the NICU, preterm infants are treated according to standardized care guidelines that might be expected to limit the association of socioeconomic deprivation with adverse outcomes. Few studies have evaluated the association of area deprivation with in-hospital outcomes.36 In this study, we found that residence in a socioeconomically disadvantaged neighborhood—as measured by the ADI—increases the risk of NICU mortality or morbidity for extremely preterm infants, even after accounting for other known risk factors. This indicates a pervasive and detrimental effect of area deprivation that may not be entirely eliminated by provision of standardized, high-quality NICU care.Socioeconomic factors play an important role in maternal health, access to prenatal care, rates of preterm birth, and infant morbidity and mortality outside of the NICU.38 Maternal stress and poor access to prenatal care have been linked with adverse birth outcomes.41 Lower maternal socioeconomic status increases the risk of preterm birth,42 and among those born prematurely, it increases the risk of adverse neurodevelopmental outcomes.44 In contrast with other studies, we did not find an association between ADI and birth weight, likely due to the fact that we limited the analysis to extremely premature infants with a narrow range of birth weights.The mechanism by which area deprivation affects neonatal outcomes may include the effect of maternal adversity on the developing fetus.46 but these analyses did not account for socioeconomic factors. As racial minority individuals proportionally endure more socioeconomic deprivation, it becomes essential to consider social disparities as a significant mediator of racial disparities. Public health efforts have been made to narrow disparities in antenatal corticosteroid use and cesarean deliveries, but gaps in these practices persist.46 Disparities in breastfeeding by race persist,10 despite overall improvements in breastfeeding initiation over time, with the lowest rate of breastfeeding at NICU discharge among infants born to non-Hispanic Black mothers.47 In our cohort, infants born to Black mothers were exposed to higher levels of deprivation in utero and had lower birth weights. Still, they did not have higher associated morbidity or mortality when accounting for these and other confounding variables. Our results suggest that the higher mortality observed among Black preterm infants compared with White infants may be partly confounded by factors captured in the ADI, including exposure to adverse social and economic conditions.We found that the association between higher deprivation and mortality remained in multivariable analysis while the association between Black race and mortality did not. These highly collinear variables make it difficult to estimate the effect of race or deprivation alone. Studies indicate that despite advances over time, racial disparities persist in neonatal outcomes and care practices,A strength of this study was the inclusion of 4 centers in geographically distinct areas of the US  with different distributions of ADI, patient racial compositions, and population densities. Although all centers are level IV referral NICUs, there were differences in the percentage of inborn infants, ranging from 64.4% to 78.6%. Interestingly, the distribution of ADI was skewed in opposite directions for infants admitted to the centers in the Midwest and South compared with the Northeast, while the Mid-Atlantic center had a nearly symmetric ADI distribution (eFigure 1 in Limitations of the study include the lack of granularity in the ADI and race data. Although block groups are the most geospatially compact census unit and the ADI can provide a localized overview of the degree of socioeconomic deprivation, its value is opaque. The relative contributions of each ADI component are not available for the most current values, making it infeasible to evaluate driving factors of the association between ADI and NICU morbidity and mortality. In addition, the exposures captured in the ADI may have differential impacts across the heterogeneous locations that we analyzed. For example, in the 2020 US Census data for just the 4 cities in which the study NICUs were located, the land area ranged from 10.24 to 302.64 square miles; population density ranged from 1365 to 29 302 per square mile; median household incomes ranged from $38 832 to $67 046; and the percentage of adults without health insurance ranged from 7.9% to 14.7%. Each of these differences likely plays a significant role in the factors that underlie the ADI calculation.49We classified race into broad groups of Black or White based on the self-reported maternal race and excluded American Indian and Alaska Native, Asian, and Hispanic patients, which may have left important interactions or outcomes undiscovered. Analyzing more refined racial and ethnic subgroups, including more than 1 race when the father’s race differs from the mother’s race, may have found differential associations between ADI and outcomes among more finely delineated racial and ethnic groups. For example, the “Hispanic paradox” refers to the paradoxical finding that Hispanic infant mortality rates lie at or below the rate of Non-Hispanic White infant mortality, despite higher socioeconomic deprivation.Our results generate questions for future studies to evaluate how interventions to reduce area deprivation or improve equity might reduce disparities in NICU outcomes for premature infants. The study’s findings also leave us wanting to know more about the mechanism of the association between ADI and NICU outcomes, but we could not answer such questions with the data available.In this cohort study of preterm infants born at a gestational age of less than 29 weeks and admitted to 4 NICUs, ADI was a risk factor for NICU mortality and morbidity after adjusting for multiple covariates. These findings highlight the need for further research on the components of the ADI that drive this association. Specific risk factors may be targets of public health measures to improve prenatal care and infant outcomes for patients from disadvantaged areas.


To evaluate the association between gestational weight gain (GWG) and preterm birth and post-term birth.This longitudinal-based research studied singleton pregnant women from the National Vital Statistics System (NVSS) (2019). Total GWG (kg) was converted to gestational age-standardized z scores. The z-scores of GWG were divided into four categories according to the quartile of GWG, and the quantile 2 interval was used as the reference for the analysis. Univariate and multivariate logistic regression analyses were performed to investigate the association between GWG and preterm birth, post-term birth, and total adverse outcome (preterm birth + post-term birth). Subgroup analysis stratified by pre-pregnancy body mass index (BMI) was used to estimate associations between z-scores and outcomes.P < 0.001], and higher GWG z-scores  were positively associated with preterm birth. Low GWG z-score  was positively associated with an increased risk of post-term birth. However, higher GWG z-scores  was associated with a decreased risk of post-term birth. In addition, low GWG z-score and higher GWG z-scores were related to total adverse outcome. A subgroup analysis demonstrated that pre-pregnancy BMI, low GWG z-score was associated with a decreased risk of preterm birth among BMI-obesity women .Of the 3,100,122 women, preterm birth occurred in 9.45%  population, with post-term birth accounting for 4.54% . The results demonstrated that low GWG z-score [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, Our result suggests that the management of GWG may be an important strategy to reduce the number of preterm birth and post-term birth.The online version contains supplementary material available at 10.1186/s12887-023-03951-0. Preterm birth is defined as birth before the completion of 37 weeks gestation, with one in 10 babies being born preterm, and every year, around 15 million babies are born preterm in the world, putting the global preterm birth rate at 11% . Post-teGestational weight gain (GWG) is necessary to ensure fetal health . GWG refThe purpose of this study was to examine the associations between GWG and preterm birth, post-term birth, and the combined outcome of preterm and post-term birth; investigate the effect of GWG on preterm birth, post-term birth, and the combined outcome of preterm and post-term birth among different pregnancy body mass index (BMI) women.https://www.cdc.gov/nchs/nvss/births.htm). We included singleton pregnant women aged 18 years or older. Women with pre-pregnancy hypertension or diabetes, height < 55 inches, gestation at < 22 weeks or > 44 weeks, fetal malformations, chromosomal disorders, and pregnant women who used assisted reproduction were excluded. The de-identified data are publicly available online, so the ethical board review of the corresponding author's institution is exempted.This longitudinal study recruited pregnant women from the National Vital Statistics System (NVSS) (2019), which is a U.S. population-based retrospective cohort study from 50 States and the District of Columbia . The NVSMaternal GWG was classified by GWG z-score of standardized maternal weight gain in gestational age, which was calculated as: /standard deviation of week-specific weight gain, with week-specific means and standard deviations . The z-s2), normal weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (≥ 30 kg/m2) , and the comparison between groups was conducted by Kruskal–Wallis test. The enumeration data were compared using the chi-square test or Fisher’s exact test, manifesting as cases and the constituent ratio (n (%)). For the handling of missing data, the simple deletion method was used to delete the cases with missing values, sensitivity analysis before and after data deletion was performed.The normally distributed measurement data were expressed as mean +—standard deviation, and the one-way analysis of variance (ANOVA) was used for comparison between groups; abnormally distributed measurement data were described as median and quartile [M , and calculated the incidence of total adverse outcome in different GWG z-scores. To determine which confounders required adjustment, directed acyclic graph (DAG) were drawn .Following our exclusions, 