Although available evidence suggests short birth intervals are associated with adverse perinatal outcomes, little is known about the extent to which birth spacing affects postnatal child growth. The present study assessed the independent association of birth interval with birth weight and subsequent postnatal growth indices.  This retrospective cohort study carried out in the rural areas of Kassena-Nankana district of Ghana compared postnatal growth across different categories of birth intervals. Birth intervals were calculated as month difference between consecutive births of a woman. The study population comprised 530 postpartum women who had delivered a live baby in the past 24 months prior to the study. z-score (WLZ), birth weight, adequacy of antenatal care (ANC) attendance, and dietary diversity of the child, the mean length-for-age z-score (LAZ) among children of short preceding birth interval (<24 months) was significantly higher than among children of long birth interval  ((0.51 versus −0.04) (95% CI: 0.24–0.87), p = 0.001). The adjusted mean birth weight of children born to mothers of longer birth interval was 74.0 g more than children born to mothers of shorter birth interval .  Using the analysis of covariance (ANCOVA) that adjusted for age of the child, gender of the child, weight-for-length  The results suggest that a short birth interval is associated positively with an increased risk of low birth weight , but birth spacing is associated negatively with the LAZ . Childhood undernutrition remains global public health concern especially in low- and middle-income countries because as many as 165 million children are estimated to be stunted and it is an underlying cause of 3.1 million child deaths annually . StuntinIn sub-Saharan Africa, it has been reported that 34% of children under 5 years are stunted .Although a multitude of risk factors have been documented, these vary from place to place and are therefore context specific. Furthermore, a full understanding of these factors and their relative effects is key to help the priority setting in designing policies and interventions to improve childhood growth.One factor that has not received full investigation in the search for solutions to child undernutrition is the relationship between birth interval and child growth. It is well documented that child nutritional status is a direct outcome of the maternal environment during gestation and that the mother's system needs a reasonable amount of time for the restoration of nutrient reserves to provide optimum nutrition during a new gestation , 8. WellStunting begins early in utero and continues for at least the first 2 years of postnatal life; the period from conception to a child's second birthday has, therefore, been identified as the most crucial window of opportunity for intervention because this is found to be one of the most critical periods for linear growth. It is time stunting that becomes prevalent and peaks in developing countries due to the high demand for nutrients along with limited quality and quantity of complementary foods . The comEvidence from past and recent studies have consistently shown that children born following shorter birth intervals have substantially higher rates of adverse pregnancy outcomes such as stillbirth, neonatal, postneonatal, and childhood mortality than those born after longer intervals , 11–14. This study investigated whether the length of birth interval preceding the index child is associated with the risk of low birth weight and postnatal child growth while controlling for potentially confounding variables in the Upper East Region of Ghana.The study was conducted in the Kassena-Nankana municipality (KNM) in the Upper East Region (UER) of Ghana. The estimated population of the KNM is 116,668 with a population density of 102 persons per square kilometre and a growth rate of 1.2%. Women in fertile age (WIFA) are estimated to be 28,008 with 4,668 expected deliveries while children aged 0–59 months constitute 21,590 [A retrospective population-based cohort of women who delivered live babies for the past 24 months were used to compare postnatal growth across different categories of birth intervals.The specific inclusion and exclusion criteria for study participants were women resident in the study area and were attending the child welfare clinic (CWC). Additionally, eligible participants should have delivered at least two children including the current index child whose birth weights were adequately recorded by the health personnel in the child health record booklet. Excluded were twin or triplets.Study participants were selected using a multistage sampling technique. All 28 health facilities rendering CWC services in the KNM constituted the sampling universe, out of which the sampling frame of health facilities rendering family planning and contraceptive services were constituted. In each facility, mother-child pairs who met the criteria for participating in the research were chosen using systematic random sampling.n represents the required minimum sample size per study group, and D represents the design effect . The sample size for this study was calculated using the following formula:P1 is the prevalence of LBW in the nonexposed group . P2 is the prevalence of LBW in the exposed group , such that the quantity (P2 − P1) is the size of the magnitude of change it is desired to be able to detect. When Zα = 1.96 and Zβ = 0.842, assuming P1 = 5.8%, the prevalence of LBW in the control group  and P2 is estimated to be 13.8%, the expected prevalence of LBW in the exposed group . Going by these assumptions, the estimated minimum sample size was 241 for each group, making a total sample size of 482, and making provision of 10% contingency, the sample size was adjusted to 530 .The population proportion was derived from a study in the Kassena-Nankana district which reported a prevalence of 13.8% in LBW . P1 is tThe data were collected from the mothers/caregivers using a structured questionnaire, which was administered through a face-to-face interview at the household level. The data included sociodemographic and economic characteristics of the participants, parity, marital status, maternal educational level, age of mother and child, occupation, antenatal care attendance, household wealth index, child illness in the past two weeks, birth spacing, and child anthropometric measures.z-score (LAZ), which is a measure of postnatal child growth.The main dependent outcomes were the birth weight  and length-for-age The main independent variable is the length of the preceding birth-to-birth interval, measured as the number of months between the date of birth of the child under study (index child) and the date of birth of the immediately preceding child to the mother. The exposed group, therefore, comprised mothers with short birth intervals and the nonexposed group were mothers with long birth intervals. A brief description of how the study variables were measured is described as follows.Birth interval was defined as the length of time between two successive live births, rather than the interconception interval. The birth interval was dichotomized as short (<24 months) versus normal (≥24 months) based on the World Health Organization (WHO) recommended birth spacing  was calculated based on the following formula: growth rate = current weight (g)–birthweight (g)/age (months).z-score (LAZ), weight-for-age z-score (WAZ), and weight-for-length z-score (WLZ) were calculated as recommended by the World Health Organization [Child growth indicators including the length-for-age nization . The LAZz-scores were below −2 SD from the median of the reference population were considered thin (wasted) or acutely malnourished. Wasting represents the failure to receive adequate nutrition in the period immediately preceding the survey. It may result from inadequate food intake or a recent episode of illness causing a loss of weight and the onset of malnutrition. WAZ is a composite index of LAZ and WLZ. Children whose WAZ were below −2 SD from the median of the reference population were classified as underweight.The WLZ index measures body mass in relation to body height or length and describes current nutritional status. Children whose z-scores. The various z-scores were transferred to the SPSS software for further analysis.Data cleaning and analysis were carried out using statistical weighted analysis in the SPSS complex samples module for windows 22.0 . This was carried out to make statistically valid population inferences and compute standard errors from the sample data obtained from cluster sampling. The nutritional indicators of the child were computed using the Anthro Plus which converted anthropometric measures into p < 0.05) with each dependent variable in the bivariate analysis were selected and adjusted for in the multivariable regression analysis. Multicollinearity among the predictor variables was checked before their inclusion in the final regression model. The level of statistical significance was set at p less than 5% with 95% confidence intervals (CI).Bivariate and multivariable regression analyses were performed to identify to assess the degree of association between explanatory and selected dependent variables. Only variables that showed a significant association , Ghana. Informed consent was also obtained after needed information and explanation. In situations where the respondent could not write or read, verbal informed consent was sought from all study participants before the commencement of any interview.In all, a total of 542 study participants were interviewed, but due to incomplete data and nonresponses, the data were trimmed to 530 valid responses constituting 97.8% response rate. The mean age of the children was 10.0 ± 6.4 months.The two groups of women that were studied were those who delivered with birth interval less than two years and those with an interval two years and above. The child's growth rate (g/month) was calculated based on the following formula: growth rate = current weight (g)–birth weight (g)/age (months). The mean child's growth rate/velocity was 0.669.0 ± 0.32 (g/month) among children aged 0–24 months.z-score (LAZ), weight-for-age z-score (WAZ), and postnatal growth rate of children were negatively associated with birth interval, but weight-for-length z-score (WLZ) was not associated. Children with shorter birth intervals (<24 months) had better postnatal growth indicators, compared with their counterparts whose birth intervals were longer . Birth weight, however, associated positively with birth interval.p < 0.001. Using the analysis of covariance (ANCOVA) that adjusted for age of the child, gender of the child, WLZ, birth weight, adequacy of ANC attendance, and dietary diversity of the child, there was still a significant difference in mean LAZ between the study groups  = 11.79, p = 0.001), although the difference reduced to 0.55 (0.51 versus −0.04) (95% CI: 0.24–0.87), p = 0.001.The unadjusted mean difference in LAZ was significantly higher among children of short preceding birth interval than among children of long birth interval (0.75 versus −0.29) (95% CI: 0.73–1.34), After controlling for age of the child, gender of the child, WLZ, and dietary diversity of the child, no significant difference in growth velocity (weight gained/month) was observed between the study groups.p < 0.03).In terms of birth weight, the long preceding birth interval was positively associated with birth weight. The adjusted mean birth weight of children born to mothers of longer birth interval was 74.0 g more than children born to mothers of shorter birth interval , dietary diversity score (DDS), adequacy of antenatal care (ANC) attendance, and birth weight.The results showed that the birth interval was a significant determinant of length-for-age p = 0.004), among children of long preceding birth interval than among children of the short birth interval. A unit increase in the age of the child leads to a reduction in LAZ by 0.33 standard units. Low birth weight born children had a lower LAZ compared to children born with birth weight of at least 2.5 kg. Mothers who had adequate antenatal care (ANC) attendance  had a higher LAZ , compared to mothers who had inadequate ANC. Female children had a higher LAZ compared to their male counterparts . A unit increase in the child dietary diversity score (DDS) was associated with an increase of 0.11 standard units in LAZ , while a unit increase in WLZ leads to a reduction in HAZ by 0.29 standard units.The adjusted mean difference in LAZ was significantly lower  and may influence postnatal growth. The findings of the current study showed that after controlling for potential confounders, a short birth interval is associated positively with an increased risk of low birth weight , but birth spacing is associated negatively with LAZ .The World Health Organization (WHO) has defined birth interval as the period from live birth to a successive pregnancy, and the recommended period is at least 24 months (2 years) . In thisz-score during the first 8 weeks of life are strongly and positively associated with attained z-scores at 12 months [The growth of children in different stages of life has been reported to be related in one way or the other. For example, it has been reported that gains in the 2 months . This maz-score (LAZ), but birth spacing was unrelated to growth velocity as measured by weight gained/month and weight-for-length z-score (WLZ).One of the main findings of this study is that a short birth interval was associated with a decreased risk of poor postnatal child growth as measured by length-for-age z-score (LAZ) values, compared with their counterparts whose birth intervals were at least 24 months?Although long birth intervals have been positively linked to postnatal child growth outcomes in previous studies, this study observed a significant negative association after controlling for key confounders. It is not clear why children with short birth intervals in our sample significantly had high mean length-for-age Some researchers do suggest that birth spacing might influence childhood undernutrition through its association with preterm birth and low birth weight (LBW). The mechanism is considered related to the “maternal depletion syndrome” which postulates that the woman may not have fully recuperated from one pregnancy before supporting the next one , 15. TheCatch-up growth represents an interaction of the child's biological growth potential with environmental factors that enhance growth, among which optimal nutrition and low morbidity are the most important. Stunted children at birth with improvements in socioeconomic conditions and diet in later childhood show catch-up in linear growth to more closely approximate their growth potential .There is currently an ongoing debate in the literature around the persistence of early childhood growth faltering and the potential for later-life catch-up growth. While some researchers argue that complete catch-up growth, even in the presence of later-life compensatory investments or behavior, is unlikely –36, othePostnatal child growth failure is controlled by a multitude of biological and environmental factors including exposure of the foetus and/or young child to nutritional deficiencies and infectious diseases. It is worthy to note that postnatal growth consists of three distinct phases: infancy, childhood, and puberty , which aApart from the foregoing explanations for what might account for the observed association between short birth spacing and postnatal child growth outcomes in this study, it could also be driven by a wide range of confounding factors that were not measured.The relationship between birth interval and postnatal growth appears inconclusive because there are inconsistent findings regarding this relationship. While past studies have reported that longer birth intervals have great potential in reducing malnutrition in children, others have been negative, and some showed no effect at all . EarlierIn one earlier systematic review that used data from 17 Demographic and Health Surveys (DHS), it was concluded that the effects of short birth intervals on nutritional status were rather moderate, and there is a weak relationship with lower attendance at prenatal care services . AnotherIn four low- and middle-income countries including Brazil, Guatemala, Philippines, and South Africa, it found increased absolute height and relative HAZ scores and lower stunting odds among children who were more widely spaced compared to children who were more narrowly spaced (<2years) . A systez-score (WHZ), dietary diversity score (DDS), antenatal care (ANC) attendance, and birth weight.Stunting prevalence  is a key indicator to evaluate a country's progress towards United Nations' Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition by 2030. Therefore, a better understanding of the factors that contribute to early linear growth faltering is necessary to accelerate progress towards reducing the prevalence of stunting. The consistent independent predictors of LAZ for children aged 0–24 months were birth interval, age of child, sex of the child, weight-for-height z-score, since LBW children had a significantly lower mean LAZ compared to children born with an appropriate birth weight of at least 2.5 kg. Put in another way, it means birth weight was positively related to postnatal linear growth during childhood. The strong and positive association of the child's birth weight with LAZ is in agreement with previous studies [Low birth weight, which is an outcome of foetal growth failure, was an independent determinant of postnatal growth as measured by height-for-age  studies , 47. Thi studies . In Guat studies . However studies . This haConsistent with other studies, more older children had lower mean LAZ  than younger ones in our study sample , 50, 51.Adequate prenatal care utilization was positively associated with length-for-age in this study sample. Mothers who had adequate antenatal care (ANC) attendance had a higher LAZ, compared to mothers who had inadequate ANC. This finding is in consonance with studies conducted in El Salvador, four low- and middle-income countries  , 45.z-score (WLZ). The causal relationship between low birth spacing is likely to be context specific and therefore requires further research.The results suggest that a short birth interval is associated positively with an increased risk of low birth weight , but birth spacing is associated negatively with LAZ . Birth spacing was unrelated to growth velocity as measured by weight gained/month and weight-for-length


The objective of this study was to analyse representative dietary patterns during pregnancy in Shanghai and explore the effects of dietary patterns during pregnancy on preterm birth. Data were derived from the ‘Iodine Status in Pregnancy and Offspring Health Cohort’ (ISPOHC) study. Multistage, stratified random sampling was used to select survey participants from 16 districts in Shanghai, which were divided into five sampling areas; 40–70 pregnant women were selected from each area. A total of 4361 pregnant women and their offspring were involved in the study. The male-to-female ratio of the babies was 1.04:1, and the incidence of single preterm birth was 4.2%. Three dietary patterns were extracted by factor analysis: a ‘Vegetarian Pattern’, an ‘Animal Food Pattern’ (AFP), and a ‘Dairy and Egg Pattern’. These patterns explained 40.513% of the variance in dietary intake. Binary logistic regression, which was used to analyse the association between birth outcomes and scores measuring maternal dietary patterns, found only the AFP was a significant risk factor for preterm birth. Higher AFP scores were positively associated with preterm birth . After adjusting for other potential contributors, a higher AFP score was still a significant risk factor for preterm birth . The incidence of preterm birth was 4.2%. A higher score of AFP was significantly associated with a higher risk of preterm birth. The animal food intake of pregnant women should be reasonably consumed during pregnancy. Preterm birth, defined as a