Background: Short birth intervals have been associated with adverse health outcomes, including infant, child and maternal mortality.Objective: We aimed to investigate the duration and determinants of inter birth intervals among women of reproductive age in Yazd, Iran.Materials and Methods: A cluster sampling technique was used to select 400 ever-married women aged 15-49 years in Yazd, Islamic Republic of Iran. Data were obtained by interview questionnaire and analyzed with life table, Kaplan-Meier survival and Cox regression analyses.Results: The mean duration of inter birth interval was 49.76 (standard error 1.82) months (95% CI: 46.19-53.34 months) with a median of 39. In 28.5% of women the birth interval was <2 years, in 28% it was 3-5 years and in 25.5% it was ≥6 years. Among explanatory variables of interest, age of marriage, and woman's education were significant predicators of the birth interval. Women who stated an ideal preference of two children constituted 59.9% of the sample and 16% had 3 children as well as 10.7% had an ideal preference for 4 or 5.Conclusion: The study recommended an educational program to have optimal birth intervals and ideal number of children per family for the prevention of adverse prenatal outcomes. Short birth intervals have been associated with adverse health outcomes, including infant, child and maternal mortality. Research has shown that inter-pregnancy interval is a risk factor for pre-term delivery and neonatal death . "Short From her study in Singapore, Martin deduced that for the best physical and mental development, a minimum of 2 years is necessary between births and if linear trends shown in her results are projected, three years between births would be even better. This might be simply speculative or perhaps a good guess . In ruraEvidence on maternal health has been provided by research managed on over a million pregnancies in 19 countries by the Latin American Center for Perinatology and Human Development. It has observed that birth intervals beyond 2 years (27-32 months) improved maternal health in terms of fewer likelihoods of developing toxemia, anemia and third trimester bleeding as well as 2.5 times less risk of maternal mortality compared to birth intervals of 9-14 months. Intervals longer than 69 months were associated with increased risk of maternal death (10%), third trimester bleeding (10%), eclampsia (80%) and post-partum hemorrhage (90%) .These determinants are the behavioral and biological mechanisms by which fertility is reduced below its biological maximum. Four proximate determinants have been identified: marriage, postpartum in fecund ability, contraception and induced abortion. Social factors such as women’s education, employment opportunities and the number and the sex of surviving children also play a role in determining child spacing -16.et al showed that there were significant correlation between birth interval with maternal age, duration of breast feeding, sex of index child, history of still births, history of infant mortality of the index child, type of contraception used, regular attendance at a family planning clinics and parity . Birth intervals determinants were analyzed with Kaplan-Meier survival, Cox regression analyses and the corresponding 95% confidence interval (CI) for Hazard ratio. Significance of results was judged at the 5% level.Data analysis was performed with Totally 408 eligible women aged 18-49 years were selected for the study and as 8 of them were not volunteered for entering in the study, finally, 400 eligible women were surveyed. Therefore, the response rate in the study was very high (98%). The mean age was 32.04 (SD=7.01) years. The mean age at marriage was 18.09 (SD=3.38) years with a median of 18 years. The number of children each woman had ranged from 1-7 with an average of 2.17 children per woman [2.17 (SD=1.25)]. On average, women had their first child after 25 months of marriage [25.06 (SD=17.87) months]. The mean duration of the inter birth interval was 49.76 (SE=1.82) months (95% CI: 46.19-53.34 months) with a median of 39. Only 28.3% had a birth interval <2 years, and 25% had a birth interval ≥6 years. With regard to Overall 13.5% of the women stated an ideal preference of 1 for the number of children. Women who stated an ideal preference of 2 children constituted 59.9% of the sample and 16% had an ideal preference for 3 children as well as 10.7% had an ideal preference for 4 or 5. Nearly 58% of women had the number of the children who matched their ideal preference. Just 28.5% of the women had not reached their ideal preference, while 23% had exceeded their ideal preference. The mean of the inter birth interval for those who reported an ideal preference of 2 for the number of children or less than 2 was 51.77 (SE=2.53) months compared with 47.52 (SE=1.83) for those who reported an ideal spacing of more 2 for the number of children. This difference was not statistically significant (p=0.178). Cox regression analysis indicated that longer inter birth interval was independently predicted by shorter age of the marriage and lower Woman's education .This paper looked at the duration of the interval between births and the factors determinant's in Yazd city, Iran. The duration between 2 most recent consecutive live births was of a median duration of 39 Months, which was greater than 3 years, however it is higher than the mean child spacing period of 27 and 26 months found for births of Saudi Arabian children born more than a decade ago , 19. ThiThe median birth-to-conception interval among women in less developed countries who breastfeed their infants is approximately three years . Therefoet al , a quarter of women had a prolonged birth interval (≥6 years) which increased the risk for a pregnancy in women age >35 years old. We recommend an educational program to prevent birth intervals beyond the optimal range which increases the risk during pregnancy.


Radek Bukowski and colleagues conducted a case control study in 59 US hospitals to determine the relationship between fetal growth and stillbirth, and find that both restrictive and excessive growth could play a role.Please see later in the article for the Editors' Summary Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms . LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms , but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.Please see later in the article for the Editors' Summary Pregnancy is usually a happy time, when the parents-to-be anticipate the arrival of a new baby. But, sadly, about 20% of pregnancies end in miscarriage—the early loss of a fetus (developing baby) that is unable to survive independently. Other pregnancies end in stillbirth—fetal death after 20 weeks of pregnancy . Stillbirths, like miscarriages, are common. In the US, for example, one in every 160 pregnancies ends in stillbirth. How women discover that their unborn baby has died varies. Some women simply know something is wrong and go to hospital to have their fears confirmed. Others find out when a routine check-up detects no fetal heartbeat. Most women give birth naturally after their baby has died, but if the mother's health is at risk, labor may be induced. Common causes of stillbirth include birth defects and infections. Risk factors for stillbirth include being overweight and smoking during pregnancy.Stillbirths are often associated with having a “small for gestational age” (SGA) fetus. Gestation is the period during which a baby develops in its mother's womb. Gestational age is estimated from the date of the woman's last menstrual period and/or from ultrasound scans. An SGA fetus is lighter than expected for its age based on observed distributions (norms) of fetal weights for gestational age. Although stillbirth is clearly associated with impaired fetal growth, the exact relationship between fetal growth and stillbirth remains unclear for two reasons. First, studies investigating this relationship have used gestational age at delivery rather than gestational age at death as an estimate of fetal age, which overestimates the gestational age of stillbirths and leads to errors in estimates of the proportions of SGA and “large for gestational age” (LGA) stillbirths. Second, many characteristics that affect normal fetal growth are also associated with the risk of stillbirth, and this has not been allowed for in previous studies. In this population-based case–control study, the researchers investigate the fetal growth abnormalities associated with stillbirth using a new approach to estimate gestational age and accounting for the effect of characteristics that affect both fetal growth and stillbirth. A population-based case–control study compares the characteristics of patients with a condition in a population with those of unaffected people in the same population.The researchers investigated all the stillbirths and a sample of live births that occurred over 2.5 years at 59 hospitals in five US regions. They used a formula developed by the Stillbirth Collaborative Research Network to calculate the gestational age at death of the stillbirths. They categorized fetuses as SGA if they had a weight for gestational age within the bottom 10% (below the 10th percentile) of the population and as LGA if they had a weight for gestational age above the 90th percentile at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms of fetal weight for gestational age. Population norms incorporate weights for gestational age from normal pregnancies and from pregnancies complicated by growth abnormalities, whereas the other two norms include weights for gestational age from normal pregnancies only. Having an SGA fetus was associated with a 3- to 4-fold increased risk of stillbirth compared to having a fetus with “appropriate” weight for gestational age based on all three norms. LGA was associated with an increased risk of stillbirth based on the ultrasound and individualized norms but not the population norms. Being more severely SGA or LGA (below the 5th percentile or above the 95th percentile) was associated with an increased risk of stillbirth.These findings indicate that, when the