3,100,122 women with live singleton births were included in the analysis , quantile 4 , and total weight-gain z-score  was associated with an increased risk of preterm birth. As for the post-term birth, the weight-gain z-score in quantile 1 was related to an increased risk of post-term birth . Nevertheless, weight-gain z-scores in 3 , quantile 4 , and total weight-gain z-score  related to a decreased risk of post-term birth. Concerning the total adverse outcome, weight-gain z-scores in quantile 1 , quantile 3 , quantile 4 , and total weight-gain z-score  were all associated with an increased risk of total adverse outcome. Associations of GWG with preterm birth, post-term birth, and total adverse outcome are presented in Table The result demonstrated that the weight-gain z-score in quantile 1 [odds ratio (OR): 1.04, 95% confidence interval (CI): 1.03 to 1.05, P < 0.001) while weight-gain z-scores in quantile 2, in quantile 4, and total weight-gain z-scores were associated with a higher risk of preterm birth.Associations of GWG with preterm birth, post-term birth, and total adverse outcome in different pre-pregnancy BMI populations are shown in Table P < 0.001), normal , overweight , and obesity , however, weight-gain z-scores in quantile 3, quantile 4, and total weight-gain z-scores were all associated with a decreased risk of post-term birth in women who were underweight, normal, overweight, and obesity.As for the post-term birth, weight-gain z-score in quantile 1 was related to an increased risk of post-term birth in women who were underweight  was associated with a decreased risk of post-term birth. In addition, a low GWG z-score and higher GWG z-scores were related to total adverse outcome. When stratified by pre-pregnancy BMI, low GWG z-score was associated with a decreased t risk of preterm birth among BMI-obesity women.In this study, we found that low GWG z-score and higher GWG z-scores were positively associated with preterm birth. In accordance with our findings, a study by Santos et al. reported that both lower and higher total gestational weight gain z-scores were associated with a higher risk of preterm birth . A studyPostdate pregnancy represents a circumstance in which labor does not occur within the physiological term of gestation; this prolongation suggests an alteration in the physiological processes regulating the onset of labor, thus representing a potential risk factor for the fetus . In addiThis study was a longitudinal-based research study and a larger sample frame that can better understand and seek the association between GWG and preterm birth and post-term birth. However, this study has some limitations. The main limitation is the retrospective nature of this study as the collected data depended entirely on the available data. In addition, although multivariable analyses were utilized to minimize the effect of confounders, potentially unknown or unidentified confounders may exist. Thereby, the associations between GWG and preterm birth, post-term birth, and an adverse outcome combining preterm birth and post-term birth need further studies.GWG was associated with preterm and post-term birth outcomes. In clinical practice, pregnant women should be guided to have a clear understanding of weight gain, regular check-ups during pregnancy, reasonable weight control, and reducing the risk of adverse neonatal outcomes from preterm and post-term birth.Additional file 1.Additional file 2.


The fertility rates of Kazakhstan have reversed to levels not seen for several decades. The striking fertility increase poses questions regarding the extent to which this new development is shared across socio-demographic groups and the nature of fertility recuperation. The current study employs UNICEF Multiple Indicator Cluster Survey data and event-history modelling to analyse parity progressions to one, two, three, and four children. The results suggest a sustained fertility increase that is not merely associated with the recuperation of delayed first births, but a genuine increase across all birth orders. This pattern is evident for both main ethnicities in Kazakhstan and across educational groups. The gradual increase of higher-order births, especially among ethnic Kazakhs, indicates a reversed fertility transition and also that the previous fertility decline in the 1990s was not part of a general transition towards below-replacement fertility but rather a reflection of economic crisis after the collapse of the Soviet Union. The Total Fertility Rate (TFR) of Kazakhstan has recently been on a roller coaster, dropping from 2.84 in 1989 to 1.80 in 1999 and rebounding back to 3.00 in 2018  Was the fertility increase that occurred in the early 2000s a temporary deviation from previous trends or part of a behavioural change that reflects a more long-term return to more elevated fertility? (2) Was the pattern of fertility recuperation a universal development or did it belong to specific subgroups of the population, reflecting ethnic and educational differences in behavioural change?To understand the fertility changes that were observed in Kazakhstan in the 1990s and 2000s, it is first worth positioning these developments within the frameworks of demographic transition theory. Demographic transition theory assumes a development from high mortality and fertility towards low mortality and fertility  or received non-cash contributions as their salaries.  emigrated from the country, while the new state at the same time initiated a programme of repatriation of ethnic Kazakhs from the countries they had migrated to during Soviet times, including China, Mongolia, Uzbekistan, Russia, Turkmenistan, Kyrgyzstan, Iran, Afghanistan, and Pakistan. According to recent official statistics, as of 2021, ethnic Kazakhs constituted 70.4% of the population in the country, while Russians remained the second largest ethnic group. (Kazakhstan ).Relatedly, notable spatial variations and regional disparities can be observed within Kazakhstan. The Northern and Eastern regions, situated closer to Russia, exhibit a higher concentration of Russian and other Slavic populations, reflecting stronger cultural ties to Russia. On the other hand, the Southern and Western parts of Kazakhstan, which are in closer proximity to other Central Asian countries, show a stronger cultural connection to the Turkic and Muslim world.Several studies  highly educated women due to their role as forerunners in other contexts, and b) ethnic Russian women due to potential similarities in fertility development with co-ethnics in other parts of the former Soviet Union.In line with findings from other contexts, increasing rates of progression to parenthood among highly educated women are expected in periods of economic growth, while increasing rates of progression toward parenthood and subsequent births are expected among less educated women in periods of economic recession.Decreasing rates of progression to third and fourth births are expected in general but especially among highly educated women, in line with the progression of the fertility transition.In this study, recent parity-specific fertility developments in Kazakhstan are studied, including the assessment of possible differences in fertility trends by ethnicity and education. Based on the theoretical framework of fertility developments, the following hypotheses will be assessed:Three rounds of the Kazakhstan Multiple Indicator Cluster Survey (MICS), collected in 2006, 2011, and 2015, have been used for analysis. The sample sizes were 14,719, 14,228, and 12,910 women for each round, respectively, with an average response rate of 98%. Only completed interviews, 41,243 (98.5% of the full sample), were used for the analysis.MICS data does not contain complete fertility histories, and only the dates of the first and the last birth in a woman’s fertility history are included. However, the birth dates of all children under 18 who live in the household are known. The survey thus does not provide information on the exact birth dates of children who are not first or last, unless they live in the household. In addition, there is information about a mother’s identification number only for children under 18. For these reasons, the sample includes only the youngest cohorts to study higher-order births: women in the 2006 round were excluded if they gave birth to a first child before 1989, before 1994 for women surveyed in 2011, and before 1998 for women surveyed in 2015.The sample is thus moderately selective based on the survival of children or cohabitation with the mother between the birth of the first and last child. Consequently, this implies that in cases where a woman's second child has passed away or left the household, and she has given birth three times, it becomes impossible to study her likelihood of a second birth due to the lack of information regarding the second child's date of birth. These exclusion criteria do not affect women who have not yet given birth to three or more children. Thus, the sample sizes for the analysis are as follows: first birth—41,242 women (no restrictions), second birth—16,920 women , third birth—10,274 (or 90.6% of women from young cohorts who have at least two children), and fourth birth—3821 (or 79% of women from young cohorts who have at least three children). The risk of first birth was analysed for 27,309 Kazakh women, 8953 Russian women, and 4980 women of other ethnicities. The risk of second birth was analysed for 11,121 Kazakh women, 3717 Russian women, and 2082 women of other ethnicities. The risk of third birth was analysed for 7462 Kazakh women, 1575 Russian women, and 1237 women of other ethnicities. The risk of fourth birth was analysed for 3197 Kazakh women, 223 Russian women, and 401 women of other ethnicities.Moreover, for birth date information taken from the household roster (covering any births between the first and last child), the 2006 household dataset does not contain information on the month of birth other than the first and last births. Thus, the month of birth was randomly imputed for around 7% of cases for the study of second-birth risks and around 4% of cases for the study of third and fourth-birth risks.To assess the reliability of the results based on MICS data, I compared the fertility estimates reported in the MICS final reports  with estimates from the civil registration