To assess the impact of being born preterm or small for gestational age (SGA) on several adult outcomes.We analyzed data for 4518 adult participants in 5 birth cohorts from Brazil, Guatemala, India, the Philippines, and South Africa.In the study population, 12.8% of males and 11.9% of females were born preterm, and 26.8% of males and 22.4% of females were born term but SGA. Adults born preterm were 1.11 cm shorter , and those born term but SGA were 2.35 cm shorter  compared with those born at term and appropriate size for gestational age. Blood pressure and blood glucose level did not differ by birth category. Compared with those born term and at appropriate size for gestational age, schooling attainment was 0.44 years lower  in those born preterm and 0.41 years lower  in those born term but SGA.Being born preterm or term but SGA is associated with persistent deficits in adult height and schooling, but is not related to blood pressure or blood glucose level in low- and middle-income settings. Increased postnatal growth is associated with gains in height and schooling regardless of birth status, but not with increases in blood pressure or blood glucose level. Growth failure in childhood, usually measured as stunting (height for age <−2.0 SDs compared with the reference population), is associated with short stature in adulthood and with lower schooling attainment.We previously reported that size at birth and growth patterns in childhood are related to attained adult heightwww.jpeds.com). The youngest cohort (South Africa) has completed data collection at age 18 years; we used those more recent data in the present analysis. All field work was conducted under protocols approved by the respective Ethical Review Committees, and all subjects  gave informed consent.The Consortium of Health-Orientated Research in Transitioning Societies is a collaborative endeavor pooling data from birth cohorts in 5 low- and middle-income countries: Brazil, Guatemala, India, the Philippines, and South Africa.In India and Guatemala, birth weight was measured by research teams. In the Philippines, birth weight was measured by birth attendants using hanging scales for home births and was obtained from hospital records for hospital births. In Brazil and South Africa, birth weight was measured by birth attendants in hospitals and was extracted from the hospital birth records. In Guatemala, India, and the Philippines, birth length was measured by the research teams using portable length boards within 15 days of delivery. Birth length was not measured in Brazil or South Africa.GA was calculated based on the reported date of the last menstrual period (LMP) and the date of delivery. In Guatemala and India, ongoing surveillance was used to identify incident pregnancies. In Brazil and South Africa, the date of LMP was extracted from the medical records. In the Philippines, the date of LMP was reported by the mother at the time of recruitment; the Ballard score, based on clinical assessment of the newborn's neuromuscular and physical characteristics,We classified subjects born at <259 days post-LMP (37 completed weeks of gestation) as preterm, and those born at ≥294 or more days post-LMP (42 completed weeks) as postterm. We classified term and postterm infants as SGA if they were below the 10th percentile of the sex-specific birth weight for GA distribution,z-scores using the current World Health Organization reference population data.Each of the 5 study cohorts collected anthropometric measures (height and weight) at study-specific intervals.In all 5 cohorts, standing height was measured using a fixed stadiometer and weight was measured with a portable scale. Blood pressure was measured using mercury sphygmomanometers in the Philippines and digital devices in the other cohorts . Appropriate cuff sizes were used, and measurements were made with the subjects seated after a 5- to 10-minute rest. Field protocols differed across the cohorts; for Brazil, India, and South Africa, the mean of 2 measurements  was used; for the Philippines and Guatemala, 3 measures were averaged. In all cohorts but Brazil, the research team collected fasting blood samples to determine glucose levels; in Brazil, random blood samples were obtained, and values were adjusted for the time since the last meal.Body mass index (BMI) was calculated as weight in kilograms divided by height squared in meters. Prehypertension or hypertension was defined as systolic blood pressure ≥120 mm Hg or diastolic blood pressure ≥70 mm Hg, or the use of antihypertensive medication (reported by <0.5% of participants).www.jpeds.com). For analyses focusing on weight or BMI, we excluded 5 individuals with missing data; for blood pressure, we excluded 110 individuals with missing data or who were pregnant; for glucose, we excluded 772 individuals with missing data or who were pregnant; and for schooling, we excluded 65 individuals with missing data.Our study population comprised the 4518 individuals  for whom data were available for sex, GA and weight at birth, length at age 12 and 24 months and in mid-childhood, and adult height. Study exclusions are summarized in We computed descriptive statistics by site for the key exposure and outcome variables. We compared adult height, BMI, blood pressure, glucose level, and schooling attainment among groups using ANOVA, and compared prevalences using categorical approaches. Specifically, we compared outcomes among 4 birth categories: those born preterm, those born term-SGA, those born term-AGA, and those born term-LGA. The latter 3 groups also included those born postterm.We assessed patterns of growth from birth to adulthood by computing the changes in length within each period of childhood, and compared these data across the 3 birth categories. To assess whether the patterns of childhood growth were differentially related to adult measures across birth status categories, we used conditional length measures to control for the tendency of growth to track over time.Because site- and sex-stratified estimates were similar, we conducted site- and sex-pooled analyses. We compared models for fasting glucose and IFG with and without adjustment for adult BMI; there were no meaningful differences, and thus only the unadjusted models are presented. All analyses were performed with SAS version 9.3 .www.jpeds.com). There were only small differences in period-specific growth increments across birth status categories  thinner, those born term-SGA were 0.78 kg/m2  thinner, and those born term-LGA had BMI values 0.56 kg/m2  higher than those born term-AGA. Blood pressure and glucose did not differ significantly by birth category. Schooling attainment was lower in those born preterm and term-SGA compared with those born term-AGA. Patterns for prehypertension/hypertension, for IFG/diabetes, and for completion of secondary school were consistent with the associations for the continuous variables. Further adjustment for adult height in models for blood pressure and prehypertension/hypertension did not change the estimates substantively. There was no evidence of heterogeneity of estimates across the cohorts, except those for schooling (www.jpeds.com).Compared with adults born term-AGA, those born preterm were 1.11 cm shorter , those born term-SGA were 2.35 cm shorter  and those born term-LGA were 2.88 cm taller  . Adults P < .05; P < .05). Fasting glucose was not significantly associated with birth weight or conditional lengths in any group. Birth weight was more strongly associated with schooling among those born term-SGA than the other birth categories (P < .05). Postnatal growth was associated with schooling attainment in all 3 birth categories, with no evidence of heterogeneity. Patterns of association for the binary variables were consistent with those derived from the continuous measures.Birth weight and conditional length at 12 months, 24 months, and mid-childhood were each positively associated with adult height, with similar estimates across birth categories, except that the coefficient for conditional length at 12 months was stronger for the preterm group compared with the other groups P < .05; . For sysWe have described patterns of association relating status at birth and postnatal growth patterns simultaneously to several important adult outcomes in 5 prospective birth cohorts in low- and middle-income countries. Both preterm birth and term-SGA birth were associated with adult shortness, thinness, and reduced school attainment, but little difference by birth status in adult blood pressure or glucose levels. Our core dataset included more than 4500 individuals, although not all provided data for all outcomes. The 5 cohorts represent a range of socioeconomic and political backgrounds. We observed little heterogeneity in postnatal growth patterns by birth status. These results extend our previous workCountry-level data for prematurity are not available for most low- and middle-income countires. Recent estimates of the prevalence of preterm births are 16.5% for Bangladesh, 12.3% for Gambia, and 23.1% for Nepal, compared with ∼15% in Brazil and ∼6.0% in the United Kingdom and Sweden,In high-income countries, most preterm infants catch up with term infants in weight and height by age 12-24 months,Our results are important because preterm births and fetal and postnatal growth restriction are common; indeed, the conflation of preterm births and SGA births may be greater in low- and middle-income countries compared with high-income countries.We were able to include data for 21.7% of the original birth cohorts in our analysis. The primary reasons for attrition were a lack of data on adult height  and missing data at 12 months . Because the reasons for attrition are not related to individual characteristics, we believe that our estimates are unlikely to be seriously biased. Because birth length was not recorded for Brazil or South Africa and was missing for some of the Guatemalan and Indian samples, we used birth weight to anchor our growth models. Birth length and birth weight correlated at 0.7, and for the 3 sites with both birth length and birth weight , the results were very similar regardless of the birth measure used. GA was estimated from the date of LMP, and ultrasound dating was not available in any of the communities at the time of field work. However, in Guatemala and India there was active surveillance of incident pregnancies, so misclassification of LMP is unlikely to have been large, and in the Philippines all low birth weight infants were examined using Ballard criteria to differentiate preterm births from term-SGA births. Ballard scores may overestimate GA in preterm infants compared with ultrasonography.Recent decades have brought major advances in the ability to ensure survival of preterm infants,Despite encouraging long-term reductions in the prevalence of stunting,We conclude that preterm or term-SGA birth is associated with shorter adult height and reduced schooling attainment in low- and middle-income countries. Increased postnatal growth is associated with gains in these outcomes, but not with increases in blood pressure or glucose level, regardless of birth status. These results are encouraging for programs seeking to improve child nutrition in the first 1000 days of life.