time of death is accounted for and norms for weight for gestational age only from uncomplicated pregnancies are used, stillbirth is associated with both restricted and excessive fetal growth. Overall, abnormal fetal growth was identified in 25% of stillbirths using population norms and in about 50% of stillbirths using ultrasound or individualized norms. Although the accuracy of these findings is likely to be affected by aspects of the study design, these findings suggest that, contrary to current practices, strategies designed to prevent stillbirth should focus on identifying both severely SGA and severely LGA fetuses and should use norms for the calculation of weight for gestational age based on normal pregnancies only. Such an approach has the potential to identify almost half of the pregnancies likely to result in stillbirth.http://dx.doi.org/10.1371/journal.pmed.1001633.Please access these websites via the online version of this summary at stillbirthThe March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on stillbirth Tommy's, a UK nonprofit organization that funds research into stillbirth, premature birth, and miscarriage and provides information for parents-to-be, also provides information on stillbirth The UK National Health Service Choices website provides information about stillbirth (in English and Spanish)MedlinePlus provides links to other resources about Stillbirth Collaborative Research Network is availableInformation about the  One in 160 births at ≥20 wk gestation in the United States is stillborn, resulting in over 25,000 stillbirths each year First, birth weight percentile is a function of birth weight and age of the fetus. Thus, studies using gestational age (GA) at delivery rather than GA at death, as an estimate of the age of the fetus, systematically overestimate the GA of stillbirths. This leads to overestimation of the proportion of birth weights considered SGA and underestimation of birth weights considered large for GA (LGA) among stillbirths.Second, a number of maternal characteristics such as weight, height, age, race/ethnicity, parity, exposures during pregnancy, smoking, and measures of placental function  have been observed to influence the magnitude of both fetal growth and risk of stillbirth Therefore, we hypothesized that accounting for time of death in determining fetal age and birth weight percentile, and determining percentiles of birth weight based on norms that account for factors affecting birth weight in normal pregnancies, will more accurately identify the proportion of stillbirths associated with abnormal growth than using traditional methods.This study was approved by the institutional review boards at each of the clinical recruiting sites and at the data coordinating center. All mothers participating in the study gave written informed consent.The Stillbirth Collaborative Research Network (SCRN) conducted a population-based case–control study of stillbirths in the United States. The study design has been previously described A stillbirth was defined by Apgar scores of 0 at 1 and 5 min, and no signs of life by direct observation. The protocol included an in-hospital maternal interview, medical record abstraction, placental pathology examination, and biospecimen collection for stillbirths and live births. For stillbirths, a standardized postmortem examination was also performed.Fetal age was based on an estimated due date and the date of delivery for live births and an estimated due date and estimated date of death for stillbirths, using an algorithm developed by the SCRN investigators The SCRN algorithm for estimating time of death and fetal age at death in stillbirths considered the following: the reliability of the estimated due date; the length of the interval between the time the fetus was last documented alive and the time fetal demise was first recorded based on information from prenatal care visits, hospitalizations, and ultrasound examinations ; and information available from postmortem examination, including degree of fetal maceration and foot length measurement. The estimated due date was considered reliable if estimated by ultrasound or by certain menstrual dating that agreed with ultrasound (within specified constraints). Briefly, (1) if the estimated due date was reliable, the fetal age at death was estimated using the due date and the date fetal demise was diagnosed  or the date at the midpoint of the time-of-death interval ; (2) if the estimated due date was unreliable, or the time-of-death interval was >7 d, GA at death was estimated using foot length, or using GA reported by the study site at screening based on clinical criteria when foot length information was not available. Precise estimates of GA at death, defined as meeting reliable dating criteria and having an interval of 1 wk or less during which the demise could have occurred, were possible for 47% of stillbirths.The fetal age at death estimated by the SCRN algorithm was used for all stillbirths in the primary analysis. For comparison, GA at stillbirth delivery, calculated using the estimated due date and the delivery date, and GA at delivery minus 2 d were also used as estimates of fetal age at death to examine the impact on birth weight percentiles. For live births, fetal age at delivery was estimated using the estimated due date if reliable and the delivery date, or if the estimated due date was unreliable, the GA reported by the study site at screening was used.Fetal weight percentiles were determined based on birth weight and the fetal age estimate for stillbirths and live births. Birth weight was obtained from medical records or postmortem examination and was compared to expected weight for GA based on three types of norms: population, ultrasound, and individualized norms SCRN) was recorded in weeks, with days retained as a fractional component. Alexander et al. reported 5th, 10th, 50th, 90th, and 95th percentiles of birth weight for completed weeks of GA derived using data from over 3 million US 1991 single live births SCRN. For interpolation, each percentile reported by Alexander et al. was taken to represent birth weight at the midpoint of the GA week range (0–6 d). For example, the 10th percentile of birth weight reported for an infant of 30 wk GA was considered the 10th percentile for 30.5 wk GA.The estimated GA at death (for stillbirths) or delivery (for live births) using the SCRN algorithm . Three infants with GASCRN>44.5 wk were assigned to the 10th–90th percentile category based on birth weight between the 10th and 90th percentiles reported for 44 wk.The observed birth weight of each infant was compared to the interpolated 5th, 10th, 50th, 90th, and 95th percentiles of birth weight for GASCRN was estimated for each infant in the SCRN cohort as the normal probability of a Z-score, ZULTRASOUND, calculated as follows:SCRN by Hadlock et al.'s equation:Hadlock et al. used in utero fetal weight, estimated with ultrasound measurements, from 392 uncomplicated pregnancies progressing to term among predominantly middle-class white women to develop a best-fitting equation for fetal weight as a function of GA Bukowski et al. developed a regression model for birth weight in a normal population using singleton births from 9,818 women with uncomplicated pregnancies INDIV280) for each SCRN infant, an individualized expected birth weight for GASCRN (eBW) was calculated using a proportion derived using Hadlock et al.'s equation HADLOCK is the predicted birth weight for GASCRN using Hadlock et al.'s equation and BWHADLOCK280 is the predicted birth weight for GA at 280 d using Hadlock et al.'s equation .After computing an individualized expected birth weight at 280 d  is an estimate of the standard deviation of the observed birth weight. The standard deviation was estimated using an estimate of the coefficient of variation at 280 d (CVINDIV280) multiplied by eBW (CVINDIV280×eBW). CVINDIV280 was taken as the reported square root of the residual mean square from the model from Bukowski et al. (358.479 g) divided by the expected birth weight at 280 d from Hadlock et al. . Thus, CVINDIV280 = 358.479/3,619.17.Finally, an individualized birth weight percentile was estimated as the normal probability of an individualized In sensitivity analyses, individualized norm percentiles were recalculated based on three different reduced prediction equations that included subsets of variables largely non-missing in the SCRN cohort, instead of the original 19 variables. First, percentiles were estimated based on a prediction equation that included the 11 variables with largely non-missing values in the SCRN cohort , with coefficients derived using data from the original Bukowski et al. population. Second, percentiles were estimated based on a prediction equation that included the six variables suggested previously Data were weighted for the analysis. The analysis weights were constructed in steps. First, weights were constructed that took into account the sampling design, including staggered enrollment starts across the 59 site hospitals, and different sampling probabilities associated with the oversampling of live births <32 wk gestation and live births at ≥32 wk gestation to women of African descent. Some women screened and determined eligible for the study were not approached, and others were approached but did not consent. Additional weight adjustments were constructed to account for this nonresponse and utilized information collected at screening to determine characteristics associated with the likelihood of participating. The final analysis weights were constructed as the product of these weighting factors. Details of the live birth sample selection procedure and construction of the analysis weights have been reported previously The analysis was restricted to singleton stillbirths and live births with non-missing birth weight and GA≥20 wk at death or delivery. Statistical significance for comparisons of characteristics between stillbirths and live births was determined by the median or chi-square test, and for comparisons between proportions among stillbirths by the McNemar test. Crude and adjusted