records. The TFR indicated in both the 2011 MICS report and the 2011 civil registration data is approximately 2.6. However, in the 2015 MICS report, the TFR was slightly higher at 3.0, compared to the TFR of 2.73 reported in the 2015 civil registration data. Previous studies in different contexts have discovered that the underestimation of single women in survey data leads to discrepancies between fertility estimates based on surveys and those based on civil registration records .Duration since last birth is the basic time factor to study the risk of second/third/fourth birth, and it is a time-varying variable. The trajectory is followed from the first/second/third birth until the arrival of the second/third/fourth birth or the time of the interview, whichever comes first.Age at last birth is a time-constant variable to study second/third/fourth birth risks.Ethnicity is one of the key predictors of the study, and it is a time-constant variable. The actual description of the variable in the raw dataset is the ethnic group of household head, and this is a limitation of the data. However, according to the 2009 census, out of all registered marriages, less than 4% of Kazakhs and 15% of Russians were involved in interethnic marriages . The Assembly of People of Kazakhstan  reports that only 6% of marriages in 2017 were interethnic.Education is measured using dynamic modelling of educational trajectories, following the advice of Hoem and Kreyenfeld , but if a student chooses his/her subsequent level as a secondary vocational school instead of university, he/she only makes 5 years of secondary school; secondary vocational school consists of 3 additional years. Higher education can consist of 4–6 years . Before joining the Bologna educational system, students were supposed to study 5 years for a ‘specialist’ degree; nowadays it is 4 years for a bachelor’s degree and 2 additional years for a master’s degree. Information on the highest grade attained allows one to differentiate between the different levels. A time-varying binary variable was constructed to indicate periods in and out of education. The respondents are coded as being in education all the time before they attained the level reported in the interview. Thus, the variable ‘education’ is time-varying and consists of 5 levels: in education, none/primary/not completed secondary, completed secondary, secondary specialized, and higher. This time-varying variable is used in the first-birth models.For the analyses of the progressions to second, third, and fourth parities, the educational attainment at the time of the interview is used, based on the assumption that women rarely continue their education after entering parenthood.Calendar year is a time-variant covariate and the main variable of interest in this study. When using a period approach, changes in behaviour are observed for synthetic cohorts over time, ‘which is an imaginary group of people who experience, hypothetically, the demographic conditions of that period throughout life’ (Willmoth, Summary statistics of exposures and occurrences by every variable and each parity are presented in Tables To analyse first-, second-, third-, and fourth-birth rates, I apply event history analysis, which is useful when analysing time-dependent processes and allows the characteristics of the respondent to change over time. I present findings as parity-specific relative risks of giving birth during 1971–2015, adjusted for the age of a woman or duration since the last birth, ethnicity, and education. Concerning second, third, and fourth births, mothers are excluded from a given parity sample if they had multiple births the first, second, or third time, respectively.Table Table KM function values at specific ages. The period 1971–1980 is not included because there are no women over the age of 20 contributing to this synthetic cohort. Age 35 is not included for 1981–1990 because there were no women over the age of 30 contributing to this synthetic cohort.Figure Figure Additionally, a three-way interaction between ethnicity, education, and calendar period (see Appendix, Fig. The relative risks of second birth for most of the control variables demonstrate expected relationships Table : second-Table Additionally, an interaction between ethnicity and calendar period did not improve the model fit (see Appendix, Fig. The interaction between education and calendar period (see Appendix, Fig. Table Table The interaction between ethnicity and calendar period (see Appendix, Fig. Table Table Figure The interaction between education and calendar period (see Appendix, Fig. This study aimed to investigate whether the previously observed fertility increases in Kazakhstan during the early 2000s were a temporary phenomenon or indicative of a sustained period of high fertility levels. Additionally, the study assessed whether the pattern of fertility recuperation was universal or specific to particular subgroups of the population, taking into consideration any variations in behaviour and outcomes based on ethnicity and education.In line with hypothesis 1, that the fertility part of Kazakhstan’s demographic transition may have gone into reverse, a gradual increase in fertility rates was observed at all birth orders after the turn of the millennium. This is especially striking for higher-order births, for which fertility developments can most convincingly be linked to changes in the progress of the demographic transition. Hypothesis 2, which posited stabilization after an initial increase during early periods of economic improvement, is not supported. This is evident as a gradual and continuous increase is observed in later periods, even in the absence of additional economic improvements. It is worth noting that while there was economic growth in terms of GDP, this might not necessarily correspond to improvements in individual real income. Furthermore, there is no apparent overall decline in the rate of first births during the study period, which could have indicated the influence of fertility postponement and been considered as evidence of progress towards a second demographic transition. There is some indication of fertility postponement among ethnic Russian women in the early twenty-first century. However, this trend later stabilized, and a continuous postponement is not observed for this group. Specifically, there is no indication of a continuous trend towards postponing motherhood among the majority group of ethnic Kazakh women.A pattern of very low progression rates to second and third births among ethnic Russian women could be seen as some evidence of progress toward the second demographic transition. However, these progression rates did not show any evidence of decline during the period under analysis. Thus, hypothesis 3b is not supported. The estimates for ethnic Kazakhs indicate increasing rates for all higher-order births, which is a development contrary to what would typically be expected from the classical demographic transition. Nevertheless, the trends by ethnicity are quite similar even though Kazakh and Russian women have entirely different levels of parity progressions. This suggests that contextual factors are at play in shaping fertility change.Business cycles and the provision of social policies may impact decisions regarding childbearing, and it would be reasonable to expect that women with varying levels of educational attainment would respond differently to changes in these factors. However, contrary to hypotheses 3a, hypothesis 4, and hypothesis 5, the results did not reveal any educational trend differentials in parity-specific fertility across the periods of the study. Although the risks were at different levels for educational groups, this homogeneity could indicate that childbearing still is an integral part of society in Kazakhstan, and even highly educated women are still eager to progress to higher-order births. It could also be seen as support for the notion of a broad-based re-traditionalization of the society.This study extends the literature on different paths of demographic change and the possibility of reversals of fertility transitions to the context of post-Soviet Central Asia. As Burger and DeLong  argue, tThe case study of Kazakhstan, as a predominantly Muslim country, may also contribute to the literature on Muslim countries as a case where public gender equality is high in relation to women’s education as well as labour force participation. Thus, the so-called MENA paradox of a mismatch between high educational attainment and low labour force participation (Buyukkececi & Engelhardt, The limitations of this study are driven by the characteristics of the available data. There is a slight selectivity in the sample of survey respondents with respect to ever being married, as well as selectivity based on the survival of children and co-residence with children in-between the first and last birth, which limits the sample to more recent birth cohorts. Panel data and more accurate measures of ethnicity, religion, and time-varying data on rural/urban residence would be beneficial for future research.Future research may explore the role of religion in keeping fertility at high levels. Patterns of parity-specific contraceptive use could also be studied to assess the change in contraceptive use and how this may have contributed to the trend reversal that is observed in fertility. If better time-varying data become available in the future, it will be worth exploring the effects of income changes as well as family policy designs on parity progressions to assess the role of widening wealth inequalities and dependence on social support in fertility change.In sum, the study provides new evidence of a sustained fertility increase in Kazakhstan during the 2000s that is associated with a genuine increase in birth rates across all birth orders, ethnicities, and educational groups. Kazakhstan appears to be an example of a reversed fertility transition with increasing progressions to higher-order births and little fertility postponement. The study also suggests that contextual factors that affect all sectors of Kazakhstani society are at play in determining childbearing behaviour. The parity-specific trends are remarkably similar for ethnic and educational groups that otherwise have had different levels and patterns of childbearing.