live birth before 37 weeks of pregnancy, was the leading cause of neonatal death . Preterm12, Vitamin E, calcium, and zinc is associated with preterm birth [Pregnancy is a complex physiological process, and nutrition during pregnancy plays an important role in the health of pregnant women and the growth and development of their babies. There is substantial evidence that inadequate nutrition, such as low levels of Vitamin D, Vitamin Brm birth ,8,9. Howrm birth . Studyinrm birth . Some form birth , a ‘vegerm birth , and a ‘rm birth  can be brm birth .Unfortunately, most of the studies on the relationship between dietary patterns during pregnancy and preterm birth are from foreign countries and there are few studies from China. This is problematic because geographical and cultural differences across countries and regions contribute to differences in diet structures and eating habits of pregnant women, leading to differences in dietary patterns. As an international metropolis, Shanghai has become an intersectional point of Chinese and Western dietary cultures and enhanced them in accordance with its own dietary characteristics. Therefore, given the uniqueness of the Shanghai diet, it is worthwhile to conduct a study on the dietary patterns of pregnant women in Shanghai. This study chose data from the study of ‘Iodine Status in Pregnancy and Offspring Health Cohort’ (ISPOHC) to explore the relationship between dietary patterns during pregnancy and preterm birth in Shanghai.This study analysed data from the ISPOHC study. This dietary survey of pregnant women was conducted in 2017 and the data on birth outcomes were collected in 2018. The study used multistage, stratified random sampling to obtain a representative sample. There are 16 districts in Shanghai, and each district was divided into five sampling areas: east, west, south, north and centre. A street was randomly selected from each sampling area, and 40–70 pregnant women were selected from each. Participants were evenly distributed in terms of the different stages of pregnancy. Only respondents with live single birth were included in the study; women who had miscarriages, stillbirth, twins, and multiple birth were excluded from the study. After a review of the literature [The Ethics Committee of the Shanghai Centre for Disease Control and Prevention approved the survey. All of the surveys were conducted after obtaining written consent from the respondents.Participants were evenly distributed in terms of the different gestational weeks . When pregnant women were confirmed to be enrolled in the study, the professionally trained investigators helped pregnant women complete a questionnaire through face-to-face interviews. The content of the questionnaire included: basic sociodemographic characteristics, behavioural factors, and the Food Frequency Questionnaire (FFQ). Food models and books containing pictures of food were used to estimate food intake. The validated and reliable FFQ  was usedThe birth information that was collected included sex, gestational age, birth weight, birth length and the head circumference of the baby. The collection of birth information was completed within 42 days after delivery.2), normal weight (BMI = 18.5–23.9 kg/m2), overweight (BMI = 24.0–27.9 kg/m2), and obese (BMI ≥ 28.0 kg/m2). As few of the pregnant women in the study were obese before pregnancy, overweight and obese women were combined into a single group for analysis. The newborns were classified as low birth weight , normal birth weight , and macrosomia (birth weight ≥ 4000 g) [According to the body mass index (BMI) classification standard in China , the pre 4000 g) . With re 4000 g) .λ > 1). The composition of the absolute value of a factor load >0.4 was retained in the common factors to name the dietary patterns. After the dietary pattern was determined, a factor score was calculated for the dietary pattern corresponding to each study participant, which was the product of the average daily food intake of each food group and its weight. The dietary patterns were divided into three equal levels  based on the pattern scores. The binary logistic regression (forward stepwise) was used for univariate analyses. Additionally, the Q1 was utilized as the reference standard. The criterion for inclusion in the binary logistic regression model was 0.05, and the criterion for exclusion was 0.10. The results are expressed as odds ratios (ORs) and 95% confidence intervals. A p-value < 0.05 was considered statistically significant.All statistical analyses were performed using SPSS 24. Since the variables were not normally distributed, the data are described as medians (interquartile ranges) and percentages. Categorical variables are presented as proportions and rates. Principal component analysis (PCA) was used to analyse the dietary patterns of the participants, which included 14 food groups; the maximum variance was used to extract the common factors. The KMO test and Bartlett spherical test were used to determine whether the data were suitable for factor analysis before dietary patterns were extracted. The exact number of common factors was obtained from the scree plot and eigenvalues  and pre-pregnancy BMI  differed significantly across the three dietary patterns (p = 0.034). No other statistically significant differences were found among women in the three dietary pattern groups.We compared differences in the general characteristics of the pregnant women and the birth outcomes of their babies across dietary patterns. The pregnant women’s pre-pregnancy body weight (patterns . PregnanAs shown in Binary logistic regression, which was used to analyse the association between scores on maternal dietary patterns and preterm birth , found hNutritional intake during pregnancy is important for the health of pregnant women and the growth and development of their babies. Dietary patterns have been commonly used in nutritional epidemiological studies because they describe food and nutrient intake as a whole. However, there has been little research in China, particularly in Shanghai, on the relationship between dietary patterns and birth outcomes, especially preterm birth, which are an important indicator of perinatal health in a country or region . TherefoStudies on dietary patterns during pregnancy generally evaluate dietary intake using the FFQ. Compared with the 24-h recall, the FFQ has the advantages of convenience, low-cost, and accuracy with respect to an individual’s long-term average intake level , so one In this study, 50.9% of the foetuses were male and 49.1% were female, so the male-to-female ratio was 1.04:1. There were 185 cases of preterm birth, representing an incidence rate of 4.2%. This preterm birth rate is lower than that reported by the WHO . A studyThe current study of the diet of pregnant women in Shanghai identified three dietary patterns: a ‘Vegetarian Pattern’, an AFP, and a ‘Dairy and Egg Pattern’. The results of binary logistic regression showed that higher scores for the AFP were associated with a higher risk of preterm birth. The AFP in this study included other aquatic products, fish, poultry and livestock. This dietary pattern is characterized by a high intake of animal foods during pregnancy; such foods are rich in fat and protein, and red meat and saturated fatty acids are especially high. There are many studies abroad that have reported results similar to ours. The common denominators in terms of food between the ‘Western-type diet’ and AFP are that they both contain a mix of meat, such as pork, beef, and veal. The Danish National Birth Cohort study, which included nearly 60,000 mother-child pairs to examine the associations of dietary patterns and preterm birth, extracted seven dietary patterns, including a ‘Western-type diet’, which contained high amounts of pork, beef veal, meat mixed, meat cold, dressing sauce, potatoes and so on. The study found a high intake of this diet increased the odds of preterm birth even after adjusting for confounding factors . The sysThe reason why a higher score for the AFP is a risk factor for preterm birth may be related to the way diet influences inflammation. A large number of studies have shown that increased systemic inflammation and increased stimulation of infections or inflammatory pathways can all increase the risk of preterm birth ,30. A coOmega-3 long-chain polyunsaturated fatty acid is also a hot topic in the current research on preterm birth, but there is still a controversy about whether it can reduce the incidences of preterm birth. Some studies claimed that higher intakes of foods containing EPA and DHA during pregnancy is an effective strategy for reducing the incidence of preterm birth ,36, whilAs far as we know, this is the first community-wide study in Shanghai to investigate the effect of dietary patterns during pregnancy on offspring birth outcomes. It has the strengths of a large sample size, good coverage, and a representative sample. However, the study also has some limitations. Firstly, recall bias could not be avoided in this investigation. Secondly, diet is a multi-dimensional exposure. Although many possible confounding factors have been controlled, there are still some uncontrollable potential confounding factors, such as the environment, etc.The incidence of single preterm birth in Shanghai was 4.2% in this study. This percentage is not high in comparison to other regions. However, due to the large population base and given the potential harm of preterm birth to the health of offspring, as well as the social burden, we still need to pay attention to it.The higher score of AFP was significantly associated with higher risk of preterm birth. Therefore, it is important to rationally control the intake of animal foods during pregnancy. We should strengthen relevant nutrition and health education, and conduct more scientific research on reasonable dietary nutrition interventions during pregnancy to reduce the incidence of preterm birth, protect the health of mothers and children, and reduce the overall social burdens that come with preterm birth.


