Since the 2000s, air pollution has generally continued to decrease in the U.S. To investigate preterm birth (PTB) risk associated with air pollutants in two consecutive pregnancies, we estimated exposures using modified Community Multiscale Air Quality models linked to the NICHD Consecutive Pregnancy Study. Electronic medical records for delivery admissions were available for 50,005 women with singleton births in 20 Utah-based hospitals between 2002–2010. We categorized whole pregnancy average exposures as high (>75th percentile), moderate (25–75) and low (<25). Modified Poisson regression estimated second pregnancy PTB risk associated with persistent high and moderate exposure, and increasing or decreasing exposure, compared to persistent low exposure. Analyses were adjusted for prior PTB, interpregnancy interval and demographic and clinical characteristics. Second pregnancy PTB risk was increased when exposure stayed high for sulfur dioxide (32%), ozone (17%), nitrogen oxides (24%), nitrogen dioxide (43%), carbon monoxide (31%) and for particles < 10 microns (29%) versus consistently low exposure. PTB risk tended to increase to a lesser extent for repeated PTB (19–21%) than for women without a prior PTB (22–79%) when exposure increased or stayed high. Area-level changes in air pollution exposure appear to have important consequences in consecutive pregnancies with increasing exposure associated with higher risk. Preterm birth has been associated with air pollution exposure, but no prior studies have examined the change in risk over time in an existing cohort. The NICHD Consecutive Pregnancy Study 2002–2010) contains detailed clinical data on deliveries for more than 50,000 women with at least two pregnancies during the study period 0 contain. During 3) and precursors of particulate matter < 2.5 microns (PM2.5), as well as a higher incidence of wildfire exposures [3, carbon monoxide (CO) and particulate matter significantly increased preterm risk [Considering that continued progress to improve air quality is challenged by the global impact of extreme weather events and climate change, which may increase pollution after decades of improvements, it is important to characterize the link between changes in exposure and population health to inform policy . Even iferm risk . Pretermerm risk . It is aerm risk . The raterm risk , can furIn addition to the potential for changes in risk associated with the ambient environment, changes in preterm birth risk over time are also influenced by women’s reproductive history. A recent meta-analysis reported an average absolute recurrent spontaneous preterm birth rate of 30%  and we oOur aim was to examine the risk of preterm birth in a second pregnancy based on the change in air pollutant exposure since the first birth in a cohort of low-risk U.S. women. This is important to demonstrate the human health impacts of improved or degraded air quality over time on preterm birth, a key indicator of population health. We hypothesized that improving air quality would be associated with a lower risk of subsequent preterm birth, and that increased preterm birth risk would be observed when air pollution stayed high over time. We also evaluated potential effect modification by prior preterm birth and hypothesized that women without a prior history, generally at lower risk, would have a higher preterm birth risk associated with air pollution exposure.The NICHD Consecutive Pregnancy Study  is based2), O3, nitrogen oxides (NOx), nitrogen dioxide (NO2), CO, particulate matter < 10 microns (PM10), and particulate matter < 2.5 microns (PM2.5) were also weighted to reflect the population density in order to discount areas where women were unlikely to live or work.Air pollution exposure was estimated for each pregnancy using modified Community Multi-Scale Air Quality models and averaged over the delivery hospital referral region fused with existing monitor data using inverse distance weighting . ExposurBased on the exposure levels in the first observed pregnancy , we cate3), race/ethnicity , marital status , insurance status , parity , smoking and alcohol use during pregnancy  and history of maternal asthma (yes/no).Relative risks and 95% confidence intervals were estimated using single-pollutant, modified Poisson regression models with robust errors  to correGiven the strength of prior preterm birth as a predictor of preterm birth in the second pregnancy, we repeated the main analyses evaluating interaction by prior preterm birth status. To assess the robustness of our findings, we also repeated the whole pregnancy average analyses using exposures truncated at 28 gestational weeks and examined the subset of consecutive pregnancies among nulliparas at study onset. To further explore the potential impact of changes over time on second pregnancy preterm birth risk, we evaluated year of conception for the second pregnancy, and the change in season of conception between the first and second pregnancy .All analyses were conducted using SAS 9.4 .Infants were delivered preterm in 7.6% of both first and second observed pregnancies . The wom2, PM10 and PM2.5. Overall, women were more likely to experience a decrease in pollutant exposure with approximately 7–12% of women having a category shift to higher exposure in the second pregnancy compared to 27–59% shifting to a lower exposure category  and SO2 (32% increase). When exposure stayed moderate, we observed an increased risk associated with SO2 (12% increase) and a decreased risk for PM2.5 exposure (18% decrease). Similar to the results for persistent high exposure, increasing exposure over time was generally associated with higher PTB risk, although the results for NOx were not significant. Decreasing exposure over time resulted in lower risk estimates, although still significantly elevated for SO2, NO2 and PM10. For example, the relative risk for SO2 when exposure increased was 1.41 versus 1.17 when exposure decreased over time.When exposures stayed high in both the first and second pregnancy, compared with persistent low exposure, the relative risk of preterm birth in the second pregnancy was significantly elevated for all pollutants except for PM2.5 . The hig2, SO2, O3 and CO. When exposure stayed high, SO2 risk was fairly consistent between women with and without a prior history , whereas greater risk was observed for NO2 among women without a prior preterm birth compared to women with a prior preterm birth . Increasing exposure suggested similar risks by prior preterm birth status for PM10 , but significantly higher risk for women without a prior preterm birth associated with increasing NO2, SO2, O3 and CO compared to women with a prior preterm birth history.Assessing the interaction by prior preterm birth status , the ris2, NO2 and PM10. When considering only women who were nulliparous at the beginning of the study , change in exposure over time was associated with a similar pattern of results as the main analysis, although increasing exposure was associated with somewhat higher point estimates in this group  among women without a prior preterm birth for NO2, CO and PM2.5. Adding year of conception for the second pregnancy or an indicator variable to measure the change in the season of conception from the first to second pregnancy into the models did not substantively change any of the findings (data not shown).Restricting the exposure windows to the first 28 weeks of gestation yielded a similar pattern of results, but the effects were somewhat attenuated . Signifiis group . For exais group , O3 was 2.5. Increasing exposure over time was associated with higher preterm birth risk, while decreasing exposure was associated with lower risk estimates. Women without a prior preterm birth experienced a higher risk for an incident preterm birth in the second pregnancy associated with pollution.In a cohort of low-risk U.S. women, we found that preterm birth risks were significantly increased in association with persistent high exposure to all criteria air pollutants except for PM2 to 59% for O3. Increasing exposure was less common, experienced by only 3% of women with respect to O3, but 30–32% of women had increased PM2.5 exposure in the second observed pregnancy compared to their first. A prior history of preterm birth is a major risk factor for preterm birth in a subsequent pregnancy [During the study period, our cohort had a preterm birth rate of 7.6% in comparison to approximately 12% for the U.S. overall. This low-risk group experienced moderate levels of chronic air pollution exposure and exposure decreased over time for a substantial proportion of the women, ranging from 27% for SOregnancy  and, in 2.5 and many of the point estimates we observed were below 1.00. It may be that our chronic average categorization is not an ideal fit for this exposure, given that the Utah Valley experiences inversions and high PM exposures during peak events in the winter. We also noted that nearly one-third of women experienced an increased average PM2.5 exposure between the first and second pregnancy, which may be due to wildfire exposures. A more detailed assessment of short-term PM2.5 exposures is warranted to consider those factors.In contrast to many studies of preterm birth ,13,14, wThis study takes advantage of a nearly decade-long observational cohort with detailed clinical information on women with more than one delivery in a defined geographic area. The women were low-risk, but still experienced significant increases in preterm birth related to moderate levels of criteria air pollutants. Given the rich clinical data available, we were able to adjust for maternal demographic characteristics and factors, such as interpregnancy interval , prior pOur categorical chronic exposure scenario was chosen to examine the bigger picture changes over time that could reasonably be observed, and that might be associated with policy-relevant changes in preterm birth risk associated with these dynamic exposures. Preterm birth risks associated with changing exposure were not influenced by changes to the season of conception between the first and second birth or adjustment for the year of conception of the second pregnancy.In this study of low-risk women with consecutive pregnancies in a large cohort, we observed increased risk over time for nearly all criteria pollutants when exposure remained high or increased over time. Decreases in exposure over time were associated with comparatively lower risk estimates. Women without a prior preterm birth experienced a higher risk for an incident preterm birth in the second pregnancy associated with pollution.These findings suggest that improvements in air quality could reduce related preterm birth risks, but failure to address persistent air pollution results in higher risk, particularly for nulliparous women and those without a prior preterm birth history.