Female LEOs of childbearing age should receive education about potential reproductive health hazards and take precautions against them. Moreover, policymakers, human resources, and healthcare providers should understand how law enforcement work might affect maternal health.Reproductive health is a considerable concern among US female law enforcement officers (LEOs). Miscarriage and preterm birth rates are significantly higher in women firefighters than published US averages. Since law enforcement and firefighting share occupational conditions and practices, adverse birth outcomes were hypothesized to be greater in female law enforcement officers (LEOs) than the US averages. Occupational hazards may place pregnant LEOs at a higher risk for complicated pregnancies and adverse birth outcomes. This study quantified pregnancy outcomes in female LEOs using a cross-sectional survey and compared them to US averages and large prospective studies. The participants  averaged 2.5 ± 1.4 pregnancies. Stress (59.1%) and shiftwork (59.8%) were the most common reported exposures. Miscarriage and preterm birth rates were 19.1% and 16.4%, respectively. Miscarriages were significantly greater among participants compared to prospective studies [χ A career in law enforcement is inherently stressful and high-risk compared to other careers . Law enfLaw enforcement is a male-dominant occupation since female officers comprise only 12.6% of sworn officers in the US . Female Female LEOs encounter a myriad of occupational risk factors that may cause adverse pregnancy and birth outcomes. Shift work, high stress, allostatic load, and environmental exposures are risk factors for adverse fetal outcomes ,19,20,21The US Bureau of Labor Statistics Standard Occupational Classifications  lists laHigh job stress has been associated with an increased risk of miscarriage and low birth weight among females ,27. The Workplace exposures to chemicals and disease-causing agents can affect a female’s reproductive health, including childbearing ability and fetal health and development . ChemicaDespite the well-documented occupational risks, data for birth outcomes among female LEOs are lacking. Indeed, to our knowledge, no study has quantified birth outcomes among female LEOs in the United States. Understanding birth outcomes can help identify potential occupational health and safety risks associated with their jobs. This information can be used to develop strategies and policies to protect the health and well-being of these officers during pregnancy and childbirth. Therefore, this study aimed to provide preliminary data on birth outcomes and highlight key risk factors for female LEOs’ reproductive health. Adverse birth outcomes such as miscarriage and preterm birth were hypothesized to be significantly higher among female LEOs than in two sizeable general population birth outcome studies ,36.A cross-sectional survey was disseminated using snowball sampling techniques . InclusiThe 78-question self-report survey was formatted similarly to female firefighter research . The surGeneral demographic questions included marital status, ethnicity, income, education attainment, and occupational information such as rank and years of service. Data about pregnancy outcome, duration, maternal age at conception, and if the pregnancy occurred while employed in law enforcement were collected. Participants answered detailed questions about each pregnancy, indicating specific job exposures during pregnancies  and the pregnancy outcome. Each reported live birth was followed with yes/no questions to determine if the baby was born light for gestational age (≤5 lbs. 8 oz), was preterm , was diagnosed as jaundice, or had failure to thrive  . The aveBirth outcomes were categorized as live birth, miscarriage, stillbirth, intended termination, still pregnant, or other. Ectopic pregnancies (n = 2) and anembryonic pregnancies (n = 1) were classified as miscarriages since these pregnancies resulted in a loss before 20 weeks and fit the miscarriage definition. We used the term miscarriage since it was the recommended terminology for pregnancy loss before viability before the mid-second trimester  and becaFrequencies of all pregnancy outcomes were calculated. Miscarriage rates were calculated for those who reported actively working as an LEO during pregnancy. Next, trends in maternal age were examined by comparing two groups: <35 years and ≥35 years  .Miscarriage definitions and classifications were aligned and age-standardized to a prospective linkage study that included maternal age and fetal outcomes for >1,000,000 pregnancies . EctopicA total of 275 individuals clicked on the survey link . Of thos2, with 56 (34.4%) classified as obese (BMI ≥ 30 kg/m2). The participants reported 402 pregnancies, averaging 2.5 ± 1.4 pregnancies per participant. Most participants  were married or with a partner, 89 (54.6%) reported annual household incomes of USD 100,000+, and 96 (58.9%) reported completing college or advanced degrees. The participants were from 32 of 50 states. The states with the most prominent response rates were New York , Nebraska , Wisconsin , California , and Kansas .The majority  were Caucasian, 13 (8.0%) were Hispanic, Latina, or of Spanish origin, 8 (4.9%) were Black or African American, and 3 (1.9%) were American Indian or Alaska Native. The largest respondent group was aged 31 to 40 see , while 1More participants had served in law enforcement for 11–15 years  and FOR 20+ years  = 20.51, p < 0.001]. LEOs under the age of 35 and ≥35 years had significantly higher miscarriage rates than the Andersen sample at χ2  = 10.72, p < 0.001.Of the 402 pregnancies analyzed for the 162 participants, 6 were currently pregnant, and 2 reported having stillbirths, leaving 394 pregnancies for analysis. Overall, pregnancy outcomes included 293 live births (74.4%), 69 miscarriages (17.5%), and 32 terminations (8.1%). The miscarriage rate was higher among those ≥35 years (24.7%) than those <35 years (15.9%). The age-adjusted pregnancy outcomes are presented in 2  = 5.15, p = 0.02]. In 15.5% (n = 45) of pregnancies, participants were diagnosed with some form of high blood pressure and gestational diabetes in 9.6% (n = 28) of pregnancies. High blood pressure was more prevalent than diabetes when stratified by pregnancy  were light for gestational age see . Almost ancy see .The participants actively responded to emergency calls 59% (n = 230) of the time after learning of their pregnancy. The participants’ most widely reported job exposure was shift work, followed by high job stress, shifts longer than 10 h, and exceptionally loud noise see . Less thThis study provides novel information for birth outcomes and key risk factors among female LEOs in the US. As hypothesized, miscarriage and preterm birth rates were significantly higher than those of two large general-population birth outcome studies ,36. AddiFew biological, socioeconomic, or behavioral factors other than increased maternal age have been consistently associated with increased miscarriage risk ,43,44,45Our study’s crude miscarriage rate was almost 6% higher than that of Andersen et al. , a largeThe preterm birth rate was significantly higher, occurring in 16.4% of our sample. The national preterm birth rate is between 9.8% and 12% ,48. OccuOver 71% of participants reported actively responding to emergency calls when they learned of their pregnancy. This was similar to Jahnke et al.  who founTo our knowledge, this study is the first to quantify birth outcomes among female LEOs. We received maternal and child health data on over 400 pregnancies among 162 female LEOs from 32 states and provided detailed information on maternal characteristics and pregnancy outcomes. Additionally, this study directly responds to the call for more research addressing tactical athletes’ reproductive health concerns ,54.However, the study limitations include the self-reported nature of our study. Self-reported retrospective pregnancy outcomes, especially loss or terminations, may be sensitive information for some participants and may not accurately represent birth outcomes. However, the survey was anonymous and was advertised as such. While most LEOs reported an average of two to three pregnancies each, some females reported as many as nine. Researchers acknowledge that recollecting details about maternal health, fetal health, and job tasks during each pregnancy would be challenging and may not be entirely accurate. While we examined age, the strongest predictor of miscarriage, we did not control for other potentially confounding variables, such as previous miscarriages, or behavioral factors, such as smoking and alcohol use during pregnancy.Further, we could not determine how representative this sample was of US female LEOs. Most of our sample identified as Caucasian; therefore, we may be missing critical