High rates of antenatal depression and preterm birth have been reported in Pakistan. Self reported maternal stress and depression have been associated with preterm birth; however findings are inconsistent. Cortisol is a biological marker of stress and depression, and its measurement may assist in understanding the influence of self reported maternal stress and depression on preterm birth.In a prospective cohort study pregnant women between 28 to 30 weeks of gestation from the Aga Khan Hospital for Women and Children completed the A-Z Stress Scale and the Centre for Epidemiology Studies Depression Scale to assess stress and depression respectively, and had a blood cortisol level drawn. Women were followed up after delivery to determine birth outcomes. Correlation coefficients and Wilcoxon rank sum test was used to assess relationship between preterm birth, stress, depression and cortisol. Logistic regression analysis was used to determine the key factors predictive of preterm birth.132 pregnant women participated of whom 125 pregnant women had both questionnaire and cortisol level data and an additional seven had questionnaire data only. Almost 20% of pregnant women  experienced a high level of stress and nearly twice as many  experienced depressive symptoms. The median of cortisol level was 27·40 ug/dl (IQR 22·5-34·2). The preterm birth rate was 11·4% (95% CI 6·5-18). There was no relationship between cortisol values and stress scale or depression. There was a significant positive relationship between maternal depression and stress. Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. Insufficient numbers of preterm births were available to warrant the development of a multivariable logistic regression model.Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. There was no relationship between stress, and depression, cortisol and preterm birth. There were high rates of stress and depression among this sample suggesting that there are missed opportunities to address mental health needs in the prenatal period. Improved methods of measurement are required to better understand the psychobiological basis of preterm birth. Preterm birth, defined as birth occurring prior to 37 completed weeks, is a worldwide health issue with a marked difference in prevalence between developed and developing countries -3. The gAntenatal depression is common during the second and third trimesters with a systematic review showing point estimates and 95% confidence intervals of 12·8% 10·7-14·8) and 12·0% 7·4-16·7), respectively [·7, respe-14·8 andThe etiologic contribution of psychosocial processes during pregnancy and preterm birth remain elusive as findings of studies examining the association between stress or depression and preterm birth have not been consistent. Although many studies demonstrate an association -15 otherStress and depression influence the hypothalamic-pituitary-adrenal (HPA) axis whereby corticotrophin-releasing-hormone (CRH) is secreted by the hypothalamus which in turn stimulates the pituitary gland to secrete adrenocorticotrophic hormone (ACTH). ACTH stimulates the adrenal cortex to secrete cortisol hormone and the adrenal medulla to secrete norepinephrine and epinephrine. Increased cortisol levels further signal the hypothalamus and pituitary gland in a negative feedback loop to decrease CRH production. However, in depressed patients the negative feedback loop malfunctions resulting in excess production of CRH; hence cortisol . The incStudies undertaken in South Asia have examined the contribution of maternal factors like maternal education, age, parity, birth interval, and antenatal visit on preterm birth -24. HoweIn this prospective cohort study, pregnant women (28 to 30 weeks gestation) completed the A-Z stress tool and the Centre for Epidemiology Studies Depression (CESD) scale, and provided blood sample for cortisol analysis after providing informed consent either in Urdu or English. The blood was drawn by a trained phlebotomist after the questionnaire was completed. Lab work was undertaken between 10:00 a.m. to 1:00 p.m. for consistency and in an attempt to control for diurnal variation in cortisol. Women were followed up after delivery to determine the birth outcome (preterm or term). Confidentiality and anonymity was maintained by using unique identification numbers on both the data collection tools and label for the blood sample. The study was approved by the Ethical Review Committee of the AKUH.Between April and May 2010 all eligible pregnant women who attended the antenatal clinics at the two centres of the Aga Khan Hospital for Women and Children (AKHWC), Kharadar and Karimabad Karachi, Pakistan were approached in the waiting area by the nurse in-charge and invited to participate in the study. Women willing to participate were referred to the researcher (KS) or a trained research assistant. The centres provide services to diverse communities which enabled recruitment of a heterogeneous sample of pregnant women. The laboratory services are provided with the collaboration of Aga Khan University Hospital (AKUH), Karachi.We enrolled all consenting pregnant women between 18 to 40 years of age who were 28 to 30 weeks gestation based on last menstrual period and planned to deliver in the same hospital. If women self-reported medical illnesses such as diabetes mellitus, thyroid disorder, chronic renal or heart disease, or uterine and cervical abnormality, or antidepressants or other psychotropic drug use during pregnancy they were excluded from the study. Women were excluded from the study if they did not deliver at the AKHWC.th quartile and those whose scores were below the 75th quartiles as having high stress levels and not high stress levels, respectively.Stress was assessed with the A-Z stress tool. The A-Z stress scale which was developed by one of the researchers (AK) and includes 30 items for which responses were captured using "yes/no" format. Construct validity, test-retest reliability and inter-rater reliability, has been established for this tool. Cronbach alpha was 0·82 for the 30 items and the item-total correlations were reported to be 0·2 to 0·8, respectively . The iteDepression in pregnant women was assessed by a multi-cultural validated 20-item CESD Scale. The scores can range from 0 to 60 with a cut off point of 16 and higher suggesting symptoms of depression. The scale has adequate test/retest reliability  and high internal consistency  .Cortisol was measured in blood serum using the AxSYM assay system which employs Fluorescence Polarization Immunoassay (FPIA) technology to quantify the level of cortisol. The sensitivity of this system is reported to be equal to or less than 1.1 ug/dL . Salivary cortisol is a non-invasive procedure and a better way to measure cortisol than other measure particularly for rapid sampling ,27,28; hPregnancy outcome and delivery information including gestational age at birth was obtained from the medical records and the postpartum wards of both the centres. Preterm birth was defined as birth occurring prior to 37 completed weeks while term birth was defined as birth between 37 and 42 weeks.The sample size was calculated based on a secondary hypothesis related to depression, as this required the largest sample size. An 18% difference in depression among mothers who deliver at term compared to mothers who deliver preterm was reported by Field et al.,  and at aData were entered in EPI Info3·5·1 and then analyzed using the Statistical Package for Social Sciences (SPSS) version 16·0. Descriptive statistics were used to compare the characteristics of participants by not high stress/high stress, non-depressed and depressed and term/preterm birth status. For categorical/ordinal level variables frequencies and percentages were calculated. Fisher's exact test was used to identify group differences when comparing categorical variable. The Mann Whitney U test was used to identify group differences when comparing ordinal level data or a continuous variable when there was evidence against normality.The Spearman's correlation coefficient was used to examine the relationship between ordinal level variables. The Wilcoxon rank sum test was used to determine the relationship between independent samples when assumptions of normality were violated. Pearson's correlation coefficient was used to determine the linear relationship between maternal stress and depression during pregnancy and preterm birth . Logistic regression analysis was used to determine factors predictive of preterm birth. In addition to stress, depression and cortisol level, variables considered were demographics , behavioral characteristics , and pregnancy characteristics . Variables were considered potential predictors if p was < 0·10 for the likelihood ratio statistic from the univariable logistic model. A multivariable model was not developed as the number of preterm births was not large enough  .187 pregnant women were assessed for eligibility of which 172 (91·9%) were eligible. 125 pregnant women completed both the questionnaire and a cortisol level. Seven women provided only questionnaire data (n = 132). Hence, data from 125 pregnant women contributed to the analysis when relationships included cortisol, and data from 132 pregnant women contributed to the analysis when the relationship did not include cortisol . Figure p = 0·81) or between maternal depression and cortisol levels . There was no significant difference  in cortisol levels of mothers with preterm infants  and those with full term infants . There was no significant difference between maternal stress during pregnancy and preterm birth  or between maternal depression during pregnancy and preterm birth . A significant positive relationship was identified between stress and depression as evident from the r value of 0·54 and p < 0·001, stress  or depression  were associated with preterm birth. Preterm birth was associated higher parity, past delivery of a male infant, and higher levels of paternal education  and depression (40·9%) in pregnant Pakistani women in this study are high. Our findings are consistent with a rate of 39·4% among Pakistani women residing in Karachi  but loweThe median cortisol value was 27·40 ug/dl (IQ = 22·5- 34·2 ug/dl) which is higher than values reported in the literature. For instance, Hobel et al.  measuredWe identified a strong positive significant relationship between maternal stress and depression. The findings of this study therefore, support Ruiz and Avant's  construcWe found no relationship between maternal stress and cortisol level. Ruiz and Avant's model of maternal prenatal stress  suggestsThe findings of this study may be explained by allostatic load which distinguishes between acute and chronic stress and suggests how chronic stress affects the hormonal, immune, and physiologic response in the body . In situWe found no relationship between maternal depression and cortisol levels, which is in contrast to Ruiz and Avant's  model anThere was no relationship between cortisol levels and preterm birth. Our findings are similar to Ruiz et al.  who alsoOur study did not reveal any relationship between cortisol, stress and depression