Each 3.25 µg/m3 increase in PM2.5 concentration in the 6th gestational month was associated with a −20.4 g  reduction in term birth weight among Hispanic women, but a 4.1 g  increase among non-Hispanic mothers (p for interaction < 0.001). Although ambient air pollutant concentrations during pregnancy were not associated with reduced term birth weight among women of all ethnicities living in Monroe County, this observed association in Hispanic mothers may be a result of less exposure misclassification and bias .Increased ambient air pollutant concentrations during pregnancy have been associated with reduced birth weight, but the etiologically relevant pregnancy time window(s) is/are unclear. In 76,500 singleton births in Monroe County, NY (2005–2016), who were 37–42 gestational weeks at delivery, we used generalized linear models to regress term birth weight against mean gestational month pollutant concentrations, adjusting for mean temperature, and maternal, infant, and medical service use characteristics. Overall, there were no clear patterns of term birth weight change associated with increased concentrations of any pollutant across gestational months. However, among Hispanic women only, increases in all pollutants, except O Further, incremental increases in PM2.5, CO, SO2, and NO2 concentrations during the 8th month of pregnancy were associated with 17–34 g decreases in term birth weight, respectively [Birth weight is an important determinant of physical, psychological, and behavioral outcomes in later life  with somIncreased risks of preterm birth  and preeWe used maternal and infant data obtained from the Finger Lakes Region Perinatal Data System (FLRPDS), a collection of birth certificates and supplemental questionnaire data for births in the nine-county Finger Lakes region in New York State. Birth registrars at each hospital obtained data from mothers through interviews or surveys and abstracted data from mothers’ and infants’ medical  records. We included only singleton births to women residing in Monroe County at the time of birth from 1 January 2005 to 31 December 2016, with a gestational age of 37–42 completed weeks and a birth weight ≥ 500 g.From the FLRPDS, we extracted data on infant and maternal characteristics, pregnancy complications, and medical service-related information. We also obtained information on the date of the last menstrual period (LMP). Gestational age was calculated primarily based on LMP, with clinical estimates used for those subjects missing the LMP date. We estimated the beginning and ending date of each gestational month , and used this to calculate mean pollutant concentrations for each gestational month. The mean pollutant concentrations for the last month was calculated for the last 31 days before the date of delivery. The primary outcome was term birth weight (in grams), but we also defined LBW as a term birth weight < 2500 g. The study was approved by the University of Rochester Medical Center Research Subjects Review Board.2.5, aerodynamic diameter < 2.5 µm), number concentrations of ultrafine particles  and accumulation mode particles , black carbon , sulfur dioxide (SO2), and ozone (O3). Temperature and relative humidity data measured at the Rochester International Airport were obtained from the National Oceanic and Atmospheric Administration (NOAA) National Climate Data Center. For each study subject’s gestational month of pregnancy, we calculated mean pollutant concentrations, temperature and relative humidity if at least 75% of the hourly pollutant, temperature, or humidity values during the specified gestational month period were reported. We then used these monthly pollutant concentrations and weather characteristics in the statistical analyses described below.Hourly concentrations of air pollutants were collected from the New York State Department of Environmental Conservation (NYSDEC) site in Rochester. This site is adjacent to two major highways (I-490 and I-590) and State Route 96 on the east side of Rochester and measures hourly mass concentrations of fine particles , year of birth (2005–2016), sex of infant, month of conception (January–December), parity , maternal education , maternal country of birth (United States or non-United States), maternal race , maternal ethnicity (non-Hispanic or Hispanic), maternal tobacco use during pregnancy (yes or no), maternal drug use during pregnancy (yes or no), pre-pregnancy body mass index (BMI) categories , previous preterm birth (yes or no), previous cesarean section (yes or no), pre-pregnancy diabetes (yes or no), pre-pregnancy hypertension (yes or no), hospital of birth, trimester of first time prenatal visit , primary provider of prenatal care , primary payer of prenatal care , and mean temperature over the same gestational month. To determine what functional form of temperature should be included in the models, separate models were fit with temperature modeled either as a continuous variable (1 df) or using a natural spline with 2–4 degrees of freedom. A natural spline with 2 degrees of freedom had the lowest Akaike’s Information Criterion value and was thus included in the model. From this model, we estimated the difference in term birth weight  associated with each interquartile range (IQR) increase in mean PM2.5 concentration in the 1st gestational month. We then reran this model for PM2.5 for each other gestational month  as well as the last month of pregnancy , and other pollutants .Using generalized linear models, we regressed each subject’s term birth weight (g) against their mean PMNext, we explored whether the association between air pollution and term birth weight varied by maternal ethnicity (non-Hispanic or Hispanic), by adding interaction terms between the mean pollutant concentration and Hispanic to our model. Similarly, we examined effect modification of the pollutant/term birth weight association by maternal employment during pregnancy (employed or not employed) as well as the presence of pregnancy complications  and/or adverse birth conditions .3 concentration from the same gestational month to each model with PM2.5, BC, UFP, AMP, or SO2 to estimate the difference in term birth weight associated with each IQR increase in pollutant concentration, independent of ozone. Second, using logistic regression with LBW as the outcome and the same set of covariates as in the main analyses, we estimated the odds of LBW associated with each IQR increase in each mean pollutant concentration during each gestational month. Data management and descriptive analyses were conducted using SAS v.9.4 , and all the GLM and logistic analyses were conducted using R (version 2.15.0).Next, we separately added the mean ODuring the study period, there were 88,401 singleton live births in Monroe County compatible with the inclusion criteria. After excluding births with missing data for covariates included in our analytic models, we based our analyses of term birth weight on 76,500 subjects . Among the study subjects, the mean term birth weight was 3431.6 (±471.6) g and the overall percentage of term LBW infants was 2.15%. As shown in Table 2 concentrations were highly correlated (0.781 > r < 0.902), while BC (0.251 > r < 0.737), UFP (0.469 > r < 0.758), and AMP (0.256 > r < 0.591) were moderately correlated. PM2.5 was only weakly correlated (0.035 > r < 0.503), while O3 was more variable, likely due to across-season patterns (−0.784 > r < 0.785). Within each gestational month, mean concentrations of PM2.5, BC, AMP, UFP, and SO2 were moderately correlated , while O3 was only minimally correlated with any other pollutant .The mean and interquartile range of pollutant concentrations and weather variables were similar across each gestational month . Consistent with our a priori hypothesis, reduced term birth weight was associated with IQR increases in UFP concentrations in the 6th gestational month  and 7th gestational month , and increased O3 concentrations in the 1st gestational month . However, increased term birth weight was associated with IQR increases in mean O3 in the 7th gestational month .Inconsistent with our a priori hypothesis, increases in gestational month pollutant concentrations were generally not associated with decreased term birth weight among term births Table . However2.5 concentration in the 3rd gestational month was associated with a 5.6 g decrease in term birth weight , while among females it was associated with a 3.1 g increase   greater increase in term birth weight  than in those pregnancies without complications   were significantly (p = 0.025) larger in magnitude than among employed mothers    during any gestational month, after adjustment for numerous maternal, infant and birth characteristics, and temporal factors . Results were similar after additional adjustment for ambient O3 concentrations, as well as when estimating pollutant effects on the odds of LBW. There were no differences in term birth weight changes associated with air pollutants by maternal employment during pregnancy, pregnancy complications, adverse birth conditions, or infant gender. However, infants born to unemployed mothers had slightly larger reductions in term birth weight associated with increased pollutant concentrations than employed mothers. Further, across all gestational months and multiple pollutants, we observed large decreases in term birth weight associated with increased gestational month pollutant concentrations among Hispanic mothers, but not among non-Hispanic mothers.Using a large dataset combining birth certificates and maternal and infant hospital discharge data in the Finger Lakes region of New York State and 12 years of air pollution monitoring data, we did not find consistent associations between term birth weight and concentrations of any pollutant  in birth weight among term births  [th month were associated with 17 g to 34 g reductions in term birth weight among term births. In the same study, pregnancies with their 8th gestational months during the 2008 Beijing Olympics (and its large declines in air pollutant concentrations during the Games) were 23 g larger  than pregnancies with their 8th months of pregnancy during the same calendar dates in 2007 or 2009 [Our finding of no association between air pollution levels during pregnancy and term birth weight among term birth is inconsistent with most previous studies. A pooled analysis of 14 European birth cohort studies reported a −7 g reduction in term birth weight  associated with each 5 µg/m³ increase in PMl weeks) . In Beij2.5 during pregnancy and term LBW. Previously, in Rochester NY, Pereira et al. reported that elevated ambient PM2.5 levels during pregnancy were associated with an increased odds of preterm birth, but not pre-labor rupture of membranes [2.5 or NO2 concentrations and gestational hypertension [With regards to other studies of air pollution and birth outcomes in residents of New York State, our findings are consistent with those of Brown et al. , who fouembranes . In anotrtension . Thus, t3 increase in PM2.5 concentration during gestation was associated with a 189 g deficit in male newborns, but only a 17 g deficit in female newborns.[Our findings of no effect modification by infant gender is consistent with some studies , 18, butnewborns. In a sysnewborns. reported2.5 concentrations from the monitoring location may be better estimates of Hispanic mothers’ exposures to ambient PM2.5 during pregnancy than non-Hispanic mothers , resulting in less underestimation of effect estimates for Hispanic mothers than non-Hispanic mothers. Thus, this may, in part, explain our findings.Our finding of decreased term birth weight associated with increased concentrations of multiple pollutants among Hispanic mothers, but not non-Hispanic mothers, may be due to several factors. Some have reported that mothers with lower socio-economic status are more vulnerable to air pollution exposure during pregnancy due in part to having residences in areas of high air pollution, and/or longer times spent commuting and thus higher traffic pollution exposures , 21. Furth percentile = 1.80 miles, 95th percentile = 15.67 miles). Thus, this likely resulted in non-differential exposure misclassification and underestimates of the true effects. Our previous work has suggested spatial heterogeneity in the PM2.5 concentrations across Rochester [Although our study had several strengths including a large sample size with resulting increased statistical power, and the use of a detailed database of linked birth certificates and hospital admissions data, there are several limitations that should be considered when making inference. First, we used pollution data from the single central monitoring site as the proxy for each pregnant woman’s individual exposure to air pollution during pregnancy, but study subjects lived a median of 5.65 miles from the monitoring station (5ochester . Howeverochester –26. Furt3, in multiple gestational months, were associated with decreased term birth weight. This may be a result of different degrees of exposure misclassification due to residential proximity to the air pollutant monitoring site, but further work is needed to understand these differences by ethnicity.In summary, among pregnant women of Monroe County, New York from 2005 to 2016, we found no clear patterns of term birth weight change associated with increased concentrations of any pollutant across gestational months. Further, there were no patterns of effect modification by infant gender, pregnancy complications, or season. However, among Hispanic women only, increases in all pollutants, except OSupplementary Tables