reproductive health information from other ethnic groups. However, 79% of US LEOs  are Caucasian [Our results justify the concern for the reproductive health of female LEOs. Future research should examine pregnancy complications, adverse birth outcomes, and potential mechanisms among female LEOs and other tactical occupations. Future epidemiological research should provide more insight into the magnitude or combinations of common LEO exposures and behavioral risk factors responsible for adverse reproductive health outcomes using regression or other statistical analytic approaches. Additional research is needed to examine the role of chronic stress and allostatic load in adverse birth outcomes for female LEOs. Future research should consider the reproductive health of dual law enforcement couples to determine if adverse birth outcomes are even greater among them. It would also be helpful to know the specific reproductive health concerns amongst female LEOs and if they impact recruitment and retention.In conclusion, our study’s findings underscore the significant disparities in miscarriage and preterm birth rates among female law enforcement officers compared to large general-population studies and established benchmarks. These disparities persist even after adjusting for age, highlighting the unique challenges that female LEOs may face in their reproductive health journeys. The data reveal that age-adjusted miscarriage rates among female LEOs are notably higher, especially in those aged 35 and older, compared to the general population and international studies. Similarly, our study identified a substantial elevation in preterm birth rates, likely influenced by occupational exposures and high job stress experienced by these officers during their pregnancies.These findings emphasize the importance of addressing occupational risks, providing the appropriate support, and considering consistent shift work schedules to safeguard the reproductive health of female law enforcement officers. Further research and policy considerations are warranted to mitigate these disparities and ensure the well-being of this vital segment of our workforce.Mandating reproductive health education for LEOs and supervisors, covering modifiable behavioral factors like caffeine intake, drug use, alcohol use, smoking, and BMI.Implementing policies such as offering shifts lasting less than 10 h, removing individuals from night shift duty, and maintaining a consistent work schedule of 40 h or less per week during the first 12 weeks of fetal gestation.Providing ongoing stress management tools to female LEOs to enhance pregnancy outcomes.Counseling females of childbearing age about potential miscarriage risks associated with occupational exposures like shift work, high occupational stress, and environmental factors.Monitoring all pregnant LEOs closely for gestational hypertension, promoting a healthy pre-pregnancy body weight, and educating them about the risks of preterm birth.Recognizing that stress management for female LEOs may contribute to minimizing reproductive harm and increasing female representation in law enforcement.To improve pregnancy outcomes for female law enforcement officers, we recommend the following:


Studies try to explain the hypothesis that maternal periodontitis may be associated with preterm birth. This is a case-control study with 120, 40 cases  and 80 controls , that were submitted to the clinical periodontal examination and subgingival biofilm collection. Bacterial DNA of subgingival biofilm was performed and processed by qPCR.p < 0.05). The proportions of Pi (p = 0.026) and Fn (p = 0.041) of subgingival biofilm were higher in the Case group. A greater number of sites with PS ≥ 4mm  and CAL ≥ 5mm  were correlated to lower gestational age. Periodontitis was statistically significant in the Case group (35%) when compared to the Control group (11.2%) and Gingival Bleeding Index (GBI), sites with PS ≥ 4mm and sites with CAL ≥ 5mm were statistically higher in the Case group (Pi and Fn at periodontal sites. Periodontitis, preterm delivery, and/or low birth weight may have a possible relationship based on clinical parameters and the ratio of  Key words:Periodontal diseases, premature birth, fusobacterium nucleatum, prevotella intermedia. Defined as a multifactorial chronic inflammatory disease, periodontitis is associated with the presence of dysbiotic biofilm with a predominance of gram-negative anaerobic microorganisms and is mediated by the inflammatory response of the host . PeriodoMany researchers have investigated the association between maternal periodontitis and premature birth and/or low birth weight babies ,4 while Fusobacterium nucleatum , IL-6, IL-8, tumor necrosis factor-α (TNF-α) or prostaglandin E2 (PGE2), in the fetal-placental unit (ucleatum .Prevotella intermedia (Pi) and Fusobacterium nucleatum (Fn) in the subgingival biofilm of postpartum women to verify if there is a relationship between the clinical and microbiological parameters of periodontitis and the birth of premature babies.The presence of DNA from periodontopathogens has already been detected in the genital tract, amniotic fluid, and placental tissues, which supports how bacterial species of oral origin can participate in placental and intrauterine infections ,9. Thus,Materials and Methods- Ethical ConsiderationsThis research was approved by the Research Ethics Committee of the University Hospital of the Federal University of Maranhão under protocol number 002673/2011-60.- Study designA case-control study was carried out at the Maternal and Child Unit of the University Hospital of the Federal University of Maranhão, with puerperal women at the bedside attended up to 48 hours postpartum. Information about the mother's and newborn's health conditions were obtained from the medical records that were made available to the researchers at the time of collection.The Case Group (A1) was formed by mothers of children born with a gestational age < 37 weeks and the Control Group (A2) by mothers of newborns with a gestational age ≥ 37 weeks.Women smokers were excluded; alcoholics; those who used fixed orthodontic appliances; mouth breathers; chronic use of antibiotics or non-steroidal or steroidal anti-inflammatory drugs in the 6 months preceding the survey; the presence of a systemic condition that could influence the assessment ; use of antihypertensive, anticonvulsant or immunosuppressant drugs or any other drug that is known to present the possibility of resulting in gingival tissue hyperplasia, twin pregnancy.- Clinical StageA previously trained professional applied the questionnaire data collected on oral hygiene habits . The clinical examination was performed with the aid of a frontal light attached to the examiner's head. The following parameters were evaluated: 1- Probing Depth (PS) recorded at 6 sites for each tooth , 2 - Clinical Attachment Level (CAL) distance in millimeters between the cementoenamel junction and the bottom of the sulcus or periodontal pocket (6 sites), 3- Visible Plaque Index (VPI) , 4- Gingival Bleeding Index (6 sites), recorded 10 seconds after probe removal North Carolina PCPUNC 156   of the periodontal pocket or sulcus .Each postpartum woman was classified according to the presence or absence of periodontitis according to the following criteria: at least 4 or more teeth with one or more sites with PS ≥ 4 mm, with CAL ≥ 3 mm in the same site, and the presence of bleeding on probing .- Biofilm CollectionThe collection of the subgingival biofilm was performed after the removal of the supragingival biofilm with sterile gauze. Samples were taken with Gracey 5-6 / 7-8 periodontal curettes  from four different sites (those with the greatest probing depth of each quadrant) throughout the same depth. The biofilms were placed in sterile tubes containing a Tris-EDTA solution (150 µL Tris-EDTA + 100 µL of NaOH solution) for freezing in a -80°C freezer (Indrel Ultra Freezer -80°C).- DNA ExtractionDNA extraction was performed as described by the QIAamp DNA User Manual (Qiagen), with modifications. 200µL of the sample, 20µL of proteinase K and 200µL of Buffer AL were added to a 2ml tube and incubated at 56°C for 10 minutes in a dry bath. Then 200µL of ethanol (96-100%)  was added and the entire solution was added to a silica column for DNA capture.500µL of washing solutions were added followed by centrifugation and finally, the column was incubated in 200µL of buffer AE for 5 minutes. DNA was collected after centrifugation at 8000rpm for 1 minute. The purified DNA was submitted to quantification in the Nanovue device  to evaluate the concentration and integrity of the DNA. All material was frozen in -80°C frfreezerIndrel Ultra Freezer -86°C).