odds ratios (ORs) and 95% confidence intervals were calculated from logistic regression models. Primary results used all stillbirths and all live births. Term stillbirth and live birth were defined as GA of 37 wk 0 d or more. To assess the association of SGA and LGA with preterm stillbirth, the logistic model was restricted to preterm stillbirth versus all live births. Multivariable models used to estimate adjusted ORs included study site (five geographic areas) and stillbirth risk factors known at the beginning of pregnancy The SCRN identified 953 women with stillbirths and 3,088 women with live births eligible for participation in the study. Of these, 663 (70%) women with stillbirths and 1,932 (63%) women with live births consented to participate. Women with stillbirths enrolled in the study did not differ from those not enrolled on maternal age, maternal race/ethnicity, insurance/method of payment, or GA at delivery p<0.001), overweight (BMI≥25 kg/m2) , single , smokers before pregnancy , and less educated (less than 12 y of school) . They were more likely to have hypertension , to have pregestational diabetes , and to be nulliparous or to have had a prior stillbirth (p<0.001) (p<0.001) and lower birth weight (p<0.001) and were more likely to have congenital malformations than live born infants   . As expep<0.001) .Some variables used to compute individualized norms were missing in a proportion of pregnancies and were set to mean, median, or weighted average . Howeverp<0.001) and individualized norms . The association between stillbirth and SGA and LGA infants was mainly due to the high risk of stillbirth among infants with birth weights in the <5th and >95th percentiles and was not substantially changed when adjusted for stillbirth risk factors . LGA birth weight was associated with a significantly increased risk of stillbirth using percentiles derived from the ultrasound and individualized norms , but not using percentiles based on the population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). Abnormal fetal growth (SGA or LGA) was identified in 25% of stillbirths using population norms and in twice as many stillbirths using ultrasound , 14.5% (9/62), and 12.5% (3/24) of stillbirths identified as LGA using the individualized, ultrasound, and population norms, respectively. LGA was associated with stillbirth in the subset of non-anomalous pregnancies, which excluded the pregnancies with hydrops .Accounting for the time of death in stillbirths to determine fetal age did influence the proportion of SGA and LGA infants . IncreasSGA and LGA birth weights based on ultrasound and individualized norm percentiles were significantly associated with an increased risk of preterm as well as term stillbirth. Using population norms, only SGA pregnancies were significantly associated with preterm and term stillbirth . There wThis study demonstrates that stillbirth is associated with both growth restriction and excess growth. The extremes of SGA and LGA (<5th and >95th percentiles) were associated with the highest risk of stillbirth.The strengths of this study lie in its geographically defined population-based design capturing live births and stillbirths, the large number of stillbirths evaluated, the accurate estimation of GA at death in stillbirths, the assessment of fetal growth using different fetal growth standards, and the ability to examine the contribution of factors affecting both birth weight and the risk of stillbirth. The systematic and standardized estimation of time of death and thus GA at death for stillbirths allowed for more accurate assessment of the association between birth weight and stillbirth and, consequently, of the association of stillbirth with LGA.Prior studies have either not accounted for the interval between time of death and time of delivery of stillbirths Studies evaluating the interval between death and delivery have shown that in 25%–50% of stillbirths the interval was longer than 7 d Many prior studies of stillbirth have focused exclusively on the association of stillbirth with SGA A recent case series reported a higher than expected proportion of LGA among stillbirths. However, the majority of the LGA stillbirths in this series were related to fetal hydrops or maternal diabetes In our study, abnormal fetal growth was identified in twice as many stillbirths using ultrasound and individualized norms as when using population norms. Although SGA was associated with stillbirth based on all three norms, the association of stillbirth with LGA was observed only when using ultrasound or individualized norms. Differences in design may account for these results. The population norms by Alexander et al. are commonly used and were developed using birth weights from all pregnancies resulting in single live births, including those with complications associated with growth abnormalities, resulting in a wide range of birth weights between the 10th and 90th percentiles, classified as AGA In a large population of uncomplicated pregnancies, population reference percentiles and, to a lesser degree, ultrasound norms were shown to overestimate the proportion of AGA and to underestimate the proportion of LGA infants In individualized norms, the predictors of fetal growth, the sizes of their effects, and the ranges of their values were derived from a carefully selected population of almost 10,000 pregnancies without pregnancy or neonatal complications Consistent with prior studies, the findings of this study show that population norms are inferior to norms derived from uncomplicated populations, either ultrasound or individualized norms The strength and pattern of the association between fetal growth and risk of stillbirth was similar in term and preterm pregnancies. SGA and LGA birth weights were associated with increased risk of stillbirth in preterm as well as term pregnancies using ultrasound or individualized norms. Using population norms, only SGA pregnancies had an increased risk of stillbirth, both preterm and term. The distribution of GA at death was similar among stillbirths classified as SGA, AGA, and LGA using ultrasound norms and also when classified using individualized norms, and the association of stillbirth with SGA and with LGA was observed when using both of these norms.The association of LGA with stillbirth in this study was not related to post-term GA or known conditions that increase fetal weight and risk of stillbirth. Among stillbirths classified as LGA, only one pregnancy was greater than 40 wk. LGA was also associated with stillbirth among the subset of pregnancies that excluded hydrops and other congenital abnormalities. Because the relationship between congenital abnormalities and birth weight is complex and depends on the type of abnormality, we conducted analyses in pregnancies with and without congenital abnormalities. Both showed similar patterns of associations. Although the effect of maceration on a stillbirth's birth weight is uncertain, if birth weight is decreased in macerated stillbirths, this would decrease the strength of the association with LGA. However, the associations between SGA and LGA and risk of stillbirth were also observed in the subset with optimal estimates of fetal age that included non-macerated stillbirth infants with a short interval of less than 7 d between the time they were last reported alive and the time they were first identified as demised. Screening for gestational diabetes is performed in the US at 24 to 28 wk. Women at increased risk with a history of gestational diabetes, impaired glucose metabolism, or obesity are additionally screened in early pregnancy A limitation of this study is that retrospective review of medical records was used to obtain birth weight, criteria for GA estimation, and certain maternal characteristics. However, these variables were recorded in medical records prospectively and thus were unlikely to be subject to substantial bias. Many of the characteristics used to determine individualized expected birth weight were missing and were replaced with reference values. However, individualized norms based on subsets of non-missing variables showed very similar findings . In thisThe mechanism of stillbirth in LGA pregnancies is not known. However, it has been suggested that LGA stillbirths may have relatively insufficiently large placentae, which, although not small per se, may be inadequate to support the metabolic demands of a large fetus, rendering it vulnerable to insults during pregnancy In summary, when accounting for time of death and using norms developed in normal pregnancies, both SGA and LGA birth weights were associated with stillbirth in our study. The association is mainly related to severe SGA and LGA pregnancies, with birth weights either below the 5th or above the 95th percentile. Thus, classifying 10% of pregnancies as abnormally grown has the potential to identify 44%–46% of future stillbirths. This would provide an opportunity for prevention of stillbirth, especially in term pregnancies, when delivery is associated with relatively low neonatal mortality and morbidity. However, the effectiveness of stillbirth prevention would be expected to be decreased by inaccuracy of the fetal growth estimates. The association between large birth weights and stillbirth cannot be captured by population norms that include pregnancies with complications associated with growth abnormalities.Our results suggest that, contrary to current practices and recommendations, the most effective approach to identifying fetal growth abnormalities for prediction and prevention of stillbirth would focus on both severe SGA and LGA (<5th and >95th percentile) pregnancies and would use norms developed from normal pregnancies, rather than population norms, for fetal growth surveillance. This strategy would identify as at risk almost half of the pregnancies that would result in stillbirth. However, the majority of stillbirths would remain unidentified either because of inaccuracy of the fetal growth assessment or because they are not associated with growth abnormalities.Table S1STROBE checklist.(DOC)Click here for additional data file.