assessed at 28 to 30 weeks. However, studies ,34,41,42In our study increased parity was identified as a risk factor for preterm birth, and it has been proposed that physiologic risk factors common in multiparous women  may partly explain the higher risk of preterm birth . The litWe found that preterm birth was associated with prior delivery of a male child. The proportion of male infants is higher among preterm births and this pattern is evident in different populations . PakistaWe found that higher levels of paternal education reduced the risk of preterm birth. Education has been used as a proxy for socioeconomic status . StudiesIn our study women with medical or obstetrical histories were excluded from this study, and limitations in medical records and poor health literacy of the mothers precluded classification into the other two subtypes of preterm birth - spontaneous preterm labour without premature rupture of chorioamniotic membranes (PROM), and preterm PROM with vaginal or caesarean section delivery ,56. ExamIn the present study, pregnant women were recruited from the AKHWC, which are private clinics. The sample was not completely representative of women in Karachi, Pakistan, thereby impacting the external validity of the study. Of the 187 women, 81 (54%) had an ultrasound done in the first trimester and 55 (36·7%) had an ultrasound in the second trimester; however all pregnant women had their LMP recorded in their patient chart. Although earlier ultrasound  provides better pregnancy dating than ultrasound in the second trimester , to ensuA longitudinal cohort study, with multiple measures of stress, depression, and cortisol levels, as well as a measures of anxiety and other stress hormone biomarkers may add new knowledge and enhance our understanding about the relationship between stress, depression, anxiety, cortisol levels and preterm birth. Lastly, in the present study, only 15 women experienced preterm birth which should be considered in interpreting the findings.Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. There was no relationship between maternal stress and depression, cortisol and preterm birth when assessed cross sectionally at a single point in gestation. A larger longitudinal cohort study, with multiple measures of stress, depression, and cortisol levels, as well as a measure of anxiety may add new knowledge and enhance our understanding about the relationship between stress, depression, anxiety, cortisol levels and preterm birth. There were high rates of stress and depression among this sample suggesting that there are missed opportunities to address mental health needs in the prenatal period in Pakistan. Improved methods of measurement are required to better understand the psychobiological basis of preterm birth.HPA: hypothalamic-pituitary-adrenal; CRH: corticotrophin-releasing-hormone; ACTH: adrenocorticotrophic hormone; AKHWC: Aga Khan Hospital for Women and Children; AKUH: Aga Khan University Hospital; SPSS: statistical package for social sciences.The authors declare that they have no competing interests.The work presented here was undertaken in collaboration with all authors. KS was a graduate student who undertook this work to fulfill the requirements for Masters of Science in Nursing. SP was the supervisor who was actively involved in all phases of the study including original idea, design, data analysis, interpretation and writing the report. ST, AK and SK gave ongoing feedback and suggestions during both the proposal phase and the conduct of the research. They have reviewed and edited the report. MSR guided the statistical analysis and data interpretation and contributed to the write up of this section. All authors have reviewed and approved the final version of the report.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/11/88/prepub


A new study of birth records from the area shows a decreased average birth weight among infants carried in utero during the wildfires with that of infants who were either born before or conceived after the wildfires. They also compared birth weights of infants exposed during the first, second, and third trimesters of pregnancy.Chronic maternal exposure to ambient particulate matter (PM) and indoor biomass smoke during pregnancy has been linked to decreased infant birth weight, although similar effects attributable to wildfire smoke have been little studied. In this study, researchers analyzed 886,034 birth records of babies delivered between 2001 and 2005 in the South Coast Air Basin, an area that overlaps the wildfire-affected regions. They compared the average birth weight of infants carried After adjusting for infant sex, gestational age at birth, and other factors known to influence birth weight, the researchers found that exposed infants weighed an average of 6.1 g (0.2 oz) less at birth than unexposed infants. Infants exposed during the second trimester showed the largest average reduction, at 9.7 g. Infants exposed during the third trimester showed an average reduction of 7.0 g, and those exposed during the first trimester showed an average reduction of 3.3 g . The trends were corroborated by a sensitivity analysis that compared pregnant mothers according to whether the air-pollution monitor nearest their residence recorded high or low PM levels during the wildfires.The small reductions in birth weight attributed to the wildfires are unlikely to have serious health effects in any given individual. However, wildfires are predicted to increase in frequency and severity as climate change progresses, and the researchers note that the proportion of low-birth-weight babies—those weighing less than 2,500 g (5.5 lb) at birth—could rise as a result. This could have important populationwide repercussions because these babies are at increased risk for a variety of poor health outcomes.PM and carbon monoxide are among pollutants released by wildfires that could plausibly contribute to the birth-weight decrease. However, the researchers note that other pathways are possible and worthy of investigation, among them the increased stress that living through a wildfire may place on pregnant women.


Several birth characteristics are associated with high mortality risk: very young or old mothers, short birth intervals and high birth order. One justification for family planning programs is the health benefits associated with better spacing and timing of births. This study examines the extent to which the prevalence of these risk factors changes as a country transitions from high to low fertility.We use data from 194 national surveys to examine both cross section and within-country variation in these risk factors as they relate to the total fertility rate.Declines in the total fertility rate are associated with large declines in the proportion of high order births, those to mothers over the age of 34 and those with multiple risk factors; as well as to increasing proportions of first order births. There is little change in the proportion of births with short birth intervals except in sub-Saharan Africa. The use of family planning is strongly associated with fertility declines.The proportion of second and higher order births with demographic risk factors declines substantially as fertility declines. This creates a potential for reducing child mortality rates. Some of the reduction comes from modifying the birth interval distribution or by bringing maternal age at the time of birth into the ‘safe’ range of 18-35 years, and some comes from the actual elimination of births that would have a high mortality risk (high parity births). A key point in advocacy for family planning is ‘family planning saves lives’. It is clear that increasing rates of family planning use lead to reductions in fertility and the number of births. The reduction in the number of births leads to fewer maternal deaths, since women are exposed less often to the risks of child bearing. The number of child deaths will also decline because of a smaller number of children exposed to the risk of mortality. Also it has long been recognized that changes in the demographic characteristics of births are associated with changes in child mortality rates . The chaResearch is ongoing to better understand the causal pathways that lead to this association between contraceptive prevalence and mortality rates. There could be a direct causal relationship arising from maternal depletion or competition among children for resources. Or there could be a relative weak effect mixed with an association that arises because both the proportion of births that are high risk and child mortality rates are related to other factors, such as poverty, access to services or individual characteristics. Other papers in this Supplement explore these topics. This paper focuses on one aspect of this question, the relationship between rising contraceptive use and the proportion of births that are high risk. In other words, as countries transition from very low levels of contraceptive use and high fertility to high levels of contraceptive use and low fertility, how much change do we expect to see in the proportion of births with short birth intervals or high birth order or to mothers who are very young or old?We use both cross section comparisons and time series comparisons to examine the relationships between contraceptive prevalence and the distribution of births by risk factor. Although we are ultimately interested in the relationship between contraceptive use and high risk births, contraception is only one factor that affects fertility behavior. The total fertility rate (TFR) is also determined by the proportion of women 15-49 who are in union, the duration of postpartum insusceptibility, sterility and abortion ,7. ThereData on the distribution of births by risk factor are available from household surveys conducted by the Demographic and Health Survey (DHS) Project since the 1980s. For this analysis we use data from 194 surveys for 80 countries. The indicators used include the following:• TFR, total fertility rate, for the three years preceding the survey• CPR, contraceptive prevalence, percentage of currently married women currently using any form of contraception including traditional methods, and by method used• Marriage, percentage of women 15-49 currently married or living together• PPI, median duration (in months) of postpartum insusceptibility following births in the three years preceding the survey. Postpartum insusceptibility is the period after a birth when a woman is not exposed to the risk of pregnancy because of postpartum abstinence or postpartum amenorrhea.• Birth distribution, the percentage of children born in the five years preceding the survey by risk factor○ Not in any high risk category.○ First birth to mothers 18-34 years of age.○ Mother’s age < 18 years.○ Mother’s age > 34 years.○ Birth interval < 24 months.○ Birth order > 3.