- Detection and Quantification by Real-Time Polymerase Chain Reaction (qPCR)For the detection and quantification of the bacteria under study, the DNA of the bacteria needs positive controls, as these are necessary to generate the standard curves of the bacterial species used in the biofilm model. Concentrations of 1-0.001ng of DNA were defined for the standard curve generation. The logarithm of the corresponding values from the quantification cycle was used to obtain a linear regression. For the quantification of bacteria in the biofilm samples, the concentration of the extracted DNA mixture was determined using the NanoDrop ND-1000.Prevotella intermedia (Pi) (5’-TTTGTTGGGGAGTAAAGCGGG-3’) and Fusobacterium nucleatum (Fn) (5’-ATT GTC GCT AAA AAT T -3’) were used , 5 µL of the sample (diluted to contain 1 ng of DNA), and 5 µL of solution of primer from the respective bacterium .Amplification took place in a StepOne thermocycler (Applied Biosystems) by initial incubation of 2 min at 50 °C and 10 min at 95 °C, followed by 40 cycles of 15 s at 95 °C and 1 min at 60 °C. Ct obtained, the DNA concentration of the sample was calculated for each organism using the theoretical genomic weight of each of the bacteria .- Statistical analysisData were analyzed using GraphPad Prism version 8 software . Descriptive statistics were performed using measures of frequency, mean and standard deviation. The results were presented through Tables, bar graphs, and ≥heat maps.p < 0.05).Categorical variables were compared between case and control groups using the chi-square or Fisher's exact test. Normality analysis of continuous variables was performed using the Shapiro-Wilk test. After this procedure, the independent student t-test was selected for the comparative analysis between the groups. In addition, Pearson's coefficient (r) was used to analyze the correlation between the variables gestational age (in weeks), the proportion of pathogens, and periodontal parameters. The significance level adopted for all analyzes was 5% (p < 0.001). The Case group also observed a lower mean number of prenatal consultations (p = 0.045). There was a concentration of younger women in the Control group (p = 0.014). Furthermore, arterial hypertension was more prevalent in the Case group (p < 0.001)  .p < 0.05).The evaluation of the periodontal condition, expressed in Pi and Fn. On the other hand, the analysis of the proportion of pathogens in the samples revealed that the proportions of Pi (p = 0.026) and Fn (p = 0.041) were higher in the Case group.Fig. p = 0.026) and CAL ≥ 5mm , to lower the gestational age. The proportions of Pi and Fn showed a strong direct\ correlation . The VPI showed an inverse correlation with the proportion of Fn . In addition, all periodontal parameters showed significant direct correlations with each other.Linear correlation analysis is illustrated in the heat map Fig. . The resPi and Fn in postpartum women with preterm delivery.The study showed the relationship between periodontitis and preterm delivery and/or low birth weight, through clinical and microbiological parameters of periodontal disease. It is noteworthy that the analysis of the proportion of pathogens in the samples revealed higher proportions of Pi and Fn between groups, however, the proportion of Pi (p=0.026) and Fn (p=0.041) within the universal DNA community of the subgingival biofilm of postpartum women were higher in the case group. Data partially corroborate another case-control study with pregnant women in which the results found an association in the clinical presentation of periodontitis, but in the microbial analysis was no significant association between preterm delivery and low birth weight with most periodontal pathogens , however, the analysis of the proportion of pathogens in the samples revealed higher proportions of Pi and Fn in the group with preterm and/or low delivery birth weight.Another relevant aspect is the methodology presented here by the use of the 16S universal primer, which allowed the identification of bacterial phenotypic sequence present in most bacteria, with subsequent use of a bacterial primer specific to the Fn and Pi, with hypertensive disorders during pregnancy, as they have been shown to have higher levels in hypertensive women than in normotensive patient groups  support the relationship between periodontitis and adverse effects of pregnancy.It is important to highlight that a systematic review of 10 case-control studies concluded that there is a relationship between periodontal disease and increased risk of preterm birth and low birth weight or low birth weight with Odds Ratios ranging between 2.04 and 4.19, and in this work, there was only one study that found no association . Thus, tet al (For Fischer et al , it is pOther studies also sought answers to possible failures in the work to explain the non-association between periodontitis and adverse effects on pregnancy, such as heterogeneity in the clinical definition of the severity and extent of periodontitis used to distinguish case and control groups. Studies fail to control for shared risk factors or confounding factors between periodontitis and adverse effects on pregnancy, and finally, most studies did not consider the spread and survival of periodontal pathogens to the placenta as a mechanism that could induce these effects regardless of ongoing disease in the oral cavity .Pi and Fn bacteria and the prematurity outcome, however, we were unable to show a causal relationship.This research presents strong bridges such as the criteria used for the diagnosis of periodontitis, the sample size respecting the case and control groups, and the robust technique for detecting periodontal pathogens through qPCR. The findings contribute to the hypothesis of an association between Pi and Fn at periodontal sites, contributing to the multifactorial nature of preterm delivery. However, we cannot assert forcefully the cause-and-effect relationship between the objects studied in the research. Thus, more studies are needed to corroborate the preliminary data of the present study.Periodontitis and preterm delivery may have a possible relationship based on clinical parameters and the ratio of


No differences were found in 5 min Apgar scores, cord pH, need for delivery room resuscitation, rate of hypoglycemia, hyponatremia, hyperbilirubinemia, need for phototherapy, temperature stability and maximal oxygen requirements. No differences were found in the total time of respiratory support, time to reaching full enteral feeds, length of stay and complications of prematurity. Unlike studies in term infants, no significant differences were found in adaptation and short-term outcomes between preterm infants with and without SSRI exposure in pregnancy.Selective serotonin reuptake inhibitors (SSRIs) are increasingly used for maternal depression during pregnancy; however, their use has been linked to adverse effects in newborns. Respiratory and feeding problems, jaundice, metabolic and temperature dysregulation and hypoglycemia have been described in term infants. However, scarce data exists on early neonatal adaptation in exposed infants born prematurely. We aimed to assess the effects of SSRI exposure on early neonatal adaptation measures in infants born prematurely. Data from preterm infants exposed to maternal SSRIs during pregnancy and from matched controls were retrospectively collected. Forty-two infants comprised the final cohort: 21 infants with SSRI exposure and 21 matched controls. 1 min Apgar score was significantly lower in the exposed group compared to the non-exposed group ( Mood disturbances such as depression and anxiety occur in up to 20% of pregnant women ,2 and arAn increased risk of preterm birth has been described across studies . One sysp < 0.001) [p = 0.002) [In utero exposure to SSRIs has been associated with poor neonatal adaptation, thought to be related either to serotonergic overstimulation or to withdrawal phenomena after birth ,11. One < 0.001) . The sym= 0.002) . HoweverMost available studies on early adaptation and respiratory and metabolic regulation were performed on term infants, while some included a mixed population of term and preterm infants, with the majority of the cohort being term infants. Less data are found exclusively on preterm infants. The purpose of this study was to assess the effect of in-utero SSRI exposure on early adaptation and short-term outcomes in infants born preterm. We hypothesized that SSRI exposure would be associated with poor respiratory and metabolic adaptation in preterm infants.This was a retrospective observational study performed in the neonatal intensive care unit (NICU) at the Carmel Medical Center. Preterm infants with prenatal SSRI exposure and matched controls without SSRI exposure were included. The study was approved by the Carmel Medical Center Research Ethics Board.