In early, mid-, and late pregnancy, the subgroup mothers with a low MCS score had infants with a lower average birth weight than those with very high scores (p < 0.05). The association between higher physical HRQoL in late pregnancy and a higher chance of having small-for-gestational-age birth needs further research. The role of mother’s mental HRQoL during pregnancy and the potential consequences for the child require further study.The objective of this study was to assess associations between maternal health-related quality of life (HRQoL) in early, mid-, and late pregnancy and birth outcomes and to assess the differences in birth outcomes between subgroups of mothers reporting relatively “low” and relatively “high” HRQoL. HRQoL was measured by the 12-item Short Form Health Survey in early (n = 6334), mid- (n = 6204), and late pregnancy (n = 6048) in a population-based mother and child cohort; Physical and Mental Component Summary (PCS/MCS) scores were calculated. Birth outcomes included pregnancy duration, preterm birth, birth weight, low birth weight, and small for gestational age. We defined very high PCS/MCS scores as the >90th percentile and very low score as the <10th percentile. The lower PCS score in late pregnancy was significantly associated with a higher chance of having small-for-gestational-age birth (per 10 points: OR = 1.20, 95% CI: 1.08, 1.33,  Preterm birth, small-for-gestational-age birth, and low birth weight are relevant indicators for new-born mortality and morbidity ,2,3. HeaHRQoL is a measure of the personal perception of the quality and value of life in the context of impairments, functional states, and opportunities as influenced by disease, injury, treatment, and policy . The ratTo our knowledge, only two relevant studies were conducted ,13. A stGiven the limited number of relevant studies, the present study aimed to investigate the associations between maternal physical and mental HRQoL in early, mid-, and late pregnancy and birth outcomes in a large prospective population-based mother and child cohort, the Generation R study . Our hypIn the Generation R Study, the participants are relatively healthy and they are expected to have a relatively high HRQoL ,16; therThe present study was embedded in a prospective population-based mother and child cohort from fetal life until adulthood in the Netherlands. Briefly, the cohort includes 9778 mothers living in the Rotterdam area and their children born between April 2002 and January 2006. The response rate was approximately 61%. Although the cohort aimed to enroll women in early pregnancy  when it was set up, enrolment was possible until the postnatal period: 7069 mothers were enrolled in early pregnancy, 1594 were enrolled in mid-pregnancy , 216 were enrolled in late pregnancy , and 899 were enrolled in postpartum phase. This cohort study has been described previously in detail ,15. The Of the 9778 women who were enrolled in the cohort study, 8879 women enrolled during the prenatal period. We excluded women with pregnancies with the following outcomes: twin birth (n = 97), induced abortion (n = 29), fetal deaths before 20 weeks of gestation (n = 75), and loss of follow-up in the prenatal period (n = 45). Additionally, we excluded women with missing data on pregnancy duration, infant’s birth weight, and the infant being small for gestational age (n = 87). Further, we excluded women with missing data on one or more 12-item Short Form Survey (SF-12) items in early (n = 2212), mid- (n = 2342), and/or late pregnancy (n = 2498). Thus, data of 6334 women in early pregnancy (dataset 1), of 6204 women in mid-pregnancy (dataset 2), and of 6048 women in late pregnancy (dataset 3) were included in the analyses See .HRQoL was measured using the 12-item Short Form Survey (SF-12) in early, mid-, and late pregnancy. It is a reliable and well-validated instrument to measure HRQoL and is widely used in studies with large sample sizes . SF-12 cInformation on pregnancy duration (weeks) and birth weight (grams) was obtained from patient records as completed by community midwives and obstetricians. Preterm birth was defined as the birth of an infant before 37.0 weeks of gestation  and low Based on a review of the literature ,24,25,26p < 0.05).Descriptive analyses were applied to characterize women enrolled in early pregnancy (n = 6334). We applied multivariate linear regression analysis (for continuous outcome variables) and logistic regression model  to assess the associations between physical/mental component summary score in early, mid-, and late pregnancy and birth outcomes. In these models, we recoded the original physical/mental component summary score, i.e., we divided by 10, so, in the regression models, 1 point reflects 10 points of the original physical and mental component summary score following the approach proposed by Mapes et al . The regDifferences in birth weight and pregnancy duration were assessed between subgroups of women reporting very low (<10th percentile) and very high (>90th percentile) physical and mental component summary scores using two independent sample t-tests. Cohen’s effect sizes (d) were calculated by dividing the difference in mean scores among subgroups by largest SD and interpreted as 0.2 ≤ d < 0.5 small difference, 0.5 ≤ d < 0.8 moderate difference, and d ≥0.8 large difference . Differep value was calculated by dividing the original p value (p = 0.05) by the number of analyses with the dependent variable, i.e., p corrected = 0.05/6 = 0.008. In our study, p < 0.008 indicated statistical significance.Because we have conducted multiple analyses with the dependent variable, a Bonferroni correction was conducted. The Bonferroni-corrected We conducted all analyses with the Statistical Package for Social Sciences (SPSS) version 21.0 for Windows .p value = 0.0006). No other significant associations between physical/mental component summary score in pregnancy and birth outcomes were found.p value, the average pregnancy duration, the average birth weight, the incidence of preterm birth, and low birth weight did not significantly differ between subgroups of women reporting a low physical component summary score and the subgroup reporting a high score in early, mid-, and late pregnancy . Having a small-for-gestational-age birth was less frequent in the subgroup mothers who reported a low physical component summary score compared to the subgroup mothers who reported a high score in late pregnancy . The average pregnancy duration, the occurrence of preterm birth, and low birth weight did not differ between subgroups of women reporting a low mental component summary score compared to women reporting a high score in early, mid-, and late pregnancy . The average birth weight of infants whose mothers reported a low mental component summary score was significantly lower than that of infants whose mothers reported a high score . The occurrence of having a small-for-gestational-age birth was significantly higher in the subgroup mothers reporting a low mental component summary score compared with the subgroup mothers reporting a high score in late pregnancy .According to the Bonferroni-corrected Our study explored the associations between women’s physical and mental HRQoL in each gestational period and birth outcomes. We found a significant association between better physical HRQoL in late pregnancy and higher chances of having a small-for-gestational-age birth. In addition, we found statistically significant differences in several birth outcomes between the subgroups of women reporting relatively high and relatively low HRQoL in pregnancy, but Cohen’s effect sizes were small.Our study did not confirm the hypothesis that worse physical HRQoL in early, mid-, and late pregnancy is associated with preterm birth, gestational duration, and (lower) birth weight. This may be because relatively healthy women were enrolled in the Generation R Study; participants were relatively often highly educated and healthy and had a relatively highly HRQoL compared to clinical study samples and compared to the general population ,26,30. Tp < 0.001). In our study, fetal growth was measured by weight; however, weight is the result of multiple phenomena including lean mass growth, length growth, and increase of head circumference. Therefore, we additionally repeated the analyses in In contrast with the findings by Mautner et al.  and by WIn the whole Generation R study sample, our findings did not confirm the hypotheses that worse mental HRQoL in early, mid-, and late pregnancy is associated with more preterm birth, shorter gestational duration, lower birth weight, and more often small-for-gestational-age birth. This is in contrast with the results of the study by Wang et al. that showed that women reporting better mental health in pregnancy (25−29 weeks) had a lower risk of having low-birth-weight infants; we did not replicate that finding in the analyses in the total sample .However, the subgroup of women reporting relatively low mental HRQoL during pregnancy in the Generation R study had infants with a lower average birth weight in comparison with the subgroup of women reporting the relatively high mental HRQoL. This confirms the abovementioned finding by Wang et al. . HoweverThis is one of the few studies regarding the association between women’s HRQoL during pregnancy and birth outcomes. The present study was embedded in large prospective population-based mother and cohort study, which enabled a large sample size for the analyses. Data on more than 6000 women in early, mid-, and late pregnancy was available. To prevent collinearity that was observed in an earlier study , we analThere are some limitations that we need to acknowledge. First, the exclusion of participants with missing data may limit the generalizability of results from the population for analysis to some extent. As shown by the nonresponse analysis, women included in the present study were more often relatively highly educated, more often Dutch, and less often had adverse birth outcomes compared to women excluded from analyses. Therefore, the results should be interpreted with caution; also, because of this, there may be an underestimation of the strength of the associations between maternal HRQoL during pregnancy and birth outcomes. Second, restricted growth or risk factors thereof may appear already at the beginning of the pregnancy. Therefore, we propose to measure women’s HRQoL before pregnancy in future cohort studies of parents who anticipate having children, such as the Generation R Next . Third, In the total study population, our findings did not confirm the hypotheses that low maternal physical and mental HRQoL in early, mid-, and late pregnancy is associated with more preterm birth, shorter pregnancy duration, and lower birth weight. In contrast, in late pregnancy, we saw that a relatively better physical HRQoL was associated with a higher chance of having a small-for-gestational-age birth. This requires further study. Our study showed small effects regarding a relatively low average birth weight and more frequent small-for-gestational-age birth in the subgroup with a relatively low mental HRQoL compared with the subgroup with a relatively high mental HRQoL. The role of mother’s mental HRQoL during pregnancy and the potential consequences for the child require further study.