○ In any avoidable high risk category.It would be ideal if we had data from a large number of countries showing the change in the distribution of births by risk factor as fertility declines from high levels to low levels. Unfortunately, the most complete source of information on this topic, the Demographic and Health Surveys, did not start early enough to capture the entire fertility transition for countries that currently have low fertility. Using cross sectional data we can explore the entire range from TFR of 7 down to 2, but the results can be affected by regional differences in fertility as well as trends within countries. We partially address this issue by including multiple surveys from the same country in the cross national data set. We also present data on changes in TFR and changes in the distribution of births within countries to reinforce the conclusions from the cross section analysis.Across all 194 surveys, there is considerable variation in the distribution of births by risk factor as shown in Table The distribution of births varies by level of TFR. Figure Figure Figures Figure The relationship between CPR and risky births is similar to that with TFR but weaker. The correlation with high order births is 0.68 versus 0.87 with TFR; for mother’s age over 34 it is 0.28 compared to 0.37 with TFR. The correlations between CPR and birth interval and young age at birth are similarly low, 0.05 and 0.06.These cross section comparisons with TFR might be misleading since the surveys with the lowest levels of TFR are all from countries in Eastern Europe, Asia and South America while those with the highest levels of TFR are mostly from Sub-Saharan Africa. For Sub-Saharan Africa alone, the correlation with high order births remains strong at 0.73 compared to 0.87 for all surveys. Notably, the correlation with birth interval increases to 0.45 for Sub-Saharan Africa compared to just 0.05 for all countries. For mother’s age the correlations are only 0.01 for age less than 18 and 0.001 for age greater than 34.The above cross section comparisons combine differences between countries with differences between surveys for the same country. Since most of the countries in this data set have more than one survey we can also compare changes in the distribution of births with changes in TFR. Figure The fertility rate is affected by a number of factors including contraceptive use, the proportion of women who are sexually active, postpartum infecundability, sterility and abortion. Here we examine each of these factors.There is a strong correlation between contraceptive prevalence and TFR. For this data set the R2 for a linear trend is 0.73. The correlation is considerably weaker (0.60) when contraceptive prevalence is limited to modern methods only, indicating that traditional methods do play a role in regulating fertility.For this analysis we are concerned more with changes than absolute levels so we also compare changes in contraceptive prevalence with changes in TFR. Figure Over the course of the fertility transition as TFR drops from 7-8 to 2 or less, contraceptive prevalence increases from less than 10% to almost 80% in the cross sectional analysis. Changes in the other proximate determinants of fertility are much smaller. The median duration of postpartum insusceptibility drops from 15 months for surveys with TFR 6 and above to about 5 months at the lowest levels of TFR. This change would lead to shorter birth intervals and higher TFR if it were not associated with increasing levels of contraceptive use. The mean age at marriage rises from about 16 at high levels of TFR to about 20 at lower levels. This change alone would lead to somewhat lower fertility but the effect is not significant when the effects of CPR are also included.modern contraceptive use to nearly zero at very high levels (as contraception replaces abortion for limiting the number of births) but has the opposite relationship to the prevalence of traditional methods of family planning (as abortion is used in the case of method failure) [Changes in abortion rates can have a significant effect on TFR. For countries with data the total abortion rate  drops from 3-4 at low levels of failure) . The proAcross all 194 surveys there is considerable variation in risk ratios for child mortality but the data confirm that these demographic factors are associated with higher risk of child mortality as shown in Table The distribution of high risk births changes dramatically as countries transition from high fertility to low fertility. The most striking changes are a reduction in births with multiple risk factors and those with high parity. This is a natural part of the transition as average number of births per woman cannot decline significantly without a reduction in the proportion of high order births.Changes in the proportion of births at maternal age 35 and above are also associated with declines in the TFR as women complete their child bearing at younger ages. There is little change in the proportion of births to mothers below the age of 18 as TFR declines. Across all countries there is not much change in the percentage of births with short birth intervals either, but this does occur in Sub-Saharan Africa. That may reflect the greater focus in the region on birth spacing as a rationale for family planning.There is a strong correlation between contraceptive prevalence and TFR. Thus, as CPR rises TFR falls and the distribution of births by risk factor changes. CPR is the major factor associated with changes in TFR. Changes in the proportion married and post partum insusceptibility are much smaller and less directly associated with TFR changes. Changes in abortion rates may also affect TFR but the data are not good enough to determine the exact relationship. One would expect that abortion would reduce the proportion of births with short intervals and reduce the number of high parity births but the degree of the effect is not clear.It is clear from these data that as contraceptive prevalence increases TFR falls and a smaller percentage of births have one or more of these four risk factors that are associated with high child mortality. This creates a potential for reducing child mortality rates. Some of the reduction comes from modifying the birth interval distribution or by bringing maternal age at the time of birth into the ‘safe’ range of 18-35 years, and some comes from the actual elimination of births that would have a high mortality risk (high parity births).This analysis does not explain the mechanisms by which these risk factors lead to higher mortality rates. But whatever the mechanisms are it seems evident that the expansion of the use of family planning is key to achieving a healthier distribution of births.The authors declare that they have no competing interests.JS and JR jointly conceived the paper and conducted the analysis. JS wrote the first draft of the paper. JS and JR reviewed and approved the final draft.


A recent meta-analysis showed no relationships between light to moderate alcohol consumption during pregnancy and the risk of low birth weight (LBW), preterm birth (PTB), or small-for-gestational-age (SGA). Here, we present the first epidemiological study on this topic in Japan.Study subjects were 1565 Japanese mothers with singleton pregnancies and the babies born from these pregnancies. Alcohol consumption during pregnancy was assessed using a self-administered diet history questionnaire. Alcohol consumption during pregnancy was classified into three categories .P for trend = 0.03). No significant relationships were observed between maternal alcohol consumption during pregnancy and the risk of LBW or SGA, and there was no material association between maternal alcohol consumption during pregnancy and birth weight.The mean birth weight of the babies was 3006.3 g. 7.7% were classified as LBW, 4.0% as PTB, and 7.8% as SGA. The range of maternal alcohol consumption during pregnancy was 0.0 to 11.7 g per day: 1356 (86.7%) mothers were abstainers and the 95th percentile value was 0.84 g per day. Compared with abstinence, alcohol consumption of 1.0 g or more per day during pregnancy was significantly associated with an increased risk of PTB with a significant positive linear trend: the adjusted OR for PTB associated with maternal alcohol consumption of 1.0 g or more per day was 2.58 (95% CI: 1.004 - 5.80, This is the first study in Japan to show that maternal alcohol consumption during pregnancy of 1.0 g or more per day was significantly positively associated with the risk of PTB, but not LBW or SGA. A systematic review by Henderson et al. found no convincing evidence that maternal alcohol consumption during pregnancy at low to moderate levels has adverse effects on miscarriage, stillbirth, intrauterine growth restriction, prematurity, birth weight, small-for-gestational-age (SGA), and birth defects including fetal alcohol syndrome . A recenThe KOMCHS is a prospective prebirth cohort study. Details of the baseline survey of the KOMCHS have been described elsewhere . EligiblIn each survey, a self-administered questionnaire was used. Participants filled out these questionnaires and mailed them to the data management center at the time of each survey. Research technicians completed missing or illogical data by telephone interview.The first part of the first questionnaire at baseline elicited information about maternal age; region of residence; number of children; family structure; maternal education; and maternal employment status. Women were classified as unemployed if they were unemployed in both the year in which the questionnaire was completed and the preceding year. The second part of the first questionnaire was a semi-quantitative, comprehensive dietary history questionnaire (DHQ) that assessed dietary habits during the month preceding the completion of the questionnaire ,14. EstiIn Japan, generally, an obstetrician’s estimate of gestational age at the time of delivery is based on early ultrasound examination and/or the first day of the last menstrual period, and birth weight is measured immediately after birth. Data such as birth weight and gestational age at birth are recorded by staff at the birth hospital or clinic in a booklet called the Maternal and Child Health Handbook. A copy of this booklet is provided to every pregnant woman by the municipality in which she resides at the start of her pregnancy; it is used to record data pertaining to prenatal checkups, postnatal health condition of both mother and baby, and growth of the child.The second self-administered questionnaire elicited information on active maternal smoking status in the first (≤ 15 weeks’ gestation), second (16–27 weeks’ gestation), and third (≥ 28 weeks’ gestation) trimesters; gestational age at birth; birth weight; and baby’s gender. With regard to gestational age at birth and birth weight, mothers were advised to refer to their Maternal and Child Health Handbook before filling in our questionnaire.LBW was defined as a birth weight less than 2500 g. PTB was defined as a birth occurring at a gestational age of less than 37 weeks. SGA was defined as a birth weight below the 10th percentile of the Japanese neonatal anthropometric norms for babies of the same gestational age, gender, and parity published by Itabashi et al. in 2010 . These nMaternal age at the time of the first questionnaire; region of residence; number of children; family structure; maternal education; maternal employment; body mass index; maternal smoking during pregnancy; gestational age at birth; and baby’s gender were selected as a priori potential confounding factors; however, gestational age at birth was removed when associations with the risk of LBW and PTB were examined. Marital status was not taken into consideration because 96.3% of the mothers lived with their husbands and there was only one single mother in the study. Alcohol consumption during pregnancy was classified into three categories ; region of residence into three ; number of children previously born to the same mother into three ; family structure into two (nuclear and extended); maternal education into three ; maternal employment into two (yes and no); and maternal smoking during pregnancy into four . Maternal age, body mass index, and gestational age at birth were used as continuous variables.Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for birth outcomes in relation to maternal alcohol consumption during pregnancy were calculated through multiple logistic regression analysis. Analysis of covariance was used to calculate adjusted means of birth weights according to maternal alcohol consumption during pregnancy with allowance for confounding factors. Trends of an association were assessed with a multiple logistic regression model or a multiple linear regression analysis assigning consecutive integers to the categories of alcohol consumption. The interaction was tested using a term of the product of two variables in a multiple logistic regression model. All computations were performed using the SAS software package version 9.2 .Among the 1565 mother-child pairs, maternal mean age at baseline was 31.3 years (Table Table P for trend = 0.03). No significant relationships were observed between maternal alcohol consumption during pregnancy and the risk of LBW or SGA. Also, there was no material association between maternal alcohol consumption during pregnancy and birth weight.Table P for trend = 0.27). In a subgroup of 138 women who had smoked during pregnancy, on the other hand, the corresponding figures were 4.76 (95% CI: 0.47 - 40.13) and 15.11 (2.22 - 142.12), respectively (P for trend = 0.004). There was no significant interaction between maternal alcohol consumption of 1.0 g or more per day and maternal smoking during pregnancy with respect to the risk of PTB (P for interaction = 0.27).In a subgroup restricted to 1427 women who had never smoked during pregnancy, the adjusted ORs for PTB for maternal alcohol consumption of less than 1.0 g and 1.0 g or more per day during pregnancy were 1.47 (95% CI: 0.55 - 3.31) and 1.73 (95% CI: 0.41 - 5.08), respectively  in women who had completed the baseline survey between the 5th and 17th weeks of pregnancy and 3.23  in women who had completed the baseline survey between the 18th and 39th weeks of pregnancy. In women who had completed the baseline survey prior to the 18th week of pregnancy, the proportion of drinkers might be underestimated; in that case, the association between maternal alcohol consumption and PTB might be attenuated. Any non-differential exposure misclassification would bias the results toward the null. Moreover, information on the timing of alcohol use and of certain consumption patterns such as binge drinking was not available in the present study.This study has some methodological limitations that should be considered. Data on alcohol consumption were derived from the DHQ, which could only approximate consumption and was designed to assess consumption for one month prior to completion of the questionnaire. In addition, alcohol consumption assessment was carried out anywhere from the 5th to the 39th week of pregnancy. When subjects were divided into two groups according to gestation at baseline, the proportion of drinkers was 11.4% in women who had completed the baseline survey between the 5th and 17th weeks of pregnancy (n = 789) and 15.3% in women who had completed the baseline survey between the 18th and 39th weeks of pregnancy (n = 776). The adjusted OR for PTB for maternal alcohol consumption of 1.0 g or more per day during pregnancy was 2.47 (95% CI: 0.67 - 7.23, In the baseline survey, we could not estimate the participation rate because we do not have exact figures for the number of pregnant women who were provided with a set of leaflets explaining the KOMCHS, an application form, and a self-addressed and stamped return envelope by the 423 collaborating obstetric hospitals. Nevertheless, the participation rate must have been fairly low, given that the present study used data from only 970 pregnant women who lived in Fukuoka Prefecture, while, according to the government of Fukuoka Prefecture, the number of childbirths was 46,393 in 2007 and 46,695 in 2008. Furthermore, our subjects were probably not representative of Japanese women in the general population. For example, a population census conducted in 2000 in Fukuoka Prefecture found that the percentages of women aged 30 to 34 years with < 13, 13–14, ≥ 15, and an unknown number of years of education were 52.0%, 31.5%, 11.8%, and 4.8%, respectively . The corThe current study did not have substantial statistical power although a significant association was detected. According to the statistical power calculation using QUANTO version 1.2 , our samIn our population, a significant positive association was found between maternal smoking during pregnancy and PTB . The posA recent meta-analysis regarding maternal alcohol consumption and birth outcomes did not include epidemiological studies conducted in Asian countries . To our CI: Confidence interval; DHQ: Diet history questionnaire; KOMCHS: Kyushu Okinawa Maternal and Child Health Study; LBW: Low birth weight; OR: Odds ratio; PTB: Preterm birth; SGA: Small-for-gestational-age.All authors declare that they have no competing interests.YM, KT, and MA contributed to the study concept and design and the acquisition of data. HO and SS were responsible for the estimation of dietary factors. YM was responsible for the analysis and interpretation of data and the drafting of the manuscript. All authors participated in critically revising the manuscript and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/14/79/prepub


The impact of anti-hypertensive treatment on fetus was unclear, and hence, remains controversial. We set out in this study to estimate the prevalence of adverse pregnancy outcomes, including low birth weight, preterm delivery and small for gestational age amongst women with chronic hypertension, and to determine whether the use of anti-hypertensive drugs increases the risk of such adverse pregnancy outcomes.A total of 2,727 hypertension mothers and 8,181 matched controls were identified from the population-based cohort. These hypertension women were divided into seven sub-groups according to different types of prescribed anti-hypertensive drugs. Multivariable logistic regressions were conducted to estimate the risk of low birth weight, preterm birth and small for gestational age. Increased risk of low birth weight , preterm birth  and small for gestational age  were all discernible within the hypertension group after adjusting for potential confounding factors. The increased ORs were found to differ with different types of anti-hypertensive drugs. Women who received vasodilators were associated with the highest risk of low birth weight , preterm birth (OR = 2.92 95% CI = 2.06–4.15) and small for gestational age .This finding is important for practitioners, because it indicates the need for caution while considering the administration of anti-hypertensive drugs to pregnant women. These observations require confirmation in further studies that can better adjust for the severity of the underlying HTN. Chronic hypertension, which is found to occur in approximately one to three per cent of all pregnancies, is one of the leading causes of maternal mortality Some of the prior studies have demonstrated that the maternal use of anti-hypertensive treatment could improve pregnancy outcomes, with one particular study indicating that early anti-hypertensive treatment was associated with a reduced probability of premature delivery On the other hand, however, there are also several studies in which it is argued that such use of anti-hypertensive treatment can lead to adverse pregnancy outcomes; for example, one meta-analysis revealed that anti-hypertensive treatment may result in fetal growth restriction, and ultimately, in low-birth-weight (LBW) babies A higher risk of premature delivery, LBW and SGA infants amongst women receiving anti-hypertensive treatment has also been observed on data from the Swedish Medical Birth Registry Hampered by inadequate sample size, none of the prior studies have been able to provide a reliable estimation of the risk in having preterm, LBW or SGA births between different types of anti-hypertensive treatment.In this study, we carry out a population-based cohort to address these undetermined issues, retrospectively. Our primary aim is to explore the association between pregnancy outcomes and maternal use of anti-hypertensive treatment, including different types of drugs, during the course of their pregnancy.The data examined in the present study are obtained from two national databases, the National Health Insurance Research Dataset (NHIRD) and the birth certificate registry. The NHIRD covers over 98 per cent of Taiwan’s 23 million citizens and contains comprehensive registration files and original claims data.The birth certificate registry, obtained from the Department of Health in Taiwan, contains birthdates of both infants and parents, as well as details on gestational weeks at birth, birth weight, gender, parity, place of birth, and parental educational level. Since the registration of all births is mandatory in Taiwan, the birth certificate data is considered to be extremely accurate and comprehensive.The information contained within the NHIRD and the birth certificate registry is linked by unique personal identification numbers for the mothers and infants. All personal identifiers are encrypted by the Bureau of National Health Insurance before being released to researchers. Whilst the NHIRD consists of de-identified secondary data released to the public for research purposes, this study is exempt from a full review by the Internal Review Board.Our study covers the period from 1 January 2005 to 31 December 2005, from which we examined a population-based cohort comprising of all pregnant women in Taiwan. If any woman had more than one pregnancy during the study period, only the first pregnancy was considered for analysis and only singletons were included. The final sample comprised of a total of 218,781 mothers and 218,781 infants.With considering that the presence of pre-eclampsia could be a major intermediary in the pathway between hypertension and preterm birth, we excluded 2,721 women diagnosed with pre-eclampsia (ICD-9-CM codes 642.5 and 642.6) and women diagnosed with gestational HTN (ICD-9-CM codes 642). Pregnant women who had been diagnosed as chronic hypertension (HTN) prior to their pregnancy were identified as the HTN group , with the definition of chronic HTN being based upon the presence of ICD-9-CM codes 401–405 at either outpatient diagnosis or inpatient discharge diagnosis.Although new data in the literature suggested that the teratogenicity of angiotensin-converting-enzyme (ACE) inhibitors is not larger than that of other antihypertensive drugs The HTN group was further divided into seven sub-groups in order to facilitate our examination of the impact on different types of anti-hypertensive drugs. One of these sub-groups was an untreated group (comprising of those within the HTN group who had not used any anti-hypertensive drugs); the remainder were separated into six sub-groups according to the different types of prescribed anti-hypertensive drugs used.