Maternal hypertensive disorders during pregnancy (HDP) have been associated with neuropsychiatric problems in offspring. We aim to investigate the associations between specific types of maternal HDP and offspring neurodevelopmental disorders and further examine whether the timing of onset and severity of HDP would affect these associations. The study population consisted of 4,489,044 live-born singletons in Denmark during 1978–2012 and Sweden during 1987–2010. Maternal HDP was categorized into chronic hypertension, gestational hypertension, and pre-eclampsia; pre-eclampsia was further stratified according to timing , or severity  of the disease. Neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID), were defined by ICD-coded register diagnosis. Cox regression was used to calculate hazard ratios (HR) while adjusting for potential confounders, and sibling analyses assessed the influence of unmeasured shared familial factors. Maternal HDP was associated with increased risks of ADHD , ASD (1.29 [1.24–1.34]), and ID (1.58 [1.50–1.66]) in offspring, respectively, which was mostly driven by pre-eclampsia. The strongest associations were observed for early-onset and severe pre-eclampsia, and the corresponding HRs for ADHD, ASD and ID were 1.93 [1.73–2.16], 1.86 [1.61–2.15], and 3.99 [3.42–4.65], respectively. The results were similar in the sibling analyses. The associations between maternal HDP and offspring neurodevelopmental disorders were consistent across the subgroups of sex, preterm status, parity, maternal age and psychiatric disorders. Maternal HDP, especially early-onset pre-eclampsia, are associated with increased risks of ADHD, ASD, and ID in particular, independent of shared familial factors.The online version contains supplementary material available at 10.1007/s10654-021-00756-2. Neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), affect about 10% of children worldwide –5, incluHypertensive disorders during pregnancy (HDP) complicate 5–10% of all pregnancies , but alsTaking advantage of national Danish and Swedish registers, we aimed to investigate the associations between specific types of maternal HDP and offspring neurodevelopmental disorders using population-based cohort and sibling designs, accounting for unmeasured familial confounding. We further examined whether the timing of onset and severity of HDP would affect these associations , 16, 17.We conducted a nationwide cohort study using data from several registers in Denmark –30 and SICD codes. The Medical Birth Registries (MBR) in both countries contain detailed information on maternal disease history and offspring birth outcomes. As in other studies [In both Denmark and Sweden, prenatal care is standardized and free of charge, which includes visits every fourth week up to 24 gestational weeks, then every second week to 36 weeks, and weekly thereafter. Information on the maternal medical and obstetric history is collected with an interview during the first antenatal visit  , 33. Aft studies –37, we h studies , 33.The health care system in both countries is government-funded and ensures equal and free of charge access to hospital care , 31, 34.Information on maternal HDP was obtained from the combination of the Medical Birth Register (MBR) and the Danish National Patient Register (DNPR) in Denmark , 29, andPre-eclampsia was divided into early-onset and late-onset pre-eclampsia according to the current consensus of disease definition of early-onset pre-eclampsia  . In SwedInternational Statistical Classification of Diseases and Related Health Problems (ICD) codes are available in Table S3 [Information on diagnosis of ADHD, ASD and intellectual disability (ID) was obtained from the DNPR and the Danish Psychiatric Central Research Register in Denmark , 28, andTable S3 , 40, 41.Based on previous research , 18, 21,Cox proportional hazards regression model with the child’s age as the time scale was used to estimate the hazard ratio (HR) with 95% confidence intervals (CI) for the association of maternal HDP with the risk of offspring neurodevelopmental disorders, taking the timing of onset and severity of HDP into account. In the final model, adjustments were made for sex, calendar year of birth, parity, maternal age at birth, maternal education level, maternal cohabitation, and maternal psychiatric disorders before the childbirth. We used the robust sandwich estimator for standard errors to account for the clustering of individuals within nuclear families bound by the same biological mother. Kaplan–Meier curves were used to illustrate the probability of the neurodevelopmental disorders diagnoses in exposed and unexposed groups.To account for unmeasured familial confounding, we performed sibling comparison analysis in which only sibling pairs discordant for both maternal HDP and offspring neurodevelopmental disorders contributed to the effect estimate . As chroICD revisions (ICD-10 was adopted in 1994 in Denmark and in 1997 in Sweden) [2), normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥ 30 kg/m2). All statistical analyses were performed using Stata, version 15.1 (StataCorp).We performed several sensitivity analyses. First, we tested whether the associations varied by the sex of the child, parity, preterm birth, and maternal factors, including maternal age and psychiatric disorders. Second, in order to assess potential effects of neonatal complications, we performed the analyses after excluding children with preterm birth , low birth weight < 2500 g), and low Apgar score at 5 min (< 7) . Third,  Sweden) , 31 and 00 g, and Sweden) –47. LastDuring the study period, we identified 184 033 (4.1%) individuals born to mothers with HDP . In Denmark, 89 240 (4.3%) were born to mothers with HDP  and in Sweden, 94 793 (4.0%) were born to mothers with HDP . Compared with unexposed offspring, exposed offspring were more likely to be born preterm or had lower Apgar scores at 5 min. Mothers of exposed offspring were more likely to be older, to have a higher parity, or more comorbid psychiatric disorders , ASD , and ID . When exploring the risk by types of HDP, we found the overall estimation was mostly driven by maternal pre-eclampsia. The HRs in offspring exposed to maternal pre-eclampsia were 1.27 (95% CI 1.23–1.32) for ADHD, 1.36 (95% CI 1.30–1.42) for ASD, and 1.70 (95% CI 1.60–1.81) for ID, respectively , ASD , and ID . We also observed increased risks among offspring exposed to severe pre-eclampsia, the risk estimates were 1.41 (95% CI 1.32–1.51) for ADHD, 1.44 (95% CI 1.33–1.57) for ASD, and 2.27 (95% CI 2.05–2.52) for ID. It is worth noting that 57.9% of early-onset pre-eclampsia was also diagnosed with severe pre-eclampsia. Therefore, we further examined the associations according to both timing of onset and severity of pre-eclampsia. The association between early-onset pre-eclampsia and the outcomes was slightly affected by severity of pre-eclampsia. For ADHD, the HR was 1.93 (95% CI 1.73–2.16) for early-onset and severe pre-eclampsia, and 1.54 (95% CI 1.32–1.79) for early-onset and moderate pre-eclampsia. On the other hand, the association between late-onset pre-eclampsia and the outcomes was similar across the severity of pre-eclampsia. For ADHD, the HR was 1.24 (95% CI 1.14–1.34) for late-onset and severe pre-eclampsia, and 1.20 (95% CI 1.15–1.25) for late-onset and moderate pre-eclampsia. The same pattern of results was found for ASD and ID  included sibling discordant for pre-eclampsia and ADHD, 6804 (0.46%) included sibling discordant for pre-eclampsia and ASD, and 4313 (0.29%) included sibling discordant for pre-eclampsia and ID. In the sibling comparison models, maternal pre-eclampsia was associated with ADHD , ASD , and ID  . Analyses excluding offspring with adverse birth outcomes such as preterm birth, low birth weight and low Apgar score yielded the similar estimates (Table S9). The proportions of the total effect mediated by gestational age for the associations between maternal HDP and ADHD, ASD, and ID, were 30.7%, 19.2% and 34.9%, respectively (Table S10). Children exposed to superimposed pre-eclampsia had higher risks of ADHD , ASD , and ID  (Table S11). When applying the Swedish approach of defining early-onset pre-eclampsia in the Danish participants, the estimates for early-onset pre-eclampsia were similar to those in the Swedish cohort (Table S12). Similar associations were observed in the analyses (1) restricted to offspring born after 1995 in Denmark and 2001 in Sweden (Table S13) when specialized outpatient diagnoses were added, or (2) excluding neurodevelopmental diagnosis before the age of three (Table S14), or (3) using the multiple imputation method (Table S15), or (4) additionally adjusting for maternal pre-pregnancy BMI (Table S16), or (5) excluding individuals with chronic hypertension (Table S17), or (6) categorizing chronic hypertension into two subgroups: primary diagnosis or secondary diagnosis (Table S18), or (7) additionally adjusting for CCI scores (Table S19).In this large population-based cohort study, we found that all the three types of maternal HDP, including chronic hypertension, gestational hypertension and pre-eclampsia, were associated with 1.2- to 1.6-fold risks of neurodevelopmental disorders in offspring, while the overall associations were mostly driven by pre-eclampsia. The strength of associations varied significantly according to the timing of onset or severity of pre-eclampsia and our findings further indicated that the timing of onset of pre-eclampsia was probably more important than the severity. The consistent results from sibling comparison analysis indicated that the observed associations are unlikely confounded by the shared genetic and environmental factors. Moreover, these results remained unchanged when taking into account of a number of important factors, such as maternal socioeconomic status, birth order, maternal history of psychiatric disorders, and adverse birth outcomes.To our knowledge, this is the largest population-based and sibling comparison study to date to investigate the link between maternal HPD and the risk of neurodevelopmental disorders in offspring. Our findings of increased risk of neurodevelopmental disorders related to maternal HDP are inconsistent with several previous studies which reported null or even a protective association between maternal pre-eclampsia and neurodevelopmental disorders in offspring , 48, 49.Our findings are in line with those in several other previous observational studies, demonstrating increased risks of neurodevelopmental disorders in offspring born to mothers with pre-eclampsia –19, 50. We are only aware of one recent birth cohort study (n = 4743) reporting that maternal severe pre-eclampsia and mild pre-eclampsia were associated with 2.0-fold and 1.4-fold risk of overall mental disorders in offspring, respectively . HoweverMost previous studies have not distinguished between gestational hypertension and pre-eclampsia , 53, 54.There is currently limited evidence on the association between chronic hypertension and neurodevelopmental disorders in offspring. A registry study in Norway showed that there was no association between maternal chronic hypertension and offspring ADHD . HoweverThe underlying mechanism linking maternal HDP and neurodevelopmental disorders remains to be elucidated. The fetal programming theory hypothesizes that adverse fetal environment or insult can affect brain development, which leads to a range of neurodevelopmental disorders . It is pOur study has several strengths. First, the large sample up to four million mother–child pairs made it possible to examine all forms of HDP, and to stratify pre-eclampsia by timing of onset or severity, which are not commonly ascertained in other studies , 14, 17.Some limitations need to be noted. First, as the data from the primary care was not available, it is likely that some mild cases could not be identified through the registers, for example, chronic hypertension is often managed in primary care particularly . HoweverOur findings suggest that all types of maternal HDP, especially early-onset pre-eclampsia, are associated with increased risks of neurodevelopmental disorders  in offspring. From a public health perspective, these findings highlight the importance of better management of maternal HDP and earlier screening and detection for neurodevelopmental disorders in their offspring.Supplementary file1 (DOCX 233 kb)Below is the link to the electronic supplementary material.