Radiofrequency ablation (RFA) of a hepatic tumour is an established treatment option with an acceptable complication rate. Formation of a pseudoaneurysm after RFA of liver metastasis is an uncommon complication. We report the case of a 69-year-old female patient developing a hepatic pseudoaneurysm after RFA of liver metastasis. On a follow-up CT scan 6 weeks later, there was spontaneous resolution of the pseudoaneurysm. Hepatic pseudoaneurysms are usually treated owing to the risk of rupture. Invasive procedures or conservative management of an asymptomatic hepatic pseudoaneurysm is still the subject of debate. The spontaneous resolution of a hepatic pseudoaneurysm in our patient suggests that an asymptomatic pseudoaneurysm maybe observed for resolution instead of being treated at presentation. There have been prior reports of symptomatic cases being treated at presentation.3Radiofrequency ablation (RFA) of a hepatic tumour is a safe procedure with an acceptable morbidity and a low mortality rate. Multicentre surveys show that mortality rates ranged from 0.1% to 0.5%. The major and minor complication rates ranged from 2.2% to 3.1% and 5% to 8.9%, respectively.A 69-year-old female patient was diagnosed with advanced cervical carcinoma Stage IIIb. She had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy, as well as completed 36 cycles of radiochemotherapy. A restaging CT scan showed a new solitary segment VIII liver metastasis measuring 3.1 (width) × 3.1 (AP) cm .In view of the solitary liver metastasis, an RFA was performed. Using the right intercostal approach, an internally cooled 15-cm single electrode with a 3 cm active tip  was inserted into the tumour’s epicentre under ultrasound guidance. No repositioning of the radiofrequency needle was carried out. Ablation was performed for approximately 12 min. No immediate complication was encountered and the patient was discharged the next day.A CT scan of the abdomen in the portal venous phase was performed 6 weeks after the ablation. There was residual tumour circumferentially. An intensely enhancing area [measuring 2.3 cm (width) × 1.4 cm (AP)] was noted within the inferolateral aspect of the ablated lesion. The degree of enhancement of the lesion was similar to portal and hepatic veins . No demoA CT scan of the abdomen 12 weeks after the ablation revealed progression of the segment VIII liver metastasis. The intensely enhancing area was no longer seen, indicating spontaneous resolution of the pseudoaneurysm. There was also progression of other intra-abdominal metastatic disease.5 Hepatic vascular damage includes portal and hepatic vein thrombosis, hepatic artery damage and pseudoaneurysm.6The clinical role of RFA is well established in the treatment of unresectable primary and metastatic hepatic tumours. RFA has been in use since the early 1990s. Complications associated with RFA are rare. The complications reported were abdominal haemorrhage (1.6%), abdominal infection (1.1%), biliary tract damage (1.0%), liver failure (0.8%), pulmonary complication (0.8%), grounding pad burn (0.6%), hepatic vascular damage (0.6%), visceral damage (0.5%), cardiac complication (0.4%), myoglobulinemia or myoglobulinuria (0.2%) and tumour seeding (0.2%).7 reported a venous pseudoaneurysm that was not apparent on a CT scan performed 4 days after the ablation but was seen on a CT scan performed 3 weeks later.A pseudoaneurysm may arise from the hepatic artery, or the hepatic or portal vein. The origin of pseudoaneurysms can be identified from multiphase contrast-enhanced CT, ultrasound Doppler or angiography studies. Most commonly, intrahepatic pseudoaneurysms arise from the hepatic artery. The enhancement of the pseudoaneurysm in the case of our patient was similar to the portal and hepatic veins, suggesting that the pseudoaneurysm arose from either the portal or the hepatic vein. Unfortunately, a multiphase contrast-enhanced CT scan was not performed to confirm the origin of the pseudoaneurysm in this patient. Hepatic venous pseudoaneurysms may have a delayed presentation. Park et al8 The hepatic vein is more susceptible to thermal injury compared with the hepatic artery and the portal vein. This is due to the lack of protective smooth muscle or perivascular connective tissue.9 Repeated repositioning of a single needle into the tumour could result in vascular injury. The chances of a mechanical injury occurring from insertion of a single electrode is less than that from a cluster of electrodes.10 In our case, we believe that the hepatic pseudoaneurysm was secondary to vessel injury from electrode insertion, as the neck of the aneurysm was along the presumed pathway of the electrode.Pseudoaneurysms after RFA are formed by thermal and mechanical injuries. Thermal injury seldom cause vessel necrosis owing to the cooling effect of blood flow.11 Rupture rates of hepatic artery aneurysms are as high as 44%, with mortality rates being as high as 82%.12 Symptomatic portal vein pseudoaneurysm is usually associated with fistulous communication such as arterioportal shunt,13 portobiliary fistula14 or portoenteric fistula.15 Hepatic pseudoaneurysms can be treated surgically or with minimally invasive techniques such as transcatheter embolization. Minimally invasive procedures have lower mortality and morbidity than surgical intervention.16 Embolization can be performed with materials such as coils and n-Butyl cyanoacrylate.19 A pseudoaneurysm with a wide neck has been successfully treated with a stent graft.20 Image-guided percutaneous injection of thrombin to treat partially occluded hepatic artery pseudoaneurysms has been reported.21 Balloon inflation may be used for temporary occlusion of fistulas prior to surgery.15Although a pseudoaneurysm is an uncommon complication, it should be kept in mind when reviewing the follow-up CT scans of post-ablation patients.8 Tessier et al16 reported spontaneous thrombosis of an iatrogenic hepatic artery pseudoaneurysm after 72 months in a patient who refused intervention. Spontaneous thromboses of post-traumatic hepatic artery pseudoaneurysms were noted a few weeks after the trauma in two reported cases.22 These cases were followed up with serial ultrasound. Pseudoaneurysms are usually treated owing to a high rate of rupture and mortality. The spontaneous resolution of an asymptomatic pseudoaneurysm in our patient and the previously reported cases suggests that not all asymptomatic hepatic pseudoaneurysms need to be treated. Soudack et al12 recommend serial ultrasound follow-up of such cases.Thrombosis and resolution of the pseudoaneurysm in our case could be owing to the low pressure of the venous system. Furthermore, the progression of the liver metastasis involving the neck of the aneurysm may have contributed to its resolution. Recurrence of tumour along the margins, as in the case of our patient, can be reduced if two cycles of ablation are performed instead of one or a larger active tip is used. Intrahepatic pseudoaneurysms that resolved 15 days after the RFA were likely due to thrombosis, as reported by Tamai et al.Hepatic pseudoaneurysm should be kept in mind when reviewing the follow-up CT scans of post-ablation patients owing to a high risk of rupture and mortality.Doppler ultrasound, multiphase contrast-enhanced CT or angiography would be needed to identify the origin of the pseudoaneurysm .A hepatic pseudoaneurysm arising from a vein after RFA is an uncommon complication.The spontaneous resolution of reported asymptomatic pseudoaneurysms suggests that not all hepatic pseudoaneurysms need to be treated. Serial imaging would be needed until resolution of the pseudoaneurysm.Written informed consent was obtained from the patient for publication of this case report, including the accompanying images. This case report has been approved for publication by the local Institutional Review Board.