α agonists, beta-blockers (BBs), combined α and BBs, calcium channels blockers, diuretics and vasodilators. The drug group made up of combined <alpha> agonists and <beta> blockers means that the drug blocked the binding to both <alpha> and <beta>receptors, for example, carvedilol and labetalol. Women who used more than one type of anti-hypertensive drugs were excluded from the analysis.Data on anti-hypertensive drugs use come from NHIRD, which consisted of all claims data during pregnancy. Among HTN women, exposure to anti-hypertensive drugs was calculated from the date of having pregnancy to the date of giving birth. The date of having pregnancy means the conception date. The definition of drug-treated hypertension was made according to the days of prescribed anti-hypertensive treatment. Thus, in order to be considered as having undergone anti-hypertensive treatment, HTN women must have received a prescription of an anti-hypertensive drug for a period of at least 30 days during any time of their pregnancy. Anti-hypertensive drugs in this study are further categorized into six types, including central For each HTN woman, three women with no diagnosis of chronic HTN were randomly selected from the same cohort, matched with both age and year of delivery. As a result of this matching process, the study sample ultimately comprised of a total of 2,727 pregnant women with chronic HTN, and 8,181 pregnant women with no chronic HTN (as the comparison group) for analysis. The study flow diagram was shown in th percentile for gestational age and gender The focus in this study is on the three pregnancy outcomes of low birth weight (LBW), preterm birth and small for gestational age (SGA). The primary outcome variable, LBW, is defined in accordance with the World Health Organization criterion, as birth weight <2,500 gm. Our secondary outcome variable, preterm birth is defined as gestational duration <37 completed weeks, and the final outcome variable, SGA, is defined as <10Covariates which might potentially influence the outcomes of interest were also considered. Infant demographic characteristics included parity, whilst maternal characteristics included age, the highest educational level, and comorbid conditions, comprising of diabetes (ICD-9-CM codes 250), anemia (ICD-9-CM codes 280–289), coronary heart disease  and hyperlipidemia (ICD-9-CM codes 272).χ2) tests were used to compare the differences in demographic factors: (i) between the HTN and comparison groups, (ii) among the seven subgroups receiving various types of anti-hypertensive drugs and the untreated group, and (iii) among the five subgroups receiving various types of anti-hypertensive drugs. The effects of chronic HTN on pregnancy outcomes were examined with conditional logistic regression models to estimate the risk of LBW, preterm birth and SGA for women with chronic HTN. We then employed logistic regression analyses amongst the HTN group only to evaluate the risk of LBW, preterm birth and SGA associated with the use of various anti-hypertensive drugs, as compared to untreated women. The previously mentioned covariates, which might potentially confound the pregnancy outcomes, were also included in the multivariable analysis. Odds ratios (ORs) and 95 per cent confidence intervals (95% CIs) were given. The analyses were undertaken using SAS version 9.1 software , with a two-sided p-value of <0.05 being considered to be statistically significant.Pearson Chi-squared (p<0.001). Differences between the mothers with normotension and HTN, in terms of infant parity, and maternal education level, were also found to be statistically significant (p<0.001).The maternal and infant characteristics of the HTN group and the age-matched comparison group are compared in p<0.05), but not for infant gender. Similar results were shown in the additional chi-square test for comparison between the six sub-groups in the HTN.p<0.001). Increased risk of LBW , preterm birth  and SGA  were also discernible amongst HTN women.The distribution and odds ratios of LBW, preterm birth and SGA, for women with and without chronic HTN, are presented in After adjusting for the mother’s parity, maternal age, education level, diabetes, anemia, coronary heart disease, and hyperlipidemia, the adjusted odds ratios of LBW, preterm birth and SGA were 2.29 (95% CI = 1.95–2.68), 2.18 (95% CI = 1.89–2.52) and 1.62 (95% CI = 1.45–1.81) higher for HTN women.The crude and adjusted ORs of preterm birth, LBW, and SGA for non-treated HTN mothers , compared to non-HTN controls  were shown in The distribution and odds ratios of LBW, preterm birth and SGA, relating to the use of various anti-hypertensive drug types are presented in The increased ORs were also found to differ with the treatment groups and untreated group. As regards the risk of LBW, vasodilators had the greatest crude and adjusted ORs , followed by central α agonists .α and BBs .As for preterm birth, vasodilators had the greatest crude and adjusted ORs , followed by central α agonists , whilst diuretics had the lowest crude and adjusted ORs . The greatest crude and adjusted ORs of SGA were found in vasodilators , followed by combined The population-based cohort adopted for this study revealed that infants born to women with chronic HTN were at an increased risk of LBW, preterm birth and SGA. Our results further demonstrate that all types of anti-hypertensive drugs are associated with significantly higher risks of such adverse pregnancy outcomes amongst women with chronic HTN, at varying levels. The greatest risk for such adverse pregnancy outcomes was found in the use of vasodilators, as compared to other anti-hypertensive drugs. The relatively safer types of anti-hypertensive drugs were found to be BBs and CCBs. We have further investigated the trimester of pregnancy for receiving anti-hypertensive treatments among HTN mothers and found most HTN women (80.8%) receiving anti-hypertensive treatments from the first trimester of pregnancy.The prevalence of chronic HTN observed in this study, at 1.2 per cent of all pregnancies fall within the range of 1 to 3 per cent reported in earlier studies in other countries The prevalence of pre-existing type I/II diabetes mellitus in our study was 2.3% in comparative cohort, which was similar with the 3.2% previously reported in Taiwan In our study, the diagnosis of diabetes was based on ICD-9-CM codes 250, including type 1 and type 2, which had been stated in Page 10, Line 168. The Swedish data in ref 8 was also using the diagnosis of diabetes to determine whether the presence of diabetes or not. Ref 24 and ref 25 used the different method to collect the disease condition. Data from ref 24 presented the survey records of 1,677 type 1 and type 2 diabetes women among 401,149 singleton pregnancies between 1996 and 2008. Data from ref 25 was collected data using standardized measures and showed the 0.4%, 0.6% and 0.7% of pre-existing diabetes, including type 1 and type 2, among women aged 25–29, 35–39 and >39 years between 1998 and 2008. The different proportion of diabetes could be due to the different method used to collect the disease condition.We observed a higher proportion of infants classified as SGA (15.3%) in comparative cohort than the nominal 10%. The rate of SGA in our study is similar to the 15.2% to 16.7% previously reported in Taiwan using the same definition way Our findings are in line with the results of several prior published works The information currently available on pregnancy outcomes relating to the effects of other types of anti-hypertensive drugs is rather limited. Our observation of increased LBW, preterm and SGA risks for HTN women exposed to CCBs or diuretics is in line with the three studies referred to above A trial conducted by Fenakel et al. revealed that infants born to women treated with CCBs tended to have more advanced gestational ages and increased weight One possible explanatory mechanism for the increased risk of delivering LBW infants amongst women using anti-hypertensive drugs is the treatment associated with intra-uterine growth retardation. In the meta-analysis referred to earlier, it was noted that for a 10 mmHg reduction in maternal blood pressure induced by anti-hypertensive treatment, there was a potential corresponding reduction of 145 gm in fetal growth α agonists and those in the placebo group were very similar In contrast to the results of the present study, few randomized trials failed to show any difference in average birth weight, prevalence of preterm birth or SGA between women treated with anti-hypertensive drugs and untreated HTN women, as did one systematic review The particular strengths of the present study are its large sample size, the valuable socioeconomic information available from the data source, and the unique ability to assess anti-hypertensive drug use with computerized pharmacy records. The computerized pharmacy records from NHIRD contain all medical claims data of pregnant women. In Taiwan, approximately 99% of all Taiwanese citizens joined in the National Health Insurance program. The NHIRD therefore has the comprehensive medical records. Our study is clearly well positioned to provide more reliable results given the large sample size, and since the study involves a population-based dataset which enables us to study all of the pregnancies in Taiwan, we can clearly minimize selection bias, as well as other preferred prescription biases.The database adopted for this study involved several important socio-economic factors, such as maternal education level, and marital status, all of which may potentially affect the association observed between anti-hypertensive drugs and adverse pregnancy outcomes; adjustments were made for these potential confounders within the multivariable analysis. Furthermore, as opposed to reliance on self-reported data, which can give rise to doubts as to the accuracy of the type of anti-hypertensive drugs reportedly used, the comprehensive pharmacy database allows precise assessment of the anti-hypertensive drugs prescribed.There are several limitations of the present study which should be taken into consideration. Given that we were unable to assess whether or not patients actually took the drugs that they were prescribed, adherence to medication remains unknown; nevertheless, given that patients are required to pay a proportion of their medication charges, there would be an increased likelihood of them actually using the prescribed