Most of the deaths among neonates in low-income and middle-income countries (LMICs) can be prevented through universal access to basic high-quality health services including essential facility-based inpatient care. However, poor routine data undermines data-informed efforts to monitor and promote improvements in the quality of newborn care across hospitals.Continuously collected routine patients’ data from structured paper record forms for all admissions to newborn units (NBUs) from 16 purposively selected Kenyan public hospitals that are part of a clinical information network were analysed together with data from all paediatric admissions ages 0–13 years from 14 of these hospitals. Data are used to show the proportion of all admissions and deaths in the neonatal age group and examine morbidity and mortality patterns, stratified by birth weight, and their variation across hospitals.During the 354 hospital months study period, 90 222 patients were admitted to the 14 hospitals contributing NBU and general paediatric ward data. 46% of all the admissions were neonates (aged 0–28 days), but they accounted for 66% of the deaths in the age group 0–13 years. 41 657 inborn neonates were admitted in the NBUs across the 16 hospitals during the study period. 4266/41 657 died giving a crude mortality rate of 10.2% (95% CI 9.97% to 10.55%), with 60% of these deaths occurring on the first-day of admission. Intrapartum-related complications was the single most common diagnosis among the neonates with birth weight of 2000 g or more who died. A threefold variation in mortality across hospitals was observed for birth weight categories 1000–1499 g and 1500–1999 g.The high proportion of neonatal deaths in hospitals may reflect changing patterns of childhood mortality. Majority of newborns died of preventable causes (>95%). Despite availability of high-impact low-cost interventions, hospitals have high and very variable mortality proportions after stratification by birth weight. Quality of inpatient care for small and sick newborns in low-income and middle-income countries (LMICs) is poor.Poor routine data undermines efforts to monitor and promote improvements in the quality of newborn care across hospitals in LMICs.Neonates (aged 0–28 days) account for almost half and two-thirds of the admissions and deaths, respectively, in the age group 0–13 years in Kenyan county hospitals.Neonatal fatality rate in newborn units (NBUs) is high and variable across hospitals and birth weight categories. Nevertheless, meaningful comparison of neonatal morbidity and mortality across different hospitals in low-resource settings is a major challenge.Lack of technologies to accurately estimate the gestation age (GA) makes birth weight categories preferred over GA when stratifying the risk of neonatal mortality. However, use of birth weight is inaccurate as low birth weight conflates both premature birth and the occurrence of small for gestational age that carry different risks of mortality.Inconsistent admission criteria in NBUs and kangaroo mother care (KMC) wards, compounded by limited or lack of KMC facilities, may lead to admission of stable preterm babies to the NBUs thus lowering the neonatal fatality rates.To allow for comparison of NBU fatality rates across different settings in addition to developing well-functioning information systems that operate at scale, there is need to harmonise: (1) GA assessment methods, (2) data capture on early neonatal deaths that occur in labour wards, (3) diagnostic criteria for common neonatal conditions and (4) standardise NBU and KMC admission criteria.Two and half million neonates die annually accounting for 47% of all under-five deaths, with 98% of the neonatal deaths occurring in low-income and middle-income countries (LMICs).We conducted a retrospective cohort study that used paediatric and neonatal inpatient data between 1 April 2018 and 31 March 2020. CIN-Neonatal data spans 16 purposively selected public hospitals (H1–H16) in 12 of the 47 counties in Kenya. For the purposes of some analyses, we also use inpatient records of all children aged 0–13 years including those admitted to hospitals’ general paediatric wards in 14 hospitals (H1–H14). We excluded data from H15 and H16 in the analysis of the burden of all neonatal admissions and mortality among all admissions 0–13 years because only NBU data were collected from these two hospitals. Kenya introduced a curfew and other measures to control the SARS-CoV-2 pandemic on 27 March 2020 and had 59 confirmed cases among all age groups by 31 March 2020. Our data are unlikely to have been affected by the pandemic.The Clinical Information Network (CIN) was established in 2013 as a collaboration between the Ministry of Health (MoH), Kenya Paediatric Association, KEMRI Wellcome Trust Research Programme, University of Nairobi and participating hospitals. The aim of CIN is to improve quality of patients’ data and their utilisation; it had an initial focus on general paediatric wards.In 2014, we began development of neonatal data collection tools and procedures in a large hospital providing exclusive maternity and neonatal services.We obtained basic descriptive data on hospital infrastructure and resources from the Kenya Harmonized Health Facility Assessment conducted in 2018/2019, the District Health Information System version 2 and directly from CIN’s focal persons.By April 2018, 12 hospitals had joined CIN-Neonatal. One hospital (H7), though in CIN-Paeds, was not enrolled until November 2018, and with guidance from MoH, one other hospital was added in November 2018 (H15) and two in December 2018 (H1 and H4). These three new hospitals were selected on the basis of having relatively high-volume NBUs. All the 16 NBUs aim to provide specialty care for small and sick newborns with capacity to provide bag and mask ventilation and oxygen, use of radiant warmers or incubators (often shared), intravenous antibiotics, intravenous fluids and nasogastric or orogastric breast milk feeding, kangaroo mother care (KMC) and phototherapy. All the 16 NBUs are higher volume non-tertiary facilities that are aspiring to reach the intermediate level of neonatal care.We use CIN-Neonatal and CIN-Paeds’ data to create two populations, population A and population B, for analyses.Population A: includes hospital admissions that contribute to both the CIN-Neonatal and CIN-Paeds databases (H1–14), thus excluding data for H15 and H16. We use data for all ages (0–13 years) to show the proportion of all admissions and deaths in county hospitals that are in the neonatal age group .Population B: includes only neonates admitted to all the 16 NBUs who are also born in the same hospital, thus excluding outborn neonates. We defined an ‘outborn’ neonate as one either born at home, referred into the NBUs from another facility or admitted from home after discharge from a facility-based birth. We excluded all outborn neonates from this analysis because our aim was to examine a relatively comparable population of newborns from each hospital. We used this population to describe characteristics of all inborn neonates disaggregated by hospital and examine morbidity patterns, mortality rates stratified by birth weight and inpatient survival over time .For analysis of the inborn neonates, population B, we used the birthweight categories described by the WHOBox 1We preferred to use birth weight over gestation age (GA) to stratify our analysis because GA data are often missing and when recorded suffers from the following limitations: (1) it is often estimated from mothers’ report of last menstrual period, (2) routine first trimester ultrasound estimation is rarely done in Kenyan public hospitals and (3) use of recognised clinical assessment tools for estimating gestation are not in regular use.Morbidity patterns are based on all causes of illness/reasons for admission on NBU as documented in the neonates’ admission and/or discharge notes by clinicians. All the NBUs have structured admission records and discharge summary forms that promote the use of common terms for common diagnoses/illness classification. We therefore neither attempted to refine the diagnoses made by the attending clinicians nor to assign a single cause of admission or death. A large majority of diagnoses are based on clinical features supported by only infrequent access to a limited range of diagnostic tests. Some diagnoses imply clinical syndromes or simply reason for admission to NBU rather than formal diagnoses based on the International Classification of Diseases (ICD)-10 system. Thus, our