®, iMDsoft, Park Atidim, Tel Aviv, Israel). Records were reviewed using MetaVision’s Query Wizard tool, identifying infants admitted to NICU during the study period with completed data on maternal drug use during pregnancy. All identified infant records were then reviewed to select the preterm infants exposed to an SSRI and the matched controls.Electronic records of all infants born during the years 2015–2022 and admitted to NICU were screened, and all preterm infants with a positive history of maternal SSRI use throughout the pregnancy were included. Controls were matched by gestational age, birth weight, sex and date of birth and a confirmed negative history of maternal SSRIs. Infants with culture-positive early-onset sepsis, maternal diabetes, major congenital anomalies or a highly suspected genetic syndrome and infants who did not survive the first week of life were not included. Infants with unknown maternal drug history, additional psychotropic medications or those in whom maternal SSRI use was discontinued before the third trimester were also excluded. Data were retrospectively collected from an electronic health record database (Metavision(a)Maternal demographics and health status, pregnancy-related complications and use of prenatal steroids;(b)Early-onset sepsis risk factors , gestational age, birth weight and sex of the newborn, need for advanced delivery room resuscitation (advanced airway or chest compressions), cord pH and Apgar scores;(c)Early respiratory and metabolic neonatal adaptation parameters including hypoglycemia episodes, need for hypoglycemia treatment, body temperature regulation, need for respiratory support, need for surfactant treatment, need for inotropes, highest bilirubin level, need for phototherapy, serum sodium levels and time to regaining birth weight;(d)Complications of prematurity such as intraventricular hemorrhage, patent ductus arteriosus, late-onset sepsis, bronchopulmonary dysplasia, necrotizing enterocolitis and retinopathy of prematurity, defined by commonly used published criteria ,16,17.Retrieved information included:®, version 16.2.2 . The sample size calculation assumed a 29% baseline rate of post-delivery respiratory distress in an unexposed population consisting mostly of late-preterm newborn infants [p-values of less than 0.05 were considered statistically significant.Data were recorded in an Excel spreadsheet  and statistically analyzed using SigmaPlot, version 11.0  and Minitab infants . Based o infants , we assuDuring the years 2015–2022, there were 826 infants born at the Carmel Medical Center who were admitted to the NICU and had completed data on maternal drug use in the department’s database. Fifty-two of the infants had a confirmed SSRI exposure during pregnancy. We excluded 29 exposed infants who were born at term, one preterm infant who had only first-trimester exposure and one preterm who had co-exposure to benzodiazepines. Twenty-one preterm infants with SSRI exposure throughout the pregnancy and twenty-one matched controls comprised the final cohort (n = 42). The baseline maternal and neonatal characteristics are presented in Due to matching the controls, the gestational age and birth weight were comparable between the exposed and non-exposed group, but no significant differences were found in other baseline parameters as well. Most preterm infants were appropriate for their gestational age.p = 0.043). Seven of the exposed infants had an Apgar score below 7 at 1 min (33.3%) versus four of the non-exposed infants (19%). No significant differences were found in the 5 min Apgar scores, cord pH or the need for advanced delivery room resuscitation. ; 8.0  and 9.0  respectively, itation. .The need for any respiratory support in the first 3 days of life was comparable between the groups, as was the need for intubation and mechanical ventilation during the first week of life, the need for surfactant treatment and maximal oxygen requirements . None ofp = 0.345). Bilirubin levels and need for phototherapy were similar.Blood glucose level and hypoglycemia episodes in the first 3 days of life were comparable between the groups, as were maximal bilirubin levels and the need for phototherapy. The mean lowest serum sodium levels during the first week of life were similar between the groups, although hyponatremia <130 meq/L occurred more often in the exposed group compared to the non-exposed group , but this difference did not reach statistical significance.No differences were found in the short-term outcomes or in the rate of complications of prematurity . The lenSSRIs increase serotonin levels by inhibiting its reuptake at the serotonin transporter at the presynaptic neuron. Their use in pregnancy has been increasing in recent years due to their relatively fewer side effects compared to other antidepressants ,13, and SSRIs cross the placenta and were shown to be present in amniotic fluid, in cord blood in correlation with maternal dose and to alter serotonin levels in the fetus ,8. By crOver the past two decades, the widespread use of SSRIs has prompted extensive research to assess the health risks associated with in utero exposure. However, inherent methodological challenges exist in this field. Isolating the drug effect from the effects of maternal depression and genetic and epigenetic factors is difficult . Even whIn our cohort, the 1 min Apgar score was significantly lower in exposed versus non-exposed infants, in agreement with previous large meta-analyses. In a systematic review and meta-analysis including 33 studies with over 25,000 cases of in utero antidepressant exposure, increased odds ratios for an Apgar score below 7 were found for both 1 and 5 min Apgar scores in exposed infants  comparedp = 1.0). In another study including preterm infants, oxygen administration in the delivery room was slightly higher in exposed versus non-exposed newborns , but the need for positive pressure respiratory support was comparable  [Advanced delivery room resuscitation was chosen in our study to reflect the need for a higher level of intervention beyond the first steps of newborn resuscitation, which are commonly required in the healthy preterm population. This outcome was similar between the groups in our cohort  . Convers = 0.85) .Overall, since the 5 min Apgar score, cord pH and need for advanced resuscitation were not influenced by SSRI exposure in our cohort, the 1 min Apgar score likely reflects an initial mild transient depression.Unlike most studies in term infants, we found no significant differences between the exposed and non-exposed groups in need of respiratory support and in need for surfactant treatment indicating respiratory distress syndrome during the first week of life, and we had no cases of persistent pulmonary hypertension. One study found a significantly higher rate of respiratory distress, mostly transient tachypnea of the newborn, in SSRI-exposed term infants n = 401) compared to non-exposed, matched controls . However01 comparContrary to reports on term infants, we did not find significant differences between the groups in rates of hypoglycemia or jaundice. Rate of hypoglycemia with exposure to SSRIs in previous reports varied between 3.5 and 19% ; howeverThe length of stay in the NICU was comparable between the groups in our cohort, in agreement with two other studies in preterm infants ,34. In oWe found no association between SSRI exposure and complications of prematurity, in agreement with another cohort of preterm infants  , the baseline rate of respiratory support in the unexposed control group was much higher than our assumptions 66% vs. 29%), probably reflecting the wide use, nowadays, of post-delivery non-invasive respiratory support, especially in preterm infants and including late preterm newborns, who were indeed the majority of our study population. Second, some methodological differences exist between our study and previous works as we aimed to avoid the bias of a mixed population of term and preterm infants by focusing exclusively on preterm infants and kept homogeneity in the length of exposure to SSRIs in the study population. In retrospect, it might have been useful to add another control group of term newborns exposed to a maternal SSRI to verify the effects of a maternal SSRI in our population of term infants, although there are plenty of studies from our country on term newborns exposed to a maternal SSRI ,24,29,30%, probabWe were not able to collect Finnegan scores because it was not done routinely in preterm infants in our department. Nonetheless, this score was designed for neonatal abstinence syndrome after opiate exposure and has not been validated for poor neonatal adaptation after SSRI exposure . Other lIn conclusion, 1 min Apgar scores were lower in preterm infants exposed to an SSRI during pregnancy compared to non-exposed matched controls. Other adaptation parameters and short-term outcomes were similar between the groups. Larger prospective studies are needed to confirm our results.