Low birth weight has been linked to an increased risk to develop obesity, type 2 diabetes, and hypertension in adult life, although the mechanisms underlying the association are not well understood. The objective was to determine whether the metabolomic profile of plasma from umbilical cord differs between low and normal birth weight newborns.th percentile, n = 20) and control . Nuclear Magnetic Resonance (NMR) was used to generate metabolic fingerprints of umbilical cord plasma samples. Simultaneously, the metabolomic profiles of the mothers were analysed. The resulting data were subjected to chemometric, principal component and partial least squares discriminant analyses.Fifty healthy pregnant women and their infants were selected. The eligibility criteria were being born at term and having a normal pregnancy. Pairs were grouped according to their birth weight: low birth weight . No significant differences were found between the two groups of mothers.Low birth weight newborns display a differential metabolomic profile than those of normal birth weight, a finding not present in the mothers. The meaning and the potential utility of the findings as biomarkers of risk need to be addressed in future studies. Low bonal age, have anonal age-6. Thereonal age.The mechanistic pathways underlying the relationship between fetal growth restriction and cardiovascular risk are poorly understood. AlthougA previous study has demonstrated that endothelial cells from umbilical cord artery derived from individuals of LBW exhibit a different phenotype when compared to that from individuals of higher birth weight. This obMetabolomics, the study of small-molecule metabolites, is a discipline that focuses on the measurement of the relative concentrations of endogenous small molecules in biofluids. This technology may be useful for understanding metabolic imbalances and for diagnosing human diseases. Recently, studies using metabolomics have been used to identify a discriminatory metabolite profile in a number of areas: preeclampsia in early pregnancy, diabeteth percentile  or appropriate birth weight for gestational age [Newborns were included if born at term , after uncomplicated pregnancies ascertained according to the Ballard method, and by  n = 30). Parents2O (as a field lock). A total of 500 μl of the mixture of each sample was then individually transferred into a 5 mm high quality NMR tube. All 1 H NMR spectra were acquired using a standard one-dimensional pulse sequence with water suppression (Bruker Avance 600 spectrometer operating at 600.13 MHz with a 1 mm 1 H/13 C/15 N TXI probe). A total of 256 FIDs (free induction decay) were collected into 64 k data points with a spectral width of 14 ppm and a recycle delay (RD) of 1 s. The water signal was saturated with weak irradiation during the recycle delay. Before Fourier transformation, the free induction decay was multiplied by a 0.3 Hz exponential line broadening.Umbilical venous cord blood and maternal peripheral venous blood were collected in EDTA-tubes, centrifuged to yield plasma, stored at −80 °C and thawed before use. For Nuclear Magnetic Resonance (NMR) analysis, 500 μl of plasma were mixed with 50 μl of D3 doublet signal at 1.475 ppm was performed in all spectra. Resonances in these spectral regions were assigned using the literature[Spectral chemical shift referencing on the Alanine CHterature and two-terature,25, whicIn the present study, binned spectral regions for blood plasma were mean-centered chemometric analyses. Relevant bins were identified in our chemometric models. The relevant spectral regions within these bins were identified and quantified by spectral integration. Chemometric and statistical analyses were performed using in-house MATLAB scripts and the PLS Toolbox . Principal Component Analysis (PCA) and Projection to Latent Structures for Discriminant Analysis (PLS-DA) were applied to NMR spectra data sets. PCA is able to find low dimensional embeddings of multivariate data in a way that optimally preserves the structure of the data. The PCA technique transforms the variables of a data set into a smaller number of new latent variables called principal components (PCs) which are uncorrelated to each other and account for decreasing proportions of the total variance of the original variables. Each new PC is a linear combination of the original variation so that a compact description of the variation within the data set is generated. Observations are assigned scores according to the variation measured by the principal component X, with those having similar scores clustering together. Where PCA proved inadequate to define clustering, a supervised approach was used.2X, R2Y, Q2 and RMSP. R2X and R2Y describe the variation in the X and Y variables, respectively. Q2 describes predictability. RMSP (Root mean squared error of prediction) gives a direct indication of the error in the predicted value.PLS-DA is a classification technique that combines the properties of Partial Least Squares regression with the discrimination power of discriminant analysis. The mai. An outlier analysis was performed, and those samples deviating from the mean by more than 2.5 times the standard deviation were excluded. A significant difference was considered present if p < 0.05. Pearson’s correlation coefficients were used to examine the relations between variables. Statistical analyses were performed using SPSS 15.0.  and GraphPad Statmate 5.0  software graphs.Values were expressed as mean ± SD for each study group. The differences in the mean values of anthropometric parameters between the groups were assessed by analysis of variance (ANOVA) adjusted by sex. The normality of the data was verified using the Kolmogorov-Smirnov test. Choline, glutamine, alanine and glycogen in the control group do not have a normal distribution, and a Kruskal-Wallis test was used for these variablesThe general characteristics of mothers and their newborns are shown in Table2X (cumulative) of 0.623, a R2Y (cumulative) of 0.871, a Q2 (cumulative) of 0.523  and a RMSP of 0.417 (medium predictive capacity). Spectral regions and peaks with the highest contribution to the loadings plot from this model were further quantified and analysed. Many metabolites may contribute to these loading plots and to the separation between classes. A total of thirty-four metabolites were tested in fifty-eight spectral regions, and the differences were evaluated by the T-Student test with the Kruskal-Wallis correction. However, only those that differed with p < 0.05 were taken into consideration.The standard 1D NMR spectrum is shown in FigureOf the 34 metabolic regions studied, 17 compounds were quantified according to the loadings of the multivariate analysis. Among the 17 metabolites, significant differences were observed for seven  between the LBW and the control group, while no differences were observed in the other seven  (data not shown).-3) from identified metabolites, and FigureTableFive metabolites  were reduced in the LBW group as compared to those for the controls. In the LBW group, proline values were 38.1% less  while free choline was 31.4% less . Glutamine , alanine  and glucose levels  were significantly lower in LBW newborns as well. In addition, LBW newborns exhibited a 15.7% increase in values of phenylalanine  and a 20.2% increase in values of citrulline . No difference in profiles between sexes was observed.2X (cumulative) of 0.512, a R2Y (cumulative) of 0.611, a Q2 (cumulative) of 0.502  and a RMSP of 0.282 (low predictive capacity). The loadings plot showed 14 spectral regions with high relative weight belonging to 10 metabolites. Table-3) from the identified metabolites. From a total of 10 metabolites, 6 were related to the amino acid group , 2 were related to the carbohydrate group (glucose and glycogen fragments), and 2 to the lipid group ). The results of the metabolomic profiling in maternal blood showed no significant differences between the two groups of mothers at either the PLS-DA score plot level and at the individual identified metabolite level , lipids  and phenylalanine was comparable between the two groups . A significant inverse association was found between citrulline and birth weight  and between phenylalanine and birth weight ; i.e., phenylalanine and citrulline increase as birth weight decreases. No relationships were identified when correlating these metabolites with blood pressure. No significant associations were found between alanine and glucose with birth weight.The present study is the first to utilize metabolomic analysis in umbilical cord blood samples from LBW children in order to identify metabolites that could be related to the abnormalities associated with the long-term development of the increased cardio-metabolic risk associated with LBW. The metabolomic profile of LBW newborns differed from that observed in a group of newborn controls. Higher values of phenylalanine and citrulline and lower levels of proline, choline, glutamine, alanine and glucose were observed. A significant relationship between some of these metabolites and birth weight was also present. Furthermore, the differences observed in the newborns were not observed in their mothers, all of whom were healthy and had similar weight gains during pregnancy. Although the significance of the observed metabolomic values is not well understood, interesting information can be derived from the present results since some of the observed data have been linked previously to the abnormal metabolic states associated with LBW.Even though the impact of fetal metabolic programming on adult health is well documented, the underlying mechanisms are poorly understood. Animal models have been used extensively to investigate the mechanism by which the early-life environment induces persistent alterations in the metabolism of offspring-30. Thes1 H resonance signals. Longer NMR T2 relaxation times, which suggest smaller molecule sizes, produce the narrow signals observed for that spectral region. Perhaps some macromolecule degradation of glycogen into smaller molecular size fragments is the cause.The absence of differences found for lipoproteins, carbohydrates, ketone bodies and fatty acids suggests that fatty acid oxidation and glucose metabolism remain unaltered. Changes, however, in the spectral region between 7.27 and 5.36 ppm, which has been assigned to glycogen fragments, may suggest alterations in carbohydrate storage. The large molecular size of glycogen makes it very difficult to observe its In the present study, the mismatch between the mother and the newborn in terms of the metabolomic profile is worth taking into consideration. While a different pattern was observed in the LBW newborns compared to controls, the mothers of both groups had a similar pattern. A trend towards reduced levels of amino acids in the umbilical cord was observed in LBW, something not observed in the mothers. The reason for the discrepancies is not well known, although suboptimal placental transport of amino acids could be involved. Impaired placental amino acid transport is often seen in association with IUGR, yet it is unclear whether the changes in amino acid transport are a cause or a consequence of IUGR,35. ExpeIn contrast to the reduction of the majority of the amino acid detected are the increased values of phenylalanine, a neutral branched amino acid, in LBW newborn. Higher levels of amino acids, branched and/or aromatic, have been associated with insulin resistance,39, and One of the greatest differences is the free choline, with low levels in the LBW group. The spectral region between 4.06 and 4.08 ppm, belonging to fragments of phosphoethanolamine, also shFinding that the lower levels of choline are associated with LBW is compatible with the epigenetic programming hypothesis. Interactions of nutrients with the epigenetic machinery lead to changes associated with the regulation of gene expression that underlies the developmental programming consequences in adult life. The epiThe differences found in choline, proline, alanine, glutamine, glucose, citrulline and phenylalanine at birth show that metabolic alterations are present in LBW. Even though it will be