Brachial plexus birth injury is one of the challenges associated with maternal delivery, with varying prevalence between countries. Brachial plexus birth injury poses negative health implications to children and also has socio-economic implications on families and the community as a whole. To treat brachial plexus birth injury, a multi-disciplinary treatment approach is recommended. Brachial plexus birth palsy (BPBP) is categorised into two-upper plexus injury  and lower plexus injury . These categories present with various degrees of injuries, with less severe injuries responding well to treatment and in most instances may resolve on their own, but serious and complicated injuries will require a multi-disciplinary treatment approach to treat and/or manage. Effective treatment and management depends on adequate knowledge of the disease condition. These include the risk factors and prevalence of brachial plexus birth palsy within a particular population at a specific period in time. The aim of this study was to determine the risk factors and the prevalence of a hospital based brachial plexus birth palsy within a five-year period (2013-2017).A five-year retrospective study design was used. The study involved selection of all clients' diagnosed with brachial plexus birth palsy, where their gender, birth weight, complications at birth, type of brachial plexus suffered, mothers' diabetes status, mother's age, birth attendant, side of affectation, presentation at birth and mode of delivery were recorded.The prevalence rate of brachial plexus birth palsy was 14.7% out of a total of three hundred and twenty (320) cases reviewed over the study period in the Volta Regional Hospital. Erb's palsy was found to be the modal type of BPBP in this population (93.6%).There is the need to provide a nationwide education on the risk factors that predispose babies to brachial plexus birth palsy. There is also the need for frequent antenatal visit by pregnant women; this will help in the provision of best antenatal history, diagnostic investigation in determining the birth weight and safe mode of delivery. Al-Qattet al.  classifiet al. . Group tet al. , 7. The et al. . The pre [et al. , the pre [et al. , reporteet al. [et al. [et al. [The prevalence of children with BPBP in Nigeria over a ten year study period showed a persistent high prevalence, averaging 15.3% per year with associated problems such as birth asphyxia, humeral fracture, clavicular fracture and shoulder dislocation . A studyet al.  it was ret al. . This woet al. . Some chet al. . This pr [et al.  that was [et al.  did not Study site: the study was conducted at the physiotherapy department of the Volta Regional Hospital (VRH), the main referral centre for the Volta region of Ghana. The hospital attends to over 177,281 inhabitants in the Ho municipality and its environs [environs .Study design: the study design employed was a retrospective quantitative study over a five-year period (January 2013 to December 2017).Ethical approval: the study was approved by the Research Ethics Committees of the University of Health and Allied Sciences and the VRH with protocol identification number UHAS-REC/A.5 (62) 17-18.Inclusion and exclusion criterion: all paediatric cases under 15 years who attended the physiotherapy clinic of the VRH over the study period were recruited. This age category is chosen because children within this age group are treated in the paediatric unit of the department. Paediatric cases above 15 years of age who reported for treatment over the study period were excluded. Also acute brachial plexus injuries not associated with delivery were also excluded.Procedure for data collection: records of all newly diagnosed clients' were retrieved to identify all paediatric conditions. Sampling of all children diagnosed with birth brachial injuries were done, and this provided a means of recording their folder numbers for further investigation. The folder numbers obtained aided in the retrieval of individual folders. The study involved all children 15 years and below who attended the physiotherapy clinic of the VRH within the study period. The second stage of data collection included children that have been diagnosed with brachial plexus birth palsy within the study year period. Demographic data and clinical profile of children and their mothers were recorded. Information such as mother's history of birth, age at delivery, maternal diabetic status, parity status as well as the mothers' occupation was recorded. Other information retrieved included the diagnosis, side of affectation, birth weight, place of delivery, complication at birth, mothers' occupation, antenatal care history, type of BPBP, presentation at birth and others were retrieved from the client folders. The clients were grouped in two categories of Erb's and Klumpke's palsy. Those who had good wrist control were in Erb's classification while those with minimal to less wrist control but good shoulder control were classified as Klumpke's palsy. Those with no control of shoulders and wrist were classified as having total BPBP. Each participant was assigned a code to ensure anonymity. The data was kept under lock and key, accessible only by the researchers.Data analysis: the data collected was entered into IBM SPSS version 20.0 analysed using descriptive statistics.th) leading cause for paediatric consultation and treatment at the physiotherapy department of the hospital.In all, the records of 47 participants who presented for BPBP were analysed. There were 28 (59.6%) female children with brachial plexus injuries, 17 (36.2%) were male children, and the gender for two (4.2%) of the cases were not documented. The average birth weight was 3.9 ± 0.5 kg. The clinical profile of the babies diagnosed with BPBP indicated that, the vast majority 44 (93%) had cephalic presentation at birth, 1 (2.1%) had breech presentation and 2 (4.2%) of the cases were not documented. Majority of the children 44 (93.6%) were delivered through spontaneous/normal vaginal delivery, 2 (4.3%) through caesarean section. However, the mode of delivery of one baby was not documented. 44 (93.6%) of the cases were diagnosed with Erb's palsy whereas 3 (6.4%) had Klumpke's palsy. Shoulder dystocia and prolonged labour were the most common complications documented; 13 (27.7%) and 20 (42.5%) respectively. 2 (4.3%) of the children had fractures of the clavicle and humerus. Unfortunately, there were no records on 12 (5.5%) of the children. In et al. [The aim of this study was to determine the prevalence of brachial plexus birth palsy (BPBP) over a five year period (January 2013-December 2017) and the predisposing factors of BPBP at a regional hospital in Ghana. The clinical profiles of 320 paediatric cases, within the study period were reviewed. The prevalence of BPBP was 14.7%, which is much lower than the prevalence (27.2%) recorded in a tertiary hospital in urban Ghana . The difet al.  also fouet al. . The impet al. [et al. [Most (93.6%) of the study participants were cephalic spontaneous vaginal delivery with only two caesarean section (4.2%) and one having no documentation on the mode of delivery. About 95% of cephalic presentations were diagnosed with Erb's palsy, with 5% diagnosed with Klumpke's palsy; a breech presentation also resulted in Erb's palsy. These results confirm with a study conducted by Hale et al. , where tet al. . The mecet al. . This poet al. , cephaliet al. . Similar [et al.  reported [et al. .The complications resulting in brachial plexus injury in this population is due to mothers not attending antenatal clinics, refusal to undergo caesarean section, delay in reporting to the hospital when labour sets in and lack of early referrals. Among the sampled population, majority of them suffered Erb's palsy (93.6%) with only 6.4% recording Klumpke's palsy. This shows that the number of children who suffered upper brachial injury was more than the lower plexus injuries. The clinical implication of this is that, clinicians and healthcare providers must be educated on the risk factors for brachial plexus injuries. Among the study population, only 19 mothers had their demographic details recorded. The average age and average birth weight of nulliparous mothers was 21 years and 3.8 kg respectively; whereas that for multiparous mothers was 34 years and 3.9 kg respectively. This shows that both nulliparous and multiparous mothers are at risk for delivering babies who may suffer birth injuries because the average birth weight is the same for both groups of women and therefore caregivers must provide the same level of care to prevent birth injuries. This study found out that age and parity status are risk free for brachial plexus injuries, since they are all at risk for the condition. This study contravenes other studies where mothers above 35 years and those below 16 years are considered as risk factors for brachial plexus injuries , 21.Limitations: this study was limited by the lack of complete and adequate maternal data. There was lack of documentation on birth weight for ten of the children and therefore conclusions about the study population cannot be representative.Recommendations: the researchers recommend the need for appropriate documentation in the hospital, and the need for healthcare professionals to be mindful of the complications and the risk factors of BPBP so as to provide immediate and appropriate care.In conclusion, the results of this study showed a BPBP prevalence of 15% and most of the Erb's palsy cases had right arm affectation. The study also showed that majority of the babies had a birth weight >4.0 kg and this may accounts for the high number of shoulder dystocia cases. The presentations at birth were predominantly cephalic and this may pose an increased risk of upper plexus injuries among the macrosomic children. Majority of babies diagnosed with Erb's palsy were macrosomic with shoulder dystocia. Increase birth weight is a risk factor for BPBP;Birth weight above 4 kg is associated with an increased risk of shoulder dystocia and prolonged labour.Increasing mothers' age was found to be directly related to the complications arising of the birth process such as prolonged labour and shoulder dystocia;Both nulliparous and multiparous mothers' are at risk for delivering babies who may suffer birth injuries because the average birth weight of children is the same for both groups of women;There is an associated increased risk of shoulder dystocia, high birth weight (macrosomia) and prolonged labour in mothers above 34 years.The authors declare no competing interests.


Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases. Metabolomics has been defined as the quantitative measurement over time of the metabolic response of a living system to pathophysiological stimuli and/or genetic modifications . This diCardiovascular diseases are the most important causes of death in all the World; every year 4.3 million people die of them in Europe and they account for 48% of all deaths (54% women and 43% men). Obesity and diabetes are also among the most important risk factors for ischemic cardiopathy and it is estimated that approximately 48 million adults in the European Union suffer from diabetes. Also to be considered is the fact that both the pathologies are on the increase ,7,8. Howet al. performed a meta-analysis [The first scholar who hypothesized the foetal origin of certain chronic diseases of the adult was Barker ,11. Thisanalysis  on the rTraditionally the definition of SGA is an infant that has a birth weight below the 10th centile for gestational age. It is known as the low birth weight is in itself closely related to infant morbidity and mortality. In addition to prematurity, intrauterine growth retardation (IUGR), is considered one of the most important causes of low birth weight . Accordimalprogramming” of the neuroendocrine circuits of the mediobasal hypothalamus that control appetite, body weight and the metabolism. It is also true that at present the nutritional practice in nurseries and neonatal intensive care units is to quickly recover the birth weight of infants, with the result that both SGAs and LGAs are fed to this end. The same can be said in the case of those with hypoglycaemia at birth: they receive the same therapy based on glycaemia values.Another important element in the pathogenesis of a metabolic syndrome appears also to be neonatal overfeeding: the results of some authors  indicateet al. [Also as concerns the single metabolites, there appear to be important analogies between SGAs and LGAs, first and foremost those of leptin. Leptin, a hormone produced by adipose tissue, acts at the level of the hypothalamus to limit appetite and lipogenesis. It is capable of activating the mammalian target of rapamycin (mTOR) kinase which by regulating cell growth is essential in mediating leptin action in the hypothalamic circuits involved in regulating the body energy balance. In the blood of obese individuals we find high levels of leptin not associated with a reduced food intake: in such cases we speak of “leptin resistance” . This caet al.  have shoet al.  were asset al. . It is iet al. . Thus itMetabolomics can be considered a valid, noninvasive instrument in the study of the components produced by the metabolism even in fetal and neonatal life. The studies published to date represent a starting point of fundamental importance in assessing the metabolic correlations between SGAs and LGAs for the purpose of identifying the single metabolites that characterize them. Feeding, as well as therapy in cases of hypoglycemia, should be customized and adapted to individual needs for both SGAs and LGAs, keeping in mind their long-term consequences. Data in the most recent publications suggest that by means of metabolomics it will be possible in the immediate future to monitor such patients over time to prevent the onset of chronic diseases in adulthood.


Birth defects contribute up to 21% of the mortality in those under 5 years of age in Latin America and the Caribbean (LAC), and that burden has been compounded by the Zika virus epidemic. In 2001, the March of Dimes launched a series of biennial assemblies called the International Conference on Birth Defects and Disabilities in the Developing World (ICBD). The latest ICBD, in 2017, convened in Bogotá, Colombia, and was attended by over 300 professionals, policymakers, and donors. The conference attendees, a majority of whom were from LAC, supported a call to action in the form of a consensus statement. The consensus statement lists key actions for maximizing birth defects surveillance, prevention, and care in LAC: 1) improving surveillance; 2) reducing risks for birth defects; 3) fortifying staple foods; 4) preventing and treating infections associated with birth defects; 5) implementing newborn screening; 6) providing care and services for people with birth defects and disabilities; 7) involving governments, civil society, and international agencies; and 8) advancing research for birth defects. Implementation and scale-up of evidence-based interventions using multisectoral and multidisciplinary collaborative approaches were endorsed. LAC countries can leverage technology and social media to advance and advocate for approaches identified in the consensus statement. The consensus statement can be used as a guide by both governments and nongovernmental agencies to take immediate steps for improving the quality of life of those living with birth defects and associated disabilities in the LAC countries. Birth defects contribute up to 21% of under-5 mortality in Latin America and the Caribbean (LAC), compared to a global average of 9% . The Unird World Health Assembly, in 2010, a resolution on birth defects was passed to address widespread concerns related to lack of recognition of the global burden of birth defects and the limited resources for prevention and management of birth defects  . Given twww.marchofdimes.org)), launched a series of biennial assemblies called the International Conference on Birth Defects and Disabilities in the Developing World (ICBD). The goal of these events has been to provide a platform for the sharing of resources and knowledge to strengthen surveillance and health care delivery for prevention and care, to influence public health policy, and to mobilize funding for birth defects in countries worldwide. The latest ICBD, in 2017 in Bogotá, Colombia, was attended by over 300 professionals, policymakers, and donors from 31 countries worldwide  and birth defects–related disability and mortality in the population.Prioritizing birth defects surveillance as a part of national or regional health systems that are backed by ministries of health.Raising public health awareness about evidence-based actions individuals and families can take to reduce their risks of having a child with birth defects. Health information should be culturally relevant and be accessible to all women regardless of their geographic location, education level, and socioeconomic status.Educating women and girls, and men and boys, about their risks in a variety of settings and using different approaches. Schools, workplaces, and community centers can serve as places for delivering health education programs. For a population-based approach, use of social media, Web, and mobile technologies and platforms for popular culture are essential and innovative tools.Maximizing the health of women and adolescent girls not only during pregnancy, but also aiming at the critical preconception period, by focusing on exposures to teratogenic substances , primary prevention, screening and treatment of infections, ensuring optimal nutrition, immunization and vector control, increasing access to family planning and contraception, and reducing environmental exposures and pollution.Training health professionals in assessing and addressing risk factors for birth defects in a primary care setting.Empowering women with health knowledge so that they can seek care and services to reduce their risks.Implementing mandatory food fortification of staples with at least iron and folic acid in all countries in LAC.Ensuring quality control of fortification standards through periodic monitoring of fortified foods in countries with existing food fortification programs. In addition, effectiveness of fortification should be evaluated through population-based biomarker analysis.Investing in developing population-based infection control programs and policies  through sustainable funding and resources.Building laboratory and clinical care capacity for timely detection of infections through serological or other confirmatory tests.Improving access to infection prevention and treatment through primary health care programs and referral chains and ensuring coverage for everyone, regardless of their ability to pay.Mandating newborn screening programs, supported by resource allocation for training and capacity-building, and monitoring for quality and cost-effectiveness.Developing centralized mechanisms for screening using standardized approaches and promoting shared laboratory capacity at national and regional levels.Improving the coverage of newborn screening to reach everyone, and ensuring inclusion of essential conditions in the screening panel, while also making sure that timely follow-up and treatment are available based on the diagnosis.Establishing a holistic approach that is multidisciplinary and multisectoral, adequately meeting health, educational, occupational, rehabilitation, and social needs of those with birth defects and disabilities throughout their life course, while increasing the number of trained professionals who can provide the aforementioned services.Ensuring timely treatment, including surgery, medications, and nutrition, and providing universal coverage to those in need. In addition, home- and community-based follow-up is essential to maximize health and well-being.Governments should support primary prevention where applicable and ensure integrated, population-based care programs. Policies, allocation of resources, and monitoring for quality and efficiency are essential parts of the governments’ role in reducing inequalities. Policies and programs should be sustained through relevant ministries within the governments, irrespective of changing political and economic environments.Civil society should actively engage in raising awareness and advocate for reducing disparity, stigma, and isolation of individuals and families affected by birth defects and disabilities. Civil society, including parents, funders, and nongovernmental organizations, should hold governments accountable to provide universal access to care and services.International agencies such as the United Nations Children’s Fund (UNICEF), WHO, and the Pan American Health Organization (PAHO) should integrate and address birth defects. This will influence the governments to accelerate efforts that will help individuals with birth defects to survive, thrive, and transform their futures.Advancing current knowledge about the causes, diagnostics, and treatment modalities through basic research.Supporting epidemiologic research to better understand the role of factors such as sociodemographic, behavioral, nutritional, environmental, and genetic ones, as well as their interactions, in influencing the risk of birth defects.Conducting implementation research on interventions for birth defects prevention and care in the population, and measuring the outcomes and impact of these interventions for a scale-up.Ensuring sustained funding, training, and mentoring of researcher, multidisciplinary, and multicountry collaborations that will support the aforementioned research activities in LAC.th ICBD. The Dar es Salaam statement recognized that children with birth defects remain left behind in policies, programs, research, and funding, and that there is little to no action in a positive direction to address these gaps with birth defects  (–2030 (6) defects . The 201 defects -15. The  defects , while r defects  and PAHO defects -23.Recently developed concepts in triple surveillance for integrated strategies to support and accelerate birth defect prevention  can be iThrough this consensus statement, the authors and the endorsing attendees of the 2017 ICBD call upon governments, nongovernmental and civil society organizations, health care service organizations, institutions of higher education, donor agencies, researchers, and other stakeholders to take actions to improve birth defects prevention and care, as well as the quality of life of those living with birth defects and associated disabilities in Latin America and the Caribbean. We also call on civil society in the LAC countries to demand accountability from their governments and other relevant stakeholders.SRW and CPH conceived the original idea. IZ, PHV, SRW, and VK collected data, interpreted the results, and wrote the first draft. JLC, RG, BG, CPH, and PD contributed to the development of the paper. All the authors reviewed and approved the final version.