Uveitis is one of the most common manifestations of juvenile idiopathic arthritis (JIA). Currently, JIA is associated with decreased gut microbiota diversity. Studies confirm that perinatal events can cause aberrant microbial colonization. The objective of this study is to determine if JIA is associated with perinatal events with a secondary focus on these variables to the development of JIA-uveitis. 369 patients with strabismus (n = 200) or JIA (n = 196) were included in the study. Completed surveys  collected data about birth route, pregnancy and labor complications, JIA medications, and the presence of eye disorders. Analysis indicates that there is no relationship between JIA development and the perinatal events investigated. Similarly, no significance was found between JIA-uveitis and birth route or labor complications. Pregnancy complications, namely gestational diabetes (GD), were statistically higher in the JIA group with uveitis compared to JIA without uveitis. The data from this survey study showed that JIA-uveitis was highly associated with pregnancy complications, particularly with GD. However, no statistically significant association was found between JIA and route of delivery, labor complications, or pregnancy complications. Further studies are needed to understand the ways that GD interrelates with the development of uveitis in JIA patients. The autoimmune disorder can manifest with symptoms of joint pain, stiffness, inflammation within joints, and an overall sense of malaise. In addition to its rheumatologic symptoms, JIA exhibits ocularimplications where uveitis—an inflammation of the middle layer of the eye—serves as one of the most common extraarticular manifestations3 with arthritic symptoms typically preceding the development of uveitis1.Juvenile idiopathic arthritis (JIA) is the most common arthritic affliction within the pediatric population4 with the co-occurrence of these disorders predicting a poor overall prognosis2. Although well documented as a common co-occurrence with JIA, the pathogenesis, etiology, and predisposing factors of JIA-uveitis remain unclear5. As such, the central objective of this investigation is twofold: first, to uncover factors, specifically perinatal, that are linked to the development of both JIA and JIA-uveitis, and second, to lay the foundation for subsequent investigations into the underlying cause of this condition.Patients with JIA associated uveitis (JIA-uveitis) often require long-term immunosuppression and close follow-ups12, JIA demonstrates a correlation with microbiota dysbiosis which plays a vital function in conferring host immunity13. Particularly noteworthy is the reduced concentration of four types of short-chain-fatty-acid-producing bacteria15 within the gut microbiota of JIA patients. This reduction in bacterial diversity potentially triggers an altered immune response to the microbiota, contributing to the augmented circulation of auto-antibodies16. Although not innately pathogenic, these findings of auto-antibody production offer insight into the potential mechanisms that underlie the developmentof JIA.Much like several other autoimmune disorders4. Despite existing research, there remains to be a significant research gap pertaining to CS delivery, perinatal complications, and the subsequent development of JIA or JIA-uveitis.Perinatal events, including cesarean section (CS) deliveries and complications during pregnancy or labor are known to modify the microbiotic diversity of an infant. In contrast to vaginal delivery, CS delivery does not facilitate the transmission of maternal microbiota to the child, preventing bacterial colonization and growthThus, the objective of this study was to determine the presence of an association between these variables. In addition to investigating the risk of JIA development with CS delivery, this study also encompasses the examination of other perinatal factors, including complications during pregnancy and labor (Supplementary table).Out of the 396 patients meeting inclusion criteria, 200 were included in the strabismus group and 196 in the JIA group. Responses were received from 56 patients via mail—18 from the strabismus group and 38 from the JIA group. Respondent data were categorized based on initial grouping: JIA  and strabismus . Demographics and pathologies collected from each cohort are listed in Tables p-values for JIA development relative to birth route, pregnancy complications, and labor complications, using the strabismus group as reference. However, no statistical relationship were observed across the variables measured .Among JIA-uveitis patients with pregnancy (n = 6), gestational diabetes affected 50% of patients (n = 3). This was statistically significant compared to JIA patients without uveitis and experiencing gestational diabetes, as shown by chi-square analysis . The link between RA and maternal smoking found in this study may suggest a link between other forms of autoimmune diseases, such as JIA, and maternal smoking as well.Environmental factors such as maternal alcohol and nicotine use as well as TORCH infections have been known to disrupt fetal development resulting in various birth defects and lowered health outcomesAlthough our study did not establish a direct relationship between pregnacy complications and JIA development, there was a positive association between gestational diabetes (GD) and uveitis within JIA patients, potentially suggesting a correlation between these factors. Surprisingly, the effects of GD were confined to its influence on uveitis in JIA patients, with no overall relationship to JIA development.34. The adverse outcomes associated with GD can increase lifetime risk of obesity as well as cardiometabolic diseases35. Changes in adiposity observed with children born of GD contribute to the increased risk of lifetime obesity in these patients39. Babu et al.35 found that obese mothers are more prone to present with GD during pregnancy which, through a process of hyperglycemia-induced fetal programming, is associated with increased neonatal adiposity37. Muhammed et al.’s39 experimental studies indicated that increased fat composition exacerbated autoimmune uveitis in mice models. This was due to the release of proinflammatory mediators with targeted ocular antigens coupled with decreased regulatory immunity that is associated with white adipose tissue28. However, a more direct analysis of the association between GD and uveitis would be needed to understand the mechanism for this relationship.Children born with GD have an increased risk of adverse perinatal outcomes including hypoglycemia, macrosomia, and birth traumaA significant constraint of this study lay in the diminished response rate which, consequently, led to a small sample size and reduced statistical power. Although most variables analyzed indicated a broad range, the study lacked racial diversity with very few non-white respondents. This is an inherent disadvantage of survey studies with little means of improvement. The study’s sample group exhibited a substantial homogeneity in terms of its size and composition, highlighting the necessity to validate the findings through subsequent research before extending them to a broader population. Nevertheless, the study provides the framework and preliminary results that can guide future studies.This was a survey-based study including patients diagnosed with JIA, while patients diagnosed with strabismus constituted the control group, selected for comparable age and lack of immunologic association. Inclusion criteria were pediatric and adult patients with a diagnosis of either strabismus (control) or JIA at the Indiana University Health System . Eligible patients were sent surveys via mail, with instructions to return them using the provided prepaid envelope. Information about the study was disclosed in the initial surveys with declaration that the return of the survey constituted as informed consent for participating in the study. This study adhered to the Declaration of Helsinki and was approved by the Indiana University Institutional Review Board.Participants were categorized into two cohorts based on initial inclusion diagnoses. For respondents with strabismus collected data included sex, date of birth, race/ethnicity, birth route, whether C-section was medically recommended or elective, gestational age at birth, complications during pregnancy, and complications during labor Similarly, data collected from returned surveys of the JIA group included information about sex, date of birth, race/ethnicity, age of JIA diagnosis, medication for JIA, presence of eye disorders, birth route, whether C-section was medically recommended or elective, gestational age at birth, complications during pregnancy, and complications during birth. A comprehensive list of the data collected from each survey can be found in supplementary data. Participant responses were gathered through the surveys and recorded electronically for data consolidation.The survey employed a combination of free response, binary (yes/no), and multiple-choice questions. Binary questions addressed sex, birth route, and whether C-section was medically recommended or not. Multiple choice questions were utilized for pregnancy complications, labor complications, JIA medication, race/ethnicity, and eye disorders. Participants selecting ‘other’ were prompted for further details in their responses. Questions requiring further elaboration or those that were challenging to categorize were managed through free responses. Date of birth, gestational age at birth, and age of JIA diagnosis were collected through free response questions.A qualitative approach was adopted to address responses necessitating further elaboration. Responses specifying medication names and complications during pregnancy or labor beyond questionnaire options underwent preliminary analysis to ensure comprehensiveness. These responses were then quantified for frequency and type during analysis.Descriptive analysis was applied to determine median and mode age for diagnosis and gestational age at birth. A binary methodology was used employed to calculate the occurrence of all other variables. Correlation between the variables of interest was assessed using chi-square analysis, as well as Fisher's exact test for smaller cell samples .Our investigation revealed no relationship between JIA and birth route, pregnancy complications, or labor complications, although the constrained respondent count limits data interpretation. In addition, JIA-uveitis cohorts demonstrated minimal association with variation in birth route and labor complications. However, pregnancy complications, namely gestational diabetes, showed statistical significance in uveitis development within the JIA patient population. In sum, these findings offer valuable insights into the plausible causal link between JIA patients born of gestational diabetes and uveitis. Subsequent research endeavors are needed to validate this relationship and uncover potential underlying mechanisms.Supplementary Table 1.