interesting and useful to clarify the mechanisms by which these metabolic changes lead to LBW consequences later in life, they are difficult to establish at present. Metabolic profile may be useful, however, in detecting differential phenotypes and in identifying those populations with the greatest potential risk. The identification of these differences can facilitate the search for alterations in tracking studies. These metabolites could be promising candidates in the search for the molecular differences capable of explaining the increased risk that LBW subjects exhibit for developing cardio-metabolic diseases later in life. That notwithstanding, whether or not these abnormalities are the source of low birth weight is difficult to establish.Our findings suggest that a substantial component of metabolic disease risk has a prenatal developmental basis. Finding discriminatory metabolites in umbilical cord blood plasma from LBW newborns with a higher risk to develop cardio-metabolic disease may lead to their being used as potential biomarkers for the early prediction of risk and with the concomitant clinical implications for follow-up.Both the presence of the differential metabolic profile, as well as the relationship of these metabolites with birth weight demonstrate that metabolic alterations are present and detectable at birth in LBW subjects. Beginning at birth, metabolic abnormalities provide information on the impact of intrauterine life. Whether these early disturbances in metabolism contribute to the development of cardio-metabolic diseases in these subjects later in life needs to be assessed in prospective studies.The authors declare that they have no competing interests.EL and CI conceived the study, designed it and wrote the manuscript. CGV informed the parents of the objectives of the research project, took the anthropometric measurements at birth and obtained the UCB samples. FJC participated in the experimental design and biochemical interpretations. DM and JMM performed the NMR measurements, NMR data analysis and biochemical interpretation of metabolomic data. All authors have read and approved the final manuscript.Figure S1. Loadings plot of the PLS-DA model for discrimination between spectra of umbilical cord blood plasma from low vs normal weight babies at birth. Figure S2. Loadings plot of the PLS-DA model for discrimination between spectra of blood plasma from mothers of low vs normal weight babies at birth.Click here for file


Understanding the main values and beliefs that might promote humanized birth practices in the specialized hospitals requires articulating the theoretical knowledge of the social and cultural characteristics of the childbirth field and the relations between these and the institution. This paper aims to provide a conceptual framework allowing examination of childbirth practices through the lens of an organizational culture theory. A literature review performed to extrapolate the social and cultural factors contribute to birth practices and the factors likely overlap and mutually reinforce one another, instead of complying with the organizational culture of the birth place. The proposed conceptual framework in this paper examined childbirth patterns as an organizational cultural phenomenon in a highly specialized hospital, in Montreal, Canada. Allaire and Firsirotu’s organizational culture theory served as a guide in the development of the framework. We discussed the application of our conceptual model in understanding the influences of organizational culture components in the humanization of birth practices in the highly specialized hospitals and explained how these components configure both the birth practice and women’s choice in highly specialized hospitals. The proposed framework can be used as a tool for understanding the barriers and facilitating factors encountered birth practices in specialized hospitals. The use of medical interventions such as epidural analgesia, electronic fetal monitoring (EFM), and induction of labor has dramatically increased in recent years in Canada. The results of a recent Canadian study showed that 57.3% of women received epidural analgesia, about 90.8% EFM, and 44% induction of labor ,2. The tThe humanization of childbirth is arguably an alternative model to the medical and technological models. Most of the previous literature defines the humanization of birth as birth without any unnecessary medical intervention. A women-centered care approach in which women are respected regarding their values, beliefs, autonomy, choices, and their control over their bodies and births are considered as key concepts of humanized birth care -10.Humanized care is a changing and developing process. Humanized birth care in high-risk pregnancies aims at enhancing patient care for the improvement of the birthing experience in hospitals . In a hiMost of the existing studies on childbirth still do not manage to stress the importance of the embedded social and cultural norms of an institution or their consequences on birth practices. Moreover, a theoretical framework for studying these issues from an organizational/cultural perspective has not yet been developed. This paper aims to provide a conceptual framework allowing examination of childbirth practices in specialized hospitals through the lens of organizational culture.We start with a discussion about the social and cultural aspects of childbirth. The feminist framework of childbirth is discussed, since this is arguably the most important scholarly model of birth that supports a humanized birth approach. We will further discuss the limits of feminist literature regarding the analysis of medicalized birth practices and characterize childbirth as an embedded organizational culture event, proposing to study it from an organizational culture perspective. Using Allaire and Firsirotu’s (1984) theory of organizational culture, we will finally propose our conceptual framework and show its application in a highly specialized hospital.Childbirth has both a biological and a cultural definition. It is also a political and social phenomenon . EspositBirth by design, has emphasized that maternity care systems must be studied in the historical, cultural, and societal settings in which they function. According to DeVries, what women want in birthing shows how women’s desires and needs at birth can both be constructed by and can construct the maternity care they receive [Considering pregnancy as a socially constructed event, Schneider 2002) assumed that “women’s views reflect, more or less, the views of the health professionals, family, friends, and those in the literature” . Klein a02 assume receive .The social features of birth including cultural ideas and social support systems have an important impact on birth practices. Social scientists have argued that a medicalized birth is determined by embedded cultural ideas in which progress and technological birth practices are defined as a victory of civilized society over the ancient feminine nature of birth. Consequently, women are controlled through more and more medical practices in order to prevent any risk to themselves and their babies . This viSocial scholars have argued that social dimensions of birth are inherent in natural childbirth whereas a modern-day, escape from society back to nature birth seems impossible because, in real situations, both women and care providers integrate elements of modern medicine into previously natural childbirth ,24. MacdThe limitation of the existing socio-cultural studies of birth practices is that they fail to explore the organizational culture dimensions of the institution and their role and power over the change in birth practices towards a more humanized one. What kind of socio-cultural opportunities or constraints are imposed on organizations trying to adopt humanized or medicalized birth approaches?In the following part, we discuss the feminist theory of childbirth as being one of the best frameworks for understanding our proposed conceptual framework. Following this discussion, we highlight our reasons for choosing the organizational culture theory for our conceptual framework.Feminist activists have provided a new insight into childbirth and opened the doors to new topics for research including the sociology of childbirth . During the nineteenth and early twentieth centuries the first wave of feminist activists argued persistently for women’s rights to relieve their own suffering, and hence to gain control over the birthing process, the right of extended choices during childbirth, and full control over their body, as well as their reproductive life. The consequences of the struggle of the first wave of feminist activists were beneficial, as women gained the right to use pain relief drugs and to express their preference for or against it; however, women lost control over the process of childbirth, as well as allowing birth to continue to shift from home to hospital ,26.In the late 1960s and early 1970s, the second wave of feminist activists began to take an active interest in the “alternative birth” or “natural birth” movement, and once more advocated home birthing as well as midwifery services ,28. TheyMost of the feminist scholars described “natural” or “normal” births as part of a social process which was based on different cultural ideas ; howevergender perspective basis [From the feminist literature it is clear that certain facets leading to the medicalization of birth have developed on a ve basis . Some have basis ,24,26,30ve basis . AlthougMoreover, birth practices have been analyzed from a cross-cultural perspective by many anthropologists and feminist scholars -34. The We also understand that African-American women had more desire for medicalized births because of their historical lack of access to appropriate medical care and mistreatment by professionals . Jewish Finally, the contemporary feminists or “third wave” of feminist activists argue about women’s choice and their positive experience of obstetric technology at birth. The feminist literature has started to uncover women’s own views on medicalized birth, and to show women’s desire for the medical model of birth, such as epidural analgesia, in a hospital setting. The contemporary group of feminists emphasizes that technology is not essentially a male-gendered product for the establishment and continuation of the obstetrician’s authority at birth, and it can serve women’s needs and purposes. Beckett (2005) argues that women can purposefully choose and benefit from the utilization of obstetric technology.To our knowledge, however, no research has so far looked at how the organizational culture of the hospital setting may change women’s decisions when choosing a specific medical intervention, such as an epidural or a cesarean section. Understanding women’s perceptions of and decisions about medical interventions is only possible if we pay attention to the commonalities and differences in the organizational culture in the environment where birth takes place.In order to improve childbirth practice, we need to understand the way in which birth is experienced by women and also the “internally consistent and mutually dependent practices and beliefs that exist around it” . NewburnMoreover, humanizing childbirth draws away a phenomenon of organizational change. To understand whether hospitals are able to transform themselves, it is not enough to study only their definite rational characteristics. Organizations also include a culture that is formed by values, beliefs, and signification, all of which constitute the foundation of organizational functioning . Study oIn the present paper, the conceptual model of “organizational culture” introduced by Allaire and Firsirotu (1984) is considered a comprehensive and appropriate theoretical model for the study of childbirth practice in specialized hospitals. This model allows researchers to explore the cultural precipitations of childbirth through the lens of an organizational/ cultural study, in order to understand which childbirth practices work best for which cultures.Consequently, we will describe the organizational culture theory. After conceptualizing