The aim of this study was to focus attention on episiotomy practice in Romanian maternity units in order to identify factors associated with the very high rate of the procedure in Romania and to consider strategies to reduce it.In this clustered cross‐sectional study, a total of 11 863 patients were recorded in eight Romanian maternity units to assess the prevalence of episiotomy. A random effects Poisson model was used to estimate the prevalence rate in univariate and multivariate models.Among the 11 863 patients included for analysis, 8475 (71.4%) had an episiotomy. The prevalence of episiotomy was 92.7% for the first vaginal birth, 73.2% for the second vaginal birth, and 35% for the third vaginal birth. The overall rate of suturing was higher than the episiotomy rate for all patients . The likelihood of exiting the maternity ward with an intact perineum after the first vaginal birth was less than 5% at the first vaginal birth.In conclusion, routine episiotomy is the norm in Romanian maternity units, with episiotomy rates among the highest in Europe. Episiotomy use is mainly driven by local professional norms, experiences, previous training, and practitioners' decisions rather than evidence, guidelines, or variations in patient needs at the time of vaginal birth. ICCintra‐class correlation coefficientPRprevalence ratio1Episiotomy is a surgical cut of the perineum performed in the second stage of labor in order to facilitate the birth of an infant by enlarging the vaginal opening.The rates of episiotomy in Europe are wide ranging, spanning 3.7% in Denmark to 75.0% in Cyprus.In many countries, including Romania, a number of obstetric health care practitioners consider that episiotomy should be used to prevent perineal trauma, pelvic floor relaxation, and its consequences, such as bladder prolapse and urinary incontinence. Furthermore, some practitioners prefer episiotomy because it is easier to repair than the laceration that results when episiotomy is not used.The present study aimed to assess the prevalence of episiotomy in Romania, to identify factors associated with the practice of episiotomy, and to suggest strategies to reduce this practice in maternity units.22.1Data were collected from the maternity wards of eight Romanian hospitals from September through December 2013. All singleton vaginal births (live births and stillbirths) that occurred during this period were included. Information was extracted from obstetric and neonatal records.2.2P < 0.001). However, with the small number of clusters (maternity units), the estimation methods to correct for clustering may not perform well, illustrating that the random effects Poisson model for estimating the prevalence rate declined when there was a high ICC and with an increasing number of clusters. We used the random‐effects Poisson model to estimate the prevalence rate in univariate and multivariate models. For all fitted models, we used the adaptive Gaussian quadrature with eight integration points to approximate the log likelihood. STATA software version 13.1 was used for statistical analysis.A total of 11 863 patients were recorded in eight Romanian maternity units in this clustered cross‐sectional study, aiming to assess the prevalence of episiotomy . There was strong evidence of clustering within maternity units  had episiotomy , Apgar score at 1 minute (P = .002), and use of oxytocin during labor (P = .003). There were non‐significant trends between episiotomy practice and maternity level  and also no evidence of association between episiotomy practice and time of birth.In the study group, 5.470 (46.1%) patients gave birth for the first time, 10.645 (89.7%) were over 20 years old, and 1.146 (9.7%) patients had a premature birth. Univariate analyses showed strong associations between episiotomy practice and parity, gestational age, age group, prematurity, birth weight and type of care provider . The necessity for sutures was three times greater in patients with episiotomy than in those without episiotomy . Controlling for parity, Apgar score at 1 minute, and care provider, there was also a strong evidence of association between episiotomy practice and birth weight (P < .001). The prevalence of episiotomy was higher in patients whose newborn weighed 1500 to 2500 g, 2500 to 3500 g, or more than 3500 g compared with those whose newborn weighed less than 1500 g.There was a strong association between episiotomy practice and Apgar score at 1 minute, after adjustment for parity, birth weight, and care provider .The “protection” of the preterm fetus is also claimed by Romanian obstetric care providers to make the use of episiotomy very popular during preterm birth care. In our study, the episiotomy prevalence rate was lower among babies with a birthweight less than 1500 g. This finding may be associated with the low rate of complete antenatal corticotherapy in Romania among preterm neonates of the same group.Our study has some limitations. The cohort included both tertiary and community hospitals, and differences in practice across institutions were not accounted for. However, including data from a wide range of settings allowed us to investigate a more generalizable patient population. As our study was based upon maternity wards birth registries, it was also limited with respect to both the depth and accuracy of the clinical information available for analysis. Another limitation of this dataset and study design is the absence of information on morbidity and long‐term outcome in the population. Further studies, developed prospectively, can overcome these limitations.5In conclusion, routine episiotomy is the norm in Romanian maternity units with rates among the highest found in the medical literature. The likelihood of a primipara to leave a Romanian maternity unit with an intact perineum is less than 5%. Episiotomy use is primarily related to local professional practice, training during residency programs, and care provider preference, rather than to the real needs of individual women at the time of vaginal birth. Without knowing the “ideal” rate of episiotomy, efforts should be made to follow the best currently available evidence in order to reduce the over‐medicalization of normal vaginal birth, without putting our patients at risk for severe perineal laceration.None declared.A.P. and D.N. contributed equally to this article and should both be considered joint first authors. A.P. and D.N. wrote the draft manuscript. C.A.I., L.P., F.S., A.C., M.D., D.C., R.B., L.P., and D.N. contributing to further drafts and comments. All authors revised the draft and approved the final submitted article.