morbidity/reason for admission analysis allows for more than one diagnosis per neonate and thus primarily indicates the need for services or interventions.In the specific case of a recorded diagnosis of low birth weight or preterm birth or of being HIV exposed, we considered these as the admission diagnosis only if no comorbidity was recorded. We describe the former as ‘uncomplicated low birth weight or preterm birth’ if no comorbidity.Clinical diagnoses of birth asphyxia, hypoxic ischaemic encephalopathy and meconium aspiration were collectively categorised as ‘intrapartum related complications’.The day of birth was considered as day 1. There was poor documentation of time of admission in the NBU.This study uses routine secondary data. Although members of the public/patients provided routine data required for care provision, no patients or the public were directly involved in the design, conduct, reporting or dissemination plans of this research.Characteristics and resources for newborn care in the 16 CIN hospitals are described in During the study period, a total of 88 578 patients were admitted in the NBUs and general paediatrics wards of the 14 hospitals (excluding H15 and H16) that contribute to both CIN-Neonatal and CIN-Paed data. After excluding 896 patients whose age was missing and 132 who were aged >13 years, we obtained 87 550 patients aged 0–13 years (population A) . Among tOverall, 9% (7806/87 550) of all patient admissions aged 0–13 years in these hospitals died. Neonates (0–28 days old) comprised of 66% (5142/7799) of these deaths, with 91% (4668/5142) of the neonatal deaths occurring among neonates aged 0–6 days. The contribution of neonatal deaths to all inpatient deaths aged <13 years also varied widely across hospitals (range 40%–87%) .After excluding 6120 outborn neonates, we obtained data on 41 657 inborn neonates (aged 0–28 days) admitted in NBUs across the 16 hospitals during the study period . In tablFour per cent (1688/38 835) of the neonates in whom HIV maternal status was documented were HIV exposed. Although, in two sites (H4 and H8), about 15% of NBU admissions were HIV exposed.There were 53 047 diagnoses/reasons of NBU admissions recorded at admission and/or discharge among the 41 657 inborn neonates. Five conditions accounted for 80% of the diagnoses in the NBUs. These included intrapartum-related complications (30%), respiratory distress syndrome (18%), neonatal sepsis (15%), jaundice (12%) and uncomplicated low birth weight (LBW)/prematurity (5%). Intrapartum-related complications was the most common  diagnosis among neonates with birth weight ≥2500 g, while respiratory distress syndrome (RDS) was the most common disorder  among those <2000 g. Neonatal sepsis and jaundice accounted for 17% (6 301/37 312) and 13% (5 009/37 312) of the disease episodes in neonates with birth weight ≥2500 g, respectively, vis-a-vis 9% (832/8772) and 7% (589/8772) of the disease episodes among neonates with birth weight <2000 g . Comorbi10.1136/bmjgh-2020-004475.supp1Supplementary data10.1136/bmjgh-2020-004475.supp2Supplementary data10.1136/bmjgh-2020-004475.supp3Supplementary dataThere were 4266 neonates who died among 41 657 inborn neonates admitted in NBUs giving a crude fatality rate of 10.2% (95% CI 9.97% to 10.55%) with wide variation in the hospital-specific neonatal fatality rates (range 5%–14%). Of the babies who died, 4132 (97%) had birth weight documented. In those with a birth weight <1000 g, median mortality was 79% (range 53%–95%), with a marked decrease to 43% (range 32%–60%) for those with birth weight 1000–1499 g and further decreases for those with birth weight 1500–1999 g, 2000–2499 g, 2500–3999 g and ≥4000 g where median mortality rates were 14% (range 7%–24%), 9% (range 5%–17%), 6% (range 3%–12%) and 2% (range 0%–14%), respectively. The median and hospital-specific mortality rates are illustrated using funnel plots. One hospital (H10) and two hospitals (H1 and H7) had consistently lower and higher mortality, respectively, for babies with birth weight 1000–1999 g. The funnel plots suggest a threefold variation in mortality observed for inborn populations with birth weights of 1000–1499 g and 1500–1999 g . This ma10.1136/bmjgh-2020-004475.supp4Supplementary dataMany deaths were among inborn neonates with multiple diagnoses and over 95% were associated with five diagnoses: intrapartum-related complications, uncomplicated prematurity/LBW, RDS, neonatal sepsis and jaundice. As with the pattern observed for morbidity, however, babies with higher birth weights who died were more likely to have a diagnosis of intrapartum-related complications (57% of the 1588 babies with birth weight ≥2500 g who died had a single diagnosis of intrapartum-related complications). In contrast, of the 2107 inborns neonates with birth weights <2000 g who died, 29% had diagnoses of uncomplicated prematurity/LBW, while 35% had prematurity/LBW complicated by RDS . Data we10.1136/bmjgh-2020-004475.supp5Supplementary dataWe sought to describe the characteristics, disease patterns and outcomes of inborn neonates admitted in NBUs in a set of Kenyan counties’ referral hospitals. This study has demonstrated that even in low-resource settings, it is possible to have clinical networks enabling multisite data collection that yields quality data that could inform policy and help in planning newborn services that are context sensitive. Neonates contribute to almost half (46%) of all admissions among medical patients aged 0–13 years, although this proportion considerably varies across hospitals. The reasons for this variation are likely to be complex and depend on admission policies in NBUs and paediatric wards, different disease patterns in paediatrics wards  and local referral patterns especially for outborn neonates.Five conditions, all to some degree preventable, accounted for 80% of the disease episodes at admission among inborn neonates in NBUs, with intrapartum-related complications being the most common (30%) cause of admission. Reducing intrapartum-related complications means having a functional health system to provide quality care during the antenatal period, labour, childbirth and immediate postnatal period.However, while better technologies may help in the management of these common neonatal conditions, they need to be carefully introduced. Where human resources for health (HRH) are limited, adding new tasks can exacerbate existing challenges of delivering high-quality care.There is high in-patient neonatal fatality in the NBUs studied across all birth weight bands. However, ELBW (<1000 g) with median mortality of 80% is almost five times higher that of HICs, while median mortality of VLBW (1000–1499 g) of 40% is about 10 times higher that of HICs.Majority (90%) of inborn neonates in the NBUs studied are admitted on their first day of life, and three out of every five deaths in the NBUs occur on the first day of admission. Poor quality of intrapartum and immediate postnatal care makes the day of birth the riskiest period for a neonate. WHO has developed guidance for continued care along the life course by integrating maternal and newborn care and promoting maternal perinatal death surveillance and response. However, the ‘P’, other than newborn resuscitation, is a weak component of these strategies.et alThere are several limitations to this study. First, these 16 study hospitals are not a representative sample of Kenyan public hospitals. So, we cannot ascertain generalisability of estimates, although there have been other reports on high NBU mortality in Kenya.In conclusion, neonatal fatality is unacceptably high, but the varied KMC and NBU admission policies challenge comparison of fatality rates across facilities. The fact that almost all the deaths are preventable offers opportunities to improve newborn survival. Care of the small and sick newborn must be included in efforts to strengthen peripartum care, and this goes well beyond neonatal resuscitation, which is the current ‘signal newborn care function’ for comprehensive emergency obstetric and newborn care training. Nevertheless, in view of the high burden of intrapartum-related complications, more work needs to be done on neonatal resuscitation training of the care providers in these health facilities. Neonates comprise almost half of all admissions and two-thirds of the deaths in the paediatric age group (0–13 years) in the hospitals studied. Thus, there is need for governments to prioritise newborn care services and appropriate resources and staffing as a key element of evidence-based hospital care.