childbirth as an organizational culture phenomenon, we will then introduce the properties of Allaire and Firsirotu’s (1984) organizational culture theory model.Understanding organizational culture is important because culture gives meaning, clarity, and direction to the action of an organization and its members . OrganizAllaire and Firsirotu (1984) were the first to propose a completely conceptual model of organizational culture, which represents an organization as three inter-related endogenous variables, these being structure, culture, and individuals, all of which are influenced by the external factors surrounding the organization, which in turn include society, history, and contingency , and allNext, we will cite factors who have contributed to the description of the internal and external components of the organizational culture model theory as explained by Allaire and Firsirotu . We willThe environment in which an organization is constructed, and how this functions, has extensive influence on the organization. Society also defines the judicial and socio-economic context to which an organization must adjust.The history of an organization includes how, and why, it has been created. This includes the founder’s vision, the values of past leaders, the successes and failures which the organization has seen, reasons for past leaderships, and finally the routines and rituals that have been exercised over the years. History shapes expectations, past histories of integration, the roots of beliefs, and the expression of the organizational culture, as well as its structural architecture.Contingency consists of the technology, economics, competition, and regulations that characterize an organization. The method of functioning and the survival of the organization are deeply adaptive to the type of cultural appearance it portrays and the structural struggles that it may be going through.These consist of the strategies, structures, policies, and management processes in the organization. They include all aspects of the organization’s functioning, such as formal goals, objectives and strategies, authority, power structure, control mechanisms, rewards and motivation, and managerial processes and style.myths, ideologies, and values. This phenomenon is observed in rites and rituals, customs, metaphors, glossaries, lexicons, acronyms, slogans, stories, legends, symbolic artifacts, design, and architecture. The history, the environment, and the contingency of an organization shape culture.Cultural factors manifest themselves strongly in These consist of people in different hierarchical levels of leadership roles, as well as passive recipients, who simply contribute to the meaning of the organization. Knowledge, cultural competence, values, assumptions, expectations, needs and motives are the factors which affect the relationships between actors and the extent to which meaning is shared with other actors in the organization.The suggested conceptual framework, adapted from both Allaire and Firsirotu (1984) and Halabi 2005), is presented in  was also an important factor. On the other hand, the stakeholders’ and managers’ aspirations for specialization rather than humanization of care in highly specialized hospitals (ambient of society) acts as a major barrier to humanized birth care.The findings of this study also showed that the presence of various organizations and groups within society, such as the “feminist activists”, have had a noticeable influence on childbirth practices in hospitals. This group showed profound support for the rights of women and their families to seek humanized care. The Minister of Health’s new “perinatal” guideline toward de-medicalization of birth in Quebec (contingency). The lack of necessary financial support from outside sources was another important contingency factor. This served as a barrier to this approach. In reality, most money in the hospital was being invested on the physical security of the patient, but investments on the psychological aspects of birth care were not significant. High-risk patients faced with losing a child or a pregnancy, for example, had access to very few psychological resources in this hospital (contingency). In certain circumstances, general shortages of staff and the lack of access to resources were the biggest barriers encountered in implementing humanized birth care practice in the studied highly specialized hospital. The stress and anxiety resulting from not having a place of birth, the possibility of not having the choice of a care provider, and the experience of long waiting hours for appointments also led to the dehumanization of birth (contingency).The hospital under study was an integral part of the University Networks Integrated to Health in Montreal and had an objective to improve the quality and continuity of care to mothers and their children, especially after discharge from hospital (history). According to the nurses interviewed, these strategies could bring normality to such a specialized environment, as well as ease stress by aiding in the provision of a more humanized form of care for women. On the other hand, becoming a referral center for high-risk pregnancies reinforced the health care provider’s utilization of technical and medical obstetric care and led to the development and implementation of more medicalized, rather than humanized, care in the studied hospital (history).Analysis of the history of this hospital revealed that the previous and present leaders of the hospital have promoted policies toward humanized birth care, such as accepting companions 24/7, accepting normal pregnancies, providing LDR rooms to all mothers, and integrating midwives into the hospital setting in the near future missions and strategies (structure) of the studied hospital concentrated on a caring and family-centered approach to childbirth based on the collaboration of family in care. This philosophy and strategy allowed the women’s family to act as partners in care, and this led to a respectful approach toward people and their needs, as well as an environment in which women and their families had the opportunity to grow, learn, and adapt according to their own potential and experiences.The internal rules and regulations (structure) of the hospital, such as the hospital’s flexible visiting and companionship rules, were perceived as facilitating factors toward humanized birth. The women participants affirmed that the humanization of birth is more prominent when the staff allows them to have their close relatives nearby, especially during medical interventions or operations. On the contrary, the rules regarding discharge in this hospital, which urged mothers to leave the hospital as soon as the discharge was signed, even if they were not psychologically and physically prepared, was seen as a barrier to humanized birth.The factors related to the (structure). Having a room in the hostel for mothers who needed to remain somewhere to breastfeed their baby on demand was an important part of the humanization of birth care in the studied hospital. Moreover, the development of the physical environment of the hospital in the near future aimed at providing a friendly and welcoming physical environment to the mother and the child while at the same time aiding the implementation of easy access to care and services and the adoption of more space and services for family cohabitation (structure). Some women and nurse professionals in this study, however, stated that there were restrictions at the hospital, such as double occupancy of rooms, a lack of space, and a lack of intimacy for families during postpartum (structure).A hostel-like service existed in the hospital to accommodate parents for a week after the mother’s discharge without extra charge in case the baby had to stay professional environment and lack of communication between health care providers. This caused delays in the transfer of documents and delayed breastfeeding, and sometimes treatment (structure). On the other hand, the training environment of the hospital and the excessive number of health care professionals interfered with women’s privacy and fostered a lack of intimacy and continuity of care (structure). The interviewed professionals stated that the lack of human resources, especially nurses and doctors, made them overflow with work, and that under such conditions it may take longer before they can face the question of the humanization of care (structure).The lack of sufficient communication and teamwork spirit among professionals in this setting was observed to be a barrier in the provision of humanized birth care. Many of the women participants complained about the ambitions for the provision of humanized birth care alongside medical interventional care. From the point of view of the professional participants, medical intervention does not exclude humanized care. These professionals intended to improve satisfaction, safety, assurance, and comfort for the women while providing humanized care . The interviewed women were also seen to value the medical and technocratic as well as humanized aspects of care .The professionals and administrators of the hospital expressed needs and expectations of the participants, most of the women participants said they needed to have the option of a completely pain-free labor and delivery. As a whole, 95 of 157 of the women received epidural analgesia during labor, although most of them had used other methods of relieving pain, such as medication, walking, changing position, breathing, and showering before deciding to have the epidural analgesia. These women felt satisfied with their painless childbirth experience. Noticeably, most of the women participants in the study also perceived that providing epidural analgesia was a humanistic care approach, as it relieved their pain and suffering and allowed them to live through a better child birthing experience .With regard to the cultural competency was another factor that helped the adaptation of multiculturalism and the immigrant population. The professionals stressed the importance of respecting families’ cultural beliefs, desires, needs, preferences, and cultural diversity. Nevertheless, language and communication difficulties between the nurses and some of the parturient women in the postpartum unit were a barrier to the humanization of care; it was undesirable for some women to give birth in a hospital when they did not understand what they were told . Most of the participants also mentioned that their motivation was to work for the love of children .The professionals’ culture, such as its festive familial customs and traditions, its ideologies when dealing with patients’ spiritual and religious beliefs, and its valuing of family, largely facilitated the implementation of humanized birth care in this highly specialized hospital. Nevertheless, the institutional culture of valuing medical performance was perceived as an obstacle to the humanized birth care approach. Many of the participants argued that both the culture of care around high-risk pregnancies in specialized hospitals and the highly esteemed medical aspects of this care acted as barriers to the humanization of birth (culture).The hospital’s The findings of this study revealed that the birthing environment of the studied hospital contained its own culture and structure as well as its own language and type of technology that mostly focused on risk and its management. In order to explore the facilitating factors and barriers toward the humanization of birth care, one must first redefine the definitions of risk, risk reduction, and risk management within such a setting. The women participants in the studied highly specialized hospital appreciated the technocratic approach to childbirth and even perceived it as a form of humanized birth care, because technology enhanced their feelings of security, assurance, and provided them with a pain-free birth. The establishment and practice of the humanized birth care model in a highly specialized hospital is thus a much greater goal than simplistic opposition to the medicalized birth care model and the technological supremacy associated with it. Empowering women