anti-hypertensive drugs. It is very likely that HTN mothers choose not to take the prescribed anti-hypertensives due to the worries of possible hazards for their babies. In this case, our analysis may give conservative results. If mothers take all prescribed anti-hypertensive drugs, the risk could be higher than what we estimated in the study.A second limitation is that details on certain covariates, such as maternal smoking, diet, obesity and the use of alternative non-prescription drugs, are not available from the administrative database. Although the current study used maternal comorbidity as possible confounders, further study incorporating maternal smoking, BMI and other possible confounders is needed to validate findings of comparison between HTN and comparative cohort from present study. Nevertheless, we believe that maternal smoking, diet, and obesity will not distribute unbalanced across the different treatment sub-groups. The impact of ignorance of these factors in the comparison between specific anti-hypertensives among HTN pregnant mother would be small. The final limitation noted here is that we had no access to patient records which would allow us to adjust for maternal blood pressure, a factor which represents the clinical severity of HTN. However, we could assume the women’s blood pressure was well-controlled under anti-hypertensive treatment. The effect of original severity of HTN would be minimized with anti-hypertensive treatment. The severity of the underlying HTN may be the cause of the found deviations and the differences between the drug treated groups may also be caused by different severity of the HTN. So, for instance it seems likely that women who only got diuretics have a milder form than women who got other anti-hypertensive drugs. The confounding by indication could not be fully excluded from our study and one should take these limitations with our results into consideration.In conclusion, our study demonstrates that those women with chronic HTN had an increased risk of preterm delivery, LBW and SGA infants. Furthermore, our data suggests that mothers treated with anti-hypertensive drugs were at a greater risk of these adverse pregnancy outcomes than untreated mothers, and it seems likely that women who only got diuretics have a milder form than women who got other anti-hypertensive drugs. Our findings demonstrate that the association between the maternal use of anti-hypertensive drugs and infants with LBW and SGA is not specific to BBs, but is also discernible amongst other types of anti-hypertensive drugs. This finding is important for practitioners, because it indicates the need for caution while considering the administration of anti-hypertensive drugs to pregnant women. These observations require confirmation in further studies that can better adjust for the severity of the underlying HTN.


Assistance by skilled birth attendants (SBAs) during childbirth is one of the strategies aimed at reducing maternal morbidity and mortality in low-income countries. However, the relationship between birth preparedness and decision-making on location of birth and assistance by skilled birth attendants in this context is not well studied. The aim of this study was to assess the influence of birth preparedness practices and decision-making and assistance by SBAs among women in south-western Uganda.Community survey methods were used to identify 759 recently delivered women from 120 villages in rural Mbarara district. Interviewer-administered questionnaires were used to collect data. Logistic regression analyses were conducted to assess the relationship between birth preparedness, decision-making on location of birth and assistance by SBAs.35% of the women had been prepared for childbirth and the prevalence of assistance by SBAs in the sample was 68%. The final decision regarding location of birth was made by the woman herself (36%), the woman with spouse (56%) and the woman with relative/friend (8%). The relationships between birth preparedness and women decision-making on location of birth in consultation with spouse/friends/relatives and choosing assistance by SBAs showed statistical significance which persisted after adjusting for possible confounders  and  respectively. Education, household assets and birth preparedness showed clear synergistic effect on the relationship between decision-maker on location of birth and assistance by SBAs. Other factors which showed statistical significant relationships with assistance by SBAs were ANC attendance, parity and residence.Women’s decision-making on location of birth in consultation with spouse/friends/relatives and birth preparedness showed significant effect on choosing assistance by SBAs at birth. Education and household assets ownership showed a synergistic effect on the relationship between the decision-maker and assistance by SBAs. Assistance by skilled birth attendants (SBAs) is one of the strategies aimed at reducing maternal morbidity and mortality in low-income countries such as Uganda Prompt decision-making is a prerequisite for reducing delay to seek care Birth preparedness, which comprises identification of skilled birth attendant, health facility, saving money, identifying transport and making other preparations for childbirth is aimed at increasing assistance by SBAs and also reducing delay in reaching place of care. Studies have indicated that women who are birth prepared are more likely to be assisted by skilled birth attendants In year 2000 the millennium summit introduced the eight Millennium Development Goals (MDGs) to achieve development in low-income countries Since 2008 the Uganda government has been implementing a road map aimed at accelerating the reduction of maternal and newborn mortality and morbidity A community survey of recently delivered women (within the last 12 months) and currently pregnant women was conducted between September 2010 and May 2011 in Mbarara district. Mbarara district is located in the south-western region of Uganda. The district covers an area of 1788 square kilometres, and had a projected population for 2010 of 427,200 with 80% working and residing in rural areas. Administratively the district is divided into three counties ; Mbarara municipality, which is the main urban centre while Kashari and Rwampara counties are largely rural with few small towns/trading centres Mbarara regional referral hospital, located in Mbarara town, is the only public hospital, which provides emergency comprehensive obstetric care services in the district. The hospital also serves as the main referral and teaching health facility for the south-western region and Mbarara University respectively. There are three private hospitals, all located in Mbarara municipality, one is purely private while the other two are owned by religious organisations and are categorised as private not for profit (PNFP). The district has 47 health centres of levels II-IV, which among other basic outpatient and inpatient health services offer maternal health care services . Kashari County has eight health centres level III and IV, which offer delivery services while Rwampara has only four. The most recent Uganda Demographic and health survey of 2006 indicates that only 32% of women residing in rural areas deliver under the care of skilled birth attendants compared to 80% of their urban counterparts Two-stage cluster sampling was used to select study participants for a broader study on pregnancy and childbirth. In the first stage, a list of villages and the respective number of households was used to independently select 58 villages in Kashari and 62 Rwampara counties. In total, one hundred and twenty villages were randomly chosen. In the second stage, households in which there was a woman who had recently delivered or currently was pregnant were consecutively identified with the assistance of village health team members . In each village, the first ten women who met the study criteria were interviewed. In case there were two or more qualifying women in one household, only one was chosen at random for the interview. The number of women to be interviewed per village was fixed to 10, which was regarded by the study team as the optimum number two research assistants could interview per day. Compared to increasing the number of respondents per cluster, increasing the number of clusters/villages is also a more efficient approach to increasing study power in a cluster survey. In total 1199 recently delivered and currently pregnant were interviewed during the survey. Only one woman declined to participate in the survey. The focus of this particular study being birth preparedness and decision-making on location of birth and assistance by SBAs, and therefore this paper only included information from the 759 women who had delivered within 12 months prior the date of the survey and had complete data on the outcome of interest (assistance by skilled birth attendant). Data from 5 women were excluded from analysis as it lacked information on the outcome of interest. Data from currently pregnant women were consequently not included in this study.A safe motherhood questionnaire developed by the Maternal Neonatal Program of JHPIEGO, an affiliate of John Hopkins University was used County of residence was coded “Kashari” or “Rwampara”. Location of residence was categorised as “rural” or “semi-urban”. Age was categorised into 2 groups “<25″ (young women 16–24), “≥25″ (older). Marriage was dichotomised so that “married/in union” was coded “married” and “single”, “widowed”, “divorced”, “separated” was coded “not married”. Highest education level completed was dichotomized so that “no formal schooling”, “primary” were coded into “<Secondary” and any education beyond primary was coded “≥Secondary”. Occupation was dichotomized so that “commercial farmer”, “trader”, “salaried employment”, were coded “regular income” while “house wife”, “casual labourer” were coded “irregular income”. Household assets ownership  were scored  so that ownership of two or more assets was classified “high” and ownership of one or none coded “low”. Travel from health facility with delivery services was coded “<1 hour” (near) and “≥1 hour” (far).Antenatal Care (ANC) attendance - was coded “less than 4 times” (<4) and “four or more times” (≥4). The variable “Parity” was divided into three groups of “1″, “2–4″, “≥5″. Birth preparedness: A woman was classified as “well birth prepared” in the most recent pregnancy if she had accomplished three of the following practices: identified skilled health professional, saved money, identified transport or had delivery kit/materials. A woman who made arrangements for birth in less than three of the four practices was classified as “not well birth prepared”.Decision-maker on location of birth: A recently delivered woman was asked the question “Who made the final decision about where you would give birth?” The respondents’ spontaneous responses were categorized into: “respondent alone”, “husband”, “respondent and husband”, “others”.Assistance by a skilled birth attendant (SBA) in the most recent birth was the outcome variable. WHO defines a skilled birth attendant as “an accredited