Low birth weight (LBW) is a major factor of neonate mortality that particularly affects developing countries. However, the scarcity of data to support decision making to reduce LBW occurrence is a major obstacle in sub-Saharan Africa. The aim of this research was to determine the prevalence and associated factors of LBW at the Yako health district in a rural area of Burkina Faso.p-value < 0.05 was considered statistically significant.A cross sectional survey was conducted at four peripheral health centers among mothers and their newly delivered babies. The mothers’ socio-demographic and obstetrical characteristics were collected by face-to-face interview or by review of antenatal care books. Maternal malaria was tested by standard microscopy and neonates’ birth weights were documented. Multivariate logistic regression was used to determine factors associated with LBW. A Of 600 neonates examined, the prevalence of low birth weight was 11.0%. Adjustment for socio-demographic characteristic, medical conditions, obstetrical history, malaria prevention measures by multivariate logistic regression found that being a primigravid mother , the presence of malaria infection , the uptake of less than three doses of sulfadoxine-pyrimethamine for the intermittent preventive treatment of malaria in pregnancy (IPTp-SP) , the presence of maternal fever at the time of delivery  and being a female neonate  were independently associated with an increased risk of LBW occurrence. The number of antenatal visits performed by the mother during her pregnancy did not provide any direct protection for low birth weight.The prevalence of LBW remained high in the study area. Maternal malaria, fever and low uptake of sulfadoxine-pyrimethamine doses were significantly associated with LBW and should be adequately addressed by public health interventions. Low birth weight (LBW) is a leading determinant of neonatal mortality worldwide that particularly affects the developing countries . In the P. falciparum resistance to SP, particularly in western and central African regions are however raising concerns regarding the efficacy of the strategy [(dhps) and dihydrofolate reductase (dhfr) genes of P. falciparum are widely reported [dhps and dhfr genes along with the emergence of septuple even octuple mutations reported in several countries is a further threat for the efficacy of the strategy and is reported to cause low birth weight in sub-Saharan Africa [To reduced malaria related adverse birth outcomes, the intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in combination with vector control approaches such as free distribution of insecticide treated bed nets (ITNs) were adopted . From anstrategy . Indeed,reported . Also, tn Africa –17.P. falciparum resistance to SP [Efforts were deployed in different countries to mitigate the effects of the SP resistance through a supervision of the administration of the drug in pregnant women and also by increasing the number of SP doses required to a minimum of three during a pregnancy course. In 2013, Burkina Faso adopted the new policy , 19 and ce to SP . The purA cross-sectional survey was conducted at four health centers of the Yako health district from August 2019 to March 2020 /i2 where p = 10% was the expected proportion, i = 2.5%, the margin of error, and Z the z-score that corresponds to the 95% confidence interval (1.96), The minimum sample size was 554 participants.At the time of the IPTp-SP policy changed, the prevalence of low birth weight in Burkina Faso was 13.4% . We hypoData was extracted from the mothers’ ANC books or obtained by interview of the mothers when the information was not available in the ANC books and subsequently recorded onto semi-structured questionnaires by trained midwives. Age, gyneco-obstetrical history, IPTp-SP uptake, educational level, occupation, and the use of bed nets the night before admission for delivery were collected. In addition to physical and obstetrical examinations, blood pressure, axillary temperature, and body weight were measured, completed by malaria diagnosis in peripheral blood samples. Due to the absence of ultrasounds, we estimated gestational age using the knowledge of the last menstrual period (LMP), or the Ballard score whenever the LMP was unknown. Neonates’ birth weights were measured with calibrated Seca® 384 electronic scales with 10 g resolution and a precision of 5 g .The outcome variable was birth weight measured within 24 h of delivery, and was dichotomized in low (< 2500 g) and normal (≥ 2500 g) birth weights . ExplanaThick and thin blood smears were prepared, dried and stained with 5% Giemsa for 30 min. Two independent microscopists examined the slides at 1000x magnification using light microscopy. Parasite densities were calculated by counting the number of asexual parasites per 200 white blood cells (WBC), and parasites per μl calculated assuming WBC count of 8000 cells per μl of whole blood. When the number of asexual parasites was less than 100 per 200 WBC, counting was done against at least 500 WBC. A slide was considered negative if no parasite was found after a review of 1000 WBC or 100 fields containing at least 10 WBC per field. In case of discrepant results (discrepant species or count difference of at least 50% between the two microscopists), a third microscopist assessed the slides and the average of the two closest reads was used.p-values were < 0.1 at univariable analysis and keeping those with p-values < 0.1 in the final model. Maternal age was not included in the model because of its strong correlation with the number of pregnancies. In addition, gravidity was dichotomized (1 or ≥ 2 deliveries) for birth weight factors assessment. The significance level was set at 5% .Data were collected on electronic questionnaires using REDcap (Research Electronic Data Capture) data collection tool and exported onto Stata version 15  for cleaning and analysis. Categorical variables were summarized on frequency tables. Mean or median with respective standard deviations or quartiles were used to summarize numerical variables. T-test was used to compare means and odds ratios (OR) with 95% confidence intervals (95% CI) calculated by univariable logistic regression. Adjusted OR (aOR) were derived by backward multivariable logistic regression of factors which A total of 684 participants were assessed, 600 (87.7%) were included and 84 (12.3%) not eligible. Reasons for non-eligibility included 12 preterm births, 18 non-singleton births, 12 stillbirths, 2 miscarriages, 5 neonatal deaths, 15 data losses due to electronic pad breakdown, 16 concurrent participations to another research and 4 very ill neonates referred with missing birth weights.Majority of women were unemployed 69.2%) with none or primary level of education (67.8%). Mean maternal age was 25 ± 6  years and 23% were aged less than 20 years. The median number of pregnancies stood at two . Regarding malaria prevention measures, 92% stated using ITN the night before admission to delivery clinic and the IPTp-SP uptake was 77, 17.0, 5.0 and 1% for 3 or more doses, 2 doses, one dose and no dose respectively. Malaria infection was diagnosed in 17.5% (105/600) of participants, among them 83.8% were asymptomatic (Table % with nop < 0.01), in neonates from mothers with less than three SP doses than those with three or more doses , and if the mothers had malaria infection . By multivariate analysis, first pregnancy, malaria infection, uptake of less than three SP doses, maternal fever and being a female neonate were independently associated with an increased risk of LBW  reported in Burkina Faso decreased the efficacy of this antimalarial to reduce adverse birth outcomes [As expected , malariaefficacy –17. Indeoutcomes . Therefooutcomes , 28, it outcomes .We noted that first pregnancy infants were at particular higher risk of LBW –32. SeveAs, already reported , female In this study we described the prevalence of low birth weight and tentatively identified some risk factors in women from Yako health district. However, some limitations are worth noting. The consideration of term pregnancy neonates and the exclusion of twin deliveries and stillbirths somehow understate the actual magnitude of low birth weight at the site. Gestational age was collected using the mother knowledge of last menstrual period or the Ballard score due to the absence of ultrasounds, and this is frequently prone to errors. Also, the cross-sectional design of the study does not guaranty causality between exposures and outcomes. However, the study is worth underlying the extent of some factors influencing adequate maternal and child health and help identify areas with the most need of interventions.Low birth weight prevalence was high in the study area. Reducing the proportion of pregnant women with low IPTp-SP uptake and malaria infection could reduce low birth weight occurrence and improve neonatal survival particularly among infants born from young mothers.


Fetal growth is affected by exposure to both prenatal stress and environmental contaminants. The attacks on the World Trade Center (WTC) resulted in exposure to chemicals and psychological stress amongst New York City residents. We measured prenatal maternal stress and exposure to persistent organic pollutants ) in 108 participants from a Columbia University WTC birth cohort. Principal component (PC) analyses were conducted to characterize the mixture of exposure to the three groups of chemicals. We evaluated the associations between geographical exposures (proximity to the WTC disaster) and both chemical exposures (PCs) and stress . We then evaluated the effect these exposures (PCs and stress) had on previously reported associations between geographical WTC exposure and birth outcomes (birth weight and birth length) in this study population to understand their individual roles in the observed associations. Geographical exposure via proximity to the WTC was associated with the PC reflecting higher PCDD exposure (PC3) . Previously reported reductions in birth weight and length associated with WTC proximity  were attenuated and no longer significant for birth weight  after adjusting for PC3, suggesting that PCDDs may act as partial mediators in this previously observed association. The results of this study can help focus future research on the long-term health effects of these prenatally exposed populations. Fetal growth has been shown to be influenced by both maternal stress ,2,3,4 anPost-traumatic stress has been well documented in WTC recovery workers ,14,26, aData for this work came from a Columbia University birth cohort designed to study the effects of WTC exposures on pregnancy outcomes and development. Detailed methods have been described previously . Singletn = 36) or weight (n = 49) from the medical record, self-reported information on these variables from the hospital interview were used. Child sex and date of birth were abstracted from the child’s medical record. Gestational age in days was also abstracted from the medical record (if missing (n = 15), date of mother’s last menstrual period from interview minus child’s date of birth was used). Gestational age on 9/11, used to determine trimester during the WTC disaster, was calculated by subtracting days since the 9/11 disaster on the child’s date of birth from the child’s gestational age in days at birth. Mothers were classified as being in their first trimester on 9/11 if their child had a gestational age of ≤91 days on 9/11 and in their second or third trimester if their child had a gestational age >91 days. Maternal age at delivery was determined by subtracting the child’s date of birth from the mother’s date of birth. Medical complications during pregnancy  and birth outcomes (child’s birth weight and length) were abstracted from the medical record or obtained from the