throughout their pregnancy and childbirth, providing psychological supports to high-risk mothers , modifyiThe conceptual framework proposed in this paper can be used as a tool for understanding the barriers and facilitating factors encountered in the humanization of birth practices in specialized hospitals, where a high level of technological and medicalized birth practices exists. The hospital culture, its social context, and its individuals are significant factors involved in the increase in the technocratic model of birth in most modernized and developed countries. The role of contingency factors, such as the rules and regulations, technology, and economic status that impact the specialized hospitals either by promoting or discouraging humanized or medicalized birth approaches, awaits full exploration, which entails the necessity of further investigation in those hospitals. Nevertheless, the conceptual framework is also applicable for examining humanized birth practices in all hospitals regardless of their level of specialty.To provide maternity care of optimal quality, public health stakeholders need to be aware of the childbirth practices in different organizations and then insure that these conform to women’s and their families’ needs. The theoretical framework of this study may not be broad enough to allow analysis of all the organizational dimensions and their influences on the provision of optimal care, but at a theoretical and practical level it still has the potential to highlight some components of humanized birth care and the facilitating factors for or barriers to such care in highly specialized hospitals.The authors declare that they have no competing interests.Four persons have fulfilled the conditions required for authorship. Author 1 (RB) has coordinated the paper from writing its protocol, taking approvals, designing the semi-structured questionnaires, collecting the data, transcriptions, analysis, and redaction of the manuscript. Author 2 (MH) supervised the project from beginning to the end, helped in implementing the research, helped in qualitative analysis and validate the methodology, and participated in drafting the manuscript. Author 3 (LG) also supervised the project, participated in the design of the study and questionnaire development. Authors 4 (WF) and 5 (CM) participated in drafting the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/13/205/prepub


Using data collected as a follow-up to a randomized trial, Melissa Gladstone and colleagues show that during the first two years of life, infants born preterm in southern Malawi are disadvantaged in terms of mortality, growth, and development. Preterm birth is considered to be associated with an estimated 27% of neonatal deaths, the majority in resource-poor countries where rates of prematurity are high. There is no information on medium term outcomes after accurately determined preterm birth in such settings.p<0.001) or wasted  with no effect of gestational age at delivery. Preterm infants more often screened positively for disability on the Ten Question Questionnaire (p = 0.002). They also had higher rates of developmental delay on the MDAT at 18 months (p = 0.009), with gestational age at delivery (p = 0.01) increasing this likelihood. Morbidity—visits to a health centre (93%) and admissions to hospital (22%)—was similar for both groups.This community-based stratified cohort study conducted between May–December 2006 in Southern Malawi followed up 840 post-neonatal infants born to mothers who had received antenatal antibiotic prophylaxis/placebo in an attempt to reduce rates of preterm birth . Gestational age at delivery was based on ultrasound measurement of fetal bi-parietal diameter in early-mid pregnancy. 247 infants born before 37 wk gestation and 593 term infants were assessed at 12, 18, or 24 months. We assessed survival (death), morbidity , growth (weight and height), and development . Preterm infants were at significantly greater risk of death . Surviving preterm infants were more likely to be underweight  in Africa has little chance of survival, while the chances of survival for a baby born at 32 weeks in North America or Europe are similar to one born at term. There are very few data on the longer term outcomes of babies born preterm in Africa and there are multiple challenges involved in gathering such information. As prenatal ultrasound is not routinely available, gestational age is often uncertain. There may be little routine follow-up of preterm babies as is commonplace in high-income countries. Data are needed from recent years that take into account both improvements in perinatal care and adverse factors such as a rising number of infants becoming HIV positive around the time of birth.We could improve outcomes for babies born preterm in sub-Saharan Africa if we understood more about what happens to them after birth. We cannot assume that the progress of these babies will be the same as those born preterm in a high-income country, as the latter group will have received different care, both before and after birth. If we can document the problems that these preterm babies face in a low-income setting, we can consider why they happen and what treatments can be realistically tested in this setting. It is also helpful to establish baseline data so that changes over time can be recorded.The aim of this study was to document four specific outcomes up to the age of two years, on which there were few data previously from rural sub-Saharan Africa: how many babies survived, visits to a health center and admissions to the hospital, growth, and developmental delay.The researchers examined a group of babies that had been born to mothers who had taken part in a randomized controlled trial of an antibiotic to prevent preterm birth. The trial had previously shown that the antibiotic (azithromycin) had no effect on how many babies were born preterm or on other measures of the infants' wellbeing, and so the researchers followed up babies from both arms of the trial to look at longer term outcomes. From the original group of 2,297 women who took part in the trial, they compared 247 infants born preterm against 593 term infants randomly chosen as controls, assessed at 12, 18, or 24 months. The majority of the preterm babies who survived past a month of age  were born after 32 weeks of gestation. Compared to the babies born at term, the infants born preterm were nearly twice as likely to die subsequently in the next two years, were more likely to be underweight (a third were moderately underweight), and to have higher rates of developmental delay. The commonest causes of death were gastroenteritis, respiratory problems, and malaria. Visits to a health center and admissions to hospital were similar in both groups.This study documents longer term outcomes of babies born preterm in sub-Saharan Africa in detail for the first time. The strengths of the study include prenatal ultrasound dating and correct adjustment of follow-up age (which takes into account being born before term). Because the researchers defined morbidity using routine health center attendances and self-report of illnesses by parents, this outcome does not seem to have been as useful as the others in differentiating between the preterm and term babies. Better means of measuring morbidity are needed in this setting.In the developed world, there is considerable investment being made to improve care during pregnancy and in the neonatal period. This investment in care may help by predicting which mothers are more likely to give birth early and preventing preterm birth through drug or other treatments. It is to be hoped that some of the benefit will be transferable to low-income countries. A baby born at 26 weeks' gestation and admitted to a neonatal unit in the United Kingdom has a 67% chance of survival; preterm babies born in sub-Saharan Africa face a starkly contrasting future.http://dx.doi.org/10.1371/journal.pmed.1001121.Please access these Web sites via the online version of this summary at UNICEF presents useful statistics on mother and child outcomespreterm birth rates worldwide, including mapping the regional distribution and has also produced practical guides on strategies such as Kangaroo Mother Care, which can be used for the care of preterm infants in low resource settingsThe World Health Organization has attempted to analyse information on initiatives taking place to improve neonatal outcomes in low income settingsHealthy Newborn Network has good information on research being conducted into preterm birthThe March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on the risks and causes of premature birthTommy's is a nonprofit organization that funds research and provides  An estimated 3.6 million neonatal deaths occur each year, accounting for 41% of deaths in children under 5 y old There is good evidence that antenatal corticosteroids and improved care in the immediate neonatal period, such as Kangaroo Mother Care, and encouragement of early breastfeeding improve neonatal survival in the first month of life Most previous studies come from high-resource countries and have focused on babies born very preterm, before 32 weeks' gestation. Almost three-quarters of preterm births occur however between 32 and 36 wk The aim of our study was to assess four specific outcomes—post-neonatal survival, morbidity, growth, and development—in a community-based sample of infants born after spontaneous preterm delivery in rural sub-Saharan Africa. All had gestational age accurately determined using prenatal ultrasound scanning.We obtained written permission from each district health officer for the four areas in which the study was conducted. The research midwives explained the purpose of the study to each child's parent or carer and obtained written informed consent to participate in the study. The study gained ethical approval from the College of Medicine Research Ethics Committee in Malawi.Malawi is considered to be one of the poorest countries in the world with a per capita income of US$290 per year 2) with a mean (standard deviation [SD]) BMI of 22.7 (2.7). More details of the APPLe cohort can be found elsewhere We carried out a cohort study assessing mortality, morbidity, development, and growth in post-neonatal infants who were known to have been born preterm (<37 completed wk gestation by ultrasound scan) (group 1) or at term (37–41 wk) (group 2). All infants for this follow-up study were born during a placebo-controlled double blind antibiotic intervention study  in southern Malawi. Birth weights were recorded for those who delivered in a health facility (65.5%). In the parent cohort population, low birth weight (<2.5 kg) was recorded in 10.0% of babies. Serial ultrasound was not available for this population, therefore making it impossible to diagnose infants as being small for gestational age (due to intrauterine growth restriction or other) during pregnancy. Nutritional status in women was measured using BMI . 48 (16.3%) infants known to have been born preterm and to have survived the neonatal period were lost to follow-up . For the comparison cohort, we selected at least double the number of term-born post-neonatal babies. This selection was done using a computer-generated random list from the APPLe parent cohort. Following this method, 678 babies born at term were identified. 593 (87.5%) were found at follow-up and included in the study. 