health professional – such as a midwife, doctor or nurse – who has been educated and trained to proficiency in the skills needed to manage normal (uncomplicated) pregnancies, childbirth and the immediate postnatal period, and in the identification, management and referral of complications in women and newborns” Collin command. The variance inflation factor for the predictors of interest was less than 2, indicating no multicollinearity. Variables whose association to assistance by SBAs was statistically significant or when an association was expected and p-value of less than 0.2, were included in multivariable analysis, a rather generous measure to assure that even rather weak confounding effects could be accounted for. Stepwise multivariable random effects logistic regression with a random intercept was carried out to determine motivating factors for assistance by SBAs and adjusted for known confounders. The potential effect modification of age, education, household assets ownership, birth preparedness on the association between decision-making and assistance by skilled birth attendants was assessed using “the departure from additivity model” All analysis accounted for the intra-cluster correlation. For selected characteristics, the proportion of participants was computed using Stata’s SVY commands. The odds of assistance by skilled birth attendant at birth were compared between categories of the independent variables using multilevel random intercept logistic regression model, the village being the grouping variable. Odds ratios and 95% confidence intervals were obtained. Multicollinearity was assessed using the stata’s The Uganda National Council of Science and Technology granted ethical clearance for the study the study. Permission was also sought from local leaders at the district, county and village levels. Participants in the study gave individual written informed consent.Seven hundred and fifty nine women who had delivered within twelve months prior to the start of the survey were included in the study. The sample had an age range of 16 to 45 years (mean 27+/- 6 years). Of the 759 recently delivered women, 68.5% were assisted by SBAs while 29.1% were assisted by non-SBAs and 2.4% had solitary births. Furthermore 67% of the deliveries were conducted in health facilities while 31% took place at home or traditional birth attendant’s residence.The parity of the woman appeared to influence the choice of assistance by SBAs. Women who had parity of one or two were more likely to choose assistance by SBAs than those who had parity of five or more . Women who had their first antenatal clinic visit with a gestation age of 1–3 months were more likely to choose assistance of skilled birth attendant than those who had their first ANC visit at gestation age of 4 months or above . Those women who attended ANC 4 times or more were more likely to choose assistance by skilled birth attendant at the time of delivery than those who had less than four ANC visits .Birth preparedness was also associated with being assisted by skilled birth attendant at the time of delivery. Women who were well prepared for childbirth were more likely to choose assistance by SBAs than those who were not well prepared . In this study the person who made the final decision on the location of birth was significantly associated with assistance by SBAs. In cases where the women made the final decision in consultation with their husbands the likelihood of choosing assistance by SBAs was significantly higher than cases in which women made the decision on location of birth alone . Similarly when other people, mostly relatives, were consulted in making the final decision on location of birth, the likelihood of choosing assistance by SBAs was greater than when women made the decision on their own .. The analyses revealed that high level of education, being birth prepared and having high household assets ownership all showed synergistic effect regarding the association between decision-maker on location of birth and assistance by SBAs.Further analyses were performed to check for possible effect modification of age, education, household assets ownership, birth preparedness on the relationship between decision-making and choosing assistance by skilled birth attendant Our results showed a clear relationship between decision-maker on location of birth and choosing assistance by skilled birth attendant among women in south-western Uganda. Similarly there was a significant association between birth preparedness and assistance by SBAs. The relationships remained statistically significant even after controlling for the potential confounding of ANC attendance, parity, education level attained, household assets ownership, place of residence  and county.Findings from our study indicate that, when women made the final decision on location of birth in consultation with either the spouse or other people, the likelihood of giving birth assisted by a skilled birth attendant was very high. However, when women made the final decision alone; the likelihood of giving birth assisted by SBAs was significantly reduced. This finding may be related to the desire expressed by women to protect their own integrity as reported in a qualitative study conducted on the community’s perception of obstructed labour in Mbarara district Internationally, particularly in lower income countries (LICs), there is a growing awareness of the need to involve men in all stages of pregnancy, childbirth and postnatal education programmes in order to achieve the MDG 5 thereby reducing maternal mortality Contrary to our findings, Amooti-Kaguna and Nuwaha, Kyomuhendo and Merchant reported from their studies in Uganda that men decide the places where their spouses should give birth from In our study birth preparedness was significantly associated with assistance by SBAs in recently delivered women. Being birth prepared is most likely an indication that the women are consciously aware of the risks inherent in pregnancy and childbirth hence the significant use of skilled birth attendant services. Our results also support findings from earlier studies conducted in Uganda, which have reported a significant increase in use of health facilities during deliveries by women who are birth prepared In this study higher education and high household assets ownership were found to have synergistic effect on the relationship between women’s decision-making in consultation with spouse/friends/relatives and assistance by skilled birth attendant. Education promotes better understanding of health messages, which empowers women to improve not only their health but also of their families, as they become enabled to make informed choices Other factors, which were identified in our study to be significantly associated with choosing to be assisted by SBAs, include ANC attendance, parity, residence and county. Antenatal care visits provide opportunity for expectant mothers to be assessed for possible risks and also provides an opportunity for women to be educated on use of maternal health care services. Women who had at least four ANC visits were more likely to deliver under the care of SBAs than those who had attended none or less than four visits. Our findings show that women who had their first or second delivery were more likely to deliver with the care of SBAs than those who have delivered 2 or more. This could possibly be attributed to the fact that women who have a history of normal deliveries may consider themselves competent to have unsupervised deliveries.Furthermore our study shows that women who reside in rural areas were less likely to be assisted by SBAs than those residing in small towns. This could possibly be attributed to lack of access of health facilities both in terms of distance and financial ability to pay for transport. Our findings that women in Rwampara were less likely to choose assistance by SBAs than those from Kashari could be attributed to the fact that the latter had access to more health centres which provide basic emergency obstetric care. Additionally Rwampara has hilly terrain, which presents transport challenges to women seeking skilled birth assistance during childbirth.To our surprise, 68% of the women in our study reported that they were assisted by SBAs, twice of what was reported to be the case in the last demographic and health survey (DHS) of 2006 Based on findings from this study, the authors defend the need to encourage joint decision-making regarding the location of birth as this clearly promotes assistance by SBAs. Similarly the practice of birth preparedness should be encouraged during the antenatal period through opening up antenatal education to include spouses and eventually other community members. Furthermore, our results supports Ahmed et al. The childbirth process is a memorable event for the woman in labour and it is highly unlikely that she will not recall the person who assisted her. We believe that if there was recall bias then it was minimal, especially since it occurred within the last 12 months in relation to this study. Taking this uncertainty into account, we find it unlikely that recall bias distorted our findings to any important degree. Selection bias was minimised by the random method used to select 120 villages included in the study. The sample of women in our study, most likely represent the population of recently delivered women in rural Mbarara district. Confounding was controlled for in the analysis by applying stepwise multivariable logistic regression. Probable confounders were introduced into the regression model stepwise and they did not have significant effect on the association between birth preparedness, decision-maker on location of birth and assistance by SBAs. However, as this study was cross-sectional in design, causal inferences cannot be deduced. Any associations identified therefore need to be studied further.Our study indicates that a significant proportion of women in rural areas of Mbarara district deliver under the care of SBAs. Analysis also showed significant association between birth preparedness, women’s decision-making on location of birth and assistance by SBAs. Women who take individual decision on location of birth are more likely not to deliver under the assistance of SBAs. Male involvement in decision-making increases the likelihood of women having attendance by SBAs at birth. Higher education, high household income strengthened the relationship between decision maker and assistance by SBAs at birth.The antenatal care programmes need to shift from the current policy of only targeting women to promoting increased male and community involvement in safe motherhood programmes. Since relatives and friends are influential in determining where pregnant women deliver from, there is need to use media to reach them with maternal health messages. Formation of community clubs focusing on sexual and reproductive health would be one avenue to reach many people with health messages. In order to achieve the health MDGs 4 and 5 there is need for substantial investment in education (MDG 2), poverty reduction (MDG 1) and gender equality and empowerment (MDG 3).