maternal interview if the medical record was incomplete. Maternal demoralization was used to determine maternal stress and was measured during the postpartum interview using the Psychiatric Epidemiology Research Instrument Demoralization scale (PERI-D). The PERI-D scale provides a measure of nonspecific psychological distress, with demonstrated reliability across different ethnic groups [n = 188). In addition, we removed from the analyses women who completed less than 36 weeks and 6 days of gestation  (n = 5) or had missing data on maternal age, demoralization, race, education, parity, pre-pregnancy BMI, trimester on 9/11, Medicaid status, pregnancy complications, home smoking exposure, child sex, and child birth weight and length (n = 28), resulting in a sample size of 108 participants.The postpartum interview was administered at the hospital in the woman’s preferred or native language . Information on maternal education, date of birth, race, parity, Medicaid status, home smoking exposure, and residential and work addresses was elicited through the interview. Residential and work addresses (for the 4 weeks starting on and following 9/11) were geocoded at the Center for International Earth Science Information Network of Columbia University’s Earth Institute, using geographic information system (GIS) software from the Environmental Systems Research Institute , including ArcGIS 8.3 and the Street Map 2003 extension . Using tc groups ,38. AnalBlood samples from the umbilical cord were collected at the time of delivery; maternal samples were typically collected on the day after delivery. On average, 30.7 mL blood was collected from the umbilical cord, and 30–35 mL blood was collected from the mother. Blood samples were transported to Columbia University laboratory facilities in Northern Manhattan and processed within hours of collection. The buffy coat, packed red blood cells, and plasma were separated and stored at −70 °C.Detailed methods regarding the analysis of the plasma samples for PBDEs at the Centers for Disease Control and Prevention have been previously described ,40. BriePCBs and PCDD/Fs were analyzed at the Centers for Disease Control and Prevention. Detailed methods regarding the analysis of PCBs and PCDD/Fs in blood have been previously described ,42. Briep < 0.01) . Analyses were restricted to compounds detected in ≥50% of maternal and cord samples for 4 PBDEs  and 10 PCBs  and only maternal samples for 3 PCDDs  because no cord samples met this threshold. No maternal or cord PCDF congeners met this threshold and were, therefore, not included in any analyses. To maximize sample sizes, we used both maternal plasma and cord blood PCB and PBDE concentrations. However, to account for differences in maternal versus cord blood samples, we used separate prediction models developed using all available PCB and PBDE samples  to transform maternal PCB and PBDE concentrations in participants with maternal measurements but no cord blood measurements. Therefore, cord measurements for these chemicals included actual cord measurements as well as maternal measurements that were transformed through prediction models to reflect what the cord value would have been for that participant had they had a true cord measurement. Prediction models were developed separately for each congener by regressing log-transformed maternal measurements on log-transformed cord measurements. Details of the transformation models are provided . We tran < 0.01) . Only maThe first aim of our analysis was to evaluate the association between our variables representing geographic exposure to the WTC site (WTC proximity exposure variables) and both maternal stress and maternal exposure to PCBs, PBDEs, and PBDDs, as well as the association between maternal stress and maternal exposure to these chemicals with birth outcomes. The second aim of our analysis was to evaluate the potential mediating role of maternal stress and maternal chemical exposure in the previously reported associations between geographic exposure to the WTC site and birth outcomes . Becausep-value from a two-sided Wald t-test on the coefficient for the two-way multiplicative term. A threshold of p < 0.05 was used to define associations as statistically significant.Medians (IQR) and percentages were used to describe sociodemographic and birth outcome variables (birth weight and length) in the study population overall and by each of the geographic WTC proximity exposure variables . Differences between participants across geographic WTC proximity exposure categories were calculated using Mann–Whitney U and chi-square tests for continuous and categorical variables, respectively. Linear regression analyses were conducted to evaluate the association between both geographic WTC exposure variables (“Lived or worked <2 miles from WTC site” and “Just lived <2 miles from WTC site”) and each of the chemical principal component (PC) variables as well as maternal demoralization. Linear regression analyses were also conducted to evaluate the association between chemical PC variables and maternal demoralization with birth outcomes. Model adjustments for these analyses were selected a priori and included maternal age, parity, race, education, pre-pregnancy BMI, family smoking status, trimester on 9/11, and child sex. In addition, linear regression analyses were also conducted to evaluate the association between both geographic WTC exposure variables and birth weight and birth length, before and after adjustment for each chemical PC as well as maternal demoralization. Model adjustments for these analyses were selected a priori to be consistent with previous exposure-birth outcome analyses in this cohort  and inclDue to the large proportion of missing data, to evaluate whether our complete case analysis was biased, in sensitivity analyses, we used inverse probability weighting in which complete cases were weighted by the inverse of their probability of being a complete case. All study variables except for our principal components were used in our model to predict whether a participant was a complete case. We also conducted sensitivity analyses with imputed missing data using multivariate imputation by chained equations (MICE). All study variables were included in the prediction of our imputation model. All study variables with missing data  were given imputed values if missing. We set our model iterations to 20 and imputations to 30, which achieved healthy convergence of the imputation model evaluated visually through trace and density plots. Because all missing data were imputed, the sample size for these analyses included the full dataset of 329 participants.For all non-supplemental tables and figures, PCB and PBDE concentrations reflect cord + transformed maternal-to-cord measurements, and PCDD concentrations reflect just maternal measurements. A correlation matrix of the 10 PCBs, 4 PBDEs, and 3 PCDDs is displayed in p = 0.004) and were more likely to be on Medicaid (p = 0.01).For the 108 subjects in the analyses, the median maternal age was 31.2 years and median maternal pre-pregnancy BMI was 22 . There wIn adjusted models, exposed groups for both geographic WTC proximity exposure categories were associated with lower birth weight and birth length . HoweverThe results from our sensitivity analyses using inverse probability weighting were consistent . The resIn this cohort of mother–child dyads who delivered in New York City, NY, in the months following the WTC disaster, we evaluated the mediating role of both chemical exposures and maternal stress in previously observed associations between proximity to the WTC site and lower birth weight and birth length. We used PCA to summarize prenatal exposure to PCBs, PBDEs, and PCDDs and the PERI-D scale  to summarize maternal prenatal stress. Four PCs captured most (85%) of the variance in chemical exposures. We found that both of our geographic WTC proximity exposure variables, mothers who lived or worked within 2 miles of the WTC site and mothers who just lived within 2 miles of the WTC site, were associated with the PC reflective of higher exposure to PCDDs. Demoralization was not associated with either geographic WTC proximity exposure variable. We also found that both our geographic WTC proximity exposure variables were associated with lower birth weight and birth length; however, this relationship was only significant for those who lived within 2 miles of the WTC site. After adjustment for each PC as well as demoralization, in separate models, the relationship between proximity to the WTC and birth outcomes remained consistent except when adjusting for the PC reflecting higher PCDD exposure. In this case, the associations were attenuated and no longer significant between living within 2 miles of the WTC site and birth weight, suggesting dioxins may act as partial mediators in these associations. There were no significant additive interactions between demoralization and PCs with birth outcomes.The attacks on the World Trade Center, and their subsequent collapse, resulted in a toxic mixture of chemical exposures to local populations and psychological stress that impacted populations across the world. The effects of these dual exposures on birth outcomes among mothers who were pregnant during the WTC disaster are incompletely understood. Several studies have tried to evaluate the association between proximity to the WTC, and therefore, likely high exposure to both chemical and psychological stressors; however, results have been inconsistent. Lipkind et al.  found noThese studies suggest an association between proximity to the WTC site and birth outcomes but do not provide information on the specific exposures driving these associations. Our analysis evaluating the association between chemical PCs and demoralization with proximity to the WTC provides evidence that PCDDs were a more significant exposure source than PBDEs, PCBs, or demoralization in populations living or living/working within 2 miles of the WTC. Further, the attenuation of the previously observed relationship  betweenThe potential partial mediating role of PCDD concentrations in the previously reported relationship between proximity to the WTC and birth outcomes in this study cohort is supported by experimental and epidemiological evidence. The majority of experimental studies focused on 2,3,7,8-TCDD (TCDD) and reported consistent associations between maternal exposure and reduced birth length and weight . In our Thus, these results, and the minimal effect adjustment for other chemical PCs or demoralization had on the relationship between proximity to the WTC and birth outcomes, suggest that other non-measured chemicals may have played a role or that our study’s demoralization variable did not accurately capture maternal stress in response to such a large disaster. Numerous studies have reported post-traumatic stress (PTS) in WTC recovery workers ,14,26, aIn conclusion, the first three PCs of our PCA revealed the three main chemical groups under study: PCBs, PBDEs, and PCDDs, respectively. The third PC, reflecting higher PCDD exposure, was associated with both living as well as living or working within 2 miles of the WTC on 9/11 among pregnant women in this study. Further, the previously reported associations between geographic WTC proximity exposure variables and birth outcomes were attenuated after adjustment for PC3, suggesting that PCDD exposure may have played the role of a partial mediator in these relationships. The results of this study suggest PCDDs were an important WTC-related prenatal exposure and can help focus future research on the long-term health effects of these prenatally exposed populations, especially in light of previous evidence suggesting that PCDD concentrations may still be elevated in these groups throughout childhood and into adolescence.