85 infants known to be born at term (12.6%) were lost to follow-up  .We aimed to assess all infants on at least one occasion at a corrected age of 12 or 18 or 24 mo. We assessed them at this precise age ±1 wk. Corrected age was defined as chronological age (time elapsed after birth) minus number of weeks born less than 40 wk Socio-demographic characteristics were gathered for each family by interviewing the mother at the time of assessment, using a standard set of questions similar to those used in the Malawi Demographic Health Survey To assess survival, we collected information on date of death, cause of death, and place of death by interviewing the mother. Cause of death was established using information gathered at verbal autopsy and classified as recommended in recent studies To assess morbidity, we collected data using a structured questionnaire. This questionnaire included whether the child was well at the time seen (as reported by the mother and observed by the research nurse midwife), the number of episodes and reasons for accessing care at a health facility, the number and reasons for being admitted to hospital in the past, and, specifically, whether the child had ever had convulsions.Growth was assessed for each child by measuring length and nude weight. Weight was measured using electronic infant weighing scales (SECA 735) with reading increments of 10 g. Length was measured to the nearest 0.5 cm using standard locally made length measurement boards based on blueprints for their construction from the World Health Organization and the US Centers for Disease Control  Development and disability were assessed using the Ten Question Questionnaire (TQQ) All data were double entered and verified, hosted on a password-protected SQL server with any discrepancies and outlying results reviewed. Mothers and babies were identified only by the mother's identification number and in the case of twins, the twin number. Data were analysed using SPSS for Windows version 17 and Stata version 10. All available data were included in the analyses.Analyses compared data for infants and their mothers in the preterm and term delivery groups. All infants were used in the analysis, except where stated otherwise. Survival of infants in each of these strata was estimated using Kaplan-Meier curves and compared using a Cox's proportional hazards model. Gender was also included in the Cox's proportional hazards analysis. When date of death was not reported (six cases) it was assumed to have been mid-way between birth and the assessment visit. For all other analyses, when data required for an analysis was missing the record was omitted from analysis. Socio-economic status was measured using principal components analysis of multiple assets following methods from the World Bank Weight-for-corrected-age (WAZ), height-for-corrected-age (HAZ), and weight-for-height z (WHZ) scores were derived using Epi-info version 3.2.2 with World Health Organization reference data Stratified Mantel-Haenszel tests were also used to examine the association between being underweight (WAZ<−2) and identification of disability on the TQQ or severe developmental delay on the MDAT. Stratification was by whether preterm or not and by age of assessment to control for the influence of these factors.A total of 840 post-neonatal infants were followed up, of whom 247 were born preterm and 593 were born at term . Among t2 = 5.05, p = 0.02. The estimated hazard ratio (95% CI) for preterm compared with term-born infants is 1.79 (1.09–2.95) . The estimated mortality rates for infants born preterm who had survived the neonatal period was almost double that of infants born at term. At 1 y, there was an estimated mortality rate of 7.7% (5.0–11.8) for preterm and 4.0% (2.7–6.0) for term infants, and at 2 y (cumulative) a rate of 13.2% (8.9–19.3%) and 7.6% (5.4–10.6), respectively  for male compared with female infants is 2.19 (1.30–3.68).Post-neonatal infants born preterm were at significantly greater risk of death (during the 6-wk to 24-mo follow-up period) than those born at term: 27/247 (10.9%) preterm and 37/593 (6.2%) term-born infants died; Cox PH χ09–2.95) . With twectively . Mortalin = 10). Within this group, only one of these was found dead on follow-up  who survived the post-neonatal period in our cohort (ollow-up . The numInformation on cause of death was available for 23 of 27 (85.2%) infants born preterm and 37 of 37 (100%) infants born at term . We idenM2 = 0.03, p = 0.86). Nonroutine reasons for attendance to the health centre included malaria, respiratory problems, diarrhoea, upper respiratory tract infections, skin rashes, and fever. Only two mothers reported going to the health centre because their child was malnourished. Visits for routine immunisations (97.4% [preterm] versus 98.9% [term]) and weighing 82.5% (preterm) versus 85.6% (term) were found to be similar.Mothers did not commonly report morbidity at the time of assessment  with 98.7% (226/229) of the preterm group and 97.9% (550/562) of the term group reported to be well at the time of interview. Despite this, reported attendance to the health centre was high in both infants born preterm (94.3%) and those born at term (91.3%) with no significant difference between the groups. The (median) numbers of times that health care was accessed were 3, 3, and 4 times at 12, 18, and 24 mo of age, and did not differ significantly between the groups (Mantel-Haenszel p = 0.13).There were no significant differences in the preterm versus term group in the number of infants reported to have been admitted to a hospital . The median number of admissions was 1.0 in each of the groups. Infants born preterm were more likely to be admitted for cerebral malaria (3.5% versus 1.8%) or anaemia (3.9% versus 2.1%), but this was not statistically significant. Similar proportions were admitted for simple malaria (9.2% versus 9.9%) and pneumonia (5.7% versus 5.0%). Other causes for admission were sepsis (reported only in four cases), meningitis (one case), and malnutrition (five cases). HIV/AIDS was not reported by parents as a cause of admission to hospital. There were no significant differences in the number of children experiencing convulsions, as reported by parents, preterm compared to term-born children: 10.4% (22/211) versus 6.9% (38/548) (p<0.001). Almost one-third (32.3%) of preterm infants were moderately underweight (below −2 SD WAZ) and 11.1% severely underweight (below −3 SD WAZ) (p = 0.08).When assessing growth/nutritional parameters for the cohorts, preterm infants were significantly more likely to be underweight ( SD WAZ) . Pretermp = 1.0). There was a trend for lower rates of breastfeeding in the preterm infants at 18 mo (80.7%) versus term infants (89.6%) (p = 0.057) and also at 24 mo for preterm (44.2%) versus term infants (48.3%) (p = 0.59), but neither were significant.Breastfeeding rates for preterm infants (100%) and term infants (98.6%) at 12 mo were very similar (p = 0.002), with 32/230 (13.9%) of the preterm infants and 38/562 (6.8%) of the term infants scoring positive on one or more questions. Serious delay in walking, standing, or sitting (question 1) (p = 0.049) or being slow in comparison to children of the same age  (p = 0.005) were the items that were significantly more frequent in infants.The post-neonatal infants born preterm were significantly more likely than term-born infants to screen positive overall on the TQQ  (p = 0.0p = 0.216), at 18 mo 22.8% versus 10.9% (p = 0.009), and at 24 mo 12.8% versus 10.7% (p = 0.274). Significant differences were also found specifically at 18 mo for language development (p = 0.033) (p = 0.02), social development , and overall development at 18 mo , and in social development  at 24 mo  . When deat 24 mo .The number of children demonstrating severe delay on the MDAT (delay greater than 2 SD from the mean expected score for the age of the child) was the same across the two groups (9/230 preterm infants [3.9%] versus 23/562 term infants [4.1%]).We analysed the association between growth and development in this cohort. We used WAZ as these were the most robust of our three measures. There was a significant association between being underweight and positive on the disability screen , or having severe delay on the MDAT (<−2 SD) . The association was similar for both term and preterm infants .This study has clearly shown that infants who are born prematurely in a rural community setting in sub-Saharan Africa, who survive the first month of life, are still up to twice as likely to die as term infants during the first 2 y of life with a cumulative mortality rate of 132/1,000 in comparison with those born at term . This cohort of preterm infants is unique because gestational age was established by ultrasound dating. We have shown that these infants are almost entirely a population of late preterm infants, but despite this, are still more likely to have higher rates of malnutrition and developmental delay than term infants. As rates of prematurity are high in sub-Saharan African settings Recent studies from high-income countries have also demonstrated this relatively increased mortality in late preterm babies; however, outcomes have mainly been measured only in the neonatal period Male infants within our cohort of infants born at term were more likely to die than female infants in the post-neonatal period. There is limited evidence that gender does have an effect on perinatal, neonatal There is little information on cause of death in infants in resource-poor settings, particularly in early infancy. Verbal autopsy tools in this population were found to be useful and we documented more deaths in preterm infants associated with respiratory problems compared to infants born at term. In the absence of an agreed definition and framework for measuring morbidity in community settings in children, we used reported health-seeking behaviour as a proxy measure. Almost all mothers reported their children as well at the time of the study taking place. Almost all mothers had visited a health centre for routine weighing and immunisation and almost one in four children had been admitted as an inpatient in the first 2 y of life. There was no difference in health-seeking behaviour between babies born preterm and those born at term. The reports from the mothers of their children being “well” at the time of the study was surprising considering the morbidity we then encountered in terms of malnutrition, developmental delay, and the high rates of admission to the health centre. Our tools for assessing morbidity were clearly not specific enough and highlight that parent-reported morbidity is not a good measure of childhood morbidity. Currently, an agreed framework or standard for measuring morbidity in children is not available and further studies using other approaches are very much warranted In our cohort, children born preterm were significantly more likely to be underweight and wasted and did not demonstrate catch-up growth in contrast to those born at term. Comparison with studies from high-income settings is difficult as most have studied very preterm or low birth weight infants Infants born preterm were twice as likely to be identified as having a disability using the TQQ as well as to fail the MDAT. Studies from high-income countries have demonstrated educational difficulties in children born late preterm. As far as we are aware, there are no similar studies on developmental outcomes in cohorts of accurately gestationally dated late preterm-born infants from a low-income setting. A study in Bangladesh measured development using a variety of more complex assessment tools adapted from those in high-income countries (Bayley II and Stanford Binet) It is widely recognised that both nutrition and prematurity have an impact on development. We confirmed that these associations are present in this population from sub-Saharan Africa, but the cross-sectional nature of this study did not allow us to evaluate this relationship in more detail—this would clearly be an interesting area for further research. We suggest that in the absence of more sophisticated screening mechanisms, weight and development could be used as “morbidity markers” and serve as an entry point for identifying other health needs especially for babies born preterm.To date, interventions in low-income settings to reduce neonatal morbidity and mortality have targeted the perinatal period. Our data show that, for surviving preterm babies who survive the immediate neonatal period, even in this mainly late preterm-born surviving group, there is ongoing disadvantage with increased risk of death, growth retardation, and developmental delay. Further detailed qualitative and longitudinal studies to assess the causal mechanisms for these problems would be extremely beneficial. Along with these studies, post-neonatal interventions need to be trialled that might improve outcomes in this group of preterm-born children.