In Africa, where low birthweight (LBW), malnutrition and high blood pressure (BP) are prevalent, the relationships between birthweight (BW), weight gain and BP later in life remain uncertain. We examined the effects of early life growth on BP among Ugandan adolescents.Data were collected prenatally from women and their offspring were followed from birth, with BP measured following standard protocols in early adolescence. Weight-for-age Z-scores (WAZ) were computed using World Health Organization references. Linear regression was used to relate BW, and changes in WAZ between birth and 5 years, to adolescents’ BP, adjusting for confounders.P-value =  0.024].Among 2345 live offspring, BP was measured in 1119 (47.7%) adolescents, with mean systolic BP 105.9 mmHg and mean diastolic BP 65.2 mmHg. There was little evidence of association between BW and systolic  or diastolic  BP. Accelerated weight gain between birth and 5 years was associated with increased BP: systolic β = 1.17, 95% CI  and diastolic β = 1.03, 95% CI . Between birth and 6 months of age, effects of accelerated weight gain on adolescent BP were strongest among the LBW  children [BW < 2.5 kg: β = 2.64, 95% CI , BW≥2.5 kg: β = 0.58, 95% CI , interaction Findings from this large tropical birth cohort in Uganda suggest that postnatal weight gain rather than BW is important in the developmental programming of BP, with fast-growing LBW children at particular risk. Efforts to control BP should adopt a life course approach. Several studies from high-income settings have linked growth in early life  with blood pressure (BP) later in life; data suggest an inverse relationship with birthweight (BW) In Africa, where low BW (LBW),,In high-income settings, LBW is mainly due to prematurity, which can be due to any of a number of factors (and their combination), including obstetric conditions, maternal body mass index (BMI), maternal smoking and alcohol intake,The relationships between BW, postnatal weight gain and BP in low-income settings may differ from those seen in high-income countries. Interventions in pregnancy such as prophylactic antimalarial drugs and anthelminthic treatment, common in these settings, have been shown to be associated with birthweight. For example, maternal treatment with mebendazole in pregnancy was associated with increased birthweight in Nepal.Understanding early life determinants of later BP could be vital in the development of interventions that prevent or control high BP before clinical manifestation of subsequent disease(s). We used data from the Entebbe Mother and Baby Study (EMaBS) birth cohort in Uganda, to investigate the relationship between (i) BW and BP in early adolescence, and (ii) accelerated weight gain in childhood and BP in early adolescence.Adolescents from the EMaBS, a randomized, double-blind, placebo-controlled trial designed to investigate the effects of worms and their treatment in pregnancy and childhood on vaccine responses and infections in the children,As previously described,At 15 months, the resulting offspring were randomized to receive quarterly albendazole or matching placebo up to age 5 years.Birthweight was measured immediately after birth using scales  for those delivered in Entebbe hospital. For offspring delivered elsewhere, BW was recorded as written on the child health card. Weight was measured at 6 weeks and 6 months of age, using CMS weighing equipment  and then annually (close to the child’s birthday) using weighing scales . Height was measured as recumbent length at age 6 weeks using an adjustable child-length measuring board , then annually (from age 1 year) using stadiometers . BMI was weight in kilograms (kg) divided by height in metres (m) squared.Children continued under follow-up after the trial intervention ended in 2011. Between 2 May 2014 and 1 June 2016, those attending their visit at ages 10 or 11 years and not presenting with an illness were enrolled in the BP study; 11-year-olds were excluded if they were previously enrolled as 10-year-olds.,Trained nurses measured BP thrice 5 minutes apart, using an appropriate-sized cuffThe study was approved by ethics committees of the Uganda Virus Research Institute, the London School of Hygiene and Tropical Medicine and the Uganda National Council for Science and Technology. Written informed consent and assent were obtained.IJE online).Data were double-entered in Microsoft Access and analysed using Stata 14 . Characteristics of cohort members enrolled and not enrolled in the BP study were compared using chi-square tests. The study outcomes were systolic and diastolic BP. The mean of the second and third day-1 BP measurements was used for analysis, as these were on average different from and lower than the first day-1 measurements  between birth and age 5 years, with shorter growth periods  also examined. The 2006 World Health Organization standard referencesPotential confounders were maternal characteristics including sociodemographic , BMI, pregnancy anthelminthic trial interventions, illness and infections , and child’s characteristics including sex, feeding status, BMI, age, childhood anthelminthic trial intervention, illness and infections .Pearson correlation coefficients between BMI at age 10–11 years and anthropometric variables  at birth, 6 weeks, 6 months and annually from 1 to 5 years were calculated. Linear regression (fitted separately for systolic and diastolic BP) was used to assess the association between each key exposure and adolescent BP. Adolescents’ age and sex were included a priori in all models. Regression models were adjusted for each potential confounder in turn, with those causing an important change in the effect of the exposure of interest on BP retained in the final model. Final models with and without current weight were fitted.For BW, we assessed whether a linear or non-linear  relationship provided a better fit to the data. Likelihood ratio test (LRT) was used to examine for effect modification by gender, original trial interventions and birth season. Since the timing of wet seasons in this setting is subject to variability, birth months were categorized as either dry or wet depending on whether the total monthly rainfall was below or above the median rainfall for all birth months.For weight gain, as well as for those confounders identified in the BW exposure analysis, the effect of each growth period was adjusted for earlier postnatal weight gain period(s) and feeding status at 6 weeks. Effect modification by gender or BW (<2.5 kg versus ≥2.5 kg) was assessed using LRT.Sensitivity analysis assessing the impact of missing values for the main exposures was conducted: missing BW values were replaced with the minimum (1.26 kg) and the maximum (5.50 kg) non-missing value of BW recorded, and final models re-run for both scenarios. Similarly, missing values for WAZ change were replaced with the smallest and largest change in WAZ for the given growth period.IJE online).Of the 2345 adolescents born into the cohort, 107 (4.6%) had died and 1119 (47.7%) were enrolled. Of those enrolled, 583 (52.1%) were males, 1100 (98.3%) were singletons, 65 (7.0%) had BW<2.5 kg, 824 (73.7%) were delivered and weighed in Entebbe hospital, 651 (58.2%) were delivered in the dry season and 36 (2.9%) were HIV-positive (IJE online), with the exceptions that enrolled adolescents were less likely to be HIV positive  but more likely to be singletons , and born to more educated  and married/cohabiting mothers , who were less likely to have had hookworm infections  at enrolment.Participants and non-participants in the BP study were similar for most characteristics (Participants’ median age was 10.2 years [interquartile range (IQR): 10.0 to 10.9], mean BW was 3.2 kg [standard deviation (SD) 0.5], mean systolic BP was 105.9 mmHg  and mean diastolic BP was 65.2 mmHg . On day 1, 117 (10.5%) had pre-hypertension , and 94 (8.4%) had hypertension  of whom 76 (80.9%) had stage one and 18 (19.1%) had stage two hypertension. Of those due for a day-2 BP assessment, 72 (76.6%) returned; of these 23 (31.9%) had pre-hypertension and 24 (33.0%) had hypertension. Finally, 18 (75.0%) of those due for a day-3 BP measurement returned, among whom six (33.3%) had pre-hypertension and seven (38.9%) had hypertension. Allowing for loss to follow-up between days 1 to 3, the estimated hypertension prevalence was 1.1%.Relationships between anthropometric variables in childhood and BMI at 10–11 years are shown in IJE online). However, confidence intervals were wide and treating BW as a categorical variable in the regression model did not improve the fit of the model to the data compared with a linear model . Regardless of whether or not BW was modelled as categorical or linear, there was no evidence for association between BW and BP; for example, linear model regression coefficients were β = 0.14, 95% CI  for systolic and β = 0.43, 95% CI  for diastolic BP , birth season  or maternal deworming drugs . Likewise, the effect of BW on diastolic BP did not differ by season of birth, child’s sex or maternal anthelminthic treatment(s). Additionally, adjusting for current weight, the regression coefficients for the effect of BW on systolic BP were -0.91 mmHg, 95% CI  and -0.35, 95% CI  for systolic and diastolic BP, respectively. Results from sensitivity analyses were consistent with the main findings (IJE online); for example, the effect of BW on systolic BP varied from a 0.04-mmHg reduction to a 0.07-mmHg increase in systolic BP .The effect of BW on systolic BP did not differ by sex ] but was strongly associated with WAZ at 6 months , 2 year  2 years  and 5 years . A similar trend was observed for diastolic BP.Rapid weight gain between birth and age 5 years was associated with increased BP. Respectively, systolic and diastolic BP increased by 1.17 mmHg and 1.03 mmHg per unit increase in WAZ between birth and 5 years of age . This reRapid weight gain during each growth period up to 2 years was independently associated with increased systolic BP, after adjusting for weight gain in the preceding periods. For example, systolic BP increased by 0.77 mmHg, 95% CI  per unit increase in WAZ between birth and age 6 months, by 1.07, 95% CI  between 6 months and 1 year, adjusting for change in WAZ between birth and 6 months, and by 1.21, 95% CI  between 1 and 2 years, adjusting for change in WAZ between birth and 6 months and between 6 months and 1 year . BetweenP-value 0.024; IJE online).The effect of accelerated weight gain to age 6 months on systolic BP was stronger among adolescents who were small at birth: β = 2.64, 95% CI  for BW < 2.5 kg and β = 0.58, 95% CI  for BW≥2.5 kg , thus potentially resulting in an underestimation of LBW prevalence or its impact on later BP. Data on prematurity and SGA were not collected, and therefore we were unable to determine the independent effect of each on later BP. Although 187 (16.7%) adolescents were missing BW data, results from sensitivity analyses were similar to the main analysis findings.Whereas 52% of the adolescents born into this cohort were not enrolled in the BP study, cohort loss to follow-up was below 60%, a level considered to introduce bias if data were missing completely at random or missing at random.Strategies in childhood that prevent excessive weight gain, especially among infants born small, could be important in preventing later high BP. Disease prevention strategies should enhance optimal growth through good maternal and infant nutrition to reduce both LBW and rapid weight gain in early childhood. Future research should seek to evaluate the impact of catch-up nutritional programmes in malnourished infants or infants born small on BP later in life.In summary, ‘nutritional mismatch’ in early life is critical in the developmental programming of BP among adolescents in developing countries. Strategies that prevent LBW and excessive weight gain in early childhood or reverse their effects on BP could prevent high BP and diseases attributable to high BP.This work was supported by the Wellcome Trust, UK, senior fellowships for A.M.E.  with additional support from the UK Medical Research Council and UK Department for International Development (DfID) under the MRC/DfID concordat. S.A.L. was supported by the Commonwealth Scholarship Commission PhD funding at the London School of Hygiene and Tropical Medicine. L.S. was supported in part by the Wellcome Trust, UK [grant number 098504/Z/12/Z]. E.L.W. was supported by the UK Medical Research Council and UK Department for International Development (DfID) under the MRC/DfID concordat [grant number MR/K012126/1].Among Ugandan adolescents, systolic and diastolic blood pressures were positively associated with accelerated weight gain in early childhood, but not with birthweight.The effects of accelerated weight gain in the first years of life on later blood pressure were similar among males and females but differed by size at birth, with the strongest effect among those who were born small.Blood pressure control strategies should adopt a life course approach rather than focusing specifically on adults or on the prenatal period.Supplementary FigureClick here for additional data file.Supplementary InformationClick here for additional data file.